Constraints on upper crustal fluid circulation and seismogenesis from in-situ outcrop quantification of complex fault zone permeability.

The permeability of fault zones plays a significant role on the distribution of georesources and on seismogenesis in the brittle upper crust, where both natural and induced seismicity are often associated with fluid migration and overpressure. Detailed models of the permeability structure of fault zones are thus necessary to refine our understanding of natural fluid pathways and of the mechanisms leading to fluid compartmentalization and possible overpressure in the crust. Fault zones commonly contain complex internal architectures defined by the spatial juxtaposition of "brittle structural facies" (BSF), which progressively and continuously form and evolve during faulting and deformation. We present the first systematic in-situ outcrop permeability measurements from a range of BSFs from two architecturally complex fault zones in the Northern Apennines (Italy). A stark spatial heterogeneity of the present-day permeability (up to four orders of magnitude) even for tightly juxtaposed BSFs belonging to the same fault emerges as a key structural and hydraulic feature. Insights from this study allow us to better understand how complex fault architectures steer the 3D hydraulic structure of the brittle upper crust. Fault hydraulic properties, which may change through space but also in time during an orogenesis and/or individual seismic cycles, in turn steer the development of overpressured volumes, where fluid-induced seismogenesis may localize.

Antihypertensive and metabolic effects of lacidipine in patients with NIDDM and/or hypertension.

Diabetes mellitus is often associated with hypertension and is an additional cardiovascular risk factor. It is therefore important that antihypertensive drugs should have no negative metabolic effects. We present here the results of two distinct studies investigating the clinical efficacy and the metabolic effects of lacidipine in hypertensive patients without concomitant diabetes. Patients in the first study (group A) were hypertensive with non-insulin-dependent diabetes mellitus (NIDDM) and stable blood glucose levels in the 3 months before entering the study. Patients in the second study (group B) were hypertensive without diabetes mellitus. Before the commencement of the study, antihypertensive treatment was discontinued in all patients for a 4-week washout period, followed by 4 weeks of run-in with placebo. Patients were then treated with lacidipine (4 mg o.d.) for 6 months. After 1-2 months, the dose was doubled in patients with uncontrolled blood pressure. Every 2 months, lipid and carbohydrate metabolism were investigated by blood chemistry analyses. The results demonstrate that lacidipine 4-8 mg o.d. is efficacious and well tolerated in hypertensive patients, even in the presence of diabetes mellitus.

Antihypertensive effect of once daily sustained release isradipine: a placebo controlled cross-over study.

To evaluate the magnitude and duration of the antihypertensive effect of sustained release (SRO) isradipine, 37 uncomplicated essential hypertensive patients (diastolic blood pressure 100-115 mm Hg after a one month run-in on placebo) were randomised to receive, according to a double-blind cross-over design, isradipine SRO 5 mg once daily and the corresponding placebo for 1 month. At the end of each treatment period, sitting blood pressure and heart rate were measured immediately before and every hour for 6 h after the last dose. Thirty-four patients [16 m, age 54 (7) y] completed the study. As compared to randomised placebo, isradipine SRO significantly reduced the systolic (SBP) and diastolic (DBP) blood pressure. Absolute DBP decrements versus placebo peaked 6 h after dosing (-8.8 mm Hg) and were not significantly lower (-8.2 mm Hg) at the end of the dose interval. At the same times, the absolute decrements in SBP were -9.8 mm Hg and -9.7 mm Hg, respectively. DBP was normalised in 19 patients (56%) at peak and in 17 (50%) at trough time. The trough to peak efficacy ratio in patients with peak DBP < or = 90 mm Hg was 70%. Heart rate was slightly increased by isradipine SRO. Adverse effects monitored with a check-list occurred in 8/36 patients (22%) on isradipine SRO and in 4/35 (11%) on randomized placebo. The data suggest that isradipine SRO is an effective antihypertensive drug, with a trough to peak efficacy ratio supporting once daily administration in most mild to moderate essential hypertensives.

Effects of perindopril on carbohydrate and lipoprotein metabolism in essential hypertension.

Fourteen outpatients with mild-to-moderate essential hypertension were treated with perindopril (4-8 mg once daily) for a 16-week period. It was observed that the drug was effective in lowering blood pressure without inducing changes in blood lipids commonly observed with other hypotensive agents. This lipid neutrality, in addition to the lack of side or toxic effects, confers on perindopril a noteworthy therapeutic value in the treatment of essential hypertension.

Clinical investigation on the hypolipidemic effect of simvastatin in primary hypercholesterolemia.

Simvastatin, 20 mg daily, was given orally to 21 hypercholesterolemic outpatients for 16 weeks. During treatment a significant reduction was found in plasma total and LDL cholesterol; plasma HDL-cholesterol levels increased during the treatment. Results indicate that simvastatin, because of its activity and lack of toxicity and side effects, can be considered a drug of first-choice for the treatment of primary hypercholesterolemia.

Antihypertensive and metabolic effects of nitrendipine in non-insulin-dependent diabetes mellitus with hypertension.

Fifteen non-insulin-dependent diabetes mellitus hypertensive patients received nitrendipine (20-40 mg) for 24 weeks. Mean systolic and diastolic blood pressure decreased significantly from 177/102 mm Hg before treatment to 153/86 mm Hg (p less than 0.001) after treatment. Meanwhile, the heart rate, body weight, indices of glycemic control (glucose, glycosylated hemoglobin, fructosamine, and serum C peptide levels), and serum lipid fractions did not change. It is concluded that nitrendipine does not impair glucose and lipid metabolism in diabetic patients while exerting its antihypertensive effect.

Nitrendipine does not impair long-term glucose control in hypertensive noninsulin-dependent diabetic patients.

The subjects, 15 noninsulin-dependent diabetic hypertensive patients (mean age, 61 years) and 15 nondiabetic hypertensive patients (mean age, 60 years), received placebo for four weeks and then 20 to 40 mg of nitrendipine once daily for 24 weeks. At the end of the placebo period their blood pressures were greater than or equal to 160 mmHg systolic or greater than or equal to 95 mmHg diastolic. Blood pressures declined significantly during treatment in both patient groups; after 24 weeks, 13 of 15 diabetic patients and 12 of 15 nondiabetic patients were normotensive (diastolic blood pressure less than 90 mmHg). Meanwhile, heart rate, indices of glycemic control (serum glucose, hemoglobin A1c, fructosamine, and C-peptide levels), and serum lipids (cholesterol, high-density cholesterol, triglycerides, apolipoprotein A1 and B levels) did not change. It is concluded that nitrendipine does not impair glucose or lipid metabolism in diabetic hypertensive patients.

Antihypertensive and metabolic effects of nitrendipine in hypertensive diabetic patients.

The subjects were 15 patients, aged 53 to 74 years, with noninsulin-dependent diabetes mellitus and mild to moderate hypertension. Each received 20 to 40 mg of nitrendipine daily for six months. Mean supine blood pressures decreased significantly from 177/102 mmHg before treatment to 164/95 mmHg at three months and continued to decline during the following three months. Diastolic blood pressure was reduced to less than 90 mmHg in eight of the 15 patients. No changes in heart rate, glycemic control (serum levels of glucose, C-peptide, glycosylated hemoglobin, and fructosamine), or serum lipid levels (cholesterol and its lipoprotein fractions, triglycerides, and apolipoproteins A1 and B) were noted. It is concluded that nitrendipine is safe and effective in the treatment of hypertension in diabetic patients.

Chlorthalidone does not increase the hypotensive effect of nifedipine in essential hypertensives: a crossover multicentre study.

To determine whether the combination of nifedipine + chlorthalidone exerts an additive antihypertensive effect when compared with single-drug treatment, we studied 66 uncomplicated essential hypertensives, with diastolic blood pressure of greater than 100 and less than 115 mmHg. At the end of a 1-month washout placebo period, using a double-blind crossover design, the patients were randomly allocated to nifedipine (20 mg twice a day), chlorthalidone (25 mg once a day), the two drugs combined at the same doses and the corresponding placebo. Compared with the randomly allocated placebo, the three active treatments significantly reduced blood pressure without changing the heart rate or body weight. Both the absolute and percentage decreases in mean blood pressure induced by nifedipine and the combination compared with placebo were similar and significantly greater than those induced by chlorthalidone. Taken together, these data show that the combination of nifedipine + chlorthalidone does not exert any additive antihypertensive effect compared with nifedipine alone. This finding indicates that the combination of a dihydropyridine calcium antagonist + a thiazide diuretic is probably devoid of any particular clinical significance in the treatment of uncomplicated essential hypertensives.

Captopril treatment in elderly hypertensive patients: efficacy and tolerability. Captopril Study Group.

Ninety-five elderly (greater than 70 years) hypertensive patients were treated for 3 months with 25-100 mg captopril daily. The mean blood pressure decrease was from 179/101 to 155/87 mmHg (P less than 0.001). The heart rate did not change. The drug was generally well tolerated (patients taking less than 100 mg captopril or captopril + chlorthalidone reported side effects) and there was no change in the biochemical parameters (glucose, uric acid, cholesterol, high density lipoprotein-cholesterol, triglycerides, apoproteins, blood urea nitrogen, creatinine, serum electrolytes). Our open study indicates that captopril is a safe and effective antihypertensive agent in elderly patients. However, some caution is necessary when high doses of captopril (100 mg/day) are used.

Multicentre comparison of the antihypertensive effect of acebutolol and hydrochlorothiazide in uncomplicated mild-moderate hypertension in the elderly.

To evaluate the efficacy of acebutolol, 400-600 mg/day in elderly hypertensive patients, and to compare it with hydrochlorothiazide 25-50 mg/day, 45 patients with mild-moderate uncomplicated hypertension were treated for 6 weeks in a multicentre, single-blind, randomized, crossover trial. Acebutolol decreased supine systolic blood pressure from 186.5 to 162.7 mmHg and diastolic blood pressure from 107.4 to 92.4 mmHg. Hydrochlorothiazide decreased systolic blood pressure from 185.0 to 166.4 and diastolic blood pressure from 107.2 to 96.4. There was no difference between the effects of acebutolol and hydrochlorothiazide on blood pressure during the trial. Both drugs proved to be safe and effective antihypertensive agents, provided the major contraindications for their use were taken into account. Beta-blockade by acebutolol was highly effective in treating mild-moderate arterial hypertension in the elderly.