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R Lewis

Publications and source records attributed to R Lewis.

At least 37 records · Page 2Linked to original sources
PubMed2000

A voxel-by-voxel analysis of [18F]setoperone PET data shows no substantial serotonin 5-HT(2A) receptor changes in schizophrenia.

Several postmortem studies have reported regionally localized decreases in serotonin(2A) receptors (5-HT(2A)R) in schizophrenia. This was not confirmed by two recent [18F]setoperone positron emission tomography (PET) studies. In these two studies relatively large regions of interest (ROIs) were used; hence, 5-HT(2A)R changes may have been missed in some brain areas. Therefore, data from one study were analyzed on a voxel-by-voxel basis using Statistical Parametric Mapping (SPM). We also used this method to examine the relationship between 5-HT(2A)R binding potential (BP) and five PANSS-derived factors: negative, positive, activation, dysphoric and autistic preoccupation. Thirteen schizophrenic patients (10 antipsychotic-naïve, 3 antipsychotic-free; 11 M, 2 F; age 31+/-7 years) and 35 age-matched control subjects (15 M, 20 F; age 30+/-7 years) were scanned. The 5-HT(2A)R BP was determined for each voxel using the pseudoequilibrium ratio method on PET data obtained between 65 and 90 min after [18F]setoperone bolus injection. The resulting parametric 5-HT(2A)R BP images were spatially normalized using a ligand specific template. Analyses of covariance were done using SPM99 with age as covariate. In tests for the effect of schizophrenia and for partial correlations between 5-HT(2A)R BP and the five factors, corrected P values <0.05 at cluster or voxel level were considered significant. No significant differences were detected between patients and control subjects, and no significant correlations were observed between 5-HT(2A)R BP and any of the five factors. Thus, in agreement with the previous ROI studies, voxel-by-voxel analysis confirmed the lack of substantial 5-HT(2A)R BP differences between schizophrenic patients and control subjects.

Adult↗
PubMed2000

Doctors' pay. What seems to be the trouble?

The long-standing method of paying GPs through a complex system of fees and allowances is under review. The proposed expansion of personal medical services pilots and an increase in the number of salaried GPs could destabilise the current system and lead to perverse outcomes. The introduction of a weighted capitation system allocating resources to health authorities and primary care trusts according to need might ensure equitable distribution of funds.

Family Practice↗
PubMed2000

Sertindole for schizophrenia.

BACKGROUND: Sertindole is an atypical antipsychotic, which is thought to give a lower incidence of extrapyramidal side effects at clinically effective doses than typical antipsychotic drugs. In December 1998, Lundbeck Ltd., the manufacturers of sertindole, voluntarily suspended the availability of the drug due to concerns about cardiac arrhythmia and sudden cardiac death associated with its use. Sertindole has therefore been withdrawn from the market pending discussion with the European Regulatory Authority over cardiac safety. OBJECTIVES: To determine the effects of sertindole compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1980-1999), The Cochrane Library (Issue 1, 1999), The Cochrane Schizophrenia Group's Register (January 1999), EMBASE (1980-1999), LILACS (1982-1996), MEDLINE (1966-1999), PSYNDEX (1977-1995) and PsycLIT (1974-1999) were undertaken. In addition, pharmaceutical databases on the Dialog Corporation Datastar and Dialog services were searched. References of all identified studies were searched for further trials. The manufacturer of sertindole and authors of trials were contacted. SELECTION CRITERIA: All randomised controlled trials that compared sertindole to placebo or other antipsychotic drug treatments were included by independent assessment. DATA COLLECTION AND ANALYSIS: Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were independently extracted. For homogeneous dichotomous data the risk ratio (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) or numbers needed to harm (NNH) were calculated on an intention-to-treat basis. For continuous data, weighted mean differences (WMD) were calculated. All data were inspected for heterogeneity. MAIN RESULTS: Two large important studies were excluded, because they did not report any usable data. The two that were included suggested that sertindole was more antipsychotic than placebo, as acceptable as placebo and better tolerated than haloperidol (NNT=9, RR 0.63 CI 0.41 to 0.96). Sertindole was associated with fewer movement disorders than haloperidol but was shown to cause more weight gain (NNH=9 RR 6.33, CI 1.92 to 20.92), rhinitis (NNH=8, RR 1.74, CI 1,28 to 2.36) and possibly male sexual dysfunction. Cardiac problems (QTc intervals of at least 500msec) were evident even in the randomised trials (NNH=13 RR 23, CI 1.37 to 386.60). REVIEWER'S CONCLUSIONS: Because of the cardiac problems, even evident within poorly reported studies, at present sertindole should, if possible, be avoided. If sertindole is to be reintroduced, gold-standard evidence of its clinical benefits will need to far outweigh its real risks.

Antipsychotic Agents↗
PubMed2000

Molindone for schizophrenia and severe mental illness.

BACKGROUND: Typical antipsychotic drugs are widely used as the first line treatment for people with schizophrenia. However, the atypical class of antipsychotic drugs is making important inroads into this approach. 'Atypical' is a term widely used to describe some antipsychotics which have a low propensity to produce movement disorders, sedation and raised serum prolactin. There is some suggestion that the different adverse effect profiles of the atypical antipsychotic group make them more acceptable to people with schizophrenia. Molindone has a similar profile to quetiapine (a novel atypical antipsychotic), with very low binding to all receptors. Some authors have suggested that molindone is safer than other 'typical' antipsychotics in that extrapyramidal adverse effects are not usually seen at clinically effective antipsychotic doses and that it should therefore be classed as an atypical antipsychotic. OBJECTIVES: To determine the effects of molindone compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1980-1999), The Cochrane Library CENTRAL (Issue 1, 1999), The Cochrane Schizophrenia Group's Register (January 1999), CINAHL (1982-1999), EMBASE (1980-1999), MEDLINE (1966-1999), LILACS (1982-1999), PSYNDEX (1977-1999), and PsycLIT (1974-1999) were undertaken. In addition, pharmaceutical databases on the Dialog Corporation Datastar and Dialog services were searched. References of all identified studies were searched for further trials. The manufacturer of molindone and authors of trials were contacted. SELECTION CRITERIA: All randomised controlled trials that compared molindone to other treatments for schizophrenia and schizophrenia-like psychoses were included by independent assessment. DATA COLLECTION AND ANALYSIS: Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were independently extracted. Data were excluded if loss to follow up was greater than 50%. For homogeneous dichotomous data the risk ratio (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, weighted mean differences (WMD) were calculated. All data were inspected for heterogeneity. MAIN RESULTS: Thirteen studies were included in the review. Data for this compound range from very short (10 day) studies of the intramuscular preparation to trials lasting over three months. For measures of global state available data do not justify any conclusions on the comparative efficacy of molindone and placebo. When compared to other typical antipsychotics no difference in effectiveness was evidenced (doctors' RR 1.13, CI 0.69 to 1.86; nurses' RR 1.23, CI 0.82 to 1.86). It is no more or less likely than typical drugs to cause movement disorders, but causes significantly more weight loss (RR 2.78, CI 1.10 to 6.99). REVIEWER'S CONCLUSIONS: The strength of the evidence relating to this compound is limited, owing to small sample size, poor study design, limited outcomes and incomplete reporting. Molindone may be an effective antipsychotic; however, its adverse effect profile does not differ significantly from that of typical antipsychotics, apart from the event of weight loss. At present there is no evidence to suggest that it may have an atypical profile.

Antipsychotic Agents↗
PubMed2000

Telemedicine versus face to face patient care: effects on professional practice and health care outcomes.

BACKGROUND: Telemedicine is the use of telecommunications technology for medical diagnosis and patient care. From its beginnings telemedicine has been used in a variety of health care fields, although widespread interest among healthcare providers has only now become apparent with the development of more sophisticated technology. OBJECTIVES: To assess the effects of telemedicine as an alternative to face-to-face patient care. SEARCH STRATEGY: We searched the Effective Practice and Organisation of Care Group's specialised register, The Cochrane Library, MEDLINE (1966-August 1999), EMBASE (to 1996), Cinahl (to August 1999), Inspec (to August 1996), Healthstar (1983-1996), OCLC, Sigle (to 1999), Assia, SCI (1981-1997), SSCI (1981-1997), DHSS-Data. We hand searched the Journal of Telemedicine and Telecare (1995-1999), Telemedicine Journal (1995-1999) and reference lists of articles. We also hand searched conference proceedings and contacted experts in countries identified as having an interest in telemedicine. SELECTION CRITERIA: Randomised trials, controlled before and after studies and interrupted time series comparing telemedicine with face-to-face patient care. The participants were qualified health professionals and patients receiving care through telemedicine. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. MAIN RESULTS: Seven trials involving more than 800 people were included. One trial was concerned with telemedicine in the emergency department, one with video-consultations between primary health care and the hospital outpatients department, and the remainder were concerned with the provision of home care or patient self-monitoring of chronic disease. The studies appeared to be well conducted, although patient numbers were small in all but one. Although none of the studies showed any detrimental effects from the interventions, neither did they show unequivocal benefits and the findings did not constitute evidence of the safety of telemedicine. None of the studies included formal economic analysis. All the technological aspects of the interventions appear to have been reliable, and to have been well accepted by patients. REVIEWER'S CONCLUSIONS: Establishing systems for patient care using telecommunications technologies is feasible, but there is little evidence of clinical benefits. The studies provided variable and inconclusive results for other outcomes such as psychological measures, and no analysable data about the cost effectiveness of telemedicine systems. The review demonstrates the need for further research and the fact that it is feasible to carry out randomised trials of telemedicine applications. Policy makers should be cautious about recommending increased use and investment in unevaluated technologies.

Communication↗
PubMed2000

CNS acetylcholine receptor activity in European medicinal plants traditionally used to improve failing memory.

Certain Lamiaceous and Asteraceous plants have long histories of use as restoratives of lost or declining cognitive functions in western European systems of traditional medicine. Investigations were carried out to evaluate human CNS cholinergic receptor binding activity in extracts of those European medicinal plants reputed to enhance or restore mental functions including memory. Ethanolic extracts were prepared from accessions of these plants and a number of other species related by genus. Amongst the plant extracts screened for contents able to displace [3H]-(N)-nicotine and [3H]-(N)-scopolamine from nicotinic receptors and muscarinic receptors, respectively in homogenates of human cerebral cortical cell membranes, the most potent extracts, prepared from one accession of Melissa officinalis, three Salvia species and Artemisia absinthium had IC50 concentrations of < 1 mg/ml. The displacement curves of some extracts were comparable with that of carbamylcholine chloride, a potent acetylcholine analogue. Choline, a weak nicotinic ligand (IC50 = 3 x 10(-4) M) was found in extracts of all plants studied at concentrations of 10(-6)-10(-5) M. These concentrations could not account for not more than 5% of the displacement activity observed. Some extracts displayed differential displacement at nicotinic and muscarinic acetylcholine receptors, with M. officinalis 0033 having the highest [3H]-(N)-nicotine displacement value and Salvia elegans with the highest [3H]-(N)-scopolamine displacement value. There was also considerable variation in cholinoreceptor interactions between different accessions of a single plant species. Although most plant extracts screened showed some nicotinic and muscarinic activity, only some showed dose-dependent receptor activity typical of materials with genuine cholinergic activity.

Asteraceae↗
PubMed2000

Roles for ephrins in positionally selective synaptogenesis between motor neurons and muscle fibers.

Motor axons form topographic maps on muscles: rostral motor pools innervate rostral muscles, and rostral portions of motor pools innervate rostral fibers within their targets. Here, we implicate A subfamily ephrins in this topographic mapping. First, developing muscles express all five of the ephrin-A genes. Second, rostrally and caudally derived motor axons differ in sensitivity to outgrowth inhibition by ephrin-A5. Third, the topographic map of motor axons on the gluteus muscle is degraded in transgenic mice that overexpress ephrin-A5 in muscles. Fourth, topographic mapping is impaired in muscles of mutant mice lacking ephrin-A2 plus ephrin-A5. Thus, ephrins mediate or modulate positionally selective synapse formation. In addition, the rostrocaudal position of at least one motor pool is altered in ephrin-A5 mutant mice, indicating that ephrins affect nerve-muscle matching by intraspinal as well as intramuscular mechanisms.

Animals↗
PubMed2000

Review of intraurethral suppositories and iontophoresis therapy for erectile dysfunction.

This brief review examines the history of the intraurethral (IU) pharmacotherapy for the treatment of erectile dysfunction (ED). Emphasis is placed on the design, study endpoints and results of a limited number of clinical trials undertaken with PGE(1)-MUSE to demonstrate the efficacy of this unique delivery system. Next, the theory of the iontophoretic technique of drug delivery is discussed. Clinical data collected while applying these methods are presented, but are thus far limited to treatment of patients with Peyronie's disease. Iontophoresis as a drug delivery alternative may gain popularity with ED patients who fail other types of therapy or in patients with other penile disorders. International Journal of Impotence Research (2000) 12, Suppl 4, S86-S90.

Alprostadil↗
PubMed2000

Accuracy of the OMRON M4 automatic blood pressure measuring device.

Despite widespread use of the automatic blood pressure (BP) measuring device OMRON M4, there is little formal validation on its accuracy. A study was conducted to assess the accuracy of the OMRON M4 compared with the true indirect BP measured by mercury sphygmomanometer (MS). A rapid method for the evaluation of automatic blood pressure measurement devices (READ) was applied for this study. The READ is based on numerous BP measurements at rest and during a standardised postural challenge in a small number of subjects who exhibit a wide range of BPs. Blood pressure measurements were done in supine position for 10 min followed by head-up tilt for 30 min and again supine for 10 min. The automatic device (AU) and the MS were connected to one arm-cuff by means of a T connector. A stethoscope with dual sets of ear-pieces was used for duplicate MS measurements (MS1 and MS2). The MS1, MS2 and AU measurements were taken simultaneously in a blinded manner. Three units of the automatic instrument were evaluated. An average of 111 measurements per unit were performed, every BP category being present in >/=15 MS measurements. The differences between MS1 and MS2 measurements (DeltaBP: MS1-MS2) were utilized to assess the consistency of true indirect BP and the differences between AU and MS measurements (DeltaBP:AU-MS2) were utilized to assess the accuracy of the AU. The following characteristics of the OMRON M4 were assessed: (1) grade of accuracy, (2) aberration pattern, (3) consistency of the aberration-pattern, and (4) correlation between levels of BP and DeltaBP: AU-MS. For MS paired readings, 92-100% of systolic and 99-100% of diastolic readings fell within 5 mm Hg difference range, that is consistent with a British Hypertension Society grade A of both. For AU compared to MS2, 29-64% of systolic and 73-94% of diastolic readings fell within 5 mm Hg and 49-86% of systolic and 86-99% of diastolic readings fell within 10 mm Hg and the devices qualified C, D and C, respectively. All devices exhibited irregular and inconsistent aberration patterns, making the design of correction formulas impractical. In conclusion, the OMRON M4 device did not meet the requirements of the British Hypertension Society and, therefore, cannot be recommended for clinical use.

Adult↗
PubMed2000

Consumer demand in the purchase and prescription of sugar-free medicines.

OBJECTIVES: To determine the current level of consumer demand in the purchase and prescription of sugar-free paediatric medicines. DESIGN: Data were collected by administered questionnaire. SETTING: The study was conducted in a Hospital Paediatric Dentistry Unit and a Community Dental Clinic, both within the Bro Taf area of south-east Wales. SAMPLE AND METHODS: The parents of 240 children attending for routine dental care responded to one of two short questionnaires, depending on whether their child had received a liquid oral medicine in the preceding month. RESULTS: Although aware of the benefits of sugar-free medicines, parents did not appear to be attempting to exercise the power of consumer demand to its full potential. They were more likely to ask a pharmacist (or pharmacist's assistant) than their general medical practitioner for a sugar-free medicine. CONCLUSIONS: We must continue to promote sugar-free medicines. While increasing the importance that health professionals attach to such products, future campaigns should also aim to increase consumer demand.

Administration, Oral↗
PubMed2000

Diabetic emergencies: Part 2. Hyperglycaemia.

Part 2 of this series explores the pathophysiology and clinical management of diabetic emergencies involving hyperglycaemia, including both diabetic ketoacidosis and the rarer hypernatremic, non-ketotic coma. Part 1 (Hypoglycaemia) was published in Accident and Emergency Nursing 7(4): 190-196.

Blood Glucose↗
PubMed2000

Effectiveness of incidence thresholds for detection and control of meningococcal meningitis epidemics in northern Togo.

BACKGROUND: Early outbreak detection is necessary for control of meningococcal meningitis epidemics. A weekly incidence of 15 cases per 100 000 inhabitants averaged over 2 consecutive weeks is recommended by the World Health Organization (WHO) for detection of meningitis epidemics in Africa. This and other thresholds are tested for ability to predict outbreaks and timeliness for control measures. METHODS: Meningitis cases recorded for 1990-1997 in health centres of northern Togo were reviewed. Weekly and annual incidences were determined for each district. Ability of different weekly incidence thresholds to detect outbreaks was assessed according to sensitivity, specificity, and positive and negative predictive values. The number of cases potentially prevented by reactive vaccination in 1997 was calculated for each threshold. RESULTS: Outbreaks occurred in 1995-1996 and in 1996-1997. The WHO-recommended threshold had good specificity but low sensitivity. Thresholds of 10 and 7 cases per 100,000 inhabitants in one week had sensitivity and specificity of 100% and increased the time available for intervention by more than one or two weeks, respectively. A maximum of 65% of cases could have been prevented during the 1997 epidemic, with up to 8% fewer cases prevented for each week of delay in achieving vaccine coverage. CONCLUSIONS: In northern Togo, thresholds of 7 or 10 cases per 100,000 inhabitants per week were excellent predictors of meningitis epidemics and allowed more time for a reactive vaccination strategy than current recommendations.

Disease Outbreaks↗
PubMed2000

Regular exercise enhances insulin activation of IRS-1-associated PI3-kinase in human skeletal muscle.

Insulin action in skeletal muscle is enhanced by regular exercise. Whether insulin signaling in human skeletal muscle is affected by habitual exercise is not well understood. Phosphatidylinositol 3-kinase (PI3-kinase) activation is an important step in the insulin-signaling pathway and appears to regulate glucose metabolism via GLUT-4 translocation in skeletal muscle. To examine the effects of regular exercise on PI3-kinase activation, 2-h hyperinsulinemic (40 mU. m(-2). min(-1))-euglycemic (5.0 mM) clamps were performed on eight healthy exercise-trained [24 +/- 1 yr, 71.8 +/- 2.0 kg, maximal O(2) uptake (VO(2 max)) of 56.1 +/- 2.5 ml. kg(-1). min(-1)] and eight healthy sedentary men and women (24 +/- 1 yr, 64.7 +/- 4.4 kg, VO(2 max) of 44.4 +/- 2.7 ml. kg(-1). min(-1)). A [6, 6-(2)H]glucose tracer was used to measure hepatic glucose output. A muscle biopsy was obtained from the vastus lateralis muscle at basal and at 2 h of hyperinsulinemia to measure insulin receptor substrate-1(IRS-1)-associated PI3-kinase activation. Insulin concentrations during hyperinsulinemia were similar for both groups (293 +/- 22 and 311 +/- 22 pM for trained and sedentary, respectively). Insulin-mediated glucose disposal rates (GDR) were greater (P < 0.05) in the exercise-trained compared with the sedentary control group (9.22 +/- 0.95 vs. 6.36 +/- 0.57 mg. kg fat-free mass(-1). min(-1)). Insulin-stimulated PI3-kinase activation was also greater (P < 0.004) in the trained compared with the sedentary group (3.8 +/- 0.5- vs. 1.8 +/- 0.2-fold increase from basal). Endurance capacity (VO(2 max)) was positively correlated with PI3-kinase activation (r = 0.53, P < 0.04). There was no correlation between PI3-kinase and muscle morphology. However, increases in GDR were positively related to PI3-kinase activation (r = 0.60, P < 0.02). We conclude that regular exercise leads to greater insulin-stimulated IRS-1-associated PI3-kinase activation in human skeletal muscle, thus facilitating enhanced insulin-mediated glucose uptake.

Adult↗
PubMed2000

The design of a practical and reliable fall detector for community and institutional telecare.

Falls are one of the greatest obstacles to independent living for frail and elderly people. Their early detection is an important step in providing people with the reassurance and confidence necessary to maintain an active lifestyle. We have investigated a worn fall detector linked to a community alarm system. A worn device is the only one which is satisfactory, provided that it generates few false alarms. The fall detector we have developed is the size of a small radio pager. It uses a two-stage detection process which senses shock and the orientation of the wearer. A fall is detected within 20 s and triggers a radio signal to a community alarm system. Tests were devised using a jointed mannequin to simulate five modes of falling to understand the effects of impact at different parts of the body. This allowed us to select the appropriate trigger threshold and wearing positions for the sensor. Prototypes were evaluated with 20 people to observe false alarms. The final design allowed reliable detection in 180 different falling scenarios.

Accidental Falls↗