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Biomedical subjects

S Williams

Publications and source records attributed to S Williams.

At least 163 records · Page 9Linked to original sources

Juvenile colloid milium associated with ligneous conjunctivitis: report of a case and review of the literature.

Juvenile colloid milium is an extremely rare skin condition with an onset prior to puberty; it can be distinguished histologically from the adult form. We report a case of juvenile colloid milium associated with ligneous conjunctivitis and gingival deposits of an amyloid-like homogenous eosinophilic material. We hypothesize that all three of these are the same pathological process occurring at different sites and review the literature on these associations.

Adolescent↗

Widely separated multiple transgene integration sites in wheat chromosomes are brought together at interphase.

We have investigated the organization of transgenes delivered by particle bombardment into the wheat genome, combining conventional molecular analysis with fluorescence in situ hybridization (FISH) and three-dimensional confocal microscopy. We selected a representative population of transformed wheat lines and carried out molecular and expression analysis. FISH on metaphase chromosomes showed that transgene integration sites were often separated by considerable lengths of genomic DNA (>1 Mbp), or could even be on opposite chromosome arms. Plants showing multiple integration sites on a single chromosome were selected for three-dimensional confocal analysis of interphase nuclei in root and embryo tissue sections. Confocal microscopy revealed that these sites lay in close physical proximity in the interphase nuclei. Our results clearly show that multiple transgenes physically separated by large intervening regions of endogenous DNA at metaphase can be brought together at interphase. This may reflect the original physical organization of the endogenous DNA at the moment of transformation, with DNA strand breaks introduced into several co-localized DNA loops by the intruding gold particles. Alternatively, the transgenes may be brought together after transformation, either by an ectopic homologous pairing mechanism, or by recruitment to a common transcription site.

Chromosome Mapping↗

Effect of verapamil on immediate recurrence of atrial fibrillation.

INTRODUCTION: The purpose of this study was to assess the effect of verapamil on immediate recurrences of atrial fibrillation occurring after successful electrical cardioversion. METHODS AND RESULTS: The effect of verapamil on the recurrence of atrial fibrillation within 5 minutes after successful transthoracic cardioversion was assessed in 19 (5%) of 364 patients undergoing electrical cardioversion. The mean duration of atrial fibrillation was 4.44+/-3.0 months. In the 19 patients, cardioversion was successful after each of three consecutive cardioversion attempts per patient; however, atrial fibrillation recurred 0.4+/-0.3 minutes after cardioversion. Verapamil 10 mg was administered intravenously and a fourth cardioversion was performed. Cardioversion after verapamil was successful in each patient, and atrial fibrillation did not recur in 9 (47%) of 19 patients (P < 0.001 vs before verapamil). In the remaining 10 patients in whom atrial fibrillation recurred, the duration of sinus rhythm was significantly longer compared with before verapamil (3.6+/-2.4 min, P < 0.001). The density of atrial ectopy occurring after cardioversion was significantly less after verapamil (21+/-14 ectopic beats per min) compared with before verapamil (123+/-52 ectopic beats per min, P < 0.001). CONCLUSION: Among patients with immediate recurrence of atrial fibrillation after electrical cardioversion, acute calcium channel blockade by verapamil reduces recurrence of atrial fibrillation and extends the duration of sinus rhythm.

Aged↗

Managers forum

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Journal Article↗

An empirical application of transaction-costs theory to organizational design characteristics.

The environmental uncertainty component of transaction-costs theory was used to predict the organizational structural characteristics of size (number of employees) and horizontal differentiation (number of vice presidents) using financial and management information from the COMPACT DISCLOSURE data base (which contains the most recent annual and periodic reports for more than 12,000 public companies). Organizations were categorized as low- or high-uncertainty industries according to Dess and Beard's (1984) Dynamism Scale, and net sales volume was controlled. As predicted, high-uncertainty companies had significantly higher horizontal differentiation than low-uncertainty firms, a finding that supports the transaction-costs expectation that organizations may require more departments or personnel to cope with increasing uncertainty. Surprisingly, low-uncertainty firms were found to have significantly more employees than high-uncertainty organizations, which is the opposite of what transaction-costs theory predicts. Possible explanations for this unexpected finding and further potential limitations are discussed.

Cost-Benefit Analysis↗

Trends in Maori mental health in Otago.

OBJECTIVE: This paper outlines the methods used, and preliminary descriptive data collected, in a study on a cohort of Maori and non-Maori patients admitted to the inpatient psychiatric services in Otago between 1990 and 1992. METHOD: The notes of 42 Maori and 217 non-Maori first admissions to psychiatric inpatients were reviewed. Information concerning this admission was entered onto a database and analysed. RESULTS: The Maori admission rate was 4 per 1000 compared with 1 per 1000 for non-Maori people. This was higher than expected based on Otago population figures. Rates of family psychiatric history did not differ between Maori and non-Maori. Although Maori were found to have higher rates of social welfare support and were more likely to have no academic qualifications the differences were not significant. The sources of referral for Maori admissions were more likely to be from the law, and Maori were more likely to have had prior psychiatric inpatient treatment. The most common diagnosis for Maori and non-Maori was depressive disorders, and suicidal behaviour was common. CONCLUSIONS: Maori are overrepresented among first psychiatric inpatient admissions in Otago. They appear to be a more disadvantaged group with respect to financial support, academic qualifications and other health problems. The most common diagnosis did not differ between Maori and non-Maori cohorts.

Adolescent↗

Encapsulation matrices for neurotrophic factor-secreting myoblast cells.

Encapsulated-cell therapy is an emerging technology that entails implantation of cell-containing devices that secrete therapeutic factors. One potential application of this technology is the delivery of neurotrophic factors to treat neurodegenerative disease. These devices typically use an internal matrix to serve as a cell scaffold. This study compares collagen-coated polyethylene terephthalate (PET) yarn scaffold versus collagen as a matrix for engineered C2C12 myoblasts. C2C12 cells transfected to secrete ciliary neurotrophic factor (CNTF) were immobilized in matrices and encapsulated into hollow fiber membrane devices. Encapsulated cells were monitored in vitro for viability, morphology, and factor secretion. Two independent methods (histology assessment and metabolic assay) were used to estimate viable cell density; a high correlation between the methods was found. After 4 weeks, encapsulated devices with PET scaffold had an almost nine-fold greater number of viable cells compared to collagen. PET matrix devices contained a thick annulus of compact, highly oriented cells. Collagen matrix devices contained sparse viable cells in a thin rim. Secretion assays showed cells in PET matrix released approximately four-fold the amount of CNTF versus cells in collagen (averaging 542 and 129 ng/day per device for PET and collagen matrix, respectively). The choice of encapsulation matrix was found to have a profound effect on cell morphology, level of secreted factor, and viability of encapsulated C2C12 cells.

Animals↗

Dietary strategies for lowering homocysteine concentrations.

BACKGROUND: Elevated plasma total homocysteine (tHcy) concentrations are associated with increased risk of vascular disease, and there is a strong inverse association between dietary and blood folate and blood tHcy concentrations. Increased folate consumption may lower the risk of tHcy-mediated cardiovascular disease. OBJECTIVES: The objective was to determine the most appropriate means of increasing dietary folate to reduce plasma tHcy. DESIGN: Sixty-five free-living subjects aged 36-71 y with tHcy concentrations >/=9 micromol/L participated in a randomized, controlled trial to compare 3 approaches for increasing dietary folate to approximately 600 microg/d: folic acid supplementation, consumption of folic acid-fortified breakfast cereals, and increased consumption of folate-rich foods. RESULTS: An intake of 437 microg folic acid/d from supplements resulted in a 27-nmol/L increase in serum folate and a 21% reduction in tHcy, relative to the change in a control group. In subjects who consumed folic acid-fortified breakfast cereal, folate intake increased by an average of 298 microg, serum folate increased by 21 nmol/L, and tHcy concentrations decreased by 24%. Increased intakes of folate-rich foods resulted in a 418-microg increase in dietary folate, a 7-nmol/L increase in serum folate, and a 9% reduction in tHcy concentrations. The decrease in tHcy was negatively correlated (r = -0.66) with the increase in serum folate. CONCLUSIONS: Daily consumption of folic acid-fortified breakfast cereals and the use of folic acid supplements appear to be the most effective means of reducing tHcy concentrations. The reduction in tHcy was significantly negatively correlated with the increase in serum folate, which may be a useful marker for measuring dietary change.

Adult↗

Air blast circuit breaker noise and hearing loss: a multifactorial model for risk assessment.

The assessment of the risk to hearing from impulse noise exposure may be a problem for the occupational physician because existing legislative and international noise exposure standards deal primarily with continuous noise, and are not valid in excess of the peak exposure limit of 200 pa (140 dB). Noise exposure in excess of this level, for example that due to firearms, is frequently perceived as harmful, but this is not necessarily the case, as impulse noise standards do, in fact, allow exposure with a maximum in the order of 6.3 kPa (170 dB). To illustrate this, a cross-sectional group of electrical transmission workers have been studied who were exposed to significant levels of impulse noise from air blast circuit breakers and firearms. Important hearing loss factors have been identified by means of a specially designed questionnaire. Using the Health & Safety Executive definition, the risk of hearing loss was determined by calculating prevalence odds ratios (ORs) for exposure to these factors. The OR for those with fewer than eight unprotected air blast circuit breaker exposures was 2.27 (95% confidence interval (CI), 1.01-5.08), whilst for those with more than eight exposures the OR was 2.10 (95% CI, 0.97-4.54). For firearm exposure, ORs of 1.61 (95% CI, 0.95-2.74) were noted in the medium exposure group and 2.05 (95% CI, 1.08-3.86) in the high exposure group. When all the factors were included in the model, the most significant factor was age. The study gives support to the impulse noise exposure criteria, confirming the borderline risk from air blast circuit breaker noise exposure and the relative safety of moderate gunfire exposure.

Adult↗

Occupational exposure to HIV and post-exposure prophylaxis in healthcare workers.

Healthcare workers are at risk of occupationally acquired HIV infection primarily due to percutaneous exposure to HIV infected blood. The average risk of HIV transmission after such exposure is approximately 0.3%. There is evidence of higher risk for exposures involving an increased volume of blood (deep injury, injury with a device visibly contaminated with source patient's blood and a procedure which involved a needle placed in the source patient's artery or vein) and exposures to source patients with a high viral load. Triple therapy with two nucleoside analogues (zidovudine, lamivudine) and a protease inhibitor (indinavir) is now widely used for post-exposure prophylaxis following occupational exposure to HIV. Most of the evidence for the efficacy of prophylaxis is based on zidovudine monotherapy. Little is known about the long-term toxicity of these drugs in non-infected individuals. Their use in these circumstances requires careful assessment of possible risks and benefits.

Anti-HIV Agents↗

Cytomegalovirus urinary excretion and long term outcome in children with congenital cytomegalovirus infection. Congenital CMV Longitudinal Study Group.

BACKGROUND: Cytomegalovirus (CMV) is the most frequent cause of congenital infection, and both symptomatic and asymptomatic infants may have long term sequelae. Children with congenital CMV infection are chronically infected and excrete CMV in the urine for prolonged periods. However, the effect of prolonged viral replication on the long term outcome of these children is unknown. OBJECTIVE: To determine whether duration of CMV excretion is associated with outcome at 6 years of life in symptomatic and asymptomatic congenitally infected children. METHODS: Longitudinal cohort study. Children congenitally infected with CMV were identified at birth and followed prospectively in a study of long term effects of congenital CMV infection. The relationship between duration of CMV urinary excretion and growth, neurodevelopment and presence and progression of sensorineural hearing loss (SNHL) at 6 years of age was determined. RESULTS: There was no significant difference in the duration of viral urinary excretion between children born with asymptomatic (median, 4.55 years) and symptomatic (median, 2.97 years) congenital CMV infection (P = 0.11). Furthermore there was no association between long term growth or cognitive outcome and duration of viral excretion. However, a significantly greater proportion of children who excreted CMV for <4 years had SNHL and progressive SNHL compared with children with CMV excretion >4 years (P = 0.019, P = 0.009, respectively). CONCLUSIONS: Children congenitally infected with CMV are chronically infected for years, but the duration of CMV urinary excretion is not associated with abnormalities of growth, or neurodevelopmental deficits. However, SNHL and progressive SNHL were associated with a shorter duration of CMV excretion.

Adolescent↗

Relationship of phenol sulfotransferase activity (SULT1A1) genotype to sulfotransferase phenotype in platelet cytosol.

Sulfation catalysed by human cytosolic sulfotransferases is generally considered to be a detoxification mechanism. Recently, it has been demonstrated that sulfation of heterocyclic aromatic amines by human phenol sulfotransferase (SULT1A1) can result in a DNA binding species. Therefore, sulfation capacity has the potential to influence chemical carcinogenesis in humans. To date, one genetic polymorphism (Arg213His) has been identified that is associated with reduced platelet sulfotransferase activity. In this study, data on age, race, gender, SULT1A1 genotype and platelet SULT1A1 activity were available for 279 individuals. A simple colorimetric phenotyping assay, in conjunction with genotyping, was employed to demonstrate a significant correlation (r = 0.23, P < 0.01) of SULT1A1 genotype and platelet sulfotransferase activity towards 2-naphthol, a marker substrate for this enzyme. There was also a difference in mean sulfotransferase activity based on gender (1.28 nmol/min/mg, females; 0.94 nmol/min/mg, males, P = 0.001). DNA binding studies using recombinant SULT1A1*1 and SULT1A1*2 revealed that SULT1A1*1 catalysed N-hydroxy-aminobiphenyl (N-OH-ABP) DNA adduct formation with substantially greater efficiency (5.4 versus 0.4 pmol bound/mg DNA/20 min) than the SULT1A1*2 variant. A similar pattern was observed with 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5b]pyridine (N-OH-PhIP) (4.6 versus 1.8 pmol bound/mg DNA/20 min).

Age Factors↗

Consistency in the observation of features used to classify duct carcinoma in situ (DCIS) of the breast.

AIM: To determine interobserver and intra-observer agreement in the assessment of cytological grade and intraduct necrosis in pure duct carcinoma in situ (DCIS) of the breast. METHODS: Sixty unselected cases with illustrated diagnostic criteria were circulated to 19 practising histopathologists. RESULTS: Overall agreement was moderate for cytological grade in three categories: 71% agreement; weighted kappa (kappa w), 0.36; intraduct necrosis in three categories (absent, present, extensive): 76% agreement; kappa w, 0.57; and the Van Nuys classification system: 73% agreement; kappa w, 0.48. Agreement was no better among observers participating in the National External Quality Assurance Programme. Intra-observer agreement for cytological assessment (69.6% agreement; kappa w, 0.52) and intraduct necrosis (68.3% agreement; kappa w, 0.48) was moderate, suggesting that individual variation rather than precision of criteria contributes to the lack of agreement. CONCLUSIONS: Moderate agreement on observations can be achieved by non-specialist pathologists, with better agreement on necrosis than cytological grade. There was evidence of consistent individual bias towards over or under scoring cytological grade, which could be corrected with adequate and prompt feedback.

Breast Neoplasms↗

Helping undergraduates repair faulty mental models in the student laboratory.

Over half of the undergraduate students entering physiology hold a misconception concerning how breathing pattern changes when minute ventilation increases. Repair of this misconception was used as a measure to compare the impact of three student laboratory protocols on learning by 696 undergraduate students at 5 institutions. Students were tested for the presence of the misconception before and after performing a laboratory activity in which they measured the effect of exercise on tidal volume and breathing frequency. The first protocol followed a traditional written "observe and record" ("cookbook") format. In the second treatment group, a written protocol asked students to complete a prediction table before running the experiment ("predictor" protocol). Students in the third treatment group were given the written "predictor" protocol but were also required to verbalize their predictions before running the experiment ("instructor intervention" protocol). In each of the three groups, the number of students whose performance improved on the posttest was greater than the number of students who performed less well on the posttest (P < 0.001). Thus the laboratory protocols helped students correct the misconception. However, the remediation rate for students in the "instructor intervention" group was more than twice that observed for the other treatment groups (P < 0.001). The results indicate that laboratory instruction is more effective when students verbalize predictions from their mental models than when they only "discover" the outcome of the experiment.

Exercise↗