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Biomedical subjects

M Goldstein

Publications and source records attributed to M Goldstein.

At least 145 records · Page 8Linked to original sources

Cystic fibrosis gene mutations do not affect sperm function during in vitro fertilization with micromanipulation for men with bilateral congenital absence of vas deferens.

OBJECTIVE: To assess the effects of cystic fibrosis transmembrane-conductance regulator (CFTR) gene mutations on sperm function and fertility in men with bilateral congenital absence of the vas deferens. DESIGN: Prospective. SETTING: Division of urologic microsurgery and associated hospital-based IVF unit. MAIN OUTCOME MEASURES: Fertilization and pregnancy rates. PATIENTS: Men referred to our fertility unit for treatment of bilateral congenital absence of the vas deferens, using sperm surgically retrieved from the epididymis with IVF and micromanipulation. RESULTS: Of 45 men with bilateral congenital absence of the vas, 54% (19/35) tested were found to be carriers of CFTR gene mutations, with one compound heterozygote. Epididymal sperm from men affected with CFTR mutations fertilized 19% (29/152) of oocytes, whereas men without mutations fertilized 22% (44/204) of oocytes. Pregnancy rates (PRs) were 36% (5/14) for cycles involving men with CFTR mutations and 33% (5/15) for other patients with congenital absence of the vas deferens but without detectable CFTR mutations. CONCLUSIONS: The presence of detectable CFTR mutations does not affect fertilization rates or PRs for men with bilateral congenital absence of the vas deferens when IVF and micromanipulation are applied.

Cystic Fibrosis↗

Memory for novel and familiar spatial and linguistic temporal distance information in hypoxic subjects.

Hypoxia is known to cause damage to the hippocampus as well as memory impairments in humans. Subjects who have experienced a hypoxic episode and age-, gender-, and education-matched control subjects were tested for memory for spatial and linguistic temporal distance information using sentences and spatial locations. Each test contained a familiar component based on information that is meaningful and is thought to be stored as part of the knowledge system (prior knowledge) as well as a novel component based on new information. Subjects were presented a list of eight-word sentences or eight spatial locations (Xs) on a grid on a Macintosh computer and tested for memory for temporal distances. Temporal distance is defined as the number of items that occur between the two test items, in the study phase. Compared to control subjects, hypoxic subjects were impaired across all temporal distances on the novel spatial and linguistic tasks. As the temporal distance increased, hypoxic subjects showed some improvement in memory performance. In addition, memory of familiar temporal distance information was also assessed. Hypoxic subjects were impaired, compared to control subjects, for familiar temporal distance information. For hypoxic subjects there was a proportionally greater impairment for novel compared to familiar spatial and linguistic temporal distance information. There was a significant difference in their performance on the familiar temporal distance tasks compared to their performance on the novel tasks. Prior knowledge appears to attenuate the deficits seen in the familiar temporal distance tasks. It appears that hypoxia may cause more selective damage to the hippocampus and this damage is sufficient to produce profound memory impairments for primarily novel and less severe memory impairments for familiar spatial and linguistic temporal distance information.

Adult↗

Antibodies to a segment of tyrosine hydroxylase phosphorylated at serine 40.

A synthetic peptide corresponding to residues 32-47 of rat tyrosine hydroxylase (TH) was phosphorylated by protein kinase A at Ser40 and used to generate antibodies in rabbits. Reactivity of the anti-pTH32-47 antibodies with phospho- and dephospho-Ser40 forms of TH protein and peptide TH32-47 was compared with reactivity of antibodies to nonphosphorylated peptide and to native TH protein. In antibody-capture ELISAs, anti-pTH32-47 was more reactive with the phospho-TH than with the dephospho-TH forms. Conversely, antibodies against the nonphosphorylated peptide reacted preferentially with the dephospho-TH forms. In western blots, labeling of the approximately 60-kDa TH band by anti-pTH32-47 was readily detectable in lanes containing protein kinase A-phosphorylated native TH at 10-100 ng/lane. In blots of supernatants prepared from striatal synaptosomes, addition of a phosphatase inhibitor was necessary to discern labeling of the TH band with anti-pTH32-47. Similarly, anti-pTH32-47 failed to immunoprecipitate TH activity from supernatants prepared from untreated tissues, whereas prior treatment with either 8-bromoadenosine 3',5'-cyclic monophosphate or forskolin enabled removal of TH activity by anti-pTH32-47. Lastly, in immunohistochemical studies, anti-pTH32-47 selectively labeled catecholaminergic cells in tissue sections from perfusion-fixed rat brain.

8-Bromo Cyclic Adenosine Monophosphate↗

Effects of hypercarbia on autoregulation of brain blood flow and cerebral metabolism in newborn piglets.

We tested the hypothesis that, in newborn piglets, hypercarbia impairs autoregulation of total and regional brain blood flow at the lower limb of the autoregulatory curve. Cerebral oxygen metabolism was measured in the same piglets to relate changes in metabolism to blood flow. Instrumented hypercarbic (n = 9) and normocarbic (n = 8) newborn piglets exposed to phlebotomy were studied during normotension and graded hypotension with mean arterial blood pressures of 55-41, 40-31 and < 30 mmHg. In the hypercarbic piglets, total brain blood flow decreased (P < 0.01) from the hypercarbic-normotensive value of 187 +/- 15 mliter min-1 100 g-1 to 139 +/- 18, 66 +/- 11 and 34 +/- 6 at mean arterial blood pressures of 55-41, 40-31 and < 30 mmHg, respectively; in the normocarbic piglets, total brain blood flow did not change from the normotensive value (70 +/- 11 mliter min-1 100 g-1) until the mean arterial blood pressure was < 30 mmHg, when brain blood flow had decreased (P < 0.01) to 49 +/- 8 mliter min-1 100 g-1. In the hypercarbic piglets, all brain regions (cerebrum, caudate nucleus, cerebellum, brainstem and medulla) demonstrated similar response patterns to that of total brain blood flow during hypotension. Thus, during hypercarbia, none of the brain regions demonstrated autoregulation. In the normocarbic piglets, cerebral blood flow decreased (P < 0.01) from the normocarbic-normotensive value of 74 +/- 6 mloter min-1 100 g-1 to 51 +/- 8 and 37 +/- 7 at mean arterial blood pressures of 40-31 and < 30 mmHg, respectively, and blood flow to the caudate nucleus, cerebellum and brainstem did not decrease significantly, and in fact increased (P < 0.01) to the medulla during hypotension. Although cerebral oxygen metabolism was compromised in the hypercarbic and normocarbic piglets, the relationship between metabolism and blood flow was altered such that the cerebral metabolic rate of oxygen per unit of blood flow was lower in the hypercarbic than the normocarbic piglets. We conclude that hypercarbia impairs total and regional brain blood flow autoregulation in newborn piglets.

Animals↗

Management of alternate level of care patients using a computerized database.

The term "alternate level of care" (ALC) refers to the status of hospitalized patients who are no longer acutely ill but cannot be discharged because posthospital plans are not yet in place. ALC is a major problem for patients, families, and hospitals. This article describes the experiences of an urban teaching hospital with ALC and the development of a computerized database to better manage the ALC population. Among the findings were that age, waiting for a nursing home placement, family-related discharge problems, and pending Medicaid eligibility all significantly contributed to length of stay beyond the acute phase of the illness. Using these data, the hospital developed an innovative program in which the preparation of Medicaid applications was transferred from the Department of Finance to the Department of Social Work Services.

Aged↗

Effects of captopril on [3H]-norepinephrine release in rat central nervous system.

1. The present study was performed to investigate the effects of captopril (an angiotensin converting enzyme inhibitor, ACE-I) on noradrenergic transmission in the rat central nervous system. 2. Slices of rat hypothalamus and medulla oblongata were prepared and prelabelled with [3H]-norepinephrine. Slices were continuously superfused with Krebs-Ringer solution, and electrical stimulation (1 Hz) was performed. 3. Captopril significantly inhibited the stimulation-evoked [3H]-norepinephrine release from rat hypothalamic slices in a dose-dependent manner (S2/S1 ratio: control 0.904 +/- 0.025, n = 6, captopril 1 x 10(-5) mol/L 0.617 +/- 0.043, n = 6, P < 0.05, captopril 5 x 10(-5) mol/L 0.547 +/- 0.037, n = 6, P < 0.05). However, the basal release of [3H]-norepinephrine was not affected by captopril. 4. Captopril also reduced the stimulation-evoked [3H]-norepinephrine release in the medulla oblongata (S2/S1 ratio: control 0.878 +/- 0.018, n = 6, captopril 3.3 x 10(-5) mol/L 0.624 +/- 0.046, n = 6, P < 0.05). 5. These results show that captopril might inhibit the stimulation-evoked norepinephrine release in rat hypothalamus and medulla oblongata. Although the precise mechanisms underlying the neurosuppressive effect of captopril are still uncertain, the finding suggests that the inhibition of noradrenergic transmission might be related to the central action of the ACE-I.

Angiotensin-Converting Enzyme Inhibitors↗

Synergistic effects of Bay K 8644 and bradykinin on norepinephrine release in the hypothalamus of spontaneously hypertensive rats.

1. In the present study, we examined the effects of Bay K 8644, a dihydropyridine (DHP)-sensitive Ca2+ channel agonist, and bradykinin on norepinephrine release in the hypothalamus of spontaneously hypertensive rats (SHR). 2. In the preliminary studies using Sprague-Dawley rats, Bay K 8644 by itself had no significant effects on the stimulation-evoked [3H]-norepinephrine release from hypothalamic slices. Bradykinin increased the stimulation-evoked [3H]-norepinephrine release in a dose-related fashion. The facilitatory effects of bradykinin on norepinephrine release were potentiated by Bay K 8644. 3. In SHR, Bay K 8644 significantly increased the stimulation-evoked norepinephrine release from hypothalamic slices. However, exposure of slices to Bay K 8644 caused no significant effects on norepinephrine release in Wistar-Kyoto (WKY) rats. The effects of Bay K 8644 in combination with bradykinin on the stimulation-evoked norepinephrine release were also greater in SHR than in WKY rats. 4. These results demonstrate that Bay K 8644 significantly potentiated the facilitatory effects of bradykinin on norepinephrine release in rat hypothalamus. The finding indicates a possible interaction of bradykinin with DHP-sensitive Ca2+ channels in the central nervous system. Furthermore, the pronounced effects of Bay K 8644 and bradykinin in SHR suggest that bradykinin-related Ca2+ channels might have a role in the regulation of norepinephrine release in the hypothalamus of SHR.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Life-sustaining treatment preferences of hemodialysis patients: implications for advance directives.

The purpose of this study was to describe the life-sustaining treatment preferences of dialysis patients and to compare the acceptability of two generic and a disease-specific advance directive (AD). Of 532 potentially eligible hemodialysis patients, 95 (17.9%) participated in the study. These patients completed two generic (the Centre for Bioethics Living Will and the Medical Directive) and one disease-specific (the Dialysis Living Will) AD in a randomized cross-over trial. Treatment preferences were measured by using the Centre for Bioethics Living Will. Acceptability of the AD was measured by using a 13-item advance directive acceptability questionnaire (ADAQ) for each AD, and the advance directive choice questionnaire (ADCQ) to elicit participants' preferred AD. Twenty-five percent of the participants wanted to continue dialysis in case of severe stroke, 19% in severe dementia, and 14% in permanent coma. Averaged across treatments, proportions of participants wanting treatment in various health states were: current health (86%), mild stroke (84%), moderate stroke (60%), severe stroke (21%), mild dementia (78%), moderate dementia (51%), severe dementia (14%), terminal illness (41%), and permanent coma (10%). Averaged across health states, proportions of participants wanting various types of treatment were: dialysis (58%), antibiotics (53%), transfusion (53%), surgery (48%), cardiopulmonary resuscitation (48%), respirator (47%), and tube feeding (41%). Mean ADAQ scores were: Dialysis Living Will, 71%; Centre for Bioethics Living Will, 70%; and Medical Directive, 60% (F = 8.27, P < 0.001 (repeat measures analysis of variance); the Dialysis Living Will and Centre for Bioethics Living Will scored significantly higher than the Medical Directive). The proportion of participants who said they would choose to complete each AD was: Dialysis Living Will, 28%; Centre for Bioethics Living Will, 38%; Medical Directive, 31%; and unsure, 3% (chi 2 = 1.465, df = 2, P = 0.48). In conclusion, twenty-five percent or less of hemodialysis patients want to continue dialysis in three specific health states: severe stroke, severe dementia, and permanent coma. Health states and illness severity, far more than treatment descriptions, influence preferences. Dialysis patients should be offered a generic AD, and some generic AD are more acceptable than others. Only a minority of dialysis patients will complete any AD, but the completion of written AD forms is only one element in the process of advance care planning.

Adolescent↗

Patency following microsurgical vasoepididymostomy and vasovasostomy: temporal considerations.

PURPOSE: We evaluate the temporal parameters of patency following vasoepididymostomy and vasovasostomy. MATERIALS AND METHODS: A series of consecutive and concurrent vasoepididymostomies (100) and vasovasostomies (100) performed by a single surgeon (M. G.) was reviewed. RESULTS: Patency rates following vasoepididymostomy and vasovasostomy were 65% and 99%, respectively (p < 0.001). Motile sperm were observed at a mean of 5.8 +/- 0.8 months (standard error) following vasoepididymostomy and 2.1 +/- 0.2 months following vasovasostomy (p < 0.01). Late failure rates were 21% for vasoepididymostomy and 12% for vasovasostomy. Pregnancy rates following vasoepididymostomy and vasovasostomy were 21% and 52%, respectively. CONCLUSIONS: Patency is rapid following vasovasostomy but requires 12 or more months following vasoepididymostomy. Intervention for azoospermia is appropriate 6 months after vasovasostomy and 1 year after vasoepididymostomy. Intraoperative cryopreservation of sperm in men undergoing vasoepididymostomy and postoperatively in all men with motile sperm will maximize fertility options.

Anastomosis, Surgical↗

The effect of varicocelectomy on serum testosterone levels in infertile men with varicoceles.

PURPOSE: We evaluated the effect of varicocelectomy on serum testosterone. MATERIALS AND METHODS: We retrospectively reviewed the effect of varicocelectomy on serum testosterone levels in 53 infertile men with varicoceles. RESULTS: Mean serum testosterone increased from a preoperative level of 319 +/- 12 to 409 +/- 23 ng./dl. postoperatively (p < 0.0004). Men with at least 1 firm testis preoperatively had a greater increase in serum testosterone (p < 0.005). An inverse correlation was noted between preoperative testosterone levels and change in testosterone after varicocelectomy (r = -0.34, p < 0.013). CONCLUSIONS: Varicocelectomy can increase serum testosterone for infertile men with varicoceles. Although improvement in serum testosterone does not necessarily cause a direct improvement in semen quality, varicocelectomy may improve hormonal and spermatogenic function.

Adult↗

CT appearance of a traumatic cataract.

We describe a case of a traumatic cataract that presented on CT as a hypodense lens with a hyderdense rim. The finding reflects the pathogenesis of this entity: a capsular tear and consequent entry of fluid into the lens.

Cataract↗

Effect of recombinant human erythropoietin on hospitalization of hemodialysis patients.

The effect of recombinant human erythropoietin (EPO) on hospitalization of patients with end-stage renal disease (ESRD) was evaluated in a controlled clinical trial. A cohort of 67 new hemodialysis patients prescribed EPO shortly after the clinical availability of EPO were the treatment group. The control group was a cohort of 67 new hemodialysis patients matched for clinical center, age, cardiovascular disease and transfusion history. These patients had not been prescribed EPO as they had started hemodialysis prior to the clinical availability of EPO. There were 21 pairs without hospitalization and 46 pairs with at least 1 member of the pair experiencing hospitalization. Among the latter group, the median follow-up was 174 and 184 days for the EPO and control patients respectively. For all hospitalizations, those treated with EPO were hospitalized 15.3 days per year compared to 23.2 days for the control patients. The difference (EPO-control) was -7.9 days (95% CI: -21.0; 7.8) for all cause hospitalization. For hospitalizations due to cardiac, infectious disease and gastrointestinal disease, the differences were 1.6, 1.8 and 1.2 days favouring EPO treated patients. For hospitalizations related to vascular access complications, the difference was 0.9 days favoring the control group. All other causes favoured EPO treated patients by 4 days. There had been 58 hospitalizations in the EPO group compared to 97 in the control group. The mean duration of hospitalization was 8.0 days for the EPO and 9.6 for the control group. The direction and magnitude of the change in all cause hospitalization represents an improvement in morbidity and an important decrease in health resource utilization.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Microsurgical autogenous sperm reservoir with simultaneous epididymal sperm aspiration: a novel approach for the man with surgically unreconstructable obstruction.

The purpose of this article is to present a technique for microsurgical marsupialization of an epididymal tubule to the tunica vaginalis to create an autogenous sperm reservoir (ASR) with simultaneous epididymal aspiration. This procedure is offered to men with bilateral congenital absence of the vas deferens (CAV) or otherwise surgically unreconstructable reproductive tracts. Sperm (mean +/- standard error of the mean, 33 +/- 13 x 10(6)) have been percutaneously recovered by fine needle aspiration of an ASR in 47% (7/15) of men. Motile sperm have been recovered as long as 2 years following surgery. Simultaneous epididymal aspiration at the time of marsupialization has yielded a mean of 20.2 +/- 6.9 x 10(6) total sperm per aspirate. Thawed sperm, recovered and cryopreserved at the time of ASR surgery, has been successfully employed for two couples in pregnancies achieved with in vitro fertilization. The microsurgical ASR is a viable alternative in the treatment of men with CAV or otherwise unreconstructable reproductive tracts. Simultaneous epididymal sperm aspiration maximizes a couples fertility options with a single surgical procedure.

Cryopreservation↗

Generalized presence of a PEC-60-like peptide in catecholamine neurones.

PEC-60, a 60-residue intestinal peptide structurally related to the pancreatic secretory type of trypsin inhibitor, has been isolated, characterized and molecularly cloned. It shows biological activity as a hormone in both the gastrointestinal tract and in the immune system. We now report immunohistochemical evidence suggesting its neural localization exclusively within central and peripheral catecholamine (CA) neurones. PEC-60-like immunoreactivity was present in cell bodies, dendrites and nerve terminals of virtually all catecholamine neurones examined and including the noradrenergic gland cells of the adrenal medulla. PEC-60-like immunoreactivity was not seen, however, within the tyrosine hydroxylase-positive but CA-negative arcuate neurones producing growth hormone releasing hormone. The findings open up the possibility that a PEC-60-like peptide may represent a generalized co-transmitter in the peripheral and central CA neurones.

Animals↗

Application of eye drops to the medial canthus.

BACKGROUND: Our purpose was to investigate the efficacy of instillation of eye drops in the medial canthus with the lids closed at the time of application. METHODS: The pupils of 50 healthy volunteers were dilated with tropicamide 0.125%. The effect of the drug on pupillary dilatation when instilled in one eye with the lids closed was compared to its effect when instilled in the conventional mode in the other eye. RESULTS: Maximal mydriasis achieved was 2.75 +/- 0.76 mm in the eye with closed lids and 2.8 +/- 0.77 mm in the eye in which eye drops were instilled in the conventional mode. CONCLUSION: Eye drop instillation in the medial canthus with the lids closed at the time of application seems to be an effective means of ophthalmic drug delivery.

Adult↗

Malignant phenotype correlating with drug resistance in two human neuroblastoma cell lines.

The main cause for the failure of chemotherapeutic treatment of advanced cancer probably lies in the emergence of drug resistance clones. In the present study we compared the sensitivity to adriamycin (ADR) and the capacity of ADR uptake in two human neuroblastoma cell lines differing in properties relevant to metastatic potential, the GP2 and MB, of low- and high-malignancy phenotype, respectively. Examination of the ADR effect on in vitro proliferative capacity of the two cell lines revealed a higher sensitivity of GP2 as compared to the MB variant. Intracellular ADR accumulation was determined by fluorocytometry, spectrofluorometry and fluorescence microscopy. According to the three methods, the GP2 line cells, representing a low-malignancy phenotype, had a higher uptake ability than the MB cells, possessing a phenotype of higher aggressiveness. The quantitative determination revealed that over a broad range of ADR concentrations, the GP2 cells accumulated 2-3.5 folds the amount of cytotoxic agent penetrating the MB cells. The FACS analysis showed that the cell population of each of the variants consisted of two subpopulations varying in their ability to accumulate ADR. In the GP2 line the high permeability subpopulation represented nearly half of the total cell population, whereas in the MB line this subpopulation represented a minority. The correlation observed between ADR uptake capacity and sensitivity to the cytotoxic agent, as evidenced by its effect on proliferative capacity, suggests that the resistance of the MB cells is due to a P-G-P modification-related mechanism.

Cell Differentiation↗