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Biomedical subjects

P Brown

Publications and source records attributed to P Brown.

At least 163 records · Page 9Linked to original sources

The risk of blood-borne Creutzfeldt--Jakob disease.

With the increasing ability of modern medicine to transfer life-giving tissues and tissue products from one individual to another comes a parallel, often life-taking consequence of the unsuspected transfer of infectious passengers. Creutzfeldt-Jakob disease (CJD) has been transmitted by contaminated stereotactic EEG electrodes, neurosurgical instruments, dura mater allografts, and cadaveric pituitary hormone therapy. Widespread concern has been voiced about the possible risks of transmitting CJD through the administration of blood or plasma products, although no such case has so far been identified by epidemiological studies of at-risk populations. Recently completed experiments using hamsters and mice showed decreasing levels of infectivity in buffy coat, plasma, cryoprecipitate (the source of anti-haemophilic factor), and fraction I + II + III (the source of immune globulin). Preliminary results from further rodent experiments indicate that little or no infectivity is detectable in plasma during the pre-clinical phase of infection, that plasma infectivity is not reduced by either leukodepletion filtration or high speed centrifugation, and that about 5-10 times more infectivity is needed to transmit disease by the intravenous than intracerebral route. Altogether, the data from these rodent studies, especially when considered together with results from similar studies underway in primates, should provide a rational foundation for policy decisions by government agencies, plasma product manufacturers, and blood banking communities.

Animals↗

Variation in time spent on the waiting list for elective vascular surgery: a case study.

OBJECTIVE: To review the variation in time spent on the waiting list for elective vascular surgery provided by a single team of specialists. DESIGN: A prospective cohort study. SETTING: An acute care hospital in Ontario. POPULATION: One thousand and eighty-four consecutive patients with vascular problems accepted for elective surgery between 1994 and 1998. INTERVENTIONS: Abdominal aortic aneurysm (AAA) repair; carotid endarterectomy (CAD); surgery for peripheral vascular disease (PVD); and arteriovenous fistula (AVF) for long-term access in patients with renal failure. OUTCOME MEASURES: Time-to-treatment curves, admission rates. RESULTS: The weekly admission rate was 9.8% on average. The proportion of patients who underwent operation was 50% at 7 weeks, 75% at 14 weeks and 90% at 26 weeks. The weekly admission rate varied according to clinical priority, from 42% in priority class 1 to 6% in class 5. In any priority class, the admission rate was not constant over time. Although the proportion of patients operated on within the maximum recommended time in classes 1, 2, 3 and 4 was 52%, 50%, 35% and 20% respectively, the last 10% of patients waited 5 to 16 weeks, 10 to 16 weeks, 16 to 37 weeks, and 25 to 39 weeks respectively. There were statistically significant differences in waiting time by surgical procedure among the least urgent cases, with median times of 7, 10 and 19 weeks for AVF, PVD and CAD procedures, respectively. CONCLUSIONS: When queuing procedures are uniform, the waiting times for access to elective vascular surgery provided by the same team of specialists differ considerably for patients with equal surgical needs and urgency. It remains to be examined whether delays in scheduling operations and cancellations affect the waiting time after adjustment for urgency and comorbidity.

Age Factors↗

Comparing the ability of different area measures of socioeconomic status to segment a population according to caries prevalence.

OBJECTIVE: to compare the ability of different area based indicators of socio-economic status to segment a population of 5-year-old children according to caries prevalence. BASIC RESEARCH DESIGN: The study population consisted of all 5-year-old children in seven districts in the North West Region of England who were examined in whole population surveys during the 1995/6 NHS epidemiological survey. This population was segmented according to caries prevalence by market penetration analyses using Super Profiles and the ONS geodemographic classifications, Jarman and Townsend (at ward and ED level) deprivation indices, the single census variables of unemployment and percentage of households without a car, and also the school that the children attended. Lorenz curves were plotted from the outputs of the penetration analyses. MAIN OUTCOME MEASURES: Overall caries prevalence for the population was 55.3%. All the indicators provided a very similar picture. Large differences were detected between the highest and lowest market penetration rankings for each indicator, ranging from 42.5% for the ONS geodemographic classification to 31.4% for the Townsend index at enumeration district level. However, for each indicator, the fall between these two extremes was gradual. This picture was represented by the similar effectiveness scores of around 10% for each indicator which were derived from the Lorenz curves. Each indicator could identify approximately 30% of those with disease in the topmost 25% of the total population in the penetration ranking. When the analysis was restricted to those children with severe disease (dmft> or =5) a similar picture was found, however the effectiveness score increased to 19%. CONCLUSIONS: There was a remarkably consistent inequitable distribution of population disease prevalence found between deprived and affluent area types, irrespective of what measuring instrument was used. Although there was a large difference in prevalence (dmft>0 and dmft>5) found between deprived and affluent areas, there was a gradual fall between the two extremes. This gradual fall has implications for oral health improvement strategies.

Child, Preschool↗

A new point mutation of the PRNP gene in Gerstmann-Sträussler-Scheinker case in Poland.

We report here a case of Gerstmann-Sträussler-Scheinker (GSS) disease with a new mutation at the codon 232 (Met to Thr) of the PRNP gene. This case was characterized by PrP-immunopositive kuru and multicentric plaques; these plaques were also seen in the cerebral cortex, hippocampus and in the deep subcortical nuclei. Diffuse PrP depositions were also detected. In the temporal cortex, a few plaques were immunopositive for both PrP and Abeta; the latter was expressed at the periphery of the PrP-immunopositive cores. This mutation was absent from 40 healthy Polish controls and from 16 other Polish CJD cases, and we therefore believe that 232Thr is a new pathogenic mutation and not a benign polymorphism.

Amino Acid Substitution↗

Novel PRNP sequence variant associated with familial encephalopathy.

Human transmissible spongiform encephalopathies (TSEs) are a group of chronic progressive neurodegenerative disorders that may be hereditary, infectious, or sporadic. Hereditary TSEs are associated with mutations in the PRNP gene on chromosome 20p12-pter. We report on a family in which seven patients developed limb and truncal ataxia, dysarthria, myoclonic jerks, and cognitive decline. The age of onset in the 30s, 40s, or 50s, prolonged disease duration, cerebellar atrophy on imaging, and the presence of synchronic periodic discharges on electroencephalogram suggested a familial encephalopathy resembling Gerstmann-Sträussler-Scheinker disease. A novel H187R mutation has been identified in affected, but not in unaffected, family members or unrelated controls suggesting a pathogenic role for this mutation. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:653-656, 1999. Published 1999 Wiley-Liss, Inc.

Adult↗

The unilateral and bilateral control of motor unit pairs in the first dorsal interosseous and paraspinal muscles in man.

1. The discharges of two motor units were identified in an intrinsic hand muscle (first dorsal interosseous, FDI) or an axial muscle (lumbar paraspinals, PSP) in ten healthy subjects. Each motor unit was situated in the homologous muscle on either side of the body (bilateral condition) or in the same muscle (ipsilateral condition). The relationship between the times of discharge of the two units was determined using coherence analysis. 2. Motor unit pairs in the ipsilateral FDI showed significant coherence over the frequency bands 1-10 Hz and 12-40 Hz. Motor units in the ipsilateral PSP were significantly coherent below 5 Hz. In contrast there was no significant coherence at any frequency up to 100 Hz in the bilateral FDI condition and only a small but significant band of coherence below 2 Hz in the bilateral PSP condition. 3. Common drive to motor units at frequencies of < 4 Hz was assessed by cross-correlation of the instantaneous frequencies of the motor units. A significantly higher coefficient was found in the ipsilateral FDI, ipsi- and bilateral PSP compared with shifted, unrelated data sets. This was not the case for the bilateral FDI condition. 4. The presence of higher frequency coherence ( > 10 Hz) in the ipsilateral FDI condition and its absence in ipsilateral PSP is consistent with a more direct and influential cortical supply to the intrinsic hand muscles compared with the axial musculature. The presence of low frequency drives (< 4 Hz) in the bilateral PSP condition and its absence in the bilateral FDI condition is consistent with a bilateral drive to axial, but not distal, musculature by the motor pathways responsible for this oscillatory input.

Adult↗

Determination of the rate of the glutamate/glutamine cycle in the human brain by in vivo 13C NMR.

Recent 13C NMR studies in rat models have shown that the glutamate/glutamine cycle is highly active in the cerebral cortex and is coupled to incremental glucose oxidation in an approximately 1:1 stoichiometry. To determine whether a high level of glutamatergic activity is present in human cortex, the rates of the tricarboxylic acid cycle, glutamine synthesis, and the glutamate/glutamine cycle were determined in the human occipital/parietal lobe at rest. During an infusion of [1-13C]-glucose, in vivo 13C NMR spectra were obtained of the time courses of label incorporation into [4-13C]-glutamate and [4-13C]-glutamine. Using a metabolic model we have validated in the rat, we calculated a total tricarboxylic acid cycle rate of 0.77 +/- 0.07 micromol/min/g (mean +/- SD, n = 6), a glucose oxidation rate of 0.39 +/- 0.04 micromol/min/g, and a glutamate/glutamine cycle rate of 0.32 +/- 0.05 micromol/min/g (mean +/- SD, n = 6). In agreement with studies in rat cerebral cortex, the glutamate/glutamine cycle is a major metabolic flux in the resting human brain with a rate approximately 80% of glucose oxidation.

Adult↗