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Biomedical subjects

P Little

Publications and source records attributed to P Little.

At least 73 records · Page 4Linked to original sources
PubMed1995

Self screening for risk of melanoma: validity of self mole counting by patients in a single general practice.

OBJECTIVE: To validate self screening by patients of high mole counts, assess the within family association of sun protection behaviour and mole counts, and estimate prevalence of risk factors for melanoma. SETTING AND SUBJECTS: Systematic sample of families from a single affluent general practice population in Wessex. DESIGN: Subjects completed a questionnaire about risk factors for melanoma and counted their moles. Subsequently a mole count was done by a general practitioner trained at dermatology clinics. MAIN OUTCOME MEASURES: Validation of self counts by observer's count. Within family association of sun protection behaviour and mole counts; self reported risk factors. RESULTS: 199/237 subjects (84%) returned the questionnaire; 212/237 (89%) were examined. High counts by patients on the front of the trunk (> 7 moles of > or = 2 mm) were reasonably sensitive (79%), predictive (75%), and specific (97%) of the observer's mole counts (kappa = 0.74), unlike arm or total body counts. Sun protection behaviour correlated between individuals and other family members (Spearman's coefficient r = 0.50, P < 0.01). In the past three months 15/114 adults (13.2%, 95% confidence interval 7.0% to 19.4%) reported any change in a mole and 6/114 (5.3%, 2.0% to 11.1%) "major" changes; 6/109 adults (5.5%, 2.1% to 11.6%) had both high mole counts and freckling. CONCLUSIONS: Asking patients to count trunk moles could be a feasible way of identifying patients at high risk of melanoma. Concentrating on reported major changes in moles should avoid considerable workload in general practice. The generalisability of these findings and the adverse effects, net benefit in earlier diagnosis and prevention, and workload implications of such self screening need further research.

Adolescent↗
PubMed1995

[Do glycoproteins IIb/IIIa participate in activation of human platelet s by low density lipoproteins?].

Low density lipoproteins (LDL) enhance the entry of Ca2+ and other bivalent cations via receptor-operated channels. The use of a synthetic peptide and antibodies blocking the glycoproteins IIb and IIIa interaction with ligands revealed that fibrinogen receptor antagonists prevent platelet aggregation without any effect on the ability of LDL to increase the cytoplasmic Ca2+ level. These data indicate that glycoproteins IIb-IIIa are not involved in the activation of the second messenger system by LDL but play a role in the proaggregant effect of LDL by providing cell-to-cell interactions.

Blood Platelets↗
PubMed1994

Genetic and physiological association of diabetes susceptibility with raised Na+/H+ exchange activity.

Insulin-dependent diabetes mellitus is a multigenic autoimmune disease, for which one of the best animal models is the nonobese diabetic (NOD) mouse strain. In both humans and NOD mice, major histocompatibility complex genes are implicated as risk factors in the disease process. Other susceptibility genes are also involved, and a number have been mapped in the mouse to specific chromosomal locations. To identify further susceptibility genes, diabetic backcross mice, produced after crossing NOD/Lt to the nondiabetic strains SJL and C57BL/6 (B6), were examined for markers not previously associated with disease susceptibility. Linkage was found to loci on chromosomes 4 and 14. Of the candidate loci on chromosome 4, the gene encoding the Na+/H+ exchanger-1, Nhe-1, was the most likely, since the NOD allele was different from that of both nondiabetic strains. NOD lymphocytes were found to have a higher level of Na+/H+ exchange activity than lymphocytes from either B6 or SJL mice. Since the chromosome 4 susceptibility gene is recessive, the B6 allele should prevent diabetes. This prediction was tested in fourth-generation backcross mice, selected for retention of the B6 allele at Nhe-1. Mice homozygous for Nhe-1 developed diabetes after cyclophosphamide treatment, but heterozygotes were largely protected from disease. These results implicate the Na+/H+ exchanger (antiporter) in the development of type 1 diabetes and may provide a screening test for at-risk individuals as well as offering prospects for disease prevention.

Alleles↗
PubMed1994

What do Wessex general practitioners think about the structure of hospital vocational training?

OBJECTIVES: To assess the views of general practitioners about the structure and content of hospital vocational training and its relation to the training year. DESIGN: Postal questionnaire. SETTING: Wessex, England. SUBJECTS: General practitioner trainees undertaking practice training year (n = 144), course organisers (n = 22), and a random sample of two thirds of trainers (n = 135). RESULTS: Questionnaires were returned from 86% (260): 84% of trainees (121), 92% of trainers (124), and 68% of course organisers (15). Most respondents in all groups (84.3%, 95% confidence interval 79.7% to 88.8%) wanted more jobs lasting two and three months to allow a greater range of hospital specialties to be experienced and some of the training year to be carried out before hospital jobs (66.3%, 60.4% to 72.1%). Most hospital specialties were rated at least 6 out of 10 as "useful" for general practice training. A substantial minority of training posts did not have regular weekly teaching (166/541; 30.7%, 26.8% to 34.6%) and had no half day (224/541; 41.4%, 37.3% to 45.6%), and over half gave no study leave (293/541; 54.2%, 50.0% to 58.4%). CONCLUSIONS: The structure of hospital training should be reviewed as it does not reflect the views of most trainees, course organisers, or trainers. Individual posts need closer supervision to ensure the availability of basic training requirements. More trainees should be allowed to spend a short time in the general practice before hospital rotations and to choose a greater range of shorter jobs.

Attitude of Health Personnel↗
PubMed1994

Parental imprinting of human chromosome region 11p15.3-pter involved in the Beckwith-Wiedemann syndrome and various human neoplasia.

Cytogenetic and DNA analyses of patients with the Beckwith-Wiedemann syndrome (BWS) enabled us to refine the localization of the syndrome at 11p15.3-pter to two distinct regions. One chromosome region (BWSCR1) is near the insulin (INS) and insulin-like growth factor 2 (IGF2) genes. The other region (BWSCR2) is more proximal near two sequences with zinc-binding finger motifs and a number of known and putative genes. This latter region, at least, seems to be associated with the development of childhood tumors. Our results strongly support the proposed involvement of parental imprinting in the etiology of BWS since all balanced chromosomal abnormalities in these patients were maternally transmitted while the mothers were phenotypically normal. We demonstrate that such an autosomal balanced rearrangement can lead to a specific maternal hypomethylation of the INS/IGF2 genes localized distal to the breakpoint. This underlines the role of these genes in the etiology of the syndrome.

Beckwith-Wiedemann Syndrome↗
PubMed1993

Hearing impairment and ear pathology in Nepal.

A stratified random cluster sample of 15,845 subjects was performed in two regions of Nepal to determine the prevalence and main causes of hearing impairment (the most common disability) and the prevalence of ear disease. Subjects reporting current ear pain, or ear discharge, or hearing impairment on direct questioning by a Nepali health worker (primary screening failed), had otoscopy and audiometry (using the Liverpool Field Audiometer) performed, and a questionnaire administered relating to past history. In every fifth house subjects who passed the primary screening (1,716 subjects) were examined to assess the false negative rate of screening. An estimated 16.6 per cent of the study population have hearing impairment (either ear worse than 30 dB hearing threshold level (HTL) 1.0-4.0 kHz, or 50 dB HTL 0.5 kHz), and 7.4 per cent ear drum pathology, equivalent to respectively 2.71 and 1.48 million people extrapolated to the whole of Nepal. Most hearing impairment in the school age group (55.2 per cent) is associated with otitis media or its sequelae. Probably at least 14 per cent of sensorineural deafness is preventable (7 per cent infectious disease, 3.9 per cent trauma, 0.8 per cent noise exposure, 1 per cent cretinism, and 1 per cent abnormal pregnancy or labour). Most individuals reporting current ear pathology (61 per cent) had never attended a health post, and of those receiving ear drop treatment, 84 per cent still had serious pathology. Of subjects who reported ear drop treatment at any time, 31 per cent still had serious pathology. The use of traditional remedies was prevalent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Movement of individuals with complex epilepsy from an institution into the community: seizure control and functional outcomes.

The successful community placement of 15 medically fragile individuals with profound mental retardation and complex epilepsy was examined. We found that simplification of anticonvulsants, early intervention for seizures, and improved staff education resulted in (a) fewer seizures, (b) decreases in emergency room visits for status seizures and drug-related side effects, and (c) increased levels of functioning as measured by activities of daily living. This program allowed for a medically fragile epileptic population to be transferred from the institution to the community.

Activities of Daily Living↗
PubMed1992

Reciprocal changes in myosin isoform mRNAs of rabbit skeletal muscle in response to the initiation and cessation of chronic electrical stimulation.

Changes in myosin heavy chain (MHC) mRNAs were studied in rabbit fast-twitch muscles during continuous electrical stimulation at 10 Hz for periods up to 3 weeks, and during the first 12 days of the recovery process that followed cessation of 6 weeks' stimulation. Two cDNA probes were used to detect MHC mRNAs specific to fast- and slow-twitch skeletal muscle in RNase protection assays and Northern- and slot-blot analyses. The isolation and base sequence of one of these probes, corresponding to the MHC gene expressed in soleus (slow-twitch), is described. At an early stage of the response to stimulation, fast MHC mRNA was replaced by slow MHC mRNA. During recovery, this process occurred in reverse but took longer. The time course of recovery was slightly faster in tibialis anterior than in extensor digitorum longus. The changes in mRNAs during both stimulation and recovery reflected changes in the corresponding muscle proteins.

Animals↗
PubMed1992

11p15.5-specific libraries for identification of potential gene sequences involved in Beckwith-Wiedemann syndrome and tumorigenesis.

Constitutional and somatic chromosomal abnormalities of the chromosome 11p15 region are involved in an overgrowth malformation syndrome, the Beckwith-Wiedemann syndrome (BWS), and in several types of associated tumors. The bias in parental origin for the different etiologic forms of this syndrome and for loss of heterozygosity in the tumors suggests that a gene (or genes) mapping to this region undergoes genomic imprinting. However, the precise localization of the locus (or loci) for the BWS and associated tumors is still unknown and more markers are required. We therefore isolated 11p15 markers from two libraries: the first one obtained by microdissection of the chromosome 11p15.5 region and the second one, a phage library, constructed from a hybrid cell line containing this region as its sole human DNA. Of 19 microclones isolated from the microdissection library, 11 were evolutionarily conserved. Four phage clones were isolated; one (D11S774) detected a highly informative variable number of tandem repeats (VNTR) and another (D11S773) a biallelic polymorphism. These clones were sublocalized using a panel of somatic cell hybrids that defines eight physical intervals in 11p15.5. Twenty-one clones map to the distal interval that harbors the BWS locus.

Animals↗
PubMed1992

Reciprocal changes in myosin isoform expression in rabbit fast skeletal muscle resulting from the application and removal of chronic electrical stimulation.

Chronic indirect electrical stimulation of adult mammalian skeletal muscle brings about a transformation from the fast-twitch to the slow-twitch type. Underlying this transformation there is a sequence of profound changes in the expression of proteins involved in all the major molecular systems of the muscle. These include qualitative changes in the expression of myosin light and heavy chain isoforms. The time course of these changes has been studied in some detail at the protein level, both during chronic stimulation and during the recovery process that follows the cessation of stimulation. Here we report on the use of cDNA probes to study corresponding changes in myosin heavy chain (MHC) and light chain (MLC) mRNAs in rabbit fast-twitch muscles during continuous electrical stimulation at 10 Hz and during the first 12 days of recovery after cessation of 6 weeks of stimulation. At an early stage of the response to stimulation, fast MHC mRNA is replaced by slow MHC mRNA. During recovery this process occurs in reverse but takes longer. Broadly similar changes are seen for MLC mRNAs, although the time course is somewhat different. These experiments contribute to a growing body of evidence that many of the protein changes induced by chronic stimulation are the result of regulatory events that take place at a pre-translational level.

Animals↗
PubMed1991

Multiple growth abnormalities in vascular smooth muscle from spontaneously hypertensive rats.

1. In tissue culture the growth characteristics of aortic smooth muscle cells isolated from spontaneously hypertensive rats (SHR) were compared with those of normotensive Wistar-Kyoto (WKY) rats. 2. Aortic smooth muscle cells from SHR exhibit enhanced proliferation when grown in the presence of low (1%) and moderate (5%) concentrations of fetal calf serum. 3. Cell quiescence in cultures of smooth muscle from SHR becomes apparent at cell densities approximately 20% higher than in cultures from WKY rats. 4. These different growth characteristics of smooth muscle between the two strains of rats may contribute to the early pre-hypertensive development of vascular hypertrophy in the SHR.

Animals↗