Biomedical subjects

J Williams

Publications and source records attributed to J Williams.

At least 343 records · Page 19Linked to original sources

PubMed1998

Stereotactic radiosurgery for brain metastases: comparison of lung carcinoma vs. non-lung tumors.

In the medical literature, stereotactic radiosurgery (SRS) for brain metastases results in rates of local control of 65 to 85 %. To define patient selection criteria, we measured the survival in a population with a high proportion of non-small cell lung carcinoma (NCS lung) metastases that occurred soon after primary diagnosis. Between 9/89 and 10/93 30 adults (21 M, 9 F) had SRS for metastatic NSC lung carcinoma (14 patients) vs. non-lung carcinomas (16 patients having breast (3), renal (3), melanoma (3), GI (2, thyroid (1) or carcinoma of unknown origin (4)). The metastases were solitary for 22 patients and multiple for 8 patients. Average ages (y) (+/-SD) were 58.6+/-10.4 for NSC lung patients and 53.4+/-12.5 (p = 0.32) for non-lung patients. The average interval (months) from diagnosis of the primary to metastasis was 23.8+/-41.4 for all patients. This interval was shorter for NSC lung patients: 3.1+/-6.0 vs. 48.0+/-51.7 (p < 0.001) for non-lung patients. Twenty seven patients had conventional radiotherapy (XRT) before (24 patients) or after (3 patients) SRS. Doses (cGy) were 3303+/-841 for 13 NSC lung patients and 4256+/-992 for 14 non-lung patients (p = 0.034). The median time from primary diagnosis to SRS was shorter for the NSC lung patients (11 mo) compared to the non-lung patients (35 mo). SRS was given for recurrence of metastases after XRT for 11/14 NSC lung patients and 13/16 non-lung patients. The doses (cGy) of SRS were 1579+/-484 vs. 1682+/-476 (p=0.45) for the NSC lung and non-lung groups, respectively. After SRS a decrease in metastasis diameter was observed in 10 of 14 NSC lung patients vs. 12 of 16 non-lung patients (p=0.85 Chi-square). Twenty-seven of the 30 patients have died. For all patients, the median survival after diagnosis of the primary and after radiosurgery was 31.3 and 8.4 months, respectively. The median survival (95% CI) from primary diagnosis was 24.3 months (13.2-27.3) for NSC lung patients and 46.5 months (39.2-65.5) for non-lung patients (p=0.005 logrank test). The median survival (95% CI) after SRS was 7.9 months (3.0-14.3) for the NSC lung patients and 8.4 (2.9-11.9) months for the non-lung patients (p=0.98 logrank test). Within the two groups, no difference in survival was observed for patients who had SRS sooner (< 1 yr for NSC lung; < 3 yr for non-lung) after primary diagnosis: 9.3 vs. 6.5 mo for NSC lung (p=0.21) and 10.5 vs. 7.2 mo for non-lung (p=0.87). In this series, the shortened intervals from primary diagnosis to SRS for NSC lung metastases was associated with post-SRS survivorship that was equivalent to the more favorable non-lung group.

Adult↗

PubMed1998

Treatment boundaries in the case management relationship: a clinical case and discussion.

Case managers provide services in a variety of settings and situations that challenge traditional ideas about professional roles and practices. The concepts of treatment boundaries, drawn from the psychotherapy literature, are helpful in conceptualizing appropriate professional norms in case management. This article reviews concepts of treatment boundaries and provides a clinical case for illustration and discussion.

Adult↗

PubMed1998

Psychological health in a non-clinical sample of obese women.

OBJECTIVES: The relationship between obesity and psychological health remains unclear. The aims of this study were to evaluate the effect of obesity on the psychological health of a non-clinical sample of obese women, to investigate binge eating in this group, and to examine the predictors of psychological distress. DESIGN: A cross-sectional comparison of women divided into three obesity groups (body mass index (BMI)= 30-34.9, 35-39.9, > or = 40) was used. PARTICIPANTS: 179 women with a BMI > 30 (mean age 45 y) returned a questionnaire included in a subscriber-only magazine for women of size 16+. MEASURES: The questionnaire asked for information on demographics, weight history and eating behaviour, and included established self-report measures of body shape assessment, body shape satisfaction, dietary restraint, mental health state and self-esteem. RESULTS: The heaviest women (BMI > 40) did not differ on measures of mental health, but expressed the greatest dissatisfaction with their body weight, shape and appearance, and had the lowest self-esteem. Frequent binge eating was reported by 25% of all women. Self-esteem and peer relationships, but not body weight, were highly significant negative predictors of poor mental health. CONCLUSIONS: Poor mental health is not the inevitable consequence even of the most extreme obesity, but is related to both low self-esteem and poor peer relationships. These, and problems with eating control, are features of psychological morbidity that require recognition and therapeutic attention.

Adolescent↗

PubMed1998

A family based association study of T102C polymorphism in 5HT2A and schizophrenia plus identification of new polymorphisms in the promoter.

Several studies have shown an association between schizophrenia and the C allele of a T-C polymorphism at nucleotide 102 and the 5HT2A receptor gene. In the present study we observed this association in a sample of 63 parent/offspring trios where the proband received a diagnosis of DSM-III-R schizophrenia using TDT analysis (chi2 = 6.26, P= 0.006, chi2 = 9.00, P=0.001 when one affected offspring was selected at random from each family, suggesting that the results are due to association rather than linkage). There was no significant difference between the transmission of C102 from heterozygous fathers and mothers, which fails to support a role for genomic imprinting in this effect. T102C does not result in an alteration of the amino acid sequence of the protein. We therefore screened the promoter of 5HT2A for polymorphisms using single-strand confirmation polymorphism analysis. An A-G polymorphism at -1438 that creates an HpaII restriction site was identified. This was found to be in complete linkage disequilibrium with T102C and is hence a candidate for the pathogenic variant in schizophrenia. Functional analysis of A-1438G using luciferase assay demonstrated significant basal promoter activity in 5HT2A expressing HeLa cells by both the A and G variants. However, comparison of the A and G variants showed no significant differences in basal activity nor when promoter activity was induced by cAMP and protein kinase C-dependent mechanisms.

Adult↗

PubMed1998

A meta-analysis and transmission disequilibrium study of association between the dopamine D3 receptor gene and schizophrenia.

We performed a meta-analysis of over 30 case-control studies of association between schizophrenia and a bi-allelic, Bali polymorphism in exon 1 of the dopamine D3 receptor gene. We observed a significant excess of both forms of homozygote in patients (P = 0.0009, odds ratio (OR) = 1.21, 95% Confidence Interval (CI) = 1.07-1.35) in the combined sample of 5351 individuals. No significant heterogeneity was detected between samples and the effects did not appear to be the product of publishing bias. In addition we undertook an independent, family-based association study of this polymorphism in 57 parent/proband trios, taken from unrelated European multiplex families segregating schizophrenia. A transmission disequilibrium test (TDT) showed a significant excess of homozygotes in schizophrenic patients (P = 0.004, odds ratio (OR) = 2.7, 95% CI = 1.35-5.86). Although no significant allelic association was observed, a significant association was detected with the 1-1 genotype alone (P = 0.02, OR = 2.32, 95% CI = 1.13-4.99). In addition when the results of the family-based association study were included in the meta-analysis, the homozygosity effect increased in significance (P = 0.0002, OR = 1.23, 95% CI = 1.09-1.38). The results of the meta-analysis and family-based association study provide independent support for a relationship between schizophrenia and homozygosity at the Bali polymorphism of the D3 receptor gene, or between a locus in linkage disequilibrium with it.

Alleles↗

PubMed1998

Further support for an association between a polymorphic CAG repeat in the hKCa3 gene and schizophrenia.

A recent study has suggested that a polymorphism in the hKCa3 potassium channel may be associated with raised susceptibility to schizophrenia. Despite its modest statistical significance, the study is intriguing for two reasons. First, hKCa3 contains a polymorphic CAG repeat in its coding sequence, with large repeats more common in schizophrenics compared with controls. This is interesting in view of several repeat expansion detection (RED) studies that have reported an excess of large CAG repeats in psychotic probands. Second, the hKCa3 gene is a functional candidate gene because studies of antipsychotic and psychotogenic compounds suggest that glutamatergic systems modulated by SKCa channels may be important in schizophrenia pathogenesis. In the light of the above, we have tested the hypothesis of an association between schizophrenia and the hKCa3 CAG repeat polymorphism using a case control study design. Under the same model of analysis as the earlier study, schizophrenic probands had a higher frequency of alleles with greater than 19 repeats than controls (chi 2 = 2.820, P = 0.047, 1-tail). Our data therefore provide modest support for the hypothesis that polymorphism in the hKCa3 gene may contribute to susceptibility to schizophrenia.

Alleles↗

PubMed1998

Supporting Pre-registration House Officers: the needs of educational supervisors of the first phase of postgraduate medical education.

The GMC's publications The New Doctor (GMC 1997) outlines an approach for the education of Pre-registration House Officers using designated educational supervisors. In order to establish appropriate means of training consultants to undertake this role, the Centre for Postgraduate and Continuing Medical Education at the Queens Medical Centre, Nottingham undertook a needs analysis. This consisted of a series of individual interviews with directors of postgraduate education in the mid-Trent region, four focus groups with consultants, and two dissemination workshops. The findings from the research have led to the development of a modular educational programme, based on the perceived needs and optimum structure indicated by the participants in the research process.

Consultants↗

PubMed1998

Rapid patterning of Dictyostelium discoideum cells under confined geometry and its relation to differentiation.

The following was recently reported by Bonner et al. (1995): (1) Rapid differentiation occurred into two zones in Dictyostelium discoideum cells confined in a fine glass capillary. The cells in the anterior zone exposed to the air appear similar to prestalk cells, while the posterior zone isolated from the air mimics prespore cells. (2) The volumes of the two zones are proportional to each other for different sized cell masses, and the proportion is the same as that in normal migrating slugs. We investigated the nature of this newly discovered rapid differentiation in a slightly modified geometry. Exponentially growing cells were harvested, washed to remove external nutrients, and pelleted by centrifugation. Subsequently, a small drop of the pelleted (starved) cells was placed on a slide glass and then confined in a two-dimensional space between the slide glass and a coverslip, with help of spacers whose thickness varied from 25 to 100 microm. As a result, a dark zone, which looked optically different, emerged within several minutes in the periphery of the disc of the confined cells, corresponding to the zonation in a capillary as previously reported. When the width of the peripheral zone was measured for more than 30 samples of different diameters for each thickness of the spacers, the width was found to be always about 100 microm, irrespective of the size difference of the cell mass placed. This seems to be contradictory to the previous observation made by Bonner et al. (1995). We also examined oxygen concentration dependence on the zone width. The zone width was found to be independent of the oxygen concentration at low concentrations, but increased rapidly at high concentrations. A reaction-diffusion mechanism for formation of the zone and possible involvement of atmospheric oxygen (O2) in the initial steps of cell differentiation and pattern formation is discussed.

Animals↗

PubMed1998

Mother and teacher reports of behaviour and perceived self-competence of children with hydrocephalus.

The present study was designed to explore the social and behavioural functioning of children with hydrocephalus. The sample comprised 14 children with hydrocephalus (without spina bifida) and 14 controls with no history of neurological impairment matched for age and gender. Children were asked to report on their self-perceptions of academic and physical competence and on peer and maternal acceptance. In addition, mothers and teachers provided reports of the behavioural adjustment of both groups and mothers completed a questionnaire measuring locus of control orientation. Mothers of children with hydrocephalus also responded to a series of open-ended questions, their thoughts and feelings about the experience of having a child with hydrocephalus. Analyses of the data revealed that there was no difference in the self-perceptions of the two groups of children, although there was a trend for children with hydrocephalus to rate themselves as being lower in physical competence. There was a clear association between the presence of hydrocephalus and behaviour problems, with evidence of internalising and externalising problems being evident in the reports of both mothers and teachers, although the extent of agreement between the two informants was low. Maternal locus of control was related to behaviour problems in children with hydrocephalus, with a more external orientation being related to more behaviour problems. It is suggested that future researchers need to 1) focus on children's behaviour in context, 2) solicit data from a range of informants and 3) consider the complex transactions between biological and psychological factors to gain a fuller understanding of how hydrocephalus shapes children's development.

Case-Control Studies↗

PubMed1998

Plasma concentrations of thyroid hormones in growing pullets and laying hens reared under two tropical climates and fed on diets with different energy concentrations.

1. Blood samples were taken from growing (14-week-old) and laying (36-week-old) hens reared in either a temperate or a hot, humid climate and fed on 2 dietary energy concentrations (10.03 or 11.7 MJ ME/kg) to determine the plasma concentrations of 3,3',5'-triiodothyronine (T3) and thyroxine (T4) by radioimmunoassay. 2. Plasma T3 concentrations were higher in birds fed on the low energy diet and higher at 14 than at 36 weeks of age, while the effects of climate were complex. 3. Plasma T4 concentrations were higher at 14 than at 36 weeks of age and interactions with the dietary and climatic factors were observed. 4. Interactions between dietary and climatic factors were observed since plasma T3 and T4 concentrations were higher at 14 weeks under the hot, humid than under the temperate climate. Furthermore, at 36 weeks plasma T3 concentrations were higher under the temperate climate and plasma T4 concentrations did not differ. 5. These findings are not easy to explain. However it may be suggested that the energy content of the diet clearly affects the plasma concentrations of thyroid hormones and that this effect is modulated by the climate to a variable degree that is linked to the age and the physiological state of the birds.

Aging↗

PubMed1998

The effects of preoperative irradiation on peripheral nerve regeneration.

The purpose of this study was to evaluate the effects of preoperative external cobalt60 beam irradiation on nerve regeneration. Ninety 250-g male Sprague-Dawley rats were studied. Peripheral nerve regeneration was measured by walking track analysis and histomorphology of the proximal, grafted, and distal nerve segments. Ninety animals were randomly assigned to one of five treatment groups, receiving a total fractionated dose of 30, 50, 70, and 90 Gy. Each animal received a 15-mm interposition nerve graft into the right posterior tibial nerve 6 weeks following completion of radiation therapy. The left leg served as a control. The remaining 10 animals received a nerve isograft subjected to a single dose of 30 Gy prior to placement (group 5). Walking track analysis was performed monthly through 8 months. At the conclusion of 120 and 240 days, sections of the proximal, grafted, and distal nerve were harvested, stained, and examined histomorphologically. Evaluation of the print length index demonstrated no statistical difference between our previously established nonirradiated controls, the irradiated groups, and the irradiated isograft group (group 5). The total number of axons per square millimeter was significantly decreased in the distal segment of all irradiated groups when compared with the controls. No statistical difference in number of axons per square millimeter was noted in the irradiated isograft group. Furthermore, no statistical difference was noted in the nerve fiber density between the control group, the preoperative irradiated groups, or the irradiated isograft group (group 5). Despite the reduction in myelinated regenerating fibers, no reduction in function was observed as measured by walking track analysis. Thus, immediate reconstruction of peripheral nerve defects in the face of preoperative irradiation may not be contraindicated.

Animals↗

PubMed1998

Prognostic significance of DNA replication errors in young patients with colorectal cancer.

OBJECTIVE: To determine the DNA replication error (RER) status in young patients with colorectal cancer (CRC), and to compare the clinical and pathologic characteristics of RER-positive and RER-negative cases. SUMMARY BACKGROUND DATA: Recent studies suggest that patients with RER-positive CRC have an improved prognosis. Further data are required to confirm this observation in young CRC patients. METHODS: All patients 40 years of age and younger with CRC admitted to the National Naval Medical Center between 1970 and 1992 were considered for inclusion in the study. After review, 36 patients for whom the original archived pathology specimen could be retrieved served as the study population. The RER status was determined using a previously described polymerase chain reaction-based assay. The clinical and pathologic features and survival data were compared to RER status. RESULTS: RER-positive tumors were found in 17 cases (47%). There was no significant difference in Dukes' stage or histologic grade at the time of diagnosis between patients with RER-positive tumors compared to RER-negative tumors. Patients with RER-positive tumors were found to have an improved prognosis: the 5-year survival probability for patients with RER-positive tumors was 68%, as compared to 32% for patients with RER-negative tumors (p < 0.05). CONCLUSIONS: RER-positive tumors are common in young patients with CRC, and patients with RER-positive tumors have a significantly improved prognosis. Because of their young age, survival data and prognosis play an important role in the overall treatment plan of young patients with CRC. Therefore, knowledge of RER status could affect initial therapy, postoperative chemotherapy, and follow-up.

Adult↗

PubMed1998

An audit of therapeutic drug monitoring service provision by laboratories participating in an external quality assessment scheme.

Therapeutic drug monitoring services were investigated in a questionnaire sent to all subscribers to the United Kingdom National External Quality Assessment Scheme for Therapeutic Drug Assays. Questions were posed on assay availability and use, target ranges, and reporting procedures for digoxin, lithium, phenytoin, phenobarbitone, carbamazepine, theophylline, and valproic acid. One hundred fifty-seven laboratories replied and, except for lithium, 45% reported in mass units, 34% in molar units, and 22% a mixture of mass and molar units. Target ranges for lithium, digoxin, carbamazepine, and phenobarbitone were highly variable but ranges for phenytoin, theophylline, and valproic acid were more consistent. Immunoassay was the most popular methodology although high-performance liquid chromatography was commonly used for anticonvulsants. Paper copies of results were provided by 93% of laboratories, 40% reported by telephone, 12% by fax, and 28% by computer. Additional data, mainly dose, time of last dose, and duration of therapy were requested by 55% to 67% of laboratories. Grades of staff authorizing results ranged from nurses to senior consultants, and collaboration with pharmacists occurred in 26% of laboratories. Most laboratories provided a daily analytical service and 73% offered a 24-hour emergency service. This audit unexpectedly identified use of a wide range of target concentrations, particularly for digoxin and lithium.

Drug Monitoring↗

PubMed1998

Function and substrate specificity of the gibberellin 3beta-hydroxylase encoded by the Arabidopsis GA4 gene.

cDNA corresponding to the GA4 gene of Arabidopsis thaliana L. (Heynh. ) was expressed in Escherichia coli, from which cell lysates converted [14C]gibberellin (GA)9 and [14C]GA20 to radiolabeled GA4 and GA1, respectively, thereby confirming that GA4 encodes a GA 3beta-hydroxylase. GA9 was the preferred substrate, with a Michaelis value of 1 microm compared with 15 microm for GA20. Hydroxylation of these GAs was regiospecific, with no indication of 2beta-hydroxylation or 2,3-desaturation. The capacity of the recombinant enzyme to hydroxylate a range of other GA substrates was investigated. In general, the preferred substrates contained a polar bridge between C-4 and C-10, and 13-deoxy GAs were preferred to their 13-hydroxylated analogs. Therefore, no activity was detected using GA12-aldehyde, GA12, GA19, GA25, GA53, or GA44 as the open lactone (20-hydroxy-GA53), whereas GA15, GA24, and GA44 were hydroxylated to GA37, GA36, and GA38, respectively. The open lactone of GA15 (20-hydroxy-GA12) was hydroxylated but less efficiently than GA15. In contrast to the free acid, GA25 19,20-anhydride was 3beta-hydroxylated to give GA13. 2,3-Didehydro-GA9 and GA5 were converted by recombinant GA4 to the corresponding epoxides 2, 3-oxido-GA9 and GA6.

Arabidopsis↗

PubMed1998

Understanding rural and remote divisions under a workforce framework.

In Australia, divisions of general practice are the organisational structures for local networks of general practitioners. They facilitate communication across the profession and with other parts of the health system and are established in urban, rural and remote areas. Funding is provided contractually to divisions through the Federal Government's Divisions and Projects Grants Program. The under-supply of doctors and other health professionals in rural and remote areas of Australia is a serious problem that has far-reaching effects. The present paper argues that if the Divisions and Projects Grants Program is to be effective in achieving its aims and objectives, then the Program's policies must be responsive to the different needs, roles, constraints, expectations and capabilities of divisions and their members as well as the structural impediments imposed by the medical workforce.

Australia↗

PubMed1998

Does short-term antiepileptic drug treatment in children result in cognitive or behavioral changes?

PURPOSE: To determine possible cognitive and behavioral effects of antiepileptic drug (AED) therapy by assessing children with newly diagnosed epilepsy before and after initiation of treatment. A comparison group of children with diabetes mellitus (DM) was included to control for the effects of practice, maturation, and chronic illness. METHODS: Baseline neuropsychological assessments were completed for children with epilepsy (n = 37) and children with DM (n = 26) recruited through outpatient clinics at a regional children's hospital. Children were reevaluated 6 months from baseline testing. At follow-up, children with epilepsy had therapeutic AED levels and controlled seizures. Statistical analysis included a between-group repeated measures ANCOVA with pretest scores serving as the covariate. RESULTS: Significant differences between groups were not found for any cognitive or behavioral factors, including attention (p < 0.24), immediate memory (p < 0.24), delayed memory (p < 0.10), complex motor speed (p < 0.19), or behavior problems (p < 0.89). CONCLUSIONS: Changes in performance on cognitive and behavioral measures were not different for children treated with AEDs and controls. Although adverse effects may be associated with prolonged treatment, results would not suggest adverse effects from AED monotherapy during the first 6 months of therapy.

Adolescent↗

PubMed1998

Differential inhibition of AE1 and AE2 anion exchangers by oxonol dyes and by novel polyaminosterol analogs of the shark antibiotic squalamine.

Oxonol and polyaminosterol drugs were examined as inhibitors of recombinant mouse AE1 and AE2 anion exchangers expressed in Xenopus laevis oocytes and were compared as inhibitors of AE1-mediated anion flux in red cells and in HL-60 cells that express AE2. The oxonols WW-781, diBA(5)C4, and diBA(3)C4 inhibited HL-60 cell Cl-/Cl- exchange with IC50 values from 1 to 7 microM, 100-1000 times less potent than their IC50 values for red cell Cl-/anion exchange. In Xenopus oocytes, diBA(5)C4 inhibited AE1-mediated Cl- efflux several hundred times more potently than that mediated by AE2. Several novel squalamine-related polyaminosterols were also evaluated as anion exchange inhibitors. In contrast to diBA(5)C4, polyaminosterol 1361 inhibited oocyte-expressed AE2 8-fold more potently than AE1 (IC50 0.6 versus 5.2 microM). The 3-fold less potent desulfo-analog, 1360, showed similar preference for AE2. It was found that 1361 also partially inhibited Cl- efflux from red cells, whereas neither polyaminosterol inhibited Cl efflux from HL60 cells. Thus, the oxonol diBA(5)C4 is >100-fold more potent as an inhibitor of AE1 than of AE2, whereas the polyaminosterols 1360 and 1361 are 8-fold more potent as inhibitors of AE2 than of AE1. Assay conditions and cell type influenced IC50 values for both classes of compounds.

Animals↗

PubMed1998

Evidence that a deferrioxamine B degrading enzyme is a serine protease.

Siderophores are organic biomolecules synthesized by a wide variety of microbes. The molecules sequester ferric ion from environments where it is present at extremely low concentrations. Siderophores are of consequence with respect to microbial nutrition, pathogenicity, virulence, and microbe-plant interactions. How siderophores are degraded and returned to the carbon and nitrogen cycles is not well understood. The catalytic activity of an enzyme from a bacterium that degrades the siderophore deferrioxamine B has been examined. While the degradation of deferrioxamine B is sensitive to sulfhydryl and metal moiety inhibitors, the data presented is most consistent with the hypothesis that the enzyme uses a hydroxyl moiety (serine peptidase) to catalyze the degradation of deferrioxamine B. If sulfhydryl and metal inhibitors are simultaneously present at concentrations that when alone only partially inhibit the enzyme, the enzyme is unable to catalyze deferrioxamine B dissimilation. Analysis of the inhibitor experiments conducted led to the conclusion that the deferrioxamine B degrading enzyme is a serine-peptidase-like enzyme that needs calcium ions and sulfhydryl groups to be fully activated or stabilized. The knowledge of the catalytic moieties of the enzyme will be exploited to purify the enzyme.

Antidotes↗