Antibiotic sensitivity testing for infections in developing countries: lacking the basics.
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Biomedical subjects
Publications and source records attributed to R C Brown.
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We report a case of severe chronic normal tissue injury following conventional irradiation in a 33-year-old patient with a strong family history of cancer. Her cultured fibroblasts exhibited a response to low-dose-rate irradiation similar to fibroblasts taken from a normal individual. For acute irradiation her fibroblasts showed a slight increased sensitivity to single doses compared to fibroblasts from a normal individual. This difference was much larger when fractionated irradiation was given. It is concluded that the hypersensitive response of this patient was due to the fractionated radiotherapy and not to the low-dose-rate brachytherapy. We believe that this is the first report of this form of cellular radiosensitivity which is mainly expressed in fractionated radiotherapy.
Passive samplers are light, convenient and cheap. However, the sample size tends to be small and a correlation exercise between the results of a passive sampler and a conventional sampler must be carried out. The design principles and mode of action of an electret-based passive dust sampler are described. The device captures dust particles at a rate independent of the velocity of air except when this is very low but dependent on the electrical properties of the dust being sampled. Experimental results are presented of measurements made in bakeries, pig farms, a dairy farm, an arable farm and a rubber-manufacturing plant. Correlation between measurements made with the passive sampler and measurements of inhalable dust performed by other means are reasonable. The results are interpreted in terms of the physical properties of the dust being sampled.
The well-known health effects following exposure to amphibole asbestos have led to some concern about the potential for other fibrous materials to cause similar diseases. This paper presents a summary of some of the inhalation experiments conducted with ceramic fibres in both rats and hamsters at the Research and Consulting Company, Geneva. One ceramic fibre (designated RCF1) was tested in rats at four exposure levels, this fibre was also tested in hamsters. Three other fibres were only tested in rats at the highest level--30 mg m-3. The increased incidence of tumours in these experiments has been contrasted with the negative results obtained with glass or mineral wools. However, there is evidence that the ceramic fibres were longer than the glass fibres and that long ceramic fibres were retained in lung tissue to a greater extent. This is sufficient to explain the results without recourse to explanations based on chemical differences between fibres.
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The toxin coregulated pilus (TCP) is required for Vibrio cholerae to colonize the human intestine. The expression of the pilin gene, tcpA, is dependent upon ToxR and upon ToxT. The toxT gene was recently mapped within the TCP biogenesis gene cluster and shown to be capable of activating a tcpA::TnphoA fusion when cloned in Escherichia coli. In this study, we determined that ToxR/ToxT activation occurs at the level of tcpA transcription. ToxT expressed in E. coli could activate a tcp operon fusion, while ToxR, ToxR with ToxS, or a ToxR-PhoA fusion failed to activate the tcp operon fusion and we could not demonstrate binding of a ToxR extract to the tcpA promoter region in DNA mobility-shift assays. The start site for the regulated promoter was shown by primer extension to lie 75 bp upstream of the first codon of tcpA. An 800-base tcpA message was identified, by Northern analysis, that correlates by size to the distance between the transcriptional start and a hairpin-loop sequence between tcpA and tcpB. The more-sensitive assay of RNase protection analysis demonstrated that a regulated transcript probably extends through the rest of the downstream tcp genes, including toxT and the adjacent accessory colonization factor (acf) genes. An in-frame tcpA deletion, but not a polar tcpA::TnphoA fusion, could be complemented for pilus surface expression by providing tcpA in trans. This evidence suggests that the tcp genes, including toxT, are organized in an operon directly activated by ToxT in a ToxR-dependent manner. Most of the toxT expression under induced conditions requires transcription of the tcpA promoter. Further investigation of how tcp::TnphoA insertions that are polar on toxT expression retain regulation showed that a low basal level of toxT expression is present in toxR and tcp::TnphoA strains. Overall, these observations support the ToxR/ToxT cascade of regulation for tcp. Once induced, toxT expression becomes autoregulatory via the tcp promoter, linking tcp expression to that of additional colonization factors, exotoxin production, and genes of unknown function in cholera pathogenesis.
OBJECTIVES: To review the scientific literature on the health effects of refractory ceramic fibres (RCFs). The adverse effects of exposure to asbestos has led to concern about the potential for other fibrous materials to cause diseases. For this reason the human populations most heavily exposed to synthetic mineral fibres have been examined for any adverse effects and many types of fibre have been studied in animal experiments. One type of man made vitreous fibres (MMVFs), refractory ceramic fibres (RCFs), are principally used in thermal insulation at high temperatures--up to 1400 degrees C. As manufactured RCFs exist in a glassy, non-crystalline (sometimes called amorphous) state, they have various compositions, physical properties, and sized fibres. METHODS: All reports on the health effects of RCFs available up to the end of 1994 have been examined and the scientific literature reviewed although all publications have not necessarily been referenced. CONCLUSIONS: In recent inhalation experiments conducted with both rats and hamsters at the Research and Consulting Company, Geneva, at the highest dose tested (30 mg/m3) there was an increased incidence of tumours in both species. Lower doses were only examined in the rat and at these doses there was no significant excess of lung tumours. Epidemiological investigations of workers engaged in the manufacture of ceramic fibres have shown a small excess of pleural plaques. This phenomenon is being further investigated but could be due to confounding exposures. The populations available for study are small and their exposures fairly short, but it is considered prudent that they should remain under surveillance for some time to come. This is despite the fact that present exposures in the ceramic fibre industry are low (< 1 f/ml) and are being reduced.
In order to determine whether they are potentially carcinogenic to the pleural mesothelium, three samples of ceramic fibre have been administered to rats by the intrapleural route. These samples were a high-duty grade refractory ceramic fibre (manufactured by Thermal Ceramics Ltd) in the as-manufactured vitreous state and two devitrified samples produced by heating the same fibre for 2 weeks at 1200 degrees C and for two weeks at 1400 degrees C. The mean lifespans of the groups of rats treated with vitrified and devitrified ceramic fibres were not significantly different from that of the control rats. In these studies none of the treated or control rats developed pleural mesothelioma, making it unlikely that ceramic fibres of this type, whether vitreous or devitrified, are potentially carcinogenic to the pleural mesothelium.
We report here the cloning of a new member of the endothelium differentiation gene (edg) subfamily of G-protein-coupled receptors. This novel cDNA sequence was cloned from the ovine pars tuberalis using a reverse transcriptase polymerase chain reaction (RT-PCR) amplification with degenerate primers homologous to the highly conserved II and VII transmembrane domains of the G-protein coupled receptor gene family. The PCR product was random primed with 32P and used as a probe to screen a size-selected cDNA ovine pars tuberalis library, which resulted in the isolation of a single clone of 2700 bp. This novel sequence was named edg-2, because its nucleic acid sequence was 55% homologous over 501nt overlap to an orphan sequence cloned from human endothelial cells, the endothelial differentiation gene, edg-1. The highest degree of aminoacid homology (42%) occurs in the seven putative transmembrane domains, particularly between the transmembrane domains III and VI (53% and 64%, respectively). The intervening hydrophilic domains are short and there are numerous putative phosphorylation sites for Ser/Thr-protein kinases in the second and third intracellular loop and in the COOH-terminal domain. Through Northern analysis of total RNA, low levels of at least four transcripts of 2.3, 2.5, 3.2 and 4 kb were found in sheep cerebral cortex and a 4.2 kb transcript was observed in NIH/3T3 fibroblasts. In addition, edg-2 transcripts (415 bp) were amplified by RT-PCR from pars tuberalis, cerebral blood vessels, hypothalamus, and retina. Serum stimulation of Chinese hamster ovary (CHO) cells expressing the edg-2 receptor resulted in increased cell proliferation, as measured by [3H]-thymidine incorporation. Edg-1 and edg-2 appear to be distinct genes that may encode protein products that bind the same or related ligand.
An in vitro dye leakage study was performed to compare the apical microleakage of a glass ionomer root canal sealer to Roth's 801 sealer. Forty-five single-rooted teeth were randomly divided into three groups: Ketac-Endo, Roth's 801, and the control group (no sealer). All groups were instrumented using a step-back technique and obturated with laterally condensed gutta-percha. The teeth were placed in a vacuum chamber under a pressure of 710 torr for 15 min and then immersed in India ink under vacuum for 24 h. The teeth were allowed to passively stain for 4 days and were cleared and evaluated for linear dye leakage using a binocular dissecting microscope. Statistical analysis revealed that sealer significantly improves the apical seal of laterally condensed gutta-percha. However, the apical seal exhibited by Ketac-Endo was not significantly different from that provided by Roth's 801 sealer.
An investigation has been made of the production of dust by hand sanders when used without dust extraction, with integral dust extraction and with external dust extraction. The apparatus used for the measurement was designed to carry out sanding in a repeatable manner, simulating normal working practice. The geometry of the wood sanded affects the dust concentration critically, whereas the effects of the sandpaper grade and of the filtration efficiency of the collection system are small. Belt sanders produce high dust levels in all situations, but they are very efficient in removing wood, which means that they need to be used for only a short period. The integral systems of orbital sanders give good dust control on flat wood but not on edges. The high air extraction rate of external systems results in much better dust control during the sanding of edges, though the performance of the two extraction systems on flat wood is broadly similar. The size distribution of the dust clouds produced by the sanding is relatively constant, but that produced by rotary sanders tends to be coarser than that produced by orbital sanders, consistent with the smoother finish given by the latter. The electric charge on the dust produced by sanding is high.
In vitro solubility testing is an important means of assessing the likely behavior of fibers that are respired and accumulate in the lung. The problem has been that such tests often do not mirror the dissolution and removal mechanisms seen in vivo. Comparison of iron and silica solubility values of various types of mineral fiber showed no obvious correlation. Treating a mineral fiber containing high levels of calcium with normal balanced salt solutions produces a precipitate of calcium phosphate on the fiber surface. This deposit was not seen in fibers isolated from the lung of exposed animals. New solutions have been developed and with variations in the methods of exposing fibers, results similar to those seen in vivo have been obtained. Suitable fluid phases have been examined in static and flow-through systems. The relationship of solubility to biological activity is discussed.
Mineral fibers, including asbestos, are ubiquitous contaminants of the environment. Asbestos fibers are generally present at levels below 1 fiber/L in air though 10 fibers/L may be found in cities; these levels do not appear to be high enough to present a hazard to health. These fibers come mostly from the use of fibrous materials as thermal and acoustic insulation in buildings, and their use as friction materials. Historically, occupational air levels were often very high and as a result there was a high incidence of fibrosis and also cancer in exposed workers, mostly among those in the industries concerned with the winning or processing of asbestos fiber. Levels high enough to produce disease have also occurred paraoccupationally in the families of asbestos workers. The effect of fire and explosion in a building is to disrupt its structure and vastly increase the level of airborne fiber for a considerable distance (kilometers) around it. Air levels of fiber can remain high for months, and as a result the earliest occupational experiences are likely to be repeated. The greatest danger is from exposure to blue and brown asbestos, and it is known that even a single high exposure can be responsible for the development of a tumor decades later.
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.
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.
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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.
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.