Search PubMed⌕ Search

Biomedical subjects

R M Weiss

Publications and source records attributed to R M Weiss.

At least 109 records · Page 6Linked to original sources

Variable expression of 5 alpha-reductase deficiency: presentation with male phenotype in a child of Greek origin.

A male infant with perineal hypospadias and a small phallus bound in chordee is described. Biochemical investigation at age 9 months after hCG stimulation revealed a testosterone to dihydrotestosterone (DHT) ratio of 40, a markedly elevated value suggestive of deficient steroid 5 alpha-reductase activity. The diagnosis of 5 alpha-reductase deficiency was confirmed by elevated urinary 5 beta/5 alpha-steroid metabolite ratios and demonstration of defective 5 alpha-reductase activity in cultured fibroblasts from the patient's scrotum and foreskin. Application of DHT cream to the patient's abdomen raised circulating levels of DHT to the adult male range. Two courses of DHT given nightly for 3 and 4 months resulted in phallic enlargement. Surgical release of the chordee and hypospadias repair have resulted in normal male appearance of the genitalia. This case illustrates the heterogeneity of the 5 alpha-reductase deficiency phenotype.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Autonomic receptors in urinary tract: sex and age differences.

As age and sex affect the function of the lower urinary tract, we studied the characteristics of adrenergic and cholinergic receptors in various parts of lower urinary tract smooth muscle of young (6 months) and old (4 1/2-5 years) male and female rabbits. Saturation experiments performed with [3H]prazosin, [3H]yohimbine, [3H]dihydroalprenolol and [3H]quinuclidinyl benzylate in rabbit bladder base, bladder dome and urethra indicate the presence of regional, sex- and age-related differences in the density of alpha-1, alpha-2, and beta adrenergic and muscarinic cholinergic receptors. Alpha-2 adrenergic receptor density is considerably higher in the female than in the male urethra of both age groups, whereas the higher density of beta adrenergic receptors in the female than in the male bladder base is observed only in the younger animals. The density of muscarinic receptors is higher in bladder dome than in bladder base or urethra in young rabbits of both sexes. In the old animals, the density of muscarinic receptors in bladder base increases to the level observed in bladder dome. Inhibition experiments with selective adrenergic agonists and antagonists indicate that the pharmacological profiles of alpha-2 adrenergic receptors in the urethra and beta adrenergic receptors in the bladder dome and bladder base are similar in both sexes and at both ages. Beta-2 adrenergic receptors are shown to be predominant in bladder base and bladder dome of rabbits. Parallel studies in rabbit urethra, adult rat cortex and neonatal rat lung show that the urethral alpha-2 adrenergic receptors are of the alpha-2A subtype.

Aging↗

Changes in lipid composition and isoproterenol- and ethanol-stimulated adenylate cyclase activity in aging Fischer rat bladders.

In the aging rat bladder dome, changes are noted in membrane composition and in the activity of the membrane-bound enzyme, adenylate cyclase (AC). When bladder domes from 22 day and 22 to 24 month Fischer rats are compared, changes in composition include: a 25% decrease in percentage of protein [(milligrams of protein per milligram of wet weight) x 100]; an approximately 40% decrease in both the total phospholipid content and in the content of the major phospholipids, phosphatidylcholine and phosphatidylethanolamine; and a 69% increase in the cholesterol to phospholipid ratio. These changes are indicative of a more rigid lipid bilayer in the aged rat bladder. Changes in AC with aging include a decrease in basal and forskolin-activated AC and a loss of the ability of isoproterenol to activate AC in the aged (22-24 month) rat bladder dome homogenate. Activation by isoproterenol (ISO; 3 microM) is 55 and 72% over 5' guanylimidodiphosphate [Gpp(NH)p; 1 microM] controls in 22 day and 90 day rat bladder dome homogenates, respectively. Activation by AC by NaF and Gpp(NH)p does not decline with aging. Ethanol, an agent that increases membrane fluidity, stimulates AC to a much greater extent in homogenates from the 22 month than from the 22 day or 90 day rat bladder dome. The ethanol-induced activation occurs not only in basal AC but also in Gpp(NH)p- and ISO-plus Gpp(NH)p-activated AC. The observed changes in AC with aging in part may reflect changes in the membrane lipid environment.

Adenylyl Cyclases↗

Ultrafast computed tomography in the diagnosis of cardiac disease.

Ultrafast computer tomography (CT) is one of the major new imaging modalities that has become available for the evaluation of patients with heart disease. With cine CT it is possible to obtain high resolution images of the heart at 58-ms intervals. The inplane resolution is 0.7 to 1.5 mm, and the slice thickness is 3 to 9 mm. Images require the intravenous injection of nonionic contrast agents to obtain quantitative information about cardiac function. Cine CT has thus far been used in 3 general areas that relate to the evaluation of patients with heart disease: evaluation of cardiac structure and function, evaluation of vein bypass graft patency and flow reserve, and measurements of regional myocardial perfusion. Because of the outstanding spatial resolution of the images, it is possible to obtain very precise information about cardiac structure and function. The weight of the left ventricle and right ventricular walls can be measured to +/- 5%, and the stroke volumes and end-diastolic volumes of all 4 cardiac chambers can also be measured with an accuracy of +/- 5%. With this technology it is possible to determine the magnitude of aortic regurgitation within +/- 5 to 8%. This modality has also proved useful in the diagnosis of surgically resectable left ventricular aneurysm and a multitude of other cardiac disorders that involve abnormalities in cardiac structure, including congenital heart defects, aortic aneurysms and constrictive pericarditis. These diagnostic procedures use the peripheral injection of usually about 100 ml of contrast media and can ordinarily be completed in less than 15 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Angiography↗

Usefulness of myocardial ischemia as predictor of training effect in cardiac rehabilitation after acute myocardial infarction or coronary artery bypass grafting.

Exercise capacity increases to a variable degree in coronary patients during cardiac rehabilitation. The effect of baseline exercise-induced ischemia on the response to a 12-week conditioning program was evaluated in 106 coronary patients. The magnitude of exercise conditioning response was greater in nonischemic patients than in ischemic patients, with maximal exercise intensity increasing 69 versus 50% (7.2 to 12.1 vs 7.1 to 10.6 METs) (p less than 0.05) and maximal oxygen consumption increasing 28 versus 10% (23.1 to 29.6 vs 23.0 to 25.4 cc/kg/min) (p less than 0.05). Markers of conditioning during submaximal exercise such as heart rate and heart rate-systolic blood pressure product were similarly reduced in both groups. The groups did not differ by age, diagnosis, resting ejection fraction, incidence of beta-blocker use, maximal exercise capacity, maximal exercise heart rate, blood pressure or intensity of actual exercise training. These results suggest that exercise-induced ischemia alters the stimulus to adapt to exercise training.

Angina Pectoris↗

Acute effects of doxorubicin on human left ventricular systolic and diastolic function.

Although the long-term cardiotoxic effects of cumulative doses of doxorubicin are well established, the short-term effects on cardiac function are uncertain. Therefore we examined the short-term effects of doxorubicin on left ventricular systolic and diastolic function following a total of 56 doses of doxorubicin in 15 patients with normal resting left ventricular function. Resting radionuclide ventriculography was performed 1 hour before and 4 hours after each dose of doxorubicin. Left ventricular ejection fraction increased significantly from 64 +/- 1% to 67 +/- 1% (p less than 0.001) after doxorubicin. In addition, peak ejection rate (p less than 0.005) and peak filling rate (p less than 0.0005) increased significantly following short-term doxorubicin administration. There was no relationship between either the individual or cumulative dose of doxorubicin and the acute ejection fraction, peak ejection rate, or peak filling rate response. Our data suggest that doxorubicin acutely increases left ventricular systolic and diastolic function.

Adult↗

Patterns of regional diastolic function in the normal human left ventricle: an ultrafast computed tomographic study.

The detailed evaluation of regional diastolic filling at multiple ventricular levels in the normal human left ventricle has not previously been reported. Ultrafast computed tomography was used to characterize global and regional early diastolic filling in the left ventricle of 11 normal male volunteers. Regional early diastolic filling data from six distinct ventricular levels (apex to base) were fit to a third-order polynomial curve, and the peak rate of diastolic filling and time of peak filling were determined. Peak filling rate was 259 +/- 17 ml/s (+/- SEM) as a global average, where peak filling rate referenced to end-diastolic volume and stroke volume across the levels examined was 3.78 +/- 0.17 s-1 and 4.83 +/- 0.20 s-1, respectively. Average filling fraction was 39 +/- 1%, and time to peak filling from end-systole was 145 +/- 5 ms. Regional (tomographic) peak filling rates, except for the most apical level examined, were not statistically different across the ventricle. Filling fraction and time to peak filling were remarkably constant from one level to another. However, reference of regional peak filling rate to regional end-diastolic volume demonstrated significant nonuniformity from apex (120% of average for all levels) to base (87% of average for all levels). Peak filling rate referenced to tomographic stroke volume was less variable and not statistically different across the ventricle as a whole.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The characterization of beta-adrenergic receptor subtypes of the upper and lower renal pelvis in rabbits.

We characterized the beta-adrenergic receptors in the upper (pacemaker) and lower (nonpacemaker) regions of the rabbit renal pelvis, using radioligand binding techniques. [3H]Dihydroalprenolol was the ligand used for determining the total density of beta-adrenergic receptors. The beta-1 and beta-2 subtypes of beta-adrenergic receptors were defined by inhibition of [3H]DHA binding by ICI 89,406, a beta-1 selective antagonist, and ICI 118,551, a beta-2 selective antagonist. Saturation studies with [3H]DHA showed that there was no significant difference in the equilibrium dissociation constant, KD, and the maximum number of binding sites Bmax, between the upper and lower renal pelvis. Although the inhibition constants of ICI 118,551 were smaller than those of ICI 89,406 in both the upper and lower pelvis, indicating a predominance of beta-2 receptors in both regions, the Ki values of ICI 118,551 were significantly greater in the upper than in lower pelvis. These data suggest that there are significant amounts of beta-adrenergic receptors in the rabbit renal pelvis without regional differences in the total density of beta receptors and that there is a greater proportion of beta-2 subtypes in the lower than in the upper renal pelvis.

Adrenergic beta-Antagonists↗

Characterization of autonomic receptors in neonatal urinary tract smooth muscle.

In the 1-day-old rabbit there are a large number of alpha-2- (labeled with [3H]yohimbine) than alpha-1- (labeled with [3H]prazosin) adrenergic receptors in the various parts of urinary tract smooth muscle, but the alpha-1 receptors are functionally more responsive to agonists than are the alpha-2 receptors. Unlike the findings in the adult rabbit, the neonatal bladder dome is functionally more sensitive to alpha-adrenergic agonists than the neonatal bladder base. The rank order of beta-adrenergic receptor densities (labeled with [3H]dihydroalprenolol) in various urinary tract smooth muscles correlates with the magnitude of the relaxant response to isoproterenol. There is a high number of functional muscarinic receptors (labeled with [3H]quinuclidinyl benzylate) in the neonatal urinary tract. The data demonstrate the existence of functional autonomic receptors in neonatal urinary tract smooth muscle.

Adrenergic Agonists↗

Effects of experimental diabetes on biochemical and functional characteristics of bladder muscarinic receptors.

Bladder dysfunction is a common complication of diabetes mellitus and is attributed in part to peripheral neuropathy. We investigated the effects of experimental diabetes on muscarinic receptors in rat bladder smooth muscle, 2, 4 and 8 weeks after i.v. injection of 65 mg/kg of streptozotocin. At all time points, diabetic animals had a lower body weight, higher serum glucose levels and reduced serum insulin levels than age-matched controls. Diabetic animals had a markedly increased urine output and significant enlargement of the bladder dome. The amount of muscarinic receptor labeled with [3H]quinuclidinyl benzylate (QNB) was higher in the bladder dome of diabetic animals than control animals, whereas the affinity of the labeled antagonist for its binding sites was similar in both groups. Muscarinic agonists and antagonists inhibited [3H]QNB binding with similar inhibitory constants (Ki) in control and diabetic dome. The rank order of Ki values in inhibition of [3H]QNB binding by muscarinic agonists and antagonists: atropine less than acetylcholine less than carbachol less than AF-DX 116 = pirenzepine less than bethanechol, is consistent with the presence of M2 muscarinic receptors in the bladder dome. In functional studies, muscarinic agonists induced a larger contractile response in bladder dome muscle strips from 8-week-diabetic animals than from controls. ED50 values were similar in control and treated groups, with the rank order of ED50 values being in good agreement with the Ki values obtained from receptor binding studies, i.e., acetylcholine less than carbachol less than bethanechol. These data show a direct correlation between the diabetes-induced biochemical and functional alterations in muscarinic receptor properties of rat bladder.

Animals↗

Epididymal and vas deferens immaturity in cryptorchidism.

Cryptorchidism is associated with impaired spermatogenesis and, at times, sterility. Early orchiopexy has been advocated as a possible means to prevent spermatogenic impairment and infertility in patients with cryptorchidism. This retrospective study is derived from data obtained from 74 cases that were observed during a period of approximately 10 years at our hospital. Particular attention was devoted to epididymal and vas deferens histological status. Of the 47 epididymides and vas deferens examined only 2 epididymides and 2 vas deferens showed histological maturity. The remainder showed varying degrees of immaturity that additionally correlated, when testicular tissue was available, with the presence of unfavorable testicular histological findings. Cryptorchidism is associated with changes in the gonads and spermatic duct system.

Adolescent↗

Ontogeny of cyclic AMP and cyclic GMP phosphodiesterase activities and of calmodulin levels in guinea pig ureter.

Cyclic AMP and cyclic GMP phosphodiesterase (PDE) activities and calmodulin levels were determined in ureters from guinea pigs of the following ages: 50 and 56 days fetuses, three, 10, 21, 50, and 90 days, and three years old. While there is little change in ureteral cyclic AMP-PDE with age, cyclic GMP-PDE increases with age. Activity of cyclic GMP-PDE in supernatants prepared from three-year-old guinea pig ureter homogenates is 462% and 216% higher than that from 50-day fetus and three-day animals, respectively. Calmodulin levels have a bimodal distribution with age; values are highest in supernatants from 10 and 21 day ureters, but also increase in the three-year ureters when compared to 50 and 90-day values.

3',5'-Cyclic-AMP Phosphodiesterases↗

Nonpalpable testes in young boys: evaluation with MR imaging.

A prospective evaluation of magnetic resonance (MR) imaging for localization of a nonpalpable testis was performed in 24 boys aged 11 months to 6 years. Definitive surgical follow-up was obtained for 15 nonpalpable testes in 14 patients who form the basis of this study. MR imaging correctly indicated the unilateral absence of a testis in six of seven patients prospectively and all seven patients retrospectively. Surgically localized undescended testes were identified with MR imaging in five of eight cases prospectively and seven of eight cases retrospectively. Like scrotal testes, undescended testes were hypointense to fat on sequences with a short repetition time (TR) and echo time (TE) in all cases, and hyperintense or isointense to fat on long TR/TE sequences in all but two cases. Inguinal testes were located along the course of a linear low-signal-intensity structure that extended to the scrotum, which may represent the remnant of the gubernaculum testis. A low-signal-intensity band through the testis, presumably the mediastinum testis, was seen in five of the undescended testes. Although MR imaging can often be used to localize a nonpalpable testis, currently MR is not sensitive enough to allow complete exclusion of the diagnosis of an undescended testis; thus failure to localize a testis with MR imaging should not defer laparoscopy or surgical exploration when indicated.

Child, Preschool↗

Insulin activation of cyclic AMP phosphodiesterase in intact ureteral segments.

Low doses of insulin (0.1-50 nM) when presented to intact ureteral segments increase cyclic AMP (cAMP) phosphodiesterase (PDE) activity in subsequently isolated supernatant and particulate fractions. The stimulation of cAMP PDE occurs within 5 to 10 min of the introduction of insulin. When cyclic GMP or high concentrations of cAMP (greater than 5 microM) are used as substrate, insulin does not increase PDE activity. Although the insulin-increased cAMP PDE exhibits the same sensitivity as control PDE from untreated preparations to isobutylmethyl xanthine, a nonspecific PDE inhibitor, and M & B 22,948, a relatively selective cyclic GMP PDE inhibitor, differences in the degree of inhibition of PDE activity are seen in the insulin-treated and untreated preparations with the low Km cAMP PDE inhibitors Ro20-1724, rolipram, amrinone and milrinone and with cyclic GMP. Pertussis toxin, which modifies GTP regulatory proteins of the adenylate cyclase enzyme and the photoreceptor PDE, blocks cAMP PDE activation by insulin.

3',5'-Cyclic-AMP Phosphodiesterases↗