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Biomedical subjects

J Rosenthal

Publications and source records attributed to J Rosenthal.

At least 127 records · Page 7Linked to original sources
PubMed1990

Physicochemical and enzyme binding kinetic properties of a new angiotensin-converting enzyme inhibitor ramipril and their clinical implications.

After oral administration, ramipril, a nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor, is transformed in the liver into its active metabolite ramiprilat. Because of its pentane ring it is at least 23 times more lipophilic than enalaprilat. The in vitro affinity for ACE is 7 times higher than for enalaprilat and 47 times higher than for captopril. The ramiprilat-ACE complex is therefore very stable and dissociates 6 times more slowly than the enalaprilat ACE complex and 72 times more slowly than the captopril ACE complex. Consequently, ramipril is pharmacologically more potent and has a longer duration of action than enalapril and captopril. The blood pressure lowering effect of ACE inhibitors is attributed to the decrease in angiotensin II in serum and locally in target organs of hypertension: heart, vessel wall, kidney and brain. Inhibition of tissue renin-angiotensin system by ramipril has been described in target organs of hypertension in animal models and in clinical studies. Possibly due to its high lipophilicity, and strong affinity to the converting enzyme a better tissue penetration and a more pronounced local ACE inhibition in the target organs has been observed, as compared to other ACE inhibitors. In a preliminary investigation a direct action of ramipril on the tissue RAS in hypertensive patients could also be demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Comparative evaluation of the acute and chronic effects of cilazapril and hydrochlorothiazide on diastolic cardiac function in hypertensive patients.

UNLABELLED: The effect of cilazapril, 2.5 to 5.0 mg and hydrochlorothiazide, 25 to 50 mg, on diastolic cardiac function was studied by echocardiography and radionuclide ventriculography, using a double-blind randomized parallel-group design with a placebo run-in period, in 30 hypertensive patients. The measurements were made before and three hours after the first dose, and after ten weeks of treatment. Both drugs lowered the elevated blood pressure and did not impair the normal systolic cardiac function. In the patients treated with cilazapril an improvement in indices of diastolic function was observed after the first dose. The normalized peak filling rate significantly increased from 2.4 +/- 0.7 to 2.7 +/- 0.7 counts and time to peak filling rate was shortened from 169.4 +/- 31.0 to 151.6 +/- 40.1 msec. This improvement was sustained or even enhanced during chronic therapy. In contrast hydrochlorothiazide acutely impaired one index of diastolic function, the normalised peak filling rate, and did not alter the other indices. Long-term treatment with cilazapril, but not with hydrochlorothiazide, caused regression of left ventricular hypertrophy. IN CONCLUSION: cilazapril is superior to hydrochlorothiazide in its effect on diastolic cardiac function in hypertensive patients. The beneficial effect is partially related to regression of left ventricular hypertrophy.

Aged↗
PubMed1990

Angiotensin I-forming angiotensinogenases in extrarenal vasculature and in the kidney.

The intention of this study was to characterize angiotensin I-forming angiotensinogenases (AIFAs) in rat extrarenal arterial walls and to clarify whether these enzymes are also present in the kidney. A further aim was to identify AIFAs in human vasculature and to establish whether they are affected in essential hypertension. Sprague-Dawley rats and vascular sections of patients undergoing corrective surgery were studied. Enzyme kinetic assays were performed using angiotensin I radioimmunoassay and purified natural angiotensinogens. Fast protein liquid chromatography was employed for biochemical characterization. A series of AIFAs with various isoelectric points, molecular weights and pH optima was detected in rat extrarenal vascular and, with differing distributions of enzyme activities, in renal tissues. In extrarenal arteries the main form of renal renin was present with a relatively low activity only. AIFAs were also demonstrable in human extrarenal vasculature and behaved like plasma renin in essential hypertension. The results indicate the existence of an intrinsic human vascular RAS in extrarenal (and renal) arteries. Extrarenal arterial AIFAs are not generally stimulated in essential hypertensives, as previously postulated.

Angiotensin I↗
PubMed1989

Therapeutic assessment of urapidil or angiotensin-converting enzyme inhibition in systemic hypertension.

The antihypertensive efficacy of urapidil, a postsynaptic alpha blocker with an additional central action, was compared with that of the angiotensin I converting enzyme inhibitor captopril under conditions of general practice (multicenter study). The study was performed in a double-blind, randomized, parallel-group fashion. After a 2-week washout and placebo phase, 295 essential hypertensive patients (World Health Organization grades I and II) were treated for 12 weeks with either urapidil or captopril, initially with urapidil, 60 mg twice daily or captopril, 25 mg twice daily, with the possibility of adjusting the dose according to blood pressure response after 2 weeks of treatment. Blood pressure values at the end of the 12-week treatment decreased significantly in the group receiving urapidil (n = 142, all dosages), from 175/103 to 154/89 mm Hg (p less than 0.001), and in the group receiving captopril (n = 153, all dosages) from 175/103 to 154/90 mm Hg (p less than 0.001); these values corresponded to 62% urapidil and 58% captopril responder rates (diastolic blood pressure less than or equal to 90 mm Hg), respectively. The computer-assisted frequency distribution of the patients with controlled diastolic blood pressure (less than or equal to 90 mm Hg) over the duration of the study demonstrated comparable efficacy for both drugs. Adverse effects were observed in 45 patients in the urapidil group and in 18 patients in the captopril group (vertigo, nausea, headache). The results revealed that the 2 antihypertensive agents with different modes of action controlled blood pressure with equal efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Case-control study of colorectal cancer and fecal mutagenicity.

Fecal mutagenicity was measured in 68 patients with colorectal cancer and in 114 controls, using Salmonella tester strains TA98 and TA100 with and without S9 activation. Samples were also tested for fecapentaenes by high-performance liquid chromatography, to permit the separation of fecapentaene and non-fecapentaene mutagenicity. Overall, no significant case-control differences in fecal mutagenicity were observed. However, when samples containing high concentrations of fecapentaenes were excluded, non-fecapentaene TA98 mutagenicity was observed in eight cases (12%) and only four controls (4%), resulting in an estimated relative risk of 4.4 (95% confidence interval = 1.0-21.1). The association of colorectal cancer risk with non-fecapentaene TA98 mutagenicity could not be explained as an artifact of diagnostic workup or gastrointestinal bleeding among the cases. Smoking could also be excluded as a source of the TA98 mutagenicity seen, but possible dietary origins are still being explored.

Adenocarcinoma↗
PubMed1989

Case-control study of colorectal cancer and fecapentaene excretion.

The fecapentaenes are potent mutagens found in high concentrations in the stools of some individuals. These compounds are produced in vivo by common species of the colonic microflora, from precursors of unknown origin. The fecapentaenes have been postulated to increase the risk of colorectal cancer. To test this hypothesis, we measured fecapentaene excretion in 69 patients with adenocarcinoma of the colon or rectum, newly diagnosed at three Washington, DC area hospitals. The cases were compared with 114 surgical controls, frequency matched to the cases on age, sex, and hospital. We attempted to measure fecapentaene excretion 4 times for each subject: before surgery; and at 1 mo; 3 mo; and 6 mo following surgery. Contrary to our study hypothesis, we found fecapentaene excretion during the four study periods to be similar or even lower in cases compared to controls. An indirect measurement of fecapentaene precursors also tended to be lower in cases. The case-control differences could not be explained as effects of bleeding or of the colorectal diagnostic workup, which was assessed in a separate group of 86 patients. We conclude from these data that the excretion of fecapentaenes does not increase the risk of colorectal cancer, at least when measured near the time of diagnosis.

Aged↗
PubMed1989

The epidemiology of blood pressure in young Mexican adults.

The distribution of blood pressure and associated factors (height, weight, body mass index, age, social class) was assessed in young Mexican adults, with a cross-sectional study of 657 male and female students enrolled at the University of Mexico, aged from 19 to 25 years. Significantly higher blood pressure levels were observed in males than in females. Borderline hypertension was found in 20.7% of the study subjects. Of all anthropometric factors, age and social class, weight was determined by stepwise regression analysis as the best predictor for blood pressure when using a linear model. However, when a quadratic model was used, a 'U' relationship and a significant variation between blood pressure and social class was detected. This relationship was magnified when blood pressure was categorized into borderline hypertension and normotensives. These findings suggest the hypothesis that hypertension has a non-linear association with social class in environments that are undergoing an intermediate step of modernization and economic transition such as is occurring in Latin American countries today.

Adult↗
PubMed1989

Abnormal thyroid hormone and thyrotropin levels in homozygous sickle cell disease.

Male patients with SS disease had significantly lower T3 and higher TSH levels than a comparison group. Stimulation with TRH in 10 male sibling pairs showed highly significant increases in T3 and TSH in both patients and sibling controls although the increase in TSH was significantly greater in SS disease. The interpretation of these findings is unclear although the thyroid indices indicate an abnormal pituitary-thyroid axis most consistent with a modest primary thyroid failure.

Adolescent↗
PubMed1989

Is increased plasma viscosity a risk factor for high blood pressure?

Data from several epidemiologic studies have suggested that, among other variables, hematocrit and fibrinogen may constitute risk factors for high blood pressure. As part of a population survey for cardiovascular risk factors, plasma viscosity and hemoglobin were measured. Blood pressure was determined under standardized conditions according to the recommendations of the AHA. A two-stage age-sex-stratified cluster sample of 5,312 persons, aged twenty-five to sixty-four years, was selected from a mixed urban/rural target population of 282,279 (total population approximately 533,000). A net response of 79.3% was achieved. Multiple logistic regression analyses including plasma viscosity, hemoglobin, body mass index, alcohol consumption, smoking behavior, and total serum cholesterol as independent variables were run controlling for both age and sex. Plasma viscosity appeared as a significant main effect in all analyses and demonstrated the strongest association with high blood pressure next to body mass index. Whether this association implies a causal relationship cannot be answered from cross-sectional data. However, even if plasma hyperviscosity represents a secondary phenomenon in hypertension, it might be of prognostic relevance. There is evidence that increased plasma viscosity may contribute to myocardial hypertrophy. Therefore hypertensives with impaired blood fluidity might constitute a subgroup at particular risk for cardiovascular complications. When antihypertensive drugs are selected, their influence on blood viscosity should be taken into account.

Adult↗
PubMed1989

[Methodologic evaluation of the relation of blood pressure and skinfold thickness: an epidemiologic approach].

The empirical evidence concerning the relationship between blood pressure and anthropometric characteristics (triceps skinfold, adiposity, and arm circumference) was assessed by means of meta-analysis. Different studies were evaluated critically for strength of design, methods and associations. It was found that the association between blood pressure and triceps skinfold holds for three different demographic categories. The question as to the independence of these associations remained unsolved. The effect of arm adiposity on the measurement of blood pressure was also discussed. Recommendations are give in order to standardize blood pressure measurements in clinical and research settings.

Adolescent↗
PubMed1989

Effect of zinc depletion on angiotensin I-converting enzyme in arterial walls and plasma of the rat.

The effect of zinc depletion and of additional angiotensin I-converting enzyme (ACE) inhibitor treatment was studied on ACE in aortic and other tissues, in plasma and on systolic blood pressure of the rat. Zinc deprivation significantly reduced plasma zinc concentration, plasma and testicular ACE activities and blood pressure, but stimulated aortic ACE while lung values remained constant. Zinc deficiency combined with ACE inhibition further suppressed plasma ACE and stimulated the aortic enzyme earlier. Zinc repletion experiments (in vitro) suggest the existence of a feedback mechanism controlling ACE synthesis depending on plasma ACE activity.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Blood pressure and lipid lowering effects of terazosin.

Treatment of hypertension reduces the risk of developing stroke, renal failure and left ventricular failure but not that of coronary heart disease. The reasons for the less favourable results of antihypertensive regimens on coronary heart disease are manifold and unresolved. Antihypertensive treatments which in addition to their blood pressure lowering effects also favourably influence serum lipids offer greater promise to lower coronary heart disease. The long-acting postsynaptic alpha-blocker terazosin was assessed in terms of multifactorial aspects of patients with various risk profiles. The results of clinical trials underline that terazosin changes blood lipids in a beneficial direction and therefore has the potential to lower coronary heart disease more effectively than conventional antihypertensive medications.

Adrenergic alpha-Antagonists↗
PubMed1989

Bacterial meningitis with initial normal cerebrospinal fluid findings.

Seven pediatric patients with bacterial meningitis but with initial normal cerebrospinal fluid (CSF) findings are presented. They represent 6.5% of all cases with bacterial meningitis seen at our medical center during a 5-year period. In all cases, the duration of symptoms before the initial lumbar puncture was short (6-24 h). The case-fatality rate was 3/7 (43%) compared with 10/100 (10%) among children with abnormal initial CSF, despite early initiation of antibiotics. Bacterial meningitis with an initial normal CSF finding is not rare and may be associated with poor outcome.

Bacterial Infections↗
PubMed1988

Clinical experience with doxazosin in general medical practice.

The antihypertensive efficacy, lipid effects, and safety of doxazosin, a selective alpha 1-inhibitor for the reduction of coronary heart disease (CHD) risk in hypertensive patients, was assessed in a general medical practice setting. Seven hundred seventy-one patients were entered into the study, which involved three phases: (1) a 2-week baseline period, (2) an 8-week period in which patients received doxazosin, 1 to 8 mg once daily, and (3) a 4-week maintenance period. From baseline to final visit there was a highly significant 27% reduction (p less than 0.001) in calculated CHD risk based on the Framingham equation as a consequence of doxazosin's favorable effects on both blood pressure and serum lipid levels. Efficacy and toleration of doxazosin therapy were good to excellent in most patients. The investigators' global assessment of efficacy of once-daily doxazosin therapy was excellent or good for 82% of patients and fair or poor for only 18% of patients. After 12 weeks, 83% of the patients were considered therapy successes (sitting diastolic blood pressure either less than or equal to 90 mm Hg or greater than or equal to 10 mm Hg reduction not reaching less than or equal to 90 mm Hg) at a mean daily dose of 3.5 mg. Seventy-one percent achieved "normalized" blood pressure control (sitting diastolic less than or equal to 90 mm Hg with a decrease of greater than or equal to 5 mm Hg) at a mean dose of 3.1 mg once daily. By the final treatment visit, systolic/diastolic blood pressures of efficacy evaluable patients were reduced by 20.6/15.3 and 21.0/15.4 mm Hg from a mean baseline of 166/104 and 165/104 mm Hg in the sitting and standing positions, respectively (p less than 0.05). Total cholesterol was significantly decreased (p less than 0.01). Most side effects were mild or moderate and disappeared with or were tolerated on continued therapy. The investigators' global assessment of patient toleration of doxazosin treatment was excellent or good for 89% of the 763 patients evaluated and fair or poor for only 11% of patients. The most commonly reported side effects were headache (8%) and dizziness (7%). No clinically significant laboratory changes were apparent, and no trends were observed with regard to organ systems or correlations with dose or duration of treatment.

Adrenergic alpha-Antagonists↗
PubMed1988

Control of coronary heart disease risk factors with doxazosin as monotherapy and in combination therapy.

Although the pathology of essential hypertension is still unclear, studies have shown that doxazosin, a selective alpha 1-inhibitor, is able to effectively control mild-to-moderate hypertension. The aim of these two, noncomparative studies was to evaluate the efficacy and toleration of doxazosin when used as monotherapy and in combination with other antihypertensive agents. In study I, 154 patients with standing and sitting diastolic blood pressures (DBPs) ranging from 95 to 115 mm Hg were treated with once-daily doxazosin (1 to 8 mg) as monotherapy for 12 weeks. Both sitting and standing blood pressures were significantly reduced by doxazosin monotherapy. Target DBP of less than or equal to 90 mm Hg was achieved in 86% of patients after 12 weeks of therapy with doxazosin, and there was no change in heart rate. Cholesterol and triglyceride levels were significantly decreased by doxazosin, but there was no change in glucose levels. Minor side effects were seen in 17.5% of patients, and 2.6% discontinued therapy. In study II, 65 patients with DBPs ranging from 95 to 115 mm Hg on existing antihypertensive therapies were concomitantly treated with doxazosin (1 to 8 mg) once daily for 12 weeks. Target DBPs of less than or equal to 90 mm Hg was achieved in 71% of patients after 12 weeks of therapy with doxazosin. There was no change in heart rate throughout the treatment period, and plasma cholesterol, triglyceride, and glucose levels remained essentially unchanged. Three patients, each receiving a beta-blocker, a diuretic, and doxazosin, were withdrawn because of side effects. Minor side effects, which were considered drug related were seen in 21% of patients. Doxazosin is a drug with good antihypertensive efficacy and is well tolerated as monotherapy and in combination with beta-blockers, thiazide diuretics, angiotensin converting enzyme inhibitors, and various combinations of these drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1988

Treatment of mild hypertension with urapidil or captopril.

The aim of this study was to compare the efficacy (lowering diastolic blood pressure to 90 mm Hg or less) of urapidil, a postsynaptic alpha-blocker with central action with that of captopril in a randomized, double-blind, multicenter study. Two hundred ninety-five essential hypertensives (WHO I/II) (140 male, 155 female, age 56-60 years) were treated for 12 weeks with either 30 to 90 mg urapidil bid or 12.5 to 50 mg captopril bid. Supine blood pressure values (mmHg, mean +/- SD) at the end of the 12-week treatment dropped for the urapidil group (n = 142) from 175/103 +/- 19/6 to 154/89 +/- 17/9 (P less than 0.001), and in the captopril group (n = 153) from 175/103 +/- 19/6 to 154/90 +/- 19/9 (P less than 0.001), corresponding to 62% urapidil and 58% captopril responder rates. The results demonstrate that the two antihypertensive medications with different modes of action control blood pressure with equal efficacy at three dose levels. A dose decrease was possible in 20% of each group, but a dose increase was necessary in 39% of urapidil and 44% of captopril group.

Adult↗