The prevalence of diabetes and thyroid related autoantibodies in Sri Lankan children with type 1 diabetes and their unaffected siblings - The utility of a new screening assay.

Background: There is limited information about diabetes and thyroid related autoantibodies in children with type 1 diabetes (T1D) or their siblings in Sri Lanka. Objectives: To assess in T1D children and their unaffected siblings the prevalence of autoantibodies to (1) glutamic acid decarboxylase (GADA), insulinoma associated antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A) using 3 Screen ICA™ (3-Screen) and individual ELISA assays; (2) insulin (IAA); and (3) thyroid peroxidase (TPOA), thyroglobulin (TgA) and the TSH receptor (TSHRA). Methods: We selected - (a) consecutive T1D children, and (b) their unaffected siblings of both sexes, from the T1D Registry at Lady Ridgeway Hospital, Colombo. Results: The median age (IQR) of 235 T1D children and 252 unaffected siblings was 11 (8.4, 13.2) and 9 (5.4, 14.9) years respectively, and the duration of T1D was 23 (7, 54) months. (1) T1D children (a) 79.1% were 3-Screen positive; (b) all 3-Screen positives were individual antibody positive (GADA in 74%; IA-2A 31.1%; ZnT8A 38.7%); (c) and were younger (p=0.01 vs 3-Screen negatives); (d) multiple autoantibodies were present in 45.1%; (e) IA-2A (p=0.002) and ZnT8A (p=0.006) prevalence decreased with T1D duration. (f) TPOA and TgA prevalence was higher in T1D children compared to unaffected siblings (28%, p=0.001 and 31%, p=0.004, respectively). (2) Unaffected siblings (a) 6.3% were 3-Screen positive (p=0.001 vs T1D), and 2.4% were positive for IAA; (b) four subjects had two diabetes related autoantibodies, one of whom developed dysglycaemia during follow-up. Conclusions: The 3-Screen assay, used for the first time in Sri Lankan T1D children and their siblings as a screening tool, shows a high prevalence of T1D related Abs with a high correlation with individual assays, and is also a helpful tool in screening unaffected siblings for future T1D risk. The higher prevalence of thyroid autoantibodies in T1D children is consistent with polyglandular autoimmunity.

Association between child maltreatment and constipation: a school-based survey using Rome III criteria.

OBJECTIVE: Child abuse leads to multiple physical and psychosomatic sequelae. The aim of the present study was to evaluate the association between child abuse and constipation among schoolchildren. METHODS: Children 13 to 18 years of age were selected from 4 semiurban schools in Gampaha District, Sri Lanka. A self-administered questionnaire was used for data collection. Information regarding sociodemographic factors and gastrointestinal symptoms, child abuse, and somatisation were collected. Constipation was diagnosed using Rome III criteria. RESULTS: A total of 1792 children were included in the analysis (boys 975 [54.4%], mean age 14.4 years, standard deviation [SD] 1.3 years). One hundred thirty-eight (7.7%) fulfilled Rome III criteria for constipation. The number of children exposed to physical, emotional, and sexual abuse were, respectively, 438 (24.4%), 396 (22.1%), and 51 (2.8%). The prevalence of constipation was significantly higher in those exposed to sexual (5.8% vs 2.6% P = 0.03), emotional (40.9% vs 20.8%, P < 0.0001), and physical abuse (41.6% vs 23.2%, P < 0.0001). Mean somatisation score was higher in the total group of abused children with constipation (mean 18.6, SD 12.5) compared with those without (mean 13.9, SD 12.3; P = 0.027). Children with a history of abuse did not seek health care more often than children without this history. Patient-perceived severity of bowel symptoms was higher in children with physical abuse (23.7 vs 19.7 P = 0.001) and emotional abuse (25.4 vs 19.3 P < 0.0001). CONCLUSIONS: Childhood constipation shows a significant association with physical, sexual, and emotional abuse. Children with constipation complain of more somatic symptoms and bowel symptoms when they are exposed to abuse.

The use of child soldiers in war with special reference to Sri Lanka.

Throughout history, the involvement of children in military operations has been extensively documented. The issue of child conscription is multi-faceted, with very few medical but more sociological aspects, including terrorism, politics, economics, history, culture and religion amongst other factors. Many United Nations Instruments as well as the International Criminal Court have documented that child conscription is detrimental to a child's development, violates Child Rights, and is a war crime. Efforts by international bodies to address conscription as child abuse have failed since the process is undertaken by groups rather than individuals, and because the law has no access to the perpetrators. The background to a conflict in Sri Lanka and various ethno-religious and political factors are discussed. The role of the diaspora community, the internet and various fund-raising mechanisms for war are discussed. The history of child conscription and studies examining reasons and the tasks assigned to them as conscripts as well as abusive aspects, especially in relation to emotional abuse, neglect and physical harm, are discussed. Documentation of conscription as child abuse needing a definition including a new definition of 'suicide by proxy' is stressed. The importance of culture and history, and the manipulation of the idealistic mind are discussed in the context of 'setting the stage' for child conscription. The toy weapon industry and the real arms industry, especially small arms, are important in maintaining conflicts, especially in the developing world. The conflicts of interests of members of the UN Security Council and the 'peace-keepers' of the world is discussed.

Gastric myoelectrical and motor abnormalities in children and adolescents with functional recurrent abdominal pain.

BACKGROUND AND AIMS: Recurrent abdominal pain is common among children and adolescents. The majority of the affected patients have no apparent cause for their symptoms. This study evaluated gastric myoelectrical activity and motility abnormalities in children and adolescents with functional recurrent abdominal pain. METHODS: Forty-two children with functional recurrent abdominal pain [19 (45.2%) males, mean 8 years, SD 3 years, 19 functional abdominal pain, 9 irritable bowel syndrome, 9 functional dyspepsia, 1 abdominal migraine, 1 aerophagia and 3 non-specific abdominal pain according to Rome III criteria] and 20 healthy children [10 (50%) males, mean 9 years, SD 2.7 years] from the same geographical area underwent electrogastrography (EGG), and ultrasonographic assessment of gastric emptying rate and antral motility. RESULTS: Average gastric emptying rate, amplitude of antral contractions and antral motility index were lower in patients (46.5%, 74.3% and 6.5 respectively) compared to controls (66.17%, 89% and 8.3 respectively) (P < 0.001). Gastric emptying rate had a negative correlation with scores obtained for severity of symptoms (r = -0.63, P < 0.0001). Postprandial dominant frequency instability co-efficient (post-DFIC) was higher in patients than in controls (27.83% vs 18.3%, P = 0.0087), and correlated with the symptom score (r = 0.26, P = 0.045). CONCLUSIONS: Gastric emptying and antral motility were significantly impaired in patients, indicating a possible role for gastric motility disturbances in the pathogenesis of childhood functional recurrent abdominal pain. Further studies, including therapeutic trials, are needed to confirm this association and for recommendation of prokinetic drugs in its management.

Aetiology of recurrent abdominal pain in a cohort of Sri Lankan children.

AIMS: Recurrent abdominal pain (RAP) has a multifactorial aetiology with many affected children having no evidence of organic pathology. This study assessed the functional and organic causes for RAP in a cohort of Sri Lankan children. METHODS: Fifty-five Sri Lankan children (45.5% males, aged 5-15 years) having RAP were screened for organic diseases. RAP was defined using Apley criteria. Children without clinical or laboratory evidence of organic diseases were classified into functional gastrointestinal diseases (FGD) using Rome II and III criteria. Thirty-nine patients with functional RAP and 20 healthy children (50% males, age 5-15 years) from same area were tested for Helicobacter pylori using a stool antigen test. RESULTS: Thirteen (23.6%) children had organic RAP. According to Rome II, 33 (60%), and according to Rome III, 39 (71%) (functional abdominal pain 19, irritable bowel syndrome nine, functional dyspepsia nine, abdominal migraine one, aerophagia one) children had FGD. Two (5.1%) patients and one (5%) control tested were positive for Helicobacter pylori (P > 0.05). Except for constipation, pain characteristics and associated symptoms were not significantly different between organic and functional RAP. CONCLUSIONS: Organic pathology accounted for symptoms in less than a quarter of Sri Lankan children with RAP. The majority had functional bowel diseases, of which the commonest was functional abdominal pain. Rome III criteria were more effective than Rome II criteria in identifying FGD. Helicobacter pylori infection did not appear to be associated with RAP.

An intervention study to monitor weight gain in infants using a home based complementary food recipe and a hand blender.

OBJECTIVES: To assess the efficacy of a home made energy dense weaning food, containing 110-130 kcal (26-30kJ) per 100 ml on prevention of growth faltering during infancy. METHODOLOGY: Infants attending four child health welfare clinics in the Medical Officer of Health (Ragama) area were recruited at the age of 4 months. The intervention group received a specially designed hand blender, recipe and advice to prepare a weaning food. The control group received weaning foods without any intervention. They were followed up monthly up to the age of 12 months. RESULTS: 152 infants completed the study (83 from intervention group). The infants in the intervention group gained significantly more weight than the control group (intervention group 2.43 +/- 0.72 kg, control group 2.02 +/-0.62 kg, p = 0.0002). Both groups showed a drop in the Z score for mean weight for age during the study period but this was less marked in the intervention group. CONCLUSIONS: A high energy density home made complementary food was effective in improving the weight gain of infants during the weaning period.

Sequential studies on thyroid antibodies during pregnancy.

Thyroid antibodies were measured sequentially in 25 pregnant women from a Sri Lankan population. A high prevalence of antithyroid antibodies, particularly antithyroglobulin antibodies (TgAb) had previously been demonstrated in female schoolchildren drawn from this population. In the present study TgAb were detected in 36.8% of nonpregnant controls while thyroid peroxidase antibody (TPOAb) positivity was present in 26.3%. The prevalence of both antibodies in the pregnancy study group showed a progressive decline compared to nonpregnant controls throughout gestation becoming undetectable in the third trimester. The results are consistent with an immunosuppressive effect of pregnancy in a population in whom high thyroid autoantibody titers may have resulted from a recent salt iodization program.

Thyroglobulin epitope recognition in a post iodine-supplemented Sri Lankan population.

OBJECTIVE: We previously reported a high prevalence of raised thyroglobulin autoantibodies (TgAb) in apparently healthy Sri Lankan schoolgirls following salt iodination. To characterize these antibodies further we determined the epitopes on thyroglobulin (Tg) with which they react and compared these with serum obtained from both healthy subjects and established autoimmune thyroid disease (AITD) patients from the UK. To extend our study to a wider population within Sri Lanka, we in addition determined the epitopes recognized by a group of AITD patients selected from a thyroid clinic in Sri Lanka, as well as apparently healthy female Sri Lankan tea workers of distinct ethnicity from the schoolgirls and AITD patients. DESIGN: Sri Lankan schoolgirls (n = 282) and adult female tea estate workers (n = 208) were examined for thyroid autoimmune markers. Sera with high TgAb (> 98 kIU/l) were selected from these two groups (n = 36 and 45, respectively) to study epitope-binding patterns. We also examined the sera from 16 AITD patients attending a thyroid clinic in Colombo, 16 patients with AITD from the thyroid clinic at the University Hospital of Wales and 16 sera from healthy control UK women with no evidence of thyroid disease. To determine the epitopes on Tg recognized by the subjects' TgAb, we employed a panel of Tg mouse monoclonal antibodies labelled with alkaline phosphatase in a competitive enzyme-linked immunosorbent assay reaction with the subjects' serum. RESULTS AND CONCLUSIONS: A majority of the Sri Lankan schoolgirls did not react with the immunodominant epitopes and did not differ significantly from healthy subjects from the UK in their Tg epitope recognition pattern. On the other hand, tea estate workers and Sri Lankan AITD patients recognized typical autoimmune thyroid disease epitopes and, in addition, recognized a separate cluster not previously associated with either the autoimmune state or the healthy state. The significance of this cluster requires further clarification.

Evolution of thyroid autoimmunity during iodine prophylaxis--the Sri Lankan experience.

OBJECTIVE: To study the evolution of thyroid autoimmunity, in relation to the change in goitre prevalence, during 3 Years of iodine prophylaxis in Sri Lanka. METHODS: Two groups of Sri Lankan schoolgirls between the ages of 10.8 and 17.5 Years were studied in 1998 (401 girls) and 2001 (282 girls). A prospective study was performed in 42 schoolgirls who were thyroid autoantibody (Ab)-positive (+ve) in 1998. Anthropometric measures, urinary iodine excretion (UIE), thyroid Volume, free thyroxine, free tri-iodothyronine, TSH, and thyroglobulin (Tg) and thyroid peroxidase (TPO) Ab were evaluated in all 683 girls. RESULTS: Goitre prevalence was significantly lower in 2001 compared with 1998 related to age (2.9% compared with 20.2%) and body surface area (11.6% compared with 40.8%), although UIE was unchanged. Prevalence of thyroid Ab in 2001 was also lower (23.4% compared with 49.9%); among those with the Ab, 34.8% had TgAb alone and 46.9% had a combination of TgAb+TPOAb, compared with 82.0% TgAb alone in 1998. In 2001, subclinical hypothyroidism was more frequent in Ab+ve (6.3%) than Ab-negative girls (1.0%). A cohort of 42 Ab+ve schoolgirls in 1998 (34 with TgAb alone, eight with TgAb+TPOAb) were evaluated again in 2001. Only 10 of them (23.8%) remained Ab+ve (mostly TPOAb+/-TgAb) in 2001. CONCLUSIONS: This study demonstrates that: (1) in 2001, goitre prevalence and thyroid autoimmunity rates were significantly lower than in 1998; (2) the pattern of thyroid Ab was different in the two surveys; (3) in 2001 alone, the occurrence of hypothyroidism was correlated with the presence of thyroid autoimmunity. These results indicate an evolution of thyroid autoimmune markers during the course of iodine prophylaxis, which has not been described before.

The effectiveness of bioaugmentation in nitrifying systems stressed by a washout condition and cold temperature.

Bioaugmentation consists of adding selected strains of microorganisms with known capabilities to a biological process to improve performance. In this study, laboratory-scale completely stirred tank reactors were bioaugmented with nitrifying bacteria while operated under high-stress conditions for the nitrifiers: a 2-day solids retention time (SRT) at 22 degrees C or a 5-day SRT at 4 degrees C. Intensive sampling was carried out to document the effects of the bioaugmentation. To quantitatively interpret the effects of biomass addition on process performance, mathematical modeling was carried out. Experimental and modeling results indicate that the maximum effect of a one-time bioaugmentation depend on the dose and decays as bioaugmented nitrifiers are washed out. Daily maintenance dosing results in long-term good performance, provided that the dose is large enough. For severe stress, almost all of the biomass in the system must be added by bioaugmentation.

Increased prevalence of thyroglobulin antibodies in Sri Lankan schoolgirls--is iodine the cause?

OBJECTIVE: Iodine deficiency was the likely cause of a high prevalence of goitre previously in Sri Lankan schoolchildren. Salt iodination was made compulsory in 1993 but there has been no recent study, using modern techniques, of its benefits or harmful effects. METHODS: Three hundred and sixty-seven schoolgirls between the ages of 11 and 16 years had ultrasound thyroid volume, free thyroxine (T4), free tri-iodothyronine (T3), thyrotrophin (TSH), anti-thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) antibodies, and urine iodine concentrations measured. RESULTS: Median ultrasound thyroid volume ranged from 4.8 ml (11-year-old girls) to 8.6 ml (16-year-old girls) with an age-related increase. Median urine iodine concentrations ranged from 105 to 152 microg/l. Free T4 and free T3 were normal in all, but TSH was elevated in four subjects (5. 53-41.29 mU/l). However, the prevalence of TgAb was markedly raised, ranging between 14.3% (11-year-old girls) and 69.7% (16-year-old girls) (P<0.03). In contrast, the prevalence of TPOAb was 10% or less in all age groups. CONCLUSIONS: Normal median thyroid volumes, iodine concentrations and thyroid function would indicate that iodine deficiency is not a major problem in this group. The high prevalence of TgAb, hitherto unreported, most likely reflects excessive iodination of Tg resulting in increased immunogenicity. There is an urgent need to continuously monitor the adequacy and risks of iodination in this population.

Attitudes towards genetic counselling and testing among medical students and newly qualified doctors.

OBJECTIVES: To determine knowledge about four genetic disorders (Down's syndrome (DS), haemophilia (haem), spinal muscular atrophy type 1 (SMA1) and Huntington's disease (HD)), attitudes towards counselling, acceptability of prenatal diagnosis and termination of pregnancies affected with these conditions. DESIGN: Questionnaire survey of a cohort of medical students and newly qualified doctors. SETTING: Faculty of Medicine, University of Ruhuna. RESULTS: 227 completed questionnaires (111 fourth year and 86 final year students, and 30 demonstrators) were analysed. Awareness of DS and haem, was higher than of SMA1 and HD, and was highest among the demonstrators. Over 80% of the cohort would not counsel directively about future pregnancies and would discuss the diseases with the family or at risk individuals. Prenatal diagnosis was found acceptable for DS, haem and SMA1 by a majority of the cohort. Attitudes to termination of affected pregnancies varied, 88%, 77%, 55% and 36% finding it acceptable for DS, SMA1, haem, and HD respectively, provided legal terminations were available and termination was requested by parents. CONCLUSIONS: This cohort of students and doctors appear to accept the principles of clinical genetics involving non-directive counselling, prenatal diagnosis and in some disorders, termination of pregnancy.

Infantile Cronkhite-Canada syndrome.

Since 1955, numerous cases of Cronkhite-Canada syndrome have been reported in adults. We present here the first Asian report of the infantile Cronkhite-Canada syndrome. While the prognosis in adults is variable, in children, it is less optimistic.

Unusual complications in siblings with marfanoid phenotype.

Marfan's syndrome has diverse manifestations that overlap with those seen in other connective tissue disorders. Visceral diverticula have been described only once in four adults with marfanoid features of recessive inheritance. Two siblings of a consanguineous marriage with marfanoid features, visceral diverticula, and diaphragmatic eventration are reported.