Biomedical subjects
Publications and source records attributed to G Leonetti.
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BACKGROUND: In 1989, the European Working Party on High Blood Pressure in the Elderly started the double-blind, placebo-controlled, Systolic Hypertension in Europe Trial to test the hypothesis that antihypertensive drug treatment would reduce the incidence of fatal and nonfatal stroke in older patients with isolated systolic hypertension. This report addresses whether the benefit of antihypertensive treatment varied according to sex, previous cardiovascular complications, age, initial blood pressure (BP), and smoking or drinking habits in an intention-to-treat analysis and explores whether the morbidity and mortality results were consistent in a per-protocol analysis. METHODS: After stratification for center, sex, and cardiovascular complications, 4695 patients 60 years of age or older with a systolic BP of 160 to 219 mm Hg and diastolic BP less than 95 mm Hg were randomized. Active treatment consisted of nitrendipine (10-40 mg/d), with the possible addition of enalapril maleate (5-20 mg/d) and/or hydrochlorothiazide (12.5-25 mg/d), titrated or combined to reduce the sitting systolic BP by at least 20 mm Hg, to below 150 mm Hg. In the control group, matching placebo tablets were employed similarly. RESULTS: In the intention-to-treat analysis, male sex, previous cardiovascular complications, older age, higher systolic BP, and smoking at randomization were positively and independently correlated with cardiovascular risk. Furthermore, for total (P = .009) and cardiovascular (P = .09) mortality, the benefit of antihypertensive drug treatment weakened with advancing age; for total mortality (P = .05), the benefit increased with higher systolic BP at entry, while for fatal and nonfatal stroke (P = .01), it was most evident in nonsmokers (92.5% of all patients). In the perprotocol analysis, active treatment reduced total mortality by 24% (P = .05), reduced all fatal and nonfatal cardiovascular end points by 32% (P<.001), reduced all strokes by 44% (P = .004), reduced nonfatal strokes by 48% (P = .005), and reduced all cardiac end points, including sudden death, by 26% (P = .05). CONCLUSIONS: In elderly patients with isolated systolic hypertension, stepwise antihypertensive drug treatment, starting with the dihydropyridine calcium channel blocker nitrendipine, improves prognosis. The per-protocol analysis suggested that treating 1000 patients for 5 years would prevent 24 deaths, 54 major cardiovascular end points, 29 strokes, or 25 cardiac end points. The effects of antihypertensive drug treatment on total and cardiovascular mortality may be attenuated in very old patients.
Pharmacokinetics of cadralazine, urinary recovery of its putative active metabolite 3-hydrazino-6-aminopiridazine derivative (ISF 2405) and clinical effects were assessed in a placebo-controlled trial in 8 hypertensive in-patients, after acute oral administration of cadralazine. After a 2-week placebo-washout period, the protocol envisaged two consecutive days of monitoring of blood pressure and heart rate. On the first day a placebo tablet was given (9 am), while on the second day patients received a 30 mg cadralazine tablet in single-blind conditions. Blood and urine samples were obtained during the active drug day until 12 h after administration. Concentration of cadralazine in plasma and urine was detected by a specific HPLC method, while the metabolite ISF 2405 was detected in urine by a GC-MS method. Cadralazine caused gradual and long-lasting pressure decrease, statistically significant in comparison to placebo between 3 and 12 hours from drug intake, accompanied by a significant increase in heart rate. Cadralazine by oral route was promptly absorbed with a mean peak time of 1.3 h. Thereafter it followed a monoexponential decay curve, with a plasma half life of 3.1 h. The relative different bioavailability of oral cadralazine among patients was not correlated with cardiovascular changes. Urine recovery of unchanged drug after 12 h was high, reaching 67.3%, while concentration of metabolite ISF 2405 was about 1/1000 of parent compound.
Doses of 10 mg b.i.d. of the new dihydropyridine calcium antagonist, felodipine, were tested for seven consecutive days in 11 hospitalized hypertensive patients. A significant reduction of both systolic and diastolic blood pressures, with patients in both the supine and upright positions, occurred immediately after the first dose and was maintained (daily average 15%) throughout the following days. An increase in heart rate was observed after the first dose (15 and 23 beats/min, in supine and upright postures), and subsequently declined to average values of 8 and 14 beats/min on the seventh day. There was a marked natriuretic response during the first and second day, during which an average negative sodium balance of 95 mmol developed; on the following days sodium output was not significantly different from control, but a negative balance averaging 135 mmol was still present on the seventh day of felodipine administration. A moderate negative potassium balance also progressively developed and reached -48 mmol on the seventh day. Glomerular filtration rate was unchanged, but renal plasma flow increased significantly during administration of felodipine. Plasma renin activity and plasma aldosterone were also increased very moderately by felodipine. Compared with previous observations by our group with higher doses of felodipine (12.5, 25, and 50 mg t.i.d.), 10 mg b.i.d. of this new calcium antagonist appear to exert a marked and prolonged blood pressure reduction, accompanied by a definite natriuretic instead of an antinatriuretic effect.
Prazosin, an antihypertensive agent that reduces blood pressure (BP) mainly through a blockade of alpha-adrenergic receptors, may, in theory, affect sympathetic control of circulation to an extent that impairs circulatory hemeostasis. This possibility was studied in subjects with essential hypertension by examining the cardiovascular effects of several stimuli that induce a powerful and diversified activation of the sympathetic noradrenergic activity (dynamic and isometric exercise, cold exposure) and of stimuli that exert a powerful inhibitory influence upon the sympathetic nervous system (carotid baroreceptor reflex). Before and after 15 days of continuous administration of prazosin (2-5 mg), 3 times a day, measurements were made of BP (intraarterial catheter), heart rate, cardiac output (thermodilution), and peripheral resistance. Prazosin reduced mean arterial pressure (10%) and peripheral resistance (9%) at rest, and it did not affect heart rate and cardiac output. Neurally mediated changes in arterial pressure, cardiac output, and peripheral resistance during dynamic or isometric exercise and cold exposure were unaffected by the drug; also unaffected were the cardiovascular responses to increase and decrease in carotid baroreceptor activity obtained by varying carotid transmural pressure through a variable neck pressure chamber device. Thus, the hypotensive and vasodilating effect of prazosin in essential hypertension is not accompanied by an impaired response to neural excitation influences upon the cardiovascular system. Also, the inhibitory influences originating from the carotid baroreflex are unchanged. These data indicate that circulatory homeostasis is largely preserved during administration of prazosin at clinically effective doses.
We used the neck chamber technique to study carotid baroreceptor control of blood pressure in 18 renovascular hypertensive subjects. Carotid baroreceptors were stimulated or deactivated for 2 minutes by applying graded reductions or increases in the neck tissue pressure (NTP) outside the carotid sinuses. The sensitivity of the baroreflex was separately calculated for these two conditions by the coefficients of the linear regressions relating the changes in NTP to the resulting changes in mean arterial pressure (MAP, catheter measurement). Baroreceptor deactivation increased MAP, and the sensitivity of the baroreflex was 0.12 /+- 0.07 in an early (5 to 1 seconds) and 0.32 /+- 0.05 in a late (90 to 120 seconds) phase of the stimulus application. Baroreceptor stimulation reduced MAP, and the baroreflex sensitivity was in this instance 0.66 /+- 0.08 and 0.05 /+- 0.08 respectively. Both these sensitivities were significantly greater than those obtained for the baroreceptor deactivation. These response entirely reproduced those of essential hypertensive subjects, but differed from those of normotensive subjects in whom baroreflex sensitivity was greater for carotid baroreceptor deactivation than for stimulation. Our findings indicate that carotid baroreceptor control of blood pressure undergoes a marked resetting in renovascular hypertension. The similarity of the baroreflex between renovascular and essential hypertension suggests as secondary origin of the resetting in man.
High pressure CO2-peritoneum for laparoscopic surgery is not indicated in patients with impairment of cardiorespiratory and renal function and in high risk patients and in obesity. On the other site the uncontrolled abdominal insufflation and the blind insertion of the first trocar in patients with extended intraperitoneal adhesions, often cause bleeding and the intestinal loops dislocation, and can determine visceral lesions. In these patients gasless technique with an abdominal laparolifter can be employed. We report an experience of 36 patients undergoing laparoscopic cholecystectomy by a subcutaneous planar retractor. It was observed a good operative exposure in 83.3%; the surgery was safely performed in 88.8%. Two suprafascial hematoma related to the insertion of the needles of the Laparo Tenser occurred. A regular post-operative discharge was observed in 84.4%. These good results supports the extension of the laparoscopic approach for the cholecystectomy to complicated or to high risk patients.
Micrometastases, (metastases smaller than 2 mm), had benn subject of several studies. In literature is documented a prognostic worsening due to their presence. Research of micrometastases in sentinel lymph node is of great interest and can allow a clinical application with profitable cost efficacy ratio. The Authors discuss about clinical, prognostical and therapeutical implicationes in case of micrometastases into sentinel lympho nodes.
Spigelian hernia is a rare abdominal hernia that occurs through Spigelian aponeurosis. The Authors present a case of Spigelian hernia associated with narrowing of sigmoid colon and diverticular pathology. They also described historical background, surgical anatomy and etiopathogenesis of this hernia. By a remarkable revision of literature, they sum up epidemiology and clinical features of Spigelian hernia. Furthermore, they discuss diagnostic and therapeutic principles.
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We studied the antihypertensive action of felodipine, a new dihydropyridine vasodilator interfering with intracellular calcium mechanisms, in 11 patients with essential hypertension whose supine blood pressure averaged 181/109 mm Hg after 5 days of placebo administration. Felodipine, 12.5 mg t.i.d., for 3 days, caused a marked reduction (-39/-19 mm Hg) of supine systolic and diastolic pressures. Doses of 25 and 50 mg t.i.d., for three consecutive days, caused only a slight further reduction of blood pressure. At the highest dose tested all patients had their supine blood pressure brought down to values below 150 mm Hg systolic and 90 mm Hg diastolic at all six daily measurements. The antihypertensive effect was of the same magnitude when the patients lay supine or stood upright. Lowering of blood pressure was accompanied by tachycardia, which was quite moderate after the 12.5 mg t.i.d. dose, but more conspicuous with the two higher doses. There was some increase in plasma renin activity and in plasma aldosterone. A significant decrease in renal sodium and water excretion occurred only during administration of the highest dose of 50 mg t.i.d., when reduction in blood pressure was pronounced and there were reflex increases in plasma renin activity and plasma aldosterone.
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