Biomedical subjects
Publications and source records attributed to N D Miller.
We have investigated the structure-activity relationships of the 1- and 3-substituents and replacements of the 5-phenyl group of GW405212X 1, a potent selective oxytocin antagonist. The effect of these modifications on oxytocin binding antagonism and on pharmacokinetic parameters is reported.
Many epidemiologists base their diagnoses of dementia on scores on brief cognitive tests, but the border between normal aging and mild dementia is so poorly understood that simple demarcations cannot adequately encapsulate the wealth of clinical material that needs to be taken into account in assigning diagnostic labels. Data from a British study of the prevalence and natural history of dementia, in which diagnoses of dementia were made by clinicians using a new, standardized interview schedule, are presented to demonstrate the effects of physical disability, psychiatric illness, and other factors on memory impairment and performance in everyday life. Our purpose is not to insist that clinicians are always correct but rather to highlight the complexities involved and the need for investigators to be more open about the way in which they distinguish between physical, psychiatric, and cognitive infirmities.
Thirty-one subjects aged 75 years and over who were identified as suffering from mild, idiopathic dementia in a large community survey were reviewed at annual intervals for 2 years. Diagnoses and severity ratings were based on defined criteria following a mental state examination, a medical and psychiatric history, detailed cognitive testing, and an interview with relatives or other key informants. Fourteen subjects became more severely demented within 2 years. The initial cognitive test battery failed to reveal any differences between respondents whose dementia advanced and those whose condition remained unchanged, but, in the former group, subjects' symptoms had been present for longer, and a greater proportion had been recognised as demented, or possibly demented, by their general practitioners. We suggest that subjects whose dementia progressed had actually been more severely disabled at the time of identification.
We describe the outcome 2 years later of elderly Cambridge residents who had been diagnosed as demented using the Cambridge Mental Disorders of the Elderly Examination. Mortality rates were high but diagnoses were confirmed for all of the 43 moderate and severe cases who survived for this period, and for 51 of the 56 subjects who had been rated initially as mildly demented; 28 of the 56 mildly demented subjects progressed to more severe levels of impairment. As many as 12 of the 24 original minimally demented cases showed evidence of intellectual deterioration, which lends weight to the validity of this experimental category.
Elderly Cambridge residents diagnosed as demented using the Cambridge Mental Disorders of the Elderly Examination (CAMDEX) were reviewed approximately 12 months later. Diagnoses were confirmed in 133 of 137 surviving cases (97%). Subjects said to have minimal dementia (cognitive impairment insufficient to warrant a diagnosis of dementia proper) had a varied outcome. Only 6 out of 29 survivors showed progressive intellectual deterioration and 13 were reclassified as normal. Subjects passed as normal in the first year of the study were reviewed using the Mini-Mental State Examination. We cannot be certain how many were actually dementing, but our findings suggest that only a small number of false negative diagnoses were made in the first year of the study.
The Mini-Mental State (MMSE) was administered to 2302 general practice patients aged 75 yr and over. Those scoring 23 or less and a sample of those scoring 24 or 25 were selected for further investigation using the Cambridge Mental Disorders of the Elderly Examination. Inter-observer reliability was high with a mean kappa value of 0.97. Eighty-six per cent of respondents judged to have organic mental disorders scored 23 or less on the MMSE and 92% of those judged to be cognitively intact scored 24 or more. However, only 55% of respondents who scored 23 or less were demented or delirious while a number of relatively well educated, mildly demented subjects scored 24 and 25. The customary cut-off point of 23/24 may need to be revised in future community studies. MMSE scores cannot be used to make even tentative psychiatric diagnoses; more detailed investigation of low scorers is essential.
General practice patients aged 75 years and over were screened for cognitive impairment using the Mini-Mental State Examination. Those scoring 23 or below and a sample of those scoring 24 or 25 were assessed using the Cambridge Mental Disorders of the Elderly Examination (CAMDEX), a structured interview schedule specifically designed to detect mild dementia. The CAMDEX includes a mental state examination, a psychiatric history, detailed cognitive testing and an information interview. The prevalence of dementia in 2311 patients was found to be 10.5%, about half that found in most earlier studies. Possible reasons for this low rate are discussed.
The known biodegradability of PHB in certain biological environments has led to its proposed use as a 'biodegradable' implant material. Monofilaments of PHB homopolymer and two PHV-PHB copolymers have been studied in vivo and in vitro and assessed for changes in mechanical properties and topography. In vivo biodegradation was only observed with PHB when pre-degraded by 10.0 Mrad of gamma-irradiation before implantation. High temperature in vitro hydrolysis suggested that PHV copolymer additions retarded the rate of degradation of PHB. Hydration reactions had most effect on the ultimate tensile properties of the materials. In contrast, the elastic properties appeared to be relatively unaffected.
The in vivo and in vitro stability of a degradable suture material, poly(glycolic acid) has been shown to be dependent on the magnitude of a pre-imposed strain. The degradation, monitored by changes in the tensile load at break, was considerably enhanced by pre-straining the material to one half of the normal extension at break, using a novel implantable device.
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