Measured haplotype analysis of the angiotensin-I converting enzyme gene

Linkage and segregation analysis have shown that circulating angiotensin-I converting enzyme (ACE) levels are influenced by a major quantitative trait locus that maps within or close to the ACE gene. The D variant of a 287 bp insertion/deletion (I/D) polymorphism in intron 16 of the gene is associated with high ACE levels and may also be related to increased risk of cardiovascular disease. Multiple variants that are in linkage disequilibrium with the I/D polymorphism have been described, but it is unknown if any of these are directly implicated, alone or in combination with as yet undiscovered variants, in the determination of ACE levels. An analysis of 10 polymorphisms spanning 26 kb of the ACE gene revealed a limited number of haplotypes in Caucasian British families due to strong linkage disequilibrium operating over this small chromosomal region. A haplotype tree (cladogram) was constructed with three main branches (clades A-C) which account for 90% of the observed haplotypes. Clade C is most likely derived from clades A and B following an ancestral recombination event. This evolutionary information was then used to direct a series of nested, measured haplotype analyses that excluded upstream sequences, including the ACE promoter, from harbouring the major ACE-linked variant that explains 36% of the total trait variability. Residual familial correlations were highly significant, suggesting the influence of additional unlinked genes. Our results demonstrate that a combined cladistic/measured haplotype analysis of polymorphisms within a gene provides a powerful means to localize variants that directly influence a quantitative trait.      

世界卫生组织与热带病防治

简述世界卫生组织之缘起、架构、工作、人事及各区域分署等,及其热带病,例如疟疾、血吸虫、丝虫病、登革热、黑热病、麻风及锥虫病的防治状况。     

Proinflammatory and anti-inflammatory cytokines in meningococcal disease

Interleukin-10 (IL-10), an anti-inflammatory cytokine, was measured in 131 children with meningococcal disease. IL-10 concentrations were significantly higher in children who died and correlated positively with proinflammatory cytokines. Children who die from meningococcal disease have high IL-10 concentrations, which do not suppress proinflammatory cytokines.     

Sputum induction for the diagnosis of tuberculosis

Confirmation of tuberculosis in young children is difficult as they seldom expectorate sputum. Gastric aspirates are invasive and stressful and like laryngeal swabs are seldom smear positive. Induction of sputum by nebulised hypertonic saline (3%) was attempted in 30 Malawian children aged 3-15 years and was successful in 29. Four sputa were smear positive and Mycobacterium tuberculosis was cultured from three of them. A further four sputa were culture positive though smear negative. In all, the diagnosis of tuberculosis was confirmed in eight (28%) of 29 children. The presence of polymorphonuclear cells in the specimen was indicative of sputum, in contrast to epithelial cells which originate from saliva. A predominance of polymorphonuclear cells in specimens was more common in older children and these specimens were more likely to be smear positive or culture positive. Sputum induction is a useful method for the confirmation of tuberculosis and is possible in young children.     

Cholesterol screening and family history of vascular disease

Hypercholesterolaemia is a major risk factor for the development of coronary heart disease (CHD). Early detection and management of hypercholesterolaemia could retard the atherosclerotic process. Given that CHD and hypercholesterolaemia cluster within families, a screening strategy based on a family history of vascular disease has been advocated. Serum total cholesterol concentrations were measured in a random stratified sample of 1012 children aged from 12-15 years old participating in a coronary risk factor surveillance study in Northern Ireland. Information about vascular disease in close family members was obtained by means of a questionnaire. The study population was divided into two groups according to total cholesterol values: (i) normal, < 5.2 mmol/l (n = 822) and (ii) raised, > or = 5.2 mmol/l (n = 190). A family history identified 63 out of 190 individuals with hypercholesterolaemia yielding a sensitivity of 33.2% and specificity of 71.5%. Our data indicated that a strategy whereby only children from high risk families are screened for hypercholesterolaemia is ineffective. While primary prevention emphasising a healthy diet for all is essential, the role of universal screening deserves further appraisal.     

Liver iron concentrations in sudden infant death syndrome

To determine the biological significance of high concentrations of non-haem iron in the livers of infants dying from sudden infant death syndrome (SIDS), liver samples were obtained at necropsy from 66 infants who died from SIDS and 28 control infants who died before 2.5 years of age. All were full term deliveries. Liver iron concentrations decreased rapidly with age in the two groups. Liver iron concentrations in the SIDS infants and controls were compared for those infants who died between 1 month and 1 year of age. The median liver iron concentration in the SIDS infants was 296 micrograms/g wet weight; significantly higher than the median of 105 micrograms/g in controls. There was an inverse relation between iron concentration and age in the two groups, but an analysis of covariance confirmed the significantly lower values in controls. The frequency (22%) of HLA-A3 in SIDS infants was similar to that expected for the United Kingdom population (25%) and does not implicate the gene for haemochromatosis as a cause of high liver iron concentrations. These findings show that the peak incidence of SIDS occurs when mean concentrations of iron in liver tissue are higher than at any other time of life. Although a primary causal connection seems unlikely, high tissue iron concentrations may lower resistance to infection and enhance free radical formation, leading to tissue damage.     

Oral disease in the elderly in long-term hospital care

OBJECTIVE: To obtain baseline information on the prevalence of oral problems and disease in institutionalized elderly in a Scottish hospital.
DESIGN: A cross-sectional clinical investigation with complementary microbiological studies as appropriate. SUBJECTS AND METHODS: A cohort of 147 elderly in five long-term care wards; collection of demographic data; clinical examination to determine: i) the dental, and denture status and associated lesions such as Candida-associated denture stomatitis and angular cheilitis, ii) oral mucosal disease; swabs as appropriate for microbiology.
MAIN OUTCOME MEASURES: Dental status, root caries prevalence; denture status and hygiene, and associated disease; oral mucosal health.
RESULTS Median period of institutionalization of 147 patients was 15 months and 65% were aged 80 years or more; the majority were significantly mentally impaired; 52% wore complete dentures, 9% were partially dentate, 19% possessed partial or incomplete dentures; 20% were neither dentate nor had dentures. Of 80 patients who verbalired their complaints, 35% complained of dry mouth and 45% had denture-related problems, principally discomfort. The commonest oral finding was a coated tongue (56%); angular cheilitis was present in 25%, and Candida-associated denture stomatitis in 19%; none had oral ulcers.
CONCLUSIONS: There was considerable unmet dental need with significant oral disease and poor levels of oral and denture hygiene in this target group; both dental and medical professionals should act in concert to deliver curative as well as preventative dental care for the elderly living in institutions to improve their quality of life.     

Fluconazole resistant opportunistic oro-pharyngeal candida and non-candida yeast-like isolates from HIV infected patients attending ARV clinics in Lagos, Nigeria

Background

Oro-Pharyngeal Candidiasis (OPC) continues to be considered the most common opportunistic fungal disease in HIV/AIDS patients globally. Azole antifungal agent has become important in the treatment of mucosal candidiasis in HIV patients. Presently, antifungal drug resistance is fast becoming a major problem particularly with the immune depleted population.

Objectives

This study was designed to investigate the: existence of OPC, species distribution fluconazole susceptibility profile of yeast cells isolated from oral specimens of HIV/AIDS patients from Lagos Nigeria, between Oct. 2004 and June, 2005.

Methodology

The venous blood samples were screened for HIV antibodies using the Cappillus HIV I and II test kit (Trinity Biotech Plc UK), and Genie II HIV I and II EIA kit (Bio-Rad France). The positive results were subsequently confirmed at the laboratory attached to each of the clinics, using the Nigerian Federal Ministry of Health approved algorithm. The samples from 213 (108 females and 105 males) HIV positive patients were plated onto SD agar. The isolates were identified by morphotyping, microscopy and speciated using germ tube test and battery of biochemical sugar fermentation and assimilation tests. Fluconazole agar diffusion susceptibility testing was carried out on each isolates.

Results

Seventy-four (34.7%) isolates were recovered including one person with double isolates. Only 70(94.6%) of the isolates could be adequately speciated. Candida albicans 30 (40.5%) was the most frequently isolated species, the rest were non-albicans species, with the frequency of C. tropicalis › C. Krusei › C. glabrata and C. neoformans for species for species having up to 4 isolates. Four (30.8%) out of 13 isolates of C. tropicalis showed germ tube formation. While one C. albicans was germ-tube negative. Out of the 74 isolates tested for fluconazole sensitivity, 58(78.4%) were sensitive, MIC d″ 8µg/ml, 9(12.1%) were susceptible Dose Dependant (SDD), MIC 16–32 µg/ml and 7(9.5%) were resistant, MICs e″ 64µg/ml. Among the C. albicans isolates, 26(86.7%) were sensitive to fluconazole. The rank of susceptibility was C. albicans > C. tropicalis > C. Krusei for the most prevalent species.

Conclusion

We conclude that fluconazole resistant strains of oro-pharyngeal yeast-like cells exist in about 9.5% of HIV/AIDS patients with the above stated species distribution. We therefore, highlight the need for routine antifungal susceptibility testing on HIV patients with cases of initial or repeat episodes of OPC.