Relationship between toll-like receptor 8 gene polymorphisms and pediatric pulmonary tuberculosis

Objectives: Genetic variants in Toll-like receptors (TLRs) are considered a potential indicator for host susceptibility to and outcome of several infectious diseases including tuberculosis. The aim of this study was to determine whether −129 C/G and Met1Val polymorphisms of TLR8 were associated with pediatric pulmonary tuberculosis in Turkish population. Methods: The −129 C/G and Met1Val polymorphisms were studied in 124 children with pulmonary tuberculosis compared to 150 age-matched healthy control subjects. Results: We did not identify any statistically significant differences between the patients with TB and control groups with regard to the frequency of genotypes GG or G/(−), CG, and CC or C/(−); and alleles G and C at rs3764879 (p > 0.05). We found a strong association with genotype A/(−) at rs3764880 with susceptibility to pulmonary TB in males (OR 2.87, 95%CI 1.38–5.98, p = 0.007). Conclusions: Our results provide evidence, for the first time, of a role for the TLR8 gene in susceptibility to pulmonary TB in male children. Additional research to verify our results are necessary. Tuberculosis in children presents particularly difficult challenges, but research priorities and advances in pediatric tuberculosis could provide wider insights and opportunities for tuberculosis control.     

Duodenal perforation and bilateral tension pneumothorax following endoscopic sphincterotomy

Endoscopic sphincterotomy is commonly used for retained bile stones. We report a 24-year-old woman who showed bilateral tension pneumothorax and duodenal perforation following endoscopic sphincterotomy performed under sedation. These complications are rare in the literature have significant mortality and morbidity.     

Interferon-gamma gene+874T-A polymorphism is associated with tuberculosis and gamma interferon response

Interferon-gamma is the most important cytokine in resistance to mycobacterial diseases and common variants of interferon-gamma gene could be related to tuberculosis susceptibility. We tested the hypothesis that the interferon-gamma+874T-A polymorphism is associated with tuberculosis disease, and affects the interferon-gamma response. We determined by pyrosequencing the distribution of the interferon-gamma+874T-A polymorphism in a Turkish population of 319 patients with pulmonary tuberculosis, 42 children with severe forms of tuberculosis and 115 healthy donors. We also analysed whether any correlation exists between this polymorphism and interferon-gamma response to Mycobacterium tuberculosis antigens by ELISPOT in 58 pulmonary tuberculosis cases, and the results were analysed according to the genotypes. We found that the minor allele (T) frequency was significantly lower in patients with pulmonary tuberculosis when compared to controls (P=0.024, OR=0.7), a similarly significant decrease in the frequency of TT genotype was observed in patients with pulmonary tuberculosis, compared to the control group (P=0.02, OR=0.49). IFN-gamma responses to PPD antigen in TT genotype was found to be significantly higher than the AA group (P>0.001). Non-parametric correlation analysis of ELISPOT data showed significant reverse correlation in PPD, CFP10 and ESAT6 values and IFN-gamma +874 genotypes. These results show that the IFN-gamma +874T-A polymorphism is related to the IFN-gamma response and the magnitude of the response decreases during transition from TT- to TA and to AA genotypes. Our data suggest that similar to various Caucasian populations, in a Turkish population the IFN-gamma+874 T-A polymorphism is also associated with tuberculosis disease and affects the magnitude of the IFN-gamma response.     

Clinical predictors of therapeutic response to clozapine in a sample of Turkish patients with treatment-resistant schizophrenia

BACKGROUND: Several lines of evidence suggest that clozapine is more effective than both first- and second-generation antipsychotic drugs in treatment-resistant schizophrenia (TRS). However, clinicians appear to be hesitant to prescribe this drug. It would therefore be extremely valuable if predictors of response to clozapine could be identified. The aim of this study was to evaluate the predictive factors of clinical responses to clozapine in a group of Turkish patients with TRS. METHODS: This was a 16-week uncontrolled open study carried out among 97 TRS patients (80 males and 17 females; DSM-IV diagnosis). All patients fulfilled the criteria for refractory schizophrenia according to the UK guidelines for the National Institute of Clinical Excellence (NICE). After all previous antipsychotic medications had run their course, the patients were started on clozapine according to a standardized titration and dosage schedule. Psychopathology was evaluated before the initiation of clozapine therapy and once every 4 weeks using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment for Positive Symptoms, and the Scale for the Assessment of Negative Symptoms. RESULTS: Of the TRS patients on clozapine, 55.7% achieved a clinical response, defined as at least a 20% decrease in BPRS. We observed a favorable effect of clozapine on both positive and negative symptoms. Logistic regression analysis showed that a good clozapine response was more likely when schizophrenia began at a later age, when negative symptoms were severe, and when patients had an early response at 4 weeks. CONCLUSION: A combination of demographic, baseline clinical, and acute treatment response variables may accurately predict response to clozapine in TRS. Priority should be given to initiating clozapine at the earliest phase of TRS, especially for patients with evident negative symptoms.     

Native valve endocarditis due to Pseudomonas mendocina in a patient with mental retardation and a review of literature

Pseudomonas mendocina, a Gram-negative non-fermentative rod, occurs in water and soil but is rarely recovered as a human pathogen. We report a native valve endocarditis due to Pseudomonas mendocina in a patient with mental retardation.     

Unusual presentation of triple A syndrome mimicking Sjögren’s syndrome

Triple A syndrome is a rare autosomal recessive disorder characterized by alacrima, achalasia, and adrenal insufficiency. Sjögren’s syndrome (SS) is a chronic inflammatory disorder manifested primarily by diminished lacrimal and salivary gland secretions, resulting in symptoms of dry eyes and dry mouth, the so-called “sicca complex”. However, a variety of other manifestations also can occur, which can be termed “nonexocrine manifestations”. One of the frequent nonexocrine manifestations is dysphagia. In this paper, we present an unusual form of Triple A disease mimicking Sjögren’s syndrome, which leads to a challenging diagnosis.