GA Genotype of the Arg280His Polymorphism on The XRCC1 Gene: Genetic Susceptibility Genotype in Differentiated Thyroid Carcinomas?

Differentiated thyroid carcinomas (DTC) are the most common form of endocrine malignancies. The role of genetic variations in the development of papillary thyroid carcinoma (PTC) is approximately 60.0-70.0%. The X-ray repair cross-complementing group 1 (XRCC1) protein has an important role in DNA repair mechanisms and genomic polymorphisms of XRCC1 gene affect the function of the protein. In the present case-control study, we aimed to compare the genotype frequency distributions of XRCC1 single nucleotide polymorphisms (SNPs) in terms of the presence of other risk factors (Hashimoto's thyroiditis, smoking, obesity, radiation exposure) in patients with thyroid nodules who had fine-needle aspiration biopsy (FNAB) and/or thyroid surgery due to thyroid cancer. The genotype frequency distributions of three common XRCC1 SNPs (Arg194Trp, Arg399Gln, Arg280His) were compared to those with DTC (n = 228), benign thyroid nodules (BTN, n = 100) and healthy controls (n = 93) in terms of certain pre defined risk factors such as the presence of Hashimoto's thyroiditis, smoking, obesity, a family history of thyroid cancer and radiation exposure. The frequency of the GA genotype of Arg280His in DTC cases was found to be higher than in those with BTN and the healthy control group (p <0.001). The DTC group had the lowest frequency of AA genotype of Arg280His (35.5%, p <0.001). Among those with a family history of thyroid cancer, 78.9% had a GA genotype and 21.1% had the AA genotype of Arg280His (p = 0.004). The Arg280His GA genotype was more common in DTC than in cancer-free controls. The GA genotype frequency was also high in DTC cases with a family history of thyroid cancer.

Surgical staging of low-risk Stage IA endometrioid endometrial cancers.

PURPOSE: Surgical staging in early endometrial cancer is not universally done and lymphadenectomy in early-stage disease is controversial. Aim of the present study was to evaluate surgical staging in patients with endometrioid histology, FIGO Stage IA endometrial cancer. MATERIALS AND METHODS: Eighty-seven patients with FIGO Stage IA, low-risk patients were included in the study. Staging surgery group included patients who had comprehensive surgical staging (hysterectomy, oophorectomy, and pelvic lymph node dissection with or without para-aortic lymph node dissection). Non-staging surgery group included patients who had hysterectomy, and bilateral oophorectomy with or without lymph node sampling. Two groups were compared for lymph node status, occult cervical involvement, other prognostic factors, and outcome were analyzed. RESULTS: In total 17.2% of patients were upstaged in final pathological examination; 12.9% in non-staging surgery group and 24.2% in staging surgery group. Upstaging was due to lymph node involvement (6%), cervical stromal invasion (13.7%), and myometrial invasion greater than 50% (1.1%). Median pelvic lymph node number was 23 and pelvic lymph node metastases was found in 3% of the patients. Median para-aortic lymph node number was 11.5 and there was one isolated para-aortic lymph node metastases (5.8%). CONCLUSION: Of the patients, 17.2% had stage migration. Until the issue is solved by future studies, surgical staging might be considered standard surgery for endometrial cancer.

Uterine tumors resembling ovarian sex cord tumors: a case report with adenomyosis and complex hyperplasia with atypia.

Uterine tumors resembling ovarian sex cord tumors (UTROSCTs) are very rare uterine neoplasms. They mostly behave in a benign fashion but cases were reported with extra-uterine spread. There are less than 50 cases reported in the literature so far according to the present authors' knowledge. We report a case of 45-year-old woman with UTROSCT concurrent with adenomyosis and complex hyperplasia with atypia of endometrium and her three-year follow up.

Clinical presentation of Von Hippel Lindau syndrome type 2B associated with VHL p.A149S mutation in a large Turkish family.

Von Hippel Lindau (VHL) syndrome is an autosomal dominant disorder characterized by benign and malignant tumors. This study presents the clinical and genetic features of VHL syndrome in a Turkish family. For the diagnosis of pheochromocytoma-related diseases, 49 family members from three generations were evaluated between March 2008 and January 2013. Family members were examined to identify components of pheochromocytoma-related genetic syndromes through physical examination, laboratory tests, and imaging methods. For the causative mutation, sequence analysis of VHL gene was performed. Nine patients were diagnosed with pheochromocytoma. Lumbal spinal hemangioblastoma and pancreatic neuroendocrine tumor without pheochromocytoma were detected in one patient. In patients with pheochromocytoma, additional tumors, such as retinal angioma, renal cell carcinoma, pancreatic serous cystadenoma, and pancreatic neuroendocrine tumors were detected. All patients were diagnosed as VHL syndrome type 2B. Sequence analysis of VHL gene revealed heterozygous p.A149S mutation in all symptomatic patients and in seven of the asymptomatic family members. This is the first study that identified VHL p.A149S mutation in a Turkish family with VHL syndrome. However, VHL p.A149S mutation was identified in an American family by Atuk et al. (J Clin Endocrinol Metab, 83:117-120, 14) and the family was defined as VHL type 2A. In our study, the family was identified as VHL type 2B. This variability in the phenotypic features suggests that further studies are required to beter assess the genotype-phenotype correlation in such cases.

Obstructive sleep apnea syndrome and its association with vitamin D deficiency.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is a widespread disorder characterized by recurrent, partial or complete episodes of apnea due to upper airway tract obstruction during sleeping period. Deficiency of vitamin D has roles in development of many diseases. Association between presence and severity of OSAS and vitamin D has recently gained research interest. AIM: The aim of our study was to investigate the association between serum 25-hydroxy [25 (OH)] vitamin D levels and severity of disease in patients with OSAS. MATERIAL AND METHODS: One hundred and fifty OSAS patients (50 patients with mild, 50 with moderate, 50 with severe OSAS) who were diagnosed by polysomnography (PSG) and 32 non-OSAS controls who were referred to the Health Ministry Ankara Numune Training and Research Hospital, Endocrinology and Metabolism Department, from January 2010 to May 2011 were included in the study. Serum 25(OH)D, PTH, calcium and phosphorus levels were evaluated in all the patients who were recruited to the study. RESULTS: There was no statistically significant difference in serum 25(OH)D levels between OSAS and controls (p>0.05). However, in subgroup analysis of OSAS, we found that the patients with severe OSAS had significantly lower levels of 25(OH)D as compared with other groups (p=0.003). Also, the number of patients with serum 25(OH)D deficiency (<10 µg/dl) were higher in OSAS group than in controls (p<0.05). CONCLUSIONS: We found that when the severity of OSAS increases, 25(OH)D deficiency becomes more pronounced.

Humoral immune response against 38-kDa and 16-kDa mycobacterial antigens in tuberculosis.

Several ELISA tests based on mycobacterial antigens have been used for the rapid diagnosis of tuberculosis (TB), although demonstration of Mycobacterium tuberculosis in a smear or culture is the most reliable method. In the present study, the diagnostic value of 16-kDa and 38-kDa mycobacterial antigens was investigated in patients who were diagnosed with tuberculosis by clinical and/or bacteriological findings in Turkey. The PATHOZYME-TB Complex Plus commercial ELISA kit was used for measuring immunoglobulin G against 38-kDa and 16-kDa recombinant antigens. Humoral immune response was analysed in a group of 179 TB patients (143 smear-positive, 19 smear-negative, eight lymphadenitis and nine pleuritis), 15 inactive TB cases and in control groups consisting of 40 healthy volunteers and 20 subjects with pulmonary diseases other than TB. The sensitivity, specifity, positive predictive value and negative predictive value of the test were determined at 52.5%, 93.3%, 95.9% and 39.7%, respectively in TB cases. Antibodies were detected at above cut-off level in three (20%) out of 15 subjects with inactive TB. In conclusion, the ELISA test has a very good specifity and an acceptable sensitivity and positive predictive value. It is thought that it could be used in combination with other methods to increase diagnostic accuracy, especially for culture-negative tuberculosis cases, which are difficult to diagnose.

Which anesthetic agent alters the hemodynamic status during pediatric catheterization? Comparison of propofol versus ketamine.

OBJECTIVE: To compare the effects of propofol and ketamine on systemic and pulmonary circulations in pediatric patients scheduled for elective cardiac catheterization. DESIGN: Prospective, randomized, and blinded. SETTING: University hospital. PARTICIPANTS: Children (n = 41) undergoing cardiac catheterization. INTERVENTIONS: All children were premedicated with oral midazolam 60 minutes before the procedure. Patients were separated into 3 groups according to shunts diagnosed by transthoracic echocardiography before the catheterization procedure: patients without cardiac shunt (Group I, n = 11), left-to-right shunt (Group II, n = 12), and right-to-left shunt (Group III, n = 18). A continuous infusion of propofol (100-200 microg/kg/min) or ketamine (50-75 microg/kg/min) was randomly started in all groups to obtain immobility during the procedure. Hemodynamic data, including systemic venous, pulmonary artery and vein, aortic saturations and pressures, were recorded; Qp/Qs were calculated. The same set of data was recorded before discontinuation of infusions at the end of the procedure. MEASUREMENTS AND MAIN RESULTS: After the propofol administration, in all 3 patient groups propofol infusion was associated with significant decreases in systemic mean arterial pressure. In groups with cardiac shunts (Group II and III), propofol infusion significantly decreased systemic vascular resistance and increased systemic blood flow, whereas pulmonary vascular resistance and pulmonary blood flow did not change significantly. These changes resulted in decreased left-to-right shunting and increased right-to-left shunting; the pulmonary-to-systemic flow ratio decreased significantly. On the other hand, after ketamine infusion, systemic mean arterial pressure increased significantly in all patient groups, but pulmonary mean arterial pressure, systemic vascular resistance, and pulmonary vascular resistance were unchanged. CONCLUSION: In children with cardiac shunting, the principal hemodynamic effect of propofol is a decrease in systemic vascular resistance. In children with intracardiac shunting, this results in an increase in right-to-left shunting and a decrease in the ratio of pulmonary to systemic blood flow, which may lead to arterial desaturation. Ketamine did not produce these changes. The authors suggested that during cardiac catheterization in children, both the anesthesiologists and cardiologists need to know that anesthetic agents can significantly alter the hemodynamic status in children with complex congenital heart defects and affect the results of hemodynamic calculations that are important for decision-making and treatment of these patients.

Prevention of intraabdominal adhesions produced by polypropylene mesh.

Polypropylene mesh (PPM) is widely used in ventral hernia repair, however is also associated with visceral adhesions when the mesh is exposed to intraabdominal organs. In this study, a composite mesh [ePTFE (expanded polytetrafluoroehylene) + PPM] and sodium hyaluronate/carboxymethyl cellulose (NaHA/CMC) membrane laid under PPM are evaluated in terms of adhesion formation in a rat model of ventral hernia repair. In this experimental study, a 2 x 1 cm of peritoneum and underlying muscle defect was created at the right side of the anterior abdominal wall of 37 male Wistar albino rats. These defects were repaired with 2.5 x 2 cm PPM in group 1 (n = 13), with composite mesh in group 2 (n = 12) and with PPM+NaHA/CMC in group 3 (n = 12). Rats were sacrificed after 14 days and the prosthetic materials were examined for the calculation of surface area percentage covered by adhesions, for organ involvement in the adhesions and for histological evaluation. There was a reduction in the adhesion-covered area in group 2 and group 3. Organ involvement was predominantly seen in group 1. Neoperitoneum was perfect in group 2. Fibrosis and inflammation were higher in group 1. All groups showed adhesiogenic potential to some extent. This potential was maximum with PPM. Both ePTFE and NaHA/CMC displayed similar effects in preventing adhesion formation.

Regulation of Na/K-ATPase gene expression by thyroid hormone and hyperkalemia in the heart.

Hypothermic hyperkalemic circulatory arrest has been widely used for myocardial protection during heart surgery. Recent data showed that administration of triiodo-L-thyronine (T3) postoperatively enhanced ventricular function. The effect of hyperkalemic arrest in conjunction with thyroid hormone on the plasma membrane enzyme sodium/potassium-adenosine triphosphatase (Na/K-ATPase), was determined in cultured neonatal rat atrial and ventricular myocytes. Exposure of ventricular myocytes to hyperkalemic medium (50 mM KCl) in the absence of T3 increased expression of the Na/K-ATPase catalytic subunit mRNAs, alpha1 and alpha3 isoforms, by 1.9- and 1.5-fold, respectively (p<0.01), which were accompanied by similar increases (1.4- and 1.8-fold) in protein content. Addition of T3 to the hyperkalemic cultures attenuated these increases in Na/K-ATPase mRNA isoforms to levels of expression observed in cells treated with T3 (10(-8) M) alone. Similarly, expression of the alpha1 mRNA isoform in atrial myocytes was increased (p<0.05) by hyperkalemic conditions, and T3 treatment attenuated this effect. In contrast, although expression of the Na/K-ATPase beta1 mRNA in both atrial and ventricular myocytes was significantly increased by hyperkalemia, addition of T3 did not prevent the hyperkalemic response, and in atrial myocytes T3 significantly increased beta1 mRNA expression 1.8-fold. These results show that expression of cardiac Na/K-ATPase is regulated by T3 and hyperkalemia in an isoform and chamber specific manner, and suggest that use of hyperkalemic cardioplegia during heart surgery may alter plasma membrane ion function.

Ethylene provides positional information on cortical cell division but is not involved in Nod factor-induced root hair tip growth in Rhizobium-legume interaction.

Nod factors secreted by Rhizobium leguminosarum bv. viciae induce root hair deformation, involving a reinitiation of tip growth, and the formation of nodule primordia in Vicia sativa (vetch). Ethylene is a potent inhibitor of cortical cell division, an effect that can be counteracted by applying silver ions (Ag+) or aminoethoxy-vinylglycine (AVG). In contrast to the inhibitory effect on cortical cell division, ethylene promotes the formation of root hairs (which involves tip growth) in the root epidermis of Arabidopsis. We investigate the possible paradox concerning the action of ethylene, putatively promoting Nod factor induced tip growth whilst, at the same time, inhibiting cortical cell division. We show, by using the ethylene inhibitors AVG and Ag+, that ethylene has no role in the reinitiation of root hair tip growth induced by Nod factors (root hair deformation) in vetch. However, root hair formation is controlled, at least in part, by ethylene. Furthermore, we show that ACC oxidase, which catalizes the last step in ethylene biosynthesis, is expressed in the cell layers opposite the phloem in that part of the root where nodule primordia are induced upon inoculation with Rhizobium. Therefore, we test whether endogenously produced ethylene provides positional information controlling the site where nodule primordia are formed by determining the position of nodules formed on pea roots grown in the presence of AVG or Ag+.