Library requirements and problem-based learning: The Medical Sciences Library, The University of the West Indies.
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Biomedical subjects
Publications and source records attributed to M Lewis.
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Thirty per cent of women aged 35 years and over suffer from heavy menstruation, but only 7% have consulted a doctor in the previous six months, suggesting that a significant number of these women do not consult a general practitioner. There is evidence that women who report heavy menstruation are more likely to have symptoms of psychological disturbance. This study sets out to determine whether the presence of symptoms of anxiety and depression might be linked to subsequent consultation for increased vaginal bleeding in primary care.
The importance of atrial fibrillation as a treatable risk factor for stroke is well established. Less is known about how to find previously unidentified cases within the community so that antithrombotic treatment can be offered to a wider group of at-risk patients. The aim of our study was to examine ways to improve the efficiency of practice-based screening for atrial fibrillation, including issues of time and financial cost. We used different combinations of pulse palpation and interpretation of 12-lead and bipolar electrocardiographs as carried out by practice nurses. The best strategy for the detection of atrial fibrillation in a practice population would appear to be to screen all eligible subjects by nurse pulse palpation, followed by 12-lead electrocardiograph readings in those who have a pulse suggestive of atrial fibrillation. The electrocardiograph interpretation can be undertaken effectively by a trained nurse.
The phylogeny of human T cell lymphotropic virus type II (HTLV-II) was investigated by using strains isolated from Amerindian and Pygmy tribes, in which the virus is maintained primarily through mother-to-child transmission via breast-feeding, and strains from intravenous drug users (IDUs), in which spread is mainly blood-borne via needle sharing. Molecular clock analysis showed that HTLV-II has two different evolutionary rates with the molecular clock for the virus in IDUs ticking 150-350 times faster than the one in endemically infected tribes: 2.7 x 10(-4) compared with 1.71/7.31 x 10(-7) nucleotide substitutions per site per year in the long terminal repeat region. This dramatic acceleration of the evolutionary rate seems to be related with the mode of transmission. Mathematical models showed the correlation of these two molecular clocks with an endemic spread of HTLV-II in infected tribes compared with the epidemic spread in IDUs. We also noted a sharp increase in the population size of the virus among IDUs during the last decades probably caused by the worldwide increase in intravenous drug use.
A variety of environmental stresses stimulate the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEKK) > stress-activated protein kinase (SAPK)-ERK kinase (SEK) > SAPK/c-Jun NH(2)-terminal kinase (JNK) stress-activated protein kinase cascade and coordinately activate the transcription factor NFkappaB. Mechanisms of stress activation upstream of MEKK1 have not been precisely determined. Redox mechanisms involving sulfhydryls are likely because N-acetyl-cysteine at millimolar concentrations blocks stress signals. Because intracellular sulfhydryl concentrations can be regulated through redox cycling involving reactive quinones (1), we tested the ability of quinone reductase inhibitors to alter stress signaling. Several quinone reductases are inhibited by dicoumarol, a coumarin derivative. Dicoumarol prevented SAPK activation in vivo by chemical cell stressors and also prevented SAPK activation induced by expression of the tumor necrosis factor alpha (TNFalpha) receptor-associated protein TRAF2 but not by expression of truncated active MEKK1. Other coumarin derivatives failed to block SAPK activation, but other inhibitors of quinone reductases, particularly menadione, similarly blocked SAPK activation. Cells deficient in a major quinone reductase, NQO1, displayed hypersensitivity to dicoumarol stress inhibition, whereas SAPK in cells reconstituted with the NQO1 gene displayed relative dicoumarol resistance. Consistent with the proposed role of overlapping upstream signaling cascades in activation of NFkappaB, dicoumarol also blocked NFkappaB activation in primary macrophages stimulated with either lipopolysaccharide or TNFalpha. In addition, dicoumarol strongly potentiated TNFalpha-induced apoptosis in HeLa cells, probably by blocking the anti-apoptotic effect of NFkappaB. The ability of dicoumarol to simultaneously inhibit SAPK and NFkappaB activation and to potentiate apoptotic cell death suggests that SAPK is not an obligate participant in apoptosis. Dicoumarol, currently in clinical use as an oral anticoagulant, represents a potential therapeutic inhibitor of the SAPK and NFkappaB response.
OBJECTIVE: To compare the clinical effectiveness of local corticosteroid injection, standard non-steroidal anti-inflammatory drugs, and simple analgesics for the early treatment of lateral epicondylitis in primary care. DESIGN: Multicentre pragmatic randomised controlled trial. SETTING: 23 general practices in North Staffordshire and South Cheshire. PARTICIPANTS: 164 patients aged 18-70 years presenting with a new episode of lateral epicondylitis. INTERVENTIONS: Local injection of 20 mg methylprednisolone plus lignocaine, naproxen 500 mg twice daily for two weeks, or placebo tablets. All participants received a standard advice sheet and co-codamol as required. MAIN OUTCOME MEASURES: Participants' global assessment of improvement (five point scale) at four weeks. Pain, function, and "main complaint" measured on 10 point Likert scales at 4 weeks, 6 months, and 12 months. RESULTS: Over 2 years, 53 subjects were randomised to injection, 53 to naproxen, and 58 to placebo. Prognostic variables were similar between groups at baseline. At 4 weeks, 48 patients (92%) in the injection group were completely better or improved compared with 30 (57%) in the naproxen group (P<0.001) and 28 (50%) in the placebo group (P<0.001). At 12 months, 43 patients (84%) in the injection group had pain scores </=3 compared with 45 (85%) in the naproxen group and 44 (82%) in the placebo group (P>0.05). CONCLUSIONS: Early local corticosteroid injection is effective for lateral epicondylitis. Outcome at one year was good in all groups, and effective early treatment does not seem to influence this.
[formula: see text] The structure of "guaninediazonium ion" in its aggregate with cytosine has been explored with ab initio and density functional methods. The hydrogen-bonded aggregate between cytosine and guaninediazonium ion, 1, is a stable minimum, 3. While the isolated enol tautomer of guaninediazonium ion, 2, is significantly more stable than 1, the tautomeric aggregate 4 that results from double-proton-transfer in 3 is almost isoenergetic with 3. Most interesting and entirely unexpected is the finding that neither 3 nor 4 is predicted to be the thermodynamically predominant structure. Instead, single-proton-transfer to cytosine results in the most stable cytosinium-guaninediazo complex, 5.
The expression of the major matrix-degrading metalloproteinase, stromelysin (SL), is modulated by a variety of cytokines and growth factors. Interferon-gamma (IFN-gamma) is a potent modulator of SL expression, either inhibiting or activating expression in a cell-specific manner. We have investigated the mechanisms involved in the regulation of SL gene expression in cultured human fibroblasts by IFN-gamma. Reverse transcription-polymerase chain reaction (RT-PCR) assays confirmed the previously reported profound inhibitory response of SL mRNA expression to IFN-gamma [Amaldi et al., 1989]. For evaluation in transient gene expression assays, 1.2-kilobase (kb) pairs (-1214 to +14 relative to the transcription start site), and shorter, deletion mutant fragments of the SL promoter were cloned into appropriate chloramphenicol acetyltransferase transferase (CAT) expression vectors. The SL promoter along this region contains an active polyomavirus enhancer A-binding protein-3 (PEA-3) site at -216 and an activator protein-1 (AP-1) site at -70. Treatment of transfected neonatal foreskin fibroblasts with 300-500 U/ml IFN-gamma resulted in down-regulation of both basal and IL-1beta-induced CAT gene expression. IFN-gamma also decreased CAT expression when placed under the control of a synthetic multimeric AP-1 site construct. Gel-shift assay data indicate a decrease in specific binding to AP-1 oligonucleotide of nuclear extract from IFN-gamma and PMA/IFN-gamma-treated cells. The suppression of SL expression by IFN-gamma, in human fibroblasts therefore is mediated through the AP-1 element.
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The OH 36 ulna derives from Upper Bed II in the Olduvai Gorge, and is dated to circa 1.1-1.2 Myr. Multivariate analyses incorporating data from samples of modern humans, common and pygmy chimpanzees, gorillas, orangutans, and two other early hominin ulnae, Omo L40-19 and KNM-BK 66, suggest that OH 36 belonged to an individual with powerful forearms consistent with a locomotor repertoire that included arboreal locomotion. However, there is no compelling evidence that it made regular use of its forelimbs as supports when travelling on the ground. When compared with levels of intra- and intertaxon size and shape variation in the comparative sample (humans, chimpanzees, gorillas), the differences between OH 36, KNM-BK 66, and Omo L40-19 are compatible with OH 36 differing from the other two fossil hominin ulnae to the extent that modern humans differ from modern great apes. KNM-BK 66 and Omo L40-19 differ from each other in overall size and shape only to the degree that would be expected within any of the individual modern comparative samples. Based on these analyses, there is no evidence to support the hypothesis that OH 36 and Omo L40-19 belong to the same species of fossil hominin, or to two species that shared a similar forelimb locomotor repertoire. We suggest that OH 36 has the greater claim to be assigned to Paranthropus boisei, and we recommend that for the time being the latter be referred to the tribe Hominini gen. et sp. indet. The surprising result of these analyses is the overall size and shape similarity between Omo L40-19 and KNM-BK 66, two fossils that are separated in time by more than 1.5 million years, and which have traditionally been assumed to represent hominin species with quite different locomotor patterns.
OBJECTIVE: How children manifest psychological distress following the discovery of sexual abuse requires a better understanding of individual differences in developmental capacities and vulnerabilities. This study examined how age at the time of the abuse discovery and gender of victim are related to psychological distress. METHOD: One hundred and sixty-nine participants (96 children, 73 adolescents) were interviewed within 8 weeks of discovery of the abuse. Multivariate analyses were used to examine how age at discovery, and gender, with abuse characteristics as covariates, were related to shame, attribution style, depression, self-esteem, and traumatic events sequelae. RESULTS: Adolescents compared to children report a higher level of depressive symptoms, negative reactions by others, and lower levels of self-esteem, social support, and sexual anxiety. Girls compared to boys report higher levels of intrusive thoughts, hyperarousal, sexual anxiety, personal vulnerability, and perceiving the world as a dangerous place and lower levels of eroticism. CONCLUSIONS: These findings suggest the importance of considering individual differences in age and gender for understanding patterns of symptom expression. Treatment strategies need to reflect these individual differences in adjustment, such as targeting issues of sexual anxiety for girls and self-esteem for adolescents.
BACKGROUND: Postnatal depression affects one in ten women within 6 months of childbirth. The most effective treatment strategy for postnatal depression is not clear. METHODS: This prospective, naturalistic study of the treatment of postnatal depression compared 30 women treated at a specialised psychiatric day hospital with 30 women treated using routine primary care (RPC). Clinical, marital and social adjustment were assessed on three occasions over 6 months using: the Edinburgh Postnatal Depression Questionnaire (EPDS); the Clinical Interview schedule (CIS); the Anxiety Subscale of the Hospital Anxiety and Depression Scale; the Dyadic Adjustment Scale (DAS); and the Work Leisure and Family Life Questionnaire-Modified (WLFLQ-M). RESULTS: There were no significant differences between the two groups at baseline. However, there were significant differences in outcome at 3 and 6 months follow-up for all outcome measures except the DAS. At 6 month follow-up 21 of the PBDU group were no longer depressed compared with 7 of the RPC group. CONCLUSIONS: A specialised day hospital is a more effective treatment setting for postnatal depression than routine primary care. LIMITATIONS OF THE STUDY: The study is not an RCT, so systematic bias is possible. The sample size is relatively small and the duration of follow-up relatively short.
Diiron proteins represent a diverse class of structures involved in the binding and activation of oxygen. This review explores the simple structural features underlying the common metal-ion-binding and oxygen-binding properties of these proteins. The backbone geometries of their active sites are formed by four-helix bundles, which may be parameterized to within approximately 1 A root mean square deviation. Such parametric models are excellent starting points for investigating how asymmetric deviations from an idealized geometry influence the functional properties of the metal ion centers. These idealized models also provide attractive frameworks for de novo protein design.
Accelerated solvent extraction (ASE) is a new sample extraction method offering a number of advantages such as low pe -extraction cost, reduced solvent and time consumption, and simplified extraction protocols. In this study, the ASE method was applied to the extraction of polycyclic aromatic hydrocarbons (PAHs) from biological samples. For recovery studies, fish tissues and ground pork were used as sample matrices. Sample aliquots fortified with 16 PAHs were extracted by ASE, and the extracts were treated with sulfuric acid and Florisil, followed by gas chromatography-mass spectrometry analysis. The PAH recoveries by the ASE method were found to be comparable with or better than those by Soxhlet extraction. The extraction and quantitation method was then applied to the determination of PAHs in several smoked meat samples obtained from a local market. Up to 12 PAHs were found to be present at concentrations ranging from 3 to 52 ng/g wet sample.
The effects of a 2-year health-related school physical education program on standardized academic achievement scores was assessed in 759 children who completed Metropolitan Achievement Tests before and after the program. Schools were randomly assigned to condition: (a) Specialists taught the Sports, Play, and Active Recreation for Kids curriculum; (b) classroom teachers were trained to implement the curriculum; and (c) controls continued their usual programs. The Trained Teacher condition was superior to Control on Language, Reading, and Basic Battery. The Specialist condition was superior to Control on Reading, but inferior on Language. Despite devoting twice as many minutes per week to physical education as Controls, the health-related physical education program did not interfere with academic achievement. Health-related physical education may have favorable effects on students' academic achievement.
A branched-DNA (bDNA) signal amplification method was used to detect the mecA gene directly from blood culture broth growing staphylococci. BACTEC blood culture bottles with positive growth indices and containing staphylococcus-like organisms as shown by Gram stain were tested for the presence of the mecA gene. Comparison of test results was done among 225 patients (one blood culture from each patient). Compared with PCR, the sensitivity and specificity of the bDNA method are 100 and 99%, respectively. The bDNA test is carried out in a 96-well format and requires approximately 6 h to perform. Our preliminary results suggest that direct detection of the mecA gene by bDNA signal amplification is (i) sensitive enough to detect mecA directly from blood culture bottles without the requirement for subculture and (ii) as sensitive and specific as the PCR-based method.
BACKGROUND: This study evaluates two in-patient units attached to community mental health centres (CMHCs) that were designed to supplement acute in-patient care and to integrate with community-based after-care services. AIM: To examine the comparative outcome of patients with severe mental illness (SMI) admitted to the two units. METHOD: All patients with SMI admitted to the acute psychiatric wards serving the two CMHCs, those transferred to the community in-patient units and those admitted directly to these units (n = 110) were compared with patients (n = 67) admitted to acute wards serving two similar catchment areas without associated community beds. Baseline clinical and social measures were made and repeated at six and 12 months. Satisfaction with services was assessed at 12 months. RESULTS: The experimental group showed significantly better outcomes, significant reduction in unmet need and better satisfaction with services. CONCLUSIONS: The use of the community beds appears to have significant benefits for patients with SMI.
BACKGROUND: Innovative approaches to the provision of psychiatric care must justify their ability to improve the quality of life within the resource constraints imposed on psychiatry. AIMS: To examine the average costs per patient of the experimental and control group services. METHOD: An individual patient costing methodology that identified, measured and valued all public and private resources. RESULTS: The experimental group was more likely to remain in contact with services over a 12-month period, had fewer acute readmissions and spent less time in acute in-patient units. There were significantly different levels and patterns of resource consumption between the groups and between the two separate catchment areas. CONCLUSION: The cost analysis should be assessed in the context of the previous outcome analysis. It is likely, but not inevitable, that such units will increase the overall costs of care provision; this largely depends on the effectiveness with which such units are integrated into existing care provision.