The management of abnormal uterine bleeding.
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Adult↗
Biomedical subjects
R M Weiss
Publications and source records attributed to R M Weiss.
Evidence for the presence of regional differences in the calcium antagonist receptors in lower urinary tract smooth muscle.
(+)-[3H]PN 200-100 (a dihydropyridine calcium channel antagonist) was utilized to characterize calcium channel binding sites in rabbit bladder dome, bladder base, and urethra. Specific binding of (+)-[3H]PN 200-110 to membrane particulates was saturable, reversible, linear to protein concentration, and of high affinity. The density of (+)-[3H]PN 200-110 binding sites (Bmax values in fmol/mg of protein) and the affinity constants for (+)-[3H]PN 200-110 (KD value in pM) in urethra, bladder dome and bladder base were 64.1 +/- 7.8 and 179 +/- 31; 21.9 +/- 3.0 and 213 +/- 36; and 18.8 +/- 4.2 and 140 +/- 28, respectively. Agonists and antagonists inhibited (+)-[3H]PN 200-110 binding with Ki values in the following rank order: nitrendipine less than nifedipine less than niguldipine much less than Bay K 8644 much less than verapamil. Although carbachol-induced contractile responses were 20-30 times smaller in muscle strips from urethra than from bladder base or bladder dome, KCl-induced contractions were only 3-4 times smaller in urethra than in bladder tissues. Nifedipine inhibited carbachol-induced contractions in urethra, bladder dome, and bladder base by 76%, 64%, and 60%, respectively, and completely inhibited KCl-induced contractions in all three tissues. IC50 values for nifedipine inhibition of both carbachol- and KCl-induced contractions were significantly smaller in urethra than in bladder base or bladder dome. Nitrendipine, niguldipine and verapamil inhibited urethral contractions induced by carbachol and KCl to the same degree as did nifedipine. The IC50 values, obtained from functional studies, for calcium channel antagonists were in good agreement with Ki values obtained from binding studies.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Effect of insulin and dietary myoinositol on muscarinic receptor alterations in diabetic rat bladder.
Previous studies from our laboratory demonstrated that there is an up-regulation of muscarinic receptor density in the bladder dome of the 8-wks diabetic rat compared to control. To determine whether the changes observed in receptor density can be corrected by insulin or dietary myoinositol, five groups of rats were maintained for eight weeks: control (C), diabetic (D), diabetic insulin-treated (DI), diabetic myoinositol-treated (DMI), and control myoinositol-treated (CMI). Diabetes was induced by i.v. injection of 65 mg./kg. of streptozotocin. D and DMI animals were smaller, had higher serum glucose and lower serum insulin levels, higher water intakes and urine outputs, and larger bladder domes than the other groups. The density of the muscarinic receptors measured by radioligand receptor binding assays using [3H]quinuclidinyl benzilate were (in fmol./mg. protein): C, 88 +/- 13; D, 176 +/- 19; DI, 94 +/- 5; DMI, 158 +/- 8; CMI, 112 +/- 10. These data indicate that insulin, but not myoinositol treatment normalized diabetes induced abnormalities observed in the general features of streptozotocin-injected rats and prevented the diabetic-induced upregulation of bladder dome muscarinic receptors.
Animals↗
Analysis of serum human chorionic gonadotrophin levels in normal singleton, multiple and abnormal pregnancies.
Some researchers claim that first trimester beta-human chorionic gonadotrophin (beta HCG) levels have a constant doubling time; others suggest doubling time increases as pregnancy progresses. This study was designed to settle the debate by analysing a large series of serial serum beta HCG determinations from 143 pregnant women whose day of ovulation was precisely determined. Regression analysis was used to evaluate linear and quadratic models for the relationship of HCG with time in normal pregnancies. Doubling times were calculated for three time periods: 10-20 days post-ovulation (period 1); 21-30 days post-ovulation (period 2); greater than 30 days post-ovulation (period 3). Analysis of variance was used to compare the mean doubling time by time period and type of pregnancy (single, multiple, spontaneous abortion and ectopic). The analysis showed that a quadratic model best described the pattern of HCG rise in early normal pregnancy. Furthermore, for normal pregnancies, the mean doubling time increased significantly with advancing gestational age between time periods 1 and 2 and between periods 2 and 3. The mean doubling time was the same for single and multiple pregnancies. The doubling time was prolonged with ectopic pregnancy in period 1; and for aborters reaching ultrasound at 8 weeks, the doubling time was normal in period 1 but prolonged in period 2. Careful observation of the doubling time may aid clinicians in the detection of abnormal pregnancies.
Abortion, Spontaneous↗
Age-related changes in calcium antagonist receptors in rabbit ureter.
(+)-[3H]PN 200-110 (a dihydropyridine calcium channel antagonist) binding sites were studied in ureters of 1-day (neonatal), 6-week (premature), 6-month (young) and 4.5- to 5-year (old) female rabbits. Specific binding of (+)-[3H]PN 200-110 to ureteral membrane particulates was saturable, reversible and of high affinity. The densities (Bmax) of (+)-[3H]PN 200-110 binding sites were 46.7 +/- 2.5, 22.6 +/- 2.0, 12.7 +/- 1.8 and 11.9 +/- 1.6 fmol/mg protein in 1-day, 6-week, 6-month and 4.5- to 5-year rabbit ureters, respectively. The affinity constants (KD) of the binding sites for (+)-[3H]PN 200-110 were similar in all groups. Calcium agonists and antagonists inhibited (+)-[3H]PN 200-110 binding to 1-day and 6-week rabbit ureters with the following rank order of Ki values: nitrendipine < nifedipine < BAY K 8644 < verapamil. There were no significant differences in Ki values between the neonatal and premature groups. The data demonstrate the presence of an age-related down-regulation of (+)-[3H]PN 200-110 binding sites in rabbit ureteral membrane particulates.
Aging↗
Muscarinic receptors in diabetic rat prostate.
To investigate the effects of experimentally-induced diabetes on prostatic muscarinic cholinergic receptors, the binding characteristics of [3H]quinuclidinyl benzilate ([3H]QNB) to prostatic membrane particulates were examined in four groups of rats: control, diabetic, diabetic insulin treated, and diabetic myo-inositol treated. Diabetes was induced by i.v. injection of streptozotocin (STZ), 65 mg/kg. Diabetic and diabetic myo-inositol-treated rats had hyperglycemia, hypoinsulinemia, glucosuria, polydipsia, and polyuria as well as significantly smaller prostates and lower body weights compared to control and diabetic insulin-treated animals. The densities of muscarinic receptors (Bmax) as determined by saturation studies with [3H]QNB in the prostatic plasma membranes of control, diabetic, diabetic insulin-treated and diabetic myo-inositol-treated rats were 80 +/- 8, 51 +/- 5, 78 +/- 3, and 47 +/- 7 fmol/mg of protein, respectively. [3H]QNB binding to muscarinic receptors was inhibited by muscarinic antagonists with the following rank order of Ki values: atropine much less than pirenzepine less than AF-DX 116. The pharmacological profile of the muscarinic receptors was similar in all groups examined and was consistent with the predominance of the M3 muscarinic receptor subtype in prostatic membrane particulates. Our data indicate that STZ-induced diabetes caused a variety of abnormalities including a down-regulation in the density of M3 muscarinic receptors in the rat prostate and that insulin, but not myo-inositol could prevent the development of these abnormalities.
Animals↗
Pigmented lesions in a patient with pulmonary tuberculosis. Pityriasis rotunda.
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Female↗
Beta adrenergic receptor alterations in diabetic rat prostate: effects of insulin and dietary myoinositol.
As sexual dysfunction is a well-recognized manifestation of diabetes mellitus and as the function of the prostate, a major accessory organ in the male reproductive system, is regulated by the autonomic nervous system, we studied beta adrenergic receptors in the prostate of streptozotocin-induced diabetic rats, using radioligand receptor binding techniques. Four groups of rats were maintained for 8 weeks: controls, diabetics, insulin-treated diabetics, and myoinisitol-treated diabetics. The diabetic and myoinisitol-treated diabetic animals were smaller, had higher blood glucose levels, higher water intake and urine output, smaller prostates, and lower serum insulin levels than the other groups. Saturation experiments with [3H]dihydroalprenolol showed that the induction of diabetes decreased the density of beta adrenergic receptors in prostatic membrane particulates. Inhibition studies with selective beta adrenergic antagonists demonstrated that these receptors were of the beta 2 subtype. Furthermore, insulin but not myoinositol treatment normalized blood glucose and insulin levels, maintained normal prostate and body weight-gain, and prevented the decrease in the density, i.e., down-regulation, of the prostatic beta adrenergic receptors.
Adrenergic beta-Antagonists↗
NG-nitro-L-arginine inhibits non-adrenergic, non-cholinergic relaxation in rabbit urethral smooth muscle.
Electrical field stimulation induced a relaxation response in female rabbit urethral smooth muscle strips precontracted with phenylephrine. The relaxation response was inhibited by tetrodotoxin, but not by atropine, propranolol, or hexamethonium. The relaxation response thus results from stimulation of inhibitory non-adrenergic, non-cholinergic nerves. The electrically induced relaxation response was inhibited by an inhibitor of nitric oxide biosynthesis, NG-nitro-L-arginine. This inhibition was overcome by addition of a precursor of nitric oxide, L-arginine. An inhibitor of soluble guanylate cyclase, methylene blue, reduced the relaxation response, and a selective cyclic GMP phosphodiesterase inhibitor, M & B 22948, potentiated the relaxation response. These data indicate that agents which affect the biosynthesis of nitric oxide are associated with the urethral relaxation response evoked by electrical field stimulation, and that cyclic GMP may mediate the relaxation response.
Adrenergic Fibers↗
Differential regulation of bladder beta-adrenergic and muscarinic cholinergic receptors in experimental diabetes.
To determine the contribution of diuresis-induced bladder hypertrophy, which accompanies the diabetic state, on the biochemical and functional alterations observed in the diabetic bladder, we compared three experimental groups: 8-wk streptozocin (STZ)-induced diabetic rats, 8-wk sucrose-fed diuretic rats, and age-matched controls. Diabetic and sucrose-fed rats had higher water intake, higher urine output, and larger bladders than controls. Diabetic rats had lower serum insulin levels, lower body weights, and higher serum glucose levels than either control or sucrose-fed animals. Receptor binding studies with [3H]quinuclidinyl benzilate in bladder dome demonstrated an upregulation of muscarinic receptors in diabetic and sucrose-fed rats compared with controls. Parallel binding studies with [3H]dihydroalprenolol and [125I]iodopindolol showed an upregulation of beta-adrenergic receptors in diabetic but not in sucrose-fed bladder domes. Carbachol induced larger contractile responses in diabetic and sucrose-fed than in control bladder dome muscle strips. isoproterenol relaxed KCl-contracted detrusor strips from both diabetic and sucrose-fed rats to a greater degree and with a higher affinity than detrusor strips from controls. Our data show that overdistension and increased workload per se contributed to the upregulation of muscarinic but not to the upregulation of beta-adrenergic receptors in STZ-induced diabetes. Furthermore, the magnitude of carbachol-induced contractions correlated with muscarinic receptor upregulation, whereas the magnitude of isoproterenol-induced relaxation did not correlate with changes in the density of the beta-adrenergic receptors. Thus, it appears that different regulatory mechanisms are involved in diabetes-induced alterations in muscarinic and beta-adrenergic receptors in bladder dome.
Animals↗
Pharmacological characterization of alpha adrenergic receptors in the young and old female rabbit urethra.
The pharmacological characteristics of alpha-1 and alpha-2 adrenergic receptors in young (6 month) and old (4.5-5 year) female rabbit urethra were studied using isolated muscle bath techniques. Norepinephrine, phenylephrine, clonidine, oxymetazoline and UK 14,304 produced concentration-dependent contractions in both age groups. The maximum contractile responses (Emax) to norepinephrine, phenylephrine, oxymetazoline and UK 14,304 were of similar magnitude and were significantly greater than the contractile responses to clonidine. The rank order of the ED50 values for these drugs was: oxymetazoline less than UK 14,304 much less than clonidine = norepinephrine = phenylephrine. Prazosin (10(-8) M) shifted the concentration-response curves to phenylephrine and UK 14,304 to the right, but did not shift the concentration-response curves to clonidine and oxymetazoline. Yohimbine (10(-7) M) shifted the concentration-response curves to clonidine, oxymetazoline and UK 14,304 to the right, but did not shift the concentration-response curve to phenylephrine. The ED50 values for phenylephrine and clonidine were smaller in the older than in the younger age group. There were no other age-dependent differences in the response to agonists. Pretreatment with chlorethylclonidine, which selectively alkylates the alpha-1B subtype, did not affect the Emax value of phenylephrine-induced contractions, but significantly shifted the curve to the right. The ratios of the Emax values in Ca++ free buffer to that in normal Ca++ buffer for phenylephrine, UK 14,304, clonidine, oxymetazoline and KCl were 0.30, 0.38, 0.08, 0.07 and 0, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic alpha-Agonists↗
Ultrafast computed tomography in cardiac imaging: a review.
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Coronary Artery Bypass↗
Malignant rhabdoid tumor of the kidney in an adult.
We report a case of rhabdoid tumor of the kidney in a 32-year-old white woman. This highly malignant tumor has been reported previously only in the pediatric age group. The clinical and pathological findings are discussed, and the literature is reviewed.
Adult↗
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↗
Age-dependent alterations in beta-adrenergic receptor function in guinea pig ureter.
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Aging↗
Clinicopathological conference. Hypo-osmotic encephalopathy following renal arteriogram.
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Adenocarcinoma↗
Ultrasound evaluation of bladder calculi.
A case is presented in which the identification of intravesical calculi by ultrasound was an aid in management. Bladder stones appear as high intensity echoes within the bladder, have an associated acoustic shadow and shift to the dependent portion of the bladder with alterations in position. Ultrasound provides a rapid, safe imaging technique to diagnose or verify the presence of bladder calculi.
Child, Preschool↗
Results of biopsy after early stage prostatic cancer treatment by implantation of 125I seeds.
We have treated 77 patients for clinically early stage carcinoma of the prostate, 9 stage A2, 63 stage B and 5 stage C, with direct implantation of 125I seeds into the prostate and pelvic lymphadenectomy. It is estimated that a minimum dose of 15,000 rad but a maximum dose of 35,000 rad is delivered to the prostate over several months. Of the 77 patients 14 (18 per cent) had metastatic disease in the pelvic lymph nodes. In 22 cases perineal needle biopsy was done 12 to 18 months after treatment and in 3 cases a second biopsy was performed after 2 to 3 years. Persistent tumor was present in 11 biopsies. Cytological changes were observed in 8 of these, primarily cytoplasmic vacuolation and nuclear pyknosis. There seemed to be no relationship between grade and stage of disease and histological evidence of persistence of tumor after radiation. One patient with persistent tumor in the postoperative biopsy has shown progression of disease after 2 years and another with a negative biopsy has a bony metastasis. The remaining 10 patients with persistent tumor have shown no sign of progression of disease during a 2 to 4-year interval.
Biopsy, Needle↗