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Biomedical subjects

J Gerber

Publications and source records attributed to J Gerber.

At least 19 recordsLinked to original sources
PubMed1999

Rifampin reduces early mortality in experimental Streptococcus pneumoniae meningitis.

Compared with beta-lactam antibiotics, rifampin releases smaller quantities of proinflammatory cell wall products from Streptococcus pneumoniae in vitro. Mice infected intracerebrally with S. pneumoniae were treated subcutaneously with 2-mg doses of rifampin or ceftriaxone (n=43 each) every 12 h for 3 days and then observed for another 3 days. Rifampin reduced overall mortality from 49% to 26% (P=.04). Kaplan-Meyer analysis revealed a substantial reduction of mortality during the first 24 h in mice receiving rifampin (difference in survival time: P=.007). Eight h after receiving a single 2-mg dose of rifampin or ceftriaxone, rifampin-treated mice had lower serum and cerebrospinal fluid concentrations of lipoteichoic and teichoic acids than did ceftriaxone-treated mice (median serum level: <0.5 vs. 27.0 ng/mL, P=.02; median cerebrospinal fluid level of pooled specimens: 97.5 vs. 206.0 ng/mL). Thus, the use of rifampin appears promising for reducing the release of proinflammatory bacterial components and decreasing early mortality in bacterial meningitis.

Animals↗
PubMed1999

Serum haptoglobin, CA 125 and interleukin 6 levels in malignant and non-malignant tumors of the ovary.

In sera of women with malignant and non-malignant ovarian tumors, concentrations of the following proteins were determined: haptoglobin, measured by the reactions either with hemoglobin (Hp-Hb) or with concanavalin A (Hp-Con A), CA 125 antigen and interleukin 6 (IL-6). Besides preoperative data, obtained from all the patients and the group of healthy women, in the patients with ovarian cancer (III/IV FIGO stages) effects of administration of cytostatics were measured by monitoring changes in the levels of the examined parameters through the course of the therapy. All the results were submitted to statistical evaluation which showed differences and correlations among definite groups (normal/non-malignant, normal/cancers, non-malignant/cancers). Similar results were obtained for Hp-Hb and CA 125 determination. Moreover, a correlation between haptoglobin level and age was found. Patterns of monitoring revealed a surprising absence of Hp-Con A interaction in some cases.

Adolescent↗
PubMed1998

Contributions of pathway and neuron to preferential motor reinnervation.

Motor axons regenerating after transection of mixed nerve preferentially reinnervate distal muscle branches, a process termed preferential motor reinnervation (PMR). Motor axon collaterals appear to enter both cutaneous and muscle Schwann cell tubes on a random basis. Double-labeling studies suggest that PMR is generated by pruning collaterals from cutaneous pathways while maintaining those in motor pathways (the "pruning hypothesis"). If all collaterals projecting to muscle are saved, then stimulation of regenerative sprouting should increase specificity by increasing the number of motoneurons with at least one collateral in a muscle pathway. In the current experiments, collateral sprouting is stimulated by crushing the nerve proximal to the repair site before suture, a maneuver that also conditions the neuron and predegenerates the distal pathway. Control experiments are performed to separate these effects from those of collateral generation. Experiments were performed on the rat femoral nerve and evaluated by exposing its terminal cutaneous and muscle branches to HRP or Fluoro-Gold. Crush proximal to the repair site increased motor axon collaterals at least fivefold and significantly increased the percentage of correctly projecting motoneurons, consistent with the pruning hypothesis. Conditioning the nerve with distal crushes before repair had no effect on specificity. A graft model was used to separate the effects of collateral generation and distal stump predegeneration. Previous crush of the proximal femoral nerve significantly increased the specificity of fresh graft reinnervation. Stimulation of regenerative collateral sprouting thus increased PMR, confirming the pruning hypothesis. However, this effect was overshadowed by the dramatic specificity with which predegenerated grafts were reinnervated by fresh uncrushed proximal axons. These unexpected effects of predegeneration on specificity could involve a variety of possible mechanisms and warrant further study because of their mechanistic and clinical implications.

Animals↗
PubMed1998

Granulocytes in the subarachnoid space of humans and rabbits with bacterial meningitis undergo apoptosis and are eliminated by macrophages.

The contribution of leukocyte apoptosis to the resolution of meningeal inflammation in bacterial meningitis was studied in the cerebrospinal fluid (CSF) and in meningeal infiltrates of humans and rabbits by in situ tailing, flow cytometry, agarose gel electrophoresis, and electron microscopy. In humans, the rate of apoptotic granulocytes was 21.0+/-20.8% (n=11) in cytocentrifuge preparations and 3.3+/-3.4 (n=14) in putrid infiltrates of autopsy cases (P=0.02). In rabbits, CSF pleocytosis peaked 8 h after the initiation of antibiotic treatment (5311+/-3122/microl). At this time, the rate of apoptotic granulocytes was 15.2+/-7.3% in CSF and 1.8+/-1.4% in the meningeal infiltrates (each group n=6, P=0.007). Thereafter, the rate of apoptotic granulocytes in CSF declined below 10%. In humans and rabbits, bands representing internucleosomal fragments of approximately 180 base pairs and multiples thereof were documented on agarose gels. Phagocytosis of apoptotic granulocytes by macrophages was visualized by light and electron microscopy. In conclusion, during resolution of subarachnoid space inflammation in bacterial meningitis, a substantial fraction of granulocytes undergoes apoptosis. These granulocytes are removed by phagocytosis by macrophages. Apoptosis is more frequent in granulocytes floating in the CSF than in adherent cells.

Animals↗
PubMed1998

Lumbar and ventricular CSF protein, leukocytes, and lactate in suspected bacterial CNS infections.

Protein concentration, leukocyte density, and lactate concentration were studied in 41 pairs of ventricular and lumbar CSF drawn at an interval of less than 24 hours from patients with suspected bacterial CNS infections. The ventriculo-lumbar ratios ranged from 0.003 to 10.2 (median=0.42) for protein and from 0.002 to 53.5 (median=0.17) for leukocytes. The uneven distribution of leukocytes and proteins in the CSF space may produce findings that fail to indicate bacterial CNS infections. Lactate was distributed more homogeneously in the CSF space than protein and leukocytes (ventriculo-lumbar ratio 0.52 to 1.66 [median=0.811).

Adult↗
PubMed1998

Training environment for inferior vena caval filter placement.

This paper describes a Virtual Environment system designed to aid in training interventional radiologists in inferior vena cava filter placement. It is being developed as part of a VE simulator for a number of surgical and interventional radiology procedures at the Laboratory for Advanced Computer Applications in Medicine at the George Washington University. In this procedure a filter is placed in the inferior vena cava to prevent blood clots from the lower portion of the body from reaching the lungs and causing a pulmonary embolus. The simulation is designed to provide both tutorial and testing modes for the filter placement procedure.

Algorithms↗
PubMed1998

[Dependence of serous activity of cathepsin B on histological types of ovarian carcinomas].

The preoperative activity of cathepsin B was determined in the serum of 110 patients with primary ovarian carcinomas and in 35 women with benign ovarian tumor. The significant increase of cathepsin B activity in ovarian carcinomas is independent of its types in comparison to benign ovarian tumor. The percentage of the results with value above the cut-off values was the highest for serous types of ovarian carcinomas. The dependence between the increase of cathepsin B activity and the FIGO stage of the disease was observed only for serous and endometrioid type of ovarian carcinomas.

Adolescent↗
PubMed1997

Implementing quality assurance programs in multigroup practices for treating hypercholesterolemia in patients with coronary artery disease.

Healthcare reform is driving the development of specialty physician practices into larger regional and national physician networks. These networks arise from the federation of > or =2 practices that negotiate with managed-care organizations for contracts. Developing cardiovascular networks and establishing and implementing lipid management quality assurance programs into the network are presented in this article. Goals of the lipid management program include enhancing the identification, diagnosis, education, and comprehensive treatment of patients with cardiovascular disease. Utilizing an integrated, coordinated, multidisciplinary approach to lipid management allows the cardiology network to improve patients' quality of life, reduce long-term costs, and gain a competitive advantage for successful contracting. A network lipid management program involves targeting eligible patients and treating them to a targeted level for low-density lipoprotein (LDL) cholesterol where possible. Among cardiologists, there is a consensus that achieving an LDL cholesterol of < 100 mg/dL for patients with pre-existing cardiovascular disease is desirable. Secondary lipid management program goals include: (1) collecting, storing, and analyzing patient demographics; (2) implementing programs involving lifestyle modification, smoking cessation, weight control; and (3) measuring clinical and economic outcomes. Convergence of several driving forces in managing hypercholesterolemia provides cardiologists with the ability to improve the process. These forces include: market-consolidated delivery systems, established lipid management guidelines, and employer-initiated policies requiring higher quality care within managed-care organizations. Methods to achieve enhanced treatment effectiveness, patient satisfaction, and control costs are discussed. Utilizing multidisciplinary teams including nurse case managers, clinical pharmacists, dietitians, and physician assistants to achieve lipid level goals and for nutritional counseling is desirable. Developing disease state management programs, treatment algorithms, databases with analytic reports, and process improvement across the network is of paramount importance for future progress and success.

Cardiology↗
PubMed1997

Cathepsin B-like activity as a serum tumour marker in ovarian carcinoma.

Serum cathepsin B-like activity was determined in 75 patients with ovarian carcinomas and in control groups. Ovarian cancers were of FIGO stages I-IV. Control groups consisted of 15 healthy women, 20 patients with myomas of the uterus, and 17 with benign ovarian cysts. Preoperative results showed elevated cathepsin B-like activity in 100% of the patients with ovarian cancers in relation to healthy subjects and patients with myomas, and in 78% in relation to benign ovarian cysts. Cathepsin B activity increased progressively with the FIGO stage of the disease, but the differences among particular stages were not statistically significant. In serous tumours cathepsin activity was significantly higher only in comparison to endometrioid ones (p < 0.001). Antipapain capacity of cystatins in the sera was also determined. No significant correlation between cathepsin B-like, and antipapain activity of cystatins was found. Serum cathepsin B-like activity may be helpful in the preoperative differential diagnosis between ovarian carcinomas and benign ovarian or uterine tumours.

Adolescent↗
PubMed1997

The effect of aging on the utilization of chemotherapy for metastatic breast cancer: a population-based study.

Older women (i.e., > or = 65 years of age) receive less adjuvant chemotherapy than younger women, in part because chemotherapy has been less effective in postmenopausal than premenopausal women in clinical trials. Metastatic breast cancer, however, does not respond differently to chemotherapy by age. Therefore, to evaluate further the effect of age on chemotherapy utilization, we conducted a population-based study of the treatment of metastatic breast cancer. Patients (n = 132) were identified by cross-tabulating death certificates from 1984 to 1991 with breast cancer cases in the Washington County Cancer Registry. Treatment information was obtained from the Tumor Registry of the Washington Country Hospital and Hospital medical records. Forty patients (74%) < 65 years old received chemotherapy compared to 11 (42%) 65-74 and 6 (12%) > or = 75 (p < 0.0001). Adjusting for other medical conditions and whether or not the patient saw a medical oncologist, there was still a significant effect of age in patients > or = 75 (p < 0.001) and a trend (p = 0.17) for patients 65-74. The different patterns of chemotherapy utilization were not associated with survival differences. Radiation therapy was also utilized significantly less frequently in older than younger patients, but the age effect was not as pronounced as with chemotherapy. There was no age effect on the utilization of hormonal therapy. Less frequent utilization of chemotherapy in older patients is probably caused by a combination of patient and physician factors and may result in less effective palliation for older patients.

Age Factors↗
PubMed1997

Clinical and pathological characterization of northern elephant seal skin disease.

From 1984 through 1992, staff at The Marine Mammal Center (TMMC, Sausalito, California, USA) examined 207 northern elephant seals (Mirounga angustirostris) with a condition of unknown etiology called northern elephant seal skin disease (NESSD). The skin lesions were characterized by patchy to extensive alopecia and hyperpigmentation, punctate or coalescing epidermal ulceration, and occasionally, massive skin necrosis. Microscopic lesions included ulcerative dermatitis with hyperkeratosis, squamous metaplasia and atrophy of sebaceous glands. All diseased seals were less than 2 years of age and suffered from emaciation, depression, and dehydration. Mortality from septicemia increased significantly with severity of skin ulceration. Compared to 14 apparently unaffected seals, diseased seals had depressed levels of circulating thyroxine, triiodothyronine, retinol, serum iron, albumin, calcium, and cholesterol. Levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, gamma glutamyl transpeptidase, blood urea nitrogen, and uric acid were elevated. Morphometrically, diseased animals were approximately 15% smaller than normal seals of the same sage. Serum and blubber concentrations of 36 polychlorinated biphenyl congeners (sigma PCB) and dichloro-diphenyl-dichloroethylene (p,p'-DDE) were negatively correlated with body mass. Mean concentrations of sigma PCB and p,p'-DDE in serum in diseased seals were elevated as compared to apparently normal seals. Etiology of this syndrome remains unknown, but the possibility of PCB toxicosis cannot be ruled out.

Alopecia↗
PubMed1997

The activities and subcellular localization of cathepsin B and cysteine proteinase inhibitors in human ovarian carcinoma.

Ovarian carcinomas exhibited a higher cathepsin B activity than did normal ovaries. The plasma membrane fractions of ovarian cancers were enriched in the activities of both cathepsin and cysteine proteinase inhibitors. The ratio of cathepsin to the inhibitors in these fractions was higher at stage IV than at stage III of the disease, classified according to the Federation of International Gynecology and Obstetrics.

Adolescent↗
PubMed1996

nm23 expression in tissue sections and tumor effusion cells of ovarian neoplasms.

The genetic changes involved in the metastatic process of ovarian epithelial cancer remain undetermined. The expression of nm23, a putative metastasis-suppressor gene product, was assessed immunohistochemically in malignant and benign ovarian neoplasms, considering histology of tumors and clinical advancement of disease. Comparison of nm23 protein content in tissue sections and respective cyst and/or ascitic fluid cells was also performed. Significant heterogeneity of nm23 immunostaining was observed, and no correlation with histological subtype of ovarian carcinoma was found. Expression of nm23 was higher in carcinomas compared with benign tumors. A significant trend to have a higher nm23 reactivity in ascitic fluid cells vs. primary tumors was observed. Our results indicate that the increase of nm23 reactivity is activated in the early stages of the disease and that the progression of ovarian carcinoma is accompanied by overexpression of nm23 protein. Our observations did not confirm the postulated role of nm23 as a suppressor gene in ovarian cancer.

Adenocarcinoma, Mucinous↗
PubMed1996

Expression of p53 protein and Ki-67 reactivity in ovarian neoplasms. Correlation with histopathology.

The expression of Ki-67 proliferation antigen and its relation to p53 protein was assessed immunohistochemically in malignant and benign ovarian neoplasms, considering the stage of disease and histology of tumors. The comparison of p53 and Ki-67 in tissue sections and respective cyst and/or ascitic fluid cells was also performed. Significant heterogeneity of staining was observed. However, the relationship between p53 and Ki-67 activity in tissue sections and loose cells in individual patients was evident. Moreover, the presence of Ki-67 antigen was closely correlated with p53 protein. It was observed the trend for serous carcinoma to have a higher Ki-67 and p53 positivity versus endometrioid and mucinous carcinomas. However, it was not statistically significant. Both growth fraction as measured by Ki-67 staining and p53 content were significantly higher in stages III and IV compared to stages I and II of ovarian carcinomas (P<.05, and P<.01, respectively). In benign ovarian neoplasms, no p53 reactivity was observed and Ki-67 staining was very low. Our results showed that p53 is not a feature of benign epithelial ovarian tumors and indicate that increased proliferative activity of cells seems to involve immunohistochemically detectable alterations in p53 gene contributing to the evolution of ovarian carcinoma.

Adenocarcinoma, Mucinous↗
PubMed1996

Anti-inflammatory treatment influences neuronal apoptotic cell death in the dentate gyrus in experimental pneumococcal meningitis.

Apoptotic neuronal death and the increase of neuron-specific enolase (NSE) in cerebrospinal fluid (CSF) were studied in a rabbit model of experimental pneumococcal meningitis after treatment with antimicrobial (ceftriaxone) and antiinflammatory agents (dexamethasone, monoclonal antibodies against the beta-subunit of beta 2-integrins [anti-CD18 mAb]). Twenty-four hours after infection, apoptotic cell death was found solely in the granular cell layer of the dentate gyrus. Neurons with DNA fragmentation were quantified with the in situ tailing (IST) reaction. Dexamethasone and anti-CD18 mAb inhibited the NSE increase in CSF significantly (p = 0.003, p = 0.011). After administration of dexamethasone the density of apoptotic neurons was significantly higher than in control animals receiving only ceftriaxone (p = 0.044). The median of the density of apoptotic neurons was lower in the dentate gyrus in animals receiving anti-CD18 mAb and ceftriaxone vs those receiving only ceftriaxone, although the difference did not reach statistic significance (p = 0.058). In conclusion, apoptotic cell death occurs in the dentate gyrus during the early phase of bacterial meningitis. The extent was influenced by antiinflammatory therapy. The systemic administration of glucocorticoids increased the quantity of apoptotic neurons in the dentate gyrus but reduced overall neuronal damage as indicated by low levels of NSE concentration in CSF.

Animals↗
PubMed1995

Measurements of haptoglobin by the reaction with concanavalin A in sera of patients with ovarian tumours.

The concentration of haptoglobin in sera of healthy women and patients with non-malignant and malignant ovarian tumours was measured by two methods, i.e. complex formation with haemoglobin and complex formation with concanavalin A. High correlation (r = 0.74) between both the methods was found in the group of healthy women, but correlation coefficients were much lower in the group of non-malignant and malignant tumours (r = 0.42 and 0.37, respectively). Direct determinations of haptoglobin, and calculation of the ratio of haptoglobin bound to concanavalin A to haptoglobin bound to haemoglobin revealed statistically significant differences among the examined groups. Comparison of two methods of haptoglobin quantitation suggest that processes connected with ovarian disorders may alter the glycosylation of haptoglobin oligosaccharide chains.

Adult↗
PubMed1994

The effect of age on the beta-adrenergic lipolytic response in healthy humans.

We evaluated the effect of age on the lipolytic response to intravenous infusion of isoproterenol in 12 elderly (age, > 60 years) and 12 young (age, 21 to 34 years) volunteers to examine if there is alteration in innervated beta-adrenergic responsiveness in tissues other than the heart. Lipolysis was evaluated by measuring the plasma concentrations of free fatty acids and glycerol. We also measured the plasma concentration of isoproterenol during infusion so that we could calculate comparable plasma isoproterenol concentrations to lipolytic responses in the two age groups. Our data show that, at equivalent infusion rates of isoproterenol, the two age groups achieved equivalent isoproterenol concentrations. The elderly had a higher concentration of free fatty acids but equivalent concentrations of glycerol as compared with the young subjects at equivalent isoproterenol plasma concentrations. However, our data were complicated by the fact that at the higher infusion rates of isoproterenol, the elderly showed a greater sympathetic stimulation than the young subjects as measured by plasma norepinephrine concentrations. Nonetheless, our data could not show that the elderly subjects were more resistant to beta-adrenergic receptor-mediated stimulated lipolysis. Thus innervated beta-adrenergic receptor hyporesponsiveness caused by aging may not necessarily extend to all organ systems.

Adult↗