Search PubMed⌕ Search

Biomedical subjects

H Williams

Publications and source records attributed to H Williams.

At least 19 recordsLinked to original sources
PubMed1999

Worldwide variations in the prevalence of symptoms of atopic eczema in the International Study of Asthma and Allergies in Childhood.

BACKGROUND: Little is known about the prevalence of atopic eczema outside Northern Europe. OBJECTIVES: We sought to describe the magnitude and variation in the prevalence of atopic eczema symptoms throughout the world. METHODS: A cross-sectional questionnaire survey was conducted on random samples of schoolchildren aged 6 to 7 years and 13 to 14 years from centers in 56 countries throughout the world. Those children with a positive response to being questioned about the presence of an itchy relapsing skin rash in the last 12 months that had affected their skin creases were considered to have atopic eczema. Children whose atopic eczema symptoms resulted in sleep disturbance for 1 or more nights per week were considered to have severe atopic eczema. RESULTS: Complete data was available for 256,410 children aged 6 to 7 years in 90 centers and 458,623 children aged 13 to 14 years in 153 centers. The prevalence range for symptoms of atopic eczema was from less than 2% in Iran to over 16% in Japan and Sweden in the 6 to 7 year age range and less than 1% in Albania to over 17% in Nigeria for the 13 to 14 year age range. Higher prevalences of atopic eczema symptoms were reported in Australasia and Northern Europe, and lower prevalences were reported in Eastern and Central Europe and Asia. Similar patterns were seen for symptoms of severe atopic eczema. CONCLUSIONS: Atopic eczema is a common health problem for children and adolescents throughout the world. Symptoms of atopic eczema exhibit wide variations in prevalence both within and between countries inhabited by similar ethnic groups, suggesting that environmental factors may be critical in determining disease expression. Studies that include objective skin examinations are required to confirm these findings.

Adolescent↗
PubMed1999

Mutations in SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness.

Thiamine-responsive megaloblastic anaemia (TRMA), also known as Rogers syndrome, is an early onset, autosomal recessive disorder defined by the occurrence of megaloblastic anaemia, diabetes mellitus and sensorineural deafness, responding in varying degrees to thiamine treatment (MIM 249270). We have previously narrowed the TRMA locus from a 16-cM to a 4-cM interval on chromosomal region 1q23.3 (refs 3,4) and this region has been further refined to a 1.4-cM interval. Previous studies have suggested that deficiency in a high-affinity thiamine transporter may cause this disorder. Here we identify the TRMA gene by positional cloning. We assembled a P1-derived artificial chromosome (PAC) contig spanning the TRMA candidate region. This clarified the order of genetic markers across the TRMA locus, provided 9 new polymorphic markers and narrowed the locus to an approximately 400-kb region. Mutations in a new gene, SLC19A2, encoding a putative transmembrane protein homologous to the reduced folate carrier proteins, were found in all affected individuals in six TRMA families, suggesting that a defective thiamine transporter protein (THTR-1) may underlie the TRMA syndrome.

Amino Acid Sequence↗
PubMed1999

A full genome scan for late onset Alzheimer's disease.

We have genotyped 292 affected sibling pairs (ASPs) with Alzheimer's disease (AD) according to NINCDS-ADRDA diagnostic criteria and with onset ages of >/=65 years using 237 microsatellite markers separated by an average distance of 16.3 cM. Data were analysed by SPLINK and MAPMAKER/SIBS on the whole sample of 292 ASPs and subsets of 162 ASPs where both members possessed an apolipoprotein E (APOE)straightepsilon4 allele and 63 pairs where neither possessed anstraightepsilon4 allele. Sixteen peaks with a multipoint lod score (MLS) >1 either in the whole sample, the straightepsilon4-positive or -negative subgroups were observed on chromosomes 1 (two peaks), 2, 5, 6, 9 (two peaks), 10 (two peaks), 12, 13, 14, 19, 21 and X (two peaks). Simulation studies revealed that these findings exceeded those expected by chance, although many are likely to be false positives. The highest lod scores on chromosomes 1 (MLS 2.67), 9 (MLS 2.38), 10 (MLS 2.27) and 19 (MLS 1.79) fulfilLander and Kruglyak's definition of 'suggestive' in that they would be expected to occur by chance once or less per genome scan. Several other peaks were only marginally less significant than this, in particular those on chromosomes 14 (MLS 2.16), 5 (MLS 2.00), 12, close to alpha2-macroglobulin (MLS 1.91), and 21, close to amyloid precursor protein (MLS 1.77). This is the largest genome scan to date in AD and shows for the first time that this is a genetically complex disorder involving several, perhaps many, genes in addition to APOE. Moreover, our data will be of interest to those hoping to identify positional candidate genes using information emerging from neurobiological studies of AD.

Age of Onset↗
PubMed1999

Changes in adult zebra finch song require a forebrain nucleus that is not necessary for song production.

Male zebra finches normally crystallize song at approximately 90 days and do not show vocal plasticity as adults. However, changes to adult song do occur after unilateral tracheosyringeal (ts) nerve injury, which denervates one side of the vocal organ. We examined the effect of placing bilateral lesions in LMAN (a nucleus required for song development but not for song maintenance in adults) upon the song plasticity that is induced by ts nerve injury in adults. The songs of birds that received bilateral lesions within LMAN followed by right ts nerve injury silenced, on average, 0.25 syllables, and added 0.125 syllables (for an average turnover of 0.375 syllables), and changed neither the frequency with which individual syllables occurred within songs nor the motif types they used most often. In contrast, the songs of birds that received sham lesions followed by ts nerve injury lost, on average, 1.625 syllables, silenced 0.125 syllables, and added 0.75 syllables, turning over an average of 2.5 syllables. They also significantly changed both the frequency with which individual syllables were included in songs and the motif variants used. Thus, song plasticity induced in adult zebra finches with crystallized songs requires the presence of LMAN, a nucleus which had been thought to play a role in vocal production only during song learning. Although the changes to adult songs induced by nerve transection are more limited than those that arise during song development, the same circuitry appears to underlie both types of plasticity.

Aging↗
PubMed1998

The activation state of p38 mitogen-activated protein kinase determines the efficiency of ATP competition for pyridinylimidazole inhibitor binding.

The serine/threonine kinase p38 is a ubiquitous, highly conserved, stress responsive, signal-transducing enzyme. It regulates the production of proinflammatory mediators and is the target of the cytokine synthesis inhibitory pyridinylimidazoles. We have expressed human p38 in Drosophila S2 cells and characterized preparations of mixed unphosphorylated/monophosphorylated (inactive) and homogeneously diphosphorylated (active) forms of the enzyme. We observed that only the active preparation of the enzyme has significant kinase activity when assayed using an ATF2-GST fusion protein as the substrate. We determined that the value of KM[ATP] in this reaction is 25 microM and that the pyridinylimidazole inhibitor of p38 kinase activity, SB203580, competes with ATP. We have found that a tritiated pyridinylimidazole, SB202190, has an equal affinity for both the active and inactive forms of the enzyme and that SB203580 competes with it equally well for binding to either form of the enzyme. However, ATP can compete with the tritiated inhibitor for binding to only the active form of the enzyme. Further, we demonstrate in vivo that at concentrations consistent with its IC50 as a cytokine inhibitor, SB203580 can inhibit stimulus-induced phosphorylation of p38 at the Thr-Gly-Tyr activation motif. Our observations suggest that pyridinylimidazoles may block the biological activity of p38 kinase by binding to the inactive form of p38 and reducing its rate of activation. Under these conditions, ATP would not effectively compete with the inhibitors in vivo.

Adenosine Triphosphate↗
PubMed1998

The Cochrane Skin Group. Preparing, maintaining, and disseminating systematic reviews of clinical interventions in dermatology.

In 1979, Prof Archie Cochrane challenged the medical profession to produce a critical summary of randomized controlled clinical trials according to specialty, which should be updated periodically. The Cochrane Collaboration, an international voluntary group of reviewers and researchers from a range of professional backgrounds dedicated to producing systematic reviews, was established in 1992 in response to Cochrane's challenge. Systematic reviews produced by the Cochrane Collaboration start with individuals who formulate questions that are important to the care of patients. Every effort is then made to locate published and unpublished evidence to answer the question, and explicit criteria are used to select studies for inclusion in the review and to assess their quality. If appropriate, meta-analysis is used to combine results from several smaller studies to produce an overall result. Reviews are published in the Cochrane Library, an electronic publication (CD-ROM or diskette form), and the reviews are updated quarterly. In December 1997, a Cochrane Skin Group was registered with the Cochrane Collaboration to prepare, maintain, and disseminate reviews on the effects of health care for people with dermatological conditions. Currently, 25 titles and 9 review protocols have been registered with the Cochrane Skin Group, and the first set of dermatological reviews will be available before the end of 1999. The Cochrane Skin Group aims to become the best source of unbiased external evidence for summarizing the effects of dermatological care.

Dermatology↗
PubMed1998

Alternative splicing of human NrCAM in neural and nonneural tissues.

Neural cell adhesion molecule NrCAM exists in a variety of isoforms as a result of alternative splicing of individual exons during RNA processing. In this report we demonstrate that many of the alternative splicing events described for chick are conserved in man and describe a novel variant of NrCAM cDNA. Furthermore, we show that NrCAM is expressed at significant levels outside the nervous system; in particular in pancreas, adrenal glands, and placenta and that expression in both brain and other tissues is accompanied by a very variable pattern of exon utilization in fetal and adult cells.

Adrenal Glands↗
PubMed1998

Urinary complications of Miami pouch: trend of conservative management.

OBJECTIVE: Continent urinary diversions have become popular among gynecologic oncologists. Much information has been gained concerning the complications and current management of patients with continent ileocolonic reservoirs. The high mortality rate associated with reoperation has led clinicians to adopt a trend toward conservative means of management. The purpose of this study was to evaluate the applicability of conservative management of complications related to the creation of the continent ileocolonic reservoir Miami pouch. STUDY DESIGN: Patients who underwent creation of the Miami pouch at the Division of Gynecologic Oncology, University of Miami School of Medicine, since 1988 have been included in this study. Management of complications, with particular emphasis on the conservative treatment, has been reviewed in detail for each patient. Open surgery and conservative treatment have been compared. RESULTS: Seventy-seven patients underwent creation of the Miami pouch from February 1988 to September 1997. Sixty (77.9%) patients were affected by recurrent cervical cancer; 72 (93.5%) were previously radiated. The perioperative mortality rate was 11.7% (9 patients). Six of these patients died as a result of sepsis; all of them underwent reoperation at least once. The most common urinary complications were ureteral stricture or obstruction (22.1%), difficult catheterization (19.5%), and pyelonephritis (13%). Conservative management strategies used for these complications included percutaneous nephrostomy, stent placement, balloon dilatation, radiologically (ultrasonography, fluoroscopy, computed tomography) guided placement of catheters, and antibiotic treatment. Eighty percent of the complications associated with the ileocolonic reservoir were resolved with conservative treatment, whereas 16.9% required surgical revision. CONCLUSION: On the basis of these findings, conservative management of urinary reservoir complications should always be considered before surgical intervention is attempted. The exact time to engage in open revision should be individualized on the basis of the clinical condition of each patient. It is our belief that the conservative approach should be instituted whenever possible but surgical intervention not be delayed when absolutely indicated.

Adult↗
PubMed1998

Hepatitis G virus infection in drug users in Liverpool.

OBJECTIVES: To establish the prevalence of hepatitis G (HGV) in drug users in Liverpool; to explore the risk factors for, and the effects of, HGV infection. METHODS: Serum samples from 129 drug users who had attended the Infectious Diseases Unit at Fazakerley Hospital, Liverpool, between January 1995 and June 1996 were examined for HGV RNA using PCR, HGV RNA results were collated with demographic data, information on drug-use behaviour, hepatitis B (HBV) and C (HCV) serology, and the results of serum bilirubin and aspartate amino-transferase (AST) measurements. RESULTS: Overall, 37 (29%) of patients were HGV RNA positive, 89 (69%) were negative, and equivocal results were obtained in three (2%) cases. Direct sequencing of PCR products of the 5' non-translated region for 13 patients showed that these were generally more closely related to the HGV than the GB virus C (GBV-C) sequence. HGV co-infection with HCV and HBV was common: of HGV-positive patients, 28 (76%) and 16 (44%) had antibodies to HCV (anti-HCV) and hepatitis B core protein (anti-HBc), respectively. Increasing duration of injecting drug use was associated with a decreasing seroprevalence of HGV RNA, dropping from 39% for 0-4 years of injecting to 14% for > 12 years injecting. Serum bilirubin and AST values were frequently elevated, but statistical analysis showed no differences between HGV-positive and HGV-negative patient groups. CONCLUSIONS: HGV infection is common in drug users in Liverpool, but HGV RNA prevalence falls with increasing duration of injecting drug use, probably as a result of viral clearance and the development of protective immunity. HGV infection does not appear to be a significant cause of hepatic dysfunction in Liverpool drug users.

Adult↗
PubMed1998

Community validation of the United Kingdom diagnostic criteria for atopic dermatitis in Romanian schoolchildren.

Although the U.K. modification of Hanifin and Rajka's diagnostic criteria for atopic dermatitis (AD) for use in epidemiological studies has demonstrated good validity and repeatability when previously tested in a U.K. community setting, little is known about its performance in other countries where different cultural, educational and linguistic factors could impair validity. We used a questionnaire to test the validity of the U.K. criteria as a point prevalence measure of AD in 1114 Romanian schoolchildren aged 6-12 years against the clinical diagnosis of a dermatologist with an interest in AD, who was unaware of the questionnaire content and responses. The sensitivity and specificity of the U.K. criteria for AD in this setting was 74% and 99%, respectively, an improvement rather than a deterioration in validity when compared with the previous U.K. study. Test-retest repeatability for all of the questions pertaining to the U.K. criteria using the chance-corrected kappa statistic was high, with values of 0.72 and over. The positive predictive value of the criteria was lower than in the U.K. study (63% compared with 80%, respectively) due to the very low prevalence of AD in this study (2.4%). The validity of a parental report of 'eczema' was poor, with a sensitivity of 22%, specificity of 97% and positive predictive value of 18%. This study suggests that the U.K. criteria perform well in settings outside the U.K., although care has to be taken when using the criteria to ascertain cases in settings where the prevalence of AD is very low.

Child↗
PubMed1998

Diogenes' syndrome in patients with intellectual disability: 'a rose by any other name'?

Diogenes' syndrome is characterized by marked self-neglect, domestic squalor, social withdrawal and hoarding of rubbish (syllogomania). The syndrome has been reported to occur in association with a wide variety of conditions, but the present authors were unable to find any previous reports of Diogenes' syndrome in patients with intellectual disability.

Activities of Daily Living↗
PubMed1998

Cellular immunity to varicella-zoster virus in patients with major depression.

The incidence of herpes zoster increases markedly with advancing age, and this appears to be causally related to an age-dependent decline in varicella-zoster virus (VZV)-specific cellular immunity. Psychologic stress has also been linked to the occurrence of herpes zoster, but the mechanism involved has not been investigated. This study examined the relationship between major depression and VZV-specific cellular immunity by comparing VZV-specific responder cell frequency (RCF) in adults with major depression (n = 11) to that in age- and sex-matched nondepressed controls (n = 11) and in a larger group of nondepressed adults who were > or = 60 years old. VZV-specific RCF in depressed patients was markedly reduced compared with the RCF in matched controls (t = 2.7, P < .02). In fact, the levels of VZV-specific RCF in the depressed patients were comparable in magnitude to the low levels found in adults > or = 60 years of age. These data indicate that major depression is associated with a marked decline in VZV-specific cellular immunity.

Adult↗