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Biomedical subjects

S Goldman

Publications and source records attributed to S Goldman.

At least 235 records · Page 13Linked to original sources
PubMed1993

The effect of epidermal growth factor on growth and differentiation of mouse preimplantation embryos in vitro.

The effect of epidermal growth factor (EGF) on embryonic growth, development, attachment and spreading in vitro was studied. EGF was added to 130 embryos at the 4-cell stage; to 128 embryos at the blastocyst stage; and to 147 embryos 24 h following spreading. Development of embryos from the 4-cell to the blastocyst stage, differentiation of the inner cell mass (ICM) and trophectoderm, and the occurrence of attachment and spreading were evaluated. Embryo development was significantly inhibited in cultures supplemented with 100 ng/ml EGF compared to the controls (P < 0.001). Development of 4-cell embryos to blastocysts occurred in 25% of the EGF group compared to 85% of controls. Spreading occurred in 20% of 4-cell embryos and 30% of blastocysts treated with EGF, compared to 80 and 90% of corresponding controls. In embryos developing from the 4-cell stage, massive growth of the ICM and inhibition of the trophectoderm occurred, whereas both ICM and trophectoderm were inhibited by EGF in embryos developing from the blastocyst stage. Following spreading, EGF caused massive growth of the ICM and regression of the trophectoderm. Our preliminary results show that EGF may be involved in the modulation and control of early embryonic growth and differentiation.

Animals↗
PubMed1993

Combination treatment with captopril and the thyroid hormone analogue 3,5-diiodothyropropionic acid. A new approach to improving left ventricular performance in heart failure.

BACKGROUND: An agent that improves left ventricular (LV) performance by non-cAMP-mediated mechanisms would be valuable in the treatment of chronic heart failure. We have shown earlier that the thyroid hormone analogue 3,5-diiodothyropropionic acid (DITPA) binds to nuclear receptors, alters transcription of T3-responsive genes, and increases +dP/dtmax in hypothyroid rats with substantially less effect on heart rate and metabolism than thyroid hormone, which makes it a selective cardiotonic agent. METHODS AND RESULTS: To determine whether DITPA might be useful in treating heart failure, we compared chronic treatment with normal saline, captopril (2 g/L), or the combination of DITPA (375 micrograms/100 g) and captopril (2 g/L) in Sprague-Dawley rats beginning 3 weeks after coronary artery ligation. Both DITPA/captopril and captopril treatment decreased LV end-diastolic pressure compared with controls (21 +/- 2 and 26 +/- 2 mm Hg, respectively, vs 34 +/- 3 mm Hg, P < .05 for each). The addition of DITPA to captopril produced a 36% increase in resting cardiac index (P < .05) and shifted the cardiac function curve upward and to the left, indicative of enhanced myocardial performance. Also, DITPA/captopril compared with captopril treatment or control produced an increase in the rate of LV relaxation, as manifested by a decrease in tau, the time constant of LV pressure decline (17.5 +/- 1.0 vs 22.2 +/- 1.7 milliseconds, P < .05) and a larger absolute value for -dP/dtmax (-4561 +/- 361 vs -3346 +/- 232 mm Hg/s, P < .05). These changes occurred without changes in heart rate, LV mass, LV systolic pressure, or peripheral resistance relative to captopril treatment (P > .05). CONCLUSIONS: The combination of DITPA and captopril improved cardiac output, increased -dP/dtmax, and increased the rate of LV relaxation to a greater extent than captopril treatment in the rat postinfarction model of heart failure. Use of a cardiotonic analogue of thyroid hormone represents a new approach to improving LV performance and may be a useful adjunct to afterload reduction for the treatment of heart failure.

Animals↗
PubMed1993

Hemibody tremor related to stroke.

BACKGROUND: Hemibody tremor is an uncommon manifestation of stroke. We describe a case investigated by both brain magnetic resonance imaging and positron emission tomography using [18F]fluorodeoxyglucose. CASE DESCRIPTION: Three months after a pure motor stroke, a 65-year-old man developed a right arm and leg tremor. The tremor was of large amplitude, intermittent at rest; its frequency was 5 to 6 Hz. Neither rigidity nor akinesia was detected, and administration of L-dopa was ineffective. Brain magnetic resonance imaging revealed an ischemic lesion in the left centrum semiovale and a left caudate lacunar infarction. We suspected that the resting unilateral tremor was related to this lacunar lesion. Positron emission tomography demonstrated glucose hypermetabolism in the left sensorimotor cortex. CONCLUSIONS: This case suggests that unilateral tremor may be related to a lacunar stroke in the caudate nucleus and may be accompanied by an increased glucose metabolism in the contralateral sensorimotor cortex.

Aged↗
PubMed1993

Positron emission tomography and histopathology in Creutzfeldt-Jakob disease.

We studied a 62-year-old man with Creutzfeldt-Jakob disease (CJD), using positron emission tomography (PET) and (18F)-2-fluoro-2-deoxy-D-glucose (FDG). Glucose metabolism was heterogeneously decreased throughout the brain. At autopsy, regional distributions of spongiosis, astrogliosis, and neuronal loss correlated with premortem regional metabolic deficits. These results suggest that PET with FDG may provide metabolic regional markers for CJD neuropathology.

Brain↗
PubMed1993

[Effect of captopril on mortality and morbidity in patients with dysfunction of the left ventricle after myocardial infarction. Results on survival and hypertrophic studies].

Left ventricular dilation and dysfunction after myocardial infarction are major predictors of death. In experimental and clinical studies, long-term therapy with captopril, an angiotension-converting enzyme inhibitor, decreased ventricular dilation and rearrangement. This study was undertaken to examine whether captopril may reduce morbidity and mortality in patients with left ventricular dysfunction following myocardial infarction. On days 3 to 16 after myocardial infarction, 2231 patients with <40% ejection fraction, but without signs of obvious heart failure ot symptoms of myocardial ischemia were studied in a double-blind study, of them 1116 took placebo and 1115 had captopril. The follow-up averaged 42 months. The mortabity due to any causes was significantly lower in the captopril group (228 deaths or 20% than in the placebo group (275 deaths or 25%). The decrease in the risk was 19 percent (95 percent confidence interval, 3 to 32 percent; p = 0.019). The incidence of fatal and grave nonfatal cardiovascular events significantly decreased in captopril-treated patients. The risk decrease was 21 percent (95 percent confidence interval, 5 to 35 percent; p = 0.014) for cardiovascular mortality; 37 percent (95 percent confidence interval, 20 to 50 percent; p < 0.001) for the development of severe heart failure; 22 percent (95 percent confidence, 4 to 37 percent, p = 0.019) for congestive heart failure requiring hospitalization; 25 percent (95 percent confidence interval, 5 to 40 percent; p = 0.015) for recurrent myocardial infarction. Thus, long-term captopril use in patients with asymptomatic left ventricular dysfunction following prior myocardial infarction resulted in survival improvement and decreased morbidity and mortality due to severe cardiovascular events. There were positive results both in patients treated with thrombolytics, aspirin or <$Ebeta>-blockers and in those untreated with the above drugs. This suggests that the use of captopril additionally improved the therapeutic outcomes in patients with prior myocardial infection.

Adrenergic beta-Antagonists↗
PubMed1993

Effects of chemotherapy and irradiation on the gonads.

As the survival of children with cancer improves, attention must now be focused on understanding and preventing long-term toxicities of treatment and improving the quality of survival. Gonadal toxicity is relatively common, particularly with radiation therapy and alkylating agents. Continued research into the pathogenesis and prevention of gonadal toxicities needs to be included in future treatment strategies for childhood cancer. This will require a multidisciplinary approach with input from pediatric hematologist/oncologists, radiation oncologists, and pediatric endocrinologists.

Adolescent↗
PubMed1993

Acetazolamide-responsive hereditary paroxysmal ataxia: report of a new family.

Five family members were examined because of occurrence since childhood of recurrent episodes characterized by vertigo, dysarthria and gait ataxia. Analysis of the pedigree was consistent with an autosomal dominant mode of inheritance. Though asymptomatic between attacks, all the patients presented on examination a gaze-evoked and rebound nystagmus associated with a saccadic pursuit, a deficient optokinetic response and an inability to suppress the horizontal oculo-vestibular reflex by fixation; hypermetric saccades and truncal ataxia were also present in most of them. A sixth family member, aged 6 years, was found to present a gaze-evoked nystagmus but was completely asymptomatic. Response of the attacks to acetazolamide therapy (250 mg twice a day) was assessed in two patients and was either partial or complete. A positron emission tomography (PET) study was realized between ataxic spells in one patient and demonstrated a decrease of glucose metabolism in the whole cerebellum, the inferior part of the temporal lobes and the thalami. These PET data as well as the detailed neuro-ophthalmological findings bring new informations about acetazolamide-responsive hereditary paroxysmal ataxia, a rare but probably often misdiagnosed and treatable disorder.

Acetazolamide↗
PubMed1993

Role of autotransplantation in neuroblastoma.

Neuroblastoma is the most enigmatic disease treated by pediatric oncologists. The same pattern of apparent metastatic spread is associated with a high rate of spontaneous regression in children under 1 year of age (stage IVS) but an invariably fatal course in older children. For these children with truly advanced neuroblastoma, recent studies have demonstrated that the possibility of complete remission and disease-free survival is increased with more intensive conventional combination chemotherapy. Supportive care with autologous marrow has enabled further significant dose escalation of cytotoxic therapy active against neuroblastoma, resulting in disease-free survival in between 25% and 50% of patients at 2 years, an improvement over historical experience with conventional chemotherapy. The development of more effective cytotoxic combinations active against neuroblastoma, improvements in ex vivo techniques to purge marrow of neuroblastoma cells, and the application of cytokines to hasten marrow recovery should further enhance the effectiveness of autotransplantation in the treatment of advanced neuroblastoma and further improve the chances for complete remission and longer remission duration. Whether this improved remission induction and duration will translate into an increased cure rate remains to be determined. Parallel advances in therapies not involving autologous marrow support will undoubtedly modify the role of autotransplantation in neuroblastoma. Currently, however, autotransplantation offers one potential solution to a major challenge in the treatment of advanced neuroblastoma--obtaining and maintaining complete remissions--and a promising basis for future therapeutic studies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

A role of fatty acid oxidation in cardiac hypertrophy.

Following a myocardial infarction the patient with a dilated heart is at greater risk for arrhythmias, congestive failure and sudden death. Studies of myocardial infarction in experimental animals have shown that, with infarcts involving up to 20% of the left ventricle, hypertrophy of surviving myocytes occurs and there are minimal hemodynamic changes. Infarctions greater than 20% induce little additional hypertrophy, and develop increased left ventricular filling pressures and cardiac dilatation. It has been suggested that inadequate hypertrophy of residual myocardium may be a reason for the progressive left ventricular dilatation which occurs after large myocardial infarcts. There are data in humans and animals suggesting that the mass of the left ventricle following a myocardial infarction correlates with improvement in systolic function. Studies from our laboratories have previously shown that 2-tetradecylglycidic acid, an inhibitor of carnitine palmitoyl transferase I, inhibits mitochondrial long-chain fatty acid oxidation and causes myocardial hypertrophy when given to rats by mouth for 7-28 days. We carried out studies to see whether induction of additional myocardial hypertrophy by means of feeding tetradecylglycidic acid might prevent pathologic dilation following a large (50%) infarct in rats. Treatment of control and infarcted rats with tetradecylglycidic acid for 10 days resulted in myocardial hypertrophy in both groups. The rats with myocardial infarction treated with tetradecylglycidic acid had an increase in peak developed left ventricular pressure during abrupt aortic occlusion and lower left ventricular end-diastolic volumes, when compared to untreated rats with myocardial infarction, while the stroke volume was maintained. Thus induction of myocardial hypertrophy with an inhibitor of long-chain fatty acid oxidation retarded the process of left ventricular dilatation and had beneficial effects on systolic function following a large myocardial infarction.

Animals↗
PubMed1993

First year experience using the Fischer ZD-Neurosurgical Localizing Unit with particular reference to the development of PET-guided stereotactic biopsy.

Initial experience using the Fischer ZD-Neurosurgical Localizing Unit is reviewed. During the first year, 26 stereotactic procedures were performed in 25 patients. Twenty-two patients underwent imaging-guided stereotactic biopsy. Among them, 20 were included in the protocol we have developed for combined positron emission tomography (PET)- and computerized tomography (CT)-guided stereotactic biopsy. The technique is briefly described and preliminary results are reported. Most low-grade tumors were found in hypometabolic/hypodense areas, glioblastomas were all diagnosed in areas with increased FDG uptake and contrast enhancement on CT while data for anaplastic astrocytomas were heterogeneous. Some of the biopsic trajectories performed in areas were there was no increased FDG uptake or in areas with increased FDG uptake but without contrast enhancement on CT were non diagnostic. This never occurred in areas with both increased FDG uptake and contrast enhancement. Other stereotactic procedures performed include 2 catheter placement for drainage of cystic lesions, 3 stereotactically guided open neurosurgical procedures and 1 third ventriculostomy. Procedural objectives were accomplished in all cases. From our experience, we found stereotactic procedures using this system safe, accurate, easy to handle and allowing a wide range of applications. Because the system is designed to be readily used in conjunction with modern planar imaging techniques (i.e. CT and magnetic resonance imaging), it allowed us to develop a technique for PET-guided biopsy which might increase the diagnostic yield of stereotactic biopsy of intracranial neoplasms.

Adolescent↗
PubMed1993

Mechanism of death in heart failure. The Vasodilator-Heart Failure Trials. The V-HeFT VA Cooperative Studies Group.

BACKGROUND: The Vasodilator-Heart Failure Trial (V-HeFT) data base provides information on the mechanism of death of male veterans entered into two trials that evaluated the effect of vasodilator therapy on survival in heart failure. METHODS AND RESULTS: Men aged 18-75 years with heart failure were recruited at 13 Department of Veterans Affairs Medical Centers. In V-HeFT I, 283 of 642 patients (44%) died during follow-up (average, 2.3 years), and in V-HeFT II, 285 of 804 randomized patients (35.5%) died during follow-up (average, 2.5 years). Mechanism of death was established centrally using a standardized classification. In V-HeFT I, 124 of the 283 deaths (43.8%) were sudden with no worsening of symptoms; in V-HeFT II, 104 of the 285 deaths (36.5%) were sudden. An average of 31.5% of the deaths (31.4% and 31.6%, respectively) in the two trials was due to pump failure. The proportion of sudden deaths that occurred without worsening of symptoms was similar in patients with and without ischemic heart failure. Sudden deaths tended to occur earlier and pump failure deaths later in both V-HeFT studies. There was a trend for a lower percentage of cardiac deaths from pump failure and a higher percentage from sudden death in subgroups with higher peak exercise oxygen consumption (VO2), higher ejection fraction, and lower plasma norepinephrine levels. The proportion of deaths that occurred suddenly was similar in placebo, prazosin, and hydralazine plus isosorbide dinitrate treatment groups but was significantly lower in the enalapril treatment group. In V-HeFT I, measures of cardiac function and VO2 predicted pump failure death and sudden death. In V-HeFT II, VO2 and cardiothoracic ratio were independent predictors of all-cause deaths and pump failure deaths; only ejection fraction was an independent predictor of both pump failure and sudden death. CONCLUSION: Although mechanistically distinct terminal events can be identified in patients with heart failure and physiological measurements can provide some insight into the risk of these disparate events, sudden death and pump failure death both appear largely to be linked to the severity of cardiac dysfunction and symptoms. Strategies to identify individuals for selective preventive therapy are not yet practical.

Cause of Death↗
PubMed1993

Plasma norepinephrine, plasma renin activity, and congestive heart failure. Relations to survival and the effects of therapy in V-HeFT II. The V-HeFT VA Cooperative Studies Group.

BACKGROUND: Congestive heart failure is a clinical syndrome characterized by neuroendocrine activation. Measurements of plasma norepinephrine and plasma renin activity were performed in the Vasodilator-Heart Failure Trial II (V-HeFT II) to characterize the effect of therapy on neuroendocrine activation and to examine the responses to therapy among patients with different degrees of activation. METHODS AND RESULTS: The baseline median plasma norepinephrine value (n = 743) was 490 pg/mL and the baseline median plasma renin activity (n = 737) was 6.9 ng.mL-1 x hr-1. Baseline plasma renin activity and plasma norepinephrine correlated poorly with each other (r = 0.12), implying that these two neuroendocrine systems are being activated by separate processes. By univariate analysis, the logarithms of the plasma norepinephrine (p < 0.0001) and the plasma renin activity (p = 0.01) were significantly related to all-cause mortality. In a multivariate analysis that included other significant univariate prognostic variables (i.e., baseline ejection fraction, peak oxygen consumption during exercise, and cardiothoracic ratio), log plasma norepinephrine but not plasma renin activity remained a significant (p = 0.02) predictor of mortality. Baseline plasma norepinephrine correlated poorly with baseline left ventricular ejection fraction (r = -0.18), peak oxygen consumption (r = -0.15), and cardiothoracic ratio (r = 0.11). Neither the plasma norepinephrine (r = 0.09) nor the plasma renin activity (r = 0.18) was closely associated with a quality of life assessment at baseline. The baseline plasma norepinephrine level in patients randomized to enalapril (mean, 593 +/- 388 [SD] pg/mL; n = 372) and to hydralazine and isosorbide dinitrate (mean, 544 +/- 297 pg/mL; n = 371) were similar. Thirteen weeks after randomization, plasma norepinephrine did not change (-5 +/- 393 pg/mL) in 312 patients randomized to enalapril but increased significantly by 74 +/- 311 pg/mL (p < 0.0001) in 300 patients assigned to hydralazine-isosorbide dinitrate. The plasma norepinephrine increased significantly more in patients assigned to hydralazine-isosorbide dinitrate than those on enalapril at both 13 weeks (p = 0.01) and at 1 year (p = 0.04) (90 +/- 302 pg/mL [n = 240] versus 14 +/- 376 pg/mL [n = 265]). Based on previous reports and examination of survival among several plasma norepinephrine strata, the baseline plasma norepinephrine data were grouped into three relatively homogeneous strata for further analysis. The cumulative mortality was significantly different between the three strata (p < 0.0001). The patients with plasma norepinephrine > 900 pg/mL had a higher mortality than those with corresponding values from 601 to 900 pg/mL or < 600 pg/mL. The survival benefit of enalapril compared with hydralazine-isosorbide dinitrate was most evident in those patients with a plasma norepinephrine value > 900 pg/mL. Although the plasma renin activity was not strongly associated with survival, patients in the upper quartile (> 16 ng.mL-1 x hr-1) had the worst prognosis. Among this group, the patients on enalapril demonstrated significantly better survival than those on hydralazine-isosorbide dinitrate (p = 0.02). CONCLUSIONS: This study confirms that plasma norepinephrine is an independent predictor of prognosis in patients with congestive heart failure. Hydralazine-isosorbide dinitrate treatment, unlike enalapril treatment, was associated with increased plasma norepinephrine concentration during the first year of follow-up. The enalapril group had a significantly lower mortality, and this survival benefit of enalapril as compared with hydralazine-isosorbide dinitrate was most evident among patients with the most marked neuroendocrine activation. Neuroendocrine activation is an important prognostic factor for patients with congestive heart failure and is an important determinant of the differential response to vasodilators.

Drug Therapy, Combination↗
PubMed1992

A repressor region in the human beta-myosin heavy chain gene that has a partial position dependency.

Expression of the human beta-myosin heavy chain (beta MHC) gene was studied by transient assay in culture and in situ by direct injection of plasmids into adult rat hearts. In this report we describe a unique repressor region located -326/-309 (5'-TTGGTGGTCGTGGTCAGT-3') of the human beta MHC gene that is conserved among the rat, rabbit, and human beta MHC genes. This sequence conferred repression onto heterologous promoters when the sequence was located 5' but not 3' to the promoters. This partial positional dependency suggests that the factor may act by limiting the binding of enhancers, located more proximally, to their DNA binding sites.

Animals↗
PubMed1992

Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators.

BACKGROUND: Left ventricular dilatation and dysfunction after myocardial infarction are major predictors of death. In experimental and clinical studies, longterm therapy with the angiotensin-converting--enzyme inhibitor captopril attenuated ventricular dilatation and remodeling. We investigated whether captopril could reduce morbidity and mortality in patients with left ventricular dysfunction after a myocardial infarction. METHODS: Within 3 to 16 days after myocardial infarction, 2231 patients with ejection fractions of 40 percent or less but without overt heart failure or symptoms of myocardial ischemia were randomly assigned to receive doubleblind treatment with either placebo (1116 patients) or captopril (1115 patients) and were followed for an average of 42 months. RESULTS: Mortality from all causes was significantly reduced in the captopril group (228 deaths, or 20 percent) as compared with the placebo group (275 deaths, or 25 percent); the reduction in risk was 19 percent (95 percent confidence interval, 3 to 32 percent; P = 0.019). In addition, the incidence of both fatal and nonfatal major cardiovascular events was consistently reduced in the captopril group. The reduction in risk was 21 percent (95 percent confidence interval, 5 to 35 percent; P = 0.014) for death from cardiovascular causes, 37 percent (95 percent confidence interval, 20 to 50 percent; P less than 0.001) for the development of severe heart failure, 22 percent (95 percent confidence interval, 4 to 37 percent; P = 0.019) for congestive heart failure requiring hospitalization, and 25 percent (95 percent confidence interval, 5 to 40 percent; P = 0.015) for recurrent myocardial infarction. CONCLUSIONS: In patients with asymptomatic left ventricular dysfunction after myocardial infarction, long-term administration of captopril was associated with an improvement in survival and reduced morbidity and mortality due to major cardiovascular events. These benefits were observed in patients who received thrombolytic therapy, aspirin, or beta-blockers, as well as those who did not, suggesting that treatment with captopril leads to additional improvement in outcome among selected survivors of myocardial infarction.

Adult↗
PubMed1992

Ontogeny of cholecystokinin receptors in the human striatum.

The distribution of cholecystokinin binding sites was studied by receptor autoradiography in the human striatum at midgestation, birth and adulthood. In the adult, cholecystokinin receptors are inhomogeneously distributed with patches of reduced labeling. In the caudate nucleus but not in the putamen these patches match the striosomal organization as revealed by acetylcholinesterase staining. At midgestation, patches of high density of cholecystokinin receptors are in register with the dopamine D1 receptor-enriched striosomes. At birth, this striosomal organization has already evolved into the adult pattern of higher matrix level in contrast to the striosomal pattern of acetylcholinesterase staining.

Acetylcholinesterase↗
PubMed1992

Induction chemotherapy with carboplatin and 5-fluorouracil in combination with radiotherapy in loco-regionally advanced epidermoid carcinoma of the anus--preliminary results.

During the last decade conservative treatment of anal carcinoma based on radiotherapy has gained popularity. Radiotherapy is often combined with concurrent chemotherapy although no firm evidence exists that such combinations are more effective than radiotherapy alone. Treatment results with respect to anal sphincter function are generally better for small tumors. In an effort to improve the treatment results for locally advanced epidermoid anal carcinoma, a selection of patients with such tumors has been treated with induction chemotherapy comprising two or three courses of a combination of carboplatin 300-350 mg/m2 i.v. and 5-fluorouracil 1,000 mg/(m2 x d) x 5 d prior to radiotherapy. Six female patients aged 37 to 74 have completed the regimen. All had complete tumor regressions at conclusion of radiotherapy. No recurrence has yet occurred but the follow-up period is still short (8-21 months). No interruption of chemotherapy due to toxic side effects was necessary and no severe toxicity registered. Further study is needed to evaluate the efficacy and toxicity of the regimen, but these early findings are promising.

Adult↗