SciPhu

Quantum Biophysical Semeiotics Demonstrates for the first Time the Water Memory-Information

noreply@blogger.com (Stagnaro) — Fri, 01 Jul 2011 17:35:00 +0000

This paper is dedicated to my friend Marcello Masci,
by whom I was told that Cem-Tech exist, even … in Italy!

Argument of large discussion, water memory is till now, 1 July 2011, a conjecture.
In fact, nobody has demonstrated that water is capable of retaining a memory (I like to add also INFORMATION) of substances once dissolved in it to arbitrary dilution.
The concept was notoriously proposed by Jacques Benveniste to explain the purported therapeutic powers of homeopathic remedies, which are prepared by diluting solutions to such a high degree that not even a single molecule of the original substance remains in most final preparations. Benveniste sought to prove this basic tenet of homeopathy by conducting an experiment to be published independently of homeopathic interests in a major journal.

Unfortunately, Jacques Benveniste and all other today’s scientists know Quantum Biophysical Semeiotics (www.semeiotica biofisica.it, and www.sisbq.org).

While some studies, including Benveniste's, have reported such an effect, double-blind replications of the experiments involved have failed to reproduce the results, and the concept is not accepted by the scientific community, in my opinion, because we are living in Mean Ages Medicine, Ages of the Enlightenment out.

In following my CLINICAL, Quantum Biophysical Semeiotic, first Demonstration of Water Memory-Information.

Importantly, such a experimental evidence can be reproduced easily and quickly, at the condition that scientists, who want reproduce it, know the quantum biophysical semeiotic method!!!

Since four days, I am suffering from gastro-entero-colitis, caused by infected food, i.e., by bacteria Gram-positive in nature; probably enterococcus (I am going to ascertain with laboratory data, but it is not important for the experiment.

BASAL QBS evaluation showed increased acute antibody synthesis (See above mentioned website www.semeioticabiofisica.it): for instance, latency time of typical BALT- and Liver- Gastric Aspecific Reflex was 5 sec. (NN = 6 sec.).
In addition, the duration of both BALT and liver oscillations was 7 sec. (NN = 6 sec.) (ibidem).

At this point, I have captured with Cem Tech two devices (crystals) frequency from my transverse (immediately before splenic curvature) and initial descendent colon, for 1 minute.

After applying the two devices on myself, upon the same sites, cited above, I assessed for the second time the intensity of BALT and Liver acute antibody synthesis: latency time resulted significantly reduced to 3 sec., while the duration of both BALT and liver oscillations raised to 9 sec. (NN = 6 sec.).

Immediately thereafter, I went away from the Cem Tech devices, and repeated the evaluation of acute antibody synthesis, which showed the identical, basal value of latency time: 5 sec., namely, the antibody synthesis, without the influence of extremely high frequency of Cem Tech devices returned to the identical, basal parameter value: 5 sec.

At this moment, I directed the extremely high frequency of Cem Tech devices towards water, present in a glass (precisely: mineral wasser…), applying the two crystals directly on the glass wall for 10 minute.

After that, I located the glass with the water on the table, 10 cm from my body: the acute antibody synthesis increased again, raising to latency time of 3 sec., while the duration of both BALT and liver oscillations raised again to 9 sec. (NN = 6 sec.).

At this point, I go away from the water in the glass, and repeated the evaluation of acute antibody synthesis, which showed predictably the same, basal value of latency time: 5 sec., namely, the antibody synthesis, without the influence of extremely high frequency present CLEARLY in the water, returned to the identical, basal parameter value: 5sec.

Soon after I drunk that water, I observed identical, significant increasing of acute antibody synthesis, as described above under two experimental conditions: latency time resulted significantly reduced to 3 sec., while the duration of both BALT and liver oscillations was 9 sec.

I like to say that cleaned glass was inactive, i.e., it did not bring about stimulation of antibody synthesis.

Interestingly, now, when I am writing three hours after the experiment, all parameter values continue to be increased, as I illustrated above.
Successively, at my further control, the action was evident also after 6 hours!

Conclusion: My quantum-biophysical-semeiotic experiment, illustrated above in details, demonstrates CLINICALLY Water Memory-Information for the first time.

Sergio Stagnaro MD
Via Erasmo Piaggio 23/8,
16039 Riva Trigoso (Genoa) Italy
Founder of Quantum Biophysical Semeiotics,
Honorary President of International Society of
Quantum Biophysical Semeiotics (SISBQ)
Who's Who in the World (and America)
since 1996
Ph 0039-0185-42315
Cell. 3338631439
www.semeioticabiofisica.it
www.sisbq.org
dottsergio@semeioticabiofisica.it

Di Bella's Oncological Terrain and Insomnia.

noreply@blogger.com (Stagnaro) — Fri, 04 Feb 2011 08:48:00 +0000

Introduction.
Living organisms have notoriously evolved internal timekeeping mechanisms to synchronize behaviour and physiology with the cycles of day and night. These biological clocks have been found in a lot of organisms, as fungi, fruit flies, hamsters, and humans. The biological clock of humans is found in the brain. There is a general agreement that in such event an important role is plaid by the path of light input to the suprachiasmatic nucleus (SCN), a collection of neurons that regulates our circadian rhythms. The SCN contains several cell types and several different peptides (including melatonin, somatostatin, vasopressin and vasoactive intestinal peptide) and neurotransmitters, and it interacts with many other regions of the brain, especially epihysis.
In a fascinating article, Authors have demonstrated that the hormone melatonin phase shifts circadian rhythms generated by the mammalian biological clock, the hypothalamic suprachiasmatic nucleus (SCN), through activation of G protein-coupled MT2 melatonin receptors (1). The pretreatment with physiological concentrations of melatonin in rat decreased the number of MT2 melatonin receptors expressed in mammalian cells in a time and concentration-dependent manner. Furthermore, MT2 melatonin receptors were internalized upon pretreatment with both physiological and supraphysiological concentrations of melatonin (1). In rats, the recovery process was partially protein synthesis dependent. Furthermore, exposure to physiological concentrations of melatonin for a time mimicking the nocturnal surge (8 h) desensitized functional responses mediated through melatonin activation of endogenous MT2 receptors (1).
The authors conclude that in vivo the nightly secretion of melatonin desensitizes endogenous MT2 melatonin receptors in the mammalian SCN, thereby providing a temporally integrated profile of sensitivity of the mammalian biological clock to a melatonin signal (1).

The Human Suprachiasmatic Nucleus

In mammals, the controlling clock component that generates a 24-hour rhythm is the suprachiasmatic nucleus (SCN), located in the hypothalamus. The SCN produces a signal that can keep the rest of the body on an approximately 24-hour schedule, but in individuals negative for Di Bella’s Oncological Terrain (2-10), as I am going to demonstrate for the first time in this article.
Even in the absence of external time cues, humans maintain a sleep-wake rhythm very close to 24 hours. Typically an organism’s circadian system is made up of components that receive environmental input, that generate the 24-hour rhythm, and that mediate rhythmic output to all the tissues of the body. In mammals, the controlling clock component that generates a 24-hour rhythm is the suprachiasmatic nucleus (SCN), located in the hypothalamus. SCN signal can keep the rest of the body on an approximately 24-hour schedule.
However, because the internal clock's period is not exactly 24 hours, environmental cues—most importantly, light—are required to reset the clock each morning and keep the organism synchronous with the external world. Notoriously sunlight represents a signal that can reset neurons in the SCN.

At the moment, Authors agree with the statement that light enters the eye activating neurons in the retina, and converting photons to electrical signals. The retinal neurons transmit the electrical signals from the retina via long axons in the optic nerve. Along the way is the optic chiasm, where the optic nerves from the left and right eye meet and cross. At the optic chiasm, visual information continues toward the back of the brain, where it is processed into images that we can consciously perceive. The neurons carrying information to the SCN, however, take a different path. They exit the optic chiasm and turn upward, toward the SCN, so called because it is located above the chiasm.

However, with the aid of Quantum Biophysical Semeiotics (See my website www.semeioticabiofisica.it and www.sisbq.org), I have demonstrated that in biological systems, beside local realm, weherin transmission happens by losing time and energy, as above described, according to classic physics, there is also no-localm realm, characterized jet by a four dimensional space/time, but showing 2 T/D and 2 S/D: the information is “simultaneous” in the space and synchronous in the time, whitout losing energy since its mechanism nature is cathalitic,according to quantum biophysics (11-21).
The SCN is a small, paired, wing-shaped structure, located at the base of the brain, exactly in the hypothalamus. Within each side of the SCN is a network of up to several thousand neurons, normally synchronized with the activity of its neighbours.
Inside a single SCN neuron, the protein product of a biological clock gene turns off production of more protein, forming a negative feedback loop. Even in the absence of external time cues, humans maintain a sleep-wake rhythm very close to 24 hours. Typically an organism’s circadian system is made up of components that receive environmental input, that generate the 24-hour rhythm, and that mediate rhythmic output to all the tissues of the body.
The SCN produces a signal that can keep the rest of the body on an approximately 24-hour schedule, as above refered. However, because the internal clock’s period is not exactly 24 hours, environmental cues—most importantly, light—are required to reset the clock each morning and keep the organism synchronous with the external world, by regulating tissue level of melatonin.
Light enters the eye and activates neurons in the retina that convert photons to electrical signals, but especially in the first phase, according to Quantum Biophysical Semeiotics, through “simultaneous” information of some occipital brain regions, as demonstrates the following clinical evidence.
When an healthy individual opens his (her) until before closed eyes, brain occipital circonvolutions show “simultaneously” microcirculatory activation, according to type I, associated, physiological (3, 22-25).
Further information reader may find in the websites http://www.semeioticabiofisica.it/microangiologia/, and www.sisbq.org.
Unfortunately, regarding retinal in-put transmission to the brain, physicians all around the world continue to think erroneously that the unique way of energy transmission is the retinal neurons transmission of the electrical signals from the retina via long axons in the optic nerve. Along the way is the optic chiasm, where the optic nerves from the left and right eye meet and cross. At the optic chiasm, visual information should contune toward the back of the brain, where it is processed into images that we can consciously perceive, losing time and energy. The neurons carrying information to the SCN, however, take a different path. They exit the optic chiasm and turn upward, toward the SCN, i.e., above the chiasm. All that happens really in the second phase of visual perception.
In a few words, such as transmission is firstly “simultaneous”, according to non local realm of biological systems, I have demonstrated in earlier articles (11-21), and secondly it happens as generally admitted, losing time and energy (13,19,20).
Role of hormones and neurotransmitters in SCN functioning.
A major function of the SCN in mammals is thought to be to generate biological rhythms with a period of about 24 hours, and these circadian rhythms are normally related to the light-dark cycle. They underly daily rhythms of activity and of hormone secretion. The involvement of the SCN was first shown by experiments in which damage to the SCN in animals resulted in abnormal activity rhythms.
In all mammals many physiological processes are governed by circadian rhythms; for example the secretion of many hormones, such as melatonin, follows a 24-hour cycle.
Specialized neurons in the ventrolateral SCN have the ability for light-induced gene expression. If light is turned on at night, a singular componen of SCN relays this information throughout the entire SCN, as demonstrates clinical evidence: in a few second, local microcirculatory activation disappears, followed by basal microvessel fluctuations (3-5, 26)
The SCN receives notoriously information via the optic nerve. However, neurons in the dorsomedial SCN can generate a 24-hour rhythm of activity that can persist even in constant darkness. The SCN sends information to other hypothalamic nuclei and the pineal gland to modulate body temperature and the production of hormones such as cortisol and melatonin.
The SCN is one of four nuclei in the brain that receive nerve signals directly from the retina, the other three are the lateral geniculate nucleus (LGN), the superior colliculus, and the pretectum.
The LGN passes information about color, contrast, shape, and movement on to the visual cortex and itself signals to the SCN. The superior colliculus controls the movement and orientation of the eyeball. The pretectum controls the size of the pupil.
However a key feature of a true circadian pacemaker, such as the SCN, is that it can produce rhythms with an approximate period of 24 hours even in the absence of any change in light. True circadian rhythms thus persist when animals are maintained in constant light or constant dark. Thus light cues do not themselves determine the rhythm, they just entrain the rhythm, keeping it locked to the light-dark cycle.
Insomnia and wakefulness are related to other important disorder, including Di Bella’s Oncological Terrain.
Epidemiologic studies indicate that disturbances in sleep and wakefulness predict the presence of current, and the emergence of future, psychiatric impairments, including depressive, anxiety, and substance use disorders (27).
At the end of the life cycle, a predictive value for disturbed sleep was demonstrated for individuals above the age of 55 by Authors (28) who presented data from 140 patients suffering from major depression disorder (MDD) consecutively visiting in a family practice setting over the course of 6 months and 140 controls, matched with respect to age and sex.
In these aged patients, improvement in mood was correlated with increased sleep quality in both depressed and nondepressed patients. However, other lifestyle indicators were not.
Young and colleagues added to the database supporting the predictive value of insomnia in psychiatric morbidity in a cross-sectional study of 49 older adults (ages 50-89) with bipolar disorder; 60% reported a history of suicidal ideation (29). Positive correlates for suicidal ideation included white race, prominent sleep difficulties in the depressed phase, and younger age.
Taken togheter, these data extend the predictive value of disturbed sleep in the psychiatric disorders to younger and older age spectra, obviously only in those individuals involved by Constitutiond-Dependent Inherited Real Risks (3, 4, 48).

For the first time, based on a sufficiently long, well established, clinical experience, I emphasise suprachiasmatic nucleus disturbances, evaluated with Quantum Biophysical Terrain, as a typical sign of Di Bella’s Oncolgocal Terrain.
As a matter of fact, among the principal neurotransmitters involved in conveying photic information to the SCN have been identified glutamate, and PACAP. Light stimulation of the retina results in direct secretion of glutamate from the Rethino Hypothalamic Tract (RHT) into the ventral VIP-containing part of the SCN (30, 31). Glutamate as a transmitter at RHT/SCN synaptic connections plays an important and critical role in mediating photic regulation of circadian rhythmicity. RHT terminals innervating the SCN show glutamate immunoreactivity associated with synaptic vesicles which confirms the role of glutamate as a neurotransmitter (32,33).
Different types of glutamate receptors were identified and localized in the SCN using in situ hybridization and immunocytochemistry (35).
My principal interest here is to underly the central role plaid in SCN disturbaces by melatonin as well as somatostatin, two paramount components of Di Bella’s Oncological Terrain, conditio sine qua non of cancer onset in SCN in bith function and disturbances (2-4,10,22).
Melatonin, the so-called darkness hormone, proved to be of great importance in the functioning of the SCN, as demonstrate the following experimental evidence: “symultaneously” to eye closure, physician observes microvessel activation of epyphysis and after one sec., also the activation of SNC microcirculation, according to type I, associated (2-4, 22).
In my clinical researches, among the most important target of melatonin in humans, there is the SCN, as it contains the highest density for melatonin receptors (4, 10, 22, 36).
A double effect of melatonin in the SCN, namely, an immediate effect and long term effect, has encouraged its worldwide use against the ill effects of jet lag. Acceleration of sleep initiation in humans at circadian phases when the SCN would normally stimulate waking is another reported action of melatonin (37).
In terms of long term effect, melatonin can phase shift and amplify circadian rhythmicity of the SCN. Melatonin application has been found to be useful in synchronizing the endogenous circadian rhythms not only in people who suffer from jet lag, but also in blind individuals, patients with dementia, and shift workers (38).

In spite of the experimental evidence favouring a very important role for melatonin in the circadian timing system, the exact role of melatonin has not been demonstrated clearly. Melatonin and seasonal rhythms are intimately related in mammals, and this has been well documented (37-40). The retinohypothalamic-pineal (RHP) axis is comparable in animals and humans. In both animals and humans melatonin is secreted exclusively at night. The RHP is capable of detecting changes in night length to make proper adjustments for the duration of nocturnal melatonin secretion so that animals can use this melatonin message to trigger seasonal changes in behaviour (41).
I have demonstrated the central role of Melatonin in the pathogenesis of Di Bella’s Oncological Terrain (2-4, 22, 23).

A second neurotransmitter lowered typically in Di Bella’s Oncological Terrain is somatostatin (SST). SST producing neurons of the SCN are located in both the core and shell portions and form a distinct peptidergic neuronal group. The shell portion of the SCN, which is likely to be involved in the regulation of overt rhythms, projects within the SCN through SST fibres. Aging effects of SCN neuropeptide expression, like the circadian profile of peptide expression, may be species specific as far as the SCN is concerned. Synapse of SS fibres on VIP and AVP neurons and presence of SST receptors in the SCN is suggestive of a regulatory role for SST on other peptidergic neurons. An inhibitory modulating role of SST on VIP rhythmicity has been demonstrated (42). Increase in SST immunoreactivity could explain the observed VIP decrease with aging, and, if enhanced SST immunoreactivity reflects a release deficit, this may lead to reduction in inhibitory action.
One must remember that VIP, a gut polypeptide, has been identified as one of the main neurotransmitters of SCN neurons and participates in SCN function. In addition, VIP signalling through its receptor serves two important functions in the SCN, namely, circadian rhythmicity in a subset of neurons and maintenance of synchrony between intrinsically rhythmic neurons. This may also mean that VIP-expressing neurons themselves are circadian pacemakers in the SCN for establishing and synchronizing rhythmic activity (42).
From the above remarks, I am allows to state that in individuals involved by Di Bella’s Oncological Terrain, characterized by lowering of both melatonin and SST, the first plays the central role in SCN disturbances.

Regarding the link between neurotransmitters and some human disorders, researchers have started to identify the role of the SCN in a lot of disease conditions. SCN dysfunction, particularly in terms of neurotransmitter content, has been associated with several chronic diseases such as hypertension, diabetes, and depression (43, 44).
An awful number of observations strongly suggest that a changed SCN may precede the development of hypertension. There is also evidence that circadian disturbances may be detected prior to the development of diabetes or hypertension (45, 46) Further evidence that the functionality of the biological clock may be affected in humans by diseases such as depression and hypertension has been provided by numerous Authors.

According to my clinical experience, all researches are fundamentally biased, since the majority of Authors ignore Quantum Biophysical Semeiotic Constitution (45).
A 55 year-long clinical experience allows me to state that the Authors, overlooking these predispositions to related disorders, cannot correlate neurotransmitters alterations with a lot of disorders, like SNC dysfunction and psychiatric diseases, hypertension, and diabetes.
In fact, these disorders can occur exclusively in presence of the related Quantum Biophysical Constitutions (2-8, 23-25, 48).
In the course of efficacious therapy, e.g., with selective serotonin reuptake inhibitors, both neuronal and cerebral evoked potentials, now-a-days assessed at the bed- side with the aid of Quantum Biophysical Semeiotics in reliable way, have to ameliorate clearly (49, 50).
In addition, under identical condition, cerebral microcirculatory functional reserve improves statistically (2-8, 10, 23-25), when bedside assessed with the aid of SPBM, i.e. "Single Patient Based Medicine" (24, 48, 49).

Melatonin Deficiency: the Link between Insonnia, Night Shift and Cancer.

In a large literature, the link between night shift, insomnia and cancer are largely described, although till now Authors mainly ignore the existence of Di Bella’s Oncological Terrain, I suggested since a decade as a the condition sine qua non of malignancy (2-10).
In 2001, in a large, and interesting prospective cohort study of shift-work and breast cancer, the risk of breast cancer was statistically significantly elevated in postmenopausal women who worked for 30 or more years on rotating night shifts, compared with those who never worked at night. (51)
A few years later, in 2009, it was reported that women in Denmark, who developed breast cancer after many years of working night shifts, received compensation despite only limited research supporting the link. Out of 78 cases notified to the national board of industrial injuries in Denmark, 38 have received compensation through their employers’ insurance schemes.
All of the women had worked night shift patterns for at least 20 years and were otherwise at low risk – they had low alcohol consumption and no family history of breast cancer. The Danish decision was based on a ruling by the International Agency for Research on Cancer (http://www.iarc.fr/) in December 2007 which stated that “shift-work that involves circadian disruption is probably carcinogenic to humans.”
Despite Oncological Terrain was overlooked, other experimental studies have indicated the majority of totally blind people whereby melatonin is never suppressed by light exposure since most totally blind women are not receptive to light, could be protected from cancer through this mechanism.
Richard Stevens, Ph.D., cancer epidemiologist at the University of Connecticut Health Center, Farmington, Conn., and colleagues published a study in the British Journal of Cancer that found breast cancer risk decreased by degree of visual impairment, from moderate low vision to totally blind. “It was initially thought that blind women might have a greater risk of developing breast cancer because some studies have reported that they have earlier menarche and delayed child-bearing age, both of which have been seen to increase the risk of breast cancer in women,” R. Stevens said. “Yet these women have been found to have a lower risk of developing the disease.” They concluded that this suggests a dose-response relationship between visible light and breast cancer risk (52).

Conclusion.

The results of my research, emphasising the insomia as another sign of Di Bella’s Oncological Terrain, need certainly to be further corroborated on a sufficiently large scale. However, on the base of their concordance, my results allow to state that Melatonin deficiency is the link between insomnia and Di Bella’s Oncological Terrain.
As a consequence, in the treatment of insomnia, physicians have to prescribe drugs, as well as physical therapy (e.g., patches emitting energy concordant with biological systems, as epiphysis and SCN), aiming to normalize melatonin tissue level in diencephalic hypothalamic nuclei and epihysis, utilizing therapy able to transform Oncological Terrain into its “residual” variant, which prove to be no dangerous (51).
To insomnia therapy with drugs and physical treatment normalizing melatonin tissue level, I shall dedicate a next paper.

* Sergio Stagnaro MD
Via Erasmo Piaggio 23/8
16039 Riva Trigoso (Genoa) Italy
Honorary President of International Society of
Quantum Biophysical Semeiotics
Founder of Quantum Biophysical Semeiotics
Who's Who in the World (and America)
since 1996 to 2010
Ph 0039-0185-42315
Cell. 3338631439
www.semeioticabiofisica.it
www.sisbq.org
dottsergio@semeioticabiofisica.it

References
1) Matthew J. Gerdin, Monica I. et al. Melatonin desensitizes endogenous MT2 melatonin receptors in the rat suprachiasmatic nucleus: relevance for defining the periods of sensitivity of the mammalian circadian clock to melatonin. The FASEB Journal. 2004;18:1646-1656.
2) Sergio Stagnaro. Il Terreno Oncologico di Di Bella. http://www.fcenews.it, 11 ottobre 2010, http://www.fceonline.it/images/docs/terreno oncologico.pdf; http://www.luigidibella.it/cms-web/upl/doc/Documenti-inseriti-dal-2-11-2007/Il Terreno Oncologico di Di Bella.pdf; http://www.altrogiornale.org/news.php?extend.6420
3) Stagnaro Sergio, Stagnaro-Neri Marina. Introduzione alla Semeiotica Biofisica. Il Terreno oncologic. Travel Factory SRL., Roma, 2004.
http://www.travelfactory.it/semeiotica_biofisica.htm
4) Stagnaro S., Stagnaro-Neri M., Le Costituzioni Semeiotico-Biofisiche.Strumento clinico fondamentale per la prevenzione primaria e la definizione della Single Patient Based Medicine. Ediz. Travel Factory, Roma, 2004. http://www.travelfactory.it/semeiotica_biofisica.htm
5) Stagnaro-Neri M., Moscatelli G. Stagnaro S., Biophysical Semeiotics: deterministic Chaos and biological Systems. Gazz. Med. It. Arch. Sc. Med. 155, 125 ,1996
6) Stagnaro Sergio. "Genes, Oncological Terrain, and Breast Cancer" World Journal of Surgical Oncology., 2005, http://www.wjso.com/content/3/1/45/comments#205475
7) Stagnaro Sergio. Relevance of Mitochondria in Cancerogenesis. Journal of Carcinogenesis. 2005, 4:1 doi:10.1186/1477-3163-4-1http://www.carcinogenesis.com/content/4/1/1/comments#136454
8) Stagnaro Sergio. Bed-Side Evaluating Breast Cancer Real Risk. World Journal of Surgical Oncology. 2005, 3:67 doi:10.1186/1477-7819-3-67. 2005.
9) Caramel S., Stagnaro S. The role of mitochondria and mit-DNA in Oncogenesis. http://ilfattorec.altervista.org/mitDNA&oncogenesis_english.pdf; http://www.quantumbiosystems.org/admin/files/QBS 2(1) 250-281.pdf.
10) Stagnaro Sergio. Oncological Terrain and Inherited Oncological Real Risk, Confitio sine qua non of Oncogenesis. www.nature.com, 21 April 2008, http://blogs.nature.com/nm/spoonful/2008/04/stress_as_a_therapy_1.html
11) Stagnaro Sergio. Non Local Realm. Response to Selection for Social Signalling Drives the Evolution of Chameleon Colour Change. (01 February 2008). www.plos.com, http://biology.plosjournals.org/perlserv/?request=read-response&doi=10.1371/journal.pbio.0060025
12) Sergio Stagnaro. Dall’Esperimento di Lory alla Diagnostica Psicocinetica. Ruolo fondamentale della Realtà Non Locale in Biologia. http://www.fcenews.it, gennaio 2010. http://www.fceonline.it/images/docs/lory.pdf
13) Stagnaro Sergio e Paolo Manzelli. Semeiotica Biofisica Endocrinologica: Meccanica Quantistica e Meccanismi d’Azione Ormonali. Dicembre 2007, www.fce.it, http://www.fcenews.it/index.php?option=com_content&task=view&id=816&Itemid=45
14) . Stagnaro Sergio e Paolo Manzelli. Natura Quantistica di una Originale Manovra Semeiotico-Biofisica di Epatopatia . Dicembre 2007, www.fce.it, http://www.fcenews.it/index.php?option=com_content&task=view&id=862&Itemid=45
15) Stagnaro Sergio e Paolo Manzelli, Semeiotica Biofisica Quantistica: la manovra di attivazione surrenalica jatrogenetica. 09-1-2008, http://www.fcenews.it/index.php?option=com_content&task=view&id=161&Itemid=63
16) Stagnaro Sergio e Paolo Manzelli. L’Esperimento di Lory. Scienza e Conoscenza, N° 23, 13 Marzo 2008. http://www.scienzaeconoscenza.it//articolo.php?id=17775
17) Stagnaro Sergio. Semiotica Biofisica Quantistica: Diagnosi di Cuore sano in un Secondo in paziente distante 200 KM! www.fce.it, 07-05-2008 http://www.fcenews.it/index.php?option=com_content&task=view&id=1316&Itemid=47
18) Stagnaro Sergio. Role of NON-LOCAL Realm in Primary Prevention with Quantum Biophysical Semeiotics. www.nature.com, 01 Feb, 2008-05-17 http://www.nature.com/news/2008/080130/full/451511a.html
19) Stagnaro Sergio e Manzelli Paolo. Semeiotica Biofisica Quantistica: Livello di Energia libera tessutale e Realtà non locale nei Sistemi biologici. www.fce.it , 29 maggio 2008, http://www.fcenews.it/index.php?option=com_content&task=view&id=1421&Itemid=47
20) Sergio Stagnaro. Il Test della Osteocalcina endogena nella Diagnosi di I e II Stadio del Diabete Mellito tipo 2. 23 novembre 2010. http://qbsemeiotics.weebly.com/uploads/5/6/8/7/5687930/osteocalcina_t2dm.pdf
21) Sergio Stagnaro. Ruolo del DNA Antenna nella Diagnosi Semeiotica Biofisica Quantistica dei Primi due Stadi del Diabete Mellito tipo 2. http://www.fcenews.it, 19 novembre 2010. http://www.fceonline.it/images/docs/dna_diabete.pdf; http://qbsemeiotics.weebly.com/uploads/5/6/8/7/5687930/dna_t2dm.pdf
22) Stagnaro S., Stagnaro-Neri M., La Melatonina nella Terapia del Terreno Oncologico e del “Reale Rischio” Oncologico. Travel Factory, Roma, 2004. http://www.travelfactory.it/semeiotica_biofisica_2.htm
23) Stagnaro S., Stagnaro-Neri M., Le Costituzioni Semeiotico-Biofisiche.Strumento clinico fondamentale per la prevenzione primaria e la definizione della Single Patient Based Medicine. Travel Factory, Roma, 2004. http://www.travelfactory.it/
24) Stagnaro S., Stagnaro-Neri M., Single Patient Based Medicine.La Medicina Basata sul Singolo Paziente: Nuove Indicazioni della Melatonina. Travel Factory, Roma, 2005. http://www.travelfactory.it/
25) Sergio Stagnaro. New Renaissance in Medicina. Prevenzione Primaria del Diabete Mellito tipo 2. Sito del Convegno, http://qbsemeiotics.weebly.com/atti-del-convegno.html, 16 novembre 2010; http://qbsemeiotics.weebly.com/uploads/5/6/8/7/5687930/newrenaissance_prevenzionet2dm.pdf; english version http://qbsemeiotics.weebly.com/uploads/5/6/8/7/5687930/report_stagnaro.pdf
26) Stagnaro S., Percussione Ascoltata degli Attacchi Ischemici Transitori. Ruolo dei Potenziali Cerebrali Evocati. Min. Med. 76, 1211, 1985 [MEDLINE]
27) American Psychiatric Association. Sleep Disorders. Diagnostic and Statistical Manual of Mental Disorders. Washington, DC: American Psychiatric Publishing, Inc; 1994:597-661.
28) Hohagen F, Kappler C, Schramm E et al. Prevalence of insomnia in elderly general practice attenders and the current treatment modalities. Acta Psychiatr Scand. 1994;90:102-108.
29) Krystal AD. The changing perspective of chronic insomnia management. J Clin Psychiatry. 2004;65(suppl 8):20-25.
30) Mrosovsky N: Locomotor activity and non-photic influences on circadian clocks. Biological Reviews 1996 , 71:343-372.
31) Meijer JH. Photic entrainment of mammals. In Handbook of Behavioral Neurobiology. Circadian clocks. Edited by: Takahashi JS, Turek FW, Moore RY. New York, Plenum; 2002:183-222.
32) Piggins HD, Samuels RE, Coogan AN, Cutler DJ. Distribution of substance P and neurokinin-1 receptor immunoreactivity in the suprachiasmatic nuclei and intergeniculate leaflet of hamster, mouse, and rat. J Comp Neurol 2001 , 438:50-65. PubMed Abstract
33) Ding JM, Chen D, Weber ET, Faiman LE, Rea MA, Gillette MU: Resetting the biological clock: mediation of nocturnal circadian shifts by glutamate and NO. Science 1994 , 266:1713-1717.
34) Gannon RL, Rea MA. In situ hybridization of antisense mRNA oligonucleotides for AMPA, NMDA and metabotropic glutamate receptor subtypes in the rat suprachiasmatic nucleus at different phases of the circadian cycle. Mol Brain Res 1994 , 23:338-344.
35) Reghunandanan V., Reghunandanan R. Neurotransmitters of the suprachiasmatic nuclei. Journal of Circadian Rhythms. 2006, 4:2.
36) Reppert SM, Weaver DR, Rivkees SA, Stopa EG. Putative melatonin receptors in a human biological clock. Science 1988 , 242:78-83.
37) Dollins AB, Zhdanova IV, Wurtman RJ, Lynch HJ, Deng MH. Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance. Proc Natl Acad Sci USA 1994 , 91:1824-1828.
38) Sack RL, Lewy AJ. Melatonin as a chronobiotic, treatment of circadian desynchrony in night workers and the blind. J Biol Rhythms 1997 , 12:595-603.
39) Wehr TA. Melatonin and seasonal rhythms. J Biol Rhythms 1997 , 12:518-527.
40) Pévet P: Melatonin: From Seasonal to Circadian Signal. J Neuroendocrinol 2003 , 15:422-426.
41) Lincoln GA, Andersson H, Loudon A. Clock genes in calendar cells as the basis of annual timekeeping in mammals – a unifying hypothesis. J Endocrinol 2003 , 179:1-13.
42) Fukuhara C, Nishiwaki T, Cagampang FR, Inouye ST. Emergence of VIP rhythmicity following somatostatin depletion in the rat suprachiasmatic nucleus. Brain Res 1994 , 645:343-346. Nielsen HS, Hannibal J, Fahrenkrug J: Vasoactive intestinal polypeptide induces per1 and per2 gene expression in the rat suprachiasmatic nucleus late at night. Eur J Neurosci 2002 , 15:570-574.
43) Pickering TG. The clinical significance of diurnal blood pressure variations. Dippers and nondippers. Circulation 1990 , 81:700-702.
44) Yamamoto M, Yamasaki Y, Kodama M, Matsuhisa M, Kishimoto M, Ozaki H, Tani A, Ueda N, Iwasaki M, Hori M: Impaired diurnal cardiac autonomic function in subjects with type 2 diabetes. Diabetes Care 1999 , 2:2072-2077
45) Borghi C, Costa FV, Boschi S, Mussi A, Ambrosioni E. Predictors of stable hypertension in young borderline subjects: a five-year follow-up study. J Cardiovasc Pharmacol 1986 , 8(Suppl 5):s138-41.
46) Eilam R, Malach R, Bergmann F, Segal M. Hypertension induced by hypothalamic transplantation from genetically hypertensive to normotensive rats. J Neurosci 1991 , 11:401-411.
47) Stagnaro Sergio. A paramount Bias in the Research. B.M.J. 2003. http://www.bmj.com/content/326/7400/1171/reply
48) Stagnaro Sergio. Reale Rischio Semeiotico Biofisico. I Dispositivi Endoarteriolari di Blocco neoformati, patologici, tipo I, sottotipo a) oncologico, e b) aspecifico. Ediz. Travel Factory, www.travelfactory.it, Roma, 2009.
49) Stagnaro S., Percussione Ascoltata degli Attacchi Ischemici Transitori. Ruolo dei Potenziali Cerebrali Evocati. Min. Med. 76, 1211, 1985 [MEDLINE]
50) Stagnaro S., Auscultatory percussion of the cerebral tumour: Diagnostic importance of the evoked potentials, Biol. Med., 7, 171-175, 1985.
51) Schernhammer Eva S., Laden F., Speizer E, et al. Rotating Night Shifts and Risk of Breast Cancer in Women Participating in the Nurses’ Health Study Journal of the National Cancer Institute, Vol. 93, No. 20, October 17, 2001
52) Pillittere D., and Miller M. J Natl Cancer Inst., Volume 92, Issue 9 Pp. 686-689, 2000.

PSYCHOKINETIC DIAGNOSTICS, QUANTUM-BIOPHYSICAL SEMEIOTICS EVOLUTION.

noreply@blogger.com (Stagnaro) — Sat, 13 Mar 2010 10:29:00 +0000

Introduction.

Since November 2007, I’ve been illustrating in numerous articles the bases of Quantum Biophysical Semeiotics (1-10). Then some famous websites have been helping me in spreading these developments of such physical semeiotics, representing a new physical tool, which proved to be reliable in bedside diagnosis, therapeutic monitoring and clinical research. For instance, with the aid of quantum-biophysical semeiotics, it’s possible in a few seconds to bedside recognize every constitution, as well as related inherited real risk, that predisposes positive individuals to the relative disorders (11-13). Starting from May 2009, some Commentaries have been posted even in the International Atherosclerosis Society website www.athero.org (14, 15)

At this point, I cannot understand the real reason why the numerous Biophysical-Semeiotic Constitutions, as well as relative inherited real risk, conditio sine qua non, e.g., of diabetes and malignancy, both solid and liquid, bedside recognized quickly with a stethoscope since birth, although such knowledge is accepted and spread among physicians by the majority of famous peer-reviews (See Bibliography in my website www.semeioticabiofisica.it), are not illustrated sufficiently and emphasised by National Health Services. In addition, traditional Medicine cannot highlight a lot of biological events, as Lory's experiment (8), because it knows exclusively local realm in biological systems, which brought about the psychokinetic diagnostics, for the first time described in this article.

As a matter of facts, in all tissues - besides local realm exists also NON-LOCAL Realm, as my friend Paolo Manzelli and I have demonstrated earlier in a lot of articles (1-10). Recognizing also a 4 Dimension Space/Time Matrix, wherein there are 2 SD and 2 TD, which provides a simultaneous information, not ruled by the old, out-moded-view of the world, deterministic, classic physics, but by quantum physics evolution (entanglement and disentanglement) we are able to understand why the first phase of hormone action is simultaneous with very beginning of whatever stimulation (for instance, intense digital pressure upon a bone, e.g., radius, is simultaneous to pancreas size increasing as response to endogenous osteocalcin!) (16) The second phase of hormone action mechanism, different in nature, is brought about by the contact of osteocalcin with relative receptors on beta-cell outer membrane of Langherans's islets (10, 21, 22).

In conclusion, mankind needs urgently open-minded physicians, Editors, and Reviewers, who are unavoidable to Medicine Progresses, as I wrote earlier (7, 24-28).

No Local Realm beside Local Realm in Biological Systems.

On the website of Harvard University Press, at http://www.hup.harvard.edu/catalog/LIBMIN.html http://www.hup.harvard.edu/catalog/LIBMIN.html, one may read such as statement:

“Most notably, Libet's experiments reveal a substantial delay--the "mind time" of the title--before any awareness affects how we view our mental activities. If all conscious awarenesses are preceded by unconscious processes, as Libet observes, we are forced to conclude that unconscious processes initiate our conscious experiences”.

I have sent the following critical comment to Contact_HUP@harvard.edu, without receiving answer, neither for courtesy or good manner!

Dear Sirs, in your wonderful website at the URL http://www.hup.harvard.edu/catalog/LIBMIN.html, I've just read "Most notably, Libet's experiments reveal a substantial delay - the "mind time" of the title - before any awareness affects how we view our mental activities. If any conscious awareness is preceded by unconscious processes, as Libet observes, we are forced to conclude that unconscious processes initiate our conscious experiences". Such as sentence is not right, from Quantum Biophysical Semeiotics view-point, www.semeioticabiofisica.it

In fact, first of all, with the aid of this clinical tool, since 30 years I've been demonstrating that it's possible, rapid, and easy to bedside assess in reliable way microcirculatory function and structure of every biological system, including brain (14-23).

Secondly, Benjamin Libet did not know Quantum Biophysical Semeiotics, I have founded in 2007, November! Energy-Information, according to my friend Paolo Manzelli, an outstanding chemist, is simultaneous and not transmitted spending time and wasting energy, as it happens throughout biological systems, identical from embryogenesis view-point, both in the same individual and from subject to subject (not necessarily twin, as in Lory’s Experiment), regardless the distance between them (1-13)

As regards the future of Medicine, I am allowed to state that it’s already begun, as far as Biology and Physical Semeiotics are concerned. In fact, biological events are more complex, i.e., difficult to understand, than generally admitted today. Fortunately, the presence of no local realm, besides local realm, in Biological Systems (1-21), highlights the patho-physiological mechanisms underlying a lot of above-mentioned events, until now unknown, or erroneously explained, like Benjamin Libet's experiments (8).

Interestingly, the fundamental knowledge, Quantum Biophysical Semeiotics is based on, indicates that in all biological systems, both in human and animal, besides local realm, there is no local realm, wherein space/time matrix is jet quadric-dimensional, but showing 2 S/D and 2 T/D (1-11).

As a consequence, this type of information is “simultaneous” in space and “synchronous” in time, as Lory's Experiment demonstrates (8). In a few words, information appears simultaneously in a human body many kilometres far away from information’s origin, starting when the examiner is “thinking” to give somebody the information to do something.

At this point, I cannot understand the real reason why the numerous predispositions to disorders (i.e., Quantum Biophysical-Semeiotic Constitutions) (11-15), like diabetes and malignancy, both solid and liquid, as well as relative inherited real risks, bedside recognized with a stethoscope already at birth in a few seconds’ time due to Quantum Biophysical Semeiotics, already accepted and spread among physicians by the majority of famous peer-reviews will be tomorrow suggested by National Health Services. In addition, traditional Medicine cannot highlight a lot of biological events, e.g. Lory's experiment (8), because it knows exclusively the Local Realm in biological systems. On the contrary, in all tissues - besides that - really exists also NON-LOCAL Realm, as my co-worker friend Paolo Manzelli and I have demonstrated recently in 6 articles (1-16). Recognizing also a 4 Dimemsion Space/Time Matrix, wherein there are 2 SD and 2 TD, which provides a simultaneous Information, not ruled by the old, out-moded deterministic, classic physics, but by quantum physics evolution (entanglement and disentanglement) we are able to understand why the first phase of hormone action is simultaneous with a very beginning of whatever stimulation. For instance, intense digital pressure upon radius or vertebra bone is simultaneous to pancreas size increasing as response to endogenous osteocalcin! The second phase, different in nature, is brought about by the contact of osteocalcin with relate receptors on beta-cell outer membrane in Langherans's islets (1-14).

As a consequence, regarding Benjamin Libet’s theory, illustrate especially in Mind Time: "The Temporal Factor in Consciousness", from the above remarks, in the light of Quantum Biophysical Semeiotics, we must conclude that a new interpretation is unavoidably necessary!

As a matter of fact, in individual of experiment, in the parietal cerebral cortex, related to foot digital movement, even if the examiner is exclusively “thinking” to give a signal for muscle movement, e.g., of right big toe the circulation at base line, the circulation at base line simultaneously shows microcirculatory activation type I, associated.

When examiner says to the subject to be ready moving right big toe contemporaneously to a conventional signal, AL + PL + DL duration increases immediately to 7 sec. (NN = 6 sec.), paralleling “readiness potentials”. Finally, soon thereafter signal begin, Plateau Line intensity raises at highest value, i.e., 9 sec. (11-13,17-20) (Fig. 1).

Fig. 1

In health, mean-intense digital pressure, applied upon parietal cerebral cortex skin projection area, brings about fluctuation of both upper and lowers ureteral reflex: vasomotion and respectivaly vasomotility. Transferred the parameter values of these fluctuations , even mentally, on cartesian axes system, doctor obtain diagram and tachygram, very rich of information.

Psychokinesis and Quantum-Biophysical Semeiotics.

The term psychokinesis (from the Greek “psyche” and “kinesis”, literally “movement from the mind”), also known as telekinesis, is a term referring to the direct influence of mind on a physical system that cannot be entirely accounted for by the mediation of any known physical energy. Examples of psychokinesis could include distorting or moving an object.

The study of phenomena said to be psychokinetic is notoriously an aspect of parapsychology.

Until now, there was no convincing scientific evidence that psychokinesis exists. However, in my opinion, based on strict interpretation of clinical experiments, quantum-biophysical in nature, I refer in following, the time has come to change our idea on it.

At the beginning of April, 2009, I started a research considering, as hypothesis 0, to falsify, the possibility that quantum entanglement could link distant patient to examining physician in a strict manner, so that trigger-points modifications in the first (patient) would bring about identical modification in the trigger points of second (doctor) and vice versa, according to the results of my earlier researches, initiated with Lory’s Experiment (1-11).

For instance, “intense” digital pressure upon patient’s precordium, i.e., heart skin projection area, even far away a lot of kilometres from examining physician, brings about “simultaneously” gastric aspecific reflex also in the later, exclusively when the first is involved by every cardiac disorders, e.g., by CAD (4-6, 15).

As a consequence, I felt myself authorized to consider such as fact, psychokinetic in nature, in the sense that doctor’s heart trigger points were “simultaneously” stimulated in the same way as patient’ ones, causing heart-gastric reflex also in doctor, but showing parameter values identical to those of distant subject: latency time, duration, intensity, and so on.

As a matter of facts, what happens under such as experimental condition is really complex, but completely enlightened by Quantum Biophysical Semeiotics (See later on). Starting from these theoretical bases – hypothesis 0, to confute – I have done a large number of experiments, in order to study what happens in “my” body, when I stimulate different trigger points by thinking, i.e., done by the mind, on a well defined subject, both healthy or ill, even a lot of kilometres far away from me, at the condition that I know him/her, at least per image, ignoring completely his (her) health condition. Obviously, I carried out such experiments also on known ill patients, but without knowing on the precise diagnosis.

Interestingly, I have subsequently applied the “mental” stimulation also on exact point of inner part of well-defined biological system, and it proved to be more precise, obviously. For instance, I suffer from outcome of lower myocardial infarct; exclusively when I stimulate “by thinking” the precise site of left ventricle involved by infarct scar, gastric aspecific reflex shows a pathological lateny time of 3 sec. Otherwise, latency time of heart-aspecific gastric reflex results normal, i.e., 8 sec., when I mentally apply digital pressure upon all diverse part of my heart. In fact, all other coronaries, both macro- and micro-coronary vessels, are normal, according to coronarographic examination, and, more precise, to quantum-biophysical-semeiotic results, which are the only to give information about coronary micro-circulatory bed (1-15).

Despite some human errors and late diagnoses, at least in initial stages of disorders, like those of Colleagues working in famous hospital, the interesting diagnoses, subsequently corroborated by means of direct examination, and then laboratory and image diagnostics, were: flu, pleuritis, pneumonitis, Oncological Terrain, breast cancer, arthrosis, a.s.o. In other words, I've examined at distance, utilising the psychokinetic diagnostics, 120 subjects, and I made their clinical diagnoses, corroborated subsequently by laboratory and image diagnostics, as the same individuals can confirm with pleasure.

Clinical Evidences demonstrate Psychokinetic Diagnostics Theory.

Firstly, we have to remember all microcirculatory events at the base of quantum-biophysical-semeiotic preconditioning (6,11-15,24-28).

In health, latency time of a reflex, e.g., heart-gastric aspecific reflex, paralleling tissue oxygenation level, at first evaluation is exact 8 sec., after 5 sec. interruption from the end of the first evaluation, raises to16 sec., doubling its basal value, due to Microcirculatory Functional Reserve physiological activation, Preconditioning is based on. Moreover, “intense” digital pressure, lasting one second, or more, upon hearth skin projection area (= Precordium), even kilometres away from examining doctor, does not bring about “simultaneously” gastric aspecific reflex, which occurs obviously after 8 sec. precisely, and lasts less than 4 sec., according to Lory’s Experiment (1-10).

At this point, if doctor apply really, for the first time, directly, “mean-intense” digital pressure on his (her) own heart skin projection, after precise 5 sec., namely performing heart preconditioning (6,26-28), the second latency time raises physiologically to16 sec., corroborating former heart distant stimulation, due to psychokinetic event: the psychocinetic diagnostic theory is thus corroborated.

To summarize in a few words, stimulating patient’s trigger-points only “by thinking”, i.e., “mentally”, despite the real distance between doctor and individual to be examined, brings about the possibility of physician’s preconditioning of every biological system, demonstrating thus the truth as well as the scientific significance of such diagnostics, made for the first time.

I term this original diagnosing method as Psychokinetic Diagnostics, which represents the paramount advancement of quantum-biophysical semeiotics: when physician is “thinking” about a well-known subject (analogously, to open radio!), i.e., having the subject on own mind, due to quantum entanglement, both peoples become part of a cosmic hologram, and can communicate each other, exchanging information (1-10).

Importantly, at this point, if Vibratory Energy (= ATP) is lowering in one or both communicating individuals, any exchange of information immediately stops. In addition, if examining doctor “imagines” the other subject as not lovely, even hateful, communication is not possible, in my opinion, demonstrating that Information Energy is LOVE!

As a consequence, in spite of the distance between them, when doctor is stimulating “by thinking” some trigger points of an individual to be examined, the related visceral reaction, e.g., aspecific gastric reflex, appears also in doctor’s stomach, showing identical value parameters.

Interestingly to understand quantum nature of these events, if either doctor or subject to examine does not breath (= Apnoea test), lowering significantly tissue energy level, subsequently worsening mitochondrial respiratory chain activity, above-illustrated events stop quickly, after only one second, indicating the real nature of these events: reducing body Vibratory Energy (= ATP), according to P. Manzelli, also Information Energy lowers rapidly, so that quantum entanglement interrupt suddenly (= disentanglement), after only one second (1-10).

References.

1) Stagnaro Sergio e Paolo Manzelli. Semeiotica Biofisica: Realtà non-locale in Biologia. Dicembre 2007, www.ilpungolo.com, http://www.ilpungolo.com/leggi-tutto.asp?IDS=13&NWS=NWS5217

2) Stagnaro Sergio e Paolo Manzelli. Semeiotica Biofisica Quantistica. http://www.ilpungolo.com/leggi-tutto.asp?IDS=13&NWS=NWS5243

3) Stagnaro Sergio e Paolo Manzelli, 09-1-2008, Semeiotica Biofisica Quantistica: la manovra di attivazione surrenalica jatrogenetica http://www.fcenews.it/index.php?option=com_content&task=view&id=161&Itemid=63

4) Stagnaro Sergio. Pollio’s Sign in bedside Recognizing renal Cancer, since its initial Stage of Inherited, Oncological Real Risk. Sunday, March 22, 2009. http://sciphu.com/

5) Stagnaro Sergio. La Diagnosi Clinica nella Semeiotica Biofisica Quantistica. www.fce.it 02-05, 2008,

http://www.fcenews.it/index.php?option=com_content&task=view&id=1285&Itemid=47

6) Stagnaro Sergio. Semiotica Biofisica Quantistica: Diagnosi di Cuore sano in un Secondo in paziente distante 200 KM! www.fce.it, 07-05-2008

http://www.fcenews.it/index.php?option=com_content&task=view&id=1316&Itemid=47

7) Stagnaro Sergio. Role of NON-LOCAL Realm in Primary Prevention with Quantum Biophysical Semeiotics. www.nature.com, 01 Feb, 2008-05-17 http://www.nature.com/news/2008/080130/full/451511a.html

8) Stagnaro Sergio e Paolo Manzelli. L’Esperimento di Lory. Scienza e Conoscenza, N° 23, 13 Marzo 2008. http://www.scienzaeconoscenza.it//articolo.php?id=17775

9) Stagnaro Sergio e Manzelli Paolo. Semeiotica Biofisica Quantistica: Livello di Energia libera tessutale e Realtà non locale nei Sistemi biologici. www.fce.it , 29 maggio 2008, http://www.fcenews.it/index.php?option=com_content&task=view&id=1421&Itemid=47

10) Stagnaro Sergio e Paolo Manzelli. Semeiotica Biofisica Endocrinologica: Meccanica Quantistica e Meccanismi d’Azione Ormonali. Dicembre 2007, www.fce.it, http://www.fcenews.it/index.php?option=com_content&task=view&id=816&Itemid=45

11) Stagnaro-Neri M., Stagnaro S. Introduzione alla Semeiotica Biofisica. Il Terreno Oncologico. Travel Factory, Roma, 2004. http://www.travelfactory.it/

12) Stagnaro S., Stagnaro-Neri M., Le Costituzioni Semeiotico-Biofisiche.Strumento clinico fondamentale per la prevenzione primaria e la definizione della Single Patient Based Medicine. Travel Factory, Roma, 2004. http://www.travelfactory.it/

13) Stagnaro S., Stagnaro-Neri M., Single Patient Based Medicine.La Medicina Basata sul Singolo Paziente: Nuove Indicazioni della Melatonina. Travel Factory, Roma, 2005. http://www.travelfactory.it/

14) Stagnaro Sergio. Stagnaro Sergio. Pre-Metabolic Syndrome and Metabolic Syndrome: Biophysical-Semeiotic Viewpoint. www.athero.org, 29 April, 2009. http://www.athero.org/commentaries/comm904.asp

15) Stagnaro Sergio. Stagnaro Sergio. CAD Inherited Real Risk, Based on Newborn-Pathological, Type I, Subtype B, Aspecific, Coronary Endoarteriolar Blocking Devices. Diagnostic Role of Myocardial Oxigenation and Biophysical-Semeiotic Preconditioning. www.athero.org, 29 April, 2009 http://www.athero.org/commentaries/comm907.asp

16) Stagnaro Sergio. Il test Semeiotico-Biofisico della Osteocalcina nella prevenzione primaria del diabete mellito. www.fce.it Febbraio 2008.

http://www.fcenews.it/index.php?option=com_content&task=view&id=909&Itemid=47 e alla URL http://www.clicmedicina.it/pagine-n-32/diabete-semeiotica.htm

17)Stagnaro S., Valutazione percusso-ascoltatoria della microcircolazione cerebrale globale e regionale. Atti, XII Congr. Naz. Soc. It. di Microangiologia e Microcircolazione. 13-15 Ottobre, Salerno , e Acta Medit. 145, 163, 1986

18)Stagnaro-Neri M., Stagnaro S., Deterministic chaotic biological system: the microcirculatoory bed. Theoretical and practical aspects. Gazz. Med. It. – Arch. Sc. Med. 153, 99, 1994

19) Stagnaro-Neri M., Stagnaro S., Auscultatory Percussion Evaluation of Arterio-venous Anastomoses Dysfunction in early Arteriosclerosis. Acta Med. Medit. 5, 141, 1989.

20) Stagnaro-Neri M., Stagnaro S. Indagine clinica percusso-ascoltatoria delle unità microvascolotessutali della plica ungueale. Acta Med. Medit. 4, 91, 1988.

21) Stagnaro-Neri M., Stagnaro S. Introduzione alla Semeiotica Biofisica. Il Terreno Oncologico. Travel Factory, Roma, 2004. http://www.travelfactory.it/semeiotica_biofisica.htm

22) Stagnaro Sergio. Newborn-pathological Endoarteriolar Blocking Devices in Diabetic and Dislipidaemic Constitution and Diabetes Primary Prevention. The Lancet. March 06 2007. http://www.thelancet.com/journals/lancet/article/PIIS0140673607603316/comments?totalcomments=1, and especially www.fce.it, http://www.fceonline.it/docs/stagnaro.pdf

24) Stagnaro Sergio. Bedside Biophysical-Semeiotic Osteocalcin Test in Diagnosing and Monitoring Diabetes. The Lancet, January 28, 2008.

http://www.thelancet.com/journals/lancet/article/PIIS0140673608601014/comments?action=view&totalComments=2; See http://www.fceonline.it/docs/stagnaro.pdf

25) Stagnaro Sergio. Comment to “Liz Wager: If comment is cheap why is peer review so expensive?”. www.BMJ.com, April 17th, 2009, http://blogs.bmj.com/bmj/2009/04/16/liz-wager-if-comment-is-cheap-why-is-peer-review-so-expensive/#comments

26) Stagnaro-Neri M., Stagnaro S., Deterministic Chaos, Preconditioning and Myocardial Oxygenation evaluated clinically with the aid of Biophysical Semeiotics in the Diagnosis of ischaemic Heart Disease even silent. Acta Med. Medit. 13, 109, 1997.

27) Stagnaro Sergio. Middle Ages of today’s Medicine, Overlooking Quantum-Biophysical-Semeiotic Constitutions and Related Inherited Real Risk. http://sciphu.com November 4, 2008. http://sciphu.com/2008/11/meadle-ages-of-todays-medicine.html

28) Stagnaro Sergio. Role of Coronary Endoarterial Blocking Devices in Myocardial Preconditioning - c007i. Lecture, V Virtual International Congress of Cardiology, 2007. http://www.fac.org.ar/qcvc/llave/c007i/stagnaros.php

* Sergio Stagnaro MD

Via Erasmo Piaggio 23/8

16039 Riva Trigoso (Genoa) Europe

Founder of Quantum Biophysical Semeiotics

Who's Who in the World (and America)

since 1996 to 2009

Ph 0039-0185-42315

Cell. 3338631439

www.semeioticabiofisica.it

dottsergio@semeioticabiofisica.it

CAD Inherited Real Risk: Nosography and Therapy. The Concept of Angiobiopathy.

noreply@blogger.com (Stagnaro) — Thu, 11 Mar 2010 13:02:00 +0000

Introduction.

Mutations in parenchimal cell n-DNA and mit-DNA are the the conditio sine qua non of the most common human disorders, like diabetes and cancer, today’s epidaemics (1-17). In fact, all these diseases are based on a particular congenital, functional, mithocondrial cytopathy, transmitted through mother, I termed Congenital Acidosic Enzyme-Metabolic Histangiopathy, CAEMH (1, 13, 14). In addition, parenchymal gene mutations cause local microcirculatory remodelling, doctor can evaluate at the bedside in a reliable manner, gathering indirect information on relative parenchymal cell inherited modifications, since biological system functional modifications parallel gene mutation , according to Angiobiopathy theory (1,18, 19).

Nosography of CAD Inherited Real Risk.

In presence of intense CAEMH in a well-defined myokardial area, involved by gene mutations in both n-DNA and mit-DNA, can brings about CAD Real Risk, charcaterized by microcirculatory remodelling from biophysical-semeiotic viewpoint, especially intense under environmental risk factors (1, 6, 7, 16). Such as congenital microvascular remodelling, including also vasa vasorum of large coronary arteries, show since birth interesting structures, i.e., newborn-pathological, type I, subtype b), Endoarteriolar Blocking Devices, EBD, localized in small arteries, according to Hammersen, I discovered (See also www.semeioticabiofisica.it/microangiologia).

Interestingly, CAD Inherited Real Risk is associated to endothelial dysfunction (there are mitochondria also in endothels, although in small amount), doctor can bedside assess in easy and reliable way, at rest as well as under stress tests (1-10, 18, 19).

As a consequence of above, briefly referred remaks, physicians are able nowadays to demonstrate the presence of typical pathological EBDs in coronary microvessel, which play a central role in CAD Inherited Real Risk.

First of all, in health, due to the non local realm, present in all biological systems beside the local realm (20, 21), as I demonstrated earlier (2-25), “intense” digital pressure on cutaneous projection area of the hearth (precordium) (= activation of the local microcirculatory blood-flow, according to type I) do not provoke “simultaneously” aspecific gastric reflex, which occurs exactly after 16 sec. of latency time (1-5, 20, 21).

On the contrary, in case of CAD Real Risk, under the indentical experimental condition, referred above, doctor observes a gastric aspecific reflex “simoultaneous to intense digital pressure”, whose intensity parallels the seriousness of underlying disorder.

Fig. 1

Aspecific Gastric Reflex:in the stomach, both body and fundus are dileted,

whereas antel-pyloric regions contracts.

As a matter of facts, the hearth-aspecific reflex, reliable and easy to apply, brought about by “mean-intense” digital stimulation of cardiac trigger-points (precordium), appears after 8 sec. physiological latency time, but lasting 4 sec. (NN = less tha 4 sec.): this is an important parameter value, corresponding to Microcirculatory Functional Reserve (MFR) activity of related coronary microvessel, thus correlated with the function and anathomy of the microcirculatory bed, or more precisely speaking, microvascular tissular-unit.

In fact, hearth-aspecific gastric reflex, when pathologically lasting 4 sec. or more (NN less than 4 sec.), indicates local microcirculatory remodelling, and thus MFR impairment due to newborn-pathological, type I, subtype b), aspecific, EBD, which reduce tissue oxygenation, through lowering microcirculatory blood-flow.

Reliable and precise information is provided by hearth preconditioning in both its Inherited Real Risk and in very initial stage of CAD (6, 11), not to speak of clinical microcirculatory analysis, which needs a thorough knowledge of the original methods (www.semeioticabiofisica.it/microangiologia).

Discussion.

From the above remarks, Angiobiopathy theory results once again corroborated. As a matter of fact, according to this theory, which carries out Tischendorf’s Angiobiotopy, every inherited pathological condition of every parenchyma associates since birth with a subsequent modification of related microcirculatory bed, so that microcirculatory remodelling give reliable information on related parenchymal cells.

First of all, analogously to all other biological systems, appears the finctional alteration of the mitochondrial respiratory chain, i.e., CAEMH), after that, come congenital gene mutations (n-DNA and mit-DNA) in myocardial cells, which cause biological alterations, and thus local microcirculatory remodelling, associated with endothelial dysfunction.

Notoriously, negative environmental risk factors can worsen already present dangerous effects of such as gene inherited modifications (inherited real risk), but cannot independently bring about them directly.

Undoubtadly, metabolic syndrome (MS) is major target in Primary Prevention of today’s epidaemias: diabetes, dyslipidaemias, hypertension, a.s.o. However, we have firstly to remember beside "classic" form of MS also the "variant" one, I described earlier with a clinical method, conditio sine qua non of lithyasis (1-8) (See http://www.semeioticabiofisica.it and http://www.semeioticabiofisica.it/microangiologia.it). In addition, I described the Pre-Metabolic Syndrome (classic and "variant", of course) that follows biophysical-semeiotic constitutions, and comes for the MS, years or decades long: "Pre-Metabolic Stage" represents the LOCUS of primary prevention (1-6).

Finally, the above remarks account for the reason that only in some cases of MS, but not in ALL, there is diabetes, which is absent in a second subgroup of individuals with MS. Notoriously, patients with MS can be subdivided in two subgroups, as regards glucose metabolism impairment (25).

In fact, besides individuals showing IIR and/or high FPG and/or PPG levels, IGT, and finally diabetes, we observe patients with IIR, who will never suffer from diabetes. My 52 year-long clinical experience allows me to state that “biophysical-semeiotic dyslipidaemic AND diabetic” constitutions account for the reason of such as different outcome. Really, only patients with inherited pancreatic islet b-cell insufficiency, can be involved – in life-span – by insulin secretion failure, due to the exhaustion of hormone production (25).

As a consequence, cigarette smoking, diabetes, dyslipidaemias, hypertension, a.s.o., do not contribute to provoke CAD in ALL individuals, but exclusively in individuals among those involved by inherited CAD real risk (1, 11-13). Therefore, in all researches, aiming to recognize risk factors of human diseases, like cigarette smoking, inappropriate diet, hypertension, diabetes, a.s.o., especially individuals with the congenital real risk have to be enrolled. From the therapeutic viewpoint, in my long well-established clinical experience, diet ethimologically speaking, Coniugated–Melatonine, and NIR-LED application in pesonalized way, proved to be really efficacious against every inherited real risk form, including cancer real risk, due to their positive influence on mitochondrial respiratory function, which results normalized or even increased (26).

* Sergio Stagnaro MD

Via Erasmo Piaggio 23/8,

16039 Riva Trigoso (Genoa) Italy

Founder of Quantum Biophysical Semeiotics

Who's Who in the World (and America)

since 1996 to 2009

Ph 0039-0185-42315

Cell. 3338631439

www.semeioticabiofisica.it

dottsergio@semeioticabiofisica.it

References.

1.Stagnaro-Neri M., Stagnaro S. Introduzione alla Semeiotica Biofisica. Il Terreno Oncologico. Travel Factory, Roma, 2004. http://www.travelfactory.it/semeiotica_biofisica.htm
2.Stagnaro S., West PJ., Hu FB., Manson JE., Willett WC. Diet and Risk of Type 2 Diabetes. N Engl J Med. 2002 Jan 24;346(4):297-298. [MEDLINE].

3.Stagnaro-Neri M., Stagnaro S., Semeiotica Biofisica: valutazione clinica del picco precoce della secrezione insulinica di base e dopo stimolazione tiroidea, surrenalica, con glucagone endogeno e dopo attivazione del sistema renina-angiotesina circolante e tessutale Acta Med. Medit. 13, 99, 1997.

4.Stagnaro-Neri M., Stagnaro S., Semeiotica Biofisica: la manovra di Ferrero-Marigo nella diagnosi clinica della iperinsulinemia-insulino resistenza. Acta Med. Medit. 13, 125, 1997.
5.Stagnaro Sergio. Endothelial cell function can ameliorate under safer drugs, such as Melatonin-Adenosine. BMC Cardiovascular disorders. http://www.biomedcentral.com/1471-2261/4/4/comments

6.Stagnaro-Neri M., Stagnaro S. Deterministic Chaos, Preconditioning and Myocardial Oxygenation evaluated clinically with the aid of Biophysical Semeiotics in the Diagnosis of Ischaeemic Heart Disease even silent. Acta Medica Mediterranea 13, 109-116, 1997.

7.Stagnaro S. A clinical efficacious maneouvre, reliable in bed-side diagnosing coronary artery disease, even initial or silent, as well as "heart coronary risk". 3rd Virtual International Congress of Cardiology, FAC,2003,

http://www.fac.org.ar/tcvc/marcoesp/marcos.htm

8.Stagnaro Sergio.Biophysical Semeiotic Constitutions, Genomics, and Cardio-Vascular Diseases. BMC Cardiovascular Disorders, 2004, http://www.biomedcentral.com/1471-2261/4/20/comments#95454

9.Stagnaro Sergio Endothelial cell function can ameliorate under safer drugs, such as Melatonin-Adenosine. BMC Cardiovascular disorders. 2004

http://www.biomedcentral.com/1471-2261/4/4/comments

10.Stagnaro S. Pre-Metabolic Syndrome: Locus primary prevention. NYAS web site. 1999 http://www.memberconnections.com/olc/membersonly/NYAS/mboards.html

11.Stagnaro Sergio. Role of Coronary Endoarterial Blocking Devices in Myocardial Preconditioning - c007i. Lecture, V Virtual International Congress of Cardiology, 2007. http://www.fac.org.ar/qcvc/llave/c007i/stagnaros.php

12.Stagnaro Sergio. Newborn-pathological Endoarteriolar Blocking Devices in Diabetic and Dislipidaemic Constitution and Diabetes Primary Prevention. The Lancet. March 06 2007. http://www.thelancet.com/journals/lancet/article/PIIS0140673607603316/comments?totalcomments=1

13.Stagnaro Sergio. New bedside way in Reducing mortality in diabetic men and women. Ann. Int. Med.2007. http://www.annals.org/cgi/eletters/0000605-200708070-00167v1

14.Stagnaro S., Stagnaro-Neri M. Istangiopatia Congenita Acidosica Enzimo Metabolica. Gazz. Med. It.- Arch. Sci. Med. 144, 423, 1985.

15.Stagnaro S., Stagnaro-Neri M. Una patologia mitocondriale ignorata: la Istangiopatia Congenita Acidosica Enzimo-Metabolica. Gazz. Med. It. - Arch. Sci. Med. 149, 67 1990.

16.Stagnaro-Neri M., Stagnaro S., Cancro della mammella: prevenzione primaria e diagnosi precoce con la percussione ascoltata. Gazz. Med. It.- Arch. Sc. Med. 152, 447 1993

17Stagnaro S., Stagnaro-Neri M., Oncological Terrain, conditio sine qua non of Oncogenesis, 2004: http://www.gutjnl.com/cgi/eletters?lookup=by_date&days=60

18.Stagnaro Sergio. "Genes, Oncological Terrain, and Breast Cancer" World Journal of Surgical Oncology., 2005, http://www.wjso.com/content/3/1/45/comments#205475

19.Sergio Stagnaro. Mitochondrial Genome of the Mastodon highlights Human Constitutions. PLOS Biology, (01 August 2007) http://biology.plosjournals.org/perlserv/?request=read-response&doi=10.1371/journal.pbio.0050207#r1725

20.Stagnaro Sergio. Biological System Functional Modification parallels Gene Mutation. www.Nature.com, March 13, 2008,

http://blogs.nature.com/nm/spoonful/2008/03/gout_gene.html

21.Stagnaro Sergio. Teoria Patogenetica Unificata, 2006, Ed. Travel Factory, Roma. 2006.

22. Stagnaro Sergio. Reale Rischio Semeiotico Biofisico. I Dispositivi Endoarteriolari di Blocco neoformati, patologici, tipo I, sottotipo a) oncologico, e b) aspecifico. Ediz. Travel Factory, www.travelfactory.it, Roma, 2009..

23.Stagnaro Sergio e Paolo Manzelli. L’Esperimento di Lory. Scienza e Conoscenza, N° 23, 13 Marzo 2008. http://www.scienzaeconoscenza.it//articolo.php?id=17775

24.Stagnaro Sergio e Paolo Manzelli, 09-1-2008, Semeiotica Biofisica Quantistica: la manovra di attivazione surrenalica jatrogenetica.

http://www.fcenews.it/index.php?option=com_content&task=view&id=161&Itemid=63

25. Stagnaro Sergio. Epidemiological evidence for the non-random clustering of the components of the metabolic syndrome: multicentre study of the Mediterranean Group for the Study of Diabetes. Eur J Clin Nutr. 2007 Sep;61(9):1143-4. Epub 2007 Feb 7. [MEDLINE]

26. Stagnaro S., Stagnaro-Neri M., La Melatonina nella Terapia del Terreno Oncologico e del “Reale Rischio” Oncologico. Travel Factory, Roma, 2004. http://www.travelfactory.it/

Bedside Recognizing Diabetes since its initial stage of Inherited Real Risk

noreply@blogger.com (Stagnaro) — Fri, 25 Sep 2009 13:50:00 +0000

Sirs,

In my opinion, there are a lot of fascinating papers on diabetes, but not useful at all in GPs day-to- day practice, since primary prevention ON VERY LARGE SCALE is far better than therapy, also in diabetic field, and GP role is central in such as enterprise!

Primary Prevention must be performed exclusively in individuals correctly recognized in a quantitative way at inherited real risk with the aid of a stethoscope; in our case, at diabetes real risk since birth.

In fact, it is generally admitted by the Authors that diabetes is a growing epidemics. However, I state that with the aid of Quantum Biophysical Semeiotics, the until now either unknown or overlooked newborn-pathological, subtype a) oncological , and b), aspecific, type I, Endoarteriolar Blocking Devices in the tissues, wherein does really exist the real risk of human common and severe diseases, as diabetes.

Obviously that happens in individuals with well-defined Quantum-Biophysical-Semeiotic Constitutions, in our case, Diabetic “and” Dislipidaemic (See Practical Applications, 6 article on Diabetes, in my website http://www.semeioticabiofisica.it) (1-6).

Interestingly, e.g., in Diabetes Primary Prevention (PP), we need new clinical tools, aiming to lower the increasing number of patients, although the present, expensive screening: in above-cited website Practical Applications: Diabetes, and Quantum-Biophysical-Semeiotic Constitutions (1-7).

For instance, in the normal Langheran’s islets microcirculatory bed, there are exclusively “normal” type II (= in arterioles, according to Hammersen), but not type I (= in small arterioles) endoarteriolar blocking devices, i.e. EBD, of first and second classes, according to S.B.Curri (See http://www.semeioticabiofisica.it/microangiologia). In health, i.e., not involved by Diabetic Constitution, we cannot observe type I, newborn- pathological, EBD in above-mentioned biological system. On the contrary, in individuals involved by diabetic constitution as well as diabetic "Inherited Real Risk" and overt diabetes, of course, we observe with the aid of Quantum Biophysical Semeiotics also type I, newborn-pathological, subtype b) aspecific , EBD, facilitating the diagnosis and consequently diabetes primary prevention. In addition, the evaluation of Insulin Secretion Acute Pick Renal Test is significantly impaired, corroborating the clinical diagnosis (1-3).

Finally, an interesting clinical tool in recognizing diabetic constitution -dependent inherited real risk, as well as in diagnosing diabetes since early stages and diabetic monitoring proved to be bedside Quantum-Biophysical- Semeiotic Osteocalcin Test (10) As a matter of fact, Pre-hypertension during Young Adulthood may be involved by Coronary Calcium Later in Life exclusively in presence of Inherited Real Risk of CAD, typical for individuals with lithyasic Constitution, present in about 50% OF ALL CASES OF Pre-Metabolic and Metabolic Syndrome (13-15).

Considering the frequent association between hypertension and diabetes, with or without CAD INHERITED REAL RISK (14, 15) more important proved to be, in my 53-year-long clinical experience, bedside recognizing diabetic predisposition, now-a-days possible since birth, utilising a lot of methods, different in difficulty, but all reliable.

For the first time, from the clinical view-point, I have recently illustrated an original manoeuvre, based on a singular activity of osteocalcin, and reliable in bedside detecting diabetes in one minute, with the aid of a stethoscope (10). In fact, osteocalcin, a product of osteoblasts, among other action mechanisms, stimulates both insulin secretion and insulin receptor sensitivity. As a consequence, osteocalcin, secreted by above-mentioned bone cells during mean-intense lasting digital pressure – for instance – applied upon lumbar vertebrae, brings about increasing pancreatic diameters, i.e., technically speaking, type I, associated, Langherans’s islet microcirculatory activation, so that doctors assess pancreas size augmentation, which in health, lasts 10 seconds exactly (1-11). After that, pancreas diameters return to basal value for 3 sec. The second pancreas size increasing lasts 20 sec., and finally the third show the highest value: 30 sec. I terme such as clinical investigation. On the contrary, in case of diabetic constitution (3, 4, 11, 13) the first pancreas increasing persists normally (10 sec.), but both the second and the third are less than physiological ones (i.e., less than 20 sec. and respectively 30 sec.). In presence of intense inherited real risk of diabetes (6), such as impairment is greater. Finally, in case of diabetes the alteration is present already in the first evaluation, wherein duration appears less than 10 sec., inversely related with disorder seriousness. Subsequently, I have ascertained that Ronald’s Manoeuvre result pathological already in individuals involved by both Diabetic Constitution and Inherited Diabetic Real Risk (1-11). Interestingly, not only in examining subject, but also in all others, even if kilometers way from him (her), according to Lory’s experiment, based of no local realm in biological systems (12), pancreas show identical modifications, allowing doctors to made clinical diagnosis until now impossible (1-13).

1)Stagnaro S., Stagnaro-Neri M. Valutazione percusso-ascoltatoria del Diabete Mellito. Aspetti teorici e pratici. Epat. 32, 131, 1986

2) Stagnaro-Neri M., Stagnaro S. Introduzione alla Semeiotica Biofisica. Il Terreno Oncologico. Travel Factory, Roma, 2004. http://www.travelfactory.it/semeiotica_biofisica.htm

3) Stagnaro S., Stagnaro-Neri M., Le Costituzioni Semeiotico- Biofisiche.Strumento clinico fondamentale per la prevenzione primaria e la definizione della Single Patient Based Medicine. Travel Factory, Roma, 2004. http://www.travelfactory.it/libro_costituzionisemeiotiche.htm

4) Stagnaro S., Stagnaro-Neri M. Single Patient Based Medicine.La Medicina Basata sul Singolo Paziente: Nuove Indicazioni della Melatonina. Travel Factory, Roma, 2005. http://www.travelfactory.it/libro_singlepatientbased.htm

5) Stagnaro S. Pivotal role of Biophysical Semeiotic Constitutions in Primary Prevention. Cardiovascular Diabetology, 2:1, 2003 http://www.cardiab.com/content/2/1/13/comments#5753

6) Stagnaro S. Stagnaro Sergio. Newborn-pathological Endoarteriolar Blocking Devices in Diabetic and Dislipidaemic Constitution and Diabetes Primary Prevention. The Lancet. March 06 2007. http://www.thelancet.com/journals/lancet/article/PIIS0140673607603316/comments?totalcomments=1. Hidden!!!. Therefore See either reference 13) or www.fce.it, http://www.fceonline.it/index.php?option=com_content&task=view&id=3736&Itemid=47

7) Stagnaro S., West PJ., Hu FB., Manson JE., Willett WC. Diet and Risk of Type 2 Diabetes. N Engl J Med. 2002 Jan 24;346(4):297-298. [Medline]

8) Stagnaro Sergio. New bedside way in Reducing mortality in diabetic men and women. Ann. Int. Med.2007. http://www.annals.org/cgi/eletters/0000605- 200708070-00167v1

9) Stagnaro Sergio. Single Patient Based Medicine: its paramount role in Future Medicine. Public Library of Science. http://medicine.plosjournals.org/perlserv/?request=read-response 2005

10) Stagnaro Sergio. Bedside Biophysical-Semeiotic Osteocalcin Test in Diagnosing and Monitoring Diabetes. The Lancet, January 28, 2008. http://www.thelancet.com/journals/lancet/article/PIIS0140673608601014/comments?action=view&totalComments=2, HIDDEN !!!! See www.fce.it, http://www.fceonline.it/index.php?option=com_content&task=view&id=3736&Itemid=47

11) Stagnaro Sergio. Il test Semeiotico-Biofisico della Osteocalcina nella prevenzione primaria del diabete mellito. www.fce.it, http://www.fcenews.it/index.php?option=com_content&task=view&id=909&Itemid=47

12) Stagnaro Sergio e Paolo Manzelli. L’Esperimento di Lory. Scienza e Conoscenza, N° 23, 13 Marzo 2008. http://www.scienzaeconoscenza.it//articolo.php?id=17775

13) Stagnaro Sergio. Pre-Metabolic Syndrome and Metabolic Syndrome: Biophysical-Semeiotic Viewpoint. www.athero.org, 29 April, 2009. http://www.athero.org/commentaries/comm904.asp

14) Stagnaro Sergio. Without CAD Inherited Real Risk no diabetic is involved by coronary disorder. CMAJ, 6 May 2009. http://www.cmaj.ca/cgi/eletters/180/9/919#127646

15) Stagnaro Sergio. Reale Rischio Semeiotico Biofisico. I Dispositivi Endoarteriolari di Blocco neoformati, patologici, tipo I, sottotipo a) oncologico, e b) aspecifico. Ediz. Travel Factory, www.travelfactory.it, Roma, Luglio 2009.

Sergio Stagnaro MD

Via Erasmo Piaggio 23/8,

16039 Riva Trigoso (Genoa) Italy

Founder of Quantum Biophysical Semeiotics

Who's Who in the World (and America)

since 1996 to 2009

Ph 0039-0185-42315

Cell. 3338631439

www.semeioticabiofisica.it

dottsergio@semeioticabiofisica.it

Renal Artery Stenosis: bedside rapid Diagnosis even in its initial stage with Quantum-Biophysical-Semeiotics

noreply@blogger.com (Stagnaro) — Mon, 25 May 2009 12:30:00 +0000

Overlooked Quantum-Biophysical-Semeiotics does really exists(1-12). See also www.semeioticabiofisica.it Interestingly, due to the presence of no local realm in all biological systems, in one second doctors may recognize that in urinary tract there is something wrong (10). Soon thereafter physicians can localize the precise site of disorder, ascertaining the real nature. As regards early diagnosis of renal artery stenosis, Quantum Biophysical Semeiotics allows doctor to bedside recognize kidney disorders, since initial stages of INHERITED Real Risk. Perhaps, for instance, available evidence does not clearly support one treatment approach over another for atherosclerotic renal artery stenosis. However, we must admit that patients with such as disorder are properly diagnosed exclusively a long time after initial disease onset, as in our case. Unfortunately, all around the world, General Practitioners know only the traditional physical semeiotics, that isn't so efficacious to allow doctor to recognize, since its first stage, Renal Artery Stenosis. Nowadays, physicians can bedside recognize SINCE BIRTH real risk of kidney diseases, both oncological and degenerative in nature (1-10). In order to recognize Renal Artery Stenosis, the following easy and quick manoeuvre proved to be really efficacious in my long year clinical experience: in health, doctor first of all delimits kidney area, as I described, e.g., in above-cited website, Technical Page N° 5 (14, 15). Subsequently, doctor increases the pressure of sthetoscope bell- piece, localized on kidney cutaneous projection, causing kidney dilation (due its congestion) immediately , than kidney size reduces (due to de- congestion)to its minimal value. At this point, in health pressure prompt interruption is "rapidly" - in 2 sec or less - followed by the return of kidney to its normal size, indicating a physiological blood flow in renal artery (15). On the contrary, in case of renal artery stenosis such as latency time results more than 2 sec., in relation to the severity of underlying disease (16). Interesting information about renal inherited real risk are illustrated in my previous paper (16).

References:

1. Stagnaro Sergio e Paolo Manzelli. Semeiotica Biofisica Quantistica. 15 Dicembre 2007 http://www.ilpungolo.com/leggi- tutto.asp?IDS=13&NWS=NWS5243

2. Stagnaro Sergio e Paolo Manzelli. Semeiotica Biofisica Endocrinologica: Meccanica Quantistica e Meccanismi d’Azione Ormonali. Dicembre 2007, www.fce.it, http://www.fcenews.it/index.php?option=com_content&task=view&id=816&Itemid=45

3. Stagnaro Sergio e Paolo Manzelli. Natura Quantistica di una Originale Manovra Semeiotico-Biofisica di Epatopatia . Dicembre 2007, http://www.fcenews.it/index.php?option=com_content&task=view&id=862&Itemid=45

4. Stagnaro Sergio e Paolo Manzelli. Semeiotica Biofisica: Realtà non- locale in Biologia. Dicembre 2007, www.ilpungolo.com, http://www.ilpungolo.com/leggi-tutto.asp?IDS=13&NWS=NWS5217

5. Stagnaro Sergio e Paolo Manzelli. Semeiotica Biofisica Quantistica: la manovra di attivazione surrenalica jatrogenetica, 09-1-2008, http://www.fcenews.it/index.php?option=com_content&task=view&id=161&Itemid=63

6. Stagnaro Sergio. Bedside Biophysical-Semeiotic Osteocalcin Test in Diagnosing and Monitoring Diabetes. The Lancet, January 28, 2008. http://www.thelancet.com/journals/lancet/article/PIIS0140673608601014/comments?action=view&totalComments=2

7. Stagnaro Sergio. Il test Semeiotico-Biofisico della Osteocalcina nella prevenzione primaria del diabete mellito. Febbraio 2008. http://www.fcenews.it/index.php?option=com_content&task=view&id=909&Itemid=47

8. Stagnaro Sergio. Esperimento di Lory e Crisi dei Fondamenti della Medicina Occidentale. www.ilpungolo.com. 17 Febbraio 2008 http://www.ilpungolo.com/leggi-tutto.asp?NWS=NWS5387&IDS=13

9. Stagnaro Sergio e Paolo Manzelli. L’Esperimento di Lory. Scienza e Conoscenza, N° 23, 13 Marzo 2008. http://www.scienzaeconoscenza.it//articolo.php?id=17775

10. Stagnaro Sergio. Reale Rischio Congenito di Cancro Renale Diagnosticato con la Semeiotica Biofisica: il Segno di Pollio. www.ilpungolo.com, 25 Marzo 2008, http://www.ilpungolo.com/leggi- tutto.asp?NWS=NWS5480&IDS=13

11. Stagnaro Sergio. Biological System Functional Modification parallels Gene Mutation. www.Nature.com,March 13, 2008, http://blogs.nature.com/nm/spoonful/2008/03/gout_gene.html 12. Stagnaro Sergio. Melanoma? Escluso in 1 Secondo con La Semeiotica Biofisica Quantistica. Il Reale Rischio Congenito di Melanoma. www.ilpungolo.com, 9 Aprile 2008, http://www.ilpungolo.com/leggi- tutto.asp?IDS=13&NWS=NWS5524

13. Stagnaro Sergio. Diagnosi clinica di cuore sano in un secondo! 7 Aprile 2008, http://www.fcenews.it/index.php?option=com_content&task=view&id=1218&Itemid=47

14. Stagnaro Sergio . Also Family Physicians are able of greatest clinical Discoveries! Annals Family Medicine,(16 April 2008), http://www.annfammed.org/cgi/eletters/6/2/175

15. Stagnaro-Neri M., Stagnaro S. Introduzione alla Semeiotica Biofisica. Il Terreno Oncologico. Ed. Travel Factory, Roma, 2004. http://www.travelfactory.it

16) Stagnaro Sergio. Renin-angiotensin blockade and kidney disease inherited real risk. The Lancet.com, September 23, 2008. http://www.thelancet.com/journals/lancet/article/PIIS014067360861212X/comments?action=view&totalComments=2#1841

Quantum-Biophysical-Semeiotic bedside Detecting Atherosclerosis from initial, asymptomatic Stage. Inherited real Risk.

noreply@blogger.com (Stagnaro) — Sat, 23 May 2009 05:25:00 +0000

Endoarteriolar Blocking Devices (EBD), derived from arteriolar medial layer, and ubiquitous in a single point of vascular wall with two (= arterioles) or more (= small arteries) layers of smooth muscle cells, according to Hammersen [1], protruding to the lumen, show very different structure and form, under physiological and pathological conditions: small cushions with wide base, polypoid formations, generally pedunculated [2-5], sphincteric formations, intimal contractile architectures. More precisely speaking, only type II, normal, physiological, EBD, localized in arterioles, are ubiquitous.

EBD are playing a primary role in local microcirculatory flow-motion regulation, as the following clinical evidence demonstrates: when they are abnormal, from both functional and structural quantum-biophysical-semeiotic viewpoint, EBD bring about Functional Microcirculatory Reserve (FMR) impairment, contributing to cause inherited real risk of disorders, like CAD, whose onset will possibly occur after years or decades, as allows me to state a 53-year-long clinical experience with the original physical semeiotics [6-19]. Under such as condition, we observe tissue acidosis, assessed as lowering of gastric aspecific reflex latency time, indicating lowered tissue oxygenation.

Interestingly, the initial stage of whatever disorder, i.e., the inherited real risk, is characterised exclusively by a reflex duration lasting 4 sec. (NN < nn =" 8" style=""> utilizing apnoea test.

In health, the duration of apnoea is inversely correlated with latency time lowering, and directly related to gastric aspecific reflex lasting time (7-9).

Quantum-biophysical Semeiotics allows doctor to find physiological, both type I and type II, EBD, the later exclusively in those biological systems which need temporarily high blood supply, as skeletal muscle, right cerebral hemisphere of individuals CAEMH-positive, and conjunctival mucosa, emphasizing their central role in microcirculatory flow-motion regulation, under physiological as well as pathological conditions,

Beside normal or physiological, either inherited or newborn, type I (= small arteries), and type II (= arterioles), EBD, according to S.B. Curri [4,5], do really exist type I, newborn-pathological EBD, until now unknown by physicians. They are sub-divided in two subtypes: a) subtype, characteristic of oncological real risk, and b) subtype, aspecific, in all other disorder inherited real risks and present in different biological systems, I discovered and described in earlier papers, (See: Physiology, and Pathology,

http://www.semeioticabiofisica.it/microangiology,) [6,7].

These microcirculatory structures play a pivotal role in the patho-physiology of most common and serious human diseases, including diabetes, hypertension, ATS, CVD, cancer, permitting to define the link existing between genetic factor and phenotype, according to Angiobiopathy theory [6-18].

In fact, decade-long clinical study of Endoarteriolar Blocking Devices has allowed me to discover and assess “quantitatively” the genetic abnormalities of all biological systems, preconditioning outcome is based on.

As a consequence of above remarks, EBD clinical evaluation proved to be a paramount tool to bedside recognize individuals at inherited real risk of the more frequent and dangerous human disorders, as well as to comprehend fully the underlying different quantum-biophysical-semeiotic constitutions, I have formerly described, since the birth [9-20].

Due to these reasons, I emphasize the essential value of knowing both anatomy and physiology of such microcirculatory structures, i.e., EBD, both physiological and pathological, at the present time unfortunately either ignored or overlooked by clinicians around the world. EBD are useful to understand the importance of Clinical Microangiology, and particularly its branch, I suggested to term Clinical Microangiology of Endoarteriolar Blocking Devices [6-21].

Furthermore, Quantum-biophysical Semeiotics allows doctor to bed-side detect the persistent opening (technically speaking, hyperstomy) of all artero-venous anastomoses (AVA), ethimologically understood, as clinical and experimental evidence suggests.

In healthy and young inividual, this reflex, that shows an intensity smaller than 2 cm, disappears rapidly if digital pressure becomes “highly intense”. In addition, if the subject hand is raised to 10-15 cm. above the heart level, “mean-intense” digital pressure applied on the finger-pulp does not cause upper ureteral reflex.

On the contrary, in arteriosclerotic patients, from initial stage of its inherited risk, “mean-intense” digital pressure, applied upon the microcirculatory bed, e.g. on the microvessels of a finger pulp, scars, great or little joints, of individuals lying down in the supine position, psycho-physically relaxed with open eyes (= melatonin secretion inhibition) brings about upper ureteral reflex (= upper ureteral tracts dilate about 2,5 cm.), lasting characteristically “stiff” also during “extreme-intense” pressure [6-21].

In other words, in health, under the later condition, AVA are closed, and simultaneously type I and II EBD contract, when evaluated as middle ureteral reflex (See later on), facilitating the blood-flow through nutritional capillaries (= type I, associated, Microcirculatory Functional Reserve activation). Furthermore, since the very early stage of arteriosclerosis, such as reflex persists “stiff” also under the latter conditions, hindering blood supply to local parenchyma.

Interestingly, this quantum-biophysical-semeiotic sign increases suddenly when the patient moves the other, vertically raised hand as waving good-bye – "slightest effort test" – because of the increasing of blood viscosity, bedside detected. Analogously, during the "simulated cold test" (= patient is thinking to dip his hands or a single finger in ice-cold water), arterio-venous anastomoses result slightly opened in healthy subjects.

On the contrary, under identical conditions, AVA opening appears to be particularly increased in patients involved by arteriosclerosis, even initial or asymtomatic: 1,5 cm. vs 2,8 cm., respectively: p<0,001,>

Finally, middle ureteral reflex, different in type, size, duration, nature, induced by digital pressure of different intensity, applied, e.g., on tissue-micro-vascular-units of finger tip, gives useful information about the diverse EBD, type I AVA as well as type II, group I, group II AVA, where present as in the foot-sole (16)

As a consequence, doctor can now-a-days assess the diverse EBDs at the bedside in easiest way, calculating the duration of heart-aspecific gastric and/or -caecal reflex duration: in presence of “normal” EBD alteration and type I newborn-pathological, type I, subtype b), EBD, reflex lasts 4 sec. or more (NN = less than 4 sec.), correlated with the seriousness of underlying disorder. Moreover, the final tonic Gastric Contraction (= intense tissue acidosis) indicates the presence of newborn-pathological, type I, subtype a), “oncological”, EBD, characterized by a large amount of smooth muscle cells.

Certainly, who knows the “direct” evaluation of middle ureteral reflexes can utilize a very refined, exhaustive, and reliable method [6-21].

Finally, knowing the precise location of physiological, type I, EBD (i.e., skeletal muscle, conjunctival mucosa, and right emisphere of individuals CAEMH-positive), doctor recognizes more quickly the type I, subtype a) and b), newborn-pathological EBD.

At this point, reader has to take into account that pathological EBD can transform in physiological type, reducing contemporaneously their number, under efficacious therapy (diet, ethimologically speaking (= BMI about 25, physical exercise, avoiding tobacco smoking, a.s.o.), Melatonin, personalized applications of NIR-LED, a.s.o.), thus ameliorating local microcirculatory blood-flow (= pH), evaluated as duration of latency time and reflex lasting.

It is well known for many years that patients with coronary heart disease may have no symptoms [20, 22], and that the electocardiographic feature of ischaemia may be induced by exercise without accompanying angina [22]. Nevertheless, such "silent ischaemia" has only recently been recognized to be an important feature of ischaemic heart disease [7, 18]. The silent ischaemia prevalence is unknown, although over a quarter of myocardial infarctions are unrecognized and half of them cause no symptoms at all [14]. According to Cohn, there are three categories of people with silent ischaemia, who may be at such risk [5]. People of type 1° have no symptoms and no history of myocardial infarction or angina; those of type 2° are symptomless survivors of myocardial infarction; fìnally, patients of type 3° have angina together with episodes of silent ischaemia, whose mechanisms in most cases are obscure.

My data suggest that quantum-biophysical-semeiotic methods, illustrated above, are reliable, helpful, and then advisable in bed-side detecting individuals, even asymptomatic, who have to undergo, promptly and rationally, whatever stress testing, such as electrocardiographic exercise test, atrial pacing, thallium stress redistribution scintigraphy, exercise radionuclide ventriculography, and spiral CT, a.s.o., during which silent ischaemia usually may be elicited, corroborating bedside diagnosis [1, 2, 21]. Furthermore, the clinical, quantum-biophysical-semeiotic selection of asymptomatic patients is interesting, because it can be applied on very large scale, helping doctors in actively searching for ischemic heart disease, particularly serious when silent, from the clinical viewpoint. As a matter of facts, a lot of data suggest that episodic, silent ischemia carries a poor prognosis in stable coronary artery disease [3, 23].

Given the accumulating evidence that ischemia, whether silent or not, carries a poor prognosis in patients with known coronary artery disease, it is justifìed to follow an active policy even in patients who are totally free of symptoms [4, 22]. Essentially, the rationale for the use of histangioprotective drugs (like L-Carnitine, Co Q10, Coniugated-Melatonin, a.s.o.), associated with personalized applications of NIR-LED, in patients with ischemic heart disease clinically silent.

Three necessary premises:

Firstly, the favourable effects of these products on lipid and glucose metabolism, ameliorating mitochondrial respiratory chain, I illustrated previously [14, 20-24].

Secondly, the positive influence of these drugs on angina pectoris as well as on myocardial ischaemic preconditioning, because they improve blood flow in cardiac tissue microcirculatory units [8, 9, 20, 23].

Thirdly, when utilized in early stage, histangio-protective drugs can ameliorate coronary microcirculatory remodelling, e.g., lowering the number of newborn-pathological type I, subtype b) EBD: the intensity of specific middle ureteral reflex significantly decreases under such treatment [23].

Practically, in order to ascertain clinically silent ischaemia it is advisable to assess shape and intensity of low ureteral reflex oscillations, i.e. vasomotion, as illustrated above, which permits doctor to calculate the fractal dimension of myocardial microvessels deterministic chaos (NN > 3 < oscillation =" 3/1">

As far as myocardial ischaemic preconditioning is concerned, it is suffìcient and hence advisable in day-to-day practice to assess the latency time of the second heart-gastric aspecific reflex, i.e., in the second evaluation, performed exactly after 5 sec. interruption, namely soon after 5 sec. from the end of basal evaluation: in health, latency time raises in a significant manner from 8 sec. (basal value) to 16 sec., i. e., to doubly value.

Another difficult, but also refined, elegant method proved to be reliable: the assessment of shortening of left ventricle enlargement duration during the above-described test (NN = from 7 sec. to 5 sec.) and/or conversely the prolonged latency time from 3 sec. to 5 sec. or more, preceding another ventricle dilation, paralleling Ejection Fraction of left ventricle. This latter evaluation, however, is a little more difficult to ascertain by doctors not experienced and skilled in the field of the original semeiotics.

From the practical view-point, both duration (NN <> 3 sec. < class="referencia">[7-10].

Actually, relevant data are easily obtained also by means of the latency time of heart-caecum and/or-aspecific gastric reflex, which informs about myocardial oxygen supply: in health, during “mean” digital pressure upon the skin projection area of heart, basal latency time value is 8 sec. However, doctor must remember that in case of CAD inherited real risk and CAD initial stage, such as parameter value is still normal (NN = 8 sec.), but reflex lasts 4 sec. or more (NN <>

In addition, in health, during "intense" digital pressure upon cutaneous projection area of the heart, as above described, and immediately after about 7 sec. apnea test or Valsalva's manoeuvre, the basal latency time of cardiac-gastric aspecific reflex (basal value = 8 sec.) raises significantly to 16 sec., as well as after preconditioning (i.e., doubly value) (p<0,02),>

In conclusion, in a long, well-established, clinical experience, the above-described quantum-biophysical-semeiotic methods proved to be reliable, easy to perform on very large scale, useful, and suitable for detecting ischemic coronary disease, even clinically silent or really initial, i.e. since CAD “real risk” [23].

Finally, Quantum-biophysical Semeiotics allows doctor to bedside recognize, in only one second, normal heart, as well as arteries [23,24-27]: in health, “intense” digital pressure, applied upon skin projection area of the heart and respectively of a large artery, does not bring about “simultaneously” gastric aspecific reflex.

References

1. Hammersen F (1968). Zur ultrastruktur der arterio-veno¨sen anastomosen. In: Hammersen F, Gross D (eds). Die Arterio-venoesen Anastomosen Anatomie, Physiologie, Pathologie, Klinik. Verlag Hans Hubert: Bern und Stuttgart. pp 24–37.

2. Bailey I.K.,Griffìth L.S.C., Rouleau J,Strauss H.W., Pitt B., ThalUum201 myocardial perfusion imaging at rest and during exercise. Comparative sensitivity to electrocardiography in coronary artery disease, Circulation, 1977, 55, 79.

3. Bonow R.O., Bacharach S.L., Gren M.V., La Fremere R.L., Ehstein S.E., Prognostic implicaiions of symptomatic versus asymtomatic (silent) myocardial ischemia induced by exercise in mild symptomatic and in asymptomatic patients with angiographically dociimented coronary artery diseas, Am. J. Cardio!., 1987, 60, 77.

4. Curri S.B. Le Microangiopatie. Inverni della Beffa, Milano, 1986.

5. Curri S.B. Pannicolopatia Mammaria da Stasi, Parte seconda. Inverni della Beffa, Milano, 1984

6. Stagnaro Sergio. Newborn-pathological Endoarteriolar Blocking Devices in Diabetic and Dislipidaemic Constitution and Diabetes Primary Prevention. The Lancet. March 06 2007. http://www.thelancet.com/journals/lancet/article/PIIS0140673607603316/comments?totalcomments=1 and especially: www.fce.it, http://www.fceonline.it/docs/stagnaro.pdf

7. Stagnaro-Neri M., Stagnaro S. Introduzione alla Semeiotica Biofisica. Il Terreno Oncologico. Travel Factory, Roma, 2004. http://www.travelfactory.it

8. Stagnaro Sergio. Teoria Patogenetica Unificata, 2006, Ed. Travel Factory, Roma.

9. Stagnaro Sergio. Role of Coronary Endoarterial Blocking Devices in Myocardial Preconditioning -c007i. Lecture, V Virtual International Congress of Cardiology. http://www.fac.org.ar/qcvc/llave/c007i/stagnaros.php
10. Stagnaro S., Stagnaro-Neri M., Single Patient Based Medicine.La Medicina Basata sul Singolo Paziente: Nuove Indicazioni della Melatonina. Ed. Travel Factory, Roma, 2005. http://www.travelfactory.it
11. Stagnaro Sergio. New bedside way in Reducing mortality in diabetic men and women. Ann. Int. Med. http://www.annals.org/cgi/eletters/0000605-200708070-00167v1
12. Stagnaro Sergio. Newborn-pathological Endoarteriolar Blocking Devices in Diabetic and Dislipidaemic Constitution and Diabetes Primary Prevention. The Lancet. March 06 2007. http://www.thelancet.com/journals/lancet/article/PIIS0140673607603316/comments?totalcomments=1

13. Stagnaro Sergio. Epidemiological evidence for the non-random clustering of the components of the metabolic syndrome: multicentre study of the Mediterranean Group for the Study of Diabetes. Eur J Clin Nutr. 2007 Sep;61(9):1143-4. Epub 2007 Feb 7. [MEDLINE]

14. Stagnaro-Neri M, Stagnaro S., Deterministic chaotic biological system: the microcirculatory bed, Gazz. Med. It.-Arch. Sci. Med., 1994, 153, 99.

15. Stagnaro S., Moscatelli G., Biophysical Semeiotics, Deterministic Chaos and Biological System, Gazz. Med. It. Arch. Sci . Med. 1996, 155, 125.

16. Stagnaro-Neri M., Stagnaro S., Auscultatory percussion evaluation of arteriovenous anastomoses dysfunction in early arteriosclerosis, Acta Medica Mediterranea, 1989, 5, 141.

17. Stagnaro-Neri M., Stagnaro S., Deterministic Chaos, Preconditioning and Myocardial Oxygenation evaluated clinically with the aid of Biophysical Semeiotics in the Diagnosis of ischaemic Heart Disease even silent. Acta Med. Medit. 13, 109, 1997.

18. Stagnaro-Neri M., Stagnare S., La manovra di Ferrero-Marigo nella diagnosi clinica di Iperinsulinemia - Insulinoresistenza, Acta Med. Medit., 1997, 13, 15.

19. Stagnaro Sergio. Role of Coronary Endoarterial Blocking Devices in Myocardial Preconditioning - c007i. Lecture, V Virtual International Congress of Cardiology, 2007. http://www.fac.org.ar/qcvc/llave/c007i/stagnaros.php

20. Stagnaro S., Stagnaro-Neri M., La Melatonina nella Terapia del Terreno Oncologico e del “Reale Rischio” Oncologico. Ed. Travel Factory, Roma, 2004.

21. Stagnaro S., Stagnaro-Neri M., Le Costituzioni Semeiotico-Biofisiche.Strumento clinico fondamentale per la prevenzione primaria e la definizione della Single Patient Based Medicine. Ed. Travel Factory, Roma, 2004.

22. Wood P., Me Gregor M., Magidson O., Writteker W. The effort test in angina pectoris, Br. Heart J., 1950, 12, 363.

23. Stagnaro Sergio. Il “Reale Rischio” Semeiotico-Biofisico. Ruolo diagnostico e fisiopatologico dei Dispositivi Endoarteriolari di Blocco, neoformati patologici tipo I, sottotipo a) e b). Ed. Travelfactory, Roma, in press.

24. Stagnaro S., Stagnaro-Neri M., La Melatonina nella Terapia del Terreno Oncologico e del “Reale Rischio” Oncologico. Ed. Travel Factory, Roma, 2004.

25. Stagnaro Sergio. Diagnosi clinica di cuore sano in un secondo! 7 Aprile 2008. www.fce.it http://www.fcenews.it/index.php?option=com_content&task=view&id=1218&Itemid=47

26. Stagnaro Sergio. Bedside Biophysical-Semeiotic Osteocalcin Test in Diagnosing and Monitoring Diabetes. The Lancet, January 28, 2008.
http://www.thelancet.com/journals/lancet/article/PIIS0140673608601014/comments?action=view&totalComments=2; See especially, http://www.fceonline.it/docs/stagnaro.pdf

27. Stagnaro Sergio. Semeiotica Biofisica Quantistica: Diagnosi Clinica di Melanoma a partire dal suo Reale Rischio Congenito. www.fcenews.it, 23 luglio 2008, http://www.fcenews.it/index.php?option=comcontent&task=view&id=1599&Itemid=45

Quantum-Biophysical-Semeiotic Bed-Side Evaluation of Endothelial Function

noreply@blogger.com (Stagnaro) — Thu, 21 May 2009 07:51:00 +0000

Introduction.

It is generally admitted that endothelial dysfunction is an important factor in both the onset and the development of atherosclerosis, as I demonstrated in earlier papers two decades ago, from the clinical view-point (1-6).

In fact, endothelium plays a pivotal role in the maintenance of vascular tone, taking part to the blood flow regulation in response to changes in tissue and organ perfusion requirements (5,6). When blood flow increases through a vessel, such as vessel dilates: from quantum-biophysical-semeiotic view-point, under such as condition, suddenly the enhancement occurs of both arterial-“in toto” ureteral reflex and arterial-gastric aspecific reflex (Fig.1), the latter easier to be assessed, (See http://www.semeioticabiofisica.it).

Fig.1

Gastric aspecific reflex ( in the stomach both fundus and body are dilated, while antral-pyloric region contracts) caused by digital pressure, applied on brachial artery of a patients in supine position, at rest.

One speaks of the phenomenon called flow-mediated dilatation (FMD). Over the past decade, a clinical quantum-biophysical-semeiotic technique has evolved to evaluate both flow-mediated vasodilation (FMD) and acethylcholine-mediated vasodilation (= Valsalva’s Manoeuvre), an important endothelium-dependent function, assessed, for instance, in the brachial artery (See website http://www.semeioticabiofisica.it/microangiologia).

In health, these stimuli provoke the endothelium to release free radical nitric oxide (NO), probably also by means of PPARS action (22), with subsequent vasodilation that can be assessed and quantified at the bed-side in different ways, as an index of vasomotor function. This technique is attractive because it is non-invasive and allows repeated measurements on very large scale. An increase in flow through the brachial artery can be induced by causing post-ischemic dilation in the downstream vascular bed of the distal forearm, that can be achieved by inflating a cuff placed around the forearm to supra-systolic pressure producing an ischemia in the distal vascular bed.

Really more simple, easier, faster to be performed, and, therefore, preferable in day-to-day practice, is the following bed-side manoeuvre: doctor applies an “intense”, obstructive digital pressure upon brachial artery, and immediately assesses the intensity of gastric aspecific reflex (or “in toto” ureteral reflex): NN = no aspecific gastric reflex happens.

On the contrary, in Arterioscleotic Constitution as well as in overt arteriopathy, of whatever nature the reflex intensity is 0,5 cm. or more, in relation ti the severity of underlying disorder (Fig.1)

After the rapid with-drawl of digital pressure (or of the cuff pressure), a sudden increase of blood flow through the dilated vascular bed occurs, due to flow-mediatedvaso-dilation. Firstly, physiologically the reflex disappears rapidly, and soon thereafter, a further reflex occurs spontaneously, showing a three times higher intensity.

In health, the significant increase in shear stress in the down-stream artery causes a NO-dependent dilation of the brachial artery, that can be evaluated clinically also in a different way, i.e., paralleling the basal value of finger pulp-gastric aspecific reflex, evaluated as latency time (in health, 8 sec., if digital pressure upon finger-pulp is “mean intense”) with the second value, which increases to 16 sec., i.e., doubled value.

The arterial dilator response to shear-stress can be almost completely blocked by pre-treatment with nitric oxide synthase inhibitors (7, 8) and therefore it has been suggested that the phenomenon is predominantly due to endothelial release of radical nitric oxide. In fact, the endothelium can no longer be viewed as a static physicalbarrier that simply separates blood from tissue. It is evidentthat disturbed endothelial function may be an early marker ofan ongoing atherosclerotic process. Thus, inherited endothelial dysfunctionhas increasingly been recognized to play an important role ina number of conditions associated with a high prevalence ofatherosclerotic CVDs (1-6), according to my Microvascular Arteriosclerosis Theory (partly illustrated in above-cited website, URL

http://www.semeioticabiofisica.it/microangiologia/Documenti/Eng/A%20Stadio%20preipertensiv%.

A 53-year-long “clinical” experience allows me to state that endothelial function assessed by this method correlates significantly with invasive testing of coronary endothelial function (7, 9) and with the severity and extent of coronary atherosclerosis (10).

Interestingly, at this point, coronary artery endothelial function can analogously be easily evaluated by means of Quantum-Biophysical Semeiotics (1, 2, 11). The precise mechanisms for the acute detection of shear forces and subsequent signal transduction to modulate vasomotor tone are not fully understood. The endothelial cell membrane contains specialized ion channels, such as calcium-activated potassium channels, that open in response to shear stress (5). The effect of potassium channel opening is to hyperpolarize the endothelial cell, increasing the driving force for calcium entry (there are no voltage-gated calcium channels in endothelial cells). Calcium activates an enzyme, endothelial nitric oxide synthase (eNOS), and the subsequent generation of NO appears to account for FMD (6).

In humans, the measurement of FMD has been widely adopted to explore endothelial function. However, a number of variations of the method have been described. Cuff placement above or below the scanned part of the artery has been described, and varying duration and pressures for cuff inflation have been used. The brachial artery has been the target artery in most studied, but radial and femoral arteries have also been measured (7). Due to these technical modifications, the normal ranges established in some laboratories differ from normal ranges observed in others (7-8).

In my long clinical experience, Valsalva’s manoeuvre proved to be quiet practical, easy, reliable, and useful, lasting only 5 sec.: in health, manoeuvre-dependent acetylcholine secretion brings about notoriously smooth muscle cells relexation, in the identical way, illustrated above.

In my opinion, based on a large number of clinical quantum-biophysical-semeiotic observations, underlying patho-physiological action mechanism of acetylcholine are more complex, acting favourably also on healthy microcirculation, increasing both vasomotility and vasomotion.

On the contrary, in case of DM, dyslipidaemia, arterial hypertension, a.s.o., doctor mainly either does not observe any change or worsening condition, in relation to the severity of underlying disorder. Diet, ethimologically speaking, and physical exercise (walkig 45 minutes/day, 120 steeps/min), Coniugated Melatonin, improve in general endothelial function rapidly, according to other authors (12).

In addition, melatonin-adenosine, a potent histangioprotective substance (21, 23), in my experience proved to increase vasomotility and vasomotion in the microcirculatory bed of both tissue, and arterial wall.

On contrast, FMD is inversely correlated with age, type 2 diabetes mellitus, dyslipidaemia, hypertension, and tobacco smoking: smokers have decreased FMD (1-6).

In addition, inactivation of endothelium-derived nitric oxide due to increased production of oxygen free radicals in the vessel wall is thought to be an important mechanism for endothelial dysfunction (13, 14-23).

As a result, much interest has focused on antioxidants, such as vitamin E, vitamin C, and other free radical scavengers, like melatonin, as I demonstrated previously, for the first time “clinically” (14-27), since they remove successfully free radicals and, therefore, improve endothelial function.

* Sergio Stagnaro MD

Via Erasmo Piaggio 23/8, CP. 42

16039 Riva Trigoso (Genoa) Europe

Founder of Quantum Biophysical Semeiotics

Who's Who in the World (and America)

since 1996 to 2009

Ph 0039-0185-42315

Cell. 3338631439

www.semeioticabiofisica.it

dottsergio@semeioticabiofisica.it

References

1) Stagnaro S., Stagnaro-Neri M., Basi microcircolatorie della semeiotica biofisica. Atti del XVII Cong. Naz. Soc. Ital. Studio Microcircolazione, Firenze ott. 1995, Biblioteca Scient. Scuola Sanità Militare, 1995, 2, 94.

2) Stagnaro-Neri M., Stagnaro S., Semeiotica Biofisica: valutazione della compliance arteriosa e delle resistenze arteriose periferiche. Atti del XVII Cong. Naz. Soc. Ital. Studio Microcircolazione, Firenze Ott. 1995, Biblioteca Scient. Scuola Sanità Militare, 2, 93.

3) Stagnaro-Neri M., Stagnaro S., Auscultatory Percussion Evaluation of Arterio-venous Anastomoses Dysfunction in early Arteriosclerosis. Acta Med. Medit. 5, 141, 1989

4) Stagnaro-Neri M., Stagnaro S. Indagine clinica percusso-ascoltatoria delle unità microvascolotessutali della plica ungueale. Acta Med. Medit. 4, 91, 1988.

5) Il test della Apnea nella Valutazione della Microcircolazione cerebrale Stagnaro S., Stagnaro-Neri M., in Cefalalgici. Atti, Congr. Naz. Soc. Ita. Microangiologia e Microcircolazione. A cura di C. Allegra. Pg. 457, Roma 10-13 Settembre 1987. Monduzzi Ed. Bologna

6) Stagnaro S., Valutazione percusso-ascoltatoria della microcircolazione cerebrale globale e regionale. Atti, XII Congr. Naz. Soc. It. di Microangiologia e Microcircolazione. 13-15 Ottobre, Salerno, e Acta Medit. 145, 163, 1986.

7) Joannides R, Haefeli WE, Linder L, et al. Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo. Circulation 1995;91:1314-19.
8) Agewall S, Hulthe J, Fagerberg B, et al. Post-occlusion brachial artery vasodilatation after ischaemic handgrip exercise is nitric oxide mediated. Clin Physiol Funct Imaging 2002;22:18-23.

9) Takase B, Uehata A, Akima T, et al. Endothelium-dependent flow-mediated vasodilation in coronary and brachial arteries in suspected coronary artery disease. Am J Cardiol 1998;82:1535-39.

10) Neunteufl T, Katzenschlager R, Hassan A, et al. Systemic endothelial dysfunction is related to the extent and severity of coronary artery disease. Atherosclerosis 1997;129:111-18.
11) Stagnaro S. A clinical efficacious maneouvre, reliable in bed-side diagnosing coronary artery disease, even initial or silent, as well as "heart coronary risk". 3rd Virtual International Congress of Cardiology, FAC, 2003, http://www.fac.org.ar/tcvc/marcoesp/marcos.htm

12) Sowers JR, Lester MA. Diabetes and cardiovascular disease. Diabetes Care. 1999;22(suppl 3):C14-C20.

13) Ohara Y, Peterson TE, Zheng B, Kuo JF, Harrison DG. Lysophosphatidylcholine increases vascular superoxide anion production via protein kinase C activation. Arterioscler Thromb 1994;14:1007-13.
14) Stagnaro-Neri M., Stagnaro S., Amlodipina: Calcio-Antagonista e Scavenger dei Radicali Liberi. Tec. 4, 43, 1993.

15) Stagnaro-Neri M., Stagnaro S., Ketanserina: antagonista dei recettori 5Ht2-serotoninergici e scavenger dei radicali liberi. Clin. Ter. 141, 465, 1992 [MEDLINE]

16) Stagnaro-Neri M., Stagnaro S., Radicali liberi e alterazioni del microcircolo nelle flebopatie ipotoniche costituzionali. Min. Angiol. 18, Suppl. 2 al N. 4, 105, 1993.

17) Stagnaro Stagnaro-Neri M., Stagnaro S., Silimarina: un potente scavenger dei radicali liberi. Studio clinico percusso-ascoltatorio. Epat. 38, 3, 1992.

18) Stagnaro S., Stagnaro-Neri M. Il danno da radicali liberi sul microcircolo. Congr. Naz. SISM., Milano,10 giugno,1991, Comun. Atti, Min. Angiologica, Suppl. 1, N°1 16,398,1991

19) Stagnaro-Neri M., Stagnaro S., Acidi grassi w-3, scavengers dei radicali liberi e attivatori del ciclo Q e della sintesi del Co Q10. Gazz. Med. It. – Arch. Sc. Med. 151, 341, 1992 (Infotrieve)

20) Stagnaro Sergio, Stagnaro-Neri Marina. Introduzione alla Semeiotica Biofisica. Il Terreno oncologico”. Travel Factory SRL., Roma, 2004. http://www.travelfactory.it/semeiotica_biofisica.htm

21) Stagnaro S., Stagnaro-Neri M., La Melatonina nella Terapia del Terreno Oncologico e del “Reale Rischio” Oncologico. Ediz. Travel Factory, Roma, 2004.

22) John A. Polikandriotis; Louis J. Mazzella; Heidi L. Rupnow; C. Michael Hart

Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25: 1810.

23) Stagnaro Sergio Endothelial cell function can ameliorate under safer drugs, such as Melatonin-Adenosine. BMC Cardiovascular disorders. 2004. http://www.biomedcentral.com/1471-2261/4/4/comments

24) Stagnaro Sergio. Role of Coronary Endoarterial Blocking Devices in Myocardial Preconditioning - c007i. Lecture, V Virtual International Congress of Cardiology, 2007. http://www.fac.org.ar/qcvc/llave/c007i/stagnaros.php

25) Stagnaro Sergio. Pre-Metabolic Syndrome and Metabolic Syndrome: Biophysical-Semeiotic Viewpoint. www.athero.org, 29 April, 2009. http://www.athero.org/commentaries/comm904.asp

26) Stagnaro Sergio. CAD Inherited Real Risk, Based on Newborn-Pathological, Type I, Subtype B, Aspecific, Coronary Endoarteriolar Blocking Devices. Diagnostic Role of Myocardial Oxygenation and Biophysical-Semeiotic Preconditioning. www.athero.org, 29 April, 2009 http://www.athero.org/commentaries/comm907.asp

27) Stagnaro Sergio. Epidemiological evidence for the non-random clustering of the components of the metabolic syndrome: multicentre study of the Mediterranean Group for the Study of Diabetes. Eur J Clin Nutr. 2007 Feb 7; [MEDLINE]

Quantum-Biophysical-Semeiotic Hypertensive Constitution.

noreply@blogger.com (Stagnaro) — Tue, 19 May 2009 10:11:00 +0000

Abstract

It's evident that neither all people become hypertensive nor all hypertensive patients are suffering from left ventricular impairment as well as from other well-known hypertension-dependent complications, regardless of environmental conditions. Indeed, the existence of biophysical-semeiotic hypertensive constitution accounts for the reason that only some individuals are hypertensive, and among them, only those with real risk in well defined biological system, are involve by myocardial failure or by other known hypertension complications. In the article, bedside diagnosis of both biophysical-semeiotic hypertensive constitution and hypertension complication real risk is fully described.

Key Words.

Biophysical-Semeiotics. Hypertensive Constitution. Hypertension. Clinical Microcirculation.

Introduction.

In the primary prevention of arterial hypertension, based on the pre-morbid, pre-metabolic stage (See: Arteriosclerotic Constitution in the website http://www.semeioticabiofisica.it, and particularly the URL

http://www.semeioticabiofisica.it/semeioticabiofisica/Documenti/Eng/Costituzione%20ipertensiv%), we have to devote a particular discussion to pre-hypertensive state of arterial hypertension (AH), component of pre-metabolic, and obviously, metabolic syndrome, classic and “variant”, often associated to other human Congenital Acidosic Enzyme-Metabolic Histangiopathy-a (CAEMH-a) -dependent diseases. CAEMH-a is a singular, functional mitochondrial cytopathy, inherited almost always by mother (1-3). For further information See above-cited website and Bibliography.

Really, the pre-hypertensive state allowed me to define clinically the hypertensive constitution, discussed in this article.

In order to understand such as topic usefully, we must remember that the primary function of blood circulation as well as of complex mechanisms, which rule pressure values (i.e., cardiac out-put, peripheral arteriolar resistance, blood volume, arterial compliance), is represented by physiological tissue supply of material-information-energy (O₂, various metabolites, enzymes, hormones, a.s.o.), and by catabolites removal, in particular CO₂ and produkts of tissue secretion.

Possible pH tissue variations bring about necessarily haemodinamic-haemorheological modificatioms, aiming to maintain metabolic “homeostasis” or, more exactly speaking, to keep in the normal ranges the physiological condition of deterministic chaos, both microvascular and parechymal, according to my Angiobiopathy theory (4).

Notoriously, blood circulation influences cellular metabolism, which, in turn, interferes on the regulation of blood pressure complex mechanisms, as prostaglandyns synthesis, thromboxane, radical NO, vasoactive amines, neurotransmitters, a.s.o., beside pH oscillations, axones reflexes and baro-receptorial mechanisms.

Our research data have, published in 1990, we demonstrated that Congenital Acidosic Enzyme-Metabolic Hystangiopaty-a (CAEMH-a) represents the conditio sine qua non “also” of essential arterial hypertension, as we suggested for a lot of years, on the base od clinical evidence (1-4).

On the other hand, all authors agree on the fundamental role played by “genetic factor” on the onset of arterial hypertension (4, 20-24).

Analogously to diabetes mellitus, arteriosclerosis, malignancies, and all other severe human diseases, also in arterial hypertension it is possible to observe an early, first stage, clinically silent, although initial tissue hypoxic disorder, particularly in skeletric muscle, which we suggested to term pre-hypertensive stage (4), on the analogy of what we wrote in the introductory article on Quantum-Biophysical-Semeiotic Constitutions (5, 9).

All individuals, which have suffered over the last years from an episode of the so-called “white-cloth” arterial hypertension (or have had arterial hypertension in the past, but now are normotensive) are under this condition, that takes a part of the so-called Grey Zone, namely the site of primary prevention.

However, nowadays, doctors belittle real significance of such hypertensive episodes, considered mainly as trivial and transitory consequence of commonplace neuro-hormonal reaction to stress situations, while they really represent the peak of an ice-berg, to which we have to pay all our attention and devote an accurate biophysical-semeiotic evaluation.

In fact, in individuals CAEMH-a positive of great intensity, particularly if localized in microvascular, e.g., muscular tissue, the reaction of smooth muscle cells of resistance vessels (i.e., small arteries and arterioles, according to Hammersen) to vasomotor physiological stimuli appears clearly exceeding, as we will say later (4, 15, 32).

In “initial” stage, however, such abnormal reaction can be still counterbalanced by vasodilation upward, i.e. in the vasa publica, according to Ratschow, and by blood re-distribution in various destricts, especially in the splancnic territory.

In other words, in pre-clinical, initial, pre-hypertensive stage, as well as in hypertensive constitution, blood pressure does not result increased at all – a part from episode of sympathetic hypertonus and/or Renine-Angiotensin-Aldosterone System (RAAS) – but peripheral blood supply is slightly “reduced”, causing tissue disorder, due to acidosis, as consequence of increased peripheral arteriolar resistances (PAR), which bring about elastic vessels dilation and opening of Arterio-Venous Anastomoses, functionally speaking, in always CAEM-a-positive individuals (5, 9, 10).

Methods.

With the aid of Biophysical Semeiotics doctor can quickly recognize bedside such as special microcirculatory situation, e.g., in skeletric muscles by the method of the preconditioning.

In healthy, at basal line, latency time of biceps muscle-gastric aspecific reflex (= in the stomach, both fundus and body dilate, while antral-pyloric junction contracts), when digital pressure stimulation is “mean-intense, results 8 sec., and it lasts for <> (= parameter value of paramount importance, duew to the fact that it is inversely correlated with Microcirculatory Functional Reserve), while at second evaluation, performed after 5 sec. exactly, latency time increases to ³ 12 sec.

On the contrary, in a subject with hypertensive constitution under identical experimental condition, basal latency time appears normal (NN = 8 sec.), but the duration results 4 sec. or more, and it does not ameliorate or sometimes lowers in the second evaluation, pathogical preconditioning, in relation to the severity of hypertensive “real risk” itself, as a consequence of impaired Microcirculatory Functional Reserve (9) (For further technical information, See

http://www.semeioticabiofisica.it/microangiologia).

In the pre-hypertensive state, which can last clinically silent years or decades, and, then, very difficult to recognize by physical orthodox semeiotics (21, 26, in 4), doctor observes the typical microcirculatory metabolic abnormalities in post-absorptive state, i.e. at least 4 hours after meels, characterized by AL + PL duration (= duration of microcirculatory wave oscillation, which parallel ureteral reflexes) of pancreatic vasomotion (for instance, more easy to detect, duration of pancreatic body inferior margin lowering: see Technical Page 5, in above-cited website) lasting more than those of muscular, hepatic and adipose tissues, evaluated by means of upper (vasomotility) and lower (vasomotion) reflex oscillations, during “light” stimulation of related trigger-points (Fig 1).

Fig.1

The figure shows physiological vasomotion of all biological systems, assessed directly (e.g., as values of pancreas periodic, deterministic chaotic oscillations: lowering of inferior pancreatic margin) or indirectly as ureteral reflexes fluctuations, upper – vasomotility – and lower – vasomotion – brought about by “light” stimulation of related trigger-points, e.g., muscular and central, adipose tissue.

In other words, there is dissociation between insulin secretive-metabolic activity and that of “peripheral” tissues, indicating, in a refined biophysical-semeiotic manner, hyperinsulinaemia-insulinresistance: “classic” metabolic syndrome (5, 6, 10, 11, 12).

On the contrary, in the “variant” metabolic syndrome, the AL + PL Phase of liver vaso-dynamics, under identical condition, i. e., in the post-absorptive state, results lower than those of adipose tissue, musculare tissue, and above all of pancreas, which is the most instense (AL + PL) of all .

In other words, in case of “variant” metabolic syndrome, exclusively hepatic insulin receptors are normally sensitive to the hormone, and, under the above-mentioned circumstance, i.e., after at least 4 hours after meels, insulin normally controls hepatic glucose secretion, but not the lipidic secretion from “central” adipose tissue (13, 14).

At this point, it is necessary to underline that insulin secretion activity, if not properly ameliorated by diet, etymologically speaking, and/or histangioprotective drugs, such as coniugated melatonine can go on slowly towards progressive its insufficiency (6), characterized by gradual, before limited, and after widespread, changing of pancreatic beta-cell insulin activity from type I, associated, (in which both vasomotility and vasomotion are intense: active hyperaemia), to type II, intermediate (origin of IGT) and, finally, to type III, dyssociated (first stage of microcirculatory insufficiency), when pancreatic tissue acidosis is highest (real begin of DM). (See also Diabetic Constitution and Diabetes Mellitus in Practical Applications, in above-cited website and in the website www.indmedica.org, 2 Cyber Lectures: Diabetic and Dyslipidaemic constitutions).

Starting from this stage, pancreatic interstitium becomes more large than the normally, mainly due to amyloid deposit, as formerly demostrated: pancreatic-“in toto” ureteral reflex results ³ 1 cm. (NN < 1 cm.) (See Diabetes mellitus, in http://www.semeioticabiofisica.it, Practical Applications, URL

http://www.semeioticabiofisica.it/semeioticabiofisica/Documenti/Eng/Diagnosis%20DM,%20amyloid.doc).

At this point, we can finally understand more clearly the really frequent association between arterial hypertension and DM, which appears “always” on the common base of a congenital inherite factor, i.e. CAEMH-a., particularly intense in both Langherans’s pancreatic isles and skeletric muscle arteriols, i.e, resitance vessel wall-

For the first time it is possible to speak of real beginning of diabetes mellitus, a term until now used without scientific support, namely in acritical manner, despite the progress of sophysticated instrumental semeiotics.

At a large number of congresses I have showed the misuse of such termin in front of well-known diabetologists, who appeared without exception surprised, annoyed and totally unable to falsify our statement (7).

DM type II, so-called NIDDM, – more than 94% of all cases – from biophysical-semeiotic viewpoint shows a precise, clear-cut beginning, which corresponds to the first onset of pancreatic isles microcirculatory activation type II, intermediate, in individuals involved by dyslipidaemic “and” diabetic constitutions, causing histangic acidosis anf further, pancreatic amyloyd deposit, and reduction of local insulin receptors sensitivity, essential factor in the self-regulation of hormone secretion.

In a few words, such characteristic microcirculatory condition parallels the activation of “only” vasomotility, evaluated at the bed-side as fluctuations of upper ureteral reflex, during “light” stimulation of pancreatic trigger-points: AL + PL, i.e. duration of oscillation wave (Fig.1), is 7-8 sec. (NN = 6 sec.), whereas vasomotion, i.e. the fluctuations of lower ureteral reflex, shows a AL + PL duration unchanged (6 sec.), due to impairment of loca AVA and especially of Endoarteriolar Blocking Devices (EBD).

From the haemoreological-microcirculatory view-point, that indicates an impairment of Microcirculatory Functional Reserve, and consequently initial abnormality of insulin secretion, according to Angiobiopathy theory.

In addition, it has to be considered that elastic artery dilation, evaluated clinically by means of Biophysical Semeiotics, as it will be once more illustrated in following, aims to counterbalance the dangers of increased peripheral artery resistance. However, repeated and acute dilation, e.g. during stresses, brings about initial alterations of endothels (denuding) and smooth muscle cells endo-reduplication, with subsequent arterial wall structural abnormalities, as intimal thikening (4, 25, 26).

At this point, we briefly remember the contemporaneous alterations of local vasa-vasorum, caused mainly by wall dilation, which brings about, in turn, further impairment of related microcirculation and consequently arterial wall damage.

In biophysical semeiotic detecting pre-hypertensive state, i.e. hypertensive constitution and hyrtension real risk, beside muscular preconditioning, illustrated above, to which we will return later, a primary role is played by the diagram of finger-pulp tissue microvascular unit, in which Phase A is reduced (gastric aspecific reflex < 1 cm.) and disappearing time of tGC results prolonged, after rapid interruption of digital pressure: Oxygen Recovery Time < 1 cm. (O₂RT) (15-17).

Interestingly, O₂RT (NN £ 2 sec.) is in relation to the recovery of normal tissue oxygenation, after interruption of jatrogenetically induced histangic acidosis, “aerobic” glycolisis restoration, H⁺washing, and, then, post-ischaemic reactive hyperaemia, strictly related to Microcirculatory Functional Reserve, always altered also in the pre-hypertensive state, as clinical and experimental evidence shows: O₂RT (NN = 2 sec.) > 2 sec., directly related to the seriousness of hypertensive constitution.

Unavoidable to evaluate pre-hypertensive state, it proved to be ausculatory percussory outlining of common femoral artery, which can be performed with the bell-piece of stethoscope, properly localized on this arterial vessel at the groin, or, in a practical way, immediately under umbelicus, at right or at left.

At this point, auscultatory percussion has to be applied, directly and “gently” from right to left and viceverse, right below umbelicus as far as hypophonetic and intense sound is perceived, indicating the cutaneous projection area of common femoral artery: if the individual, which is examined, performes boxer’s test or, apnea test or Restano’s manoeuvre (contemporaneously, he performes the two tests), in healthy, the artery dilates clearly; on the contrary, in hypertensive state as well as in hypertensive patients, of course, the vessel dilate just a little or does not dilate at all (70).

Quantum-Biophysical-Semeiotic evaluation of hypertensive constitution and hypertension real risk.

By recognizing the pre-clinical condition, pre-hypertensive stage or hypertensive constitution, as well as hypertension real risk, which may evolve to arterial hypertension, doctor has to consider accurately a lot of parameters, really different in bed-side evaluation difficulty.

1) Systolic arterial pressure (SAP).

2) Diastolic arterial pressure (DAP)

3) Mean arterial pressure (MAP = SAP – DAP/3 + DAP)

4) Heart rate (HR).

5) Systo-diastolic oscillations of left ventricle at rest and during boxer’s test (NN = 1 and, respectively, 2 cm.): this paramter may be overlooked, although it is really interesting.

6) Tissue pH, evaluated as latency time of Critical Point (CP) of 5 cm. in tissue-microvascular-unit diagram. In healthy young, CP is generally absent (Fig. 2).

7) O₂Recovery Time (O₂RT), assessed as latency time of tGC disappearing (NN = 2 ± 0,5 sec.) .

8) Arterial peripheral resistance (APR = MAP/10 x O₂RT); normal value £ 20.

9) Basal arterial diameter (BAD), evaluated, e.g., as diameter of cutaneous projection of common iliac artery in a relaxed patient (NN £ 2 cm.).

10) Dilation index (DI = Max AD/BAD; NN ³ 2 cm.); artery diameter is assessed at basal line and, then, during boxer’s test, for instance.

11) Arterial compliance (Co = DI x 10 / O₂RT; NN = 8-17).

12) Skeletal muscle preconditioning.

In practice, the preconditioning can be performed at the level of biceps muscle (or other muscle, of course). It is a simple, and reliable manoeuvre, which permits rapidly by itself to diagnose hypertensive constitution: in healthy, in supine position and psycho-physically relaxed with open eyes to avoid melatonin secretion, doctor evaluates basal lt of biceps muscle-gastric aspecific reflex and/or caecal reflex by mean of “mean-intense” pressure (NN = 8 sec.).

After 5 sec. “exactly” – preconditioning – the same parameter is evaluated for the second time: in healthy, latency time appears prolonged significantly, while in the individual with hypertensive constitution, and, of course, in hypertensive patient, latency time is either unchanged or lowered, in inverse relation to the seriousness of arterial hypertension.

Without going on in the pathophysiology discussion, in which we are not concern at this moment, this method allows doctor to “quantify” peripheral arterial resistance. In a 50-year-long well established experience, the method proved to be reliable in 100% of cases.

It is easy to understnd that DI is related directly to distension ability of arterial wall, i.e., to arterial wall elasticity, impoortant factor of arterial compliance, evaluated by a different, more refined method (12-14).

In individuals under 60 years of age, DI is ³ 2 cm., when evaluated as cutaneous projection area of vessel, while over 60 years DI appears reduced to less than 2 cm.

Clinical and experimental evidence suggests that O₂RT is related to PAR, as we demonstrated in an our research: r = + 0,84; tr = 4,378; p <>

Generally, Co is assessed by Bramwell and Hill’s formula, which consider the speed of wave puls and vascular elasticity, observed with sophysticated methods.

However, at the bed-side it proved reliable the datum obtained by this formula, opportunely modified, using DI, which gives information about common iliac artery elasticity ( or, of course, of other artery) and O₂RT inversely related to blood-flow in tisssue-microvascular unit, during the phase of post-ischaemic hyperaemia (exclusively because of calculation reasons, DI is multiplied for 10). In aging, over 60 years, Co results <>

At this point, it is possible clinically to face the aethiopathogenetic problems of AI in a new way, i.e., trying to define pre-hypertensive state, which shows a particular hypertensive constitution, analogously at what we described as regards the diabetic, migraine constitution rheumatic arteriosclerotic constitution, and other constitution, such the oncological terrain.

Exclusively in this way it is possible to bed-side recognize pre-clinic stage of arterial hypertension, whose knowledge is essential for the primary prevention of hypertension.

Among young individuals, CAEH-a positive, with blood pressure in normal ranges, it is relatively easy to regognize those with increased PAR (> 20), even during stress test, DI < 2 cm., O₂RT > 2 sec. and Co < style=""> physiological conditions.

Biophysical-Semeiotic Evaluation of Natriuretic Peptides.

From practical view-point, I advice such as “easy” evaluation of NP, offering a lot of usefull and interesting information on NP biological activity, particularly as hypertensive constitution is concerned.

In fact, individuals with hypertensive consitution (pre-hypertensive state) as well as overt hypertension, show a significantly decreased renal biological activity of natriuretic peptides, as patients involved by CAD, when down-regulation of renal specific receptors is caused by high levels of NP.

As a consequence, the impaired biological renal activity of natriuretic peptides plays a paramount role in bedside detecting hypertensive biophysical-semeiotic constitution. (For further technical information, See in above-mentioned website, the URL

http://www.semeioticabiofisica.it/semeioticabiofisica/Documenti/Eng/BNP%20engl.doc .

In following, an easy way reliable in such evaluation is described: in healthy, lying down in supine position, “intense”, sub-occlusive digital pressure is applied upon phemoral artery at the groin (or on another great muscular artery); the subsequent artery dilation upstrem brings about left cardiac atrial and left ventrical dilation, and then NP_s secretion. After about 15 sec., kidney does not fluctuates as usually, showing congestion for 30 sec. exactly.

On the contrary, in individuals with hypertesive constitution and obviously overt hypertension, kidney congestion lasts for a time varying between 20 sec. and less than 30 sec., in relation to the severity of underlying disorder.

Hypertensive Constitution

PAR > 20

DI < 2 cm.

O₂RT > 2 sec.

Co <>

Muscolar Preconditioning pathologic

Evaluation of Natriuretic Peptides

Getting rid of abnormalities of pre-clinical, pre-metabolic stage, we can hpefully prevent the serious diseases, which otherwise can onset, and, mainly the well-known complications in different biological systems.

On the contrary, we must rely only on treatments of high arterial pressure, often apparently efficacious, due to the fact that complication are already present and therapeutic monitoring is based exclusively upon lowered pressure values, gathered by the aid of a sphygmomanometer, which nothing are able to say about what really happen in target organs and tissue.

Actually, at the beginning of third millennium, doctors, for the fist time, agree with those few colleagues, who over years state that arterial hypertension, evaluated untill now at the level of vasa publica in a large variety of ways, is not significant as regards what really happens in tissue-microvascular-units under the same conditions.

In other words, the urgency of assessing organs damage begins to play the deserving role, also in the mind of those with scarse ability of criticism and creative imagination.

Really, since the descovery of CAEMH I stated without success that our colleagues would pay a great deal of attention to this mitochondrial cytopathology, overlooked for too long time, since I have realized that the war against the most serious human diseases, including arterial hypertension, can obtain the best results only in case of a prompt selection of individuals at “real risk” for them, so that they undergo “clincal” tests, reliable in “quantifying” such as risk, initiating rapidly the correct diet, etymologically speaking, that normalizes the muscular reactions, pathological at the beginning during boxer’s test, simulated stress test, “sucking simulation test, in which rythmic mamma palpation physiologically brings about – by nervous reflex, inhibiting dopamine neurons of TIDA – increase of PRL secretion, which enhances peripheral arteriolar resistance as well as insulin secretion, and negative consequences, we previously described (4, 10).

It is worth for saying that primary prevention of AH allows doctors to prevent contemporaneously also disorders and syndromes (ATS, DM, gout, malignancies, in indivuals, of course, with “oncological terrain”, a.s.o.) with favorable influences, both individual and social (20-22).

In fact, clinical evidence demonstrates that, beside AH, in the same patient there are frequently other serious disorders, cause of morbidity and mortality, based upon the commom genetic factor, i.e. CAEMH

The authors agree generally on both exsistence and importance of “genetic factor” of arterial hypertension, which has to explain following facts:

1) sympatethic hypertonus;

2) “intense and rapid “ response of a-adrenergic receptors, present in fifferent way in arterial and venous districts;

3) “rapid and intense” response of the vessels, which dilate;

4) “rapid and intense” congestion and subsequent similar decongestion of splancin organs, a part from intestine.

Clinical evidence in favour of pre-hypertensive state.

In hypertensive state, in fact, in a previous research performed on 249 individuals CAEMH-a, negative for AH, in the age between 15-80 years, the duration of kidney congestion during boxer’s test, resulted 4-5 sec., while in 467 individuals, comparable to age, CAEMH-a positive, among them 175 hypertensive (37,5%), and the other normotensive, but with family history positive for AH (292; 62,5%), kidney congestion duration was <>

CAEMH-a – as we demonstrated previously (2-4, 9, 10, 11, 14, 18, 19) – represents the conditio sine qua non of ATS, migraine, DM, autimmune disorders, incuding Acute Benigne Variant Polymyalgya Rheumatica (18, 19), tumours (10), solid and liquid, : “all” hypertensive individuals, we observed over the last 50 years, are or were involved by the mitochondrial cytopathology, I described, as allows us to state also the clinical evidence: digital pressure, applied on a nail-fold, e.g. of the big toe, of a young CAEMH-a negative, causes temporary dilation of homolateral common iliac artery (0,5 cm.), while both aorta and controlateral common iliac artery “practically” show unchanged diameters.

On the contrary, in the young CAEMH-a positive homolateral iliac artery shows a dilation ³ 1 cm. and, simultaneously, both aorta and controlateral common iliac artery dilate clearly and significantly, permitting thus pressure values to be normal.

Really, CAEMH-a is the genetic factor, clinically “quantifiable”, at the base of various formes of neuro-vegetative dystonia (8), of particular a₂-receptors overactivity, as in case of alexytimia, frequently associated to AH (4, 28). The incapacity for speaking correctly and describe emotions by Autonomous Nervous System, due to internal tensions, plays a primary role in the pathogenesis of AH associated with this nervous disorder.

From the above remarks, in order to prevent efficaciously AH we have to be considered, in “healthy subjects, i.e. without AH or other clinical phenomenology, but CAEMH-a positive, the possibility of assessing hemoreological-haemodynamic as well as metabolic-biochemical modifications (post-absorptive state with abnormalities in central and peripheral vessels dynamics), even caused by numerous tests: boxer’s test, simulated stress, apnea test, sucking simulated test, Restano’s manoeuvre, a.s.o.

We must consider interesting the data collected, as usually, by tissue-microvascular-unit of finger-pulp or nail-foild, in which A Phase is characteristically of small intensity and O₂RT is > 2 sec.

Beside the family history, the results of this evaluation allow to recognize promptly individuals at “real” risk for arterial hypertension, starting from the initial stage, we suggested to term pre-hypertensive state of AH, in which tissue pH appears to be lowered, O₂RT prolonged, PAR increased, DI abnormal, arterial Co pathological, according to the values, illustrated above in the scheme.

These individuals show metabolic-biochemical conditions, characteristic of pre-morbid state, in which is present hyperinsulinaemia-insulinresistance,observable, the first, by specific renal test (brief kidney congestion and prolonged decongestion; NN 4-5 sec. and, respectively, 10 sec.) and by suprarenal glands evaluation (reduced microvascular activity since the third fluctuation), during insulinaemic acute pick secretion, due to the phenomenon of down-regulation of kidneys insulin receptors as well as insulin “vasocostriction” action caused by functional dysendotelization, as we observe as regards acethyl-choline

In conclusion, by a large number of biophysical semeiotic methods, of different difficulty and refinement (we illustrated above some among the less difficult methods, although reliable and practically easy to perform) nowadays is possible to recognize individual at risk for AH, since the first two decades of life, in a “quantitative” manner, due to the severity of their hypertensive constitution.

Consequently, now we can perform fortunately the primary prevention of this widespread and dangerous disease, notoriously complicated, if diagnosed to late, by morbidity and mortality, which can nowadays be prevented, because we can detect the disease in its pre-morbid stage, before complications onset, clinically, and, therefore, on very large scale.

* Sergio Stagnaro MD

Via Erasmo Piaggio 23/8, CP. 42

16039 Riva Trigoso (Genoa) Europe

Founder of Quantum Biophysical Semeiotics

Who's Who in the World (and America)

since 1996 to 2009

Ph 0039-0185-42315

Cell. 3338631439

www.semeioticabiofisica.it

dottsergio@semeioticabiofisica.it

Referencees

1) Stagnaro S., Istangiopatia Congenita Acidosica Enzimo-Metabolica condizione necessaria non sufficiente della oncogenesi. XI Congr. Naz. Soc. It. di Microangiologia e Microcircolaz. Abstracts, pg 38, 28 Settembre-1 Ottobre, Bellagio, 1983.

2) Stagnaro S., Istangiopatia Congenita Acidosica Enzimo-Metabolica. X Congr. Naz. Soc. It. di Microangiologia e Microcircolazione. Atti, 61. 6-7 Novembre, Siena, 1981.

3) Stagnaro S., Istangiopatia Congenita Acidosica Enzimo-Metabolica. Gazz Med. It. – Asch. Sci, Med. 144, 423, 1985.

4) Stagnaro-Neri M., Stagnaro S., Stadio pre-ipertensivo e monitoraggio terapeutico della ipertensione arteriosa. Omnia Medica Therapeudica. Archivio, 1-13, 1989-90.

5) Stagnaro-Neri M., Stagnaro S. Introduzione alla Semeiotica Biofisica. Il Terreno Oncologico. Travel Factory, Roma, 2004. http://www.travelfactory.it/semeiotica_biofisica.htm

6) Stagnaro-Neri M., Stagnaro S., Sindrome di Reaven, classica e variante, in evoluzione diabetica. Il ruolo della Carnitina nella prevenzione del diabete mellito. Il Cuore. 6, 617, 1993.

7) Stagnaro S., Risk of Type 2 Diabetes. N Engl J Med. 2002 Jan 24;346(4):297-298. letter [MEDLINE].

8) Stagnaro-Neri M, Stagnaro S., Valutazione clinica percusso-ascoltatoria del sistema nervoso vegetativo e del sistema renina-angiotensina, circolatorio e tessutale. Arch. Med. Int. XLIV, 17378, 1992.

9) Stagnaro S., Stagnaro-Neri M., Le Costituzioni Semeiotico-Biofisiche.Strumento clinico fondamentale per la prevenzione primaria e la definizione della Single Patient Based Medicine. Travel Factory, Roma, 2004. http://www.travelfactory.it/libro_costituzionisemeiotiche.htm

10) Stagnaro-Neri M., Stagnaro S. Introduzione alla Semeiotica Biofisica. Il Terreno Oncologico. Travel Factory, Roma, 2004. http://www.travelfactory.it/semeiotica_biofisica.htm

11) Stagnaro Sergio. Bedside Assessing ANS, RAAS, and IIR: a complex Relation to type 2 Diabetes. Cardiovascular Diabetology,15 November 2005. http://www.cardiab.com/content/4/1/15/comments#215501

12) Stagnaro Sergio. Microalbuminuria and Diabetes Mellitus: a primary predictor. CMAJ. 22 August, 2002. http://www.cmaj.ca/cgi/eletters/163/5/561.

13) Stagnaro Sergio. Single Patient Based Medicine: its paramount role in Future Medicine. Public Library of Science. 2005.http://medicine.plosjournals.org/perlserv/?request=read-response.

14) Stagnaro S., Stagnaro-Neri M. Single Patient Based Medicine.La Medicina Basata sul Singolo Paziente: Nuove Indicazioni della Melatonina. Travel Factory, Roma, 2005. http://www.travelfactory.it/libro_singlepatientbased.htm

15) Stagnaro-Neri M., Stagnaro S. Indagine clinica percusso-ascoltatoria delle unità microvascolotessutali della plica ungueale. Acta Med. Medit. 4, 91, 1988.

16) Stagnaro-Neri M., Stagnaro S., Semeiotica Biofisica: valutazione della compliance arteriosa e delle resistenze arteriose periferiche. Atti del XVII Cong. Naz. Soc. Ital. Studio Microcircolazione, Firenze Ott. 1995, Biblioteca Scient. Scuola Sanità Militare, 2, 93, 1995.

17) Stagnaro-Neri M., Stagnaro S., Auscultatory Percussion Evaluation of Arterio-venous Anastomoses Dysfunction in early Arteriosclerosis. Acta Med. Medit. 5, 141, 1989.

18) Stagnaro S., Auscultatory Percussion of Rheumatic Diseases. X European Congress of Rheumatology. Moscow. 26 June-July, Proceedings, pg 175, 1983.

19) Stagnaro S., Polimialgia Reumatica Acuta Benigna Variante. Clin. Ter. 118, 193,1986 [Medline]

20) Kannel W.B., Schatzkin A. — Analisi dei Fattori di Rischio. Progressi in Patologia Vascolare,Vol. XXVII, 5.-9, 1984

21) Malamani V. — L'evoluzione del pensiero medico in tema di ipertensione. Fed. Med. XXXVIII, 5, 511-516,1985.

22) Patzscheke U. Milde Hypertonie: Behandein Oder Nicht Behandein? Med. Klin. 21, 80, 574-578, 1985.

23) Ratschow M. Angiologia. Patologia, Clinica E Terapia Dei Disturbi Circolatori Periferici. I Ed. Italiana Pag. 115 Casa Editrice Ambrosiana. Milano, 1962.

24) Zanchetti A. Ipertensione Arteriosa: Filosofia Attuale Di Un Trattamento Flessibile E Personalizzato. Il Polso, Ottobre 1987, Pag. 41-47.

25) Pickering G. High Blood Pressure. Ii Ed. London. J. &A. Chruchill, 1986, Pg. 35.

26) Schirosa G. Le Malattie Del Cuore. I Ed. Vol. Ipag. 61 Società Editrice Universo. Roma 1970.

27) Schwartz S.M., Ross R. La Proliferazione Cellulare Nell'arteriosclerosi E Nell'ipertensione. Progressi In Patologia Vascolare, Voi. XXVII, N° 4, 63-81, 1984.

28) Ciraolo O., Quartarone M., Barbera N. E Coli. Alexitimia E Ipertensione. Atti Ix Congr. Naz. Soc. It. Patologia Vascolare. Copanello 6-9 Giungo 1987. Pg. 639-644 Monduzzi Editore Bologna 1987.

Quantum Biophysical Semeiotics: The Theory of Angiobiopathy

noreply@blogger.com (Stagnaro) — Mon, 11 May 2009 09:24:00 +0000

Introduction.

Microvessels and microcirculation play a paramount role in Quantum Biophysical Semeiotics.

In reality, chaotic-determinist dynamics of the biological systems, present in the three zones, Zone White (health), Grey Zone (pre-pathology) and Black Zone (disease) (1-5), are caused by the analogous oscillations of the single structures of relative tissue microvascular units, i.e., microcirculatory bed, according to Anglo-Saxon Authors (6-10). From the conceptual point of view, problematics regarding micro-circle and the microcirculation, are comprised, as well as analyzed, in the best way, when we are thinking, for analogy, to the street map of a city or country: from the large peripheral street begin wide roads, to only sense, different for number, directed towards the centre. The main roads, in double sense, progressively go shrinking itself till to become small street. In the vascular structure, the wider roads correspond to the Ratschow’s "vasa publica", while smallest, under 100 micron, represents for analogy the "vasa privata" , that participate to the formation of tissue microvascular unit (11). Naturally, blood “return” is realized by micro and the venous macro-vessel and the lymphatic ones.

The Theory of Angiobiopathy

For the first time in clinical way (V. http://www.semeioticabiofisica.it), thanks to Quantum Biophysical Semeiotics, has been realized biological-molecular study of parenchimal activity by studying the related micro-vessels and microcirculation in the biological systems, both at rest and under utilization of numerous substances, completing the assessment during dynamic tests, much rich of information. This theory, Angiobiopathy Theory, completes usefully Angiobiotopy theory, according to F. Tischendorf, brilliant student of microvessel anatomy, friend and collaborator of my Master of Microangiology-Microcirculation, S.B. Curri.

According to Angiobiopathy Theory a determined parenchyma is supplied of a specific microvascular system, really complex from the structural point of view, result of an co-organization happened in the course of evolution. In reality, such anatomy of tissue-micro-vascular unit can modify within the same apparatus, due to physiological reasons, correlated constantly with particular situations of the local tissue, as it happens in the skin microcirculation of lower limb. Tischendorf’s definition of Angiobiotopy as reagards the Zone White (Health), emphasises the anatomical aspect, and it has been completed from the Angiobiopathy Theory, that emphasizes parenchimal-microvessel correlations also in the pre-pathological conditions, Grey Zone ("locus" of the primary prevention), and in the several diseases, Black Zone, as I have illustrated in previous papers (1-6). In other words, between parenchyma and relative micro-vascular system is present constantly an anatomical and functional correlation, bedside assessed not only in physiological but also in pre-pathological and pathological conditions, as clinical evidence demonstrates.

To this point, I call for attention to above-mentioned analogy, in order to comprise in details these Medicine advances, really fundamental for Clinical Microangiology. We think next to the existing relationship between the houses of a country or a quarter and the local roads, ways, alleys, but also the water, gas, etc. In fact, as the vessels of every tissue, they supply material-energy-information for the life of the inhabitants and provide to remove the harmful debris, catabolites, events of essential importance for the survival of residents (7-21).

We still continue with the aid of the same analogy in order to explain a fundamental concept in the Quantum Biophysical Semeiotics: from the movement of the several feeding goods, materials, newspapers, books, a.s.o., and flowing drinkable water, as well as black water, sewer, or drainage white water, in a limited city area, can obtain precise information on the culture, understanding broadly speaking, of a community and on the way people face the several existential problems. Therefore, the reader can easily comprise that the way “to be and to work” of the microvessels, included the vase vasorum (12), studied now also with Clinical Microangiology, using a stethoscope (the 6-10) (www.semeioticabiofisica.it/microangiologia), gives information, anatomo-functional in origin, about correspondent biological system, aim of doctor’s evaluation.

In health, the micro-vascular oscillations as well as macro-oscillations, are chaotic-determinist, unforeseeable, apparently stocastic, showing an intensity (0,5 - 1,5 cm., conventional measure) and duration of the cycles (oscillating between 9 and 12 sec., i.e., 6 circle /sec.), but regulated, in reality, from a more refined order, than binds them inside of a strange attractor in the space phase (1-11).

From the above microcirculatory remarks, derives that Clinical investigation allows doctor to gather, for the first time clinical, precious information on the biological system function and structure, through the data observed on the structure and activity of the relative microcirculatory system, both at rest and during stress tests. The evaluation of biological activity is based above all on bedside analysing micro-vascular system of several parenchymas under different situations, normal or not, according to Angiobiopaty theory.

In reader’s interest, to comprise the real significance of Angiobiopaty, whose role is fundamental in the Quantum Biophysical Semeiotics, is firstly unavoidable to examine in details the concept of Angiobiotopy , according to Tischendorf.

First of all, it is not surprising the fact that the biological systems adapt, so to speak, the relative tissue-micro-vascular units to the single request of their various regions. For example, the system of the so-called “preferential channels” represents, for still unknown reasons, a structural particularitity of intestine and eye conjunctive, while the formation of meshes of the arterioles and the venules characterises the skeletal musculature. Naturally, a structural disposition of both above-mentioned vessel types can be observed - in less or more intense way - also in other organs and tissue, for instance, to mesentery and pia mater. In mesentery the formation of ring-like anastomoses of the arteries and the veins is limited generally to the branches of greater bore, while the smallest arteries and the arteriole are subdivided dycotomically of new, like branches of a tree, in order to end in the capillaries. Moreover, during their transformation in smaller vessels its diameter constantly becomes conical: for this their form is not still cylindrical, but conical and is fine. According to S.B. Curri, we may admit the hypothesis that these structural differences regarding microvessel modifications are not connected exclusively to the various function of the supplied tissues, but also to their various disposition it spaces, and therefore, to topographical factors. Thus as an example the micro-structure of the human skin constitutes one of the more meaningful aspects of the combination between the "structural principle to net" and the dycotomic subdivision of the capillaries. While in derma deeper regions micro-vessels form the artero-arterioses and veno-venose anastomoses in the subpapillare plex, cutaneous arterial and venous, the capillaries in epidermis from small arteries end in smallest vessels: these are found horizontal under epidermis, circulating itself in a capillary after other that heads vertically towards high; or they go directly towards the epidermis layer bases, circulating in many capillaries to form of small bush. An other example of micro-vessel structure is represented from the capillary beds of the liver and of the spleen, that show how much clearly the anatomical structure of an organ and its specific functions are in a position to modifying distribution model space of the little vessels, radically different from the two above-mentioned fundamental models.

It can be said therefore that the rules of the architectonic plan of the capillary nets are subordinated to the organ-specific architectonic peculiarities. From above shortly reported information, one comprehends that the structure of the capillary beds cannot be identical, always the same, and that differences are present, so that various structural principles can coexist. On the other hand, there are body regions, e.g., eye conjunctive, whose circle ends much irregular and it seems un-forseable: thus, it’s possible one or another type of microcirculatory bed. As states my Master, main goal of the future researches is to determine for every important region of an organ or tissue - from patho-physiological view-point – what is the constructive plan of the capillary bed. The intuition, before, and the demonstration, then, of the correlation tightened between structure and function of every parenchyma and that one of the relative micro-vascular system represents the central aspect of the Angiobiopathy theory, that has opened revolutionary new way to diagnosis, differential-diagnosis, therapeutic monitoring and clinical research.

Krogh was right!

As Krogh had previewed in its Lecture in occasion of the Nobel Prize ceremony in 1920 (1), the study of the micro-vessels shows today fortunately its original, essential and reliable utilization in bedside examination of all biological systems, beside obviously macro- and micro-circulatory system, in physiological and pathological conditions, emphasising a paramount value in diagnosing and researching, thanks to Quantum Biophysical Semeiotics.

In fact, the clinical study of the micro-circle and the microcirculation of every apparatus and tissue, allows to doctor bedside gathering reliable information on structure and functions of all biological system, as well as to recognize and analyze biological and biological-molecular events of the relative parenchyma, under different conditions. Moreover, in every biological systems there is no-local realm, I have demonstrated for the first time, wherein information is simultaneous, beside the well-known local realm. At this point, I have to thank my friend Paolo Manzelli, discoverer of the triadic nature of information (12-24), for his precious advices on Quantum Physics.

Interestingly, the "intense" digital pressure, applied, e.g., upon trigger-points of the neuronal centres for release hormone, provokes the simultaneous associated microcirculatory activation of type I, physiological, in all nervous system, including the above-mentioned centres.

In health, “simultaneously” with the beginning of the stimulation, the stomach does not show any modification of its form and volume, which occurs only after the physiological latency time, as aspecific gastric reflex. In other words, under this experimental condition, is absent the simultaneous non-specific gastric reflex at the beginning of the test.

On the contrary, in presence of whatever cerebral lesion, both structural and functional in nature, like CAEMH (1-7), we simultaneously observe aspecific gastric reflex, whose intensity in cm. parallels th seriousness of underlying disorder (12-24. Therefore, on the base of the no-local realm in Biology, it is possible to bedside recognize, with a stethoscope, in a second, in reliable, elegant, and quick way, brain disorders, and analogously those of different parenchyma, by means of the evaluation of the relative tissue-microvascular units, “simultaneously” activated in the correspondent biological system by such “intense” stimulation of the relative trigger-points (10-25). The data, quickly gathered, direct subsequently the physical examination towards the really suffering biological system or tissue, allowing to utilise it at the best loosing less time.

References

Stagnaro-Neri M., Stagnaro S. Introduzione alla Semeiotica Biofisica. Il Terreno Oncologico. Travel Factory, Roma, 2004. http://www.travelfactory.it
Stagnaro S., Stagnaro-Neri M., La Melatonina nella Terapia del Terreno Oncologico e del “Reale Rischio” Oncologico. Travel Factory, Roma, 2004.
Stagnaro S., Stagnaro-Neri M., Le Costituzioni Semeiotico-Biofisiche.Strumento clinico fondamentale per la prevenzione primaria e la definizione della Single Patient Based Medicine. Travel Factory, Roma, 2004.
Stagnaro S., Stagnaro-Neri M., Single Patient Based Medicine.La Medicina Basata sul Singolo Paziente: Nuove Indicazioni della Melatonina. Travel Factory, Roma, 2005.
Stagnaro Sergio. Teoria Patogenetica Unificata, 2006, Ed. Travel Factory, Roma.
Stagnaro Sergio. Semeiotica Biofisica Quantistica: La Teoria dell’Angiobiopatia. www.fce.it, http://www.fcenews.it/index.php?option=com_content&task=view&id=1451&Itemid=47
Stagnaro S., Istangiopatia Congenita Acidosica Enzimo-Metabolica. Gazz Med. It. – Asch. Sci, Med. 144, 423, 1985.
Stagnaro-Neri M., Stagnaro S., Auscultatory Percussion Evaluation of Arterio-venous Anastomoses Dysfunction in early Arteriosclerosis. Acta Med. Medit. 5, 141, 1989.
Stagnaro-Neri M., Moscatelli G., Biophysical Semeiotics: deterministic Chaos and biological Systems. Gazz. Med. It. – Arch. Sc. Med. 155, 125, 1996.
Stagnaro-Neri M., Stagnaro S., Deterministic Chaos, Preconditioning and Myocardial Oxygenation evaluated clinically with the aid of Biophysical Semeiotics in the Diagnosis of ischaemic Heart Disease even silent. Acta Med. Medit. 13, 109, 1997.
Stagnaro Sergio. Diagnosi clinica di cuore sano in un secondo! 7 Aprile 2008. www.fce.it http://www.fcenews.it/index.php?option=com_content&task=view&id=1218&Itemid=47
Stagnaro Sergio e Paolo Manzelli. Semeiotica Biofisica Endocrinologica: Meccanica Quantistica e Meccanismi d’Azione Ormonali. Dicembre 2007, www.fce.it, http://www.fcenews.it/index.php?option=com_content&task=view&id=816&Itemid=45
Stagnaro Sergio e Paolo Manzelli. Natura Quantistica di una Originale Manovra Semeiotico-Biofisica di Epatopatia. Dicembre 2007, www.fce.it, http://www.fcenews.it/index.php?option=com_content&task=view&id=862&Itemid=45
Stagnaro Sergio e Paolo Manzelli. Semeiotica Biofisica Quantistica. http://www.ilpungolo.com/leggi-tutto.asp?IDS=13&NWS=NWS5243 2007
Stagnaro Sergio e Paolo Manzelli, Semeiotica Biofisica Quantistica: la manovra di attivazione surrenalica jatrogenetica. 09-1-2008, http://www.fcenews.it/index.php?option=com_content&task=view&id=161&Itemid=63
Stagnaro Sergio e Paolo Manzelli. L’Esperimento di Lory. Scienza e Conoscenza, N° 23, 13 Marzo 2008. http://www.scienzaeconoscenza.it//articolo.php?id=17775
Stagnaro Sergio. Non Local Realm. Response to Selection for Social Signalling Drives the Evolution of Chameleon Colour Change. (01 February 2008). www.plos.com, http://biology.plosjournals.org/perlserv/?request=read-response&doi=10.1371/journal.pbio.0060025
Stagnaro Sergio. La Diagnosi Clinica nella Semeiotica Biofisica Quantistica. www.fce.it 02-05-2008, http://www.fcenews.it/index.php?option=com_content&task=view&id=1285&Itemid=47
Stagnaro Sergio. Semiotica Biofisica Quantistica: Diagnosi di Cuore sano in un Secondo in paziente distante 200 KM! www.fce.it, 07-05-2008 http://www.fcenews.it/index.php?option=com_content&task=view&id=1316&Itemid=47
Stagnaro Sergio. Role of NON-LOCAL Realm in Primary Prevention with Quantum Biophysical Semeiotics. www.nature.com, 01 Feb, 2008-05-17 http://www.nature.com/news/2008/080130/full/451511a.html
Stagnaro Sergio e Manzelli Paolo. Semeiotica Biofisica Quantistica: Livello di Energia libera tessutale e Realtà non locale nei Sistemi biologici. www.fce.it , 29 maggio 2008, http://www.fcenews.it/index.php?option=com_content&task=view&id=1421&Itemid=47
Stagnaro Sergio. SEMIOTICA BIOFISICA Quantistica. Scienza&Conoscenza, 8-10-2008 http://www.scienzaeconoscenza.it/articolo.php?id=21568
Stagnaro Sergio. Benjamin Libet’s experiments: Quantum Biophysical Semeiotics view-point! The General Science Journal. 31 Dec. 2008. http://www.wbabin.net/comments/stagnaro.htm
Stagnaro Sergio. Quantum Biophysical Semeiotics Enlightens Benjamin Libet’s Experiments. www.fce.it, 14 gennaio 2009. http://www.fceonline.it/index.php?option=com_content&task=view&id=2194&Itemid=45
Stagnaro Sergio. Ruolo dell’Angiobiopatia nella Semeiotica Biofisica Quantistica, www.ilpungolo.com, 29 Maggio 2008, http://www.ilpungolo.com/leggi-tutto.asp?IDS=13&NWS=NWS5609

* Sergio Stagnaro MD

Via Erasmo Piaggio 23/8, CP. 42

16039 Riva Trigoso (Genoa) Europe

Founder of Quantum Biophysical Semeiotics

Who's Who in the World (and America)

since 1996 to 2009

Ph 0039-0185-42315

Cell. 3338631439

www.semeioticabiofisica.it

dottsergio@semeioticabiofisica.it

Quantum Biophysical Semeiotics Evaluation of pancreatic beta-Cell Function by means of acute pick stimulation of GH-RH secretion.

noreply@blogger.com (Stagnaro) — Thu, 07 May 2009 08:17:00 +0000

Introduction.

Among other well-known biological activities, Growth Hormone (GH) plays an important role in metabolism, as well as in regulating insulin secretion from the b-pancreatic cells, additionally controlling GH-RH secretion (analogously, e.g., thyroid hormone) (1-8).

Interestingly, the emerging age of Quantum Biophysical Semeiotics allows doctors, especially General Practitioners, to assess pancreas chaotic-determinist oscillations (fluctuations – 6 x sec. – of pancreatic body vertical diameter) (1-8), correlated with functional endocrine activity of the gland, according to Angiobiopathy theory (6-12).

(For technical information,See http://www.semeioticabiofisica.it, Technical Page 4).

The acute stimulation of GH-RH secretion, is brought about by “mean-intense” digital pressure applied on the related trigger-points (Fig.1 and 2).

Consequently, with the aid of Quantum Biophysical Semeiotics, physicians can evaluate bedside endocrine pancreas efficiency during the acute stimulation of the GH-RH and, thereby, obtaining useful and reliable GH information regarding current insulin secretion activity and efficiency (1, 2, 4, 7, 8).

Moreover, quantum-biophysical-semeiotic preconditioning (9), (also http://www.semeioticabiofisica.it ), enables the the practitioner can assimilate information (using the variables of Auscultatory Percussion and so-called Auscultatory Percussion-Reflex-Diagnostic, which studies non-linear dynamics of all biological systems) regarding the patient’s condition, as well as the possible insulin secretion evolution: physiological insulin secretion, hypersecretion of insulin (IIR) with or without initial failure of the pancreatic b-cells (prediabetes), overt type 1 and type 2 diabetes mellitus, even in early phase.

Finally, bedside evaluation can also reveal pancreatic endocrine activity, employing analogously other “endogenous” hormones of insulin counter-regulation (i.e., thyroid hormone, glucagone, adrenalin) (6, 7).

Method.

With the subject in supine position, psycho-physically relaxed (eyes open to avoid the melatonin secretion), the practitioner performs repetitive auscultatory percussion of a short tract of the lower pancreatic margin, assessing accurately its fluctuations, chaotic-determinist under physiological condition (Fig. 1).

For comprehensible reasons, the gathered data are meal-dependent, showing different parametric values in relation to the meals, i.e., in the absorptive or in the post-absorptive state.

However, in the practice, such as fact results neither important nor significant.

Notoriously, in overt type 2 diabetes, that is to say in manifest disorder, the dimensionality (i.e., value of deterministic chaos in a determined biological system, in our case the pancreas) fluctuations appear significantly and gradually reduced, all equal, and minimal, showing the fractal dimension of 1, i.e., topological dimension (6).

At this point, General Practitioner applies “mean-intense” digital pressure on the trigger-points of GH-RH neuronal centre, that is located 2 cm. over external auditory meatus (Fig. 2), evaluating accurately the pancreatic size behaviour.

In health, after approximately 6 seconds, the pancreas decongests suspending temporarily its secretive activity: the lower margin of the pancreatic body rises and remains in this higher position for 10 sec. exactly. In the absorptive state, the duration is approximately 11-12 seconds (in a non significant manner).

Under this experimental condition, pancreatic microcirculation shows the phenomenon of “microcirculatory disactivation”, characterized from minimal microvessel activity, resulting from the lesser flow-motion: in both vasomotility and vasomotion, according to Hammersen (7) fluctuation intensity is hardly 0,5 cm., and the durartion of AL + PL phase appears to be 5 sec., (6, 8, 10,11, 12) (See the above cited web site http://www.semeioticabiofisica.it/microangiologia).

On the contrary, in the subject with insulin hypersecretion (IIR), the pancreas decongestion (i.e., pancreatic functional rest) appears prolonged (12-14 sec. significantly) in direct relationship with the intensity of insulin secretion (i.e., hyperinsulinaemia).

The behavior of the pancreas during the biophysical-semeiotic preconditioning is briefly illustrated, allowing the practioner to immediately recognize insulin hypersecretion (IIR), with or without slow tendency to the b-pancreatic cell failure, and, lastly, overt type 2 diabetes.

In diabetes mellitus, even in its initial phases, the duration of pancreatic decongestion appears significantly reduced (£ 9 sec.), in obvious relation the severity of the underlying disorder.

Beside evaluation can result in important data regarding insulin secretion using quantum-biophysical-semeiotic preconditioning. (After accurately assessing the duration of pancreatic decongestion brought about by the acute peak of the GHRH secretion, withdraw the digital pressure, consequently removing the hormonal hypersecretion of GH, for 5 seconds exactly. Immediately repeat the evaluation a second time, as described above.)

In a healthy patient, the duration of the pancreatic decongestion rises from exactly 10 sec. (i.e., normal basal value) to 14 sec., in a statistically significant way, a result of the physiological activation of local Microcirculatory Functional Reserve (9, 10).

Interestingly, in hyperinsulinsecretion (IIR), one observes a large number of parameter (i.e., duration) behaviours, which parallel the present functional efficacy of the endocrine pancreas activity, in individuals with or without diabetic constitution (11):

a) in preconditioning, the duration of pancreatic decongestion can arise either to more than 14 sec. or hardly to 11-12 sec. in not meaningful way, in relation to the efficiency condition of insulin secretion;

b) the duration does not show modification, so that it persists unchanged in the comparison of the initial, basal value;

c) this parametric value (= duration length) results reduced, e.g., 9 sec., indicating the “quantitative” alteration of b-cell secretion.

Identical are the data collected also, for example, using the stimulation of the TSH-RH (Fig.2), that provokes the acute peak of thyroid hormone secretion, as demonstrates the contemporaneous associated microcirculatory activation, type 1, in the thyroid (8, 9): “variant” biophysical semeiotics test.

Discussion and conclusions.

Today, literature worldwide reflects an increased urgency for early recognition of the Metabolic Syndrome, and its risk factors (CAD, CVD, type 2 DM, etc.) as well as its pathophysiological and clinical definition (13-15).

From quantum-biophysical-semeiotic view-point (6, 12, 14, 15), Pre-Metabolic Syndrome, always precedes Metabolic Syndrome for years and even decades, (V. also http://www.semeioticabiofisica.it/microangiologia), and involves both sexes, with or without diabetes, but “all” experiencing dyslipidaemic complication..

For this reason, we can finally understand why glucose metabolism alterations and type 2 diabetes are present only in well-defined patient population with metabolic syndrome, as well as why doctors can now fortunately recognize numerous early clinical stages of the metabolic syndrome resulting in positive and favorable benefits in primary prevention..

Because of the numerous and dangerous complications of Metabolic Syndrome in individuals with both dyslipidaemia and diabetes, large scale optimal primary prevention of metabolic syndrome, is needed to allow doctors the diagnostic “clinical” tool, to determine pancreatic endocrine complications and enabling future monitoring.

As recent as four years ago, Biophysical Semeiotic testing became a reliable and useful means for clinicians, to assess insulin-secretion conditions, physiological and pathological, including functional failure of pancreatic b-cells, even in the initial stage.

In conclusion, Quantum-Biophysical Semeiotic testing, above briefly described, is a useful tool for diagnosis, therapeutic monitoring, and clinical research.

References.

1) Stagnaro S., Stagnaro-Neri M. Valutazione percusso-ascoltatoria del Diabete Mellito. Aspetti teorici e pratici. Epat. 32, 131, 1986.

2) Stagnaro-Neri M., Stagnaro S., Il Segno di Bilancini-Lucchi nella diagnosi clinica del diabete mellito. The Pract. Ed. It. 176, 30,1993.

3) Stagnaro-Neri M., Stagnaro S., Sindrome di Reaven, classica e variante, in evoluzione diabetica. Il ruolo della Carnitina nella prevenzione del diabete mellito. Il Cuore. 6, 617, 1993 [Medline]

4) Stagnaro S., Diet and Risk of Type 2 Diabetes. N Engl J Med. 2002 Jan 24;346(4):297-298. letter [Medline]

5) Stagnaro S. Pre-metabolic syndrome: the real initial stage of metabolic-syndrome, type 2 diabetes and arteroscleropathy. Cardiovascular Diabetology 2004, 3:1

http://www.cardiab.com/content/3/1/1/comments.

6) Stagnaro Sergio, Stagnaro-Neri Marina. Introduzione alla Semeiotica Biofisica. Il Terreno oncologico”. Travel Factory SRL., Roma, 2004.

http://www.travelfactory.it/semeiotica_biofisica.htm.

7) Cited in: S.B. Curri. Le Microangiopatie. Inverni della Beffa, Verona, 1986.

8) Stagnaro-Neri M., Stagnaro S., Semeiotica Biofisica: valutazione clinica del picco precoce della secrezione insulinica di base e dopo stimolazione tiroidea, surrenalica, con glucagone endogeno e dopo attivazione del sistema renina-angiotesina circolante e tessutale. Acta Med. Medit. 13, 99, 1997.

9) Stagnaro-Neri M., Stagnaro S., Semeiotica Biofisica: la manovra di Ferrero-Marigo nella diagnosi clinica della iperinsulinemia-insulino resistenza. Acta Med. Medit. 13, 125,1997.

10) Stagnaro-Neri M., Stagnaro S., Deterministic Chaos, Preconditioning and Myocardial Oxygenation evaluated clinically with the aid of Biophysical Semeiotics in the Diagnosis of ischaemic Heart Disease even silent. Acta Med. Medit. 13, 109,1997.

11) Stagnaro S., Stagnaro-Neri M., Le Costituzioni Semeiotico-Biofisiche. Strumento clinico fondamentale per la prevenzione primaria e la definizione della Single Patient Based Medicine. Ediz. Travel Factory, Roma, 2004. http://www.travelfactory.it/semeiotica_biofisica.htm

12) Stagnaro S., Stagnaro-Neri M., Single Patient Based Medicine.La Medicina Basata sul Singolo Paziente: Nuove Indicazioni della Melatonina. Travel Factory SRL., Roma, 2005. http://www.travelfactory.it/semeiotica_biofisica.htm

13) Kahn R., Buse J., Ferrannini E. and Stern M. The Metabolic Syndrome: Time for a Critical Appraisal.Joint statement from the American Diabetes Association and the European Association for the Study of Diabetes . Diabetes Care 28:2289-2304, 2005.

14) Stagnaro Sergio. Pre-Metabolic Syndrome and Metabolic Syndrome: Biophysical-Semeiotic Viewpoint. www.athero.org, 29 April, 2009. http://www.athero.org/commentaries/comm904.asp
15) Stagnaro Sergio. CAD Inherited Real Risk, Based on Newborn-Pathological, Type I, Subtype B, Aspecific, Coronary Endoarteriolar Blocking Devices. Diagnostic Role of Myocardial Oxigenation and Biophysical-Semeiotic Preconditioning. www.athero.org, 29 April, 2009 http://www.athero.org/commentaries/comm907.asp

Cerebral Tumour detected by Quantum-Biophysical Semeiotics since its Inherited Real Risk.

noreply@blogger.com (Stagnaro) — Tue, 05 May 2009 16:03:00 +0000

Introduction

From its initial stage, brain oncological process, occupying space, provokes local circulatory modifications of both hyperemic and ischemic type, secondary to biochemical and/or compressive events. Quantum Biophysical Semeiotics (BS) permits doctor to observe microcirculatory phenomena as well as variations of the tissue pH at the bed-side (See: my website www.semeioticabiofisica.it) (1-8).

Furthermore, the cerebral potentials (1, 5), whether spontaneous or evoked, clearly altered or totally absent in case of tumour, may be evaluated “quantitatively” with the aid of BS, even in early stage.

In following, it is referred both the usefulness and reliability of such as semeiotics in diagnosing cerebral tumour, even in the initial phase of Inherited Real Risk (6, 9-14).

Method

As regards QBS of cerebral tumour, it is enough to know, from the technological point of view, the auscultatory percussion of the stomach (in above-cited website, Technical Page N° 1), which is performed with digital percussion, directly and “gently”, applied on abdominal skin, from outer areas towards the bell-piece of stethoscope along radial and centripetal lines, as indicated in Fig.1

When percussion is applied on organ or viscera skin projection areas, percussory sound is perceived as altered, modified, dull or hyperfonetic, in relation to the density of investigated structure, in any case “as originating from a site close to the doctor’s ears”.

Obviously, a complete knowledge of QBS permits doctor to gather further information.

There are a large number of other Quantum Biophysical Semeiotics data referring to cerebral tumour; however, as follows, are referred only some unavoidable signs, easy to evaluate and reliable in bed-side detecting cerebral tumour.

Quantum Biophysical Semeiotic Signs of Cerebral Tumour

At first doctor has to ascertain the so-called oncological terrain (6), conditio sine qua non of malignancy , and is composed particularly of:

1) Congenital Acidosic Enzyme-Metabolic Histangiopaty (CAEMH). Briefly, digital pressure of “middle” intensity upon skin projection area, e.g., of temporal convolutions (temporal lobe), brings about a gastric aspecific reflex more intense when right cerebral lobe is stimulated, due to the right cerebral dominance, typical for CAEMH: dominance of the right Planum temporale. (2,10).

2) Psycho-neuro-endocrine-immunological system dysfunction (6): in a easy manner doctor ascertains this pathological condition inviting the patient to close intensively his (her) eyes (= dark increases melatonin secretion, which in turns stimulates the secretion of endogenous oppioids, the so-called orchestra directors of immunological system): after 15 sec.

In health, digital pressure of small intensity, directly applied ,e.g., on a breast gland, causes gastric aspecific reflex with latency time of 3 sec.( i.e. acute antibody synthesis syndrome).

On the contrary, when eyes are open, latency time is 6 sec.(i.e. chronic antibody synthesis syndrome).

3) Suck simulated test to provoke Prolactin Secretion: repeated palpation of mammary gland provokes, in healthy individuals of both sexes and of middle age, gastric aspecific reflex of exact 6 sec. duration. In case of inflammatory process, as flu, however, duration results prolonged (7 sec. exactly). Finally, in subject with oncological terrain duration appears ³ 7 sec., in a direct relation to the degree of the psycho-neuro-endocrine-immunological system dysfunction.

The duration is very prolonged, of course, in case of tumour. Physiologically, the test presents the most elevated duration in pregnacy, due to the particular endocrine situation, since initial stage.

In a patient, who presents with a symptomatology suggestive of cerebral tumour (or in asymptomatic patient, of course) other QBS signs are properly investigated.

An interesting sign, particularly useful and reliable in bed-side detecting the presence of “something wrong” in the head is the following:

4) Aspecific gastric-oculo reflex. In health, the appearance of gastric aspecific reflex, physiologically symmetric, during digital pressure on the eye-ball (when patient’s eyes are closed, naturally) after a latency time 6 sec. and 1-2 cm. in intensity.

On the contrary, in case of cerebral neoplasia as well as other cerebral disorder, when pressure is exerted on the homolateral eye-ball, doctor observes initially a gastric aspecific reflex (lt 3 sec.; intensity > 2 cm.; duration 3 sec.), and, soon thereafter, the “autoimmune syndrome”: gall-bladder and stomach contract (gastric tonic contraction = GTC) and spleen become empty of blood: in practice, it is sufficient for the diagnosis ascertaining GTC.

In diagnosing clinically the cerebral tumour, a major role is played by the:

5) Cerebral-gastric aspecific reflex: finger-pulp as well as finger-nail pressure (type I and type II, respectively) on skin projection area of the tumour provokes the “autoimmune syndrome”, as described above. Finally, in the presence of cerebral malignancy, there is always the:

6) Reticulo-Endothelial System Hyperfunction Syndrome (RESHS) of “complete” type, that corresponds to BSR, but it is more sensitive and sensible.

In health, finger-pulp pressure on the middle line of sternal-body, iliac crests and skin projection area of the spleen causes aspecific gastric reflex after a latency time = 10 sec.exactly.

On the contrary, in case of cerebral cancer latency time results lowered, in relation to disorder seriousness.

Finally, one must remember that acute phase proteins are augmented and both the acute autoantibody secretion syndrome and circulating immuncomplex syndrome (boxer’s test, i.e. patient is clenching his or her fists, brings about gastric tonic contraction -GTC-, after appearing gastric aspecific reflex lasting 3 sec.) are present (2-9).

Due to the lack of reader’s Quantum Biophysical Semeiotic knowledge, at this moment I do not illustrate numerous other signs of cerebral tumour.

To summarize, QBS diagnosis of cerebral tumour is based (at least) on the following signs:

1) Congenital Acidosic Enzymo-Metabolic Histangiopathy (CAEMH), which plays a primary role in the psycho-neuro-endocrine-immunological system dysfunction, I termed as Oncological Terrain.

2) Oncological terrain (1-6);

3) Reticulo Endothelial System Hyperfunction Syndrome (RESHS) type “complete” (4);

4) Oculo-gastric aspecific reflex and then gastric tonic contraction (GTC) (1-6, 9,14);

5) Cerebro-gastric aspecific reflex (type I and II) followed by GTC(1-6, 9,14);

5) Acute phase proteins augmentation (3, 6);

6) Acute autoantibody secretion syndrome ((1-6, 9,14);

7) Circulating Immunocomplex Syndrome, above-described .

In addition, a lot of clinical microangiological signs, gathered at the bed-side by evaluating both vasomotility and vasomotion of cerebral microvessels, are actually interesting and precious in recognizing also cerebral malignancy since its first stage: due to reader’s inadequate Quantum Biophysical semeiotic knowledge: I will illustrate these signs next, in the future.

As far as Cerebral Evoked Potentials is concerned, it is well-known that visive, auditory and somato-sensorial stimuli, through nervous in-puts, provoke physiologically the activation of corresponding nervous centres by mean of depolarization. Consequently, local cerebral microcirculation results more or less activated, allowing doctor to evaluate these events by means of Quantum Biophysical Semeiotics.

If a subject looks at a light source, e.g., due to the stimulation of optic channels, impulses reache the bilateral cortical-occipital region and activate it, that is, they evoke electrical potentials, demonstrating the anatomo-functional integrity of such nervous structures. Analogously, auditive and somato-sensorial stimuli (the later really more practical and therefore advisable) provoke electrical potentials, obviously in corresponding cortical centres.

Experimental (an individual is invited, e.g., to move or to “think of moving “ a hand) and clinical (epileptic focus, e.g.) evidence suggests that the cerebral evoked potentials can be evaluated by means of Quantum Biophysical Semeiotics, because of the hemoreological and microcirculatory phenomenology of the active hyperemic areas (In termes of Cinical Microangiology: activation type I, associated, of both vasomotility and vasomotion). In fact, the finger-pulp pressure of “middle” intensity on the cutaneous projection of an activated cerebral zone causes gastric aspecific reflex. Consequently, in case of cerebral malignancy, the absence of the cerebral evoked potentials shows the suffering of precise nervous channels, due to a disorder, easily ascertained at the bed side.

References

1) Stagnaro S., Stagnaro-Neri M. Auscultatory Percussion in Detection Focal Liver Lesions even Clinically Silent. Acta Med. Medit. 8, 89-94, 1992.

2) Stagnaro S., Auscultatory percussion of the cerebral tumour: Diagnostic importance of the evoked potentials, Biol. Med., 7, 171-175, 1985.

3) Stagnaro-Neri M., Stagnaro S., Cancro della mammella: prevenzione primaria e diagnosi precoce con la percussione ascoltata. Gazz. Med. It. – Arch. Sc. Med. 152, 447, 1993.

4) Stagnaro S., Sindrome percusso-ascoltatoria di Iperfunzione del Sistema Reticolo-IstiocitarioMin. Med. 74, 479, 1983 [MEDLINE].

5) Stagnaro S., Percussione Ascoltata degli Attacchi Ischemici Transitori. Ruolo dei Potenziali Cerebrali Evocati. Min. Med. 1985, 76, 1211 [MEDLINE].

6) Stagnaro Sergio, Stagnaro-Neri Marina. Introduzione alla Semeiotica Biofisica. Il Terreno oncologico”. Travel Factory SRL., Roma, 2004.

7) Stagnaro S., Stagnaro-Neri M., Le Costituzioni Semeiotico-Biofisiche.Strumento clinico fondamentale per la prevenzione primaria e la definizione della Single Patient Based Medicine. Ediz. Travel Factory, Roma, 2004.

8) Stagnaro Sergio. Bed-Side Prostate Cancer Detecting, even in early stages (“Real Risk” of Cancer): BMC Family Practice, 6:24 doi:10.1186/1471-2296-6-24 http://www.biomedcentral.com/1471-2296/6/24/comments#202466

9) Sergio Stagnaro Mitochondrial Bed-Side Evaluation: a new Way in the War against Cancer (21 December 2005). Cancer Cell International http://www.cancerci.com/content/5/1/34/comments#218502

10) Stagnaro S. Genes and Cancer: a clinical view-point. The Oncological Terrain. BioMed Central Informatics, 2004. http://www.biomedcentral.com/1471-2105/5/21/comments#10454

11) Stagnaro S., Stagnaro-Neri M., Oncological Terrain, conditio sine qua non of Oncogenesis, GUT, 2004. http://www.gutjnl.com/cgi/eletters?lookup=by_date&days=60

12) Stagnaro Sergio. "Genes, Oncological Terrain, and Breast Cancer", World Journal of Surgical Oncology. 2005, http://www.wjso.com/content/3/1/45/comments#205475

13)Stagnaro Sergio. GPs , Quantum Biophysical Semeiotics, and bedside cancer diagnosis. 08 July 2007, International Seminar of Surgical Oncology, http://www.issoonline.com/content/4/1/11/comments#281539

14) Stagnaro Sergio. Overloking Oncological Terrain and oncological Real Risk, no paper is up-dated! 18 January 2008 Ann. Intern Med. http://www.annals.org/cgi/eletters/147/11/775

MICROALBUMINURIA: CARDIOVASCULAR RISK FACTOR OR SIGN OF “ARTERIOSCLEROTIC CONSTITUTION”?

noreply@blogger.com (Stagnaro) — Sun, 26 Apr 2009 11:59:00 +0000

Introduction.

Before illustrating the contribution of Biophysical Semeiotics to enlighten significancy and etiopathogenesis of microalbuminuria, as follows, theorical and practical interesting aspects of such renal pathology are investigated, which, without the aid of this original physical semeiotics, persists for years or decades unrecognized, untreated and, therefore, worsening.

Although the association between microalbuminuria and cardiovascular disease was initially described in individuals with diabetes, it is now well established that microalbuminuria is associated with a 1,5- to 4-fold increased risk of cardiovascular disease among individuals with and without diabetes. However, the pathophysiological mechanism linking microalbuminuria to cardiovascular disease is unknown (1, 2). It is important to stress that the association between microalbuminuria and cardiovascular disease is unlikely to reflect a direct, causal pathway, because there is no plausible mechanism that can directly link the quantitatively trivial urinary loss of albumin (15-300 mg per 24 hours) to atherothrombosis.

Authors do not agree on causal relation, due to the fact that are lacking acceptable mechanisms, which should link the trivial urinary loss of albumin (15-300 mgr/24 ore) to arteriosclerosi.

In following, I will examine the present view-point on this argument and will illustrate the original biophysical-semeiotic interpretation.

Association between Microalbuminuria and Cardiovascular Diseases: the common point of view.

Microalbuminuria is associated with several cardiovascular risk factors, notably age, male gender, hypertension, smoking, obesity, dyslipidemia (high triglyceride and low HDL-cholesterol), diabetes, hyperhomocysteinemia and, among diabetic individuals, glycemic control. According to some investigators, microalbuminuria is also associated with insulin resistance, but this is controversial.

An obvious hypothesis, therefore, is that the association of microalbuminuria with cardiovascular disease simply reflects, and can be explained by, the association of microalbuminuria with one or more of these well-known cardiovascular risk factors. However, and perhaps somewhat surprisingly, epidemiological studies show that the association between microalbuminuria and cardiovascular disease remains when such conventional cardiovascular risk factors are taken into account, even though all these risk factors have been associated with the development of microalbuminuria in prospective studies, i.e. they may play a role in its pathogenesis (www.ATHERO-ORG..com, 3 July 2002, Coen D.A. Stehouwer, MD PhD, Professor of Medicine, Department of Internal Medicine,
Institute for Cardiovascular Research, and Institute for Research in Extramural Medicine,
Vrije Universiteit Medical Center).

Finally, although there is not agreement among authors, hyperinsulinemia-insulinresistance has been correlated with microalbuminuria, as corroborate personal research (data unpublished). It seems, therefore, that a strong relation probably exists between one or more well-known cardiovascular risk factors and the loss of small amount of albumine in urine.

On the contrary, and really not surprisingly, epidemiological study demonstrate that the association between microalbuminuria and cardiovascular disease is unsolved, even when the common risk factors, cited above, show to end, over the time, in albuminuria, indicating, therefore, to play a “possible” role in its pathogenesis.

At this point, it is advisable to examine an interesting aspect of the problem, on which all authors are in agreement, summarized in a fascinating way by Coen D.A. Stehouwer (paper cited above), who suggested me the following biophysical-semeiotic considerations on the relation between microalbuminuria, inflammation, endothelial dysfunction, and atherosclerosis. I assessed such parameters “clinically” with the aid of Biophysical Semeiotics.

The most commonly held view is that microalbuminuria reflects a pathophysiological process predisposing to atherothrombosis. Atherothrombosis is a low-grade inflammatory disease of the vessel wall characterized by endothelial dysfunction and increased transendothelial passage of leukocytes. These features, therefore, could be the pathogenic factor linking microalbuminuria to cardiovascular disease.

In support of this hypothesis, increased levels of C-reactive protein (CRP), which reflect inflammatory activity, increased plasma levels of von Willebrand factor (vWf), a marker of endothelial dysfunction, and increased plasma levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), an adhesion molecule which reflects recruitment of leukocytes into the vessel wall (1, 2), have all been associated not only with the increased risk of cardiovascular events, but also with the development of microalbuminuria.

Such associations, moreover, were independent of conventional cardiovascular risk factors. These findings indicate, on the one hand, that inflammatory activity, endothelial dysfunction and leukocyte adhesion play a role in the pathogenesis of microalbuminuria, and, on the other hand, that these processes may, perhaps, explain microalbuminuria's link with cardiovascular disease (Stehouwer CDA:, above-cited article).

In other words, above-referred data, on the one hand, show that the inflammatory activity, endothelial dysfunction and cellular adhesion play a role in the pathogenesis of albuminuria, and, on the other hand, these processes can, probably, enlighten some-how the link between microalbuminuria and cardiovascula diseases.

At the moment, without disclosing biophysical-semeiotic view-point on the significancy and real nature of urinary loss of small amount of albumin, it is opportune, however, to underscore a remarkable fact: in the really “initial”, and “primary” stages of microalbuminuria, I observed at first “clinically”, and then coroborated by laboratory data, hepato-aspecific gastric reflex, type II, which is physiologically negative (= Acute Phase Proteins absent) (See in my site, HONCode, N° 233736, http://www.semeioticabiofisica.it, Practical Applications, and Article N° 2, Appendicitis, in the Page, I hold weekly in the italian site www.katamed.it), as well as all other biophysical semeiotic signs of inflammation: Rethiculo-Endothelial System Hyperfunction Syndrome, Antibody Synthesis, a.s.o.

Etiopathogenesis of Microalbuminuria: Biophysical-Semeiotic view-point.

From a renal pathophysiological point of view, microalbuminuria must be caused by increased glomerular permeability to albumin, increased glomerular pressure, and (or) decreased tubular albumin reabsorption. The renal endothelium is intimately involved in the regulation of these processes, but how endothelial dysfunction and increased leukocyte adhesion cause microalbuminuria in molecular terms is not completely understood.

In addition, it is plausible that low-grade inflammation is causally related to the development of microalbuminuria. The main stimulators of production of acute phase reactants such as CRP are proinflammatory cytokines. Interleukin-6 may be an important mediator of mesangial cell proliferation and matrix overproduction, but also of an increase in general vascular permeability without involvement of the kidney. Thus, increased proinflammatory cytokines, as reflected by increased acute phase reactants such as CRP, may cause microalbuminuria through both renal and non renal vascular mechanisms.

As I will refer later in detail, biophysical-semeiotic data, at least in initial stages, do not agree with those of such, otherwise interesting, theories. Infact, in initial stage we can not observe neither increase of Acute Phase Proteins APP), nor body’s defence reactions (Rethiculo-Endothelial System Hyperfunction Syndrome, Antibody Synthesis, a.s.o.). In addition, there is no inflammation at glomerular level (= renal-aspecific gastric reflex, type II, i.e., caused by ungueal stimulation of kidney trigger-points, is absent).

In fact, the above-referred results should invite us to consider inflammatory activity and endothelial dysfunction as probable, and even plausible, causes of microalbuminuria, on the one hand, and atheroscleorsis, on the other hand, enlightening, by such way, the link between microalbuminuria and cardiovascular disease. However, the link between microalbuminuria and cardiovascular disease cannot be explained by increased inflammatory activity or endothelial dysfunction.

The findings reviewed above raise the possibility, and even the plausability, that inflammatory activity and endothelial dysfunction may cause microalbuminuria on the one hand and atherothrombosis on the other, and thus explain the link between microalbuminuria and cardiovascular disease. However, two recent studies (1, 2) (quite unexpectedly) show that the association between microalbuminuria and cardiovascular disease or mortality is not affected by adjustment for these determinants of microalbuminuria. Thus, inflammatory activity, endothelial dysfunction, and leukocyte adhesion apparently cannot explain the association between microalbuminuria and cardiovascular mortality, either in individuals with or without diabetes. Therefore, the problem persists unsolved: what then can explain the link between microalbuminuria and risk of cardiovascular motality?

“One possibility is that microalbuminuria reflects a prothrombotic state or another, as yet unidentified cardiovascular risk factor. Alternatively, microalbuminuria may reflect a certain susceptibility to the vascular adverse effects of a variety of cardiovascular risk factors. This concept is supported by the observation that determinants of the development of microalbuminuria, such as diabetes, hypertension, inflammatory activity, and endothelial dysfunction, do not appear to confound the microalbuminuria-cardiovascular disease link. These possibilities require further study. For the present, microalbuminuria is a clinically useful marker of increased cardiovascular disease risk, even though the pathophysiological explanation of the association remains enigmatic”, states Coen D.A. Stehouwer, author of the fascinating article, posted in the site www.ATHERO-ORG.com., often cited in the present paper, who thinks, in my opinion, in a compelling way, that microalbuminuria could be either the expression of pre-thrombotic state or of different condition, such as cardiovascular risk factor, untill now unidentified.

“Alternatively, microalbuminuria may reflect a certain susceptibility to the vascular adverse effects of a variety of cardiovascular risk factors”, the author suggests.

With this point of view is in agreement the observation, corroborated also by biophysical-semeiotic method, that determinant causes of albuminuria occurrence, such as DM, hypertension, inflammatory activity, endothelial dysfunction, are acceptable in linking microalbuminuria to cardiovascular disease. These possibilities, the author concludes, require further study.

Biophyical-Semeiotic Contribution to clarifying relation between Microalbuminuria and Cardiovascular Disease.

In order to understand, in the best and successful way, the following topic, it is unavoidable studying all articles on “Biophysical-Semeiotic Constitutions”, posted in the site http://www.semeioticabiofisica.it

In my mind, from the healthy state, white zone, slowly, really slowly, one reaches the morbid state, blach zone – DM, ATS, arterial hypertension, gouthy, dyslipidemia, malignancy, a.s.o. – going through a long, very long, intermediate stage – pre-morbid stage, pre-metabolic stage – or grew zone, which, if undiagnosed, can last years or decades, without whatever clinical syntomatology, which is the subject of present consideration, as regards arteriosclerotic coronary diseases.

The grew zone is made up of an initial stage, or Zero Stage, and by successive poli-metabolic syndrome, X syndrome or Reaven’s synrome, both classic and “variant”, we described previously (3, 4), which mostly goes before the black zone.

Due to this reason we define the grew zone as pre-morbid or pre-metaolic syndrome. (See papers also in http://www.semeioticabiofisica.it/microangiologia, in www.Staibene.it, November 2001, and in the article N° 13 of the Page, I hold in www.katamed.it).

Reaven’s syndrome, both classic and “variant”, is based on Congenital Acidosic Enzyme-Metabolic Hystangiopathy-a (CAEMH-a), that represents a functional mitochondrial cytopathology, inherited by mother, completely asyntomatic at the beginning, and over many years or decades, before ending up with poli-metabolic syndrome (5, 6, 7 and the sites, above referred).

In order to understand and recognize “quantitatively” the “real” arteriosclerotic risk of an individual, it could be of interest the knowledge of the nature of link exsisting between microalbuminuria and arteriosclerotic cardiovascular disease, but, in my opinion, going “beyond microalbuminuria” gives doctor more information.

Certainly, primary problem, we face with, is bed-side recognizing and defining molecular-biological events, which characterize the grew zone, including its Zero Stage, with the aid of an efficacious method, reliable and rapidly to perform on very large scale, as Biophysical Semeiotics.

We desire that such as method allows us to recognize, in a clinical and quantitative way, the Zero Stage of grew zone, and classic and “variant” Reaven’s syndrome, i.e., pre-morbid, pre-metabolic syndrome, which is the locus (space-time) of primary prevention of the most serious human diseases (8) (See above-cited sites).

First of all, we must find a key-stone (a new reading way), biophysical-semeiotic in origin, totally different from that based upon “classic” signs and symptoms of the traditional physical semeiotics, including the microalbuminuria, completely absent in pre-morbid, pre-metabolic syndrome, that permits us to make the proper bed-side diagnosis in a “quantitative” way, during the common physical examination, in whatever patient.

Let’us consider, therefore, what happen at metabolic-endocrine level in both extreme situations, at first, in white zone and, then, in black zone in order to underline existing differences, usefull to our aim, i.e., to recognize and describe the intermediate, asymptomatic stage, I named grew zone.

In fact, different metabolic-endocrine behaviour of healthy individual, and, respectively, of patient involved by classic and “variant” Reaven’s syndrome, will help us to recognize, clinically on a very large scale and during the common physical examination, people apparently “healthy”, but who absolutely need intense and accurate consideration, due to their “real” risk for cardiovascular diseases, even at the moment without microalbuminuria, that is not always present, neither in successive stages.

Arterial Abnormalities in Off-sprimg of Patients involved by Myocardial Infarction, even premature.

Among a large number of important risk factors for cardiovascular disorders is coronary artery disease in family history (9, 10).

We discusse, therefore, although briefly, the relation between relatives and parents’s CAD and offspring’s cardiovascular disorder, that we corroborated clinically by means of Biophysical Semeiotics, since it represents a perfect introduction to explaining our microcirculatory theory of arteriosclerosi,s as well as to comprehending microalbuminuria pathogenesis.

The numerous theories of arteriosclerosis pathogenesis show clearly our present insufficient knowledge of this argument, although the well-known progresses of sophysticated semeiotics, including that with images.

All authors agree, recently, about primary importance of initial endothelial damage: I will examine its underlying pathological mechanisms later on.

As knows reader, who visites the above-cited sites, over last three decades we tried to persuade the colleagues to pay accurate attention, from the “clinical” biophysical-semeiotic view-point, to the primary role played by endothelial cells in both physiology (for instance, in Microcirculatory Funcional Reserve activation) and in pathology (for instance, in the onset of cardiovascular disease).

Interestingly, the risk of ischaemia, as elechtrocardioram shows, is about 40% higher, and mortality risk due to cardiac events is 2,5% larger in individuals with “positive” family history for premature CAD than in people without such as family history (11).

Among a large variety of similar evidences, we remember that arteriosclerotic lesions were found at autoptic examinations of very young patients with family history for coronary artery disease (12). Over last decades, B-mode ultrasonography at high resolution proved to be a valid and reliable tool in order to detect the initial arteriosclerotic alterations in vessel wall (13).

Intimal and media thickening of carotid artery wall has been observed in individuals involved by risk factors for cardiovascular diseases, proving to be a remarkable marker of the presence of coronary arteriosclerosis and its complications.

Skilled reader knows perfectly that Biophysical Semeiotics allows doctor to recognize such macrovascular lesions both directly (= vessel-aspecific gastric and -caecal reflex; pathological preconditioning, a.s.o.), and indirectly by evaluating local vasa vasorum (= type II or dissociated activation) as I will demonstrate later (See in former above-cited site: Arteriosclerotic Constitution).

In a few words, in healthy, supine and psycho-physically relaxed, “intense” digital pressure, e.g., applied on brachial artery brings about “in toto” ureteral reflex (= ureter dilates) (Fig.1) of about 1 cm. in intensity (NN £ 0,5 cm), while, during Valsalva’s manoeuvre, ureter diameter increases at least two-fold, when compared with basal value, due to well-known reasons (acethyl-choline increases, as well as endothelial radical NO and GTP synthesis: vessel smooth muscle cells are relaxed).

On the contrary, starting from “really” initial stage of arteriosclerosis, arterial compliance appears clearly compromised. In our “clinical” research, performed and concluded a lot of years ago, we demonstrated the reduced responsiveness of brachial artery, observed at bed-side, by the use of sphygmomanometer at different pressure levels to stimulate the artery (14).

Finally, we remember that brachial artery responsiveness, blood-flow-mediated, is compromised in persons with overt arteriosclerosis as well as in symptomless individuals with coronary risk factors (16).

In healthy, finger-pulp-aspecific gastric reflex, provoked by “mean-intense” digital pressure on a finger-pulp of the subject at rest, shows a latency time (lt) of 8 sec., while, assessed a second time after exact 5 sec., starting from blood-flow recovery, and rapidly applied, lt rises to a ³ 10 sec.

By contrast, in case of “real” arteriosclerotic risk and, obviously, of arteriosclerosis, lt persists unchanged (basal value £ 8 sec.) or, respectively, lowered in a clear-cut manner.

As regards the easiest performance of our method, doctor assesses the intensity of “in toto” ureteral reflex (= ureteral dilation, Fig 1) during “intense” digital pressure on brachial artery (or, of course, in whatever other artery) evaluating precisely its value in cm.

Contemporaneously, it appears also the artery-aspecific gastric reflex, which is more easy to performe by doctor not jet expert of the new semeiotics.

Fig.1

(Figure shows the correct location of the bell-piece of stethoscope and lines upon which doctor must apply digital percussion, gently and directly, in order to draw,at least in mind, cutaneous projection areas of kidney and ureter).

At this point, patient is invited to perform Valsalva’s manoeuvre (= acethyl-choline increase) lasting about 10 sec., and assesses, soon thereafter, the value of the same reflexes parameter for a second time. In healthy, the intensity of both “in toto” ureteral reflex and aspecific gastric reflex results two-fold greater or, in any case, significantly increased.

Clinical evidence shows that arteriosclerosis seriousness and the intensity reduction of “in toto” ureteral reflex and/or aspecific gastric reflex, during Valsalva’s manoeuvre, are inversely correlated.

Another easy biophysical evaluation of the same events is the comparison between basal data and those observed during boxer’s test, lasting at least 5 sec., which dilates arteries up-wards resistance vessels, and contemporaneously activates vasomotor activity of vasa vasorum, quantified by Biophysical Semeiotics, as skilled reader knows: in healthy, during such a test, the intensity of artery-“in toto” ureteral reflex results practically two-fold when compared with the basal value, and the latency time of artery- caecal reflex clearly prolonged (= histangic acidosis, temporarily reduced, as during Valsalva’s manoeuvre).

In fact, there is a clear coherence between basal -caecal and -aspecific gastric reflexes, which appear double (two-fold) after acethyl-choline secretion, induced by Valsalva’s manoeuvre and, in the second experiment, after physiological production of free-radical NO.

The same results are gathered during the test of insulin secretion acute pick and confronting the observed result with basal parameter value (See in above-cited site: Diabetes Mellitus and Glossary).

The data gathered by these dynamic methods, on the contrary, result pathologically modified in those individuals at “real” risk for arteriosclerosis, even in the first two decades of life, as we referred in former papers (17, 18, 19, 20).

These facts, we observed in a long clinical experience, corroborate, without any doubt, our microangiological theory of arteriosclerosis, since they clearly underline the earliest functional and structural lesion of arterial wall, secondary to, however, as will be said later on, Endoarteial Blocking Devices (EBD) abnormality in related microvessel, that represents, in my mind, the first of all and essential alteration, genetically inherited.

As a matter of fact, it has been demonstrated that family history of CAD points out an independent risk factor for cardiovascular diseases, showing in a clear manner “inherited” component of such as disorder (we identified as CAEMH-a).

These anamnestic data have been enclose to guide-lines fo CAD prevention and is at present utilized in paediatric cardiology, beside genetic study of gene mutation, codifying lipoproteins receptors, a research surely complex and expensive, not possible to apply on very large scale.

Since, at the present, we cannot know when the first vascular (and parenchymal) abnormalities occur, an useful “clinical” method, reliable in recognizing the presence and in quantifying the seriousness of such vascular alterations, appears to be an important event.

The data of our researches parallel, and agree with, those of other authors, carried out with sophysticated methods, in the sense that they show, as markers of early arteriosclerosis, the association between reduced reactivity of brachial artery and/or carotyd intimal-media thickening, observable in young individuals with positive family history for previous myocardial infarction. Such an association is really interesting, due to the fact that abnormal vasodilatory response to acethyl-choline as well as endogenous insulin can be easy evaluated at the bed-side, as we referred in previous papers in individuals formerly involved by inherited alterations of microvessels, including particularly Arterial-Venous Anastomose (AVA), functionally speaking (19, 21, 22).

In other words, arteriosclerotic earliest abnormalities are “pre-clinical”, i.e., pre-clinical lesions; they come before decades the so-called fatty-streaks. Now-a-days, for the first time, with the aid of the original physical semeiotics, doctor is able to recognize at the bed-side these alterations, primarily functional, also by means of analogous modifications of anastomoses, including EBD, as well as of reduced arterial vasodilation – caused by a large variety of methods – always associated with intimal-media thickening or functional-structural endothelial lesions, in our opinion, taking part of primitive alteration of vasa vasorum, CAEMH-a-mediated.

At this points, one must remember that arteriosclerosis is notoriously a systemic disorder, which involves all circulatory tree and notably, sooner or later, is accompanied by other common diseases.

Consequently, functional and structural alterations, observed in loco, are present also in other locations in youg men, completely asymptomatic, i.e., without any clinical phenomenology. In addition, such as association between altered vascular reactivity-intimal-media thickening, observed by many authors, has been corroborated by us in a clinical way. The same we can say also as regards hypertensive patients as well as patients with suspected CAD (23, 24).

These fact, on which almost all authors agree, are referred and discussed in detail because they offer further evidence to our microcirculatory theory of arteriosclerosis: endothelial suffering, provoked by CAEMH-a and worsened by numerous environmental risk factors, partly known (at least 300), due to reduced synthesis of free-radical NO, augmented secretion of vasoconstrictor factors and endothelial-dependent imbalance of haemostatic system, can predispose to monocytes and platelets adhesion, proliferation of media vascular smooth muscle cells and their migration towards intima, storage of monocytes-derived macrophages, and lipoproteins in arterial wall.

Surely, numerous other factors, as inflammation, can take part of pathogenesis of arteriosclerosis, but later, in our opinion, and always in well-defined individuals. However, the genetic factor is of primary, essential importance. It is necessary in enlightening the various moments of natural history of arteriosclerosis.

To conclude, beyond practical aspects, as early bed-side recognizing primitive functional alterations of artery wall, and successively “anatomical” modifications in symptomless individuals, unavoidable to can define arteriosclerotic constitution, former discussion about the relation, surely existing, between altered reactivity of arterial wall and initial intimal-media thickening introduces to the explanation of our “intuition” on the existence of a particular constitution, conditio sine qua non of atherogenesis, which allows to give precise answers, we lack untill now, useful to primary prevention, hopefully efficacious when applied on very large scale.

Biophysical-Semeiotic Arteriosclerotic Constitution.

Clinical evidence suggests the existence of arteriosclerotic constitution:

a) Acute Myocardial Infarction, for instance, can involve an individual “without” well-known risk factors, but “always” CAEMH--a-positive (as in my personal case).

Moreover, the so-called minimal changes are already present at an age, when known risk factors surely are absent;

b) not “all” dyslipidemic and/or diabetic and/or hypertensive and/or hyperomocysteinaemic patients die due to ictus, myocardial infarction or other arteriosclerotic complications;

c) not “all” hypertensive patients are going to suffer from generalized or localized (CAD) arteriosclerosis; by contrast, are described cases (15-19) of people died from arteriosclerotic complications during the first two life decades, “without” presenting well-known risk factors (18);

d) even in presence of well-known risk factors, arteriosclerosis involves defined, limited areas of arterial wall, rather than “all” wall;

Therefore, arteriosclerotic constitution does really exist, as that diabetic, osteoporotic, rheumatic, artrosic, hypertensive, glaucomatos, oncological, i.e., Oncological Terrain (See above cited site, and article N° 13 in italian site www.katamed.it, as well as two articles on Oncological Terrain in www.Staibene.it, November 2001).

In the same individual, of course, can be present contemporaneously diverse constitutions, which, in fact, originate always on the base of common inherited alteration: CAEMH--a.

In following, easy clinical methods to recognize as well as to quantify the “real” arteriosclerotic risk with the aid of Biophysical Semeiotics, since two first life decade, are described. Most accurate and refined ascertaining requires necessarily a very good knowledge of original diagnostic method (19, 20, 27).

1) In healthy, “mean-intense” digital pressure, applied on whatever artery (brachial, femoral, carotid artery, a.s.o.) of a supine, psycho-physically relaxed individual, brings about aspecific gastric reflex (Fig.2) after latency time (lt) of 8-10 sec., age-dependent value.

Moreover, after artery preconditioning (doctor evaluates such a parameter value a second time, after exact 5 sec. interval) lt raises to ³ 12 sec.

Fig.2

Figure indicates the correct location of the bell-piece of stethoscope and lines upon which doctor must apply digital percussion, directly and gently, in order to define the limit of stomach cutaneous projection area of the stomach great curve. It is sufficient to delimit a small segment of curve for assessing the reflex. Aspecific gastric reflex: in the stomach, both fundus and body dilate, while antral-pyloric region contracts.

On the contrary, in a subject at “real” arteriosclerotic risk, and obviously in arteriosclerotic patient, basal artery-aspecific gastric reflex shows a lt £ 8 sec., inversely related to the intensity of risk or underlying disease. In addition, really interesting from diagnosis view-point, artery preconditioning results pathological: second evaluation, performed exactly after 5 sec. from the former, shows a lt either unchanged (e.g., 8 sec.) or reduced in a clear-cut manner, when compared with basal value, in relation to the seriousness of arteriosclerotic constitution or, in case of basal value lower than normal, of underlying disease.

Identical data as those of preconditioning, one can collect at the bed-side with Valsalva’s manoeuvre, which brings about increase of acetyl-choline secretion, indicating internal and external coherence of biophysical-semeiotic theory (= loss of production and secretion of free-radical NO, due to endothelial alteration and consequently arterioles and small arterioles smooth muscle cells contractions, due to direct stimulation by acetyl-choline.

Moreover, in case of vessel wall calcium deposit (calcification involves exclusively individuals positive for “variant” Reaven’s syndrome), aspecific gastric reflex, after reaching its highest intensity, and soon thereafter lowers of a third of it.

The reader understands correctly that it is easy to evaluate the actual condition of whatever arterial vessels, for example, coronary arteries (25) and cerebral arteries (26) (See above-cited site, Practical Applications: CAD and Cerebral Tumour).

2) the subject, doctor is examining, clenches his fists: boxer’s test. In healthy, after a latency time of 10 sec. appears the aspecific gastric reflex of £ 1 cm. (Fig. 2), whereas in presence of either arteriosclerotic constitution or overt arteriosclerosis, lt results, once again, £ 10 sec. and reflex intensity is > 1 cm.

If doctor performs such as evaluation, applying boxer’s test, after exact 5 sec. from the first one (preconditioning), the data observed are the same of those formerly illustrated at point 1).

In conclusion, these two easy methods, applied also in “dynamic” way, are reliable and sufficient to allow recognizing arteriosclerotic constitution, that can be quantified with the aid of parameter values, observed during basal and dynamic evaluation.

Without facing physiopathological discussion of biophysical-semeiotic signs, certainly interesting, but not pertinent to the aims of present article, the illustrated physical examination allows doctor to collect useful information on function as well as structure of adventitial microcirculatory bed, steadly correlated with nutritional condition of local artery wall, i.e., with local Microcirculatory Functional Reserve.

It is easy to understand that the very good knowledge of this new physical semeiotics permits doctor to gather a large variety of clinical microangiological signs, really abundant of information.

Among these interesting signs, I am going to illustrate only some, which allow a refined evaluation of anatomy and function of microcircle, including the adventitial microvessels – vasa vasorum – both at rest and during activation:

1) in healthy, “mean-intense” (but not highest) digital pressure, applied upon a finger-pulp of a supine and psycho-physically relaxed individual, causes upper ureteral reflex (= dilation of upper third of ureter), which gives information on type II, group B AVA, according to Bucciante. At this point, if digital pressure becomes highest, reflex disappears, underscoring the normal structur-function (elasticity) of the same anastomoses, which physiologically control microcirculatory blood-flow.

2) under identical circumstances, the behaviour of mean ureteral reflex (= mean third of ureter dilation) appears the same: it gives information on the real situations of local Endoarteriolar Blocking Devices (EBD) (Fig.3)

Fig. 3

Arrow indicates a particular endoarteriolar formation, like elephant trunk (EBD), whose contraction increases the flow-motion towards, and along, capillaries and post-capillaries venules. On the contrary, the relaxation of EBD smooth muscle cells decreases the blood-flow towards nutritional capillaries. (For kind permission of Prof. S.B.Curri, whose as much excellent as large literature in the field of microcircle and microcirculation originated my enthusiasm about the study of this fascinating and almost ignored branch of Medicine)

3) “mean-intense” digital pressure, applied as illustrated above, provokes upper ureteral reflex (See example 1), which shows the opening of type II, group B AVA. However, if the individual arises his (her) arm in vertical position, the reflex rapidly disappears: closure of AVA, aimed to supply a larger amount of blood flow, and, consequently, to control histangic pH also during such posture test;

4) under identical condition, described above at point 3), if the subject lowers vertically his (her) arm, the intensity of upper third ureteral reflex increases rapidly: type II, group B AVA augment their diameter, and, therefore, their haemoderivative function increases, aiming to maintain a physiological microcirculatory blood-flow in normal ranges, under different positions. Such as physiological microcirculatory adaptations clearly suggest the normal functioning of venular-arteriolar reflex (VAR):

5) in healthy, “mean-intense” digital pressure on a finger-pulp brings about aspecific gastric reflex after a latency time of about 10 sec. (lt value is obviously age-dependent). This value persists unchanged, under physiological condition, when the arm is located in every of three posture positions, due to functional microvessel adaptations, explained above.

All these dynamic tests result altered, obviously of a different degree, in case of arteriosclerosis, starting from the earliest stage, i.e., arteriosclerotic constitution.

BIOPHYSICAL-SEMEIOTICS OF MICROALBUMINURIA.

In table 1, is summarized the diagnostic biophysical-semeiotic iter, usefull and reliable in bed-side recognizing presence and nature of nephrone disease, even clinically silent and localized.

Really, Biophysical Semeiotics does not allow doctor to make “clinical” diagnosis of microalbuminuria, but surely permits to exclude it (100%) or to suspect it, in rational way, conditio sine qua non of ascertaining the real nature of an aspecific damage of nephrone, even limited in some areas of kidney.

In fact, facing the problems of kidney showing normal size, i.e., when are absent biophysical-semeiotic signs of inflammation, parameter values of kidney-aspecific gastric and –caecal reflexes are still in “extreme” limits of normality or clearly pathological, preferably when assessed in selective way, by stimulating, at first, renal trigger-points of upper third, then those of mean third, and finally those of lower third.

Nephrone suffering, even circumscribed, is outlined by renal preconditioning, whose results – lt of kidney-aspecific gastric reflex unchanged or pathological, i.e., reduced in second evaluation – is aspecific expression of nephropathy.

Of essential importance proved to be the “selective” evaluation of renal vasomotion, which shows the characteristic type II, dyssociated microcirculatory activation or, in initial and slight forms, type III, dyssociated microcirculatory activation: the fluctuations of upper third of ureter (vasomotility: arterioles and small arterioles, according to Hammersen) are increased with AL + PL of 7-8 sec. (NN = 6 sec.), while the oscillations of lower third of ureter (vasomotion: nutritional capillaries and post-capillary venules) are normal with AL + PL of 6 sec., but large “in toto” ureteral reflex: > 1 cm.(= interstitium).

In conclusion, from biophysical-semeiotic data, it is likely that the base of microalbuminuria is an inherited microvascular-microcirculatory alteration of nephrone, even circumscribed, primarily functional, acidosic, that cause function abnormality of the vascular smooth muscle cells and, then, of Endoarterial Blocking Devices (EBD), involved selectively, although systematically (including vasa vasorum), by a particular mitochondrial cytopathology, CAEMH-a, influencing in negative manner both microvessel dynamics and haemoreology (hyperviscosity) under sympathetic hypertonus conditions, ischaemia, and hormonal impairement (IIR), as we observe frequently in pre-morbid or pre-metabolic syndrome, as wel as in subsequent Reaven’s syndrome, classic and “variant” (3, 4).

Therefore, from the above-referred data, gathered by the aid of Biophysical Semeiotics, microalbuminuria, if present, does not represent a “causal factor” of CAD, and , in general, of ATS, but an early microvascular functional CAEMH-a-induced abnormality of the nephrones, whose patho-physiological mechanisms are the same of ATS, according to our microcirculatory theory of arteriosclerosis, which allows doctor to foresee only the future onset of CAD.

In performing efficacious prevention of arteriosclerosis, applied on very large scale, I suggest to go “beyond microalbuminuria”, that is present “exclusively” in case of selective microvessel suffering of the nephrone, caused by the mitochondrial cytopathology, we termed Congenital Aciodosic Enzyme-Metabolic Histangiopathy, conditio sine qua of the most serious human diseases (5, 6, 6, 7).

BIOPHYSICAL- SEMEIOTIC DIAGNOSTIC ITER OF GLOMERULAR-TUBULAR SUFFERING

KIDNEY AUSCULTATORY PERCUSSION

TEST OF SIMULATED URINATION

INFLAMMATORY SIGNS (RESHS “COMPLETE”, ACUTE PHASE PROTEINS, A.S.O.)

CIRCULATORY IMMUNOCOMPLEXES SYNDROME

AUTOIMMUNE LOCAL SYNDROME

TYPE I AND II KIDNEY-ASPECIFIC GASTRIC REFLEX

KIDNEY-CAECAL REFLEX

RENAL PRECONDITIONING

ERITHROPOIETINE TEST

VASOMOTILITY AND VASOMOTION OF KIDNEY

Tab. 1

Sergio Stagnaro MD

Via Erasmo Piaggio 23/8

16039 Riva Trigoso (Genoa) Europe

Founder of Quantum Biophysical Semeiotics

Who's Who in the World (and America)

since 1996 to 2009

Ph 0039-0185-42315

Cell. 3338631439

www.semeioticabiofisica.it

dottsergio@semeioticabiofisica.it

Bibliografia.

1. Jager A, van Hinsbergh VW, Kostense PJ, Emeis JJ, Nijpels G, Dekker JM, Heine RJ, Bouter LM, Stehouwer CD. C-reactive protein and soluble vascular cell adhesion molecule-1 are associated with elevated urinary albumin excretion but do not explain its link with cardiovascular risk. Arterioscler Thromb Vasc Biol 2002;22:593-98.
2. Stehouwer CD, Gall MA, Twisk JW, Knudsen E, Emeis JJ, Parving HH. Increased urinary albumin excretion, endothelial dysfunction, and chronic low-grade inflammation in type 2 diabetes: Progressive, interrelated, and independently associated with risk of death. Diabetes 2002;51:1157-65.

3. Stagnaro S.-Neri M., Stagnaro S., Sindrome di Reaven, classica e variante, in evoluzione diabetica. Il ruolo della Carnitina nella prevenzione del diabete mellito. Il Cuore. 6, 617, 1993 (Pub-Med indexed for Medline).

4. Stagnaro-Neri M., Stagnaro S., La “Costituzione Colelitiasica”: ICAEM-a, Sindrome di Reaven variante e Ipotonia-Ipocinesia delle vie biliari. Atti. XII Settim. It. Dietol. ed Epatol. 20, 239, 1993.

5. Stagnaro S., Istangiopatia Congenita Acidosica Enzimo-Metabolica. X Congr. Naz. Soc. It. di Microangiologia e Microcircolazione. Atti, 61. 6-7 Novembre, 1981, Siena.

6. Stagnaro S., Istangiopatia Congenita Acidosica Enzimo-Metabolica condizione necessaria non sufficiente della oncogenesi. XI Congr. Naz. Soc. It. di Microangiologia e Microcircolaz. Abstracts, pg 38, 28 Settembre-1 Ottobre, 1983, Bellagio.

7.Stagnaro S., Istangiopatia Congenita Acidosica Enzimo-Metabolica. Una Patologia Mitocondriale Ignorata. Gazz Med. It. – Arch. Sci. Med. 144, 423,1985 (Infotrieve).

8) Stagnaro S., West PJ., Hu FB., Manson JE., Willett WC. Diet and Risk of Type 2 Diabetes. N Engl J Med. 2002 Jan 24;346(4):297-298. [MEDLINE].

9) Phillips R.L., Lilienfeld A.M., Kagan A. Frequency of coronary heart disease and cerebrovascular accidents in parents and sons of coronary heart disease index cases and controls. Am. J. Epidemiol. 100, 87-100, 1974.

10) Friedlander Y., Siscovic D.S., Weinmann S. et al Phillips R.L., Lilienfeld A.M., Kagan A. Family history as a risk factor for primary cardiac arrest. Circulation. 97, 155-60, 1998.

11) De Bacquer D., De Backer G., Kornitzer M., Blacburn H.Parental history of premature coronary heart disease mortality and signs of ischemia on the resting electrocardiogram. J.Am.Coll.Cardiol. 33, 1491-8, 1999.

12) Kaprio J., Norio R., Pesonen E, Sarna S. Intimal thickening of the coronary arteries in infants in relation to family history of coronary artery disease.Circulation. 87, 1960-8,1993.

13) Gaeta G., De Michele M., Cuomo S., et al. Arterial abnormalities in the offspring of patients with premature myocardial infarction. N.Engl.J.Med. 343,840-45,2000.

14) Celermajer D.S., Sorensen K.E., Gooch V.M., et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of artheriosclerosis. Lancet. 340, 1111-8,1992.

15) Stagnaro-Neri M., Stagnaro S., Il diagramma venoso nelle arteriopatie obliteranti periferiche. Atti Congr. Naz. Soc. It. Flebologia Clinica e Sperimentale. Firenze 10-12 Dicembre 1990. A cura di G. Nuzzaci, pg. 169, Monduzzi Ed. Bologna.

16 Neunteufl T., Katzenschlager R., Hassan A., et al. Systemic endothelial dysfunction is related to the extent and severity of coronary artery disease. Atherosclerosis. 129, 111-8, 1997.

17) Stagnaro S., Valutazione percusso-ascoltatoria della microcircolazione cerebrale globale e regionale. Atti, XII Congr. Naz. Soc. It. di Microangiologia e Microcircolazione. 13-15 Ottobre, Salerno, e Acta Medit. 145, 163, 1986.

18) Stagnaro-Neri M., Stagnaro S., Aneurisma Aortico Addominale: una Diagnosi clinica con la Semeiotica Biofisica. Acta Cardiol. Medit. 14, 17, 1986.

19) Stagnaro-Neri M., Stagnaro S., Auscultatory Percussion Evaluation of Arterio-venous Anastomoses Dysfunction in early Arteriosclerosis. Acta Med. Medit. 5, 141, 1989.

20) Stagnaro-Neri M., Stagnaro S., Modificazioni della viscosità ematica totale e della riserva funzionale microcircolatoria in individui a rischio di arteriosclerosi valutate con la percussione ascoltata durante lavoro muscolare isometrico. Acta Med. Medit. 6, 131-136, 1990

21) Stagnaro S., Stagnaro-Neri M., Valutazione percusso-ascoltatoria degli attacchi ischemici transitori e della insufficienza cerebrovascolare cronica in pazienti trattati con mesoglicano. Atti, IX Congr. Naz. It. Patologia Vascolare. Copanello, 6-9 Gennaio 1987. A cura di R. Del Guercio, G. Leonardo e G. Zanini. Pg. 765, Monduzzi Ed. Bologna, 1987.

22) Stagnaro-Neri M., Stagnaro S., Microangiologia clinica della ipertrofia prostatica benigna. Ruolo patogenetico delle modificazioni del sistema microlovascolotessutale valutate con la Semeiotica Biofisica. Acta Cardiol. Medit. 14, 21, 1986.

23) Ghiadoni L., Taddei S., Virdis A, et al. Endothelial function and common carotid artery thickening in patients with essential hypertension. Hypertension. 32, 25-32, 1998.

24) Enderle M.D., Scroeder S., Ossen R., et al. Comparison of peripheral endothelial dysfunction and intimal media tickness in patients whit suspected coronary artery disease. Heart. 80, 349-54, 1998.

25) Stagnaro-Neri M., Stagnaro S., Deterministic Chaos, Preconditioning and Myocardial Oxygenation evaluated clinically with the aid of Biophysical Semeiotics in the Diagnosis of ischaemic Heart Disease even silent. Acta Med. Medit. 13, 109, 1997.

26) Stagnaro S. Depression, Anxiety and Psychosis. B C Medical Journal, Volume 43, Number 6, page 321, July-August, 2001.

27) Stagnaro-Neri M., Stagnaro S. Indagine clinica percusso-ascoltatoria delle unità microvascolotessutali della plica ungueale. Acta Med. Medit. 4, 91 ,1988.

28) Stagnaro Sergio. New bedside way in Reducing mortality in diabetic men and women. Ann. Int. Med.2007. http://www.annals.org/cgi/eletters/0000605-200708070-00167v1

29) Stagnaro-Neri M., Stagnaro S. Introduzione alla Semeiotica Biofisica. Il Terreno Oncologico. Ed. Travel Factory, Roma, 2004. http://www.travelfactory.it/

30) Stagnaro Sergio. Newborn-pathological Endoarteriolar Blocking Devices in Diabetic and Dislipidaemic Constitution and Diabetes Primary Prevention. The Lancet. March 06 2007. http://www.thelancet.com/journals/lancet/article/PIIS0140673607603316/comments?totalcomments=1, and especially www.fce.it, http://www.fceonline.it/docs/stagnaro.pdf

31) Stagnaro Sergio. Biophysical-Semeiotic Bed-Side Detecting CAD, even silent, and Coronary Calcification. 4to Congreso International de Cardiologia por Internet, 2005, http://www.fac.org.ar/ccvc/marcoesp/marcos.php.

32) Stagnaro Sergio. Role of Coronary Endoarterial Blocking Devices in Myocardial Preconditioning - c007i. Lecture, V Virtual International Congress of Cardiology. http://www.fac.org.ar/qcvc/llave/c007i/stagnaros.php

33) Stagnaro Sergio. Bedside Evaluation of CAD biophysical-semeiotic inherited real risk under NIR-LED treatment. EMLA Congress, Laser Helsinki August 23-24, 2008. "Photodiagnosis and photodynamic therapy", Elsevier, Vol. 5 suppl 1 august 2008 issn, Page S17.

PRE-METABOLIC SYNDROME, CLASSIC AND VARIANT, PRECEEDES FOR DECADES THE METABOLIC SYNDROME.

noreply@blogger.com (Stagnaro) — Mon, 20 Apr 2009 06:40:00 +0000

Introduction।

First of all, before studying an argument playing a primary role in the Clinical Microangiology, such as microcirculatory activation in the post-absorptive state, under physiological as well as pathological conditions, unavoidable in bedside diagnosing Pre-Metabolic Syndrome, it is necessary that reader has steady knowledge of the topics illustrated in earlier articles on Microcirculatory Physiology (1-11) (See my website www.semeioticabiofisica.it and www.semeioticabiofisica.it/microangiologia, especially URL

(http://www.semeioticabiofisica.it/microangiologia/Documenti/Eng/Pre-metabolic%20syndrome%).

Doctor must be skilled at auscultatory percussion of both kidney and ureter, which allows to outline properly skin projection area of urinary tract and evaluate three ureteral reflexes, i.e., upper, middle, and lower, caused by “light” stimulation of trigger-points of the diverse examined biological systems (Fig 1). In fact, upper, middle, and lower ureteral reflexes give information on both functional and structural conditions of small arteries and arterioles, according to Hammersen (= upper ureteral reflex), Endoarterial Blocking Devises (EBD) (= middle reflex), as well as capillaries and post-capillary venules (= lower reflex) (1-4).

At the begin of third millennium, the researchers on type 2 Diabetes Mellitus initiate fortunately to find new ways in the prevention, diagnosis, therapeutic monitoring, in a direction, I have indicated more than 20 years ago (1-3).

My old Rapid Response to BMJ proved to be really warning: Sergio Stagnaro. “Pre-Metabolic Syndrome. Locus of Type 2 Diabetes Primary Prevention”. 1 August 2003, (http://bmj.com/cgi/eletters/327/7409/266#35204.

Nowadays physician’s opinion has clearly changed on the fasting glycemia (FPD), considering the post-prandium glycemia (PPG) more predicative of so-called “complications”, since it is somehow related to the endocrine-metabolic situation of post-absorptive state, which we can fortunately evaluate from biophysical-semeiotic view-point, as follows.

Over the last two decades, I have suggested to distinguish, in a clear-cut way, Glycemology from Diabetology; the later includes, unfortunately, less physicians among its followers than the first (1).

Indeed, the value of PPG is a reliable barometer of diabetic condition, physiologically based, because its abnormalities are predicative of the disease, and, thus, represents an useful data for the prevention as well as for glycosilated hemoglobins intensity, to which is related. Moreover, there is an increasing number of authors, who consider PPG abnormalities related to, and predicative of, future micro- and macro-scopic diabetic complications.

As it is easy to understand, scholars agree generally nowadays with the direction clinically provided with the aid of Quantum-Biophysical Semeiotics (1, 2, 3), and, in our mind, this event represents an epoch-making time in the war against diabetes mellitus, as I wrote earlier (bmj.com, 10 June 2001, in the Rapid Response: “Bed-side primary prevention is the major step in the war against diabetes mellitus”).

In fact, apart from the therapy, based on the utilization of a-glucosidase-inhibitors and fast insulines, such a thinking change, originated from physio-pathological, epidemiological, endocrine-metabolic findings, correlates with microcirculatory phenomena, which cause diabetes mellitus onset, on the base of diabetic constitution-dependent inhereted real risk, i.e. genetically directed, such as diabetic as well as dyslipidemic constitutions (See my website, www.semeioticabiofisica.it, “Biophysical-Semeiotic Constitutions: URL www.semeioticabiofisica.it/constitutions.htm) we have some years ago indentified clearly, and described as Congenital Acidosic Enzyme-Metabolic Histoangiopathy, at the URL: www.semeioticabiofisica.it/Documenti/Eng/istangiopatia cong.acidos.enzimo, initially evolved to pre-metabolic syndrome, and, then, to metabolic syndrome, both classic and “variant”, slowly worsening to diabetes (1, 2, 3).

Physiological and pathological microcirculatory activation in the post-absorptive state.

If doctors do not know the original physical semeiotics, and consequently the large variety of essential results of the research, performed in the diabetology by the aid of this precious clinical tool, they must pay a particular attention to PPG, surely of greater significance than that of FPG, as regards the primary prevention of diabetes mellitus, since it represents for such authors the early alteration, predicative of the future disease and its complications.

At this point, we briefly remember (this argument, certainly interesting, is beyond article’s aims) that PPG increases oxidative processes as well as activates PKC, bringing about vascular spasms and histangic lesion, as we have demonstrated by the original semeiotics, at which we will come back later on (4).

However, in our opinion, such as change of thinking among physicians must be considered of great value, even as the beginning of a long way, which over time, hopefully short, will reach a point, where micorcirculatory abnormalities, in particular the microcirculatory activation, playing a primary role, will be considered expression of alterations predicative of diabetes mellitus, and, thus, characteristic signs of the primary prevention locus.

Indeed, the phenomenon of type I, associated, type II, dissociated, and type III incomplete or “variant” form of the type II, microcirculatory activation plays a pivotal role in physiology and, respectively, in the pathogenesis of most common and dangerous human diseases, including diabetes mellitus, which originate on the base of CAEMH (1-4).

From the above remarks it follows that the early bed-side recognising microcirculatory abnormalities, as well as their “quantification” with the aid of Quantum-Biophysical Semeiotics represents, in our mind, a milestone in natural history of this syndrome, i.e., pre-metabolic syndrome, of physical semeiotics in general, and particularly of primary prevention.

On this subject, we must briefly remember, especially as regards the macroangiopaties, that the estimation of both microcirculatory function and structure, including the adventitial one, plays a primary role in bed-side diagnosing these common and serious diseases, starting from initial, subclinical stage. In fact, clinical and experimental evidence suggests that partial occlusion of a muscular artery – vasa publica, according to Ratschow – provokes quickly the compensatory, associated, type I, microcirculatory activation, in both local adventitial vasa privata and in distal related tissues.

Doctor must bear in mind that the microcirculatory bed represents the “peripheral heart”, which increases its autochthonus, sphygmic activity, when local blood supply decreases, even in a light manner, due to haematologic (anemia) as well as vascular causes, or cardiac insufficiency, which act up-wards. If these disorders, of course, are not promptly eliminated, such an activation of vasomotility and vasomotion slowly ends in the dangerous micorcirculatory insufficiency and, ultimately, of failure of local microcirculatory bed, characterized by the spatial inhomogeneity, accurately illustrated in some papers of my above cited site www.semeioticabiofisica.it/microangiologia.

Adventitial microcirculatory biophysical-semeiotic evaluation, in case of aortic aneurism, gives us an example of the preventive-diagnostic value of evaluating local microcirculatory situation (See URL: Practical Application, Abdominal Aortic Aneurism,

www.semeioticabiofisica.it/Documenti/Eng/Aneurism A Aorti_eng.doc). The anatomical lesion of aortic wall, really, can be evaluated at the bed-side by assessing adventitial microcirculatory activity of aneurism.

Pathophysiology of the “peripheral heart” Failure.

One can easily understand that microcirculatory activation aims to maintain physiological blood-flow in the nutritional capillaries and post-capillary venules, and, thus, to supply related parenchyma with sufficient material-energy-information.

As regards diagnosis as well as prevention, it is plain the usefulness of knowing the course of these adaptable microcirculatory events, never observed till now at the-bed side, i.e. clinically, by data collected with a simple stethoscope during physical examination.

As clinical and experimental evidence demonstrates, e.g., in case of partial, incomplete jatrogenetic occlusion of ileo-phemoral artery, in healthy, cutaneous, sub-cutaneous, muscular microcirculation downwards, at least in the first minutes, is activated, according to type I, associated. Clearly, such event can be observed also in case of non complete obstruction of wathever other vessel, for instance, the carotid, which brings about in related distal tissues the greatest increase of cerebral “vasomotion” (“vasomotion” indicates both vasomotility and vasomotion) (5, 6, 7, 8) (Fig 1, 2, 3).

Once again, the final result of Microcirculatory Functional Reserve (MFR) is maintaining tissue energy in normal range, which unfortunately is often only transitory, since till now doctor was not able to recognize “clinically” this dangerous situation of “unstable compensation” of the peripheral heart and, thus, of blood-flow, flow- and flux-motion, maintained in physiological ranges, although at lower levels, in related tissue components.

In other words, at the bed-side, till now, doctor is not capable to recognize the minimal, initial, rapid reactions of “distal” microcirculatory activation, secondary to macroangiopathy in its early and asymptomatic stage. MFR activation can last “silent” even years before clinical phenomenology occurs, obviously related to “peripheral heart decompensation”.

From the above remarks it follows that, in an individual psychophysically relaxed and in supine position, i.e. in a state of complete rest, recognizing type I, associated, microcirculatory activation by “light” digital pressure, e.g., on the skin of a limb or on a finger-pulp, allows doctor to assess three ureteral reflexes and, then, diagnosing without doubt the presence of macrovascular disorder up-wards, even initial and/or in early, symptomless stage, which can be diagnosed by numerous biophysical-signs, characteristic of the angiopathy (See above-cited sites).

“At rest”, the presence of type I, associated, peripheral microcirculatory activation in an apparently healthy individual indicates a “silent” macroangiopathy up-wards, i.e., in related vasa publica, according to Ratschow, that doctor must assess accurately and promptly treat.

By contrast, if the patient presents with clinical signs, characteristis of pripheral vascular disorders, such as intermittens claudicatio, the micocirculatory activation (“peripheral heart” activated) modifies over time and becomes of type II, dissociated, and, ultimately, ends in the dangerous situation of pathological functional microcirculatory “rest”, due to microvessel sphygmicity failure: vasomotion shows AL + PL £ 5 sec. ( NN = 6 sec. at rest), I = 0,5 cm. ( NN = 0,5 – 1,5 cm.), periods fixed at 10 sec. ( NN = 9 – 12 sec.) (Fig.s At URL (http://www.semeioticabiofisica.it/microangiologia/Documenti/Eng/Pre-metabolic%20syndrome%).

From the clinical-microangiological point of view, such as situation characterizes “peripheral heart” failure. The above-described pathological condition can be localized in a very small area of a limb – finger, calf, a.s.o.), where patient feels the “ischaemic” pain.

In conclusion, bed-side evaluation of microcirculatory activation (activation of MFR) represents a noteworthy progress in the field of physical semeiotics or, more precisely speaking, in Biophysical-Semeiotic Clinical Microangiology, playing a primary role, from now on, in the diagnosis, prevention, prognosis, therapeutic monitoring and research of all biological systems.

Bed-side recognizing microcirculatory activation, localized in various, well-defined biological systems, easy and rapid to perform, in a long experience proved to be reliable and useful in both phsiological and pathological conditions, offering original ways of clinical research.

Post-Prandial and Post-Absorptive State Activation, in physiological and pathological conditions: Pre-Metabolic Syndrome.

The microcirculatory behaviour in post-absorptive state, i.e., at least 3-4 hours after meals (this time, however, can be lower, because it is in relation to the food amount, the subject has eaten, his digestion as well as absorption capacity, insulin-secretion and insulin-receptors sensitivity), in the liver, scheletric muscle, adipose tissue, both central and peripheral, brain, pancreas, is essential in order to assess the particular metabolic-endocrine situation, as well as the complete and deep understanding the pre-metabolic syndrome, scientifically defined.

The assessment of the microcirculatory activation of pancreas, liver, striated muscle, adipose tissue, both central and peripheral, under physiological as well as pathological conditions, allowed to define precisely the pre-metabolic syndrome , i.e. the grey zone.

In fact, it is not possible to realize the essence of this particular condition of biological systems, real locus (site) of the primary prevention of most common and serious human disorders, without the steady biophysical semeiotic knowledge of both absorptive state and post-absorptive state, more or less abnormally modified, when the slow transition initiates from CAEMH to pre-metabolic syndrome, frstly, to metabolic syndrome subsequently, or Reaven’s syndrome, both classic and “variant”, and ultimately to the diseases.

With reference to the “variant” form of metabolic syndrome, we previously described (2), it is interesting to note that under such as condition only epatic microcirculation behaviour appears physiological, as regards insulin action, since local insulin-receptors are normally functioning, helping, thus, to defining and recognizing it by a refined way (10, 11). In a few words, hepatic and pancreatic microcirculation is identical, in the sense that the former parallels the later (Fig.1 and 2).

To recognize at the bed-side the presence of these bridge-events in a “quantitative” manner, which link the “whithe zone”, physiological, to the “black zone”, pathological, representing, thus, the “grey zone”, or pre-morbid stage, or better speaking pre-metabolic syndrome, that can last for years or decades, it is unavoidable that doctor has a steady knowledge of this original clinical method, which allows him to estimate “quantitatively” the microcirculatory condition, both functional and structural, in the different tissues, beginning generally from thre-four hours after meals. Fortunately, the preconditioning of diverse biological systems, mentioned above, facilitates enormously the diagnose of pre-metabolic state (See later on).

In fact, as the reader undestands easily, clinical evaluation of metabolic situation thre-four hours after meals, i.e. in the post-absorptive state, is adaptable also in evaluating metabolic condition, regarding glucose, lipids and proteins, soon thereafter the meals (absorptive state): for example, interesting data are collected by the evaluation of pancreatic, hepatic, muscular, abdominal sub-cutaneous adipose tissue (very different is the metabolism of “distal” adipose tissue, e.g. thigh,whose insulin-receptors are always physiologically functioning) microcirculation under both rest condition and after giving two coffee-spoons of sugar dissolved in water. After two minutes, or less, appears gastric hypermia, due to digestive phenomena, increased peristaltic gastric wave velocity (= period 12 sec. versus 18 sec.), and glucose absorption: gastric “vasomotion” results clearly increased according to type I. Soon thereafter, doctor observe the activation of pancreatic microcirculation, and, then, successively, the hepatic, muscular and adipose tissue microcirculatory activation.

At empty stomach, swallowing 2-3 coffee-spoons of sugar dissolved in water, allows doctor to estimate functional gastric digestive activity, and, successively the functional metabolic capacity of pancreas, liver, skeletal muscle, adipose tissue, both central and peripheral, and heart.

As far as pancreatic microcirculatory activation after giving two coffee-spoons of sugar dissolved in water is concerned, we must remember that this test proved to be of diagnostic value in diabetology greater than that of the OGTT, which is surely more expensive and complex.

In healthy, there is enlargement solely of the pancreatic interstitium (= “in toto” ureteral reflex ³ 1 cm.), indicating pulsated ormonal secretion, actually, as demonstrates also the deterministic-chaotic behaviour of interstitiomotility

In contrast, during the test (as well as in the absorptive state), in all biological systems, referred above, doctor observes the phenomenon of absorption, characterized by “in toto” ureteral reflex of smallest degree: < 1 cm. We underscore that these data, reader must know perfectly, play a paramount role in recognizing such as metabolic condition, i.e. pre-metabolic syndrome. In fact, there is a strict relation between “in toto” ureteral reflex intensity, on the one hand, and both absorption or tissue secretion-output, on the other hand.

The “in-toto” ureteral reflex intensity < 1 cm. during “light-moderate” stimulation of trigger-points of a biological system indicates a condition of tissue absorption of material-energy-informaton, while the intensity ³ 1 cm. is expression of actual secretion, or output of metabolites or hormons.

Moreover, it is easy to understand that pancreas interstititum is steadily large (“in toto” ureteral reflex ³ 1 cm.), although according to a deterministic-chaotic behaviour, related to insulin secretion pulsatility, as shows clearly the pancreatic diagram as well as pancreatic microvascular fluctuations.

Such as biophysical-semeiotic knowledge allows doctor, for the first time, to recognize if the individual, he examines, is fasting or not: the examination gives a lot of information, but, at times, it is missleading due to erroneous estimate in the transition from absorptive to post-absorptive state, which really lasts only for a few minutes.

This doubt can be easily resolved by dynamic tests, which stimulate (as VI dermatomere-pancreatic reflex during “middle-intense” stimulation) or restrain (“intense” stimulation of pancreatic trigger-points, apnea test, boxer’s test, Restano’s manoeuvre) insulin secretion: in former case, in fact, hepatic interstitium immediately appears smaller, i.e. < 1 cm., while it increases clearly during stress tests, that notoriously cause reduction of the insular hormone secretion.

In addition, interestingly appears the perfect agreement of AL + PL duration of both vasomotility and vasomotion in all aforementioned biological systems.

By contrast, in hyperinsulinemia-insulinresistance, where lacking is the increase of kidney volume during insulin acute pick secretion (evaluation test of insulin secretion, of greatest value) as well as suprarenal glands show a diagramm of disactivated microcirculation (See: test of hyperinsulinemia-insulinresistance by renal and suprarenal gland diagrams: Glossary), AL + PL in “peripheral biological systems is 7 sec., while the pancreatic AL + PL is > 7 sec., in direct relation to glicidic dysmetabolism (Fig. 1 and 2).

In absorptive state, the dissociation of AL + PL of vasomotility values between pancreas and peripheral tissue, e.g., pancreatic AL + PL > 7,5 sec., while the value in other biological systems is 7 sec., indicates glicidic dysmetabolism as well as hyperinsulinemia-insulinresistance.

It is important for doctor to know that the unique exception, under above-mentioned condition, is the “normal” microcirculatory activation of “peripheral” adipose tissue (for example, thigh adipose tissue), whose insulin receptors are normally sensitive to hormone in “all” cases.

As a matter of fact, during the absorptive state AL + PL of vasomotility duration is identical to that of the pancreas, while obviously in the post-absorptive state results the shortest of all, because the sensitivity of these insulin receptors in a moment of hyperinsulinemia capable to restrain the hepatic glucose output and FFA output from adipose tissue: pancreatic AL + PL 8 sec., hepatic (in classic Reaven’s syndrome, but not in the “variant” form) and “central” adipose tissue parameter value 7 sec., while in “peripheral” adipose tissue only 6 sec.

In the “variant” Reaven’s syndrome, under the same condition, hepatic “vasomotion” AL + PL lowers to only 6 sec., due to physiological response of the local insulin receptors, that characterizes such as particular form, conditio sine qua non of lithyasis as well as tissue calcium deposit, including vasal wall.

A long well established experience allows us to state that, at the moment, biophysical-semeiotics clinical evaluation of the absorptive state and post-absorptive state microcirculation represents the uppermost attained goal, as well as the most fruitful area of research in Clinical Microangiology.

Bed-side diagnosing pre-metabolic syndrome by means of biophysical-semeiotic preconditioning.

Biophysical-semeiotic preconditioning of pancreas, lever, skeletric muscle, adipose tissue, both central and peripheral, allows doctor to recognize the pre-metabolic syndrome easily and rapidly; it is performed in two different ways, micro- and macroscopic (fully illustrated in the site www.semeioticabiofisica.it/microangiologia, at the URL:

www.semeioticabiofisica.it/microangiologia/Documenti/Eng/A PRECONDIZIONAMENTO%:

1) macroscopic way: direct and quantitative evaluation of non-linear dynamic behaviour of a biological system (e.g., pancreas), by drawing the relative diagram, and /or, more practical in every day practice, by caecal and/or gastric aspecific reflex latency time (lt);

2) microscopic way: quantitative evaluation of local microcirculatory activation type and intensity.

As an example of the former way, i.e., “macroscopic”, of assessing the preconditioning we consider that cardiac, earlier illustrated (2): “mean-intense” digital pressure with the aid of bell-piece of stethoscope, placed on left heart ventricle projection area, in healthy, provokes ventricular dilation, lasting for 7 sec. Continuing such as stimulation – or if it is again applied after an interval of exact 5 sec. for one or two times – this periods lowers to 6 sec. and ultimately to 5 sec. (BioMedCentral, Biophysical Semeiotics is really useful in order to bed-side recognizing heart ischaemic disease, even before its onset, i.e., real risk of coronary artery disease.

http://www.biomedcentral.com/1471-2261/3/12/comments/comments).

By contrast, in case of ischaemic heart disease, for example, initial, first duration is ³ 7 sec., in relation to the seriousness of coronary disorder, and persists unchanged during successive evaluations. Identical results are gathered in case of valvular, hypertensive and amiloydosis cardiopathy.

Contemporaneously, in healthy, lt of the cardio-caecal and –gastric aspecific reflexes rises from 8 sec. to 10 sec. (age-dependent), while it is unchanged (about 8 sec.) in the initial or not severe disease – intermediate preconditioning, type II - , whereas it worsens in the advanced disease – pathological precoditioning, type III – nth expression of internal and external coherence of the biophysical-semeiotic theory.

In the later way, “microscopic”, i.e., in assessing tissue-microvascular unit activation, basal vasomotility as well as vasomotion show the typical physiological deterministic-chaotic behaviour.

At the end of the third stimulation, caused by pressure of the bell-piece of stethoscope, as above referred, we observe microcirculatory activation, type I, associated: AL + PL of the fluctuations of III upper (vasomotility) and of third lower (vasomotion) ureter persist for 7-8 sec. (NN = 6 sec.); it is necessary to estimate togheter, as an identical parameter, AL + PL, wich indicate the velocity, intensity and duration of arterioles and, respectively capillaries and post-capillaries venules opening, according to a synergistic model.

In fact, the transition from the rest state to the activation occurs by degrees: firstly PL increases (3 sec.® 5 ® 6 sec. ® 7 sec. ® 8 sec.), whereas intensity and height of oscillation wave remain the same. Subsequently, all fluctuations become highest spikes (HS), aiming to supply gradually a greater flow-motion (Fig. at URL

(http://www.semeioticabiofisica.it/microangiologia/Documenti/Eng/Pre-metabolic%20syndrome%).

With reference to this topic, it is necessary to remember the important function, played by EBD in this original clinical investigation, where their opening becomes more and more intense and prolonged during physiologic preconditioning occurrence, while “closure” duration progressively shortens. On the contrary, in pathology it is always observable ab initio, an alteration, firstly functional, and, then, structural, of the endoarteriolar blocking devices so that estimating EBD, from both functional and structural view-point, gives the same information as the preconditioning, expression of strict logic connection of theory, we support.

To summarize, in healthy the preconditioning brings about, as natural consequence, an optimal tissue supply of material-information-energy, by increasing local flow-motion as well as flux-motion.

At this point, we come back to the former example: in the initial phase of coronary heart disease, what evolves very slowly toward successive phases, “basal” biophysical-semeiotic data can “apparently” result normal. However, under careful observation, the duration of cardio-gastric aspecific reflex results prolonged: > 4 sec. (NN £ 4 sec.), indicating a local microcirculatory disorder.

Really, in these conditions, EBD function is clearly compromised, but for some time the increased vasomotility counterbalances efficaciously the impaired supply of normal blood amount to parenchyma: also the vasomotion, at rest, shows parameter values oscillating in physiological ranges, due to the augmented arteriolar sphygmicity; such a condition can be “technically” defined peripheral heart compensation.

Noteworthy, from the diagnostic point of view, are also the cardio-caecal and -gastric aspecific reflexes, when accurately assessed: after a lt still normal (8 sec.), doctor observes a reflexes duration, before the successive one initiates, of 4,5 sec. (NN £ 4 sec.), and a differential lt (= duration of reflex disappearing before the beginning of the following) of only 3 sec. (NN > 3 <>

Clinical recognizing of these “slight” abnormalities, really useful in diagnosing initial and/or symptomless disorders, altough not difficult to perform, requests a good knowledge, a steady experience and a precise performance of the new semeiotics.

In these cases, preconditioning allows in simple and reliable manner to recognize the pathological modifications, mentioned above, which indicate the altered physiological adaptability, even initial or slight, of the biologial system to changed conditons as well as to increased tissue demands (Tab.1).

Physiological, type I Preconditioning ® Tissue-microvascular unit activation ® MFR normal ® outcome +

(Physiological DEB Function) type I, associated

Intermediate, type II Preconditioning ® Tissue-microvascular unit activation ® MFR compromised ® outcome ±

(EBD function slightly modified: closure) type II

Patological, tipo III Precondizioning ® Tissue-microvascular unit activation ® MFR absent ® outcome -

(EBD function pathological) type II, dissociated

Tab. 1

From the above remarks it appears plain that the various parameters of caecal, gastric aspecific and choledocic reflex, type of activation and, then, EBD function, related to a defined biological system, parallel the data of preconditioning.

Another example to clarify the abstract value of the concept: in healthy, pancreatic-gastric aspecific and –caecal reflex is characterized by lt of about 12-13 sec., D of £ 4 sec. and differential lt or fractal dimension > 3 <> (NN = 3,81). Contemporaneously “basal” pancreatic “vasomotion” shows the typical deterministic-chaotic behaviour, known to reader by now, in which AL + PL lasts 6-7 sec. physiologically, fluctuations intensity varies from 0,5 to 1,5 cm. (conventional value), the period fluctuates between 9 sec. to 12 sec., average value 10,5, fractal number (8).

Soon therafter pancreatic preconditioning (“mean-intense” cutaneous pinching of VI thoracic dermatomere for 15 sec., repeated three times with 5 sec. interval exactly), in healthy, caecal-, gastric aspecific-, and choledocic-reflexes show lt of 14 sec. (NN basal value = 12 sec.), duration £ 3,5 sec., and differential lt > 3,81 £ 4. Simultaneously, occurs pancreatic microcirculatory activation, according to type I, associated, with AP + PL of 7-8 sec., intensity of the ureteral fluctuations, both upper and lower, greatest (1,5 cm.), as we observe in HS, EBD physiologically activated:middle ureteral reflex intensity, brought about by “mean” stimulation of related trigger-points of 1,5-2 cm., reflex duration 22-24 sec. (basal 20 sec.), and duration of its disappearance 4 sec. (basal 6 sec.).

By contrast, in impaired glucose tollerance (IGT), above-referred parameters, at least in its initial phase (= pre-metabolic syndrome) and in slight cases, do not modify, but worsen statistically exclusively in advanced stages, in relation to disease seriousness: lt decreases to £ 11 sec., while the duration rises to ³ 4 sec., and differential latency time results smaller than that initial, border-line (= 2,5-3 sec.): <> Under this condition, microcirculatory activation is of type II, dissociated, indicating the actual situation of pre-morbid state in an individual completely symptomless, even for decades.

Interestingly, the preconditioning can be easily applied in estimating both function and structure of all biological systems, which at this moment, at rest, can reveal apparently normal conditions, but, in reality, show clear-cut abnormalities of numerous parameters values of the biophysical-semeiotic signs (Tab. 2).

HEALTH

Tl 12 - 14 sec.

Duration <> sec

Differetial lt >3£4

mvtU. activation type I associated

IGT in slow diabetic evolution

Tl normal or £ 11 sec.

Duration ³ 4 sec.

Tl differenziale

£ 3 - 2,5

mvtU. activation typeII dissociated

Tab. 2

Parameters of pancreatic-gastric apecific and –caecal reflex after the preconditioning in healthy and in a individual with impaired glucose tollerance in slow diabetic evolution.

(explanation in the text).

Gradual worsening of the parameters values of reflexes, observed bed-side with the preconditioning, related to the actual functional and structural conditions of the investigated biological systems, can be “geometrically” represented, in a refined way, by the temporal changes of the “strange attractor”, apparently such at rest, which, after proper tissue stimulations, firstly becomes a “close-loop attractor”, and, ultimately, a “fixed-point attractor”: from the biological view-point, the life is the trajectory of the strange attractor of biological systems”.

**Tissue microcirculation in the post-absorptive state in various diabetic stages.**

In the interest of reader, to facilitate the understanding of following argument, we refer briefly some fundamental knowledges of the original semeiotics, remembering elementary concepts of glycidic metabolism after three-four hours, at least, after meals, in healthy, in case of IGT, and finally in diabetes mellitus, showing that, at every moment of the day, doctor is able to evaluate insulin-secretion, as well as insulin-resistance at the bed-side by means of Biophysical Semeiotics (1, 2, 9, 10, 11). In this connection, both acute pick of insulin-secretion test (See later on) and post-prandial glycemia (PPG) are really fundamental.

In fact, doctor is able to recognize “clinically” initial abnormalities of glycidic metabolism, since insulinemic pick results always reduced, even in different degree (assessed as latency time, duration and intensity of pancreatic-aspecific gastric reflex, for instance (NN = lt 12-13 sec., D 3 < productid="1,5 cm" st="on">1,5 cm.), and prescribe early, in selective and rational way, the best therapy, including diet, etymologically speaking, carrying out efficaciously diabetes mellitus primary prevention on a very large scale.

If doctor evaluates over and over again, at least three times, with unavoidable intervall of 5 sec. – biophysical semeiotic preconditioning – the acute pick of insulin secretion, he observes the described diabetic pathological condition, even initial and/or slight, characterized by various degrees of basal parameters values: at basal line, in diabetes mellitus the VI thoracic dermatomere-gastric aspecific reflex lt (i.e. acute pick of insulin secretion) is <> (NN = 12-13 sec.), D > 4 sec (NN > 3 <>differential lt before the occurring of successive reflex <>(= > 3 <>

In reality, it appears very interesting that these values are statistically modified, in the pathological sense, in case of both IGT and its different stages during diabetic evolution, particularly after biophysical semeiotic preconditioning: lt appears reduced over time, lowering from 12-13 sec. or > 13 sec. in case of insulin hypersecretion, to 10 sec. or £ 9 sec., inversely related to the seriousness of hormone secretion impairement.

In contrast, in healthy, pancreatic islets preconditioning brings about a clear-cut amelioration of all pancreatic-gastric aspecific reflex parameters, by significant way. Contemporaneously, both pancreatic and peripheral microcirculatory bed is activated, according to type I, associated, where vasomotility as well as vasomotion clearly increased in the pancreas: AL + PL rises from 6 sec. to 8 sec., I becomes maximal, i.e. 1,5 cm. (HS) and DEB result activated (closure duration <> 20 sec.) (Fig. 1, 2, 3).

As regards the peripheral tissues, the values depend on the presence or absence of classic or “variant” metabolic syndrome, as referred above.

On the contrary, in case of IGT, the values of ureteral reflex parameters are the same of those typical of dissociated microcirculatory activation, where only the vasomotility appears increased, while the vasomotion is lowered, and, as usually, is observable DEB dysfunction, more or less intense (Fig. 2).

It follows that doctor observes histangic disorder, acidosic in origin, indicating the real pathogenetic role played by microcirculatory activation, type II, dissociated, in whom, in our mind, the abnormal activity of Endoarterial Blockomg Devises (DEB), ubiquitarious in contrast to AVA, type II, group A and B, as well as AVA, type I, according to Bucciante) plays a primary role in the onset of most common and dangerous human diseases, degenerative, connective and neoplastic in nature.

Histangic different response to endogenous insulin, in physiology, in Pre-Metabolic Syndrome and in pathology.

Biophysical-semeiotic evaluation of pre-metabolic syndrome, characterized by the absence of disease due to compensation, even unstable, as regards receptorial hyporesponsiveness, is based chiefly on clinical and quantitative evaluation of insulin-resistance (11) in insulin-dependent tissues, as liver, striated muscle, “abdominal” adipose tissue, bresat and thorax, whose metabolic behaviour is clearly more “vulnerable” than the peripheral adipose tissue.

Physiologically, endogenous insulin, secreted by means of the stimulation of VI thoracic dermatomere due to digital pressure or prolonged pinching of the related skin, activates various microcirculatory systems also of these biological systems.

By contrast, interestingly, since the first stage of slow and progressive evolution of CAEMH to metabolic syndrome, classic or “variant”, i.e., in the above-illustrated condition termed pre-morbid or pre-metabolic state, insulin brings about type II microcirculatory activation, dissociated, and consequently tissue acidosis, subsequent to the reduction of insulin-receptor activity (responsiveness) toward its hormone, as well as nor-epinephrine (nor-adrenalin) as well as epinephrine (adrenalin), and, thus, compensatory increase of insulin, epinephrine and nor-epinephrine (= enhancement of suprarenal glands macro-fluctuations as well as microcirculatory oscillations), causing the well-known abnormal consequences.

At the begin of this paper we have remembered that, in healthy, the insulin activates the microcircle, while under pathological conditions, such as hyperinsulinemia-insulinresistance, evolving slowly towards diabetes mellitus, provokes increase of free radicals and Protein-Kinase-C (PKC), which, in turn, causes macro-and micro-vascular spasms (Millennium of Diabetes Treatment, Medscape 2000), as we previously demonstrated clinically (2, 9,11). It follows that the microcirculatory bed is activated, according to activation type II, dissociated.

To recognize and “quantify” clinically the interesting and dangerous hyperinsulinemia-insulinresistance, clinically silent, by the easiest way doctor performs the basal evaluation of lt of finger-pulp-gastric aspecific or caecal reflex. After acute pick of insulin secretion (=cutaneous pinching, lasting about 15 sec., inwards to the crossing point of hemiclavicular line and homolateral costal arch: VI thoracic dermatomere), doctor assesses for the second time lt of the same reflexes, which physiologically rises from 7-8 sec. to 9-10 sec., while in the later, pathological condition, i.e, in pre-metabolic stage, characterized by hyperinsulinemia-insulinresistance, the lt first appears unchanged and, then, becomes shorter, in inverse relation to the seriousness of dysmetabolic condition.

In this condition, hyperinsulinemia causes the microcircultory activation, type II, dissociated, and, then, the “centralization” of flow-motion.

Doctor observes characteristic behaviours of insulin receptors at renal level, which account for the reason of the renal test of hyperinsulinemia-insulinresistance, mentioned above (See Glossary in the site Semeiotica Biofisica): receptorial down-regulation, consequence of the increased hormonal blood level, hinders the physiological response of kidneys to acute pick of insulin secretion, characterized by microcirculatory activation, type I, associated, wich explains the insulin-dependent modifications of kidney diagramm: in healthy, after a lt of 3 sec., the kidney enhances intensely its size (congestion) for 10 sec., while in the diabetic lt rises to only 6 sec. with slight and short increase of its diameters and prevailing renal decongestion.

In the pre-metabolic syndrome and in the steady IGT, one speaks of insulin-resistance if AL + PL value of both pancreatic vasomotility and vasomotion in the post-prandial state is higher than that osserved in the liver (with the exception of “variant” metabolic syndrome), striated muscle and abdominal adipose tissue.

In other words, under such as situation, peripheral metabolic activity needs a more amount of insulin to counterbalance insulinreceptors abnormal sensitivity, and thus to maintain in physiological ranges the glico-lipidic metabolism, by the aid of hyperinsulinemia (2, 9). In this condition, the renal test of hyperinsulinemia results negative, i.e., pathological, as described above.

However, when endocrine pancreas goes on slowly toward functional insufficiency, even with different intensity, in the post-absorptive state the duration of AL + PL is greater in peripheral tissues (liver, “central” adipose tissue, striated muscle) than in the pancreas. From the metabolic-biochemical view-point, these events are explained by the fact that the insulin dos not reach sufficient blood level to “check” glucose secretion by the liver as well as FFA by abdominal-thorax adipose tissue away from the meals. Notoriously, physiological amount of hormone controls, on the one hand, glucagone activity (hepatic glucogenolysis and no-glucogenogenesis) and, on the other hand, lipolysis (free fatty acids secreted in the blood).

The curbing insulin action influences, of course, microvascular system function in diverse tissues, where vasomotility and vasomotion show the same intensity.

In fact, as I demonstrated clinically, there is a strict functional relation between parenchyma and relative microcircle (Introduzione alla Semeiotica Biofisica), which allows bed-side anatomo-functional evaluation of a precise parenchyma by assessing the relative microcircle, representing, thus, the climax of Clinical Microangiology.

At this point, as regards what is illustrated above, it is of great interest the fact that, if the parenchyma is activated in the sense of absorption and/or synthesis (for example, the liver synthesizes glucogen, as we observe in post-prandial state), intertitium appears “minimal” (= “in toto” ureteral reflex, brought about in the first 6 sec., after “light” stimulation, is really small: < 1 cm. (NN = 0,5 cm.), while in case of microcirculatory activation indicstes the presence of secretion (FFA or glucose output in blood stream) the interstitium is clearly “large” : > 1 cm. (12, 13, 14, 15).

In contrast, when glycidic metabolism is altered, even in initial and/or silent stage, rceptor insulin sensitivity results reduced and consequently we observe hyperinsulinemia in order to counterbalance such hormone insufficiency, increase of hepatic glucoeogenesis as well as glicogenolysis, initially properly controlled ba periheral absorption (adipose tissue and muscles, including the myocardium), achieving, thus, a new steady state plamatic glycidic concentration (1, 2, 9, 11, 12).

In this metabolic situation, which can last for years or decades, the microcirculation in the diverse tissues is necessarily activated, i.e., the vasomotility and vasomotion are showing progressively basal conditions and, then, a large variety of microcirculatory situations, different from both quantitative and qualitative point of view, whose investigation open new and fascinating ways in medicine and particularly in primary prevention.

Pre-Metabolic Syndrome: microcirculatory activaton in initial phases of principal diseases. Two pressures test.

In following, we refer the data of our research, initiated in October 1998 in patients with pre-metabolic syndrome, to study the microcircle in the initial phases of principal human diseases. These results appear to be, from now on, really interesting altough referred exclusively to some diseases, though very frequent to observed in day-to-day practice: diabetes mellitus, arteriosclerosis, dyslipidemia, ischaemic heart disease, arterial hypertension, kidney and gall-bladder-stones, and malignancies.

From at least 20 years, we claim unheeded that CAEMH-a represents the conditio sine qua non of most common, serious, human pathologies (1-6, 18-20). The unavoidable way from this functional mitochondrial cytopathology to various diseases has been clinically recognized and indentified by us as poli-metabolic alteration, metabolic X syndrome, we termed untill now as Reaven’s Syndrome, of whose we described the so-called “variant” form (2, 9), which preceeds and then can be associated with kidney and gall-bladder-stones, as well as the calcium deposit in all tissues, incuding arterial walls, and consequently we consider it the conditio sine qua non of lythiasic disorders.

The microangiological data, observed in the post-absorptive state, corroborate our former statements, enlightening the complexity of physio-pathological mechanisms at the base of malignancies (See in the above-cited site: Oncological Terrain) as well as metabolic and infectious diseases, unfortunately nowadays not complicately utilized on large scale.

In addition, this biophysical-semeiotic microangiological study allows to gather at the bed-side essential information, which provides the possibility of the interpretation of the real nature of the passage from health stage – white zone – to that of disease – black zone – explaining, although incompletely, clinical significance and suggesting, thus, nosological definition of the term pre-metabolic state, premetabolic syndrome, Grey Zone, place of the “primary” prevention, rationally and individually realized.

White Zone ® Pre-Metabolic Syndrome or Grey Zone ® Black Zone

The activation of tissue-microvascular system is not a monotonous event, always identical. The transit from basal state, or at rest, to that of “active hyperemia” is dependent from the primitive parenchyma activation.

After the end of post-prandial stage, i.e. about 3 hours after the meal, in healthy, insulin secretion modulates the glucagonic activity, hepatic glycogenolysis and lipolysis. Consequently, physiologically, in the post-absorption state, we observe in the pancreas, striated muscle, adipose tissue, both “central” and “peripheral”, and in the liver a functional situation, characterized by a “vasomotion” showing periods and intensity with deterministic-chaotic behaviour and normally functioning AVA.

The physiological steady-state of glycemia indicates that glycemic concentration are normal on an empty stomach, since there is perfect relation between vasomotility as well as vasomotion in all tissues: AL + PL = 7 sec.; I = 1 - 1,5 cm.; fD = 3, and AVA, including EBD, normally functioning (Fig. 1, 2, 3).

It is plain that it exsists “always” microcirculatory activation in the tissues, although time-dependent of different intensity: biological systems are systems open to exchange of material-energy-information.

It follows that the caecal reflex (= caecal dilation, caused by mean digital pressure on whatever biological system) latency time appears physiological in all tissues, mentioned above (pancreas = 12 sec.; liver = 10 sec.; adipose tissue = 10 sec.; striated muscle = 10 sec. and, ultimately, brain and heart = 6 and respectovely 8 sec., age-dependent, of course).

The two pressure test gives rapidly interesting information as regards parameters values of tissue oxygenation. In fact, they allow to recognize promptly the physiological “vasomotion”: soon therafter caecal reflex appears, doctor increases manual, digital pressure (even the pressure caused by the bell-piece of stethoscope), in relation to the type of stimulation, enhancing, thus, the intensity of related trigger-points stimulation.

In our case, i.e., stimulation with a lasting “light-moderate” pinching, doctor increases its intensity, obviously. Temporaneously, the reflex rapidly disappears for th duration, in healthy, of > 3 sec.<>

The referred results, i.e. the information given by the two pressure test, is related to the activation intensity of local microcirculatory system (FMR, functional microcirculatory reserve), causing a greater O₂ and metabolites supply to tissues, resulting in clear amelioration of of tissue pH, and, thus, caecal reflex disappearing, wich indicates, therefore, histangic acidosis.

In contrast, when the microcircle is already activated, as during the gland secretion, and basal lt is physiological (= normal tissue oxygenation), the two pressure test results abnormal, showing value lowered to <>

Microcirculatory activation in glucose metabolism impairment.

At this point, to understand properly the essence of pre-metabolic syndromewe, we must consider the vasomotility and vasomotion in early stages of IGT during the absorptive state and, then, in post-absorptive state. Of course, these are different events related to residual insulin secretory activity of Langheran’s islets cells, variable from individual to individual, as well as in the same subject, over time. We must remember the normal function of insulin receptors of lever, characteristically present in the “variant” form of metabolic syndrome (2, 21).

In the IGT, in initial stage, insulin secretion in general appears substantially “increased”, likely due to reduced insulin receptor sensitivity, including the same receptors of Langheran’s b-pancreatic cells (the question about the relation between insulin-resistance and hyperinsulinemia untill now are not clarified, although doctors speak about compensatory hyperinsulinemia)

At the beginning of the process, both hepatic glycogenolysis and neoglycogenesis are normal, successively glycogenolysis enhances, analogously to the lipolysis in adipose tissue, depending from receptor sensitivity, as well as responsivity as far as insulin is concerned.

It follows that the microcirculatory activation in the liver, brain, adipocytes and in striated muscle shows always a pathologial behaviour, although different from case to case, as referred above in case of pre-metabolic syndrome.

From biophysical-semeiotic view-point, glucose dysmetabolism is characterized by the “dissociation” between pancreatic microcirculatory activation, assessed as AL + PL duration, and that peripheral. In brief, in presence of reduced receptor sensitivity, obviously, in the absorptive state, i.e., untill 3-4 hours after meals, the opening duration of microvessels is more intense at level of pancreatic cells (AL + PL = 8 sec.) rather than in the striated muscle, liver (in the absence of “variant” form” metabolic syndrome) or adipose tissue of thorax and abdomen, where AL + PL persits for 7,5 sec., exclusively in the vasomotility (Fig. 1).

It is now well known that, under this condition, in thight adipose tissue there is a microcirculatory activation similar to the Langheran’s pancreatic islets (AL + PL = 8 sec.), because local insulin receptors are physiologically functioning.

On the contrary, during the post-absorptive state, due to the reduced “curbing” insulin action – hyperinsulinemia-insulinresistance – we observe microcirculatory events completely opposite: pancreatic AL + PL really intense, showing value of 7-8 sec., while in the liver AL + PL is 8-9 sec. (apart from “variant” type of metabolic syndrome, where the value is 7-8 sec. as that pancreatic), as well as in thoracic and abdominal adipose tissue.

Once again, at level of thigh adipose tissue, the microcirculation appears similar to that in pancreas: AL + PL = 7-8 sec. Interestingly, in striated muscle microcirculatory activation is usually reduced (AL + PL = 6-7) in comparison with the pancreatic one, since muscular tissue is always in greater or less absorption state, actually in presence of reduced insulin receptor sensitivity.

Therefore, in the initial stages of IGT, local microcirculatory activation is capable to maintain, “at rest”, an apparently normal supply of material-energy-information to parenchymas, whereas in advanced IGT, when “peripheral” microcirculatory pattern, related to “vasomotion” in post-absorptive state, it results as follows: AL + PL = 8-9 sec., I = 1,5 (HS), caecal reflex lt normal, D > 4 sec. £ 5 sec.

In contrast, under the same condition, we observe pancreatic microcirculatory activation dissociated, type II, with AL + PL (Fig. 2), exclusively at the level of vasomotility, clearly increased (8 sec.), showing differential lt of the pancreatic-caecal reflex <>test of two pressures results pathological (increasing pinching intensity at level of VI thoracic dermatomere causes the disappearance of caecal and/or gastric aspecific reflex for solely 1 sec.).

In realty, interestingly, the accurate biophysical-semeiotic evaluation in IGT allows doctor to ascertain that the lt of pancreatic-gastric aspecific and/or caecal reflex is normal (12 sec.), but reflexes duration is greater (³ 4 sec.) and differenzial lt (= duration of reflex disappearance) shorter (fD £ 3 sec.), indicating clearly the conditon of unstable metabolic equilibrium, which can be recognized by the precious tool of preconditioning.

It is impossible to request further performances to a similar microcircle, which is functioning, at rest, even in initial phase, at maximal level of its activity, and successively goes on toward a slow and progressive failure, as the test of two pressures clearly demonstrates.

Hyperinsulinemia-insulinresistance as independent risk factor of the most severe human diseases.

The following clinical and expermental evidence, formerly illustrated, demonstrates clearly the primary role of hyperinsulinemia-insulinresistance, in the pathogenesis of a large number of human diseases, as we claim from the clinical view-point: after assessing basal parameters of finger-pulp – caecal reflex, as well as local vasomotility and vasomotion, doctor provokes, by mean (not to much intense) pinching of VI thoracic dermatomere, the acute pick of insulin secretion (2, 9, 11). Soon thereafter, doctor estimates the reflex parameters for the second time: in healthy, physiological microcirculatory activation ameliorates tissue O₂, likely to what occurs during the two pressures test, while in the IGT the favourable influences become more and more smaller and finally disappear, in inverse relation to the impairement degree of glucose metabolism or, more exactly speaking, in relation to the reduced sensitivity of insulin receptors as well as to “vasocontraction”, present in this pathologic situation.

The vascular response to the acute pick of insulin secretion in healthy is clearly different from that we observe in hyperinsulinemia-insulinresistance: in the former, in fact, there is microcirculatory activation, whilst in the later, there is progressive disactivation and subsequent histangic lesion.

Finally, when metabolic syndrome, both classic and “variant”, is leading to DM, “endogenous” insulin worsens transitory all reflex parameters during the test of acute pick of insulin secretion.

From Clinical Microangiology view-point, noteworthy in the pre-metabolic stage are functional and structural AVA abnormalities, in particular those of EBD, as well as the progressive, variable in intensity, dissociation between vasomotility and vasomotion (1, 2, 9, 11, 21), which allows to realize a subdivision of microcirculatory activation, useful for bed-side diagnosing as well as therapeutic monitoring.

As a matter of fact, two are the chief types of microcirculatory activation (it exists also the microcirculatory activation type III, incomplete, as the reader knows well: Type I, associated, global or circumscribed, in whom both the vasomotility and the vasomotion show increase of their fluctuations and AL + PL duration of 7-8 sec., while AVA are predominantly “closed” (Fig.2); Type II, dissociated, global or confined, when only the vasomotility is increased, whilst the vasomotion, initially is normal (AL + PL of 6 sec.), but progressively becomes reduced, characterized by short (<>plateau line and from a period fixed at 10 sec. The AVA are mainly “open” in hyperstomy stage (we remember that the adjactive “open” indicates the intense blood-shunt along arterious-venous anastomoses) (Fig. 3). Between these two “extreme” types, we may observe a large variety of intermediate forms.

In the type I, global, physiological microcirculatory activation (involving all tissues, mentioned above: the so-called active hyperemia) and in the type II, global, pathological, really we encounter a large variety of microcirculatory patterns during the post-absorptive state, whose evolution will lead over time to different disorders, if doctor does not suggest the correct and prompt therapy.

For example, in cancer the microcirculatory bed shows type II, dissociated, pathological activation, characterized by intense vasomotility with AL + PL of 8 sec. as well as maximal oscillations (1,5 cm.= HS), but the vasomotion shows AL + PL of only 5 sec., whose intensity is minimal and fixed at 0,5 cm., and AVA in hyperstomy phase. Such as behaviour is extrem from the pathological point of view, preceded and accompanied by an intense oncological terrain.

From the above remarks it is plain that we face interesting microcirculatory problems, really original, and that we are moving in a field of research, interesting and fascinating, due to its implications.

The doctor, who rightly shares our enthusiasmus, will necessarily share also the need, we are feeling strong, to reach all possible goals, conducting our research on a ground “to which not even the angels would dare to put their foot”.

When these targets will be attained, it will start and hopefully perform successfully the “primary” prevention of the most common and serious human diseases, invalidating or deadly, conducted in a personal, prompt manner, in rationally selected individuals, on a very large scale, by means of Biophysical Semeiotics.

In NIDDM (but even in IDDM) pancreatic microcirculatory activation is, of course, of type II or dissociated. In fact, in type 2 diabetes mellitus the stady-state is laying at a glicemic level higher than that physiological, but the hepatic glucose secretion as well as its perpheral utilization (due to the mass-effect of glucose) are the same. Performing the acute pick of insulin secretion does not normalize micorcirculation in these disease, at the most reduces its activation.

Really, we can observe cases of IDDM in which extra-pancreatic microcircle, or a part of it, result normally functioning. In other words, the pathological microcirculatory activation in diabetes mellitus doen not involve all tissue-microvascular units of the patient, since CAEMH-a, due to its definition, varys from subject to subject, from tissue to tissue and, finally, from part to part of the same tissue.

In ischemic heart disease doctor observe microcirculatory activation, type II and coronary EBD disactivation, and sometime in adipose tissue, as in dyslipidemia, even if it was present solely over the past years. In ATS one recognizes the pathological adventitial microcirculatory activity of the involved arteries. In these conditions, obviously, the AVA are hyperfunctioning (blood-shunting in microcirculatory bed) and subsequent tissue hypoxia. The acute pick of insulin secretion reduces the microcirculatory activation: AL + PL decreases from 8 sec. to about 6 sec., with clearly pathological consequences.

Interestingly, one observes a microcirculatory pattern typical of the dysplipidemia, actually present or not, in which firstly there is microcirculatory activation of type II “partial” (striated muscle and adipose tissue), to which follows the type II also in the liver and myocardium, when insulin-resistance and hyperinsulinemia pathologically activate the microcircle, so that over time microvascular activation pattern changes slowly.

At the moment, the biophysical-semeiotic research in pre-morbid stage is a long way within the bounds of it possibilities. However, we are allowed to state that the metabolic syndrome, classic or “variant” (2), represents the link from CAEMH-a to DM, arterial hypertension, dyslipidemia, gout, ATS, cancer, a.s.o.

Between CAEMH and metabolic syndrome, classic and “variant”, there is the territory, until now “unexplored”, i.e. Pre-Metabolic Stage, locus of the primary prevention of most common and severe human diseases.

Likely, as monstrates the tissue-microvascular unit activation during the postabsorptive state, hyperinsulinelia-insulinresistance, as an effect re-acting on its cause, worsens the histangic acidosis: e.g., the adventitial microcircle or vasa vasorum, is not capable to eliminate the catabolite from the arterial wall, which consequently appears damaged by the excess response – responsivity – to arteriosclerotic risk factors, according to our “Microcirculatory Arteriosclerotic Theory”, at the base of CAD (23, 24).

Clinical and experimental evidence shows that it is more dangerous for the tissues the abnormal elimination of the local catabolites, than analogous reduction of blood-supply to the same tissue: in healthy, digital “intense” pressure of the thumb finger-pulp against that of forfinger, brings about caecal reflex (= tissue acidosis) after latency time of 8 sec. (age-dependent, of course). After the beginn of digital pressure on brachial artery, obstructing it “partially” so that “radial pulsations” result clearly less intense than before, for 5 sec., lt of caecal reflex decreases to 6 sec. By contrast, a “light” pressure for 5 sec. upon inner surface of the same arm, able to ostruct exclusively brachial vein and local superficial lymphatics, causes caecal reflex after only 4 sec., as a consequence of interstitial stasis, compromised elimination of catabolites anf hydrogenions, and, then, the greater tissue lesion.

In conclusion, we have always to remember that during the slow evolution of pre-metabolic syndrome toward hyperinsulinemia-insulinresistance, IGT, type II DM, and/or Arterial Hypertension, Dyslipidemia (metabolic syndrome, both classic and “variant”) the microcirculatory activation, type I, becomes of type II, showing really a large variety of patterns, which shows a progressive dissociation, until “vasomotion” appears characterized by AL + PL of 5 sec. and I of 0,5 cm., while AVA dysfunction results more and more intense, characterized by permanent hyperstomy. Bed-side recognizing microcirculatory activation “even” at rest, and classifying it correctly by a clinical method, open new and promising outlooks on the primary prevention.

Bibliografia

1) Stagnaro S., Stagnaro-Neri M. Valutazione percusso-ascoltatoria del Diabete Mellito. Aspetti teorici e pratici. Epat. 32, 131, 1986.

2) Stagnaro S.-Neri M., Stagnaro S., Sindrome di Reaven, classica e variante, in evoluzione diabetica. Il ruolo della Carnitina nella prevenzione del diabete mellito. Il Cuore. 6, 617, 1993. [Medline]

3) Stagnaro S. Diet and Risk of Type 2 Diabetes. N Engl J Med. 2002 Jan 24;346(4):297-298. [Medline]

4) Stagnaro Sergio. Newborn-pathological Endoarteriolar Blocking Devices in Diabetic and Dislipidaemic Constitution and Diabetes Primary Prevention. The Lancet. March 06 2007. http://www.thelancet.com/journals/lancet/article/PIIS0140673607603316/comments?totalcomments=1, and especially www.fce.it, http://www.fceonline.it/docs/stagnaro.pdf

5) Stagnaro S., Valutazione percusso-ascoltatoria della microcircolazione cerebrale globale e regionale. Atti, XII Congr. Naz. Soc. It. di Microangiologia e Microcircolazione. 13-15 Ottobre, Salerno, e Acta Medit. 145, 163, 1986.

6) Stagnaro-Neri M., Stagnaro S., Auscultatory Percussion Evaluation of Arterio-venous Anastomoses Dysfunction in early Arteriosclerosis. Acta Med. Medit. 5, 141, 1989.

7) Stagnaro-Neri M., Stagnaro S., Modificazioni della viscosità ematica totale e della riserva funzionale microcircolatoria in individui a rischio di arteriosclerosi valutate con la percussione ascoltata durante lavoro muscolare isometrico. Acta Med. Medit. 6, 131-136, 1990.

8) Stagnaro-Neri M., Stagnaro S., Deterministic Chaos, Preconditioning and Myocardial Oxygenation evaluated clinically with the aid of Biophysical Semeiotics in the Diagnosis of ischaemic Heart Disease even silent. Acta Med. Medit. 13, 109, 1997.

9) Stagnaro S., Stagnaro-Neri M., Valutazione percusso-ascoltatoria del sistema degli oppioidi endogeni nei pazienti cefalalgici. Contributo alla definizione della costituzione emicranica. Epat. 33, 35, 1987.

10) Stagnaro-Neri M., Stagnaro S., Semeiotica Biofisica: valutazione clinica del picco precoce della secrezione insulinica di base e dopo stimolazione tiroidea, surrenalica, con glucagone endogeno e dopo attivazione del sistema renina-angiotesina circolante e tessutale – Acta Med. Medit. 13, 99, 1997

11) Stagnaro-Neri M., Stagnaro S., Semeiotica Biofisica: la manovra di Ferrero-Marigo nella diagnosi clinica della iperinsulinemia-insulino resistenza. Acta Med. Medit. 13, 125, 1997.

12) Signorelli S. Regional Pathology of the smole vessels and diabetic microangiopathy. Acta Diabetol. Latina, pag.367-370, Vol. XXII, 104,1985.

13) Gaehtgens P. Relevance of the Microcirculation for Ischemic Disease. In: Microcirculation and Ischaemic Vascular Disease. Advances in Diagnosis and Therapy. Proceedings of Congress. Munich, 1980,pag. 3-7.Edited by Messmer, Abbott,USA.

14) Hassmann F. Patterns and Structure of the Microcirculatory Bed. In: Microcirculation and Ischaemic Vascular Disease. Advances in Diagnosis and Therapy. Proceedings of Congress. Munich, 1980pag. 3-7.Edited by Messmer, Abbott,USA.

15) Schmidt-Schonbein H. Physiology and Pathophysiology of the Microcirculation and Consequences of its treatment by Drugs. In: Microcirculation and Ischaemic Vascular Disease. Advances in Diagnosis and Therapy. Proceedings of Congress. Munich, 1980, pag. 12-16. Edited by Messmer, Abbott,USA.

16) Stagnaro S., Istangiopatia Congenita Acidosica Enzimo-Metabolica condizione necessaria non sufficiente della oncogenesi. XI Congr. Naz. Soc. It. di Microangiologia e Microcircolaz. Abstracts, pg 38, 28 Settembre-1 Ottobre, Bellagio, 1983.

17) Stagnaro S., Istangiopatia Congenita Acidosica Enzimo-Metabolica. X Congr. Naz. Soc. It. di Microangiologia e Microcircolazione. Atti, 61. 6-7 Novembre, Siena, 1981.

18) Stagnaro S., Istangiopatia Congenita Acidosica Enzimo-Metabolica. X Congr. Naz. Soc. It. di Microangiologia e Microcircolazione. Atti, 61. 6-7 Novembre, Siena 1981

19) Stagnaro S., Istangiopatia Congenita Acidosica Enzimo-Metabolica. Una Patologia Mitocondriale Ignorata. Gazz Med. It. – Arch. Sci. Med. 144, 423,1993. (Infotrieve)

20) Dinnoen S., Gerich J., Rizzo R.: Carbohydrate Metabolism in non insulin-dipendent Diabetes Mellitus. N.Engl.J.Med. 327,707-708,1992.

21) Stagnaro-Neri M., Stagnaro S., La “Costituzione Colelitiasica”: ICAEM-a, Sindrome di Reaven variante e Ipotonia-Ipocinesia delle vie biliari. Atti. XII Settim. It. Dietol. ed Epatol. 20, 239, 1993.

22) Stagnaro-Neri M., Stagnaro S., Deterministic Chaos, Preconditioning and Myocardial Oxygenation evaluated clinically with the aid of Biophysical Semeiotics in the Diagnosis of ischaemic Heart Disease even silent. Acta Med. Medit. 1997, 13, 109.

23) Stagnaro Sergio. Role of Coronary Endoarterial Blocking Devices in Myocardial Preconditioning - c007i. Lecture, V Virtual International Congress of Cardiology, 2007. http://www.fac.org.ar/qcvc/llave/c007i/stagnaros.php

24) Stagnaro Sergio. Bedside Evaluation of CAD biophysical-semeiotic inherited real risk under NIR-LED treatment. EMLA Congress, Laser Helsinki August 23-24, 2008. "Photodiagnosis and photodynamic therapy", Elsevier, Vol. 5 suppl 1 august 2008 issn, Page S17.

* Sergio Stagnaro MD

Via Erasmo Piaggio 23/8

16039 Riva Trigoso (Genoa) Europe

Founder of Quantum Biophysical Semeiotics

Who's Who in the World (and America)

since 1996 to 2009

Ph 0039-0185-42315

Cell. 3338631439

www.semeioticabiofisica.it

dottsergio@semeioticabiofisica.it

Type 2 Diabetes Mellitus begins as dyslipidemic and diabetic Quantum-Biophysical-Semeiotic Constitutions and related Inherited Real Risk.

noreply@blogger.com (Stagnaro) — Sat, 18 Apr 2009 05:43:00 +0000

In my opinion, based on a 53 year-long clinical experience, the primary prevention of type 2 diabetes mellitus and its well-known and harmful so-called “complications”, which precede really for decades diabetes occurrence, as well as the prevention of all other serious and common human diseases, often associated to form Pre-Metabolic, and then Metabolic Syndrome, is nowadays possible on very large scale if we want it.

As a consequence, doctor may initiate a “particular” type of primary prevention, easy and efficaciously realized at the bed-side, i.e., with the aid of a stethoscope (See http://www.semeioticabiofisica.it, Biophysical-Semeiotic Constitutions). In a few words, performing an efficacious primary prevention of type 2 diabetes mellitus, we must go “beyond obesity, adiposity, LDL raised blood level, and even hyperinsulinemia-insulin-resistance” in the sense that doctors must know and recognize “quantitatively the “biophysical-semeiotic diabetic constitution”. In other words, every screening programme for whatever disease and its complications, including diabetes and cancer, needs efficacious "clinical" tools to obtain the best results. In fact, for instance, it is generally admitted that non-insulin-dependent diabetes mellitus (i.e. about 95% of diabetic disorders) may occur at least 12 years before the clinical diagnosis of DM is made, i.e., after long time of IIR, adiposity, obesity, a.s.o., and retinopathy can develop at least 7 years before the diagnosis. In a few words, national screening programmes for diabetic complications should be intended for people who don't present any clinical symptomatology, at the moment, a part from “diabetic and dislipidemic constitutions” with related Inherited Real Risk. Actually, during the time that diabetes is "undiagnosed" and untreated, complications, that could be avoided by a different, really efficacious prevention, are developing. Therefore, early diagnosis must certainly be established in "asymptomatic" patients who are evolving slowly towards diabetes mellitus, i.e. long time before disease onset, in order to avoid those complications. In fact, to prevent well known diabetic complications, including diabetic retinopathy, it is extremely necessary that doctors use a clinical tool reliable in diagnosing early diabetes mellitus stages, i.e. from its initial stages, i.e., even before Reaven’s syndrome, both classic and “variant”, I described previously (1, 2, 3, 5). Until now, unfortunately, diabetes mellitus is too often diagnosed accidentally, e.g. by occasional urinary or blood tests. Furthermore, epidemiological studies indicate that 50% of individuals with 2-hour postglucose challenge values over 200 mg/dL, a value diagnostic for diabetes, were not previously diagnosed as being diabetic (3, 4). Fortunately, it is now easy to realize "clinically" an efficacious DM primary prevention, as well as the prevention of other common human diseases, including malignancies, in a simple manner, with the aid of some biophysical-semeiotic signs, reliable in recognizing the different ”constitutions”, in a quantitative way. Certainly, we can prevent type2 diabetes mellitus if we know the above-referred clinical method, easy to perform, which can be Authors agree with such statement, written in

Medscape(http://boards.medscape.com/forums?10@33.MZq8as0jbdr^0@.ee99d0a): "Diabetes is, of course, a disease of complications. But landmark studies such as the Diabetes Control and Complication Trial have shown that achieving tight glycemic control can directly reduce the risk of complications, especially microvascular complications. New screening tools and potential new treatments also hold promise for making microvascular complications such as retinopathy and neuropathy more manageable and less inevitable". I agree with it, of course, exclusively regarding diabetes occurrence. Unfortunately, this statement indicates that now-a-days, even skilled diabetologists all over the world, ignore or, worse, overlook the existence of quantum-biophysical-semeiotic "diabetic and dislipidemic" constitutions, recongnised at the bed-side in a "quantitative" way, which allows us to perform diabetes mellitus PRIMARY PREVENTION, conditio sine qua non of all diabetic so-called “complications”, including the microvasculopathies disorders.

Finally, in doing that, we do not need, at least initially, laboratory methods, as oral glucose tollerance test, PPG, FG, in order to recognize individuals at inherited real risk of type 2 diabetes mellitus (4-9). Thanks to a new physical semeiotics, i.e. Quantum-Biophysical Semeiotics (http://www.semeioticabiofisica.it) doctors can, all around the world with the aid of a simple stethoscope, recognize and quantitatively evaluate the presence of "diabetic, and dislipidemic constitutions", by means of bed-side assessing microcirculatory conditions of the Langheran's islets, as I described previously (2, 3, 7-12). In facts, in both absorptive and post-absorptive state, we can "clinically" assess pancreatic histangium acidosis, correlated with local microcirculatory blood-flow situation or more precisely evaluating local Microcirculatory Functional Reserve (MFR) in Langheran's islets: in healthy, lasting cutaneous pinching of VI thoracic dermatomere, brings about gastric aspecific reflex after a latency time (lt) of 12 sec. exactly, which is the measure of local histangium acidosis. By contrast in subjects at "inherited real" risk of type 2 diabetes and obviously in diabetic patients, reflex latency time is less than 12 sec, in inverse relation to pancreatic islets impairment. In addition, biophysical-semeiotic “preconditioning” (doctor assess for a second time the same parameters after an intervall of exact 5 sec.) give useful information: in healthy, lt is more than 12 sec.; on the contrary, in subject at real risk of type 2 diabetes latency time either appears unchanged or clearly reduced, in relation to the severity of underlying metabolic disorder.

For further information See other article in www.schiphu.com an especially my website www.semeioticabiofisica.it .

1) Stagnaro S., Istangiopatia Congenita Acidosica Enzimo-Metabolica condizione necessaria non sufficiente della oncogenesi. XI Congr. Naz. Soc. It. di Microangiologia e Microcircolaz. Abstracts, pg 38, 28 Settembre-1 Ottobre, 1983, Bellagio

2) Stagnaro S., Istangiopatia Congenita Acidosica Enzimo-Metabolica. X Congr. Naz. Soc. It. di Microangiologia e Microcircolazione. Atti, 61. 6-7 Novembre, 1981, Siena

3) Stagnaro S., Istangiopatia Congenita Acidosica Enzimo-Metabolica. Una Patologia Mitocondriale Ignorata. Gazz Med. It. Arch. Sci. Med. 144, 423, 1985 (Infotrieve).

4) Stagnaro S. Diet and Risk of Type 2 Diabetes. N Engl J Med. 2002 Jan 24;3 (Medline) 5) Stagnaro-Neri M., Stagnaro S., Semeiotica Biofisica: la manovra di Ferrero-Marigo nella diagnosi clinica della iperinsulinemia-insulino resistenza. Acta Med. Medit. 13, 125, 1997.

6) Stagnaro-Neri M., Stagnaro S., Semeiotica Biofisica: valutazione clinica del picco precoce della secrezione insulinica di base e dopo stimolazione tiroidea, surrenalica, con glucagone endogeno e dopo attivazione del sistema renina-angiotesina circolante e tessutale Acta Med. Medit. 13, 99, 1997.

7) Stagnaro Sergio. Newborn-pathological Endoarteriolar Blocking Devices in Diabetic and Dislipidaemic Constitution and Diabetes Primary Prevention. The Lancet. March 06 2007. http://www.thelancet.com/journals/lancet/article/PIIS0140673607603316/comments?totalcomments=1, and especially www.fce.it, http://www.fceonline.it/docs/stagnaro.pdf

8) Stagnaro Sergio. New bedside way in Reducing mortality in diabetic men and women. Ann. Int. Med. http://www.annals.org/cgi/eletters/0000605-200708070-00167v1

9) Stagnaro S., Stagnaro-Neri M. Valutazione percusso-ascoltatoria del Diabete Mellito. Aspetti teorici e pratici. Epat. 32, 131, 1986.

10) Stagnaro S., Stagnaro-Neri M., Le Costituzioni Semeiotico-Biofisiche.Strumento clinico fondamentale per la prevenzione primaria e la definizione della Single Patient Based Medicine. Travel Factory, Roma, 2004. http://www.travelfactory.it/

11) Stagnaro S., Stagnaro-Neri M., Le Costituzioni Semeiotico-Biofisiche.Strumento clinico fondamentale per la prevenzione primaria e la definizione della Single Patient Based Medicine. Travel Factory, Roma, 2004. http://www.travelfactory.it/

12) Stagnaro S., Stagnaro-Neri M., Single Patient Based Medicine.La Medicina Basata sul Singolo Paziente: Nuove Indicazioni della Melatonina. Travel Factory, Roma, 2005. http://www.travelfactory.it/

INSULIN SECRETION ACUTE PICK TEST AND RENAL TEST OF HYPERINSULINEMIA-INSULINRESISTANCE.

noreply@blogger.com (Stagnaro) — Thu, 16 Apr 2009 16:12:00 +0000

Introduction.

Since decades, it is generally admitted that insulin represents an hormone or signal, which comunicates to muscular, hepatic and adipose cells the information necessary to blood glucose up-take, and utilize it in order to produce energy, unavoidable to survival.

As regards Quantum-Biophysical Semeiotics and especially Clinical Microangiology, “endogenous” insulin, obtained by the acute pick test of insulin secretion, is useful, due to its different and opposite action on tissue-microvascular unit of various biological systems under physiological and pathological conditions, even if the later are initial or early or “potential”, as demonstrates the particular microcirculatory activation in post-absorptive state as well as in absorptive state, described previously (See www.semeioticabiofisica.it, and the linked website www.Microangiology.it).

Really, insulin is also a growth-factor, which modulates proteasomic activity and stimulates ILGF₁-receptors, beeng active similarly on parenchyma and related microcircle.

Analogously to GH, as I demonstrated clinically (See Bibliography in the site), in both tissues at “real” risk for disease, i.e., in the so-called pre-morbid-stage, grew zone, pre-metabolic syndrome and in initial or light morbid phase, without any clinical phenomenology, the acute pick test of insulin secretion provokes exclusively the increase of arteriolar blood-flow and, thus, “opening” of AVA, functionally speaking (EBD obviously appear “closed” for a time longer than normal under similar conditions) and, then, it follows that there is microcirculatory activation, dissociated, type II or III (intermediate), i.e., increased vasomotility, but contemporaneously reduced or respectively “normal” vasomotion (1-13), so that it is present the dangerous micorcirculatory phenomenon of the “centralization” of blood-flow, more or less severe, throughout microvessels.

Such as pathological phenomenon accounts for the reason that tissue O₂as well as locale pH are reduced, as doctor can assess in a quantitative manner by Quantum-Biophysical Semeiotics: both gastric aspecific and caecal reflex show a reduced latency time, a prolonged duration (³ 4 sec.) and lowered differential lt (= reduced fractal dimension of both tissue and microvascular non-linear dynamics of the studied biological system), while choledocic reflex , i.e. choledocic contraction, during apnea test shows a duration lasting more than the physiological one (NN > 3 < style=""> fD).

Once again, these parameters values underscore the internal and external coherence of the biophysical-semeiotic theory, to which we shall come back often, due to its epistemological significance: as we have really frequently stated, internal and external coherence of whatever scientific theory does not surely coincide with its “thrut”, but it represents the conditio sine qua non of such as thrut.

Insulin Microvascular Action Mechanisms: Insulin-Secretion Acute Pick Test.

The dual effect of insulin through receptor activation is nowadays generally admitted, as follows: one is based on the insulin receptor substrates (IRSs); the other goes through a different class of molecules known as Shc, which leads to the activation of the mitogen-activated protein kinase (MAPK) pathway. Under insulin resistance condition, there is a pro-atherogenic effect that is mediated through activation of MAPK activated by the increased insulin levels, while the non-atherogenic pathway through phosphatidylinositide-3-kinase (PI3-kinase) activation, responsible for glucose transport, as well as nitric oxide (NO)-mediated-vasodilation are attenuated. Activation of the angiotensin II receptor further magnifies the pro-atherogenic effect (14). Since now, we can understand already the real reason of vasoconstriction brought about by insulin in presence of insulin-resistance.

In other words, insulin-dependent “pathological” vasocostriction parallels insulin-resistance. In addition, although the majority of patients with IGT have the metabolic syndrome (IIR), the latter can also be present in individuals before they develop IGT (14), i.e., in the Pre-Metabolic Syndrome, possibly evolving to Metabolic Syndrome, as I suggested previously, for long time (See the linked website www.microangiology.it: Pre-Metabolic Syndrome).

At this point, one must consider the primary role played by central adiposity in the occurrence of IIR and pre-metabolic and metabolic syndrome, all authors agree with. Patients with insulin resistance have low adiponectin levels that can improve, e.g., after weight loss (See www.semeioticabiofisica.it, Practical Applications). Resistin, another adipokine, appears to antagonize the effects of insulin on glucose homeostasis and to contribute to insulin resistance in animals (15) Further studies are necessary to clarify the role in human physiology and pathophysiology. Abdominal or visceral fat cells are also responsible for the formation and release of toxic proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and serum amyloid A (16). These cytokines contribute to insulin resistance and play an important role in accelerating the atherogenic process. Finally, central adiposity is also associated with high levels of PAI-1, causing impaired fibrinolysis and contributing to the development and progression of CVD (16).

In diseased parenchymas, even seemingly healthy from the clinical view-point, insulin induces tissue-microvascular modifications of great diagnostic importance: for instance, digital “light-moderate” pressure, applied on whatever joint at “real” risk of rheumatic disease or, of course, involved slightly or initially by a form of connectivitis, e.g., causes the occurrence of deterministic chaotic fluctuations of both upper and lower ureteral reflexes, showing a fD of 3,81, or slightly altered.

In other words, both vasomotility and vasomotion appear to be apparently normal or show really slight modification, so that rheumo-gastric aspecific reflex and/or caecal reflex latency time results only slight reduced or normal (NN = 8 sec.), reflex duration slight prolonged, i.e., ³ 4 sec. (NN <> 4 sec.: f D = 3,8).

By contrast, after the acute pick of insulin secretion, under above-mentioned pre-morbid situation, we observe intense microcirculatory modifications of “vasomotion”, i.e., blood-flow “centralization”, reduced blood supply to parenchyma, and consequently histangic acidosis, which brings about reduced insulin- as well as adrenergic-receptors sensitivity.

In other words, the secretion of acute insulin pick displays the “latent” abnormality of Microcirculatory Functional Reserve in biological systems or their regions, in which there is not at this moment any disorders, causing a behaviour changing similar to that induced by biophysical- semeiotic preconditioning (See Glossary in the website www.semeioticabiofisica.it), which is a clinical tool really efficacious in the research, diagnosis, and therapeutic monitoring. Such as topic has been in detail discussed in former article in the site www.microangiologia.it.

Other numerous applications of this test provide doctor bed-side useful information, allowing the refined investigation of all biological systems, starting from the potential or initial stages of the local disorder, for instance, in “real risk” of malignancy.

In healthy, digital pressure applied on radial artery is followed by occurrence of “in toto” ureteral reflex, 1 cm. in intensity, which increases after the test illustrated above: normal arterial compliance.

On the contrary, in case of reduced arterial compliance, as it happens, e.g., in both arterial hypertension and arteriosclerosis, starting from the stage of “real” risk, i.e., early stage, characterized generally by hyperinsulinemia-insulinresistance, detected by Quantum-Biophysical Semeiotics, basal “in toto” ureteral reflex is < 1 cm. and it lowers after insulin secretion acute pick test, due to pathological vasoconstriction (17-20).

Notoriously, under such as conditions the hormone brings about negative phenomena in micro-and macro-vessels, characterized by “vasospasm”, as consequence of the increase of PKC as well as of free oxygen radicals. caused by insulin in pathological conditions, even initial, as grew , pre-morbid stage or grew zone. It is a matter of vessel behaviour similar to that observed in case of acetyl-choline, which in healthy dilates the arteries, while in presence of functional or structural endothelial damage brings about notoriously vasospasm.

In conclusion, both tissue and microvascular response to transitory endogenous jatrogenetic hyperinsulinemia is really different in healthy subject, in individual at “inherited real risk” of degenerative, metabolic or oncological disease (See biophysical constitutions in the first website) and, of course, in diseased subject, even in absence of clinical phenomenology, as consequence of diverse receptor response to the hormone under different conditions.

Therefore, it is possible to utilize the twofold behaviour of biological systems in case of increased insulin blood level (insulin secretion acute pick test) aiming to diagnosis and prevention, utilizing the different, opposite, receptors responsiveness of smooth muscle cells to insulin, but also to catecholamines (apnea test or Restano’s manoeuvre) as well as to acetylcholine (Valsalsa’s manoeuvre)

From the above remarks, it appears clear the patho-physiology of histangic ph lowering during the test, where whatever diease is already present or it will occur.

Consequently, it is not surprising our opinion, based on a long clinical experience, that CAEMH-a represents the conditio sine qua non of most common and dangerous human diseases: DM, Dyslipidemia, ATS, Rheumatic disorders, malignancies, Arteral Hypertension, a.s.o.

The relation, we demonstrated “clinically” and surely existent, between insulin and sympathetic nervous system, as well as that between hyperinsulinemia and insulinresistance, is not nowadays interpreted in the same way by the authors. In other words, authors do not agree on the primary cause between the two hormonal alterations.

The following biophysical-semeiotic experimental evidence – “insulin secretion acute pick test” – demonstrates, in healthy, that jatrogenetic hyperinsulinemia is immediately followed by type I, associated microcirculatory activation of supra-renal gland (AL + PL = 8 sec.) and, then, by “sympathetic hypertonus”, event on which all authors agree, and we demonstrated by sophysticated semeiotics: lower mesenteric plexus-caecal reflex (= in practice, digital pressure on the area below umbelicus, slightly at right) shows a basal duration > 10 sec. (NN = 10 sec.). In fact, under normal condition, digital pressure brings about caecal dilation of about 3 cm., lasting 10 sec. exactly.

By contrast, after 10 sec. from the beginning of Restano’s manoeuvre (= sympathetyc hypertonus: see Glossary) reflex duration is > 10 sec. due to sympathetic hypertonus, while after 7-10 sec. from Valsalva’s manoeuvre starting the duration of caecal dilation lowers significantly to <>

To summarize, hyperinsulinemia, beside all other actions, provokes notoriously sympathetic hypertonus, as allows us to state Quantum-Biophysiacal Semeiotics. On the other site, the stimulation of supra-renal trigger-point (the skin of hypocondrium immediately below the costal arch along anterior ascellar line) brings about increasing of supra-renal gland volume, and successively that pancreatic one, with subsequent augmentation of insular hormonal secretion.

The data, referred above, demonstrate that both biological systems activate each other reciprocally by positive feed-back mechanisms. At this point, however, in health, the positive arm of the “biological cross” of psycho-neuro-endocrine-immunological system, i.e., SST, melatonin, endogenous oppioids, which controls insulin, epinephrine and nor-epinephrine secretion, leading it in normal ranges in an opposite way to that occurs in presence of “Oncological Terrain” (See Oncological Terrain in my above-cited website).

With regards to this argument, it is useful to underline the importance of dismetabolic-dishormonal components – hyperinsulinemia-insulinresistance – as well as that of sympathetic hypertonus in the pathological pre-morbid condition, I termed “Oncological Terrain”.

Hyperinsulinemia-Insulinresistance Renal Test.

As follows, it is described a further interesting and reliable test to evaluate hyperinsulinemia-insulinresistance: hyperinsulinemia-insulinresistance renal test (See Glossary in above-cited website).

In health, acute pick of insulin secretion, performed as illustrated formerly, after a latency time < productid="3 cm" st="on">3 cm. with duration of 10 sec. precisely.

“Vasomotion” duration last (AL + PL Phase) 8 sec. (NN = 6 sec.), analogously to what we observe during the atrial natriuretic peptides renal test (See above-cited website in Practical Application).

Similarly to what doctor observes in both cardiac failure and coronary artery disease, as regards “atrial” natriuretic peptides, due to renal receptors down-regulation, the physiological increasing of kidney augmentation during acute pick of insulin secretion test appears to be slightest, not significant, very short or absent (= intensity < 2 cm. and duration £ 8 sec.), allowing bed-side assessment of a pathological situation, really dangerous, and otherwise impossible to be recognized, because it is at the moment completely asymptomatic: hyperinsulinemia-insulinresistance.

Moreover, the “quantitative” evaluation of increasing lt of renal diameters during the performance of acute pick insulin secretion test as well as augmentation rate of kidney size permit to “quantify” the seriousness of underlying pathological disorder.

In conclusion, renal test of hyperinsulinemia-insulin resistance results both quantitatively and qualitatively “abnormal” in disorders, even initial, of glucose metabolism: in Diabetes Mellitus, kidney does not increase the size or the increase of their diameters is not at all significant from the statistical view-point.

References.

1) Stagnaro-Neri M., Stagnaro S. Indagine clinica percusso-ascoltatoria delle unità microvascolotessutali della plica ungueale. Acta Med. Medit. 4, 91 ,1988.
2) Stagnaro-Neri M., Stagnaro S., Auscultatory Percussion Evaluation of Arterio-venous Anastomoses Dysfunction in early Arteriosclerosis. Acta Med. Medit. 5, 141, 1989

3) Stagnaro-Neri M., Stagnaro S., Il Glutatione nella terapia microvascolare. Act Med. Medit. 7, 11, 1991

4) Stagnaro-Neri M., Stagnaro S., Sul meccanismo d’azione di Sulodexide a livello di correlazioni istangiche acrali patologicamente alterate: studio clinico percusso-ascoltatorio. Giornate Naz. di Angiologia. Milano, 23-29 Giugno 1991. Atti Min. Med., 40, 1991 (Infotrieve)

5) Stagnaro S., Stagnaro-Neri M. Il danno da radicali liberi sul microcircolo. Congr. Naz. SISM., Milano, 10 giugno 1991, Comun. Atti, Min. Angiologica (Suppl. 1 al N° 1) 16,398, 1991.

6) Stagnaro-Neri M., Stagnaro S., Modificazioni della viscosità ematica totale e della riserva funzionale microcircolatoria in individui a rischio di arteriosclerosi valutate con la percussione ascoltata durante lavoro muscolare isometrico. Acta Med. Medit. 6, 131-136, 1990.

7) Stagnaro S., Stagnaro-Neri M., Basi microcircolatorie della semeiotica biofisica. Atti del XVII Cong. Naz. Soc. Ital. Studio Microcircolazione, Firenze ott. 1995, Biblioteca Scient. Scuola Sanità Militare, 1995, 2, 94.

8) Stagnaro S., Stagnaro-Neri M., Il test della Apnea nella Valutazione della Microcircolazione cerebrale in Cefalalgici. Atti, Congr. Naz. Soc. Ita. Microangiologia e Microcircolazione. A cura di C. Allegra. Pg. 457, Roma 10-13 Settembre 1987. Monduzzi Ed. Bologna, 1987.

9) Stagnaro S., Valutazione percusso-ascoltatoria della microcircolazione cerebrale globale e regionale. Atti, XII Congr. Naz. Soc. It. di Microangiologia e Microcircolazione. 13-15 Ottobre, Salerno, e Acta Medit. 145, 163, 1986.

10) Stagnaro-Neri M., Stagnaro S., Deterministic chaotic biological system: the microcirculatoory bed. Theoretical and practical aspects. Gazz. Med. It. – Arch. Sc. Med. 153, 99, 1994.

11) Stagnaro-Neri M., Stagnaro S., Radicali liberi e alterazioni del microcircolo nelle flebopatie ipotoniche costituzionali. Min. Angiol. 18, Suppl. 2 al N. 4, 105, 1993.

12) Stagnaro S., Stagnaro-Neri M. Il danno da radicali liberi sul microcircolo. Congr. Naz. SISM., Milano, 10 giugno 1991, Comun. Atti, Min. Angiologica (Suppl. 1 al N° 1) 16,398. 1991.

13) Stagnaro-Neri M., Stagnaro S. Introduzione alla Semeiotica Biofisica. Il Terreno Oncologico. Travel Factory, Roma, in stampa.

14) Pantaleo A., Zonszein J. Using Insulin as a Drug Rather Than as a Replacement Hormone During Acute Illness: A New Paradigm, http://www.medscape.com/viewarticle/463524_print , Heart Dis 5(5):323-334, 2003.

15) Janke J, Engeli S, Gorzelniak K, et al. Resistin gene expression in human adipocytes is not related to insulin resistance. Obes Res. 2002;10:1-5.

16) Kahn BB, Flier JS. Obesity and insulin resistance. J Clin Invest. 2000;106:473-481.

17) Stagnaro S., West PJ., Hu FB., Manson JE., Willett WC. Diet and Risk of Type 2 Diabetes. N Engl J Med. 2002 Jan 24;346(4):297-298. [Medline]

18) Stagnaro Sergio. Newborn-pathological Endoarteriolar Blocking Devices in Diabetic and Dislipidaemic Constitution and Diabetes Primary Prevention. The Lancet. March 06 2007. http://www.thelancet.com/journals/lancet/article/PIIS0140673607603316/comments?totalcomments=1 SEE particularly URL: http://www.fceonline.it/docs/stagnaro.pdf

19) Stagnaro S. Pre-metabolic syndrome: the real initial stage of metabolic-syndrome, type 2 diabetes and arteroscleropathy. Cardiovascular Diabetology 3:1 http://www.cardiab.com/content/3/1/1/comments

20) Stagnaro Sergio. Bedside recognizing diabetics with or without CHD real risk or silent CHD. BMC Cardiovascular Disorders 2006, 6:41 http://www.biomedcentral.com/1471-2261/6/41/comments#243544

BIOPHYSICAL SEMEIOTIC DIAGNOSIS OF ACUTE APPENDICITIS .

noreply@blogger.com (Stagnaro) — Thu, 16 Apr 2009 05:29:00 +0000

Introduction.

In former articles about acute appendicitis diagnosis, the Authors constantly ignore the clinical diagnosis made with the aid of auscultatory percussion, for the first time described in 1987 (5) (See: www.semeioticabiofisica.it, Practical Applications), which recently was enriched by numerous signs, collected at the bed-side by means of the Biophysical Semeiotics (1,2,3,6), method of investigation based chiefly on auscultatory percussion, and completely described as follows.

Because of the insufficient reliability of the traditional physical semeiotics and since the classic history of anorexia and periumbilical pain, followed by right lower quadrant pain and vomiting, is present in fewer than 60% of cases, 30% of surgical operations are made, unfortunately, on healthy appendix [does it really exsist the white appendicitis?] and surely a larger percentage regards late operations.

Really, at least in some cases, there is neuroproliferation in the appendix, in association with an increase in cytochines and neurotransmitters SP and VIP; this event may be involved in the pathophysiology of acute right abdominal pain in the absence of an acute inflammation of the appendix (8). In my opinion, due to the relation between neurologic system and immunological system (See Oncological Terrrain in my site HONCode 233736 at URL www.semeioticabiofisica/oncological.htm) it is possible the existence of neuroappendicitis.

Biophysical Semeiotics, based on auscultatory percussion, auscultatory percussion reflex-diagnostics, and on the use of mathematical models of non-linear physics allows doctor to recognise rapidly as well as easily a large number of signs, among them tonic Gastric Contrection Sign (tGC), Berti-Riboli’s Sign, and Bella’s Sign, present in 100% of the cases, regardless the location and the severity of appendicitis, as a 45-year-long clinical experience permits me to state (1-6).

Biophysical-semeiotic diagnosis of the appendicitis. Tonic Gastric Contraction, Berti-Riboli’s, and Bella’s signs.

Tonic Gastric Contraction (tGC) permits by itself to evaluate both the presence and the seriousness of appendicitis, i.e. therapeutic monitoring, performed also with the aid of other numerous biophysical semeiotic signs, which are divided in “common” – inflammation signs observed in all processes, infective, connectival, tumoural in origin – and “specific” , i.e. present exclusively in the appendicitis (1,2,3,5).

Among other important signs of inflammation, I remember at first the Rethiculo-Endothelial System Hyperfunction Syndrome (RESHS), now known as Monocytes-Macrophages System (2,3), Acute Antibodies Synthesis Syndrom (AASS), and the increase of Acute Phase Proteins production (4,5) (See in my above-cited site, Practical Applications).

RESHS corresponds to the ESR raising and to altered proteins electrophoresis, but is of both more sensitive as well as specific (1,2,3,6). To detect these signs and syndromes, from the technical viw-point, doctor has to know only the Auscultatory Percussion of the stomach (Fig.1), really easy to perform, described even in the classic text-books , such as Rasario, IX edition.

At this point, in the interest of reader, who is not yet skilled of biophysical semeiotic technique, in the following I refer particularly some signs, which doctor can easily observe at the bed-side by auscultatory percussion evaluation of the stomach.

Fig. 1 Fig. 2

In practice, a short segment of stomach great curvature in its lower part, as indicated in Fig.1 (arrows upwards), is detected, useful in ascertaining some important, above-describred signs, unavoidable to recognize the appendicitis: with the bell-piece of sthetoscope (bps) properly located – a patient’s finger fixes the bps – doctor applies digital percussion as usually, i.e. with middle finger slightly bended, functioning as “a little hammer”, directly and gently (i.e. with slight intensity) on the skin, two times on the same point, moving than towards the bell piece of stethoscope, along radial and centripetal lines, starting from te umbelical horizontal line.

When digital percussion is applied “directly” on cutaneous projection area of the stomach (or of whatever viscera, e.g. caecum), percussion sound is perceived clearly modified, hyperfonetic, and “it seems to originate near to the doctor’s ears” (5).

In healthy, the reflex lasts > 3 sec. < time =" fractal">

The doctor evaluates the RESHS by the aid of digital pressure of “mean” intensity applied on the median line of sternal (breast-bone) body, iliac crests and cutaneous projection area of the spleen: in healty individual, after a latency time (lt) of 10 sec. exactly, both fundus and body of the stomach dilate – 1-2 cm. – whereas antro-pyloric region contracts (Fig.2) (gastric aspecific reflex, vagal type) (See: Technical Page N° 1, in Home-Page).

On the contrary, in whatever infectious (caused by Gram +) as well as connective disorder, malignant tumour, a.s.o., lt appears lower than normal, i.e. 6 sec. ( 3 sec. in case of cancer, apart from the initial stages), in relation to the degree of disorder, and dilation is > 2 cm.: RESHS “complete”.

As a matter of facts, there are two other types of this syndrome: a) RESHS “incomplete”, characteristic of flu: spleen does not synthesize acutely antibodies (where lt of spleen-gastric aspecifix reflex is 3 sec. during slight digital pressure), consequently pressure of “mean” intensity on spleen projection area cannot bring about the gastric aspecific reflex after pathological lt; b) RESHS “intermediate” is typically present in case of infectious diseases, caused by bacteria Gram -, as E.coli e H.pylori, characterized by the fact that gastric aspecific reflex is clearly less intense when digital pressure stimulates splenic trigger-points. In other words, in case of Gram- infections, splenic-gastric aspecific reflex is present, but “smaller” than breast-bone or iliac crests-gastric aspecific reflex, allowing doctor to recognize at the bed-side the real nature of bacteriological agents, causing the disease. The reduction of spleen antibodies synthesis accounts for the reason that the RESHS is termed “intermediate”.

In very initial stages of whatever disorder, if this syndrome appears to be negative, doctor has to evaluate RESHS in a “sensitive” manner, i.e. with boxer’s test, apnea test, Restano’s manoeuvre (= the two tests are simultaneously applied), lasting roughly 10 sec. (sympathetic hypertone): after 3 sec. a gastric aspecific reflex appears, ³ 2 cm in intensity, with a reinforcing after <> (NN: 1 cm. and reinforcing lt ³ 9 sec., respectively) (See. Glossario in Home-Page).

The Antibodies Synthesis Syndrome (ASS) can be easily ascertained by means of gastric aspecific reflex, caused by “slight” digital pressure, applied on whatever MALT (mucose associated lymphatic tissue) site, e.g. on cutaneous projection area of the liver, appendix, breast, anterior thorax wall, along mean clavicular line (BALT), on spleen (except for flu), a.s.o.: in healthy, lt is 6 sec. exactly and intensity 1-2 cm.: ASS type chronic. On the contrary, in case of acute appendicitis, lt drops to 3 sec. exactly and the reflex intensity is > 2 cm.: ASS type acute.

Interestingly, a diseased appendix does not synthesize antibodies at all; therefore, are locally absent both ASS acute and chronic. Identical behaviour show all other biological systems, which physiologically synthetize antibodies: in case of wathever local disorder, regional antibodies synthesis appears interrupted. For instance, in a breast involved by cancer, even in initial stage, acute type of ASS is locally absent, at least in the precise area of the tumour. (I can not describe “here and now” interesting modifications of the microcirculation in cancer, due to technical lack of reader’s knowledge).

At this point, in order to recognize and “quantitatively” evaluate the tGC Sign doctor applies digital pressure on appendix cutaneous projection, possibly localized by auscultatory percussion; after a latency time £ 6 sec. (NN = 10 sec.), digital pressure brings about intense gastric aspecific reflex, followed by tGC.

Thereafter, doctor asks the patient “to press down its abdomen as to evacuate” (simulated evacuation test); practically patient is invited to carry out Valsalva’s manoeuvre, that causes the same sign – Berti-Riboli’s Sign – likely when physician (the manoeuvre is most refined) applies digital pressure precisely on cutaneous projection area of the inflammed appendix, previously localized by means of auscultatory percussion (Fig.2): immediatly (1-3 sec.) stomach dilates (i.e. the gastric aspecific reflex suddenly appears), then, after 3 sec. precisely, stomach contracts rapidly in intense manner: TGC Sign of ³ 2 cm. (3,6) (Fig.2).

In healty individual, in identical condition, gastric aspecific reflex lt is 10 sec., duration > 5 sec. and, finally, TGC <>

In case of retrocaecal appendicitis, until now really difficult to recognize clinically with the aid of old, accademic, physical semeiotics, the patient bends its stretced right leg towards abdomen: the “spontaneous” TGC suddenly appears (100% of cases), after a gastric aspecific reflex with 1-2 lt and lasting once more 3 sec.: Bella’s Sign “classic” (Bella’s Sign “variant”: patient bends the left leg in identical manner as described above, with the same results in case of appendix located in left ileo-pelvic region).

In healthy, in identical above-described conditions, lt of gastric aspecific reflex is 10 sec., duration >5 sec. and TGC intensity is < 2 cm. Interestingly, the degrees of reflexes paramaters are the same in both signs, pointing out internal and external coherence of biophysical semeiotic theory.

As regards the evaluation of Acute Phase Proteins, completely described in my above-cited site, it is sufficient to stimulate hepatic trigger-point by a finger-nail and assess the patological hepato-gastric aspecific reflex, absent in healthy, showing a latency time of 3 sec., which becomes greater untill disappears when appendicitis ameliorates as far as the restitutio ad integrum.

BIOPHYSICAL-SEMEIOTIC SIGNS OF APPENDICITIS

“COMPLETE” RESHS

ACUTE PHASE PROTEINS AND OTHER SIGNS OF INFLAMMATION ANTIBODY SYNTHESIS ACUTE SYNDROME

BERTI-RIBOLI’S SIGN

DI BELLA’S SIGN

APPENDIX ENLARGEMENT

ABSENCE OF PHYSIOLOGICAL PERISTALSIS

CLINICAL MICROANGIOLOGICAL SIGNS

Tab.1

Clinical microangiology of acute appendicitis.

Other numerous biophysical semeiotic signs (detectable by doctor skilled of the new method) and described in earlier articles (16-22), are illustrated in following.

Auscultatory percussion, accurately performed, allows doctor to recognize the increase, even small, of appendix transverse diameter: ³ 1 cm. (NN = 0,5 cm.), due to edema-infiltration-endoluminal effusion. Contemporaneously, physiological appendicular peristalsis is absent: in healthy, every 18 sec. one can observe, with the aid of auscultatory percussion, a wave moving from a pace-maker localised at the bottom of viscera as far as to its meatus.

In a 45-year-long bed-side experience, infact, clinical-microangiological signs proved to be really essential in corroborating appendicitis diagnosis, made on the base of above-described signs (Tab.1), so that in folowing they are illustrated in detail.

From the practical point of view it is sufficient and reliable to evaluate periods as well as intensity of low ureteral reflex oscillation (= vasomotion), for example, during mean digital pressure, applied upon the middle third of biceps muscle, compressing it between thumb and other fingers, of a supine individual, psychophysically relaxed. The pressure on whatever scheletric muscle (e.g. biceps muscle between the thumb and the other fingers) allows doctor to examine resistance microvessels dynamics and flowmotion along nutritional capillaries.

However, the original morphological analysis of vasomotion, i.e., the precise evaluation of low ureteral reflex oscillations, interestingly reveals the actual condition of related tissue-micro vascular-units, in a synergetic model. In order to realize this analysis, it is unavoidable to transfer upon Cartesian coordinates intensity (ordinate, cm) and duration (abscisse, sec.) of three successive fluctuations of low ureteral reflex, observed, for example, in the above-mentioned situation, during biceps muscle microvascular units stimulation.

In healthy, we observe a characteristic diagram (Fig. 3).

Fig. 3

Interestingly, in 3 sec (ascending line: AL in Fig.4) oscillation reaches its highest intensity (normal intensity is varying from 0,5 to1,5 cm); the "plateau" line (PL) lasts physiologically 3 sec, then in 1 sec (descending line: DL) the line returns to the basal value (i.e. abscisse), where persists for 2-5 sec, varying the periods from 9 to 12 seconds under physiological conditions.

On the contrary, in pathological situations, e.g. essential hypertension, the diagram results interestingly modified (Fig.4): AL as well as DL are normal, 3 sec. and 1 sec respectively; intensity is approximately 0,5 cm, in a "predictable" manner; the physiological highest waves, i.e. highest spikes of 1.5 cm intensity (HS), are absent.

Fig.4

Finally, in case of hyperfunctioning tissues, e.g. the bone-marrow during infective disorders of whatever nature, digital pressure upon the middle line of breast bone, brings about low ureteral reflex oscillations, characterized by PL of 5 or more sec, intensity as well as periods practically identical each other (Fig. 5). Intensity and PL of every oscillation are directly correlated: more high the intensity, more prolonged appears PL and consequently more efficacious is the flow-motion of related nutritional capillaries.

Fig. 5

This clinical evidence underlines the inner consistence of Biophysical Semeiotics.

In addition, superimposing the parameters of three subsequent oscillations of low ureteral reflex, in accordance with the lenght of single period, we realize really interesting figures. In healthy people the obtained area shows a "strange" shape, like a "strange" attractor (Fig. 6): fractal dimension (fD) >3 (16-19), that corresponds to the space occupied by a fractal structure.

Fig. 6

Strange attractor: healthy subject.

On the contrary, under pathological condition, e.g. essential hypertension as far as biceps muscle microcirculatory bed is concerned, the area obtained in this manner appears quite small, resembling an attractor at fixed point (Fig. 7).

Fig. 7

Fixed point attractor: hypertensive patient

Finally, the area corresponding to hyperfunctioning microcirculatory units results the largest one, due exclusively to its large Euclidean perimeter; its shape, however, resembles clearly a deformed circle, corresponding to a “closed loop” attractor (Fig. 8) (23, 24).

Fig. 8

Closed loop attractor in hyperfunctioning bone-marrow.

From the above remarks it results that morphological analysis of vasomotion, by means of Biophysical Semeiotics, in physiological as well as in pathological conditions, represents an original, reliable and usefull tool in clinics, research, and therapeutic monitoring, as allows me to state a long, well established experience. (For further information on this topic, See my site www.semeioticabiofisica.it/microangiologia).

Discussion.

The general practitioner, who knows Biophysical Semeiotic in a safe, satisfactory manner, certainly is able to diagnose, promptly and clinically, the appendicitis, regardless of its clinical phenomenology, seriousness of the disease or site of appendix, even with the above-described signs.

A long, well established experience allows me to state that, by means of Biophysical Semeiotics, the diagnosis of appendicitis is a clinical one. Unfortunately, now-a-days bed-side diagnosing appendicitis is still often difficult and actually this fact accounts for the reason that a large number of patients are operated to late.

In fact, although acute appendicitis is the most common disease of the appendix, other potential pathologic conditions affecting the appendix include swallowed foreign bodies, pinworms, fecaliths, carcinoids, cancer, villous adenomas, and diverticula. The appendix may also be involved in idiopathic ulcerative colitis or the ileocolitis of Crohn's disease (15).

Except for hernia, acute appendicitis is the most common cause in the USA of an attack of severe, acute abdominal pain that requires abdominal operation. Because symptoms and signs vary widely and because delay before operation is so hazardous, it is accepted that nearly 15% of operations for acute appendicitis lead to other findings at laparotomy or even to findings of no disease.

Acute appendicitis is common, but its aetiology remains "vague and indefinite" (8). The causes of appendicitis are not well understood, but it is believed to occur as a result of one or more of these factors: an obstruction within the appendix, the development of an ulceration (an abnormal change in tissue accompanied by the death of cells) within the appendix, and the invasion of bacteria.

Under these conditions, bacteria may multiply within the appendix. The appendix may become swollen and filled with pus (a fluid formed in infected tissue, consisting of while blood cells and cellular debris), and may eventually rupture. Signs of rupture include the presence of symptoms for more than 24 hours, a fever, a high white blood cell count, and a fast heart rate.

However, skilled doctor knows very well that the disease in a large number of cases goes on in a really different way: clinical phenomenology appears difficult and surely not useful in bed-side diagnosing appendicitis.

In the latter part of the 19th century, an eminent text noted that it had become quite common in "highly civilized countries such as Great Britain", with lower occurrence rates in Denmark and Sweden (9). A perforated appendix found in an Egyptian mummy, however, indicates that the disease has been around since ancient times (10).

Originally known as perityphlitis (Greek; peri, around + typhlos, blind + -itis, inflammation), the disease was described by John Hunter in a case at autopsy in 1769 (10); the first use of "appendicitis" is credited to Fitz, who used the term at the inaugural meeting of the Association of American Physicians in 1886 (10).

One of the earliest aetiological theories for acute appendicitis (to which our mothers still subscribe) is that a small foreign body, such as a seed, might lodge in the appendix, thus initiating an acute inflammatory reaction (11). Such as cause of appendicitis is surely possible, but really rare (12).

In 70% of patients with acute appendicitis, the diagnosis is made clinically based on classic signs and symptoms. In the remaining 30% of patients with uncertain clinical findings, radiologic imaging is needed to establish the diagnosis, obviously if doctor ignores the Biophysical Semeiotics. Both graded compression sonography or CT can be utilized, when it is possible, of course, to evaluate patients with suspected appendicitis, but certainly not on large scale. Advantages with sonography include lower cost and real-time observation of bowel peristalsis, which can be evaluated by means of the original physic semeiotics. Ultrasound is also superior to CT in diagnosing gynecologic diseases which may mimic appendicitis: as well known Biophysical Semeiotics allows doctors to proceed without doubt in the differential diagnosis. CT is performed in patients with marked obesity, tense ascites or severe pain in whom sonography may be technically difficult or non-diagnostic. CT is also preferred in patients likely to have an abscess (13). Every doctor, particularly if general practitioner, knows that at the bed-side such sophysticated semeiotics are not to be utilized at all.

Sonographic criteria for acute appendicitis include a noncompressible appendix with an outer AP diameter of at least 7 mm, mural thickness of 3 mm or greater, or presence of an appendicolith in an appendix of any size. Presence of a hypoechoic fluid collection containing an appendicolith or a fluid collection adjacent to a gangrenous appendix is diagnostic of a periappendiceal abscess. Percutaneous drainage of large periappendiceal abscesses prior to appendectomy can be performed under both CT or ultrasound guidance.

In experienced hands, graded compression sonography has a greater than 90% accuracy for diagnosing acute appendicitis, surely less than the accuracy of the sign of Gastric tonic Contraction. False-negative diagnoses may occur in retrocecal appendicitis, perforated appendicitis or in pregnant patients, when Biophysical Semeiotics permitts easily to recognize appendicitis, even retrocecal and in pregnant woman. False-positive results may be seen in women with a dilated fallopian tube or in inflammatory conditions such as tubo-ovarian abscess or Crohn's disease, which may secondarily affect the appendix.

The majority of patients imaged for right lower quadrant pain do not have acute appendicitis. In up to 70% of these patients, sonography may detect alternative diagnoses such as salpingitis, Crohn's disease, bowel obstruction, ureteral calculi or degenerating uterine leiomyomas, that is, diagnoses correctly made with properly applyied Biophysical Semeiotics (1, 3, 5) (See above-cited site).

Researchers have developed a more accurate method of diagnosing appendicitis that may spare thousands of children who develop the potentially fatal problem unnecessary pain and complications, if doctor is ot skilled of Biophysical Semeiotics. A new study documents for the first time in children the diagnostic accuracy of a technique known as computerized tomography with rectal contrast (CTRC), a procedure that uses computerized enhancements of X-ray images (14).

Conclusion.

A careful examination, possibly with the aid of Biophysical Semeiotics, of course, is the best way to diagnose appendicitis. It is often difficult, infact, even for experienced physicians to distinguish the symptoms of appendicitis from those of other abdominal disorders only by means of the traditional, acàdemic, physical semeiotics. Therefore, very specific questioning and a thorough biophysical-semeiotic examination are crucial. The physician, at first, should ask questions, such as where the pain is centered, whether the pain has shifted, and where the pain began. Soon thereafter, the physician should press on the abdomen to judge the location of the pain and the degree of tenderness. However, of essential importance it is to evaluate the above-described biophysical-semeiotic signs.

The typical and classical sequence of symptoms, in fact, is present in about 50% of cases. In the other half of cases, however, less typical patterns may be seen, especially in pregnant women, older patients, and infants. In pregnant women, appendicitis is easily masked by the frequent occurrence of mild abdominal pain and nausea from other causes. Elderly patients may feel less pain and tenderness than most patients, thereby delaying diagnosis and treatment, and leading to rupture in 30% of cases. Infants and young children often have diarrhea, vomiting, and fever in addition to pain.

The correct and carefull performance of Biophysical Semeiotics allows doctor to make the proper diagnosis in “every” case of appendicitis, a part from location, severity, clinical phenomenology, a.s.o.

While laboratory tests cannot establish the diagnosis, an increased white cell count, often absent, may point to appendicitis. Urinalysis may help to rule out a urinary tract infection that can mimic appendicitis for doctor who ignores the new, original physical semeiotics, of course.

Under these conditions, patients whose symptoms and physical examination are compatible with a diagnosis of acute appendicitis are usually taken immediately to surgery, where a laparotomy (surgical exploration of the abdomen) is done to confirm the diagnosis. Often, without the aid of the new physical semeiotics, the diagnosis is not certain until an operation is done. To avoid a ruptured appendix, surgery may be recommended without delay if the symptoms point clearly to appendicitis and diagnosis is corroborated by the original semeiotics (1-4).

Now-a-days there would be no possibility that, as in the past years in case of appendicitis was strongly suspected in a woman of child-bearing age, a diagnostic laparoscopy (an examination of the interior of the abdomen) was sometimes recommended before the appendectomy in order to be sure that a gynecological problem, such as a ruptured ovarian cyst, was not causing the pain.

As regards sophysticated semeiotics, a part from their limited use in bed-side diagnosing appendicitis, particularly by general pratitioners, they show limited sensitivity, as continuous research of new tool demonstrates.

Now-a-days, all around the world, physician skilled of Biophysical Semeiotics is able to recognize “whatever” appendicitis, regardless its location, clinical symptomatology, and seriousness, evaluate its severity, and in case monitor it over the time, so that a normal appendix is not jet discovered, as in the last years, in about 10-20% of patients who undergo laparotomy, because of suspected appendicitis.

In conclusion, my 45-years-long clinical experience allows me to state that the diagnosis of acute appendicitis is a “clinical” diagnosis, regardless location of appendix and seriousness of disease.

I dedicated these signs to:

* Prof. Edoardo Berti-Riboli, docente Semeiotica Chirurgica Department, Genoa University

**Luigi Bella, Assistente Semeiotica Chirurgica Department, Genoa University

as a token of my friendship and esteem.

References.

1) Stagnaro-Neri M., Stagnaro S., Appendicite. Min. Med. 87, 183, 1996 [Medline].

2) Stagnaro S., Sindrome percusso-ascoltatoria di Iperfunzione del Sistema Reticolo-Istiocitario. Min. Med. 74, 479, 1983. [ Medline].

3) Stagnaro S., Il Ruolo della Percussione Ascoltata nella “difficile Diagnosi” di Appendicite. Biol. Med. 8, 71,1986.

4) Stagnaro-Neri M., Stagnaro S., Semeiotica Biofisica del torace, della circolazione ematica e dell’anticorpopoiesi acuta e cronica. Acta Med. Medit. 13, 25, 1997.

5) Stagnaro S., Rivalutazione e nuovi sviluppi di un fondamentale metodo diagnostico: la percussione ascoltata. Atti Accademia Ligure di Scienze e Lettere. Vol. XXXIV, 1978.

6) Stagnaro-Neri M., Stagnaro S., Cancro della mammella: prevenzione primaria e e diagnosi precoce con la percussione ascoltata. Gazz. Med. It. – Arch. Sc. Med. 152, 447,1993.

7) Stagnaro-Neri M., Stagnaro S.,Deterministic Chaos, Preconditioning and Myocardial Oxygenation evaluated clinically with the aid of physical Semeiotics in the Diagnosis of ischaemic Heart Disease even silent. Acta Med. Medit. 13, 109,1997

8) Pierluigi Di Sebastiano, Thorsten Fink, et al. Neuroimmune appendicitis. Lancet 1999; 354: 461-66.

9) Williams RS. Appendicitis: historical milestones and current challenges. Med J Aust 1992; 157: 784-787.

10) Bouchier IAD, Allan RN, Hodgson HJF, Keighley MRB. Textbook of gastroenterology. London: Bailliere Tindall, 1984: 733
11) Jacobi A. The intestinal diseases of infancy and childhood. Detroit: GS Davis, 1887: 234-235.

12) Roger W Byard, Nicholas D Manton and Richard H Burnell. Acute appendicitis in childhood: did mother know best? A pathological analysis of 1409 cases. A kernel of truth?

MJA 1998; 169: 647-648.

13) BrighamRAD Teaching Case Database:http://brighamrad.harvard.edu/education/online/tcd/tcd.html.
14) Garcia Pena BM., Mandel KD, et al. JAMA 1999; 282:1041-1046. Ultrasonography and Limited Computed Tomography in the Diagnosis and Management of Appendicitis in Children
15) The Merck Manual of Diagnosis and Terapy. Section 3^rd. Gastrointestinal Disorder. Chapter 25. Acute Abdomen and Surgical Gastroenterology. T1614 he Merck Manual of Diagnosis and 1. 16)Stagnaro-Neri M, Stagnaro S. Flebopatie ipotoniche istangiopatiche. Minerva Angiol, 19, 5, 1994

17) Stagnaro-Neri M, Stagnaro S. Flebopatie ipotoniche istangiopatiche: effetti dell'eparansolfato sulle alterazioni primitive della unita microvascolotessutale. Min. Angiol.18, Suppl. 2 al N 4, 105, 1993

18) Stagnaro-Neri M, Stagnaro S. Vasomotility e Vasomotion nelle flebopatie ipotoniche istangiopatiche. Sui meccanismi d'azione dell'eparansolfato. Giornate Naz. di Angiologia, Milano 23-29 Giugno 1991 Dicembre 12, 1995. Atti Min. Med., 40

19) Stagnaro-Neri M, Stagnaro S. Vasomotility e Vasomotion nelle flebopatie ipotoniche istangiopatiche: caos deterministico e unita microvascolotessutale. Comun. Congresso Naz Soc It Flebologia Clin e Speriment, Cata-nia, 4-7/12/1993.

20) Stagnaro-Neri M, Stagnaro S. Valutazione percusso-ascoltatoria del sistema nervoso vegetative e del sistema renina angiotensina, circolante e tessutale. Arch Med Int 1992;3:173-92.

21) Stagnaro-Neri M, Stagnaro S. Sindrome di Reaven, classica e variante, in evoluzione diabetica. II ruolo della carnitina nella prevenzione primaria del diabete mellito. II Cuore 1993;6:6l7-24. [ Medline]

22) Stagnaro-Neri M, Stagnaro S. Radicali liberi e alterazioni del microcircolo nelle flebopatie ipotoniche istangiopatiche. Minerva Angiol 1993;4(Suppl 2):105-8.

23) Peitgen HO, Richter PH. La bellezza dei frattali. Immagini di sistemi dinamici complessi. Torino: Ed Bollati Boringhieri, 1991.

24) Ruelle D. Caso e caos. Torino: Ed Bollati Boringhieri, 1992.

Osteocalcin Quantum-Biophysical-Semeiotic Manoeuvre in bedside Recognizing Diabetes, even in initial stage of diabetic Constitution.

noreply@blogger.com (Stagnaro) — Thu, 16 Apr 2009 05:18:00 +0000

Prehypertension during Young Adulthood may be involved by Coronary Calcium Later in Life exclusively in presence of Inherited Real Risk of CAD, typical for individuals with lithyasic Constitution, present in about 50% OF ALL CASES of Pre-Metabolic and Metabolic Syndrome (www.semeioticabiofisica.it; Constitutions and Bibliography). Regarding the frequent association between hypertension and diabetes, in my opinion based on 53-year-long clinical experience, is more important bedside recognizing diabetic predisposition, now-a-days possible since birth, utilising a lot of methods, different in difficulty, but all reliable in day-to-day practice.

For the first time, from the clinical view-point, I have formerly illustrated on The Lancet.com an original manoeuvre, based on a singular activity of osteocalcin, and reliable in bedside detecting diabetes in one minute, with the aid of a stethoscope (1). In fact, osteocalcin, a product of osteoblasts, among other action mechanisms, stimulates both insulin secretion and insulin receptor sensitivity. As a consequence, osteocalcin, secreted by above-mentioned bone cells during mean-intense lasting digital pressure, for instance, applied upon lumbar vertebrae, brings about increasing pancreatic diameters, i.e., technically speaking, type I, associated, Langherans’s islet microcirculatory activation, so that doctors assess pancreas size augmentation, which in health, lasts 10 seconds exactly (1-7). After that, pancreas diameters return to basal value for 3 sec. The second pancreas size increasing lasts 20 sec., and finally the third show the highest value: 30 sec. On the contrary, in case of diabetic constitution (3, 4) the first pancreas increasing persists normally (10 sec.), but both the second and the third are less than physiological ones (i.e., less than 20 sec. and respectively 30 sec.).

On the contrary, in presence of intense inherited real risk of diabetes (6), such as impairment is present usually in the second and third evaluations. In fact, osteocalcin manoeuvre proved to be pathological already in individuals involved by both Diabetic Constitution and Inherited Diabetic Real Risk (7-9).

Finally, in case of diabetes the alteration is present already in the first evaluation, wherein duration appears less than 10 sec., inversely related with disorder seriousness.

Interestingly, not only in examining subject, but also in all others, even if kilometers way from him (her), according to Lory’s experiment, based of no local realm in biological systems (10), doctor’s pancreas shows surprisingly identical modifications, allowing doctors to made clinical diagnosis until now impossible (11-15)

Figure shows Pancreas Auscultatory Percussion, unavoidable in bedside evaluating pancreas size, i.e., its diameter values. For further information, See

http://www.semeioticabiofisica.it/semeioticabiofisica/Documenti/Eng/pagina4pancreas_eng.doc and http://www.semeioticabiofisica.it/semeioticabiofisica/Documenti/Eng/A%20Picco%20insulin.%20Test%20engl.doc

1) Stagnaro Sergio. The Lancet, January 28, 2008. Bedside Biophysical-Semeiotic Osteocalcin Test in Diagnosing and Monitoring Diabetes.
http://www.thelancet.com/journals/lancet/article/PIIS0140673608601014/comments?action=view&totalComments=2; See better http://www.fceonline.it/docs/stagnaro.pdf

2) Stagnaro Sergio. Il test Semeiotico-Biofisico della Osteocalcina nella prevenzione primaria del diabete mellito. www.fce.it,

http://www.fcenews.it/index.php?option=com_content&task=view&id=909&Itemid=47 .
3) Stagnaro-Neri M., Stagnaro S. Introduzione alla Semeiotica Biofisica. Il Terreno Oncologico. Ed. Travel Factory, Roma, 2004 www.travelfactory.it

4) Stagnaro-Neri M., Stagnaro S., Semeiotica Biofisica: la manovra di Ferrero-Marigo nella diagnosi clinica della iperinsulinemia-insulino resistenza. Acta Med. Medit. 13, 125, 1997
5) Stagnaro S., Stagnaro-Neri M., Le Costituzioni Semeiotico-Biofisiche.Strumento clinico fondamentale per la prevenzione primaria e la definizione della Single Patient Based Medicine. Travel Factory, Roma 2004

6) Stagnaro S., West PJ., Hu FB., Manson JE., Willett WC. Diet and Risk of Type 2 Diabetes. N Engl J Med. 2002 Jan 24;346(4):297-298. [Medline]
7) Stagnaro Sergio. Newborn-pathological Endoarteriolar Blocking Devices in Diabetic and Dislipidaemic Constitution and Diabetes Primary Prevention. The Lancet. March 06 2007. http://www.thelancet.com/journals/lancet/article/PIIS0140673607603316/comments?totalcomments=1 SEE particularly URL: http://www.fceonline.it/docs/stagnaro.pdf

8) Stagnaro Sergio. New bedside way in Reducing mortality in diabetic men and women. Ann. Int. Med.2007. http://www.annals.org/cgi/eletters/0000605-200708070-00167v1

9) Stagnaro S., Stagnaro-Neri M., Le Costituzioni Semeiotico-Biofisiche.Strumento clinico fondamentale per la prevenzione primaria e la definizione della Single Patient Based Medicine. Travel Factory, Roma, 2004. http://www.travelfactory.it/
10) Stagnaro Sergio e Paolo Manzelli. 03 Gennaio 2008, http://www.ilpungolo.com/leggi-tutto.asp?IDS=13&NWS=NWS5267 Limiti della Medicina Ufficiale. L’Esperimento di Lory.

11) Stagnaro Sergio e Paolo Manzelli. L’Esperimento di Lory. Scienza e Conoscenza, N° 23, 13 Marzo 2008. http://www.scienzaeconoscenza.it//articolo.php?id=17775

12) Stagnaro Sergio. Reale Rischio Congenito di Cancro Renale Diagnosticato con la Semeiotica Biofisica: il Segno di Pollio. www.ilpungolo.com, 25 Marzo 2008, http://www.ilpungolo.com/leggi-tutto.asp?NWS=NWS5480&IDS=13
13) Stagnaro Sergio. Melanoma? Escluso in 1 Secondo con La Semeiotica Biofisica Quantistica. Il Reale Rischio Congenito di Melanoma. www.ilpungolo.com, 9 Aprile 2008, http://www.ilpungolo.com/leggi-tutto.asp?IDS=13&NWS=NWS5524

14) Stagnaro Sergio. Diagnosi clinica di cuore sano in un secondo! 7 Aprile 2008. www.fce.it http://www.fcenews.it/index.php?option=com_content&task=view&id=1218&Itemid=47

15) Stagnaro Sergio e Paolo Manzelli. L’Esperimento di Lory. Scienza e Conoscenza, N° 23, 13 Marzo 2008. http://www.scienzaeconoscenza.it//articolo.php?id=17775

Oncological Terrain and Oncological Terrain-Dependent Inherited Real Risk in Malignancy Primary Prevention.

noreply@blogger.com (Stagnaro) — Wed, 15 Apr 2009 09:23:00 +0000

“Not to autumn I will yield, not to winter even”
(W.B.Yeats).

Summary. 1
Introduction. 1
Congenital Acidosic Enzyme-Metabolic Histangiopathy- (CAEMH-). 2
Reticulo-Endothelial System Hyperfunction Syndrome. 2
Restano’s Manoeuvre Type A and Type B. 4
Oncological Terrain. 6
Simulated Sucking Test and Oncological Terrain. 9
Biophysical Semeiotic Evaluation of Epiphysial Secretion of Melatonin. 10
The Inherited “real risk” of cancer. 11
Conclusion. 11
References. 13

Summary.

Malignancy efficacious primary prevention will be possible when doctor will bedside recognize, in a quantitative way and on very large scale, individuals at inherited real risk of tumour, allowing to direct rationally current diagnostic and therapeutic strategies. In the paper, biophysical-semeiotic diagnostic method, reliable in bed-side fast detecting and quantifying Oncological Terrain, i.e., oncological constitution, as well as Inherited Real Risk of malignancy, conditio sine qua non of cancer, solid as well as liquid, are fully described.

Introduction.

Before illustrating Clinical Microangiology of malignant tumours, both solid and liquid, it is necessary to describe in details the oncological terrain or oncological constitution, where is constantly present the Congenital Acidosic Enzyme-Metabolic Histangiopathy (CAEMH), conditio sine qua non also of the oncological terrain, and, therefore, of malignancy, elsewhere exhaustively illustrated (1, 4, 5, 6) (See web site http://www.semeioticabiofisica.it).
CAEMH-, a congenital, functional, mythocondrial cytopathology, inherited almost from the mother, lasts all life long, although variable in intensity in relation to life-style, diet and employment of both bioactive products and histangioprotective drugs.
On the contrary, oncological terrain, originated on the basis of CAEMH-, can disappears under favorable condition, or increased by unfavourale enviromental situations, by improper diet, etymologically speaking, which acts in a negative manner on the CAEMH- severity as well as on the biological system controlling oncogenesis.
In other words, oncological terrain, wherein CAEMH- plays a major role, can be induced and fortunately reversed, almost completely, with the aid of correct diet, etymologically speaking, and by means of histangioprotective treatment (See later on).
Biophysical Semeiotics allows doctor to recognize and evaluate “quatitatively” the oncological constitution, i.e. oncological terrain, by the aid of a large number of methods, different in simplicity, refinement, practical application and amount of information. The usefulness of all these clinical methods, in general practitioner’s day-to-day work, is pointed out by the fact that absence of oncological terrain rules out the presence of malignancy, influencing remarkebly further diagnostic iter, large scale screening, and ultimately therapeutic monitoring.
In fact, age, sex, familiarity have now , i.e. from biophysical semeiotic point of view, a very little value in oncological prevention, because exclusively clinical recognition of oncological terrain requires urgently that patient undergoes instrumental and sophisticated semeiotics, promptly, in a rational manner, after ascertaining the microcirculatory activation type II, non-associated (1, 2) = pathological preconditioning in above-sited site  even in a small part of well defined biological system, where preconditioning results pathological, besides to other numerous biophysical semeiotic signs.
In every human, there are about 1013 cells: not all of these cells, but almost all, can grow and replicate to present as a clinical cancer in every time, due mutations occuring during cellular reproduction. However, cancer is a rare disease at the cellular level. As a matter of facts, up to 30% of all individuals in the developed countries will present clinically with one of a wide variety of cancer at some time of their life. Consequently, if the number of cell at risk is taken into account, given the relatively small cases of malignancies, solid and liquid, it is obvious that this disease only rarely escapes normal protective systems. Therefore, tumours can originate and grow exclusively when psycho-neuro-endocrine-immunological system is profoundly modified. As regards both primary prevention and clinical diagnosis of malignancy, in my opinion, essential is answering to the following question:
“What does carachterize oncological terrain from the clinical point of view?”.
In fact, in order to achieve efficacious prevention on very large scale it is unavoidable that all the modifications occurring in the biological controll system could be easily and promptly ascertained and properly evaluated with the aid of clinical method, i.e. by the use of a sthetoscope, and certainly without application of sophysticated semeiotics, that can not be applied on all individuals, and, moreover, only a few doctors can utilize them.
If the reply is affirmative, a second question immediately follows:
“The oncological terrain, which certanly can be induced, is also in some way reversible?”
It is urgent and necessary to know if the oncological terrain can be reversed, i.e. it can totally or greatly disappeare, with the aid of drugs or diet, etymologically speaking, which exert a favourable influence on modifications of the psicho-neuro-endocrine-immunological system.

Congenital Acidosic Enzyme-Metabolic Histangiopathy- (CAEMH-).
Reticulo-Endothelial System Hyperfunction Syndrome.

At first, we must both face and resolve essential problems concerning oncological terrain, discussing, once more, accurately the pathological mitochondrial condition, which represents its fundamental basis, when it is particularly severe: CAEM-. (3, 4, 5, 8-15) (See Congenital Acidosic Enzymo-Metabolic Histangiopaty in above-cited web site)
CAEM-, conditio sine qua non of oncological terrain and all other biophysical-semeiotic constitutions (See: Constitutions in web-site), represents really a severe alteration of mitochondrial oxidative phosphorilation processes, i.e. ATP synthesis, as well as nucleophyl substitution, variable in intensity from individual to individual, from tissue to tissue and from area to area of the same tissue.
From morphological view-point, it is well-known that CAEM- is characterized by prevalence of right cerebral hemisphere – right cerebral dominance – or more correctly said, of right Planum temporale, which is notoriously located between Heschl’s convolution (gyrus) and posterior part of Silvio’s fissure.
One can ascertain CAEM- as elsewhere described (See above). However, it is advisable an easiest manner, briefly illustrated in following: in healthy individual in supine position and psycho-physically relaxed, doctor applies its left hand, at first, on right parietal-temporal region of the subject, and then on the left one, when the individual to be examined presses forefinger-pulp and thumb-pulp together, obviously at first, of the left hand and, subsequently, of the right one; at the same time doctor evaluate somatosensorial evoked potentials (SEPs) (7-10) = in pratice, latency time of the cerebral-gastric aspecific reflex, as illustrated in Fig. above located.
In case of CAEM-, latency time (lt) of the reflex is 6 sec. when trigger-points of right hemisphere are stimulated, whereas lt results 7 sec. if left cerebral trigger-points are activated; in later situation, intensity of gastric aspecific reflex appears clearly smaller: 2 cm versus 1 cm. respectively. Of course, the degrees of reflex intensity are reversed in presence of dominance of left cerebral hemisphere.
At this point, in order to observe the interesting evolution from CAEM- to oncological terrain, one must remember, once a time, an usefull biophysical semeiotic syndrome, really helpful to general pracitioner in everiday activity : the Rethyculo-Endothelial System Hyperfunction Syndrome (RESHS), that is subdivided in “complete”, “intermediate” and “incomplete” type (6).
As far as clinical significance is concerned, CAEM- corresponds to increased ESR and proteins electrophoresis alterations, but surely is of both more sensitive, specific and, therefore, reliable. In fact, in case of a slight attack of flu, e.g., ( or, even, in advanced malignancy) it often turns out that both laboratory tests are in normal ranges, while RESHS “incomplete”, carachteristic of this viral disease, is always present since the first, asyntopmatic stage, when evaluated by aid of the Restano’s maneouvre = patient clinches fists and does not breath, i.e. boxer’s and simultaneously apnea test: sympathetic hypertonus (See later on): in healthy young person, psycho-physically relaxed, in supine position, digital pressure of “mean” intensity, applied on mean line of breast-bone, iliac crests and spleen projection area, provokes the gastric aspecific reflex after a latency time of 10 sec.: physiological RESHS (Fig.1).
In case of bacterial infection, contagious diseases of infancy, viral in origin, connective tissue disorders (Rheumatoid Arthritis, Lupus Erithematosus, a.s.o.), malignant tumours, a.s.o., lt decreases to 6 sec. with a latency time of reinforcing = augmentation of reflex intensity of 8  1 sec.: RESHS “complete”.
On the contrary, in commom viral diseases, as in flu, digital pressure, applied on cutaneous projection area of spleen does not brings about any gastric aspecific reflex, because white germ centres of splenic (red) pulp are not activated in these conditions: RESHS “incomplete”.
On the contrary, in Herpes Zoster as well as in common infectious diseases of infancy, caused by viral, interestingly doctor observes type “complete” RESHS
Finally, in bacterial disorders, provoked by Gram-negative, i.e. in common acute cystitis (E.coli) or in antritis brought about by H. pylori, RESHS turns out to be “intermediate” (Tab.1).

Fig. 1

Reticulo-Endothelial System Hyperfunction Syndrome: in the stomach, both fundus and body are clearly dilated, while antral-pyloric region contracts (= gastric aspecific reflex), when digital pressure of mean intensity is applied on middle line of breast-bone, iliac crests and, only in the “complete” type, also on cutaneous projection area of the spleen (See text and Tab 1).

RESHS: types and clinical significances.

Type “complete” Trigger points: breast-bone, iliac crests, skin projection area of spleen Bacterial diseases, viral contagious diseases of infancy, rheumatisms, malignancy
Type “intermediate” Splenic trigger point provokes a g.a. riflex of lower intensity Disorders caused by Gram-negative (Cistytis by Esch. coli; antritis by HP)
Type “incomplete” Spleen is not trigger-point Flu viruses

Tab. 1

Interestingly, RESHS allows doctor to monitoring in objective manner the course of wathever disorder in objective manner. As a matter of facts, the degree of both lt and lt of reflex reinforcing provides essential information about the course of the underlying illness.
From the practical view-point, it is of interest that exclusively during the changing of RESHES, from “incomplete” to “complete” type, doctor has to prescribe immediatly, without delay, antibiotic drugs.
A 46-year-long, well-established experience allows me to state that doctor can recognize easily, with the aid of Biophysical Semeiotics, individuals CAEMH-a-positive at oncological risk, quantifying it and estimating the probability of tumour in well-defined part of whatever biological system (11).

Restano’s Manoeuvre Type A and Type B.

In 85% of malignant tumours, both solid and liquid, in initial stage and in 100% when malignancy is sufficiently advanced, RESHS shows the “complete” type, chracterized by latency time (lt) of only 3 sec. and latency time of reinforcing of 5,5 ± 0,5 sec.
On the contrary, in common viral diseases of infancy and in bacterial disorders, connectivitis, a.s.o., lt is 6 sec. and latency time of reinforcing is 8,5±0,5 sec.; p <0,001. nn =" 10">10 sec.)
Healthies without familiarity for tumours CAEMH-a-neg. 8,5 ±0,5 sec. (10 sec.) 9,5±0,5 sec. (>10 sec.)
P.CAEMH-a-positive but at oncological risk and 15% P. with initial neoplasm 3 sec. (10 sec.) 7±1 sec. (>10 sec.)

Tab. 2

Restano’s manoeuvre

type A: lt 3 sec gastric aspecific reflex I £ 1 cm. tl II ³ 9 sec.
tipo B: tl 3 sec. gastric aspecific reflex I > 1 cm. tl II 6-8 sec.
Tab. 3

At this point, doctor must remember the essential role, Restano’s manoeuvre plays in moving from CAEMH-a syndrome to cancer growing. Restano’s manoeuvre represents, indeed, the activation of Reticulo-Endothelial-System (RES), at the present time termed Monocyte-Macrophage System. As indicates Tab. 3, there are two type of such as manoeuvre: type A and type B.
In order to perform correctly and to evaluate “quantitatively” the manoeuvre, subject, who undergoes examination, is invited not to breath for 10 sec. (apnea test), or alternatively doctor applies intense, occlusive digital pressure on a brachial artery for the same time (10 sec.), i.e. “variant” Restano’s manoeuvre, as well as to clinching fists: sympathetic hypertonus.
Before the individual keep again to normally breath, doctor applies digital pressure on middle line of breast-bone (or on iliac crests or cutaneous prjection area of the spleen) for evaluating RESHS = lt of gastric aspecific reflex,i.e. sundus and body of the stomach appear dilated, while antral-pyloric region contracts, and lt of reflex reinforcing (Tab. 1).
As described-above, Restano’s manoeuvre points out RES activation. As a matter of facts, e.g. during infectious disorder, it appears earlier type A, and then type B, and finally, “complete”, “incomplete” or “intermediate” type RESHS, in relation to the nature od underlying disese.
On the other hand, when therapy ameliorates disorder and patient improves, first of all RESHS disappears, and therafter also type B of the manoeuvre is not ascertained, while appears type A , which lasts as far as patient completely recovers.
The presence of Restano’s manoeuvre type B, i.e. the activation of Reticulo-Endothelial System, is due to the fact that marrow products mononuclear cells, which migrate to the thymus and lymphoid tissues, as well as myelopeptides, that stimulate antibodies synthesis, in order to increase biological defense. Consequently, there is marrow microcirculatory activation type I, associated = “light” digital pressure on breast-bone, e.g., provokes three ureteral reflexes, which permit doctor to evaluate vasomotility and vasomotion of marrow microcirculation, by the intensity of reflexes fluctuation. See web site www.semsioticabiofisica.it/microangiologia .
Following experimental evidence corroborates my above-illustrated interpretation: in healthy, “intense” digital pressure on trigger-points for evaluating RESHS (middle line of breast-bone, iliac crests) after about 20 sec. increases the antibodies biophysical semeiotic syndrome (12) = light digital pressur, applied on MALT skin projection, i.e. breast-, liver-, spleen-, urinary bladder-, appendix-, middle clavicular line- a.s.o., cutaneous projection areas, provokes physiologically after 6 sec. gastric aspecific reflex of 2 cm. in intensity: chronic antibodies synthesis syndrome, that from the chronic type becomes clearly of acute type, where lt appears to be 3 sec. and intensity > 2 cm.
On the contrary, in individual with oncological terrain stimulation of antibodies synthesis appears to be whether absent or not statistically significant (lt of MALT-gastric aspecific reflex: 5-6 sec.). Moreover, in healthy, digital pressure on middle line of breast-bone, after a lt of about 20 sec., increases the diameters of BALT cutaneous projection area ( 3 cm.), while in oncological terrain they increase only £ 1 cm. = auscultatory percussion of both posterior and anterior thoracic wall, allows doctor to ascertained , along middle scapular and, respectively, clavicular line, three round hypophonetic area – BALT - of a diameter oscillating in a chaotic-deterministic manner, 6 times/min, from 0,5 cm. to 1,5 cm., with a period varying from 9 sec. to 12 sec.- mean value 10,5, a fractal number, as do all biological systems.
Interestingly, in healthy individual digital pressure of mean intensity, applied on breast-bone provokes, after about 20 sec., intense increasing ( 2 cm.) of BALT cutaneous projection areas, with augmentation of antibodies synthesis (12) = lt of MALT-gastric aspecific reflex lowers from 6sec.to 3 sec. and reflex intensity clearly increases to  2 cm., while in presence of oncological terrain the encreases is £ 1 cm.).
To demonstrate both internal and external coherence of biophysical theory it is whortwhile that simultaneously, during Restano’s manoeuvre, all sites of antibodies synthesis (MALT) show biophysical semeiotic features of active hyperemia, more precisely speaking, the microcirculatory activation type I, associated (See earlier), of course of different intensity in relation to causal agent, indicating the acute phase of antibodies production.
Notably, the following clinical evidence corroborates this interpretation: in healthy, subcutaneous injection of desensitizing vaccine, according to Besredka, or, eg., anti-flu vaccine, induces first the type A, and later type B manoeuvre and finally RESHS.
While in Restano’s manoeuvre type A is always contemporaneously present Selye’s syndrome, variable in intensity, beside type B doctor observe characteristic modifications of psycho-neuro-endocrine-immunological system, as in malignancy, liquid or solid, as well as in patients, who successfully underwent to surgery. I have termed this pathological situation of biological systems for protecting against cancer as “oncological terrain”.
As regards the evaluation of neuro-stimulatotors, neuro-modulators, hormonal neuro-modulators, free-oxygen-radicals, and preconditioning see above cited web site.

Oncological Terrain.

Biophysical Semeiotics allows doctor to both recognize and “quantitatively” assess at the bed-side the biological terrain, on which cancer can originate and grow (Tab.4 and 5).

Increasing : G. H. I.G.F.s PRL free Radicals Hyperinsulinemia-insulinresistance
Reducing:: SST Oppioid Vit. A E Co. Q 10 Carnetine

Tab.4

ONCOLOGICAL TERRAIN:
DIAGNOSIS AND QUANTITATIVE EVALUATION

BALT WITH CLOSED EYES LT> 5 SEC. I <> 5 SEC. I <> 5 SEC. I <> 5 SEC. I <> 20 SEC.
SIMULATED SUCKING TEST D > 7 SEC.
CAEMH- PRESENT (100%) G.aspecific REFL.> 2 CM.
HIPERINSULINEMIA-INSULINRESISTANCE D > 12 SEC.(AS LT REFLEX.GASTRIC-ASPECIFIC)
GH E MICROCIRCULATORY ACTIVATION TIPO II , DISSOCIATED
PRECONDITIONING PATHOLOGICAL
ETC.
Tab.5

Complete, exhaustive biophysical semeiotic evaluation of psycho-neuro-endocrine-immunological system as well as of products, indicated in Tab.5, needs obviously a years-long study and exprience at the bed-side. Due to lack of space, I invite the reader, who like to complete this topic, to see former articles (1-7) as well as Bibliography, in above-cited site.
However, I describe a method, easy to performe, reliable in detecting the presence of oncological terrain, as follows: in healthy, supine and psycho-physically relaxed, during rythmic palpation of breast (similuated sucking test, SST) the mammary gland-gastric aspecific reflex lasts 7 sec. exactly. On the contrary, in oncological terrain the duration augments to 8-9 sec. (p < nn =" 7" nn =" 3" nn ="="" nn =" 7" nn =" 10" nn =" 5" nn =" 9,12" nn =" <" nn =" 5" nn =" 5"> 10 sec., once again in correlation with the increasing of hormonal secretion, showing the possibility of evaluating simultaneously different disorders by means of Biophysical Semeiotics, since the numerous biological systems are connetted very closely from both structural and functional point of view.

At this point, oncological terrain is recognized and can be “quantitatively” evaluated, as follows:

4) assessment of endogenous opiates, the so-called “immunological orchestra directors”;

5) estimation of melatonin level, as described above.

As far as the evaluation of endogenous opiates system concerns, that can be activated also by melatonin and myelopeptides, a refined method is represented by assessment of cerebral-gastric aspecific reflex intensity, first, at basal line (NN ³ 2 < 3 cm.) and, then, after intense digital pressure on mandibular nerve for 25 sec., during Cerebral Evoked Potentials (8, 9, 10):
in healthy, intensity of cerebral gastric aspecific reflex is reduced to half., due to the restraining action of endogeous opiates as regards the neurotransmission;
By contrast, oncological terrain, carachterized by deficiency of b-endorphins as well as met-enkephalin, provokes a very small decreasing of cerebral-gastric aspecific reflex intensity under described condition.
As regards the rocognizing “real risk” of cancer, referred avove, doctor have to ascertain the impairement of latency time of gastric aspecific reflex, its duration, and above all the precious data of preconditioning.
In conclusion, one method, easy and rapid to perform, reliable in both diagnosing and “quantitatively” evaluating oncological terrain, in my opinion, is the following: closed eyes enhance melatonin epiphysial secretion, constantly reduced in oncological terrain, although whith different degree. Notoriously, melatonin stimulates diencephalohypophysial secretion of SST-RH as well as of endogenous opiates, particularly in arcuate nucleus. In addition, melatonin, somatostatin, and particularly endogenous opiates stimulate antibodies synthesis. Consequently, BALT cutaneous projection area, evaluated at rest and after 5 sec. eyes closure ( patient closes intensively his eyes) appears clearly modified and doubled in healthy for ³ 20 sec., whereas in oncological terrain, in relation to its intensity, changes are minimal (£ 1 cm.) for only £ 10 sec.
For further information, reader can see Bibliography in above-cited web site and in previous papers (1-5).

References.

1) Stagnaro Sergio, Stagnaro-Neri Marina. Introduzione alla Semeiotica Biofisica. Il Terreno oncologico”. Travel Factory SRL., Roma, 2004. http://www.travelfactory.it/semeiotica_biofisica.htm
2) Stagnaro-Neri M., Stagnaro S., Deterministic Chaos, Preconditioning and Myocardial Oxygenation evaluated clinically with the aid of Biophysical Semeiotics in the Diagnosis of ischaemic Heart Disease even silent. Acta Med. Medit. 1997; 13: 109-112.
3) Stagnaro S. A clinical efficacious maneouvre, reliable in bed-side diagnosing coronary artery disease, even initial or silent, as well as "heart coronary risk". 3rd Virtual International Congress of Cardiology, FAC, 2003, September-November. http://www.fac.org.ar/tcvc/marcoesp/marcos.htm
4) Stagnaro S., Istangiopatia Congenita Acidosica Enzimo-Metabolica condizione necessaria non sufficiente della oncogenesi. XI Congr. Naz. Soc. It. di Microangiologia e Microcircolaz. 1983; Abstracts, pg 38, 28 Settembre-1 Ottobre, Bellagio1983
5) Stagnaro S., Istangiopatia Congenita Acidosica Enzimo-Metabolica. X Congr. Naz. Soc. It. di Microangiologia e Microcircolazione 1981. Atti, 61. 6-7 Novembre, Siena,1981.
6) Stagnaro S., Istangiopatia Congenita Acidosica Enzimo-Metabolica. Una Patologia Mitocondriale Ignorata. Gazz Med. It. – Arch. Sci. Med. 1985;144: 423-429 (Infotrieve)
7) Stagnaro S., Sindrome percusso-ascoltatoria di Iperfunzione del Sistema Reticolo-Istiocitario. Min. Med. 1983;74: 479-480 (Medline)
8) Stagnaro S., Stagnaro-Neri M., Valutazione percusso-ascoltatoria del sistema degli oppioidi endogeni nei pazienti cefalalgici. Contributo alla definizione della costituzione emicranica. Epat. 1987; 33: 35-40.
9) Stagnaro-Neri M., Stagnaro S., Cancro della mammella: prevenzione primaria e diagnosi precoce con la percussione ascoltata. Gazz. Med. It. – Arch. Sc. Med. 1993; 152: 447-451.
10) Stagnaro-Neri M. Stagnaro S., Diagnosi percusso-ascoltatoria e monitoraggio terapeutico della sindrome Magnesio-carenziale. Gazz. Med. It. – Arch. Sc. Med. 1988;147: 259-305.
11) Stagnaro-Neri M., Stagnaro S., Acidi grassi W-3, scavengers dei radicali liberi e attivatori del ciclo Q della sintesi del Co Q10. Gazz. Med. It. – Arch. Sc. Med. 1992;151: 341-346.
12) Stagnaro Sergio. A paramount Bias in the Research. J. Clin. Invest. http://www.jci.org/cgi/eletters/115/3/664
13) Stagnaro Sergio. Bed-Side Prostate Cancer Detecting, even in early stages (“Real Risk” of Cancer): BMC Family Practice, 2005, 6:24 doi:10.1186/1471-2296-6-24
http://www.biomedcentral.com/1471-2296/6/24/comments#202466 .
14) Stagnaro Sergio. There is another clinical, and overlooked tool, reliable in breast cancer prognosis evaluation (06 July 2005). BMC Cancer.
http://www.biomedcentral.com/1471-2407/5/70/comments#204473
15) Stagnaro Sergio. Genes, Oncological Terrain, and Breast Cancer. (22 July 2005). World Journal of Surgical Oncology. http://www.wjso.com/content/3/1/45/comments#205475
16) Stagnaro S., Stagnaro-Neri M., La Melatonina nella Terapia del Terreno Oncologico e del “Reale Rischio” Oncologico. Travel Factory, Roma, 2004.
http://www.travelfactory.it/semeiotica_biofisica_2.htm
17) Stagnaro S., Stagnaro-Neri M., Le Costituzioni Semeiotico-Biofisiche.Strumento clinico fondamentale per la prevenzione primaria e la definizione della Single Patient
Based Medicine. Travel Factory, Roma, 2004. http://www.travelfactory.it/libro_costituzionisemeiotiche.htm 2004
18) Stagnaro S., Stagnaro-Neri M., Single Patient Based Medicine.La Medicina Basata sul Singolo Paziente: Nuove Indicazioni della Melatonina. Travel Factory, Roma, 2005.

* Sergio Stagnaro MD
Via Erasmo Piaggio 23/8
16039 Riva Trigoso (Genoa) Europe
Founder of Quantum Biophysical Semeiotics
Who's Who in the World (and America)
since 1996 to 2009
Ph 0039-0185-42315
Cell. 3338631439
www.semeioticabiofisica.it
dottsergio@semeioticabiofisica.it

Pollio’s Sign* in bedside Recognizing renal Cancer, since its initial Stage of Inherited, Oncological Real Risk.

noreply@blogger.com (SciPhu) — Sun, 22 Mar 2009 08:15:00 +0000

Sergio Stagnaro MD
Founder of Quantum Biophysical Semeiotics
Biophysical Semeiotics Research Laboratory
Riva Trigoso (Genova) Italy

Renal Cancer (RC) represent about 3% of all malignancies and are continuously increasing: in Italy 4.000 persons are involved yearly by RC, and 27.000 new cases are diagnosed in Europe. The early diagnosis is the conditio sine qua non of the best therapeutic results. Unfortunately, RC are mainly recognized later, since for years or decades they are silent from the clinical syntomatology, in spite is originates as renal Inherited Oncological Real Risk. Analogously to all other malignancy, RC may occur exclusively in individuals involved by both Oncological Terrain “and” Oncological Terrain-Dependent Inherited Oncological Real Risk in the kidney, bedside recognized even at birth with the aid of Quantum Biophysical Semeiotics (1-7).
In health, “light-moderate” persisting stimulation by cutaneous pintching of renal trigger-points, i.e., VIII-X thoracic dermatomeres (= lateral abdominal quadrants), after exact 8 sec. latency time, brings about aspecific gastric reflex: in the stomach, both fundus and body dilate, while antral-pyloric region contracts: www.semeioticabiofisica.it. Reflex duration lasts LESS than 4 sec.: such as parameter value, paralleling local Microcirculatory Functional Reserve, plays a central role in bedside diagnosing RC, starting from the first stage of Inherited Oncological Real Risk.
On the contrary, in individual involved by urinary way cancer Inherited Oncological Real Risk, the identical stimulation causes aspecific gastric reflex, showing normal latency time (NN = 8 sec.), BUT its duration is 4 sec. or more, i.e. pathological. Really, these two parameter values are inversely and respectively directly related to the seriousness of underlying disorders. Immediately there after, appears tonic Gastric Contraction, characteristic of tumoural lesion: Pollio’s Sign..
Due to no local realm of biological systems (8-10), when renal trigger-points stimulation is “intense”, all components of urinary tract are “simultaneously” stimulated: in health, reflex latency time raises cannot brings about gastric aspecific reflex, allowing rapidly doctor to exclude urinary tract lesion!
On the contrary, in case of renal cancer, even in the stage of Inherited Oncological Real Risk, simultaneously appears the reflex, followed suddenly by tonic gastric contraction, typical of lesion, oncological in nature, because locally free energy is increased, due to type I, associated, microcirculatory activation (3-7).
To summarize, in subject involved by both Oncological Terrain and Inherited Oncological Real Risk in whatever part of urinary system (kidney, urther, urinary bladder, prostate), “intense” stimulation of a SINGLE trigger-point causes simultaneously intense aspecific gastric reflex, immediately followed by tonic Gastric Contraction: Pollio’s Sign, which surely will play a paramount role in RC as well as in urinary tract malignancies primary prevention. Subsequently, physicians will localized tumoural lesion with the aid of a lot of well-known biophysical-semeiotic signs (1-7)

* Pollio’s Sign. In memory of my dear friend, Fabrizio Pollio MD, brilliant gynaecologist surgeon, dead at age of 34 years for renal cancer.

References.

1) Stagnaro Sergio. (7 February 2008). Bedside diagnosing prostate cancer inherited oncological real risk and its therapy. Annals of Internal Medicine.
http://www.annals.org/cgi/eletters/0000605-200803180-00209v1
2) Stagnaro Sergio. Oncogenesis is possible exclusively in individuals Oncological Terrain-positive. www.thescientist.com 2007. http://www.the-scientist.com/blog/print/53498/
3) Stagnaro-Neri M., Stagnaro S. Introduzione alla Semeiotica Biofisica. Il Terreno Oncologico. Ed. Travel Factory, Roma, 2004. http://www.travelfactory.it
4) Stagnaro S., Stagnaro-Neri M., La Melatonina nella Terapia del Terreno Oncologico e del “Reale Rischio” Oncologico. Travel Factory, Roma, 2004. http://www.travelfactory.it/
5) Stagnaro S., Stagnaro-Neri M., Le Costituzioni Semeiotico-Biofisiche.Strumento clinico fondamentale per la prevenzione primaria e la definizione della Single Patient Based Medicine. Travel Factory, Roma, 2004. http://www.travelfactory.it/
6) Stagnaro S., Stagnaro-Neri M., La Melatonina nella Terapia del Terreno Oncologico e del “Reale Rischio” Oncologico. Travel Factory, Roma, 2004. http://www.travelfactory.it
7) Stagnaro Sergio. Oncological Terrain and Inherited Oncological Real Risk: New Way in Malignancy Primary Prevention and early Diagnosis. International Seminars in Surgical Oncology, 2007. http://www.issoonline.com/content/4/1/25/comments#290565
8) Stagnaro Sergio e Paolo Manzelli. Semeiotica Biofisica: Realtà non-locale in Biologia. Dicembre 2007, www.ilpungolo.com, http://www.ilpungolo.com/leggi-tutto.asp?IDS=13&NWS=NWS5217
9) Stagnaro Sergio e Paolo Manzelli. Semeiotica Biofisica Quantistica. http://www.ilpungolo.com/leggi-tutto.asp?IDS=13&NWS=NWS5243
10) Stagnaro Sergio. Esperimento di Lory e Crisi dei Fondamenti della Medicina Occidentale. www.ilpungolo.com. 17 Febbraio 2008 http://www.ilpungolo.com/leggi-tutto.asp?NWS=NWS5387&IDS=13

Middle Ages of today’s Medicine, Overlooking Quantum-Biophysical-Semeiotic Constitutions and Related Inherited Real Risk.

noreply@blogger.com (SciPhu) — Mon, 03 Nov 2008 12:42:00 +0000

Sergio Stagnaro MD

Via Erasmo Piaggio 23/8,Riva Trigoso (Genoa) Europe. Founder of Quantum Biophysical Semeiotics Who's Who in the World (and America) since 1996 to 2009.
Ph 0039-0185-42315, Cell. 3338631439 www.semeioticabiofisica.it,dottsergio@semeioticabiofisica.it

At first sight, it could seem paradoxical, absurd, incomprehensible, my former definition of Middle Ages of today’s Medicine, but it contains an important, really distressing, disheartening truth (1-9).
In this brief paper I explain in clear manner what accounts for the reason of the justification of my definition Middle Ages of present Medicine (MAM), or Age of Darkness.

To begin with, I underscore the fundamental bias, scientists all around the world agree with, i.e., according to which, “all men are created equal”, so that Evidence Based Medicine (EBM) is the only theory at the base of every research in western countries. On the contrary, beside this theory, interesting more sponsoring drug producers than single patient, I have demonstrated firstly that individuals are different from biological view-point, and secondly that Single Patient Based Medicine theory really exists (10-13).
In following, I illustrate in a simple, clear way, easy to understand, what accounts for the reason of my term MAM, subdividing the argumentation in specific, distinct, particular paragraphs.

A) All around the world scientists are considering as truth the belief, according to which cancer can involves all individuals, though with diverse incidence. In other words, almost all physicians are overlooking both Oncological Terrain (OT) and OT-dependent Inherited Real Risk, localized in one (or more) biological system (14-24). As a consequence, today’s women are told that it is unavoidable necessary, e.g., to undergo periodically mamma echotmography and mammography, while all men are controlling periodically their PSA blood level, in order to prevent breast cancer and, respectively, prostate cancer.
The truth is that only women involved by both Oncological Terrain and breast cancer Inherited Real Risk in one (rarely in more) mamma quadrant can suffer from breast malignancy (15-23).
This is valid, of course, for carcinogenesis in every biological systems.

Overlooking above-mentioned original scientific concepts, physicians think that all individuals must be enrolled in cancer primary prevention, which will result useless and expensive, generating an avoidable Psychological Terrorism.

Please, reflect on the following message of mine posted recently in Nature.com:

Surely, climate change is real, as states wisely Obama. On the contrary, I believe that NHS Programs are unfortunately stable all around the world, generating the present Middle Ages of Medicine and - as a consequence - Psychological Terrorism. For instance, read
http://www.nature.com/news/2008/081006/full/news.2008.115”.

In addition, in every present research, aiming to study drugs usefulness in cancer primary prevention, are enrolled also individuals negative for both Oncological Terrain and OT-dependent Inherited Real Risk, e.g. in the lung. Therefore, research conclusion may be that – for instance – tobacco smoking is a tool of paramount importance in lung cancer primary prevention: a paradigmatic example of MAM.

B) All around the world scientists are considering as truth the belief that all women (and men?) can be involved by osteoporosis. Overlooking osteoporotic constitution, present war against osteoporosis is lost for ever (24-26). In spite of wise, prudent, indifferent advices of drugs companies and machines producers, all women after 40 years must be regularly controlled as far as bone calcium is concerned. In fact, nowadays to prevent osteoporosis, doctors are following precise, but clearly no-updated, WHO Guide Lines, according to which periodical MOC (Bony Computerized Mineralometria), is necessary for all women over 40 years, with and without osteoporosis constitution and ostoporotic inherited real risk; This is another outstanding example of MAM.

C) All around the world scientists are considering as truth the belief that all women and men can be involved in their life by type 2 diabetes, which is a serious today’s growing epidemics. In other words, unfortunately according to present medicine knowledge, all individuals are at different risk of diabetes. Therefore, it is nowadays advisable for everybody controlling fasting and postprandial glucose blood level, aiming to recognize in “early” symptomless patients glucose metabolism impairment. Overlooking Quantum Biophysical Semiotics, a large percentage of men involved by both diabetic “and” dyslipidemic constitutions, conditio sine qua non of diabetes, aren’t controlled, and thus not recognized as diabetics.

At this point, we must remember that so-called diabetic complications are already present when diabetes early diagnosis is made, since they occur years or decades before disorder onset (10, 11, 20, 27, 28) (S. www.semeioticabiofisica.it, Practical Applications, Diabetes).

From the above, briefly referred, remarks, it is clear without doubts that whatever diabetes primary prevention, performed overlooking diabetic “and” dyslipidemic constitutions, results unavoidably an expensive lack of success. This is another excellent example justifying the term MAM, i.e., Middle Ages of Medicine.

D) All around the world scientists are considering as truth the belief that all individuals with high blood levels of cholesterol (especially, LDL, No-HDL,TG, a.s.o.), homocysteine, uremia, as well as “every” hypertensive subject, tobacco smokers, obese individuals, stressed humans, and so on, are at risk of cardiovascular disease (CVD), and particularly, Coronary Artery Disease (CAD). In other, few words, in spite of wise, indifferent, neutral advices of lipid lowering drugs producers, the above mentioned pathological conditions are considered risk factors (sometimes, causes!) of CVD, including acute coronary disease.
Frankly speaking, what accounts for the reason of such as great mistake, compromising the primary prevention against an epidemics of present age, is the distressing fact that the large majority of Authors, Editors, Reviewers, University Professors, General Practitioners, National Health Service Authorities, specialized journalist, and also lay-men ignore the existence of Inherited CVD (CAD) Real Risk! (29-33)

At this point, I discuss some current differential diagnosis, since they symbolizing today’s Middle Ages of Medicine.

E) All around the world scientists are considering as truth the belief that ALL individuals with Precordialgia, “could be” affected by CAD, so that they think urgently carry out ECG (electrocardiogram). In fact, laboratory- and image department-dependent physicians advice usually, first of all, an ECG to ALL patient with pain in the central part of their chest, to ascertain possible acute coronary disorder. To ECG follow immediately thorax X-rays, oesophagus-gastro-duodeno-endoscopy, and a long series blood examination, looking for a precise diagnosis, which is really a “bedside” diagnosis, if doctors know Quantum Biophysical Semeiotics. As a matter of fact, when intense digital pressure, applied upon a single heart trigger-point, does not bring about simultaneously gastric aspecific reflex, CAD is excluded in reliable manner (7, 32-35).
Analogously, physicians are able to exclude at te bedside whatever chest disorder, when intense digital pressure, applied upon a single thorax trigger-point, does not bring about simultaneously gastric aspecific reflex. As regards the presence of hiatal hernia, even associated with cholelithiasis and colon diverticulosis (Saint Syndrome), doctors can recognize such as syndrome in 10 seconds (36, 37).
As a consequence, further examinations will follow exclusively when pathological physical semeiotic data are observed. To summarize, current diagnostic procedure in case of precordialgia is a paradigmatic display of MAM.

F) All around the world scientists are considering as truth the belief that ALL individuals with joint pain could be suffering from rheumatic disorders, so that they agree with the necessity, according to Guide Lines, of laboratory research, aiming to recognize possible rheumatism.
As a consequence, patients undergo lab analyzes, joint X-rays, TAC, NMR, a.s.o., in order to make possibly the differential diagnosis and diagnosis.
Unfortunately, overlooking both biophysical semeiotic rheumatic constitution and rheumatic inherited Real Risk doctors cannot recognize individuals who can be involved by such as disorders, separating them from those who surely will never suffer from joint disorder, rheumatic in nature (10, 11). The above remarks, briefly referred, account for the reason of psychological terrorism and today’s Middle Ages of Medicine.

I like conclude the article, illustrating in details a common problem of today’s Medicine, brought about by diffuse utilization of Echographical examination, in every patient presenting abdominal disorders, but more frequently in normal subjects!

G) The patient with a focal liver lesion may present difficult detection and management problems, in particular when upper abdominal symptoms are completely absent. In fact, the wider application of ultrasound and more recently computed tomography and NMR, have identified increasing numbers of patients with no symptoms related to their hepatic lesions.
On the contrary, there are a lot of quantum biophysical semeiotic signs valuable and reliable in bedside finding out and diagnosing focal liver lesions, even clinically silent, as well as in monitoring the course of the diseases (1). Due to clinical phenomenology in the right upper abdominal quadrant, related to retro-ciecal and/or sub-hepatic atypical localization, appendicitis must be considered in differential diagnosis (39,40). Moreover, the usefulness of quantum biophysical semeiotics in both avoiding unnecessary over-investigation and in selecting patients who might benefit from high quality specialist studies has to be emphasized.
At least during a long period of time, focal liver lesions may occur without upper abdominal symptoms. In other words, the majority of focal lesions of the liver are clinically silent, so that an increasing numbers of patients, with no symptoms related to their hepatic disorders, has been identified by wider application of ultrasound and computed tomography (41).
Although there is no widely accepted protocol for assessing these lesions, both sophisticated examinations are definitely included in various suggested algorithms (41, 42). Small haemangiomas and some hydatid cysts, however, have atypical computed tomography and ultrasound appearances (43, 44).
On the other hand, hepatic haemangioma represents the most common benign tumour of the liver and its clinical instrumental diagnosis is often difficult. The lack of diagnostic accuracy of echoscintigraphic detection, furthermore, in assessing a solitary hepatic lesion is well known (38). As a matter of fact, with only the aid of echothomography, for example, is not possible the differential diagnosis between hepatic abscess and solid lesion. On the contrary, ultrasound scanning permits early separation into cystic or solid lesions in almost all cases and also excludes large bile ducts obstruction. It may also identify multiple hepatic lesions.
However, technical difficulties with ultrasound scanning may arise in some patients, due, for instance, to obesity and/or overlying bowel-gas and is then necessary CT, which has an increased overall accuracy compared with ultrasound (38). All patients, observed in the past year, were routinely assessed by means of AP for evidence of hepatic tumor, first by detecting CAEMH, B, II, conditio sine qua non of tumors both benign and malignant, solid or liquid; then the "boxer's test" was carefully examined in order to ascertain the cystic syndrome, in particular starting 4 sec. after test beginning.
As regards the detection of cystic syndrome, we prefer to evaluate the upper third urethral reflex. In all positive cases AP of the liver was then carried out to find one (or more) suspected area. In the patients of the series, finger pressure on cutaneous projection area of focal suspected lesions, induced gastric aspecific reflex and cystic syndrome, thus allowing the clinical evaluation of lesion shape and size. Hepatic neoplasms, primary or secondary, must be taken into account in differential diagnosis, even when primary localization is yet unknown.
AP differential diagnosis between benign and malignant liver tumours is based also on the positivity ofRHSH "complete type" and autoimmune syndrome, both of them present exclusively in the malignancies. Moreover, "simulated defecation test", as well as "simulated micturation test", has proved useful in localizing focal lesions respectively in abdominal organs and urinary tract (unpublished work). When there are abdominal symptoms in the right upper quadrant, among other differential diagnoses, also appendicitis - in atypical retrocecal and/ or subhepatic localization - must be kept in mind, in order to avoid a misdiagnosis full of risk.
On the other hand, a patient with a focal lesion in the liver can be also involved by an appendicitis. From the auscultatory percussion point of view, despite its position, appendicitis is characterized by RESH "complete type" and especially by "tonic gastric contraction sign" (tgc), induced by both simulated defecation test (38, 43) and digital pressure on skin projection of diseased appendix, exactly localized by AP of the cecum. The intensity of the specific sign, furthermore, is directly related to the severity of the illness. On the contrary, the latency time before tgc enhancing is inversely correlated with the seriousness of underlying disease (e.g. from 4 to 8 sec.). As a result of these observations, AP appears to be very useful in diagnosing and differential diagnosing - of course - as well as in monitoring the evolution of appendicitis, apart from any atypical localization.
To return to hepatic focal lesions, it seems easy to separate by mean of AP haemangiomas from both cysts and neoplasms (only in the letter ones there is RESH and autoimmune syndrome). In fact, during the boxer's test, haemangioma size increases, whereas cyst diametre clearly decreases for 3 sec. Obviously, solid focal lesions of the liver do not vary their size during the test.
The above remarks are quite important, because haemangiomas and occasionally hydatid cysts - as a wide literature reports - may have atypical apperarances on initial investigation, and percutaneous biopsy may result in life-threatening hemor-rage, anaphylaxis or hydatic dissemination (24, 38).

In conclusion, although above-remarks represent partial data of my 53-year-long clinical experience, I’ am sure they are sufficient to corroborate the term Psychological Terrorism of today’s Middle Ages of Medicine. My hope is to can go out of both, as soon as possible, with the precious aid of Quantum Biophysical Semeiotics.

References.

1) Stagnaro S. www.nature.com. The Great Beyond, July 11, 2008
http://blogs.nature.com/news/thegreatbeyond/2008/07/hey_pharma_leave_those_kids_al.html
2) Stagnaro Sergio. Semeiotica Biofisica Quantistica: Precisazione sulla Vaccinazione anti HVP nella Prevenzione del Cancro Cervicale. www.fcenews.it , 24 ottobre 2008, http://www.fcenews.it/index.php?option=com_content&task=view&id=1899&Itemid=45
3) Stagnaro Sergio. Role of NON-LOCAL Realm in Primary Prevention with Quantum Biophysical Semeiotics. www.nature.com, 01 Feb, 2008-05-17 http://www.nature.com/news/2008/080130/full/451511a.html
4) Stagnaro Sergio. The Lancet, January 28, 2008. Bedside Biophysical-Semeiotic Osteocalcin Test in Diagnosing and Monitoring Diabetes.
http://www.thelancet.com/journals/lancet/article/PIIS0140673608601014/comments?action=view&totalComments=2
5) Stagnaro Sergio e Paolo Manzelli. Semeiotica Biofisica Endocrinologica: Meccanica Quantistica e Meccanismi d’Azione Ormonali. Dicembre 2007, www.fce.it, http://www.fcenews.it/index.php?option=com_content&task=view&id=816&Itemid=45
6) Stagnaro Sergio e Paolo Manzelli. Semeiotica Biofisica: Realtà non-locale in Biologia. Dicembre 2007, www.ilpungolo.com, http://www.ilpungolo.com/leggi-tutto.asp?IDS=13&NWS=NWS5217
7) Stagnaro Sergio. Role of Coronary Endoarterial Blocking Devices in Myocardial Preconditioning - c007i. Lecture, V Virtual International Congress of Cardiology. http://www.fac.org.ar/qcvc/llave/c007i/stagnaros.php
8) Stagnaro Sergio e Paolo Manzelli. 03 Gennaio 2008, Limiti della Medicina Ufficiale. L’Esperimento di Lory.
http://www.ilpungolo.com/leggi-tutto.asp?IDS=13&NWS=NWS5267
9) Stagnaro Sergio e Paolo Manzelli. L’Esperimento di Lory. Scienza e Conoscenza, N° 23, 13 Marzo 2008. http://www.scienzaeconoscenza.it//articolo.php?id=17775
10) Stagnaro S., Stagnaro-Neri M., Le Costituzioni Semeiotico-Biofisiche.Strumento clinico fondamentale per la prevenzione primaria e la definizione della Single Patient Based Medicine. Travel Factory, Roma, 2004. http://www.travelfactory.it/
11) Stagnaro S., Stagnaro-Neri M., Single Patient Based Medicine.La Medicina Basata sul Singolo Paziente: Nuove Indicazioni della Melatonina. Travel Factory, Roma, 2005. http://www.travelfactory.it/
12) Stagnaro Sergio. Single Patient Based Medicine: its paramount role in Future Medicine. Public Library of Science.
http://medicine.plosjournals.org/perlserv/?request=read-response
13) Stagnaro Sergio. Single Patient Based Medicine, Therapeutic Monitoring and proper Drugs Prescription. Nature Medicine.com. April, 4, 2008.
http://blogs.nature.com/nm/spoonful/2008/04/trust_noone.html#comments
14) Stagnaro S., Stagnaro-Neri M. Una patologia mitocondriale ignorata: la Istangiopatia Congenita Acidosica Enzimo-Metabolica. Gazz. Med. It. - Arch. Sci. Med. 149, 67 1990. 2) Stagnaro S. New bedside way in reducing mortality in diabetic men and women. Ann. Int. Med. http://www.annals.org/cgi/eletters/0000605- 200708070-00167v1
15) Stagnaro-Neri M., Stagnaro S., Cancro della mammella: prevenzione primaria e diagnosi precoce con la percussione ascoltata. Gazz. Med. It. - Arch. Sc. Med. 152, 447 1993
16) Stagnaro-Neri M., Stagnaro S. Introduzione alla Semeiotica Biofisica. Il Terreno Oncologico. Ed. Travel Factory, Roma, 2004.
http://www.travelfactory.it/semeiotica_biofisica.htm
17) Stagnaro S., Stagnaro-Neri M., Oncological Terrain, conditio sine qua non of Oncogenesis, 2004: http://www.gutjnl.com/cgi/eletters?lookup=by_date&days=60
18) Stagnaro Sergio. "Genes, Oncological Terrain, and Breast Cancer" World Journal of Surgical Oncology., 2005, http://www.wjso.com/content/3/1/45/comments#205475
19) Stagnaro S. Reale Rischio Semeiotico-Biofisico. Ruolo diagnostico e patogenetico dei Dispositivi Endoarteriolari di Blocco neoformati patologici tipo I, sottotipo a) oncologici e b). Ed Travel Factory, Roma, www.travelfactory.it, in press
20) Stagnaro S. Newborn-pathological Endoarteriolar Blocking Devices in Diabetic and Dislipidaemic Constitution and Diabetes Primary Prevention. The Lancet. March 06 2007. http://www.thelancet.com/journals/lancet/article/PIIS0140673607603316/comments?totalcomments=1
21) Stagnaro Sergio. Bedside diagnosing Pancreas Cancer , even in its inherited real Risk.
Cases Journal BMC. 31 October 2008. http://www.casesjournal.com/content/1/1/280/comments#313610
22) Stagnaro Sergio. Bedside Detecting Lung Cancer Inherited Real Risk. Variant Baserga’s Sign. Medical News Today’s, 23 Oct 2008. http://www.medicalnewstoday.com/youropinions.php?opinionid=33875
23) Stagnaro Sergio. Bedside Diagnosing Pheochromocytoma, since its initial stage of Inherited Real Risk. Cases Journal 2008, http://www.casesjournal.com/content/1/1/30/comments#304598
24) Stagnaro Sergio. Bedside diagnosis of osteoporotic constitution, real risk of inheriting ostoporosis, and finally osteoporosis. Theoretical Biology and Medical Modelling 21 June 2007. http://www.tbiomed.com/content/4/1/23/comments#285569
25) Stagnaro-Neri M., Stagnaro S., Diagnosi Clinica Precoce dell’Osteoporosi con la Percussione Ascoltata. Clin.Ter. 137, 21 -27 1991 [Medline].
26) Stagnaro S. Co Q10 in the prevention and treatment of primary osteoporosis. Preliminary data. Clin Ter.;146(3):215-9 [MEDLINE]
27) Stagnaro S., Stagnaro-Neri M. Valutazione percusso-ascoltatoria del Diabete Mellito. Aspetti teorici e pratici. Epat. 32, 131, 1986.
28) Stagnaro S., West PJ., Hu FB., Manson JE., Willett WC. Diet and Risk of Type 2 Diabetes. N Engl J Med. 2002 Jan 24;346(4):297-298. [Medline]
29) Stagnaro Sergio. Role of Coronary Endoarterial Blocking Devices in Myocardial Preconditioning - c007i. Lecture, V Virtual International Congress of Cardiology. http://www.fac.org.ar/qcvc/llave/c007i/stagnaros.php
30) Stagnaro Sergio. Biophysical-Semeiotic Inherited Coronary Real Risk, conditio sine qua non of CAD.17 August 2007.
http://www.annals.org/cgi/eletters/0000605-200708070-00167v1#19068
31) Stagnaro Sergio. Reale Rischio Congenito di CAD: Nosografia e Terapia. www.fce.it 22 maggio 2008 http://www.fcenews.it/index.php?option=com_content&task=view&id=1390&Itemid=47
32) Stagnaro Sergio. Bedside recognizing Inherited CAD Real Risk. www.natura.com 21 May, 2008. http://network.nature.com/forums/pmgs/1587?page=1#reply-4262
33) Stagnaro Sergio. Bedside Recognizing CAD Inherited Real Risk and silent CAD with Biophysical Semeiotics. Lipid in Health and Disease. (29 May 2008) http://www.lipidworld.com/content/7/1/19/comments#299588
     34) Stagnaro Sergio. Bedside Evaluation of CAD biophysical-semeiotic inherited real risk under NIR-LED treatment. EMLA Congress, Laser Helsinki August 23-24, 2008. "Photodiagnosis and photodynamic therapy", Elsevier, Vol. 5 suppl 1 august 2008 issn 1572-1000.
     35) Stagnaro Sergio. Diagnosi clinica di cuore sano in un secondo! 7 Aprile 2008. www.fce.it http://www.fcenews.it/index.php?option=com_content&task=view&id=1218&Itemid=47
     36) Stagnaro Sergio. Saint’s Syndrome. Bed-side Diagnosis by means of Biophysical-Semeiotics. www.semeioticabiofisica.it
http://www.semeioticabiofisica.it/semeioticabiofisica/Documenti/Eng/Sindrome%20di%20Saint%20engl.doc
     37) Stagnaro Sergio. Hiatal Hernia, Oesofageal Peristalsis Modificazions And Gastro-Oesofageal Reflux Disease (Gerd): Clinical Diagnosis By Means Of Biophysical Semeiotics.
www.semeioticabiofisica.it http://www.semeioticabiofisica.it/semeioticabiofisica/Documenti/Eng/Ernia%20Jatale_eng.doc
38) Stagnaro S., Stagnaro-Neri M. Auscultatory Percussion in Detection Focal Liver Leions even Clinically Silent. Acta Med. Medit. 8, 89-94, 1992.
39) Stagnaro S. Bed-side diagnosing acute appendicitis and gastrointestinal diseases. Gut.j.on line, 2003: http://gut.bmjjournals.com/cgi/eletters/52/5/770-a#100
40) Stagnaro-Neri M., Stagnaro S., Appendicite. Min. Med. 87, 183, 1996 [Medline]
41) Thompson J.N., Gibson R., Czerniack A., Blumgart L.H., Focal liver lesions: a plan for management,
Brit. Med. L, 1985, 290, 1643.
42) Scheible W., A diagnostic algorhitm for liver masses, Semin. Roemtgenol., 1983, 18, 84.
43) Johnson C.M., Sheedy P.P., Stanson A.W., Stephens D.H., Hattery R.R., Adson M.A., Computed
tomography and angiography of cavernous hemangiomas of the liver, Radiology, 1981, 138, 115.
44) Snow J.H., Goldstein H.M., Wallace S., Comparison of scintigraphy, sonography and computed
tomography in the evolution of hepatic neoplasm, A.T.R., 1979, 132, 915.

Sergio Stagnaro MD
Via Erasmo Piaggio 23/8
Riva Trigoso (Genoa) Europe
Founder of Quantum Biophysical Semeiotics
Who's Who in the World (and America)
since 1996 to 2009
Ph 0039-0185-42315
Cell. 3338631439
www.semeioticabiofisica.it
dottsergio@semeioticabiofisica.it

In Defense of Pharmacogenetics

noreply@blogger.com (SciPhu) — Wed, 28 May 2008 11:09:00 +0000

Author: Nils Reinton
Furst Medical Laboratory, Søren Bullsv. 25, N-1051 Oslo, Norway (nreinton_at_furst.no)

Pharmacogenetics is the analysis of specific genetic markers informing you of how efficiently you metabolize a given drug. When it comes to metabolism of drugs used for treating psychiatric disorders (ranging from mild depression to severe psychosis), three genes are commonly analyzed: Cyp2C9, Cyp2C19 and Cyp2D6. Of course, other things than genetics also influence how you respond to a drug, like compliance, diet and smoking, but individual genetic variation have profound stand-alone effects. If your genetic test shows the presence of clinically relevant genetic variants you will be grouped as a Poor Metabolizer (higher risk for unwanted side effects) or Ultrarapid Metabolizer (not responding to medication or in need of very high dosage). For a patient experiencing adverse events or no response at all when taking his medicine, pharmacogenetics can be a tremendous help in choosing more fitting medications (change dosage or use another (sub)class of drugs). Pharmacogenetics is thus, a vital part of personalized medicine.

Recently a commentary - "A Case Study of Personalized Medicine" by Katsanis et al., was published in Science (subscription may be required), where the use of pharmacogenetics before choosing upon medication was discouraged. The reason for this was the finding that doctors failed to follow up on recommendations based on test-results. I will try to argue against such a negative approach towards pharmacogenetics and attempt to show that pharmacogenetis is in fact a valuable tool, especially for patients on psychoactive drugs who experience adverse events or lack of effect.

Claim 1: Doctors fail to follow medication recommendations based on pharmacogenetic lab-results.

Counter argument: Physicians either not understanding the test-results or ignoring lab results (due to personal conviction of some sort, be it based on clinical experience or not) reflects a general problem not restricted to pharmacogenetics. Health professionals lack of understanding is especially common for genetic tests. One could argue then, that tests that are too difficult for doctors to interpret should not be made available. But, one could easily counter argue that such an approach would be a major obstacle to medical progress. New tests will always need a time-window of learning and enlightenment. To narrow this window, the following message needs to driven home:

A patient that has to try many different drugs to achieve the desired effect without adverse reactions, is mistreated in a costly manner. Pharmacogenetics constitutes a once in a life-time test allowing a targeted approach straight towards the medication most likely to be suitable. When recommendations based on lab-results are implemented in the treatment regime, pharmacogenetic testing is cost effective and in the best interest of the patient.

Claim 2: Physicians seem to be unable to pick the right patients, and pharmacogenetic testing becomes an inefficient (as well as over hyped and expensive) general screening method, also lacking subsequent changes in medication-therapy. That the frequency of mutant alleles in the normal population does not differ from that in a given patient population, supports this notion.

Counter argument: The overall frequency in a population is irrelevant to the patient, as finding his individual response to the drug is what matters. This counter argument however, is an argument favoring screening in any given field of medicine and one may still claim that the overall cost-effectiveness is insufficient. But, in our laboratory, we do not normally get requests for pharmacogenetic testing prior to medication. Physicians using our service send samples from patients already on medication. They have come to their doctor with either adverse events or a lack of clinical effect. In our opinion these are the right patients to test. We have no reason to believe that the physicians resist changing to other medications based on our lab results when the case presented to them is as defined as this. Thus, pharmacogenetics in our hands, is targeted diagnostics rather than general screening. In addition, we have done a small study (a panel of 12 SNP's and 2D6 copynumber variation on 595 patients) to show that the allele frequency in our patient population is either at the high end of normal variation, or above that seen in a normal population (see figure, European country codes in parentheses):

Similar results (see figure) are obtained when looking at frequency of poor and ultra rapid metabolizers (PM and UM respectively).

Consequently, it seems that physicians are able to pick the right patients. And, our results support the notion that pharmacogenetic testing constitutes targeted diagnostics in the best interest of the patient.

Reinton, N.In Defense of Pharmacogenetics. Sciphu.com

The Swedish Chlamydia Mystery

noreply@blogger.com (SciPhu) — Tue, 27 May 2008 13:43:00 +0000

Authors: Nils Reinton and Amir Moghaddam
Furst Medical Laboratory, Søren Bullsv. 25, N-1051 Oslo, Norway (nreinton_at_furst.no)

In 2006, Swedish researchers noticed a peculiar trend in the number of positive Chlamydia trachomatis cases. The number of infected patients was down by as much as 25 %. This was unexpected since there had been no public health (or preventive medical) actions to explain such a drastic decrease. Also, the numbers tested for C.trachomatis was similar to previous years. In addition, this trend had not been observed anywhere else. Something strange was happening to sexually active individuals in Sweden in particular.

The reason they found, was not due to calculation error or changes in sexual habits, but in molecular diagnostics, or more precisely, the genetic flexibility of C.trachomatis (1). A genetic change had appeared creating a novel strain that was given the name "nvC.trachomatis.". This strain had a deletion in its "cryptic plasmid". The deletion was situated in the middle of the target sequence used by diagnostic kits from Abbott and Roche. Consequently, labs using kits from these suppliers (almost everyone in Sweden were using Roche) would misdiagnose any patient infected with the variant as negative for C.trachomatis infection. As a consequence of a diagnostics driven selection pressure, nvC.trachomatis may have reached almost 40 % of total C.trachomatis infections in Sweden (2). Numbers as high as 78 % were reported in some Swedish counties (3). Rapidly then, new tests were introduced to detect the strain and subsequent changes of laboratory routines in Sweden restored normal C.trachomatis detection specificities. Thus, the problem was fixed and everyone thought the mystery was solved.

Not so it seems. The real mystery started when neighboring countries started looking for the variant. Since there is extensive traveling and exchange of labor between the Nordic countries it would seem only natural that the variant C.trachomatis should spread rapidly to other countries as well. Curiously, that did not happen. By now, there have been studies in Norway (4), Denmark (5), England and Wales (6), Ireland (7) and the Netherlands (8). The only other countries nvC.trachomatis was detected was Norway where two out of 47 positives had the variant (one of these was a Swedish citizen) and Denmark which had only two cases out of a total of 383 positives. The conclusion from S Hoffmann and JS Jensen (reference 5) summed it up nicely:

"Sexually transmitted infections are unlikely to respect national borders, especially in an extended period of time. It was therefore an unexpected finding that only one case of the new CT variant was detected among 3,770 specimens tested during a five-month period. The samples were submitted from the whole of Denmark, although the majority came from the Copenhagen area. Considering the intense daily traffic between the Copenhagen area in Denmark and southern parts of Sweden, it is surprising that the spread occurred so late."

The spread is still limited. So far (April 2008) other labs in Norway have failed to find any cases at all, while our laboratory (in Oslo Norway, doing more than 20 000 C.trachomatis analyses a year) only rarely have cases of nvC.trachomatis infection. Consequently, by large the nvC.trachomatis strain remains Sweden-specific. A bug that is specific for only one given nationality is surely a novelty in epidemiology.

Finding the reason seems be far off at the moment. Because: is it likely that Swedes have strong sexual preferences towards other Swedes only ? Or are there biological differences that makes Swedes more prone to nvC.trachomatis infection ? Sexual behavior and biological signature-attributes either in the infectious agent or in the host, are usually the starting points for STD epidemiology. But in this case either scenario is unlikely. So far then, the mystery remains unsolved.

The lesson learned in diagnostics however, was probably useful for future development of diagnostic tests as pointed out by Björn Hermann (reference 3):

"What can we learn from the emergence of this new variant ofchlamydia? This thrilling story provides several lessons. Firstly,how to design a diagnostic test. The new variant is a strikingexample of diagnostics driven evolution that must be consideredwhen new methods are designed. Since routine diagnostics forchlamydia uses high volume testing based on nucleic acid detection,it is important that the targets used are not only conservedgenetic elements but also essential for the organism."

Also, comfort can be taken in knowing that the variant C.trachomatis has lost its evolutionary advantage since due to these events, diagnostics manufacturers have changed their kits to be able to detect all known variants of C.trachomatis. And, in addition, one can hope that through this curious epidemiology event, awareness of STDs have been raised further.

Constant awareness is surely needed given the continuous rise in positive C.trachomatis cases (regardless of variant strains). Unfortunately, a growing number of C.trachomatis-cases raises the probability of other new strains emerging through natural selection. This time it was easy to adapt to the new situation by changing the diagnostic method. The next time a variant bug appears it may not be this easy to find a fix. Treating the bug and stopping its spread (to achieve eradication) is what we should aim for. This story is just another one of the many wake-up calls given to us in the fight against disease-causing microorganisms over the recent years.

Reinton, N., Moghaddam, A.The Swedish Chlamydia Mystery. Sciphu.com

Use of polyethylene glycol for drying polyacrylamide gels to avoid cracking

noreply@blogger.com (SciPhu) — Wed, 26 Mar 2008 08:59:00 +0000

Authors: Amir Moghaddam and Nils Reinton

Furst Medical Laboratory, Søren Bullsv. 25, N-1051 Oslo, Norway (amoghaddam_at_furst.no).

Electrophoretic separation of proteins in non-denaturing and denaturing polyacrylamide gels remains a common technique in life science and discovery laboratories. When polyacrylamide gel electrophoresis is the last step in experimental investigation, the gel is dried down for storage, photography or exposure to X-ray film. There are two common methods for drying down polyacrylamide gels. The first and the older method is to place the gel on filter paper, to cover the gel with a plastic film and to dry the gel under vacuum and heat. Once the gel has dried, the plastic film can be removed. This method has been reproducibly used for decades for gels with low percentage polyacrylamide, such as less than 10%. If analysing relatively low molecular weight molecules, such as peptides, then higher percentage polyacrylamide gels is required and drying these gels becomes irreproducible and sometimes impossible. The gels would often crack. Several recommendations have been made to overcome the cracking problem, mainly by soaking gels in diluted glycerol. High percentage polyacrylamide gels, soaked in glycerol do not reproducibly dry with this method without cracking.

The second and newer method of drying polyacrylamide gels is to sandwich the gel with 2 cellophane sheets and to clamp the whole cellophane sandwich. The polyacrylamide gels needs to be soaked in 1-3% glycerol before drying and the cellophane sheets need to be soaked in 10% glycerol. As the cellophane dries, it shrinks and stops the gels cracking. The cellophane method is much more reliable for drying high percentage polyacrylamide gels than drying on filer paper, although the problem of cracking remains for 12 to 16% gels. However, there is one major draw back. The cellophane cannot be removed from the gel as it is irreversibly stuck to the gel. This becomes a problem if the gel is to be exposed to X-ray film and if the radiolabel is a or b emitter, such as ³⁵S. For example, Metabolically labelled ³⁵S-methionine and ³⁵S-cysteine labelled proteins, separated on a polyacrylamide gel and dried in a cellophane sandwich cannot be exposed to X-ray film as the emitted particles do not cross the cellophane membrane. If fluorography is to be used, then the gels have to be soaked in a fluorophore and that increases the chances of cracking while drying.

We have overcome the problem of drying high percentage polyacrylamide gels without cellophane sticking by simply soaking our polyacrylamide gels in 20% polyethylene glycol (PEG)-400 (1) prior to drying. This technique is reliable and versatile and works with both gel-drying methods, drying on filter paper and drying in a cellophane sandwich. Figures 1 and 2 show the effectiveness of drying a 16.5% SDS-polyacrylamide gel by soaking in a solution containing 20% PEG-400 and 50% methanol for 15 minutes compared to soaking in glycerol.

Fig. 1:

Figure 1.

16.5% SDS-polyacrylamide gel was used for separation of proteins prior to fixing and staining with coomassie brilliant blue. The gels were not destained completely to allow easier photography.After destaining, the gels were soaked in 20% PEG-400 and 50% methanol (A) or 10% glycerol (B) for 15 minutes before placing on a wet 3 mm think filter paper (Whatman) and placed in a gel dryer and dried under vacuum at 75 ^oC for 2 hours.

Fig. 2:

Figure 2. 16.5% SDS-polyacrylamide gel was used for separation of proteins prior to fixing and staining with Coomassie brilliant blue. The gels were not destained completely to allow easier photography.After de-staining, the gels were soaked in 20% PEG –400 + 50% methanol for 15 minutes (A) or 3% glycerol for 60 minutes before sandwiching between two cellophane sheets. The sheets were soaked in water before hand according to the manufacturer’s instructions (Bio-rad). The gels were dried overnight.

We also tested whether PEG would interfere with fluorography. We found that we could supplement the fluorophore, Amplify^TM(Amersham), with PEG-400 to aid drying of the gel.Radiolabelled proteins on these gels would produce a stronger signal on an X-ray film compared to the same preparation radiolabelled proteins exposed to film without soaking in the fluorophore (figure 3). We could not assess the intensity of bands on an X-ray film, if the gel was exposed to fluorophore alone without PEG, as the gels would consistently crack into many pieces during drying.

Fig. 3:

Figure 3. An antibody and protein-A sepharose was used for immunoprecipitation of its target antigen from cells radiolabelled with ³⁵S-methionine. The immunoprecipitate was boiled in Laemmli buffer and was loaded onto two lanes of a 16.5% polyacrylamide gel, half in each lane. After separation, the gels was fixed. One lane was soaked in Amplify™ supplemented with PEG-400 to 20% and the other in 20% PEG-400 alone. After drying, the plastic sheet was removed and the gels were exposed to X-ray film.

Many modern laboratories are equipped with cellophane cassettes and not heated vacuum gel dryers. For exposure of gels with b-emitting radiolabels to X-ray film, it remains necessary to remove cellophane sheet from one side of gel. In this case, one side of the gel can be covered with a plastic film, that has been cut to the same size as the gel, before putting on the cellophane. After drying the gel, the plastic film and cellophane from one side of the gel can be pealed off to expose the gel (not shown).

In summary, 20% PEG-400 is a good substitute to glycerol for drying polyacrylamide gels. It works with heated vacuum gel dryers and cellophane sheets and allows cellophane sheets to be peeled off if necessary. 20% Methoxy-PEG (poly(ethylene glycol methyl ether)-350 (1) can also be for drying gels with the same apparent effectiveness and versatility (data not shown).