Relationship between Intracranial Granulomas and Cerebrospinal Fluid Levels of Gamma Interferon and Interleukin-10 in Patients with Tuberculous Meningitis

Cerebrospinal fluid gamma interferon (IFN-γ) and interleukin-10 levels in 39 patients with tuberculous meningitis were serially measured. Cytokine levels did not predict intracranial granuloma (IG) development, but IFN-γ levels in the top quartile after 1 month of therapy were highly associated (odds ratio = 18) with detection of an IG by computed tomography scanning.     

TAC-101, a benzoic acid derivative, inhibits liver metastasis of human gastrointestinal cancer and prolongs the life-span

We examined the anti-tumor effect of a novel benzoic acid derivative, TAC-101 (4-[3,5-bis(trimethylsilyl) benzamide] benzoic acid) on models with liver metastasis. Oral administration of TAC-101 significantly inhibited spontaneous liver metastasis of AZ-521 (human gastric cancer ) by orthotopic implan-tation to athymic nude mice. It also inhibited both the liver metastasis of AZ-521 induced by intrasplenic injection and the secondary lung metastasis from the liver. In addition, TAC-101 inhibited the proliferation of Co-3 (human colon adenocarcinoma) that formed a single nodule in the liver of athymic nude mice by intrahepatic implantation. The growth inhibitory effect of TAC-101 on AZ-521 experimental liver metastasis was observed when treatment was started on day 7, 14, or 21 which may correspond to the progressive stage of liver metastasis in clinical settings. Multiple administration of TAC-101 (8 mg/kg/day) significantly prolonged survival time of the animals with liver met astasis by intrasplenic injection of AZ-521 (T/C = 230%) and A549 (human lung adenocarcinoma; T/C = 186%). These effects of TAC-101 were stronger than those of 5-FU, CDDP or ATRA. Furthermore, TAC-101 inhibited the binding of AP-1 to DNA on electrophoretic mobility shift assay using nuclear extract of AZ-521 cells, although ATRA did not inhibit. These findings suggested that TAC-101 may be a candidate for a new class of anti-cancer agents for liver metastasis. © Rapid Science Ltd.     

Epidemiology of rotavirus diarrhea in Egyptian children and implications for disease control.

Reliable epidemiologic data are essential for formulating effective policy to control rotavirus disease through immunization. The objective of this study was to describe the epidemiology of rotavirus diarrhea in a population-based cohort of children under 3 years of age residing in Abu Homos, Egypt, in 1995-1996. Rotavirus diarrhea incidence rates (episodes per person-year) were 0.13 for infants aged <6 months, 0.61 for those aged 6-11 months, 0.17 for those aged 12-23 months, and 0.15 for those aged 24-35 months. Fifty-six percent of children with rotavirus diarrhea had clinical dehydration; 90% of rotavirus diarrheal episodes occurred between July and November. In infants under 1 year of age, receipt of breast milk was associated with a lower incidence of rotavirus diarrhea. No other sociodemographic or environmental factor was found to be significantly associated with rotavirus diarrhea. Of 46 rotavirus isolates with strains identified, 41 (89%) were G serotypes 1 and 2. Rotavirus diarrhea was a major cause of morbidity in this cohort. Promotion of breastfeeding may exert a protective effect in young infants in this setting, but improvements in water and sanitation are unlikely to be effective preventive measures. The use of effective immunization against rotavirus in early infancy should be considered a public health priority.     

Analysis of Dietary Habits and Nutritional Status of Children with Down Syndrome in the Context of Lipid and Oxidative Stress Parameters

Introduction: The risk of obesity in children with Down syndrome is high. Undoubtedly, proper nutrition plays an important role in the prevention of excess body weight and is associated with a reduction of metabolic complications. The aim of the study was to assess the problem of disturbances in the nutritional status and eating habits of children with DS. Methods: A total of 39 patients were included in the study. The nutritional status was assessed by anthropometric tests and Dual X-ray Absorptiometry. Eating habits were assessed using the Child Eating Behavior Questionnaire and the Food Frequency Questionnaire. Blood samples were taken to determine the oxidative stress and lipid parameters. Results: Obesity was recognized in 15% of subjects and 23% were overweight. Children that were overweight were characterized by higher levels of triglycerides, atherogenic index of plasma, and apoA2 and apoE levels. Fat mass, fat mass/height² index, and visceral fat mass correlated with thiobarbituric acid reactive substances and advanced oxidative protein product level. The analysis of the Child Eating Behavior Questionnaire showed that children struggling with being overweight were more interested in food compared to those with normal body weight. A positive correlation was identified between waist circumference and food interest categories. Insufficient consumption of dairy products, vegetables, whole grain products, as well as fruits, seeds, nuts, and fatty fish was noted. Patients were less likely to consume products that are a good source of mono- and polyunsaturated fatty acids. Conclusions: In children with Down syndrome and obesity, disturbances in lipid and oxidative stress parameters are observed. Abnormal eating habits in all children with Down syndrome regardless of their nutritional status were noted. Proper nutritional education, nutritional control, and management of metabolic problems are essential in this group of patients.     

Laboratory-based Japanese encephalitis surveillance in Nepal and the implications for a national immunization strategy

We report on two years of Japanese encephalitis (JE) surveillance in Nepal and the implications for a national immunization strategy. From May 2004 to April 2006, 4,652 patients with encephalitis were evaluated. A serum or cerebrospinal fluid specimen was collected from 3198 (69%) patients of which 1,035 (32%) were positive by Japanese encephalitis IgM ELISA. Most cases (N = 951, 92%) were from the 24 Terai districts (i.e., southern plains, 12.3 million persons) with the majority (N = 616, 65%) from four western Terai districts (population = 1.8 million). The case fatality ratio was 14.7% and 6.3% and the proportion of cases under 15 years old was 52% and 62% in the four western and 20 non-western Terai districts, respectively. Japanese encephalitis immunization targeting residents one year of age and older in the western districts and one through 14 years old in the non-western Terai districts may have reduced Japanese encephalitis cases by 84% and deaths by 92%, nationally.     

Factor XIa and tissue factor activity in patients with coronary artery disease

It has been established that inflammation and enhanced pro-coagulant activity are associated with the pathogenesis of atherosclerotic vascular disease. We evaluated and compared the contributions of the factor (F)XIa and tissue factor (TF) activity in plasma of patients with coronary artery disease (CAD). Citrate plasma was obtained prior to therapy from 53 patients with stable angina (29 with a history of previous myocardial infarction; CAD-MI) and 30 with acute coronary syndrome (ACS) within 12 hours from pain onset. Four ACS patients treated with heparin were excluded. FXIa and TF activity were determined in clotting assays based upon the prolongation of clotting time by inhibitory monoclonal antibodies. Twenty-five of 26ACS patients (96%) and 22 of 29 CAD-MI patients (76%) had quantifiable FXIa (50 +/- 33 and 42 +/- 45pM, respectively). Ten of 26 (38%) ACS patients and only three of 53 (6%) stable CAD patients showed TF activity (<0.4pM). No FXIa or TF activity was observed in age-matched healthy controls (n = 12). For both CAD-MI and ACS patients, there were correlations (p < 0.05) between FXIa and interleukin-6 (R(2) = 0.59 and 0.39, respectively) and between FXIa and TAT (R(2) = 0.64 and 0.63, respectively). In conclusion, the majority of ACS and CAD-MI patients have circulating FXIa that correlates with markers of coagulation and inflammation.     

Reduced clot permeability and susceptibility to lysis in patients with acute coronary syndrome: effects of inflammation and oxidative stress

BackgroundStable angina is associated with unfavorable fibrin structure/function. It is not known how acute coronary syndromes (ACS) affect fibrin architecture.ObjectiveWe investigated fibrin clot properties and their determinants in ACS patients.Patients and methodsClot permeability, turbidity and fibrinolysis were assessed in 40 patients with ACS versus 40 controls with stable angina matched for age, sex, and risk factors.ResultsPatients with ACS had lower clot permeability (p = 0.001), faster fibrin polymerization (p = 0.008), and prolonged fibrinolysis time (p < 0.0001) than controls. C-reactive protein (CRP) and 8-epi-prostaglandin F_2α, a marker of oxidative stress, were the only independent predictors of clot permeability (R² = ?0.74; p < 0.0001 and R² = ?0.65; p < 0.0001, respectively) and fibrinolysis time in ACS patients (R² = 0.60; p < 0.0001 and R² = 0.59; p = 0.0002, respectively). In angina patients, fibrinogen and CRP predicted permeability (R² = ?0.71; p < 0.0001 and R² = ?0.62; p < 0.0001), and D-dimer predicted lysis time (R² = 0.54; p = 0.0005). In regression analysis models incorporating all patients, the only independent predictor of all clot variables was being an ACS patient (R² 0.51 to 0.85; p < 0.001).ConclusionsThis first study of clot properties in patients during an ACS demonstrated that compared with stable angina patients, their clots are composed of dense networks that are more resistant to lysis and these features are correlated with raised CRP and oxidative stress.     

Expanding the clinical spectrum of the ‘HDAC8‐phenotype’ – implications for molecular diagnostics,counseling and risk prediction

Cornelia de Lange syndrome (CdLS) is a clinically heterogeneous disorder characterized by typical facial dysmorphism, cognitive impairment and multiple congenital anomalies. Approximately 75% of patients carry a variant in one of the five cohesin‐related genes NIPBL, SMC1A, SMC3, RAD21 and HDAC8. Herein we report on the clinical and molecular characterization of 11 patients carrying 10 distinct variants in HDAC8. Given the high number of variants identified so far, we advise sequencing of HDAC8 as an indispensable part of the routine molecular diagnostic for patients with CdLS or CdLS‐overlapping features. The phenotype of our patients is very broad, whereas males tend to be more severely affected than females, who instead often present with less canonical CdLS features. The extensive clinical variability observed in the heterozygous females might be at least partially associated with a completely skewed X‐inactivation, observed in seven out of eight female patients. Our cohort also includes two affected siblings whose unaffected mother was found to be mosaic for the causative mutation inherited to both affected children. This further supports the urgent need for an integration of highly sensitive sequencing technology to allow an appropriate molecular diagnostic, genetic counseling and risk prediction.     

Antimicrobial susceptibility trends among Escherichia coli and Shigella spp. isolated from rural Egyptian paediatric populations with diarrhoea between 1995 and 2000

Antimicrobial susceptibility testing was performed on 3,627 isolates of Escherichia coli and 180 isolates of Shigella spp. collected in rural locations from 875 Egyptian children with diarrhoea between 1995 and 2000. The cumulative rates of resistance for E. coli and Shigella spp. were high (respectively, 68.2% and 54.8% for ampicillin, 24.2% and 23.5% for ampicillin-sulbactam, 57.2% and 42.5% for trimethoprim-sulphamethoxazole, and 50.9% and 75.4% for tetracycline). Non-enterotoxigenic E. coli (NETEC) isolates had a consistently higher level of antimicrobial resistance than did enterotoxigenic E. coli (ETEC) isolates. Trend testing showed significant decreases in resistance to ampicillin, ampicillin-sulbactam and tetracycline among all E. coli isolates. Increasing rates of resistance were observed for trimethoprim-sulphamethoxazole in ETEC isolates and Shigella spp., but not in NETEC isolates. Low levels of resistance were observed for all other antimicrobial agents tested. Overall, high levels, but decreasing trends, of resistance to commonly used antimicrobial agents were detected among isolates of E. coli and Shigella spp. from children in rural Egypt.