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Biomedical subjects

J Belcher

Publications and source records attributed to J Belcher.

At least 19 recordsLinked to original sources

Effects of anti-rheumatic gold salts on NF-kappa B mobilization and tumour necrosis factor-alpha (TNF-alpha)-induced neutrophil-dependent cytotoxicity for human endothelial cells.

We have previously shown that the gold-containing disease-modifying anti-rheumatic drugs, auranofin (AF) and gold sodium aurothiomalate (GSTM) reduce human umbilical vein endothelial cell (HUVEC) adhesion molecule expression and neutrophil (PMN) adherence. AF diminishes E-selectin and intercellular adhesion molecule-1 (ICAM-1) on cytokine-activated HUVEC, while GSTM decreases only E-selectin. Since tight adhesion is critical for PMN to damage EC, we tested whether these drugs modulated human PMN-mediated injury to TNF-alpha-activated HUVEC in vitro (as measured by 51Cr release). Here we show that TNF-alpha caused a prominent PMN-mediated cytotoxicity that was dose-dependently reduced when AF and GSTM were added to the assay system. We also found that a potent inhibitor of NF-kappaB, pyrrolidine dithiocarbamate (PDTC) in a dose-dependent manner impaired TNF-alpha-induced cytotoxicity, indicating a role of NF-kappaB activation in cytokine-induced endothelial injury. To examine the effects of AF and GSTM on TNF-alpha-induced NF-kappaB activation this was measured in HUVEC nuclear extracts by an electrophoretic mobility shift assay. AF, but not GSTM, decreased TNF-alpha-induced NF-kappaB activation in HUVEC. Thus, in this in vitro model of vasculitis, AF and GSTM dose dependently reduced TNF-alpha-mediated neutrophil-dependent cytotoxicity for HUVEC, and AF, but not GSTM, inhibited NF-kappaB mobilization, thereby providing possible mechanisms for effects of AF and GSTM.

Antirheumatic Agents↗

Delays in orthopaedic trauma treatment: setting standards for the time interval between admission and operation.

Delay in operating on trauma patients leads to increased morbidity, mortality, length of hospital stay and overall cost. The urgency of operative intervention depends on the injury sustained. There are no published guidelines on what constitutes a reasonable delay between admission and operation. As part of the clinical governance in our unit, an audit was undertaken to examine the structure and process of trauma operating. Patients were allocated to groups defined by the Bath Orthopaedic Department, according to urgency of need for surgery. Group A: patients (for example, open fractures and dislocations) should have definitive treatment within 6 h of admission. Group B: patients (for example, hip fractures, long bone injuries and ankle fractures) should have operations on the day that they are presented to the consultant trauma meeting, or on the day that they are declared fit/ready for theatre. Group C: patients (for example, tendon injuries, simple hand fractures) should have operations within 5 days of presentation to the trauma meeting. Over 3 months, there were 401 acute orthopaedic admissions requiring surgery (61 group A, 277 group B, 63 group C). 78% of group A patients, 58% of group B patients and 86% of group C patients were operated on within the target times. In total, 137 out of 401 operations (34%) missed the targets set. 119 of these (87%) were delayed due to lack of available operating time. This was despite the fact that 59 operations (15% of total) were done on lists normally used for elective operating. Most of the other delays were due to the need for an appropriately experienced surgeon to be available. If these targets are to be achieved for the majority of patients, the trauma theatre must become more efficient, or more flexible time must be made available during evenings or weekends to clear the backlog of trauma operations.

Emergencies↗

The effect of patient technique and training on the accuracy of self-recorded peak expiratory flow.

The aim of the study was to investigate the difference between encouraged self-recorded peak expiratory flow (PEF) with unobserved readings and to investigate any long-term changes in PEF self-recording. Patients were trained in the PEF technique and asked to keep 2-hourly PEF records until the next clinic visit. The patients PEF were then rechecked at the second clinic visit by a series of two unobserved, an observed and an encouraged PEF measurement. A subgroup of patients were reassessed at a third clinic visit. Forty-one patients produced serial PEF readings. Significant differences between unobserved and encouraged PEF readings were detected; there was a mean decrement of 21 L x min(-1) and limits of agreements suggested that the decrement could be as high as 60 L x min(-1). Visual and statistical analysis of the serial PEF provided showed a consistent deterioration in PEF over the record in 54% and 39% of cases, respectively. No significant differences were found in the subgroup who attended a third clinic visit. The results suggest that significant inaccuracies in unobserved peak expiratory flow readings can occur between clinic visits and this can be reflected as a consistent deterioration in some. This should be kept in mind when interpreting self-recorded peak expiratory flow measurements. Re-evaluation at the third visit following the retraining effect of the second visit on peak expiratory flow technique appears to reduce inaccuracies. It is believed that peak expiratory flow technique should be reevaluated at each clinic visit.

Adolescent↗

Development of an expert system for the interpretation of serial peak expiratory flow measurements in the diagnosis of occupational asthma. Midlands Thoracic Society Research Group.

If asthma is due to work exposures there must be a relation between these exposures and the asthma. Asthma causes airway hyperresponsiveness and obstruction; the obstruction can be measured with portable meters, which usually measure peak expiratory flow, or sometimes forced expiratory volume in 1 second (FEV1). These can be measured serially (for instance 2 hourly) over several weeks at and away from work. Once occupational asthma develops, the asthma will be induced by many non-specific triggers common to non-occupational asthma. The challenge is to identify changes in peak expiratory flow due to work among other non-occupational causes. Standard statistical tests have been found to be insensitive or non-specific, principally because of the variable period for deterioration to occur after exposure, and the sometimes prolonged time for recovery to occur, such that days away from work may initially have lower measurements than days at work. A computer assisted diagnostic aid (Oasys) has been developed to separate occupational from non-occupational causes of airflow obstruction. Oasys-2 is based on a discriminant analysis, and achieved a sensitivity of 75% and a specificity of at least 94%; therefore peak expiratory flow monitoring combined with Oasys-2 analysis is better to confirm than to exclude occupational asthma. A neural network version in development has improved on this. Both have been based on expert interpretation of peak flow measurements plotted as daily maximum, mean, and minimum, with the first reading at work taken as the first reading of the day. Oasys has been evaluated with independent criteria against measurements made in a wide range of occupational situations. Oasys is sufficiently developed to be the initial method for the confirmation, although less so for exclusion of occupational asthma.

Asthma↗

Comparative clinical and physiological features of Maori, Pacific Islanders and Europeans with sleep related breathing disorders.

UNLABELLED: Recent studies have suggested that there is a familial association of sleep apnoea syndrome and that this is not entirely explained by inheritance of known risk factors. Maori (M) and Pacific Islanders (PI) have many of the body habitus features associated with sleep apnoea and therefore might be expected to exhibit more severe disease than Europeans (E). OBJECTIVE: To compare the clinical and physiological characteristics of the different ethnic groups and to determine if race was an independent predictor of severity of sleep apnoea. METHODOLOGY: A prospective evaluation of patients attending the Sleep Disordered Breathing Clinic which serves the whole of Auckland (population 1.1 million), New Zealand was conducted for the period July 1994 to August 1995. The evaluation included history including a 26 question questionnaire, Epworth sleepiness score, examination, and where indicated, full polysomnography. RESULTS: A total of 233 patients (154 E, 48 M and 33 PI), underwent full polysomnography. Forty-one (85%) of the M and 31 (94%) of PI had obstructive or mixed sleep apnoea compared with only 74 (49%) of the E (P < 0.0001; chi 2). There were few racial differences in the responses to the sleep questionnaire. M and PI were shown to have much greater neck and waist circumference and body mass indices. Severity parameters (apnoea-hypopnoea index, wake and minimum oxygen saturation, and apnoea duration) were greater for both M and PI compared with E (P < 0.001; Mann-Whitney U-test). Stepwise regression identified neck size, body mass index and age as independent predictors of severity. CONCLUSION: When other factors were controlled for, race was not an important independent predictor of severity of sleep apnoea.

Adult↗

A randomized controlled trial of strict glycemic control and tertiary level obstetric care versus routine obstetric care in the management of gestational diabetes: a pilot study.

OBJECTIVES: The purpose of this study was to determine whether strict maternal glycemic control for the treatment of gestational diabetes lessened the risk of fetal macrosomia, birth trauma, neonatal hypoglycemia, and operative delivery. The aim of the pilot study was to prepare for a multicenter trial by assessing patient acceptance of the study, by determining realistic accrual rates, and by detecting any major adverse outcomes in the control group that received routine obstetric care. STUDY DESIGN: The study was a prospective randomized controlled trial comparing fetal-neonatal and maternal outcomes in 300 women with gestational diabetes. Women randomized to the treatment arm were managed by strict glycemic control and tertiary level obstetric care, and women in the control arm received routine obstetric care. RESULTS: Three hundred women with gestational diabetes mellitus were studied. There was no difference in maternal age, weight, or length of gestation between groups. The treatment mean birth weight was 3437 +/- 575 gm compared with 3544 +/- 601 gm in the control group, a difference of 107 gm (not significant). Macrosomia rates were similar. There was no birth trauma in either group. The frequency of neonatal hypoglycemia and other metabolic complications was the same. The mode of delivery also showed similar patterns. The treatment group had significantly lower preprandial and postprandial glucose levels by 32 weeks' gestation, which continued to term. CONCLUSION: This pilot study suggests that intensive treatment of gestational diabetes mellitus may have little effect on birth weight, birth trauma, operative delivery, or neonatal metabolic disorders. It has demonstrated the safety of proceeding to a multicenter trial of sufficient sample size to confirm these findings.

Adult↗

The descriptive assessment for psychiatric art. A new way of quantifying paintings by psychiatric patients.

This pilot study reports the development of a coding system for quantitative analysis of paintings produced by psychiatric patients. Color, color intensity, quality of line, space covered, and subjectively judged emotional tone as characteristics of paintings were recorded in each section of a grid superimposed over the picture. A sample of 39 psychiatric patients were classified into 4 groups using ICD-10 criteria: depression, psychosis, brain injury, and drug abuse. Six independent raters achieved excellent reliability across all scales on each of eight pictures. Analysis of variance results show that each diagnostic group differed on 4 of 13 variables: yellow, orange, color intensity, and line (p < .02). The prospects for further research are discussed.

Adult↗

Development of OASYS-2: a system for the analysis of serial measurement of peak expiratory flow in workers with suspected occupational asthma.

BACKGROUND: Serial peak expiratory flow (PEF) measurement is usually the most appropriate first step in the confirmation of occupational asthma. Visual assessment of the plotted record is more sensitive and specific than statistical methods so far reported. The use of visual analysis is limited by lack of widespread expertise in the methods. A computer assisted diagnostic aid (OASYS-2) has been developed which is based on a scoring system developed from visual analysis. This removes the requirement for an experienced interpreter and should lead to the more widespread use of the technique. METHODS: PEF records were collected from workers attending an occupational lung disease clinic for investigation of suspected occupational asthma and from workers participating in a study of respiratory symptoms in a postal sorting office. PEF records were divided into two development sets and two gold standard sets. The latter consisted of records from workers in which a final diagnosis had been reached by a method other than PEF recording. An experienced observer scored individual work and rest periods for the two development set PEF records; linear discriminant analysis was used to compare measurements taken from development set 1 records with visual scores. Two equations were produced which allowed prediction of scores for individual work or rest periods. The development set 2 was used to determine how these scores should be used to produce a whole record score. The first gold standard set was used to determine the whole record score which best separated those with and without occupational asthma. The second set determined the sensitivity and specificity of the chosen score. RESULTS: Two hundred and sixty eight PEF records were collected from 169 workers and divided into two development sets (81 and 60 records) and two gold standard sets (60 and 67 records). Linear discriminant analysis produced equations predicting the score for work periods incorporating five indices of PEF change and one for rest periods using seven indices. These equations correctly predicted the score for development set 1 work and rest periods on 61% of occasions (kappa = 0.47). The whole record score for development set 2 records, after weighting for definite or definitely no occupational effect, correlated with the visual score (correlation coefficient 0.86). Comparison with gold standard set 1 identified a cut off which proved to have a sensitivity of 75% and a specificity of 94% for an independent diagnosis of occupational asthma when applied to gold standard set 2. CONCLUSIONS: These results suggest that the sensitivity and specificity of analysing PEF records for occupational asthma using OASYS-2 approaches that of visual analysis, but it should be absolutely reproducible. The performance of OASYS-2 is more specific and approaches the sensitivity of other statistical methods of analysis. The evaluation of a large number of PEF records from workers exposed to different sensitising agents suggests that these results should be robust and should be repeatable in clinical practice.

Asthma↗

Can one induce premenstrual symptomatology in women with prior hysterectomy and bilateral oophorectomy?

Nine women who had undergone hysterectomy and oophorectomy and who previously suffered from severe premenstrual syndrome (PMS) were given estrogen and progesterone in a naturalistic single-blind paradigm. The 13-item Beck Depression Inventory, Spielberger State Anxiety Inventory, Menstrual Distress Questionnaire and the Daily Ratings Form of the Premenstrual Assessment Form were all given daily. Estradiol and progesterone concentrations were estimated. When results from all subjects were considered together, these measures were not correlated with hormonal status. However, individual subjects showed correlations between some symptom scores and serum progesterone concentrations. We conclude that women diagnosed as having PMS do not respond in a uniform fashion to ovarian hormones. Further quantitative studies are needed to relate these individual differences to the syndrome of PMS.

Drug Therapy, Combination↗

Serologic evidence of Chlamydia trachomatis infection and risk of preterm birth.

OBJECTIVE: To determine whether serologic evidence of Chlamydia trachomatis during pregnancy is a risk factor for preterm delivery (before 37 weeks' gestation). DESIGN: Chart review. SETTING: Antenatal clinics associated with a teaching hospital. PATIENTS: A group of 103 unselected consecutive patients presenting for routine prenatal care. OUTCOME MEASURES: Pregnancy outcome and C. trachomatis serologic status. RESULTS: A total of 21 women (20%) were found to be seropositive for IgG antibodies to C. trachomatis. They were similar to the seronegative women with respect to maternal age, parity, history of preterm birth, obstetric or medical problems, smoking status, history of drug abuse, educational status and psychosocial stressors. The seropositive women were significantly more likely than the seronegative women to have a preterm birth (24% [5/21] v. 7% [6/82]i p = 0.029, odds ratio 3.96, 95% confidence interval 1.08 to 14.57), an infant with a lower mean gestational age at birth (262 [standard deviation (SD) 19] days v. 273 [SD 15] days; p = 0.0052) and an infant with a lower mean birth weight (3125 [SD 692] g v. 3473 [SD 696] g; p = 0.0434). The positive predictive value of a seropositive result for preterm birth was 31% (5/16); the negative predictive value of a seronegative result for preterm birth was 8% (6/76). CONCLUSION: Women with serologic evidence of C. trachomatis may be at risk for preterm birth. Further study is required to determine whether serologic testing for C. trachomatis should be a routine part of prenatal care.

Adult↗

Predicting mental health problems in general practitioners.

A total of 704 general practitioners completed questionnaires enquiring about mental health problems (response rate = 82.0%). Excessive anxiety was reported by 31.1%, troublesome depression by 13.4%, exhaustion or stress (on three or more weekdays) by 60.7%, and sleep difficulties by 47.6%. General practitioners aged 40-49 years old were most likely to report anxiety, exhaustion or stress, sexual and sleep difficulties. Retired doctors reported mental health problems markedly less often. Predictive factors for anxiety were depression, one or more nights on-call per week, and exhaustion or stress; predictive factors for depression were anxiety, and exhaustion or stress; predictive factors for exhaustion or stress were anxiety, depression, no hobbies, paperwork on three or more evenings per week, and sleep difficulties. Gender, country of origin, being single-handed, excessive alcohol consumption, and having no coping methods were not predictive factors for mental health problems.

Adult↗

Chlorthalidone attenuates the reduction in total cholesterol and small, dense LDL cholesterol subclass associated with weight loss.

Thiazide diuretics are known to raise total and LDL cholesterol. To assess whether chlorthalidone affected levels of putatively atherogenic small, dense LDL (LDL 3), we conducted a 12 week double blind randomized, placebo controlled clinical trial in 34 nonsmoking men aged 35 to 57 years with mild hypertension (DBP 90 to 104 mm Hg). Our a priori hypothesis that chlorthalidone raised LDL 3 levels was not confirmed. However, the fall in LDL 3 (P = .03) and total cholesterol (P = .08) associated with weight loss was attenuated by chlorthalidone. Since weight loss is commonly prescribed during the clinical management of hypertensives with concomitant hypercholesterolemia, consideration should be given to the attenuating effect of chlorthalidone on cholesterol reduction in the management of these patients.

Adult↗

Haemophilus influenzae infection of human respiratory mucosa in low concentrations of antibiotics.

We examined the effects of 0.25 and 0.5 minimal inhibitory concentrations (MIC) of amoxicillin, loracarbef, and ciprofloxacin on the interaction of a clinical isolate of nontypable Haemophilus influenzae (NTHi) with human adenoid organ culture. Adenoid tissue was embedded in agar so that only the mucosal surface was exposed. Minimum essential medium containing NTHi with or without antibiotics was added to the organ culture and incubated with 5% CO2 at 37 degrees C for 24 h. The organ cultures (n = 6) were assessed for several parameters by light microscopy (LM) and transmission electron microscopy (TEM). Bacterial viable counts after 24 h were not significantly different in all organ cultures. Compared with uninfected controls at 24 h, infection with NTHi caused significant (p < 0.05) damage to epithelium as assessed by LM: reduced ciliary beat frequency (CBF), disruption of epithelium integrity, and reduced number of ciliated sites. TEM showed extrusion of cells from the epithelial surface, loss of cilia from ciliated cells, cytoplasmic blebbing, and mitochondrial damage. In the presence of 0.25 and 0.5 MIC of all three antibiotics, the mucosal damage was significantly less (p < 0.05). We conclude that in the presence of sub-MIC levels of amoxicillin, loracarbef, and ciprofloxacin, NTHi infection causes less functional (CBF) and structural damage.

Adenoids↗

Comparison of the health and lifestyle of general practitioners and teachers.

A total of 704 general practitioners and 588 teachers responded to a questionnaire about their health and lifestyle in 1991 (response rates 82% and 87%, respectively). The results for lifestyle measures were compared with those of a similar questionnaire completed by about half of each group two years before--there were no changes in the answers of either occupational group in the intervening two years. In 1991, 9% of general practitioners and 15% of teachers drank 22 units of alcohol per week or more; 13% of general practitioners and 23% of teachers reported troublesome depression and 31% of doctors and 37% of teachers excessive anxiety in the preceding 12 months. Teachers had more sickness absence, and significantly more experienced a need for daily alcohol and binge eating, and reported sleep difficulties, depression and anxiety than general practitioners. Self-medication among general practitioners was common and overall accounted for 83% of the medication taken by doctors. A follow-up survey of non-respondents found that only 11% of general practitioners and 11% of teachers indicated they had a health problem they wished to conceal or that they felt the questions were too intimate. General practitioners' lifestyle habits are better than those of teachers and published figures for the general population. The frequency of reported mental health problems in both professions gives cause for concern.

Adult↗

Work patterns of general practitioners before and after the introduction of the 1990 contract.

A questionnaire survey was undertaken to examine the work patterns of general practitioners before and after the introduction of the 1990 contract. A total of 408 and 697 general practitioners responded to the questionnaire in 1989 and 1991, respectively (response rates of 47% and 82%). In 1991 general practitioners reported spending significantly more evenings on paperwork than in 1989 and significantly more reported being exhausted or stressed at the end of five or more working days. General practitioners were significantly less likely to work four or more sessions per week outside the practice in 1991 than in 1989. There was no difference between 1989 and 1991 in the number of surgeries carried out per week or the number of nights spent on call in a month. In 1991 there was no correlation between the Jarman index allocated to a practice principal and the numbers of surgeries per week, sessions worked outside the practice per week, nights on call per month, weekdays exhausted or stressed, or evenings each week spent on paperwork. Older doctors in 1991 were significantly more likely to work 12 or more nights on call per month, to spend more time doing paperwork in the evenings and more likely to report exhaustion than younger doctors. Women doctors in 1991 were significantly more likely to report doing 10 or more surgeries per week than their men colleagues. It has become more common for general practitioners to complete paperwork at home and report exhaustion or stress since the introduction of the 1990 contract.

Adult↗

Reference intervals for 21 clinical chemistry analytes in arterial and venous umbilical cord blood.

Reference intervals were determined for 21 clinical chemistry analytes in umbilical cord arterial and venous blood from healthy term infants. Nonparametric analysis (rank number) was used to determine the central 95% reference interval. No significant differences were observed between male and female infants. Reference intervals for glucose, urea, creatinine, urate, phosphate, calcium, albumin, total protein, cholesterol, triglycerides, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, creatine kinase, lactate dehydrogenase, gamma-glutamyltransferase, and magnesium all were significantly different from adult values.

Blood Chemical Analysis↗

Survey of outpatient sputum cytology: influence of written instructions on sample quality and who benefits from investigation.

OBJECTIVES: To evaluated quality of outpatient sputum cytology and whether written instructions to patients improve sample quality and to identify variables that predict satisfactory samples. DESIGN: Prospective randomised study. SETTING: Outpatient department of a district general hospital. PATIENTS: 224 patients recruited over 18 months whenever their clinicians requested sputum cytology, randomized to receive oral or oral and written advice. INTERVENTIONS: Oral advice from nurse on producing a sputum sample (114 patients); oral advice plus written instructions (110). MAIN MEASURES: Percentages of satisfactory sputum samples and of patients who produced more than one satisfactory sample; clinical or radiological features identified from subsequent review of patients' notes and radiographs associated with satisfactory samples; final diagnosis of bronchial cancer. RESULTS: 588 sputum samples were requested and 477 received. Patients in the group receiving additional written instructions produced 75(34%) satisfactory samples and 43(39%) of them one or more sets of satisfactory samples. Corresponding figures for the group receiving only oral advice (80(31%) and 46(40%) respectively)were not significantly different. Logistic regression showed that radiological evidence of collapse or consolidation (p<0.01) and hilar mass (p<0.05) were significant predictors of the production of satisfactory samples. Sputum cytology confirmed the diagnosis in only 9(17%) patients with bronchial carcinoma. CONCLUSIONS: The quality of outpatients' sputum samples was poor and was not improved by written instructions. Sputum cytology should be limited to patients with probable bronchial cancer unsuitable for surgery. IMPLICATIONS: Collection of samples and requests for sputum cytology should be reviewed in other hospitals.

Bronchial Neoplasms↗