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Biomedical subjects

J Rabinowitz

Publications and source records attributed to J Rabinowitz.

At least 73 records · Page 4Linked to original sources

Characterization of endogenous cytokine concentrations after high-dose chemotherapy with autologous bone marrow support.

Endogenous cytokines are thought to mediate numerous biologic processes and may account for some adverse effects experienced following the administration of recombinant proteins. This study describes the pattern of endogenous cytokine exposure following high-dose chemotherapy. Blood concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), macrophage colony-stimulating factor (M-CSF), and erythropoietin (EPO) were measured by enzyme-linked immunosorbent assay (ELISA) methods in 68 patients receiving the same ablative chemotherapy regimen (cyclophosphamide, cisplatin, carmustine). Patients were grouped according to cellular support (autologous bone marrow [BM] CSF-primed peripheral blood progenitor cells [PBPCs]) and prescribed growth factor (recombinant human granulocyte or granulocyte-macrophage colony-stimulating factor [rHuG-CSF or rHuGM-CSF]). Leukocyte reconstitution was most accelerated in the groups treated with PBPCs and rHuG-CSF. IL-6, M-CSF, and TNF-alpha concentrations were higher in the groups treated with rHuGM-CSF and without PBPCs. Maximal endogenous cytokine concentrations occurred approximately 12 days after BM reinfusion. High concentrations of EPO occurred in patients experiencing significant hypotension despite routine transfusions for hematocrit < 42%. High M-CSF and IL-6 levels were associated with increased platelet transfusion requirements. Concentrations of all four cytokines were significantly higher in patients experiencing renal or hepatic toxicity, with elevations occurring in a predictable sequence and M-CSF elevations occurring first. This report shows that endogenous cytokine concentrations may be influenced by either cellular or CSF support and are associated with differences in platelet reconstitution and organ toxicity.

Adult↗

Why and how to establish a computerized system for psychiatric case records.

Based on experience with successful implementation of an on-line computerized psychiatric case record system in a psychiatric hospital in Israel, the authors discuss the advantages of such systems and outline the process of converting paper records to computerized records. Computerized records can save time by automatically issuing routine reports, improve clinical practice, simplify quality assurance, and ease collection and analysis of data for research. The process of converting paper records to computerized records can begin with analysis of the hospital's reporting requirements and creation and pilot testing of structured paper forms with a multiple-choice format that is eventually incorporated into the computer program. The authors recommend an on-line computerized record system with direct input of data because such a system can be used for case audits and can generate reports, treatment plans, and medication orders without removing records from circulation. Other advantages include the system's usefulness in electronic communication within and outside the hospital.

Attitude of Health Personnel↗

Disposition of recombinant human granulocyte-macrophage colony-stimulating factor in patients receiving high-dose chemotherapy and autologous bone marrow support.

Recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) produces dose-related therapeutic and toxic effects; however, relationships between its pharmacokinetics and pharmacodynamics have not been extensively evaluated. The following studies were undertaken to investigate patterns in the disposition of rHuGM-CSF administered after high-dose chemotherapy (cyclophosphamide, cisplatin, carmustine) and autologous bone marrow support. Continuous 14 or 21 day intravenous infusions or daily 4-hour infusions were studied at doses of 1.2 to 19.2 micrograms/kg/d. GM-CSF was measured by an enzyme-linked immunosorbent assay from serum and urine samples collected throughout drug administration. Pharmacokinetic parameters were determined by compartmental (4-hour infusions) or noncompartmental methods (continuous infusions). GM-CSF was rapidly eliminated from the serum. Average systemic exposure increased with dose, although wide interpatient variability was evident. Approximately one half of the patients receiving continuous infusions demonstrated increasing GM-CSF clearance that corresponded to the appearance of white blood cells in the periphery. Conversely, clearance decreased in those experiencing renal dysfunction during the infusion. The percentage of a GM-CSF dose found in 24-hour urine collections was substantially reduced in the latter group. A subset of patients who developed renal dysfunction also experienced significant hypotension. Rapidly increasing serum GM-CSF concentrations corresponded to the hypotensive episodes. GM-CSF serum concentration monitoring may be useful for evaluation of therapeutic and toxic effects in patients receiving high-dose chemotherapy with autologous bone marrow support.

Antineoplastic Combined Chemotherapy Protocols↗

Diminished ratio of estrogen receptors to progesterone receptors in breast carcinomas of women who have had multiple miscarriages.

We examined the relationship of a history of miscarriage to the ratio of tumor estrogen receptors to progesterone receptors in 74 women with breast carcinoma evaluated between 1988 and 1990. Only women who had been pregnant and whose tumor contained both estrogen and progesterone receptors were included. Women with breast carcinoma and a history of two to four miscarriages had significantly lower ratios (less than 1) of tumor estrogen receptors to progesterone receptors than women with a history of zero or one miscarriage (greater than 1). This finding may be the result of a genetic anomaly in breast cancer patients that also affects the uterine environment during the reproductive years.

Abortion, Habitual↗

Pulmonary manifestations of HIV infection in children.

We retrospectively reviewed the spectrum, course, and outcome of pulmonary diseases in 66 children with AIDS, hospitalized between 1982 and 1988, prior to the use of zidovudine. Fifty-two of the 66 (79%) patients developed pulmonary problems. In fifty-two percent of all patients, a pulmonary problem was the first symptom of HIV infection. The most common respiratory illness requiring hospitalization was an episode of respiratory distress with normal PaO2 and unchanged X-ray with a 9.7 +/- 6.8 days mean duration of hospitalization. Bacterial pneumonia, Pneumocystis carinii pneumonia (PCP) and pulmonary lymphoid hyperplasia/lymphoid interstitial pneumonia occurred in 30%, 32% and 22% of the patients, respectively. Bacterial pneumonia and PCP were associated with a high mortality rate. Sixty-eight percent of the patients died within 24 months of the onset of pulmonary disease. In 50% of the children, pulmonary disease was a primary cause of death. The results of this study can be useful in developing prospective studies for the prevention and treatment of pulmonary complications of HIV infection.

Acquired Immunodeficiency Syndrome↗

Determinants of molecular reactivity as criteria for predicting toxicity: problems and approaches.

We discuss the physicochemical basis for mechanisms of action of toxic chemicals and theoretical methods that can be used to understand the relation to the structure of these chemicals. Molecular properties that determine the chemical reactivity of the compounds are proposed as parameters in the analysis of such structure-activity relationships and as criteria for predicting potential toxicity. The theoretical approaches include quantitative methods for structural superposition of molecules and for superposition of their reactivity characteristics. Applications to polychlorinated hydrocarbons are used to illustrate both rigid superposition methods, and methods that take advantage of structural flexibility. These approaches and their results are discussed and compared with methods that afford quantitative structural comparisons without direct superposition, with special emphasis on the need for efficient automated methods suitable for rapid scans of large structural data bases. Quantum mechanical methods for the calculation of molecular properties that can serve as reactivity criteria are presented and illustrated. Special attention is given to the electrostatic properties of the molecules such as the molecular electrostatic potential, the electric fields, and the polarizability terms calculated from perturbation expansions. The practical considerations related to the rapid calculation of these properties on relevant molecular surfaces (e.g., solvent- or reagent-accessible surfaces) are discussed and exemplified, stressing the special problems posed by the structural variety of toxic substances and the paucity of information on their mechanisms of action. The discussion leads to a rationale for the use of the combination of theoretical methods to reveal discriminant criteria for toxicity and to analyze the initial steps in the metabolic processes that could yield toxic products.

DDT↗

Noise and "pedagogic efficiency" in school activities.

A group of 8 pupils born in 1962 and a group of 8 future teachers between 25 and 40 years of age, were submitted in 1975 to two types of tests in the presence of environment noises at various levels (45 to 75 dBa), in order to assess the influence of this nuisance on the pedagogic efficiency. The results show a nocivity threshold for the pupils at around 55 dBA and for the teachers at aroung 65 dBA. Furthermore, backward pupils suffer more in this context from the interference of noise than the advanced ones.

Adolescent↗