Cancer risks by sex and variant type in PTEN hamartoma tumor syndrome.

BACKGROUND: PTEN Hamartoma Tumor Syndrome (PHTS) is a rare syndrome with a broad phenotypic spectrum, including increased risks of breast (BC, 67%-78% at age 60 years), endometrial (EC, 19%-28%), and thyroid cancer (TC, 6%-38%). Current risks are likely overestimated due to ascertainment bias. We aimed to provide more accurate and personalized cancer risks. METHODS: This was a European, adult PHTS cohort study with data from medical files, registries, and/or questionnaires. Cancer risks and hazard ratios were assessed with Kaplan-Meier and Cox regression analyses, and standardized incidence ratios were calculated. Bias correction consisted of excluding cancer index cases and incident case analyses. RESULTS: A total of 455 patients were included, including 50.5% index cases, 372 with prospective follow-up (median 6 years, interquartile range = 3-10 years), and 159 of 281 females and 39 of 174 males with cancer. By age 60 years, PHTS-related cancer risk was higher in females (68.4% to 86.3%) than males (16.4% to 20.8%). Female BC risks ranged from 54.3% (95% confidence interval [CI] = 43.0% to 66.4%) to 75.8% (95% CI = 60.7% to 88.4%), with two- to threefold increased risks for PTEN truncating and approximately twofold for phosphatase domain variants. EC risks ranged from 6.4% (95% CI = 2.1% to 18.6%) to 22.1% (95% CI = 11.6% to 39.6%) and TC risks from 8.9% (95% CI = 5.1% to 15.3%) to 20.5% (95% CI = 11.3% to 35.4%). Colorectal cancer, renal cancer, and melanoma risks were each less than 10.0%. CONCLUSIONS: Females have a different BC risk depending on their PTEN germline variant. PHTS patients are predominantly at risk of BC (females), EC, and TC. This should be the main focus of surveillance. These lower, more unbiased and personalized risks provide guidance for optimized cancer risk management.

Serum soluble Fas ligand levels and peripheral blood lymphocyte subsets in patients with drug-induced maculopapular rashes, dress, and viral exanthemas

BACKGROUND: Fatty acid synthetase (Fas)/Fas ligand (FasL)-dependent apoptotic pathways have been reported as being involved in the pathogenesis of drug-induced maculopapular rashes. OBJECTIVE: We investigated serum soluble FasL (sFasL) levels and peripheral blood lymphocyte subtypes to discriminate maculopapular drug eruptions (MPDE) from viral exanthema (VE). Patients/methods: Children with confirmed MPDE (group I), VE (group II), and drug rashes with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS) (group III) were included. Serum sFasL levels and peripheral blood lymphocyte subtypes were analyzed in groups I-III on admission, and repeated twice (only once for group IV - controls). RESULTS: There were no significant serum soluble FasL level differences among the groups for all the samples. In the initial samples, CD19+ cell numbers in group II were significantly higher than in group IV, and the CD4+/CD8+ ratio was higher than groups I and IV. In the second samples, CD4+ and CD19+ cell numbers were significantly higher in group II than group I. In the final samples, CD4+ cell numbers in group II were significantly higher than group I and group III. CD19+ cells numbers in group III were significantly lower than the other groups for all samples. CONCLUSION: Serum sFasL levels were not found to be useful in discriminating viral exanthemas from other drug rashes. The significant differences between MPDE, VE, and DRESS were high CD4+ and CD19+ cell-count numbers in VE but low B-cell numbers in DRESS. This might be important for discriminating VE from DRESS, and the low B-cell count in early symptoms might be a useful predictor of DRESS development

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Serum soluble Fas ligand levels and peripheral blood lymphocyte subsets in patients with drug-induced maculopapular rashes, dress, and viral exanthemas.

BACKGROUND: Fatty acid synthetase (Fas)/Fas ligand (FasL)-dependent apoptotic pathways have been reported as being involved in the pathogenesis of drug-induced maculopapular rashes. OBJECTIVE: We investigated serum soluble FasL (sFasL) levels and peripheral blood lymphocyte subtypes to discriminate maculopapular drug eruptions (MPDE) from viral exanthema (VE). PATIENTS/METHODS: Children with confirmed MPDE (group I), VE (group II), and drug rashes with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS) (group III) were included. Serum sFasL levels and peripheral blood lymphocyte subtypes were analyzed in groups I-III on admission, and repeated twice (only once for group IV - controls). RESULTS: There were no significant serum soluble FasL level differences among the groups for all the samples. In the initial samples, CD19+ cell numbers in group II were significantly higher than in group IV, and the CD4+/CD8+ ratio was higher than groups I and IV. In the second samples, CD4+ and CD19+ cell numbers were significantly higher in group II than group I. In the final samples, CD4+ cell numbers in group II were significantly higher than group I and group III. CD19+ cells numbers in group III were significantly lower than the other groups for all samples. CONCLUSION: Serum sFasL levels were not found to be useful in discriminating viral exanthemas from other drug rashes. The significant differences between MPDE, VE, and DRESS were high CD4+ and CD19+ cell-count numbers in VE but low B-cell numbers in DRESS. This might be important for discriminating VE from DRESS, and the low B-cell count in early symptoms might be a useful predictor of DRESS development.

Does thromboprophylaxis cause bleeding after laparoscopic cholecystectomy?

OBJECTIVES: This study reports the results of a single center experience on the use of pharmacological venous thromboembolism (VTE) prophylaxis in laparoscopic cholecystectomy patients. BACKGROUND: The prevention of VTE is of crucial importance in surgical practice. However, the severity of thromboembolism risk and the necessity of thromboprophylaxis for laparoscopic cholecystectomy is still being debated. METHODS: The data of the patients, who underwent laparoscopic cholecystectomy for symptomatic cholelitiasis in a single center between the years 2005 and 2015 were analysed retrospectively for incidents of symptomatic VTE and bleeding complications. Fisher Exact Test was used to compare the outcomes of the patients who did and did not receive thromboprophylaxis. RESULTS: Of the 1485 patients who were included in the study, 307 (20.67 %) having a low VTE risk, did not receive any thromboprophylaxis; while 1178 (79.33 %) with a medium, high or a very high risk received VTE prophylaxis. A bleeding complication occurred in 14 (1.18 %) patients receiving prophylaxis and in 2 (0.65 %) patients not receiving prophylaxis (p = 0.548). No patients in this study experienced clinically symptomatic VTE. CONCLUSIONS: The findings of this study indicate that the selective use of thromboprophylaxis does not significantly increase the risk of bleeding after laparoscopic cholecystectomy and probably decreases the incidence of symptomatic thrombotic complications (Ref. 18) Keywords: laparoscopic cholecystectomy, bleeding, venous thromboemboly, prophylaxis, low molecular weight heparin.

Is the fourth port routinely required for laparoscopic cholecystectomy? Our three-port laparoscopic cholecystectomy experience.

BACKGROUND: There have been many changes in number and place of trocars that have been described, since the first laparoscopic cholecystectomy (LC), but, in fact, all authors agree that laparoscopic procedure is accepted as gold standard. However, four trocars use in standard laparoscopic cholecystectomy, it has been argued that the fourth port is not necessary for grasping fundus of gallbladder so as to expose Calot's triangle. The aim of this study is to establish the safety of three-trocar LC in symptomatic gallbladder disease and also to determine the ratio of technical requirements of the fourth trocar. METHODS: Between August 2010 and January 2016, 291 cases were operated in Kocaeli Derince Education and Research Hospital, department of general surgery for symptomatic gallbladder disease with three-port LC, and their records were examined retrospectively. RESULTS: Two hundred and twenty patients were female (75.6 %) and seventy one (24.4 %) were male. Two hundred and eighteen of two hundred and ninety-one cases (74.92 %) were operated with three- port LC in a secure way. In seventy-three cases (25.08 %), one more port was needed to use. Mean operative time was 33.76 ± 11:18 min. (15-90 min). In these cases, major complications, such as main bile duct injury or bile leakage, that may increase the mortality and morbidity, did not occur. Only in one case (0.34 %) postoperative bleeding was seen from the liver bed, which was required exploration. CONCLUSION: We concluded that in experienced hand, LC with three ports is safe and feasible technique if it is not endanger the course of the surgery.

Mechanisms of MicroRNA Deregulation and MicroRNA Targets in Gastric Cancer.

Gastric cancer is a genetically heterogeneous disease that causes cancer-related deaths worldwide. Although many studies on this disease have been performed, the molecular mechanisms of gastric tumorigenesis, invasion, and metastasis have still not been identified. MicroRNAs (miRNAs) are endogenously coded small RNA molecules, 18-25 nucleotides in length, that regulate gene expression at the post-transcriptional level. They are required for physiological activities in the cell, including development, proliferation, differentiation, and apoptosis. Research has now indicated their importance in carcinogenesis, with miRNA profiling revealing differences in the tumor and the normal tissue in several cancers. This difference in the expression pattern might lead to disrupted regulation of genes such as tumor suppressor genes and proto-oncogenes that are involved in cell cycle control, proliferative pathways, apoptosis, and metastasis in gastric carcinogenesis. Genes encoding miRNAs have been characterized as novel proto-oncogenes and tumor-suppressor genes based on findings that these miRNAs control malignant phenotypes. miRNA deregulation promotes cell-cycle progression, confers resistance to apoptosis, and enhances invasiveness and metastasis. Deregulated miRNAs affect the regulation of their target genes. Knowing the targets of miRNAs is of great importance for identifying the molecular mechanisms behind gastric carcinogenesis and forms the focus of this review.

Symmetrical drug-related intertriginous and flexural exanthema induced by two different antibiotics

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Safety of balloon pre-dilatation in the treatment of severe carotid artery stenosis.

AIM: To assess early outcome of predilatation prior stenting of severe carotid artery stenosis and to evaluate early major adverse cardiovascular and cerebral events (MACCE). PATIENTS AND METHODS: The study group consisted of 265 consecutive patients (200 males, 65 female, mean age 66.7 ± 8.6 years) in whom 275 percutaneous transluminal angioplasty (PTA) procedures of carotid arteries were performed. Staged carotid stenting was performed in patients with bilateral carotid stenosis. Neuroprotection with a distal protection device was used in all cases. The patients were divided into two groups: direct carotid stent implantation without previous pre-dilation was performed in 233 patients (direct stenting group) and predilatation was performed in 42 patients (predilatation group). Early events were recorded and analyzed subsequently. RESULTS: We treated 275 carotid stenoses and the stent was implanted in all patients. Ten patients (3.7%) were treated by staged carotid artery stenting (CAS) due to bilateral carotid artery disease. The technical success rate was 97.1%. During 1-month follow-up, the prevalence of primary endpoint was 2.18%. The prevalence of MACCE at 30 days was higher in the predilatation group (2.4% vs. 2.1%; p = 0.924). Also periprocedural rate of hypotension was higher in predilatation group (7.1% vs. 1.7%; p = 0.04). CONCLUSIONS: Balloon predilatation prior to stenting can be performed to treat severe carotid artery stenosis with acceptable periprocedural complication rate.

Elevated uric acid and functional mitral regurgitation in dilated cardiomyopathy.

BACKGROUND: Recent findings suggest that there is a close relationship between chronic heart failure and uric acid. AIMS: The aim of the study was to assess whether increased uric acid levels in patients with dilated cardiomyopathy might correlate with the degree of functional mitral regurgitation (MR). MATERIALS AND METHODS: Sixty two consecutive patients diagnosed with dilated cardiomyopathy were included in the study. The patients were classified according to severity of functional MR into two groups: mild-moderate functional MR (ERO < 0.2 cm2) and severe functional MR. RESULTS: The patients with severe functional MR had significantly higher serum uric acid levels compared to patients without severe functional MR (6.34 ± 1.61 mg/dL vs 5.43 ± 1.17 mg/dL respectively, p = 0.012). Furthermore, tenting area, an important predictor of functional MR severity, was moderately correlated with the serum uric acid levels (r = 0.351, p = 0.005). It was also shown that the serum uric acid concentrations were inversely correlated with left ventricular (LV) ejection fraction, and positively correlated with LV volumes. There was also a significant relation between the serum uric acid and left atrial volumes and also brain natriuretic peptide (BNP) levels. CONCLUSIONS: In conclusion, this study demonstrates that elevated serum uric acid levels in patients with dilated cardiomyopathy are correlated with the severity of functional MR and echocardiographic volume indices.

The reliability and validity of Turkish version of Childhood Asthma Control Test.

INTRODUCTION: The reliability and validity of Turkish version of Childhood Asthma Control Test (C-ACT). PURPOSE: The management of asthma is an important as well as difficult issue of physician's daily practice particularly in busy clinical settings. C-ACT was created to identify asthma control levels in children aged 4-11 years. Our aim was to evaluate the reliability, validity and responsiveness of C-ACT in a Turkish sample of children with asthma. METHOD: In this multicenter study, 368 children were enrolled. C-ACT was completed every month by parents and patients who were evaluated in 3 visits within 2 month intervals. At each visit, physicians interpret the control level and decided for the treatment step as established in GINA guidelines. RESULTS: The internal consistency reliability of the Turkish version of C-ACT (C-ACT1 to C-ACT5) was found to be 0.82, 0.83, 0.82, 0.82 and 0.80, respectively (reliability statistics, Cronbach's alpha). Test-retest reliability was 0.71. There was significant correlation between C-ACT and physician's assessment of asthma control at visit 1 (r = 0.65, P < 0.001). CONCLUSIONS: Turkish version of C-ACT is an accurate and reliable tool to evaluate asthma control in children aged 4-11 years. Its widespread use may facilitate appropriate assessment of asthma control and may lead to decrease the number of uncontrolled patients.

Lung tissue apoptosis in abdominal hypertension : Apoptosis and necrosis of lung tissue in abdominal hypertension.

OBJECTIVES: The aim of this study was to evaluate lung tissue histopathologic changes and the number of apoptosis with the increase of abdominal pressure. METHODS: The study rats were randomly assigned into the following five groups: a sham operated group and groups 1, 2, 3 and 4, in which the intra-abdominal pressure was increased to 11, 15, 18 and 22 mmHg for 60 min, respectively. Lungs were harvested for histopathologic changes and the tissue apoptotic analysis were carried out in a blinded manner. RESULTS: All of the data showed that the number of apoptotic cells and necrosis were increased in accordance with the pressure level. However, this increase was statistically significant, especially in groups 3 and 4 (18 and 22 mmHg, respectively; p < 0.05) when compared to the sham operated rats. There were no differences observed between groups 1 and 2 (11 and 15 mmHg, respectively) and the sham operated rats. There was also no difference between groups 1 and 2. There were findings of coagulation necrosis and the number of apoptotic cells linearly increased when the abdominal pressure was increased. The cut-off value was 15 mmHg. CONCLUSION: The available findings suggest that intra-abdominal pressure greater than 15 mmHg could irreversibly damage pulmonary cells and both coagulation necrosis parameters and the number of apoptosis increase in accordance with the pressure level.

ß-Catenin-independent noncanonical Wnt pathway might be induced in gastric cancers.

BACKGROUND/AIMS: Abnormal Wnt signaling is often observed in human cancers. Wnt5a is a representative Wnt ligand that can activate both ß-catenin-dependent canonical and ß-catenin-independent noncanonical Wnt pathways. However, the role of Wnt5a in carcinogenesis is controversial. This study was designed to understand whether Wnt5a in the Wnt pathway and its key downstream molecules such as MMP-7 and ß-catenin are involved in gastric cancers. METHODS: We analyzed the expressions of Wnt5a, MMP-7 and ß-catenin genes in 40 primary gastric normal and tumor biopsies by RT-PCR and the subcellular localization of ß-catenin by immunohistochemistry. RESULTS: Our results showed a specific combination of genes expressed significantly in the gastric tumor tissues: 65% of the tumor samples containing non-nuclear ß-catenin were Wnt5a-positive, 42.5% were MMP-7-positive, and 35% of the samples involved both. Interestingly, normal samples did not show any relevant coexpression of Wnt5a and MMP-7 in the ß-catenin-containing samples. CONCLUSIONS: These results suggest that the noncanonical Wnt pathway might be critically important in gastric carcinogenesis.

Synthesis, Raman, FT-IR, NMR spectroscopic characterization, antimicrobial activity, cytotoxicity and DNA binding of new mixed aza-oxo-thia macrocyclic compounds.

Series of new mixed aza-oxo-thia macrocyclic ligands 1,9(2,6)-ditriazina-2,8,10,16-tetraaza-3,7,11,15-tetraoxo-5,13-dithia-cyclohexadecaphan-1(4),9(4)-diphenyl (L(1)); 1,10(2,6)-ditri azina-2,9,11,18-tetraaza-3,8,12,17-tetraoxo-5,6,14,15-tetrathia-cyclooctadecaphan-1(4),10(4)-diphenyl (L(2)); 1,11(2,6)-ditriazina-2,10,12,20-tetraaza-3,9,13,19-tetraoxo-6,16-dithia-cyclocosa-phan-1(4),11(4)-diphenyl (L(3)); 1,12(2,6)-ditriazina-2,11,13,22-tetraaza-3,10,14,21-tetraoxo-6,7,17,18-tetrathia-cyclodocosaphan-1(4),12(4)-diphenyl (L(4)) were synthesised. The structural features of the compounds have been studied by elemental analyses, Mass, FT-Raman, FT-IR, (1)H and (13)C NMR spectroscopy. The antimicrobial activities of the ligands were evaluated using disk diffusion method in dimethyl sulfoxide (DMSO) as well as the minimal inhibitory concentration (MIC) dilution method, against several bacteria and yeast cultures. The obtained results from both methods were assessed in side-by-side comparison with commercial antibacterial and antifungal agents. In most cases, the compounds show strong antifungal activity in the comparison tests. Cytotoxic activities of the ligands against two different human cancer cell lines, stomach (23132/87) and lung (A549) were determined by MTT assay. DNA fragmentation assay tested cell lines were used to analyze the DNA ladder formation which is a characteristic of apoptotic cell death. The binding of the ligands with calf thymus DNA (CT-DNA) has also been investigated by absorption spectroscopy.

Indoor airborne fungal spores and home characteristics in asthmatic children from Edirne region of Turkey.

BACKGROUND: The contribution of indoor fungal exposure to childhood asthma is not completely clear. OBJECTIVE: To investigate airborne fungal flora within the homes of asthmatic and control children, and to assess the influence of housing characteristics regarding indoor fungi. METHODS: Forty-seven atopic asthmatic and 23 nonatopic control children were studied. Allergen sensitivity was determined by skin prick tests. A thorough assessment, using a questionnaire and inspection surveys, was carried out. Home visits were made between October 2000 and February 2001. Samples of airborne fungal spores were collected from four rooms by the "open Petri dish" method. Indoor temperature and humidity were measured. RESULTS: The total indoor fungal colony counts from the living rooms and bedrooms were significantly higher in the asthma group than in controls (p = .012 and p = .003, respectively). The most commonly isolated genus was Cladosporium. Twelve of the asthmatic patients (25.53 %) were found to be sensitive to fungal allergens. The factors found to be associated with indoor fungal growth in logistic regression were visible fungal patches in the bathrooms [(odds ratio (OR) = 5.75; 95 % CI 1.19 to 27.70)], and the age of the house [OR = 4.24; 95 % CI 1.34 to 13.45]. Total fungal colony numbers did not correlate with indoor temperature or humidity. CONCLUSION: Fungal colony numbers were higher in the homes of asthmatic children than in those of controls. Therefore, indoor fungal exposure may contribute to childhood asthma. Bathrooms were the main source of fungal propagules. Old houses were more prone to fungal growth.

Indoor airborne fungal spores and home characteristics in asthmatic children from Edirne region of Turkey

Background: The contribution of indoor fungal exposure to childhood asthma is not completely clear. Objective: To investigate airborne fungal flora within the homes of asthmatic and control children, and to assess the influence of housing characteristics regarding indoor fungi. Methods: Forty-seven atopic asthmatic and 23 nonatopic control children were studied. Allergen sensitivity was determined by skin prick tests. A thorough assessment, using a questionnaire and inspection surveys, was carried out. Home visits were made between October 2000 and February 2001. Samples of airborne fungal spores were collected from four rooms by the "open Petri dish" method. Indoor temperature and humidity were measured. Results: The total indoor fungal colony counts from the living rooms and bedrooms were significantly higher in the asthma group than in controls (p = .012 and p = .003, respectively). The most commonly isolated genus was Cladosporium. Twelve of the asthmatic patients (25.53 %) were found to be sensitive to fungal allergens. The factors found to be associated with indoor fungal growth in logistic regression were visible fungal patches in the bathrooms [(odds ratio (OR) = 5.75; 95 % CI 1.19 to 27.70)], and the age of the house [OR = 4.24; 95 % CI 1.34 to 13.45]. Total fungal colony numbers did not correlate with indoor temperature or humidity. Conclusion: Fungal colony numbers were higher in the homes of asthmatic children than in those of controls. Therefore, indoor fungal exposure may contribute to childhood asthma. Bathrooms were the main source of fungal propagules. Old houses were more prone to fungal growth (AU)

Historial: La contribución al asma infantil a causa de la exposición a hongos de interior no está totalmente clara. Objetivo: Intentamos investigar la flora de hongos que se encuentra en el aire dentro de los hogares de los niños asmáticos y los niños controlados, así como determinar la influencia de las características de la casa respecto a los hongos de interior. Métodos: Cuarenta y siete niños asmáticos y veintitrés niños controlados no alérgicos. La reacción alérgica se determinó mediante pruebas de alergia. Se llevó a cabo una evaluación exhaustiva utilizando un cuestionario y encuestas de inspección. Las visitas domiciliarias fueron realizadas entre octubre de 2000 y febrero de 2001. Las muestras de las esporas de hongos aerotransportadas fueron recogidas en cuatro habitaciones por el método de la "placa de Petri abierta". Se midió la temperatura y la humedad interior. Resultados: El número total de hongos de interior en las salas de estar y en los dormitorios era notablemente más elevado en el grupo de asmáticos que en el otro grupo (p = ,012 y p = ,003, respectivamente). El género aislado más común fue el Cladosporium. Doce de los pacientes asmáticos (25,53 por ciento) resultaron ser sensibles a los hongos. La regresión logística puso en evidencia que las manchas de hongos visibles en los cuartos de baño [(cociente de las probabilidades (O) = 5,75; 95 por ciento del ci 1,19 a 27,70)], y la antigüedad de la casa [O = 4,24; 95 por ciento del ci 1,34 a 13,45], estaban correlacionados con el crecimiento de los hongos de interior. El número total de hongos de la colonia no está relacionado con la temperatura o la humedad interior. Conclusión: El número de hongos de la colonia era más elevado en los hogares de niños asmáticos que en los controlados. Por lo tanto, la exposición a hongos de interior puede contribuir al desarrollo del asma infantil. Los cuartos de baño eran la fuente principal de propagación de hongos. Las casas viejas eran más propensas al crecimientote los hongos (AU)

Egg and milk allergy in asthmatic children: assessment by immulite allergy food panel, skin prick tests and double-blind placebo-controlled food challenges.

There is a perception that asthmatic symptoms may be worsoned by ingestion of certain foods. This study aimed to investigate whether ingestion of cow's milk or egg might induce respiratory symptoms in asthmatic children. Fifty asthmatic children aged 1.5 to 6 years old, with positive Immulite Food Panel FP5 test results were included in the study. Fifty healthy children within the same age group were accepted as control group. Total serum IgE levels were measured and skin prick tests for food allergens including milk and egg were performed. All of the subjects underwent oral, double-blind, placebo-controlled challenge with fresh egg and cow's milk powder. Two medical histories were confirmed by double-blind, placebo-controlled challenge in 9 patients (22.2%). Skin prick tests were positive in 9 patients (18%) with milk and 18 patients (36%) with egg antigen. Two children experienced wheezing, one after ingesting milk and the other after egg challenge (4%). In the control group no positive reactions were seen with egg or milk challenges. Our findings confirm that food allergy can elicit asthma in children, but its incidence is low, even with major allergens such as egg and milk. History, specific IgE determinations and skin prick tests are not reliable in diagnosing food reactions. Since any diet can cause rapid deficiencies in infancy, diet restrictions must not be applied, without performing double-blind, placebo-controlled challenge.