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Biomedical subjects

T Rosenthal

Publications and source records attributed to T Rosenthal.

At least 73 records · Page 4Linked to original sources
PubMed1995

Calcium antagonists. Drug interactions of clinical significance.

The interaction of calcium antagonists, including the dihydropyridine calcium antagonists (e.g. nifedipine), verapamil and diltiazem, with drugs from other classes has major clinical ramifications as the use of drug combinations increases in frequency. Combinations are used in the treatment of disorders ranging from hypertension to cardiac rhythm disturbances, angina pectoris and peripheral vasospastic disease. In this era of organ transplantation, drugs like cyclosporin are coming into potential conflict with an ever-growing list of drugs. Drug combinations used as part of long term therapies are also making their appearance in toxic drug reactions, including antituberculous and anticonvulsant agents. Bronchodilators and H2-blockers also fall into this category of potential culprits of combined drug toxicity, and the interactions of calcium antagonists with beta-blockers and antiarrhythmic agents are also becoming a matter of concern.

Anesthetics↗
PubMed1995

Altered circadian rhythm of blood pressure in shift workers.

The effect of shift work on the circadian rhythm of blood pressure (BP) was studied in male bakery workers. The study group consisted of 28 men, blue collar non-rotating shift workers, 20-60 years of age, and the control group comprised 30 men, blue collar, day workers in the same age group. BP was evaluated in all subjects by 24h BP monitoring. Day workers showed typical circadian rhythm with a drop in both systolic and diastolic BP at night. This pattern was reversed in night workers. The peak SBP for night workers was at 11 pm and among day workers at 4 pm. Peak DBP was recorded among night workers at 10 pm and among day workers at 3 pm. All subjects showed a highly significant cyclic variation in BP. Whereas the range for SBP was similar in these two age groups (P > 0.05), the amplitude of DBP tended to be smaller in young workers. Therapeutic decisions for night shift workers with hypertension should take into account their altered BP cycle.

Adult↗
PubMed1995

Generalized pustular eruption associated with converting enzyme inhibitor therapy.

A 67-year-old man presented with a high fever and a generalized rash. His extended hospital stay was characterized by fever with repeated staphylococcal bacteremia and the appearance of axillary lymphadenopathy and splenomegaly. Skin lesions became hyperpigmented, dry, and atrophic with areas of exfoliation and uclers. Examination of skin and lymph node biopsy specimens showed findings consistent with mycosis fungoides. The patient unexpectedly recovered on discontinuation of captopril. A positive macrophage inhibiting factor response for both captopril and enalapril indicated that the non-sulfhydryl moiety was the antigenic stimulant for the lesion resembling mycosis fungoides.

Aged↗
PubMed1994

Hemodynamic and humoral effects of the angiotensin II antagonist losartan in essential hypertension.

Losartan (DuP 753) is a novel orally active angiotensin II antagonist that lowers blood pressure. The present study evaluates the hemodynamic and humoral effects of losartan in essential hypertension. Fifteen patients (12 men, 3 women; mean age, 46 +/- 2 years; range, 33 to 64 years) with a diastolic blood pressure (DBP) between 95 and 115 mm Hg after 2 weeks of placebo participated in the study. Initially the patients were treated with losartan (50 mg) once daily for 1 month. Then, if the trough DBP was > or = 93 mm Hg, hydrochlorothiazide (HCTZ), 6.25 to 12.5 mg daily, and nifedipine, 30 to 60 mg daily, were added as needed. Ten patients completed 12 months of treatment. Trough blood pressure, heart rate, plasma creatinine, potassium, uric acid, cholesterol, renin activity (PRA), aldosterone, and norepinephrine were measured at baseline and after 1 and 12 months of treatment. Losartan lowered mean arterial pressure significantly from 119 +/- 2 mm Hg at baseline to 113 +/- 2 mm Hg (P < .05) after 1 month of treatment. Coadministration of HCTZ and nifedipine further decreased the mean arterial pressure to 103 +/- 2 mm Hg after 12 months of treatment. Plasma levels of creatinine, potassium, uric acid, cholesterol, and norepinephrine remained unchanged. PRA increased and plasma aldosterone decreased significantly (P < .05). The decrease in mean arterial pressure was related to baseline PRA (r = 0.53, P < .05). and to the change in PRA (r = 0.52, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Clinical pharmacokinetics of ramipril.

Ramipril is a long-acting nonsulfhydryl angiotensin converting enzyme (ACE) inhibitor introduced for clinical use about a decade ago. Ramipril is a prodrug that undergoes de-esterification in the liver to form ramiprilat, its active metabolite. Ramipril rapidly distributes to all tissues, with the liver, kidneys and lungs showing markedly higher concentrations of the drug than the blood. After absorption from the gastrointestinal tract, rapid hydrolysis of ramipril occurs in the liver. In the therapeutic concentration range, protein binding of ramipril and ramiprilat is 73 and 56%, respectively. Ramiprilat binds to ACE with high affinity at concentrations similar to that of the enzyme and establishes equilibrium slowly. Although ramipril is metabolised by hepatic and renal mechanisms to both a glucuronate conjugate and a diketopiperazine derivative, most of the drug is excreted in the urine as ramiprilat and the glucuronate conjugate of ramiprilat. Elimination from the body is characterised by a relatively rapid initial phase with a half-life of 7 hours and a late phase with a half-life of about 120 hours. No clinically significant pharmacokinetic interactions between ramipril and other drugs have been reported. The drug has been generally well tolerated with the most prevalent adverse effects being dizziness (3.4%), headache (3.2%), weakness (1.9%) and nausea (1.7%). Ramipril is an effective and well tolerated drug for the treatment of hypertension and congestive heart failure in all patients, including those with renal or hepatic dysfunction, and the elderly.

Drug Interactions↗
PubMed1994

Left ventricular mass in hypertension: correlation with casual, exercise and ambulatory blood pressure.

The purpose of this work was to assess the best haemodynamic determinant of left ventricular hypertrophy (LVH) in patients with essential hypertension. We studied the relationships between left ventricular mass (LVM) and casual, exercise and 24h ambulatory blood pressure monitoring (ABPM) in 60 newly discovered patients with mild to moderate essential hypertension. LVM was only weakly related to both casual and exercise blood pressure, while it was significantly related to average ABPM values. Diastolic hypertensive load, calculated as the percentage of diastolic measurements > 90 mmHg, was the best predictor of the development of LVH (r = 0.51, P < 0.001). Six of six patients with a diastolic load > 50% had LVH, whereas only two of 18 patients (11%) with a diastolic load < 10% had LVH (P < 0.001). In conclusion, in patients with mild to moderate essential hypertension, LVM is poorly related to both casual and exercise blood pressure, but is related to ABPM. Blood pressure load is the best determinant of LVH. These findings suggest that blood pressure load should be considered when analysing ABPM.

Adolescent↗
PubMed1994

Spectral analysis of the systolic blood pressure signal in secondary hypertension: a method for the identification of phaeochromocytoma.

OBJECTIVE: To seek in hypertensive patients rhythmic variations of the systolic blood pressure signal obtained by ambulatory blood pressure monitoring of any inherent cycle of intermediate value between 1 and 24 h. DESIGN: Subjects (62 hypertensive, 39 normotensive) were evaluated by 24-h ambulatory blood pressure monitoring. The hypertensive group consisted of 48 patients with essential hypertension, nine with renovascular hypertension and five with phaeochromocytoma. The groups were matched for age and weight. METHODS: The ambulatory systolic blood pressure recording served as the input for a filtering procedure that rejected unacceptable values according to predetermined criteria. The whole-day systolic blood pressure series thus obtained were subjected to Fourier analysis to obtain a spectral analysis of daily systolic blood pressure fluctuations. Daily (first 12 h), nightly (second 12 h) and whole-day average systolic blood pressure values were calculated and compared for the various groups. RESULTS: The average nocturnal systolic blood pressure was found to be lower than its daily counterpart in the normal subjects and in the patients with essential hypertension, whereas in the patients with renovascular hypertension or phaeochromocytoma no such nocturnal decrease was found. The power spectrum of patients with phaeochromocytoma was statistically different from that of other aetiologies of hypertension. This was achieved due mainly to a statistically significant difference in the power spectrum integral over the low-frequency band (0-0.2 cycles/h) of the power spectrum of the 24-h systolic blood pressure signal. Resection of the phaeochromocytoma normalized the power spectrum as found by analysis of the postoperative ambulatory blood pressure monitoring data in two patients who underwent a repeat recording. CONCLUSIONS: The technique described enables the discrimination of patients with phaeochromocytoma as a cause of hypertension from other aetiologies of hypertension. Patients with renovascular hypertension could not be distinguished from those with essential hypertension on the basis of their power spectrum. However, this technique may prove to be a valuable modality for characterizing hypertensive patients of different aetiologies.

Activity Cycles↗
PubMed1993

The role of atrial natriuretic peptide in the diuretic effect of Ca2+ entry blockers.

The effect of three calcium entry blockers--verapamil, nifedipine and felodipine--on diuresis, natriuresis, the renin-aldosterone axis, and atrial natriuretic peptide (ANP) levels was studied in 30 previously untreated patients with mild to moderate essential hypertension. All three blockers produced significant antihypertensive effects after 2 and after 24 h. Heart rate tended to decrease, but did not change significantly after verapamil, but increased significantly 1-2 h after nifedipine and felodipine. Plasma renin activity (PRA) did not change significantly with any treatment, and plasma aldosterone decreased with all three agents. ANP levels did not change significantly after verapamil, but increased significantly after nifedipine and felodipine. There was a significant positive correlation between the maximal change in ANP level and urinary sodium after nifedipine and felodipine. The increase in urinary sodium after verapamil was not significant. The role of the direct renal effect of calcium entry blockers in their persistent natriuretic action is discussed, as well as their short-term enhancement of ANP levels, which may account for the initial diuretic and natriuretic effects seen with this class of dihydropiridines.

Adult↗
PubMed1993

Ventricular arrhythmias in rehabilitated and nonrehabilitated post-myocardial infarction patients with left ventricular dysfunction.

The incidence of ventricular arrhythmias in rehabilitated post-myocardial infarction (MI) patients with left ventricular dysfunction included in a long-term rehabilitation program was assessed and compared with that in similar patients who were not in such a program. Thirty-eight post-MI patients (2 to 19 years after the acute event) with ejection fraction < 40% were investigated by 48-hour Holter monitoring. They were divided into the following 3 groups: group I, 11 patients who underwent arm training for 60 months; group II, 11 patients who underwent calisthenics for 36 months; and group III, 16 patients who were not in any rehabilitation program; the age of the patients was 61 +/- 7, 61 +/- 6 and 61 +/- 9 years, respectively, (p = not significant). Ejection fraction at rest was 31 +/- 9 for group I, 29 +/- 7 for group II, and 29 +/- 7 for group III (p = not significant). There were no significant differences concerning the location of MI, and antiarrhythmic treatment received by patients from all groups. At the conclusion of 48-hour Holter monitoring, 2 blood samples were obtained for assessment of norepinephrine (at rest and after postural change). Quality of life was determined by a detailed questionnaire, including questions concerning social activity, life satisfaction and sexual function. After 36 and 60 months, an improvement in hemodynamic condition of patients in group I was noted. Quality of life was higher in the rehabilitated patients, with enhanced emotional stability, satisfaction with work and social life, and a high percentage of return to work (82 vs 40%).(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗
PubMed1993

Reduction of thromboxane A2 synthesis in pregnancy by polyunsaturated fatty acid supplements.

OBJECTIVE: High-dose supplements of fish oil reduce thromboxane synthesis in nonpregnant human subjects and were therefore proposed as a means of preventing various small-vessel disorders, including preeclampsia. The effect of fish oil on thromboxane metabolism in pregnancy was investigated in our study. STUDY DESIGN: Sixteen normal pregnant women in the third trimester of pregnancy were treated with a daily ingestion of 6 gm fish oil capsules containing 1.6 gm of n-3 fatty acid. In five patients the treatment was stopped because of severe-flavored reflux and hiccups. Eleven patients completed 3 weeks of treatment. Twenty-four-hour urinary 11-dehydro-thromboxane B2 was measured by means of radioimmunoassay before and after completion of the study protocol in these 11 patients and in seven control pregnant women who did not receive the oil treatment. RESULTS: A decrease ranging from 32% to 71%, in 24-hour urinary 11-dehydro-thromboxane B2 excretion (mean reduction from 1606 pg/mg creatinine to 779 pg/mg creatinine, p < 0.001) was found among the 11 fish oil-treated women. No change in excretion was found among the control women. No maternal, fetal, or neonatal bleeding disturbances occurred, and no laboratory changes in coagulation markers were observed. CONCLUSIONS: High-dose n-3 fatty acid intake in pregnancy significantly reduces maternal thromboxane A2 synthesis. These results may provide a basis for a possible role of fish oil in managing patients at risk for preeclampsia.

Adult↗
PubMed1993

Hemodynamic and neurohumoral effects of fish oil in hypertensive patients.

Recent studies showed that supplementation of a large dose of fish oil is effective in lowering blood pressure. Whether supplementation of a low dose of fish oil is also effective in lowering blood pressure is controversial. The present study evaluates the hemodynamic and humoral effects of low-dose dietary fish oil supplementation in patients with mild hypertension. Eleven patients with mild hypertension were given 3 g/day of n-3 polyunsaturated fatty acids for 6 week. Twenty-four hour blood pressure monitoring and humoral parameters were recorded before and during fish oil treatment. In five patients, blood pressure response to angiotensin II (AII) infusion (1, 2, 3, 6, 9 ng/kg/min) was also recorded before and during treatment. Casual mean arterial pressure was unchanged (111 +/- 1 mm Hg v 109 +/- 3 mm Hg; P = NS). Average 24-h mean arterial pressure (MAP) also did not change during fish oil treatment (98 +/- 2 mm Hg v 99 +/- 3 mm Hg; P = NS). Fish oil supplementation did not attenuate the vascular reactivity to AII infusion. Maximal MAP following AII infusion (9 ng/kg/min) was 128 +/- 5 mm Hg before and 129 +/- 7 mm Hg during fish oil treatment (P = NS). Plasma levels of norepinephrine, renin activity, aldosterone, and atrial natriuretic peptide remained unchanged during treatment. Plasma levels of total cholesterol slightly increased from 200 +/- 10 mg/dL to 211 +/- 9 mg/dL (P < .05), but plasma levels of high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides were unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

The Cohen diabetic (non-insulin-dependent) hypertensive rat model. Description of the model and pathologic findings.

The available diabetic hypertensive models are of type I chemically induced diabetes in one-clip Goldblatt rat or in the spontaneously hypertensive (SHR) rat. We describe here a genetic type II diabetic hypertensive model (CDHM) developed by cross breeding the Cohen diabetic rat (CDR) and the SHR. In the succeeding generations, sibling pairs with the highest spontaneous blood glucose (SBG) and blood pressure (BP) were selected and mated. In the sixth selected generation, non-insulin-dependent overt diabetes and hypertension were evident. Blood pressure was 171 +/- 1.2 mm Hg, spontaneous blood glucose 340 +/- 22 mg/dL, and plasma insulin at 60 min following intragastric (IG) glucose load 83.3 +/- 10.2 microU/mL. In the CDHM there was severe diffuse diabetic glomerulosclerosis and severe hypertensive changes in arteries and arterioles, characterized by fibrinoid necrosis and/or "onion skin" lesions, as well as by smooth muscle cell hyperplasia. Such vascular changes were not observed in the CDR or in the SHR. Myocardial changes were prominent, with foci of ischemic necrosis and hyperplastic vascular changes. This model may be useful in probing the mechanisms potentiating cardiovascular and renal morbid events in the setting of spontaneous hypertension and diabetes.

Animals↗
PubMed1993

Oral yohimbine increases blood pressure and sympathetic nervous outflow in hypertensive patients.

Yohimbine is an alpha 2-adrenoceptor antagonist that is FDA approved for treatment of impotence. The drug is an indolalkylamine alkaloid chemically similar to reserpine and is believed to act through sympatholysis. We examined effects of oral yohimbine on blood pressure (BP) and plasma levels of catechols in patients with essential hypertension, a condition in which most drug treatments can produce impotence. In 25 unmedicated hypertensive subjects, vital signs were measured and blood samples were obtained through an indwelling antecubital venous catheter at baseline and 1 and 2 h after subjects ingested 4 5.4-mg tablets of yohimbine. Mean blood pressure (MBP) increased by an average of 5 mm Hg (p < 0.01), plasma norepinephrine (NE) levels increased by 66% (p < 0.001), and plasma dihydroxyphenylglycol (DHPG) levels increased by 25% (p < 0.01) at 1 h after drug administration. The magnitude of the pressor response was unrelated to baseline MBP but positively correlated with the baseline NE level (r = 0.61, p < 0.01) and with the yohimbine-induced increment in plasma NE (r = 0.4, p < 0.01). The results indicate that yohimbine does not inhibit and actually stimulates sympathetically mediated NE release in humans and that the increased NE release produces a pressor response. Yohimbine should be administered with caution to patients with high BP, especially in individuals with evidence for increased basal sympathetic outflow or those undergoing concurrent treatment with tricyclic antidepressants or other drugs that interfere with neuronal uptake or metabolism of NE.

Administration, Oral↗
PubMed1993

Human immunodeficiency virus type 1-specific cytotoxic T lymphocytes release gamma interferon, tumor necrosis factor alpha (TNF-alpha), and TNF-beta when they encounter their target antigens.

Human immunodeficiency virus type 1 (HIV-1) infection is associated with elevated levels of inflammatory cytokines in the serum and cerebrospinal fluid of infected persons, but the sources of these proteins as well as the specific stimuli which trigger their production and release have not been fully defined. In this study, we evaluated the ability of HIV-1-specific cytotoxic T-lymphocyte (CTL) clones derived from seropositive persons to release gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and TNF-beta upon contact with target cells presenting viral antigen. Peripheral blood- and cerebrospinal fluid-derived HIV-1-specific CD3+ CD4- CD8+ CTL clones as well as freshly isolated peripheral blood mononuclear cells from infected persons were tested in parallel for HIV-1-specific cytotoxicity and cytokine release. Target cells consisted of autologous and allogeneic B-lymphoblastoid cell lines sensitized with synthetic HIV-1 peptides containing the epitopes recognized by these CTL. Cytokine production was measured by specific enzyme-linked immunosorbent assay of culture supernatant fluid. HIV-1-specific CTL clones directed at envelope, Gag, reverse transcriptase, and Nef epitopes specifically released IFN-gamma, TNF-alpha, and TNF-beta upon contact with their relevant target epitopes but not following contact with irrelevant epitopes. These cytokines were released in an HLA class I-restricted fashion, and release was detectable as early as 4 to 6 h of incubation and remained elevated at 48 h. Fresh peripheral blood mononuclear cells from a seropositive person likewise released IFN-gamma in an antigen-specific and HLA class I-restricted manner when incubated with target cells presenting a peptide containing a CTL epitope, paralleling the HIV-specific cytolytic activity of these cells. These studies indicate that in addition to mediating direct cytotoxicity, HIV-1-specific CTL may affect other immune responses by releasing IFN-gamma, TNF-alpha, and TNF-beta. Elevated levels of these cytokines which have been detected in serum and cerebrospinal fluid of infected persons may be due at least in part to the persistent HIV-1-specific CTL response.

Amino Acid Sequence↗
PubMed1993

Immunoreactive endothelins in human follicular fluid.

Endothelin levels were measured by means of [125I]endothelin-1,2,3 radioimmunoassay in the follicular fluids of 22 mature ovarian follicles of 11 patients, obtained during ovum pickup. In all but 1 of the follicles, endothelin levels were detectable and ranged between 0.2 and 3.6 pg/ml (mean 1.47 +/- 0.99). In this preliminary study, no correlation was found between follicular endothelin levels and oocyte fertilization or the hormonal ovarian response during the follicular phase.

Endothelins↗
PubMed1993

Effects of nisoldipine on hypertension and glomerulosclerosis in Cohen diabetic rat with Goldblatt hypertension.

Nisoldipine treatment for five months prevented a rise in blood pressure in Cohen diabetic rats with Goldblatt hypertension, compared to a significant elevation in untreated controls. Blood creatinine and urea also decreased significantly in the treated animals, and renal lesions were less severe. The prevalence of glomerulosclerosis, however, remained unaltered in both the treated and control groups. These findings indicate that increased blood pressure aggravates renal changes, while reducing it eliminates the aggravation.

Animals↗
PubMed1993

Ischaemic heart disease risk factors in young black Africans from urban Zaire.

Blood pressure, pulse and body mass index were measured in 64 healthy black men, aged 20-44 years, from an urban region in Zaire. A required blood test for AIDS was extended to include plasma renin activity (PRA), total cholesterol (TC), triglycerides (TG) and high density lipoprotein cholesterol (HDL-C). Mean BMI was 21.99. Mean BP was 132.2/85.3 mmHg and hypertension (> 160/95 mmHg) was found in 17.2% of subjects. Very low PRA was found in 28 subjects and high PRA in one normotensive man. Mean PRA was 1.3 +/- 1.2. Mean plasma TC, TG and HDL-C were 136, 84, and 46 mg/dl, respectively, and mean TC/HDL-C ratio was 3:1. The frequency of hypertension in this study population is higher than that previously described for a different segment of the same population. It is, however, offset by a more favourable lipid profile that determines a more favourable overall cardiovascular risk profile.

Adult↗