Improved diagnostic yield of neuromuscular disorders applying clinical exome sequencing in patients arising from a consanguineous population.

Neuromuscular diseases (NMDs) include a broad range of disorders affecting muscles, nerves and neuromuscular junctions. Their overlapping phenotypes and heterogeneous genetic nature have created challenges in diagnosis which calls for the implementation of massive parallel sequencing as a candidate strategy to increase the diagnostic yield. In this study, total of 45 patients, mostly offspring of consanguineous marriages were examined using whole exome sequencing. Data analysis was performed to identify the most probable pathogenic rare variants in known NMD genes which led to identification of causal variants for 33 out of 45 patients (73.3%) in the following known genes: CAPN3, Col6A1, Col6A3, DMD, DYSF, FHL1, GJB1, ISPD, LAMA2, LMNA, PLEC1, RYR1, SGCA, SGCB, SYNE1, TNNT1 and 22 novel pathogenic variants were detected. Today, the advantage of whole exome sequencing in clinical diagnostic strategies of heterogeneous disorders is clear. In this cohort, a diagnostic yield of 73.3% was achieved which is quite high compared to the overall reported diagnostic yield of 25% to 50%. This could be explained by the consanguineous background of these patients and is another strong advantage of offering clinical exome sequencing in diagnostic laboratories, especially in populations with high rate of consanguinity.

Antidiabetic and hepato-renal protective effects of medicinal plants in STZ induced diabetic rats.

The antidiabetic and hepato-renal protective effects of Citrullus colocynthis and Momordica charantia ethanol extracts were investigated in streptozotocin (STZ) induced diabetic male albino rats. Diabetic rats were treated with C. colocynthis, M. charantia or C. colocynthis + M. charantia mixed extract at a dose of 250 mg /kg body weight per oral per day for 21 days. The mean body weight of all the diabetic rat groups on day 1 of treatment (day 10 of diabetes) was significantly lower than the normal control rat group (P<0.05). The blood glucose level of all the diabetic rat groups on day 1 of treatment (day 10 of diabetes) was significantly (P<0.05) higher (> 200 mg/dl) than the normal control rat group (95.5 ± 2.7). At the end of treatment (day 21), the diabetic rats treated with plant extracts showed significant increase (P<0.05) in body weight and significant (P<0.05) reduction in blood glucose level when compared to diabetic control animals. Significant increase (< 0.05) was observed in the serum bilirubin, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), urea and creatinine levels of diabetic control rat group. The serum levels of these liver and kidney-related parameters of diabetic rats treated with plant extract were significantly lower when compared to diabetic control rat group (p < 0.05). Photomicrographs of liver and kidney microsections from diabetic rats treated with these plant extracts showed amelioration in the hepato-renal histoarchitectures. It was concluded that the C. colocynthis and M. charantia methanol extracts are antidiabetic and hepato-renal protective in STZ induced diabetic male rats. Treatment of the diabetic rats with C. colocynthis + M. charantia mixed extract is more effective in the amelioration of diabetes and hepato-renal injuries in STZ induced diabetic male rats.

Evaluation of the measles-rubella mass vaccination campaign in the population covered by Tehran University of Medical Sciences.

We evaluated the measles-rubella mass vaccination campaign in the Islamic Republic of Iran in December 2003. Vaccination coverage, community awareness of the campaign and the quality of vaccination services were assessed in the population covered by Tehran University of Medical Sciences. At the end of the campaign 96.4% (95% CI: 94.6%-98.2%) of the population sample (n = 390) had been vaccinated. Awareness of the campaign was 80.59% of the sample (n = 190) at the start, rising to 96.8% during and 100.0% at the end of the campaign. None of the 24 vaccination teams sampled were over the threshold for unacceptable performance. The mass media and vaccination teams demonstrated good performance and have achieved their goals.

Bionomics of Anopheles stephensi Liston in the malarious area of Hormozgan province, southern Iran, 2002.

Anopheles stephensi Liston is an important malaria vector in Hormozgan province, where it is the most prevalent anopheline mosquito. It shows two annual activity peaks, one in spring and another in the autumn. In mountainous areas the second peak starts earlier than in coastal regions. Adults are endophilic and endophagic, but in the hot season when people sleep outside buildings they frequently bite outdoors. Larvae are found in a wide-range of habitats, both natural and man-made. All three biological forms of the species, occur in the province, i.e. An. stephensi stephensi (type form), An. stephensi mysorensis, and the intermediate form. An. stephensi mysorensis is found only in rural-mountainous areas, whereas the type and intermediate forms occur in urban-coastal regions and the rural plains, with the type form predominant. The presence of the type form in urban areas and mysorensis in rural areas is consistent with the available epidemiological data for malaria in the region and with the finding in India that the type form is an efficient malaria vector inhabiting urban areas whereas mysorensis is rural and has a lower vectorial capacity. Insecticide susceptibility tests on field collected adult mysorensis and adults from laboratory strains of the type and intermediate forms were carried out according to WHO standard methods. These showed that all three forms are susceptible to bendiocarb, propoxur, malathion, fenitrothion, deltamethrin, permethrin, cyfluthrin, and lambdacyhalothrin, but are resistant to DDT and show low level of tolerance to dieldrin. Examination of the larvicidal activity of malathion, fenitrothion, temephos and chlorpyrifos at diagnostic doses showed that these stephensi forms are susceptible to all larvicides except fenitrothion. Irritability tests to pyrethroid insecticides showed high levels of irritability to permethrin and lambdacyhalothrin, but low irritability to cyfluthrin and deltamethrin. The importance of these findings for the epidemiology and control of malaria in the region are discussed.

Sodium Valproate versus Propranolol in paediatric migraine prophylaxis.

In a randomized clinical trial the effect of Sodium Valproate in pediatric migraine prophylaxis was compared with that of Propranolol. One hundred and twenty patients with common migraine (migraine without aura) aged from 3 to 15 years who met the defined criteria enrolled into the study. Randomly the patients were divided in two groups of A and B, treating with sodium Valproate and Propranolol, respectively. Three phases of baseline period (phase I), titration and adjustment period (phases II) and fixed -dose treatment period (phase III) have been designed. A total of 57 patients in group A, and 58 patients in group B completed all phases of the trial. Seventy two percent of patients in group A and 69% of patients in group B have responded to Sodium Valproate and Propranolol, respectively, as a reduction of more than 50% in headache frequency per month. Further more both drugs have shown efficacy in reducing the severity and duration of headache and also better response to rescue medications (p value <0.01). There was no significant difference in all previously mentioned therapeutic effects between two groups (p value <0.05).

Larval habitats of main malaria vectors in Hormozgan province and their susceptibility to different larvicides.

Hormozgan Province is located in the south of Iran bordering the Persian Gulf. In this area, malaria is still considered a major health problem. In the province, eleven species of Anopheles were identified: An. pulcherrimus, An. sergenti, An. apoci, An. multicolor, An. subpictus, An. turkhudi, An. fluviatilis, An. stephensi, An. d'thali, An. superpictus, and An. culicifacies, among which only the last five species play an important role in malaria transmission. Larval habitats of malaria vectors varied from clean to brackish water, as well as sewage water, under palm trees, marshland, pools, pounds, drainage, irrigation canals, wells, and water containers. Malathion, fenitrothion, chlorpyrifos, and temephos were tested against An. stephensi, An. fluviatilis and An. d' thali larvae at diagnostic doses recommended by WHO. The results showed susceptibility to malathion, chlorpyrifos and temephos, but fenitrothion was not able to yield 100% mortality.

Development of the Regional Malaria Training Centre in Bandar-e Abbas, Islamic Republic of Iran.

The resurgence of malaria has highlighted the need for training health professionals in malaria control planning. The course described here was organized jointly by the World Health Organization, the Ministry of Health and Medical Education and the School of Public Health in Iran. The first course was held in 1997 and the fifth WHO-approved course is now in progress. The course focuses on dynamic, interactive, practical and problem-solving learning methods. It provides the participants with the knowledge, skills, competence and confidence to be able to analyse the malaria problem. The course fulfils the requirements of the Roll Back Malaria campaign. In the 8-week training period subjects such as basic bio-statistics and epidemiology, microcomputing, malaria parasitology, malaria entomology, vector control, case management, epidemiological approach to malaria control, field work and planning for malaria control are taught. Each participant is evaluated in each subject. A total of 71 participants from 17 countries in the WHO African and Eastern Mediterranean Regions, mainly those with a malaria problem, have graduated.

Spatial analysis and mapping of malaria risk in an endemic area, south of Iran: a GIS based decision making for planning of control.

Bashagard district is one of the important malaria endemic areas in southern Iran. From this region a total of 16,199 indigenous cases have been reported in recent years. The aim of this study was to determine the situation of the disease and provide the risk map for the area. ArcGIS9.2 was used for mapping spatial distribution of malaria incidence. Hot spots were obtained using evidence-based weighting method for transmission risk. Environmental factors including temperature, relative humidity, altitude, slope and distance to rivers were combined by weighted multi criteria evaluation for mapping malaria hazard area at the district level. Similarly, risk map was developed by overlaying weighted hazard, land use/land cover, population density, malaria incidence, development factors and intervention methods. Our results reveal that the disease mainly occurs in north and east of the study area. Consequently the district is divided into three strata. Appropriate interventions are recommended for each stratum based on national malaria policy. Malaria hazard and risk map, stratification based on relevant information and data analyzing provide a useful method preparedness and early warning system for malaria control, although regular updating is required timely.

Clinical features of juvenile lupus erythematosus in Iranian children.

OBJECTIVE: Analysis of the clinical and laboratory features of childhood onset systemic lupus erythematosus (JSLE). PATIENTS AND METHOD: Forty five children, aged below 16, were enrolled in this retrospective multicenter study. All patients fulfilled the American College of Rheumatology revised criteria 1982 for the diagnosis of SLE and had shown clinical manifestations of the disease before the age of 16. RESULTS: The female to male ratio was 8:1. The mean age at onset was 10.5 (ranged between 3 and 16 years). Thirty patients (66%) were correctly diagnosed before referring to our Center. The clinical manifestation in different organs were as follows: 40 patients (88.8%) had skin involvement, 35 patients (77.7%) experienced musculoskeletal involvement, 29 children (64.4%) suffered from renal disease, hematological abnormalities were detected in 25 patients (55.5%), 12 patients (26%) had cardiovascular disease, 10 patients (17%) presented central nervous system involvement, and 5 patients (11%) experienced SLE-related pulmonary disease. During the follow up period, four patients died, two from renal failure, one from CNS complications of JSLE, and one due to severe sepsis. CONCLUSION: Clinical manifestations of Juvenile SLE are diverse and often severe. Similar studies should be undertaken in different geographic areas in order to provide a good insight of the disease towards a correct diagnosis of JSLE.