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Biomedical subjects

A Hopkins

Publications and source records attributed to A Hopkins.

At least 19 recordsLinked to original sources

Field performance of transgenic tall fescue (Festuca arundinacea Schreb.) plants and their progenies.

Tall fescue (Festuca arundinacea Schreb.) is a hexaploid, outcrossing grass species widely used for forage and turf purposes. Transgenic tall fescue plants were generated by biolistic transformation of embryogenic cell suspension cultures that were derived from single genotypes of widely used cultivar Kentucky-31. Primary transgenics from two genotypes, their corresponding regenerants from the same genotypes and control seed-derived plants were transferred to the field and evaluated for 2 years. Progenies of these three classes of plants were obtained and evaluated together with seed-derived plants in a second field experiment. The agronomic characteristics evaluated were: heading date, anthesis date, height, growth habit, number of reproductive tillers, seed yield and biomass. The agronomic performance of the primary transgenics and regenerants was generally inferior to that of the seed-derived plants, with primary transgenics having fewer tillers and a lower seed yield. However, no major differences between the progenies of transgenics and the progenies of seed-derived plants were found for the agronomic traits evaluated. Primary transgenics and regenerants from the same genotype were more uniform than plants from seeds. Progenies of transgenics performed similarly to progenies of the regenerants. The addition of a selectable marker gene in the plant genome seems to have had little effect on the agronomic performance of the regenerated plants. No indication of weediness of the transgenic tall fescue plants was observed. Our results indicate that outcrossing grass plants generated through transgenic approaches can be incorporated into forage breeding programs.

Biolistics↗

Assignment of the horse grey coat colour gene to ECA25 using whole genome scanning.

The dominant grey coat colour gene of horses has been mapped using a whole genome scanning approach. Samples from a large half-sibling pedigree of Thoroughbred horses were utilized in order to map the grey coat colour locus, G. Multiplex groups of microsatellite markers were developed and used to efficiently screen the horse genome at a resolution of approximately 22 cM, based on an estimated map length for the horse genome of 2720 cM. The grey gene was assigned to chromosome 25 (ECA25), one of the smaller acrocentric horse chromosomes. Based on the current state of knowledge of conserved synteny and coat colour genetics in other mammalian species, there are no obvious candidate genes for the grey gene in the region.

Animals↗

2-Amino-6-arylsulfonylbenzonitriles as non-nucleoside reverse transcriptase inhibitors of HIV-1.

A series of 2-amino-5-arylthiobenzonitriles (1) was found to be active against HIV-1. Structural modifications led to the sulfoxides (2) and sulfones (3). The sulfoxides generally showed antiviral activity against HIV-1 similar to that of 1. The sulfones, however, were the most potent series of analogues, a number having activity against HIV-1 in the nanomolar range. Structural-activity relationship (SAR) studies suggested that a meta substituent, particularly a meta methyl substituent, invariably increased antiviral activities. However, optimal antiviral activities were manifested by compounds where both meta groups in the arylsulfonyl moiety were substituted and one of the substituents was a methyl group. Such a disubstitution led to compounds 3v, 3w, 3x, and 3y having IC50 values against HIV-1 in the low nanomolar range. When gauged for their broad-spectrum antiviral activity against key non-nucleoside reverse transcriptase inhibitor (NNRTI) related mutants, all the di-meta-substituted sulfones 3u-z and the 2-naphthyl analogue 3ee generally showed single-digit nanomolar activity against the V106A and P236L strains and submicromolar to low nanomolar activity against strains E138K, V108I, and Y188C. However, they showed a lack of activity against the K103N and Y181C mutant viruses. The elucidation of the X-ray crystal structure of the complex of 3v (739W94) in HIV-1 reverse transcriptase showed an overlap in the binding domain when compared with the complex of nevirapine in HIV-1 reverse transcriptase. The X-ray structure allowed for the rationalization of SAR data and potencies of the compounds against the mutants.

Anti-HIV Agents↗

Onchocerciasis and epilepsy: a matched case-control study in the Central African Republic.

The occurrence of epileptic seizures during onchocercal infestation has been suspected. Epidemiologic studies are necessary to confirm the relation between onchocerciasis and epilepsy. A matched case-control study was conducted in dispensaries of three northwestern towns of the Central African Republic. Each epileptic case was matched against two nonepileptic controls on the six criteria of sex, age (+/-5 years), residence, treatment with ivermectin, date of last ivermectin dose, and the number of ivermectin doses. Onchocerciasis was defined as at least one microfilaria observed in iliac crest skin snip biopsy. A total of 561 subjects (187 cases and 374 controls) were included in the study. Of the epileptics, 39.6% had onchocerciasis, as did 35.8% of the controls. The mean dermal microfilarial load was 26 microfilariae per mg of skin (standard deviation, 42) in the epileptics and 24 microfilariae per mg of skin (standard deviation, 48) in the controls. This matched case-control study found some relation (odds ratio = 1.21, 95% confidence interval 0.81-1.80), although it was nonstatistically significant.

Adolescent↗

Right ventricular perforation with cardiac tamponade associated with use of a temporary pacing wire and abciximab during complex coronary angioplasty.

We describe our recent experience of right ventricular perforation leading to cardiac tamponade associated with a complex coronary angioplasty in which abciximab and a temporary pacing wire were used. This is to highlight the possibility that the combined use of temporary pacing wires and the IIb/IIIa receptor antagonists may be associated with an increased risk of this serious complication. Cathet. Cardiovasc. Intervent. 48:388-389, 1999.

Abciximab↗

An audit of children referred with suspected epilepsy.

Members of the British Paediatric Neurology Association were invited to participate in a national audit of children presenting with a possible diagnosis of epilepsy. The audit was based on a 'standard' or set of pre-determined questions drawn up by an advisory audit group. The audit form comprised a total of 30 questions divided into four sections addressing history, examination, investigation, treatment and communication. Information for the audit was obtained retrospectively from the child's case notes. Each participating centre or consultant was asked to audit the case notes of 20 children. At the end of the 12-month recruitment period three centres responded, contributing audit forms on 50 children. The required information was provided for the majority of the questions in each of the four sections, thereby meeting the audit 'standard'. Within the history section, only 32 of the 50 (64%) case notes had recorded whether or not there was 'any obvious provoking factor or circumstance to the episodes'. Communication was the least satisfactorily completed section with between none and 48% of the case notes documenting that the child's family had been informed of the existence of a voluntary epilepsy organization. Despite the simplicity of the audit form, the response for this national audit was considerably lower than anticipated.

Adolescent↗

Cardiac rehabilitation services in England and Wales: a national survey.

We sent a short postal questionnaire to 244 centres in England and Wales that admitted patients with cardiac conditions. In total, 199 (81%) of the centres claimed to provide a cardiac rehabilitation service. Of these, 25 were randomly selected as a representative sample and visited in order to obtain detailed information concerning the provision of services. Most (18 (72%)) of the centres had commenced their rehabilitation programme within the previous 5 years, usually at the instigation of interested staff. Patient entry to cardiac rehabilitation programmes was restricted; women (who represented only 15% of attenders), elderly people (excluded in 10 (40%) centres), and those with more complex problems, such as angina or heart failure, were under-represented. The central components of all programmes were education and exercise training but there was a wide range in the quantity and quality of service provision. Most (22 (88%)) programmes were hospital out-patient based, one (4%) was hospital in-patient based, one (4%) was community-based and one (4%) was home-based. The staffing and funding of programmes was variable, with 7 (28%) having no identified funding. There are wide variations in the resources currently available for the rehabilitation of patients with coronary heart disease. There is a need for clearer direction of these services, in particular to determine minimum service provision. Guidelines are necessary to give a framework for this relatively new and rapidly expanding service.

Aged↗

An audit of the organization of adult epilepsy services in the UK: a comparative review of epilepsy and general neurology clinics.

A survey of all consultant neurologists was carried out to investigate the current provision of hospital-based adult epilepsy services in the UK and to compare the level of services offered by epilepsy and general neurology clinics. The valid response rate was 75%. Fifty-four epilepsy clinics were identified led by 43 neurologists in 46 hospitals. Over half the major neurological centres represented in the dataset had epilepsy clinics (31/58). Epilepsy clinics were significantly more likely than general neurology clinics to have on-site provision of a wide range of relevant investigations and associated specialists, and also shorter waiting times to see new patients with suspected seizures. There were also significant differences between epilepsy clinics and general neurology clinics in the provision of written information and counselling. Epilepsy clinics have definite advantages for patients over general neurology clinics in improving access to investigations and specialists and provision of psychosocial support, but the extent to which these translate into positive health outcomes needs further evaluation. A second survey of directors of public health concerning purchasing arrangements for epilepsy services confirmed that purchasers, as yet, are making little use of the contracting process to influence the quality of epilepsy services offered by providers of care.

Ambulatory Care Facilities↗

Good practice in the management of adults with malignant cerebral glioma: clinical guidelines. Working Group, Royal College of Physicians.

This paper proposes guidelines for good practice in the management of adults with malignant cerebral glioma. These guidelines were developed by a working group comprising representatives of the medical specialties involved in patient care, specialist nursing staff, purchasers, charitable bodies, and patient and relative representatives. Both the research literature on the effectiveness of medical intervention, and the views of patients and relatives about the care they had received were considered. The document proposes a consensus view about ways to improve patient care and considers several stages of the illness and its care: I, the diagnostic phase; II, deciding on an appropriate treatment plan; III, the organization of follow-up services; IV, the management of transitions from hospital to community settings; and V, purchasing care for patients with malignant brain tumours. An audit package derived from the guidelines is available which will enable staff within a treatment centre to compare their practice against these standards. A final section suggests topics which require further research, and sets out the core requirements for studies that will help answer questions about treatment and the benefits for patients in terms of improved quality of life.

Adult↗

Blindness and visual impairment in a region endemic for onchocerciasis in the Central African Republic.

AIMS: A population based survey of blindness and visual impairment was conducted in the district of Bossangoa, Central African Republic. METHODS: A total of 48 communities were randomly selected, and 6086 people examined. RESULTS: The prevalence of blindness (visual acuity in the better eye less than 3/60) was 2.2%, and visual impairment 3.0% (6/24 to 3/60 in the better eye). The major causes of blindness were onchocerciasis (73.1%), cataract (16.4%), trachoma (4.5%), and glaucoma (2.2%). CONCLUSION: Around 95.5% of all blindness could potentially have been prevented or treated. Ivermectin mass distribution is hoped to prevent 50% of all forms of visual loss in the future.

Adolescent↗

Malignant cerebral glioma--I: Survival, disability, and morbidity after radiotherapy.

OBJECTIVE: To describe survival, disability, and morbidity after radiotherapy for malignant glioma. DESIGN: Two year prospective study with home interviews with patients and relatives. SETTING: Seven neurosurgical and radiotherapy centres in London. SUBJECTS: 105 patients aged 21 to 75: 59 had biopsy; 46 had partial macroscopic resection; 92 received radiotherapy; and 13 received steroids alone. MAIN OUTCOME MEASURES: Survival, time free from disability, and changes in disability after treatment. RESULTS: Six and 12 month survival for radiotherapy patients was 70% and 39%, respectively. Age, World Health Organisation clinical performance status, extent of surgery, and history of seizures before diagnosis each influenced survival. The Medical Research Council prognostic index was also significantly related to survival. Multivariate analysis showed that initial clinical performance status was the most important component of the index. Most (80%; 49/61) patients with a clinical performance status of 0, 1, or 2 lived at least six months before becoming permanently disabled. Most patients who had initially had a good clinical performance status (0-2) and who were alive six months after radiotherapy (68%; 36/52), however, had experienced either clinical deterioration or severe tiredness after treatment. In 17% (9/52) of these some permanent loss of function remained. These adverse effects were associated with increasing radiotherapy dose. Severely disabled patients (clinical performance status 3 or 4) gained little benefit. CONCLUSION: Severely disabled patients gain little physical benefit from radiotherapy, whereas those not so disabled may experience considerable adverse effects.

Activities of Daily Living↗

Malignant cerebral glioma--II: Perspectives of patients and relatives on the value of radiotherapy.

OBJECTIVE: To explore the experiences of patients and relatives after the diagnosis and treatment of malignant cerebral glioma. DESIGN: Two year prospective study with home interviews. SETTING: Six neurosurgery and radiotherapy centres in London. SUBJECTS: 75 patients and 66 close relatives interviewed at diagnosis, 58 patients interviewed after radiotherapy, and 27 interviewed after recurrence. MAIN OUTCOME MEASURES: Awareness of likely prognosis, distress, dissatisfaction with radiotherapy, and perception of severe problems in everyday life. RESULTS: As they began radiotherapy most patients understood that they suffered from a brain tumour (95%; 71/75), but only one quarter (19/75) seemed fully aware of the poor prognosis. Others were unaware (43%; 32/75) or only partly aware (32%; 24/75). The more aware patients were more distressed. Relatives were three times more likely to be aware of the prognosis (67%; 44/66) and were more distressed. Although 39% (29/75) of patients initially made negative comments about radiotherapy, only 17% (13/75) were completely dissatisfied. The decision to accept radiotherapy could be discussed directly with 19 fully aware patients. Twelve found radiotherapy acceptable if it were medically advised or if it improved survival. Assessed by their own reports of problems only 40% of patients achieved a period of stability or remission, yet dissatisfaction with treatment did not increase. CONCLUSIONS: Most patients with malignant glioma initially seemed unaware or only partly aware of the poor prognosis. Relatives were more aware, more distressed, and often concerned to protect patients from full awareness, which made it difficult to explore with patients directly the possible trade off between quality and length of life. Conceptualising the question as a rational choice ignores the social and emotional context of life threatening disease.

Activities of Daily Living↗

Can contracts drive clinical care?

The instrument through which a commissioner purchases health services from a provider is, as in other walks of life, a contract, so considerable importance has been attached by the NHS Executive to the contracting mechanism. A contract should in theory influence the quality of the service provided, but they are in many cases an inappropriate vehicle for driving clinical care. Much clinical activity is related to the management of chronic diseases and the effects of aging. The implicit contract here is based not on process and outcome measures but on mutual trust between doctors and patients that the doctors will provide the best care they can within budgetary constraints.

Budgets↗