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Biomedical subjects

M Lewis

Publications and source records attributed to M Lewis.

At least 55 records · Page 3Linked to original sources
PubMed2000

Carpal tunnel syndrome: a nested case-control study of risk factors in women.

Risk factors for the development of carpal tunnel syndrome in women were studied by means of a nested case-control analysis of a prospective cohort study of the health effects of oral contraception in British women. A total of 1,264 women who had a diagnosis of carpal tunnel syndrome reported by their general practitioner between 1968 and 1993 were compared with 1,264 age-matched control women who did not have this diagnosis. The syndrome was associated in older women with some hormonal factors, notably past use of oral contraception (adjusted odds ratio in women aged 40 years and over = 1.38, 95 percent confidence interval: 1.08, 1.76) and more generally with obesity (adjusted odds ratio = 1.68, 95 percent confidence interval: 1.29, 2.18). However, the strongest link was with a previous history of another musculoskeletal complaint for which consultation had been sought (adjusted odds ratio = 1.98, 95 percent confidence interval: 1.61, 2.42). Previous findings of a higher risk in women with diabetes and myxoedema were confirmed, but these contribute only a small proportion of all cases in women. There was no link with psychologic problems or nonmusculoskeletal pain complaints. The previously described increased incidence of carpal tunnel syndrome in women may be partly due to hormonal factors, but is also related to an underlying propensity to musculoskeletal problems and their higher overall frequency in women.

Adult↗
PubMed2000

Gemcitabine and vinorelbine in advanced nonsmall cell lung carcinoma: a phase II study.

BACKGROUND: The authors conducted a Phase II study to evaluate the activity of the combination of gemcitabine and vinorelbine in patients with advanced nonsmall cell lung carcinoma (NSCLC). METHODS: Patients were eligible if they had Stage IIIB (malignant pleural effusion) or Stage IV NSCLC, no prior chemotherapy, and Cancer and Leukemia Group B performance status (PS) 0-2. Patients with brain metastases were eligible if they were neurologically stable after brain irradiation. Thirty-three patients from participating institutions were enrolled. One patient was ineligible due to untreated brain metastases. Patients were treated with gemcitabine 1250 mg/m(2) over 30 minutes (1000 mg/m(2) for the first 6 patients) and vinorelbine 25 mg/m(2) over 6 minutes, both administered intravenously on Days 1 and 8 every 21 days. Treatment was planned for a total of six cycles or more if the patient had persistent benefit. Growth factors were not allowed. RESULTS: Among all 32 eligible patients, there were 8 partial responses, for an overall response rate of 25% (95% confidence interval [CI], 11.5-43. 4%). The median survival time was 8.3 months and the 1-year survival rate was 38% (95% CI, 24-59%). Patients with PS 0-1 had a median survival of 11.7 months and a 1-year survival rate of 48%. Grade 3 and 4 neutropenia was observed in 13% and 25% of the 148 treatment cycles, respectively. One patient died of neutropenic sepsis. Only 2 episodes of Grade 3 and 4 thrombocytopenia were observed. Nonhematologic toxicity was minimal. CONCLUSIONS: Gemcitabine and vinorelbine is an active and well-tolerated regimen in patients with advanced NSCLC, with response and survival rates at least comparable to those achieved with standard platinum-based regimens. This combination may be particularly suitable for the elderly or for patients who cannot tolerate more toxic platinum-based regimens.

Aged↗
PubMed2000

Atypical antipsychotics in ordinary clinical practice: a pharmaco-epidemiologic survey in a south London service.

The introduction of atypical antipsychotics has triggered a reevaluation of treatment strategies in schizophrenia. Although research findings inform about the efficacy and safety of drugs, it is the decisions made daily in ordinary practice that affect the vast majority of patients. The aim of this paper was to examine the use of atypical antipsychotics in clinical care, by means of a survey of prescribing practices for clozapine, risperidone, olanzapine, sertindole and quetiapine for all patients treated for DSM-IV schizophrenia within a psychiatric service. Seventy-five (26%) of the 286 patients identified were on atypical antipsychotics. Patients on clozapine were mostly male, had more than 15 years of contact with psychiatric services and were poor responders. Patients prescribed other atypicals had responded to prior treatment with typical neuroleptics and had less than five years of contact with psychiatric services. Gender distribution was equal in this group. The use of research criteria for treatment resistance identified only one patient, as prolonged use of high-dose neuroleptics was uncommon. The new atypical antipsychotics appear to be replacing older neuroleptics as the first-line treatment of schizophrenia while clozapine is mostly reserved for poor responders. Clinicians' definition of treatment resistance was variable and below the threshold used in research.

Adult↗
PubMed2000

A closer view of the conformation of the Lac repressor bound to operator.

Crystal structures of the Lac repressor, with and without isopropyithiogalactoside (IPTG), and the repressor bound to operator have provided a model for how the binding of the inducer reduces the affinity of the repressor for the operator. However, because of the low resolution of the operator-bound structure (4.8 A), the model for the allosteric transition was presented in terms of structural elements rather than in terms of side chain interactions. Here we have constructed a dimeric Lac repressor and determined its structure at 2.6 A resolution in complex with a symmetric operator and the anti-inducer orthonitrophenylfucoside (ONPF). The structure enables the induced (IPTG-bound) and repressed (operator-bound) conformations of the repressor to be compared in atomic detail. An extensive network of interactions between the DNA-binding and core domains of the repressor suggests a possible mechanism for the allosteric transition.

Allosteric Regulation↗
PubMed2000

Flogging the dead horse: the myth of nursing empowerment?

With the move towards a more 'open' National Health Service, a new deal for staff, and greater staff involvement the way ahead for nursing seems bright. The proposals in the governmental White Paper (1997) The New NHS: Modern, Dependable reflect the need for greater co-operation and for a greater empowerment of nurses. If the aims of such major change in the NHS are to be achieved we need to consider both the real effects of nursing empowerment from past history, and the problems involved in greater nursing involvement in the NHS as an organization. As such our discussion may throw some light on the possible ways to progress during such fundamental change. It is from such lessons that positive future progress may be made. Firstly a discussion of the concept and its relationship to health and effective self-image is considered. Opportunities in respect of changing environments, and a move to more transformational change within the NHS could allow greater empowerment and feelings of self-efficacy. Such large scale change is essentially cultural and attitudinal; central to governmental proposals for NHS reform. The authors consider the real effect of nursing empowerment; based in part on the work of Kanter (1993) in the USA and work on empowerment and the role of nursing; and of power relationships within the organization. The links with the nurse's role in primary care groups and clinical governance are strong, with subsequent lessons for the British nurse during these initial changes. The potential for positive benefit is high; but coupled with this is a discussion on the relationship of NHS management, and a brief analysis of managerial practice and attitude, which may mitigate against empowerment. The authors put the case that structural changes are not sufficient to allow greater empowerment; which in its present form may only be an ideal. A greater effort by all is required if the myth is to be made a true reality.

Attitude of Health Personnel↗
PubMed2000

An evaluation of hospital cleaning regimes and standards.

A four-part study assessing cleanliness in up to 113 environmental surfaces in an operating theatre and a hospital ward is reported. Surfaces were assessed visually, using microbiological methods and ATP bioluminescence. Results from a preliminary random survey indicated variability in cleanliness. These results were then used to select sites for monitoring before and after routine cleaning, over a 14-day period. Using published microbiological and ATP specifications 70 and 76% of these sites were unacceptable after cleaning. Visual assessment was a poor indicator of cleaning efficacy with only 18% considered unacceptable. Sites most likely to fail in the ward were in the toilet and kitchen, areas which are frequently implicated in the spread of infectious intestinal disease. Operating theatre sites had lower ATP results but 61% of sites would be considered unacceptable. There was no significant difference in general microbiological or ATP results overall before and after routine cleaning. Although some important hand contact sites showed no significant difference, overall there was a significant decrease in staphylococcal and enterobacteria counts in the ward but not in the operating theatre after cleaning. The routine cleaning programmes used did not include a biocide and cleaning using a hypochlorite based sanitizer gave much lower values. The results are discussed in relation to infection control, cleaning audits and cleaning schedules: an integrated cleaning monitoring programme using ATP bioluminescence in conjunction with visual and microbiological assessments is recommended.

Adenosine Triphosphate↗
PubMed2000

Recurrent use of newer oral contraceptives and the risk of venous thromboembolism.

The epidemiological studies that assessed the risk of venous thromboembolism (VTE) associated with newer oral contraceptives (OC) did not distinguish between patterns of OC use, namely first-time users, repeaters and switchers. Data from a Transnational case-control study were used to assess the risk of VTE for the latter patterns of use, while accounting for duration of use. Over the period 1993-1996, 551 cases of VTE were identified in Germany and the UK along with 2066 controls. Totals of 128 cases and 650 controls were analysed for repeat use and 135 cases and 622 controls for switching patterns. The adjusted rate ratio of VTE for repeat users of third generation OC was 0.6 (95% CI:0.3-1.2) relative to repeat users of second generation pills, whereas it was 1.3 (95% CI:0.7-2.4) for switchers from second to third generation pills relative to switchers from third to second generation pills. We conclude that second and third generation agents are associated with equivalent risks of VTE when the same agent is used repeatedly after interruption periods or when users are switched between the two generations of pills. These analyses suggest that the higher risk observed for the newer OC in other studies may be the result of inadequate comparisons of pill users with different patterns of pill use.

Adult↗
PubMed2000

Characterization of an atrazine-degrading Pseudaminobacter sp. isolated from Canadian and French agricultural soils.

Atrazine, a herbicide widely used in corn production, is a frequently detected groundwater contaminant. Fourteen bacterial strains able to use this herbicide as a sole source of nitrogen were isolated from soils obtained from two farms in Canada and two farms in France. These strains were indistinguishable from each other based on repetitive extragenic palindromic PCR genomic fingerprinting performed with primers ERIC1R, ERIC2, and BOXA1R. Based on 16S rRNA sequence analysis of one representative isolate, strain C147, the isolates belong to the genus Pseudaminobacter in the family Rhizobiaceae. Strain C147 did not form nodules on the legumes alfalfa (Medicago sativa L.), birdsfoot trefoil (Lotus corniculatus L.), red clover (Trifolium pratense L.), chickpea (Cicer arietinum L.), and soybean (Glycine max L.). A number of chloro-substituted s-triazine herbicides were degraded, but methylthio-substituted s-triazine herbicides were not degraded. Based on metabolite identification data, the fact that oxygen was not required, and hybridization of genomic DNA to the atzABC genes, atrazine degradation occurred via a series of hydrolytic reactions initiated by dechlorination and followed by dealkylation. Most strains could mineralize [ring-U-(14)C]atrazine, and those that could not mineralize atrazine lacked atzB or atzBC. The atzABC genes, which were plasmid borne in every atrazine-degrading isolate examined, were unstable and were not always clustered together on the same plasmid. Loss of atzB was accompanied by loss of a copy of IS1071. Our results indicate that an atrazine-degrading Pseudaminobacter sp. with remarkably little diversity is widely distributed in agricultural soils and that genes of the atrazine degradation pathway carried by independent isolates of this organism are not clustered, can be independently lost, and may be associated with a catabolic transposon. We propose that the widespread distribution of the atrazine-degrading Pseudaminobacter sp. in agricultural soils exposed to atrazine is due to the characteristic ability of this organism to utilize alkylamines, and therefore atrazine, as sole sources of carbon when the atzABC genes are acquired.

Agriculture↗
PubMed2000

Social class, smoking and the severity of respiratory symptoms in the general population.

STUDY OBJECTIVE: The prevalence of respiratory symptoms has been found in some studies to vary with social class. One explanation of this link may be the effect of exposure to cigarette smoke. To investigate this, the relation between social class, smoking and respiratory symptoms was explored in a population based survey. DESIGN: A cross sectional survey using a validated questionnaire. SETTING: Two general practices in Staffordshire, United Kingdom. PATIENTS: A random sample of 4237 patients aged 16 and over from two general practices in Staffordshire were mailed a questionnaire enquiring about respiratory symptoms and their severity. MAIN RESULTS: The severity of respiratory symptoms increased with increasing exposure to cigarette smoke and was greater among manual social classes. Current smokers (odds ratio (OR) = 2.9, 95% confidence limits (CI) 2.3, 3.6), past smokers (OR = 1.5, 95% CI 1.2, 1.8) and passive smokers (OR = 1.4, 95% CI 1.0, 1.8) were more likely to report the more severe respiratory symptoms compared with non-smokers. Responders from social class V (OR = 2.4, 95% CI 1.3, 4. 4) were more likely to report the more severe respiratory symptoms compared with social class I, as were responders from social classes IIIM (OR = 1.3, 95% CI 0.9, 1.9) and IV (OR = 1.4, 95% CI 0.9, 2.1). These effects were independent of each other. CONCLUSIONS: This study has shown that social class is linked to the severity of respiratory symptoms, independently of smoking. Although the need to reduce and quit smoking in manual class households remains a crucial preventive issue, other mechanisms by which social class differences may influence symptom occurrence and severity need to be explored.

Adolescent↗
PubMed2000

Does psychological status predict the presentation in primary care of women with a menstrual disturbance?

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.

Adolescent↗
PubMed2000

Atrial fibrillation: a comparison of methods to identify cases in general practice.

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.

Aged↗
PubMed2000

Community care management. Advanced practice nurses as care managers.

A group of advanced practice nurses partnered with a major insurer in the design and implementation of a care coordination model for high-risk older adults. This article will discuss the process of such an undertaking, highlighting the successes and barriers encountered. The key elements of this program included early identification and regular reassessment of each member's acuity level; fostering close partnerships between individual or teams of APRNs and groups of physicians; and uninterrupted clinical management of high-risk members across the health care continuum. This model was designed to achieve the following outcomes: to support the physician management of high-risk, chronic individuals; to increase or maintain the health of members; and to reduce health care costs. Outcome studies have demonstrated a substantial net savings by decreasing acute care admissions by 54%, reducing hospital days by 42%, and trimming primary care physicians' and specialists' visit costs by 37%. There was a 33% reduction in the overall costs of health care for members enrolled in this program. Physicians and members both rated their satisfaction with the APRN-based model of care as very high.

Aged↗
PubMed1999

Different population dynamics of human T cell lymphotropic virus type II in intravenous drug users compared with endemically infected tribes.

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.

Biological Evolution↗
PubMed1999

Quinone reductase inhibitors block SAPK/JNK and NFkappaB pathways and potentiate apoptosis.

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.

Apoptosis↗