Spontaneous abortion in the British semiconductor industry: An HSE investigation. Health and Safety Executive.

BACKGROUND: The UK Health and Safety Executive (HSE) conducted a study to examine the risk of spontaneous abortion (SAB) in British female semiconductor industry workers, following reports from the USA which suggested an association between risk of SAB and work in fabrication rooms and/or exposure to ethylene glycol ethers. METHODS: A nested case-control study based on 2,207 women who had worked at eight manufacturing sites during a 5-year retrospective time frame was established; 36 cases were matched with 80 controls. RESULTS: The overall SAB rate in the industry was 10.0%. (65 SABs/651 pregnancies) The crude odds ratio (OR) for fabrication work was 0.65 (95% CI 0.30-1.40). This was essentially unchanged after adjustment for a range of potential confounding factors in the first 3 months of pregnancy and was reduced to 0.58 (95% CI 0.26-1.30) after adjustment for smoking in the previous 12 months. There were no statistically significantly elevated ORs for any work group or any specific chemical or physical exposure in the industry. CONCLUSIONS: There is no evidence of an increased risk of SAB in the British semiconductor industry. Am. J. Ind. Med. 36:557-572, 1999. Published 1999 Wiley-Liss, Inc.     

Evidence-based policy-making in the NHS: exploring the interface between research and the commissioning process.

BACKGROUND: The UK National Health Service (NHS) R&D strategy acknowledges the importance of developing an NHS where practice and policy is more evidence-based. This paper is based on a qualitative study which aimed to identify factors which facilitate or impede evidence-based policy-making at a local level in the NHS. METHODS: The study involved a literature review and case studies of social research projects which were initiated by NHS health authority managers or general practitioner (GP) fundholders in one region of the NHS. Data were collected through in-depth interviews with lead policy-makers, GPs and researchers working on each of the case studies and analysis of project documentation. RESULTS: An over-arching theme from the analysis was that of the complexity of R&D in purchasing. The two worlds of research and health services management often sit uncomfortably together. For this reason it was not possible to describe a 'blueprint' for successful R&D, although several important issues emerged. These include sharing an appropriate model for research utilization, the importance of relationships in shaping R&D, the importance of influence and commitment in facilitating evidence-based change, and the resourcing of R&D in purchasing. CONCLUSIONS: These issues have important implications for the strategic development of R&D as well as for individual project application. Moving beyond the rhetoric of evidence-based policy-making is more likely if both policy-makers and researchers openly acknowledge this complexity and give due concern to the issues outlined.     

Antibacterial resistance in the intensive care unit: mechanisms and management

The incidence of multiple antimicrobial resistance of bacteria which cause infections in the intensive care unit is increasing. These include methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, penicillin-resistant Streptococcus pneumoniae and cephalosporin and quinolone resistant coliforms. More recently, pan antibiotic resistant coliforms, including carbapenems, have emerged. The rapidity of emergence of these multiple antibiotic-resistant organisms is not being reflected by the same rate of development of new antimicrobial agents. It is, therefore, conceivable that patients with serious infections will soon no longer be treatable with currently available antimicrobials. Strict management of antibiotic policies and surveillance programmes for multiple resistant organisms, together with infection control procedures, need to be implemented and continuously audited. As intensive care units provide a nidus of infection for other areas within hospitals, this is critically important for prevention of further spread and selection of these resistant bacteria.     

Localization of GABA(B) (R1) receptors in the rat hippocampus by immunocytochemistry and high resolution autoradiography, with specific reference to its localization in identified hippocampal interneuron subpopulations

Immunocytochemical and autoradiographic methods were used to localize the GABA(B) receptor in the normal rat hippocampus. GABA(B) receptor 1-like immunoreactivity (GBR1-LI) was most intense in presumed GABAergic interneurons of all hippocampal subregions. It was also present throughout the hippocampal neuropil, where it was most intense in the dendritic strata of the dentate gyrus, which are innervated by the perforant pathway and inhibitory dentate hilar cells, and in strata oriens and radiatum of area CA3. The dendritic regions of area CA1 exhibited less GBR1-LI than area CA3. GBR1-LI was detectable in the somata of CA1 pyramidal cells, but was minimal or undetectable within the somata of dentate granule cells and CA3 pyramidal cells. GBR1-LI was similarly minimal in the dentate hilar neuropil, and in stratum lucidum, the two regions that contain granule cell axons and terminals. Nor was GBR1-LI detectable in the inhibitory basket cell fiber systems that surround hippocampal principal cell somata. Fluorescence co-localization studies indicated that significant proportions of interneurons expressing somatostatin, neuropeptide Y, cholecystokinin, calbindin, or calretinin also expressed GBR1-LI constitutively. Conversely, parvalbumin-positive GABAergic basket cells of the dentate gyrus and hippocampus, which form GABA(A) receptor-mediated inhibitory axo-somatic synapses, rarely contained detectable GBR1-LI. High resolution autoradiography with the GABA(B) receptor antagonist CGP 62349 revealed a close correspondence between receptor ligand binding and GBR1-LI, with several notable exceptions. Ligand binding closely matched GBR1-LI throughout the hippocampal, cortical, thalamic, and cerebellar neuropil. However, the hippocampal interneuron somata and dendrites that exhibited the most intense GBR1-LI, and the GBR1-positive somata of CA1 pyramidal cells, did not exhibit a similar density of [3H]-CGP 62349 binding. These data clarify the relationship between immunocytochemically identified receptor protein and potentially functional receptors, indicating that GBR1-LI reflects both non-functional cytoplasmic GBR1 and the ligand-bindable form of the protein, both before dimerization with GBR2 and after translocation to functional sites within cells. The staining and binding patterns further suggest that GBR1 is constitutively expressed in specific neuronal populations, and may exist in higher concentration in the axons of inhibitory hippocampal pathways that innervate dendritic zones, than in axo-somatic inhibitory terminals. Whether GBR1 is inducible in cells that contain GBR1 mRNA, but no detectable constitutive protein, remains to be determined in experimental studies.     

Effect of a long-term low tryptophan diet on the prolactin responses to the 5-HT1A and 5-HT2C agonists, 8-OH-DPAT and mCPP in the male rat

The study was undertaken to assess the long term effects of tryptophan (TRP) depletion through diet on the prolactin (PRL) responses to the serotonin (5-hydroxytryptophan, 5-HT) agonists m-chlorophenyl-piperazine (mCPP) and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in the male rat. The low TRP diet caused significant reductions in both plasma total TRP and brain cortical 5-HT content together with a significant increase in the PRL responses to mCPP. In contrast the PRL responses to 8-OH-DPAT in animals on the low TRP diet for 1 week and 6 weeks were similar to control rats. However, a small but significant increase in PRL was observed at 2 min after dosing in the 1-week group. At the same time the 3H-8-OH-DPAT binding parameters, Kd and Bmax, were similar in both control and TRP depleted animals. The results confirm that long-term TRP depletion causes a deficiency of brain TRP and a subsequent reduction of brain 5-HT. This is associated with an enhanced PRL response to mCPP probably resulting from a functional up-regulation of post-synaptic 5-HT2C receptors. The small or transient changes brought about by long-term TRP depletion on post-synaptic 5-HT1A receptors, suggests that these receptors may be less susceptible to 5-HT depleting effects than the 5-HT2C subtype.     

Thoracolumbar disc degeneration in young fast bowlers in cricket: a follow-up study

OBJECTIVE: To determine the progression of thoracolumbar disc degeneration in young fast bowlers in cricket. DESIGN: Prospective fast bowling technique and MRI follow-up study. BACKGROUND: Previous studies on high-performance young fast bowlers have found that lumbar spine pathology was related to the mixed bowling technique. METHODS: Nineteen young male fast bowlers (mean age 13.6 years) underwent MRI scans to detect the presence of intervertebral disc abnormalities. Subjects were also filmed laterally (200 Hz) and from directly above (100 Hz) whilst bowling two maximum velocity deliveries (session 1). Subjects were tested using an identical methodology 2.7 years later (session 2). RESULTS: At session 1, the incidence of thoracolumbar disc degeneration was 21%; however, at session 2, the incidence significantly (P = 0.008) increased to 58%. Furthermore the increase in the incidence of back pain between session 1 and session 2 was also significant (P = 0.002). The progression of disc degeneration was found to be significantly (P = 0.015) related to the group of fast bowlers who utilized the mixed technique during both session 1 and 2 when compared to those who used this technique during one session only. CONCLUSIONS: Thoracolumbar disc degeneration and back pain increase significantly during the time period examined in this study. Further, bowlers who utilize the mixed bowling technique stand a greater chance of developing degenerative changes of the spine.     

Enhanced therapeutic effect of amsalog (CI-921) in combination with cisplatin in vitro and in vivo

CI-921, the 5-methyl-4-carboxamide analog of amsacrine, in combination with cisplatin produced a 6-fold better cell kill in vitro than expected based on additive effects. The combination of CI-921 and cisplatin was subsequently evaluated in three in vivo model systems: intraperitoneally (TP) and intravenously (IV) implanted P388 leukemia, and advanced stage subcutaneously (SC) implanted LC-12 squamous cell carcinoma. All drug treatments were administered IP on an intermittent treatment schedule which was optimal for both agents. Combination therapy was superior to therapy with the best single agent alone, CI-921, in all three model systems. Against IP implanted P388 leukemia, combination therapy produced greater than 8 logs of net tumor cell kill with 60-day survivors (cures). This level of activity was 50-fold greater (1.7 log) than that obtained with CI-921 alone. An IV implant of P388 leukemia was used in a confirmatory study to provide a more rigorous evaluation against disseminated disease. Combination therapy against IV implanted P388 leukemia produced greater than 7.7 logs of net tumor cell kill, which was 630-fold greater (2.8 logs) than that obtained with CI-921 therapy alone. Against advanced stage LC-12 (200-1000 mg tumors at initial treatment), combination therapy improved tumor cell kill by 0.6 log (4-fold) over that obtained with CI-921 therapy alone and also produced greater numbers of 120-day survivors than did single agent therapy with CI-921. The combination of carboplatin and CI-921 was also evaluated against IV implanted P388 leukemia to determine if the enhanced therapeutic effect of CI-921 and cisplatin could be extended to include CI-921 and carboplatin. Combination therapy with CI-921 and carboplatin increased net log tumor cell kill by 0.8 and 1.5 log in two separate tests (6- and 32-fold, respectively) over that obtained with CI-921 therapy alone. The data indicate that combination therapy with CI-921 and platinum containing anticancer agents may have clinical application.