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Biomedical subjects

E Shapiro

Publications and source records attributed to E Shapiro.

At least 19 recordsLinked to original sources

Comparative, in vitro, studies of hippocampal tissue from homing and non-homing pigeon.

The purpose of this research was to characterize morphologically and electrophysiologically tissue slices obtained from the hippocampus of homing and non-homing pigeons. When hippocampal slices from the brain of homing and non-homing pigeons are observed under the dissecting microscope, diffuse fiber paths can be seen. These fiber pathways appeared to be identical with the medial fiber tract (VM) previously described histologically in the hippocampus of homing pigeon. Visualization of these tracts in living slices allowed placement of stimulating and recording electrodes in corresponding locations in these slices in both homing and non-homing pigeons. Extracellular potentials recorded from VM regions of the brains of both homing and non-homing pigeons were sensitive to CNQX indicating that glutamate may be a neurotransmitter in this area of pigeon hippocampus. These potentials could undergo long-term potentiation (LTP) following high frequency stimulation. This LTP was blocked by NMDA receptor antagonist APV in the hippocampus of homing pigeon, but was APV-resistant in the hippocampus of non-homing pigeon. Extracellular potentials from the hippocampus of homing pigeons were increased in amplitude when slices were perfused with Mg(2+)-free Ringer, while potential recorded from hippocampal slices from non-homing pigeons wre unaffected by Mg(2+)-free solutions. Intracellular recordings from the hippocampal slices of homing pigeons revealed that about half the cells demonstrated excitatory synaptic potentials evoked by extracellular stimulation. The EPSP was sometimes large enough to trigger an action potential. Neurons filled with the fluorescent dye, Lucifer Yellow, in the hippocampus of homing pigeons showed multipolar structure. The response of these cells to extracellular stimulation provides the activity responsible for the extracellular potentials which can undergo LTP.

6-Cyano-7-nitroquinoxaline-2,3-dione

Comparison of the cellular composition of benign prostatic hyperplasia in Chinese and Caucasian-American men.

OBJECTIVES: To compare the cellular composition of benign prostatic hyperplasia (BPH) in Chinese and Caucasian-American men. METHODS: Surgical specimens of the prostate were obtained from 9 Chinese and 8 Caucasian-American men undergoing cystoprostatectomy for invasive transitional cell carcinoma. The mean ages of the Chinese and Caucasian-American men were 66.8 years and 66.4 years, respectively (P = 0.94). The mean prostate weight of the Chinese and Caucasian-American men was 53.4 g and 32.1 g, respectively (P = 0.01). Double immunoenzymatic staining with antibodies against actin and prostatic acid phosphatase and computer-assisted color image analysis were performed on whole-mount tissue sections. The percent area density of smooth muscle (SM), connective tissue (CT), epithelium (E), and epithelial lumen (L) were obtained by analyzing 30 fields from each specimen. RESULTS: The mean percent area density of SM, CT, E, and L in the prostate of Chinese men was 32%, 9.1%, 10.8%, and 48.5%, respectively. The mean percent area density of SM, CT, E, and L in the prostate of Caucasian-American men was 52.5%, 27.9%, 12.8%, and 7%, respectively. Overall, the prostates of Chinese men contained significantly more glandular lumen and significantly less SM and CT. CONCLUSIONS: The present study demonstrates that the cellular composition of BPH in the prostates of Caucasian-American and Chinese men is different. These cellular differences may account for previously observed differences in the incidence of clinical BPH.

Aged

Noninvasive measurement of tissue magnesium and correlation with cardiac levels.

BACKGROUND: Intracellular magnesium ([Mg]i) plays an important role in the regulation of myocardial metabolism, contractility, and the maintenance of transsarcolemmal and intracellular ionic gradients. An understanding of the role of magnesium in the clinical setting, however, is hampered by the lack of an assay of intracellular tissue magnesium levels. METHODS AND RESULTS: We used energy-dispersive x-ray analysis to measure [Mg]i in sublingual epithelial cells and to correlate the level with those in atrial biopsy specimens from the same patients during cardiopulmonary bypass. Levels were also measured in acute myocardial infarction (AMI) patients before and after intravenous magnesium sulfate administration and compared with those from intensive care unit (ICU) patients and healthy individuals. A strong correlation between sublingual epithelial cell (mean, 32.1 +/- 0.3 mEq/L) and atrial tissue (mean, 32.1 +/- 0.3 mEq/L) [Mg]i was present in 18 cardiac surgery patients (r = .68, P < .002). Epithelial and atrial [Mg]i levels were lower than in healthy individuals (33.7 +/- 0.5 mEq/L, P < .01) studied at that time and correlated poorly with serum magnesium. Mean [Mg]i in 22 AMI patients was 30.7 +/- 0.4 mEq/L, which was significantly lower than in 21 ICU patients and 15 healthy individuals (35.0 +/- 0.5 mEq/L and 34.5 +/- 0.7 mEq/L, respectively, P < .001). Intravenous magnesium sulfate was administered to most of the AMI patients (mean dose, 36 +/- 6 mmol). [Mg]i rose significantly in the AMI patients over the first 24 hours, and the magnitude of the increase was greater in those who received higher doses of intravenous magnesium sulfate. CONCLUSIONS: Sublingual epithelial cell [Mg]i correlates well with atrial [Mg]i but not with serum magnesium. [Mg]i levels are low in patients undergoing cardiac surgery and those with AMI. Intravenous magnesium sulfate corrects low [Mg]i levels in AMI patients. Energy-dispersive x-ray analysis determination of sublingual cell [Mg]i may expedite the investigation of the role of magnesium deficiency in heart disease.

Aged

Stereochemistry of the Aplysia neuronal 12-lipoxygenase: specific potentiation of FMRFamide action by 12(S)-HPETE.

Nervous tissue of the marine mollusc, Aplysia californica, generates arachidonic acid metabolites in response to neurotransmitters such as histamine or FMRFamide. In addition, identified neurons of Aplysia respond to the pharmacologic application of some of these products, particularly those of the 12-lipoxygenase pathway. We investigated the chirality of the initial Aplysia 12-lipoxygenase product, 12-HPETE, in preparation for more detailed metabolic studies and for the analysis of the physiological activity of the endogenous lipid. Neural homogenates and intact ganglia exclusively generate 12(S)-HPETE as do the better characterized mammalian lipoxygenases. The direct application of 12(S)-HPETE to cultured sensory neurons induced a hyperpolarization which averaged 2.6 mV. We did not find any difference between the response to the naturally-occurring 12(S)-HPETE and its diastereomer, 12(R)-HPETE which is not generated in Aplysia. Both isomers were significantly more effective than 15(S)-HPETE. In contrast, 12(S)-HPETE, but not 12(R)-HPETE, was a potent modulator of the action of the molluscan neuropeptide, FMRFamide. Prior application of 12(S)-HPETE to cultured sensory neurons increased the subsequent response to a submaximal dose of FMRFamide by 60%. On the other hand, 12(R)-HPETE reduced the subsequent response to the peptide by 30%. The lack of stereospecificity in the direct effect of the lipids differs markedly from their stereospecific effects as modulators of FMRFamide action. This suggests that there may be an important neurophysiologic role for these lipid modulators which is distinct from their direct effects, and also indicates that there are multiple sites and mechanisms by which lipid hydroperoxides act on neurons in Aplysia.

Animals

Effects of nitric oxide on human and canine prostates.

OBJECTIVES: To determine whether nitric oxide (NO) is a mediator of prostatic smooth muscle activity. METHODS: Pharmacologic experiments using electrical field stimulation (EFS) were performed on strips of human and canine prostate. RESULTS: EFS alone elicited frequency-dependent contractions in preparations of human and canine prostates. The greatest contractile activity was achieved at 30 Hz. In the presence of 10(-5) M guanethidine (GUA) and 2 x 10(-6) M atropine (ATR), EFS elicited relaxation of canine prostate strips relative to baseline tension. A weak biphasic response consisting of initial relaxation and subsequent contraction relative to baseline tension was observed in the human prostate strips exposed to similar conditions. The smooth muscle activity observed in the presence of GUA plus ATR was attributed to nonadrenergic, noncholinergic (NANC) nerve transmission. 10(-4) M L-NG-nitroarginine methylester (NAME) significantly increased EFS-elicited NANC smooth muscle activity both in human and canine prostates. L-arginine, 10(-2) M, reversed the effect of L-NAME in human and canine prostates. Sodium nitroprusside, 10(-4) M, a donor of NO, caused relaxation of both human and canine prostates. The mean magnitude of the relaxant response/cross-sectional area in human prostate (2.64 +/- 0.4 g/cm2) was significantly greater than in the canine prostate (1.09 +/- 0.17 g/cm2) (P < 0.005). CONCLUSIONS: These results provide compelling evidence that NO plays a role in mediating contractile function of human and canine prostates.

Animals

An evaluation of type A and B alcoholics.

Evaluations of 1539 alcohol-dependent subjects (including 512 women) were carried out in an attempt to replicate the Type A/B dichotomy suggested by Babor et al. (1992). The subjects are participants in the Collaborative Study on the Genetics of Alcoholism (COGA), and each was evaluated using a face-to-face structured interview. Following the procedure of Babor et al. (1992), data were used to create 17 domains, and a k-means clustering method was invoked to generate a two-cluster solution. Thirty-one per cent of the males and 25% of the females fell into the Type B group, with overall R2 of 0.22 and 0.24 for males and females, respectively. The scores in each of the 17 domains and the analyses of the clinical characteristics for Type A and B subjects were, in general, consistent with the earlier onset and more severe course for Type B men and women. The ability of the domains to identify subgroups of alcoholics remained robust even after the exclusion of alcohol dependent subjects with antisocial personality disorder (ASPD) and those with an onset of alcohol dependence before age 25 years. The present analyses suggest that five of the 17 domains might be especially useful in identifying Type A and B groups.

Adult

Using the information system to assess change: the impact of downsizing the acute sector.

A population-based approach was used to monitor impact of hospital bed closures in Winnipeg, Manitoba. Four years of administrative data were analyzed. Access to hospital services was not adversely affected: The reduction in beds resulted in increases in outpatient surgery and earlier discharges. In addition, access favored the admission of persons with more health care needs. Quality of care, as measured by mortality within 3 months of admission, readmission rates within 30 days of discharge, and increased contact with physicians within 30 days of discharge, did not change. The health status of the Winnipeg population, measured by premature mortality, did not change. However, health status and hospital use was found to be strongly related to socioeconomic status. In light of this gradient, the authors conclude that well designed and evaluated experiments that focus on the determinants of health, rather than on providing more health care services, could help identify ways of reducing hospital use.

Adolescent

Interleukin-1 mediates increased plasma levels of eicosanoids and cytokines in patients with sepsis syndrome.

The purpose of this was to study evaluate the effects of interleukin-1 (IL-1) inhibition by human recombinant IL-1 receptor antagonist (IL-1ra) on plasma prostaglandin, leukotriene, and cytokine levels in sepsis syndrome. As part of a multisite, prospective, randomized, double-blind, placebo-controlled clinical trial, 19 septic patients received IL-1ra in a 100 mg bolus followed by 2.0 mg/kg/h i.v. for 72 h (n = 10) or placebo (n = 9). Plasma thromboxane B2 (TXB2), prostaglandin 6-keto-F1 alpha (PGI), leukotriene B4 (LTB4), leukotrienes C4D4E4 (LTC4D4E4), IL-1 beta, IL-6, and tumor necrosis factor alpha (TNF) were measured by ELISA before study drug infusion (baseline) and at 24, 48, 72, and 96 h after the beginning of the study drug infusion. Differences between placebo and IL-1-ra for plasma LTB4 and TNF were not significant. Plasma TXB2, PGI, LTC4D4E4, and IL-6, expressed as % baseline, were significantly lower in patients receiving IL-1ra than in the placebo group (p < .05), while plasma IL-1 was increased significantly. IL-1 may be a necessary mediator of increased circulating PGI, TXB2, LTC4D4E4, and IL-6 levels in patients with sepsis syndrome. Plasma IL-1 is increased with infusion of IL-1ra. The clinical significance of IL-1 in modifying circulating eicosanoid and cytokine concentrations in clinical sepsis is not clear from the data.

Adolescent

Multiple cholesterol emboli syndrome--six cases identified through the spontaneous reporting system.

Six cases of suspected multiple cholesterol emboli syndrome were identified by a review of reports contained in the company's records of adverse event reports. Antecedent risk factors in these reports included cardiac catheterization, thrombolytic therapy, translumbar aortography, renal arteriography, subclavian arteriography, abdominal aortography, and heparinization. Unlike the commonly reported subacute presentation, onset occurred during or immediately after catheterization in 5 of the 6 patients reported. Acute renal failure; hypertension; back, leg, and/or abdominal pain; and livedo reticularis were the events most frequently reported. Angiographers should consider multiple cholesterol embolization when multiple organ system dysfunction occurs during or immediately after intraarterial catheterization.

Aged

Localization of the alpha 1A-adrenoceptor in the human prostate.

PURPOSE: We determined the tissue localization of the alpha 1a-adrenoceptor in the human prostate. MATERIALS AND METHODS: Autoradiographic localization of the alpha 1a-adrenoceptor in the human prostate was determined by performing competitive displacement experiments on slide mounted tissue sections using the ligand 125iodine-2-(-[4-hydroxyphenyl]-ethyl-aminomethyl)tetralone (125I-Heat), and the alpha 1-antagonists WB-4101 (4 x 10(-8) M.) and 5-carboxamido-2,6-diethyl-1,4-dihydro-3-[N-(3-[4-hydroxy-4-phenylpipe ridin- yl]propyl)]carboxamido-4-(4-nitrophenyl) (SNAP 5272, 3 x 10(-7) M.). Under these experimental conditions, WB-4101 and SNAP 5272 are selective alpha 1a/alpha 1d-adrenoceptor and alpha 1a-adrenoceptor antagonists, respectively. The autoradiographs were quantitatively analyzed using a computer image analysis system. RESULTS: Specific 125I-Heat binding associated with the epithelium and stroma were independently analyzed. WB-4101 and SNAP 5272 inhibited 100% of the specific 125I-Heat binding in the stroma, suggesting that all of the stromal alpha 1-adrenoceptors are of the alpha 1a subtype. WB-4101 inhibited none of the specific 125I-Heat binding in the epithelium, suggesting that the alpha 1-adrenoceptor in the epithelium is of the alpha 1b subtype. SNAP 5272 displaced only 25% of the specific 125I-Heat binding in the epithelium, suggesting that a relatively small percentage of the epithelial alpha 1-adrenoceptor is of the alpha 1a subtype. CONCLUSIONS: To our knowledge, our study represents the first cellular localization of the alpha 1-adrenoceptor subtypes in the human prostate using highly selective alpha 1-adrenoceptor antagonists and is consistent with the physiological observation that the activity of prostatic smooth muscle is mediated by the alpha 1a-adrenoceptor.

Adrenergic alpha-Antagonists

Regional concentration of basic fibroblast growth factor in normal and benign hyperplastic human prostates.

Basic fibroblast grown factor (bFGF) is a potent mitogen for mesenchymal cells, including fibroblasts cultured from prostate, and has been postulated to play a role in the development of benign prostatic hyperplasia (BPH). If this is the case, it might be expected that bFGF levels would be elevated in the adenomas of BPH and in the periurethral region of the prostate where BPH is believed to arise. This study was undertaken to test this hypothesis. The concentration of bFGF was evaluated in 31 prostates, 13 normal glands and 18 with BPH. A method for quantitating bFGF by radioimmunoassay was developed that enabled growth factor levels to be correlated to the geographic region of the prostate and the histopathology of the specimen. A 2- to 3-fold higher concentration of bFGF (ng./g. of tissue) was noted in the benign hyperplastic prostates when compared with the adult normal glands. Pubertal specimens demonstrated low growth factor levels comparable to those observed in the normal adult group. Two prepubertal prostates analyzed had high levels similar to those measured in the hyperplastic glands. While the levels of bFGF in the normal adult prostates were highest in the periurethral region, statistical analysis failed to demonstrate a significant difference. Similarly, quantitative morphometric evaluation failed to demonstrate any significant differences in bFGF concentration related to the proportion of stromal, epithelial, or lumenal elements in the tissue sections.

Adolescent

Pathophysiology of clinical benign prostatic hyperplasia.

The pathophysiology of clinical BPH has been attributed to bladder outlet obstruction resulting from the enlarged prostate. A direct relationship does not exist between prostate size, symptom severity, or bladder outlet obstruction. The pathophysiology of prostatism is most likely multifactorial. Elucidating the factors contributing to symptoms will likely provide the foundation for the development of new pharmacological alternatives for the medical treatment of BPH.

Humans

Case management in long-term care: exploring its status, trends, and issues.

After briefly reviewing the goals of long-term care, the goals of case management, and the models in which they currently function, this article focuses on the importance of recognizing the differences in culture, values, ideology, and policies in which case management takes place and the main issues confronting case managers. These issues can be divided into two broad categories: (a) policies that have serious implications for case management but over which case managers have little or no individual control; and (b) those in which case managers are directly involved, partly because of the context in which they work and partly because of the case management function itself. The issues must be addressed so that case managers individually and collectively can do the best possible job in serving vulnerable subpopulations in need of long-term care.

Humans

Making managed care work for you. Tips on setting up a cost-effective practice.

Making a practice cost-effective and profitable does not have to come at the expense of quality care. By incorporating managed care into their practices, the authors were able to find a successful balance. In this article, they lay out tips that would benefit physicians thinking of setting up their own managed-care centers as well as those looking to fine-tune or expand their current practices.

Administrative Personnel

Invasive bacterial infections in children born to women infected with human immunodeficiency virus type 1.

To determine the rates and characteristics of invasive bacterial infections in children infected with the human immunodeficiency virus type 1 (HIV-1), we conducted a prospective, longitudinal, observational cohort study of infants born to HIV-1-infected mothers between Dec. 1, 1985, and Sept. 30, 1989. Of 104 subjects whose HIV-1 infection status could be definitively determined, 21 were infected with HIV-1 and 83 were not. In all, 11 (48%) of 23 invasive infections occurred among 10 HIV-1-infected patients and 12 (52%) of 23 occurred among 11 uninfected subjects. Infections with Streptococcus pneumoniae (n = 8), all of which were community acquired, accounted for the greatest proportion (35%) of the organisms isolated from either the blood or the cerebrospinal fluid. Five episodes of pneumococcal bacteremia occurred in the HIV-infected patients; all resolved promptly after treatment was begun, and no serious focal infections developed. Of 13 instances of bacteremia with an organism other than S. pneumoniae, seven were nosocomial. The rate of community-acquired invasive bacterial infections among the HIV-infected children was nearly three times higher than the rate in the non-HIV-infected children (overall, 1.02 infections per 100 person-months vs 0.37 infection per 100 person-months; rate ratio, 2.8; p = 0.05). Most of the increased risk occurred in children > 1 year of age. In contrast, the difference in the rates of infection between those patients in the two groups who were less than 12 months of age was not significant (1.3 infections per 100 person-months vs 0.81 infection per 100 person-months; rate ratio, 1.6; p = 0.47). We conclude that the rate of invasive bacterial infection is higher in HIV-infected children than in their peers, especially after 1 year of age.

Age Factors

Loss of elasticity in dysfunctional bladders: urodynamic and histochemical correlation.

To store adequate volumes of urine at low safe pressures an elastic bladder wall is required. We developed 2 new techniques to measure this ability in our urodynamic laboratory: pressure specific bladder volume, which measures the bladder capacity at a given pressure, and dynamic analysis of bladder compliance. Recently, morphometric and histochemical techniques have been used to determine the relative volume of connective tissue in the bladder wall and to measure the 2 major types (I and III) of collagen within the bladder wall. These methods quantitate 3 parameters of bladder ultrastructure: 1) relative volume of per cent connective tissue, 2) ratio of connective tissue to smooth muscle and 3) ratio of type III to type I collagen. These parameters have been shown to be abnormally elevated in patients with dysfunctional bladders compared to normals. The purpose of the study was to describe the ultrastructural changes that occur in the wall of dysfunctional bladders and to determine the ability of these new urodynamic techniques to detect reliably the clinical effect of these histological changes. The study included 29 consecutive patients with dysfunctional bladders necessitating bladder augmentation. All patients had upper tract changes and/or were incontinent despite treatment with clean intermittent catheterization and pharmacotherapy. Preoperative urodynamic evaluation included measurement of the total bladder capacity, pressure specific bladder volume and dynamic analysis of bladder compliance. Full thickness bladder biopsies were obtained from the dome of the bladders during augmentation. The per cent connective tissue and the ratio of connective tissue to smooth muscle were determined for all patients, and 4 unselected patients from this group had the ratio of type III to type I collagen determined. These histological results were compared to previously established normal values. All 29 patients had a decreased pressure specific bladder volume and dynamic analysis of bladder compliance, whereas 9 had a normal total bladder capacity. The per cent connective tissue was 35.19 +/- 2.84 and ratio of connective tissue to smooth muscle was 0.60 +/- 0.08 compared to normal values of 10.6 +/- 0.020 and 0.131 +/- 0.021, respectively (p < 0.05). Ratio of type III to type I collagen was also significantly elevated in the 4 samples analyzed (30.53 +/- 1.37 versus 24.00 +/- 2.50, p < 0.05). We conclude that poor storage function of poorly compliant bladders is secondary to an alteration in the connective tissue content of the bladder wall. Furthermore, these pathological ultrastructural changes are universally reflected by an abnormally low pressure specific bladder volume and dynamic analysis of bladder compliance. This strong association validates the use of these parameters and suggests that they are urodynamic indicators of a loss of elasticity in bladder wall.

Adolescent