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Sulphadoxine/pyrimethamine versus amodiaquine for treating uncomplicated childhood malaria in...
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Tuesday, 12 February 2008
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Background:
In Gabon, further to the adoption of amodiaquine/artesunate combination (AQ/AS) and of sulphadoxine/pyrimethamine (SP) as malaria first-line treatment and preventive intermittent treatment in pregnant women, respectively, a clinical trial of SP versus AQ was conducted in sub-urban area. This is the first such study carried out in Gabon according to the WHO guideline.
Methods:
Efficacy of AQ (10 mg/kg/day x 3d) randomly compared with the efficacy of a single dose of SP (25 mg/kg of sulphadoxine/ 1.25 mg/kg of pyrimethamine) were assessed in children under five years with uncomplicated falciparum malaria in sub-urban area according to the 28-day WHO therapeutic efficacy test. In addition, molecular genotyping was performed to distinguish recrudescence from reinfection and to determine the frequency of the dhpsK540E mutation as molecular marker predicting SP-treatment failure.
Results:
The day-28 PCR-treatment failures adjusted for SP and AQ were 11.6% (8/69; 95% IC: 5.5-22.1) and 28.2% (20/71; 95% CI: 17.7-38.7) respectively, indicating that SP was significantly superior than AQ (P= 0.019) in the treatment of uncomplicated childhood malaria and for preventing recurrent infections. Both treatments were safe and well tolerated, with no serious adverse reaction recorded. The dhpsK540E mutation was not found among 76 parasite isolates.
Conclusion:
The AQ-resistance level observed in the present study may compromise efficacy and use duration of the AQ/AS combination, the new malaria first-line treatment. Gabonese policy-makers should plan through the country prompted and close surveillance of AQ/AS efficacy to determine whether those new recommendations related to the uncomplicated malaria treatment remain valid.
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Influence of pregnancy and labor on the occurrence of nerve fibers expressing the capsaicin...
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Tuesday, 12 February 2008
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Background:
Cervical ripening is a prerequisite for a normal obstetrical outcome. This process, including labor, is a painful event that shares features with inflammatory reactions where peripheral nociceptive pathways are involved. The capsaicin and heat receptor TRPV1 is a key molecule in sensory nerves involved in peripheral nociception, but little is known regarding its role in the pregnant uterus. Therefore, the aim of this study was to investigate human corpus and cervix uteri during pregnancy and labor and non-pregnant controls for the presence of TRPV1.
Methods:
We have investigated human uterine corpus and cervix biopsies at term pregnancy and parturition. Biopsies were taken from the upper edge of the hysterotomy during caesarean section at term (n=8), in labor (n=8) and from the corresponding area in the non-pregnant uterus after hysterectomy (n=8). Cervical biopsies were obtained transvaginally from the anterior cervical lip. Serial frozen sections were examined immunohistochemically using specific antibodies to TRPV1 and nerve markers (neurofilaments / peripherin).
Results:
In cervix uteri, TRPV1-immunoreactive fibers were scattered throughout the stroma and around blood vessels, and appeared more frequent in the sub-epithelium. Counts of TRPV1-immunoreactive nerve fibers were not significantly different between the three groups. In contrast, few TRPV1-immunoreactive fibers were found in nerve fascicles in the non-pregnant corpus, and none in the pregnant corpus.
Conclusions:
In this study, TRPV1 innervation in human uterus during pregnancy and labor is shown for the first time. During pregnancy and labor there was an almost complete disappearance of TRPV1 positive nerve fibers in the corpus. However, cervical innervation remained throughout pregnancy and labor. The difference in TRPV1 innervation between the corpus and the cervix is thus very marked. Our data suggest that TRPV1 may be involved in pain mechanisms associated with cervical ripening and labor. Furthermore, these data support the concept that cervix uteri may be the major site from which labor pain emanates. Our findings also support the possibility of developing alternative approaches to treat labor pain.
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Simultaneous fitting of real-time PCR data with efficiency of amplification modeled as Gaussian...
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Tuesday, 12 February 2008
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Background:
In real-time PCR, it is necessary to consider the efficiency of amplification (EA) of amplicons in order to determine initial target levels properly. EAs can be deduced from standard curves, but these involve extra effort and cost and may yield invalid EAs. Alternatively, EA can be extracted from individual fluorescence curves. Unfortunately, this is not reliable enough.
Results:
Here we introduce simultaneous non-linear fitting to determine - without standard curves - an optimal common EA for all samples of a group. In order to adjust EA as a function of target fluorescence, and still to describe fluorescence as a function of cycle number, we use an iterative algorithm that increases fluorescence cycle by cycle and thus simulates the PCR process. A Gauss peak function is used to model the decrease of EA with increasing amplicon accumulation. Our approach was validated experimentally with hydrolysis probe or SYBR green detection with dilution series of 5 different targets. It performed distinctly better in terms of accuracy than standard curve, DART-PCR, and LinRegPCR approaches. Based on reliable EAs, it was possible to detect that for some amplicons, extraordinary fluorescence (EA > 2.00) was generated with locked nucleic acid hydrolysis probes, but not with SYBR green.
Conclusions:
In comparison to previously reported approaches that are based on the separate analysis of each curve and on modelling EA as a function of cycle number, our approach yields more accurate and precise estimates of relative initial target levels.
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Ankle blood pressure as a predictor of total and cardiovascular mortality
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Tuesday, 12 February 2008
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Background:
The ankle blood pressure is commonly used as a ratio to the brachial blood pressure, called ankle-brachial index (ABI). Very few studies have considered the independent value of the ankle blood pressure without indexing it to the brachial blood pressure. We examined the value of ankle blood pressure, together with the exercise blood pressure, as a predictor of cardiovascular (CVD) and total mortality.
Methods:
A prospective follow-up study of 3,858 consecutive ambulatory patients (mean age 51 years, 65,9 % male) referred to a symptom-limited exercise test between August 1989 and December 1995. The cohort was followed up for all-cause and CVD mortality until December 31, 2004, by record linkage with the National Causes-of-Death Register. The independent value of ankle blood pressure as a predictor of cardiovascular and total mortality was assessed using Cox proportional hazards modelling.
Results:
The average follow-up time was 14 years, during which 346 persons died, 108 of them due to CVD. Persons with normal (<140 mmHg) resting brachial blood pressure, ankle blood pressure < 175 mmHg and exercise blood pressure at moderate exercise level <=215 mmHg at baseline investigation, had the best prognosis and were taken as the reference category. Among persons with elevated ankle blood pressure (>=175 mmHg) but normal or borderline resting brachial pressure and normal exercise blood pressure (<=215 mmHg) at moderate exercise level the multivariate-adjusted hazard ratios (HR, 95% confidence interval) for CVD and total mortality were 2.70 (1.52 a 4.80) and 2.13 (1.58 a 2.85), respectively. Similar and equally significant HRs were observed in persons with both elevated ankle blood pressure and elevated exercise blood pressure, as well as in those persons with elevated exercise blood pressure but ankle blood pressure < 175 mmHg.
Conclusions:
These results suggest that the ankle blood pressure has an independent value as a marker of arterial stiffness or subclinical atherosclerosis and a risk of future mortality in middle-aged, asymptomatic persons.
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Psychological and weight-related characteristics of patients with anorexia nervosa- restricting...
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Tuesday, 12 February 2008
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Background:
Patients with anorexia nervosa-restricting type (AN-R) sometimes develop accompanying bulimic symptoms or the full syndrome of bulimia nervosa (BN). If clinicians could predict who might change into the bulimic sub-type or BN, preventative steps could be taken. Therefore, we investigated anthropometric and psychological factors possibly associated with such changes.MethodAll participants were from a study by the Japanese Genetic Research Group for Eating Disorders. Of 80 patients initially diagnosed with AN-R, 22 changed to the AN-Binge Eating/Purging Type (AN-BP) and 14 to BN for some period of time. The remaining 44 patients remained AN-R only from the onset to the investigation period. Variables compared by ANOVA included anthropometric measures, personality traits such as Multiple Perfectionism Scale scores and Temperament and Character Inventory scores, and Beck Depression Inventory-II scores.
Results:
In comparison with AN-R only patients, those who developed BN had significantly higher current BMI (p<0.05) and maximum BMI in the past (p<0.05). They also scored significantly higher for the psychological characteristic of parental criticism (p<0.05) and lower in self-directedness (p<0.05), which confirms previous reports, but these differences disappeared when the depression score was used as a co-variant. No significant differences were obtained for personality traits or depression among the AN-R only patients irrespective of their duration of illness.
Conclusions:
The present findings suggest a tendency toward obesity among patients who cross over from AN-R to BN. Low self-directedness and high parental criticism may be associated with the development of BN by patients with AN-R, although the differences may also be associated with depression.
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Transduction of the rat brain by Bovine Herpesvirus 4
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Tuesday, 12 February 2008
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Bovine herpesvirus 4 (BoHV-4) is a gamma-herpesvirus with no clear disease association. A recombinant BoHV-4 (BoHV-4EGFPITK) expressing Green Fluorescent Protein (EGFP), was successfully used to infect F98 rat glioma cells. BoHV-4EGFPITK was injected into the lateral ventricle of the rat brain. Histology and immunohistochemistry showed that ependymal and rostral migratory stream cells were transduced while neurons were not. Clinical scores, evaluated for 90 days, indicated that the virus was non neuropathogenic, suggesting this virus is a suitable vector for brain tumor gene therapy.
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Ligand-induced sequestering of branchpoint sequence allows conditional control of Splicing
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Tuesday, 12 February 2008
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Background:
Despite tremendous progress in understanding the mechanisms of constitutive and alternative splicing, an important and widespread step along the gene expression pathway, our ability to deliberately regulate gene expression at this step remains rudimentary. The present study was performed to investigate whether a theophylline-dependent asplice switcha that sequesters the branchpoint sequence (BPS) within RNA-theophylline complex can regulate alternative splicing.
Results:
We constructed a series of pre-mRNAs in which the BPS was inserted within theophylline aptamer. We show that theophylline-induced sequestering of BPS inhibits pre-mRNA splicing both in vitro and in vivo in a dose-dependent manner. Several lines of evidence suggest that theophylline-dependent inhibition of splicing is highly specific, and thermodynamic stability of RNA-theophylline complex as well as the location of BPS within this complex affects the efficiency of splicing inhibition. Finally, we have constructed an alternative splicing model pre-mRNA substrate in which theophylline caused exon skipping both in vitro and in vivo, suggesting that a small molecule-RNA interaction can modulate alternative splicing.
Conclusion:
These findings provide the ability to control splicing pattern at will and should have important implications for basic, biotechnological, and biomedical research.
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Cancer mortality differences among urban and rural residents in Lithuania
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Tuesday, 12 February 2008
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Background:
The aim of this study was to describe and to compare the cancer mortality rates in urban and rural residents in Lithuania.
Methods:
Cancer mortality has been studied using the materials of the Lithuanian cancer registry. For the period 1993-2004 age-standardized urban and rural population mortality rates (World standard) were calculated for all malignant neoplasmas and for stomach, colorectal, lung, prostate, breast and cervical cancers. The annual percentage change (APC) was calculated using log-linear regression model, two-sided Mantel-Haenzel test was used to evaluate differences in cancer mortality among rural and urban populations.
Results:
For males in rural population cancer mortality was higher than in urban (212.2 and 197.0 cases per 100000) and for females cancer mortality was higher in urban population (103.5 and 94.2 cases per 100000, p<0.05). During the study period the age-standardized mortality rates decreased in both sexes in urban residents. The decreasing mortality trend in urban population was contributed by decline of the rates of lung and stomach cancer in male and breast, stomach and colorectal cancer in female. Mortality rates in both urban and rural population were increasing for prostate and cervical cancers.
Conclusions:
This study shows that large rural and urban inequalities in cancer mortality exist in Lithuania. The contrast between the health of residents in urban and rural areas invites researchers for research projects to develop, implement, and enhance cancer prevention and early detection intervention strategies for rural populations.
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Intent to migrate among nursing students in Uganda: measures of the brain drain in the next...
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Tuesday, 12 February 2008
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Background:
There is significant concern about the worldwide migration of nursing professionals from low-income countries to rich ones, as nurses are lured to fill the large number of vacancies in upper-income countries. This study explores the views of nursing students in Uganda to assess their views on practice options and their intentions to migrate.
Methods:
Anonymous questionnaires were distributed to nursing students at the Makerere Nursing School and Aga Khan University Nursing School in Kampala, Uganda, during July 2006, using convenience sampling methods, with 139 participants. Two focus groups were also conducted at one university.
Results:
Most (70%) of the participants would like to work outside Uganda, and said it was likely that within five years they would be working in the U.S.A. (59%) or the U.K. (49%). About a fourth (27%) said they could be working in another African country. Only eight percent of all students reported an unlikelihood to migrate within five years of training completion. Survey respondents were more dissatisfied with financial remuneration than with any other factor pushing them towards emigration. Those wanting to work in the settings of urban, private, or U.K./ U.S. practices were less likely to express a sense of professional obligation and/or loyalty to country. Those who have lived in rural areas were less likely to report wanting to emigrate. Students with a desire to work in urban areas or private practice were more likely to report an intent to emigrate for financial reasons or in pursuit of country stability, while students wanting to work in rural areas or public practice were less likely to want to emigrate overall.
Conclusions:
Improving remuneration for nurses is the top priority policy change sought by nursing students in our study. Nursing schools may want to recruit students desiring work in rural areas or public practice to lead to a more stable workforce in Uganda.
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Mathematical models for lymphatic filariasis transmission and control: challenges and prospects
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Tuesday, 12 February 2008
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Background:
Mathematical models developed for describing the dynamics of transmission, infection, disease and control of lymphatic filariasis (LF) gained momentum following the 1997 World Health Assembly resolution and the launching of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) in 2000. Model applications could provide valuable inputs for making decisions while implementing large scale programmes. However these models need to be evaluated at different epidemiological settings for optimization and fine-tuning with new knowledge and understanding on infection/disease dynamics.DiscussionEPIFIL and LYMFASIM are the two mathematical simulation models currently available for lymphatic filariasis transmission and control. Both models have been used for prediction and evaluation of control programmes under research settings. Their widespread application in evaluating large-scale elimination programmes warrants validation of assumptions governing the dynamics of infection and disease in different epidemiological settings. Furthermore, the predictive power of the models for decision support can be enhanced by generating knowledge on some important issues that pose challenges and incorporating such knowledge into the models. We highlight factors related to the efficacy of the drugs of choice, their mode of action, and the possibility that drug resistance may develop; the role of vector-parasite combinations; the magnitude of transmission thresholds; host-parasite interactions and their effects on the dynamics of infection and immunity; parasite biology, and progression to LF-associated disease.SummaryThe two mathematical models developed offer potential decision making tools for transmission and control of LF. In view of the goals of the GPELF, the predictive power of these models needs to be enhanced for their wide-spread application in large scale programmes. Assimilation and translation of new information into the models is a continuous process for which generation of new knowledge on a number of uncertainties is required. Particularly, a better understanding of the role of immune mechanisms in regulating infection and disease, the (direct or immune mediated) mode of action of current drugs, their effect on adult worms, their efficacy after repeated treatment, and the population genetics of drug resistance are important factors that could make the models more robust in their predictions of the impact of programmes to eliminate LF. However, if these models are to be user-friendly in the hands of programme managers (and not remain as research tools), it would be necessary to identify those factors which can be considered as the minimum necessary inputs/outputs in operational settings for easy evaluation and on-site decision making.
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