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Biomedical subjects

E Shapiro

Publications and source records attributed to E Shapiro.

At least 163 records · Page 9Linked to original sources
PubMed1989

Comparison of muscarinic cholinergic and alpha adrenergic receptors in canine ileum, colon, intestinal urinary reservoirs and bladder.

The muscarinic cholinergic (MCh) and alpha 2 adrenergic receptor densities in canine ileum, colon, ileal and colonic urinary reservoirs and bladder were determined using radioligand receptor binding methods in order to provide a rational basis for pharmacologic management of urinary incontinence following bladder replacement with intestinal segments. Muscarinic cholinergic and alpha 2 adrenergic receptor binding sites were studied in these tissues using saturation experiments with 3H-NMS and 3H-rauwolscine, respectively. The mean equilibrium dissociation constants for 3H-NMS binding (0.13 to 0.17 nM) in these tissues were similar (p greater than 0.05) indicating homogeneity of muscarinic cholinergic binding sites. The mean equilibrium dissociation constants for 3H-rauwolscine binding (1.27 to 1.98 nM) in these tissues were also similar (p greater than 0.05). A substantial density of MCh (1.06 to 1.22 fmol/mg. wet wt.) and alpha 2 adrenergic (0.47 to 1.11 fmol/mg. wet wt.) binding sites was identified in the intestinal tissues assayed. The density of ileal and colonic MCh and alpha 2 adrenergic binding sites was not altered following construction of urinary intestinal reservoirs. The presence of a substantial density of MCh and alpha 2 adrenergic binding sites in the intestinal tissues suggests that MCh and alpha 2 adrenergic analogs may be utilized for the management of urinary incontinence following bladder replacement with intestinal urinary reservoirs.

Animals↗
PubMed1989

Muscarinic cholinergic receptors in normal pediatric and myelodysplastic bladders.

Radioligand receptor binding experiments and in vitro muscle contractile studies were performed to determine the binding and functional properties of detrusor muscarinic cholinergic receptors in control and myelodysplastic bladders. Control bladder tissue was obtained from 8 children with primary vesicoureteral reflux undergoing ureteral reimplantation and 1 child at the time of organ transplant harvesting. Bladder specimens also were obtained from 10 children with myelomeningocele undergoing augmentation cystoplasty. Preoperative cystograms revealed that all children with vesicoureteral reflux had a smooth-walled bladder with normal capacity, whereas those with myelomeningocele undergoing augmentation cystoplasty had a small capacity bladder with trabeculations. Experiments were performed on detrusor tissue obtained from the bladder body in all cases. Radioligand receptor binding experiments with the 3H-N-methylscopolamine revealed that the equilibrium dissociation constant in control and myelodysplastic bladders was 0.44 +/- 0.09 and 0.40 +/- 0.10 nM., respectively. The equilibrium dissociation constant was similar in control and myelodysplastic bladders. The muscarinic cholinergic receptor density (Bmax) in control and myelodysplastic bladders was 0.66 +/- 0.12 and 0.24 +/- 0.03 fmol. per micrograms, protein, respectively. The significantly lower density of muscarinic cholinergic receptors in the myelodysplastic bladders may be explained by either a down regulations or by the histologically observed development of fibrosis. Concentration response experiments were performed on 7 control and 6 myelodysplastic bladders using carbachol and potassium chloride. The carbachol and potassium chloride concentrations producing half of the maximal response were similar in the control and myelodysplastic bladders, suggesting that detrusor dysfunction in myelodysplasia is not associated with detrusor supersensitivity. The maximal response (Emax) for potassium chloride was less in the myelodysplastic bladders than in the control bladders but the carbachol Emax was not significantly different. Concentration inhibitory experiments with oxybutynin and imipramine demonstrated that the myelodysplastic and control bladders were identically inhibited by these antagonists. Radioligand receptor binding studies and in vitro contractile experiments indicate that the detrusor dysfunction associated with myelomeningocele is not mediated by changes in the binding or functional properties of detrusor muscarinic cholinergic receptors.

Child↗
PubMed1989

Prenatal fetal adrenal suppression following in utero diagnosis of congenital adrenal hyperplasia.

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency can result in marked virilization of the external genitalia of affected female subjects. Theoretically, suppression of the fetal pituitary-adrenal axis with glucocorticoid during gestational weeks 9 to 17 should prevent the development of ambiguous genitalia in the female fetus. Prenatal diagnosis of congenital adrenal hyperplasia can be made on elevated amniotic fluid 17-hydroxyprogesterone and adrenal androgen concentrations, and HLA typing of cultured amniotic fluid cells. However, these tests cannot be completed before 16 to 17 weeks of gestation, and maternal therapy would have to be instituted before the exact genetic status of the fetus is known. Chorionic villus sampling during the first trimester provides an alternative to second trimester diagnosis in patients who are at risk for bearing offspring with congenital adrenal hyperplasia. We report the use of dexamethasone suppression at 8 weeks of gestation in a 34-year-old woman whose son had congenital adrenal hyperplasia due to severe salt-losing 21-hydroxylase deficiency and whose biopsy revealed a 46XX chromosomal pattern. Cultured cells from the biopsy confirmed the fetus to be of identical HLA haplotype to the previous affected sibling. At 41 weeks the patient delivered a female neonate with minimal prominence of the clitoris, mildly rugated labia, a single perineal opening and minimal posterior labial fusion. Postnatal tapering of maternal steroids was performed with no long-term sequelae.

Adrenal Hyperplasia, Congenital↗
PubMed1989

Muscarinic cholinergic receptors in the normal and neurogenic human bladder.

Bladder dysfunction secondary to neurologic conditions occurs in all age groups and is associated with significant morbidity. The role of neuroreceptors in the development of detrusor dysfunction has not been studied previously. Control bladder tissue specimens were obtained from eight children with ureterovesical reflux undergoing ureteral reimplantation and 14 adults with bladder carcinoma undergoing cystectomy. Neurogenic bladder specimens were obtained from 10 children with myelomeningocele and five adults with neurogenic bladder dysfunction undergoing augmentation cystoplasty. Saturation experiments using 3H-N-methylscopolamine (3H-NMS) were performed in these control and neurogenic bladder homogenates. The mean equilibrium dissociation constants in the neurogenic and control bladders were 0.41 nM and 0.55 nM, respectively. The mean density of muscarinic cholinergic (MCh) receptor binding sites in the neurogenic and control bladders was 0.34 fmol/mg wet wt. and 0.65 fmol/mg. wet wt., respectively. Competitive binding experiments with 3H-NMS and various unlabelled MCh antagonists indicated that the pharmacology of MCh binding sites was similar in neurogenic and control bladders. Age was not significantly correlated with MCh receptor density in the control and neurogenic bladders. Muscarinic cholinergic binding sites are homogeneous in neurogenic and control bladders. The lower density of MCh receptors in the neurogenic bladders may represent down regulation of MCh receptors or a replacement of smooth muscle by fibrosis.

Adult↗
PubMed1989

Bridging the gap between service delivery and research.

Home care research is important. In fact, it is too important to be left exclusively to researchers even if the currently existing barriers to such investigations were to disappear. Finally, governments can have a major impact by recognizing the importance of encouraging practitioners to be investigators and by helping them improve the quality of their proposals. Paradoxically, improving the skill of practitioners to do research may also increase trust and co-operation between them and researchers.

Canada↗
PubMed1989

Formation and action of 8-hydroxy-11,12-epoxy-5,9,14-icosatrienoic acid in Aplysia: a possible second messenger in neurons.

In Aplysia neural tissue, the release and metabolism of arachidonic acid are stimulated by histamine or by activation of the identified L32 nerve cell circuit of the abdominal ganglion. Previously we found that histamine and intracellular stimulation of L32 cells, which are putatively histaminergic neurons, cause the production of 12-hydroxy-5,8,10,14-icosatetraenoic acid (12-HETE), a product of the 12-lipoxygenase pathway formed through 12-hydroperoxy-5,8,10,14-icosatetraenoic acid (12-HPETE). 12-HPETE, but not 12(S)-HETE, mimics the dual-action response of L14 ink motor neurons to histamine and stimulation of L32. 12-HPETE can also be further metabolized to 8-hydroxy-11,12-epoxy-5,9,14-icosatrienoic acid (8-HEpETE) which was identified by HPLC, enzymatic hydrolysis, and GC/MS. Production of 8-HEpETE is specific, as its positional isomer 10-hydroxy-11,12-epoxy-5,8,14-icosatrienoic acid is not formed after physiologic stimulation. 8-HEpETE can elicit the late component (hyperpolarization) of the dual-action response in L14 cells, suggesting that it may be a second messenger in Aplysia.

8,11,14-Eicosatrienoic Acid↗
PubMed1989

12-keto-eicosatetraenoic acid. A biologically active eicosanoid in the nervous system of Aplysia.

The lipoxygenase product 12-hydroperoxy-5,8,10,14-eicosatetraenoic acid (12-HPETE), stimulates the synaptic response produced by the modulatory transmitter histamine and the neuroactive peptide Phe-Met-Arg-Phe-amide (FMRFamide) in identified neurons of the marine mollusk Aplysia californica. The 12-lipoxygenase pathway has not yet been fully characterized, but 12-HPETE is known to be metabolized further. Therefore, we began to search for other metabolites in order to investigate whether the actions of 12-HPETE might require its conversion to other active products. We have identified 12-keto-5,8,10,14-eicosatetraenoic acid (12-KETE) as a metabolite of 12-HPETE formed by Aplysia nervous tissue. 12-KETE was identified in incubations of the tissue with arachidonic acid using HPLC, UV spectrometry, and gas-chromatography/mass spectrometry. [3H]12-KETE is formed from endogenous lipid stores in nervous tissue, labeled with [3H]arachidonic acid upon stimulation by application of histamine. In L14 and L10 cells, identified neurons in the abdominal ganglion, applications of 12-KETE elicit changes in membrane potential similar to those evoked by histamine. Another metabolite of 12-HPETE, 12(s)-hydroxy-5,8,10,14-eicosatetraenoic acid [12(S)-HETE], is inactive. These results support the hypothesis that 12-HPETE and its metabolite, 12-KETE, participate in transduction of histamine responses in Aplysia neurons.

Animals↗
PubMed1989

Does a small minority of elderly account for a majority of health care expenditures? A sixteen-year perspective.

Canadian and American analysts commonly find that a small proportion of the elderly is responsible for a large share of health care expenditures. Data on a representative cohort in Manitoba indicate that the longer the time frame studied, the less health care usage concentrates in a single small group of elderly people. Over the sixteen-year period treated, the average older person's risks of using hospital and nursing home services is nevertheless notably higher than reported to date; yet, one-half of the elderly make relatively minimal demands on the health care system. The results reinforce calls for targeting the needs of intensive consumers of health care services and highlight the variability of cumulative usage patterns among older Manitobans.

Aged↗
PubMed1989

Aplysia synaptosomes. II. Release of transmitters.

A subcellular fraction (P3) from Aplysia is enriched in synaptosomes (Chin et al., 1988) and is capable of accumulating 5-HT and choline. At an external 3H-5-HT concentration of 1.8 microM, the P3 fraction took up 0.12 nmol/mg protein in 30 min. Uptake was dependent on external Na+. Electron microscopic autoradiography showed that much of the accumulated 3H-5-HT is localized to synaptosomes. At 0.5 microM 3H-choline, P3 took up 0.11 nmol/mg protein in 30 min and converted 40% to 3H-ACh. This synaptosomal fraction was also capable of releasing transmitter. After 3H-5-HT or 3H-choline was taken up, P3 released about 5% of the total radioactive transmitter in a Ca2+-dependent manner during a 30 sec exposure to a depolarizing concentration of K+ (100 mM). Identified, prelabeled synaptosomes were prepared by injecting 3H-choline into the large cholinergic neuron L10. The abdominal ganglia containing the injected cells were then fractionated, yielding synaptosomes containing radioactivity derived from L10. After this synaptosomal fraction was exposed to high K+, 2% of the radioactivity was released in a Ca2+-dependent manner. This release was completely blocked by 0.1 mM histamine, a modulatory transmitter that has previously been shown to cause presynaptic inhibition in L10.

Acetylcholine↗
PubMed1989

Is health care use changing? A comparison between physician, hospital, nursing-home, and home-care use of two elderly cohorts.

This study used log-linear survival analysis, and log-rank tests to compare 1) the characteristics of two elderly cohorts; 2) their use of physician, hospital, nursing-home and home-care services over 8.5 years; and 3) physician and bed supplies during the two periods. Both cohorts were similar in health status and in their use of hospital, nursing-home, and home-care resources despite a steady decrease in hospital beds during both periods and a shrinking supply of nursing-home beds for the later cohort. Although physician supply increased more rapidly for the first (1971) than for the second (1976) cohort, the later cohort used significantly more ambulatory care than the earlier cohort. Home care appears to substitute for year-to-year variations in nursing-home admissions but not for variations in hospital lengths of stay.

Aged↗
PubMed1989

Trends in cesarean section rates.

Analysis of rates of primary cesarean section by level of perinatal designation and of individual hospitals with rates in excess of 20 percent show the increased utilization of cesarean sections between 1967 and 1986. Recommendations are made for reducing the utilization of cesarean sections at the hospital and physician levels.

Cesarean Section↗
PubMed1989

In search of psychological markers of bipolar manic-depressive illness (BMDI): commonalities in psychological functioning between adult euthymic BMDI patients and offspring of BMDI-affected parents.

Detection of probable psychological trait markers of Bipolar Manic Depressive Illness (BMDI) was attempted by conducting two investigations: in the first, Rorschach behavior of adult euthymic BMDI patients was compared with normal control subjects; in the second, Rorschach behavior of nonclinical children of BMDI patients was compared with matched normal controls. Comparison of investigation results revealed psychological characteristics shared by both adult euthymic BMDI patients and clinically-tested children of BMDI-affected parents, including: 1) impaired synthetic functioning; 2) complexity avoidance; 3) experiential and ideational constriction; 4) impaired perceptual accuracy and thought disorder: 5) low conventionalism; and 6) impaired object relatedness.

Adult↗