House, Senate at work on health issues affecting dentists.
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Biomedical subjects
Publications and source records attributed to R Wiener.
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We studied the relationship between age, sex, serum thyroxine concentrations, and serum thyrotropin concentrations in 202 patients with primary hypothyroidism whose ages ranged from 10 to 89 years. The results from two groups of patients were analysed, both combined and separately, by multiple linear regression analysis of the factors age, sex, group, and serum free T4 index or serum T4 concentration, to predict serum TSH. The serum free T4 index or T4 values and age were negatively correlated with the serum TSH concentrations (p less than 0.001) for all comparisons. In contrast, there was no significant relationship between sex and serum TSH concentrations in these hypothyroid patients. The age-related decline in serum TSH concentrations in hypothyroidism was apparent during adolescence and early adult life (ages 10 to 39 years) and in elderly subjects (ages 61 to 89 years). We conclude that age is a determinant of TSH secretion independent of the level of thyroid secretion.
Using a combination of standardized and Likert-type measures of health, disability, and psychological adjustment, this study compared the quality of life reported by thirty-seven inpatients and thirty-six outpatients approximately eight months after completing treatment. While both patient groups reported treatment-related changes, inpatients were significantly more dysfunctional than outpatients both before and after treatment. The pattern of perceived improvement among inpatients reflected particular changes in narcotic use and in "up" time. For outpatients, the pattern of change pointed to increased periods of activity. The data are interpreted to reflect the need for treatments that are tailored to meet the differing levels of dysfunction of patients who present with chronic pain syndromes. Methodological problems of this and other clinical studies that compare treatment effects on patients demonstrating different levels of dysfunction are discussed.
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DNA synthesis in rat and rabbit polyvinyl sponge induced granulation tissue has been studied using thymidine (methyl-3H). Synthesis was determined by measurement of thymidine incorporation into cold trichloroacetic acid insoluble material and by autoradiography. Granulation tissue was removed and immediately incubated in vitro in the presence of thymidine (methyl-3H) for three hours. The label was incorporated into the nuclei of fibroblasts and, to a lesser extent, of endothelial cells. The labeled material was 93% lysable by DNase and its synthesis was inhibited by hydroxyurea and bleomycin. In this system synthesis was linear for two hours and then ceased. A marked increase in DNA synthesis occurred in tissue harvested at 44 hours after sponge implantation. This rise was confirmed by autoradiographic studies which showed an increase in nuclear labeling at two days after implantation. Neutropenia produced by injections of antineutrophil serum or cyclophosphamide failed to inhibit activation of DNA synthesis in fibroblasts or endothelial cells. Amonocytosis also had no effect on this process. Rates of thymidine incorporation into DNA and thymidine phosphates in vivo were similar to those found during in vitro incubations of granulation tissue.
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A model system for the study of inflammation in vivo has been developed using the 16-h polyvinyl sponge implant in the rat. This system allows for simultaneous measurement of in vivo chemotaxis, volume of fluid influx, and fluid concentrations of lysosomal and lactic dehydrogenase (LDH) enzymes. In addition, the enzyme content of inflammatory fluid neutrophils may also be determined. A parallel time course of neutrophil and lysosomal enzyme influx into sponge implants was observed. This was characterized by an initial lag phase and a rapid increase between 5 and 16 h. The origin of supernatant LDH and lysosomal enzymes was studied with anti-neutrophil serum to produce agranulocytic rats. Inflammatory fluid in these rats was almost acellular and contained decreased concentrations of beta glucuronidase (-96%) and LDH (-74%). In control rats all of the supernatant beta glucuronidase could be accounted for by cell death and lysis, as estimated from measurements of soluble DNA. Only 15-20% of the LDH activity could be accounted for on the basis of cell lysis. The remainder was derived from neutrophil-mediated injury to connective tissue cells. Large intravascular doses of methylprednisolone markedly inhibited neutrophil influx into sponges and adjacent connective tissue. Secondary to decreased neutrophil influx, fewer neutrophils were available for lysis, and lysosomal enzyme levels in inflammatory fluid decreased. No evidence for intracellular or extracellular stabilization of neutrophil lysosomal granules by methylprenisolone was found.
Quantitative histopathologic and biochemical comparisons were made between polyvinyl sponge capsular and sponge tissue in the rabbit on different days after subcutaneous implantation. Up to 9 days the predominant cell type in the capsular tissue is the fibroblast and in the sponge it is the neutrophil. During this time period the sponge tissue shows lower rates of (14C) proline and (14C) cytidine incorporation and lower rates of total (14C) collagen synthesis than the surrounding capsule. Different gel electrophoretic patterns of isolated radioactive proteins are found in sponge and capsule at 6 days. These biochemical differences appear to be related to the small number of fibroblasts, relative to granulocytes present in sponges during the first 9 days after implantation. It is suggested that future biochemical investigations of the early phase of connective tissue reactions (first 9 days) in this model utilize sponge capsular tissue within 1 cm of the sponge edge instead of the sponge and its contents.
Beta glucuronidase obtained from rat inflammatory fluid and granulocytes was studied kinetically. Linear increases in activity occurred with time and enzyme concentration. No evidence of enzyme degradation during incubation was obtained. Supernatant and granulocyte enzyme activity was identical in relation to Km, and pH optima and resistance to high NaCl concentration. Minimal contributions to supernatant activity occur from plasma and red cells.
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