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Biomedical subjects

J Wasson

Publications and source records attributed to J Wasson.

At least 19 recordsLinked to original sources
PubMed2006

Optimizing training opportunities for otolaryngology senior house officers: an audit.

Implementation of the European Working Time Directive and the Modernising Medical Careers initiative will mean junior surgeons must be trained in fewer hours over a shorter period. For this reason, junior surgeon training opportunities must be optimized. We undertook a departmental audit to identify where opportunities to train senior house officers (SHOs) in theatre were being lost, so that appropriate timetable changes could be made in order to optimize exposure to suitable surgical cases. During the first audit cycle, the SHOs followed their existing timetable and theatre attendance was monitored prospectively over a two-week period. Only 30 per cent of theatre sessions were attended and case participation was only 27 per cent. Simple timetable changes were made to maximize SHO theatre attendance, and a second prospective two-week audit was undertaken. The new rota yielded 46 per cent theatre attendance and 48 per cent case participation.

Education, Medical, Graduate↗
PubMed2006

Did Ludwig's angina kill Ludwig?

Wilhelm Frederick von Ludwig first described in 1836 a potentially fatal, rapidly spreading soft tissue infection of the neck and floor of the mouth. The condition was later named 'Ludwig's angina', a term which persists in medicine to this day. A gold medallist at 19 and professor at 25, Ludwig also served as president of the Württemberg Medical Association and chief physician to the royal family. His outstanding contribution to medicine was rewarded with the title Excellence upon retiring in 1855. Ludwig died at the age of 75, ironically, days after developing an inflammation of the neck. Could it be that Ludwig died of his own condition? This article combines a biography of Wilhelm Frederick von Ludwig with an overview of his eponymous condition and its management.

Eponyms↗
PubMed2005

Mice conditionally lacking the Wolfram gene in pancreatic islet beta cells exhibit diabetes as a result of enhanced endoplasmic reticulum stress and apoptosis.

AIMS/HYPOTHESIS: Wolfram syndrome is an autosomal recessive disorder characterised by childhood diabetes mellitus, optic atrophy and severe neurodegeneration, resulting in premature death. The aim of this study was to investigate the mechanisms responsible for the phenotype of carbohydrate intolerance and loss of pancreatic beta cells in this disorder. MATERIALS AND METHODS: To study the role of the Wolfram gene (Wfs1) in beta cells, we developed a mouse model with conditional deletion of Wfs1 in beta cells by crossing floxed Wfs1 exon 8 animals with mice expressing Cre recombinase under the control of a rat insulin promoter (RIP2-Cre). Complementary experiments using RNA interference of Wfs1 expression were performed in mouse insulinoma (MIN6) cell lines (WfsKD). RESULTS: Male knockout mice (betaWfs(-/-)) began developing variable and progressive glucose intolerance and concomitant insulin deficiency, compared with littermate controls, by 12 weeks of age. Analysis of islets from betaWfs(-/-) mice revealed a reduction in beta cell mass, enhanced apoptosis, elevation of a marker of endoplasmic reticulum stress (immunoglobulin heavy chain-binding protein [BiP]), and dilated endoplasmic reticulum with decreased secretory granules by electron microscopy. WfsKD cell lines had significantly increased apoptosis and elevated expression of the genes encoding BiP and C/EBP-homologous protein (CHOP), two markers of endoplasmic reticulum stress. CONCLUSIONS/INTERPRETATION: These results indicate that (1) lack of expression of Wfs1 in beta cells was sufficient to result in the diabetes mellitus phenotype; (2) beta cell death occurred by an accelerated process of apoptosis; and (3) lack of Wfs1 was associated with dilated endoplasmic reticulum and increased markers of endoplasmic reticulum stress, which appears to be a significant contributor to the reduction in beta cell survival.

Animals↗
PubMed2004

Diabetes mellitus and optic atrophy: a study of Wolfram syndrome in the Lebanese population.

Wolfram syndrome (WFS) is a rare hereditary neurodegenerative disorder also known as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). WFS seems to be a heterogeneous disease that has not yet been fully characterized in terms of clinical features and pathophysiological mechanisms because the number of patients in most series was small. In this study we describe 31 Lebanese WFS patients belonging to 17 families; this, to our knowledge, is the largest number of patients reported in one series so far. Criteria for diagnosis of WFS were the presence of insulin-dependent diabetes mellitus and optic atrophy unexplained by any other disease. Central diabetes insipidus was found in 87% of the patients, and sensorineural deafness confirmed by audiograms was present in 64.5%. Other less frequent features included neurological and psychiatric abnormalities, urodynamic abnormalities, limited joint motility, cardiovascular and gastrointestinal autonomic neuropathy, hypergonadotropic hypogonadism in males, and diabetic microvascular disease. New features, not reported in previous descriptions, such as heart malformations and anterior pituitary dysfunction, were recognized in some of the patients and participated in the morbidity and mortality of the disease. Genetic analysis revealed WFS1 gene mutations in three families (23.5%), whereas no abnormalities were detected in mitochondrial DNA. In conclusion, WFS is a devastating disease for the patients and their families. More information about WFS will lead to a better understanding of this disease and hopefully to improvement in means of its prevention and treatment.

Adolescent↗
PubMed2001

Panel-based pain management in primary care. a pilot study.

Although pain is an extremely common symptom presenting to primary care physicians, it frequently is not optimally managed. The purpose of this feasibility study was to develop and pilot-test an efficient, rapid assessment and management approach for pain in busy community practices. The intervention utilized the Dartmouth COOP Clinical Improvement System (DCCIS) and a telephone-based, nurse-educator intervention. Patients from four primary care practices in rural New Hampshire and Vermont were screened by mail for the presence of persistent pain. Patients with mild to severe pain were randomized to either the usual care control group (n = 383) or the intervention group (n = 320). Patients who reported pain but no psychosocial problems received a summary of identified problems and targeted educational material via mail (DCCIS). Patients who reported pain and psychosocial problems received the DCCIS intervention and calls from a nurse-educator who provided pain self-management strategies and a problem-solving approach for psychosocial problems. Post-treatment evaluation revealed that patients in the intervention group scored significantly better on the Pain, Physical, Emotional, and Social subscales of the SF-36 and on the total score of the Functional Interference Scale, as compared to a usual care control group. Feasibility and acceptability of the approach were demonstrated; however, the conclusions based on analyses of the post-treatment outcomes were tempered by baseline imbalances across groups.

Feasibility Studies↗
PubMed1999

Measuring costs in multisite randomized controlled trials: lessons from the VA Cooperative Studies Program.

OBJECTIVES: The interest in the economic impact of new health care interventions has increased dramatically over recent years; however, the results can be highly variable depending upon the economic assumptions made and the approaches taken in collecting the data and in conducting the analyses. This paper describes experiences from the VA Cooperative Studies Program in measuring health care utilization and costs for studies that evaluate clinical interventions. METHODS: Experiences from two multisite randomized clinical trials (RCTs) are highlighted to illustrate strategies used to measure costs by directly measuring health care utilization and economic data within the context of the trials. CONCLUSIONS: Despite the substantial resources required to gather evidence about the cost of care for health care innovations, future VA multisite studies should include accepted health economic approaches to make important contributions to health planning and health policy within and outside the VA health care system.

Costs and Cost Analysis↗
PubMed1998

Mapping of the human insulin receptor substrate-2 gene, identification of a linked polymorphic marker and linkage analysis in families with Type II diabetes: no evidence for a major susceptibility role.

Insulin receptor substrate 2 (IRS-2) is a substrate of the insulin receptor and mediates the action of the insulin. Disruption of the IRS-2 gene in mice results in peripheral insulin resistance and relative insulin deficiency. It is therefore possible that defects in the IRS-2 gene contribute to Type II (non-insulin-dependent) diabetes mellitus. We have examined the gene for evidence of linkage to Type II diabetes in Ashkenazi Jewish families. Radiation hybrid panel mapping was used to refine the map position of the IRS-2 gene and, in the absence of polymorphic markers within the gene, to identify nearby markers. The IRS-2 gene was placed 23cR from the marker D13S1265 on chromosome 13q34. 200 affected sib-pairs were genotyped for three markers across the region. Nonparametric linkage analysis (GENEHUNTER) used with this data found no evidence of excess allele sharing in the IRS-2 gene region. We therefore concluded that variation in the IRS-2 gene is unlikely to contribute to Type II diabetes in this discrete Caucasian population.

Animals↗
PubMed1998

A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome).

Wolfram syndrome (WFS; OMIM 222300) is an autosomal recessive neurodegenerative disorder defined by young-onset non-immune insulin-dependent diabetes mellitus and progressive optic atrophy. Linkage to markers on chromosome 4p was confirmed in five families. On the basis of meiotic recombinants and disease-associated haplotypes, the WFS gene was localized to a BAC/P1 contig of less than 250 kb. Mutations in a novel gene (WFS1) encoding a putative transmembrane protein were found in all affected individuals in six WFS families, and these mutations were associated with the disease phenotype. WFS1 appears to function in survival of islet beta-cells and neurons.

Adult↗
PubMed1997

Mapping novel pancreatic islet genes to human chromosomes.

A strategy was developed to generate expressed sequence tags (ESTs) from human pancreatic islet gene products using differential display of mRNA. Screening of over 2,000 cDNA amplification products identified 42 cDNAs that were preferentially expressed in pancreatic islets relative to exocrine tissue. Public database analysis showed that 29 (69%) corresponded to novel genes, in contrast with only 66 of 250 (26.4%) cDNA clones randomly selected from a human islet library. Reverse transcription-polymerase chain reaction (RT-PCR) and/or Northern analysis of RNA from multiple tissues confirmed that expression was enhanced in human islet cell RNA for 11 of 15 tested cDNAs. Sequence-tagged sites developed from 19 islet cDNAs were used to map these genes to human chromosomes using a combination of monochromosomal somatic-cell hybrids, genome-wide radiation hybrids, and mega-yeast artificial chromosome analysis. These results indicate that this PCR-based cDNA selection strategy yields information on a distinct subset of pancreatic islet transcribed sequences, which complements ongoing human EST identification efforts based on random cDNA selection. These mapped ESTs may be used to assist in the positional cloning of diabetes susceptibility genes.

Animals↗
PubMed1996

Cloning of human pancreatic islet large conductance Ca(2+)-activated K+ channel (hSlo) cDNAs: evidence for high levels of expression in pancreatic islets and identification of a flanking genetic marker.

Insulin secretion from pancreatic beta cells is dependent on membrane potential changes that result from the concerted regulation of multiple ion channels. Among the distinct K+ channels known to be expressed in beta cells, large conductance Ca(2+)-activated K+ channels have been suggested to play an important role in stimulus-secretion coupling. In the course of a strategy to identify transcripts that are enriched in human pancreatic islet cells, we isolated a partial cDNA encoding a human large conductance Ca(2+)-activated K+ channel mRNA (hSlo). Northern analysis of mRNA showed that among a panel of human tissues hSlo is expressed at its highest levels in pancreatic islets. Screening of human insulinoma and islet cDNA libraries with the partial cDNA resulted in the isolation of 19 hSlo cDNAs. These comprised three splice variants: one shared the common underlying structure of previously reported Slo cDNAs, another variant encoded a novel 60-amino acid insertion in the putative Ca(2+)-sensing domain of hSlo, while the third group of clones had an alternate exon encoding eight amino acids in the predicted COOH-terminal end. Analysis of somatic-cell hybrids containing different portions of chromosome 10 indicated that hSlo maps to chromosome 10q22.2-q23.1. Furthermore, high resolution localization was obtained by analysis of genome-wide radiation hybrids and the CEPH "B" mega-YAC library, both of which identified for the first time a highly polymorphic genetic marker (D10S195) linked to hSlo. These studies provide tools with which to explore the physiological role of Ca(2+)-activated K+ channel proteins in pancreatic islets, and also to investigate the contribution of this locus to the inherited susceptibility to non-insulin-dependent diabetes mellitus.

Alternative Splicing↗
PubMed1996

Reduction of length of stay and cost of transurethral resection of the prostate by early catheter removal.

OBJECTIVE: To determine whether early removal of the indwelling Foley catheter after transurethral resection of the prostate (TURP) significantly shortens the hospital stay without causing additional morbidity and thus saves costs. PATIENTS AND METHODS: For the year commencing 1 July 1991, 119 patients who had undergone TURP had their indwelling catheter removed on the first day after surgery. The results and morbidity of this group of patients were compared with those in 152 patients undergoing TURP during the previous year. The economic consequences of this protocol were calculated using both Medicare and CHAMPUS data. RESULTS: The demographics of the patients in both groups were similar. Post-operative complications occurred in 5% of the study patients and in 6.6% of controls; a transfusion was required in 2.5% and 1.3%, clot retention developed in 1.7% and 3.3% and the hospital stay was reduced from 3.1 to 1.28 days in the study and control patients, respectively. Using Medicare data, the mean cost saving of early catheter removal would be $829 and $1406 for patients aged < 70 and > 70 years, respectively. For CHAMPUS patients, the cost saving would be $1983. CONCLUSION: Early removal of the catheter after TURP did not increase morbidity and maintained the efficacy of the procedure. If this practice was adopted nationally, the savings resulting from the reduction in hospital stay would be considerable.

Aged↗
PubMed1996

Identification of trinucleotide repeat-containing genes in human pancreatic islets.

In the search for diabetes genes, the combined approaches of positional cloning with random markers and subsequent evaluation of candidate genes mapping to areas of interest will be increasingly used. For islet candidate genes of unknown function, expressed trinucleotide (triplet) repeats represent a unique subset. It is unlikely that abnormal expansion of expressed islet triplet repeats would be a major cause of diabetes, yet the triplet repeats are frequently polymorphic and can thus be used to map the genes in the human genome. In this study, a human islet cDNA library was screened with (CGG)7 and (CAG)7, and 23 triplet repeats were isolated. Sequencing revealed four known and six novel islet genes containing 4-15 triplet repeats. The four known cDNAs included ferritin, the major iron-binding protein in cells; HSGSA2R, a full-length clone of the alpha-subunit of the G-regulatory protein; HUMSATB1A, a DNA-binding protein expressed predominantly in thymus; and HUMPPA-PRO, a ribosomal protein. The triplet repeats in ferritin and HUMPPAPRO were found to be monomorphic. Characterization of the six unique novel expressed islet triplet cDNAs revealed that they were 0.6-1.5 kb in size, contained 4-15 triplet repeats, and were expressed in islets and all other tissues examined. Four of the novel clones, CGG-isl 10, CGG-isl 11, CAG-isl 6, and CAG-isl 7, were mapped to human chromosomes 19, 16, 12, and 3, respectively, via somatic cell hybrids. One islet cDNA, CAG-isl 7, contained a repeat that was highly polymorphic, with 14 alleles (4-18 triplets) in African-Americans (heterozygosity = 0.86) and 6 alleles (heterozygosity = 0.77) in whites. Northern analysis indicated that the mRNA was abundant in pancreatic islets. A putative full-length clone contained an open reading frame encoding 213 amino acids with a variable number of alanines (4-18) within the COOH-terminal. The gene was uniquely mapped with odds > 1,000:1 on chromosome 3p in Centre d'Etude du Polymorphisme Humain pedigrees. There were no differences in CAG-isl 7 allele frequencies between African-American patients with NIDDM (n = 108) and control subjects (n = 116), nor was expansion above 18 repeats noted. Linkage analysis in 14 nonglucokinase maturity-onset diabetes of the young pedigrees showed a cumulative logarithm of odds score of -33.19 at theta = 0.00. Abnormal expansion was not observed in 20 IDDM patients with one NIDDM parent. While these data suggest no major role for CAG-isl 7 in diabetes, at least four of the six novel islet triplet genes are coexpressed in pancreatic islets and neural tissue, and these genes can now be considered as candidates for diabetes and/or neuropsychiatric diseases.

Amino Acid Sequence↗