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Biomedical subjects

A S Dobs

Publications and source records attributed to A S Dobs.

52 records · Page 3Linked to original sources
PubMed1993

Long-term endocrine function in hypercholesterolemic patients treated with pravastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor.

Steroid hormone production within the gonads and adrenals requires a continuous supply of cholesterol derived from de novo synthesis within the gland and from uptake of circulating plasma lipoproteins. Steroid hormone secretion was prospectively studied over 24 months in 64 hypercholesterolemic subjects (group I, aged 52 +/- 1 years [mean +/- SEM], 61% male) participating in a randomized double-blind clinical trial of pravastatin (20 to 80 mg daily), a new 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, compared with patients taking cholestyramine or other lipid-lowering drugs (group II). Attempts were made in both groups to maintain serum low-density lipoprotein cholesterol (LDL-C) levels between the 25th and 50th percentile for age and gender. At 24 months, serum LDL-C level decreased by 42% +/- 3% in group I and 44% +/- 1% in group II (P < .001 v baseline, NS between groups). Basal secretion of cortisol, aldosterone, and dehydroepiandrostenedione sulfate (DHEA-S) was maintained throughout the study. However, the serum DHEA-S secretory response to Cortrosyn (Organon, West Orange, NJ) diminished in both treatment groups at 6 and 12 months (P < .05). In men, basal serum testosterone levels and the testosterone response to human chorionic gonadotropin (HCG) did not change. There was some diminution of sperm motility noted in both treatment groups at 6 and 12 months in the subset of men undergoing semen analysis (n = 14, P < .05). In conclusion, pravastatin had no significant effect on steroid metabolism. Changes noted in DHEA-S were not specific for pravastatin, suggesting that this impairment is related to lipid-lowering effects.

Adult↗
PubMed1991

Testicular dysfunction with amiodarone use.

Amiodarone, an antiarrhythmic drug approved for use in patients who survive cardiac arrest, has been associated with infiltration of or inflammatory changes in various tissues. To date thyroid dysfunction has been the only endocrine disturbance noted. In an initial group of seven amiodarone-treated men undergoing evaluation for sexual dysfunction, an elevation in serum gonadotropin concentration was detected, suggesting testicular dysfunction. Because of this finding, gonadal function was prospectively evaluated in 44 men (18 who had been treated with amiodarone for greater than 1 year and 26 survivors of cardiac arrest who had been treated with antiarrhythmic drugs other than amiodarone). Amiodarone-treated men had higher serum follicle-stimulating hormone (41.8 +/- 22.8 vs. 14.4 +/- 10.4 mIU/ml, p less than 0.001) and luteinizing hormone (34.8 +/- 26.4 vs. 10.1 +/- 5.2 mIU/ml, p less than 0.001) concentrations compared with control subjects. Although serum total and free testosterone levels were comparable between the two patient groups, these levels were inversely correlated (r = -0.53, p less than 0.05; r = -0.62, p less than 0.01, respectively) with cumulative amiodarone dose. Hyperresponsiveness to the administration of gonadotropin-releasing hormone was noted in the 10 amiodarone-treated men evaluated by this diagnostic test. Sexual dysfunction was common in both groups (70% of control subjects and 82% of amiodarone-treated subjects), although atrophic testes were more commonly observed in amiodarone-treated men (p less than 0.05). Because of the elevated serum gonadotropin level, it is concluded that testicular dysfunction may result from prolonged amiodarone treatment.

Adult↗
PubMed1991

Effects of pravastatin, a new HMG-CoA reductase inhibitor, on vitamin D synthesis in man.

The HMG-CoA reductase inhibitors, a new class of lipid-lowering agents being used with increasing frequency, inhibit synthesis of cholesterol in vivo. Thus, one potential side effect of these drugs is alteration of other metabolic pathways requiring intermediates in the cholesterol biosynthetic pathway. We hypothesized that pravastatin, a new HMG-CoA reductase inhibitor, may impair vitamin D3 synthesis in the skin and alter mineral homeostasis by diminishing the availability of vitamin D precursors. Basal serum levels of calcium, phosphorus, parathyroid hormone (PTH), vitamin D3, and 1,25-dihydroxyvitamin D were measured, and dietary intakes of calcium and vitamin D were calculated in a control hypercholesterolemic group and an experimental group treated with pravastatin 10, 20, and/or 40 mg orally twice daily for at least 3 months. Basal parameters of mineral metabolism were similar in the two groups. To assess the capacity of the skin to synthesize vitamin D3 and as an indirect measure of its precursors, all subjects received whole body ultraviolet irradiation (UVI) in a phototherapy chamber for varying time intervals. Subjects in both groups showed significant (P less than .001) dose-dependent increases in vitamin D3 production after equivalent UVI exposures. However, for equivalent UVI exposure, the serum vitamin D3 response was identical in controls versus pravastatin-treated subjects. We conclude that hypercholesterolemic patients have normal mineral metabolism and the use of pravastatin at these doses for up to 3 months does not alter vitamin D3 synthesis in the skin.

Adult↗
PubMed1991

Lipid-lowering diets in patients taking pravastatin, a new HMG-CoA reductase inhibitor: compliance and adequacy.

We examined seven 1-d diet records kept during 1 y by 272 men and women instructed to follow a lipid-lowering diet while participating in a clinical trial of pravastatin, a new 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor. The mean percentage of calories from total fat and saturated, unsaturated, and monounsaturated fatty acids was similar throughout the year even though the patients knew they were taking an effective lipid-lowering agent. However, the diets of greater than 40% of women included less than two-thirds of the recommended dietary allowance (RDA) of folic acid, vitamins B-6 and D, and calcium and zinc; in men, folic acid and zinc intakes were low. We conclude that patients comply with lipid-lowering diets even when they know that they are receiving an effective serum lipid-lowering agent. However, for both men and women special attention should be given to the intake of several nutrients.

Adult↗
PubMed1991

Alterations in the hypothalamic-pituitary-adrenal axis in actively drinking alcoholics.

The impact of chronic alcohol abuse on the hypothalamic-pituitary-adrenal (HPA) axis was investigated in actively drinking, nondepressed alcoholics with no evidence of liver disease. Fourteen male alcoholics and 13 matched nonalcoholics were studied. Although alcoholics and controls had similar decrements in cortisol levels after metyrapone blockade, plasma ACTH and 11-deoxycortisol levels in alcoholics were 60% (P less than 0.05) and 40% (P less than 0.05), respectively, of control values. To further clarify defects in the HPA axis of the alcoholic group, each subject underwent a CRH stimulation test. Compared to control subjects, alcoholics had a significantly blunted plasma ACTH response to CRH stimulation (P less than 0.05). Timing of the peak plasma ACTH response was altered in alcoholics. Whereas all control subjects had a peak plasma ACTH response 30 min after CRH administration, 50% of alcoholics demonstrated a peak plasma ACTH response 60 min after CRH administration, and 50% demonstrated a peak plasma ACTH response 30 min after CRH. To determine if adrenal function was also impaired, alcoholics and controls underwent a standard (250 micrograms) and a submaximal (0.250 micrograms) Cortrosyn stimulation test. Controls demonstrated a significant cortisol response to both standard and low dose Cortrosyn. Although alcoholics had a cortisol response similar to that of controls after the standard dose of Cortrosyn, they did not have a statistically significant rise in cortisol after the submaximal dose of Cortrosyn. Twenty-four-hour urinary free cortisol levels were 2-fold higher in alcoholics compared to controls. In summary, although a subset of alcoholics demonstrated enhanced basal production of cortisol, most alcoholics had a blunted response to acute intervening stress, including CRH, low dose ACTH-(1-24), and metyrapone blockade. These data suggest that alcoholics have ethanol-induced HPA axis injury, resulting in an inappropriately reduced response to nonethanol-induced stress.

Alcohol Drinking↗
PubMed1990

Efficacy and safety of pravastatin in patients with primary hypercholesterolemia. I. A dose-response study.

This multicenter, double-blind, placebo-controlled, dose-response study was conducted in patients with primary hypercholesterolemia to examine the effects of pravastatin, a selective inhibitor of HMG-CoA reductase, on plasma lipids and lipoproteins. A total of 306 patients on cholesterol-lowering diets received twice daily doses of 5 mg, 10 mg, 20 mg pravastatin, or placebo for 12 weeks. Marked reductions in low density lipoprotein (LDL) cholesterol and total cholesterol were observed after 1 week of treatment; maximum lipid-lowering effects occurred at 4 weeks and were sustained for the duration of the trial. At week 12, pravastatin treatment resulted in dose-dependent mean reductions from baseline in LDL cholesterol of 17.5%, 22.9%, and 30.8% for the 3 doses tested (P less than or equal to 0001 compared with baseline and placebo). The reduction in LDL cholesterol was log-linear with respect to dose; each doubling of dose reduced LDL cholesterol an additional 6.5%. Dose-dependent reductions in total cholesterol from 12.9% to 23.3% also occurred (P less than or equal to 0.001). Triglycerides decreased by as 15.4% (P less than or equal to 0.001) and high-density lipoprotein (HDL) cholesterol increased approximately 7% (P less than or equal to 0.01), but these effects were not dose-dependent. No patient receiving pravastatin was discontinued during the 12-week trial. Transient episodes of rash and headache occurred. Slight increases in mean serum levels of ASAT and ALAT occurred, and 2% of both placebo- and pravastatin-treated patients reported myalgia although there was no clinically significant elevation of creatine kinase. These data indicate that pravastatin favorably affects all lipid parameters and is well tolerated.

Anticholesteremic Agents↗
PubMed1989

Regulation of insulin synthesis in an insulin-producing cell line (RINm5F): long-term experiments.

The insulin-producing cell line RINm5F, has been used in short-term experiments to evaluate insulin secretion. We sought to maintain the responsiveness of these cells to stimuli for up to 2 days. We examined the course of new insulin synthesis over this period by measuring at intervals immunoreactive insulin (IRI) in two parts: IRI in the medium (M) and IRI extracted from the cells (C). Control cells were incubated in RPMI 1640/2.8 mM glucose/10% fetal bovine serum/200 micrograms/ml bacitracin (to prevent insulin degradation). The addition of dibutyryl cAMP 10 mM to the experimental dishes significantly increased total (M + C) IRI at 48 hr to 37% above the insulin content of the control dishes (p less than 0.01). Theophylline 10 mM increased total (M + C) IRI by 24% over control (p less than 0.05) after 24 hrs. Glucose, glyceraldehyde, leucine, arginine, glucagon and tolbutamide, other stimulants of insulin production, had no effect. Under the experimental conditions reported here, including the use of bacitracin, IRI synthesis can be studied for up to 48 hr.

Animals↗
PubMed1989

Nutritional management of plasma lipid disorders.

Prevention of vascular disease and acute pancreatitis is the goal of hyperlipidemia treatment. The risk of coronary heart disease (CHD) increases with increasing plasma cholesterol levels because low-density lipoprotein (LDL), the major carrier of cholesterol in the plasma, is atherogenic. High-density lipoprotein (HDL), especially the HDL2 subfraction, protects against CHD. Hypertriglyceridemia, although not an independent risk factor for CHD, is generally accompanied by low HDL cholesterol (HDLch), which may predispose to CHD. Reducing plasma LDL and raising HDL levels are thus goals in preventing CHD. Serum LDL levels may be lowered by reducing saturated fat and cholesterol intake; weight loss may decrease LDL but is more effective in lowering plasma triglycerides and raising HDLch. The percent of total calories from polyunsaturated, monounsaturated, and saturated fats should be less than 10%, up to 10-15%, and less than 10%, respectively. High cholesterol intake increases the flux of cholesterol, which may be harmful to arterial walls, but beyond a certain point does not increase plasma cholesterol levels. Some diets change the composition rather than the level of LDL and apoproteins. Weight reduction and maintenance are the most effective dietary measures to lower plasma triglycerides; omega-3 fatty acids (fish oils) have shown promise in reducing triglyceride but not cholesterol levels. Substitution of starch for sugar lowered triglyceride levels toward normal in hypertriglyceridemia patients. Fasting triglyceride levels rise in all individuals fed high-carbohydrate diets, but the high levels persist in hypertriglyceridemia patients. Weight loss, cessation of cigarette smoking, increased physical activity, good control of diabetes, and moderate alcohol use all raise HDLch levels. Vitamin E deficiency causes neurological sequelae in children with severe malabsorption problems due to abetalipoproteinemia or cholestatic liver disease.

Acute Disease↗
PubMed1988

Endocrine disorders in men infected with human immunodeficiency virus.

Gonadal, adrenal, and thyroid functions were evaluated in 70 men seropositive for human immunodeficiency virus (HIV) infection, clinically categorized as asymptomatic (n = 19), AIDS-related complex (ARC) (n = 9), or acquired immunodeficiency syndrome (AIDS) (n = 42). Twenty of 40 men (50 percent) with AIDS were hypogonadal. Mean serum testosterone concentrations in both ARC (292 +/- 70 ng/dl) and AIDS (401 +/- 30 ng/dl) men were significantly less than in asymptomatic (567 +/- 49 ng/dl) or normal men (608 +/- 121 ng/dl). Of these hypogonadal men, 18 of 24 (75 percent) had hypogonadotropic hypogonadism. Seven of eight hypogonadal men (88 percent) had a normal gonadotropin response to gonadotropin-releasing hormone administration. Hypogonadism correlated with lymphocyte depletion and weight loss. Adrenal cortisol reserve, evaluated by adrenocorticotropin stimulation, was normal in 36 of 39 patients (92 percent) with AIDS. Indices of thyroid function were normal with the exception of one ARC man with a low free thyroxine index. In conclusion, hypogonadism is common in men with HIV infection and may be the first or most sensitive endocrine abnormality.

AIDS-Related Complex↗
PubMed1986

Pedigree analysis of the 5' flanking region of the insulin gene in familial diabetes mellitus.

Non-insulin-dependent diabetes mellitus (NIDDM) has been reported to be associated with an insertion polymorphism in the 5' flanking region of the human insulin gene. We have attempted to examine linkage of this polymorphism to the phenotype of NIDDM by studying multiple pedigrees. We evaluated 142 individuals (120 white, 22 black), 80 of whom were from 7 pedigrees (5 white, 2 black) ranging in size from 4 to 37 members. Of these, 52 subjects had NIDDM, 10 had insulin-dependent diabetes mellitus (IDDM), and 80 were nondiabetics (ND). DNA was extracted from leukocytes and after digestion with Sst 1, and electrophoresis, the DNA was blotted to nitrocellulose filters and hybridized to a alpha 32P-labeled insulin gene probe. Two alleles of 6.0 and 7.6 kb in size were detected, the latter corresponding to the common previously described insertion polymorphism. In these families, the 7.6 kb allele occurred in 32 of 57 ND, 3 of 5 IDDM, and 10 of 18 NIDDM (P = 0.98). When sibships were analyzed the 7.6 kb allele occurred in 6 of 13 ND, 3 of 5 IDDM, and 8 of 12 NIDDM (P = 0.58). In examining 72 unrelated subjects, including 12 spouses from the pedigrees, the 7.6 kb allele was documented in 16 of 36 ND, 1 of 5 IDDM, and 16 of 31 NIDDM (P = 0.59). In these individuals and in the multiple families studied the insertion polymorphism flanking the insulin gene showed Mendelian inheritance and assorted independently of the phenotype of diabetes mellitus.

Adolescent↗
PubMed1985

Diagnosis of human endocrine disorders using recombinant DNA techniques.

In this chapter we have reviewed several present and potential examples of DNA studies of hereditary endocrine disorders of humans. For the former, recombinant DNA studies have provided insights into the location and types of molecular derangements underlying these diseases. The gene alterations detected have in turn explained the aetiology of quantitative or qualitative alterations in the hormone product. The same methods used in these studies should be applicable to determining the aetiology of many other genetic disorders that affect these, as well as other, hormones for which specific DNA probes are or will become available.

Arginine Vasopressin↗
PubMedDate not supplied

Visual and quantitative computerized assessment of disease severity on peripheral angiograms.

PURPOSE: This study was designed to determine and compare the intra- and interobserver variability of visual and computerized assessment of peripheral arterial disease (PAD) severity from lower extremity angiograms, and to correlate quantitative angiographic measures with clinical predictors of PAD. PATIENTS AND METHODS: Peripheral angiograms of 13 segments from the ilio-femoral-popliteal system were evaluated on two separate occasions by nine radiologists and with a quantitative computerized method. In a separate study, images from 18 patients undergoing diagnostic lower extremity angiography were analyzed with use of quantitative angiography and the results were compared with clinical and lipid risk factors. RESULTS: The data demonstrate that computerized assessment of peripheral angiograms is associated with lower intra- and interobserver variability than visual assessment of the same films. Despite this, there was excellent intraobserver and good interobserver agreement on the presence or absence of a severe lesion with visual assessment. Quantitative computerized measures of disease severity correlate with several known predictors of large vessel PAD. CONCLUSION: Computerized assessment of peripheral angiograms may be a useful tool in the clinical and investigational evaluation of PAD.

Aged↗
PubMedDate not supplied

Androgen replacement in the treatment of Klinefelter's syndrome: efficacy and safety of a nonscrotal permeation-enhanced testosterone transdermal system.

OBJECTIVE: To report the efficacy and safety of a permeation-enhanced nonscrotal testosterone transdermal (TTD) system for the treatment of Klinefelter's syndrome. METHODS: Fifteen male patients with Klinefelter's syndrome, including 12 patients who received previous intramuscular (IM) treatment with testosterone esters, were part of the study population from three phase III clinical studies; 13 completed the studies. Patients applied two TTD systems nightly for 6 months or more. Nocturnal erections were assessed by RigiScan monitoring; sexual function was evaluated by using the Watts and Davidson questionnaires. Hypogonadal symptoms were determined by direct patient questioning. RESULTS: Mean morning serum testosterone levels increased to within normal range in all 13 patients (from 5.9 +/- 3.2 nmol/L at hypogonadal baseline to 22.3 +/- 5.6 nmol/L at 6 months). Luteinizing hormone levels decreased to within normal range in six patients and showed clinically significant decreases in four of the other seven patients (from 25 +/- 12 IU/L at hypogonadal baseline to 17 +/- 11 IU/L at 6 months). Nocturnal erections improved significantly during TTD system therapy in comparison with the hypogonadal state. Patient self-reported measures of sexual functioning were comparable to those during prior IM testosterone treatment and better than during the hypogonadal state. Hypogonadal symptoms decreased during TTD therapy in comparison with hypogonadal baseline. No clinically significant changes were noted in prostate volume, prostate-specific antigen, or lipid values. Three patients experienced anxiety or depression during TTD treatment, requiring discontinuation of therapy in one case and use of antidepressants in the other two. CONCLUSION: The testosterone patches were generally well tolerated in all patients. The nonscrotal TTD system for testosterone replacement is a safe and effective treatment for patients with Klinefelter's syndrome.

Journal Article↗
PubMedDate not supplied

Central hypogonadism: distinguishing idiopathic low testosterone from pituitary tumors.

OBJECTIVE: To attempt to determine clinical or hormonal characteristics that could help distinguish benign idiopathic low testosterone (ILT) from pituitary tumor. METHODS: On retrospective review of medical records of patients encountered by Johns Hopkins endocrine staff between 1985 and July 1995, 64 patients who fulfilled our enrollment criteria--27 men with ILT and 37 patients with imaging-proven pituitary tumor--were identified. Men 21 years of age or older needed to have had serum testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin levels measured before hormonal replacement therapy or pituitary tumor extirpation (or both) and a high-quality imaging scan (computed tomography or magnetic resonance imaging) done and interpreted by the Johns Hopkins radiology staff. RESULTS: In comparison with men who had ILT, men with pituitary tumors had similar serum testosterone levels and significantly higher serum levels of LH, FSH, and prolactin. In addition, significantly more men with pituitary tumors had visual field abnormalities, headaches, and symptoms of hypothyroidism in comparison with the men with ILT. In contrast, the group with ILT complained significantly more of impotence, erectile dysfunction, and depression than did the group with pituitary tumors. The age at initial assessment was comparable in both study groups. CONCLUSION: Although age at initial manifestation did not predict the presence of pituitary tumor, the group of men with tumors were more likely than those with ILT to have serum testosterone levels <150 ng/dL, higher serum gonadotropin and prolactin levels, and visual field abnormalities and less likely to have sexual dysfunction. Therefore, on the basis of our data, we recommend that men with these findings should be referred for a magnetic resonance image to exclude the presence of a tumor.

Journal Article↗
PubMedDate not supplied

Treatment of hyperlipidemia in women.

Coronary artery disease (CAD) is the most common cause of death in the United States. It is responsible for the deaths of 480,000 people annually. Half of these fatalities are in women. More women die of CAD than due to all cancers combined. The clinical presentation of women with CAD can be very subtle, and atypical as compared to men. Furthermore, women also face a worse prognosis than men following surgical therapy for CAD. Hyperlipidemia is a well-known risk factor for CAD in women, particularly elevated triglycerides and low HDL cholesterol levels. Although estrogen replacement therapy has been considered a primary modality to alleviate some cardiovascular risk in post menopausal women, the results of the recently published HERS trial highlight the need for more research in this field.

Adult↗