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Biomedical subjects

M Goldstein

Publications and source records attributed to M Goldstein.

At least 235 records · Page 13Linked to original sources

The no-scalpel vasectomy.

A refined method of delivering the vas deferens for vasectomy has been developed and used in China since 1974. This method eliminates the scalpel, results in fewer hematomas and infections, and leaves a smaller wound than conventional techniques. An extracutaneous fixation ring clamp encircles and firmly secures the vas without penetrating the skin. A sharp curved hemostat punctures and dilates the scrotal skin and vas sheath. The vas is delivered, cleaned and occluded by the surgeon's preferred technique. The contralateral vas is delivered through the same opening. The puncture wound contracts to about 2 mm., is not visible to the man and requires no sutures for closure. The reported incidence of hematoma in 179,741 men followed in China was 0.09%. No hematomas or infections were identified in the first 273 procedures performed by a surgeon in the United States. The operating time in China and for the last 50 United States procedures has ranged from 5 to 11 minutes. The disadvantage of the technique is the hand-on training and number of cases necessary to gain proficiency. However, the advantages for surgeons and patients should enhance the popularity of vasectomy.

Anesthesia, Local↗

Basic FGF is present in dopaminergic neurons of the ventral midbrain of the rat.

Immunocytochemistry procedures and 6-hydroxy-dopamine-induced degeneration of dopamine nerve cells provided evidence that practically all tyrosine hydroxylase immunoreactive (IR) neurons of the substantia nigra and ventral tegmental area contain cytoplasmic basic fibroblast growth factor immunoreactivity (bFGF IR), while many astroglial cells in the neostriatum and substantia nigra contain nuclear bFGF IR. RNA blot analysis demonstrated strong expression of a major 3.7 kb bFGF mRNA in the substantia nigra and ventral tegmental area. These results indicate that bFGF may be a significant growth factor in the DA neurons.

Animals↗

A bioinformational systems perspective on tobacco dependence.

Recent thinking about tobacco dependence has been influenced largely by a focus on the pharmacological effects of nicotine. We advocate a return to earlier views of dependence as comprising both pharmacological and non-pharmacological aspects. Moreover, we suggest that it may be profitable to reformulate research on dependence in terms of a bioinformational process model. The basic tenets of such a model are outlined, as are the challenges in exploring the nature of dependence simultaneously across the cognitive, physiological and behavioral domains of function.

Arousal↗

Tyrosine hydroxylase mRNA expression by dopaminergic neurons in culture: effect of 1-methyl-4-phenylpyridinium treatment.

To enable us to study expression of tyrosine hydroxylase [TH; tyrosine 3-monooxygenase; L-tyrosine tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2] as a measure of dopaminergic neuron function in future experiments, methods were developed to quantify TH mRNA levels in cultures of dopaminergic mesencephalic cells. The model of selective dopaminergic toxicity of 1-methyl-4-phenylpyridinium (MPP+) was used to verify the specificity of our methods. Fetal (embryonic day 15) rat ventral mesencephalic cell cultures were treated with 15 microM MPP+ for 48 h, conditions previously shown to reduce the number of TH-immunoreactive neurons, TH activity, and dopamine uptake to 5-10% of control values. This treatment decreased the number of neurons labeled by TH in situ hybridization to 9% of untreated controls and caused a strong reduction of the abundance of TH mRNA in Northern blots. Our findings establish TH mRNA expression as a parameter for future studies of toxic and trophic effects on cultured dopaminergic neurons, and they support the view that MPP+ destroys dopaminergic neurons.

1-Methyl-4-phenylpyridinium↗

Integration of conservative surgery, radiotherapy, and chemotherapy for the treatment of early-stage, node-positive breast cancer: sequencing, timing, and outcome.

The optimal means of combining breast-conserving surgery, radiation therapy, and chemotherapy for the treatment of patients with early-stage, node-positive breast cancer is not known. We reviewed the results in 295 patients treated at the Joint Center for Radiation Therapy and affiliated institutions from 1976 to 1985. All patients had positive axillary nodes on dissection, had no gross residual disease in the breast or axilla after surgery, and received breast irradiation (with or without nodal irradiation) and three or more cycles of a cyclophosphamide, methotrexate, and fluorouracil (CMF)-based or doxorubicin-containing regimen. Median follow-up in patients without any failure was 78 months. Breast failure rates were assessed in relation to the sequencing of radiotherapy and chemotherapy. The different sequences were not randomly assigned, and the characteristics of the sequence groups differed. The actuarial 5-year breast failure rate was 4% in 99 patients receiving radiotherapy before chemotherapy; 8% in 54 patients sequentially receiving some chemotherapy, then radiotherapy without concurrent chemotherapy, then further chemotherapy; and 6% in 116 patients receiving concurrent chemotherapy and radiotherapy. However, the failure rate was 41% in 26 patients who received all chemotherapy before radiotherapy. The crude incidences of local failure within 4 years of treatment in these groups were 3%, 2%, 4%, and 15%, respectively (P = .065 for all four groups not being the same). The actuarial 5-year local failure rate was 5% for 252 patients irradiated within 16 weeks after surgery compared with 35% for 34 patients irradiated more than 16 weeks after surgery. The 4-year crude incidences were 4% and 12% for the two groups, respectively (P = .06). These results suggest that delaying the initiation of radiotherapy may result in an increased likelihood of local failure. Formal randomized controlled trials will be needed to confirm these results and to improve the integration of these treatment modalities.

Actuarial Analysis↗

Direct and sex-specific enhancement of bone formation and calcification by sex steroids in fetal mice long bone in vitro (biochemical and morphometric study.

The study was carried out to examine the direct effect of the sex hormones 17 beta-estradiol (E2) and testosterone on the modeling of cultured fetal mouse long bones separated according to their sex. The culture system used allowed for the simultaneous assessment of bone growth, mineralization, and resorption on each bone. Bones from 16-day-old male and female mouse fetuses were cultured in BGJ medium, supplemented with either 10% fetal calf serum or 4 mg/ml BSA (serum-free medium) for 48 h. The bones were harvested, and their length; the length of their diaphyses; their hydroxyproline, calcium, and phosphorus contents; and their 45Ca release were measured. Histomorphometric analyses on midlongitudinal sections of bones from parallel experiments were also performed. The results indicate that in medium supplemented with 10% fetal calf serum, E2 had a dose-dependent stimulatory effect on bone formation and mineralization at 10(-7) and 10(-9) M, with no effect on bone resorption. This effect was specific to bones from female mice and to E2, since 17-alpha-estradiol had no effect. Testosterone had similar effects specific to bones from male mice, resulting in the stimulation of bone formation and mineralization at 10(-7)- and 10(-9)-M concentrations. These effects were absent when serum-free medium was used. E2 and testosterone had an anabolic effect on endochondral and periosteal bone formation and mineralization, but no effect on bone resorption. This effect is dependent on the presence of a serum factor(s).

Animals↗

Alterations in catecholamine release in the central nervous system of spontaneously hypertensive rats.

The aim of the present study was to investigate alterations in catecholamine release in the central nervous system of spontaneously hypertensive rats. Slices of hypothalamus, medulla oblongata and striatum were prepared from spontaneously hypertensive rats (SHR: 9-10 weeks old) and age-matched Wistar Kyoto rats (WKY). The slices were incubated with (3H)norepinephrine (NE) or (3H)dopamine (DA), superfused with Krebs-solution in vitro, and the release of the catecholamines was compared between the two strains. The basal release of hypothalamic (3H)NE did not differ between SHR and WKY slices. However, stimulation (1 Hz)-evoked (3H)NE release was significantly greater in SHR than in WKY (percent fractional release of total tissue NE: WKY 0.494 +/- 0.019%, n = 6, SHR 0.730 +/- 0.053%, n = 6, p less than 0.05). The stimulation-evoked (3H)NE release from the medulla oblongata did not differ significantly between SHR and WKY slices. Finally stimulation-evoked release of striatal (3H)DA was significantly depressed in SHR (percent fractional release of total tissue DA: WKY 2.048 +/- 0.24%, n = 6, SHR 1.460 +/- 0.068%, n = 6, p less than 0.05). These results indicate that the release of hypothalamic NE and striatal DA are altered in SHR. It is suggested that enhanced hypothalamic noradrenergic activity and reduced striatal dopaminergic activity can increase sympathetic outflow to the periphery, which may play a role in the pathogenesis of this form of hypertension.

Animals↗

Isolated coronary artery bypass grafting in one hundred consecutive octogenarian patients. A multivariate analysis.

One hundred consecutive patients aged 80 or older underwent isolated coronary artery bypass grafting for New York Heart Association functional class III (24%) or IV (76%) disease in our institution from 1985 to 1989. The operations were elective in 36 patients, urgent in 52, and emergent in 12. Twenty-eight patients had significant disease of the left main coronary artery, with the remainder having an average of 2.8 diseased coronary vessels. Preoperative left ventricular ejection fraction was considered good (greater than 50%) in 62 patients, fair (30% to 50%) in 24 patients, and poor (less than 30%) in 14 patients. An average of 2.8 grafts were performed per patient, and the internal mammary artery was used in 10 patients. Univariate analysis of 36 perioperative factors followed by multivariate logistic regression analysis of the significant variables (p less than 0.05) revealed that the urgency of the operation and left ventricular ejection fraction were independent predictors of operative mortality. There were 12 in-hospital deaths, and the mortality was significantly lower in the elective cases (2.8%) than in the urgent (13.5%) and emergent cases (33.3%). Major complications occurred in 14% of the elective cases, in 21% of the urgent cases, and in 67% of the emergent cases. The operative mortality rates for good, fair, and poor left ventricular ejection fraction were 4.9%, 12.5%, and 42.9%, respectively. Long-term follow-up averaging 22 months revealed a 77% actuarial probability of survival at 24 months and 51% at 48 months, with only two cardiac-related deaths. We conclude that coronary artery bypass grafting can be performed in octogenarians with a favorable outcome when done electively in patients with normal to moderately depressed left ventricular function.

Aged↗

[The effect of chronic treatment of deprenyl in animal models of Parkinson's disease].

Recent studies have demonstrated that deprenyl can delay the progression of parkinsonian syndrome. Deprenyl selectively and irreversibly inhibits the activity of monoamine oxidase-type B (MAO-B), and subsequent enzyme activity requires de novo synthesis of MAO-B. In this study we investigated (1); the effects of deprenyl on striatal dopamine (DA) levels in MPTP-lesioned and undamaged mice and (2); the effect of deprenyl on L-DOPA induced rotational movements in a hemiparkinsonian model monkey. In MPTP-lesioned mice, deprenyl increased the striatal DA levels by 123%, 78% immediately and one week after termination of deprenyl treatment respectively, while by 31%, 24% in MPTP-undamaged mice, respectively. Four weeks after termination of treatment, and the striatal DA was not significant. It shows that deprenyl is effective in elevation of striatal DA at least one week after termination of treatment, and the degree of increase of striatal DA following deprenyl treatment is greater in MPTP-treated mice than in undamaged mice. Deprenyl seemed to be effective longer in a hemiparkinsonian monkey than in rodents. The result suggests that less frequent administration of deprenyl may be effective in controlling side effects of L-DOPA without reducing therapeutic efficacy.

Animals↗

Nutritional dwarfing: is it a consequence of disturbed psychosocial functioning?

Nutritional dwarfing refers to a condition in which maladaptive eating patterns play a primary role in poor linear growth and delayed pubertal development. The present controlled study assesses whether nutritionally dwarfed children and adolescents differ in their psychosocial adjustment from healthy children and adolescents of comparable height in ways that might account for their undernutrition. Children with nutritional dwarfing (n = 16) were compared by standardized questionnaires with a short-stature (ie, heights below the fifth percentile) control group composed of children and adolescents with constitutional growth delay and/or familial short stature (n = 31). Scores on a self-report screening questionnaire for eating disorders did not differentiate the groups. Moreover, the vast majority of nutritionally dwarfed patients expressed a desire to have a heavier physical appearance. Whereas the groups were generally similar in self-perceptions of domain-specific competencies and positive psychosocial adjustment, the parents of nutritionally dwarfed children reported that their children showed significantly fewer externalized behavior problems. These findings suggest the existence of an eating disturbance that compromises growth in childhood and/or adolescence which, unlike anorexia nervosa, is not associated with evidence of psychopathology.

Adolescent↗

Echocardiographic signs of cardiac rejection during the first week after cardiac transplantation.

The early recognition of acute rejection after heart transplantation remains an important clinical problem. In this study we explored the value of echo-Doppler techniques to identify the rejection during the first week after cardiac transplantation. The study included 22 patients with an average age of 48 +/- 9 years. Ultrasonic measurements were obtained by 2-dimensional 84 degrees phased array sector scanner with pulsed Doppler incorporated. The stroke index (SI), the peak outflow blood velocity pulsed (POBVP), the peak outflow blood acceleration pulsed (POBAP), the peak flow velocity in early diastole (PFVE), the peak flow velocity during atrial systole (PFVA), the PFVA/PFVE ratio, the mitral valve pressure half-time (PHT) and the fractional shortening (FS) were calculated. On the seventh day after transplantation, a percutaneous right ventricular endomyocardial biopsy was systematically performed. For the entire group, the SI, PHT and the FS relation were not significantly influenced during the week of evaluation. The POBVP and the POBAP transiently decreased but returned to baseline on the seventh day. An increment in the PFVA/PFVE ratio was observed in 4 patients, and acute allograft rejection was documented in 3 of them. On day 7 after transplantation, PFVA and PFVA/PFVE were significantly higher in patients with rejection. No patient with normal PFVA/PFVE ratio had allograft rejection. No patient with rejection showed signs of altered systolic function as measured by SI, POBVP, POBAP and FS. These data therefore indicate that the assessment of the diastolic function using Doppler techniques (PFVA/PFVE) can be helpful to detect signs of acute allograft rejection occurring early after heart transplant.

Echocardiography, Doppler↗

Effects of calcitonin gene-related peptide on [3H]norepinephrine release in medulla oblongata of spontaneously hypertensive rats.

We now describe the effects of calcitonin gene-related peptide (CGRP) on [3H]norepinephrine (NE) release in medulla oblongata of spontaneously hypertensive rats (SHR). CGRP inhibited stimulation-evoked [3H]NE release in a dose-dependent manner in Sprague-Dawley rats, although the basal release of [3H]NE was not affected by the peptide. In SHR, the inhibitory effect of CGRP on stimulation-evoked [3H]NE release was significantly attenuated compared with Wistar Kyoto rats. These results suggest that CGRP might be involved in the regulation of central sympathetic nervous activity in hypertension.

Animals↗

Intranigral substance P stimulation of striatal dopamine release is inhibited by spantide II: a new tachykinin antagonist without apparent neurotoxicity.

The effects of intranigral injections of Spantide II, a novel tachykinin antagonist, on extracellular dopamine, and dihydroxyphenylacetic acid (DOPAC) levels in the rat striatum were studied using in vivo microdialysis. The ability of Spantide II to inhibit intranigral substance P or neurokinin A stimulation of striatal dopamine levels was also studied. A unilateral injection (all substances were injected in a volume of 0.2 microliter) of Spantide II (0.7 nmol) into the substantia nigra, pars reticulata (SNR) of halothane anaesthetized rats produced a short-lasting decrease in dopamine levels in the ipsilateral striatum. Striatal DOPAC levels showed no change after Spantide II. A unilateral injection of substance P (0.07 nmol) into the SNR produced an increase in ipsilateral striatal dopamine levels, which was prevented when substance P was co-administered with Spantide II (0.7 nmol). A unilateral injection of neurokinin A (0.09 nmol) into the SNR produced an increase in ipsilateral striatal dopamine levels, which was not modified when neurokinin A was co-administered with Spantide II (0.7 nmol). Immunohistochemical analysis using antisera to tyrosine hydroxylase and neuropeptide K, as well as Cresyl violet staining, revealed that intranigral injections of Spantide II (0.7 nmol) did not produce significant damage in the substantia nigra. The results indicate that Spantide II is not 'neurotoxic' when injected intranigrally, and that it is a selective antagonist of substance P in the substantia nigra. Furthermore, the reduction of striatal dopamine levels after intranigral Spantide II injections suggests that the nigrostriatal dopamine projection is tonically stimulated by striatonigral substance P.

Amino Acid Sequence↗

3-Acetylpyridine results in degeneration of the extrapyramidal and cerebellar motor systems: loss of the dorsolateral striatal dopamine innervation.

3-Acetylpyridine (3-AP) administration to rats results in degeneration of the dopamine (DA) innervation of the striatum as well as degeneration of the olivocerebellar system. We now report that administration of this pyridine neurotoxin results in a decrease in striatal DA concentration which is restricted to the dorsolateral aspects of the caudatoputamen. 3-AP treatment did not alter DA levels in the ventromedial striatum, the nucleus accumbens, or the anteromedial prefrontal cortex. Both 3-AP and another pyridine neurotoxin, 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP), potently inhibited in vitro MAOB activity and in contrast weakly inhibited MAOA activity. However, in vitro inhibition of MAOB by the selective inhibitor deprenyl did not prevent or attenuate 3-AP-induced striatal DA depletion. These data indicate that 3-AP administration to rats not only results in degeneration of the olivocerebellar system, but also effects degeneration of the DA innervation of the dorsolateral striatum, the striatal sector thought to subserve motoric and sensorimotor function. 3-AP-induced nigrostriatal degeneration differs from that elicited by MPTP in that the former is not prevented by deprenyl pretreatment. The 3-AP-induced degeneration of both extrapyramidal and cerebellar motor systems may offer insight into the mechanisms involved in degeneration of the two motor systems in certain strains of rodents (such as the Weaver mutant mouse), and suggests that the sequelae of administration of this pyridine may serve as a useful model for olivopontocerebellar atrophy-associated parkinsonism.

Animals↗

Evidence for the existence of angiotensin II like immunoreactivity in subpopulations of tyrosine hydroxylase immunoreactive neurons in the A1 and C1 area of the ventral medulla of the male rat.

By using double immunolabelling techniques the possible coexistence of tyrosine hydroxylase (TH)- and angiotensin II (ANG II)-like immunoreactivities (IR) has been studied within the noradrenaline A1 and adrenaline C1 areas of the ventral medulla of the rat. In the A1 area 20-30% of the TH IR nerve cell bodies were ANG II IR and in the C1 area 5-40% of the TH IR nerve cell bodies displayed ANG II IR. These results suggest the existence of ANG II/NA and ANG II/A costoring neurons in the A1 and C1 group, respectively, opening new possibilities for ANG II-catecholamine interactions in cardiovascular and neuroendocrine regulation.

Animals↗

Effects of neuropeptide Y on norepinephrine release in hypothalamic slices of spontaneously hypertensive rats.

We describe the effects of neuropeptide Y (NPY) on [3H]norepinephrine (NE) release from hypothalamic slices of spontaneously hypertensive rats (SHR). The electrical stimulation (1 Hz)-evoked [3H]NE release was significantly greater in hypothalamic slices of SHR than in those of Wistar Kyoto rats (WKY). NPY inhibited the stimulation-evoked [3H]NE release in a dose-dependent manner. The inhibitory effect of NPY was significantly attenuated in SHR compared with WKY. The results may indicate that the less inhibitory effect of NPY on NE release induces increased sympathetic nerve activity in the hypothalamus of SHR.

Animals↗

Regulation and molecular characterization of dopamine D2 receptors in a prolactin-secreting 7315a anterior pituitary tumor.

The regulation and molecular properties of the dopamine (DA) D2 receptors were compared in the prolactin-secreting 7315a anterior pituitary tumor with those in the striatum of rats. Chronic treatment with haloperidol increases the maximal binding for [3H]spiroperidol in tumor and striatum, but the percent increase is much higher in tumor than in striatum. Photoaffinity labelling of DA D2 receptors with N-(p-azido-m-[125I]iodophenethyl)spiperone ([125I]N3-NAPS) yielded a major specifically labeled peptide with the Mr of 32-34 kDa in tumor, and two specifically labeled peptides with Mr of 32-34 and 92-94 kDa in striatum. The analysis of DA D2 receptor mRNA shows that the size is similar in tumor and striatum. The DA D2 receptor mRNA in tumor is very low and chronic treatment with haloperidol produces a considerable increase of the specific mRNA. It is postulated that the reported defect in regulation of prolactin release by DA agonists might be due to posttranslational changes in the tumor DA D2 receptor.

Animals↗