Considerations on pulsoplethysmographic changes in fingers due to iontophoresis with methacholine in subjects with Raynaud's phenomenon.

This paper presents a study of plethysmographic changes induced by methacholine (a derivative of acetylcholine) administered via iontophoresis in a population of 41 young women with apparently primary Raynaud's disease. All patients presented with a very clear statistically significant sphygmic increment, obviously connected with the vasodilatation caused by methacholine. Moreover, in nearly half of the 23 cases whose reaction to passive postural variations was successively examined by plethysmography, the district circulatory response was characterised by persistent neurogenous vasoconstriction due to methacholine or by inadequate vasomotor EDRF mediated modulation. The authors believe that their findings serve as further evidence of the pathogenetic mechanisms of Raynaud's disease. This is because they highlight the role played by "balance of vessel motility" which would guarantee district circulatory homeostasis. Concrete proof thus corroborates well known indirect evidence that a pathological vasospasm can be triggered and persist when two fundamental conditions are met: a) intense vasoconstriction initially of neurological origin and successively reinforced by biohumoural synergic stimuli; b) the breakdown of the capacity for EDRF mediated intrinsic vasomotor modulation. It is suggested that the prevalence of one or the other factor would lead to a variety of clinical pictures denoting vascular acrosyndromes of this type. The ability to single out such clinical pictures by adding the iontophoresis test with methacholine to routine screening procedures for the presence of Raynaud's disease, would allow physicians to make more accurate diagnosis and improve therapy.

[Occupational vascular acrosyndromes. Considerations on plethysmographic changes in the fingers resulting from postural variations of the arms: do they have diagnostic relevance or just physiopathologic significance?]. / Acrosindromi vascolari professionali. Riflessioni sulle modificazioni pulsopletismografiche digitali da variazioni posturali degli arti superiori: hanno valore diagnostico o solo significato fisiopatologico?

334 subjects all with anamnesis indicating a vascular acrosyndrome (mostly due to their working conditions) were studied using the pulsoplethysmographic method to evaluate whether a relationship exists between the absence of increases to physiological acral posture and the presence of Raynaud's disease successively induced by Cold Test. The results obtained showed marked correlation (which for some of the subgroups examined was also statistically significant) between the lack of postural regolation and abnormal or frankly phatological plethysmographic findings following the Cold Test. The results appeared to be of some relevance in the physiopathologic interpretation of vascular acrosyndromes. According to the authors, the findings constitutive further proof of the reole played by changes in the "balance of vessel motility" in maintaining district circulatory homeostasis and may indicate the prevalence of vasoconstriction over endotelially mediated vasodilation. Consequently, the adoption of a routine test to evaluate postural sphygmic changes, before the traditional Cold Test, would allow more precise diagnosis and prognosis, particularly in the area of professional angiopathies.

[Occupational exposure to vibration: Raynaud's phenomenon and the vascular response to methacholine iontophoresis]. / Esposizione professionale a vibranti: fenomeno di Raynaud e risposta vascolare a ionoforesi con metacolina.

A homogeneous group of 34 subjects exposed to occupational vibratory stress were studied to determine their vasodilatory response to methacoline. The methacoline was administered by iontophoresis. Methacoline is an acetylcholine derivate with the same pharmacological properties of acetylcholine. The 34 study subjects were divided into 3 groups according to their plethysmographic response to a preliminary cold test: group 1, had a typical Raynaud's response; group 2 had normal response to cold, and group 3 had an "intermediate" response. The subjects in group 1 did not respond to methacoline with vasodilation, suggesting endothelial damage at the arterial and arteriolar level, those in group 2 responded with clear vasodilation, and those in group 3 had an intermediate plethysmographic response to methacoline--modest, slowed vasodilation. Based on the results obtained, the authors believe that the true pathogenetic mechanism is an alteration in the vasomotor stability. This change in circulatory homeostasis occur after a vasoconstrictive stimulus, due to vascular endothelium disfunction, in its turn damaged by vibratory microtrauma. This would be the basis for diminished autonomic vascular regulation, mediated by EDRF at the arterial and arteriolar level. It is also probable that the pathogenesis of Raynaud's syndrome in workers exposed to physical or chemical stress has a similar mechanism.

[Aberrant papillary muscle causes wall motion alterations: diagnostic implications]. / Muscolo papillare accessorio quale causa di alterazioni della cinetica parietale: implicazioni diagnostiche.

We report a case of 77 year old man who never complained cardiac symptoms, with progress septal myocardial infarction diagnosed by electrocardiographic signs and akinesia of the septum-apical segment, detected by echocardiography. He underwent a new echocardiographic examination that pointed out an aberrant papillary muscle in the left ventricle which base (19 mm) was situated on the middle of the anterior-septum and apex connected with the apical portion of the lateral wall, inducing a dissinergic movement of the septum-apical segment as for the adjacent wall segments and with a reduced sistolic thickening. An exercise myocardial perfusion scintigraphy (Tl 201) detected no reversible or irreversible uptake defects, continuous ecg monitoring and an exercise test did not show any ischemic event. We discuss the electrogenetic and wall motion implication due to an aberrant papillary muscle that can be errorly considered secondary to a progress myocardial infarction.

[Echocardiographic assessment of alcohol consumers in different clinical stages]. / Valutazione ecocardiografica di alcolisti in differenti stadi clinici.

In relation to the importance of cardiac damage in alcohol drinkers this study aims to check the modifications of some cardiac sonographic parameters in drinkers examined at different stages of alcohol intoxication. Seventy-seven male subjects (43 +/- 9 years old) were divided into 3 groups in relation to the biohumoral alterations used for the diagnosis of chronic alcoholism (increase of GGT and MGV). EF, interventricular septum hypertrophy, LVEdD and the presence of left ventricular diastolic failure were considered. All these cardiac sonographic parameters "in toto" were first compared with the same parameters of a group of normal subjects and then the differences of these sonographic parameters between the 3 groups of drinkers were evaluated. These data confirm the early onset of cardiac damage and also that the cardiac alterations may occur before the modifications of the biohumoral parameters considered too. The alterations of the cardiac sonographic parameters considered in this study seem to be a good marker for the identification, quantification and staging of cardiac damage. Interventricular septum hypertrophy, EF and EDV (in this sequence) are to be considered usefull for the diagnosis of cardiac damage in alcohol drinkers. However also LVEdD and the presence of left ventricular diastolic failure are to be evaluated before any therapy.

[The diagnosis of occupational hand-arm syndromes. 2. The quantification of the plethysmographic changes due to the cold test]. / La diagnosi delle acrosindromi professionali. Parte 2: Quantificazione delle modificazioni pletismografiche da Cold Test.

The diagnostic utility of digital volumetric pulse plethysmography with the cold test in well known for the study of subjects vibrations exposed and symptomatic for acrosyndrome. In this study the authors show how to perform this test and how to analyse the results quantitatively (in particular the time-course of the vascular modifications during cold test) to improve the clinical interpretation and to allow a comparison during the years. The parameters studied are: the morphologic pattern of each wave; the entity, duration and the regression pattern of the modifications after cold test; the existence of hemorrheologic predisposing conditions to vasospasm. To each of these parameters it has attributed a score and all the scores together represent the sphygmic answer to the cold test.

[The diagnosis of occupational hand-arm syndromes. 1. The state of the art]. / La diagnosi delle acrosindromi professionali. Parte 1. Stato attuale delle conoscenze.

Alterations of the microcirculation are, at our latitudes, the most common distal manifestations of the hand-arm syndrome, and of a number of other work-related diseases. Diagnostic investigations aimed at providing documentary evidence for microvascular damage or disfunction are, therefore, of particular importance. This paper discusses the currently available diagnostic approaches for professional acrosyndromes. The biohumoral alterations associated with cold-induced angiospasm are also described, but their diagnostic utilization is not recommended. The technical aspects of the "cold tests", as well as its advantages and drawbacks, are finally presented. On the basis of a personal experience with over 4.500 subjects, the authors conclude that, in the field of prevention, digital volumetric pulse plethysmography in association with the "cold test" should be adopted to evaluate the worker fitness for specific tasks.

[Early ECG changes after experimental focal cerebral ischemia. A pathogenetic hypothesis of the brain-heart syndrome]. / Alterazioni ecgrafiche precoci dopo ischemia focale cerebrale sperimentale. Una ipotesi patogenetica della sindrome cerebro-cardiaca.

Primary CVT alterations and arrhythmias, occurring one hour after embolization were detected in several experiments about focal cerebral ischaemia in rabbits. 62 animals were fed on a standard diet and 15 on an atherogenic diet. Primary CVT alterations and arrhythmias occurred in 4 rabbits fed on a standard diet and in 6 rabbits fed on an atherogenic diet. These results gave statistic evidence of a relationship between more frequent and serious electrocardiographic alterations and an atherogenic diet. The information coming out of these experiments are discussed. Considering the data coming out of other experiments and the data of the literature it is supposed that the pathogenesis of "the cerebro-cardiac syndrome" is linked to several biohumoral alterations occurring after the stroke. If these alterations occur in animals (or in subjects) with damaged coronary arteries cardiac alterations occurring after the stroke are greater and more important than the cardiac alterations occurring in the same conditions in the animals in which coronary arteries are not jet damaged.

The brain-heart syndrome: remarks on early ecgraphic changes following focal cerebral ischemia in healthy and in experimentally hyperdyslipidemic rabbits.

Early cardiac effects of focal cerebral ischemia in two groups of rabbit, one of which made hyperdyslipidemic with an atherogenic diet, were detected in several experiments. In the group of 62 animals fed on a standard diet, primary CVT alterations and arrhythmias occurred in 4 rabbits (6.4%), in the group of 15 animals fed on an atherogenic diet the same cardiac alterations occurred in 6 rabbits (40%). A marked statistically significant prevalence of ECGraphic changes was observed in hyperdyslipidemic group. These results and the data coming out of other experiments and literature suggest that the pathogenesis of the "cerebro-cardiac syndrome" is linked to several biohumoral alterations occurring after the stroke. If these events affect functionally damaged endothelia, or occur in the presence of atherosclerotic plaques, cardiac alterations occurring after the stroke are greater than cardiac alterations observed in the same condition when coronary are intact or little damaged.

Blood hypercoagulability secondary to experimental cerebral ischemia in the rabbit: influence of a hyperdyslipemia induced by an atherogenic diet.

Within the framework of a research carried out at the Neurological Institute of Pavia on experimental cerebral ischemia some biohumoral determinations were done on two groups of rabbits: one kept on a standard diet and the other on an atherogenic diet to induce dyslipemia. The aim was to find out whether induced ischemia produces an activation of the hemocoagulation processes and whether hyperdyslipemia constitutes an aggravating factor. In the animals on a standard diet there was a statistically significant increase in factor X A and a nonsignificant increase in parameter (r + k) on TEG (thromboelastogram) and of factor VIII C after embolization. In the hyperdyslipemic group the changes were definitely more marked and, in the case of factor VIII C and parameter (r + k), statistically significant, accompanied by slight variations in APTT and factor IX pointing in the same direction. We discuss the meaning of our findings.

[Occupational syndromes of the extremities. The role of endothelin in the cold-test vasospasm: a pathogenetic hypothesis]. / Acrosindromi professionali. Ruolo dell'Endotelina nel vasospasmo da Cold Test: una ipotesi patogenetica.

UNLABELLED: In 34 subjects (29 subjects vibrations exposed and 5 controls), the variations of seric levels of endothelin (Et) after Cold Test were investigated, while vasomotor modifications were monitored and recorded by forefinger volumetric pulsoplethismography. Blood sampling for Et dosage (from dorsal vein of the hand) was done in 17 subjects after 2' Cold Test and in 17 subjects after 5' Cold Test. RESULTS: 1) Et levels are always increased after Cold Test but level increase is statistically significant only after 5' Cold Test. 2) There is no evidence of relations between Et level increase and pulsoplethismographic alterations showing acral vasospasm. It is evident that in Raynaud phenomenon Et increase is not the only factor but takes part in the occurring of this acrosyndrome. When endothelium has a reduced activity opposing cold induced vasoconstriction, seric Et increased level may represent a biohumoral factor enhancing entity and duration of vasospasm.

EEG changes and platelet aggregation in experimental cerebral focal ischemia in rabbits.

Nine white New Zealand rabbits were submitted to internal carotid embolization with microspheres which caused a histologically verified focal cerebral ischemia. Six animals were sham-operated. EEG, QEEG, ECG, blood pressure, rectal temperature and platelet aggregation were monitored in basal conditions and one hour after ischemia. Embolized animals showed an increase in power density spectrum (PDS) and delta activity (0.15-3.70 Hz) and the appearance of platelet aggregation. The QEEG changes were correlated to the degree of platelet aggregation after ischemia.

[Multicenter study of the effectiveness and tolerance of clotiazepam in cardiology]. / Studio policentrico sull'efficacia e tollerabilità del clotiazepam in cardiologia.

In a phase IV study with clotiazepam 9 cardiologists were involved to treat 86 patients (52 female, 32 male, mean age 51 years) effected by cardiovascular diseases and anxiety. The dosage was 5-10 mg TID, and the treatment lasted for 3 weeks. Variations of the dosage were requested in 21% of patients and generally at the 2nd week of treatment. The safety of clotiazepam was good: only in the 14% of patients side-effects were observed (especially drowsiness 9.3% and asthenia 2.3%). Clotiazepam was judged to be effective in 75% of patients. The Hamilton psychiatric rating scale for anxiety showed a progressive decrease both of the total score and of the scores of every item; the cardiovascular symptoms particularly improved at both the controls.

[Angiopathy caused by vibrating tools: cold test and prostaglandin balance]. / Angiopatia da vibranti: cold test e bilancia prostaglandinica.

A study was made on a group of workers occupationally exposed to tools producing medium-to-low frequency vibrations, and on a comparable control group. The subjects underwent a plethysmographic examination with the cold test, which revealed a greater number of sphygmic alterations in the exposed group; at the same time spontaneous platelet aggregation, blood levels of 6-K-PGF-1 alpha and TXB2 and urinary levels of BTGU were determined in basal conditions and after the cold test. Except for the slight, and not statistically significant, increase in TXB2, the results did not reveal any alterations in the constituents of the prostaglandin balance after the cold test. This therefore indicates that biohumoral changes of this type were not involved in producing cold-induced vasomotor alterations in the group under study. However, further investigations are recommended which will take account of the age and working history of the subjects, and particularly of the physical characteristics of the vibrations produced by the tools used, especially the Hz number.

[Type A behavior and cardiovascular reactivity. Preliminary findings]. / Tipo comportamentale "A" e reattività cardiovascolare. Rilievi preliminari.

In view of reports of a connection between ischaemic cardiopathies and "A" type behaviour, the response of certain cardiocirculatory parameters to given physical stimuli was investigated in a group of people doing high stress work. The data did in fact reveal a tendency to more pronounced cardiovascular reactivity in the A group, a difference that was statistically significant in the cold pressor and cold tests. The possible links between enhanced vasomotor response and increased risk of coronary heart disease are pointed out with emphasis on recent hypotheses about the possible pathogenic role of enhanced 5-OH-tryptamine release and particular alterations in the alpha/beta adrenergic receptor balance.

[Spontaneous platelet aggregation after experimental focal ischemia in the rabbit. "Sensitivity", "specificity" and value of the test used]. / Considerazioni sull'aggregabilità piastrinica spontanea dopo ischemia focale sperimentale nel coniglio. "Sensibilità", "specificità" e validità del test impiegato.

Within the framework of an investigation at present under way at the Neurological Clinic of Pavia on experimental focal ischaemia, the peculiarities of platelet aggregation observed, have led to a more accurate assessment of both the phenomenon itself and the validity of the method used. In a group of 30 rabbits (17 of them submitted to embolization by means of microspheres introduced into the carotid and 13 used as controls), biohumoral electrical and histological parameters were examined. The spontaneous platelet aggregation test proved significantly related to the extent of changes taking place, as measured by PDS levels and QEEG "delta" activity (respectively, P less than 0.005 and P less than 0.05). Platelet aggregation, in relation to the occurrence or absence of focal ischaemia, revealed a "sensitivity" of 80% and a "specificity" of 92.3%. When not only the onset of but also the increase in aggregation is taken into account, the "sensitivity" figure appears to go up to 93.3%. Endothelial damage and "cascade" platelet aggregation appeared to be a prerequisite for the occurrence of the changes found. In these changes, the pathogenetic role of the regional vasospasm as opposed to mere mechanical obstruction seems to be confirmed. On the basis of these findings, it is concluded that the identification of spontaneous platelet aggregation using K. Breddin's method and its quantification based on Born's turbidimetric principle, may be usefully employed to assess the risk factor constituted by an abnormal tendency to platelet hyperaggregation.

[Vibration-induced angiopathy: significance of urinary beta-thromboglobulin increase after cold test]. / Angiopatia da vibranti: sul significato di un incremento della BTGU dopo Cold Test.

Twenty subjects working with tools generating 100-400 Hz vibrations were submitted to volumetric pulse-plethysmography with cold Test (C.T.) and to the measurement of BTGU, a thromboxane urinary catabolite. After C.T. an increase of BTGU was observed, which attained statistical significance in the subgroup with the most evident plethysmographic modifications. The meaning of these findings is discussed, also in the light their apparent contrast with some literature data. The AA believe that the prostaglandin balance can actually play a role in the pathogenesis of C.T.-induces vasomotor changes, if the tools used generate a sufficiently high number of Hz and if the workers are still rather young. This last condition corresponds to a greater intactness of endothelia and thus to the ability to modulate the vasomotor response ("hunting reaction"). This would lead to the activation of more complex pathogenetic mechanism (also biohumoral ones) among which is thromboxane release.

Quantified EEG, somatosensory evoked potentials and cerebral blood flow in monitoring experimental brain ischemia.

Cerebral ischemic lesions were induced in rabbits through internal carotid artery embolization by means of microspheres. Different models of stroke ranging from single focal cortical lesion to massive bilateral brain edema were reproduced and monitored up to the 24th hour by electroencephalogram (EEG and QEEG), somatosensory evoked potentials (SEPs), cerebral blood flow (CBF), platelet aggregation. The site and extent of the lesions were verified by histological examinations. Results obtained and physiopathological implications are discussed.

[Cardiocirculatory findings in a group of workers exposed to nitro derivatives. A pathogenetic hypothesis of withdrawal hazard]. / Rilievi cardiocircolatori in un gruppo di lavoratori esposti a nitroderivati. Una ipotesi patogenetica del "withdrawal hazard".

After briefly recalling the professional pathology characteristics of workers exposed to nitro derivatives and the perplexities surrounding the actual pathogenetic mechanism of the "Withdrawal hazard", the AA report the results of an investigation carried out among the workers of a dynamite producing plant. In the study, the NG and EGDN environmental levels were checked and the workers were submitted to ECG tracings, ECG D according to Holter, and monitoring of postural pressure changes both during exposure to the substances and during time-outs. The results obtained showed that the concentrations found in the plant were practically within the recommended TLV values, with no pathological modifications of the parameters examined. The AA put forward a pathogenetic hypothesis based on these findings and analyzing epidemiologic data on coronary sudden death as well as the mechanisms regarded as responsible for the disorders described in the literature in professionally exposed subjects. According to such hypothesis, the "Withdrawal hazard" (if any) would not be due to the cessation of the vasodilation effect of the nitro derivatives but would be a "rebound" phenomenon following the NG - and EGDN - inhalation induced stimulation to the production of endothelial prostaglandins, and of EDRF in particular, in exposed workers. The withdrawal of nitro derivatives inhalation would thus eliminate a vascular and coronary protection mechanism in the case of pathogenetic noxae at cardiovascular level. Such an interpretation would at last account for the time elapsing between cessation of work and occurrence of the disorders, which would not be justified by the cessation of the mere vasodilating action, since this wears out within a few hours.(ABSTRACT TRUNCATED AT 250 WORDS)