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Objectives: Clinical studies have documented a familiar tendency to develop preeclampsia and patients with impaired endothelial health are at increased risk. We studied genetic polymorphisms associated to cardiovascular disease and impaired endothelial function in women with and without preeclampsia., Methods: 241 African and 279 Caucasian women were recruited for genetic testing of the polymorphisms epoxide hydrolase 1 (EPXH1), endothelial nitric oxide synthase (NOS3) on exon 7 and variable nucleotide tandem repeats in intron 4 (NOS3I4a/b), angiotensinogen and the estrogen receptor1 polymorphism in intron 1., Results: Of 241 African women, 95 developed preeclampsia and out of the 279 Caucasian women 81 had preeclampsia. Carriers of the NOS3I4a/b polymorphism had a 1.7-fold increased risk to develop preeclampsia. There was no difference in distribution of the other tested polymorphism. Furthermore we could show a fourfold reduction to encounter severe course of preeclampsia (defined as occurrence of HELLP-syndrome or eclampsia) in carriers of the EPHX1 polymorphism encoding histidine., Conclusions: Our data reveal a highly significant association of the NOS3I4a/b polymorphism with increased risk to develop preeclampsia in pregnancy. The shown association of EPXH1 polymorphism with the severity of preeclampsia strengthen the concept, that individual susceptibility determines the capability of the maternal organism to deal with the pregnancy derived agents causing preeclampsia., (Copyright © 2013. Published by Elsevier B.V.)

Recently, evidence has emerged indicating that assessment of KRAS mutations before anti-epidermal growth factor receptor therapy improves outcome in patients with metastatic colorectal cancer (CRC). We report here a novel reverse-hybridization (RH) assay to screen for KRAS mutations in formalin-fixed paraffin-embedded colorectal tissue samples. We combined mutant-enriched PCR based on peptide nucleic acid clamping and RH of amplification products to nitrocellulose test strips that contained a parallel array of oligonucleotide probes targeting 10 frequent mutations in codons 12 and 13 of the KRAS gene. DNA mixing experiments, which included eight different tumor cell lines with known KRAS mutations, were performed to examine the sensitivity of mutation detection. All KRAS mutations present in tumor cell lines were unambiguously identified by the RH assay with 1% of each cell line DNA diluted in normal DNA. RH was then used to screen for KRAS mutations in 74 colorectal tumor and 4 normal control samples. Twenty-six (35%) of the 74 tumor samples showed KRAS mutations. No mutation was found in the four samples of normal colorectal tissue. DNA sequencing without previous mutant enrichment, however, failed to detect four (15%) out of 26 KRAS-positive formalin-fixed paraffin-embedded samples (FFPE). This finding suggests that even after microdissection, mutant sequences in a given DNA isolate can be rare and more sensitive methods are needed for mutation analysis.

Neurotensin (NT) receptors in pancreatic and other neuroendocrine tumors are promising targets for imaging and therapeutic purposes. Here, we report on the effect of distinct changes in the peptide chain on catabolism in vitro for five radiolabeled [99mTc] neurotensin analogues having high affinity for neurotensin receptors. Substitution of NT(1-7) by (NalphaHis)Ac--the Tc-binding moiety--combined with a reduced bond 8-9 (CH2NH), N-methylation of peptide bonds or replacement of Ile(12) by tertiary leucin (Tle) led to peptide stabilization of various degrees. Biodistribution studies in nude mice bearing HT29 xenografts showed higher tumor uptake with more stable peptides, yielding high tumor to blood ratios of up to 70.

Blood transfusions are an important route for HIV transmission in Africa. To explore whether transfusions are necessary in the case management of childhood anemia, a randomized trial was performed in Ifakara, Tanzania, a holoendemic malaria region. 116 children were randomized to receive either treatment for malaria and hookworm alone or, in addition, a transfusion of whole blood which had been tested negative for antibodies against the human immunodeficiency virus. Mean packed cell volume (PCV) at admission was 14.0% in the transfusion and 14.4% in the no transfusion group. Children were followed up for 8 weeks with measurements of PCV at 2 days, 4 weeks and 8 weeks after study entry. PCV was similar in both groups after 4 and 8 weeks (22.9% in the transfusion and 23.6% in the no transfusion group). There was a trend towards more hospital admissions and deaths in the no transfusion group; however, 95% confidence intervals included both a beneficial and an adverse effect of blood transfusions. The costs and benefits of transfusion for childhood anemia in countries with a high HIV prevalence need to be considered carefully before a rational treatment policy can be adopted. For that purpose, a larger randomized trial is urgently needed.

Urine samples from 3548 individuals residing in six of the eight districts which comprise Bong County, Liberia, the project area of the Bong County Agricultural Development Project (BCADP), and fecal specimens from 3408 of these individuals were examined for schistosome ova. A total of 164 water sites, including rice paddies, were surveyed for schistosome vector snails and monthly changes in snail population density and infection rate were determined in selected water sites. Bulinus globosus was more widely distributed than Biomphalaria pfeifferi but the latter species showed a higher infection prevalence (12.3%) than the former one (10.3%). Snail population density and infection rate fluctuated with season, being higher in the dry season and lower during periods of heavy rainfall. Dessication and/or heat stress may have contributed to the contraction of snail population size at the end of the dry season. More water sites contained infected snails during December through February than at any other time of the year. In selected water sites examined at monthly intervals, mean snail density was higher in rice paddies than in other water contact sites but the latter showed a higher prevalence of infected snails than the former. The overall prevalence of Schistosoma mansoni (24.8%) was significantly higher than that of S. haematobium (22.7%) but the difference in prevalence rates of two species in school children was not statistically significant. The intensity of S. haematobium infection (13.2 means G) was significantly higher than that of S. mansoni (6.3 means G). Mixed infections in school children did not have a significant effect on egg output. The prevalence and intensity of S. haematobium showed a dramatic decline between the age groups 0-15 and 20-50 + years old; the differences between these age groups in S. mansoni infection were unremarkable. In Zota, Jorquelle and Kokoya Districts, prevalence rates of S. haematobium were higher than those of S. mansoni; the reverse was observed in Suakoko and Panta-Kpai Districts but relative prevalence rates varied according to specific locality in each district. A south to north stratification of schistosomal infection prevalence was observed similar to the west to east gradient reported by Saladin et al. (1980). New rice paddies developed during the three year operational period of the BCADP contained little or no vector snails and schistosomal infections in farm families of these paddies reflected the characteristic of the disease in corresponding localities.(ABSTRACT TRUNCATED AT 400 WORDS)

Human infection with Schistosoma haematobium and/or Schistosoma mansoni is known to be widespread in central Liberia, but no information is available about its clinical manifestations or its significance for public health. Details of a cross-sectional morbidity study are reported. A sample from hospital out-patients and samples from 3 villages situated in areas with different transmission patterns (lack of transmission, transmission of only S. haematobium and transmission of both S. haematobium and S. mansoni) were examined. All 184 individuals were examined by standardized case history, clinical and parasitological investigations, including a skin snip for onchocerciasis and a count of schistosomal and other intestinal worm eggs from stool and urine. A complete blood count, urine analysis, urine cultures, hepatitis-B surface antigen determination and abdominal X-rays were also carried out. Schistosomal egg counts ranged from 1 to 6200/10 ml urine for S. haematobium and from 1 to 228/g stool for S. mansoni. Difficulties for the definition of accurate morbidity indices are discussed. Except for haematuria and dysuria, the overall morbidity in the study area was not striking, neither for S. haematobium nor for S. mansoni infection. No cumulative pathology was observed in patients with mixed infection. The frequency of hypertension, hepato- and splenomegaly, ascites and bacteriuria was low and no relationship to schistosomiasis could be established. Bladder calcifications were found in 10% of people living in an area of transmission of S. haematobium. Although the intensity of infection is low for both S. haematobium and S. mansoni, long-term follow-up studies are essential for a more accurate assessment of the public health importance of these parasites.

Multiple sleep latency tests were performed in 42 drug-free outpatients with excessive sleepiness: 12 narcoleptics, 9 sleep apneics, 7 primary depressives, and 14 patients with miscellaneous disorders. Among-group comparisons were made by one-way ANOVA for each nap (time-of-day effect) and using four-nap means of EEG sleep variables. Four-nap means were significantly different among groups for percent awake, percent time spent asleep, stage 1 latency, and REM latency. Of 22 significant pairwise comparisons (P less than 0.05, LSD test), 77.3% occurred at 12.00 and 14.00. Depressives showed lower sleep percentage (more arousal) and fell asleep later than narcoleptics or apneics. Patients with miscellaneous disorders occupied a middle position. Sleep percentage was gradually reduced during the day in depressives but remained high or rose further in apneics, narcoleptics, and miscellaneous patients. Naps were SOREMP-positive (sleep onset REM) 60.4% of the time in narcoleptics, 25.0% in apneics, 3.5% in depressives, and 5.4% in miscellaneous patients. SOREMP distribution across naps (10.00, 12.00, 14.00 and 16.00) was 19%, 31%, 19% and 31%, respectively. REM latency was significantly shorter in narcolepsy than in apnea. In summary, results show a continuum of excessive daytime sleepiness (EDS), demonstrating MSLT application in the differential diagnosis of EDS and significant diurnal variation in sleep measures.

The frequencies of haematuria and proteinuria among children of two rural communities with different Schistosoma haematobium endemicity from Liberia and Tanzania were compared. Although the prevalence and intensity of S. haematobium infections were lower in the Tanzanian community, the frequencies of haematuria and proteinuria were significantly higher when compared to the Liberian community. The semi-quantitative dip stick tests for haematuria and proteinuria showed a comparable, good specificity (haematuria 85%, proteinuria 80%), but a community-specific sensitivity. The dip stick test for haematuria detected 85% (proteinuria 82%) of all S. haematobium infected subjects in Tanzania compared to 68% (proteinuria 57%) in Liberia. The significance of these observations in relation to S. haematobium related morbidity is discussed.

In an area of high transmission of Schistosoma haematobium and S. mansoni in Central Liberia, populations of five villages and intermediate host snails were surveyed for two years. In three of these villages focal application of molluscicide (niclosamide) in the main transmission sites was combined with mass chemotherapy of a target population representing 76 to 90% of the contamination index. In the two other villages, which served as control, the prevalence indexes remained stable or increased a little during the period of this study. A three dose metrifonate mass treatment was applied in one village with only S. haematobium infections. The compliance was very poor for the second and third dose but the quantity of eggs eliminated by the whole population present before and after mass treatment was reduced by 50%. No snails were found after molluscicide applications but as the incidence remained unchanged it is suspected that inhabitants have been reinfected by going to their fields. Concurrent metrifonate and niridazole mass treatment in one dose was applied in another village with only S. haematobium infections. Molluscicide applications reduced the snail population by 80% but did not affect the transmission. Prevalence indexes were almost the same before and after this intervention. In the last village, praziquantel (40 mg/kg in 1 dose) was used because both S. haematobium and S. mansoni infections were present. Molluscicide applications reduced the snail population by 99% and 87% for Bulinus globosus and Biomphalaria pfeifferi, respectively. This intervention stopped the transmission of S. haematobium for at least one year and reduced the prevalence from 21% to 4.6%. On the contrary for S. mansoni infections, the incidence remained very high (50%) and the prevalence was unchanged after one year follow-up. This could be explained by lower efficacy of praziquantel against S. mansoni (cure rate: 53%) and of molluscicide application against B. pfeifferi, which are highly susceptible to S. mansoni (infection rate 44%). The importance of migration in these villages is emphasized. Prevalence indexes were largely influenced by the arrival of newcomers who played a more important role in the maintenance of transmission after target mass chemotherapy than the infected persons excluded from this treatment. The costs per capita protected were 3.33 US $ for metrifonate, 1.53 for metrifonate and niridazole combined and 1.67 US$ for praziquantel. These figures do not include costs for parasitological examinations.(ABSTRACT TRUNCATED AT 400 WORDS)

121 persons from rural areas of central Liberia were examined for possible interactions between helminthic infections and the retinol (vitamin A) and retinol binding protein (= RBP) status. About 2/3 of this mainly adult population had retinol and RBP serum concentrations less than or equal to 400 micrograms/l and less than or equal to 40 micrograms/ml, respectively. Only one person had a serum retinol concentration less than 100 micrograms/l which is critical for the appearance of xerophthalmia. The retinol and RBP concentrations showed a linear, positive correlation. 19 parasitologically helminth free individuals had mean serum retinol and RBP concentrations of 414 micrograms/l and 43 micrograms/ml, respectively, while the corresponding values of 20 individuals with schistosomiasis as the only helminthic infection were 339 micrograms/l and 35 micrograms/ml. 65 other persons with mixed intestinal and/or tissue helminthiases, and 9 persons with pure Onchocerca volvulus infection exhibited intermediate mean concentrations. 32 persons without serological evidence of helminthic infections had higher serum concentrations of retinol and RBP than 32 individuals in whose sera at least one raised antibody titer was found in the enzyme-linked immunosorbent assay with 3 different helminthic test antigens. In addition to age, sex and pregnancy schistosomiasis might be a further risk factor of latent retinol and RBP deficiency among adults and teenagers living in a schistosomiasis endemic area.