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Biomedical subjects

M Clarke

Publications and source records attributed to M Clarke.

At least 163 records · Page 9Linked to original sources
PubMed1995

Predictors of survival with Alzheimer's disease: a community-based study.

Factors associated with reduced survival were investigated in elderly people diagnosed as having Alzheimer's disease (AD) and in those free of dementia at diagnosis. The study population comprised 155 people free of dementia and 222 with AD; all were aged 75 years and over and were part of a two-stage prevalence study of dementia during 1988 in Melton Mowbray, Leicestershire. An increased risk of death was found for those with a history of heavy alcohol use, lower cognitive function, a history of heart failure and those in institutional care, these factors acting in the same manner for persons free of dementia and those with AD. For the non-demented group a greater risk of death was found with increasing age and for those with a history of cancer. A greater risk of death was found for males with AD compared to females with the risk increasing over time. The longer survival of women over men may explain the sex differences found in the prevalence of AD without accompanying differences in incidence.

Activities of Daily Living↗
PubMed1995

Genetic and physiologic modulation of the prestarvation response in Dictyostelium discoideum.

Throughout vegetative growth, Dictyostelium amoebae secrete an autocrine factor, prestarvation factor, PSF, which accumulates in proportion to cell density. During late exponential growth, PSF induces the expression of several genes whose products are needed for cAMP signaling and cell aggregation. Among these genes are discoidin-I and the 2.4-kb transcript of cyclic nucleotide phosphodiesterase (PDE). We have identified several parameters that modulate expression of one or both of these prestarvation response genes; all effects were monitored in cells growing exponentially on bacteria. Under these conditions, axenic mutants produce higher levels of PSF activity than wild-type cells. Consistent with the high PSF levels, the 2.4-kb PDE transcript is more abundant in axenic strains than wild-type cells at the same cell density. In contrast, the density-dependent induction of discoidin-I is greatly delayed in axenic strains, occurring only at the very end of exponential growth. Analysis of axenic strains of independent origin suggested that this negative effect on discoidin-I expression is attributable to the axenic mutations themselves. The effects of two environmental factors that inhibit the prestarvation response (the bacteria upon which the cells feed and a bacterial product, folic acid) were also analyzed. We found that folate does not account for the inhibitory effect of bacteria. Cells deficient in the G-protein beta subunit, which is thought to be common to all heterotrimeric G-proteins in Dictyostelium, respond to PSF in the same manner as G beta+ cells, and this response is inhibited by bacteria. However, folate has no inhibitory effect on g beta- cells, indicating that folate inhibition is mediated by a heterotrimeric G-protein. In cells lacking the catalytic subunit of protein kinase A, the prestarvation response is severely impaired, but about 3% of the pka- cells manifest an apparently normal density-dependent induction of discoidin-I. This behavior and the heterogeneity of the prestarvation response in wild-type cells lead us to speculate that protein kinase A may not be required for PSF signal transduction per se, but rather may render the cells responsive to PSF. Based on analysis of adenylyl cyclase mutants (aca-), the effect of protein kinase A is not cAMP-dependent.

Aminopterin↗
PubMed1995

Population laboratories and health needs assessment.

In the 1960s Walter Holland established a series of epidemiological studies in a defined geographical population in southeast London. This endeavour was an example of the ambition held by generations of epidemiologists to study human populations under actual conditions of community life. Early examples of American population laboratories were mainly concerned with studies of aetiology whereas p.c. (post-Cochrane) studies have aimed to identify both aetiological factors and to assess need for effective and efficient health services. The case is made for the value of a population laboratory in facilitating mortality follow-up studies, undertaking health care needs assessments and evaluating new technologies.

Epidemiologic Methods↗
PubMed1995

Borderline personality disorder: a challenge for mental health services.

OBJECTIVE: This study had two main aims: to determine the stability over time of the diagnosis borderline personality disorder (BPD) in a psychiatric hospital population; and to assess the quality and effectiveness of treatment offered within state mental health service. METHOD: The case notes of 47 psychiatric hospital patients followed up for 3 years after the index admission were analysed. RESULTS: The mean number of previous psychiatric hospital admissions was 9.0, and at least 74% of the sample had further admissions (mean 3.7) during the 3 year follow-up. Comorbidity with schizophrenia and schizoaffective disorder was rare, and was only 13% with major depression. Longitudinal stability of diagnosis was very high. CONCLUSIONS: The study firmly supported BPD as a valid diagnosis. Its treatment within the state mental health system was generally haphazard and ineffective. Post-discharge plans were implemented for only 3 subjects. Current moves toward community psychiatric treatment represent a unique opportunity for improving treatment of BPD by using existing resources more effectively.

Activities of Daily Living↗
PubMed1994

Operations research survey and computer simulation of waiting times in two medical outpatient clinic structures.

Outpatient services are increasingly recognised as an important component of health care provision and may be improved through the application of modern management techniques. We have performed a time and role audit of consultation and waiting times in two medical clinics using different queuing systems: namely, a serial processing clinic where patients wait in a single queue and a quasi-parallel processing clinic where patients are directed to the shortest queue to maintain clinic flow. Data collected were used to construct a computer simulation of patient flows in clinic. Assessment of patient satisfaction in the clinic process was determined using a self-administered questionnaire. Mean waiting time was shorter in the quasi-parallel processing clinic: 26 (SD 17) minutes compared with 36(24) minutes in the serial processing clinic. In the serial processing clinic 61% of patients waited more than 30 minutes compared with 41% in the quasi-parallel processing clinic. In the serial processing clinic 8% of 142 patients surveyed complained of the time spent waiting. The computer simulation we produced was able to determine waiting times with different clinic structures. The simulation showed that reductions in waiting time up to 30% might be achieved by changing our serial processing clinic to a quasi-parallel processing one. Performance of medical outpatient clinics can be improved by examining and changing clinic management. Computer simulation of outpatient clinics offers a means of assessing the impact of such changes on waiting time in clinic and on waiting lists.

Algorithms↗
PubMed1994

Railway suicide in England and Wales, 1850-1949.

According to the official statistics of the Registrar General, the first railway suicide occurred in 1852 and more than 10,000 suicides recorded during the period 1852-1949. Throughout this time the number of male cases always exceeded the number of female cases and the railway accounted for a greater proportion of male than female suicides in all but two years. By the early decades of the twentieth century, the railway was used in 5-6% of male suicides and 3-4% of female suicides. The incidence of railway suicide was correlated with the growth of the railway system offering some evidence for the relationship between availability of a lethal means and suicide rates.

Adult↗
PubMed1994

Spatio-temporal stages in face and word processing. I. Depth-recorded potentials in the human occipital, temporal and parietal lobes [corrected].

Evoked potentials (EPs) were used to help identify the timing, location, and intensity of the information-processing stages applied to faces and words in humans. EP generators were localized using intracranial recordings in 33 patients with depth electrodes implanted in order to direct surgical treatment of drug-resistant epilepsy. While awaiting spontaneous seizure onset, the patients gave their fully informed consent to perform cognitive tasks. Depth recordings were obtained from 1198 sites in the occipital, temporal and parietal cortices, and in the limbic system (amygdala, hippocampal formation and posterior cingulate gyrus). Twenty-three patients received a declarative memory recognition task in which faces of previously unfamiliar young adults without verbalizable distinguishing features were exposed for 300 ms every 3 s; 25 patients received an analogous task using words. For component identification, some patients also received simple auditory (21 patients) or visual (12 patients) discrimination tasks. Eight successive EP stages preceding the behavioral response (at about 600 ms) could be distinguished by latency, and each of 14 anatomical structures was found to participate in 2-8 of these stages. The earliest response, an N75-P105, focal in the most medial and posterior of the leads implanted in the occipital lobe (lingual g), was probably generated in visual cortical areas 17 and 18. These components were not visible in response to words, presumably because words were presented foveally. A focal evoked alpha rhythm to both words and faces was also noted in the lingual g. This was followed by an N130-P180-N240 focal and polarity-inverting in the basal occipitotemporal cortex (fusiform g, probably areas 19 and 37). In most cases, the P180 was evoked only by faces, and not by words, letters or symbols. Although largest in the fusiform g this sequence of potentials (especially the N240) was also observed in the supramarginal g, posterior superior and middle temporal g, posterior cingulate g, and posterior hippocampal formation. The N130, but not later components of this complex, was observed in the anterior hippocampus and amygdala. Faces only also evoked longer-latency potentials up to 600 ms in the right fusiform g. Words only evoked a series of potentials beginning at 190 ms and extending to 600 ms in the fusiform g and near the angular g (especially left). Both words and faces evoked a N150-P200-PN260 in the lingual g, and posterior inferior and middle temporal g.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1994

Spatio-temporal stages in face and word processing. 2. Depth-recorded potentials in the human frontal and Rolandic cortices.

Evoked potentials (EPs) were recorded directly from 650 frontal and peri-Rolandic sites in 26 subjects during face and/or word recognition, as well as during control tasks (simple auditory and visual discrimination). Electrodes were implanted in order to localize epileptogenic foci resistant to medication, and thus direct their surgical removal. While awaiting spontaneous seizure onset, the patients gave informed consent to perform cognitive tasks during intracerebral EEG recording. The earliest potentials appeared to be related to sensory stimulation, were prominent in lateral prefrontal cortex, and occurred at peak latencies of about 150 and 190 ms. A small triphasic complex beginning slightly later (peak latencies about 200-285-350 ms) appeared to correspond to the scalp N2-P3a-slow wave, associated with non-specific orienting. Multiple components peaking from 280 to 900 ms, and apparently specific to words were occasionally recorded in the left inferior frontal g, pars triangularis (Broca's area). Components peaking at about 430 and 600 ms were recorded in all parts of the prefrontal cortex, but were largest (up to 180 microV) and frequently polarity-inverted in the ventro-lateral prefrontal cortex. These components appeared to represent the N4-P3b, which have been associated with contextual integration and cognitive closure. Finally, a late negativity (650-900 ms) was recorded in precentral and premotor cortices, probably corresponding to a peri-movement readiness potential. In summary, EP components related to early sensory processing were most prominent in lateral prefrontal, to orienting in medial limbic, to word-specific processing in Broca's area, to cognitive integration in ventro-lateral prefrontal, and to response organization in premotor cortices.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Dictyostelium discoideum mutants with conditional defects in phagocytosis.

We have isolated and characterized Dictyostelium discoideum mutants with conditional defects in phagocytosis. Under suspension conditions, the mutants exhibited dramatic reductions in the uptake of bacteria and polystyrene latex beads. The initial binding of these ligands was unaffected, however, indicating that the defect was not in a plasma membrane receptor: Because of the phagocytosis defect, the mutants were unable to grow when cultured in suspensions of heat-killed bacteria. The mutants exhibited normal capacities for fluid phase endocytosis and grew as rapidly as parental (AX4) cells in axenic medium. Both the defects in phagocytosis and growth on bacteria were corrected when the mutant Dictyostelium cells were cultured on solid substrates. Reversion and genetic complementation analysis suggested that the mutant phenotypes were caused by single gene defects. While the precise site of action of the mutations was not established, the mutations are likely to affect an early signaling event because the binding of bacteria to mutant cells in suspension was unable to trigger the localized polymerization of actin filaments required for ingestion; other aspects of actin function appeared normal. This class of conditional phagocytosis mutant should prove to be useful for the expression cloning of the affected gene(s).

Animals↗
PubMed1994

Non-invasive beat to beat arterial blood pressure during non-REM sleep in obstructive sleep apnoea and snoring.

BACKGROUND: Obstructive sleep apnoea, and possibly snoring, are associated with a poorly understood increase in cardiovascular mortality which may be explained by their effects on systemic blood pressure during sleep. This study compares changes in mean blood pressure during obstructive sleep apnoea and snoring without apnoeas with those in matched control subjects during non-REM sleep. METHODS: Eighteen men with obstructive sleep apnoea, 16 men who snored without apnoeas, and 34 control subjects matched for age, sex, obesity, smoking, and alcohol intake were studied. During polysomnography non-invasive mean blood pressure (Finapres) was recorded from each cardiac cycle during non-REM sleep and averaged over a 10 minute period. This was compared with the blood pressure during 10 minutes before sleep onset. The changes in the patients' sleeping blood pressure were compared with those in their individually matched control subjects. RESULTS: Compared with the control subjects the change in mean (SD) arterial blood pressure between being awake and asleep was higher during obstructive sleep apnoea (+6.5 (9) mm Hg v-2 (6.5), difference 8.5 (11)), and the rise from wakefulness to sleep in the obstructive sleep apnoea group was itself significant. The average mean arterial pressure was not raised in those who snored without apnoeas compared with either the control subjects or during wakefulness. CONCLUSIONS: Average mean arterial pressure is higher during obstructive sleep apnoea than it is during wakefulness, while normal subjects show a fall in blood pressure at sleep onset. This sleep related rise in blood pressure may contribute to the excess cardiovascular morbidity and mortality experienced by patients with this condition.

Blood Pressure↗
PubMed1994

General professional training in public health medicine--the Leicestershire Senior House Officer scheme.

BACKGROUND: This study investigates the subsequent careers of the Senior House Officers (SHOs) who have passed through the Leicestershire SHO training scheme in public health medicine since its inception in 1981 and their views of the scheme. METHODS: Postal questionnaires were sent to past and current SHOs, using addresses compiled from personnel records, the Medical Directory and the General Medical Council Medical Register. One reminder letter was sent to non-responders. RESULTS: Of the 21 past SHOs, one is now a consultant and four are currently trainees in public health medicine. Other past SHOs have followed diverse careers but the largest group are now in general practice. The four past SHOs who are now trainees in public health gained no further clinical experience before obtaining registrar or lecturer posts. All past SHOs responded favourably when asked about the benefits of the scheme regardless of their subsequent career choice. CONCLUSION: The continuing need for high-calibre recruits to the specialty and the favourable response from past SHO trainees suggests that this scheme, and no doubt other similar schemes, should be making their benefits known to a wider audience.

Career Choice↗