venerdì 25 settembre 2009

Bedside Recognizing Diabetes since its initial stage of Inherited Real Risk


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 (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 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.

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.

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

5) Stagnaro S. Pivotal role of Biophysical Semeiotic Constitutions in Primary Prevention. Cardiovascular Diabetology, 2:1, 2003

6) Stagnaro S. Stagnaro Sergio. Newborn-pathological Endoarteriolar Blocking Devices in Diabetic and Dislipidaemic Constitution and Diabetes Primary Prevention. The Lancet. March 06 2007. Hidden!!!. Therefore See either reference 13) or,

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. 200708070-00167v1

9) Stagnaro Sergio. Single Patient Based Medicine: its paramount role in Future Medicine. Public Library of Science. 2005

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

11) Stagnaro Sergio. Il test Semeiotico-Biofisico della Osteocalcina nella prevenzione primaria del diabete mellito.,

12) Stagnaro Sergio e Paolo Manzelli. L’Esperimento di Lory. Scienza e Conoscenza, N° 23, 13 Marzo 2008.

13) Stagnaro Sergio. Pre-Metabolic Syndrome and Metabolic Syndrome: Biophysical-Semeiotic Viewpoint., 29 April, 2009.

14) Stagnaro Sergio. Without CAD Inherited Real Risk no diabetic is involved by coronary disorder. CMAJ, 6 May 2009.

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,, Roma, Luglio 2009.

lunedì 25 maggio 2009

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

Overlooked Quantum-Biophysical-Semeiotics does really exists(1-12). See also 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).


1. Stagnaro Sergio e Paolo Manzelli. Semeiotica Biofisica Quantistica. 15 Dicembre 2007 tutto.asp?IDS=13&NWS=NWS5243

2. Stagnaro Sergio e Paolo Manzelli. Semeiotica Biofisica Endocrinologica: Meccanica Quantistica e Meccanismi d’Azione Ormonali. Dicembre 2007,,

3. Stagnaro Sergio e Paolo Manzelli. Natura Quantistica di una Originale Manovra Semeiotico-Biofisica di Epatopatia . Dicembre 2007,

4. Stagnaro Sergio e Paolo Manzelli. Semeiotica Biofisica: Realtà non- locale in Biologia. Dicembre 2007,,

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

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

7. Stagnaro Sergio. Il test Semeiotico-Biofisico della Osteocalcina nella prevenzione primaria del diabete mellito. Febbraio 2008.

8. Stagnaro Sergio. Esperimento di Lory e Crisi dei Fondamenti della Medicina Occidentale. 17 Febbraio 2008

9. Stagnaro Sergio e Paolo Manzelli. L’Esperimento di Lory. Scienza e Conoscenza, N° 23, 13 Marzo 2008.

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

11. Stagnaro Sergio. Biological System Functional Modification parallels Gene Mutation.,March 13, 2008, 12. Stagnaro Sergio. Melanoma? Escluso in 1 Secondo con La Semeiotica Biofisica Quantistica. Il Reale Rischio Congenito di Melanoma., 9 Aprile 2008, tutto.asp?IDS=13&NWS=NWS5524

13. Stagnaro Sergio. Diagnosi clinica di cuore sano in un secondo! 7 Aprile 2008,

14. Stagnaro Sergio . Also Family Physicians are able of greatest clinical Discoveries! Annals Family Medicine,(16 April 2008),

15. Stagnaro-Neri M., Stagnaro S. Introduzione alla Semeiotica Biofisica. Il Terreno Oncologico. Ed. Travel Factory, Roma, 2004.

16) Stagnaro Sergio. Renin-angiotensin blockade and kidney disease inherited real risk. The, September 23, 2008.

venerdì 22 maggio 2009

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

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,,) [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.


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. and especially:,

7. Stagnaro-Neri M., Stagnaro S. Introduzione alla Semeiotica Biofisica. Il Terreno Oncologico. Travel Factory, Roma, 2004.

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.
Stagnaro S., Stagnaro-Neri M., Single Patient Based Medicine.La Medicina Basata sul Singolo Paziente: Nuove Indicazioni della Melatonina. Ed. Travel Factory, Roma, 2005.
11. Stagnaro Sergio. New bedside way in Reducing mortality in diabetic men and women. Ann. Int. Med.
12. Stagnaro Sergio. Newborn-pathological Endoarteriolar Blocking Devices in Diabetic and Dislipidaemic Constitution and Diabetes Primary Prevention. The Lancet. March 06 2007.

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.

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.

26. Stagnaro Sergio. Bedside Biophysical-Semeiotic Osteocalcin Test in Diagnosing and Monitoring Diabetes. The Lancet, January 28, 2008.; See especially,

27. Stagnaro Sergio. Semeiotica Biofisica Quantistica: Diagnosi Clinica di Melanoma a partire dal suo Reale Rischio Congenito., 23 luglio 2008,

giovedì 21 maggio 2009

Biophysical-Semeiotic Bed-Side Evaluation of Endothelial Function


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


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

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-mediated vaso-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 physical barrier that simply separates blood from tissue. It is evident that disturbed endothelial function may be an early marker of an ongoing atherosclerotic process. Thus, inherited endothelial dysfunction has increasingly been recognized to play an important role in a number of conditions associated with a high prevalence of atherosclerotic CVDs (1-6), according to my Microvascular Arteriosclerosis Theory (partly illustrated in above-cited website, URL

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


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.
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,

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.
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.

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.

24) Stagnaro Sergio. Role of Coronary Endoarterial Blocking Devices in Myocardial Preconditioning - c007i. Lecture, V Virtual International Congress of Cardiology, 2007.

25) Stagnaro Sergio. Pre-Metabolic Syndrome and Metabolic Syndrome: Biophysical-Semeiotic Viewpoint., 29 April, 2009.

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., 29 April, 2009

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]

martedì 19 maggio 2009

Quantum-Biophysical-Semeiotic Hypertensive Constitution.


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.


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


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

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).



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, 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, Practical Applications, URL,%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) O2 Recovery Time (O2 RT), assessed as latency time of tGC disappearing (NN = 2 ± 0,5 sec.) .

8) Arterial peripheral resistance (APR = MAP/10 x O2 RT); 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 .

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 NPs 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

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