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BACKGROUND: A recent study showed that 60-s paranasal air suction results in an immediate pain relief in acute migraine. This is the study to assess the Nitric Oxide (NO) and Carbon Monoxide (CO) concentration in nasal-paranasal sinus air of migraine patients and to compare it with healthy controls. METHODOLOGY: The NO and CO levels of air sucked out from nasal-paranasal sinuses of 20 migraine adolescent and young adults among school students, aged 16 -19 years, and 22 healthy similar aged school students as controls were measured as key responses using a portable NO and a portable CO analyzer. RESULTS: Patients had comparatively high values compared to the controls for paranasal NO (both left and right sides), paranasal CO (both left and right sides), Fraction Exhaled NO (FeNO) and Fraction Exhaled CO (FeCO). Patients had median paranasal NO contents of 132.5 ppb and 154 ppb on left and right sides respectively compared to 36 ppb and 34.5 ppb corresponding values in controls (P <  0.0001). Similar pattern was observed with paranasal CO (P <  0.0001). FeNO and FeCO content were also higher in patients (P <  0.0001). Receiver characteristic operating curves of all gas measurements showed that they all could classify patients and controls effectively and NO was the most effective followed by paranasal CO. After air suction, the mean pain scores of general headache and tenderness dropped by a very large margin in migraine patients (P <  0.0001). CONCLUSIONS: Suctioned out high nasal-paranasal sinus NO and CO levels can be used to distinguish migraine patients from healthy subjects. In fact, suctioned out paranasal NO measurements of both sides with a cutoff point of 50 ppb provided a perfect classification of patients and controls. Increased sinus NO and CO during acute episode of migraine is an observation we had and we agree that further studies are needed to conclude that NO and CO can be a causative molecule for migraine headache. TRAIL REGISTRATION: Clinical Trial Government Identification Number - 1548/2016. Ethical Clearance Granted Institute - Medical Research Institute, Colombo, Sri Lanka (No 38/2016). Sri Lanka Clinical Trial Registration number: SLCTR/ 2017/018 (29/06/2017). Approval Granting Organization to use the device in the clinical trial- National Medicines Regulatory Authority Sri Lanka (16/06/2018), The device won award at Geneva international inventers exhibition in 2016 and President award in 2018 in Sri Lanka. It is a patented device in Sri Lanka and patent number was SLKP/1/18295. All methods were carried out in accordance with CONSORT 2010 guidelines.

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BACKGROUND: Migraine is a primary headache disorder and is the most common disabling primary headache disorder that occurs in children and adolescents. A recent study showed that paranasal air suction can provide relief to migraine headache. However, in order to get the maximum benefit out of it, an easy to use effective air sucker should be available. Aiming to fulfil the above requirement, a randomized, double blind control clinical trial was conducted to investigate the efficacy of a recently developed low-pressure portable air sucker. METHODS: Eighty-six Sri Lankan school children of age 16-19 years with migraine were enrolled for the study. They were randomly allocated into two groups, and one group was subjected to six intermittent ten-second paranasal air suctions using the portable air sucker for 120 s. The other group was subjected to placebo air suction (no paranasal air suction). The effect of suction using portable air sucker was the primary objective but side of headache, type of headache, and gender were also studied as source variables. The primary response studied was severity of headache. In addition, left and right supraorbital tenderness, photophobia, phonophobia, numbness over the face and scalp, nausea and generalized tiredness/weakness of the body were studied. The measurements on all those variables were made before and after suction, and the statistical analysis was performed based on before and after differences. As a follow-up, patients were monitored for 24-h period. RESULTS: There was a significant reduction in the severity of headache pain (OR = 25.98, P < 0.0001), which was the primary outcome variable, and other migraine symptoms studied, tenderness (left) (OR = 289.69, P < 0.0001), tenderness (right) (OR > 267.17, P < 0.0001), photophobia (OR = 2115.6, P < 0.0001), phonophobia (OR > 12.62, P < 0.0001) nausea (OR > 515.59, P < 0.0001) and weakness (OR = 549.06, P < 0.0001) except for numbness (OR = 0.747, P = 0.67) in the treatment group compared to the control group 2 min after the suction. These symptoms did not recur within 24-h period and there were no significant side effects recorded during the 24-h observation period. CONCLUSION: This pilot study showed that low-pressure portable air sucker is effective in paranasal air suction, and suction for 120 s using the sucker can provide an immediate relief which can last for more than 24-h period without any side effects. TRAIL REGISTRATION: Clinical Trial Government Identification Number - 1548/2016. Ethical Clearance Granted Institute - Medical Research Institute, Colombo, Sri Lanka (No 38/2016). Sri Lanka Clinical Trial Registration No: SLCTR/2017/018 . Date of registration = 29/ 06/2017. Approval Granting Organization to use the device in the clinical trial- National Medicines Regulatory Authority Sri Lanka (16 Jan 2018), The device won award at Geneva international inventers exhibition in 2016 and President award in 2018 in Sri Lanka. It is a patented device in Sri Lanka and patent number was SLKP/1/18295. All methods were carried out in accordance with CONSORT 2010 guidelines.

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BACKGROUND: Migraine is a primary headache disorder, which cause significant disability in adolescence. This double blind, randomized clinical trial assessed the immediate effects of suction of paranasal sinus air during an acute migraine episode. METHODS: A randomized, double blind study was conducted with 56 selected Sri Lankan school children of 16-19 years of age. Participants who met International Headache Society criteria for migraine (with or without aura) were included in the study. Subjects were randomly allocated into 2 groups where one group was subjected to three intermittent 10 sec paranasal air suctions with a ten sec suction free interval between two suctions for each nostril and the other group was subjected to placebo air suction (no paranasal air suction) in similar arrangement. Severity of headache and sub-orbital tenderness before and after suction were recorded using standard pain rating scale. RESULTS: After dropouts, treated and placebo groups consisted of 27 and 23 subjects respectively. The mean headache pain score drop in the treated group was significantly higher compared to that of the control group. Moreover, there was a difference in the treatment response between the types of headache (with or without aura). With respect to tenderness there was a statistically significant drop in the treated group compared to the control. In general, airflow rates in left and right nostrils were different in these subjects. However such difference was not seen in the tenderness on two sides. Nevertheless it was revealed that airflow rate has a slight negative correlation with the tenderness irrespective of the side. CONCLUSION: Sixty-second paranasal air suction can provide an immediate pain relief for acute migraine in adolescents. We did not assess pain outcomes beyond 60 s, but the initial responses suggests the need to further study the efficacy of paranasal suction in migraine. A further study is suggested to evaluate the acute effects, efficacy and side effects of paranasal air suction using follow up over a prolong period. TRIAL REGISTRATION: Sri Lanka Clinical Trials Registry SLCTR/2017/018 , 29 Jun 2017. Retrospectively registered.

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Corticosteroids are used therapeutically for a broad spectrum of diseases including autoimmune, allergic and inflammatory diseases. However in trials, the evidence for using corticosteroids in dengue is inconclusive and the quality of evidence is low. This systemic review is conducted to review clinical trials on dengue and steroid therapy to identify the current strength and weakness of evidence for the use of corticosteroids. We searched MEDLINE/PUBMED and Google scholar for publications on steroid use in dengue and the relevant authors of the study were contacted for additional information, as required. This review includes thirteen studies enrolling 1293 children and adult participants. There was no evidence of viremia and no significant side effects after the administration of low and high doses of oral corticosteroids and high doses of intravenous corticosteroids. Beneficial therapeutic effects were seen in some studies, which used high doses or multiple doses of steroids. The effectiveness of corticosteroids in dengue is depended upon sustained therapeutic blood levels of corticosteroids for an adequate duration and using a steroid with higher receptor affinity. Further clinical trials using pharmacologically and immunologically accepted standard steroid protocols are warranted to validate this conclusion.

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Introduction: Chronic kidney disease (CKD) is a major complication of diabetes mellitus and it contributes to increased hospital mortality and morbidity. Microalbumin test is used to identify the first sign of deteriorating kidney function but it is an expensive test. Alternatively, measurement of urine total protein-to-creatinine ratio (TPCR) is a simple and inexpensive method. Objective: To find whether the urine TPCR can predict the presence of microalbuminuria in patients with diabetic nephropathy. Method: A cross sectional study was performed on 216 patients with diabetes mellitus at General Hospital, Ampara over a period of 4 weeks. Urine albumin, urine creatinine and urine total protein were analysed on first voided urine samples and urine albumin to creatinine ratio (ACR) and total-protein-to-creatinine ratio were calculated. Regression analysis and Spearman's rank correlation were used to study the linear relationship between two variables. Results: Among 216 patients, 56 (26.1%) were males and 160 (73.9%) were females. The mean urine total-protein-to-creatinine ratio was 89.3 ± 231.6 mg/g and albumin to creatinine ratio was 43.1±76.3 mg/g. Sixty four (29%) patients were newly detected as having microalbuminuria (n=61; 28%,) or macroalbuminuria (n=3; 1%,). There was a significant correlation between urine total-protein-to-creatinine ratio and urine albumin to creatinine ratio (R2 = 0.824, ACR = [TPCR + 18.421]/ 2.5026) in the total sample (p < 0.001). The total-protein-to-creatinine ratio showed a significant correlation with urine albumin to creatinine ratio in the range of microalbuminuria (30-300 mg/g creatinine) (R2 = 0.798; p < 0.001). The regression equation was ACR = [TPCR ­ 5.0491]/1.2633. Conclusion: The urine total-protein-to-creatinine ratio showed a positive significant correlation with urine albumin to creatinine ratio, which is clinically important to identify early stage of diabetic nephropathy. This can be used in rural areas as it is inexpensive.

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Introduction: Chronic Kidney Disease (CKD) has significant economic impact on both patients' households and the country. Objectives: To assess the out-of-pocket (OOP) expenditure of accessing health services among CKD patients in Anuradhapura District Methods: This community based cross-sectional study included a representative sample of 1174 registered CKD patients from all 19 Medical Officer of Health areas in the District of Anuradhapura. Trained para-medical staff visited the households and administered an interviewer administered questionnaire to gather information. Results: A total of 1118 CKD patients participated. Mean age was 58.3 (SD 10.8) years. Fifty nine (5.3%) patients had been hospitalized during the six months preceding data collection. The total OOP for a hospital admission for one patient was Rs. 3625 (IQR 1650-8760). Thirty eight (3.4%) patients were on dialysis. The median direct cost per patient for an episode of dialysis was Rs.595 (IQR 415-995) while the median direct cost for a dialysis patient per month was Rs.5490 (IQR 3950-10934). In the study population a total of 1095 (98.0%) had attended clinic at least once during the six months preceding the study. The OOP expenditure for a single clinic visit for one patient was Rs.434 (IQR 200- 860). Conclusions: CKD patients living in the Anuradhapura District spent significant amounts on accessing health care which can worsen their economic hardships. Planned interventions are warranted in order to improve their quality of life and financial situation.

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Activating mutations in the receptor tyrosine kinase KIT, most notably KIT D816V, are commonly observed in patients with systemic mastocytosis. Thus, inhibition of KIT has been a major focus for treatment of this disorder. Here we investigated a novel approach to such inhibition. Utilizing rational drug design, we targeted the switch pocket (SP) of KIT, which regulates its catalytic conformation. Two SP inhibitors thus identified, DP-2976 and DP-4851, were examined for effects on neoplastic mast cell proliferation and mast cell activation. Autophosphorylation of both wild-type and, where also examined, KIT D816V activation was blocked by these compounds in transfected 293T cells, HMC 1.1 and 1.2 human mast cell lines, and in CD34(+)-derived human mast cells activated by stem cell factor (SCF). Both inhibitors induced apoptosis in the neoplastic mast cell lines and reduced survival of primary bone marrow mast cells from patients with mastocytosis. Moreover, the SP inhibitors more selectively blocked SCF potentiation of FcɛRI-mediated degranulation. Overall, SP inhibitors represent an innovative mechanism of KIT inhibition whose dual suppression of KIT D816V neoplastic mast cell proliferation and SCF-enhanced mast cell activation may provide significant therapeutic benefits.

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Although the ABO blood group of the human host has been reported to influence malarial infection, there have been few clinical observations on this effect. A hospital-based, comparative study was therefore performed to investigate the relationship between blood-group type and severe disease i nPlasmodium falciparum malaria. Overall, 243 cases of malaria (163 uncomplicated and 80 severe) and 65 patients with severe, non-malarial infections were studied. In terms of ABO-blood-group composition, the patients with severe malaria were significantly different from the patients with the uncomplicated disease (P<0.001) and also from a population control described previously (P<0.0001). The patients with uncomplicated malaria or severe but non-malarial disease were, however, similar to the population control. The cases of severe malaria were significantly less likely to be of blood group O (P=0.0003), and significantly more likely to be of group AB (P<0.0001), than the patients with nonsevere malaria. It appears that individuals who are of blood-group O are relatively resistant to the severe disease caused by P. falciparum infection.

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We have investigated the association between alleles of the genes for tumour necrosis factor-alpha (TNF-alpha) and TNF-beta and severity of disease during malarial (Plasmodium falciparum) and other infections in the Sri Lankan population. Patients were categorized as having either (i) uncomplicated malaria, (ii) severe and complicated malaria, or (iii) severe and complicated infection in which a diagnosis of malaria had been excluded. For all the patients, as well as for a group of matched healthy controls, TNF-alpha and TNF-beta allelic types were identified using the polymerase chain reaction (PCR) and allele-specific oligonucleotide probes and restriction enzyme digestion. The odds in favour of carrying the TNFalpha*2 allele, mainly of the heterozygous genotype (TNFalpha*1,*2), were two to three times greater among individuals with severe disease, of either malarial or other infectious origin, relative to healthy controls or to those with uncomplicated malarial infections. No significant risk was associated with either of the alleles of TNF-beta.

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The dose uniformity across a junction between two abutting photon fields can be optimised by creating non-divergent field edges using independent collimators. Current linear accelerator specifications for the positional accuracy of such collimators are not rigorous enough to ensure that a clinically acceptable match is produced. Confirmation of the junction dose is required prior to clinical use and additional quality assurance is necessary to ensure that the strict requirement for positional accuracy is maintained.

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