Biomedical subjects
Publications and source records attributed to H Fraser.
An amblyopia, or lazy eye, is an eye that is healthy in all respects but which has defective vision, even after the fitting of correcting lenses for a refractive error. Amblyopia can be a strongly hereditary condition. The author describes the predisposing conditions and discusses methods of assessment and the effectiveness of its present treatment.
BACKGROUND: There is a pressing need to identify which interventions are definitely effective in the prevention of stroke and in the treatment and rehabilitation of stroke patients, which interventions are definitely ineffective, and which interventions require further research. This information is most reliably obtained from reviewing all the available evidence from randomized controlled trials in a systematic way. SUMMARY OF COMMENT: There have been many (at least 8000) randomized controlled trials relevant to stroke. It would be difficult for any one individual to keep track of all these trials, and therefore most clinicians, therapists, and researchers are dependent, to some degree, on reviews of this literature. However, most current reviews are unsystematic and tend to be either incomplete or biased, so that their recommendations can be seriously flawed. Until now there has been no attempt to systematically identify all randomized controlled trials relevant to stroke (including subarachnoid hemorrhage), to review the data they contain, and to keep these reviews up-to-date in the light of new evidence. The Stroke Review Group has now been established within the Cochrane Collaboration to try to perform these tasks. There are presently 40 collaborators from 13 countries working on approximately 25 reviews. CONCLUSIONS: Identifying and reviewing all randomized controlled trials relevant to stroke should bring important benefits to patients and all those involved in purchasing or providing care for patients with stroke. The Cochrane Collaboration Stroke Review Group has started this process and would welcome help from anyone interested in collaborating in this enormous task.
The presence of cytokines, prostaglandins and lipocortin-1 was investigated in terminally affected mice in two models of scrapie. There was marked induction of glial interleukin-1 beta, tumour necrosis factor alpha, prostaglandin E2, prostaglandin F2 alpha and lipocortin-1 immunoreactivity in those areas of the brain showing the characteristic vacuolation of scrapie. A comparison of these staining patterns with those of GFAP and F4/80 showed that their expression occurred predominantly in astrocytes. It is possible that cytokines play a significant role in the pathogenesis of neurodegeneration in scrapie.
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Transmissions of bovine spongiform encephalopathy (BSE) from seven unrelated cattle sources have given remarkably uniform disease characteristics in mice, differing from over twenty previous and contemporary transmissions of sheep and goat scrapie. Transmissions to mice of spongiform encephalopathy from six species (including sheep and goats) which have been experimentally or naturally infected with BSE have given similar results to direct BSE transmissions from cattle. Therefore the BSE agent has retained its identity when passaged through a range of species and the 'donor' species has little specific influence on disease characteristics in mice, adding to evidence for an agent-specific informational molecule. On transmission of BSE or scrapie to mice the incubation periods are long compared with subsequent mouse-to-mouse passages (the 'species barrier'). Contributing factors include a low efficiency of infection on interspecies transmission, the apparent failure of intracerebrally injected 'foreign' inoculum to establish infection directly in mouse brain and the selection of variant strains of agent which replicate most readily in the new host species.
Macerates of bovine brain infected with bovine spongiform encephalopathy (BSE) agent, and rodent brain infected with the 263K or ME7 strains of scrapie agent, were subjected to porous-load autoclaving at temperatures between 134 and 138 degrees C for < or = 60 min. Bioassay in rodents showed that none of the regimens produced complete inactivation. Homogenates of BSE-infected bovine brain were exposed for < or = 120 min to solutions of sodium hypochlorite or sodium dichloroisocyanurate containing < or = 16,500 ppm available chlorine. There was no detectable survival of infectivity after the hypochlorite treatments but none of the dichloroisocyanurate solutions produced complete inactivation. Homogenates of BSE-infected bovine brain, and rodent brain infected with the 263K and ME7 strains of scrapie agent, were exposed for < or = 120 min to 1M or 2M sodium hydroxide but no procedure produced complete inactivation of all agents tested.
Five percent of incident patients with MND in Scotland 1989-1990 had a family history of this disease. This paper assesses the demographic and clinical features of this group.
The nature of the glial and inflammatory cell responses to infection in scrapie-affected brains was studied in terminally-affected mice of five scrapie models. There were marked astrocytic and microglial responses. Microglia showed increased staining of the surface antigens F4/80, leucocyte-common antigen, type 3 complement receptor, and elevated endocytotic and lysosomal activity. In all models, the astrocytic and microglial responses were largely restricted to anatomical regions of the brain showing vacuolation and/or plaque formation and pathological accumulations of PrP. Expression of MHC Class II was patchy and present on microglia in the neuropil of areas with the most intense microglial activation and on occasional perivascular macrophages. This microglial response may represent a modified form of inflammatory response.
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Effects of salt loading by drinking 0.9% NaCl solution on the myocardial performance in nondiabetic and diabetic Wistar rats were studied using the isolated working heart apparatus. Body weight and fluid and food intakes of these animals were monitored. Blood pressure and plasma levels of glucose, insulin, cholesterol, and triglycerides were also measured. Diabetes was induced by intravenous injection of streptozotocin (60 mg/kg). Diabetic rats were found to develop myocardial dysfunction at 8 weeks after STZ injection, accompanied by significant increases in food and fluid intakes, slowed body weight gain, hyperglycemia, hypoinsulinemia, and hyperlipidemia but without significant changes in blood pressure. Salt loading did not cause significant changes in any of the parameters studied in nondiabetic rats. However, in streptozotocin-diabetic rats given saline to drink, the impaired myocardial function was significantly improved and was associated with a significant reduction in hyperphagia and hyperlipidemia. Plasma glucose levels significantly decreased at weeks 1-3 but increased to the levels of untreated diabetic animals at weeks 4-7. There was an increase in fluid intake, but neither blood pressure nor plasma insulin levels were significantly affected. It is suggested that the improvements in cardiac function and hyperlipidemia in diabetic rats by salt loading may be related to each other; however, the mechanisms for these effects are not clear but are unlikely to be due to changes in glycemic control.
Spongiform encephalopathy has been confirmed in both 'positive' and 'negative' lines of Cheviot sheep (selected for their differential response on experimental exposure to scrapie) after intracerebral injection or oral dosing with brain homogenate derived from cattle with bovine spongiform encephalopathy (BSE). With either challenge the incubation period of the disease ranged from 440 to 994 days in both lines of sheep. In a similar experiment, three Anglo-Nubian goats developed the disease 506 to 570 days after intracerebral infection with the same BSE homogenate, and two of three goats developed the disease 941 and 1501 days after oral dosing; the other goat and some sheep from each of the experimental groups remain alive 1720 days after exposure. This is the first report of the experimental transmission of BSE to sheep and goats.
The Scottish Motor Neuron Disease Register (SMNDR) is a prospective, collaborative, population-based project which has been collecting data on incident patients since 1989. In this report we present the clinical features of 229 patients with motor neuron disease (218 sporadic and 11 familial) diagnosed in 1989 and 1990 and compare their prognosis with previous studies of survival. The overall 50% survival from symptom onset was 2.5 years (95% CI, 2.2-3.0) and 5-year survival 28% (95% CI, 20-36%). The presence of progressive bulbar palsy (PBP), either at presentation or developing during the course of the illness, significantly reduced survival and was the most important prognostic indicator. Patients who survived longer than 5 years from symptom onset did not have PBP as part of their presenting illness. The prognosis was worse for women, and this was in part related to the higher frequency of PBP in older women, but age was also an independent adverse risk factor. Differences in survival between this and previous series can probably be explained on the basis of variation in case definition and ascertainment methods.
Mice were infected with one of two strains of scrapie by instilling brain homogenate into the conjunctiva to establish whether infection could be initiated. Of the 55 mice infected with ME7 scrapie, 23 developed clinical disease 323 +/- 8 (mean +/- standard error) days later. Three out of 12 mice infected with 79A scrapie developed disease after 232 +/- 35 days. The ME7 incubation period is similar to that for the oral route of infection. We feel that these results emphasize the need for adequate eye protection when handling tissues infected with spongiform encephalopathies.
The main diagnostic histology in the spongiform encephalopathies consists of a degenerative and usually symmetrical vacuolation of neurons and a spongiform lesion in the neuropil. Sometimes there can be asymmetry. This pathology is usually confined to grey matter, but an additional white matter vacuolation is sometimes typical. The degeneration can progress to neuronal necrosis, with reactive glial changes. Photoreceptor loss in the retina occurs in some experimental models. Cerebral amyloidosis is conspicuous in many types of scrapie-like pathology in animals, but is sometimes not recognised or may be absent. Abnormal immunolabelling with anti-PrP is always associated with both the degenerative and amyloid lesion and precedes the occurrence of the degeneration in experimental scrapie models. All aspects of the pathology are closely controlled by host genetic factors and by the strain of the infecting, causal agent.
OBJECTIVES: To determine the accuracy of (1) hospital discharge data and (2) death certificates, coded as motor neuron disease (MND). DESIGN: Comparison of data from The Scottish Motor Neuron Disease Register (SMNDR) with routinely collected Scottish Hospital In-Patient Statistics (SHIPS) and death certificate coding. SETTING: Scotland UK. PATIENTS: 1) 379 adults (> 15 years) discharged for the first time from a Scottish hospital in 1989-90 and (2) 281 deaths in the same period assigned to the International Classification of Diseases (ICD)-9, category 335 (MND). MAIN OUTCOME MEASURES: The sensitivity and positive predictive value of a diagnosis of MND as retrieved by (1) the Information and Statistics Division of the Common Services Agency for the Scottish Health Service for morbidity data and (2) the Registrar General's office for mortality data, using the SMNDR as the 'gold standard'. RESULTS: (1) Thirty per cent of adult patients identified as having MND by SHIPS did not have this disease and 23% of patients with MND did not appear on SHIPS. The sensitivity of a diagnosis of MND, as retrieved by SHIPS, was 84% and the positive predictive value was 70% overall. Miscoding of patients with pseudobulbar palsy caused by cerebrovascular disease was the major source of false positive error. The incidence of adult onset sporadic MND was over estimated by SHIPS by a factor of 1.6. (2) Mortality data were more accurate, with a false negative rate of 6% and a positive predictive value of 90%. CONCLUSIONS: Coded hospital discharge data are an inaccurate record of a diagnosis of MND and cannot, in their present form, be used as a reliable measure of disease incidence in Scotland. Greater care is required in the preparation of discharge summaries and coding if these data are to be useful for health care planning and epidemiological research. SHIPS is, however, an important source of information to achieve a complete sample of patients with MND. There is also a problematic false positive rate for mortality data but this source more closely approximates true incidence.
In order to identify risk factors for the subsequent development of motor neuron disease (MND) we have carried out a case-control study of incident patients in Scotland, identified using the Scottish Motor Neuron Disease Register. A standard questionnaire was given to 103 patients and the same number of community controls matched on a one to one basis using the general practitioner's (GP) age and sex register. Recall bias was minimised by using GP records to verify the subject's report. There was an overall lifetime excess of fractures in patients, odds ratio (OR) = 1.3 (95% confidence interval (CI), 0.7-2.5) and this was highest in the 5 years before symptom onset (OR = 15, 95% CI, 3.3-654). There was no association with non-fracture trauma but the OR for a manual occupation in patients was 2.6 (95% CI, 1.1-6.3). Both occupational exposure to lead (OR = 5.7, 95% CI, 1.6-30) and solvents/chemicals (OR = 3.3, 95% CI 1.3-10) were significantly more common in patients. No consistent association was found between MND and factors reflecting socioeconomic deprivation in childhood; childhood infections or social class. Our results identify a number of different factors which may contribute to the aetiology of MND.
A stratified random sample of 464 persons aged 40 to 79 years, drawn from enumeration registers in the Bridgetown area of Barbados, participated in this survey. The prevalence of hypertension (defined as systolic blood pressure of at least 160 mm Hg, diastolic blood pressure of at least 95 mm Hg, or use of antihypertensive medication) was 47% and 43% for women and men, respectively. Diabetes was present in 17% of all subjects (18% of women and 15% of men). Of the 209 hypertensive subjects, 82% were aware of their blood pressure status. The proportion of previously diagnosed hypertensive subjects on medication was 72% for men and 68% for women. Fifty-three percent of men and 42% of women were overweight (body mass indices [weight in kilograms divided by height in meters squared] between 25 and 30). However, 30% of women and 10% of men were obese (body mass indices over 30), supporting the growing recognition of the marked gender disparity in obesity among persons of African origin in the Caribbean. Body mass index was positively associated with hypertension (OR = 1.33; 95% CI: 1.1-1.6). Obese persons experienced a 2.6 times greater risk of hypertension compared to those with body mass indices below 25. Similar statistically significant associations were observed between diabetes and body mass index: OR comparing body mass index over 30 with body mass index under 25 was 2.5 (95% CI: 1.3-5.1) for all subjects, 1.0 (0.3-4.1) for men only, and 5.2 (1.9-14) for women only. Preventing obesity in this population could reduce the incidence of hypertension and diabetes by approximately 30% and 33% among men and women, respectively.