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Biomedical subjects

R C Brown

Publications and source records attributed to R C Brown.

At least 91 records · Page 5Linked to original sources
PubMed1993

Dry and tight: sexual practices and potential AIDS risk in Zaire.

Both men and women in central Zaire like a 'dry, tight' vagina because it increases pleasure during sexual intercourse. In focus group interviews, they described wiping and washing procedures, as well as 30 different substances, mostly leaves and powders, that women can insert into the vagina to produce the desired effects. Women who use leaves said they crush them, insert them for several hours, then remove them before intercourse. Women who insert powders leave them in place during intercourse. Individual interviews with 99 women (half of them unmarried prostitutes and half married women) showed that over one-third of each group had used intravaginal drying or tightening substances at some time. Vaginal examinations by a physician revealed that several of the substances cause inflammatory lesions of the vagina and cervix. Furthermore, some products cause extreme dryness that could foster epithelial trauma during coitus, both for the woman and for her partner. Breaks in the epithelium may promote the passage of organisms that cause AIDS and other sexually-transmitted diseases. Thus the sexual practices of drying and tightening the vagina may be increasing the risk of infection.

Acquired Immunodeficiency Syndrome↗
PubMed1993

A reappraisal of the carcinogenicity of surface modified asbestos fibres.

A previous study using intrapleural administration of surface-modified amosite asbestos showed a difference in the number of pleural mesotheliomas induced with C18-hydrocarbon derivatised fibres compared to native amosite asbestos. The study has been repeated with larger groups of animals (30) under specific pathogen free conditions, resulting in an increase in the mean animal survival time for both fibre-treated groups. Under these conditions there was no significant difference between the numbers of pleural mesotheliomas induced by C18 hydrocarbon-modified amosite asbestos and native amosite asbestos. The major difference between the two studies was the mean time to death from tumour of rats exposed to fibres. The C18 amosite treated rats in the first study may not have had a mean survival time long enough to allow mesotheliomas to develop.

Animals↗
PubMed1993

Urinary growth hormone excretion as measured by a sensitive immunochemiluminometric assay.

A sensitive immunochemiluminometric assay with a detection limit of 1.1 microU/L was developed for the measurement of urinary growth hormone (UGH). The assay was shown to be specific and precise. There was a good correlation between serum growth hormone (GH) and UGH concentrations in 20 patients with acromegaly and six volunteers following an intravenous injection of recombinant GH. We concluded therefore that UGH measurements appear to provide a satisfactory index of GH secretion. The use of the assay in the investigation of growth disorders was assessed. We studied 11 pre-pubertal children, six of normal stature, and five of short stature, over a 6-month period. Sequential fortnightly measurements of UGH were carried out and height velocity was determined. The children of short stature grew at a slower rate and excreted less GH than the children of normal stature. However, we observed considerable within-individual variability in GH excretion in both groups (CV 22-98%). We therefore recommend that sequential UGH analyses should be carried out and the results interpreted in conjunction with growth measurements. However, further investigations into the renal handling of GH are needed to establish optimum sampling regimes.

Acromegaly↗
PubMed1993

Asbestos fibre length-dependent detachment injury to alveolar epithelial cells in vitro: role of a fibronectin-binding receptor.

A short and a long fibre sample of amosite asbestos were tested for their effects on cells of the human Type 2 alveolar epithelial cell-line A549 in vitro. The long amosite sample was found to cause a rapid detachment of the epithelial cells live from their substratum. At the highest dose, on average 28% of the cells present were detached in this way. Studies on the mechanism of the detachment injury showed that it did not involve oxidants since it was not ameliorated by scavengers of active oxygen species. Neither was the effect reduced by treatment of the fibres with the iron chelator Desferal. Treatments reported to increase the interaction between fibres and cells, serum and poly-L-lysine, did not influence the detachment injury, nor did lung lining fluid. Conversely, the fibronectin tripeptide RGD alone could cause detachment which suggested that a fibronectin-binding integrin was involved. This receptor could be reduced in activity by long fibre exposure, leading to detachment. The detaching effect of fibre could be mimicked by the protein kinase C activator PMA, and so the second messenger system of the cell could also be involved. This type of injury could be important in the pathology associated with exposure to long fibres.

Asbestos↗
PubMed1992

Preparation of a chemiluminescent imidoester for the non-radioactive labelling of proteins.

A chemiluminescent aryl acridinium ester was synthesized which possesses an imidate ester group capable of reacting with proteins under mild conditions. The compound can be detected at levels as low as 5.2 x 10(-19) mol using commercially available luminometers and can therefore be used to produce high specific activity labelled antibodies for use in immunochemiluminometric assays. The imidate ester compares favourably with a previously reported N-succinimidyl ester in terms of its labelling properties but is easier to synthesize, requiring one less step. The compound was used to label affinity purified to synthesize, requiring one less step. The compound was used to label affinity purified sheep antibodies to human parathyroid hormone to demonstrate its utility in a two-site immunochemiluminometric assay for the measurement of intact parathyroid hormone.

Acridines↗
PubMed1992

Menogaril in the treatment of relapsed multiple myeloma. A phase II trial of the Cancer Center of Wake Forest University.

Fifteen patients with relapsed multiple myeloma (MM) were treated with menogaril 160 mg/m2 intravenously (IV) every 28 days. No responses were seen: 8 patients had stable disease, 4 progressed after one course of therapy, and 3 patients were removed from study after 1 course for other reasons. Four of the 8 patients with stable disease had an improved performance status, and 3 had a decrease in analgesic use. The major toxicity was myelosuppression. The median progression-free interval was 3.0 months with a range of 0.7 to 22 months and median survival was 11.3 months with a range of 0.7 to 39+ months. Menogaril displays little activity in patients with previously treated MM.

Antineoplastic Agents↗
PubMed1992

The relationship between adenoma weight and intact (1-84) parathyroid hormone level in primary hyperparathyroidism.

The relationship between preoperative serum levels of intact parathyroid hormone (PTH), serum calcium, and the weight of parathyroid adenoma has been investigated in 44 patients undergoing surgery for primary hyperparathyroidism due to single gland disease. There was no significant correlation between preoperative serum calcium and either intact PTH concentration or adenoma weight (r = 0.465 and 0.381, respectively). Although there was a significant correlation between PTH concentration and adenoma weight (r = 0.850, p less than 0.0005), this correlation was lost when two unusually heavy adenomas weighing 10.98 and 15.23 g were removed from the analysis. Clearly, a preoperative direct prediction of gland weight determined from PTH level was not possible. Patients with adenomata heavier than 750 mg had a significantly lower circulating PTH level per mg of adenoma than patients with glands lighter than 750 mg. PTH secretion in vitro in low calcium medium by adenoma cells from glands weighing less than 1 g was higher than secretion by cells from adenomas heavier than 1 g. Larger parathyroid adenomata appear to secrete less PTH per unit weight in vivo and per unit cell in vitro under conditions of maximal stimulation.

Adenoma↗
PubMed1992

The effects of heating and devitrification on the structure and biological activity of aluminosilicate refractory ceramic fibres.

Three grades of ceramic fibre have been examined for their composition, structures and biological effect in several in vitro assay systems. The fibres were examined in the 'as-manufactured' state and after heating at 1200 and 1400 degrees C. Devitrification of the fibres at 1200 degrees C probably gave mullite crystals on the surface and caused the formation of the high-temperature form of cristobalite and, in zirconia grade fibres, the high-temperature, tetragonal form of zirconia as well. Further heating changed surface structure and led to zircon production in the zirconia fibres. Heating reduced the affinity of the fibres for the surface of V79-4 cells and lowered fibre toxicity toward these cells and towards macrophage-like cells. These changes in toxicity were not due to a reduction in the fibrous nature of the materials although they did become more brittle and powders prepared from them contained more isometric particles than those from as-manufactured materials. This suggests that the devitrification occurring during the use of these materials in high-temperature environments will not necessarily enhance their adverse biological activities despite the production of one phase of crystalline silica.

Aluminum Silicates↗
PubMed1992

Measurements of the efficiency of respirator filters and filtering facepieces against radon daughter aerosols.

The filtration efficiencies of respirator filters and filtering facepieces have been tested against radon daughters in a fluorspar mine. The test method involved the use of sampling filters exposed to natural radon daughters in air filtered by the test respirators. Respirators with a filtration efficiency high enough for them to be considered suitable for use against toxic dusts generally reduced radon daughter levels by 90% or more, though nuisance dust masks were ineffective. The measured penetration of radon daughters through the former types of filter correlated reasonably well with the penetration of 0.1 microns neutralized monodisperse aerosols, and with that of the BS 4400 sodium chloride aerosol, measured in the laboratory. To simulate exposure in working conditions mine air containing radon daughters was drawn through the test filters for 8 h, but their performance was not affected and they were not measurably radioactive as a result.

Aerosols↗
PubMed1991

The production of an amine-modified derivative of 5-aminosalicylic acid by activated neutrophils. Roles for myeloperoxidase and chloride ions.

Following incubation with activated neutrophils, two metabolites of 5-aminosalicyclic acid (5-ASA) were identified by HPLC. These two metabolites accounted for approximately 60% and 20% of the original 5-ASA. The formation of the major metabolite was prevented by pre-incubation with the peroxidase inhibitor, azide, and reduced by the omission of chloride ions from the incubation medium, or the presence of catalase. A similar product was generated by sodium hypochlorite or myeloperoxidase/H2O2, mass spectroscopical analysis being consistent with it being 5-nitroso-salicylate. Our finding suggests that the efficacy of 5-ASA results from its ability to react with and so scavenge hypochlorite ions. The amount of amine-modified 5-ASA in the faecal stream may thus provide an indicator for hypochlorite production in the bowel.

Aminosalicylic Acids↗
PubMed1991

Two new uses of 8-F feeding tube in performing injecting urethrograms.

A modification of a previously described method for visualizing the urethrovesical junction is described. This modification is easier to perform, less messy, and obtains superior images to the method now used. A new method for outlining urethral strictures is also described. Both methods use an 8-F feeding tube.

Catheterization↗
PubMed1991

Carcinogenicity of the insulation wools: reassessment of the IARC evaluation.

In assessing the health evidence concerning man-made mineral fibers, the chemical composition, surface activity, durability, and size of fibers have to be taken into account. Special-purpose fine glass fibers need to be separated from the insulation wools (glass, rock, and slag wool). The epidemiological evidence is sufficient to conclude that there has been no mesothelioma risk to workers producing or using glass wool, rock wool, or slag wool. The epidemiological studies have been large and powerful, and they show no evidence of a cause-effect relationship between lung cancer and exposure to glass wool, rock wool, or slag wool fibers. There is some evidence of a small cancer hazard attached to the manufacturing process in slag wool plants 20 to 50 years ago, when asbestos was used in some products and other carcinogenic substances were present. However, this hazard is not associated with any index of exposure to slag wool itself. Animal inhalation studies of ordinary insulation wools also show that there is no evidence of hazard associated with exposure to these relatively coarse, soluble fibers. The evidence of carcinogenicity is limited to experiments with special-purpose fine durable glass fibers or experimental fibers, and only when these fibers are injected directly into the pleural or peritoneal cavity. Multiple chronic inhalation studies of these same special-purpose fine glass fibers have not produced evidence of carcinogenicity. It is suggested that the present IARC evaluation of the carcinogenic risk of insulation wools should be revised to Category 3: not classifiable as to carcinogenicity to humans.

Animals↗
PubMed1991

Design, synthesis, and physicochemical properties of a novel, conformationally restricted 2,3-dihydro-1,3,4-thiadiazole-containing angiotensin converting enzyme inhibitor which is preferentially eliminated by the biliary route in rats.

Two novel series of dihydrothiadiazole ring containing inhibitors of angiotensin converting enzyme have been designed and synthesized. The compounds are highly potent enzyme inhibitors and, as a consequence of conformational restriction, chemically stable with respect to undesirable cyclization reactions. The most interesting compound from this series, 5a (FPL 63547), is the monoethyl ester prodrug of the highly potent "aminocarboxy" inhibitor 5b (FPL 63674). It produces an antihypertensive effect of long duration in animal models after oral dosing. Unlike other ACE inhibitors, 5b is eliminated almost entirely by biliary clearance in the rat. The favorable pharmacological properties of 5a and 5b are rationalized in terms of their unique physicochemical profiles. The clear preference for biliary clearance seen with 5b is consistent with its lipophilicity and its high degree of net ionization at physiological pH, which results from the very low pKa of the C-terminus carboxylic acid function. FPL 63547 is presently undergoing clinical investigation in man.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Factors affecting the interaction of asbestos fibres with mammalian cells: a study using cells in suspension.

One of the earliest events in pathogenesis by mineral fibres must be an interaction between fibre and cell surfaces. Using a simple technique in which cells in suspension were incubated with fibres and adhesion monitored by separation on a density gradient it has been shown that such interactions occur through two distinct mechanisms. The first, a charge-mediated effect, occurs with positively charged fibres such as chrysotile asbestos. The second, with amphibole or glassy fibres, is mediated by fibronectin which first binds to the fibre. The bound protein then attaches to RGD receptors on the cell surface; calcium and magnesium ions are necessary for optimal adhesion. The RGD receptors bind to a tripeptide region on the protein and small peptides containing the RGD sequence block fibre-cell interaction. If the surface silanol groups on the fibre were chemically coupled to trialkylsilyl groups then interaction was slowed.

Amino Acid Sequence↗