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Biomedical subjects

D Wilson

Publications and source records attributed to D Wilson.

At least 163 records · Page 9Linked to original sources
PubMed1999

Genetic studies suggest a multicentric origin for Hb G-Coushatta [beta22(B4)Glu-->Ala].

Hb G-Coushatta [beta22(B4)Glu-->Ala] is found in geographically separated ethnic groups. Commonest along the Silk Road region of China but also present in the North American Coushatta, we sought to determine whether this variant had a unicentric or multicentric origin. We examined the haplotype of the beta-globin gene cluster in two Chinese families and in five Louisiana Coushatta heterozygous for this mutation. Chinese and Louisiana Coushatta had different haplotypes associated with the identical Hb G mutation. These haplotypes were defined by the presence of a HindIII restriction site in the Agamma-globin gene and AvaII restriction site in the beta-globin gene in Chinese subjects and their absence in the Louisiana Coushatta. We found a CAC at codon beta2 (beta-globin gene framework 1 or 2) linked to the Hb G-Coushatta gene in Chinese, and a CAT (framework 3) in Louisiana Coushatta, indicating different beta-globin gene frameworks. Both the Hb G-Coushatta mutation (GAA-->GCA) and the codon 2 CAC-->CAT polymorphism are normal delta-globin gene sequences, suggesting the possibility of gene conversion. We conclude that Hb G-Coushatta had at least two independent origins. This could be due to separate mutations at codon beta22 in Chinese and Louisiana Coushatta, a mutation at this codon and a beta-->delta conversion, or two beta-->delta gene conversion events.

China↗
PubMed1999

A double-blind placebo-controlled trial of paroxetine in the management of social phobia (social anxiety disorder) in South Africa.

BACKGROUND: Social phobia, also known as social anxiety disorder, is a highly prevalent disorder with significant morbidity. Patients with social phobia frequently develop co-morbid psychiatric disorders such as depression and substance abuse, and the disorder impacts significantly on social and occupational functioning. It has been suggested that the selective serotonin reuptake inhibitors (SSRIs) are useful in the management of this disorder, but few controlled trials have been undertaken in this regard. There are also few data on the pharmacotherapy of social phobia in South Africa. METHODS: A double-blind randomised placebo-controlled multi-site flexible-dose trial of paroxetine was undertaken over 12 weeks among patients with a primary diagnosis of social phobia. Primary response measures were the Global Improvement item on the Clinical Global Impression scale (CGI) and mean change from baseline in the patient-rated Liebowitz Social Anxiety Scale (LSAS) total score. Ninety-three patients participated at 9 South African sites; their data are reported here. RESULTS: There was a significant drug effect on both the CGI Global Improvement score and the LSAS at 12 weeks. In addition, there was no significant difference in overall rate of adverse experiences between those on paroxetine and those on placebo. CONCLUSIONS: Paroxetine is both effective and safe in the acute treatment of social phobia. The findings here are consistent with those of previous controlled studies of the SSRIs as well as with previous work done in the USA on the use of paroxetine in the treatment of this disorder. Early diagnosis and treatment of social phobia should be encouraged. However, further research on long-term pharmacotherapy of social phobia is needed.

Adult↗
PubMed1999

A comparison of the clinical and laboratory features of thin basement membrane disease (TBMD) and IgA glomerulonephritis (IgA GN).

AIM: The aim of this study was to determine the clinical and laboratory characteristics that distinguished thin basement membrane disease (TBMD) from IgA glomerulonephritis (IgA GN) at presentation and at follow-up. PATIENTS AND METHODS: Seventy-one patients with TBMD and 31 with IgA GN were studied. Males accounted for 11/71 (15%) patients with TBMD, and 20/31 (65%) of those with IgA GN (p < 0.001). RESULTS: At presentation, patients with TBMD had hematuria (42%) or proteinuria (42%), and sometimes both (24%), while those with IgA GN usually had both hematuria and proteinuria (71%, p < 0.0001). Furthermore, patients with IgA GN were more likely to have higher urinary RBC counts (p < 0.001), and more proteinuria (p < 0.001) than those with TBMD. An elevated serum creatinine or blood pressure did not distinguish between TBMD and IgA GN at presentation. At review, fewer individuals with IgA GN had elevated levels of urinary RBC and protein, and the proportions were not different from those in patients with TBMD. This was presumably because the acute episode had resolved. CONCLUSION: The outcome was worse in patients with IgA GN, with 8/31 (26%) having an elevated serum creatinine and 3/31 (10%) with end-stage renal failure, compared with an elevated serum creatinine in 3/61 (5%) patients with TBMD (p < 0.02) and no patients with renal failure (p < 0.05).

Adolescent↗
PubMed1999

Common source outbreak of salmonellosis in a food factory.

Seventy-three employees at a food processing factory employing 2700 staff reported vomiting, diarrhoea, or abdominal pain between 30 July and 3 August 1997. Salmonella enteritidis phage type (PT) 4 was isolated from 47 symptomatic cases and five asymptomatic canteen staff. The epidemic curve suggested a point exposure to a common source: 60% of cases reported illness on 31 July. An uncooked dessert containing raw shell eggs was identified as a possible vehicle of infection. Caterers are reminded that pasteurised egg should be substituted for shell egg in dishes that are eaten raw or only lightly cooked.

Disease Outbreaks↗
PubMed1998

TAP- and tapasin-dependent HLA-E surface expression correlates with the binding of an MHC class I leader peptide.

BACKGROUND: The human major histocompatibility complex (MHC) class lb molecule HLA-E is transcribed in most tissues but little is known about its localisation within the cell. We have recently shown that HLA-E binds signal-sequence-derived peptides from human MHC class I molecules in vitro. RESULTS: Using a newly characterised antibody recognising HLA-E, we show that HLA-E is expressed at the cell surface. We demonstrate that HLA-E surface expression is correlated with the presence of MHC class I molecules which provide suitable leader sequence peptides capable of binding to HLA-E. Further studies on the interaction of HLA-E with molecules in the endoplasmic reticulum revealed that HLA-E associates with the transporter associated with antigen processing (TAP) and calreticulin, and that HLA-E expression is TAP-dependent and tapasin-dependent. In addition, HLA-E dissociates from TAP upon binding of MHC class I leader sequence peptides. CONCLUSION: These experiments establish that surface expression of HLA-E is regulated by the binding of a restricted pool of peptides from the leader sequence of MHC class I molecules. The correlation between HLA-E and MHC class I surface expression might be relevant to the function of HLA-E. Our results also show that, although these HLA-E binding peptides are derived from signal sequences, they may be released back into the cytosol and subsequently translocated by the TAP complex and loaded onto HLA-E molecules.

Alleles↗
PubMed1998

The effects of regulation and competition in the NHS internal market: the case of general practice fundholder prices.

The 1989 reforms of the UK National Health Service introduced competition in supply within a tightly regulated framework. The paper examines whether this competition affects the prices posted by sellers of medical services. We argue that despite regulation market forces may have an impact on price. We test this using the posted prices for one of the two types of buyer, General Practice Fundholders. We find the regulatory rules are not observed, and some evidence of the impact of market forces on price.

Budgets↗
PubMed1998

Hydroxylation of macrolactones YC-17 and narbomycin is mediated by the pikC-encoded cytochrome P450 in Streptomyces venezuelae.

BACKGROUND: . Streptomyces venezuelae produces two groups of antibiotics that include the 12-membered ring macrolides methymycin and neomethymycin, and the 14-membered ring macrolide pikromycin. Methymycin and pikromycin are derived from the corresponding precursors, YC-17 and narbomycin, respectively, by hydroxylation of the tertiary carbon position (C-10 in YC-17 or C-12 in narbomycin) on the macrolactone ring. In contrast, neomethymycin is derived from YC-17 by hydroxylation of the secondary carbon (C-12) of the propionyl starter unit sidechain. RESULTS: . Using a genetic and biochemical approach we have characterized a single P450 hydroxylase (PikC) in the methymycin/pikromycin biosynthetic gene cluster (pik) from S. venezuelae. Inactivation of pikC abolished production of all hydroxylated macrolides, with corresponding accumulation of YC-17 and narbomycin in the culture medium. The enzyme was produced efficiently and purified as a His-tagged protein from recombinant Escherichia coli cells. Purified PikC effectively converts YC-17 into methymycin and neomethymycin and narbomycin into pikromycin in vitro. CONCLUSIONS: . These results demonstrate that PikC is responsible for the conversion of YC-17 to methymycin and neomethymycin, and narbomycin to pikromycin in S. venezuelae. This substrate flexibility is unique and represents the first example of a P450 hydroxylase that can accept 12- and 14-membered ring macrolides as substrates, as well as functionalize at two positions on the macrolactone system. The broad substrate specificity of PikC provides a potentially valuable entry into the construction of novel macrolide- and ketolide-based antibiotics.

Amino Acid Sequence↗
PubMed1998

Diabetes complications and risk factors in an Australian population. How well are they managed?

BACKGROUND: This study aimed to explore the relationship between complications and risk factors in the type 2 diabetes population, and to assess the level of assistance people with diabetes receive in controlling their risk factors. METHODS: Participants were recruited from representative population surveys of South Australians aged over 18 years. Participants were asked a series of questions about their risk factors and the advice and assistance they received from their general practitioner (GP) in modifying their risk factors. Additionally, participants were clinically tested for a number of macro and microvascular complications. RESULTS: South Australians with type 2 diabetes have a high prevalence of risk factors, with the majority being overweight or obese, doing no vigorous exercise and having high blood pressure. They also have a high prevalence of complications, with 53% having at least one macrovascular complication and 66% having at least one microvascular complication. Additionally, participants reported high levels of GP advice and assistance on the risk factors where pharmacological controls were available, but low levels of assistance where non-pharmacological interventions were needed to control the risk factor. CONCLUSIONS: The prevalence of diabetes risk factors and complications among South Australians with type 2 diabetes is a cause for concern, as is the lack of assistance offered by GPs to modify risk factors. Multi-disciplinary approaches to the control of risk factors and patient self-management and education are critical to the progression and success of diabetes care.

Adult↗
PubMed1998

Impact of infection on mortality and hospitalization in the North East of England.

BACKGROUND: Current modes of presentation of mortality and hospitalization data, based on codes in Chapter 1 of the International Classification of Diseases (ICD), hide the true importance of infection and other microbial diseases (infections). Our aim was to produce a new aggregation of ICD-9 to estimate their true impact. METHODS: ICD-9 codes for infections, irrespective of ICD-9 chapter, were extracted to form the new aggregation. We reanalysed routine mortality (1979-1983 and 1989-1993) and hospital finished consultant episode data (FCEs) (1989-1993) in the area of the former Northern Regional Health Authority (population approximately 3 million) using the new aggregation of codes. This area is in the North East of England. Age- and sex-specific rates of death and FCE from infection were calculated using mid-1981 and mid-1991 population estimates. RESULTS: Using ICD-9 Chapter 1 codes, 839 (0.4 per cent) deaths in 1989-1993 were classified as due to infection, compared with 12655 (6.7 per cent) with the new aggregation. In 1979-1983, 10.3 per cent of all deaths were due to infection. The highest rates of infection death were in the oldest age groups and infants. FCEs for infections were 1.2 per cent using ICD-9 Chapter 1 codes, but 5.4 per cent using the new aggregation. The highest rates of infection FCEs were in infants. Most infection deaths and hospitalizations were for respiratory disorders. Using the new aggregation, infection moved from the 13th ranking cause of death to the third ranking cause; and from the 15th ranking cause of hospitalization to the 10th. CONCLUSIONS: The usual method of presenting data coded by ICD-9 chapters greatly understates the contribution of infection to morbidity and mortality and may mislead policy makers assessing the priority to be given to infections.

Adolescent↗
PubMed1998

Congenital reflux nephropathy and severe unilateral fetal reflux.

PURPOSE: When prenatal ultrasound reveals urinary tract dilatation, fetal reflux is suspected. Postnatal voiding cystourethrography confirms the diagnosis. The origin of reflux nephropathy is controversial, and the roles of urinary tract infection and pressure effects of sterile reflux on the developing kidneys are debatable. We evaluate the relationship between sterile reflux and renal scarring. MATERIALS AND METHODS: We reviewed the records of 100 infants and children seen during a 15-year period in whom fetal reflux had been diagnosed, including 81 with bilateral and 19 with unilateral vesicoureteral reflux. In 12 of the 19 patients voiding cystourethrography revealed unilateral grade IV or V reflux, and they comprise the study group. Split renal function was measured in all 12 patients by radionuclide renal scan shortly after birth and before urinary tract infection developed. RESULTS: Individual renal function was 0 to 40% in all refluxing renal units. Split renal function was less than 10% in 3 kidneys, 10 to 30% in 5 and 30 to 40% in 4. There were 2 nonfunctioning kidneys. In the remaining 10 kidneys isotope distribution on the nuclear scan indicated decreased renal length and mass. Subsequently 7 patients had breakthrough urinary tract infections while on antibiotic chemoprophylaxis. Nephrectomy, and nephroureterectomy and ureteral reimplantation with or without tapering were performed in 3 and 9 refluxing ureters, respectively. Pathological examination of the 3 nephrectomy specimens revealed severe renal dysplasia consisting of persistent primitive ducts and nests of metaplastic cartilage. CONCLUSIONS: Our study supports the notion that renal impairment associated with severe fetal reflux is present at birth, and it is likely due to congenital dysplasia.

Child↗
PubMed1998

A South Australian Salmonella Mbandaka outbreak investigation using a database to select controls.

UNLABELLED: Between April and June 1996, 15 persons with Salmonella enterica serovar Mbandaka infection were reported in South Australia (population 1.6 million) compared with 12 over the previous five years. To identify a possible source for the infections a case control study was conducted. METHODS: Trained interviewers asked 15 cases and 45 controls about their consumption of 105 foods. Controls were matched to case residential location and age. They were selected from a previously constructed database of 3,014 randomly selected South Australian households. RESULTS: Thirteen of the 15 cases ate 'generic' or 'retail store' brands of peanut butter produced by the same factory in another state, compared with five of the 45 controls (p < 0.01). Salmonella Mbandaka was isolated from three opened jars of peanut butter from case households, and from three unopened jars from retail outlets. Further investigation implicated roasted peanuts from a third Australian state as the source of the Salmonella contamination. DISCUSSION: This is the first recorded outbreak of salmonellosis resulting from the consumption of peanut butter. The SA outbreak investigation comprised a matched case control study to identify possible common food sources. Such investigations need be conducted rapidly to maximise public health benefits, and the utility of selecting controls from a population based database can improve timeliness.

Adolescent↗