Use of intravenous N-acetylcysteine in acute severe hepatitis due to severe dengue infection: a case series.

BACKGROUND: Dengue fever is a common mosquito borne viral infection. Severe dengue fever associated severe hepatitis carries high mortality. Based on the beneficial effect of N-acetylcysteine (NAC) in paracetamol poisoning and non-acetaminophen induced liver failure, it is used in dengue fever associated hepatitis in clinical practice. We aim to study the reversal of liver enzymes with NAC in the setting of severe hepatitis due to severe dengue infection. METHODS: A retrospective analysis was conducted on hospitalized 30 adults with severe dengue fever with severe hepatitis. These 30 patients had aspartate transaminase (AST) and alanine transaminases (ALT) more than 500 U/L and/or PT INR (prothrombin time and international normalized ratio) more than 1.5. They were treated with NAC infusion of 100 mg/h for 3 to 5 days. RESULTS: The mean age of the group was 49.9 ± 11.46 years and 18 (60%) patients were males. Nineteen patients (63%) developed dengue shock. Of them 12 patients (40%) developed hepatic encephalopathy. Median AST on the day of administration of NAC was 1125 U/L interquartile range (IQR) 1653.25 while median ALT was 752 (IQR 459.25). There was a statistically significant reduction of both ALT (p = 0.034) and AST (p = 0.049) from day 1 to 4 after NAC infusion. Rise of platelet count between day 1 and day 4 also showed statistically significant difference (p = 0.011) but the reduction of prothrombin time and international normalized ratio (PT/INR) from 1 to day 4 did not show statistical significance difference. Mean duration of treatment with NAC was 3.61 ± 0.75 days while mean length of hospital stay was 6.2 ± 1.27 days. Only one patient died (3.3%). None of the patients reported adverse drug reaction due to NAC. CONCLUSION: Majority of patients demonstrated marked clinical and biochemical improvements and they recovered fully. We observed faster and significant recovery of liver enzymes following administration of NAC. Based on the above findings, this study provides preliminary evidence for the beneficial effect of NAC in severe hepatitis in dengue infection with greater survival benefits.

Impact of Histological and Molecular Parameters on Prognosis of Oral Squamous Cell Carcinoma: Analysis of 290 Cases.

BACKGROUND: Nodal metastasis is a critical factor in predicting the prognosis of oral squamous cell carcinoma (OSCC). When patients present with a clinically positive neck, the treatment of choice is radical neck dissection. However, management of a clinically negative neck is still a subject of significant controversy. AIM: This study was carried out in order to propose a model to predict regional lymph node metastasis of OSCC using histological parameters such as tumour stage, tumour size, pattern of invasion (POI), differentiation of tumour, and host immune response, together with the expression levels of six biomarkers (periostin, HIF-1α, MMP-9, ß-catenin, VEGF-C, and EGFR), and, furthermore, to compare the impact of all these parameters on recurrence and 3 yr and 5 yr survival rates. Materials and Method. Histological materials collected from the archives were used to evaluate histological parameters and immunohistochemical profiles. Standard methods were used for immunohistochemistry and for evaluation of results. Data related to recurrence and survival (3 and 5 years) was also recorded. Clinical data was collected from patients' records. RESULTS: Male to female ratio was 3 : 1. The commonest site of OSCC was the buccal mucosa, and majority of them were T3 or T4 tumours presented at stage 4. 62.5% of the tumours were well differentiated. Three-year and 5-year survival rates were significantly associated with lymph node metastasis and recurrence. POI was significantly correlated with tumour size, stage, 3-year survival, EGFR, HIF-1α, periostin, and MMP-9 (p < 0.05). Expression of EGFR showed a direct association with metastasis (p < 0.05). CONCLUSION: POI, level of differentiation, and expression of EGFR are independent prognostic markers for lymph node metastasis. Therefore, these parameters may help in treatment planning of a clinically negative neck.

Association of the leptin receptor Q223R (rs1137101) polymorphism with obesity measures in Sri Lankans.

OBJECTIVE: The role of genetic factors in the development of obesity is largely unreported in Sri Lankans. The Q223R (rs1137101) single nucleotide polymorphism (SNP) of the leptin receptor (LEPR) gene has been associated with obesity measures in various ethnicities. We investigated the association of the Q223R polymorphism with obesity related anthropometric measures and biochemical parameters fasting blood glucose and lipid profile in a sample of 530 Sri Lankan adult subjects (age 18-70 years) representing both urban and rural areas of residence. RESULTS: The LEPR Q223R variant G allele frequency was 0.54. The polymorphism was associated with body mass index (p = 0.04) and waist circumference (p = 0.02) measures in overweight and obese (BMI ≥ 25 kgm-2) subjects with the variant allele conferring a greater risk of adiposity. Residency in urban areas eliminated the protective effect of the non-risk genotype (AA) in the development of obesity.

A Predictive Model to Determine the Pattern of Nodal Metastasis in Oral Squamous Cell Carcinoma.

BACKGROUND: Developing histological prediction models that estimate the probability of developing metastatic deposit will help clinicians to identify individuals who need either radical or prophylactic neck dissection, which leads to better prognosis. Identification of accurate predictive models in oral cancer is important to overcome extensive prophylactic surgical management for neck nodes. Therefore, accurate prediction of metastasis in oral cancer would have an immediate clinical impact, especially to avoid unnecessary radical treatment of patients who are at a low risk of metastasis. METHODS: Histologically confirmed OSCC cases with neck dissection were used. Interrelation of demographic, clinical, and histological data was done using univariate and multivariate analysis. RESULTS: 465 cases were used and presence of metastasis and extracapsular invasion were statistically well correlated with level of differentiation (p < 0.001) and pattern of invasion (p < 0.001). Multivariate analysis showed level of differentiation, pattern of invasion, and stage as predictors of metastasis. CONCLUSIONS: The proposed predictive model may provide some guidance for maxillofacial surgeons to decide the appropriate treatment plan for OSCC, especially in developing countries. This model appears to be reliable and simple and may guide surgeons in planning surgical management of neck nodes.

Efficacy of intravenous hydrocortisone administered 2-4 h prior to antivenom as prophylaxis against adverse drug reactions to snake antivenom in Sri Lanka: An open labelled randomized controlled trial.

The prevention of adverse drug reactions to antivenom serum poses a formidable challenge in the management of snakebite. Hydrocortisone is being used concurrently with antivenom in order to prevent these adverse drug reactions without a proven benefit. However, all previous studies seemed to ignore the testing of effectiveness of hydrocortisone therapy during its pharmacological effects, which come hours later. On this principle, we aimed to test the effectiveness of intravenous hydrocortisone given 2 h or more prior to the commencement of antivenom therapy to reduce adverse drug reactions to antivenom. In an open-labelled randomized controlled trial, patients with a history of snakebite were randomly assigned to receive either 500 mg intravenous hydrocortisone bolus given 2 h or more prior to antivenom therapy (Group A) or at the time of antivenom therapy (Group B). The primary endpoint was the reduction of adverse drug reactions to antivenom of any grade of severity within the first 48 h. This trial has been registered with the "Sri Lanka Clinical Trials Registry", number SLCTR/2010/005. A total of 236 patients were randomized to group A or Group B. In the group A, 38 participants received hydrocortisone 2 h before administration of antivenom whilst 33 received hydrocortisone less than 2 h before administration of antivenom. In the Group B, 84 participants received hydrocortisone at the time of antivenom therapy. In Group A (n, 38), and Group B (n, 84), 15 patients (39%) and 29 patients (35%) developed reactions respectively and the difference is not significant (p = 0.598). Moreover, hydrocortisone therapy did not significantly reduce the occurrence of antievnom reactions of any grade of severity. Further, it didn't delay the occurrence of antivenom reactions in patients who received hydrocortisone either more than 2 h or less than 2 h before the antivenom as opposed to the control group (group B). Intravenous hydrocortisone shows no difference in the timing, rate or severity of adverse drug reactions to antivenom when administered simultaneously and up to 4 h prior to antivenom.

The regional sero-epidemiology of rhinosporidiosis in Sri Lankan humans and animals.

No data is available in the world literature on serum anti-rhinosporidial antibody levels in animals, and as far as we aware this is the first report. Although rhinosporidiosis in farm and domestic animals has been widely reported from other countries, rhinosporidiosis in animals has not been reported in Sri Lanka, though this country has the highest world-wide prevalence of human rhinosporidiosis on a unit-population basis. Serum IgG titres in 6 species of Sri Lankan animals (buffalo, cat, cattle, dog, goat, horse; total 291) were assayed by the Immuno blot (dot-ELISA) method on nitrocellulose paper and were compared with serum IgG titres in normal Sri Lankan human subjects (total 211) in different geographical areas, and in human Sri Lankan patients with rhinosporidiosis as reference values (total 36). Sensitization to rhinosporidial antigen(s) was detected in all 6 species of animals and the highest titres (1/3200) were found in cats, and free-grazing horses. Cattle showed higher levels of antibody than buffaloes. The titres in these animals are compared with world reports on overt rhinosporidiosis in these species, and with titres in normal Sri Lankan humans. Human, but not animal titres showed variations compatible with the regional prevalence of rhinosporidiosis. The variations in titres in animals especially horses, were probably more related to their mode of feeding, while in humans the titres in normal persons were probably related to the rhinosporidial-endemicity of their respective regions. No conclusions from sero-positivity in animals could be made regarding the absence of reports on rhinosporidiosis as an overt disease in these Sri Lankan animal species but the possibility of a genetically-determined insusceptibility to rhinosporidiosis in Sri Lanka, is considered. Rhinosporidium seeberi-specific PCR positive reactions were obtained with nasal scrapings from cattle that microscopically showed PAS+ bodies that were compatible with rhinosporidial sporangia. Sequence-analysis of the reactions products from five positive R. seeberi-specific PCR samples (four in this study and 1 in a previous study) gave results confirmatory of R. seeberi.

The association of iron status with educational performance and intelligence among adolescents.

INTRODUCTION: The aim was to identify the association of iron status with educational performance and intelligence of adolescents. METHOD: This was a cross sectional comparative study among adolescents aged 13-15 years. Each iron deficient student was matched with an iron sufficient student from the same school, class and sex. Iron status was based on haemoglobin and serum ferritin levels. The marks for mathematics, science, Sinhala language and social science were considered to assess educational performance. Intelligence was measured by Raven's Standard progressive matrices. All the possible confounders and effect modifiers were considered. Home visits to a sub-sample checked the quality of data. RESULTS: The final analysis included 188 students (94 matched pairs). Neither educational performance nor intelligence showed significant associations with the iron status. The severity of the iron deficiency did not relate to these cognitive variables either. Twenty-three and 8 co-variables showed statistically significant associations with educational performance and intelligence respectively. Following a multiple regression analysis intelligence, the enthusiasm of the student towards learning, occupational ambition, household possession, problems at home and private tuition for mathematics were key factors predicting educational performance. Stunting and educational level of the mother were important factors influencing intelligence. CONCLUSION: Iron status does not play a major role in educational performance and intelligence of school going adolescents. Several factors affect educational performance and intelligence. This study highlights the difficulty in extrapolating the findings of similar studies to different ecological settings.

Efficacy of low dose dexamethasone in severe thrombocytopenia caused by dengue fever: a placebo controlled study.

BACKGROUND: The use of corticosteroids in the management of thrombocytopenia in dengue fever remains untested. OBJECTIVES: To test whether intravenous low dose dexamethasone is efficacious in increasing platelet count in acute severe thrombocytopenia in dengue infection. METHODS: We undertook a placebo controlled study at the Teaching Hospital, Peradeniya, Sri Lanka in July 2004. Patients with thrombocytopenia (platelet count <50x10(9)/l) were allocated to the treatment and placebo groups using the sealed envelop method. The treatment group received an initial intravenous dose of 4 mg dexamethasone, followed by 2 mg doses every 8 h for 24 h, and the placebo group received normal saline. The primary outcome was the degree of mean platelet count rise. RESULTS: Each group comprised 100 patients and their baseline data and other variables (headaches, nausea, flush, temperature, pulse, blood pressure, haematocrit, white cell count and haemoglobin) were similar. The primary outcome--mean platelet count (x10(9)/l)--increased steadily in both groups from day 1 to 4 and showed no significant difference between the two groups (p>0.05): day 1, 35 vs 35 (p = 0.70); day 2, 47 vs 43 (p = 0.19); day 3, 64 vs 59 (p = 0.31); day 4, 72 vs 78 (p = 0.55). Analysis of variance (ANOVA) statistics showed a significant linear association of mean platelet counts by days in either group (p<0.001). Regression analysis identified the day of the illness and patient age as the independent predictors of platelet count change. CONCLUSION: At a low dose regimen, dexamethasone was not effective in achieving a higher rise of platelet count in dengue infection.

Is oral penicillin an effective chemoprophylaxis against leptospirosis? A placebo controlled field study in the Kandy District, Sri Lanka.

Leptospirosis poses a severe threat to the lives of farmers in Sri Lanka, thus, development of an effective chemoprophylaxis is deemed essential. We tested oral penicillin as chemoprophylaxis against leptospirosis in high transmission areas in central Sri Lanka in October 2005. Eight hundred active farmers were randomly assigned to take either oral penicillin (500 mg bid) or a similar looking placebo over a month during active farming season. The primary study point was the incidence of serologically confirmed leptospirosis. Data were available for 602 subjects of whom 319 (152 taking penicillin and 167 taking placebo) had good compliance, shown by tablet count. Of 5 subjects hospitalized with fever, 3 had serological evidence of leptospirosis, all of whom belonged to the placebo group. Therefore, oral penicillin may be effective chemoprophylaxis against leptospirosis.

Cardiac complications of a dengue fever outbreak in Sri Lanka, 2005.

A high incidence of cardiac complications was observed in an outbreak of dengue fever at General Hospital, Peradeniya, Sri Lanka, in 2005. This report describes 120 serologically confirmed dengue fever patients who presented during the outbreak. Seventy-five (62.5%) of these patients had electrocardiogram changes (T inversion, ST depression, bundle branch blocks) and were assigned to the 'cardiac group' (50 females, 25 males; median age 34 years, range 13-76). These patients were more susceptible to fatigue, dyspnoea, low peripheral oxygen saturation in room air (P=0.001), chest pain (P=0.001) and flushing of skin (P=0.05) than 45 (37.5%) patients who had normal electrocardiograms and made up the 'non-cardiac group'. In the cardiac group there were 31 primary and 44 secondary dengue patients. In the cardiac group, 17 (23%) patients had hypotension and 58 (77%) developed tachycardia and bradycardia (P<0.001) compared to four (9%) in the non-cardiac group, suggestive of significant cardiac dysfunction. There was no correlation between pulse rate and body temperature: cardiac group (r=0.05; P=0.63); non-cardiac group (r=0.11, P=0.46). RT-PCR detected DEN-3 in three cardiac patients.

Admission to medical schools in Sri Lanka: predictive validity of selection criteria.

OBJECTIVE: To assess the extent to which current selection criteria predict success in Sri Lanka's medical schools. METHODS: The study sample consisted of all students selected to all six medical schools in two consecutive entry cohorts. The aggregate marks of these students at the General Certificate of Education (GCE) Advanced Level examination, the district of entry, admission category, candidate type (school/private) and gender, were identified as entry point variables. Success in medical school was measured in four ways: the ability to pass the first summative examination and the final examination at the first attempt, and obtaining honours in either examination. Multivariate analysis using logistic regression was used to assess the extent to which these entry point factors predict variability in outcome measures. RESULTS: Aggregate scores among the 1740 students in the study sample ranged from 212 to 356, with a median of 285. The male:female ratio was 1.4:1. Private candidates (taking the examination for the third time) accounted for 22% of students. Being a school candidate, female and having a higher aggregate score, were the only independent predictors of success for all four outcome measures. The aggregate score alone accounted for only 1-7% of the variation in performance in medical school. CONCLUSIONS: Marks obtained at the A Level examination (the only academic criterion currently used for selection of medical students in Sri Lanka) is a poor predictor of success in medical school.

Routine antibiotic therapy in the management of the local inflammatory swelling in venomous snakebites: results of a placebo-controlled study.

OBJECTIVE: To evaluate the value of routine antibiotic therapy in the management of the local swelling of patients with venomous snakebites. METHODS: A prospective, placebo-controlled study at the General Hospital, Anuradhapura, Sri Lanka where 144 patients with envenoming and local swelling in the leg were allocated to receive either antibiotics (Group A = test group) or placebo (Group B = controls). Benzyl penicillin 2 mega units intravenously 6 hourly and metronidazole 500 mg by intravenous infusion 8 hourly for 5 days from the first day of the bite were given to Group A. Ethical committee approval was obtained from the Committee of General Hospital, Anuradhapura. MAIN OUTCOME MEASURES: Circumference difference between the affected limb and the normal limb, length of the swelling measured in centimetres, and the physical characteristics of the local swelling of both groups were compared. RESULTS: Group A had 69 patients and the Group B 75. The mean circumference difference (MCD) of the leg between the groups showed no significant difference for 4 days (P > 0.05), except at the site of the bite on the third day when the Group B showed a significant improvement (p = 0.02). There was no significant difference in the length of the local swelling or the score of physical characteristics between the two groups (P > 0.05). The proportions of recovery of the local swelling on the fourth and fifth day had no significant difference between the groups (P > 0.05). CONCLUSION: The routine use of antibiotics (penicillin and metronidazole) does not seem to be of value in reducing the local inflammatory swelling in venomous snakebite.

Anti-rhinosporidial antibody levels in patients with rhinosporidiosis and in asymptomatic persons, in Sri Lanka.

The only report hitherto, from India in 1982, on anti-rhinosporidial antibody levels in patients with rhinosporidiosis recorded that antibody was not detected in Indian patients. The present report describes the use of the dot-ELISA assay of serum anti-rhinosporidial IgG, IgM and IgA and salivary sIgA in patients with diverse clinical presentations, in rural asymptomatic persons who had bathed in ground waters that probably harboured the causative pathogen, Rhinosporidium seeberi, and in laboratory persons who were exposed to R. seeberi. Ultrasonic extracts of purified endospores and sporangia of R. seeberi were used as antigen. The geometric mean (reciprocal) titres of serum antibody detected in patients were IgM 142.1, IgG 178.5, IgA 84.6, with ranges of 0-640, 30-960 and 0-160 respectively, salivary sIgA titres ranged from 0 to 18 with a mean of 4.6. The levels of antibody had no correlation with the site, the number of sporangia, duration and recurrence of the disease. Asymptomatic persons from the same endemic area as patients showed mean titres of IgM 89.6, IgG 69.1, IgA 95.5, with salivary sIgA titres of 3.1. Asymptomatic personnel who had been working in a laboratory where rhiniosporidial work was being done, showed mean titres of 169.6 IgM, 62.8 IgG, and 6.5 salivary sIgA. These results indicate that an anti-rhinosporidial antibody response occurs in rhinosporidial patients, as well as in asymptomatic persons who were exposed to R. seeberi in the environment. Anti-R. seeberi antibody does not appear to be protective in rhinosporidiosis since appreciable titres were present in patients with recurrent, single, multiple or disseminated lesions of long duration.

Survival pattern in patients with acute organophosphate poisoning receiving intensive care.

BACKGROUND: Approximately 35% of patients acutely poisoned with organophosphates (OP) in developing countries like Sri Lanka require intensive care and mechanical ventilation. However, death rates remain high. OBJECTIVE: To study the outcomes and predictors of mortality in patients with acute OP poisoning requiring intensive therapy at a regional center in Sri Lanka over a period of 40 months. METHODS: Retrospective analysis of all intensive care records of patients with acute OP poisoning admitted to the Intensive Care Unit (ICU) between March 1998 and July 2001. RESULTS: During the study period, 126 subjects were admitted to the ICU with acute OP poisoning. Records of 10 patients were lost and those of 37 were incomplete and hence were excluded. All the remaining 71 patients (59 male) had required endotracheal intubation and mechanical ventilation for a period of four (median) days (range 1-27) in addition to gastric lavage and standard therapy with atropine and oximes and adequate hydration. Of these 71 patients, 36 (28 male) had died. Life table analysis demonstrated a steep decline in the cumulative survival to 67% during the first three days. Systolic blood pressure of < 100 mmHg and FiO2 of >40% to maintain a SpO2 of >92% within the first 24 h were recognized as poor prognostic indicators among mechanically ventilated patients. CONCLUSION: Mortality following OP poisoning remains high despite adequate respiratory support, intensive care, and specific therapy with atropine and oximes. One-third of the subjects needing mechanical ventilation and reaching intensive care units die within the first 72 h of poisoning. Systolic blood pressure of less than 100 mmHg and the necessity of a FiO2>40% to maintain adequate oxygenation are predictors of poor outcome in patients mechanically ventilated in the ICU.

A seroepidemiological study of toxocariasis and risk factors for infection in children in Sri Lanka.

A seroepidemiology study using TES-ELISA was carried out in 1,020 children aged 1-12 years in the Hindagala Community Health Project, Sri Lanka. Toxocariasis seroprevalence was 43% with 16.6% showing high antibody levels. Unconditional logistic regression analysis showed 7-9 year olds to be at the highest risk (OR 3.0820; CI = 1.95-4.87). Dog ownership, especially puppies (OR 29.28; CI = 7.40-116.0), and geophagia-pica (OR 6.3732; CI = 3.87-10.50), were significant risk factors. Family clustering of toxocariasis was significant (chi2 = 88.000; p = 0.0001). Abdominal pain (45%), cough (30%), limb pain (23%) and skin rashes (20%) were significantly associated with seropositivity indicating that toxocariasis causes covert morbidity. These findings are, overall, applicable to other areas in Sri Lanka. However, in the dry zone, survival of infective eggs in the soil could be affected by the climate while more importantly, in agricultural areas with a high buffalo population, Toxocara vitulorum could account for human toxocariasis. Using a species specific double sandwich ELISA based on 57 kDa protein of T. canis ES antigen, it is demonstrated that 91% of the seropositives were due to T. canis. Thus along with rabies and dirofilariasis, toxocariasis is an important zoonotic health hazard from dogs in Sri Lanka and prevention is indicated.