Celiac disease in patients with severe liver disease: gluten-free diet may reverse hepatic failure

BACKGROUND & AIMS: Mild liver abnormalities are common in patients with celiac disease and usually resolve with a gluten-free diet. We investigated the occurrence of celiac disease in patients with severe liver failure. METHODS: Four patients with untreated celiac disease and severe liver disease are described. Further, the occurrence of celiac disease was studied in 185 adults with previous liver transplantation using serum immunoglobulin A endomysial and tissue transglutaminase antibodies in screening. RESULTS: Of the 4 patients with severe liver disease and celiac disease, 1 had congenital liver fibrosis, 1 had massive hepatic steatosis, and 2 had progressive hepatitis without apparent origin. Three were even remitted for consideration of liver transplantation. Hepatic dysfunction reversed in all cases when a gluten-free diet was adopted. In the transplantation group, 8 patients (4.3%) had celiac disease. Six cases were detected before the operation: 3 had primary biliary cirrhosis, 1 had autoimmune hepatitis, 1 had primary sclerosing cholangitis, and 1 had congenital liver fibrosis. Only 1 patient had maintained a long-term strict gluten-free diet. Screening found 2 cases of celiac disease, 1 with autoimmune hepatitis and 1 with secondary sclerosing cholangitis. CONCLUSIONS: The possible presence of celiac disease should be investigated in patients with severe liver disease. Dietary treatment may prevent progression to hepatic failure, even in cases in which liver transplantation is considered.     

CD14 Influences Host Immune Responses and Alternative Activation of Macrophages during Schistosoma mansoni Infection

Antigen-presenting cell (APC) plasticity is critical for controlling inflammation in metabolic diseases and infections. The roles that pattern recognition receptors (PRRs) play in regulating APC phenotypes are just now being defined. We evaluated the expression of PRRs on APCs in mice infected with the helminth parasite Schistosoma mansoni and observed an upregulation of CD14 expression on macrophages. Schistosome-infected Cd14^−/− mice showed significantly increased alternative activation of (M2) macrophages in the livers compared to infected wild-type (wt) mice. In addition, splenocytes from infected Cd14^−/− mice exhibited increased production of CD4⁺-specific interleukin-4 (IL-4), IL-5, and IL-13 and CD4⁺Foxp3⁺IL-10⁺ regulatory T cells compared to cells from infected wt mice. S. mansoni-infected Cd14^−/− mice also presented with smaller liver egg granulomas associated with increased collagen deposition compared to granulomas in infected wt mice. The highest expression of CD14 was found on liver macrophages in infected mice. To determine if the Cd14^−/− phenotype was in part due to increased M2 macrophages, we adoptively transferred wt macrophages into Cd14^−/− mice and normalized the M2 and CD4⁺ Th cell balance close to that observed in infected wt mice. Finally, we demonstrated that CD14 regulates STAT6 activation, as Cd14^−/− mice had increased STAT6 activation in vivo, suggesting that lack of CD14 impacts the IL-4Rα-STAT6 pathway, altering macrophage polarization during parasite infection. Collectively, these data identify a previously unrecognized role for CD14 in regulating macrophage plasticity and CD4⁺ T cell biasing during helminth infection.     

CDC Kerala 13: Antenatal,Natal and Postnatal Factors Among Children (2–6 y) with Autism – A Case Control Study

Objectives

To compare antenatal, natal and postnatal factors among children between 2–6 y of age with autism and a control group of normal children.

Methods

One hundred and forty three confirmed cases of 2–6 y-old children with autism, attending autism clinic of Child Development Centre, who had a CARS score of ≥?30 were included in the study. Two hundred normal children in the same age group were recruited from the well-baby/immunization clinic of SAT Hospital, Thiruvananthapuram. Data was collected using a structured pre-piloted questionnaire consisting of 21 antenatal, 8 natal and 6 postnatal risk factors.

Results

The multivariate analysis on antenatal, natal and postnatal possible risk factors for autism showed statistically significant high odds ratios for (i) excess fetal movement (OR?=?11.44; 95 % CI: 2.85 – 45.98); (ii) maternal respiratory infection/asthma (OR?=?6.11; 95 % CI: 1.56–24.02; (iii) maternal vaginal infection (OR?=?5.20; 95 % CI: 1.72 – 15.73); (iv) maternal hypothyroidism (OR?=?4.25; 95 % CI: 1.38–13.07) and (v) family history of neuro-developmental disorders (OR?=?2.90; 95 % CI: 1.72 – 4.88).

Conclusions

This case control study involving 143 children between 2 and 6 y with autism as per CARS criteria and a control group of 200 normal children has shown that excess fetal movement, maternal respiratory infection/asthma, maternal vaginal infection, maternal hypothyroidism and family history of neuro-developmental disorders are possible risk factors for autism.

     

CDC Kerala 15: Developmental Evaluation Clinic (2–10 y) – Developmental Diagnosis and Use of Home Intervention Package

Objective

To describe the last 5 years' experience of Child Development Centre (CDC), Kerala Developmental Evaluation Clinic II for children between 2 and 10 y, referred for suspicion of developmental lag in the preschool years and scholastic difficulty in the primary classes with specific focus on developmental profile and the experience of the home based intervention package taught to the mothers.

Methods

A team of evaluators including developmental therapist, preschool teacher with special training in clinical child development, speech therapist, special educator, clinical psychologist and developmental pediatrician assessed all the children referred to CDC Kerala. Denver Developmental Screening Test (DDST-II), Vineland Social Maturity Scale (VSMS) and Intelligent Quotient (IQ) tests were administered to all children below 6 y and those above 6 with apparent developmental delay.

Results

Speech/delay (35.9 %), behavior problem (15.4 %), global delay/ intellectual disability (15.4 %), learning problem (10.9 %), pervasive developmental disorders (7.7 %), seizure disorder (1.7 %), hearing impairment (0.7 %), and visual impairment (0.7 %) were the clinical diagnosis by a developmental pediatrician. Each child with developmental problem was offered a home based intervention package consisting of developmental therapy and special education items, appropriate to the clinical diagnosis of the individual child and the same was taught to the mother.

Conclusions

The experience of conducting the developmental evaluation clinic for children between 2 and 10 y has shown that a team consisting of developmental therapist, speech therapist, preschool teacher, special educator, clinical child psychologist and developmental pediatrician, using appropriate test results of the child could make a clinical diagnosis good enough for providing early intervention therapy using a home based intervention package.

     

CDC Kerala 16: Early Detection of Developmental Delay/Disability Among Children Below 6 y — A District Model

Objective

To develop a district model for establishing early detection of childhood disability below 6 y of age and to develop appropriate referral linkages for confirmation of the diagnosis and establish home based early intervention therapy to all needy children.

Methods

Trained Accredited Social Health Activist (ASHA) workers conducted the preliminary survey for identifying developmental delay/disability among children below 6 y of age using Trivandrum Developmental Screening Chart (TDSC) (0–6 y) and a team of experts assessed the screen positives in developmental evaluation camps conducted at primary health centres (PHCs).

Results

Community survey was carried out and 1,01,438 children below 6 y of age in Thiruvananthapuram district were screened by ASHA workers and 2,477 (2.45 %) positive cases (TDSC two or more item delay) were identified and these children were called for the developmental evaluation camps conducted at 80 PHCs in the district. Among the 1,329 children who reached the evaluation camps 43.1 % were normal. 24.98 % children had speech and language delay and 22.95 % children had multiple disabilities. Developmental delay was observed among 49.89 % children and cerebral palsy in 8.43 % and intellectual disability 16.85 % were confirmed. Visual impairment in 3.31 % and neuromuscular disorders in 1.35 were found among children evaluated in the camp.

Conclusions

The results of this district wide early detection of disability survey by trained ASHA workers among children below 6 y of age showed a community prevalence of 3.08 % observed, based on two or more item delay in TDSC and among these children, 43.1 % were normal, 49.89 % had developmental delay, 24.98 % had speech and language delay and 22.95 % had multiple disabilities.

     

Downregulation of CPPED1 Expression Improves Glucose Metabolism In Vitro in Adipocytes

We have previously demonstrated that the expression of calcineurin-like phosphoesterase domain containing 1 (CPPED1) decreases in adipose tissue (AT) after weight reduction. However, the function of CPPED1 in AT is unknown. Therefore, we investigated whether the change in CPPED1 expression is connected to changes in adipocyte glucose metabolism. First, we confirmed that the expression of CPPED1 decreased after weight loss in subcutaneous AT. Second, the expression of CPPED1 did not change during adipocyte differentiation. Third, CPPED1 knockdown with small interfering RNA increased expression of genes involved in glucose metabolism (adiponectin, adiponectin receptor 1, and GLUT4) and improved insulin-stimulated glucose uptake. To conclude, CPPED1 is a novel molecule involved in AT biology, and CPPED1 is involved in glucose uptake in adipocytes.Lifestyle modification improves glucose metabolism and results in a substantial reduction in the risk of type 2 diabetes in the long-term (1). In searching new putative genes related to obesity and type 2 diabetes, we have previously demonstrated a multitude of changes in adipose tissue (AT) gene expression in response to weight reduction in individuals with metabolic syndrome (2,3). Among the downregulated genes was calcineurin-like phosphoesterase domain containing 1 (CPPED1) (2); its function in AT is completely unknown.Therefore, we continued to study the role of CPPED1 in AT in more detail. Interestingly, the experiment using a Simpson-Golabi-Behmel syndrome (SGBS) cell strain demonstrated an impact of CPPED1 small interfering RNA (siRNA) on insulin-stimulated glucose uptake in mature adipocytes. Overall, the results demonstrate that CPPED1 is a novel molecule expressed in AT and is related to adipocyte function.     

Carotid artery intima-media thickness and elasticity in relation to glucose tolerance

The association between diabetes and subclinical atherosclerosis is well established. The effect of non-diabetic glucose intolerance on early atherosclerosis is not as straightforward, and the data regarding sex-related differences in this matter are limited. Therefore, our aim was to investigate these associations in men and women separately. We studied 1,304 Finnish men and women over 45?years of age who participated in the Finnish Health 2000 Survey. Ultrasonically determined carotid artery intima-media thickness and elasticity were used as markers of early atherosclerosis. Glucose tolerance was categorized according to the American Diabetes Association criteria for diabetes mellitus. Age-adjusted means for carotid artery intima-media thickness and elasticity indices were significantly (P?<?0.05) associated with glucose tolerance status in both sexes. There was a trend of increasing early atherosclerosis with the worsening of glucose tolerance in men and women. These associations were weakened in both sexes after further adjustments for other cardiovascular risk factors. In women, but not in men, significant (P?<?0.05) associations between glucose tolerance status and carotid artery elasticity were seen even after these further adjustments. Diabetes and non-diabetic glucose intolerance are associated with increased early carotid atherosclerosis compared with normal glucose tolerance in both sexes. Our results suggest that women with glucose intolerance may be in greater risk than men.