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Biomedical subjects

R Davies

Publications and source records attributed to R Davies.

At least 235 records · Page 13Linked to original sources

Is conversion of thyroxine to triiodothyronine and reverse triiodothyronine autoregulated? Studies with short term suppression of thyroid function with 3'isopropyl 3,5-diiodothyronine.

We investigated the effect of a 6 days course of 20 micrograms of a thyromimetic thyronine analogue 3'isopropyl, 3,5-diiodothyronine (DIIP) on serum thyroid hormone and TSH levels in 10 normal male volunteers. TSH was inhibited progressively during the 6 days of DIIP treatment. By the third day after stopping the treatment this trend had already reversed. Of the serum thyroid hormones the T3 level had decreased by 32% and was the first to increase 5 days after stopping treatment. Serum T4 fell by 35% and returned later to normal. The next effect was an increase in the T3/T4 ratio which was most marked 5 days after treatment had stopped. Kinetic studies with 125I-T3 and 125I-reverse T3 were performed at this time. In comparison to pretreatment kinetics no change in MCR was obtained. It is therefore suggested that at least part of the more rapid increase of T3 than T4 after stopping the suppression therapy reflects an increased conversion.

Adult↗

An assessment of models of a health system.

A variety of stochastic and deterministic non-optimizing techniques have been used both predictively and for comparing policy options for patient treatment. Models of the system of the treatment of kidney patients are reviewed and are shown to be based on too small a subsystem to be useful for planning and budgeting. Other drawbacks include poor user-credibility and lack of robustness. Discrete-event simulation is shown to be the most appropriate technique which does not limit the type of distribution functions that may be used and can model patient attributes, resource use and constraints.

Health Resources↗

Cytogenetic, immunological, and haematological effects in workers in an ethylene oxide manufacturing plant.

Samples of blood were collected from a group of plant workers engaged in the manufacture of ethylene oxide (EO) for periods of up to 14 years and also from a group of control personnel matched by age and smoking habits. Peripheral blood lymphocytes were cultured for cytogenetic analysis. Selected immune and haematological parameters were also investigated. The results of these studies showed no statistically significant difference between the group of plant workers and the control group in respect of any of the biological parameters investigated in this study. Nevertheless, duration of employment in EO manufacturing was positively correlated (p less than 0.05) with the frequency of chromosome breaks and with the percentage of neutrophils in a differential white blood cell count and negatively correlated (p less than 0.05) with the percentage of lymphocytes. As the values of these parameters remained within the normal limits of control populations, the correlations were considered to have no significance for health. Atmospheric concentrations of EO were determined using personnel air samplers and were generally below the detection limit (less than 0.05 ppm) during stable plant operations, although transient concentrations of up to 8 ppm were occasionally recorded. The amount of alkylation (2-hydroxyethyl groups) of the Nt atom of histidinyl residues in haemoglobin was also measured in an attempt to gauge recent individual exposures to EO. Variable but, in most instances, readily measurable amounts of Nt-(2'-hydroxyethyl)-L-histidine (Nt represents the N3 atom of histidine) were found in the haemoglobin of plant workers and in the control group who had not knowingly been exposed to an exogenous source of EO. There was no statistically significant difference between the results obtained in the control group and in the group of plant workers.

Adult↗

Osteoporosis.

Osteoporosis is the most common bone disorder in the United States. Bone mass is decreased, and porosity and fragility are increased. Dual-beam photon absorptiometry is currently considered the best detection technique. Prevention involves increased calcium intake and avoidance of diets high in protein and phosphates, excessive alcohol consumption and smoking. Estrogen therapy is recommended for most oophorectomized or postmenopausal women, at least for a few years. The addition of progestins to the regimen reduces the risk of endometrial cancer.

Aged↗

A microenzyme-linked immunosorbent assay for urinary albumin, and its comparison with radioimmunoassay.

Interest in early albuminuria ('microalbuminuria') has intensified recently, particularly in the area of diabetes. We describe a sandwich type enzyme-linked immunoassay for urinary albumin and compare it with a conventional radioimmunoassay (RIA) using the same commercial antiserum. The assay ranges for ELISA and RIA were 7.5-500 micrograms/l and 20-5000 micrograms/l respectively and the corresponding sensitivities were 1.5 ng and 2.0 ng. The correlation coefficient between ELISA and RIA in the measurement of albumin in overnight urine samples from 74 children was r = 0.89 (P less than 0.001). ELISA has several practical advantages over radioimmunoassay, and we believe it has the potential to replace RIA in the screening and study of albuminuria.

Albuminuria↗

A role for intracellular calcium and calmodulin in the release of triiodothyronine from human thyroid-cell monolayer cultures.

Human thyroid cells in monolayer responded to acute stimulation by TSH with an increase in the secretion of T3. This process appeared to be dependent on a rise in the cytosolic calcium concentration since the antagonist of intracellular calcium mobilization, TMB-8, was found to inhibit the release of T3 in response to TSH. The importance of intracellular calcium was further shown using the agent veratridine which increases the free calcium level within cells; veratridine potentiated the stimulation of T3 secretion by TSH and itself stimulated the release of T3 to a level higher than that seen in the presence of TSH alone. The calcium ionophore A23187 produced a biphasic effect on T3 secretion from human thyroid monolayers; at low concentrations, A23187 caused a decrease in both unstimulated and TSH-stimulated T3 secretion but above a concentration of 1 microM, T3 secretion was increased. The calmodulin antagonist W7 was found to inhibit T3 release in response to TSH, indicating a role for calmodulin in mediating the effects of intracellular calcium on T3 secretion.

Calcimycin↗

Fatal pneumococcal epiglottitis in lupus overlap syndrome.

A 35-year-old woman with a six-year history of polymyositis, having developed a vasculitic skin rash in the first trimester of her first pregnancy and biopsy-proven lupus glomerulonephritis during the third trimester is described. Investigations performed one month post-partum revealed high DNA binding, the presence of RNP antibodies, a serum CH50 of 0% and a serum C2 of 1%. Despite marked clinical and serological improvement and the reduction of her prednisolone dose to 5 mgs./day, she died at one-year post-partum of acute pneumococcal epiglottitis.

Adult↗

The early effects of sympathectomy on bone blood flow.

Several laboratories, including our own, have investigated the physiology of bone blood flow by perfusion of the tibia via the nutrient artery. Any damage caused to the nerve supply by cannulation of the artery might affect the results. The possible effect of such damage was investigated by measuring blood flow to the dog tibia using a microsphere technique, before and after sympathectomy. No effect was found and the tibial nutrient artery is therefore a suitable vessel for perfusion when estimating nutrient exchange in bone.

Animals↗

Psychosis associated with thymoma.

The case history of a 19-year-old black woman who died the day after she was treated for psychosis is described. The remarkable finding in her mental status was hyper-religiosity and in postmortem was a thymoma. The report discusses the relationship between thymoma and psychosis as well as the need to look for an organic etiology in patients manifesting a sudden psychotic regression with hyper-religiosity.

Acute Disease↗

In vitro macrophage cytotoxicity of five calcium silicates.

Five calcium silicate minerals (two naturally occurring and three synthetic compounds) with defined morphology and chemical composition were compared for their cytotoxic and lysosomal enzyme releasing effects on unstimulated mouse peritoneal macrophages in vitro. One synthetic material, a fibrous tobermorite, was cytotoxic towards the cells, and two naturally occurring wollastonites induced selective release of beta-glucuronidase from the cells.

Animals↗

In vitro cytotoxicity and quantitative silica analysis of diatomaceous earth products.

Mouse peritoneal macrophages were used to evaluate the relative cytotoxicity of a series of diatomaceous earth products in vitro. The amorphous and crystalline silica content of the products was determined by a combination of infrared spectroscopy and x ray powder diffraction techniques. The cytotoxicities of the high cristobalite content flux calcined materials were similar to that of the standard cristobalite ; both the natural and straight calcined materials had significantly greater activities than the flux calcined materials. Thus within the limitations of the macrophage cytotoxicity test the hypothesis that crystalline content is the only determinant of fibrogenicity of diatomaceous earth is not supported.

Animals↗

Blood flow and clearance in tendons. Studies with dogs.

Blood flow in intact tendons in dogs was measured using 57Co-labelled microspheres and compared with the simultaneous clearance of a diffusible radionuclide, 85Sr, by the same tendons. Clearance was significantly greater than flow in all tendons, indicating that diffusion from surrounding tissues may be important in the nutrition of normal tendons.

Animals↗

The cytotoxicity of kaolin towards macrophages in vitro.

The inhalation of china clay dust by man can cause pneumoconiosis. In an attempt to identify the factors responsible the cytotoxicity in vitro of china clay dust towards mouse peritoneal macrophages was examined. Respirable dusts collected at china clay drying plants were cytotoxic towards the cells. This activity was caused by kaolinite (the major mineral in china clay) and was not due to the presence of ancillary minerals. The cytotoxicity of kaolinite was not due to particle morphology and the positively charged edges of the mineral contributed only slightly to cytotoxicity. An electron microscope study showed that macrophages phagocytosed PVPNO-coated kaolinite particles indicating that the low cytotoxicity of these particles was not due to poor phagocytosis. Residence of china clay in rat lungs appeared to reduce its cytotoxicity. It was concluded that the cytotoxicity of kaolinite was probably related to the proposed amorphous silica-rich gel coating on the particles. The relevance of the findings in vitro to the effects in vivo of china clay is discussed.

Animals↗

Response to ultraviolet radiation: ear swelling in hairless mice.

Ear swelling, as measured by an engineer's micrometer, shows a positive relationship to doses of ultraviolet radiation (over a range of 0 to 7.4 times the minimally damaging dose) during the first 4 d after irradiation. Subsequently, doses greater than 3 D (see text) caused significant thickening associated with scab formation. Doses of 3 D and lower continued to show a well-correlated dose-response to the end of the study. Changes in ear thickness afford a metric indication (non-invasively and repetitively) of the severity of a skin response to UV.

Animals↗

Cytotoxicity of talc for macrophages in vitro.

The cytotoxicity of seven specimens of respirable talc dust for mouse peritoneal macrophages in vitro was studied. All talcs showed modest but consistent macrophage cytotoxicity and would be expected to be fibrogenic in vivo. Available data suggest that under certain circumstances respirable talc can cause lung fibrosis in animal inhalation studies. As most of the talc specimens under investigation were of high purity it seemed unlikely that the cytotoxicity was due to the presence of small quantities of contaminating minerals.

Animals↗

The electrophoretic mobilities of minerals determined by laser Doppler velocimetry and their relationship with the biological effects of dusts towards macrophages.

The role of surface charge in the pathogenicity of mineral dusts has been little studied, partly due to the time consuming nature of such determinations using conventional microelectrophoresis apparatus. In this work the use of laser Doppler velocimetry proved to be a rapid method of determining the electrophoretic mobility of mineral dusts. Ceramic ball milling of fibrous minerals, whilst dramatically reducing the cytotoxicity of the dusts towards macrophages, had only a small effect on electrophoretic mobility. It is concluded that some other factor, possibly fibre morphology, is important for observed biological effects. The coating of quartz and kaolinite with poly-2-vinyl pyridine-N-oxide dramatically lowered their cytotoxicity towards macrophages. The dusts' electrophoretic mobilities were also lowered. The significance of these findings is discussed.

Animals↗