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Biomedical subjects

D Lewis

Publications and source records attributed to D Lewis.

At least 37 records · Page 2Linked to original sources
PubMed2002

Modulite: a means of designing the aerosols generated by pressurized metered dose inhalers.

Although popular, the pressurized metered dose inhaler generates coarse, fast moving clouds so that the fraction reaching the lung is small. These shortcomings can be redressed by Modulite which permutes the following variables: the non-volatile components of a solution formula, the actuator orifice geometry, the volume of the metered solution and the vapour pressure of the propellants. This permits the design of aerosols with chosen particle size and plume speed. This facilitates co-ordination of dose generation with inspiration, reduces oropharyngeal deposition and provides a mechanism for targeting drug delivery to different parts of the lung. These principles are exemplified by designing an HFA-propelled beclometasone dipropionate product which closely matches existing products which use chlorofluorocarbons.

Aerosol Propellants↗
PubMed2002

Photoperiodic control of oestrous cycles in Syrian hamsters: mediation by the mediobasal hypothalamus.

To assess whether the mediobasal hypothalamus (MBH) is necessary for photoperiodic control of oestrous cycles and prolactin secretion, we tested intact female Syrian hamsters (controls) and those that had sustained unilateral or bilateral lesions of the MBH. All hamsters displayed 4-day oestrous cycles postoperatively in the long-day photoperiod (14 h light/day); control females and those with unilateral MBH damage ceased to undergo oestrous cycles approximately 8 weeks after transfer to a short-day photocycle (10 h light/day), whereas 12 of 15 females with bilateral MBH lesions continued to generate 4-day oestrous cycles throughout 22 weeks in short days. Serum prolactin concentrations were either undetectable or low in all hamsters 8 or 14 weeks after the transfer to short-day lengths, but increased above long-day baseline values by week 22. We conclude that melatonin-binding sites in the MBH mediate suppression of oestrous cycles but not prolactin secretion by short-day lengths; recovery of prolactin secretion in females during prolonged exposure to short-day lengths reflects development of refractoriness to melatonin in a substrate distinct from the MBH. These findings suggest that separate neural pathways mediate photoperiodic control of gonadotropin and prolactin secretion in female hamsters.

Animals↗
PubMed2002

Brain SPECT: a controlled, blinded assessment of intra-reader and inter-reader agreement.

A detailed assessment of intra- and inter-reader variation in the interpretation of brain SPECT scans has been performed. A random sample was selected from scans performed at a community/teaching hospital in Seattle. Scans were interpreted independently by three experienced readers who were blinded to all patient information. Forty-eight scans were interpreted twice by each reader, for a total of 288 readings. Readers recorded detailed assessments of individual lesions and overall impressions using a standardized reporting form. Intra-observer agreement as reflected in per cent agreement for severity scores ranged from 65% to 100%. Intra-observer agreement on the 'overall impression' was very good for Alzheimer's pattern (kappa=0.73-1.00), and fair to good for the 'heterogeneous pattern' (kappa=0.30-0.63). Inter-observer agreement, as reflected in per cent agreement, ranged from 29% to 100%. Inter-observer agreement about the 'overall impression' was fair to moderate for Alzheimer's pattern (kappa=0.24-0.54) and was poor for the descriptors 'heterogeneous' and 'normal'. It is concluded that brain SPECT has great potential value in many important conditions. This study demonstrates a need for further work in the areas of pattern definition and reduction of observer variation.

Adult↗
PubMed2002

Workload and stress in consultant medical microbiologists and virologists: a questionnaire survey.

AIMS: To document demography, changing workload patterns, job satisfaction, morale, and prevalence of stress and psychological morbidity among UK consultant medical microbiologists and virologists. METHOD: A questionnaire survey of all identified UK practising consultant medical microbiologists and virologists (n= 464). RESULTS: Among 367 respondents (79%), there were 33 virologists and at least 89 single handed consultants. Over half the respondents (58%) were working a 1 : 1 or 1 : 2 on call rota during the week and a similar proportion (51%) at weekends. Of all consultants (including those working part time), 56% were working more than 48 hours weekly. Working more than 48 hours weekly, and being on call 1 : 1 or 1 : 2 at weekends, were both independently associated with increased psychological morbidity. Those on call 1 : 1 or 1 : 2 at weekends were also more likely to have low or very low morale. Female consultants were more likely to have higher stress scores. More than half of the respondents (208 of 363; 57%) were making active financial provision to retire early, and 198 of 363 (55%) did not intend to work beyond the age of 60. CONCLUSIONS: The long hours worked by many consultant microbiologists and virologists are in breach of the European Working Time Directive and are associated with a higher degree of psychological morbidity. For most consultants, the frequency of on call commitments is demanding and job satisfaction and morale have deteriorated. Urgent action is needed, particularly to support those working more than 48 hours each week and those on call at weekends 1 : 1 or 1 : 2. However, a major expansion of the consultant establishment cannot be achieved rapidly, and will be slowed further if early retirements become more frequent.

Adult↗
PubMed2002

Parental confidence in measles, mumps and rubella vaccine: evidence from vaccine coverage and attitudinal surveys.

BACKGROUND: The measles, mumps and rubella (MMR) vaccine has been the focus of considerable adverse publicity in recent years. AIM: To describe recent trends in parental attitudes to, and coverage of, MMR vaccine. DESIGN OF STUDY: Routine surveillance of vaccine coverage and cross-sectional surveys of parental attitudes. SETTING: All health authorities in England (vaccine coverage) and 132 enumeration districts in England (attitude survey). METHOD: Quarterly MMR vaccine coverage for all resident children in England at two years of age was requested from computerised child health information systems. Data was also obtained from 26 English health authorities/trusts on MMR coverage at 16 months of age. The proportion of mothers who believed that MMR vaccine was safe or carried only a slight risk, and the proportion who intended to fully vaccinate any future children, was obtained from biannual interviews with a national representative sample of over 1000 mothers of children under three years of age. RESULTS: Vaccine coverage at two years of age fell 8.6% (95% confidence interval [CI] = 8.4 to 8.8) between April and June 1995 and between April and June 2001. In September 2001, 67% of mothers reported that the MMR vaccine was safe or carried only a slight risk and 92% of mothers agreed with the statement: 'If I had another child in the future I would have them fully immunised against all childhood diseases'. CONCLUSIONS: Despite considerable adverse publicity, the fall in MMR coverage has been relatively small, mothers' attitudes to MMR remain positive, and most continue to seek advice on immunisation from health professionals. As the vast majority of mothers are willing to have future children fully immunised, we believe that health professionals should be able to use the available scientific evidence to help to maintain MMR coverage.

Attitude to Health↗
PubMed2001

[Economic assessment of the use of tinzaparin in the treatment of acute pulmonary embolism in France].

OBJECTIVE: This pharmacoeconomic study was conducted to determine the cost of using tinzaparin, a low-molecular-weight heparin (LMWH), administered intravenously, in comparison with non-fractionated heparin (NFH) for the treatment of acute pulmonary embolism (PE) in France. METHODS: A decision algorithm indicating the therapeutic schedules and their consequences was constructed from data collected during a large-scale multicentric study and from data obtained from interviews with French physicians implicated in the treatment of pulmonary embolism. This model was used to estimate costs and to compare per patient expenditures for the two therapeutic schedules. RESULTS: Cost of instituting treatment per patient (excluding costs common to both schedules) was 202 euros for NFH and 77 euros for tinzaparin (delta 125 euros in favor of tinzaparin). Including follow-up costs for the 90 day analysis period, tizaparin reduced costs by 123 euros per patient (211 versus 334 euros for patients treated with NFH). Taking into account the sole cost of management of the two critical events that occurred during NFH or tinzaparin (8 first days) treatment, tinzaparin reduced costs by 137 euros per patient (112 euros versus 249 euros respectively). CONCLUSION: Tinzaparin reduced health care costs for pulmonary embolism due to easier administration, less complex laboratory tests, and personnel time savings. The robustness of the results was confirmed by the sensitivity analysis.

Acute Disease↗
PubMed2001

Determination of methadone in urine using ion trap GC/MS in positive ion chemical ionization mode.

Methadone is a potent analgesic and sedative. It is widely used in the treatment of heroin addiction and is often encountered in forensic specimens. In electron impact (EI) gas chromatography/mass spectrometry (GC/MS) mode, methadone produces predominantly a m/z 72 ion, which is not sufficiently characteristic for identification. Determination of the molecular ion, which can be achieved using chemical ionization (CI) provides diagnostic information and better identification of the drug. This paper describes the development of a positive ion CI GC/MS procedure, using a liquid reagent gas and ion trap instrumentation, for the determination of methadone and its metabolites in urine. CI generally produces a single molecular ion spectrum, but optimization of the reagent gas parameters increases the fragmentation of the molecule, allowing determination of ion ratios if required. The procedure is sensitive, diagnostic and is currently in routine use in our laboratory.

Gas Chromatography-Mass Spectrometry↗
PubMed2001

The fate of Escherichia coli O157 in soil and its potential to contaminate drinking water.

The survival and transport of Escherichia coli and E. coli O157 after cattle slurry application were studied on drained plots in both grassland and arable stubble at three sites in Scotland. Leaching losses were between 0.2% and 10% of total E. coli and were dependent on rainfall. Recovery of E. coli in grass and soil declined with approximately first order kinetics. Residual numbers, in excess of background declined more slowly. The pattern was similar for both grass and arable plots. Laboratory incubations of soil cores, with applied slurry containing E. coli and E. coli O157 were performed in soils with different moisture contents at two temperatures for clay loam and sandy loam soils. Both E. coli populations were measured over a 4-week period. Using a dual population approach, the die off of the susceptible pool was linear with a half-life of 3-4 days, and was faster at the higher temperature and lowest moisture content. The resistant pool was not strongly affected by temperature or moisture and had a half-life for die off of between 18 and 24 days. After a 4-week period, < 100 cfu g/soil of E. coli and E. coli O157 remained. The die off rate of E. coli O157 was the same or slightly faster than that of the commensal E. coli population, indicating that the field behaviour of E. coli O157 can be studied by monitoring the total population of E. coli applied with slurry. The risk of significant pollution of water by E. coli is highest immediately after application of slurry, and the first increments of drainflow carry significant concentrations. Thereafter, the risk of pollution is very low. If weather conditions are dry after application on well-drained sandy soils, it is unlikely that any significant losses of organisms to drains will occur. Such data can be used to control and minimise the risk of E. coli O157 contaminating drinking water.

Animals↗
PubMed2001

General practice or drug clinic for methadone maintenance? A controlled comparison of treatment outcomes.

The model for management of opiate dependence in the United Kingdom includes long term methadone maintenance. A consequence is either long waiting lists for treatment or that treatment capacity is expanded. General practitioners are encouraged to prescribe methadone for opiate dependent patients, but little is known about the differences between patients or outcomes in primary or secondary care settings. This paper compares patients' characteristics and treatment outcomes in a specialist drug clinic and a general practice operating a shared care policy (with the specialist clinic). We undertook a retrospective review of patient records. All patients prescribed methadone maintenance during a 2 year period in one general practice were compared with one in three patients treated at a drug clinic during the same period. Outcome was determined at the end of a treatment episode or on 30 June 1997 (whichever was sooner). Eighty-nine drug clinic and 36 general practice patients were followed up for a minimum of nine months each. Patient characteristics were similar at the start of treatment. A 'good' outcome (remaining in treatment or becoming drug free) was equally likely in either setting. Patients treated in the general practice setting were significantly more likely to be immunised (or have known natural immunity) against hepatitis B (adjusted odds ratio 6.0). Our findings suggest that with similar patient groups this model of care in general practice can produce results at least as good as those of a drug clinic.

Journal Article↗
PubMed2001

The role of the M6-M7 loop (L67) in stabilization of the phosphorylation and Ca(2+) binding domains of the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA).

The amino acid sequence (L67) intervening between the M6 and M7 transmembrane segments of the Ca(2+) transport ATPase was subjected to mutational analysis. Mutation of Pro(820) to Ala interferes with protein expression even though transcription occurs at normal levels. Single mutations of Lys(819) or Arg(822) to Ala, Phe, or Glu allow good expression, but produce strong inhibition of ATPase activity. The main defect produced by these mutations is strong interference with enzyme phosphorylation by ATP in the presence of Ca(2+), and also by P(i) in the absence of Ca(2+). The Lys(819) and Arg(822) mutants undergo slight and moderate reduction of Ca(2+) binding affinity, respectively. Reduction of overall steady state ATPase velocity is then due to inhibition of phosphorylated intermediate formation. On the other hand, a cluster of conservative mutations of Asp(813), Asp(815), and Asp(818) to Asn interferes strongly with enzyme activation by Ca(2+) binding and formation of phosphorylated enzyme intermediate by utilization of ATP. Enzyme phosphorylation by Pi in the absence of Ca(2+) undergoes slight or no inhibition by the triple aspartate mutation. Therefore, the triple mutation interferes mainly with the calcium-dependent activation of the ATPase. The effect of the triple mutation can be to a large extent reproduced by single mutation of Asp(813) (but not of Asp(815) or Asp(818)) to Asn. Functional and structural analysis of the experimental data demonstrates that the L67 loop plays an important role in protein folding and function. This role is sustained by linking the cytosolic catalytic domain and the transmembrane Ca(2+) binding domain through a network of hydrogen bonds.

Animals↗
PubMed2001

Item characteristics of the Michigan Alcoholism Screening Test.

Items of the Michigan Alcoholism Screening Test (MAST) were individually evaluated regarding disproportional responding. The item with the lowest degree of endorsement (Item 18, related to liver problems) was found to have correspondingly low relationships with other MAST items and with the total score. Weighted items concerned with drug-related arrests were found to detract from the otherwise relatively homogeneous MAST items. Traditional statistical approaches for homogeneity suggest high level internal consistency with the deletion of the aforementioned items. A factor analytic test of homogeneity was confirmed. Recommendations are presented concerning modification of the MAST scoring procedures.

Adolescent↗
PubMed2001

Respiratory symptoms among crab processing workers in Alaska: epidemiological and environmental assessment.

BACKGROUND: Crab processing workers may develop respiratory symptoms and specific IgE responses, but the risk factors have not been fully described. METHODS: In 1998, 107 workers at a crab processing facility completed a survey both at the beginning and end of the processing season. The surveys included standardized symptom questionnaires, spirometry, and serological testing, as well as measurement of workplace airborne crab allergens and microscopic analysis of aerosolized materials. RESULTS: Over the crab processing season, asthma-like symptoms developed in 26% of study participants and bronchitic symptoms in 19%. Only 9% of those with new asthma-like symptoms were IgE-sensitized to crab at the end of the season. Among the crab processing jobs, butchering and degilling workers had the highest incidence of respiratory symptoms. CONCLUSIONS: Both personal and process-related factors appear to affect the development of respiratory symptoms in crab processing workers. In this study, crab specific IgE was not detected in most of the workers with new symptoms. Published 2001 Wiley-Liss, Inc.

Adolescent↗
PubMed2001

Percutaneous coronary intervention versus coronary artery bypass graft surgery for patients with medically refractory myocardial ischemia and risk factors for adverse outcomes with bypass: a multicenter, randomized trial. Investigators of the Department of Veterans Affairs Cooperative Study #385, the Angina With Extremely Serious Operative Mortality Evaluation (AWESOME).

BACKGROUND: Percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABG) are being applied to high-risk populations, but previous randomized trials comparing revascularization methods have excluded a number of important high-risk groups. OBJECTIVES: This five-year, multicenter, randomized clinical trial was designed to compare long-term survival among patients with medically refractory myocardial ischemia and a high risk of adverse outcomes assigned to either a CABG or a PCI strategy, which could include stents. METHODS: Patients from 16 Veterans Affairs Medical Centers were screened to identify myocardial ischemia refractory to medical management and the presence of one or more risk factors for adverse outcome with CABG, including prior open-heart surgery, age >70 years, left ventricular ejection fraction <0.35, myocardial infarction within seven days or intraaortic balloon pump required. Clinically eligible patients (n = 2,431) underwent coronary angiography; 781 were angiographically acceptable; 454 (58% of eligible) patients consented to random assignment between CABG and PCI. RESULTS: A total of 232 patients was randomized to CABG and 222 to PCI. The 30-day survivals for CABG and PCI were 95% and 97%, respectively. Survival rates for CABG and PCI were 90% versus 94% at six months and 79% versus 80% at 36 months (log-rank test, p = 0.46). CONCLUSIONS: Percutaneous coronary intervention is an alternative to CABG for patients with medically refractory myocardial ischemia and a high risk of adverse outcomes with CABG.

Aged↗
PubMed2001

Lateralized seizure termination: relationship to outcome following anterior temporal lobectomy.

Determination of side of seizure onset is critical for a successful outcome following epilepsy surgery. Little is known about the significance of lateralized seizure termination. Sustained seizure activity contralateral to side of seizure onset, following termination of ictal activity ipsilateral to side of onset, may suggest the presence of an independent focus. Such activity, if present, should predict a poor outcome. We studied side of seizure termination in 13 patients undergoing monitoring with bitemporal depth electrodes and correlated this to outcome following anterior temporal lobectomy (ATL). Side of seizure onset was determined for all seizures during that evaluation. Based on side of final cessation of ictal activity, patients were classified as having ipsilateral final termination or simultaneous termination (Group 1; N=6) or contra-lateral or mixed final termination (Group 2; N=7). The Duke outcome classification system was used. At the end of 2 years follow-up, 6/6 patients in Group 1 and 3/7 patients in Group 2 were seizure free. We conclude that lateralized seizure termination during evaluation with depth electrodes may be useful in predicting outcome following ATL. Continued seizure activity contralateral to side of seizure onset (following termination of ictal activity ipsilateral to side of onset) predicts a poor outcome. This may indicate the presence of an independent seizure focus opposite to the side of surgery.

Adolescent↗
PubMed2001

Attitudes toward integration of complementary and alternative medicine with hospital-based care.

OBJECTIVE: To characterize those who have used, expect to use, or are opposed to the use of holistic therapies, especially in a conventional medical (hospital) setting. SAMPLE DESCRIPTION AND METHODS: Cross-sectional survey of a random sample of Hamilton-Wentworth residents between March and June 1998 (n = 416; response rate, 63%); analysis used logistic regression. RESULTS: Thirty-seven percent (37%) used at least one holistic therapy in the previous year: the three most common were chiropractic, massage, and herbal/phytology. The three most common reasons for use were general health, fatigue, and arthritis. Thirty-three percent (33%) would use holistic therapy in the future. Barriers to use were lack of information, perceived ineffectiveness, and cost; approximately 40% agreed they would only use holistic therapies with medical advice. Approximately 13% were opposed to holistic therapy and objected to its use in hospitals. Younger age, preference for holistic therapy over conventional medicine, and prior use of holism independently predicted high likelihood for future use. Lower income and high self-perceived health were associated with negative attitude toward use of holistic therapies in hospital. CONCLUSION: Most respondents would accept integration of holistic techniques into a hospital; therapies would be more acceptable if there were clear evidence of their efficacy. A few might find their opinion of a sponsoring hospital lowered by such integration.

Adult↗