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Biomedical subjects

M Goldstein

Publications and source records attributed to M Goldstein.

At least 163 records · Page 9Linked to original sources
PubMed1994

Epididymal micropuncture with in vitro fertilization and oocyte micromanipulation for the treatment of unreconstructable obstructive azoospermia.

OBJECTIVE: To provide fertility to couples in whom the man has surgically unreconstructable obstructive azoospermia. DESIGN: Prospective. SETTING: Hospital-based IVF unit, including associated division of urologic microsurgery. PATIENTS: Couples referred to our fertility unit for treatment of men with surgically unreconstructable reproductive tract obstruction, including congenital absence of the vas deferens. MAIN OUTCOME MEASURES: Fertilization, pregnancies, and live births. RESULTS: Of 51 cycles in which sperm and eggs were retrieved, 67% (34/51) resulted in fertilization and 27.5% (14/51) developed clinical pregnancy. Clinical pregnancy rate per couple was 33% (14/43). A total of 15 live births have been obtained in 11 couples with one ongoing pregnancy. Epididymal length was the best predictor of sperm quality and pregnancy results. For couples with at least the corpus epididymis present, 41% (9/22) of cycles resulted in clinical pregnancies. CONCLUSIONS: Pregnancy rates are optimized using sperm retrieved from the epididymis by micropuncture and when micromanipulation is available for use during IVF.

Cell Survival↗
PubMed1994

Gender dependent effects of testosterone and 17 beta-estradiol on bone growth and modelling in young mice.

This study examined the effects of estrogen (17 beta-estradiol) and testosterone on the growth of long bones in male and female mice, with and without gonadectomy. Weight and nose-to-tail length were determined at 3 weeks of age at time of gonadectomy, 7 days later at the onset of hormone therapy, and throughout the treatment period. Gonadectomized mice exhibited an initial weight gain during the pretreatment period but length was unaffected. Hormone treatment altered weight gain in surgical and intact animals in a gender- and hormone-dependent manner. Estradiol enhanced weight gain in intact mice, but inhibited weight gain in ovariectomized mice. Lower doses of estradiol increased weight gain in orchiectomized mice at early time points. Testosterone increased weight in intact females and males, but not in gonadectomized mice. Estradiol increased nose-to-tail length in intact females at early time points, but inhibited length in ovariectomized females at later times, and it decreased length in intact males. Testosterone increased length in normal females and normal males. Serum Ca was unaffected by ovariectomy, but orchiectomy resulted in decreased levels. Estradiol reduced serum Ca in gonadectomized animals; serum Ca was increased by estradiol treatment in intact females. Changes in tibial bone weight, ash weight and mineral composition, and relative sizes of epiphyseal and metaphyseal bone were gender-, gonadectomy- and hormone-specific. Bone weight was greater in ovariectomized mice. Ash weight per bone was comparable, but there was an increase in Ca and P content with ovariectomy. Estradiol increased bone weight, ash content, and bone Ca and P in ovariectomized and intact females. Orchiectomy alone did not alter bone weight, ash content, or Ca and P, but orchiectomized mice were sensitive to estradiol; all parameters were increased in the orchiectomized animals treated with estradiol. Analysis of the ash content and Ca and P per mg bone, rather than per bone, demonstrated estradiol and testosterone alter net bone formation, but not the amount of mineral per unit bone. Ovariectomy increased hypertrophic cartilage. While estradiol did not alter tibial area in ovariectomized mice, it caused an increase in intact females. The total amount of growth plate cartilage in ovariectomized animals was decreased by estradiol to levels typical of intact animals due to a greater decrease in the hypertrophic cartilage in the ovariectomized mice, as well as a greater increase in metaphyseal bone area. Testosterone had no effect on these parameters in the females. Orchiectomy decreased the amount of growth plate cartilage, but increased the hypertrophic zone.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Phencyclidine- and dizocilpine-induced hyperlocomotion are differentially mediated.

The dopamine (DA) D2 agonist quinpirole and the D2 receptor antagonists, haloperidol, raclopride, and remoxipride, were examined for their ability to block the locomotion induced by the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists phencyclidine (PCP) and dizocilpine, both given in equipotent doses. Quinpirole, given in a "DA D2 autoreceptor selective" dose (0.01 mg/kg), failed to influence the motor stimulation by PCP. On the other hand, the locomotor response induced by dizocilpine was significantly reduced by quinpirole. The three DA receptor antagonists blocked dose dependently the motor stimulation produced by both the low (2 mg/kg) and the high dose (3 mg/kg) of PCP. Haloperidol and remoxipride also blocked dose dependently and fully the stimulation produced by the low dose (0.1 mg/kg) of dizocilpine, whereas raclopride partially reduced the effect. The motor stimulation produced by the high doses of dizocilpine (0.2 mg/kg) and PCP (3 mg/kg) was reduced by haloperidol and raclopride only in cataleptogenic doses. Remoxipride, in contrast, fully blocked the effects of both PCP (3 mg/kg) and dizocilpine (0.2 mg/kg) in noncataleptogenic doses. These data suggest that different mechanisms of action may account for the motor stimulatory effects of PCP and dizocilpine. At the presynaptic level, PCP and dizocilpine may differ in the way they act on "regulatory" NMDA receptors controlling neuronal activity in midbrain neurons, and at the postsynaptic level they may interact with subtypes of NMDA receptors differentially coupled to subpopulations of D2 receptors.

Analysis of Variance↗
PubMed1994

Consistent condom use in relationships between seropositive injecting drug users and sex partners who do not inject drugs.

OBJECTIVES: To study how condom use in injecting drug users' (IDU) relationships differs according to whether they are HIV-infected, and to whether their sex partner is an IDU. DESIGN AND METHODS: A total of 317 street-recruited IDU were HIV-antibody tested and interviewed about 421 relationships with particular sex partners. RESULTS: Condoms were consistently (100%) used in sex between partners (during the previous 30 days) in 33% of these relationships, and their use was significantly more frequent in relationships of seropositive IDU and in relationships with non-IDU partners. In relationships between seropositive IDU and non-IDU, consistent condom use was reported to be high (68%); this remained unchanged under multivariate controls. CONCLUSIONS: Self-reported condom use by IDU in New York, with its relatively mature epidemic, appears to be concentrated where it may most reduce the spread of HIV to non-IDU heterosexuals, i.e., in relationships between infected IDU and non-IDU partners. Differential condom use by serostatus and by partners' drug injection should be incorporated into mathematical models of the HIV epidemic. Causes of the high level of condom use in this subset of relationships may include drug injector altruism and pressure by sex partners; prevention programs should develop ways to use both of these factors to motivate increased condom use.

Adult↗
PubMed1994

Success rates in producing sympathetic blockade by paratracheal injection.

OBJECTIVE: Cervical paratracheal local anesthetic injections (stellate ganglion blocks) are performed to determine the sympathetic contribution to painful and other conditions of the head, neck, and arm. A block is useful for diagnosis only if the desired physiological effect is confirmed, but the frequency with which sympathetic function is successfully blocked is unclear. The goal of this study is to examine the rates of achieving various endpoints of sympathetic interruption by these injections, using commonly available measures of sympathetic change. DESIGN: Retrospective review. SETTING: Training center. PATIENTS: One hundred unselected consecutive blocks in 40 patients. INTERVENTION: Paratracheal sympathetic block at sixth cervical level. OUTCOME MEASURES: Bilateral hand temperature, ophthalmic changes. RESULTS: Horner's syndrome was successfully produced in 84 blocks and the ipsilateral hand warmed by > or = 1.5 degrees C in 60 blocks. However, the contralateral hand also warmed in 31 blocks so that ipsilateral warming exceeded contralateral warming in only 27 blocks, with diminished success by this criterion when the hand was warm before the block. CONCLUSIONS: We conclude that (a) identifying a Horner's syndrome and ipsilateral warming are not by themselves adequate to confirm selective sympathetic blockade; (b) selective sympathetic blockade of the arm is confirmed only if the temperature increase of the blocked side exceeds that of the contralateral side; and (c) cervical paratracheal blocks frequently fail to produce evidence of sympathetic interruption to the arm. Pathophysiological inferences based on these blocks should be made with caution and only with adequate documentation of physiological evidence of sympathetic blockade.

Anesthesia, Local↗
PubMed1994

Cardiovascular effects of hypoxia/hypercarbia and tension pneumothorax in newborn piglets.

OBJECTIVES: To test the hypothesis that, in newborn piglets, the presence of a tension pneumothorax modifies the cardiovascular responses to hypoxia/hypercarbia. DESIGN: Prospective laboratory study. SETTING: Perinatal cardiovascular research laboratory at a university school of medicine. SUBJECTS: Seven newborn piglets. INTERVENTIONS: We sequentially exposed the piglets to a baseline (control I) measure, hypoxia/hypercarbia, tension pneumothorax with normoxia/normocarbia, and tension pneumothorax with hypoxia/hypercarbia added. MEASUREMENTS AND MAIN RESULTS: Brain and systemic blood pressures and blood flow (radionuclide-microspheres) were measured. Hypoxia/hypercarbia resulted in increased brain perfusion (207 +/- 61% of control, mean +/- SEM, p < .05) and heart perfusion (176 +/- 58% of control, p < .05) and decreased gastrointestinal perfusion (-37 +/- 9% of control, p < .05). Tension pneumothorax with normoxia/normocarbia reduced the cardiac output (-70 +/- 8% of control, p < .05), which was redistributed toward the brain (p < .05) at the expense of the gastrointestinal tract (p < .05). Although this redistribution in cardiac output persisted during tension pneumothorax with hypoxia/hypercarbia added, sustained reductions in cardiac output (-57 +/- 11%, of control, p < .01) were associated with smaller increases in perfusion to brain (55 +/- 54 vs. 207 +/- 61% of control, tension pneumothorax with hypoxia/hypercarbia added, and hypoxia/hypercarbia time periods, respectively, p < .05) and heart (65 +/- 49 vs. 176 +/- 58% of control, tension pneumothorax with hypoxia/hypercarbia added, and hypoxia/hypercarbia time periods, respectively, p < .05) and larger decreases in blood flow to gastrointestinal tract, pancreas, and kidneys (p < .05) than with hypoxia/hypercarbia alone. CONCLUSIONS: Tension pneumothorax-induced reductions in cardiac output limit the hypoxia/hypercarbia-mediated increases in perfusion to brain and heart and accentuate the hypoxia/hypercarbia-related decreases in perfusion to kidneys and splanchnic organs.

Analysis of Variance↗
PubMed1994

Inhibitory effects of verapamil on [3H]-acetylcholine release in the central nervous system of Sprague-Dawley rats.

1. The purpose of the present study was to investigate the effects of verapamil, a Ca2+ channel blocker, on acetylcholine (ACh) release in the CNS. 2. Striatal slices of rats, prelabelled with [3H]-ACh, were superfused with Krebs'-Ringer solution. The slices were stimulated by electrical pulses (1 Hz) or by an excitatory amino acid, L-glutamate and the effects of verapamil on the release of ACh were examined. 3. Electrical stimulation produced an increase in [3H]-ACh release from the striatal slices. Exposure of the slices to verapamil significantly inhibited the stimulation-evoked [3H]-ACh release. 4. An endogenous excitatory amino acid, L-glutamate, also elicited the release of [3H]-ACh. Verapamil significantly reduced the L-glutamate-induced release of [3H]-ACh and the inhibitory effect of verapamil was more pronounced in the presence of Mg2+ in the medium. 5. The results of the present study demonstrate that verapamil inhibited both electrically- and chemically-stimulated [3H]-ACh release from the rat striatum. The inhibition of cholinergic transmission by verapamil might be related to the central effect of the Ca2+ channel blocker.

Acetylcholine↗
PubMed1994

Effects of diltiazem on [3H]-acetylcholine release in rat central nervous system.

1. In the present study, we examined the effects of a Ca2+ channel blocker, diltiazem, on [3H]-acetylcholine (ACh) release in the rat CNS. 2. Diltiazem inhibited the electrically stimulated [3H]-ACh release in a dose-related fashion striatal slices of Sprague-Dawley (SD) rats. The basal release of [3H]-ACh was not significantly affected by diltiazem except at a high concentration. 3. The stimulation-evoked [3H]-ACh release was not different between spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. 4. The inhibitory effect of diltiazem on the stimulation-evoked [3H]-ACh release was significantly greater in SHR than in WKY rats. 5. The results show that diltiazem inhibited the stimulation-evoked ACh release in the rat CNS. The pronounced effect of diltiazem in SHR suggests that the inhibition of central cholinergic activity might contribute, at least partially, to the hypotensive mechanisms of the Ca2+ channel blocker.

Acetylcholine↗
PubMed1994

Probability of thrombosis of vascular access among hemodialysis patients treated with recombinant human erythropoietin.

The objective was to evaluate the effect of the treatment of anemia with recombinant human erythropoietin (EPO) on thrombosis of the vascular access used for hemodialysis. The research design was a prospective cohort study comparing EPO-treated hemodialysis patients with a comparison group matched for type of vascular access, clinical center, and age. All patients commencing hemodialysis in the study centers between March 1988 and July 1991 were eligible if either a graft or fistula had been used as a first permanent vascular access. There were 64 matched fistula pairs and 38 matched graft pairs. There were more patients with a history of cardiovascular disease in the EPO group than in the comparison group for both fistulae and grafts, 34 versus 14% for the former and 37 versus 5% for the latter. There was no difference between EPO and comparison groups with respect to time to first thrombosis of fistula, 11.3 versus 10.6%, respectively, by thrombosis of grafts among those treated with EPO--33.6 versus 11.2% (P = 0.02). EPO treatment does not increase the probability of fistula thrombosis, but there is an association with an increased probability of graft thrombosis.

Actuarial Analysis↗
PubMed1994

The Clostridium cellulovorans cellulosome.

The Clostridium cellulovorans cellulosome is comprised of a large, nonenzymatic scaffolding protein called the cellulose binding protein A (CbpA) and a number of endoglucanases/xylanases. The CbpA contains several functional domains, including a signal peptide, a cellulose binding domain (CBD), a hydrophilic domain (HLD) present four times, and a hydrophobic domain (HBD) present nine times. The functions of the domains were studied by the construction of minigenes containing the putative functional domains and by expression of the minigenes in Escherichia coli. The purified product of the CBD was able to bind to various crystalline forms of cellulose and chitin with a Kd of 1 microM. The binding capacity for CBD was a function of the crystallinity of the cellulose sample. Furthermore, the binding of CBD to Avicel was not inhibited by cellobiose or carboxymethylcellulose, suggesting that the CBD binding target was a three-dimensional structure found only in crystalline forms of cellulose. The HBD was tested for its ability to bind endoglucanases by an interaction Western as well as a sandwich enzyme immunoassay technique. The HBD was able to bind both EngB and EngD, indicating that the HBD contained an endoglucanase binding domain (EBD). Because there are nine EBD domains, it is possible that CbpA can bind up to nine endoglucanases. The role of the HLDs remains elusive. The data indicate that the cellulosome is a complex enzyme containing a scaffolding protein (CbpA) to which is attached a number of endoglucanase molecules. This arrangement allows the complex to bind and degrade crystalline cellulose, which resists degradation by the free forms of cellulosomal endoglucanases.

Amino Acids↗
PubMed1994

Dopamine deficiency in a genetic mouse model of Lesch-Nyhan disease.

We have examined several aspects of neurotransmitter function in the brains of mice carrying a deletion mutation in the gene encoding the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). During the first 6 weeks of postnatal development, dopamine levels in whole-brain extracts from the mutant mice (HPRT-) failed to increase at rates comparable to normal animals, resulting in 40% lower dopamine levels throughout adulthood. Regional analysis in adult animals showed the caudoputamen to be the most severely affected region, with dopamine deficits of 48-64%. Dopamine levels in other regions were normal or less severely affected. The decrease in dopamine was accompanied by a decrease in tyrosine hydroxylase (TH) activity, the rate-limiting step in dopamine synthesis. Kinetic analysis of TH extracted from the caudoputamen of normal and HPRT- mice demonstrated a 45% decrease in Vmax with an increased affinity for the tetrahydropterin cofactor in the mutants. Labeling of midbrain dopamine neurons using TH immunohistochemistry revealed no obvious deficits in the number of midbrain dopamine neurons, but quantitative autoradiographic studies revealed significant reductions in the binding of 3H-N-[1-(2-benzo(beta)thiophenyl)cyclohexyl]piperidine (3H-BTCP) to dopamine uptake sites in the forebrain of the mutants. In contrast to these abnormalities of the dopamine systems in the mutant mice, other neurotransmitter systems appeared relatively unaffected. Norepinephrine, 5-HT, tryptophan hydroxylase, and glutamic acid decarboxylase were present at normal levels in the brains of the mutants. ChAT activity was slightly lower than normal in the caudoputamen of the mutant animals, but was normal in all other brain regions examined. These results indicate that HPRT deficiency is associated with a relatively specific deficit in basal ganglia dopamine systems that emerges during the first 2 months of postnatal development.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Glutamatergic regulation of [3H]-noradrenaline release in the medulla oblongata of normotensive and spontaneously hypertensive rats.

OBJECTIVE: To assess in vitro the role of glutamate receptors in the regulation of noradrenaline release from the medulla oblongata of normotensive and hypertensive rats. DESIGN AND METHODS: The effects of L-glutamate (an endogenous ligand for glutamate receptors), glycine (an allosteric agonist for the N-methyl-D-aspartate type of glutamate receptors) and MK-801 (an antagonist for N-methyl-D-aspartate receptors) on [3H]-noradrenaline release were examined in slices of rat medulla oblongata. RESULTS: L-Glutamate elicited [3H]-noradrenaline release from slices of rat medulla oblongata in magnesium-free medium. Glycine also increased the release of noradrenaline. Moreover, the effect of L-glutamate on noradrenaline release was significantly potentiated by glycine. MK-801 inhibited the increase in noradrenaline release evoked by L-glutamate. In spontaneously hypertensive rats (SHR) the facilitatory effect of L-glutamate on noradrenaline release was significantly more pronounced than in Wistar-Kyoto (WKY) rats. Furthermore, glycine alone and in combination with L-glutamate increased the noradrenaline release to a greater extent in SHR than in WKY rats. CONCLUSION: The present results show that the excitatory amino acids might increase noradrenaline release from rat medulla oblongata, which was partially dependent on the N-methyl-D-aspartate type of glutamate receptors. The greater effect of L-glutamate and glycine in SHR suggests that these amino acids might be involved in the regulation of noradrenaline release in the medulla oblongata of hypertension.

Animals↗
PubMed1994

Decade of the brain. An agenda for the nineties.

On July 25, 1989, President George Bush, in response to reports written by the National Advisory Councils of the National Institute of Neurological Disorders and Stroke and the National Institute of Mental Health and at the urging of Congress, signed a presidential declaration designating the 1990s to be the "Decade of the Brain" and called on the United States to observe the decade with appropriate activities. At mid-decade, scientific accomplishment has been spectacular; however, both public support and increases in research resources have been minimal. It can be anticipated that scientific progress will continue to be impressive for the remainder of the decade, but many research opportunities will either not be addressed or will be postponed. At mid-decade, the time has come to re-evaluate the research agenda and the public strategy for the remainder of the decade.

Brain↗
PubMed1994

Improved response to erythropoietin in peritoneal dialysis patients as compared to hemodialysis patients: role of iron deficiency.

Various studies have shown that peritoneal dialysis patients may require less erythropoietin (rHuEPO) than maintenance hemodialysis patients. Iron deficiency in hemodialysis patients may contribute to the difference in response. This study compares the response to rHuEPO in 24 patients on CAPD to 33 patients on hemodialysis. All the hemodialysis patients received intravenous iron to prevent iron deficiency. Peritoneal dialysis patients received rHuEPO subcutaneously twice weekly. Erythropoietin was administered intravenously thrice weekly in hemodialysis patients. In peritoneal dialysis patients, hematocrit was 23.1% and 30.1%, rHuEPO dose was 80.9 and 89.0 u/kg/wk, while in hemodialysis patients hematocrit was 22.2% and 31.2%, and rHuEPO dosage was 140.2 and 154.3 u/kg/wk at initiation, and six months after therapy (p < 0.05 for dose, hemodialysis vs CAPD). Serum iron and transferrin saturation remained normal both in peritoneal and hemodialysis patients. These findings suggest that hemodialysis patients require a higher dosage of rHuEPO than peritoneal dialysis patients for a comparable rise in hematocrit, even when iron deficiency is prevented with parenteral iron. The improved efficacy of rHuEPO in CAPD patients may be due to the better removal of the inhibitors of erythropoiesis and/or the subcutaneous route of administration.

Anemia↗
PubMed1993

Evidence that striatal synthesis-inhibiting autoreceptors are dopamine D3 receptors.

The activation constants (KA; dose required to occupy 50% of receptors) for reversal of gamma-butyrolactone (GBL)-induced elevation of striatal L-3,4-dihydroxyphenylalanine (L-DOPA) levels via stimulation of presynaptic dopamine receptors were determined for apomorphine and two dopamine D3 receptor-selective agonists, quinpirole and LY163502 (quinelorane). The KA values correlated significantly with the affinities (Ki) of the agonists for the D3 (r = 0.999, P < 0.05) but not the D2 (r = -0.13) receptor, suggesting that striatal synthesis-inhibiting autoreceptors are of the D3 rather than the D2 subtype.

4-Butyrolactone↗