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.     

Pancreatic cancers require autophagy for tumor growth

Macroautophagy (autophagy) is a regulated catabolic pathway to degrade cellular organelles and macromolecules. The role of autophagy in cancer is complex and may differ depending on tumor type or context. Here we show that pancreatic cancers have a distinct dependence on autophagy. Pancreatic cancer primary tumors and cell lines show elevated autophagy under basal conditions. Genetic or pharmacologic inhibition of autophagy leads to increased reactive oxygen species, elevated DNA damage, and a metabolic defect leading to decreased mitochondrial oxidative phosphorylation. Together, these ultimately result in significant growth suppression of pancreatic cancer cells in vitro. Most importantly, inhibition of autophagy by genetic means or chloroquine treatment leads to robust tumor regression and prolonged survival in pancreatic cancer xenografts and genetic mouse models. These results suggest that, unlike in other cancers where autophagy inhibition may synergize with chemotherapy or targeted agents by preventing the up-regulation of autophagy as a reactive survival mechanism, autophagy is actually required for tumorigenic growth of pancreatic cancers de novo, and drugs that inactivate this process may have a unique clinical utility in treating pancreatic cancers and other malignancies with a similar dependence on autophagy. As chloroquine and its derivatives are potent inhibitors of autophagy and have been used safely in human patients for decades for a variety of purposes, these results are immediately translatable to the treatment of pancreatic cancer patients, and provide a much needed, novel vantage point of attack.     

Failure of combination therapy with imidocarb dipropionate and toltrazuril to clear <Emphasis Type="Italic">Hepatozoon canis</Emphasis> infection in dogs

Current treatments with imidocarb dipropionate for infected dogs with Hepatozoon canis do not always provide parasitological cure. The objective of this study is to determine whether concomitant use of toltrazuril may potentiate the effect of imidocarb dipropionate in the management of H. canis infection (HCI). Twelve dogs were determined to have naturally HCI based on clinical signs, identification of the parasite in blood smears, and serologic assay. The animals were allocated randomly to one of two groups (n = 6 in each group). Dogs in Imi group were given imidocarb dipropionate at a dose of 6 mg/kg body weight subcutaneously in two injections 14 days apart. Imi plus Toltra group was given imidocarb dipropionate as dose mentioned above and toltrazuril at 10 mg/kg/day orally for the first five treatment days. Clinical findings, blood counts and parasitaemia levels in blood before and 14, 28 and 56 days after the initial treatment were performed to evaluate treatment response. The overall clinical efficacy of imidocarb dipropionate with and without toltrazuril was 83.3% and 66.7%, respectively; with a mean recovery time of 21.0 and 25.6 days, respectively. A substantial main effect of time on mean PCV, Hb, WBC, neutrophil and PLT and gradual reduction of parasitaemia were significantly observed in both groups (P < 0.05), whereas no significant difference was noticed between the studied protocols. The parasitologic cure rate at the end of eight weekly observation period was 16.6% and 33.3% in Imi and Imi plus Toltra groups, respectively. Similar clinicopathologic and parasitologic responses were observed in both treated groups; thus, it was concluded that toltrazuril does not reveal additional benefit to imidocarb therapy in dogs with HCI.     

Solitary angiokeratoma of the tongue treated with diode laser

Angiokeratoma is a muco-cutaneous disorder that is usually associated with a number of metabolic disorders. Involvement of the tongue with solitary angiokeratoma, without a systemic or metabolic disease, is very rare. To the best of our knowledge, we report the second case of solitary angiokeratoma of the tongue arising in a 16-year-old woman who was treated with diode laser (810 nm) in our department. This case was partially presented as poster presentation at the 12th Congress of the BaSS, 12–14 April 2007, Istanbul, under the auspices of the Balkan Stomatological Society. An erratum to this article can be found at     

The role of standing flexion-extension radiographs for spondylolisthesis following single level disk surgery

OBJECTIVES: Spondylolisthesis is the forward displacement of a lumbar vertebra relative to the adjacent vertebra, occurs as result degeneration or surgery and is a special type of lumbar instability. There is no consensus about which radiologic modality or findings truly reflect the lumbar instability and the exact incidence after single level disk surgery is unknown. METHODS: In this prospective study, we have included 90 patients who were operated by the same surgeon with single level disk herniation. We aimed at evaluating the post-operative lumbar spondylolisthesis, with flexion and extension lateral radiographs in addition to standard magnetic resonance imaging (MRI). RESULTS: We have seen spondylolisthesis in six of 90 cases with standing lateral flexion-extension radiographs, which were undefinable with MRI. Pain intensity and functional-economic rating scale (Prolo scale) were unremarkable. DISCUSSION: We have concluded that standing flexion-extension radiographs should be routinely combined in patients with failed back surgery syndrome and even if lumbar instability is clinically suspected, especially when conventional MR examination is normal. When the MR examination showed spondylolisthesis, standing flexion-extension radiographs could not give additional information.     

Deep brain stimulation in movement disorders

Deep brain stimulation (DBS) is used for advanced and medically intractable patients with Parkinson's disease (PD), essential tremor (ET), and dystonia who meet strict criteria after a detailed motor, cognitive, and psychiatric evaluation. The potential targets are the ventral intermediate nucleus (VIM) of the thalamus for tremor, the globus pallidus interna (GPI) and the subthalamic nucleus (STN) for PD, and GPI for dystonia. The optimal target for PD has not been determined yet, although STN DBS has been performed more frequently in recent years. The mechanism of DBS effect is believed to be associated with disruption of pathological network activity in the cortico-basal ganglia-thalamic circuits by affecting the firing rates and bursting patterns of neurons and synchronized oscillatory activity of neuronal networks. Good candidates should be free of dementia, major psychiatric disorders, structural brain lesions, and important general medical problems. Although the risk for complications with DBS is less than with lesioning techniques, there is still a small risk for major complications associated with surgery. Bilateral procedures are more likely to cause problems with speech, cognition, and gait.     

P wave dispersion in patients with rheumatoid arthritis: its relation with clinical and echocardiographic parameters

P wave dispersion (PWD) is a sign for the prediction of atrial fibrillation (AF). The aim of this study was to assess P wave dispersion and its relation with clinical and echocardiographic parameters in patients with rheumatoid arthritis (RA). Thirty RA patients (mean age 49 ± 10 years) and 27 healthy controls (mean age 47 ± 8 years) were included in the study. We performed electrocardiography and Doppler echocardiography on patients and controls. Maximum and minimum P wave duration were obtained from electrocardiographic measurements. PWD defined as the difference between maximum and minimum P wave duration was also calculated. Maximum P wave duration and PWD was higher in RA patients than controls (P = 0.031 and P = 0.001, respectively). However, there was no significant difference in minimum P wave duration between the two groups (P = 0.152). There was significant correlation between PWD and disease duration (r = 0.375, P = 0.009) and isovolumetric relaxation time (r = 0.390, P = 0.006). P wave duration and PWD was found to be higher in RA patients than healthy control subjects. PWD is closely associated with disease duration and left ventricular (LV) diastolic dysfunction.     

A rare cause of sudden vision loss in a young male: papillary fibroelastoma of the aortic valve

Cardiac papillary fibroelastoma (CPF) is a rare cardiac neoplasm predominantly affecting the cardiac valves. Although it is most commonly an incidental finding, it can result in life-threatening complications, such as coronary and cerebral embolism, acute valvular dysfunction, and sudden death. In this report, we describe a case of a patient with aortic valve papillary fibroelastoma, which presented with sudden vision loss due to branch retinal artery occlusion. To the best of our knowledge, this is the third case of CPF-related retinal artery embolism in English literature.     

Is there any relation between insulin resistance and cognitive function in the elderly?

BACKGROUND: Vascular risk factors are blamed as being involved in the pathogenesis of cognitive dysfunction in the elderly. Alzheimer's disease or vascular-type dementia could be part of a metabolic syndrome. The aim of this study was to evaluate whether there is any relation between insulin resistance and cognitive status of the elderly regarding normal, mild cognitive impairment (MCI), Alzheimer's disease (AD), vascular dementia (VaD) and mixed dementia.METHODS: 267 elderly patients admitted to an outpatient geriatrics clinic were evaluated medically and cognitively in this study. The patients were diagnosed using ARDRA and DSM-IV criteria for AD; NINDS-AIREN and DSM-IV criteria for VaD; and Petersen criteria for MCI. Insulin resistance was calculated using both the homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) formulas.RESULTS: The mean values of HOMA and QUICKI scores were 2.79 (SD+/-3.56) and 0.346 (SD+/-0.036) for the normal group, 2.81 (SD+/-3.06) and 0.354 (SD+/-0.047) for AD group, 2.20 (SD+/-1.82) and 0.360 (SD+/-0.048) for VaD group, 2.87 (SD+/-1.81) and 0.339 (SD+/-0.038) for mixed dementia group, 2.79 (SD+/-2.81) and 0,349 (SD+/-0.042) for MCI group, respectively. There were no statistically significant differences between HOMA and QUICKI scores of all the groups.CONCLUSION: This is the first study of the possible relation between insulin resistance and cognitive function in people categorized according to five forms of cognitive status. Unfortunately the results do not allow generalizations. Further prospective cohort studies that follow a normal cognitive group and MCI patients with and without insulin resistance are necessary.