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Biomedical subjects

D Wilson

Publications and source records attributed to D Wilson.

At least 19 recordsLinked to original sources

G protein-coupled receptor 101 mRNA expression in the mouse brain: altered expression in the posterior hypothalamus and amygdala by energetic challenges.

GPCR101 is a recently identified orphan G protein-coupled receptor (GPCR) expressed abundantly in the human and mouse hypothalamus. In the absence of a ligand, a direct approach to determine the function(s) of this receptor is not possible. However, clues to the possible functions of GPCR101 may yield from information on the distribution of the receptor and the effect of in vivo manipulation upon the expression level of the receptor. In situ hybridisation on mouse brain sections revealed GPCR101 expression in a number of nuclei, including the amygdala, lateral parabrachial nucleus and nucleus of the solitary tract, as well as in the arcuate nucleus, posterior hypothalamus and paraventricular nucleus of the hypothalamus. Food-deprivation was found to increase GPCR101 mRNA level in the posterior hypothalamus and amygdala. In obese mice bearing the ob gene mutation, GPCR101 mRNA level decreased in the posterior hypothalamus and remained unaltered in the amygdala. By contrast, in both nuclei, GPCR101 mRNA level did not change significantly in obese ob/ob mice after intraperitoneal injection of leptin or in mice fed with a high fat diet. These data suggest that GPCR101 mRNA expression in the posterior hypothalamus and amygdala is regulated by a factor(s) other than leptin. Dual in situ hybridisation was used to establish the relationship between GPCR101 and neuropeptides expressed in the hypothalamus. In the arcuate nucleus, GPCR101 mRNA was expressed in approximately half of the population of neurones expressing the mRNA for the anorexigenic neuropeptide, pro-opiomelanocortin, which suggests a potential functional relationship.

Amygdala↗

Preoperative cardiac drug administration in general surgical patients: A completed audit.

The aim of this study was to audit the preoperative administration of regular cardiac medication in general surgical patients and to determine if this can be improved with simple ward-based education. The notes and drug charts of 102 general surgical adult inpatients undergoing elective operations were analysed prospectively. It was noted whether the patient was on regular morning cardiac medication, whether this was given and, if not, whether a reason was recorded on the drug chart. An information sheet and brief verbal reinforcement was given to nursing staff and junior doctors and the review repeated in 111 patients. There was no significant difference in the number of patients on regular cardiac medication between the two review groups; 42% patients had one or more drugs omitted in the initial review. After education this reduced significantly to 20% (p = 0.023). When omissions on medical instruction were excluded, this became highly significant (p = 0.0029). There was also a significant decrease in the number of times 'nil by mouth' was stated as the reason for omission. As a general principle, all regular cardiac medication should be given preoperatively even when nil by mouth as there is evidence that abrupt withdrawal can have serious consequences. This audit demonstrates that with simple education, the proportion of regular cardiac drugs administered preoperatively can be significantly increased.

Cardiovascular Agents↗

Sex worker health: San Francisco style.

OBJECTIVES: To describe the characteristics of sex workers accessing care at a peer based clinic in San Francisco and to evaluate predictors of sexually transmitted infections (STI). METHODS: We conducted an observational study of sex workers at St James Infirmary. Individuals underwent an initial questionnaire, and we offered screening for STI at each clinic visit. We performed univariate, bivariate, and multivariable analyses to assess for predictors of STI in this population. RESULTS: We saw 783 sex workers identifying as female (53.6%), male (23.9%), male to female transgender (16.1%), and other (6.5%). 70% had never disclosed their sex work to a medical provider. Participants represented a wide range of ethnicities, educational backgrounds, and types of sex work. The most common substance used was tobacco (45.8%). Nearly 40% reported current illicit drug use. Over half reported domestic violence, and 36.0% reported sex work related violence. Those screened had gonorrhoea (12.4%), chlamydia (6.8%), syphilis (1.8%), or herpes simplex virus 2 (34.3%). Predictors of STI included African-American race (odds ratio (OR) 3.3), male gender (OR 1.9), and sex work related violence (OR 1.9). In contrast, participants who had only ever engaged in collective sex work were less likely to have an STI (OR 0.4). CONCLUSIONS: The majority of sex workers have never discussed their work with a medical provider. Domestic violence is extremely prevalent as is work related violence. Working with other sex workers appears to be protective of STIs. STI prevention interventions should target African-American and male sex workers. Addressing violence in the workplace and encouraging sex workers to work collectively may be effective prevention strategies.

Adolescent↗

The Postpartum Bonding Questionnaire: a validation.

This is a validation of a self-rating questionnaire designed to detect disorders of the mother-infant relationship. 125 subjects filled in the questionnaire, and were also interviewed using the 5(th) Edition of the Birmingham Interview for Maternal Mental Health. On the basis of these interviews and the case records, we made consensus diagnoses of various forms and degrees of mother infant relationship disorder, according to criteria published in this paper. We calculated specificity, sensitivity and positive predictive value of the four scale scores generated by the questionnaire. Scale 1 (a general factor) had a sensitivity of 0.82 for all mother-infant relationship disorders. Scale 2 (rejection and pathological anger) had a sensitivity of 0.88 for rejection of the infant, but only 0.67 for severe anger. The performance of scale 3 (infant-focused anxiety) was unsatisfactory. Scale 4 (incipient abuse) selected only a few mothers, but was of some value in identifying those at high risk of child abuse. Revision of the thresholds can improve sensitivity, especially of scale 2, where a cut-off point of 12 = normal, 13 = high better identifies mothers with threatened rejection. These new cut-off points would need validation in another sample.

Adolescent↗

Multi-center evaluation of analytical performance of the microparticle enzyme immunoassay for sirolimus.

OBJECTIVES: This study evaluated the analytical characteristics of the new Abbott microparticle enzyme immunoassay (MEIA) for sirolimus. DESIGN AND METHODS: The protocol consisted of nine sections: evaluation of antibody specificity, linearity, detection limit, quantification limit, endogenous interferents, exogenous interferents, precision, proficiency testing panel, and method comparison. RESULTS: The mean analytical detection limit was 0.68 microg/L. The sirolimus concentration corresponding to a total CV of 20% was 1.5 microg/L. Linearity of response was demonstrated across the dynamic range of the assay. Total precision (CVs) at QC control levels from 5 to 22 microg/L ranged from 5.7 to 12.6%. Assay standardization was found to be in good agreement with LC/MS/MS as compared with target values for spiked sirolimus proficiency samples from an international sirolimus proficiency testing program. Good correlations (R values) of the immunoassay were observed in comparisons to LC/MS/MS. R values tended to be lower in comparisons with LC/UV methods. Across both LC-based methods and all study sites, there was approximately 25% overall positive slope bias due to cross reactivity of the MEIA antibody to metabolites of sirolimus. The assay cross-reactivity to metabolites of sirolimus parent drug ranged from 6 to 63%. Assay interferences were minimal with the exception of hematocrit, which presented a negative relationship to measured sirolimus concentration. CONCLUSIONS: The MEIA demonstrated acceptable analytical characteristics for use for routine monitoring of sirolimus immunosuppressive therapy, and is a viable alternative to HPLC-based methods for sirolimus monitoring.

Calibration↗

Cassini observes the active south pole of Enceladus.

Cassini has identified a geologically active province at the south pole of Saturn's moon Enceladus. In images acquired by the Imaging Science Subsystem (ISS), this region is circumscribed by a chain of folded ridges and troughs at approximately 55 degrees S latitude. The terrain southward of this boundary is distinguished by its albedo and color contrasts, elevated temperatures, extreme geologic youth, and narrow tectonic rifts that exhibit coarse-grained ice and coincide with the hottest temperatures measured in the region. Jets of fine icy particles that supply Saturn's E ring emanate from this province, carried aloft by water vapor probably venting from subsurface reservoirs of liquid water. The shape of Enceladus suggests a possible intense heating epoch in the past by capture into a 1:4 secondary spin/orbit resonance.

Extraterrestrial Environment↗

Laparoscopic colposuspension and tension-free vaginal tape: a systematic review.

BACKGROUND: Advances in surgical techniques have led to the availability of a number of minimal-access procedures to treat urodynamic stress incontinence (USI). These procedures have been individually compared with the 'gold standard' open Burch colposuspension; however, it now seems appropriate to compare like with like and compare these minimal-access techniques with each other. OBJECTIVES: To determine the effectiveness of laparoscopic colposuspension with tension-free vaginal tape (TVT) for the treatment of USI. SEARCH STRATEGY: Randomised trials in woman with USI, which compared laparoscopic colposuspension with TVT in the arms of the trial, were identified from the Cochrane Incontinence Review Group's Specialised Register of Controlled Trials. SELECTION CRITERIA: The trials were evaluated for methodological quality and appropriateness for inclusion by the reviewers using the Incontinence Group's assessment criteria. DATA COLLECTION AND ANALYSIS: The data were extracted independently, and when appropriate, meta-analysis was undertaken to calculate pooled estimates and their confidence intervals (CI). The main outcomes measured were: subjective cure, objective cure, quality of life (QoL) measurements, surgical outcomes and health economic measures. MAIN RESULTS: Seven trials compare laparoscopic colposuspension (n= 264) with TVT (n= 290). There was no statistically significant difference in the reported subjective cure rate between laparoscopic colposuspension and TVT within 18 months (relative risk [RR] 1.12, 95% CI 0.98-1.29). However, within the same time period, the overall objective cure rate was statistically significantly higher for TVT (RR 1.16, 95% CI 1.07-1.25). There were no significant differences between the two procedures with regards to perioperative complication, de novo detrusor overactivity, voiding dysfunction, procedural costs and QoL scores. However, TVT procedure is quicker to perform and has a shorter hospital stay. CONCLUSIONS The evidence so far appears to be in favour of the TVT as the minimal-access technique of choice for USI in comparison with laparosopic colposuspension; however, long-tem data are needed. Further well-designed trials with standardized outcomes are required to draw accurate conclusions from this comparison.

Colposcopy↗

Diagnosing smear-negative tuberculosis using case definitions and treatment response in HIV-infected adults.

OBJECTIVE: To assess the diagnostic utility of expanded case definitions for HIV-associated smear-negative pulmonary tuberculosis (PTB) and extra-pulmonary TB (EPTB), and to derive objective criteria for response to anti-tuberculosis treatment. DESIGN: A prospective cohort study of HIV-infected adults who met expanded clinical case definitions for smear-negative PTB and EPTB. METHODS: All participants were started on rifampicin-based anti-tuberculosis treatment after mycobacterial cultures from multiple sites. At weeks 2, 4 and 8, response to treatment (RTT) was assessed by measuring changes in weight, haemoglobin, C-reactive protein, Karnofsky performance score and symptom count ratio. RESULTS: Of 147 participants enrolled, 105 (71%) were diagnosed with definite (culture-positive) or probable (histological features) TB and 25 (17%) with possible TB (treatment response). The positive predictive value for the most common case definitions ranged from 89% to 96%. Significant improvements in all the RTT parameters occurred in the subjects with confirmed TB (P < 0.001). Clinically relevant RTT criteria were derived, two or more of which were met at week 8 in 97.5% of subjects with confirmed TB, 91.3% of subjects with possible TB and none of the subjects without TB. CONCLUSION: Expanded case definitions could enhance the diagnosis of PTB and EPTB in HIV-infected adults in resource-limited settings. Using objective criteria, RTT can be assessed within 8 weeks of initiating anti-tuberculosis treatment.

AIDS-Related Opportunistic Infections↗

Interventions for growth failure in childhood Crohn's disease.

BACKGROUND: Crohn's disease in childhood is a chronic relapsing condition. Fifteen to forty per cent of children with Crohn's disease have growth retardation (Griffiths 1993a). Some treatment modalities including corticosteroids have been implicated in growth failure but it is thought mainly to be secondary to uncontrolled disease activity (Motil 1993; Markowitz 1993). Growth is fundamental to the practice of pediatrics, so by taking growth as the primary outcome measure we address issues important to both patients, their families and pediatricians. OBJECTIVES: To evaluate the effectiveness of the different modalities available for the treatment of childhood Crohn's disease with regard to the reversal of growth failure and the promotion of normal growth. SEARCH STRATEGY: Searches were made of the following databases using the Collaborative Review Group Search Strategy: EMBASE (1984-2004), MEDLINE (1966-2004), The Cochrane Central Register of Controlled Trials, The Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group Specialized Trials Register and the Science Citation Index. Abstracts from the major gastrointestinal research meetings and references from published articles were also reviewed. SELECTION CRITERIA: Randomized controlled trials pertaining to children less than 18 years of age with Crohn's disease were selected. Those with growth as an outcome measure were included in the review. DATA COLLECTION AND ANALYSIS: Data extraction and assessment of the methodological quality of each trial was independently reviewed by two reviewers. Only one good quality randomized controlled trial was included in the review and therefore no statistical analysis was possible. MAIN RESULTS: Three randomized controlled trials were identified. One was of good methodological quality (Markowitz 2000). This study looked at the use of 6-mercaptopurine (6-MP) as a steroid sparing agent. No difference in linear growth was observed between the intervention and placebo groups, although the total steroid dose received over the 18 month follow up period was reduced in the group receiving 6-MP. The two remaining randomized controlled trials (Sanderson 1987; Thomas 1993a) consider the use of enteral feeding versus corticosteroids for induction of remission, with height velocity standard deviation score at 6 months as an outcome measure. Although of less rigorous methodological quality, the results of these studies are discussed in detail in the review. In both studies height velocity standard deviation scores were significantly increased in the enteral feeding group compared with the corticosteroid group. AUTHORS' CONCLUSIONS: In addition to these randomized controlled trials, a body of lower quality evidence does exist relevant to two other important interventions; the use of supplemental enteral nutrition (Morin 1980; Belli 1988; Israel 1995) and the judicious use of surgical interventions in pre-pubertal children with refractory disease (Alperstein 1985; Lipson 1990; McLain 1990). Newer treatments, such as infliximab, are now becoming more widely used and may offer advantages in promoting growth. These effects are as yet unstudied. This review highlights the need for large, multi centre studies of the different treatment options in paediatric Crohn's disease and the importance of standardised measurements of growth, such as height velocity standard deviation scores and height standard deviation scores as outcome measures.

Adrenal Cortex Hormones↗

Review of second-line chemotherapy for advanced gastric adenocarcinoma.

Palliative chemotherapy has been shown to improve survival compared with best supportive care alone in patients with unresectable or recurrent gastric cancer. However, patients receiving chemotherapy eventually develop progressive disease. At this stage, no standard second-line chemotherapy can be offered. No randomised-controlled trial data suggest a benefit of second-line chemotherapy compared with supportive care alone. We review the published data concerning the use of second-line chemotherapy in gastric adenocarcinoma. Response rates to second-line therapy in phase II trials are similar to those seen for other cancers that are more commonly retreated. In addition, data suggest that patients who respond to second-line therapy consistently survive longer compared with non-responders, and, perhaps more importantly, symptomatic benefit may be obtained from second-line therapy.

Adenocarcinoma↗

[Paediatric musculoskeletal ultrasound].

Ultrasound examination is often the most effective and sometimes the only practical means of examining children with soft tissue, tendon and joint diseases. This review will cover the important application of diagnostic ultrasound in children musculoskeletal disorders. We will consider topics where ultrasound is the only sensible means of examination such as developmental dysplasia of the hip, where it is the best choice of several possible methods such as painful hip and when it provides an alternative or adjunct to other imaging such as the examination of soft tissue masses.

Child↗

A novel reduced-intensity stem cell transplant regimen for nonmalignant disorders.

Bone marrow transplantation (BMT) benefits nonmalignant diseases but is limited by regimen-related toxicity, graft-versus-host disease (GVHD), donor availability, and graft rejection (GR). To overcome some of these barriers, we developed a new conditioning strategy for these patients. In total, 16 patients received Campath-1H (33/48 mg; days -21 to -19), fludarabine (150 mg/m(2); days -8 to -4), melphalan (140/70 mg/m(2); day -3), and transplant using related/unrelated stem cells. GVHD prophylaxis included cyclosporine/methylprednisolone for cord cells. Other recipients also received methotrexate. Risk factors for GR included multiple transfusions (6), low stem cell numbers (1), and immunologic/metabolic disorders (3). Donor engraftment was present in 14/16 recipients. Neutrophils (ANC>0.5 x 10(9)/l) and platelets (>50 x 10(9)/l) engrafted at a median of 13 and 24 days. Two patients died of Pseudomonas sepsis prior to engraftment, one of CMV disease, and another of intracranial hemorrhage. With median follow-up of 281 days (78-907), 12/16 are stable/improved, or cured. Acute GVHD was absent (n=10) or mild and transient (grade1-2 skin) (n=4). There was no chronic GVHD. Toxicities were predominantly early infections within 100 days, and correlated with lymphopenia (CD4+ T and B cells). Stable engraftment and low incidence of significant GVHD, irrespective of age or stem cell source, make this reduced-intensity regimen attractive for nonmalignant disorders.

Adolescent↗

Glaucoma electronic patient record--design, experience and study of high-risk patients.

AIM: To set-up a glaucoma electronic patient record (GEPR) and study referral details to a new glaucoma service, concentrating on high-risk patients. METHOD: A GEPR was designed using the pre-existing hospital information technology (IT) infrastructure. Referral details of all new patients to the glaucoma service were completely electronically entered and analysed. RESULTS: A GEPR was successfully established. A total of 402 referrals were studied. In all, 43% (40) of high-risk clinic patients (IOP>29 mmHg, or C/D ratio >0.8 or moderate to advanced visual field defects) had to wait longer than 8 weeks from GP referral to be seen at the glaucoma service. Of these, nine patients lost more than one line of Snellen's visual acuity attributable to glaucoma. The optometrist failed to document IOP in 17%, fundoscopy in 30%, and visual fields in 45% of all referrals. CONCLUSIONS: A GEPR can be introduced in an NHS setting without disruption of clinical care and ophthalmic training, and facilitates detailed, accurate and rapid audit. Study of high-risk glaucoma referrals showed inadequate optometric referral details and poor prioritisation of urgent cases. This information is being utilised with the cooperation of local optometrists to refine the pattern of glaucoma referrals.

Glaucoma↗

Collaborative study to establish the first international standard for quantitation of anti-HPA-1a.

BACKGROUND AND OBJECTIVES: This report describes the production of a freeze-dried preparation of pooled human plasma, containing immunoglobulin G (IgG) antibodies against the human platelet antigen 1a (HPA-1a). The material, coded 03/152, is proposed as an International Standard containing 100 arbitrary units of anti-HPA-1a for use in quantitative assays to determine the anti-HPA-1a activity in clinical samples. MATERIALS AND METHODS: Plasma samples containing potent anti-HPA-1a were pooled and freeze dried in 1-ml ampoules. In addition, three individual plasma samples were selected which had varying levels of anti-HPA-1a activity. The anti-HPA-1a activity of these three samples was determined by using a variety of quantitative assays with the proposed standard as a reference. RESULTS: An international collaborative study, which was part of the 2004 ISBT Platelet Immunology Workshop, involved 39 laboratories in 24 countries and showed that the anti-HPA-1a activity in three test samples could be reliably determined by using the proposed standard. CONCLUSIONS: Laboratories can use this standard to measure the anti-HPA-1a activity in patient's samples. Further studies are required to determine the relationship between anti-HPA-1a activity and clinical outcome in patients with neonatal alloimmune thrombocytopenia (NAIT).

Antibodies, Monoclonal↗

Methodology for constructing guidance.

Although guidance exists for the use of many laboratory tests in a wide range of clinical situations, this guidance is spread among a range of literature sources, and is often directed at laboratory specialists rather than test users. Individual general practices display large variations in standardised test requesting, yet much of their testing activity involves a relatively small range of tests. This paper describes a methodological approach to review the available evidence and guidance and to extract relevant primary research work to examine a range of testing scenarios in general practice, with the aim of formulating guidance based on the best available evidence or consensus opinions.

Clinical Laboratory Techniques↗

Best practice in primary care pathology: review 1.

This first best practice review examines four series of common primary care questions in laboratory medicine, namely: (i) measurement and monitoring of cholesterol and of liver and muscle enzymes in patients in the context of lipid lowering drugs, (ii) diagnosis and monitoring of vitamin B12/folate deficiency, (iii) investigation and monitoring of paraprotein bands in blood, and (iv) management of Helicobacter pylori infection. The review is presented in a question-answer format, referenced for each question series. The recommendations represent a précis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents, and evidence based medicine reviews, supplemented by MEDLINE EMBASE searches to identify relevant primary research documents. They are not standards but form a guide to be set in the clinical context. Most are consensus rather than evidence based. They will be updated periodically to take account of new information.

Algorithms↗

Birth weight and systemic lupus erythematosus.

The fetal environment may be a contributing factor in the etiology of some adult diseases. This study examined whether birth weight, birth length and gestational age are associated with the subsequent development of systemic lupus erythematosus (SLE). The Marshfield Clinic Lupus Registry was searched to identify patients who were born at Saint Joseph's Hospital in Marshfield, Wisconsin, USA. Birth data on each case and five age-, sex-, and race-matched controls were recorded from medical and delivery room register records. Perinatal data were obtained for 23 cases and 115 controls. The unadjusted mean birth weight was similar for cases (3407 +/- 581 g) and controls (3422 +/- 514 g). Birth length was not different between groups. Birth weight adjusted for gestational age, analysed by conditional logistic regression, was not statistically significantly different between groups. We concluded that birth weight and length were similar among SLE cases and controls, suggesting that these perinatal characteristics are not associated with subsequent SLE.

Apgar Score↗

A drug dosage table is a useful tool to facilitate prescriptions of antiretroviral drugs for children in Thailand.

Scaling up of antiretroviral treatment (ART) for children in countries like Thailand will require decentralization and management by non-specialist doctors. We describe (a) the formulation of a standardized drug dosage table to facilitate antiretroviral drug (ARV) prescriptions for children, (b) the acceptability of such a table among doctors and (c) the safety and efficacy of drug doses in the table. Acceptability was assessed using a questionnaire. Safety and efficacy were assessed on the basis of incidence of adverse effects and virological response to treatment, respectively. Of all doctors (n=18), 17 (94%) found that the table was practical to use, avoided miscalculations and made them more confident with prescriptions. Of 49 children prescribed ARVs, less than 5% had adverse side-effects. All ARV-naïve children achieved undetectable viral loads within six months of ART. In our setting, a standardized drug dosage table provided a simple and reliable tool that facilitated ARV prescriptions for children.

Anti-HIV Agents↗