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Biomedical subjects

R Goldschmidt

Publications and source records attributed to R Goldschmidt.

At least 19 recordsLinked to original sources
PubMed2000

Bacteremic pneumonia due to multidrug-resistant pneumococci in 3 patients treated unsuccessfully with azithromycin and successfully with levofloxacin.

Three patients with bacteremic pneumonia caused by multidrug-resistant Streptococcus pneumoniae were treated unsuccessfully with azithromycin. One S. pneumoniae isolate carried a mef determinant for an efflux pump; a second isolate had an erm determinant. All 3 patients were successfully treated with levofloxacin, an antipneumococcal fluoroquinolone.

Adult↗
PubMed2000

Inhibitors of bacterial two-component signalling systems.

Bacterial two-component regulatory systems (TCS) play a pivotal role in the process of infection. These signal transduction systems enable bacterial pathogens to mount an adaptive response and cope with diverse environmental stresses, including nutrient deprivation, antibiotic onslaught and phagocytosis. Interest in these systems as novel bacterial targets has been rekindled by the recent discovery of several essential systems in important Gram-positive and Gram-negative pathogens. Several series of TCS inhibitors derived from broad screening approaches have been reported in the literature, however, most appear to suffer from poor selectivity, excessive protein binding and/or limited bioavailability. Consequently, pharmaceutical chemists have turned to alternate strategies, such as the design of substrate-based inhibitors, the generation of combinatorial libraries and the isolation of natural products, to identify inhibitors with more desirable properties. Recent structural studies of the histidine protein kinase and response regulator proteins that constitute TCS may provide a foundation for a structure-based design approach to TCS inhibitors.

Animals↗
PubMed2000

Effectiveness of fluoroquinolones against gram-positive bacteria.

Fluoroquinolones are broad-spectrum and therapeutically effective antibacterial agents that have retained high activity against methicillin-susceptible Staphylococcus aureus (MSSA) and streptococci. Primary targets of these agents in Gram-positive bacteria are DNA topoisomerase and DNA gyrase. High-level resistance is associated with at least two mutations in either target, or combinations of at least two mutations in multiple targets, particularly affecting the ParC subunit of topoisomerase IV and the GyrA subunit of DNA gyrase. This resistance may be enhanced when combined with mutations that increase fluoroquinolone efflux. Data from fluoroquinolone-resistant clinical isolates suggest that as yet unidentified mutations may also be involved in clinical resistance.

Animals↗
PubMed1997

Prognostic significance of occult lymph node metastases in node-negative breast cancer.

BACKGROUND: Lymph node status, established by a single hematoxylin and eosin (H&E) section from each node, remains an important prognostic indicator in patients with breast cancer, but used alone it is insufficient to identify patients who will develop metastatic disease. This study was conducted to assess the significance of detecting occult metastases in 86 patients with breast cancer originally reported to be histologically node negative. None of the patients received adjuvant systemic therapy. METHODS: Five additional levels from formalin-fixed, paraffin-embedded nodes were examined at 150-microns intervals with H&E staining and a cocktail of antikeratin antibodies (AE1/AE3) recognizing low molecular weight acidic keratins. RESULTS: Nodes from 11 (12.8%) of 86 patients contained occult metastases. All metastases identified by cytokeratin antibody were also detected in H&E-stained sections. With median follow-up of 80 months, distant metastases occurred in five of 11 occult node-positive patients (45%) and 13 of 75 patients whose nodes were negative on review (17%). Median time to recurrence was 89 months for occult node-positive patients and not yet reached for node-negative patients (p = 0.048). The disease-specific 5-year survival rate was 90% for occult node-positive patients and 95% for node-negative patients. CONCLUSIONS: The presence of occult metastases shortened the disease-free interval and suggested that more diligent axillary staging would more accurately identify patients who would benefit from systemic adjuvant treatment.

Biomarkers, Tumor↗
PubMed1992

Uptake of [3H]serotonin and [3H]glutamate by primary astrocyte cultures. I. Effects of different sera and time in culture.

Na(+)-dependent, fluoxetine-sensitive high-affinity uptake of serotonin and Na(+)-dependent uptake of glutamate were studied in primary astrocyte cultures from 1-day-old rat neocortex. This uptake was independent of time in culture from 1 to 6 weeks. High-affinity serotonin uptake was decreased when cells were grown in horse serum as compared to fetal bovine serum and was almost absent when cells were grown in chemically defined medium. In contrast, glutamate uptake was unaffected by the composition of the medium in which the cultures were grown. The serum effect on serotonin uptake was not due to the greater level of serotonin in the fetal bovine serum and was only reversed by a change of serum over a time period of days.

Animals↗
PubMed1992

Prevalence of HIV antibodies in transsexual and female prostitutes.

Human immunodeficiency virus (HIV) prevalence was studied in an unselected group of 216 female and transsexual prostitutes. Subjects were asked about age, biological sex, marital status, children, length of occupation, sexual practices, and drug abuse history. Blood was drawn on site. All 128 females who did not admit to drug abuse were seronegative; 2 of the 52 females (3.8%) who admitted to intravenous drug abuse were seropositive. In contrast, 11.1% of the 36 male transsexuals (including 3 out of 32 non-drug abusers) were seropositive. The results support the notion that vaginal transmission of HIV is less effective than anal transmission.

Adolescent↗
PubMed1989

Biological grading of breast cancer using antibodies to proliferating cells and other markers.

Quantitation of immunohistochemical staining by image analysis was performed on 50 breast cancers stained with the monoclonal antibody Ki-67 to determine the growth fraction and its correlation with tumor grade. A high degree of correlation was shown. For each case the DNA ploidy was determined by quantitation of the DNA Feulgen stain by computerized microdensitometry. DNA content of breast tumor cells correlated to the histopathologic grade at which poorly differentiated tumors are more likely to be aneuploid. Quantitation of immunohistochemistry for estrogen and progesterone receptors had a high degree of correlation with the steroid binding assay, such as dextran-coated charcoal assay (DCCA), and were weakly correlated to histologic grade. In summary, our results indicated that quantitation of Ki-67-positive nuclear area and of DNA content by image analysis provides an objective method for assessing tumor cell growth fraction and DNA ploidy. Quantitation of steroid receptors by immunohistochemistry is a better and easier technique than those currently used to determine the best therapy for postmenopausal women. These methods can be performed on small frozen sections or needle aspirates in quantities that are insufficient for current steroid binding assays. Thus, this method is prognosticly useful even for patients with small breast lesions.

Antibodies, Monoclonal↗
PubMed1986

Effect of ganglioside treatment on number of nerve fibres after nerve crush in rats.

The sciatic nerve of the left hind leg of male Wistar rats was crushed using a standardized procedure. From the day of the crushing onwards rats were treated subcutaneously with 10 mg/kg of a ganglioside mixture and compared with a control group which received phosphate buffer only. From day 5 to 20 after nerve damage, histological evaluation of the sciatic nerve was performed and the number of nerve fibres determined. We found that from day 12 onwards on all days of observation the number of fibres was higher in the ganglioside-treated group than in the control group. The number of nerve fibres as a criterion of regeneration was statistically significant at days 12, 13 and 15 compared to control animals.

Animals↗
PubMed1984

Effect of gangliosides on nerve regeneration in rats.

The objective of the study was to investigate the effects of gangliosides on the regeneration of the sciatic nerve after a crush injury in the rat. After a temporary complete interruption of axonal conduction, nerve conduction velocity was again measurable on the 13th day. On that day and at all subsequent measuring times, the conduction velocity of the damaged nerves was greater in the ganglioside-treated rats than in the control animals which were treated only with the solvent and reached significant values on day 15 and 18.

Action Potentials↗
PubMed1983

Reversible inhibition of poxvirus replication by cycloheximide during the early phase of infection.

Infection of primary chick embryo fibroblasts with Vaccinia WR, IHD-W, and cowpox virus even at high m.o.i. does not cause drastic early inhibition of host cell protein synthesis. This contrasts with the infection by these viruses of many eucaryotic cells. Cellular protein synthesis of mouse L cells is also only partially inhibited after infection with cowpox virus up to a m.o.i. of 2500 e.b. As predicted by Moss and Filler (1970, J. Virol. 5, 99-108) no irreversible inhibition of poxvirus replication is observed in these cells following the addition of cycloheximide early after infection. The viral cores which accumulate in chick embryo fibroblasts in the presence of cycloheximide are further uncoated after removal of the protein synthesis inhibitor. These poxvirus host cell systems can be used to identify in vivo immediate and putative delayed early viral gene products. Formation of progeny virus, viral DNA synthesis, the sequential formation of viral proteins, and sensitivity to interferon has been demonstrated in chick embryo fibroblasts after reversal of the cycloheximide block. These studies indicate a synchronized replication cycle of poxvirus after reversal of the cycloheximide block.

Animals↗
PubMed1983

Mechanisms of colchicine neurotoxicity in the dentate gyrus: dissociation of seizures and cell death.

Extracellular field potentials and the EEG were studied in the dentate gyrus of the rat after intrahippocampal injections of colchicine, which is a relatively selective neurotoxin for dentate granule cells. Injection of colchicine (0.5 microliters of a 5-mg/ml solution of colchicine in deionized water) resulted in granule cell hyperexcitability manifested by multispike field potentials in response to stimulation of the excitatory projections from the entorhinal cortex. In anesthetized rats, this state of granule cell hyperexcitability was occasionally accompanied by interictal epileptic spiking or brief electrographic seizures, but granule cell death was observed even in the absence of epileptic activity. Injection of colchicine into the CA1 area of the hippocampus also resulted in multispike field potentials in response to stimulation of the CA3 commissural pathway, but CA1 pyramidal cells were not destroyed by colchicine. Colchicine has been reported to act as a convulsant agent in the dentate gyrus, but it is a relatively selective neurotoxin for dentate granule cells even in the absence of epileptic activity.

Animals↗
PubMed1982

Infective endocarditis caused by Paecilomyces varioti.

The first reported case of Paecilomyces varioti endocarditis occurring on a porcine heterograft prosthesis is presented and the clinical and pathological features described in the four previously reported cases of prosthetic valvular endocarditis caused by this organism are reviewed. In each case, infection became apparent more than two months after cardiac surgery. Three of the four patients with infected aortic prosthesis developed outflow obstruction secondary to valvular vegetations. All patients died regardless of medical or surgical intervention. Appropriate therapy remains unknown.

Adult↗