YSDD: a novel mutation in HBV DNA polymerase confers clinical resistance to lamivudine

The emergence of drug-resistant virus in hepatitis B virus (HBV) patients treated with lamivudine is well documented. In this study, we determined the mutations occurring in the tyrosine-methionine-aspartate-aspartate (YMDD) amino acid motif of the HBV DNA polymerase gene, as well as upstream and downstream of this region, in patients with breakthrough virus during lamivudine therapy. Thirty-one Turkish patients (20 patients HBeAg positive, 11 patients HBeAg negative and anti-HBe positive) with chronic HBV infection who completed at least 104 weeks of lamivudine treatment were investigated. All patients received lamivudine, (150 mg/day), for 104 weeks, with or without 4 months of interferon (IFN) combination. HBV-specific sequences were amplified by polymerase chain reaction (PCR) from sera of patients with breakthrough virus, and the PCR products were directly analysed by sequencing. Breakthrough virus was detected in seven of the 31 patients (22.6%) between 9 and 18 months of therapy. Of the seven patients, six were HBeAg positive at baseline, and four had a double mutation consisting of rtM204V and rtL180M, while two had an rtM204I change. In one patient, two base substitutions at rt204 (ATG --> AGT; T to G and G to T) lead to a methionine to serine change (YMDD --> YSDD). This novel DNA pol mutation was detected at month 18 of lamivudine treatment. In addition, this new variant had the rtL180M mutation and a 12 base pair deletion in the pre-S1 region between nucleotides 43-54. The YSDD mutation was still present 6 months after lamivudine discontinuation. In vitro transfection studies also confirmed that the YSDD strain is resistant to lamivudine. In conclusion, the results indicate that, in addition to a Met --> Val and Met --> Ile change in YMDD, a Met --> Ser change at rt204 (YMDD --> YSDD) associated with the rtL180M change can also emerge during lamivudine treatment, which confers lamivudine resistance in vivo and in vitro, leading to virological breakthrough and ALT increases.     

A laryngeal foreign body misdiagnosed as asthma bronchiale.

Laryngotracheal foreign bodies, although less common than bronchial foreign bodies, are potentially more dangerous. We report a 10-year-old girl with Down syndrome with asthma bronchiale symptoms, which was later found to be the result of a thin bone lamella impacted in her larynx. There was no clear history of foreign body aspiration. She was treated with the initial diagnosis of asthma bronchiale. It took a month before the final diagnosis was made. The foreign body was removed via direct laryngoscopy. It was a white and thin bone lamella with sharp edges, measuring 28 x 19 x 2 mm. We thought the case was worth presenting because of its rare location, the size of the foreign body, and the long duration before the final diagnosis was made.     

Biology of stem cells in human umbilical cord stroma: in situ and in vitro surveys

Cells in the umbilical cord stroma have gained attention in recent years; however, differentiation to certain lineages in humans has been demonstrated in few studies. Unlike bone marrow MSCs, human umbilical cord stroma cells (HUCSCs) are far from being well characterized. This study attempts to describe proliferation, structural, and differentiation properties of these cells to account for their exceptional nature in many aspects. Cellular dynamics, cellular structure, and the degree of transformations during expansion and differentiation into mesenchymal and neuronal lineages were examined in vitro over a 10-month period. Comparisons with human bone marrow MSCs regarding differentiation were performed. HUCSCs in culture revealed two distinct cell populations, type 1 and type 2 cells, that possessed differential vimentin and cytokeratin filaments. Corresponding cells were encountered in cord sections displaying region-specific localization. alpha-Smooth muscle actin and desmin filaments, which were evident in cord sections, diminished through passages. No difference was noted regarding type 1 and type 2 cells in differentiation to chondrogenic, adipogenic, and osteogenic lineages, whereas a preferential differentiation was noted in neuronal lineage. Relative success was achieved by production of chondrocytic spheres and osteogenic monolayers, whereas adipocytes were immature compared with bone marrow MSCs. The presence of neuronal markers suggests that they transform into a certain state of maturity under neurogenic induction. Conclusively, HUCSCs retain their original phenotype in culture without spontaneous differentiation, have a limited lifespan, and bear multipotent stem cell characteristics. Given these characteristics, they may be generally considered progenitor cells if manipulated under appropriate conditions and deserve further study to be potentially used in cell-based therapies.     

Chronic constrictive tuberculous pericarditis: risk factors and outcome of pericardiectomy.

OBJECTIVE: Data on long-term outcome of pericardiectomy are limited. This retrospective study aimed to investigate risk factors and early and late outcomes of pericardiectomy for constrictive tuberculous pericarditis. DESIGN: Seventy patients with chronic constrictive pericarditis who underwent pericardiectomy between January 1990 and August 2005 were reviewed for perioperative and long-term survival. RESULTS: Patients (49 males; median age 40 years) had a median duration of symptoms of 24 months (range 8-72) before surgery. Perioperative mortality was 8.6%. During follow-up (mean 66.4 +/- 56.4), late mortality rates at 5 and 10 years were 1.6% and 9.7%, respectively. The mean censored survival in all patients was 155.2 months (SEM 8.3, 95%CI 138.8-171.6). Readmission-free survival was 68.6% over 10 years (mean 125.4 months, SEM 10.3, 95%CI 105.2-145.6). Ascites and duration of symptoms were found to be predictors of perioperative mortality (P = 0.047 and 0.036, respectively). CONCLUSIONS: The optimal time of pericardiectomy is most important in its management. Total or near-total pericardiectomy should always be performed as early as possible.     

Dose-dependent effect of radiation on resorbable blast material titanium implants: an experimental study in rabbits

Background: Radiotherapy is a commonly used treatment modality in head and neck cancer; however, it also negatively affects healthy structures. Direct damage to oral soft and hard tissue frequently occurs with radiotherapy. In this study, we aimed to evaluate the effect of radiotherapy on bone surrounding titanium dental implants via biomechanical and molecular methods.

Materials and methods: Fifty-four implants were inserted in the left tibiae of 18 adult male New Zealand rabbits (3 implants in each rabbit). After 4 weeks of the implant surgery, the left tibiae of 12 rabbits were subjected to a single dose of irradiation (15?Gy or 30?Gy). Four weeks after the irradiation, rabbits were sacrificed and removal torque test was done for the biomechanical evaluation. Bone morphogenetic protein-2 (Bmp-2) and fibroblast growth factor-2 (Fgf-2) expression analyses were performed with Real-time PCR. Statistical analysis was done using SPSS.

Results: The control group showed significantly higher removal torque value than the 15 and 30?Gy irradiation groups, and the 15?Gy irradiation group had higher removal torque value than the 30?Gy irradiation group (p?p?p?p?Conclusion: Radiotherapy with 15 and 30?Gy doses can adversely affect osseointegration of implants by reducing the quality of bone and impairing the bone-to-implant contact. The mechanism of action seems to be related to alterations in Bmp-2 and Fgf-2 mRNA expressions.     

Role of apparent diffusion coefficient values and diffusion-weighted magnetic resonance imaging in differentiation between benign and malignant thyroid nodules

ObjectiveThe purpose of the study was to differentiate between benign and malignant thyroid nodules using nodule-spinal cord signal intensity and nodule apparent diffusion coefficient (ADC) ratios on diffusion-weighted magnetic resonance imaging (DW-MRI).Materials and MethodsForty-four patients (27 females, 17 males; mean age, 49 years) with nodules who underwent DW-MRI were included in this study. The images were acquired with 0, 50, 400 and 1000 s/mm² b values. ADC maps were calculated afterwards. Fine needle aspiration biopsies (FNAB) were performed at the same day with DW-MRI acquisition. The diagnosis in patients where malignity was detected after FNAB was confirmed by histopathologic analysis of the operation material. The signal intensities of the spinal cord and the nodule were measured additionally, over b-1000 diffusion-weighted images. Nodule/cord signal intensity (SI) ratios were obtained and the digital values were calculated by dividing to ADC values estimated for each nodule. Statistical analysis was performed.ResultsThe (nodule SI-cord SI)/nodule ADC ratio is calculated in the DW images, and a statistically significant relationship was found between this ratio and the histopathology of the nodules (P<.001). The ratio was determined as 0.27 in benign and 0.86 in malignant lesions. The result of receiver operating characteristic (ROC) analysis was statistically significant, and the area under curve (100%) was considerably high. The threshold value was calculated as 0.56 according to the ROC analysis. According to this threshold value, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy rates for (nodule SI/cord SI)/ADC ratios in differentiating benign from malignant thyroid nodules are calculated as 100%, 97%, 83%, 100%, and 98%, respectively.ConclusionWe have found that (nodule/cord SI)/nodule ADC ratio has the highest values for sensitivity and specificity among the tests defined for characterization of nodules.     

Is it possible to differentiate between hydatid and simple cysts in the liver by means of diffusion-weighted magnetic resonance imaging?

ObjectiveOur aim was to evaluate the contribution of diffusion-weighted imaging to the differentiation of hydatid cysts (HCs) from the simple cysts and to the identification of the HC subtypes.Materials and methodsA total of 37 patients were included in this retrospective study. Fifty of these patients had diagnosed liver cysts (28 HCs and 22 simple cysts) of at least 1 cm in size. All of the cysts were examined with sonography and magnetic resonance imaging, and the HCs were classified according to the World Health Organization criteria.ResultsTwenty-eight of the total 50 cysts were HCs, and 22 were simple cysts. When the apparent diffusion coefficient (ADC) values of all HCs were compared with the ADC values of the simple cysts, a statistically significant relationship was found (P=.001). The optimal ADC threshold value was established as 2.5 s/mm². The sensitivity, specificity, positive predictive value, negative predictive value and accuracy rates were 60%, 95%, 94%, 65% and 76%, respectively.ConclusionDiffusion-weighted imaging–magnetic resonance imaging is a considerably helpful technique for differentiating between HCs and simple cysts and for differentiating between HC subtypes.