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Biomedical subjects

I Harvey

Publications and source records attributed to I Harvey.

At least 127 records · Page 7Linked to original sources

Formation in vivo, purification and crystallization of a complex of the gamma and epsilon subunits of the F0F1-ATPase of Escherichia coli.

A complex comprising the epsilon subunit of Escherichia coli F1-ATPase (ECF1-ATPase) and a glutathione-S-transferase gamma subunit (of ECF1-ATPase) fusion protein was formed in vivo and purified from cell extracts by binding to glutathione-agarose beads. The glutathione-S-transferase was released from the complex by digestion with thrombin and the gamma/epsilon complex purified by cation-exchange chromatography. Crystals of the complex were grown by vapour diffusion using PEG8000 as precipitant. The crystals are orthorhombic, space-group P2(1)2(1)2 with a = 161.9 A, b = 44.1 A and c = 63.4 A. The volume of the asymmetric unit is consistent with the presence of a complex of one gamma subunit and one epsilon subunit.

Chromatography, Ion Exchange↗

Crystallization and preliminary crystallographic characterization of the copper-containing amine oxidase from pea seedlings.

The copper-containing amine oxidase from pea seedlings has been crystallized using lithium sulfate as precipitant at pH 5.2. The unit cell is orthorhombic, space group P2(1)2(1)2(1), with dimensions a = 89.3 A, b = 113.4 A, c = 199.0 A. The mass of the asymmetric unit is 131(+/- 13) kDa, consistent with independent evidence that the molecule has two approximately 66 kDa subunits. The crystals diffract to 2.5 A in a synchrotron X-ray beam.

Amine Oxidase (Copper-Containing)↗

Reduction of cortical volume in schizophrenia on magnetic resonance imaging.

The MRI scans of 48 schizophrenic patients, fulfilling RDC criteria, were compared to those of 34 healthy controls matched for age, ethnicity and parental social class. The volume of the frontal and anterior parietal lobes was significantly reduced in the schizophrenic group as a result of a selective decrease in cortical volume, with a corresponding increase in the volume of sulcal fluid. Reduction in the volume of the temporal grey matter was more marked on the right, but was not in excess of the loss of volume observed in other areas of the cortex. MRI abnormalities correlated poorly with clinical parameters, although both unemployment and poor pre-morbid adjustment predicted reduced cerebral volume and increased sulcal volume. These results question whether the medial temporal lobes are the only site of structural pathology in schizophrenia.

Adult↗

Enhancing appropriateness of acute bed use: role of the patient hotel.

OBJECTIVE: This study aimed to assess the appropriateness of bed use by determining patients' suitability for patient hotel accommodation and day treatment and by examining timeliness of discharge, and to assess patient and staff views about patient hotels. DESIGN: Patients were assessed by a doctor and nurse in terms of an agreed case definition for patient hotel use. Patient suitability was validated and patient acceptability measured by semi-structured interviews with a random sample of patients judged suitable for hotel accommodation. All senior medical and nursing staff completed a further questionnaire. SETTING: The study took place at University Hospital of Wales, Cardiff (856 beds), and all specialties, except intensive care wards, participated. SUBJECTS: Patients occupying a total of 3972 bed days, accumulated over seven randomly chosen census days, were studied. RESULTS: Data were available for 88% of eligible inpatients. Ten per cent (405 of 3972) of patients were judged suitable for a patient hotel. Specialties indicating major use were obstetrics and gynaecology, general surgery, and general and geriatric medicine. Sixty three per cent (254 of 405) of these subjects required low level investigation or treatment. Preoperative and postoperative and antenatal patients were often suitable also. Three per cent (119 of 3972, 95% confidence interval 2.5, 3.6%) of inpatients were judged suitable for day treatment/investigation. Seventy nine per cent (291 of 369) of patients suitable for discharge were discharged on the same or the next day. The patient hotel idea was acceptable to 58 of 68 (85%) randomly selected patients and to 84 of 93 (90%) staff. CONCLUSIONS: With allowance for non-response, our study indicates that a general hospital of this size generates the need (inpatients, relatives, and ward attenders) for a mean of 72 patient hotel beds. There is also residual scope for increasing day treatment/investigation and for releasing beds by speeding discharge. The patient hotel idea is highly acceptable to both patients and staff and should be widely considered as a means of making patient care more efficient.

Adolescent↗

Can a surgical treatment centre reduce waiting lists? Results of a natural experiment.

STUDY OBJECTIVE: To determine the effectiveness of the Welsh general surgery (hernia and varicose veins) treatment centre established as part of the NHS reforms, in terms of its impact upon throughput and waiting lists. DESIGN: This was a natural experiment with two control groups--other surgical specialties without treatment centre provision, and general surgery in districts that made only minor use of the facility. SETTING: General Surgery Treatment Centre, Bridgend General Hospital. SUBJECTS: All patients referred between 1 April 1990 and 31 March 1991. MEASUREMENTS AND MAIN RESULTS: Main outcome measures were throughput for hernia and varicose vein operations, non-urgent inpatient waiting list lengths before and after the opening of the centre and patient satisfaction. Altogether 1097 patients were referred during the year. Of these, 160 (15%) did not attend outpatient assessment and 79 (8%) of those who did were unsuitable for surgery. A total of 750 operations were performed--448 (60%) for varicose veins and 261 (35%) hernia repairs. Among the residents of the four main districts using the centre (with valid data available), there was a significant increase in the total number of varicose vein operations performed but no significant increase in hernia repairs. In the six districts that made major use of the centre, general surgery waiting lists for non-urgent cases fell significantly (p < 0.0001) while those for ear, nose, and throat showed no significant change and gynaecology lists lengthened significantly (p < 0.0001). In the three districts that made minor use of the centre general surgery waiting lists showed no change. CONCLUSIONS: Relations between inputs and waiting lists are often unpredictable, but after controlling for confounding trends there is sound evidence that such a centre provides an acceptable and effective approach to the waiting list problem.

Age Factors↗

'Inside-out', back-to-front: a model for clinical population genetic screening.

Developments in DNA technology have resulted in a dramatic increase in the number of genes identified. With the localisation of a gene it is possible to devise procedures suitable for mass carrier screening programmes. Until recently mass carrier screening was only possible for a limited number of disorders, for example, Tay-Sachs disease and haemoglobinopathies. Counselling possible carriers was based on estimations of risk. The momentum towards mass carrier screening is likely to be increased by gene therapy. Carrier screening for cystic fibrosis alone will have dramatic implications for genetic service provision as 4 to 5% of the UK population carry the CF gene. The potential for genetic screening of multifactorial diseases, for example, cancers, should also be considered. The existing organisation of genetic services is likely to be inadequate. A new specialty of clinical population genetics is required. A model is proposed of clinical population genetic screening programmes, organised under a 'common umbrella' led by a public health physician, while screening and follow up will remain the responsibility of the appropriate clinician.

Female↗

Volume measurement of multiple sclerosis lesions with magnetic resonance images. A preliminary study.

The ability to visualise multiple sclerosis lesions in vivo with magnetic resonance imaging suggests an important role in monitoring the course of the disease. In order to help the long-term assessment of prospective treatments, a semi-automated technique for measuring lesion volume has been developed to provide a quantitative index of disease progression. Results are presented from a preliminary study with a single patient and compared to measurements taken from lesion outlines traced by a neuroradiologist, two neurologists and a technician. The semi-automated technique achieved a precision of 6% compared to a range of 12-33% for the manual tracing method. It also reduced the human interaction time from at least 60 min to 15 min.

Brain↗

Compensation for harm: the implications for medical research.

The rising incidence of medical litigation in the 1980's led to a relatively minor modification in January 1990 of the United Kingdom's negligence-based system of medical compensation, as a result of which employing Health Authorities now accept full vicarious liability for the negligent (but not other) actions of employed clinicians (Crown indemnity). During the same period, by contrast, bodies such as the Royal College of Physicians have strongly influenced locally established Research Ethics Committees towards favouring no-fault compensation for harm resulting from medical research. The discordance between these two approaches to compensation has caused anxiety during the last year. There has been particular concern about the possible discouragement of non-commercially sponsored research. Hitherto however, no data has been available to inform this discussion. This paper reports the findings of a questionnaire survey of all research ethics committees in the United Kingdom (64% response rate), which indicates that 61% of committees require no-fault compensation for at least some projects and that 33% of these committees have rejected projects solely or mainly due to the lack of such provision. Rejection is significantly more common in Health Districts which contain teaching hospitals. Our critical analysis of the arguments advanced in favour of no-fault provision for research subjects suggests that they do not place adequate emphasis upon respect for the autonomy of individuals. We consider that it is in general more consistent with such respect fully to inform research subjects of the available compensation arrangements, rather than for ethics committees to make no-fault compensation a general requirement before ethical approval is given.

Compensation and Redress↗

Auditing and improving notification and chemoprophylaxis in bacterial meningitis.

STUDY OBJECTIVE: The aim was to audit, against agreed standards, the control of bacterial meningitis, in particular completeness of notification and appropriateness of distribution of chemoprophylaxis to contacts; and to implement appropriate changes and monitor their impact. DESIGN: The first phase involved determination, for the years 1983 and 1984, of completeness of notification by comparison with a comprehensive case register. Information about chemoprophylaxis was obtained from case notes, questionnaires to general practitioners and other records. The second phase involved introducing a programme of clinician education in the hospital with the poorest observed notification performance and re-examining performance during 1988. Districtwide education regarding chemoprophylaxis was undertaken and the situation re-examined in 1988. SETTING: The study took place in Mid Glamorgan Health Authority (population 536,000), with four acute hospitals. POPULATION: Consisted of all the residents of Mid Glamorgan Health Authority. MAIN RESULTS: During the first phase of the audit only 28 out of 79 cases of bacterial meningitis were notified (35%). Performance in one hospital was significantly worse than in the other three. Chemoprophylaxis was distributed to 20 out of 26 (77%) cases of meningococcal meningitis but inappropriate drugs were used in four cases and prophylaxis was distributed more widely than is recommended in 10 cases. In the phase 2 re-examination, a significant improvement in notification was observed in the hospital where special measures were taken, with no change in a "control" hospital. Chemoprophylaxis improved throughout the District, although rifampicin continued to be distributed too widely. CONCLUSIONS: As a result of this audit, measurable improvements in both infectious disease notification and chemoprophylaxis practice were obtained by the education of clinicians. The study provides a good example of a completed audit cycle in public health medicine.

Communicable Disease Control↗

Psychophysiological investigations of patients with unilateral symptoms in the hyperventilation syndrome.

Anxiety states sometimes lead to hyperventilation (HV) which may, in turn, give rise to a variety of physical symptoms. One way in which HV may present is with unilateral somatosensory symptoms, often left-sided. We report nine such cases. The mechanisms of lateralisation was examined using EEG and bilateral somatosensory evoked potentials which were carried out before and after HV. No difference in conduction velocity was found between affected and unaffected arms, but non-specific abnormalities were frequently noted in the EEGs. The results support the role of a central rather than a peripheral mechanism in the production of unilateral symptoms in HV.

Adult↗

Potential availability of cadaver organs for transplantation.

OBJECTIVE: To determine the potential number of cadaver kidney donors by applying defined donor criteria to people dying in hospital. DESIGN: Prospective study of all deaths occurring in 21 hospitals from 1 September 1988 to 31 August 1989. Questionnaires were administered to medical and nursing staff and families of potential donors aged 1-69. SETTING: Acute care hospitals in Gwent, South Glamorgan, Mid Glamorgan, West Glamorgan, Pembrokeshire, and East Dyfed health authorities, serving a population of 2.2 million. MAIN OUTCOME MEASURES: Cause of death, age, ventilation at time of death, diagnosis of brain death, and consideration of consent. RESULTS: Adequate data were available for 9840 of 10,095 hospital deaths (97.5% coverage). 188 patients aged 0-69 were identified as potential organ donors (widest definition), and of these 108 died without being ventilated at the time of death. Tests of brain stem death were formally completed in 57 cases, and organ donation was considered by the families of 47 of these potential donors. 26 patients became organ donors. Patients aged 50-69 with stroke were less likely to be ventilated than those aged less than or equal to 49 (21/96 v 24/34). Families of potential donors aged 20-39 were least likely to give permission. CONCLUSIONS: The supply of donor organs (specifically kidneys) could be increased by altering the management of patients aged 50-69 dying of severe cerebrovascular disease in general medical wards, in particular by increasing the proportion ventilated. The ethics of elective ventilation for the purposes of organ donation require discussion.

Adolescent↗

The effect of chlorpromazine and methylprednisolone on NMR relaxation times in the normal cat brain.

This small experimental study describes the effects on the NMR relaxation times in normal cat brain of a 5-day course of high dose methylprednisolone and, separately, a 1-month course of standard dose daily chlorpromazine. Methylprednisolone had no influence on T1 or T2 in these tissues, but chlorpromazine produced a transient fall of T1 of thalamus, and rise in T2 of white matter: both normalize after 4 weeks. The mechanism of these changes is unknown. It is concluded that these drugs should not interfere with the quantitative MRI monitoring of brain abnormalities in patients receiving them, although the unlikely occurrence of longer term effects of chlorpromazine has not been excluded.

Animals↗