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Biomedical subjects

T Rosenthal

Publications and source records attributed to T Rosenthal.

At least 37 records · Page 2Linked to original sources
PubMed1998

Stress reaction to intense sound exposure under different arousal levels in guinea pigs.

The general impact of high intensity sound exposure on 25 guinea pigs was investigated at three different levels of arousal: 10 during general anaesthesia. 10 during partial arousal, and 5 during complete arousal. Parameters recorded before and during noise exposure were mean arterial blood pressure, pulse rate, and plasma norepinephrine levels. The anaesthetized group showed no increase in the three parameters during sound exposure. Under partial arousal, pulse rate and norepinephrine level increased significantly: pulse rate from 224.5 beats/min before exposure to 278.6 beats/min during exposure, and norepinephrine level from 558 pg/ml before sound exposure to 1276 pg/ml during exposure. At the time of the complete arousal state norepinephrine and pulse rates increased significantly during noise exposure, while blood pressure showed no additional increase as a result of sound exposure.

Acoustic Stimulation↗
PubMed1998

Enhanced Na+/H+ exchange in Cushing's syndrome reflects functional hypermineralocorticoidism.

BACKGROUND: Patients with Cushing's syndrome exhibit a bimodal distribution of maximal rates of the erythrocyte amiloride-sensitive Na+/H+ exchange (NHE). Enhanced erythrocyte NHE has recently been found in patients with primary aldosteronism. OBJECTIVE: To test the hypothesis that occult hypermineralocorticoidism in a subset of patients with Cushing's syndrome is responsible for the greater than normal NHE. METHODS: NHE was measured as maximal initial rate (Vmax) of amiloride-inhibited efflux of H+ into an alkaline Na+-containing medium, for 47 patients with hypercortisolism (20 with pituitary adenomas, 18 with adrenal adenomas, and nine with ectopic production of adrenocorticotropin). Clinical appearance, blood pressure levels, plasma aldosterone and deoxycorticosterone levels, serum electrolytes, and urine (tetrahydrocortisol plus 5-alpha-tetrahydrocortisol) : tetrahydrocortisone ratios were assessed for all patients. Twenty patients (10 with greater than normal NHE and 10 with low-to-normal NHE) were randomly selected from 47 patients with hypercortisolism, and treated with 200 mg/day spironolactone for 7 days. NHE in these patients was assessed before starting the treatment and 2 days after its cessation. RESULTS: Greater than normal NHE (Vmax) was associated with peripheral edema, high diastolic blood pressure, hypokalemia, and high urine (tetrahydrocortisol plus 5-alpha-tetrahydrocortisol) : tetrahydrocortisone ratios. The enhanced NHE was rapidly normalized by treatment with spironolactone. CONCLUSION: Erythrocyte NHE in patients with hypercortisolism and functional hypermineralocorticoidism is greater than normal due to incomplete peripheral conversion of cortisol (which binds to mineralocorticoid receptors) into metabolically inactive cortisone.

Adult↗
PubMed1998

Contribution of bradykinin to the beneficial effects of ramipril in the fructose-fed rat.

The contribution of nondegraded bradykinin to the metabolic effects of the angiotensin-converting enzyme (ACE)-kininase II inhibitor ramipril was evaluated in rats rendered hypertensive, hyperinsulinemic, and hypertriglyceridemic by a fructose-enriched diet. The response of blood pressure, insulin, and triglyceride levels to concomitant administration of ramipril and the bradykinin antagonist HOE 140 was studied. Rats that received ramipril, HOE 140, or not treated at all served as controls. Treatment with ramipril reduced levels of both insulin (from 6.6 +/- 2.0 to 3.6 +/- 1.7 ng/ml; p < 0.05) and triglycerides (from 292 +/- 88 to 164 +/- 35 mg/dl; p < 0.001) as well as blood pressure (from 144 +/- 6 to 116 +/- 6 mm Hg; p < 0.001). In contrast, treatment with HOE 140 did not alter any of these parameters. The combined treatment, however, blunted the beneficial metabolic effects of ramipril on insulin (7.8 +/- 4.4 ng/ml before and 7.7 +/- 2.9 ng/ml after treatment) and triglycerides (290 +/- 135 mg/dl before and 285 +/- 152 mg/dl after treatment), whereas the hypotensive effect of ramipril was preserved (151 +/- 8 mm Hg before and 122 +/- 6 mm Hg after treatment (p < 0.001). The data suggest that whereas the hypotensive effect is mostly angiotensin-II dependent, the advantageous metabolic affect of ramipril is highly dependent on the accumulation of bradykinin.

Adrenergic beta-Antagonists↗
PubMed1998

Dietary cardiovascular risk factors and serum cholesterol in an Old Order Mennonite community.

OBJECTIVES: Dietary and coronary heart disease risk factors in Old Order Mennonite men and women were examined. METHODS: A food frequency questionnaire was mailed to 250 Mennonites who had participated in a previous study of coronary heart disease risk factors. RESULTS: Mennonites consumed a diet high in total fat, saturated fats, and cholesterol. Men had lower average serum cholesterol levels (174 mg/dL) than women (191 mg/dL). CONCLUSIONS: The Mennonites' diet was similar to that of the overall US population in saturated fat percentage and higher in cholesterol. Serum cholesterol levels, adiposity, and blood pressure were lower than expected among Mennonite men, perhaps because of their higher levels of physical activity.

Adolescent↗
PubMed1998

Study population and treatment titration in the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT).

OBJECTIVES: To ascertain the baseline characteristics of the high-risk hypertensive patients entering the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT). To determine the success of single and combination therapy in achieving target blood pressures in such a population. DESIGN: INSIGHT is a double-blind, prospective outcome trial comparing the efficacy of the calcium channel blocker, nifedipine GITS, and the thiazide, co-amilozide, in preventing myocardial infarction and stroke. We recruited 2996 men and 3454 women, aged 55-80 years, with blood pressure during placebo run-in >150/95 mmHg or isolated systolic blood pressure >160 mmHg from nine countries. Treatment allocation to nifedipine GITS 30 mg daily or co-amilozide (hydrochlorothiazide 25 mg/amiloride 5 mg) once daily was performed by minimization rather than randomization to balance additional risk factors. This was followed by four optional increases in treatment: dose-doubling of the primary drug, addition of atenolol 25/50 mg or enalapril 5/10 mg, and then any other hypotensive drug excluding calcium blockers or diuretics. Target blood pressure was 140/90 mmHg or a fall > or = 20/10 mmHg. RESULTS: Blood pressure at randomization was 172+/-15 / 99+/-9 mmHg. Thirteen per cent of the patients were previously untreated. The proportions of each additional risk factors were: smoking > 10/day, 29%; cholesterol > 6.43 mmol/l, 52%; family history of premature myocardial infarction or stroke, 21%; diabetes mellitus 20%; left ventricular hypertrophy, 10%; previous myocardial infarction, other presentations of coronary heart disease, and peripheral vascular disease, each 6%; proteinuria, 3%. Fifty-five per cent of patients had one additional risk factor, whereas 33%, 9% and 3% had two, three or more additional risk factors, respectively. The blood pressure (and falls in blood pressure) at the end of titration and at 1 year after minimization was 139+/-12 / 82+/-7 mmHg (33+/-15 / 17+/-9) in the 5226 patients still on randomized treatment The numbers requiring the four treatment increments were, respectively, 1591, 780, 597 and 294, meaning that almost 70% of patients on randomized treatment in INSIGHT are receiving only the primary drug. At one year, 69% of patients had a blood pressure < or = 140/90 mmHg. CONCLUSION: INSIGHT is one of the first double-blind comparisons of active antihypertensive treatments, requiring high-risk patients to achieve sufficient power. Despite this requirement, it is possible to achieve good blood pressure control in most patients without the addition of multiple additional treatments that may dilute any differences between the primary agents.

Aged↗
PubMed1997

[Red cell Na+/H+ exchange and role of protein kinase C in its stimulation in diabetes mellitus, essential hypertension and nephropathy].

Na+/H+ exchange (NHE) was measured as maximal initial velocity of pH-dependent H+ efflux from red cells into an alkaline medium containing Na+ in patients with insulin-dependent or noninsulin-dependent diabetes, with and without hypertension and in normoglycemic, essential hypertensives and normal controls (50 subjects in each subgroup). Maximal velocities of NHE were found in microalbuminuric patients in all subgroups, and NHE correlated with the rate of micro-albuminuria (r = 0.61, p = 0.02). Daily insulin requirements were greater in those with elevated NHE (84 +/- 8 vs 42 +/- 4 U/day). There was no correlation between NHE and levels of plasma glucose, HbA1 and plasma aldosterone and lipid profile and PRA. NHE was correlated with plasma prolactin (r = 0.51, p = 0.02) and PTH r = 0.24, p = 0.05). In uremic patients, NHE was inversely correlated with creatinine clearance (r = -0.48, p = 0.03). Since calphostin C, a selective inhibitor of protein kinase C, lowered increased NHE in vitro, the protein kinase C-dependent pathway of the exchanger regulation was concluded to be responsible for NHE activation in diabetes mellitus and essential hypertension.

Adult↗
PubMed1997

Amiloride-sensitive Na+/H+ exchange in erythrocytes of patients with NIDDM: a prospective study.

Intensive treatment of non-insulin-dependent diabetes mellitus (NIDDM) decreases the rate of microvascular complications, but is associated with increased incidence of cardiovascular morbidity. Enhanced permeability of plasma membranes for sodium (e.g. sodium-hydrogen exchange, NHE) may predict the subset of diabetic patients for whom intensive modalities of treatment are indicated despite their potential risk. However, the accuracy of NHE as a marker of microangiopathy has not been assessed. In this study NHE as initial velocity of amiloride-inhibited H+ efflux from erythrocytes (pHi 6.35-6.45) into an Na(+)-containing medium (pHo 7.95-8.05), was estimated during 8 years of follow-up in 138 non-microalbuminuric diabetic patients (74 women, 64 men, age 52 +/- 4 years) treated with antihyperglycaemic drugs for 14 +/- 2 years. Appearance of microalbuminuria, overt proteinuria, azotaemia and retinopathy was assessed annually. Enhanced erythrocyte NHE predicted diabetic nephropathy alone and in association with a family history of hypertension and/or nephropathy with a sensitivity of 86 and 93%, respectively. No association was found between NHE and retinopathy in NIDDM. It is concluded that assessment of erythrocyte NHE can identify a subset of patients likely to develop renal damage, for whom an aggressive treatment approach might be considered.

Albuminuria↗
PubMed1997

Epinephrine pharmacokinetics and pharmacodynamics following endotracheal administration in dogs: the role of volume of diluent.

OBJECTIVE: to define the optimal volume of dilution for endotracheal(ET) administration of epinephrine (EPI). DESIGN: prospective, randomized, laboratory comparison of four different volumes of dilution of endotracheal epinephrine (1, 2, 5, and 10 ml of normal saline). SETTING: large animal research facility of a university medical center. SUBJECTS AND INTERVENTIONS: epinephrine (0.02 mg/kg) diluted with four different volumes (1, 2, 5, and 10 ml) of normal saline was injected into the ET tube of five anesthetized dogs. Each dog served as its own control and received all four volumes in different sequences at least 1 week apart. Arterial blood samples for plasma epinephrine concentration and blood gases were collected before and 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 10, 15, 20, 25, 30 and 60 min after drug administration. Heart rate and arterial blood pressure were continuously monitored with a polygraph recorder. MEASUREMENTS AND MAIN RESULTS: higher volumes of diluent (5 and 10 ml) caused a significant decrease of PaO2, from 147 +/- 8 to 106 +/- 10 torr, compared with the lower volumes of diluent (1 and 2 ml), from 136 +/- 10 to 135 +/- 7 torr (P < 0.05). These effects persisted for over 30 min. Mean plasma epinephrine concentrations significantly increased within 15 s following administration for all the volumes of diluent. Mean plasma epinephrine concentrations, maximal epinephrine concentration (Cmax) and the coefficient of absorption (Ka) were higher in the 5 and 10 ml groups. The time interval to reach maximal concentration (Tmax) was shorter in the 5 and 10 ml groups. Yet these results were not significantly different. Heart rate, systolic and diastolic blood pressures did not differ significantly between the groups throughout the study. CONCLUSIONS: Dilution of endotracheal epinephrine into a 5 ml volume with saline optimizes drug uptake and delivery without adversely affecting oxygenation and ventilation.

Animals↗
PubMed1997

The effects of a combined low-sodium, high-potassium, high-calcium diet on blood pressure in patients with mild hypertension.

Nutritional sodium, potassium and calcium are considered to be important regulators of blood pressure (BP). The present study evaluates the effects of combined low-sodium (LS), high-potassium (HK), high-calcium (HCa) diet on BP in patients with mild essential hypertension. Thirty-six patients (26 M, 10 F), 24-67 years of age (mean 46 +/- 8), participated in the study. Patients were divided into three groups and given a diet consisting of three 1-month segments, which they followed in different order. Group 1 (n = 11) received LS diet followed by the addition of HCa and then HK. The order in Group 2 (n = 12) was HK-LS-HCa; and in Group 3 (n = 13) it was HCa-HK-LS. The third month of the study all patients were eating a combined LS, HK and HCa diet. Urinary electrolytes were measured to confirm compliance with the diets. After 1 month of the LS diet urinary sodium excretion decreased significantly by 25 mmols/day (95% CI, 1-48 mmols/day); (P < 0.05). Eighteen patients did not comply with the diet. Systolic BP (SBP) only slightly decreased, from 142 mm Hg (95% CI, 137-146 mm Hg) to 138 mm Hg (95% CI, 133-142 mm Hg); (P = 0.11). The change in SBP was related to the change in urinary sodium excretion (R = 0.46; P = 0.006). After 1 month of the HK diet, urinary potassium excretion increased by only 5 mmols/day (P = NS). BP was unaffected by HK and HCa diet. At the end of the study, urinary sodium excretion decreased from 183 mmols/day (95% CI, 155-211 mmols/day) to 148 mmols/day (95% CI, 131-165 mmols/day); (P < 0.05), urinary potassium excretion slightly increased from 75 mmols/day (95% CI, 68-82 mmols/day) to 85 mmols/day (95% CI, 76-94 mmols/day); (P = 0.09), and urinary calcium excretion remained unchanged. BP did not decrease. It is concluded that only the LS diet may be advantageous in patients with mild essential hypertension.

Adult↗
PubMed1997

Enhanced red cell sodium-hydrogen exchange in microvascular angina.

OBJECTIVES: Enhanced calcium content in arterial smooth muscle cells and altered reactivity of coronary vessels to alkalinization have been reported in angina pectoris due to impaired motility of coronary arteries. An altered function of sodium-hydrogen exchange, a ubiquitous membrane transport system that links proton efflux to calcium drifts, may mediate these phenomena. DESIGN AND SUBJECTS: Twenty patients with microvascular angina (stable effort angina, reversible perfusion defects during effort thallium 201 heart scintigraphy, and angiographically normal coronary arteries) were compared to 20 patients with stable effort angina due to coronary atherosclerosis and 20 healthy subjects. The sodium-hydrogen exchange was defined as the initial fraction of the amiloride-sensitive proton efflux from red cells with inhibited anion exchanger (pHi 6.00-6.05) into an Na(+)-containing medium (pHo 8.00-8.05). 12-0-tetradecanoylphorbol-13-acetate (TPA, 600 nmol.l-1) and staurosporine (100 nmol.l-1) were used as phosphorylation modulators in vitro. RESULTS: The mean red blood cell Na+/H+ exchange was increased in patients with microvascular angina (451 +/- 37 vs 142 +/- 17 and 124 +/- 21 umol H+.1 cells-1.min-1, P < 0.01). TPA and staurosporine abolished differences between the groups. CONCLUSIONS: Microvascular angina is associated with enhanced Na+/H+ exchange in erythrocytes, probably due to more extensive phosphorylation of the membrane antiporter sites.

Cell Membrane↗
PubMed1997

Peripartum cardiomyopathy occurring in a patient previously treated with doxorubicin.

We present a 28-year-old primigravida woman in whom congestive heart failure developed 3 months after delivery of a neonate. The patient underwent doxorubicin treatment 10 years previously. The combined cardiotoxicity of prior doxorubicin treatment and pregnancy is considered, and the importance of careful follow-up of cardiac function during pregnancy and postpartum in patients previously treated with doxorubicin is stressed.

Adult↗
PubMed1997

Nifedipine GITS replacing nifedipine SR: ambulatory blood pressure assessment of efficacy.

The relative efficacy of two formulations of nifedipine, slow release (SR) and gastrointestinal therapeutic system (GITS), to lower blood pressure in hypertensive patients was evaluated in a prospective study. Nifedipine GITS 30 mg/day replaced nifedipine SR, 20 mg b.i.d. in 38 patients, 23 monitored by routine blood pressure measurements and 15 by ambulatory monitoring. Nifedipine GITS achieved a marked reduction in blood pressure with a smaller dose than nifedipine SR: 30 versus 40 mg/day, respectively. It is concluded that patients with hypertension controlled on a twice-daily dose of nifedipine prolonged action can be converted to a lower once-daily dose of nifedipine GITS without experiencing any increase in blood pressure. Tolerability and compliance improved when switching to the GITS formulation.

Adult↗
PubMed1997

Effects of enalapril, losartan, and verapamil on blood pressure and glucose metabolism in the Cohen-Rosenthal diabetic hypertensive rat.

We undertook the present study to examine the effect of the angiotensin-converting enzyme inhibitor enalapril, the angiotensin II antagonist losartan, and calcium antagonist verapamil on systolic pressure and spontaneous blood glucose levels in rats from the Cohen-Rosenthal diabetic hypertensive strain. Genetic hypertension and diabetes developed in this strain after crossbreeding of Cohen diabetic and spontaneously hypertensive rats. The new rat strain was fed their usual copper-poor sucrose diet, which is essential for the development of this model, and for 4 weeks received either enalapril, losartan, or verapamil. Systolic pressure was reduced significantly compared with controls in all treated groups. Chronic treatment with enalapril or verapamil, but not with losartan, succeeded in lowering spontaneous blood glucose, indicating improved diabetic control. Data suggest that angiotensin-converting enzyme inhibition by enalapril, but not angiotensin II antagonism by losartan, can improve glucose metabolism in addition to its hypotensive effect in a genetic diabetic hypertensive rat strain. This confirms that the drop in glucose with converting enzyme inhibition is highly dependent on bradykinin accumulation. Data further suggest that calcium channel blockade by verapamil can also improve glucose metabolism. The question remains whether the reduction in glucose by verapamil was a result of inhibition of glucogenesis.

Angiotensin II↗
PubMed1997

Membrane ion transport in Bartter's syndrome: evidence for a new syndrome subtype.

Fifteen patients with Bartter's syndrome (hyponatremic hypochloremic hypokalemic metabolic alkalosis) were compared with 15 healthy volunteers. Red blood cell Na+/H+ and Cl-/HCO3- exchanges were enhanced in all patients with Bartter's syndrome. In calciuric normomagnesemic patients, sensitive to nonsteroidal anti-inflammatory drugs (classic Bartter's syndrome), red blood cell Na+,K+,2Cl- cotransport was markedly reduced, calcium-dependent K+ permeability was moderately increased, and up to 60% of sodium permeability was represented by cAMP-activated fraction (presumably human analog of beta-isoform of Na+/H+ exchange). In noncalciuric hypomagnesemic patients insensitive to indomethacin (Gitelman's syndrome), Na+,K+,2Cl- cotransport was enhanced, Na+ permeability was increased due to calmodulin-dependent fraction, and calcium-dependent K+ permeability was markedly enhanced. A new subtype of Bartter-like syndrome ("variant Bartter's syndrome") has been described in which calciuria, hypomagnesemia, and insensitivity to nonsteroidal anti-inflammatory drugs were associated with decreased Na+,K+,2Cl- cotransport, enhanced calmodulin-activated fraction of Na+ influx, and reduced calcium-dependent K+ permeability.

Adolescent↗