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Biomedical subjects

C Langley

Publications and source records attributed to C Langley.

16 recordsLinked to original sources
PubMed2002

Prediction of successful application for disability benefits for people with arthritis using the Health Assessment Questionnaire.

BACKGROUND: Many eligible people with arthritis do not receive disability benefits. Application forms are lengthy and complex, and doctors and nurses are often unsure which patients would qualify. AIM: To investigate how severe disability on the Health Assessment Questionnaire (HAQ) relates to successful application for disability benefits by people with osteoarthritis (OA) and rheumatoid arthritis (RA). METHOD: RA patients attending a hospital out-patient rheumatology clinic and patients with OA or RA in two general practices completed an HAQ and were asked about receipt of disability benefits. Those scoring 2 or more on the HAQ (severe disability) and not in receipt of benefits were offered professional help to complete applications for Disability Living Allowance (DLA) or Attendance Allowance (AA). RESULTS: Eighty per cent of patients with an HAQ score of 2 or more were already in receipt of benefits. Seventy-nine per cent of the new applicants applied successfully, the average benefit being in excess of 2580 pounds per annum. CONCLUSION: This initial study suggests that people who score 2 or more on the HAQ should be encouraged to apply for disability benefits. A test of the generalizability of these findings and the success rate associated with lower HAQ scores should be undertaken.

Adult↗
PubMed2001

Characteristics of persons with syphilis in areas of persisting syphilis in the United States: sustained transmission associated with concurrent partnerships.

BACKGROUND AND GOAL: In areas with persistent syphilis, to characterize persons at higher risk for transmitting syphilis. STUDY DESIGN: Cohort study. Structured interviews of persons with early syphilis from four research centers were linked to outcomes of partner tracing. RESULTS: Of 743 persons with syphilis, 229 (31%) reported two or more partners in the previous month, and 57 (8%) received money or drugs for sex in the previous three months. Persons with at least one partner at an earlier stage of syphilis than themselves were defined as transmitters; 63 (8.5%) of persons with early syphilis met this definition. Having concurrent partners (two or more in one week in the last month) was independently associated with being a transmitter. CONCLUSION: Sexual network/behavioral characteristics of syphilis patients and their partners, such as concurrency, can help identify persons at higher risk for transmitting syphilis who should receive emphasis in disease prevention activities.

Adult↗
PubMed2000

Clinicians' attitudes to recruitment to randomised trials in cancer care: a qualitative study.

OBJECTIVES: To explore attitudes to and problems experienced with recruitment into randomised trials in cancer care. METHODS: In-depth semi-structured interviews with a purposive sample of 20 hospital clinicians in the South West of England identified from 192 participants in a larger postal survey. Interviews were recorded on audiotape and fully transcribed. Data were analysed by comparing transcripts and describing emergent themes. RESULTS: Clinicians do not always find it easy to identify key randomised trials in their area of interest. Even when they identify those trials in which they would like to participate, they are not always able to recruit patients. Although recruitment can be hindered by the time and administration involved and the resources needed, the attitudes of clinicians to research in general, the design of randomised trials, clinicians' concerns regarding individual patients and patients' preferences for different treatments also present major barriers. Other factors of concern include the imposition of strict eligibility criteria and the expense and complexity of monitoring and follow-up. CONCLUSION: Barriers to recruitment depend on the clinicians' individual situations and on a complex combination of factors. Action is needed to promote awareness of randomised trials under way, to ensure that trials address issues of importance, are acceptable to patients and clinicians, and that practical support is provided for participating centres.

Attitude of Health Personnel↗
PubMed1999

A phase I evaluation of multitargeted antifolate (MTA, LY231514), administered every 21 days, utilizing the modified continual reassessment method for dose escalation.

PURPOSE: To determine toxicities, maximally tolerated dose (MTD), pharmacokinetic profile, and potential antitumor activity of MTA, a novel antifolate compound which inhibits the enzymes thymidylate synthase (TS), glycinamide ribonucleotide formyltransferase (GARFT), and dihydrofolate reductase (DHFR). METHODS: Patients with advanced solid tumors were given MTA intravenously over 10 min every 21 days. Dose escalation was based on the modified continual reassessment method (MCRM), with one patient treated at each minimally toxic dose level. Pharmacokinetic studies were performed in all patients. RESULTS: A total of 37 patients (27 males, 10 females, median age 59 years, median performance status 90%) were treated with 132 courses at nine dose levels, ranging from 50 to 700 mg/m(2). The MTD of MTA was 600 mg/m(2), with neutropenia and thrombocytopenia, and cumulative fatigue as the dose-limiting toxicities. Hematologic toxicity correlated with renal function and mild reversible renal dysfunction was observed in multiple patients. Other nonhematologic toxicities observed included mild to moderate fatigue, anorexia, nausea, diarrhea, mucositis, rash, and reversible hepatic transaminase elevations. Three patients expired due to drug-related complications. Pharmacokinetic analysis during the first course of treatment at the 600 mg/m(2) dose level demonstrated a mean harmonic half-life, maximum plasma concentration (Cpmax), clearance (CL), area under the curve (AUC), and apparent volume of distribution at steady state (Vdss) of 3.08 h, 137 microg/ml, 40.0 ml/min per m(2), 266 microg. h/ml, and 7.0 l/m(2), respectively. An average of 78% of the compound was excreted unchanged in the urine. Partial responses were achieved in two patients with advanced pancreatic cancer and in two patients with advanced colorectal cancer. Minor responses were obtained in six patients with advanced colorectal cancer. CONCLUSIONS: The MTD and dose for phase II clinical trials of MTA when administered intravenously over 10 min every 21 days was 600 mg/m(2). MTA is a promising new anticancer agent.

Adult↗
PubMed1999

General practitioners' use of guidelines in the consultation and their attitudes to them.

BACKGROUND: There is concern about the apparent lack of uptake of management and referral guideline information by general practitioners (GPs) in their day-to-day consultations with patients. Little is understood about the barriers to the uptake of guidelines as perceived by GPs. AIMS: To explore how GPs gain access to and use guidelines, including computer-based guidelines, in day-to-day consultations with their patients; and to identify the perceived problems and barriers to the use of guidelines in such situations. METHOD: Postal questionnaires enquiring about the practices and attitudes towards the use of guidelines in general practice were completed by 391 of 600 randomly selected GPs in the South and West NHS region. RESULTS: GPs found guidelines a useful method of accessing expert information. Key factors in their uptake were brevity, an authoritative and unbiased source of evidence, and resonance with the GP's usual practices; they also needed to be flexible enough to incorporate individual viewpoints. Guidelines were perceived as being valuable to enable safe delegation of care to other health professionals and for sharing decision-making with patients. Dissemination of guidelines through the medium of computers was acceptable to the majority of GPs. Virtually all (93%) responders reported adapting guidelines to the needs of individual patients. Older GPs from non-fundholding practices were least likely to show a positive attitude towards guidelines. CONCLUSION: In principle, there is a very positive attitude towards the use of guidelines in general practice. However, those developing guidelines for use by GPs in the consulting room need to be aware of the factors that facilitate their use in practice. Educational strategies aimed at increasing the use of guidelines need to take into account the significant proportion who show negative attitudes towards guidelines, whose characteristics have been identified in this study.

Attitude of Health Personnel↗
PubMed1999

General practitioners' use of computers during the consultation.

This study documents the extent of reported computer use by general practitioners (GPs) in consultations with patients, and identifies barriers to their use. There was a 65% response rate from a random sample of 600 GPs in the South and West National Health Service (NHS) region who were sent a questionnaire. Ninety-one per cent (357) had a desktop computer terminal in their consulting rooms. Of these, 98% used the computer to look up information or prescribe medication, 75% entered details about selected problems presented by patients, and 36% entered information about the patient's presenting problem at every consultation. Only 18% used computers to access reference information. Use of the computer for anything other than looking up patient information or prescribing was positively associated with fundholding status and use of a personal computer at home, and was independent of number of years in practice. Sixty-five per cent of responders had positive attitudes to the inclusion of management guidelines on the computer software, and 45% of responders held positive views towards the idea of integrating management guidelines with the patient's personal computerized medical record. Consideration should be given to targeting training at those GPs who appear to be reluctant to use computers during the consultation.

Attitude to Computers↗
PubMed1998

Use of guidelines in primary care--practitioners' perspectives.

BACKGROUND AND OBJECTIVES: Concern about the inadequate take-up of guidelines in general practice has concentrated on problems arising from the process of their development and implementation. However, these perspectives fail to take account of the needs, attitudes and problems of GPs themselves. In this study we aimed to identify barriers to the use of guidelines and opportunities for tackling them, from the point of view of the GP, so that future guideline development and policy could be more sensitive to the needs of GPs in the environment in which they work. METHOD: Twenty in-depth semi-structured interviews were audiotaped with GPs from within the Avon Health Authority area, representing GPs with different backgrounds and working environments. The transcribed data collected were analysed using a grounded theory approach. RESULTS: Utilization of guideline information is complex. GPs' appraisals of the value of guidelines interact with prior knowledge and beliefs, practicalities of existing information storage and retrieval systems, and individual working practices. Conditions where guidelines are most likely to be referred to may be those either very rarely or very commonly presenting in general practice. Key issues for the uptake of guidelines in the consultation are: general preference for certain formats of presentation; reputability and ownership; use of guidelines in shared decision-making; scope for computer-based systems; and GPs' attitudes to time pressures on information-seeking in relation to tolerance of uncertainty. CONCLUSION: Local initiatives might usefully explore the possibilities of supporting development of guideline-retrieval systems customized for individual GPs or practices. Novel means of stimulating 'ownership' and demonstrating reputability should be sought. The analysis provides a framework for understanding the complexities of the processes of GPs' use of guidelines in practice which can be useful in explaining the results of trials of guideline effectiveness. Guideline implementation occurs in the context of conflicting pressures for clinical autonomy and professional standardization and quality improvement.

Attitude of Health Personnel↗
PubMed1996

Update on chancroid: an important cause of genital ulcer disease.

Chancroid is a major cause of genital ulcer disease worldwide, and occurred at epidemic rates in the United States in the late 1980s. Though the recent epidemic in the U.S. appears to be waning, a number of areas continue to report significant numbers of cases. Chancroid is a particular concern, because, like other diseases that cause genital ulceration, it is associated with an increased risk for transmission or acquisition of human immunodeficiency virus (HIV). Recent studies have advanced the understanding of chancroid epidemiology, and new diagnostic tests may improve the ability to recognize and appropriately treat chancroid. Increased awareness of chancroid, with appropriate treatment for suspected lesions, along with public health efforts to implement prevention in high-risk populations, will be critical to prevent ongoing transmission of chancroid, and potentially ongoing transmission of HIV.

Anti-Bacterial Agents↗
PubMed1995

Initial phase I evaluation of the novel thymidylate synthase inhibitor, LY231514, using the modified continual reassessment method for dose escalation.

PURPOSE: To determine the toxicities, maximal-tolerated dose (MTD), pharmacokinetic profile, and potential antitumor activity of LY231514, a novel thymidylate synthase (TS) inhibitor. PATIENTS AND METHODS: Patients with advanced solid tumors were administered LY231514 intravenously over 10 minutes, weekly for 4 weeks, every 42 days. Dose escalation was based on the modified continual reassessment method (MCRM), with one patient treated at each minimally toxic dose level. Pharmacokinetic studies were performed in all patients. RESULTS: Twenty-five patients were administered 58 courses of LY231514 at doses that ranged from 10 to 40 mg/m2/wk. Reversible neutropenia was the dose-limiting toxicity. Inability to maintain the weekly treatment schedule due to neutropenia limited dose escalation on this schedule. Nonhematologic toxicities observed included mild fatigue, anorexia, and nausea. At the 40-mg/m2/wk dose level, the mean harmonic half-life, maximum plasma concentration, clearance, and apparent volume of distribution at steady-state were 2.02 hours, 11.20 micrograms/mL, 52.3 mL/min/m2, and 6.64 L/m2, respectively. No major antitumor responses were observed; however, minor responses were achieved in two patients with advanced colorectal cancer. CONCLUSION: The dose-limiting toxicity, MTD, and recommended phase II dose of LY231514 when administered weekly for 4 weeks every 42 days are neutropenia, 40 mg/m2, and 30 mg/m2, respectively.

Adult↗
PubMed1985

Measurement of rat-intestinal cefuroxime axetil esterase activity: comparison of an h.p.l.c. and coupled-enzyme assay.

An alternative method to h.p.l.c. for determining cefuroxime axetil esterase (CAE) activity has been developed which involves coupling acetaldehyde, produced in the esterase reaction, with alcohol dehydrogenase (ADH) to provide a direct reading spectrophotometric assay. The optimum temperature and concn. of NADH, cefuroxime axetil and ADH for the assay are 37 degrees C, 160 microM, 2.9 mM and 160 U/ml, respectively. The coupled assay was more reproducible but less sensitive than the h.p.l.c. assay, and the two methods gave results that were not significantly different (P greater than 0.05). Both assays responded linearly when CAE activity was measured as a function of protein concn., however, the coupled assay was impaired at ionic strengths greater than 0.2 M NaCl, whereas no adverse effects were seen with the h.p.l.c. assay up to 0.5 M NaCl.

Alcohol Dehydrogenase↗
PubMed1976

Multilocus behavior in random environments. I. Random Levene models.

In this paper the consequences of natural selection acting on several loci simultaneously in a spatially fluctuating environment are described. The fitnesses of the genotypes are assumed to be additive both within and between loci. The environment is assumed to be made up of a very large (effectively infinite) number of patches in which fitnesses are assigned at random. The resulting deterministic model is called a Random Levene Model and its properties are approximate by a system of differential equations. The main equilibrium properites are that (1) the linkage disequilibrium is zero and (2) the correlations in fitness between alleles at different loci are the principle determinants of the dynamic inter-locus interactions. Although there is no epistasis as conventionally defined, the equilibrium state at the two loci are highly interdependent, the governing principle being that two alleles at different loci whose fitness are negatively correlated across environments have a higher overall fitness due to the reduction in their variance in fitness through the negative correlation. When a large number of loci are considered, they naturally fall into correlation groupings which lead to an enhanced likelihood for polymorphism over that predicted by single-locus theory.

Biological Evolution↗
PubMed1973

Recombination in Drosophila melanogaster male.

T-007 strain of Drosophila melanogaster is known to show recombination in males. The present study established the following points: (1) Clustering occurrence of recombinant, unequal recovery of complementary products of recombination, relatively high frequency of recombination around centromeric region, and relatively frequent occurrence of mosaic phenontype flies-all of these seem to indicate that a considerable fraction of male recombination in the T-007 strain is of premeiotic, or somatic origin, although a fraction still could be of meiotic origin; (2) Male recombination occurs in the third as well as in the second chromosomes, and the frequencies of recombinations are comparable between these two chromosome pairs.

Animals↗
PubMedDate not supplied

Cervical intraepithelial neoplasia and human papillomavirus infection among Senegalese women seropositive for HIV-1 or HIV-2 or seronegative for HIV.

Studies in various regions of the world have shown that women infected with HIV-1 are at increased risk for cervical human papillomavirus (HPV) infection as well as for cervical cancer precursor lesions. HIV infection and cervical cancer are both widespread in West Africa, but little is known about the relationship between HPV and HIV-2, which is the predominant type of HIV in the general population of many West African countries. To address this issue, we collected cervical samples for cytology and HPV analysis from 93 women presenting to the University of Dakar Infectious Disease Service (18 women with HIV-1 infection, 17 with HIV-2 infection, and 58 HIV seronegative controls). Compared to those without HIV infection, HIV seropositive women were 13.1 (95% CI = 2.4, 128) and 11.0 (95% CI = 3.5, 35.8) times more likely to have HPV detected using Southern transfer hybridization (STH) and the polymerase chain reaction (PCR) respectively. Detection of high and intermediate risk HPV types were significantly associated with HIV-1 and HIV-2 infection. Among HPV positive women, those with, as compared to those without HIV infection were more likely to harbour high risk HPV types (OR = 9.2, 95% CI = 0.97, 433). HIV-1 and HIV-2 seropositive women were 23.3 (95% CI = 2.9, 209) and 9.3 (95% CI = 1.1, 79) times more likely to have cytological diagnosis of dysplasia, respectively, than were HIV seronegative women. Biopsy-proven CIN 3 was found in one woman with HIV-1 and invasive cancer was found in one woman with HIV-2.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Southern↗