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Biomedical subjects

H Williams

Publications and source records attributed to H Williams.

At least 55 records · Page 3Linked to original sources

Comparison of external dacryocystorhinostomy and 5-fluorouracil augmented endonasal laser dacryocystorhinostomy. A retrospective review.

PURPOSE: To compare the success rates of external dacryocystorhinostomy (EXT-DCR) with 5-fluorouracil (5-FU) augmented endonasal laser dacryocystorhinostomy (ENL-DCR) and to record the complications associated with 5-FU augmented ENL-DCR MATERIALS AND METHODS: This was a retrospective non-randomised study. Forty-one patients with primary acquired nasolacrimal duct obstruction underwent an EXT-DCR (19 patients) or an ENL-DCR (22 patients) over a 3-year period. A Holmium YAG laser (Ho:YAG) was used in the latter group of patients. Silicone tubes intubated in all patients were removed at three months. 5-FU was applied intraoperatively at the site of the ostium in the ENL-DCR patients. The median follow-up was 12 months (range 3-24 months) for the ENL-DCR group and 22 months (range 6-28 months) for the EXT-DCR group. The patency of the lacrimal system and the severity of epiphora were assessed at a final-review. RESULTS: The median age of the EXT-DCR group was 77 years (range 53-87) and that of the ENL-DCR group was 71 years (range 23 to 84). There were 12 female patients in the former group and 19 in the latter. The percentage of success in the EXT-DCR group was 94.7% (95% confidence interval (CI) = 75.4-99.1) = ), and 63.6% in the ENL-DCR group (95% CI= 43.0-80.3). The confidence interval for the difference of 31.1% was 5.6-52.2. There was a statistically significant difference between the two groups, p=0.024 (Fisher exact test). CONCLUSIONS: These data suggest that EXT-DCR provides better results than 5-FU augmented ENL-DCR. However, ENL-DCR is the procedure of choice in certain circumstances such as in elderly, frail or medically unfit patients. Our results of 5-FU augmented ENL-DCR compare favourably with other published series.

Administration, Topical↗

Association of human herpesvirus 7 with cytomegalovirus disease in renal transplant recipients.

BACKGROUND: Recent studies have linked human herpesviruses 6 (HHV-6) and 7 (HHV-7) with posttransplant cytomegalovirus (CMV) disease. METHODS: Thirty-seven renal transplant recipients were monitored weekly for CMV, HHV-6, and HHV-7 DNA and serological responses for 12 weeks after transplantation. Plasma CMV load and the occurrence of CMV disease was related to HHV-6 and -7 detection. RESULTS: CMV disease was identified in 12 patients. In a logistic regression analysis, factors significantly associated with CMV disease were the detection of HHV-7 DNA in peripheral blood leucocytes and donorrecipient CMV serostatus. Patients with detectable HHV-7 DNA had significantly higher peak plasma CMV loads (P=0.01). CONCLUSIONS: An association was found between HHV-7, but not HHV-6, DNA detection and CMV disease, suggesting a possible role of HHV-7 in its pathogenesis.

Cytomegalovirus↗

Prediction and diagnosis of cytomegalovirus disease in renal transplant recipients using qualitative and quantitative polymerase chain reaction.

BACKGROUND: Preemptive antiviral therapy against cytomegalovirus (CMV) disease after transplantation requires information from suitable laboratory markers. We examined the use of qualitative and quantitative polymerase chain reaction (PCR) to monitor renal transplant recipients. METHODS: A cohort of 77 renal transplant recipients was monitored using an in-house and a commercial (Amplicor; Roche Diagnostic, Basel, Switzerland) PCR on leukocytes and plasma. Quantitative plasma viral load was determined using a commercial PCR kit (CMV Monitor; Roche Diagnostic). Patients were analyzed according to their pretransplantation CMV serological status (R- or R+). RESULTS: Seventeen patients developed CMV disease after transplantation. Qualitative leukocyte PCRs had the best overall sensitivity (54-69%) and specificity (75-87%) in identifying R- recipients with CMV disease before onset. The specificities of qualitative PCRs for R+ recipients were poor and, if used, could result in unnecessary preemptive treatment in up to 50% of patients. Symptomatic and asymptomatic R+, but not R-, recipients could be distinguished using a plasma viral load of 25,000 copies/ml. An increase in viral load of >0.7 log (fivefold) per week also distinguished between symptomatic and asymptomatic R+ recipients with high sensitivity (100%) and specificity (95%). CONCLUSIONS: Qualitative leukocyte PCRs were the best assays to predict CMV disease for R- recipients who received R+ kidneys. None of the qualitative assays could be used to guide preemptive therapy of R+ recipients, but plasma viral load and its incremental rate could be used as diagnostic tools in R+ recipients.

Adult↗

A 6-Mb high-resolution physical and transcription map encompassing the hereditary prostate cancer 1 (HPC1) region.

Several hereditary disease loci have been genetically mapped to the chromosome 1q24-q31 interval, including the hereditary prostate cancer 1 (HPC1) locus. Here, we report the construction of a 20-Mb yeast artificial chromosome contig and a high-resolution 6-Mb sequence-ready bacterial artificial chromosome (BAC)/P1-derived artificial chromosome (PAC) contig of 1q25 by sequence and computational analysis, STS content mapping, and chromosome walking. One hundred thirty-six new STSs, including 10 novel simple sequence repeat polymorphisms that are being used for genetic refinement of multiple disease loci, have been generated from this contig and are shown to map to the 1q25 interval. The integrity of the 6-Mb BAC/PAC contig has been confirmed by restriction fingerprinting, and this contig is being used as a template for human chromosome 1 genome sequencing. A transcription mapping effort has resulted in the precise localization of 18 known genes and 31 ESTs by database searching, exon trapping, direct cDNA hybridization, and sample sequencing of BACs from the 1q25 contig. An additional 11 known genes and ESTs have been placed within the larger 1q24-q31 interval. These transcription units represent candidate genes for multiple hereditary diseases, including HPC1.

Base Sequence↗

How well are randomized controlled trials reported in the dermatology literature?

OBJECTIVE: To assess the methodological quality of the design and reporting of randomized controlled trials published in one major dermatology specialty journal. DESIGN AND DATA SOURCES: In a survey of all published parallel group randomized controlled trials, we found 73 reports with allocation described as randomized from all issues of Clinical and Experimental Dermatology from its inception in 1976 through 1997. MAIN OUTCOME MEASURES: Direct and indirect measures of the adequacy of randomization, trial sample size, baseline comparisons, and intention-to-treat analysis. RESULTS: Hand searching identified 73 randomized controlled trials, but only 31 of these were found by searching MEDLINE for the publication type clinical trials. Of the 73 randomized controlled trials, 68 contained sufficient information to include in the analysis. Only 1 study (1%) reported the method of random sequence generation, and only 5 studies (7%) reported adequate concealment of allocation. Among 38 trials that used simple randomization, the sample sizes in the comparison groups were identical in 22 occasions, raising the possibility that simple randomization might not have been adequately generated or concealed. Most trials (88%) excluded some randomized participants from their analysis. The median sample size was 23 per trial. Only 1 trial reported sample size and statistical power considerations and had an a priori main hypothesis. CONCLUSIONS: Hand searching is important for locating all relevant trials. There is the need for higher methodological quality in clinical trial reporting in dermatology journals. The adoption of the CONSORT (Consolidated Standards of Reporting Trials) statement and checklist for the reporting of trials should enhance the validity of and strengthen the evidence from clinical trials reports.

Data Collection↗

Outcome measures of disease severity in atopic eczema.

BACKGROUND: An essential component of evidence-based medicine is the use of valid and reliable outcome measures in clinical trials. There is much confusion in the field of atopic eczema regarding how to best measure disease severity objectively. OBJECTIVE: To establish the extent to which existing objective clinical scales for atopic eczema have been tested for validity, reliability, sensitivity to change, and acceptability. DESIGN: An electronic bibliographic search was performed for published data on all currently available named atopic eczema scales. RESULTS: Thirteen scales were identified in total. Data on construct or criterion validity were available for 10 scales. Only 5 scales had been tested for reliability (interobserver variability, intraobserver variability, or internal consistency). Data on responsiveness to change were available for 8 scales. An estimated time to administer the measure had been given for 3 scales. The only severity scale for which published data could be found on validity, reliability, sensitivity, and acceptability testing was the Severity Scoring of Atopic Dermatitis index, although problems occurred with interobserver variation of the index. CONCLUSION: The rapidly increasing number of severity scales for atopic eczema, many of which have been inadequately tested, has made the interpretation of patient outcomes confusing, and comparison of results between studies almost impossible. Consensus among clinicians and researchers on the use of severity scales for atopic eczema should be based on evidence of adequate validity), reliability, sensitivity to change, and ease of use.

Clinical Trials as Topic↗

Urban-rural mortality differentials: controlling for material deprivation.

This paper investigates the relationship between premature mortality and material deprivation, and the differences in this relationship between urban and rural areas. We examine, given comparable measures of affluence or deprivation, whether residual differences exist between urban and rural areas for all-causes of death and, separately, for cancers, circulatory and respiratory diseases. Using 1990-92 mortality data for the 908 wards of Wales we apply statistical analyses based on tabular data and parametric Poisson regression models. Contrasts are sought between six urban and rural categories defined in terms of settlement sizes and the employment structure of rural areas. Inequalities in all-cause premature mortality are widest in the cities, narrowest in the deeper rural areas, and of intermediate and comparable value in other areas of Wales. This is largely a reflection of the different distributions of material deprivation in these areas. After controlling for differences in socio-economic characteristics, using deprivation measures, the tendency for lower mortality in deeper rural areas is substantially reduced. Residual mortality differences between urban and rural areas are shown to be dependent on the way deprivation is measured and the disease group under study. For cancers there are no residual mortality differences, while for respiratory and circulatory diseases some of the residual variation can be accounted for by employment variables, particularly previous employment in the coal mining industry.

Humans↗

Fatal antidepressant overdose among drug abusers and non-drug abusers.

OBJECTIVE: This study examined the predictors, extent and pattern of fatal antidepressant overdose (FAO) in all psychoactive drug-related deaths and compared these in drug abusers and non-drug abusers. METHOD: Inquest data on 491 psychoactive drug-related cases in England and Wales were analysed. We examined predictors of FAO relative to other drug-related deaths in drug abusers and non-abusers using logistic regression, and compared the relative fatality of different antidepressant classes using the Proportionate Fatality Index (PFI). RESULTS: The overall FAO prevalence ratio was 10% (male = 7.1%, female = 18.5%). FAO was twice as likely to occur among cases aged 45 years and over than in younger cases (MOR = 2.6, 95% CI = 1.4-4.9), and eight times more likely to occur in cases with no history of drug abuse (MOR = 8.2, 95% CI = 4.0-18.4). Ingestion of prescribed antidepressants is the only common predictor of FAO among drug abusers and non-abusers, and co-ingestion of a combination of antidepressants of two different classes is a potent risk for FAO in the cases studied. CONCLUSION: The results highlight the need to develop appropriate therapeutic strategies for managing treatment-resistant depression.

Adult↗

Use of the atypical antipsychotics Olanzapine and Risperidone in adults with intellectual disability.

The present study was designed to monitor the use of atypical antipsychotics in adults with intellectual disability and to evaluate the clinical effectiveness of these drugs. Twenty-one patients were commenced on an atypical antipsychotic: 12 on Olanzapine and nine on Risperidone. The ICD-10 diagnoses of the subjects were mild (13 cases) or moderate (8 cases) mental retardation, and psychiatric disorders (17 cases) with significant impairment of behaviour in 10 cases. Tolerability was good for 15 patients experiencing minimum or no side-effects, and medication was only stopped as a result of side-effects in one case. Clinical global outcome was rated as minimally improved or better for 16 cases. The present findings suggest that the atypical antipsychotics Olanzapine and Risperidone are well tolerated by patients with intellectual disability and psychiatric disorders, and are broadly effective against target symptoms.

Adult↗

Hypothyroidism and aging: the Rosses' survey.

An earlier impression of a high prevalence of hypothyroidism in a general practice (4,190 patients including 1,544 adult females aged 18 years or more with 544 aged 50 years or more) in the Rosses, a coastal area in the northwest of Ireland was confirmed by this study. The accumulated prevalence of overt spontaneous primary hypothyroidism was 8.6% in 544 females aged 50 years or more but only 0.9% in the 1,000 females between 18 and 50 years of age. This prevalence was approximately twice that of an Irish National general practice population sample of 4,314 females aged 50 years or more (8.6% vs. 4.6%) p < 0.001. The reasons for this difference are unclear but may reflect the high level of opportunistic screening carried out in West Donegal. Thyroid peroxidase antibodies measured by radioimmunoassay were found in 75.6% of hypothyroid patients compared to 18.6% of practice controls (p < 0.01). Neither HLA-DRB1, DQA1, and DQB1 phenotype frequencies nor dietary iodine intake (median urinary iodine excretion 104 microg/L) appeared to be contributory factors. The finding of an 8.6% accumulated prevalence of hypothyroidism in females greater than 50 years of age when a population is aggressively investigated demonstrates the relative importance of its contribution to total morbidity and suggests that the disorder may be underdiagnosed, thus supporting the concept of targeted screening in this age group.

Aging↗

Comparison of two commercial methods for measurement of cytomegalovirus load in blood samples after renal transplantation.

A cohort of 77 renal transplant recipients was prospectively studied for comparison of two commercially available cytomegalovirus (CMV) load assays, i.e., the COBAS AMPLICOR CMV Monitor test (Amplicor), using plasma samples, and the Murex Hybrid Capture System (HCS), using whole blood. The manufacturer of the HCS assay changed the version of the test from 1.0 (HCS-1) to 2.0 (HCS-2) after the first 37 patients had been tested. Despite the differences in principle and type of specimen used, the Amplicor and HCS assays gave comparable results. The regression line correlating the HCS-1 assay to the Amplicor assay was similar to that correlating the HCS-2 assay to the Amplicor assay. The HCS results could be converted to Amplicor-equivalent units by using linear-regression equations [log(10) HCS-1 result = 0.49 (log(10) Amplicor result) + 2.58, and log(10) HCS-2 result = 0.61 (log(10) Amplicor result) + 2.18]. The HCS-2 assay appeared to have the lowest detection limit, followed by the Amplicor assay and then the HCS-1 assay. When a sliding scale of cutoff values in Amplicor-equivalent units (>1,000, >2,500, >6,000, >16,000, >40,000, and >100,000 copies/ml) was applied to diagnose CMV disease, similar patterns of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were observed with the Amplicor and HCS assays. A cutoff value of >40,000 copies/ml has a low sensitivity (Amplicor, 29.4%; HCS, 41.2%) but is specific (Amplicor, 96.7%; HCS, 93.3%) and can be used for the differential diagnosis of CMV disease (PPV, 71.4% [Amplicor] or 63. 6% [HCS]; NPV, 82.9% [Amplicor] or 84.8% [HCS]). A lower cutoff value of >1,000 copies/ml improves the sensitivity (Amplicor, 76.5%; HCS, 82.4%) and has a high NPV (Amplicor, 91.8%; HCS, 94.2%) but, due to the low PPV (Amplicor, 46.2%; HCS, 56%), is useful only for exclusion of CMV disease.

Cohort Studies↗

Clinical standards for inpatient specialist rehabilitation services in the UK.

OBJECTIVE: To develop a set of clinical standards for specialist inpatient rehabilitation services in the UK and to undertake a preliminary survey of consultants who provide those services. DESIGN: The proposed set of standards was developed by group consensus followed by an iterative consultation process. A postal survey was conducted on behalf of the British Society for Rehabilitation Medicine (BSRM) amongst its consultant members in the UK (n = 163), who were asked to assess their services in relation to these standards, and to comment on the standards themselves, their usefulness and applicability. RESULTS: The response rate was 61%, of which 81 respondents ran an inpatient rehabilitation service. Overall, the standards appeared to be acceptable to most, and mainly struck the right level, being attained by the majority of services. Specific suggestions were incorporated into the revised standards. Further work is required to establish agreed outcomes that are systematically measured and recorded: only half the respondents (50%) routinely recorded a standardized outcome measure, and only a quarter (26%) routinely reviewed patients to record long-term outcome. CONCLUSIONS: Clinical standards have been developed for specialist inpatient rehabilitation services in the UK. The BSRM proposes to adopt these standards for a test period of 2-3 years in the first instance. It is likely that they will require further refinement with time, and modification is required to adapt them to different subspecialities and settings.

Guideline Adherence↗

APOE epsilon 4 influences the manifestation of Alzheimer's disease in adults with Down's syndrome.

BACKGROUND: Recent studies of the relationship between the apolipoprotein E (APOE) gene and Alzheimer's disease in adults with Down's syndrome have revealed inconsistent results. AIMS: To assess the role of the APOE gene in the manifestation of Alzheimer's disease in adults with Down's syndrome. METHOD: We studied the APOE genotypes of 24 adults with dementia and 33 non-demented adults with Down's syndrome over 35 years of age, and an additional group of 164 non-learning disabled adults. We also carried out a meta-analysis of all previously published studies of association between APOE and Down's syndrome, incorporating the current data. RESULTS: We observed a non-significant excess of APOE epsilon 4 and a reduction of epsilon 2 in adults with dementia compared with non-demented adults with Down's syndrome in our sample. However, meta-analysis showed a significantly higher frequency of epsilon 4 in adults with dementia compared with non-demented adults with Down's syndrome (odds ratio = 2.02, 95% CI 1.33-3.07, P = 0.001), but no significant reduction in the frequency of epsilon 2. CONCLUSIONS: The APOE epsilon 4 allele acts as a risk factor for the age-specific manifestation of Alzheimer's disease in people with Down's syndrome.

Adult↗