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Biomedical subjects

M Lloyd

Publications and source records attributed to M Lloyd.

At least 19 recordsLinked to original sources
PubMed1995

Primary antiphospholipid syndrome evolving into systemic lupus erythematosus.

Since 1983 we have followed a total of 165 patients with antiphospholipid syndrome (APS). During the median followup period of 78 mo (range 12-336 mo), 3 of 80 patients with primary APS subsequently developed features of systemic lupus erythematosus (SLE) or lupus-like disease. One patient developed lupus-like disease 4 yrs and the other 2 developed full blown SLE more than 10 yrs after initial presentation of primary APS. Tissue typing in patients who developed SLE showed HLA antigens A2, A3, B35, Bw6, Cw4, DR7, DRw53, and DQ2 (Case 2); and A1, A3, B7, B8, Bw6, Cw7, DR4, DR15, DR51, DRw53, and DQ1 (Case 3). We report clinical features and genetic associations of these 3 patients.

Adolescent↗
PubMed1992

Complete rescue of photoreceptor dysplasia and degeneration in transgenic retinal degeneration slow (rds) mice.

retinal degeneration slow (rds) is a semidominant mutation of mice with the phenotype of abnormal development of rod and cone photoreceptors, followed by their slow degeneration. The rds gene has been putatively cloned and its novel protein product initially characterized biochemically. In the present study we undertook to correct in vivo the retinal phenotype of mice with the rds mutation. We assembled a transgene containing a regulatory segment of the opsin gene positioned upstream of the wild-type rds coding region. Mice from three transgenic lines, homozygous for the rds mutation, were analyzed for expression of the transgene and for their retinal phenotypes. In two high expressing lines, we observed complete reversion to wild-type retinal morphology. In a third, low expressing line, we observed a retinal phenotype intermediate between wild type and rds/rds, suggesting partial rescue of the mutation. These results constitute formal proof that we have cloned the rds gene.

Animals↗
PubMed1992

Characterization and comparison of Australian human spotted fever group rickettsiae.

The microbiological and molecular characteristics of the rickettsiae isolated from humans with Queensland tick typhus (QTT) caused by Rickettsia australis and the recently described Flinders Island spotted fever (FISF) were compared. Clinically and serologically, the diseases are similar. Cell culture reveals differences in the plaque-forming abilities of the isolates. Characterization of the gene encoding the genus-specific 17-kDa antigen of R. australis revealed a unique nucleotide sequence unlike those of the FISF isolate and Rickettsia rickettsii. Southern blot analysis of rickettsial DNA from the isolates with a 17-kDa-antigen gene probe revealed the presence of this gene in all isolates but no difference in banding patterns. When a probe for the rRNA genes was used, clear differences in banding patterns of isolates from patients with QTT and FISF were revealed. Thus, the rickettsiae isolated from patients with FISF differ from those from patients with QTT and may represent a new rickettsial species.

Antigens, Bacterial↗
PubMed1992

Regulation of intestinal lactase in adult hypolactasia.

Relative deficiency of intestinal lactase activity during adulthood, adult hypolactasia, is a common condition worldwide. We studied the regulation of lactase-phlorizin hydrolase in normal and adult hypolactasic subjects by correlating transcript abundance in intestinal biopsies with relative synthetic rates for the protein in cultured intestinal explants. After metabolic labelling studies in six subjects, precursor lactase-phlorizin hydrolase was identified in amounts directly proportional to the enzyme-specific activity suggesting that levels of intestinal lactase are regulated by synthetic rate. Total intestinal RNA was extracted from biopsies of these subjects and three hypolactasic adults who had participated in previous biosynthesis studies. Transcript levels were markedly reduced in deficient subjects who demonstrated diminished lactase-phlorizin hydrolase synthesis. The sequence of 1 kb of 5'-flanking region of the lactase-phlorizin hydrolase gene was determined in two hypolactasic subjects and two controls. No sequence variability was identified to account for differences in mRNA levels or biosynthetic rates between the two groups. A single hypolactasic subject previously characterized as demonstrating delayed posttranslational processing, showed message levels intermediate between other deficients and controls. These results suggest that in the majority of our subjects, pretranslational mechanisms account for the predominate regulatory control of lactase-phlorizin hydrolase expression in the proximal intestine.

Adult↗
PubMed1991

Computer analysis of the shape of spread of epidemics on a grid.

Models concerned with the spatial features of epidemic spread are often defined in terms of a nearest-neighbor grid network. It has been strongly conjectured, and can be proved in certain cases, that the infected area has an asymptotically well-defined shape. The present work concerns computer analysis of the shape of spread of a discrete-time single-parameter infection process on an eight-neighbor lattice. Results of extensive simulation are displayed using up-to-date exploratory data analysis software, and various attempts at fitting functions to the probability surfaces are considered.

Computer Simulation↗
PubMed1991

Factors influencing the communication skills of first-year clinical medical students.

The aim of this study was to examine the factors influencing medical students' communication skills. The sample comprised all first-year clinical students. Thirty-two received teaching in communication skills during the year; the remaining 56 did not. Students' career preferences, attitudes towards communication skills and confidence in their ability to communicate with patients were assessed by questionnaire at the beginning and end of the year. At the end of the year each student was videotaped interviewing a simulated patient. Students' communication skills were assessed on the basis of this interview by raters using a standardized rating scale, and by patient questionnaires. While there was some evidence that brief communication skills training improved skills, sex of student was a more significant predictor of level of skill. Students who perceived communication skills as less relevant to medicine and those who were more confident about their own communication skills were more likely to prefer a career in hospital medicine. Students' judgements of their ability to communicate effectively were poor. In the main there was no relationship between confidence and level of skill: where they were related, the association was negative. The benefits from communication skills training might be enhanced by involving hospital doctors in the teaching, and providing students with detailed video feedback on their skills at the outset.

Attitude of Health Personnel↗
PubMed1991

Smoking during pregnancy and its effects on child cognitive ability from the ages of 8 to 12 years.

Maternal smoking during pregnancy and subsequent child cognitive development and ability were examined in a birth cohort of New Zealand children studied to the age of 12 years. Analysis at a bivariate level showed that children whose mothers smoked during pregnancy scored significantly lower on standardised tests of intelligence, reading and mathematical ability than children whose mothers did not smoke. However, after adjustment for confounding covariates, the results showed no detectable relationship between smoking during pregnancy and child cognitive ability. These results suggest that children whose mothers smoked during pregnancy fared worse on tests of cognitive ability not because of possible causal effects of smoking, but rather because these children tended to come from families which provided a relatively disadvantaged home environment.

Child↗
PubMed1991

Confirmatory factor models of attention deficit and conduct disorder.

The paper presents four alternative confirmatory factor models to represent the structure of measures of attention deficit and conduct disorder obtained from multiple sources. These models range in complexity from a simple one-factor model with no method effects to a two-factor model with method effects. These models were fitted to data gathered on maternal, teacher and self-report of attention deficit and conduct disorder for a sample of New Zealand children studied at ages 9 and 10 years. The analysis strongly suggests that the best representation of the data was a two-factor model in which there were distinct factors of attention deficit and conduct disorder with these factors being highly correlated (r = 0.87-0.88). It is suggested that the most suitable clinical nomenclature may be to describe conduct disorder and attention deficit generically as externalizing disorders, subscripting this classification with clauses which describe the relative contributions of conduct disorder and attention deficit. The implications of this finding for the measurement, classification and explanation of conduct disorder and attention deficit disorder are discussed.

Attention Deficit Disorder with Hyperactivity↗
PubMed1991

Characteristics of physicians with obstetric malpractice claims experience.

This study compared the demographic and practice characteristics of physicians with and without obstetric malpractice experience. The sample consisted of 387 family physicians and 204 obstetricians in Washington state who were insured for obstetrics by a major malpractice carrier between January 1982 and June 1988. Fifty-three physicians (9%) had an obstetric malpractice claim during the study period. The approximate overall rate of obstetric malpractice claims was low: 0.32 per 1000 deliveries. The higher the total delivery volume (exposure), the greater the chance of having malpractice experience. Although physicians with practices of over 200 deliveries per year were more likely to have had malpractice experience, their risk of malpractice experience per delivery was lower than that of providers doing fewer than 200 deliveries per year. Our work suggests that insurers might consider basing obstetric malpractice premiums on numbers of deliveries rather than specialty.

Female↗
PubMed1990

The biosynthetic basis of adult lactase deficiency.

The intestinal brush-border enzyme lactase splits lactose into its component monosaccharides, glucose and galactose. Relative deficiency of the enzyme during adulthood is a common condition worldwide and is frequently associated with symptoms of lactose intolerance. We studied the synthesis and processing of lactase in normal and adult hypolactasic subjects using human intestinal explants in organ culture. Metabolic labeling experiments in our control subjects with [35S]methionine followed by immunoprecipitation, sodium dodecyl sulfate-polyacrylamide-gel electrophoresis, and fluorography demonstrated that newly synthesized lactase is initially recognized as a precursor molecule with a relative molecular weight (Mr) of 205,000. Over the course of several hours most of the labeled lactase was converted to a mature form of 150,000 Mr. Transiently appearing forms of 215,000 and 190,000 Mr were identified and were felt to represent intermediary species generated during intracellular processing. We identified two distinct alterations in lactase biosynthesis accounting for adult hypolactasia. Studies in three deficient subjects demonstrated markedly reduced synthesis of the precursor protein though posttranslational processing appeared identical to normal. Multiple studies in a fourth deficient subject demonstrated synthesis of ample amounts of precursor lactase but reduced conversion to the mature active form of the enzyme.

Adult↗
PubMed1990

Why do physicians stop practicing obstetrics? The impact of malpractice claims.

We studied all physicians who purchased obstetric malpractice insurance from the Washington State Physicians Insurance Exchange and Association between January 1, 1982 and July 1, 1988. Of the 690 physicians studied, 171 (32% of the family physicians and 10% of the obstetricians) discontinued obstetrics but remained in practice. Physicians who discontinued obstetric practice were older, more likely to practice in an urban area, and more likely to be in solo practice than those who did not. Obstetricians who discontinued obstetric practice had a higher rate of new obstetric malpractice claims than did those who did not quit practicing obstetrics--14.5 versus 6.2 claims per 100 physician-years of coverage. By contrast, those family physicians leaving obstetrics had a lower rate of new claims than their peers who did not quit. We conclude that older physicians--particularly those in urban and solo practice--are most likely to stop practicing obstetrics, regardless of specialty. In addition, being named as the target of an obstetric malpractice claim plays a significant role in the decision of some obstetricians to discontinue obstetric practice.

Attitude of Health Personnel↗
PubMed1988

Synthesis and intracellular processing of aminooligopeptidase by human intestine.

Aminooligopeptidase is an intrinsic glycoprotein of the brush border membrane important for hydrolysis of the oligopeptide products of intraluminal protein digestion. To study its synthesis and intracellular processing, we performed pulse-chase experiments using [35S]methionine to label proteins of cultured human intestinal explants obtained by endoscopic biopsy. Aminooligopeptidase was isolated by immune precipitation with a monoclonal antibody and its molecular size was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography. A precursor of relative molecular weight (Mr) 127,000 appeared within 10 min of chase and appeared to begin conversion to an Mr 150,000 form (the size of brush border membrane aminooligopeptidase) within 60 min. To determine if the change in molecular size was the consequence of alterations in glycosylation, we studied the susceptibility of the two forms to endo-beta-N-acetylglucosaminidase H, which cleaves immature high-mannose N-linked carbohydrate chains, and to peptide: N4-(N-acetyl-beta-glucosaminyl)asparagine amidase, which cleaves both the high-mannose and complex N-linked carbohydrate chains. Only the early Mr 127,000 aminooligopeptidase was sensitive to endo-beta-N-acetylglucosaminidase H, suggesting that the larger form results from trimming of high-mannose cores and adding terminal sugars in the Golgi complex. Both forms were sensitive to peptide: N4-(N-acetyl-beta-glucosaminyl)asparagine amidase, generating an Mr 114,000 species. The kinetics of the synthesis and processing of aminooligopeptidase and sucrase-isomaltase were compared by immunoprecipitation of both proteins from the same tissue after separating the microvillous membrane from the remainder of the cellular membranes. Labeled aminooligopeptidase was present intracellularly in its mature form within 60 min and was detected exclusively in the brush border membrane by 90 min. Most of the labeled sucrase-isomaltase pool had not yet undergone complex glycosylation during the same period. These data demonstrate that although human intestinal aminooligopeptidase undergoes N-linked glycosylation like sucrase-isomaltase, the synthesis of aminooligopeptidase differs from that of sucrase-isomaltase in respect to the absence of a high-molecular-weight precursor and more rapid pre-Golgi processing.

Aminopeptidases↗
PubMed1987

Painful bone end sclerosis. Variant of renal osteodystrophy simulating osteonecrosis.

Painless sclerotic change in bone ends occurring as a manifestation of renal osteodystrophy has been reported in two previous cases. The sclerotic change can, however, be accompanied by nonspecific periarticular pain. Radiologic changes in "bone ends" may mimic osteonecrosis. Nuclear bone scanning may show increased radionuclide uptake early in both conditions but late uptake may be less in "bone end sclerosis." The "rugger jersey" spine occurring in the usual osteosclerosis of renal osteodystrophy has been consistently absent in this variant. Osteonecrosis should be excluded in making the diagnosis of "bone end sclerosis."

Adult↗