Effects of benazepril and nicardipine on microalbuminuria in normotensive and hypertensive patients with diabetes.

Diabetic nephropathy is the most frequent cause of chronic renal failure. The onset of microalbuminuria in patients with diabetes mellitus, which seems to be related to blood pressure and the control of glycemia, is predictive of the development of true proteinuria. This multicenter, single-blind, randomized study examined the effects of benazepril and nicardipine on overnight microalbuminuria in 57 normotensive and 46 hypertensive diabetic patients. At the end of a 3-month placebo run-in period, the patients were stratified on the basis of the presence or absence of arterial hypertension and, within each stratum, randomized to receive one daily tablet of 10 mg benazepril or one tablet of 20 mg nicardipine twice daily for 6 months. Renal hemodynamics was investigated in 25 patients. Both drugs decreased overnight microalbuminuria throughout the study period, but benazepril was more effective than nicardipine (p = 0.025); in the patients with hypertension, both drugs led to a similar marked reduction in systolic and diastolic blood pressure. This study shows that benazepril was more effective than nicardipine in reducing overnight microalbuminuria in patients with diabetes mellitus, independently of their antihypertensive properties.

Effects of isradipine sustained release on platelet function and fibrinolysis in essential hypertensives with or without other risk factors.

The aim of this study was to assess the chronic effects of a highly selective dihydropiridine calcium channel blocker, israpidine, in its sustained release form (I-SRO), on platelet functions and fibrinolytic parameters in subjects with essential hypertension (EH) combined or not with other well-known cardiovascular risk factors, such as cigarette smoking (EH+S) and type II diabetes mellitus (EH+DM). Thirty-six patients with essential hypertension with sitting diastolic blood pressures of 96-104 mmHg without (EH, n = 12) or with other risk factors (EH+S, n = 12, EH+DM, n = 12) were enrolled. After a 4-week, single-blind, placebo run-in period, the subjects received I-SRO 5 mg once daily for 18 weeks. After both placebo and 6 and 18 weeks of I-SRO treatment, the following parameters were measured: sitting blood pressure by mercury sphygmomanometer; platelet aggregation, plasma beta-thromboglobulin (BTG), platelet factor-4 (PF4), and plasminogen activator inhibitor 1 (PAI-1) by means of ELISA methods; and euglobulin lysis time before (ELT) and after standardized (10 min) venous occlusion (ELT-VO). In the group of patients as a whole compared with placebo, I-SRO significantly reduced SBP/DBP platelet aggregation, BTG, PF4, ELT, and ELT-VO. Significant reductions in these parameters were also observed in each group. In addition to the antihypertensive effect, I-SRO chronic treatment may favorably affect the platelet function and fibrinolytic system in essential hypertension with or without other cardiovascular risk factors.

Effects of lisinopril and amlodipine on microalbuminuria and renal function in patients with hypertension.

Many patients with arterial hypertension have abnormal urinary excretion levels of albumin. This study was aimed at examining the effects of lisinopril and amlodipine on urinary excretion of albumin and kidney function. Thirty-six previously untreated patients with essential arterial hypertension were divided randomly into two groups. The first group received lisinopril 20 mg daily for 12 weeks followed by 10 mg amlodipine daily for another 12 weeks. The second group received 10 mg amlodipine daily for 12 weeks followed by 20 mg lisinopril daily for another 12 weeks. The arterial pressure decreased in a similar way with both therapies in both groups. In both groups urinary albumin excretion decreased in patients receiving lisinopril (p < 0.01). No significant changes were observed with amlodipine. This study shows that lisinopril, but not amlodipine, is able to reduce urinary excretion of albumin in patients with essential hypertension independently of its effective antihypertensive properties. It is probable that the positive effect of lisinopril on microalbuminuria is attributable to the modifications in intrarenal hemodynamics or to a change in glomerular permeability.

[Antihypertensive action of nicardipine retard in 24 hours and its effect on stress]. / Azione antiipertensiva della Nicardipina Retard nelle 24 ore e suo comportamento nello stress.

Thirty-six patients (17 males and 19 females), aged between 40 and 70 years old (mean age 55.9), suffering from slight or moderate arterial hypertension, were monitored for four weeks after 14 days of placebo treatment. In a double-blind and random study 24 patients were treated with Nicardipine Retard (40 mg twice a day) whereas a further 12 received placebo twice a day. Sphigomanometric controls carried out after two and four weeks showed a significant reduction in arterial pressure only in those patients receiving active treatment. 24-hour out-patient monitoring of arterial pressure, carried out using Spacelabs 5300, showed a reduction in both systolic and diastolic arterial pressure throughout the day in subjects treated with calcium-antagonists compared to the placebo group. The normal physiological 24-hour trend of arterial pressure was always taken into account. The pressure response to a cold pressor test, mental arithmetic test, isometric and dynamic effort tests, measuring using a cycloergometer, was not modified by anti-hypertensive treatment, thus confirming the preservation of normal physiological behaviour during daily activities. There was no significant change in heart rate and the drug was well tolerated.

Glucose and lipid metabolism in essential hypertension: effects of diuretics and ACE-inhibitors.

Various aspects of carbohydrate and lipid metabolism were studied in two groups of patients with mild hypertension before and after 6 months' treatment with either lisinopril (n = 10) or hydrochlorothiazide (n = 10). A significant reduction of arterial blood pressure was seen after both treatment regimens. Circulating plasma glucose, insulin, C-peptide and triglyceride concentrations were measured at hourly intervals from 8.00 a.m. to 5.00 p.m. in patients on an isocaloric diet (35 cal/kg/day). Plasma glucose concentrations remained unchanged, while insulin and C-peptide concentrations were higher in association with hydrochlorothiazide treatment. Conversely, lisinopril-treated patients had lower C-peptide concentrations after treatment. The changes in daylong plasma glucose and insulin-stimulated glucose uptake increased after hydrochlorothiazide treatment and decreased following lisinopril. Lastly, plasma cholesterol concentrations did not change after lisinopril therapy, whereas plasma high density cholesterol decreased as a result of hydrochlorothiazide treatment.

Free and total serum concentrations of carbamazepine and carbamazepine-10,11-epoxide in infancy and childhood.

Total and free serum concentrations of carbamazepine (CBZ) and carbamazepine-10,11-epoxide (CBZ-E) at steady state were determined in 10 infants (ages 4-13 months), 10 preschool children (ages 3-5 years), and 11 school children (ages 7-11 years) receiving equivalent doses of CBZ alone. Free and total CBZ levels tended to increase with increasing age, while CBZ-E levels did not show any significant age dependency. As a result, CBZ-E/CBZ ratios were higher in infants and preschool children than in the older age group. The degree of plasma protein binding of CBZ and CBZ-E did not show any important differences among the various groups. These data provide evidence that, within a pediatric population, CBZ shows age-related dispositional changes which may be clinically important.

Alpha 1-acid glycoprotein concentration and serum protein binding of carbamazepine and carbamazepine-10,11 epoxide in children with epilepsy.

The relationship between the serum protein binding of carbamazepine (CBZ) and carbamazepine-10,11 epoxide (CBZ-E) and the concentration of alpha 1-acid glycoprotein (AAG) and albumin (HSA) was examined in 39 CBZ-treated epileptic children aged 4 months to 12 years. A significant inverse correlation was found between the free fraction of both compounds and serum AAG, even though changes in AAG concentration explained only part of the variation in binding. No correlation was found between the free fraction of CBZ and CBZ-E and HSA, probably due to the small intersubject variation in HSA concentration. In vitro experiments showed that both CBZ and CBZ-E were bound to HSA and to a lesser extent to AAG. At equivalent HSA concentrations, the binding of CBZ and its metabolite increased proportionately with increasing AAG concentration within the range occurring clinically.

Acute hepatitis in a patient treated with carbamazepine.

A case of serious acute hepatic damage probably induced by carbamazepine (CBZ) is described. A 4-year-old patient with generalized tonic-clonic seizures was started on CBZ after various ineffective therapies. On the 10th day of CBZ therapy, he was readmitted to the hospital because of reappearance of fits, and went into hepatic coma. On the hypothesis that he was suffering an acute toxic reaction to CBZ, the drug was withdrawn (the serum level was not toxic) and the patient was subjected to peritoneal dialysis. The patient was discharged after 15 days in general conditions similar to those preceding the comatose state. The type of hepatic damage revealed by the laboratory tests and the early appearance of the clinical symptoms with non-toxic serum CBZ levels support the hypothesis of an idiosyncratic reaction to CBZ.

Nocturnal headache: systemic arterial pressure and heart rate during sleep.

In order to evaluate autonomic nervous system changes occurring before nocturnal headache attacks, we studied three subjects (one male, two females) suffering from chronic migraine. All three patients underwent a nocturnal polygraphic recording including continuous monitoring of systemic arterial pressure and heart rate. Two subjects showed increases and irregularities of arterial pressure before awakening with headache. These changes began during N-REM sleep and lasted during REM sleep preceding the awakening with headache. Heart rate did not change before the attacks. These findings do not support the hypothesis that autonomic instability during REM sleep represents the precipitating factor of the attacks.

Intrathecal IgG synthesis in multiple sclerosis: comparison between isoelectric focusing and quantitative estimation of cerebrospinal fluid IgG.

Isoelectric focusing of CSF and serum IgG followed by crossed immuno isoelectric focusing and direct immunofixation as well as quantitative assay of IgG and albumin were performed in 64 clinically definite multiple sclerosis patients. Intrathecal IgG synthesis was calculated according to the CSF IgG index and de novo CNS IgGsyn. Isoelectric focusing showed abnormal IgG fractions i CSF indicating increased intrathecal synthesis of oligoclonal IgG in 99% of patients. Only 62% and 70% of multiple sclerosis patients showed values of CSF IgG indices and de novo CNS IgGsyn higher than in controls. Increased intrathecal IgG synthesis was indicated more frequently by de novo CNS IgGsyn in patients with a normal CSF IgG index than by the CSF IgG index in patients with normal de novo CNS IgGsyn. All patients with blood CSF barrier damage had increased de novo CNS IgGsyn, but only 40% had an increased CSF IgG index. Isoelectric focusing seemed to be a more sensitive method to detect an increased intrathecal oligoclonal IgG synthesis than quantitative methods. Identification of abnormal IgG fractions can be performed easily and with more reproducible results by direct immunofixation than by crossed immuno isoelectric focusing. The formula for de novo CNS IgGsyn seemed more sensitive and less influenced by blood-CSF barrier damage than the CSF IgG index to detect increased intrathecal IgG synthesis in multiple sclerosis patients. No correlation was found between the CSF IgG pattern or amounts and age, duration, clinical course or therapy of the disease.