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Biomedical subjects

S Hay

Publications and source records attributed to S Hay.

At least 37 records · Page 2Linked to original sources

Technical basis for EPA's proposed regulation on the cleanup of sites contaminated with radioactivity.

The U.S. Environmental Protection Agency is proposing a regulation for the protection of the public from radioactive contamination at sites that are to be cleaned up and released for public use. The rule will apply to sites under the control of Federal agencies, and will impose limits on radiation doses to individuals living or working on a site following cleanup; it will thereby provide site owners and managers with uniform, consistent cleanup criteria for planning and carrying out remediation. This paper presents an overview of EPA's approach to assessing some of the beneficial and adverse effects associated with various possible values for the annual dose limit. In particular, it discusses the method developed to determine how the choice of cleanup criterion affects (1) the time-integrated potential numbers of non-fatal and fatal radiogenic cancers averted among future populations, (2) the occurrence of radiogenic cancers among remediation workers and the public caused by the cleanup process itself, and (3) the volumes of contaminated soil that may require remediation. The analytic methods described here were used to provide input data and assumptions for the Regulatory Impact Analysis (RIA) that supports the proposed regulation; the RIA also considered non-radiological benefits and costs (i.e., public health, economic, and ecological) of the standards.

Radiation Injuries↗

[Clinical and therapeutic aspects of hepatic amebiasis in Cambodia].

Amoebic liver abscess is a common disease in developing countries. Although therapy is now perfectly standardized, errors and inaccuracies are frequent in daily practice. A study was performed at the Calmette Hospital in Phnom Penh (Cambodia) to evaluate and improve this situation. Diagnostic criteria and the outcome of treatment with oral or parenteral metronidazole were analyzed in 38 patients presenting amoebic liver abscess. Hepatalgia was observed in 100% of cases. Hyperleukocytosis and enhancement of the sedimentation rate occurred in 95% of cases. Diagnosis was confirmed by ultrasonography. Serodiagnosis, given its high cost, was not indispensable. Metronidazole was of comparable effectiveness and tolerance (90%) whether administered by the oral or parenteral route. The parenteral route should be used only for patents presenting digestive intolerance. Drainage of the abscess is necessary in cases characterized by immediate complications, abscesses with diameters greater than 120 mm and absence of improvement after 5 days of treatment.

Adult↗

Serum ionised calcium and its relationship to parathyroid hormone after tibial fracture.

The changes in serum adjusted ionised calcium and parathyroid hormone (PTH) were prospectively studied in 32 patients with isolated tibial fractures, treated conservatively. We measured serum albumin, adjusted total calcium, phosphate, pH, adjusted ionised calcium and PTH at intervals until the fractures had healed. The mean ionised calcium adjusted for pH fell within 24 hours of injury, and then rose to a peak at between four and six weeks. These changes cannot be explained by changes in serum pH or PTH. The restoration of normal ionised calcium levels after fracture coincided with the period when the callus was being calcified. Analysis of the changes in ionised calcium, phosphate and PTH suggests that PTH levels alter in response to changes in ionised calcium levels. PTH is highest immediately after fracture and lowest, often not recordable, at six weeks. The cause of the changes in the ionised calcium level has yet to be elucidated.

Adolescent↗

The differences in toxicity and release of bone-resorbing mediators induced by titanium and cobalt-chromium-alloy wear particles.

We investigated the relationship between the toxic effects of metal wear particles and their ability to stimulate the release of inflammatory mediators implicated in bone resorption. In vitro studies were carried out with use of rat peritoneal macrophages, which were exposed to either cobalt-chromium-alloy or titanium-aluminum-vanadium particles, milled from the metal components of hip prostheses. The particles were in the size-range of, and at concentrations similar to, those found in the tissues surrounding failed prostheses in humans. The titanium-aluminum-vanadium particles showed little toxicity even at high concentrations, while the cobalt-chromium particles were very toxic. The titanium-aluminum-vanadium particles induced significantly more release of prostaglandin E2 than did the cobalt-chromium particles, and this was true for a wide range of concentrations. Exposure to titanium-aluminum-vanadium increased the release of prostaglandin E2, interleukin-1, tumor necrosis factor, and interleukin-6. In contrast, exposure to cobalt-chromium particles was associated with a decreased release of prostaglandin E2 and interleukin-6, and it had little effect on the release of interleukin-1 and tumor necrosis factor.

Alloys↗

The synovial response to intraarticular injection in rats of polyethylene wear particles.

To study the effect on tissues of wear particles commonly released from the articulating surfaces of joint prostheses, ultra-high-molecular-weight polyethylene particles were prepared in a joint simulator and injected into rat knees. The particles caused synovial proliferation and induced a macrophage and multinucleate giant-cell response in the subsynovium. Of particular interest was the macrophage response to particles ranging from 5 microns in maximum dimension to the limits of resolution of the light microscope; the multinucleate giant-cell response occurred in response to larger particles and aggregates of small particles. These findings emphasize the importance of wear particles in causing an adverse tissue response around joint replacements having a polyethylene component. The difference in cellular response to wear particles of different size suggests that not only the prosthesis material but also the pattern of wear and size of wear particles produced at the articulating surfaces of a prosthesis will determine the type of cellular response.

Animals↗

Effect of different carbohydrates on growth, polysaccharidase and glycosidase production by Bacteroides ovatus, in batch and continuous culture.

Bacteroides ovatus was grown in batch culture on 12 different carbon sources (five polysaccharides, seven monosaccharides and disaccharides). Specific growth rates were determined for each substrate together with polysaccharidase and glycosidase activities. Growth rates on polymerized carbohydrates were as fast or faster than on corresponding simple sugars, demonstrating that the rate of polysaccharide depolymerization was not a factor limiting growth. Bacteroides ovatus synthesized a large range of polymer-degrading enzymes. These polysaccharidases and glycosidases were generally repressed during growth on simple sugars, but arabinose was required for optimal production of alpha-arabinofuranosidase. Polysaccharidase and glycosidase activities were measured in continuous cultures grown with either xylan or guar gum under putative carbon limitation. With the exception of beta-xylosidase, activities of the polymer-degrading enzymes were inversely related to growth rate. This correlated with polysaccharide utilization which was greatest at low dilution rates. These results show that Bact. ovatus is highly adapted for growth on polymerized carbohydrate in the human colon and confirm that the utilization of polysaccharides is partly regulated at the level of enzyme synthesis.

Bacteroides↗

A study of protein turnover in preterm neonates using 15N enrichment of urinary ammonia.

Hydrolysed yeast protein labelled with 15N was used to measure protein turnover, protein synthesis and protein breakdown in preterm infants. The yeast tracer was given as a bolus intragastric dose and protein turnover was determined from the 15N enrichment of urinary ammonia over known periods of about 12 h. Six boys (birthweight less than 1500 g) with gestation of 27-35 weeks were studied either two or three times at post-natal ages ranging from 13 to 54 d. There was no significant correlation between protein turnover with increasing post-conceptional or post-natal age. There was considerable interindividual variation and reproducibility varied between different infants. We suggest that this is a convenient non-invasive technique for monitoring serially nitrogen and protein metabolism in infants and that as such it merits further assessment.

Ammonia↗

Effect of cyclosporine-A on connective tissue deposition in experimental inflammatory lesions.

The effect of cyclosporine-A, a potent immunosuppressant, on the development of experimental inflammatory lesions in rats was studied both histologically and biochemically. Continuous treatment with cyclosporine was begun after the implantation of sponges impregnated with heat-killed Mycobacterium tuberculosis and continued for up to 63 days. Cyclosporine-A significantly reduced the numbers of neutrophil polymorphonuclear leukocytes and lymphocytes present during both the acute and chronic phases. In addition, greater amounts of mature fibrous tissue were present in the sponges removed from animals which had been treated with cyclosporine-A. Biochemical analyses of the collagen and glycosaminoglycan content of the sponges at varying times confirmed that cyclosporine-A can influence the deposition of connective tissue macromolecules. These data provide additional evidence that cyclosporine-A affects not only the inflammatory response but also influences subsequent connective tissue metabolism.

Animals↗

Influence of mucin on glycosidase, protease and arylamidase activities of human gut bacteria grown in a 3-stage continuous culture system.

Human intestinal bacteria were grown in a 3-stage continuous culture system on a medium containing complex polysaccharides and proteins as carbon and nitrogen sources. Selected bacterial populations were enumerated and glycosidase, protease and arylamidase activities measured. Comparison of arylamidase and glycosidase activities in the multichamber system (MCS) and faeces showed that the predominant faecal enzymes were also produced by bacteria growing in the MCS. After 48 d operation, porcine gastric mucin (5.8 g/d) was independently fed to vessel 1. Elevated levels of volatile fatty acid (VFA) formation showed that the glycoprotein was actively fermented. The increase in carbohydrate availability as a result of breakdown of the mucin oligosaccharides stimulated bacterial growth and activities. The enzymological measurements showed that mucin increased production of both cell-bound and extracellular glycosidases, such as beta-galactosidase, alpha-glucosidase and N-acetyl-beta-glucosaminidase. Protease activities were profoundly influenced by mucin. These were largely cell-bound in non-mucin cultures but were predominantly extracellular and collagenolytic when mucin was present. Experiments with protease inhibitors showed that cysteine proteases were the major cell-bound and extracellular enzymes in both mucin and non-mucin cultures, but that serine and metalloproteases were also present. The effect of mucin on arylamidase formation was less marked, although there was increased production of these enzymes in vessels 1 and 2 of the MCS. These results suggest that host-produced substances such as mucin glycoprotein may play a role in modulating the growth and activity of bacteria growing in the human large intestine.

Aminopeptidases↗

Significance of microflora in proteolysis in the colon.

Protease activities in human ileal effluent and feces were compared by using a variety of native and diazotized protein substrates. In many cases the diazotized proteins had altered susceptibilities to hydrolysis compared with the native proteins. Proteolytic activity was significantly greater than (P less than 0.001) in small intestinal effluent than in feces (319 +/- 45 and 11 +/- 6 mg of azocasein hydrolyzed per h per g, respectively). Moreover, fecal proteolysis was qualitatively different in that ileal effluent did not hydrolyze the highly globular protein bovine serum albumin, whereas all fecal samples tested degraded this substrate. Inhibition experiments provided further evidence that fecal protease activity differed from that in the small intestine. Physical disruption of fecal bacteria released large quantities of proteases, indicating that the lysis of bacteria in the colon may contribute to the extracellular proteolytic activity in feces. Protease inhibition studies with washed fecal bacteria showed that they produced serine, cystine, and metalloproteases, and experiments with synthetic p-nitroanilide substrates indicated that low levels of trypsin- and chymotrypsin-like activities were associated with whole cells. An elastase-like enzyme was bound to the outer membranes of some fecal bacteria.

Bacteria↗

15N tracer studies of protein metabolism in low birth weight preterm infants: a comparison of 15N glycine and 15N yeast protein hydrolysate and of human milk- and formula-fed babies.

Nitrogen flux and protein synthesis and degradation were estimated using a single oral bolus of 15N glycine or 15N yeast protein hydrolysate and measuring the 15N enrichment of urinary ammonia in five low birth wt infants fed a low birth wt formula and in six who were receiving their own mother's breast milk. Results derived from using 15N-glycine and 15N-yeast hydrolysate tracers in a randomized crossover study in 10 studies on seven infants showed, with one exception, higher turnover rates and more interindividual variation with the 15N yeast. Both tracers showed good reproducibility in two infants who had repeated studies. Although wt gain was similar in both groups, nitrogen intake and retention were greater (p less than 0.01) in the formula-fed group. Mean nitrogen turnover was similar in both groups, but there was a greater variance in the human milk-fed group which also had a greater nitrogen turnover/U absorbed nitrogen (p less than 0.025) and a lower excretion of nitrogen/U flux.

Humans↗

Measurement of bone mineral content in the term and preterm infant.

We tested the best anatomic site, reliability, and reproducibility of single-photon absorptiometric bone density measurements in premature and term newborns. Humerus and radius measurements were compared using a commercially available densitometer. The humerus was a more reliable site of measurement, particularly in the very-low-birth-weight infant. Normal ranges of humerus bone mineral content (BMC) were defined for infants of 24 to 42 weeks' gestational age at birth. Humerus BMC correlated with gestational age and birth weight of patients. We conclude that bone densitometer measurements can be successfully performed, even in very-low-birth-weight infants, when the humerus is used as the measurements site. We define normal humerus BMC values for use in diagnosis and evaluation of efficacy of treatment in infants who are at higher risk for osteopenia of prematurity.

Age Factors↗

Pre-exercise food and heart rate during submaximal exercise.

The heart rates of 20 movement studies students were measured during multi-stage cycle ergometer tests. The tests were repeated on five occasions following the ingestion of different pre-exercise meals and the results compared. A glucose solution taken three hours prior to the exercise (G3) resulted in the lowest heart rates at each work rate. The highest heart rates at each work rate were recorded following the ingestion of glucose or protein one hour before the exercise (G1 and P1 respectively). The heart rate values during G3 were on average 10.3 beat.min-1 lower than those used during G1 and P1. Intermediate heart rates were obtained with protein taken three hours prior to the exercise or a complete fast for 12 to 14 hours. The results have implications for those attempting to predict maximum oxygen uptake from submaximal heart rates.

Adult↗

Influence of prednisolone and methotrexate on cellular and biochemical aspects of acute and chronic inflammation studied in subcutaneously implanted sponges in rats.

The effects of prednisolone and methotrexate on the histology and the content of collagen and proteoglycans of the inflammatory tissue in polyurethane sponges impregnated with heat killed M. tuberculosis and implanted subcutaneously in hooded Wistar rats for up to 63 days were studied. Drugs were administered during the 6-day period before sponge removal 7, 21, 35, 49 and 63 days after implantation. Our findings indicate that prednisolone and methotrexate have profound effects on the cellular events of acute and chronic inflammation, and influence the synthesis or degradation of connective tissue macromolecules at certain stages of the inflammatory process.

Acute Disease↗

Extraocular muscles: light microscopy and ultrastructural features.

Thirty extraocular muscles (EOM) from 20 patients were evaluated by light microscopy (LM), electron microscopy (EM), and enzyme histochemistry (EZH). Twenty-one EOM were obtained from 13 patients with strabismus, 9 EOM from 4 patients undergoing eye surgery for other reasons and from 3 autopsy cases. One mum thick sections revealed marked variation in muscle fibre shape and size and in myofibrillar structure; also noted were small, hypertrophied, whorled, and ringbinden fibres. Dense and granular material in the central portion of some fibres and sarcomere disruption in 2--3 mum sections was observed. EZH revealed the absence of the classical mosaic pattern usually found in skeletal muscles. ATPase studies were inconsistent and did not correlate with the expected reciprocal activity of NAD-H diaphorase, particularly on the large fibres. Ultrastructural features consisted of vacuoles within myofilament bundles, "smearing" of Z bands, and "nemaline rods". Occasional myelin figures and lipid-like droplets were observed in subsarcolemmal spaces, associated with scattered clusters of glycogen granules. Abnormal mitochondria and subsarcolemmal inclusions of dense and granular material were conspicuous. "Leptomeric" profiles, "Zebra bodies", or "striated bodies" were noted in 8 EOM's, and an Hirano body was found in 1. The intramuscular nerves contained structures resembling "Luse bodies" in 7 cases. These observations suggest that EOM from individuals with and without strabismus possess unique structural characteristics suggestive of developmental and morphological disarrangement of contractile elements. Some of these changes might play a role in the pathogenesis of strabismus and in the development of clinical symptoms. These features are significantly different from striated skeletal muscle. Therefore the criteria used in the pathological evaluation and diagnosis of skeletal muscle disorders cannot be unequivocally applied to EOM investigations. These data establish the necessity to determine histological norms, ultrastructural patterns, and develop new enzyme histochemistry criteria for the evaluation of EOM. Only then can an acceptable comparison of EOM and skeletal muscle be made.

Adenosine Triphosphatases↗

Water fluoridation and congenital malformations: no association.

The incidence of selected congenital malformations in areas with fluoride supplementation of public water supplies was compared with the incidence in areas where the water supply is deficient in fluoride. Comparison of the incidences of several common birth defects (including Down's syndrome) in fluoridated and nonfluoridated areas revealed no substantial or significant differences in which there was a consistent pattern for both sets of data.

Adult↗