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We performed a multicentre study to evaluate the agreement between the direct clinical diagnosis and the telediagnosis of 43 cutaneous pigmented lesions. Digital clinical and dermoscopic images of the 43 pigmented skin lesions (11 melanomas, 23 melanocytic naevi, three basal cell carcinomas, three lentigines, two seborrhoeic keratoses and one angiokeratoma) were sent by email to 11 colleagues (six dermatologists, two residents in dermatology, one oncologist, one specialist in internal medicine and one general practitioner) in 10 centres. These 11 colleagues had different degrees of experience in dermoscopy. With histopathology as the gold standard, an average of 85% of the telediagnoses were correct, with results varying from 77% to 95%, whereas face-to-face diagnosis by an expert dermatologist was correct in 91% of cases. The kappa value for all participants ranged from 0.35 to 0.87. The results confirm that teledermoscopy can be a reliable technique for the diagnosis of pigmented skin lesions but one that will depend on the expertise of the observer.

In order to obtain accurate measurements of coronary sinus blood flow (CSBF), a new catheter (7 French) with a radiopaque, flexible, and basket-shaped tip was developed for guiding a standard 3 Fr Doppler catheter in the coronary sinus (CS) in man. The radiopaque "basket" tip of the catheter allows the operator to stabilize the position of the Doppler transducer in the center of the CS and to accurately measure the CS internal diameter radiologically. CSBF was calculated as the product of CS cross-sectional area by mean CSBF velocity. Doppler-derived CSBF values at rest and during handgrip were compared with those obtained by the local thermodilution technique in 16 patients undergoing diagnostic coronary angiography. During handgrip, mean CSBF increased from 154+/-23 (rest) to 299+/-34 mL/min by the Doppler method and from 148+/-22 to 288+/-32 mL/min by the thermodilution technique. A good correlation (r = 0.86) between the CSBF values with the two techniques was observed. The authors conclude that the intravascular Doppler technique associated with the use of the basket guide catheter provides an accurate and simple tool for monitoring CSBF in patients.

The widespread diffusion of echocardiography requires to rationalize clinical examination archives; the recent improvement in computer processing speed and the addition of image processing capabilities on standard personal computer by using multimedia technology provide a low-cost solution to improve video digital acquisition and base management. Furthermore, the diffusion of computer networks supports the possibility of sending images in digital format from a work station to another. In this study we describe the setting-up of a system for echocardiographic image acquisition, storage, base management and analysis based on a standard multimedia Macintosh personal computer using readily available not-dedicated software. We tested the overall efficiency of this system in terms of time required to perform hardware and software procedures, storage capacity of the archive and possibility to exchange information with other wire-linked computer work-stations or via modem. This system has proven to require an acceptable time to perform all the procedures showing a high level of connectivity with other standard personal computer work-stations; however, some limitations with regard to time required in sending via modem long movie files need to be pointed out. In conclusion, in our experience new multimedia personal computer could offer to every physician with a minimum informatic knowledge the well known advantages of digital-video, at a reasonable cost.

Muir-Torre syndrome (MTS) is an autosomal dominant disorder characterized by the presence of at least one sebaceous gland tumour and a minimum of one visceral malignant tumour. Recently, microsatellite instability (MSI) has been detected in the tumours of patients with MTS and germline mutations of the hMSH2 and hMLH1 mismatch repair genes have been detected in some patients with this syndrome. To determine if the tumours of patients with MTS have widespread genomic instability and whether loss of heterozygosity (LOH) in the chromosomal regions containing hMSH2 and hMLH1 is detectable, MSI and LOH were examined at 10 dinucleotide repeats on chromosomes 2p, 3p, 5q, 9p, 17p and 18q. Data were obtained from six sebaceous gland tumours and two adenocarcinomas of the colon from three patients of two Muir-Torre families. MSI was detected at more than half of the loci tested in all sebaceous tumours examined. In addition, there was LOH at D2S119 in one sebaceoma and one sebaceous carcinoma from one patient. The colon carcinomas from two patients showed MSI at five of the 10 loci analysed. These results show that widespread MSI is a feature of tumours in patients with MTS. In addition, the finding of LOH at D2S119, a marker located in the vicinity of hMSH2, in sebaceous tumours of one patient indicates that this gene may have a pathogenetic role in this patient.

We analyzed microsatellite instability (MSI) and loss of heterozygosity (LOH) at 17 microsatellite markers located on chromosomes 2p, 3p, 5q, 6q, 9p, 9q, 17p and 18q in 19 randomly selected keratoacantomas (KAS), in one cutaneous lesion that histologically could not unequivocally be differentiated from squamous cell carcinoma, and in one patient with multiple KAs of longstanding duration. The goals of our study were to determine whether, in a similar manner to some visceral carcinomas, genomic instability could be detected in KAs and to clarify whether molecular analysis might be useful to further characterize KA. MSI was observed in 2 of 21 cases (9.5%) at 5 of 17 loci examined. In one patient with a solitary KA, the presence of MSI and a family history of visceral malignant tumours suggested that the patient might have belonged to a family with Muir-Torre syndrome. In one other MSI+ KA, a definite differential diagnosis in relation to squamous cell carcinoma could not be established. In addition, one sample displayed LOH at 2 of 17 loci analysed whereas in the patient with multiple KAs, LOH at one locus was the only alteration found. In conclusion, the low frequency of MSI and LOH detected in our study suggests that these genetic events are uncommon in KA unless it is associated with a familial disease (e.g. Muir-Torre syndrome) or it has more aggressive histological features.

We assessed the acute effects of 2.5 mg oral cilazapril on systemic and coronary hemodynamics in seven renovascular hypertensive patients with a chronically overactive renin-angiotensin system (RAS), but with no electrocardiographic or echocardiographic signs of left ventricular hypertrophy. Cilazapril resulted in a significant decrease in mean arterial pressure and coronary vascular resistance, together with a prolonged increase in coronary sinus blood flow (CSBF). Post-cilazapril handgrip resulted in larger increases in CSBF in response to a given increase in myocardial oxygen requirements. It is concluded that the chronic activation of the RAS exerts an adverse influence on the control mechanisms of CSBF and that converting enzyme inhibition reverses the effects of angiotensin II on coronary hemodynamics. Converting enzyme inhibitors may have a cardioprotective role in renovascular hypertension.

Coronary hemodynamics were investigated invasively at rest and during handgrip exercise in two groups of mild essential hypertensive subjects and in one group of renovascular hypertensive patients. The former subjects received either furosemide (50 mg/day for one week) to ensure activation of the renin-angiotensin system or an intravenous infusion of angiotensin II (AngII) at a subpressor dose (3 ng/kg/min for 15 minutes) and at a pressor dose (13 ng/kg/min for 15 minutes). Furosemide induced a significant reduction in coronary blood flow (CBF), a significant increase in coronary vascular resistance (CVR) and also blunted the increase in CBF during handgrip exercise. Captopril restored CBF and CVR to pretreatment values. Infusion of the subpressor dose of AngII decreased myocardial oxygen supply, both at rest and during exercise; the pressor dose increased myocardial oxygen supply at rest and blunted the expected increase in myocardial oxygen supply during exercise. Converting-enzyme inhibition in renovascular hypertension caused mean arterial pressure to decrease and CBF to increase significantly. The performance of handgrip exercise after cilazapril resulted in higher increases in CBF for a given increase in myocardial oxygen requirements. These data suggest that there is a negative interference by abnormally high plasma levels AngII with myocardial perfusion and that the AngII-induced effects on coronary hemodynamics are reversed by converting enzyme inhibition.

1. The present investigation was carried out to elucidate the possible role of the renin-angiotensin system in modulating coronary vasomotor responses in eight patients with uncomplicated mild essential hypertension with no electrocardiographic-echocardiographic evidence of left ventricular hypertrophy. 2. Systemic and coronary haemodynamics were monitored at baseline and during intravenous infusion of angiotensin II at a subpressor dose (3 ng min-1 kg-1 for 15 min) and at a pressor dose (13 ng min-1 kg-1 for 15 min) both at rest and during handgrip exercise. Infusion of the subpressor dose of angiotensin II decreased coronary sinus blood flow at rest (207 +/- 10 versus 182 +/- 9 ml/min, P less than 0.05) without a significant change in mean arterial pressure, heart rate or mean right atrial pressure. The performance of handgrip at baseline and during infusion of the subpressor dose of angiotensin II resulted in 55% (321 +/- 13 versus 207 +/- 10 ml/min) and 44% (263 +/- 16 versus 182 +/- 9 ml/min) increases in coronary sinus blood flow, respectively, in response to comparable increments in the rate-pressure product. At rest, infusion of the pressor dose of angiotensin II increased both coronary sinus blood flow (235 +/- 11 versus 207 +/- 10 ml/min, P less than 0.01) and the rate-pressure product (134 +/- 5 versus 111 +/- 8 mmHg beats/min, P less than 0.01). The increase in coronary sinus blood flow during isometric exercise was less than control (309 +/- 18 versus 321 +/- 13 ml/min, P less than 0.01). 3. It is thus concluded that (1) the opposite effects of angiotensin II on coronary blood flow are dose-dependent, and that (2) angiotensin II competes with the ability of the coronary arteries to dilate during handgrip exercise.

The effects of converting enzyme inhibition on coronary and systemic hemodynamics in the presence of a chronically activated renin-angiotensin system were investigated in five renovascular hypertensive patients with no ECG/echocardiographic evidence of left ventricular hypertrophy. Coronary blood flow (CBF, thermodilution technique), intra-arterial blood pressure, AVO2 difference (coronary sinus), heart rate, and coronary vascular resistance were measured at rest, during isometric exercise (handgrip to 50% of maximal effort for 3 min) before and 60 min after 2.5 mg of oral cilazapril. The drug induced a prompt, significant decrease in mean arterial pressure and a sustained increase in CBF. The performance of handgrip after cilazapril resulted in higher increases in CBF for a given increase in myocardial oxygen requirements. These observations suggest that angiotensin II (Ang II) maintains the ability to alter the control mechanisms of CBF even under long-term conditions and that converting enzyme inhibition reverses the Ang II-induced effects on coronary hemodynamics.

The effects of converting-enzyme inhibition (25 mg oral captopril) on coronary hemodynamics in the presence and absence of activation of the renin-angiotension system were studied in 10 patients with mild essential hypertension with no evidence of ischemic heart disease. Coronary blood flow was determined by thermodilution before and after 1 week of diuretic therapy in six patients and before and after placebo in four patients. The diuretic (50 mg/day furosemide) reduced coronary blood flow and increased coronary vascular resistance; in these same patients, captopril reduced mean arterial pressure and the rate-pressure product but increased coronary flow significantly. There was no change in any of these variables after captopril in the placebo group. Similar results were obtained in normotensive rats treated with hydrochlorothiazide; the increase in coronary flow after captopril correlated significantly with the control plasma renin activity. These results in hypertensive humans and normotensive experimental animals indicate that diuretic therapy reduces coronary blood flow significantly, and angiotensin can play a significant role in modulating coronary vascular resistance under conditions associated with activation of the renin-angiotensin system.

In order to determine whether gravity influences the growth of terrestrial mammals, systolic blood pressure, heart rate, urinary output and body weight were measured at 10-day intervals from the age of 30 days (weaning) to 150 days in 12 male Sprague-Dawley rats. Six rats were grown in a gravitational environment. 'Dry' water immersion was used to subject six rats to a microgravitational environment between the ages of 30 and 90 days. A downward shift in systolic blood pressure and body weight maturation curves was observed in the microgravitational group from the age of 60 days. After the 'dry' water immersion was stopped, the fully developed rats showed a significant increase in systolic blood pressure, which returned to control values, but not in body weight. We conclude that the physiological increase in systolic blood pressure taking place in rats during growth is partly dependent on gravity.

We studied the hemodynamic mechanism responsible for the antihypertensive effect of indapamide in eight patients with mild essential hypertension. Systemic and pulmonary hemodynamics were measured using direct techniques (right heart catheterization and thermodilution method), before and 7-10 days after oral treatment with indapamide (2.5 mg/day). Indapamide reduced mean arterial blood pressure from 120 +/- 1.6 (mean +/- SE) to 101 +/- 1.4 mm Hg (p less than 0.01), and mean pulmonary artery pressure from 21 +/- 0.59 to 17 +/- 1.05 mm Hg (p less than 0.01). Total peripheral vascular resistance (TPR) and pulmonary vascular resistance were reduced from 36 +/- 0.85 to 29 +/- 0.72 U/m2 (p less than 0.01) and from 4.3 +/- 0.17 to 3.8 +/- 0.18 U/m2 (p less than 0.01), respectively. Indapamide did not change cardiac index (CI) (3,311 +/- 61.6 vs. 3,325 +/- 72.1 ml/min/m2), heart rate (HR) (75 +/- 1.7 vs. 75 +/- 9 beats/min), mean rate of left ventricular ejection index 140 +/- 2.04 vs. 139 +/- 1.99 ml/s/m2, and stroke index (44 +/- 5.6 vs. 43 +/- 5.8 ml/m2). Mean pulmonary wedge pressure decreased from 7 +/- 0.6 to 5 +/- 0.5 mm Hg (p less than 0.05). Body weight, 24-h urinary volume, and hematocrit were unchanged after treatment. We conclude that the hemodynamic mechanism responsible for the antihypertensive action of indapamide is a reduction in TPR without changes in CI and HR.

Right and left ventricular function was evaluated in 21 men with cirrhosis and tense ascites during staged removal of ascitic fluid. During paracentesis it was observed (1) that there was a significant increase in cardiac output, stroke volume, right and left ventricular stroke work and mean rate of systolic ejection; (2) that up to a certain stage of drainage (about 5,000 ml), there was a relationship between the amount of fluid removed and the intraabdominal and right atrial pressures and (3) that there was a direct relationship between improvement of cardiac function and normalization of right atrial pressure. It is believed that the increased intra-abdominal hydrostatic pressure acting upon the diaphragm affects the intrathoracic pressure to such an extent that the transmural filling pressure of the heart is reduced, and the mean pressure and respiratory pulsations of the right atrium increased, all of which impede venous return. Improved cardiac function during paracentesis appears to be due to an augmented filling of the heart and to a larger venous return.

In a patient suffering from Prinzmetal angina pectoris, ischemic attacks of the anterior left ventricular wall were associated with the following changes: fall in cardiac output; increased left ventricular diastolic pressure (LVDP) and volume; flattening of the septal motion; marked reduction of the mitral valve early diastolic amplitude and rate of opening; and marked reduction of the systolic closure velocity. It is suggested that LVDP rise depends, at least in part, on variations in left ventricular diastolic volume and segmental wall motion, and that disruption of the mitral valve motion derives from changes in LVDP and flow through the mitral orifice.

The following conclusions can be drawn : (1) The nervous outflow to the heart may be varied from the baseline to opposite directions by different stressful stimuli. (2) ST-T alterations may be induced and abolished by adrenergic activation and inhibition respectively. (3) These effects are dissociated from or not necessarily associated with an exaggerated responsiveness of the cardiac beta receptors. (4) The adrenergic influences on the ST-T abnormalities of myocardial ischemia and hypertension are limited.

Angiotensin is a potent coronary vasoconstrictor, but little is known of the effects of long-term activation of the renin-angiotensin system on coronary reserve in humans. The effects of exercise on coronary hemodynamics were determined in eight patients with mild essential uncomplicated hypertension, before and after treatment with furosemide (50 mg, to ensure activation of the renin-angiotensin system). Coronary sinus blood flow was measured by thermodilution technique, intra-arterial blood pressure was measured from the ascending aorta, and plasma renin activity was determined by radioimmunoassay. Oxygen supply and demand were derived (using coronary sinus blood flow multiplied by the arteriovenous oxygen difference to equal oxygen supply and heart rate multiplied by the mean systolic blood pressure to equal oxygen demand) both at rest and during isometric exercise (handgrip to 50 percent of maximal effort for three minutes). The study was a single-blind crossover (furosemide versus placebo) design. Furosemide produced a significant reduction in coronary sinus blood flow, associated with an increase in coronary vascular resistance. Changes in mean arterial pressure and heart rate were insignificant. Slight reductions in plasma volume and mean right atrial pressure were observed. During isometric exercise, the increase in oxygen supply for a given increment in oxygen demand was attenuated by furosemide. The contribution of the renin-angiotensin system to this effect was determined by the short-term administration of 25 mg of the angiotensin converting enzyme inhibitor captopril. Forty-five minutes after oral captopril, coronary reserve was restored to pretreatment values. In conclusion, furosemide modulates coronary reserve, and it is likely that this is because furosemide mediates activation of renin-angiotensin system, thus reducing the vasodilatory capacity of the coronary arteries.

Twelve men suffering from the primary hyperkinetic heart syndrome (PHHS) displayed palpitation, rapid and forceful heart action, increased pulsations of the large arteries, cardiac systolic murmur, and the following circulatory values (averages): systolic arterial pressure (SAP) =154 mm Hg; heart rate (HR)=91 b/min; cardiac index (Ci) =5494 ml/min/m2; left ventricular mean systolic ejection rate index (SMEJR) =227 ml/min/m2; left ventricular mean pre-ejection delta P/delta t (delta P/delta t) = 1.32 mm Hg/msec. A two-year followup during which propranolol was administered (80-160 mg/day) revealed good subjective improvement and disappearance of signs of circulatory hyperkinesis. At the end of this period the hemodynamic functions were as follows: SAP=134; HR=69; Cl=3489; MSEJR=171; delta P/delta t=0.89. Substitution of placebo for the active drug caused prompt reappearance of symptoms of cardiac overactivity in each patient, and brought the circulatory functions back to these levels: SAP=157; HR=96; Cl=5530; MSEJR=245; delta P/delta t=1.33. These findings lend further credence to the concept that the PHHS is, indeed, a definable disease entity; they also document that propranolol ameliorates the symptoms of the disease but is ineffective for the underlying disorder.

The possibility that noncardiac massive peripheral edema reduces venous distensibility was investigated in eight patients in the supine and 80-degree head-up tilt position before and after diuretic therapy. After clearance of the edema with diuretic therapy, total blood volume (TBV) was not significantly decreased; therefore, in the supine position the significant (2p less than 0.001) decrease of right atrial pressure, stroke volume, cardiac output, and cardiopulmonary blood volume (CBV) by the diuretics was due to an improvement in venous compliance which resulted in peripheral redistribution of CBV since the ratio CBV/TBV was decreased during diuretic therapy (2p less than 0.001). Furthermore, before diuretic therapy, tilt significantly decreased right atrial pressure, stroke volume, cardiac output, CBV, and the ratio CBV/TBV; but after diuretic therapy, the decrease of the same variables during tilt was significantly (2p less than 0.001) greater. These results indicate that marked peripheral edema considerably decreases venous compliance which can be improved with diuretic therapy.

Oral (17 cases) or sublingual (9 cases) administration of nifedipine (10 mg), a new coronary dilator, induced a prompt and large pressure reduction in patients with severe primary hypertension. Pressure started to fall within 20 and 5 min after oral and sublingual administration, respectively, and reached the lowest levels in the next 10 min. Maximal mean arterial pressure reduction averaged 36 mm Hg; 120 min after the drug, mean arterial pressure was diminished by 19.5% of control. The hypotension was mediated through diminished peripheral resistance associated with rise of cardiac output and pulse rate. Nifedipine was also administered siblingually in 3 cases with hypertensive encephalopathy and acute left ventricular failure with average systemic and pulmonary arterial pressures from 307/164 and 91/55 mm Hg, respectively, which fell to 237/115 and 68/35 mm Hg 15 min after 10 mg of the drug, and were further reduced to 176/89 and to 47/19 mm Hg by an additional 10 mg.

The purpose of the study was to evaluate the functional changes which may occur in the human hypertensive heart following treatment with beta-blocking agents. In 54 primary hypertensive men investigated in the control state and after three weeks of treatment with propranolol (320 mg/day) it was seen that: (a) beta-adrenergic blockade depresses the pre-ejection, and probably the ejection left ventricular function; (b) the former effect is unrelated to changes in peripheral circulation, while the latter result may be either potentiated or overcome, depending on the direction to which treatment shifts the vascular resistance; (c) variations of impedance, rather than of blood pressure, influence the ejection left ventricular function; and (d) withdrawal of the adrenergic support to the heart, due to beta-blockade, is probably the primary factor responsible for the abnormal ventricular adaptation to an augmented impedance.

In a patient with a normal electrocardiogram, normal treadmill exercise test, normal coronary arteriogram and no symptoms to suggest angina pectoris, continuous monitoring during several days exhibited repetitive (one to two per hour) S-T segment elevations in the precordial electrocardiographic leads and hemodynamic changes typical of Prinzmetal's angina (reduction in arterial pressure and cardiac index and increase in systemic peripheral resistance and pulmonary wedge pressure). This case demonstrates that electrical and dynamic cardiac alterations of Prinzmetal's angina can occur even in the absence of angina pectoris.

Hypertension develops in about 10% to 50% of patients with nephrosis or cirrhosis and peripheral edema, but the hemodynamic mechanism of the hypertension and its reversal by diuretic therapy has not been elucidated. In eight patients with marked edema and mild hypertension, diuretics (furosemide and spironolactone) decreased mean arterial pressure because of concurrent decrease in cardiac output and total peripheral resistance. Neither total blood volume nor plasma volume were decreased by the diuretics and the decrease in body weight was therefore attributed to the decrease in interstitial fluid volume. This, in turn, resulted in increased venous capacitance (as can be judged from the diuretic-induced decrease in the ratio of cardiopulmonary blood volume/total blood volume).

The effects of dopexamine on the renal circulation have been examined to show whether any augmentation of renal blood flow (RBF) was secondary to the effect of the drug on cardiac output (CO) or whether it had any additional direct renal vasodilator activity. Eight male patients with mild to moderate hypertension, who were undergoing renal vein catheterization for renin estimation, were studied. Dose related increments in RBF (baseline (B) = 504 ml X min-1; after treatment (D) = 605 ml X min-1), CO (B = 5.9 l X min-1; D = 6.7 l X min-1), heart rate (B = 77 beats/min; D = 100 beats/min) and systolic blood pressure (B = 143 mmHg; D = 166 mmHg) were observed on administration of dopexamine 3 micrograms X kg-1 X min-1, with insignificant changes in diastolic blood pressure (B = 84.4 mmHg; D = 90 mmHg) and total peripheral resistance (B = 17.85; D = 17.25 Units). There was a slight but significant reduction in renal vascular resistance (B = 20.59, D = 18.75). The ratio of RBF to CO (%) confirmed that the increase in RBF due to dopexamine hydrochloride was greater that attributable to the increase in CO or perfusion pressure alone (RBF/CO B = 8.5%, D = 9%), consistent with selective renal vasodilatation. The fall in renin activity and lack of systemic vasodilatation suggest that this was a DA1-receptor mediated effect.