Validation of serum cytokines as potential biomarkers in acute dengue infection

Objectives: Serum IL-10, Macrophage inhibitory factor (MIF) and interferons have been found to be associated with fatal dengue. We set out to investigate the possibility of using these cytokine as biomarkers to predict severe dengue. Methods: Serum IL-10 levels were determined by quantitative ELISA in 215 adult patients with confirmed acute dengue infection (ADI). Serum IFNα and IFNγ levels were done in 79 patients. Serial recording of clinical features and laboratory investigations were done to determine clinical disease severity. Results: 33 (17.46%) patients were classified as severe dengue (SD). Serum IL-10 levels were significantly higher (p=0.0034) in patients with SD (median= 121.9, range= 24.98 to 3271 pg/ml) when compared to those with non SD (median= 78.28, range= 7.18 to 1343 pg/ml). In the 29 patients with paired serum samples, serum IL-10 levels rose in all 6 patients with SD whereas in 20/23 patients with non SD, serum IL-10 levels fell in the critical phase.  Although serum MIF values were higher in patients with SD (mean 70774, SD± 59874 pg/ml) when compared to those with non SD (mean 45362, SD± 26891 pg/ml), this was not statistically significant. The IFNγ levels were significantly higher (p=0.038) in patients with shock (median= 77.55, range= 18.21 to 468.4 pg/ml) when compared to those who did not develop shock (median= 35.25, range= 4.050 to 733.1 pg/ml). Conclusion: Serum IL-10 levels appear to be associated with SD. It would be crucial to investigate the possible role of this cytokine in the pathogenesis of SD

Brief reports Banding of oesophageal varices using locally improvised materials

Bleeding from oesophageal varices is the commonest cause of significant upper gastrointestinal bleeding in Sri Lanka. Endoscopic band ligation is an effective method in the management of varices. But the cost of banding equipment is high, unaffordable for a majority of our patients. We have devised a cheap method to carry out banding of varices. Banding of varices using this technique was carried out in 235 patients. In the patients who were followed up, there was a reduction in the size of varices across all grades of varices. No complications due to banding were noted, and only 10 patients developed re-bleeding. Since the initial experience on efficacy and safety of this technique is encouraging, we believe that its widesprea

Resection of the large bowel suppresses hunger and food intake and modulates gastrointestinal fermentation.

OBJECTIVE: To assess appetite and gut hormone levels in patients following partial (PR) or total resection (TR) of the large bowel. METHODS: A comparative cross sectional study was carried out with healthy controls (n = 99) and patients who had undergone PR (n = 64) or TR (n = 12) of the large bowel. Participants consumed a standard (720 kcal) breakfast meal at 0830 (t = 0) h followed by lactulose (15 g) and a buffet lunch (t = 210 min). Participants rated the subjective feelings of hunger at t = -30, 0, 30, 60, 120, and 180 min. Breath hydrogen (BH) concentrations were also evaluated. In a matched subset (11 controls, 11 PR and 9 TR patients) PYY and GLP-1 concentrations were measured following breakfast. The primary outcome measure was appetite, as measured using visual analogue scales and the buffet lunch. The secondary outcome was BH concentrations following a test meal. RESULTS: PR and TR participants had lower hunger and energy intake at the buffet lunch meal compared to controls. PR subjects had higher BH concentrations compared to controls and TR subjects. BH levels correlated with circulating GLP-1 levels at specific time points. CONCLUSIONS: PR or TR of the large bowel reduced feelings of hunger and energy intake, and PR increased gastrointestinal fermentation

Erectile dysfunction is a strong predictor of poor quality of life in men with Type 2 diabetes mellitus.

AIMS: To identify predictors of poor quality of life among men with diabetes from a comprehensive set of sexual, clinical, socio-economic and lifestyle variables. METHODS: This was a cross-sectional observational-study of 253 men with Type 2 diabetes, randomly selected from a clinic in Colombo, Sri Lanka. Erectile dysfunction was assessed using the five-item International Index of Erectile Function and quality of life was assessed using the Sri Lankan version of the 36-item short form health survey questionnaire and the disease-specific Psychological Impact of Erectile Dysfunction scale. The presence of premature ejaculation, reduced libido, socio-demographic and lifestyle data was obtained using an interviewer-administered questionnaire. Significant predictors of quality of life were identified by stepwise multivariate linear regression models for short form-36 subscales, summary scales and two scales of Psychological Impact of Erectile Dysfunction. RESULTS: Significant predictors on the physical summary scale of the 36-item short form were erectile dysfunction (β = 7.93, 95% CI 3.70-12.17, P < 0.001) and reduced libido (β = 5.20, 95% CI 0.82-9.59, P < 0.05). Predictors on the mental health summary scale of the 36-item short form were erectile dysfunction (β = 5.82, 95% CI 2.26-9.37, P < 0.01), BMI > 27.5 kg/m(2) (β = 9.12, 95% CI 1.38-17.44, P < 0.05), ischaemic heart disease (β = 6.39, 95% CI 0.74-12.04, P < 0.05) and insulin therapy (β = 5.28, 95% CI 0.34-10.22, P < 0.05). Significant predictors in the sexual experience scale of the Psychological Impact of Erectile Dysfunction were erectile dysfunction (β = 6.57, 95% CI 4.63-8.51, P < 0.001), reduced libido (β =4.33, 95% CI 2.34-6.32, P < 0.001) and postural hypotension (β = 3.99, 95% CI 0.13-7.85, P < 0.05). Predictors on the emotional life scale of the Psychological Impact of Erectile Dysfunction were erectile dysfunction (β = 2.96, 95% CI 1.37-4.58, P < 0.001), reduced libido 2.75 (β = 2.75, 95% CI 1.12-4.40, P < 0.01), younger age (β = 1.05, 95% CI 0.35-1.75, P < 0.01) and postural hypotension (β = 3.39, 95% CI 0.35-6.45, P < 0.05). CONCLUSION: Erectile dysfunction was a strong predictor of poor generic and disease-specific quality of life among other sexual and clinical variables in men with diabetes

Erectile dysfunction among men with diabetes is strongly associated with premature ejaculation and reduced libido.

INTRODUCTION: Among men with diabetes, little attention has been given to premature ejaculation (PE), reduced libido, and their associations with erectile dysfunction (ED), despite the presence of physical and psychologic factors that could predispose to all three. AIM: To estimate the prevalence and inter-associations of ED, PE, and reduced libido among diabetic men and to describe the associated clinical, socioeconomic, and lifestyle parameters. METHODS: Cross-sectional observational study of 253 men with type 2 diabetes randomly selected from a clinic in Colombo, Sri Lanka. MAIN OUTCOME MEASURES: Erectile function was assessed using the five-item version of the International Index of Erectile Function scale. The presence of PE, reduced libido, sociodemographic, and lifestyle data was obtained using an interviewer-administered questionnaire. Clinical data were obtained from relevant physical examination, patient records, and laboratory tests, which included glycosylated hemoglobin, serum cholesterol, serum creatinine, and electrocardiogram. RESULTS: One hundred and eighty-five (73.1%) of the individuals had some degree of ED, while 84 (33.2%) had severe to complete ED. After excluding men with complete ED, the prevalence of PE was 68 (40.2%). The overall prevalence of reduced libido was 64 (25%). In the multivariate analysis, the strongest associations with ED were PE (odds ratio [OR] = 4.41, 95% confidence interval [CI] = 2.08-9.39) and reduced libido (OR = 4.38, CI = 1.39-13.82) followed by lower income (OR = 2.16, CI = 1.32-3.52), advancing age (OR = 2.06, CI = 1.44-2.95), and duration of diabetes (OR = 1.48, CI = 1.09-2.01). In addition, ED was univariately associated with lower educational level (P = 0.05), the presence of hypertension (P = 0.005), and no alcohol intake (P = 0.001). The only significant association of PE was the severity grade of ED. Associations of reduced libido in the multivariate analysis were ED (OR=1.61, CI = 1.23-2.70), advancing age (OR = 1.7, CI = 1.4-2.2), and absence of masturbation (OR = 3.3, CI = 1.2-8.8). CONCLUSIONS: ED was strongly associated with PE and reduced libido. Diabetic patients presenting with one of these three conditions should be screened for the other two

Brief Communication - Dengue viral infections as a cause of encephalopathy

The aim of this study was to determine the clinical characteristics and poor prognostic factors associated with high mortality in dengue encephalopathy. Fifteen patients with confirmed dengue infections, who developed encephalopathy, were recruited from two tertiary care hospitals in Colombo, Sri Lanka. Among the factors that contributed to encephalopathy were: Acute liver failure (73%), electrolyte imbalances (80%) and shock (40%). Five (33.3%) patients developed seizures. Disseminated intravascular coagulation was seen in five (33.3%). Secondary bacterial infections were observed in 8 (53.3%) of our patients. The overall mortality rate was 47%

Cellular and cytokine correlates of severe dengue infection.

BACKGROUND: The occurrence of dengue haemorrhagic fever (DHF) is thought to result from a complex interplay between the virus, host genetics and host immune factors. Existing published data are not consistent, in part related to relatively small sample sizes. We set out to determine possible associations between dengue virus (DEN-V) NS3 specific T cells and cytokine and chemokine levels and the pathogenesis of severe disease in a large cohort of individuals with DHF. METHODOLOGY/PRINCIPAL FINDINGS: By using ex vivo IFNγ ELISpot assays we determined DENV-NS3 specific responses in patients with varying severity of DHF. Other cytokines produced by DENV-NS3 specific T cells were determined by using multiple bead array analysis (MBAA). We also determined the serum cytokine levels using MBAA, lymphocyte subsets and Annexin V expression of lymphocytes in patients with varying severity of DHF. Of the 112 DHF patients studied, 29 developed shock. Serum IL-10 and IP-10 levels positively and significantly correlated with T cell apoptosis while IL-10 levels inversely correlated with T cell numbers. In contrast, TGFß showed a very significant (P<0.0001) and positive correlation (Spearman's R = 0.65) with the platelet counts, consistent with platelet release. We found that whilst patients with severe dengue had lower total T cell numbers, the DV-NS3 specific T cells persisted and produced high levels of IFNγ but not TNFα, IL-3, IL-13, IL-2, IL-10 or IL-17. CONCLUSIONS/SIGNIFICANCE: Our data suggest that serum IL-10, TNFα and TGFβ differentially associate with dengue disease severity