Tissue factor pathway inhibitor and thrombin-activatable carboxypeptidase B for prediction of early atherosclerosis in gouty arthritis

Background

Gouty arthritis (GA) is a chronic inflammatory arthritis in which both clinical and subclinical atherosclerosis are more frequent. The dynamic equilibrium between coagulation and fibrinolysis is impaired in inflammatory diseases. We determined TFPI and TAFI antigen levels in GA patients and evaluated their association with subclinical atherosclerosis.

Methods

We included 45 GA patients (41 males, 4 females; mean age: 51.6 years) and 25 asymptomatic hyperuricemic (AHU) subjects (19 males, 6 females; mean age: 48.1 years). Cardiovascular risk factors were determined. TAFI and TFPI levels were determined by ELISA. B-mode ultrasonography was used to detect subclinical atherosclerosis.

Results

Cardiovascular risk factors were similar in both groups. The carotid IMT was significantly higher in GA group than in AHU group (0.74 ± 0.23 mm vs. 0.61 ± 0.13 mm, p = 0.009). TFPI level was significantly higher in GA group than in AHU group (86.2 ± 48.9 ng/mL vs. 25.8 ± 21.4 ng/mL, p < 0.001); TAFI antigen was significantly higher in AHU group (22.6 ± 3.6 ng/mL vs. 25.7 ± 5.3 ng/mL, p = 0.006) than in GA patients. Atherosclerotic plaque formation was more frequent in GA group (p = 0.041). When GA patients with and without plaques were compared, the first group had significantly higher mean age (p = 0.01) and TFPI level (p = 0.028). TFPI level correlated with carotid IMT (r = 0.302; p = 0.028). Logistic regression analysis showed that age (OR: 1.236, 95%CI: 1.059-1.443, p = 0.007) and TFPI (OR: 1.031, 95%CI: 1.008-1.054, p = 0.008) were independent risk factors for the presence of plaques.

Conclusions

GA patients had more frequent subclinical atherosclerosis than subjects with AHU. Higher TFPI levels in GA patients –probably associated with enhanced endothelial damage- were related to subclinical atherosclerosis. Lower TAFI levels in GA pointed to impaired fibrinolysis.     

Does anti-tnf therapy cause any change in platelet activation in ankylosing spondylitis patients?

Recently, it has been reported that ankylosing spondylitis (AS) was characterised by endothelial dysfunction and the development of atherosclerotic complications. In this study, we evaluated platelet and endothelial activation parameters in AS patients. Fiftynine AS patients and 22 healthy controls were included. The clinical features and acute phase parameters were evaluated. In all patients and healthy controls, platelet-monocyte complexes (PMC), platelet-neutrophil complexes, basal and ADP-stimulated P-selectin (CD62P) expression were determined by flow cytometry; soluble E-selectin (sE-selectin) and soluble CD40L (sCD40L) were determined by ELISA. AS patients were divided into two groups as active and inactive by using BASDAI. In 15 AS patients, the evaluated parameters were assessed before and after 12 weeks of anti-TNF therapy. PMC and sCD40L levels in AS patients were significantly higher than in the control group (P values 0.013 and 0.016). The evaluated variables were similar in active and inactive AS groups (P > 0.05). There were no significant changes in platelet and endothelial activation parameters in AS patients after anti-TNF therapy (P > 0.05). Platelet activation which is reflected by high levels of PMC and sCD40L might be responsible for the increased frequency of atherosclerosis in AS. The platelet activation in our AS patients was not associated with disease activity and did not improve after anti-TNF therapy.     

Distribution of gene mutations associated with familial normosmic idiopathic hypogonadotropic hypogonadism

Objective: Normosmic idiopathic hypogonadotropic hypogonadism (nIHH) is characterized by failure of initiation or maintenance of puberty due to insufficient gonadotropin release, which is not associated with anosmia/hyposmia. The objective of this study was to determine the distribution of causative mutations in a hereditary form of nIHH. Methods: In this prospective collaborative study, 22 families with more than one affected individual (i.e. multiplex families) with nIHH were recruited and screened for genes known or suspected to be strong candidates for nIHH. Results: Mutations were identified in five genes (GNRHR, TACR3, TAC3, KISS1R, and KISS1) in 77% of families with autosomal recessively inherited nIHH. GNRHR and TACR3 mutations were the most common two causative mutations occurring with about equal frequency. Conclusions: Mutations in these five genes account for about three quarters of the causative mutations in nIHH families with more than one affected individual. This frequency is significantly greater than the previously reported rates in all inclusive (familial plus sporadic) cohorts. GNRHR and TACR3 should be the first two genes to be screened for diagnostic purposes. Identification of causative mutations in the remaining families will shed light on the regulation of puberty.     

Comparison of microscopic (pT3a) and gross extravesical extension (pT3b) in pathological staging of bladder cancer: analysis of patient outcomes

Objective

To determine the prognostic value of pT3 bladder urothelial carcinoma substaging in patients without lymphatic involvement.

Patients and methods

Pathologic and clinical data were reviewed on patients who underwent radical cystectomy for urothelial carcinoma between 1991 and 2010. Of the 460 reviewed patients, 74 patients were diagnosed with pathologic T3No urothelial carcinoma of the bladder. The impact of pathologic substaging (pT3a vs. pT3b) was examined to determine the effect on overall and disease-specific survival.

Results

Five years disease-specific and overall survival rates were 46.9 % and 39.6 % for patients with pT3aNo tumor, whereas these ratios were 34.4 and 30.3 %, respectively, for patients with pT3bNo tumor (p > 0.05). Mean disease-specific survival time was 43.94 ± 6.50 months for pT3aNo, while it was 39.01 ± 7.19 months for pT3bNo (p = 0.539). In multivariate cox regression analysis, age (p = 0.459), gender (p = 0.710), urinary diversion type (p = 0.088), and pT3 substaging (p = 0.554) were not noticed as an independent predictive factor for survival.

Conclusion

Macroscopic extravesical extension (pT3b) is not associated with a worse outcome than pT3a disease in lymph node-negative cases of bladder urothelial carcinoma.     

Effect of octenidine dihydrochloride on viability of protoscoleces in hepatic and pulmonary hydatid diseases

BACKGROUND: Use of effective scolicidal agents during puncture, aspiration or injection of a scolicidal agent and reaspiration (PAIR) and surgery for hydatid cysts are essential to reduce the recurrence rate. In this in vitro study, we tried to determine the scolicidal property of a new agent, octenidine dihydrochloride, and of various agents in different concentrations and exposure times. MATERIAL AND METHODS: Echinococcus granulosus protoscoleces were obtained from six patients with liver (n=3) and lung (n=3) hydatid cysts. Various concentrations of octenidine dihydrochloride (0.1%, 0.01% and 0.001% diluted form), povidone iodine (10%, 1% and 0.1% diluted) and 20% saline were used in this study. Viability of protoscoleces was determined with dye-uptake (0.1% eosin) and flame cell activity. RESULTS: Octenidine dihydrochloride 0.1% had strong scolicidal effect in 15 min and octenidine dihydrochloride 0.01% in 30 min. Sixty percent of protoscoleces lost viability at 5 min with octenidine dihydrochloride 0.1%. Viability ratio decreased to 20% at 10 min, and all of them died at 15 min. Povidone iodine 10% and 1% had strong scolicidal effects after 15- and 30 min of exposure, respectively. Saline 20% killed all the protoscoleces in 30-min exposure. CONCLUSION: Because of the rapid and strong scolocidal effectiveness of octenidine dihydrochloride on protoscoleces, it may be used as a scolocidal agent during both perioperative and in the PAIR method.     

Trunk muscle strength in relation to balance and functional disability in unihemispheric stroke patients

OBJECTIVE: To evaluate trunk muscle strength in unihemispheric stroke patients and to assess how it relates to body balance and functional disability in this patient group. DESIGN: This prospective case-comparison study investigated isometric and isokinetic reciprocal trunk flexion and extension strength at angular velocities in 38 unihemispheric stroke patients and 40 healthy volunteers. The Berg balance scale was used to assess balance and stability, and the FIM instrument was used to evaluate functional disability in the patient group. Patients were evaluated as soon as they were able to stand long enough for testing. RESULTS: Peak torque values for trunk flexion and extension were lower in the stroke patients than in the controls. The differences were significant for trunk flexion and for trunk extension. In both groups, peak torque values for trunk flexors were greater than peak torque values for trunk extensors. There was a significant positive correlation between trunk muscle strength and Berg balance scale score at discharge. Trunk muscle strength was not correlated with FIM total score or FIM motor score, but the locomotion-transfers FIM subscore at discharge was positively correlated with trunk muscle torque values, except for isometric extension. CONCLUSION: The findings indicate trunk flexion and extension muscle weakness in unihemispheric stroke patients, which can interfere with balance, stability, and functional disability.     

Rectum mucinous adenocarcinoma metastasis to bilateral breast in a male patient: A case report

A 47‐year‐old male presented to our clinic with complaints of mass in both breasts. In the patient's history, he had undergone low anterior resection for rectum mucinous adenocarcinoma 2 years ago. The masses in both breasts of the patient were excised. Mucinous adenocarcinoma metastases were reported in the pathologic evaluation of the masses. Metastasis should be considered in patients with bilateral breast mass and previously diagnosed cancer even if the patient is male.     

Identification of Three Novel and One Known Mutation in the WFS1 Gene in Four Unrelated Turkish Families: The Role of Homozygosity Mapping in the Early Diagnosis

Objective:Bi-allelic mutations in the wolframin gene (WFS1) cause Wolfram syndrome 1 (WS1 or DIDMOAD) characterized by non-autoimmune diabetes mellitus, optic atrophy, diabetes insipidus, sensorineural deafness, urinary tract abnormalities, and neuropsychiatric disorders. Patients presenting with an incomplete phenotype of WS1 were evaluated using homozygosity mapping and subsequent whole-exome sequencing.Methods:Four unrelated consanguineous Turkish families, including seven affected children, and their unaffected parents and siblings were evaluated. Homozygosity mapping was performed, followed by whole-exome sequencing of WFS1. Mutations were classified according to results of “in silico” analyses, protein prediction, and functional consequences.Results:Homozygosity mapping confirmed shared homozygous regions on chromosome 4 (chr4p16.1) between the affected individuals, that was absent in their unaffected siblings. Exome sequencing identified three novel (c.1215T>A, c.554G>A, c.1525_1540dup) and one known (c.1522_1523delTA) mutations in WFS1. All mutations were predicted to cause stop codon leading to early termination of protein synthesis and complete loss-of-function. All patients were found to be homozygous for the change, with parents and other unaffected siblings being carriers.Conclusion:Our study expands the mutation spectrum of WSF1 mutations with three novel mutations. Homozygosity mapping may provide enrichment for molecular genetic analysis and early diagnosis of WS1 patients with incomplete phenotype, particularly in consanguineous pedigrees.