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Biomedical subjects

J May

Publications and source records attributed to J May.

At least 55 records · Page 3Linked to original sources

HLA-DQB1*0501-restricted Th1 type immune responses to Plasmodium falciparum liver stage antigen 1 protect against malaria anemia and reinfections.

Protective immunity against Plasmodium falciparum requires constant exposure to the pathogen. T cell-mediated immune responses are induced by T cell epitopes of pre-erythrocytic stage antigens of P. falciparum and involve HLA-restricted CD4 and CD8 cells. Cytotoxic T cell responses to a conserved epitope of P. falciparum liver stage antigen (LSA) type 1 are restricted by the HLA class I allele Bw53. The role of HLA class II alleles in mediating cellular responses against P. falciparum LSA-1 has not yet been demonstrated. In a longitudinal study performed for >4 years, associations were found between the HLA class II allele DQB1*0501 and protection from malaria anemia and malarial reinfections in Gabonese children. Children carrying DQB1*0501 had a higher frequency of interferon-gamma responses to LSA-1 T cell epitopes, compared with noncarriers.

Alleles↗

Plasma interleukin-10:Tumor necrosis factor (TNF)-alpha ratio is associated with TNF promoter variants and predicts malarial complications.

In individuals with severe malarial anemia, plasma levels of tumor necrosis factor (TNF)-alpha tend to exceed those of interleukin (IL)-10. In this study, IL-10:TNF plasma level ratios <1 were found to be a risk factor for both cerebral malaria and severe anemia (P=.009), whereas higher IL-10:TNF ratios were observed more frequently in hyperparasitemic individuals. When considering allelic variants of the TNF promoter in children with severe malaria, carriers of the wild type more frequently had an IL-10:TNF ratio >1 (P=.008). In contrast, individuals with a mutation at position -238 of the TNF promoter (TNF(-238A) and TNF(-376A/-238A)) consistently had lower IL-10 than TNF plasma levels (IL-10:TNF ratio <1; P=.003). Our results show that, in children with severe malaria, TNF promoter variants influence the balance of IL-10:TNF in the plasma, which, in turn, affects the outcome in terms of clinical complications.

Child↗

Promoter variants of the human mannose-binding lectin gene show different binding.

Mannose-binding lectin (MBL) levels in the plasma of humans are highly variable. The level is influenced by gene mutations in exon1 and the promoter. Here we describe the distribution of three point mutations linked with a deletion in the MBL gene promoter in populations of Central Africa, Thailand, and Papua New Guinea. Among African children we find 20% with the wild-type allele, 53% are heterozygous, and 27% are homozygous for the mutation. In Thailand we find 65% with the wild-type allele, 33% are heterozygous, and 2% are homozygous for the variant. In Papua New Guinea the polymorphism is not found. The occurrence of the mutation was associated with MBL levels in the plasma (P = 0.043). Oligonucleotides derived from the variant promoter regions bind proteins differently according to their DNA sequence. The binding of proteins can be influenced by induction with interleukin-6.

Base Sequence↗

The Australian experience in training and certification of vascular surgery.

Training in vascular surgery in Australia and New Zealand has been closely related to the policies and politics of the Royal Australasian College of Surgeons. It has evolved from being part of the training for General Surgery through a two year post Fellowship training program in Vascular Surgery commencing in 1985 to the establishment in 1996, by the College, of a Board in Vascular Surgery responsible for training and examining in Vascular Surgery as specialty independent of the Board in General Surgery.

Australia↗

Red cell glucose-6-phosphate dehydrogenase status and pyruvate kinase activity in a Nigerian population.

Glucose-6-phosphate dehydrogenase A- (G6PD A-) deficiency is a common enzymopathy in Africa that sporadically leads to manifest haemolytic anaemia. It is not exactly known how far the haematological status of individuals with either homozygous or heterozygous G6PD A- deficiency differs from that of individuals with normal G6PD activity. In a field study in Nigeria, we determined G6PD gene variants, the corresponding G6PD and pyruvate kinase (PK) activities, and basic haematological parameters in clinically healthy individuals, who were, in part, asymptomatically infected by malaria parasites. Red blood cell counts and haemoglobin levels were lower in G6PD A- deficient than in G6PD normal subjects. PK activities were higher in G6PD deficients, indicating a younger red cell population in these individuals. These findings suggest that G6PD A- deficiency is accompanied by chronic subclinical haemolysis. As a consequence, the reduced life span of red cells leads to an impaired diagnosis of G6PD heterozygosity when applying routine biochemical methods.

Adolescent↗

Life-table analysis of primary and assisted success following endoluminal repair of abdominal aortic aneurysms: the role of supplementary endovascular intervention in improving outcome.

AIM: the aim of this study was to analyse the effect of supplementary endovascular intervention on the outcome of primary endoluminal repair of abdominal aortic aneurysm (AAA). METHODS: between May 1992 and December 1998, 266 patients underwent endoluminal repair of AAA. Minimum period of follow-up was 6 months. Those patients in whom the endoprosthesis could not be deployed were converted to open repair at the primary operation. Patients developing an early endoleak, within 31 days, were treated by a period of observation and secondary endovascular intervention in persistent cases. Patients developing a late endoleak were treated similarly, without a period of observation. Outcome was analysed by the life-table method. Primary success was defined as exclusion of the aneurysm from the circulation resulting from the original operation. Assisted success occurred when aneurysms with endoleaks became excluded from the circulation as a result of supplementary endovascular intervention. RESULTS: endoluminal repair failed in 17 patients requiring conversion to open repair at the original operation. Supplementary endovascular intervention was undertaken in 26 patients, with early endoleaks (n=6) and late endoleaks (n=20). Interventions involved deployment of secondary endoluminal grafts within the primary grafts (n=22), and coil embolisation (n=4). Successful exclusion of the aneurysm sac was achieved in 22 of 26 (85%) patients undergoing supplementary endovascular procedures. Conditional cumulative incidence of primary graft failure and secondary graft failure in the presence of all-cause mortality at 6 years was 47% and 25% respectively. CONCLUSIONS: supplementary endovascular intervention is an important adjunct to endoluminal AAA repair with the potential to improve outcome and avoid conversion to open repair. Successful supplementary endovascular intervention was achieved in 85% of patients in whom it was attempted. Life-table analysis showed these supplementary procedures to be durable in the long term.

Aged↗

Comparison of first- and second-generation prostheses for endoluminal repair of abdominal aortic aneurysms: a 6-year study with life table analysis.

PURPOSE: The outcome of endoluminal repair of abdominal aortic aneurysms with two generations of prostheses was analyzed and compared. METHODS: Between May 1992 and December 1998, 266 patients underwent elective endoluminal repair of an AAA. First-generation prostheses were used in 118 patients (group I), and second-generation prostheses were used in 148 patients (group II). The two groups were similar in age, sex, and size of AAA. The proportion of patients with comorbidities was higher in group I than in group II, but not significantly. First-generation devices were characterized by large (24F internal diameter) delivery systems, one-piece construction, and a lack of metallic support throughout their length. Second-generation devices had smaller (21F or smaller internal diameter) delivery systems, modular construction, and a metallic frame throughout the length of the prostheses. The major end-point criteria were survival and successful endoluminal repair. Success was defined as the exclusion of the aneurysm sac from the circulation, with stability or the reduction in AAA maximum transverse diameter. Persistent endoleaks were classified as failures, irrespective of whether they were subsequently corrected by means of secondary endovascular intervention. The minimum follow-up period was 5 months for each of the 266 patients. Analysis was performed by means of the life-table method. RESULTS: Perioperative mortality was not significantly different between group I (4.2%) and group II (2.7%). There was a statistically significant difference between the survival curves of the two generations, which favored group II (P =.012). There was a significant (P <.001) difference between the two generations of patients in their conditional probability of graft failure when the competing risk of all-cause mortality was considered. Second-generation patients were at a lower risk of graft failure than first-generation patients. The probability of failure, expressed as a proportion of grafts failing at 2 years, was 0.15 for patients with second-generation prostheses and 0.33 for patients with first-generation prostheses. CONCLUSION: Endoluminal AAA repair is a safe procedure, whether first- or second-generation prostheses are used. Survival and probability of graft success were significantly higher with second-generation prostheses than with first-generation prostheses. This improvement in outcome resulted from a combination of increasing clinical experience and advances in technology. A more accurate evaluation of the role of the endoluminal method in AAA repair would be achieved by studying patients in whom second-generation devices were used, rather than longer term studies in which first- and second-generation devices were used.

Aged↗

Time-kill studies of tea tree oils on clinical isolates.

Tea tree oil has recently emerged as an effective topical antimicrobial agent active against a wide range of organisms. Tea tree oil may have a clinical application in both the hospital and community, especially for clearance of methicillin-resistant Staphylococcus aureus (MRSA) carriage or as a hand disinfectant to prevent cross-infection with Gram-positive and Gramnegative epidemic organisms. Our study, based on the time-kill approach, determined the kill rate of tea tree oil against several multidrug-resistant organisms, including MRSA, glycopeptide-resistant enterococci, aminoglycoside-resistant klebsiellae, Pseudomonas aeruginosa and Stenotrophomonas maltophilia, and also against sensitive microorganisms. The study was performed with two chemically different tea tree oils. One was a standard oil and the other was Clone 88 extracted from a specially bred tree, which has been selected and bred for increased activity and decreased skin irritation. Our results confirm that the cloned oil had increased antimicrobial activity when compared with the standard oil. Most results indicated that the susceptibility pattern and Gram reaction of the organism did not influence the kill rate. A rapid killing time (less than 60 min) was achieved with both tea tree oils with most isolates, but MRSA was killed more slowly than other organisms.

Anti-Infective Agents, Local↗

Comparative in vitro activity of gemifloxacin.

Gemifloxacin is a new quinolone and, like moxifloxacin, trovafloxacin, grepafloxacin and clinafloxacin, is more potent in vitro than ciprofloxacin or ofloxacin against Gram-positive aerobes. Gemifloxacin was the most potent of the quinolones tested against streptococci and most ciprofloxacin-resistant pneumococci were susceptible to gemifloxacin. Gemifloxacin, like moxifloxacin, trovafloxacin, grepafloxacin and clinafloxacin, was more potent than ciprofloxacin or ofloxacin against all staphylococci and many ciprofloxacin-resistant isolates were susceptible to these quinolones. Against Gram-negative aerobes gemifloxacin was as potent as or slightly less potent than ciprofloxacin, and isolates resistant to ciprofloxacin were also resistant to gemifloxacin and to moxifloxacin, trovafloxacin and grepafloxacin. Gemifloxacin was also the most potent quinolone against Gram-positive anaerobes and fusobacteria but trovafloxacin was the most potent agent tested against other Gram-negative anaerobes.

Anti-Infective Agents↗

Comparison of cation-adjusted Mueller-Hinton broth with Iso-Sensitest broth for the NCCLS broth microdilution method.

Comparison of MIC results obtained in different parts of the world is currently difficult because of variations in methods. In this study, cation-adjusted Mueller-Hinton broth, the NCCLS-recommended medium, was compared with Iso-Sensitest broth, which is widely used in Europe. Microbroth dilution testing, using the NCCLS procedure, was performed on 124 Gram-positive (staphylococci and enterococci) and Gram-negative (Enterobacteriaceae and Pseudomonas aeruginosa) isolates from the CDC reference set, with the only variable being the medium used. Twelve antimicrobial agents were tested: amoxycillin-clavulanic acid, ampicillin, ciprofloxacin, erythromycin, gentamicin, imipenem, levofloxacin, oxacillin, gemifloxacin, trimethoprim- sulphamethoxazole, tetracycline and vancomycin. Vancomycin, erythromycin and oxacillin were only evaluated for the Gram-positive organisms. Trimethoprim-sulphamethoxazole was only evaluated for a subset of Gram-negative organisms because of off-scale results. The 124 isolates were tested in one American and one UK laboratory with two batches of cation-adjusted Mueller-Hinton broth and two of Iso-Sensitest broth. A statistical evaluation of the data used a 24 fully specified factorial analysis to determine if there were significant differences in results owing to Gram reaction, site of testing and type and/or batch of broth. In addition, the cumulative results for each antimicrobial agent in each broth were plotted against the range of MIC dilutions tested. MICs of ciprofloxacin, levofloxacin, gemifloxacin, gentamicin and tetracycline were slightly higher (half a doubling dilution) with Iso-Sensitest broth than with Mueller-Hinton broth. MIC results for the other antimicrobial agents were equivalent. Essential and category agreement rates were comparable for all agents (88.4-100% and 88.2-99.0%, respectively).

Anti-Bacterial Agents↗

Hearing conservation for farmers: source apportionment of occupational and environmental factors contributing to hearing loss.

Those who work on farms continue to have a strikingly high prevalence of hearing loss, despite efforts to promote hearing conservation in agriculture. To develop improved hearing conservation programs, we performed a source apportionment analysis for hearing loss in a large, multiphasic health survey, the New York Farm Family Health and Hazard Survey. We used information from audiometric, otoscopic, and tympanometric examinations; detailed general health and farm exposure interviews; and a second interview that focused on additional potential determinants of hearing loss. Hearing loss on audiometry was significantly associated with increased age, male gender, education through high school or less, lifetime years of hunting with guns, lifetime years of use of a grain dryer, and a history of spraying crops during the previous year. Hearing conservation programs for farmers should thus be directed toward reduction in noise exposure, both from occupational and non-occupational sources. Additional study is needed to evaluate the association seen between crop spraying and hearing loss.

Adult↗

Concentrations of chloroquine and malaria parasites in blood in Nigerian children.

Consumption of chloroquine (CQ) and subtherapeutic drug levels in blood are considered to be widespread in areas where malaria is endemic. A cross-sectional study was performed with 405 Nigerian children to assess factors associated with the presence of CQ in blood and to examine correlations of drug levels with malaria parasite species and densities. Infections with Plasmodium species and parasite densities were determined by microscopy and PCR assays. Whole-blood CQ concentrations were measured by high-performance liquid chromatography. Plasmodium falciparum, P. malariae, and P. ovale were observed in 80, 16, and 9% of the children, respectively, and CQ was detected in 52% of the children. CQ concentrations were >17 and <100 nmol/liter in 25% of the children, 100 to 499 nmol/liter in 14% of the children, and > or =500 nmol/liter in 13% of the children. Young age, attendance at health posts, and absence of parasitemia were factors independently associated with CQ in blood. With increasing concentrations of CQ, the prevalence of P. falciparum infection and parasite densities decreased. However, at concentrations corresponding to those usually attained during regular prophylaxis (> or =500 nmol/liter), 62% of children were still harboring P. falciparum parasites. In contrast, no infection with P. malariae and only one infection with P. ovale were observed in children with CQ concentrations of > or =100 nmol/liter. These data show the high prevalence of subcurative CQ concentrations in Nigerian children and confirm the considerable degree of CQ resistance in that country. Subtherapeutic drug levels are likely to further promote CQ resistance and may impair the development and maintenance of premunition in areas where malaria is endemic.

Age Factors↗