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Biomedical subjects

C D Wolfe

Publications and source records attributed to C D Wolfe.

At least 73 records · Page 4Linked to original sources

Corticotrophin-releasing hormone-binding protein in human fetal plasma.

During pregnancy maternal plasma corticotrophin-releasing hormone (CRH) levels rise 1000-fold whilst fetal plasma levels are often 100-fold higher than the concentrations seen in normal non-pregnant human plasma. Despite these high CRH levels neither the maternal nor fetal pituitary releases excessive amounts of ACTH. A specific CRH-binding protein (CRHBP) exists in the maternal circulation which is able to bind and inactivate the ACTH releasing activity of CRH. In this study we have used a specific CRHBP radioimmunoassay to determine the level of CRHBP in fetal and maternal plasma samples. Fetal samples were collected by cordocentesis between 20 and 33 weeks gestation and matched maternal samples were taken by venepuncture at the same time. In a second study, plasma samples were collected from 8 women at fortnightly intervals from week 20 to term, at labour and post-partum. A fetal sample, taken from the umbilical vein, was collected immediately post-delivery. The mean maternal CRHBP concentration for the samples collected between 20 and 33 weeks (n = 23) was 8.12 nmol/l and the fetal level was 8.62 nmol/l. Data from the second study showed that at term the maternal CRHBP concentration decreased significantly (P < 0.025) to 6.32 nmol/l. The fetal CRHBP level also decreased significantly (P < 0.001) at term to a level of 5.84 nmol/l. The CRHBP in both fetal and maternal plasma was shown to be functional by 125I-CRH binding and gel permeation chromatography. The capacity of maternal and fetal plasma to bind 125I-CRH decreased at term in agreement with the quantitation of plasma CRHBP by radioimmunoassay.

Carrier Proteins↗

Variations in the incidence, management and outcome of stroke in residents under the age of 75 in two health districts of southern England.

BACKGROUND: The aim of the study was to determine the incidence, outcome and health service resources consumed by stroke care in defined populations. METHODS: Patients under the age of 75 experiencing their first stroke between August 1989 and July 1991 were assessed at the onset, and at three and 12 months after their stroke. The settings were West Lambeth (WL) and Tunbridge Wells (TW) health authorities in southern England. The main outcome measures used were: age- and sex-specific incidence rates, hospital admission rates, length of stay and use of rehabilitation services. Functional disability was assessed using the Barthel scale. RESULTS: Four hundred and fifty-six strokes were registered. The annual incidence rates/1000 population aged under 75 years old [with 95% confidence interval (CI)] were 0.77 (0.67-0.87) in WL and 0.66 (0.58-0.75) in TW. The age- and sex-standardized incidence ratios were significantly higher in WL (126; 95% CI 110-144) than in TW (84%; 95% CI 74-95) (p < 0.001). There were independent associations of incidence with age group (p < 0.001), sex (p < 0.001) and ethnic group (p < 0.001). One year case-fatality was 36% (80/225). At one year, 11% (14) of surviving patients were moderately to severely disabled and 23% (28) mildly disabled. Seventy-one percent (326) of patients were admitted to hospital and the average health service cost per case was pound 3800 in WL and pound 2650 in TW, 93% of the cost being for in-patient care. CONCLUSION: The study has demonstrated a significantly increased incidence of stroke in an inner-city district compared with a district in rural southern England. It has also established ethnic group as a significant independent risk factor for stroke in the United Kingdom. The cost of care to the health services is considerable, and largely reflects nursing costs in hospital rather than effective treatment packages for stroke.

Adult↗

The attitudes of women and feasibility of screening for ovarian and endometrial cancers in inner city practices.

The study aimed to assess the attitudes of women and the feasibility of screening for ovarian and endometrial cancers using vaginal ultrasound should screening prove to be effective. A total of 4873 women aged 45-74 were registered with 9 general practices in inner London. Of these, 1469 (30%) were ineligible for screening for ovarian and endometrial cancers as they proved to be the wrong age, had moved, or had undergone a total abdominal hysterectomy and bilateral salpingo-oophorectomy. The proportion of ineligible women varied between practices (24-39%) (P < 0.001). The adjusted response rate to a questionnaire on attitudes to ovarian and endometrial screening was 56% (1833/3360). Of the women, 1395 (76%) were willing to be screened with a significant difference between age groups, those over 65, at increased risk, being less willing (P < 0.001). Non-caucasians were more willing to be screened (P < 0.001) but educational attainment did not influence attitude to screening. Those women who were not very worried about vaginal instrumentation were more willing to be screened than those who were very worried (P < 0.001). The uptake rate for ovarian and endometrial screening, which is currently of unproven value, was 43% (1480/3360) with a significant difference between practices (33-49%) (P < 0.01).

Aged↗

Predicting the disability of first-time stroke sufferers at 1 year. 12-month follow-up of a population-based cohort in southeast England.

BACKGROUND AND PURPOSE: The purpose of this study was to predict the functional outcome at 1 year of first-time stroke patients aged younger than 75 years in relation to the severity of stroke and demographic characteristics. METHODS: Population registers in three districts of southeast England were established in August 1989, with notification by stroke registry field-workers, general practitioners, and rehabilitation practitioners. Assessments were made using the Barthel index for activities of daily living at the time of maximum impairment and at 3 and 12 months after the stroke. RESULTS: Of 639 registered stroke patients, 392 without previous disability survived and were assessed for disability at 3 months, of whom 34 (9%) were severely disabled and 60 (15%) moderately disabled. Initial incontinence was the best single predictor of disability with a sensitivity of 60% and a specificity of 78%. Two hundred twenty-five patients (35%) were eligible for 12-month follow-up; 11% had moderate or severe disability, for which initial incontinence was the best predictor. CONCLUSIONS: There is no evidence from this study of an association between demographic characteristics and the disability status of stroke survivors in the medium term. Multivariable predictors of disability had little advantage over incontinence within 24 hours of the stroke. The estimates of the prevalence of disability from this large population-based study are relevant when assessing the medium-term needs of stroke patients.

Activities of Daily Living↗

Does the incidence, severity, or case fatality of stroke vary in southern England?

STUDY OBJECTIVES: To determine differences in incidence and case fatality of stroke in district health authorities with differing standardised mortality ratios (SMR) for stroke in residents aged under 65 years in whom death from stroke is considered 'avoidable'. DESIGN: Registration of first ever strokes in three district health authorities. Patients were assessed and followed up over one year by one of three observers. SETTING: West Lambeth, Lewisham and North Southwark, and Tunbridge Wells District Health Authorities in south east England. PARTICIPANTS: Patients under the age of 75 years having a first ever in a lifetime stroke between 15 August 1989 and 14 August 1990. MEASUREMENTS AND MAIN RESULTS: Age specific incidence rates and survival time from stroke to death. Severity was assessed in terms of the level of consciousness and the presence of speech, urinary, and motor impairment within the first 24 hours of the stroke. Altogether 386 strokes were registered. There was a significant difference in the incidence rate between district health authorities in those aged under 65 (p < 0.01). The overall case fatality was 26% at three weeks with no significant difference between the districts. Poor survival was associated jointly with increased age and with coma, incontinence, and swallowing impairment in the first 24 hours after a stroke. CONCLUSIONS: The SMRs for stroke in those aged under 65 in these three health districts reflect the incidence of stroke. Case fatality at three weeks does not vary between these districts and consequently would not be a sensitive indicator of the quality of care. This also suggests that differences in services between the districts did not lead to changes in prognosis. In districts with high SMRs for stroke there is a need for further study and reduction of risk factors, thereby reducing the incidence and burden of stroke locally. This study provides a framework for assessing the needs for stroke prevention and treatment in both rural and urban areas without an elaborate protocol and detailed neurological assessment.

Adult↗

Patterns of acute stroke care in three districts of southern England.

OBJECTIVE: To quantify the use of health care services by acutely ill stroke patients in three district health authorities. DESIGN: A follow up study of all patients recorded in population based registers who had a first ever stroke in three district health authorities, with assessment following the onset and three months after the stroke. SETTING: West Lambeth, Lewisham and North Southwark, and Tunbridge Wells District Health Authorities in south east England. SUBJECTS: All first time stroke patients under the age of 75 years who presented between 15 August 1989 and 14 August 1990. MEASUREMENTS AND MAIN RESULTS: Hospital admission rates, rates of use of rehabilitation services, and contact with medical practitioners together with assessment of disability and handicap were determined. A total of 386 strokes were registered. Seventy eight per cent were treated in hospital and younger and incontinent patients were significantly more likely to be admitted. The median stay was 21 days. Patients in West Lambeth, those paralysed, and those who stayed longer in hospital were more likely to receive physiotherapy. Altogether 265 patients were followed up, 117 having died within three months of the stroke. During the three months, 150 (57%) had seen a hospital physician and 181 (69%) their general practitioner, but 18 (7%) had seen neither. Sixty seven (26%) patients were moderately or severely disabled. Twenty seven per cent of inpatients had received no inpatient physiotherapy and 67% of all patients no outpatient physiotherapy during the three months. CONCLUSIONS: The hospital admission rates were high, with long lengths of stay. There were significant differences in the amount of rehabilitation received in each district. This was low overall, especially for those not admitted to hospital. As expected, patients admitted for long periods were the most likely to receive therapy. Before district policies for admission and management of stroke patients can be drawn up, increased knowledge of which aspects of stroke management are effective is needed. Policies should aim to provide planned, coordinated care between hospital and the community. It is striking that many patients received no form of rehabilitation therapy.

Acute Disease↗

Corticotropin releasing hormone-binding protein (CRH-BP): plasma levels decrease during the third trimester of normal human pregnancy.

In pregnancy, maternal plasma corticotropin releasing hormone (CRH) concentrations rise substantially in the third trimester and fall rapidly post-partum. A binding protein (BP) specific for CRH exists in the human circulation which inactivates CRH, thus possibly explaining why maternal ACTH does not rise outside normal limits throughout gestation. We here describe the measurement of CRH-BP directly in plasma during human pregnancy using a radioimmunoassay that is not affected by the presence of the high plasma levels of CRH that occur at this time. In 119 healthy non-pregnant individuals, mean CRH-BP levels were 4.46 nmol/L +/- 1.0 (SD), with a wide range of 1.81-7.24 nmol/L. Plasma CRH-BP in 34 pregnant women randomly sampled during the first and second trimesters also averaged 4.46 nmol/L +/- 1.54, with individual values ranging from 1.59-7.51 nmol/L and there was no correlation of CRH-BP levels with gestational age. In a group of 14 women sampled sequentially throughout the third trimester, plasma CRH-BP averaged 4.56 nmol/L +/- 1.70 at 30-35 weeks gestation and fell dramatically to 1.84 nmol/L +/- 0.43 at weeks 38-40 (P < 0.001). The post partum recovery in CRH-BP levels occurred within 48 hours of delivery. These results indicate that there is an increase in the availability of free, potentially bioactive CRH at term to stimulate the release of ACTH from the maternal pituitary and/or to act at a peripheral, non-pituitary CRH receptor(s).

Adult↗

Plasma measurements of corticotrophin-releasing hormone-binding protein in normal and abnormal human pregnancy.

Using corticotrophin-releasing hormone-binding protein (CRHBP) purified from human plasma and a 25 amino acid peptide corresponding to the C-terminus of CRHBP we have been able to produce rabbit polyclonal antisera specific for CRHBP. This has allowed the development of a radioimmunoassay which is able to detect CRHBP specifically in human plasma regardless of the presence of endogenous CRH. We have used this assay to estimate the level of CRHBP in non-pregnant human plasma to be approximately 20 nmol/l with a range of 9.1-40.6 nmol/l. We have also examined sequential plasma samples taken from 84 normal pregnant women at fortnightly intervals from 16 weeks gestation through to term. Four women were also sampled during labour and the first week postpartum. The median plasma level of CRHBP at week 16 of normal pregnancy was 21.59 nmol/l, levels rose slightly during the early part of the third trimester (26.76 nmol/l at week 30, (P < 0.01) and fell markedly towards term (19.72 nmol/l, P < 0.01) with only 8.70 nmol/l at labour. CRHBP levels returned to normal non-pregnant levels within 48 h of parturition suggesting a role for the fetoplacental unit in CRHBP production. In eight pregnancies complicated by diabetes, CRHBP levels at each gestational age were similar to those recorded for normal pregnancy. However, in pregnancies complicated by pre-term labour (n = 9) and pre-eclampsia (n = 7), plasma CRHBP levels were significantly reduced (P < 0.01).

Carrier Proteins↗

Is stroke mortality on the decline in England?

This paper challenges the assumption that mortality from stroke will remain constant or decline over the next few decades. A decline in stroke mortality could be brought about by changes in factors acting close to the time of death (period effect) or by risk factors determined by the generation into which a person is born (cohort effect). Age-specific death rates for stroke (1931-1985) in England and Wales were analyzed to estimate the influence of these different effects. There were significant effects for age, period, and cohort on mortality from stroke with significantly different age and period effects in each sex. The effect of age was linear, with an increasing mortality with age in both sexes. Cohort analysis demonstrated a deceleration away from the previous trend in the mortality rates associated with birth cohorts born after 1880, followed by an acceleration in the trend of mortality rates in cohorts born after 1910. These relative increases in risk for cohorts born after 1910 were offset by a deceleration in mortality associated with periods from around 1951-1954. Since cohort effects are likely to be associated with a lifetime increase in risk of stroke mortality, it is difficult to predict the extent of any long-term fall in stroke incidence.

Adult↗

Assessment of scales of disability and handicap for stroke patients.

BACKGROUND AND PURPOSE: The purpose of the study is to compare the reliability of the Barthel activities of daily living score, which assesses disability, with the Rankin scale, which assesses handicap, and to determine their mutual agreement. METHODS: Fifty patients with stroke of varying severity were identified by a community-based stroke register and interviewed by two of three research nurses on two occasions that were 2-3 weeks apart. RESULTS: There was no evidence of a systematic difference between the first and second measurements. Repeatability was assessed using a kappa statistic with quadratic disagreement weights (kappa w) to take account of extreme differences. This measure was very good for both Barthel (kappa w = 0.98) and Rankin (kappa w = 0.95) scales. There was also excellent agreement between raters for the Barthel scale (kappa w greater than or equal to 0.88), but some indication of disagreement (kappa w = 0.75) between raters for the Rankin scale. Analysis of variance confirmed these findings. A conversion from the Barthel to the Rankin scale can be derived by assigning the most common Rankin score for the subjects with a given Barthel score, producing a kappa w of 0.91 for agreement. CONCLUSIONS: The Barthel scale is a more reliable and less subjective scale for assessing disability, from which a Rankin handicap score can then be derived to enable those managing stroke patients to assess aspects of handicap as well as disability.

Activities of Daily Living↗

Consumers' views of the maternity services: implications for change and quality assurance.

The feasibility and usefulness of consumer surveys for quality assurance and planning maternity services were assessed in a postal survey of 1807 women in four health districts representing a range of social and demographic characteristics. A response rate of 79 per cent was achieved. Scope was identified for some reduction in length of stay: 43 per cent of postnatal women wished for a shorter stay than they have actually experienced. The Domino system and a 1-2 days stay were the preferred options (25 and 24 per cent respectively). Six per cent of postnatal women would have preferred a longer stay than experienced and consisted mainly of women with birth complications including caesarean deliveries, women with lack of help at home and Afro-Caribbeans. Schemes to increase continuity of care and make the delivery suite more home-like would be favoured by a large proportion of women. Sixty-five per cent of women regarded continuity of midwifery care and familiarity with the delivering midwife as important. Seventy-five per cent considered a home-like environment in the delivery suite as important, and gave specific suggestions of how this might be achieved. The results show that consumers' surveys are feasible, with a good response rate and range of views expressed by the study population. They can assist in monitoring quality and provide guidance for planning at local and regional levels.

Adult↗