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Biomedical subjects
Publications and source records attributed to S Goodwin.
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Forty-one women with idiopathic postmenopausal osteoporosis have been followed for 2 years after initiation of sodium fluoride at 40-50 mg/day, given together with a daily calcium supplement of 1 gram and vitamin D2, at 50,000 IU weekly. Histological and histomorphometric analyses were done on bone biopsies taken prior to and after 1 year of treatment (mean 1.25 +/- 0.35 years). Thirty patients (74%) developed the histological fluoride effect of hyperosteoidosis, while the remaining 11 patients (26%) had no change from pretreatment biopsies. Hyperosteoidosis was based on increased values for osteoid volume and/or thickened osteoid with greater than 3 lamellar bands. Based on previously reported findings, this histological evidence of hypersoteoidosis within 12-18 months of initiation of therapy provides a useful predictor of ultimate satisfactory fluoride response in terms of bone mineral accretion. No increases in bone mass (measured by neutron activation analysis) were observed at the time of the posttreatment biopsy but, according to this previous work, increases are anticipated over a further 2-3 years of treatment. Factors affecting the development of hyperosteoidosis were analyzed. Hyperosteoidosis was associated with a significantly higher dose of sodium fluoride and a significantly higher level of bone fluoride retention but without significant increase in fasting serum fluoride. Results suggest that fluoride retention depends not only on fluoride dose but also on body size, renal function, and intestinal absorptions of calcium and fluoride. There were no differences in the initial investigations between patients with and without hyperosteoidosis, with respect to age, years of postmenopause, estrogen use, initial biochemistry, or initial bone histology.(ABSTRACT TRUNCATED AT 250 WORDS)
Hydrogen transformation kinetic parameters were measured in sediments from anaerobic systems covering a wide range of environmental pH values to assess the influence of pH on hydrogen metabolism. The concentrations of dissolved hydrogen were measured and hydrogen transformation kinetics of the sediments were monitored in the laboratory by monitoring hydrogen consumption progress curves. The hydrogen turnover rate constants (kt) decreased directly as a function of decreasing sediment pH, and the maximum hydrogen uptake velocities (Vmax) varied as a function of pH within each of the trophic states. Conversely, the half-saturation concentrations (Km) were independent of pH. The steady-state hydrogen concentrations were at least 2 orders of magnitude lower than the half-saturation constants for hydrogen uptake. Dissolved hydrogen concentrations were at least fivefold higher in sediments from eutrophic systems than from oligotrophic and dystrophic systems. The rates of hydrogen production determined from the assumption of steady state decreased with sediment pH. These data indicate that progressively lower pH values inhibit microbial hydrogen-producing and -consuming processes within sedimentary ecosystems.
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The dynamics of anaerobic digestion were examined in the low-pH sediments of Crystal Bog in Wisconsin. The sediments (pH 4.9) contained 71% organic matter and the following concentrations of dissolved gases (micromoles per liter): CO2, 1,140; CH4, 490; and H2, 0.01. The rate of methane production was 6.2 mumol/liter of sediment per h, which is slower than eutrophic, neutral sediments. Microbial metabolic processes displayed the following pH optima: hydrolysis reactions, between 4.2 and 5.6; aceticlastic methanogenesis, 5.2; and hydrogen-consuming reactions, 5.6. The turnover rate constants for key intermediary metabolites were (h-1): glucose, 1.10; lactate, 0.277; acetate, 0.118; and ethanol, 0.089. The populations of anaerobes were low, with hydrolytic groups (10(6)/ml) several orders of magnitude higher than methanogens (10(2)/ml). The addition of carbon electron donors to the sediment resulted in the accumulation of hydrogen, whereas the addition of hydrogen resulted in the accumulation of fatty acids and the inhibition of hydrogen-producing acetogenic reactions. Strains of Lactobacillus, Clostridium, and Sarcina ventriculi were isolated from the bog, and their physiological attributes were characterized in relation to hydrolytic process functions in the sediments. The present studies provide evidence that the pH present in the bog sediments alter anaerobic digestion processes so that total biocatalytic activity is lower but the general carbon and electron flow pathways are similar to those of neutral anoxic sediments.
Detailed physiological studies were done to compare the influence of environmental pH and fermentation end product formation on metabolism, growth, and proton motive force in Sarcina ventriculi. The kinetics of end product formation during glucose fermentation in unbuffered batch cultures shifted from hydrogen-acetate production to ethanol production as the medium pH dropped from 7.0 to 3.3. At a constant pH of 3.0, the production of acetate ceased when the accumulation of acetate in the medium reached 40 mmol/liter. At a constant pH of 7.0, acetate production continued throughout the entire growth time course. The in vivo hydrogenase activity was much higher in cells grown at pH 7.0 than at pH 3.0. The magnitude of the proton motive force increased in relation to a decrease of the medium pH from 7.5 to 3.0. When the organism was grown at pH 3.0, the cytoplasmic pH was 4.25 and the organism was unable to exclude acetic acid or butyric acid from the cytoplasm. Addition of acetic acid, but not hydrogen or ethanol, inhibited growth and resulted in proton motive force dissipation and the accumulation of acetic acid in the cytoplasm. The results indicate that S. ventriculi is an acidophile that can continue to produce ethanol at low cytoplasmic pH values. Both the ability to shift to ethanol production and the ability to continue to ferment glucose while cytoplasmic pH values are low adapt S. ventriculi for growth at low pH.
Changes in the structure of a practice and the gender of the partners were accompanied by the abandonment of a personal list system. Doctors' opinions about the consulting behaviour of patients in the practice were determined by questionnaire. The notes of 100 patients registered with each of the six partners were examined to determine the nature and number of consultations with each doctor for the years 1980 and 1984. Doctors were found to be unaware of the reasons for which patients consulted different partners. In addition, doctors' opinions about how patients should consult did not correlate with patients' consulting behaviour. It was also found that women consulted the female partners in the practice more commonly than the male partners only after the number of women partners in the practice had increased from one to two.
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Twenty-one patients with postmenopausal osteoporosis were studied for 4 years after initiation with sodium fluoride (NaF), 20-25 mg b.i.d., elemental calcium, 1.0 g/day, and vitamin D2, 50,000-100,000 I.U. weekly. Histomorphometry was carried out on bone biopsies taken prior to and while on NaF treatment. The total bone mineral mass of the central third of the skeleton was measured by neutron activation analysis at 0.5-1.0 year intervals, and the result expressed as the Calcium Bone Index (CaBI), which normalizes the mineral mass to values for normal subjects of the same size. Twelve patients (57%) who developed, within the first 2 years of treatment, histological effects of fluoride (F) (increased bone formation surfaces together with thickened osteoid seams or hyperosteoidosis) increased their CaBI significantly (P less than 0.01) over the 4 year period, from 0.64 +/- 0.02 to 0.78 +/- 0.03 (or 21.0 +/- 2.9%). No other agent is known to stimulate bone growth to this degree. The remaining nine patients showed no histological evidence of F stimulation and no increase in CaBI (from 0.67 +/- 0.03 to 0.66 +/- 0.03 over 4 years). The results suggest that the histological findings of hyperosteoidosis are prerequisite for the increases in bone mass of osteoporotic patients. Although serum and bone F levels were higher in patients with F response compared to those without response, there was considerable overlap in values between the two groups so that these parameters of F retention were not reliable for predicting F response. Histological evidence of hyperosteoidosis appears to be a more reliable predictor of subsequent increase in bone mass. The effect on fracture prevention of the hyperosteoidosis associated with the increases in bone mass remains to be shown.
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