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Abstract Background The WHO guidelines were revised recently to identify patients with severe dengue (SD) early. We proceeded to determine the usefulness of the warning signs in the new WHO guidelines in predicting SD and we have also attempted to define other simple laboratory parameters that could be useful in predicting SD. Methods Clinical and laboratory parameters were recorded in 184 patients in 2011, with confirmed dengue viral infections, admitted to a medical ward in two tertiary care hospitals in Colombo, Sri Lanka. Results We found that the presence of 5 or more dengue warning signs were significantly (p = 0.02) associated with the development of SD (odds ratio 5.14, 95% CI = 1.312 to 20.16). The AST levels were significantly higher (p = 0.0001) in patients with abdominal pain (mean 243.5, SD ± 200.7), when compared to those who did not have abdominal pain (mean 148.5, SD ± 218.6). Lymphocyte counts 3 were significantly (p = 0.005) associated with SD (odds ratio 3.367, 95% CI 1.396 to 8.123). High AST levels were also significantly associated (p 3, were again significantly associated (p Conclusions The presence of 5 or more warning signs appears to be a predictor of SD. Lymphocyte counts 3, platelet counts 3 and raised AST levels were associated with SD and could be used to help identify patients who are likely to develop SD.

Background: Several studies have shown that serum IL-10, IFNγ and MIF are elevated in patients in severe dengue (SD) and could be used as potential biomarkers. We proceeded to determine if these cytokines could be used as biomarkers in a large cohort of adult dengue patients with varying severity of dengue infection.Methods: Serum IL-10 levels were determined in 259 of whom 40 had severe dengue infection. Serum IFNγ and IFNα levels were done in 78 and MIF levels were done in 65 patients with acute dengue infection. Clinical features and laboratory investigations were undertaken during the febrile and critical phase.Results: We found that serum IL-10 levels were significantly higher (p = 0.001) in patients with SD, when compared to those with non SD. Serum IL-10 levels significantly and inversely correlated with white cell counts (R = -0.23, p = 0.0002) and lymphocyte counts (R = -0.29, p < 0.0001) but significantly and positively correlated with aspartate tranaminase levels (R = 0.16, p = 0.01) and alanine transaminase levels (R = 0.22, p = 0.007). However, IL-10 levels did not have a good predictive value in discriminating those who were likely to develop SD (AUC = 0.66). Serum IFNγ levels were also significantly higher (p = 0.04) in patients with SD when compared to non SD. There was no difference (p = 0.34) in serum IFNα levels and serum MIF levels (p = 0.15) in patients with SD and non SD.Conclusion: Although serum IL-10 was significantly elevated in patients with SD it had a poor discriminatory value in identifying those with SD and non SD and therefore, is unsuitable to be used as a robust biomarker in this cohort. [ABSTRACT FROM AUTHOR]

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., (© 2016 The Obesity Society.)

An alteration in the oxidation/reduction (redox) status of humans infected with virus infections may contrioute to tefl pariiogeiiesin anu ciniiua1 manifestations of the disease. Alterations in redox markers begin prior to the onset of clinical symptoms, suggesting early changes in the oxidant/antioxidant balance. Early identification of redox markers may be of clinical usefulness in the management of patients with dengue virus infection. We conducted a hospital based comparative cross sectional study of 55 patients serologically confirmed to have dengue infection and 55 clinically healthy age and sex matched subjects as controls to assess oxidative stress in acute dengue virus infection. Blood samples were drawn on the fifth day after symptom onset and analyzed for Trolox equivalent antioxidant capacity (TEAC), reduced glutathione (GSH), glutathione peroxidase (GPx) and paraoxonase (PON) activity. The results showed significantly lower levels of plasma TEAC, serum PON and erythrocyte GSH and GPx activity among dengue patients than in controls. Of the antioxidants investigated, PON appeared to be the most sensitive marker of oxidative stress in dengue virus infection. Serum PON may be a potentially useful marker of oxidative stress in patients with dengue virus infection.

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., (© 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.)

Background: The purpose of the linguistic validation of the Sexual Inhibition and Sexual Excitation Scales (SIS/SES) was to produce translated versions in five South Asian languages (Hindi, Urdu, Panjabi, Tamil and Sinhalese) that was "conceptually equivalent" to the original U.S. English version, for use in the Oxford Sexual Dysfunction Study (OSDS)., Methods: Initially an expert committee was appointed to carry out the task of linguistic validation. This committee included the principal investigator, project coordinator and the associate project manager of the OSDS and a language consultant for each of the South Asian languages. The process of translation and validation was conducted in the following order; a) production of two independent forward translations, b) comparison and reconciliation of the translations, c) backward translation of the first reconciled version, d) comparison of the original version of SIS/SES and the backward version leading to the production of the second reconciled version and e) pilot testing and finalization., Results: Several linguistic and conceptual issues arose during the process of translating the instrument. Problems were also encountered with cultural differences in acceptability of certain concepts, and with semantic difficulties in finding an appropriate translation. In addition, the researchers had to find culturally acceptable equivalents for some terms and idiomatic phrases. The problems encountered in pilot testing, during cognitive debriefing and clinicians' review, were categorized as cultural or conceptual/semantic. Cultural issues describe the acceptability of using certain terms and phrases in a particular socio-cultural milieu. The conceptual and semantic difficulties reflect the inability to deliver the idea/meaning of a source statement in the target language. The current paper describes a selection of these issues., Conclusions: We applied a rigorous translation method to ensure conceptual equivalence and acceptability of SIS/SES in the five different South Asian languages prior to its utilization in the OSDS. However, to complete the cultural adaptation process, future psychometric validation of the translated versions is required among the different language speakers.

Background: Elevated IL-10 has been shown to be associated with severe dengue infection (DI). We proceeded to investigate the role of IL-10 in the pathogenesis of acute DI., Materials and Methods: Ex vivo and cultured IFNγ ELISpot assays for dengue virus (DENV) NS3 protein and non dengue viral proteins were carried out in 26 patients with acute DI (16 with dengue haemorrhagic fever) and 12 healthy dengue seropositive individuals from Sri Lanka. DENV serotype specific (SS) responses were determined by using a panel of SS peptides., Results: Serum IL-10 level were significantly higher (p = 0.02) in those who did not have in vitro responses to DENV-SS peptides (mean 144.2 pg/ml) when compared to those who responded (mean 75.7 pg/ml). DENV-NS3 specific ex vivo IFNγ ELISpot responses were also significantly lower (p = 0.0001) in those who did not respond to DENV-SS peptides (mean 42 SFU/million PBMCs) when compared to those who responded to DENV-SS peptides (mean 1024 SFU/million PBMCs). Serum IL-10 levels correlated significantly (p = 0.03) and inversely (Spearmans R = -0.45) with ex vivo DENV-NS3 specific responses but not with ex vivo non DENV specific responses (Spearmans R = -014, p = 0.52). Blockage of IL-10 in vitro significantly increased (p = 0.04) the ex vivo IFNγ ELISpot DENV-NS3 specific responses but had no effect on responses to non DENV proteins., Conclusion: IL-10 appears to contribute to the pathogenesis of acute dengue infections by inhibiting DENV-specific T cell responses, which can be restored by blocking IL-10.

Determining previous infecting dengue virus (DENV) serotypes has been difficult due to highly cross-reactive immune responses from previous DENV infections. Determining the correlates of serotype-specific immune responses would be crucial in understanding dengue transmission in the community and would also help to determine the correlates of protective immune responses. Therefore, we set out to define highly conserved, serotype-specific regions of the DENVs. Serotype-specific and highly conserved regions of the four DENV serotypes were identified using Basic Local Alignment Search Tool (BLAST) searches and custom perl scripts. Using ex-vivo and cultured enzyme-linked immunospot (ELISPOT) assays, we identified serotype-specific T cell epitopes within the four DENV serotypes in healthy adult donors from Sri Lanka. We identified T cell responses to 19 regions of the four DENV serotypes. Six peptides were from the NS2A region and four peptides were from the NS4A region. All immune donors responded to peptides of at least two DENV serotypes, suggesting that heterologous infection is common in Sri Lanka. Eight of 20 individuals responded to at least two peptides of DENV-4, despite this serotype not being implicated previously in any of the epidemics in Sri Lanka. The use of these regions to determine past and current infecting DENV serotypes will be of value to characterize further the dynamics of silent dengue transmission in the community. In addition, these T cell responses to these regions could be used to characterize DENV serotype-specific immune responses and thus possibly help us to understand the immune correlates of a protective immune response., (© 2012 The Authors;Clinical and Experimental Immunology © 2012 British Society for Immunology.)

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.

Background: HLA class I and class II alleles have been shown to be associated with the development of dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) in different populations. However, the majority of studies have been based on limited numbers of patients. In this study we aimed to investigate the HLA-class I and class II alleles that are positively and negatively associated with the development of DSS in a cohort of patients with DHF and also the alleles associated with development of DHF during primary dengue infections in a Sri Lankan population., Methodology/principal Findings: The allele frequencies of HLA class I and class II alleles were compared in 110 patients with DHF and 119 individuals from the population who had never reported a symptomatic dengue infection at the time of recruitment. We found that HLA-A*31 (corrected P = 0.01) and DRB1*08 (corrected P = 0.009) were associated with susceptibility to DSS when infected with the dengue virus, during secondary dengue infection. The frequency of DRB1*08 allele was 28.7 times higher than in the normal population in patients with DSS. HLA-A*31 allele was increased 16.6 fold in DHF who developed shock when compared to those who did not develop shock. A*24 (corrected P = 0.03) and DRB1*12 (corrected P = 0.041) were strongly associated with the development of DHF during primary dengue infection., Conclusions/significance: These data suggest that certain HLA alleles confer susceptibility/protection to severe dengue infections. As T cell epitope recognition depend on the HLA type of an individual, it would be now important to investigate how epitope specific T cells associate with primary and secondary dengue infections and in severe dengue infections.

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.

Background: Recent years have seen an increase in dengue infections among adults in Sri Lanka, with similar trends seen in many other countries. Data on the natural history and outcome of dengue in adults are quite limited., Aim: To study clinical and laboratory findings in adult dengue patients hospitalized in Sri Lanka during a recent major dengue epidemic., Design: Prospective observational study., Methods: Clinical, laboratory and demographic information were collected from adult patients with confirmed dengue infections (n = 108) treated in a general medical ward in Sri Lanka from 24 April to 31 July 2004., Results: There were 68 male and 40 female patients, mean age 26.6 years. Dengue fever (DF) was seen in 33 (30.6%) and dengue haemorrhagic fever (DHF) in 75 (69.4%). Of the 37 (34.3%) with primary dengue infections, 19 (51.4%) developed DF and 18 (48.6%) developed DHF. Overall, 42 patients (38.9%) had bleeding manifestations. These adults showed differences in clinical and laboratory findings, disease severity and mortality, compared to children seen during the same epidemic. Secondary dengue infections were significantly associated with development of severe disease (OR 5.0, 95%CI 1.9-13.5, p < 0.001). Mortality was 3.7%., Discussion: Pooling data on adult dengue patients from different regions should help us to understand the natural history of disease in this group. It would also help in developing evidence-based treatment guidelines and allocating limited and scarce health resources. Our data contribute towards this goal.

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 widespread adoption in Sri Lanka would be cost effective and life-saving.