Cyclospora cayetanensis among expatriate and indigenous populations of West Java, Indonesia.

From January 1995 through July 1998, we investigated the occurrence of Cyclospora cayetanensis infection associated with gastrointestinal illness or diarrhea in foreign residents and natives of West Java, Indonesia. We found that C. cayetanensis was the main protozoal cause of gastrointestinal illness and diarrhea in adult foreign residents during the wet season. The parasite rarely caused illness in the indigenous population or in children

Bladder cancer cells acquire competent mechanisms to escape Fas-mediated apoptosis and immune surveillance in the course of malignant transformation

Mechanisms of resistance against Fas-mediated cell killing have been reported in different malignancies. However, the biological response of immune escape mechanisms might depend on malignant transformation of cancer cells. In this study we investigated different mechanisms of immune escape in 2 well-differentiated low-grade (RT4 and RT112) and 2 poorly differentiated high-grade (T24 and TCCSUP) bladder cancer cell lines. Fas, the receptor of Fas-ligand, is expressed and shedded by human transitional bladder carcinoma cell lines RT4, RT112, T24 and TCCSUP. Cytotoxicity and apoptosis assays demonstrate that in spite of the Fas expression, poorly differentiated T24 and TCCSUP cells are insensitive towards either recombinant Fas-ligand or agonistic apoptosis-inducing monoclonal antibody against Fas. In poorly differentiated T24 and TCCSUP cell lines we were able to detect marked Fas-ligand protein by flow cytometry and Western blot analysis. In grade 1 RT4 and RT112 cells only minor expression of Fas-ligand possibly because of proteinase action. Fas-ligand mRNA translation or post-translational processing seems to be regulated differentially in the cancer cell lines depending on malignant transformation. In co-culture experiments we show that poorly differentiated cells can induce apoptosis and cell death in Jurkat cells and activated peripheral blood mononuclear cells. This in vitro study suggests that bladder cancer cells can take advantage of different mechanisms of immune evasion and become more competent in avoiding immune surveillance during transformation to higher-grade malignant disease. © 2001 Cancer Research Campaign www.bjcancer.co

Dominant Mutations in GRHL3 Cause Van der Woude Syndrome and Disrupt Oral Periderm Development

Peer reviewe

Dominant Mutations in GRHL3 Cause Van der Woude Syndrome and Disrupt Oral Periderm Development

Mutations in interferon regulatory factor 6 (IRF6) account for ∼70% of cases of Van der Woude syndrome (VWS), the most common syndromic form of cleft lip and palate. In 8 of 45 VWS-affected families lacking a mutation in IRF6, we found coding mutations in grainyhead-like 3 (GRHL3). According to a zebrafish-based assay, the disease-associated GRHL3 mutations abrogated periderm development and were consistent with a dominant-negative effect, in contrast to haploinsufficiency seen in most VWS cases caused by IRF6 mutations. In mouse, all embryos lacking Grhl3 exhibited abnormal oral periderm and 17% developed a cleft palate. Analysis of the oral phenotype of double heterozygote (Irf6+/−;Grhl3+/−) murine embryos failed to detect epistasis between the two genes, suggesting that they function in separate but convergent pathways during palatogenesis. Taken together, our data demonstrated that mutations in two genes, IRF6 and GRHL3, can lead to nearly identical phenotypes of orofacial cleft. They supported the hypotheses that both genes are essential for the presence of a functional oral periderm and that failure of this process contributes to VWS

Prevalence and Factors Associated with Intestinal Parasitic Infection among Children in an Urban Slum of Karachi

Background:Intestinal parasitic infections are endemic worldwide and have been described as constituting the greatest single worldwide cause of illness and disease. Poverty, illiteracy, poor hygiene, lack of access to potable water and hot and humid tropical climate are the factors associated with intestinal parasitic infections. The study aimed to estimate prevalence and identify factors associated with intestinal parasitic infections among 1 to 5 years old children residing in an urban slum of Karachi Pakistan. Methods And PrincipalFindings:A cross sectional survey was conducted from February to June 2006 in Ghosia Colony Gulshan Town Karachi, Pakistan. A simple random sample of 350 children aged 1-5 years was collected. The study used structured pre-tested questionnaire, anthropometric tools and stool tests to obtain epidemiological and disease data. Data were analyzed using appropriate descriptive, univariate and multivariable logistic regression methods. The mean age of participants was 2.8 years and 53% were male. The proportions of wasted, stunted and underweight children were 10.4%, 58.9% and 32.7% respectively. The prevalence of Intestinal parasitic infections was estimated to be 52.8% (95% CI: 46.1, 59.4). Giardia lamblia was the most common parasite followed by Ascaris lumbricoides, Blastocystis hominis and Hymenolepis nana. About 43% children were infected with single parasite and 10% with multiple parasites. Age {Adjusted Odds Ratio (aOR) = 1.5, 95% CI: 1.1, 1.9}, living in rented households (aOR = 2.0, 95% CI: 1.0, 3.9) and history of excessive crying (aOR = 1.9, 95% CI: 1.0, 3.4) were significantly associated with intestinal parasitic infections.Conclusion:Intestinal parasites are highly prevalent in this setting and poverty was implicated as an important risk factor for infection. Effective poverty reduction programmes and promotion of deworming could reduce intestinal parasite carriage. There is a need for mass scale campaigns to create awareness about health and hygiene

Hydroxyurea and sickle cell anemia: effect on quality of life

BACKGROUND: The Multicenter Study of Hydroxyurea (HU) in Sickle Cell Anemia (MSH) previously showed that daily oral HU reduces painful sickle cell (SS) crises by 50% in patients with moderate to severe disease. The morbidity associated with this disease is known to have serious negative impact on the overall quality of life(QOL) of affected individuals. METHODS: The data in this report were collected from the 299 patients enrolled in the MSH. Health quality of llife (HQOL) measures were assessed in the MSH as a secondary endpoint to determine if the clinical benefit of HU could translate into a measurable benefit perceptible to the patients. HQOL was assessed with the Profile of Mood States, the Health Status Short Form 36 (SF-36), including 4-week pain recall, and the Ladder of Life, self-administered twice 2-weeks apart pre-treatment and every 6 months during the two-year, randomized, double-blind, treatment phase. The effects of factors including randomized treatment, age, gender, pre-treatment crises frequency, Hb-F level mean, daily pain from 4-week pre-treatment diaries, and 2-year Hb-F response level (low or high) were investigated. RESULTS: Over two years of treatment, the benefit of HU treatment on QOL, other than pain scales, was limited to those patients taking HU who maintained a high HbF response, compared to those with low HbF response or on placebo. These restricted benefits occurred in social function, pain recall and general health perception. Stratification according to average daily pain prior to treatment showed that responders to HU whose average daily pain score was 5–9 (substantial pain) achieved significant reduction in the tension scale compared to the placebo group and to non-responders. HU had no apparent effect on other QOL measures. CONCLUSION: Treatment of SS with HU improves some aspects of QOL in adult patients who already suffer from moderate-to-severe SS

The risks and benefits of long-term use of hydroxyurea in sickle cell anemia: A 17.5 year follow-up.

A randomized, controlled clinical trial established the efficacy and safety of short-term use of hydroxyurea in adult sickle cell anemia. To examine the risks and benefits of long-term hydroxyurea usage, patients in this trial were followed for 17.5 years during which they could start or stop hydroxyurea. The purpose of this follow-up was to search for adverse outcomes and estimate mortality. For each outcome and for mortality, exact 95% confidence intervals were calculated, or tests were conducted at alpha = 0.05 level (P-value \u3c0.05 for statistical significance). Although the death rate in the overall study cohort was high (43.1%; 4.4 per 100 person-years), mortality was reduced in individuals with long-term exposure to hydroxyurea. Survival curves demonstrated a significant reduction in deaths with long-term exposure. Twenty-four percent of deaths were due to pulmonary complications; 87.1% occurred in patients who never took hydroxyurea or took it for \u3c5 years. Stroke, organ dysfunction, infection, and malignancy were similar in all groups. Our results, while no longer the product of a randomized study because of the ethical concerns of withholding an efficacious treatment, suggest that long-term use of hydroxyurea is safe and might decrease mortality