Treatment of thromboangiitis obliterans (Buerger's disease) with bosentan

<p>Abstract</p> <p>Background</p> <p>This study assessed the effectiveness and safety of bosentan when administered to thromboangiitis obliterans (Buerger's disease) patients.</p> <p>Methods</p> <p>A clinical pilot study was designed in which patients with ulcer and/or pain at rest were treated with bosentan p.o. at a dose of 62.5 mg twice daily during the first month, which was thereafter up-titrated to 125 mg twice daily. The study endpoints were clinical improvement rate, major or minor amputation rate, haemodynamic changes, changes in endothelial function and angiographic changes.</p> <p>Results</p> <p>Seven out of 12 patients were male (58%). Median age was 39 years (range 29-49). The median follow-up was 20 months (range 11-40). All patients were smokers. With bosentan treatment, new ischaemic lesions were observed in only one patient. Overall, clinical improvement was observed in 12 of the 13 extremities (92%). Only two out of 13 extremities underwent amputation (one major and one minor) after bosentan treatment. After being assessed by digital arteriography with subtraction or angio-magnetic resonance imaging, an increase of distal flow was observed in 10 out of the 12 patients. All patients experienced a statistically significant improvement in their BAFMD values (mean: 1.8 at baseline; 6.6 at the end of the treatment; 12.7 three months after the end of the treatment; p < 0.01).</p> <p>Conclusion</p> <p>Bosentan treatment may result in an improvement of clinical, angiographic and endothelial function outcomes. Bosentan should be investigated further in the management of TAO patients. Larger studies are required to confirm these results.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01447550">NCT01447550</a></p

changes for osteogenesis: In a rat model

The aim of this study is to investigate the effects of type I collagen on bone defects and on genes specifically for osteogenesis in a rat model. Two millimeter drill hole bone defect was created in the femur of rats. In the experimental group, type I collagen was applied in bone defects whereas in control group defects were left empty. Inflammation, development of connective tissue, osteogenesis, and foreign body reaction parameters evaluated with histologically and genes evaluated by blood samples. In the experimental group, the histopathologically significant change was found in favor of bone healing only at the first week. A significant increase was found in genetic expressions of BMP-1, 2, 3, 4, 5, 6, 7, TGF-RII, Smad-1, IL-6, BMPR-IA, BMPR-IB, Eng, BMPR-II, c-fos, Cdkn1a, Chrd, Gdf-5, Id-1, PDGF-, IGF-1, Serpine-1, and TGF-RI at the first hour. At the first, third, and sixth week, no significant increase was found in any of the gene expressions. Type I collagen is found to be effective in favor of bone healing through increased inflammatory cytokines and expression of BMP genes in the early stages of fracture healing.C1 [Yigiter, Ozgur] Denizli State Hosp, Dept Orthoped & Traumatol, Denizli, Turkey.[Yorukoglu, Ali Cagdas; Demirkan, Ahmet Fahir] Pamukkale Univ, Dept Orthoped & Traumatol, Fac Med, TR-20070 Denizli, Turkey.[Sentuerk, Nilay] Pamukkale Univ, Dept Pathol, Fac Med, Denizli, Turkey.[Dodurga, Yavuz] Pamukkale Univ, Dept Med Biol, Denizli, Turkey

Accuracy of ovarian reserve tests

Several tests predict ovarian reserve in women undergoing assisted reproductive technologies. However, the accuracy of these tests in assessing the number of the remaining follicles within the ovary (ovarian reserve) has not been previously validated. The aim of this study was to assess the accuracy of ovarian reserve tests, namely basal and clomiphene-stimulated follicle stimulating hormone (FSH) concentrations and gonadotrophin-releasing hormone (GnRH) agonist stimulation test in predicting the number of the follicles within the ovaries. The ovaries of 22 parous women over 35 years of age who underwent oophorectomy were examined histologically for follicle number. Early follicular phase serum FSH, clomiphene citrate challenge tests (CCCT) and GnRH agonist stimulation test (GAST) were performed in the menstrual cycle prior to the surgery, The predictive value of these tests was then assessed. A positive correlation was detected between basal serum oestradiol concentrations and follicles per unit tissue but no significant correlation was detected between basal and clomiphene-stimulated FSH and follicles per unit tissue. The receiver operator characteristic curves indicated that the clomiphene citrate challenge test was the most accurate of the three tests assessed. In conclusion, none of the tests in this study accurately reflects ovarian reserve

Renal, gastric and thyroidal amyloidosis due to familial Mediterranean fever

Chronic renal failure developed in a 10-year-old girl due to renal amyloidosis secondary to familial Mediterranean fever (FMF), During management of the chronic renal failure by hemodialysis and of FMF with colchicine, goiter and hypothroidism were observed. Thyroid fine-needle aspiration and gastric endoscopical biopsies, performed when recurrent abdominal pain could not be controlled, revealed amyloid deposits in both thyroid and gastric tissues. After 6 months' therapy with colchicine and levothyroxine, there was no significant change in the thyroid volume. This is the first case in which gastric amyloidosis secondary to FMF in childhood has been demonstrated. Patients with amyloidosis secondary to FMF who have thyroid enlargement and unexplained gastrointestinal symptoms despite adequate therapy should be evaluated with imaging studies and biopsy examinations

Predictive value of the international prostate symptom score for positive prostate needle biopsy in the low-intermediate rostate-specific antigen range

Purpose: Serum prostate-specific antigen (PSA) has a restricted predictive value for prostate cancer in the low-intermediate PSA range (2.5 - 10 ng/ ml). Our aim was to determine the predictive value of the International Prostate Symptom Score (IPSS) for positive prostate needle biopsy (PNB) in patients who underwent transrectal ultrasound (TRUS)- guided prostate biopsy with a low-intermediate PSA level. Patients and Methods: Between 2001 and 2004, the data of 389 consecutive patients applying for any urologic complaint to our department and who underwent TRUS- guided prostate biopsy due to an elevated serum PSA and/ or abnormal digital rectal examination (DRE) were retrospectively analyzed. A total of 158 eligible patients with a low- intermediate PSA level were included in the study. The patient's age, PSA, free PSA, free/ total PSA, prostate volume, PSA density (PSAD), pre- biopsy IPSS were compared in the positive and negative biopsy groups. Results: Fifty- eight of 158 patients (37%) who underwent TRUS- guided prostate biopsy had positive PNBs. Forty- eight patients (30%) had abnormal DREs. In the positive PNB group, the mean age was older and PSAD was higher, but the means of the prostate volumes and total IPSS were lower (p < 0.05). Multivariate analysis demonstrated that age and IPSS were independent predictors of a positive PNB ( p < 0.05). The odds ratio of mild IPSS for positive PNB controlled for age was 3.0 (95% CI 1.5 - 6.7). Receiver- operating characteristics analysis revealed a mild IPSS (AUC = 0.640) and was a considerable predictor for positive PNB as well as PSAD (AUC = 0.648). The sensitivity and specifi city of IPSS with a cutoff value of 7.5 points were 31 and 87% for prediction of prostate cancer detection. Conclusion: In the low- intermediate PSA range, mild IPSS may be a predictive factor for positive PNB with a similar specifi city of PSAD. Copyright (c) 2005 S. Karger AG, Basel

Reproducibility and prognostic value of WHO1973 and WHO2004 grading systems in TaT1 urothelial carcinoma of the urinary bladder

Background: European treatment guidelines of TaT1 urinary bladder urothelial carcinomas depend highly on stage and WHO1973-grade but grading reproducibility is wanting. The newer WHO2004 grading system is still debated and both systems are currently used. Aims: To compare reproducibility and prognostic value (of stage progression) of the WHO1973 and WHO2004. Methods: One hundred and ninety-three primary urothelial carcinomas were reviewed. Follow-up data were retrieved from the patient records. Kappa statistics and Harrell's C-index were used. Results: Median follow-up was 75 months (range 1–127). 17 patients (9%) progressed, 82% of these within and 18% after 60 months. The distribution of WHO73-grades 1, 2 and 3 was 23%, 51% and 26%, interobserver agreement for each individual grade was 66% (kappa = 0.68), while for grades 1&2 versus 3 89% (kappa = 0.68). Intraobserver reproducibility was 68–63% for WHO73 and 88–89% for WHO73 as 1&2 vs.3. Progression free survival rates at 5 years were 95% (grade 1), 98% (grade 2) and 82% (grade 3) and 96% and 82% for grades 1&2 versus 3 (Hazard Ratio, HR, 5.4, p = 0.003). Using WHO2004, 62% were low grade and 38% high grade, inter-observer agreement 87% (kappa = 0.70), intraobserver reproducibility 93%, and progression free 5-year survival rates 97% and 85% (HR 6.6, p = 0.004). Positive and negative predictive values for stage progression within 5 years for the WHO73 (1&2 vs. 3) were 18% and 96%, and 15% and 97% for the WHO04. Using Harrell's C-index, none of the grading systems was prognostically superior. Conclusion: None of the grading systems is prognostically stronger than the others. Most importantly, inter-observer reproducibility and sensitivities for stage progression of both systems are low and need improvement for optimal treatment

Small cell Carcinomas of the bladder highly express somatostatin receptor type 2A: Impact on prognosis and treatment-a multicenter study of urooncology society, Turkey

Small cell carcinoma (SmCC) is a rare and aggressive neuroendocrine carcinoma of the bladder. Neuroendocrine carcinomas expressing somatostatin receptors (SSTR) in other viscera such as lung, pancreas, and gastrointestinal system respond to therapy with somatostatin analogs. In the present study, expressions of SSTRs 1 to 5 including type 2A are investigated by immunohistochemistry (IHC) and their relationship with clinicopathologic factors was evaluated. Hundred primary bladder SmCC cases were collected from 12 centers in Turkey. Forty-three cases were pure SmCC. Other cases had mostly papillary urothelial carcinoma as a second component. The percentage of the SmCC component ranged from 5% to 100%. SSTR-2A expression was membranous, whereas the other receptors showed cytoplasmic staining. The percentages of positive cases for SSTR-1, SSTR-2A, SSTR-3, SSTR-4, and SSTR-5 were 4% (3/75), 61.4% (54/88), 2.4% (2/84), 24.4% (20/82), and 6.25% (5/80), respectively. The percentage of SmCC component was positively correlated with the percentage of SSTR-2A expression (P=0.003) while negatively correlated with patient age (P=0.032). SSTR-2A expression was correlated with survival as a bad prognostic factor (P=0.018). SSTR-1, SSTR-3, SSTR-4, and SSTR-5 expressions did not show any statistical significance with any parameter. In conclusion, although the limited number of cases with adequate term follow-up, SSTR-2A expression could be a prognostic factor and somatostatin analogs therapeutic candidate for SmCCs of the bladder as these tumors show high percentage of SSTR-2A expression. © 2016 Wolters Kluwer Health, Inc. All rights reserved

Quality score compression improves genotyping accuracy

To the Editor: Most next-generation sequencing (NGS) quality scores are space intensive, redundant and often misleading. In this Correspondence, we recover quality information directly from sequence data using a compression tool named Quartz, rendering such scores redundant and yielding substantially better space and time efficiencies for storage and analysis. Quartz is designed to operate on NGS reads in FASTQ format, but it can be trivially modified to discard quality scores in other formats for which scores are paired with sequence information. Discarding 95% of quality scores resulted, counterintuitively, in improved SNP calling, implying that compression need not come at the expense of accuracy.Hertz FoundationNational Institutes of Health (U.S.) (NIH grant GM108348