In most regions of the world, chloroquine (CQ) has been the standard treatment for Plasmodium vivax malaria for more than 40 years. Recently, however, CQ-resistant P. vivax has been reported from Oceania, several parts of Asia, and South America. The therapeutic efficacy of CQ in the treatment of acute, P. vivax malaria has now been assessed in two areas of the Turkish province of Sanliurfa: the towns of Karacadag and Sekerli. On admission and on days 2, 3, 7, 14, 21, and 28, all 112 patients investigated were examined clinically and blood samples were collected and smeared. Treatment consisted of 10 mg CQ/kg on day 0, the same dose on day 1, and 5 mg CQ/mg on day 2, each dose being supervised. Worryingly, 14.7% of the patients from Karacadag and 10.3% of those from Sekerli showed apparent treatment failure between days 3 and 28. In Sanliurfa province, in south-eastern Turkey, there therefore seems to be a high risk of therapeutic failure in patients given CQ to cure P. vivax malaria, probably because of CQ resistance.

Acute Disease↗

PubMed2003

Genetic maps for Pinus elliottii var. elliottii and P. caribaea var. hondurensis using AFLP and microsatellite markers.

Genetic maps for individual Pinus elliottii var. elliottii and P. caribaea var. hondurensis trees were generated using a pseudo-testcross mapping strategy. A total of 329 amplified fragment length polymorphic (AFLP) and 12 microsatellite markers were found to segregate in a sample of 93 interspecfic F(1) progeny. The male P. caribaea var. hondurensis parent was more heterozygous than the female P. elliottii var. elliottii parent with 19% more markers segregating on the male side. Framework maps were constructed using a LOD 5 threshold for grouping and interval support threshold of LOD 2. The framework map length for the P. elliottii var. elliottii megagametophyte parent (1,170 cM Kosambi; 23 linkage groups) was notably smaller than the P. caribaea var. hondurensis pollen parent (1,658 cM Kosambi; 27 linkage groups). The difference in map lengths was assumed to be due to sex-related recombination variation, which has been previously reported for pines, as the difference in map lengths not be accounted for by the larger number of markers mapping to the P. caribaea var. hondurensis parent - 109 compared with 78 in P. elliottii var. elliottii parent. Based on estimated genome sizes for these species, the framework maps for P. elliottii var. elliottii and P. caribaea var. hondurensis covered 82% and 88% of their respective genomes. The pseudo-testcross strategy was extended to include AFLP and microsatellite markers in an intercross configuration. These comprehensive maps provided further genome coverage, 1,548 and 1,828 cM Kosambi for P. elliottii var. elliottii and P. caribaea var. hondurensis, respectively, and enabled homologous linkage groups to be identified in the two parental maps. Homologous linkage groups were identified for 11 out of 24 P. elliottii var. elliottii and 10 out of 25 P. caribaea var. hondurensis groups. A higher than expected level of segregation distortion was found for both AFLP and microsatellite markers. An explanation for this segregation distortion was not clear, but it may be at least in part due to genetic mechanisms for species isolation in this wide cross.

Genetic Markers↗

PubMed2003

How evidence based are therapeutic decisions taken on a medical admissions unit?

OBJECTIVES: To audit the proportion of drug treatments started on a medical admissions unit that is justified by published evidence, and the proportion for which no justification could be found. METHODS: Retrospective review of randomly selected case notes to identify drug treatments started and the problem(s) for which they were prescribed, followed by literature searches. RESULTS: A total of 132 treatment-problem pairs were found, comprising 85 unique treatment-problem pairs. An evidence base was found in support of 78 of the treatments started (59.1%). A further 41 treatment-problem pairs could be argued to be reasonable practice (sometimes included in guidelines), even though no published trial data support them. Ninety per cent of drug treatments started on the medical admissions unit have either an evidence base or are accepted practice. CONCLUSIONS: Regular audit of this nature could be carried out on units admitting acute medical patients. Similar audits in internal medicine have delivered consistent results (50%-60%); there is a baseline level against which units can compare themselves. Clinical audit is an integral feature of clinical governance; all wards admitting acute medial patients could conduct similar audits on a random sample of patients.

Admitting Department, Hospital↗

PubMed2003

Leukotriene receptor antagonists as add-on therapy for adults with asthma.

Assessment of the current evidence for the use of leukotriene receptor antagonists as add-on therapy at steps 3 and 4 of the guidelines for adults with moderate to severe asthma.

Administration, Inhalation↗

PubMed2003

Phase I safety & preliminary acceptability of nonoxynol-9 vaginal pessary as a vaginal microbicide in low risk women in Pune, India.

BACKGROUND & OBJECTIVES: Though nonoxynol-9 (N-9) is available in India as a spermicidal pessary, data on its safety as a potential microbicide among Indian women are not available. Nonoxynol-9 containing compounds have shown anti-HIV activity in in vitro studies and protection against cervical infections. Nonoxynol-9 is being extensively evaluated as a vaginal microbicide world-wide. We assessed the safety and preliminary acceptability of nonoxynol-9 pessary as a vaginal microbicide in women at low risk for human immunodeficiency virus (HIV) infection and sexually transmitted diseases (STDs). METHODS: Twenty three HIV seronegative women enrolled in the study were given Today pessarys containing 5 per cent of nonoxynol-9 for vaginal use at bedtime for 14 days. Colposcopy was done at enrollment and on day 14 and speculum examination on day 7 to assess the local toxicity. RESULTS: Most of the women (16/23, 69.6%) did not experience any symptoms of genital irritation. The remaining 7 (30.4%, 95% CI 11.6-49.2) women reported 11 episodes of mild irritative symptoms of short duration. On clinical examination, three adverse events were reported of which one could have been product related. Eight (34.8%) women showed willingness to use the product for protection against HIV transmission if it was approved. INTERPRETATION & CONCLUSION: Nonoxynol-9 vaginal pessary was found to be safe and acceptable in once daily dose in low risk women after consecutive use for 14 days. Willingness for future use, if found safe and effective for HIV prevention was shown by 8 (34.8%) women.

Administration, Intravaginal↗

PubMed2002

Abnormal splicing of hepatocyte nuclear factor 1 alpha in maturity-onset diabetes of the young.

AIMS/HYPOTHESIS: Mutations in the HNF-1 alpha gene result in maturity-onset diabetes of the young (MODY); an early-onset, dominantly inherited form of diabetes caused by pancreatic beta-cell dysfunction. Splice site mutations represent approximately 10% of reported HNF-1 alpha mutations. No studies to date have investigated the effect of splice site mutations on mRNA processing because the tissues with abundant HNF-1alpha expression (liver, pancreas, kidney and gut) are not easily accessible for analysis. This study aimed to define the pathogenic mechanism in three novel splice site mutations by analysing illegitimate transcripts. METHODS: To assess the consequence of potential HNF-1 alpha splice site mutations we developed a nested reverse transcriptase PCR (RT-PCR) assay for the amplification of illegitimate HNF-1 alpha transcripts in Epstein Barr virus transformed lymphoblastoid cell lines. RESULTS: Sequencing the illegitimate HNF-1 alpha transcripts showed that the splice donor site mutation IVS8nt+1G>A leads to complete skipping of exon 8, the splice acceptor site mutation IVS4nt-2A>G causes skipping of exon 5 with the recruitment of a cryptic splice acceptor site within intron 5 and the cryptic splice acceptor site mutation (IVS7nt-6G>A) resulted in the skipping of exon 7. All three changes are predicted to result in premature termination of the HNF-1alpha protein, providing further evidence for their role as pathogenic mutations. CONCLUSION/INTERPRETATION: We conclude that the sequencing of illegitimate transcripts from lymphoblastoid cell lines is helpful in the assessment of intronic variation in HNF-1 alpha that could alter splicing. This analysis of the mRNA is required to define mutational mechanisms and confirm pathogenic status.

Adult↗

PubMed2002

Health and social factors for health visitor caseload weighting: reliability, accuracy and current and potential use.

The reliability and validity of data collection and recording for a health visitor caseload weighting system operating in a large combined acute and community trust in Bristol was examined. Client families were recruited from all participating (service) health visitors and were interviewed by a research health visitor attached to the project. The presence or absence of 28 health needs factors, selected for their known impact on health in the longer term, was subsequently compared with the service health visitor's own caseload records and with the computer record derived from them. Substantial differences were determined in the records obtained between the service and research health visitors and between the written and computerised records. Whilst the mean total score recorded for each family by the service health visitor was 2.0, the average of the differences in the total number of health factors recorded by the service and research health visitors was 1.9. Discrepancies were mostly associated with differences in interpretation of definitions, knowledge of recent events, changing circumstances and issues of confidentiality. Health factors at particular risk of being misinterpreted and those associated with other health factors were identified in order to propose a reduced factor set with greater inherent reliability and validity. At the level of the ward, the caseload weighting score, as currently defined, is highly correlated with standard deprivation indices in widespread common use. The results of this study indicate the need for users of the caseload weighting data to decide on the primary function of this data set - area-based community profiling or identification of at-risk client families in the community. This decision will inform further efforts to identify the most useful factors, tighten definitions, streamline data collection and train health visitors in their use. Interpretation of data will be facilitated by a scientifically developed scoring system. This work will assist trusts, both locally and nationally, in rationalising their allocation of health visiting activities to areas of greatest need.

Community Health Nursing↗

PubMed2002

Heterogeneity in young adult onset diabetes: aetiology alters clinical characteristics.

AIMS: To describe the characteristics of hepatocyte nuclear factor (HNF) 1 alpha mutation carriers diagnosed with diabetes after 25 years and compare them with young-onset Type 2 diabetic patients (YT2D) diagnosed at the same age. SUBJECTS AND METHODS: We studied 44 (21 male, 23 female) patients with HNF-1 alpha mutations diagnosed with diabetes at ages 25-45 years and 44 YT2D subjects matched for sex and age of diagnosis. RESULTS: Median age of onset of diabetes was 35 years in both groups. The HNF-1 alpha group demonstrated: lower body mass index (25.1 vs. 30.7 kg/m2; P < 0.001) and lower fasting triglycerides (1.37 vs. 2.96 mmol/l; P = 0.001) with similar fasting cholesterol level. They had lower glycated haemoglobin A1c (7.3 vs. 8.5%; P = 0.015) despite greater duration of diabetes (24 vs. 16 years; P = 0.02) and less frequent treatment with insulin (21% vs. 55%; P = 0.002). They were less likely to be treated for hypertension (13.3% vs. 56.3%; P = 0.009). Importantly, no difference was observed in reported parental history of diabetes between the two groups (65.9% vs. 63.6%; P = 0.92). Logistic regression showed that triglyceride levels and presence of anti-hypertensive treatment were the most important independent variables. CONCLUSIONS: Patients with HNF-1 alpha mutations may present with diabetes as young adults between the ages of 25-45 years. In this age range a wide differential diagnosis of diabetes is observed. Conventional criteria of age of onset and family history will not differentiate HNF-1 alpha mutation carriers from YT2D subjects in this age range, but features of the metabolic syndrome, in particular fasting triglycerides and hypertension, are helpful. In patients diagnosed before 45 years without features of insulin resistance the diagnosis of HNF-1 alpha should be considered.

Adult↗