RESUMO
OBJECTIVES: The omega-3 (n-3) fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are known to play an important role in maintenance and modulation of neuronal functions. There is evidence that omega-3 fatty acids may have anticonvulsant effects. The effect of DHA and EPA on seizure rate in patients with drug-resistant epilepsy (DRE) was investigated. METHODS: A double-blind, randomized, placebo-controlled clinical trial included ninety-nine (nâ¯=â¯99) subjects with DRE, aged 5-16â¯years (nâ¯=â¯85) and 17-45â¯years (nâ¯=â¯14). After randomization, subjects were given two, four, or six capsules per day of DHA (417.8â¯mg DHA and 50.8â¯mg EPA/capsule, nâ¯=â¯33), EPA (385.6â¯mg EPA and 81.2â¯mg DHA/capsule, nâ¯=â¯33), or placebo (high oleic acid sunflower oil, nâ¯=â¯33) for one year. The primary endpoint was the effect of treatment on rate of seizure. Random-effects negative binomial regression models were fitted to model the patients' total count of seizures per month. The treatment effects on seizure incidence rate ratio (IRR) were tested after controlling for the covariate effects of gender, age, rate of seizure per week at enrollment, type of seizure, and number of antiepileptic drug (AED) combinations used at enrollment. RESULTS: Fifty-nine subjects (nâ¯=â¯59) completed the study (59.6%). The average number of seizures per month were 9.7⯱â¯1.2 in the EPA group, 11.7⯱â¯1.5 in the DHA group, and 16.6⯱â¯1.5 in the placebo group. Age, gender, and seizure-type adjusted seizure IRRs of the EPA and DHA groups compared with the placebo group were 0.61 (CIâ¯=â¯0.42-0.88, pâ¯=â¯0.008, 42% reduction) and 0.67 (CIâ¯=â¯0.46-1.0, pâ¯=â¯0.04, 39% reduction), respectively. There was no difference in IRR between the EPA and DHA groups (pâ¯=â¯0.56). Both treatment groups had a significantly higher number of seizure-free days compared with the placebo group (pâ¯<â¯0.05). SIGNIFICANCE: This study demonstrates that EPA and DHA are effective in reducing seizure frequency in patients with DRE.
Assuntos
Anticonvulsivantes/farmacologia , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/farmacologia , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Ácido Eicosapentaenoico/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Adolescente , Adulto , Anticonvulsivantes/administração & dosagem , Criança , Pré-Escolar , Ácidos Docosa-Hexaenoicos/administração & dosagem , Método Duplo-Cego , Combinação de Medicamentos , Ácido Eicosapentaenoico/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Little is known about the parasite/host factors that lead to Post Kala-azar Dermal Leishmaniasis (PKDL) in some visceral leishmaniasis (VL) patients after drug-cure. Studies in Sudan provide evidence for association between polymorphisms in the gene (IFNGR1) encoding the alpha chain of interferon-γ receptor type I and risk of PKDL. This study aimed to identify putative functional polymorphisms in the IFNGR1 gene, and to determine whether differences in expression of interferon-γ (IFNG) and IFNGR1 at the RNA level are associated with pathogenesis of VL and/or PKDL in Sudan. METHODS: Sanger sequencing was used to re-sequence 841 bp of upstream, exon1 and intron1 of the IFNGR1 gene in DNA from 30 PKDL patients. LAGAN and SYNPLOT bioinformatics tools were used to compare human, chimpanzee and dog sequences to identify conserved noncoding sequences carrying putative regulatory elements. The relative expression of IFNG and IFNGR1 in paired pre- and post-treatment RNA samples from the lymph nodes of 24 VL patients, and in RNA samples from skin biopsies of 19 PKDL patients, was measured using real time PCR. Pre- versus post-treatment expression was evaluated statistically using the nonparametric Wilcoxon matched pairs signed-rank test. RESULTS: Ten variants were identified in the 841 bp of sequence, four of which are novel polymorphisms at -77A/G, +10 C/T, +18C/T and +91G/T relative to the IFNGR1 initiation site. A cluster of conserved non-coding sequences with putative regulatory variants was identified in the distal promoter of IFNGR1. Variable expression of IFNG was detected in lymph node aspirates of VL patients before treatment, with a marked reduction (P = 0.006) in expression following treatment. IFNGR1 expression was also variable in lymph node aspirates from VL patients, with no significant reduction in expression with treatment. IFNG expression was undetectable in the skin biopsies of PKDL cases, while IFNGR1 expression was also uniformly low. CONCLUSIONS: Uniformly low expression of IFN and IFNGR1 in PKDL skin biopsies could explain parasite persistence and is consistent with prior demonstration of genetic association with IFNGR1 polymorphisms. Identification of novel potentially functional rare variants at IFNGR1 makes an important general contribution to knowledge of rare variants of potential relevance in this Sudanese population.
Assuntos
Interferon gama/genética , Leishmaniose Cutânea/genética , Leishmaniose Visceral/genética , RNA Mensageiro/metabolismo , Receptores de Interferon/genética , Pele/metabolismo , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Leishmaniose Cutânea/etiologia , Leishmaniose Visceral/complicações , Masculino , Polimorfismo Genético , Regiões Promotoras Genéticas , Sudão/epidemiologia , Adulto Jovem , Receptor de Interferon gamaRESUMO
OBJECTIVE: Human papillomavirus (HPV) gained momentum as a potential etiological factor for many types of cancers. Therefore, the aim of this study was to assess the prevalence of HPV-16 infection among Sudanese patients diagnosed with Squamous Cell Carcinoma (SCC) and Salivary Gland Carcinoma. A descriptive, hospital-based study was conducted. 150 formalin-fixed paraffin-embedded blocks were collected. RESULTS: The study population included a total of 150 patients aged between 18 to 87 years with a mean age of 48.8 ± 11.9 years. Based on gender, females constituted 46.7% while males constituted 53.3%. The 150 patients were classified into 40 (26.0%) esophageal, 30 (20.0%) nasopharyngeal, 18 (12.0%) conjunctival, 18 (12.0%) tongue 12 (8.0%) laryngeal, 8 (5.3%) lip, 6 (4.0%) oropharyngeal, 6 (4.0%) mucoepidermoid, and 6 (4.0%) adenoid cystic, and 6 (4.0%) myoepithelial carcinomas. Odds ratio for male and female diagnosed with carcinoma was 1.025 [0.439-2.394, 95% CI]. Molecular detection of HPV-16 revealed a prevalence of 26 (17.3%) patients were positive for HPV-16. According to cancer diagnosis, esophageal SCC patients showed a high proportion of HPV-16; 14/40 (35.0%). A statistically significant difference was seen for the distribution of HPV-16 positive patients based on cancer diagnosis, P value 0.001.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/epidemiologia , DNA Viral , Feminino , Papillomavirus Humano 16/genética , Humanos , Masculino , Pessoa de Meia-Idade , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Glândulas Salivares , Adulto JovemRESUMO
Background: Vancomycin is an antibiotic of growing importance in the treatment of hospital-acquired infections; with a particular emphasis on its value in the fight against Methicillin-resistant Staphylococcus aureus. Increasing reports of Vancomycin resistance have raised concerns about the effectiveness of this drug. Drug utilization evaluation has an important role in controlling rational use of antibiotics to prevent the emergence of resistance. Methods: We conducted a retrospective 6-months study at Jafar Ibn Auf pediatric hospital. Data including patient's demographics, diagnosis, Dosage regimen, and treatment duration were reviewed. The concordance of practice with the Hospital Infection Control Practices Advisory Committee (HICPAC) guidelines and principles of antibiotic therapy was assessed. Results: 127 medical records were reviewed in this study. Sepsis (29%) and Pneumonia (19.6%) were the most common indications. Culture test was requested in 20.5% of patients. Monitoring of serum creatinine was carried in 81.1% of patients. Based on HICPAC guidelines vancomycin was administered appropriately in 67.7% percent of cases. Considering the infusion rate, most of patients with specific order were received vancomycin in 1 hour. Conclusions: The results showed that vancomycin was used empirically without subsequent adjustment of the antimicrobial agent according to culture and sensitivity data and lack of paying enough attention to the infusion rate and serum creatinine monitoring.
RESUMO
BACKGROUND: Genetic susceptibility to type 2 diabetes (T2D) is multifactorial. A growing number of genes have been identified as risk factors for T2D across multiple ethnicities in trans-ancestry meta-analysis of large-scale genome-wide association studies. Few studies have looked at these genes in Sub-Saharan African populations. This study was undertaken to look for associations between T2D and single nucleotide polymorphisms (SNPs) in a number of the top candidate genes in a selected Sudanese population. METHODS: A total 240 T2D cases and 128 unrelated healthy control subjects were included in this study. Age, sex, weight and height were recorded, blood pressure and biochemical profiles of glucose and lipids were analysed. Single nucleotide polymorphism (SNP) genotyping was performed using the Sequenom MassARRAY® system. Fourteen SNPs were selected across 7 genes: CAPN10 (rs2975760 and rs5030952), PPARG (rs17036314 and rs1801282), IGF2BP2 (rs4402960 and rs1470579), CDKAL1 (rs9465871), HHEX (rs1111875), TCF7L2 (rs7903146, rs11196205 and rs12255372), and KCNJ11 (rs5215, rs1800467 and rs5219). Allelic and haplotype association analyses were performed under additive models in PLINK. P ≤ 0.007 (=0.05/7 genes) was the P-value required to achieve correction for multiple testing. RESULTS: A significant genetic association between the SNPs rs7903146 (odds ratio 1.69, 95 % confidence interval 1.21-2.38, P = 0.002) and rs12255372 (odds ratio 1.70, 95 % confidence interval 1.20-2.41, P = 0.003) at TCF7L2 and T2D was found in Sudanese population. These associations were retained after adjusting for age, sex and BMI (e.g. rs7903146: odds ratio 1.70, P adj:age/sex/BMI = 0.005). The strongest haplotype association (odds ratio 2.24; P adj:age/sex/BMI = 0.0003) comprised the two point haplotype T_C across rs7903146 and rs11196205. Stepwise logistic regression demonstrated that SNP rs7903146 added significant main effects to rs11196205 or rs12255372, whereas the reverse was not true, indicating that the main effect for association with T2D in this population is most strongly tagged by SNP rs7903146. Adjusted analyses also provided support for protection from T2D associated with minor alleles at SNPs rs2975760 at CAPN10 (odds ratio 0.44, 95 % confidence interval 0.20-0.97, P adj:age/sex/BMI = 0.042) and rs1111876 at HHEX (odds ratio 0.60, 95 % confidence interval 0.39- 0.93, P adj:age/sex/BMI = 0.022). CONCLUSIONS: Multiethnic associations between T2D and SNPs at TCF7L2, CAPN10 and HHEX extend to Sub-Saharan Africa, specifically Sudan.