The Anti-Inflammatory and Antioxidant Effects of Propofol and Sevoflurane in Children With Cyanotic Congenital Heart Disease.

OBJECTIVE: The authors aimed to compare the anti-inflammatory and antioxidant effects of propofol and sevoflurane in children with cyanotic congenital heart disease (CCHD) undergoing cardiac surgery with cardiopulmonary bypass. DESIGN: Prospective, randomized, double-blind study. SETTING: Single center, university hospital. PARTICIPANTS: Children ages 1-10 years with CCHD undergoing elective cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Children were randomized to receive general anesthesia with either sevoflurane (group S) or propofol (group P). Systemic inflammatory response syndrome (SIRS) occurrence was assessed at the end of the surgery and at the sixth, 12th, and 24th postoperative hours. Blood samples were obtained at 4 times: after anesthesia induction (T0), after release of the aortic cross-clamp (T1), at the end of the surgery (T2), and at the postoperative 24th hour (T3). The serum levels of interleukin 6 and tumor necrosis factor alpha, and the total antioxidant status (TAS) and total oxidant status, were analyzed. RESULTS: SIRS was more common in group S than in group P at all times (p = 0.020, p = 0.036, p = 0.004, p = 0.008). There were no significant differences between the groups in the mean tumor necrosis factor alpha and interleukin 6 levels at any time. The TAS level at T2 was higher in group P than group S (p = 0.036). The serum TAS level increased at T2 compared with T0 in group P, but it decreased in group S (p = 0.041). CONCLUSION: The results showed that propofol provided a greater antioxidant effect and reduced SIRS postoperatively more than sevoflurane in children with CCHD undergoing cardiac surgery.

Role of calcium metabolism in ADHD: The relationship between parathyroid hormone and ADHD symptom severity.

Background: Vitamin D has been found to be associated with the pathogenesis of attention deficit hyperactivity disorder (ADHD). However, the potential role of parathyroid hormone (PTH) is still unclear. Aim: We aimed to investigate the association between calcium metabolism and ADHD symptomatology. Methods: We included 106 participants aged between 7 and 13 years old (51 ADHD patients, mean age: 9.54 ± 1.77, 55 healthy controls mean age: 9.97 ± 0.94) to this study. K-SADS-PL and Conners' Parent/Teacher Rating Scales, Stroop Test were performed. Blood samples to measure serum levels of Vitamin D, PTH, calcium (Ca), magnesium (Mg), phosphorus (P), and alkaline phosphatase (ALP) were collected in the spring (March-April-May) to prevent seasonal variability. Results: PTH, P, and ALP values were significantly lower and Vitamin D, Ca, and Mg values were significantly higher in the ADHD group (P < 0.05, for all). Both groups had Vitamin D deficiency. Control group has lower Vitamin D levels than the ADHD group (respectively; 17.66 ± 9.07, 21.99 ± 10.99, P < 0.05). There was a negative correlation between PTH and CTRS hyperactivity, CGI-RI and CGI-EL sub-scores, CGI-Total, DSM-IV-Inattention, DSM-IV Hyperactivity/Impulsivity, DSM-IV-Total scores (P < 0.05, for all). Conclusions: We found lower PTH levels in ADHD patients and a strong and negative correlation between PTH and symptom severity. Future studies are needed to clarify if these findings are due to the key role of PTH in ADHD pathology or PTH's function in activating vitamin D.

Utilization of biological variation data in the interpretation of laboratory test results - survey about clinicians' opinion and knowledge.

INTRODUCTION: To interpret test results correctly, understanding of the variations that affect test results is essential. The aim of this study is: 1) to evaluate the clinicians' knowledge and opinion concerning biological variation (BV), and 2) to investigate if clinicians use BV in the interpretation of test results. MATERIALS AND METHODS: This study uses a questionnaire comprising open-ended and close-ended questions. Questions were selected from the real-life numerical examples of interpretation of test results, the knowledge about main sources of variations in laboratories and the opinion of clinicians on BV. A total of 399 clinicians were interviewed, and the answers were evaluated using a scoring system ranked from A (clinician has the highest level of knowledge and the ability of using BV data) to D (clinician has no knowledge about variations in laboratory). The results were presented as number (N) and percentage (%). RESULTS: Altogether, 60.4% of clinicians have knowledge of pre-analytical and analytical variations; but only 3.5% of them have knowledge related to BV. The number of clinicians using BV data or reference change value (RCV) to interpret measurements results was zero, while 79.4% of clinicians accepted that the difference between two measurements results located within the reference interval may be significant. CONCLUSIONS: Clinicians do not use BV data or tools derived from BV such as RCV to interpret test results. It is recommended that BV should be included in the medical school curriculum, and clinicians should be encouraged to use BV data for safe and valid interpretation of test results.

The Evaluation of Killer Cell Immunoglobulin-Like Receptor Gene Polymorphism in Glioblastoma Patients.

AIM: To assess the distribution of genetic polymorphisms of killer cell immunoglobulin-like receptors (KIRs) to predict the clinical course of glioblastoma, report on the genetic mechanisms, and provide guidance on potential therapeutic methods. MATERIAL AND METHODS: Our study included 31 adult patients who were admitted to the Department of Neurosurgery at our institution and diagnosed with glioblastoma between October 2013 and January 2014 together with 50 control subjects. RESULTS: The mean age of the patients was 53.5 vs. 53.9 years, respectively, and the gender distribution (male/female: 64.5/35.5% vs. 64/36%, respectively) was comparable among patients and controls (p > 0.05). Sixteen different KIR genes including inhibitory, activating, and pseudogenes were investigated for each sample, and the framework genes including KIR2DL4, 3DL2, 3DL3, and 3DP1 were present in all patients and controls. In addition, the inhibitory KIR genes and the 2DL3 gene were significantly more common in patients compared to controls (p < 0.05). CONCLUSION: This study demonstrated that the inhibitory KIR gene 2DL3 has a predisposition for glioblastoma. Identifying the potential link between glioblastoma cells and immune system genetics is critical in predicting familial predisposition and early diagnosis. In addition, this clue may be a key factor in developing post-surgery individual immunotherapy models in the future.

Early propranolol treatment ameliorates endothelial dysfunction in experimental septic lung.

BACKGROUND: Recent reports have indicated an improved prognosis in sepsis with ß-blocker agents; however, the underlying action mechanism is still under debate. OBJECTIVES: The aim of this study was to investigate the potential effect of propranolol on endothelial dysfunction in septic rats. MATERIAL AND METHODS: The cecal ligation and puncture model (CLP) was used to generate sepsis. Adult male Wistar-Albino rats were divided into 4 groups: group 1 was a sham group, group 2 received sterile saline, group 3 received 10 mg/kg of propranolol 3 days before the intervention, and group 4 received 10 mg/kg of propranolol 30 min after CLP. Six rats from each group were sacrificed 24 h postoperatively. The remaining rats were followed for survival. We have also evaluated the effects on systemic inflammation, coagulation and the lung tissue with immunohistochemical and electron microscopic evaluation. RESULTS: Serum tumor necrosis factor alpha (TNF-α) and plasminogen activator inhibitor-1 (PAI-1) levels, as well as tissue TNF-α scores were elevated in septic rats. Electron microscopic examination of the lung tissue showed endothelial dysfunction in the sepsis group. Pretreatment significantly improved survival. Moreover, pre-treatment altered serum vascular endothelial growth factor receptor-1 (VEGFR-1) levels and post-treatment reduced serum PAI-1 and VEGFR-1 levels. In both the preand post-treatment groups, electron microscopic examination revealed improvement of the destroyed lung endothelium and showed only mild alterations in the cytoplasmic organelles, especially in the mitochondria of the endothelial cells. CONCLUSIONS: These results suggest that the improved outcome with ß-blockers in sepsis may be due to the ameliorated endothelial dysfunction. Further studies focusing on the potential effect of ß-blockers on the endothelium may lead to a better understanding of sepsis.

The frequency of diastolic dysfunction in patients with sarcoidosis and it's relationship with HLA DRB1* alleles.

BACKGROUND: Impaired systolic function is common in sarcoidosis however the frequency of diastolic dysfunction (DD) and it's possible genetic basis has not been fully elucidated yet. The aim of this study is to evaluate the frequency of left ventricular DD(LVDD) and right ventricular DD(RVDD) and it's possible relationship between Human Leukocyte Antigen(HLA)-DRB1* alleles in patients with sarcoidosis. METHODS: Seventy seven patients (51 females, mean age 41.1±8.2yrs) without known sarcoid related or any other structured heart disease and 77 healthy controls with a similar age and gender (38.7±7.8yrs,51 females) were included in the case control study. DD was diagnosed with echocardiography. RVDD was defined as early(E)/late(A) ratio<1 or >2 on tricuspit valve. LVDD was defined as E/A ratio<1 or >2 on mitral valve, with isovolumetric relaxation time(IVRT)>90 miliseconds(msn) or deceleration rate of early diastolic flow(Edec)>220msn respectively. All patients were HLAtyped with the Sequence Specific Oligonucleotide Probe(SSOP) method. RESULTS: The frequencies of LVDDs and RVDDs were significantly higher in sarcoidosis patients than the controls (26.0% vs. 2.6% for LVDD; and 42.9% vs. 18.2% for RVDD)(p<0.05). No significant difference was found in patients according to the presence of RVDD and LVDD in terms of age, gender or respiratory function test parameters. Although the frequency of HLA DRB1* alleles were comparable among patients with RVDD, HLA DRB1*14 alleles were more frequent in patients with LVDD. CONCLUSIONS: Biventricular DD is common in patients with sarcoidosis without manifest cardiac involvement. HLA DRB1*14 allele seems to be related with LVDD in this study population.

Early prediction of sarcoidosis prognosis with HLA typing: a 5 year follow-up study.

Background: A wide range of HLA-DR alleles have been associated with sarcoidosis either in terms of disease phenotype or extra pulmonary involvement, however the effect on non-resolution in different ethnic groups is not fully understood. The aim of this study was to investigate whether disease characterics and HLA-DRB1 alleles may early reflect non resolution in sarcoidosis. Methods: 91 patients who were diagnosed in Cukurova University Faculty of Medicine Department of Chest Diseases between 1993-2012 and were followed up until June 2017 were included in the study. All patients underwent HLA analysis by the Sequence Specific Oligonucleotide Prob (SSOP) method. Fifteen of them were excluded from the study group due to lost of follow-up (n=6) and not yet passed 5 years since diagnosis (n=9). Complete resolution at 5th year was defined according to the predefined standard criteria (ACCESS). Results: The resolution rate was 51.3%. The HLA-DRB1*14 allele was significantly higher in patients without resolution (11.8 vs 1.3%)(p=0.006). According to multivariate logistic regression analysis the independent risk factors of non resolution were female gender (OR: 12.6; 95%CI: 2.1-74.9, p=0.005), HLA DRB1*14 allele (OR:51.9; 95%CI: 3.6-735.8, p=0.000), baseline TLCO<75%(predicted) (OR:3.8; 95%CI: 1.1-13.7, p=0.028), extra-pulmonary involvement (OR:3.7; 95%CI: 1.0-13.1, p=0.038) and advanced stage at baseline (OR: 8.3; 95%CI: 1.9-35.4, p=0.001). Conclusions: HLA-DRB1*14 alleles, lower baseline TLCO, advanced stage, female gender or the presence of extra-pulmonary involvement could predict long term non-resolution in sarcoidosis. Early prediction of long term prognosis may affect treatment decisions and avoid further deterioration in these patient groups. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 184-191).

Biological variations of some analytes in renal posttransplant patients: a different way to assess routine parameters.

BACKGROUND: Biological variation (BV) data of analytes have been used to evaluate the significant changes in serial results (reference change value, RCV) of healthy individuals in clinical laboratories. However, BV data of healthy subjects may not be identical to the analytes of patients with ongoing clinical condition. The aim of this study was to calculate intra-(CVw) (coefficient of variation for intra-individual BV) and inter-individual (CVg) BV, index of individuality, and RCV of nine serum analytes of renal posttransplant patients. METHODS: Six serum specimens were obtained in an interval of two months in a one-year period from 70 transplant patients who had been stable for three years. Each time creatinine, uric acid, urea, sodium, potassium, calcium, inorganic phosphate, total protein, and albumin of these patients were analyzed with an integrated clinical chemistry/immunoassay auto-analyzer. ANOVA tests were used to calculate the variations. Results were compared with the data of healthy subjects obtained from BV database. RESULTS: CVw of all nine analytes of the renal transplant patients were higher than the healthy subjects. RCVs of these analytes were calculated as 14.5% for creatinine, 16.5% for urea, 13.7% for urate, 12.57% for albumin, 8.26% for total protein, 3.25% for sodium, 12.81% for potassium, 5.88% for calcium, and 21.57% for inorganic phosphate. CONCLUSION: RCV concept for predicting the clinical status in posttransplant population represents an optimization of laboratory reporting and could be a valuable tool for clinical decision.

Evaluation of KIR genes in recurrent miscarriage.

PURPOSE: Natural killer (NK) cells express killer immunoglobulin-like receptors (KIRs) which recognize HLA class I molecules on trophoblasts. KIRs could either activate NK cells or inhibit them to produce soluble factors necessary for the maintenance of pregnancy, thus they are suspected of being involved in the causes of recurrent miscarriage. The aim of this study was to evaluate whether there is any possible association between KIR genes, genotypes and recurrent miscarriage. METHODS: The present study was carried out on 40 women who had unexplained recurrent miscarriage and 90 controls. Sequence-specific oligonucleotide probes analysis were used to investigate 16 KIR genes. All data were statistically analyzed by Fisher Exact Test. RESULTS: The rate of Bx genotypes that consists elevated number of activating KIR genes was significantly higher (p = 0.014) in women with recurrent miscarriage when compared with the control group. Additionally, the frequency of AA genotype (AA1) of the subjects in the study group was significantly lower than the frequency of the subjects in the control group (p = 0,014). Furthermore, there were no statistically significant differences in the frequencies of the individual KIR genes between women with recurrent miscarriage and the control group. CONCLUSIONS: Inclined balance of KIRs toward an activating state in NK cells may contribute to recurrent miscarriage.

Killer cell immunoglobulin-like receptor genes in patients with breast cancer.

Killer cell immunoglobulin-like receptors (KIRs) contribute to the pathogenesis of diverse kind of diseases. Previous studies have shown associations between KIR genes, their ligands and either protection or susceptibility to leukemias or virally associated solid tumors. However, the possible roles of KIR gene polymorphisms in the development of breast cancer remain largely unknown. To investigate the association of KIR gene polymorphisms with breast cancer, we carried out the present study on 33 breast cancer patients and 77 healthy controls by means of sequence-specific oligonucleotide probes analysis, and then all data were statistically analyzed by Fisher exact test. Our results showed that the frame genes KIR2DL4, 3DL2, 3DL3, and 3DP1 were found in all patients and all controls. The rate of activating KIR2DS1 was much higher in patients with breast cancer than that in healthy controls (P = 0.032) while the allelic types of activating 2DS4 (2DS4 003/4/6/7) were lower in patients with breast cancer compared with healthy controls (P = 0.028). Additionally, there was a statistically significant negative correlation between 2DL1 genes and breast cancer development (P = 0.025). In conclusion, this study suggests that the activating KIR2DS1 may trigger breast cancer development, while 2DL1 gene and 2DS4 003/4/6/7 alleles are possibly protectors for breast cancer.

HLA class-II allele frequencies in Turkish breast cancer patients.

Class-II human leukocyte antigens (HLA) present tumor antigenic peptides on the cell surface in order to be recognized by T lymphocytes. Thereby, these molecules can play an important role in the immune response to breast cancer tumor antigens. The aim of this study was to determine the relation between breast cancer and HLA class-II alleles in Turkey. The study groups consisted of 69 breast cancer patients and 45 healthy controls. Typing of HLA-DRB1 and HLA-DQB1 from DNA samples was performed by Sequence Specific Oligonucletide Hybridisation. Significant negative correlations were observed between HLA-DRB1 03 and HLA-DQB1 02 alleles and breast cancer (p1 = 0.019; p2 = 0.019) and also between HLA-DQB1 02 allele and postmenopausal breast cancer (P = 0.022) and c-erb-B2 positivity (P = 0.038). Furthermore, there was a significant positive correlation between HLA-DRB1 13 and HLA-DQB1 06 alleles and progesteron receptor positivity (p1 = 0.012; p2 = 0.001); and a significant negative correlation between HLA-DQB1 03 allele and progesteron receptor positivity (P = 0.009) in breast cancer. Additionally, another significant positive correlation was seen between HLA-DRB1 04 allele and c-erb-B2 positivity (P = 0.036). As a result, while HLA-DRB1 03, HLA-DQB1 02, HLA-DRB1 13, and HLA-DQB1 06 alleles were found to be involved in protectiveness against breast cancer and good prognosis; HLA-DQB1 03 and HLA-DRB1 04 alleles were found to be involved in poor prognosis. In conclusion, by determining allele types showing predisposition to breast cancer, a systematical screening and follow up systems can be developed for patients who are at high risk.

Diversity of killer cell immunoglobulin-like receptor genes in Southern Turkey.

Killer cell immunoglobulin-like receptors (KIRs) are a family of inhibitory and activating receptors expressed by natural killer (NK) cells and regulate NK cells' activity. KIR genes are highly polymorphic markers, characterized by a wide diversity, and can therefore be considered as good population genetic markers. The aim of this study was to determine KIR gene frequencies, ratios of haplotypes and genotypes in Southern Turkey and also to compare the data with other worldwide populations studied previously. The study group consisted of 200 non-related individuals from Southern Turkey. The percentage of each KIR gene in the population group was determined by direct counting. Differences between populations in the distribution of each KIR gene and genotype profile were estimated by two-tailed Fisher Exact test. The most frequent non-framework KIR genes detected in Southern Turkey population were: KIR 2DL1 (97%), KIR 3DL1 (91%), KIR 2DS4 (92%) and the pseudogene 2DP1 (96%). Fourty different genotypes were found in 200 subjects and AA1 genotype was the most frequent (27%). Among 40 different genotypes, ten of these were described for the first time in this study and were added to the database ( http://www.allelefrequencies.net ) numerized as genotype ID from 400 to 409. Gene frequencies and found genotypes demonstrated similarity of Southern Turkey's KIR repertoire with the KIR repertoires of Middle East and European population. High variability seen in KIR genome in this region is thought to be formed as a result of migration and settlement of different civilizations in this region and heterogenity formed in time.

Vacuum-assisted closure therapy leads to an increase in plasma fibronectin level.

An extensive research has been performed to investigate the mechanisms of action by which the application of subatmospheric pressure to wounds increases the rate of healing. Increased blood flow with vacuum-assisted closure (VAC) use is the most popular aspect. Fibronectin, which is an adhesion molecule, has several functional domains mediating chemotaxis, adhesion and migration. This is thereby involved in differentiation, proliferation, inflammation and thus in wound healing. In this study, plasma fibronectin levels were measured before and after VAC in patients with wounds. The results showed that there was an increase in pre- and post-VAC levels of plasma fibronectin. This statistically significant increase could be another explanation of how VAC therapy promotes wound healing.

The role of apoptosis in traumatic versus nontraumatic nasal septal cartilage.

BACKGROUND: Nasal surgery is occasionally performed to correct traumatic nasal deformity. Septal cartilage is the main tissue to be corrected and is a graft source when needed. A risk in engrafting with cartilage is the possibility of resorption as a result of either necrosis or apoptosis. The authors evaluated the rate of apoptosis in deviated and straight cartilage to investigate the cause of resorption of cartilage tissue. METHODS: Twenty-five patients with traumatic nasal septum deviation (group I) and 13 patients with nontraumatic nasal septum deviation (group II) were prospectively enrolled. After correction of the deviation, two small samples of cartilage were harvested, one from the deviated site (group Ia or IIa) and the other from the straight site (group Ib or IIb), immediately frozen at -70 masculineC, and evaluated for apoptosis using DNA agarose gel electrophoresis. RESULTS: Apoptosis was detected in 14 (56 percent) of the deviated and two (8 percent) of the straight cartilage samples in traumatic patients, whereas it was detected in only one deviated sample (7.7 percent) and none of the straight samples in nontraumatic patients. The apoptosis rates in group Ia were statistically significant when compared with groups Ib (p = 0.0007) and IIa (p = 0.0007). CONCLUSIONS: The present study demonstrates that apoptosis occurs in traumatized nasal septal cartilage. Apoptosis might be the factor leading to cartilage resorption, weakness, and warping when used as a graft. Thus, cartilage grafting materials should be taken from the nontraumatized portion of the septum and should not be traumatized either during harvesting or before placement.

The frequency of UDP-glucuronosyltransferase 1A1 promoter region (TA)7 polymorphism in newborns and it's relation with jaundice.

Increased bilirubin formation and decreased bilirubin conjugation play an important role in the pathogenesis of the newborn jaundice. Although physiologic jaundice is seen in most of the newborns, there are many risk factors that affect the severity and duration of hyperbilirubinemia. The latest studies showed that the frequency and severity of neonatal jaundice have been increased when mutations of the gene coding UDP-glucuronosyltransferase(UGT)1A1 coexist with other risk factors. Healthy term newborns weighing over 2500 g. were included in this study. The patient group consisted of 107 newborns either with total bilirubin level over 15 mg dl(-1) within 7 days or 5 mg dl(-1) after 15 days of age. The control group consisted of 55 newborns with bilirubin levels in physiological ranges. We investigated the frequency of promoter region [thymine-adenine(TA)]7 polymorphism in UGT1A1 gene. Factors which might cause pathologic and prolonged jaundice with coexisting polymorphism were also investigated. UGT1A1 6/7 genotype was found to be 11% in patient group and 13% in the control group. The difference between patient and control groups was not statistically significant. (TA)7 allele frequency was 0.069 and it is concluded that UGT1A1 promoter region polymorphism was not a risk factor for neonatal jaundice.

Cyanoacrylate adhesive provides efficient local drug delivery.

Biodegradable drug delivery systems have advanced treatment of a wide spectrum of musculoskeletal problems. However, their lack of availability and cost can restrict use. To find an easily available and inexpensive biodegradable implant, we tested a widely used tissue adhesive, n-butyl-2-cyanoacrylate, as a drug-trapping material. We tested vancomycin with commercially available absorbable gelatin-sponge pieces as the scaffold. We evaluated the in vitro and in vivo drug release profiles and in vivo inflammatory response. A mouse muscle pouch model was used for in vivo evaluations. The released vancomycin level was measured by fluorescence polarization immunoassay technique, and a leukocyte count-based grading system was used to evaluate inflammatory response. Our findings suggest the proposed implant provides effective drug release for as much as 42 days in vitro and 14 days in vivo. The presence of n-butyl-2-cyanoacrylate led to a local inflammatory response which decreased after 3 weeks in the group with less adhesive. These results showed that n-butyl-2-cyanoacrylate could efficiently trap and slowly release a drug when used in the structure of a biodegradable local drug delivery device.

Leukotriene C4 synthase A-444C gene polymorphism in patients with allergic rhinitis.

OBJECTIVE: To determine the frequency of leukotriene C4 synthase A-444C polymorphism in allergic rhinitis patients. STUDY DESIGN AND SETTING: A prospective, randomized, case-controlled study. Blood samples were obtained from 85 patients with allergic rhinitis and 95 healthy individuals. After the extraction of DNA from the blood samples, the leukotriene C4 synthase A-444C polymorphism was studied by a real-time polymerase chain reaction method. RESULTS: The AC and CC genotype frequencies were statistically higher in the study group (P = 0.048 and P = 0.037, respectively). In addition, the AC polymorphism carried an increased risk of developing allergic rhinitis (odds ratio = 2.18, 95% confidence interval, 1.173-4.053, P = 0.014). CONCLUSION: The C allele of the leukotriene C4 synthase gene increases the risk of developing allergic rhinitis. SIGNIFICANCE: The leukotriene C4 synthase A-444C gene polymorphism is important in susceptibility to allergic rhinitis and this is the first study of this gene polymorphism in allergic rhinitis. EBM RATING: B-3b.