Klinefelter syndrome and cutis verticis gyrata.
Explore the source record for details and available documents.
Acromegaly↗
Biomedical subjects
C Williams
Publications and source records attributed to C Williams.
Retention of women enrolled in a prospective study of human immunodeficiency virus infection: impact of race, unstable housing, and use of human immunodeficiency virus therapy.
Even though women and people of color represent an increasing proportion of US acquired immunodeficiency syndrome (AIDS) cases, few research studies include adequate representation of these populations. Here the authors describe recruitment and retention of a diverse group of human immunodeficiency virus (HIV)-infected and at risk HIV-uninfected women in a prospective study operating in six sites across the United States. Methods used to minimize loss to follow-up in this cohort are also described. For the first 10 study visits that occurred during a 5-year period between 1994 and 1999, the retention rate of participants was approximately 82%. In adjusted Cox analysis, factors associated with retention among all women were older age, African-American race, stable housing, HIV-infected serostatus, past experience in studies of HIV/AIDS, and site of enrollment. In an adjusted Cox analysis of HIV-infected women, African-American race, past experience in studies of HIV/AIDS, site of enrollment, and reported use of combination or highly active antiretroviral HIV therapy at the last visit were significantly associated with retention. In adjusted Cox analysis of HIV-uninfected study participants, only the site of enrollment was significantly associated with study retention. These results show that women with and at risk for HIV infection, especially African-American women, can be successfully recruited and retained in prospective studies.
Adult↗
Serological analysis of human anti-human antibody responses in colon cancer patients treated with repeated doses of humanized monoclonal antibody A33.
Mouse monoclonal antibody A33 (mAb A33) recognizes a M(r) 43,000 cell surface glycoprotein (designated A33) expressed in human colonic epithelium and colon cancer but absent from most other normal tissues. In patients, mAb A33 localizes with high specificity to colon cancer and is retained for up to 6 weeks in the cancer but cleared rapidly from normal colon (5-6 days). As a carrier of (125)I or (131)I, mAb A33 has shown antitumor activity. Induction of strong human anti-mouse antibody (immunoglobulin; HAMA) responses in patients, however, limits the use of the murine mAb A33 to very few injections. A humanized version of this antibody (huAb A33) has been prepared for Phase I and II clinical studies in patients with colon cancer. In those studies, immunogenicity of huAb A33 has been monitored using a novel, highly sensitive BIACORE method, which allows measurement of human anti-human antibodies (HAHAs) without the use of secondary reagents. We found that 63% (26 of 41) of the patients treated with repeated doses of huAb A33 developed HAHAs against a conformational antigenic determinant located in the V(L) and V(H) regions of huAb A33. Detailed serological analysis showed two distinct types of HAHAs. HAHA of type I (49% of patients) was characterized by an early onset with peak HAHA levels after 2 weeks of treatment, which declined with ongoing huAb A33 treatment. HAHA of type II (17% of patients) was characterized by a typically later onset of HAHA than in type I and by progressively increasing HAHA levels with each subsequent huAb A33 administration. Colon cancer patients with type I HAHAs did not develop infusion-related adverse events. In contrast, HAHA of type II was indicative of infusion-related adverse events. By using this new method, we were able to distinguish these two types of HAHAs in patients while on antibody treatment, allowing patients to be removed from study prior to the onset of severe infusion-related adverse events.
Amino Acid Sequence↗
Prolonged exposure to one percent carbon monoxide causes a leucoencephalopathy in un-anaesthetised sheep.
A total of 15 Levine-prepared adult un-anaesthetised sheep were exposed to 1% carbon monoxide (CO) in air for between 45 and 150 min. This exposure caused a reversible increase in blood carboxyhaemoglobin concentration and heart rate, and a similarly reversible decrease in electroencephalographic frequency and level of consciousness. sheep were either normotensive or slightly hypertensive. Sheep brains were subsequently examined for histopathological changes at either 5 or 14 days post- exposure. No dead neurons or apoptotic cells were seen, but most sheep given a prolonged exposure to CO had some axonal damage and associated gliosis. This damage was concentrated about necrotic micro-foci in the peri-ventricular white matter. These results suggest that a leucoencephalopathy is a primary consequence of acute and sub-acute CO toxicity.
Animals↗
A virus binding assay for studying the antigenic landscape on intact, native, primary human immunodeficiency virus-type 1.
This protocol describes a simple assay that can be used to study the nature of exposure of antigenic epitopes and antigenic relatedness of different intact, native HIV-1 strains. The assay is based on the principle that mAbs coated on microtiter wells bind to epitopes on the surface of intact, native virions. The bound virion is then lysed to release p24, which is then quantitated (pg/ml) to give a measure of the amount of virion bound to the mAb. High p24 levels released after lysis correlate with high level capture of virions by mAbs, and as such, reflect good exposure of the epitope on the virion. Likewise, binding patterns of a specific mAb with different virus strains reveal information on their antigenic relatedness. In establishing this assay, the nature of exposure of antigenic epitopes and the antigenic relatedness of six intact, native HIV-1 virions of clades A, B, C, D, F and G were examined using anti-HIV-1 mAbs directed at epitopes in the V2, V3, CD4bd and C5 of gp120, and in clusters I and II of the gp41 region. Analysis of the binding data shows that mAbs directed at epitopes in the V3, C5 and gp41 Cluster I region bound best to the viruses examined, suggesting that these are the regions most exposed and conserved on intact, native HIV-1 virions of different clades. Epitopes in the V2 and CD4bd of gp120, and in gp41 cluster II, are not exposed on intact, native virions.
Antibodies, Monoclonal↗
Baseline rates of disease may account for some arrhythmia risk.
Explore the source record for details and available documents.
Arrhythmias, Cardiac↗
Flexible alignment of small molecules.
A method is presented for flexibly aligning small molecules. The method accepts a collection of small molecules with 3D coordinates as input and computes a collection of alignments. Each alignment is given a score, which quantifies the quality of the alignment both in terms of internal strain and overlap of molecular features. The results of several computational experiments on pairs of compounds with known binding conformations are used to systematically and objectively tune the parameters for the method. The results indicate the method's utility for the elucidation of pharmacophores and comparative field analysis.
Databases, Factual↗
Concomitant chemotherapy and radiation therapy for cancer of the uterine cervix.
BACKGROUND: The National Cancer Institute (USA) alert in February 1999 stated that concomitant chemoradiotherapy should be considered for all patients with cervical cancer, based on evidence from five randomised controlled trials. OBJECTIVES: To review all known randomised clinical controlled trials (RCTs) comparing concomitant chemotherapy and radiation therapy with radiotherapy for locally advanced cervical cancer. SEARCH STRATEGY: We searched electronic databases, trials registers and reference lists of published trial reports and review articles were also searched. SELECTION CRITERIA: This review includes RCTs in cervical cancer comparing concomitant chemotherapy and radiotherapy with radiotherapy. In the experimental arm, further adjuvant chemotherapy was allowable. Hydroxyurea was considered inactive and allowable. Trials using radiosensitisers or radioprotectors in the experimental arm were excluded. DATA COLLECTION AND ANALYSIS: Two authors reviewed trials for inclusion and extracted data. For meta-analyses of time-to-event outcomes (survival, progression-free survival), a hazard ratio (HR) was extracted or estimated from trial reports, where possible. Only overall rates of local and distant recurrence were presented in many reports so only an odds ratios (OR) of recurrence rates could be calculated, which takes no account of time to recurrence or censoring. The HRs and ORs for individual trials were combined across all trials, using the fixed effect model. Few trials reported acute toxicity adequately. Data were therefore grouped and the number of toxic events was used to calculate a single OR for each site and grade. Late toxicity was rarely described so could only be reviewed qualitatively. MAIN RESULTS: Nineteen trials (17 published, two unpublished) were identified including 4580 patients, although due to patient exclusion and differential reporting 62-78% were available for the various analyses. The review strongly suggests chemoradiation improves overall survival and progression free survival, whether platinum was used or not with absolute benefits of 12% and 16% respectively. There was, however, statistical heterogeneity for these outcomes There was some evidence that the effect was greater in trials including a high proportion of stage I and II patients. Chemoradiation also showed significant benefit for both local and distant recurrence. Haematological and gastrointestinal toxicity was significantly greater in the concomitant chemoradiation group. Details of late morbidity were sparse. REVIEWER'S CONCLUSIONS: Concomitant chemotherapy and radiotherapy appears to improve overall survival and progression-free survival in locally advanced cervical cancer. It also reduces local and distant recurrence suggesting concomitant chemotherapy may afford cytotoxic and sensitisation effects. Some acute toxicity is increased, but data on long term side effects were sparse.
Combined Modality Therapy↗
Comparison of nicardipine versus placebo to control hemodynamic responses during emergence and extubation.
OBJECTIVE: To compare 2 different doses of intravenous nicardipine versus placebo to control heart rate and blood pressure responses to emergence and extubation. DESIGN: Prospective, randomized, double-blind, placebo-controlled. SETTING: University hospital, single-institutional. PARTICIPANTS: Forty-five American Society of Anesthesiologists (ASA) class I through III adult patients. INTERVENTIONS: General endotracheal anesthesia was with oxygen and isoflurane and muscle relaxation. At the end of surgery, with at least 2 twitches present by nerve stimulator and end-tidal isoflurane <0.4%, reversal was accomplished with neostigmine and glycopyrrolate. Two minutes post-reversal, the study drug (nicardipine, 0.015 mg/kg; nicardipine, 0.03 mg/kg; or a saline placebo) was given. Heart rate and blood pressure were measured for every minute up to 10 minutes and at 15 minutes postreversal. MEASUREMENTS AND MAIN RESULTS: There were no significant differences among groups in age, gender, ASA class, weight, or heart rate. The nicardipine groups, 0.015 and 0.03 mg/kg, had lower blood pressure values than the placebo group. There was a significant difference in blood pressure among groups, with greater and more consistent attenuation of blood pressure occurring with the larger nicardipine dose. There were no episodes of hypotension or adverse events. CONCLUSIONS: Compared with placebo, both nicardipine doses attenuated blood pressure but not heart rate responses during emergence and extubation. Greater blood pressure control occurred with the larger nicardipine dose of 0.03 mg/kg.
Adult↗
Regulation of the serotonin transporter by interacting proteins.
The serotonin transporter (SERT) plays a critical role in the maintenance of normal neurotransmission by serotonin [5-hydroxytryptamine (5-HT)]. Recent evidence suggests that SERT and other neurotransmitter transporters are tightly regulated. Activation of protein kinase C results in a decrease in SERT-mediated 5-HT uptake, which is due to an internalization of the transporter. However, to date little is known about the mechanism and proteins involved in the down-regulation of the transporter. One candidate SERT-regulatory protein is the SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor) protein, syntaxin 1A (Syn1A), which has recently been implicated in the regulation of ion channels as well as the SERT-related gamma-aminobutyric acid- and glycine-transporters. Using 5-HT uptake assays, confocal microscopy and glutathione S-transferase (GST) pull-down assays we showed that Syn1A also interacts with SERT and alters the subcellular localization of the transporter, resulting in a reduction of 5-HT transport. In addition, we have used the yeast two-hybrid system to search for novel regulatory proteins that interact with the cytoplasmic N-terminal domain of SERT. By screening rat brain cDNA library we have identified six potential SERT-binding proteins. Here we also present progress towards the elucidation of the biological relevance of these proteins and their potential role for the regulation of the serotonin transporter.
Animals↗
Anaesthetic machine checklists 1.
Explore the source record for details and available documents.
Anesthesia, Inhalation↗
Pre-registration house officer rotations incorporating general practice: does the order of rotation matter?
CONTEXT: In relation to pre-registration house officer (PRHO) rotations incorporating general practice, previous research has recommended that where possible, no PRHO should undertake general practice as the first placement, because of the difficulties encountered. It was recognized that logistically, this could make such schemes almost unworkable. Within the context of a larger qualitative evaluation comparing how 24 PRHOs learned in hospital and general practice settings, the issue of rotation order was explored. METHODS: In-depth semistructured interviews were conducted with the 12 PRHOs who were involved in general practice rotations. They were interviewed at the beginning and end of the PRHO year, and following their return to hospital work after the general practice placement. RESULTS: Each rotation order had both advantages and disadvantages, with no particular rotation order being obviously better or worse for the PRHOs involved. CONCLUSIONS: This small qualitative evaluation has highlighted a number of advantages and disadvantages specific to each rotation order, and makes some practical recommendations to help alleviate the problems encountered. It is important that future evaluations of similar schemes consider this issue, as there are conflicting reports about the significance of the rotation order.
Attitude of Health Personnel↗
A randomized, controlled, single-blind trial of teaching provided by a computer-based multimedia package versus lecture.
BACKGROUND: Computer-based teaching may allow effective teaching of important psychiatric knowledge and skills. AIMS: To investigate the effectiveness and acceptability of computer-based teaching. METHOD: A single-blind, randomized, controlled study of 166 undergraduate medical students at the University of Leeds, involving an educational intervention of either a structured lecture or a computer-based teaching package (both of equal duration). RESULTS: There was no difference in knowledge between the groups at baseline or immediately after teaching. Both groups made significant gains in knowledge after teaching. Students who attended the lecture rated their subjective knowledge and skills at a statistically significantly higher level than students who had used the computers. Students who had used the computer package scored higher on an objective measure of assessment skills. Students did not perceive the computer package to be as useful as the traditional lecture format, despite finding it easy to use and recommending its use to other students. CONCLUSIONS: Medical students rate themselves subjectively as learning less from computer-based as compared with lecture-based teaching. Objective measures suggest equivalence in knowledge acquisition and significantly greater skills acquisition for computer-based teaching.
Algorithms↗
The doctor-patient relationship: from undergraduate assumptions to pre-registration reality.
OBJECTIVES: To describe the ways in which the doctor-patient relationship experienced by newly qualified pre-registration house officers (PRHOs) differed from their undergraduate expectations. DESIGN: Qualitative study in which in-depth semistructured interviews were carried out with each PRHO within 4-6 weeks of the start of their first job. SETTING: Three teaching hospitals, three district general hospitals and four general practices in south-east England. PARTICIPANTS: 24 newly qualified PRHOs. RESULTS: A number of differences were identified by PRHOs. These were caused in part by the impact of factors such as the shortage of time, which could lead to emotional 'blunting'. Some PRHOs were changing their ideas about what constitutes a 'good' doctor, and were redefining the meaning of a 'professional' relationship. The relationships of PRHOs with patients were also affected by the attitudes of their senior colleagues. For example, where PRHOs tried to maintain a patient-centred relationship, they could be identified by colleagues as working too slowly. PRHOs working in general practice were able to utilize and improve their communication skills with patients, but found it difficult to transfer these skills back into the hospital setting. CONCLUSIONS: Despite receiving substantial undergraduate education on how best to communicate with patients, a variety of factors conspired to prevent hospital-based PRHOs from utilizing this information. Building on these findings, a number of recommendations are made to help improve practice.
Communication↗
The clinical and educational experiences of pre-registration house officers in general practice.
AIMS: To describe aspects of the clinical experience and educational supervision gained by pre-registration house officers (PRHOs) in general practice, and to relate these to the current General Medical Council (GMC) aims for general clinical training in general practice. DESIGN: Qualitative evaluation, part of which involved semistructured interviews with 12 PRHOs who were experiencing a general practice rotation. Interviews were conducted at the beginning and the end of the pre-registration year, and following return to hospital work after completion of the general practice placement. SETTINGS: Three teaching hospitals, two district general hospitals and six general practices in south-east England. PARTICIPANTS: 12 PRHOs who were involved in rotations incorporating a general practice placement. RESULTS: To varying degrees, the GMC aims for training in general practice were met for all the participants. All PRHOs recognized the value of the clinical experience and educational supervision they received in general practice. They particularly valued aspects such as having an individual training programme based on their own needs, and the interlinking of theory and practice, which aided learning. Most felt that having responsibility for their own patients acted as an important incentive for learning, and in general, PRHOs appreciated having the time to learn which general practice allowed. CONCLUSIONS: For the majority of PRHOs, the time spent in general practice was seen as a positive clinical and educational experience. In a variety of ways, the general practice placement encouraged PRHOs to develop the self-directed learning skills seen as essential to the lifelong learning advocated by the GMC. A number of recommendations are made to help improve the integration of the hospital and general practice components of these rotations.
Clinical Competence↗
Occurrence and significance of gastric colonization during acid-inhibitory therapy.
There are now a wide variety of drugs available that are able profoundly to reduce the production of gastric acid. These drugs are currently widely prescribed for the treatment of peptic ulceration and gastro-oesophageal reflux disease. One of the main functions of gastric acid is to kill ingested bacteria. Colonization of the gastric lumen occurs in patients on anti-secretory medication, the degree of bacterial overgrowth depending upon the degree of elevation of the pH. There have been concerns that these bacteria may produce carcinogenic nitrosamines and increase the risk of gastric cancer, but there is at present no definitive evidence in support of this. A profound suppression of gastric acid may also facilitate the colonization of the upper small intestine, leading to deconjugation of the bile salts and malabsorption. There is some evidence that profound gastric acid suppression may decrease the number of ingested pathogens required to produce enteric disease. This chapter discusses these potential bacterial complications of therapeutic acid suppression and the evidence for them.
Achlorhydria↗
Muscle soreness and damage parameters after prolonged intermittent shuttle-running following acute vitamin C supplementation.
Exercise-induced free-radical production may be partly responsible for muscle soreness and damage following demanding exercise. A number of studies have investigated the effect of antioxidant supplementation although there is a paucity of information regarding vitamin C. Therefore the aim of the present study was to investigate the effect of vitamin C supplementation on exercise-induced muscle soreness and damage. Nine habitually active males consumed a 1 g dose of vitamin C 2 h before exercise, and on another occasion consumed an identical placebo. The exercise comprised a 90 min intermittent shuttle-running test, which was designed to simulate the multiple-sprint sports. Vitamin C supplementation increased plasma concentrations of vitamin C before exercise, and plasma concentrations continued to increase during the shuttle-run to reach a peak of approximately 200 micromol x l(-1) immediately after exercise. However, muscle soreness, and markers of both muscle damage (creatine kinase and aspartate aminotransferase) and lipid peroxidation (malondialdehyde) were elevated to an equal extent after exercise in placebo and supplemented trials. Therefore acute supplementation with vitamin C had no beneficial effects although it is possible that such short-term vitamin C supplementation was ineffective because it occurred at an inappropriate time.
Administration, Oral↗
Screening for amblyopia in preschool children: results of a population-based, randomised controlled trial. ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood.
INTRODUCTION: The rationale for preschool vision screening programmes has recently been questioned. Evidence about the effects of early treatment is needed, but it is not known how early the target conditions can reliably be detected. In this study, an intensive programme comprising several different screening methods, used at different ages up to 37 months, was compared with the usual practice of visual surveillance and ad hoc referrals. METHODS: Two groups were randomly selected from children in a population birth cohort study. The control group (n = 1461) received visual surveillance only. The intervention group (n = 2029) was offered in addition a programme of regular visual assessments by orthoptists testing visual acuity, ocular alignment, stereopsis and non-cycloplegic photorefraction. RESULTS: The intervention group programme yielded more children with amblyopia (1.6% vs. 0.5%, p < 0.01), and was more specific (95% vs. 92%, p < 0.01), than the control programme. The individual components of the intervention programme were compared. The cover test and visual acuity tests were poorly sensitive until the children were 37 months, but were always >99% specific. Photorefraction was more sensitive than acuity testing at all ages below 37 months, with specificity >95% at 31 and 37 months. CONCLUSIONS: Photorefraction would have detected more children less than 37 months of age with straight-eyed amblyopia than did visual acuity testing, but with more false positives. At 37 months, photorefraction plus a cover test would have been comparable in effectiveness to visual acuity testing plus a cover test.
Amblyopia↗