Biomedical subjects
Publications and source records attributed to M Griffiths.
This paper adds further comments to a case description by Young on addictive use of the Internet. Brief comments relating to the Internet as a behavioural addiction and the problem of to what users are actually addicted, are discussed.
Preliminary observational data relating to slot machine gamblers in two amusement arcades were collected over 3 mo. in the winter in Plymouth (south-west England). Arcades were frequented largely by males most of whom appeared to be adolescent. Slot machine gambling seemed to be an essentially solitary activity even when people entered the arcades in groups.
Health care economic efficiency is important. Adult tonsillectomy is a common operation. The decision to operate is made at an out-patient consultation and is based on information in the general practitioner's (GP) referral letter. This study aims to define what proportion of adult tonsillectomies are suitable for listing with an out-patient consultation (direct listing). GPs were informed of the indications (six episodes of tonsillitis in the last year) and contraindications (tonsillectomy for another reason and general ill health) for direct listing. All referrals for 1 year were screened by an otolaryngologist and suitable patients were listed directly. Patients were then reviewed in the anaesthetic pre-admission clinic and inappropriate listings were cancelled and reasons noted. Of all patients, 50% were suitable for direct listing. Of these 3% were later deemed inappropriate. None of the cancellations were due to a flaw in the direct listing process. This would result in savings to the NHS of 2 million pounds per annum.
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A series of 101 peptides each 20 amino acids in length (10-residue overlap) spanning the helical portion of the mature alpha-chain of human type II collagen (CII) was synthesized. DBA/1 (H-2q) mice were immunized with individual peptides, and draining lymph node cells were challenged in vitro. Strong responses were measured to three peptides: peptide I (residues 74-93), peptide 14 (residues 254-273), and peptide 81 (residues 924-943). B10.Q (H-2q) mice were responsive to peptides I and 81 but not to peptide 14. B10.RIII (H-2r) mice, which are resistant to arthritis induction following immunization with human CII, were unresponsive to peptides I, 14, and 81. Using single amino acid truncated peptides, we determined minimal immunostimulatory lengths for peptides I and 81. Residues critical to antigenicity were identified by introducing alanine and glycine substitutions into minimal length immunostimulatory peptides. The determinants within peptides I and 81 are 100% homologous to mouse CII and are autoantigens. Peptide 81 has homology to viral proteins. Peptide 14 is 90% homologous to mouse CII and has homology to heat shock proteins.
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There is growing evidence that children and adolescents who gamble excessively on fruit machines may engage themselves in stealing and commit other criminal offences to fund their habit yet there has been little evidence from the legal professions themselves. The aim of the survey conducted was to see if there was any relationship between criminal activity (most notably theft) and gaming machine use. During a 1-year period, police officers in Plymouth (South West England) collected information from 1851 juvenile offenders with whom they came into contact. The results revealed approximately 4% of juvenile crime was associated with gaming machine use and the survey offers evidence that a minority of individuals commit crimes in order to supplement their fruit machine playing.
Current research into the aetiology of the dementias is focused upon genetic factors which give rise to the disease process. Recently the Apolipoprotein E gene (APO E) and in particular the epsilon 4 allele has been shown to be a risk factor for late onset Alzheimer's disease (AD) where there is an increased frequency of the epsilon 4 allele. The epsilon 4 allele has also been shown to reduce the age at onset of dementia in AD in a dose dependent manner, with the epsilon 2 allele having an opposing effect. We have genotyped a large series of clinically and neuropathologically confirmed cases of AD and found the expected increase in the Apolipoprotein epsilon 4 allele frequency when compared to a control population. Similarly, in Lewy Body Dementia (LBD) an increased epsilon 4 frequency is also found though a normal epsilon 2 frequency exists, unlike in AD where the epsilon 2 frequency is reduced. No changes in APO E allele frequencies were found in presenile AD, Parkinson's disease with or without dementia, or in Down's syndrome. No association was found between any of the APO E alleles and the histopathological indices of AD, cortical senile plaques and neurofibrillary tangles, in any disease category. Neurochemical indicators of AD, loss of choline acetyltransferase activity was also unaffected by APO E genotype. Whilst their appears to be a strong association between the APO E allele and AD and also in LBD, other related neurodegenerative disorders associated with dementia do not show such a linkage. Changes in the epsilon 2 allele frequency may indicate a genetic difference between AD and LBD. The epsilon 4 allele does not appear to influence the burden of AD type pathology and this is particularly relevant given the relative lack of NFT in LBD indicating that factors other than SP or NFT may govern the onset of dementia.
Most national surveys into gambling have concluded that there are more gamblers than non-gamblers. Although most gamblers can control their gambling behaviour, a small minority can suffer from pathological gambling. The acquisition, development and maintenance of pathological gambling is an area that is continually disputed and was only recognized as a bona fide mental disorder in the third edition of the Diagnostic and Statistical Manual (DSM-III, American Psychiatric Association 1980). The exact causes and reasons for continuing gambling behaviour seem to be dependent upon the individual, but there does seem to be some general underlying factors and reoccurring themes. This paper reviews the prevalence and history of pathological gambling and traces the phases of the pathological gambler's career. It is concluded that explanations of gambling behaviour (and particularly excessive gambling) are best served by an integrated biopsychosocial model, which stresses the individuality and idiosyncratic nature of the development of gambling problems.
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High affinity (-)nicotine ([3H]nicotine), alpha-bungarotoxin ([125I]alpha-bungarotoxin) and muscarinic binding ([3H]N-methyl scopolamine) in the human cerebellum were compared between the foetal period (23-39 weeks gestation) and young adulthood (14-34 years) in an autoradiographic study. To estimate proportions of muscarinic receptor subtypes variable wash times and displacement with pirenzepine were employed. [3H]Nicotine binding and total muscarinic binding in foetuses exceeded that in young adults by a factor of 6 and 2 respectively in the dentate nucleus, and by a factor of 3 in white matter. [3H]Nicotine and muscarinic binding was also higher in the foetal external granule cell layer than in the internal granule cell layer of adult, [125I]alpha-Bungarotoxin binding was raised in the dentate nucleus of the foetus compared with the adult. The M2 subtype appeared to be the predominant muscarinic receptor in the cerebellum, however it tended to represent a lower proportion of the muscarinic binding in the foetus than the adult. All 3 receptor types were highest in the foetal brainstem where the M3 + M4 muscarinic subtypes appeared to predominate. The p75 nerve growth factor receptor, measured by immunocytochemistry, in common with cholinergic receptors, paralleled choline acetyltransferase activity which has previously been reported to be high in the cerebellum during late foetal development and to fall in adulthood.
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Glomerulonephritis with proteinuria of sufficient degree to manifest the nephrotic syndrome followed aplastic crises induced by human parvovirus (B19) in seven patients with homozygous sickle-cell disease, within 7 days in five patients and 6-7 weeks in two. Segmental proliferative glomerulonephritis was found in all four patients who underwent acute renal biopsies and focal segmental glomerulosclerosis was found in the fifth patient who had a biopsy 4 months later. One patient recovered completely, one died in chronic renal failure after 3 months, and the others had impaired creatinine clearance, four with continuing proteinuria.
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The uptake of glucose into mammalian cells, catalysed by members of the GLUT family of glucose transporters, is regulated by a variety of hormones, growth factors and other agents. In adipocytes, skeletal muscle and heart the principal regulator is the hormone insulin, which rapidly stimulates glucose uptake by bringing about the translocation of the GLUT4 glucose transporter isoform from an intracellular vesicular compartment to the cell surface. Recent studies have implicated the C-terminal hydrophilic region of this protein as being primarily responsible for its insulin-regulated trafficking. In an attempt to identify the protein machinery involved in this trafficking, we have used glutathione S-transferase fusion proteins bearing hydrophilic domains of various GLUT transporters in affinity purification experiments on detergent-solubilized extracts of 3T3-L1 adipocyte intracellular membranes. The C-terminal region of GLUT4 was found specifically to bind a number of polypeptides in these extracts, which are therefore candidates for components of the trafficking machinery. Although these proteins did not bind to the corresponding region of the more widely-distributed GLUT1 glucose transporter isoform, regulation of this transporter also appears to be of physiological importance in some cell types. To study such regulation we have used as a model system the interleukin-3 (IL-3)-dependent haemopoietic cell line IC.DP. These cells express a temperature sensitive mutane of the v-abl tyrosine kinase, whose activation at the permissive temperature permits cell survival in the absence of IL-3 by suppression of apoptosis, although the growth factor is still required for proliferation. Both IL-3 and activation of the kinase were found to stimulate glucose transport by promoting the translocation of GLUT1 to the cell surface. Moreover, inhibition of glucose uptake by addition of transport inhibitors markedly increased the rate of apoptosis, an effect which could be reversed by the provision of alternative energy sources. These observations suggest that the trafficking of GLUT1, regulated by growth factors or oncogenes, may play an important role in the suppression of apoptosis in haemopoietic cells.
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A microprocessor-based system of photoplethysmography and its use in measuring skin blood flow is described. The system was designed specifically for use over long periods and for the analysis of the output to be handled by a personal computer. The photoplethysmograph described in this paper is shown to be a qualitative method for assessment of changes in peripheral skin blood flow. There is potential for use of this instrument in a variety of clinical conditions.