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We aimed to determine the relationships between iron overload and HFE gene mutation in chronic liver disease in Turkey. One hundred thirteen chronic liver disease patients and 138 healthy controls were evaluated regarding their clinical, biochemical, and genetic parameters. Each group was divided into two subgroups according to transferrin saturation (TS) (45% and >45%). HFE gene mutation was analyzed by the PCR-RFLP method. C282Y homozygote, heterozygote, and wild-type mutation rates were 1.7%, 0%, and 98.3% in patients and 0%, 1.4%, and 98.6% in controls, respectively. H63D homozygote, heterozygote, and wild-type mutation rates were 1.8%, 24.7%, and 73.5% in patients and 1.4%, 24%, and 74.6% in controls, respectively. Mutation rates were not statistically different in patients with high and normal TS. Iron overload was positively correlated with biochemical activity and Child-Pugh score (P < 0.05). In multivariate analysis, H63D homozygotic mutation was an independent factor for the development of hepatocellular carcinoma (P = 0.004). We conclude that C282Y mutation is very rare in Turkey. Iron overload is not related to H63D mutation but is positively correlated with biochemical activity and Child-Pugh score in chronic liver diseases.

Background: The cyclin D1 gene (CCND1) is a proto-oncogene playing a critical role in the transition through the G1 to the S phase of the cell cycle and is overexpressed in many tumors. G870A polymorphism at the exon4/intron4 splicing region of the CCND1 gene may play a role in pituitary tumorigenesis and invasiveness. The objective of this study was to examine CCND1 polymorphism in patients with different types of sporadic pituitary adenomas., Material/methods: One hundred thirty patients (38 male, 92 female, mean age: 45.37+/-13.55 SD years) with sporadic pituitary adenomas (PA group) and 129 healthy controls (HC group) were included in the study. The CCND1 G870A polymorphism in PA and HC were genotyped by PCR-RFLP using peripheral blood samples. CCND1 expression was also evaluated with an immunohistochemical method in tumor tissues of 39 patients of the PA group., Results: The genotype distribution in the PA [AA: 30 (23.1%), AG: 90 (69.2%), GG: 10 (7.7%)] was statistically different from the HC group [AA: 36 (27.9%), AG: 64 (49.6%), GG: 29 (22.5%), p=0.001]. Patients carrying the AG genotype were more frequent compared with the control group. Tumor type, volume, and invasion were not related to the genotype. Immunohistochemically, 21 of the 39 tumors showed nuclear positivity for CCND1, varying between 1 and 40% of tumor cells. Positive staining was observed more intense in patients carrying the AG genotype., Conclusions: CCND1 polymorphism may be an early event in tumorigenesis, but it is not a reliable prognostic criterion.

Objective: Hypertension and left ventricular hypertrophy (LVH) are important causes of morbidity and mortality in the population. Angiotensinogen (AGT) M235T polymorphism has been associated with LVH, left ventricular dimensions, coronary artery disease and antihypertensive drug response in previous studies. We examined relationship between AGT M235T polymorphism and echocardiographic left ventricular indices in a Turkish population of treated hypertensive patients with normal coronary arteries., Methods: In this cross-sectional study a Turkish population of 92 hypertensive patients treated in our outpatient clinic were enrolled. All patients had normal coronary angiographic examinations. Genotypes for AGT M235T were determined from peripheral leukocytes. Left ventricular dimensions, mass and function indices, after adjustment for clinical covariates were analyzed by multiple regression analysis according to genotypes., Results: Genotype frequencies for AGT M235T were MM-24.7%, MT-52.8% and TT-22.5%. Left ventricular end-systolic (LVES) dimensions for AGT M235T MM, MT, TT genotypes were 17.9+/-4.2 mm, 19.4+/-6.2 mm, and 16.4+/-2.9 mm, respectively (p=0.08). Angiotensinogen M235T TT genotype showed a trend towards a lower LVES dimension but results were not statistically significant. Left ventricular ejection fractions for AGT M235T MM, MT, TT subgroups were 61.3+/-15.0%, 59.4+/-14.0%, and 67.8+/-8.5%, respectively (p=0.07). Angiotensinogen M235T TT genotype showed a tendency towards lower left ventricular mass index but results were not statistically significant. None of the AGT M235T genotypes predicted left ventricular dilatation, mass or function in treated hypertensive patients with normal coronary arteries., Conclusion: Angiotensinogen M235T polymorphism was not useful to predict left ventricular mass, function, hypertrophy or dilatation in a small population of treated Turkish hypertensive patients with normal coronary arteries.

SOCS-1, an important protein in the JAK/STAT pathway, has a role in the down stream of BCR-ABL protein kinase. We investigated 56 CML patients and 16 controls for the methylation status of SOCS-1 gene promoter and Exon 2 regions. Exon 2 was found to be methylated in 58.9% of the patients and 93.8% of the controls [P = 0.020, OR = 0.121(0.015-0.957)%95CI]. The promoter region was found unmethylated in all patient samples and controls. Although previous studies revealed a relation between SOCS1 gene Exon-2 hypermethylation and CML development or progression, the results of this study showed no such correlation. On the contrary, our results might be indicating hypomethylation in CML patients, this hypothesis need to be studied in larger study population.

Leukemia-specific chromosome translocations involving the nucleoporin CAN/NUP214 lead to expression of different fusion genes including DEK-CAN, CAN-ABL, and SET-CAN. DEK-CAN and CAN-ABL1 are associated with acute myeloid leukemia and T-cell acute lymphoblastic leukemia, respectively, whereas SET-CAN was identified in a patient with acute undifferentiated leukemia. In addition, SET is overexpressed in solid tumors of the breast, uterus, stomach, and rectum. Ectopic expression of SET-CAN inhibits vitamin-D(3)-induced differentiation of the human promonocytic U937cells, whereas ectopic SET expression induces differentiation. Here, we assessed the leukemogenic potential of SET-CAN in the hematopoietic system of transgenic mice. Although SET-CAN mice showed expansion of an early progenitor cell pool and partial depletion of lymphocytes, the animals were not leukemia-prone and did not show shortening of disease latency after retroviral tagging. This suggests that SET-CAN expression in acute undifferentiated leukemia might determine the primitive phenotype of the disease, whereas secondary genetic lesions are necessary for disease development. Surprisingly, SET-CAN mice developed spontaneous hyperplasia of the stomach mucosa, which coincided with overexpression of beta-catenin and vastly increased numbers of proliferating gastric mucosa cells, suggesting a role of SET-CAN in proliferation of certain epithelial cells.

Hereditary hemochromatosis is an autosomal recessive disorder associated with the mutation of the HFE gene. C282Y and H63D mutations in this gene have been described. Hereditary hemochromatosis is primarily associated with the C282Y mutation; the importance of H63D is not well known. In previously reported studies, the C282Y mutation was not detected in Turkey. We herein present a family in which the C282Y mutation was detected. A consanguineous marriage produced 10 children. A 33-year-old man (index case) was diagnosed with hemochromatosis (transferrin saturation rate 80%, ferritin 514 ng/ml, liver biopsy showed +3 iron accumulation, liver involvement in MRI), and genetic analysis showed homozygous C282Y mutation. With family screening, another brother was also diagnosed with hemochromatosis. Transferrin saturation rate was high (>45%) in seven healthy brothers and the father. Genetic analysis revealed two cases with C282Y homozygous mutations, three with C282Y/H63D compound heterozygous mutations, one C282Y heterozygous and three H63D heterozygous among the family members. This is the first family in Turkey in which the C282Y mutation has been detected.

The current curative therapeutic option for the treatment of chronic myeloid leukemia (CML) in the chronic phase is still allogeneic stem cell transplantation (SCT). For the patients who are not candidates for allogeneic SCT, Imatinib is the treatment of choice. It was found that high dose chemotherapy with autologous stem cell rescue prolongs the disease-free survival and may also restore sensitivity to interferon. Here we report the results of Imatinib treatment in three late-phase CML patients who were submitted to autologous SCT following resistance to interferon. Complete cytogenetic response and major molecular response were achieved in the three cases. Imatinib has the potential to induce late molecular remissions during the course of treatment and its effect may be optimized by a previous autologous SCT in this type of patients.

Objective: Familial Mediterranean fever (FMF) is associated with more than 70 missense mutations in the MEFV gene. The purpose of this study was to investigate the relative expression of messenger RNA (mRNA) for the MEFV gene in peripheral blood leukocytes (PBLs) obtained from patients with FMF during attacks of acute abdominal inflammation as well as during asymptomatic periods., Methods: We studied 16 patients with FMF during an attack of acute peritonitis and 17 otherwise healthy individuals who were undergoing surgery because of acute appendicitis. Blood samples were collected from both groups of patients during both acute inflammatory and asymptomatic periods. Relative levels of MEFV mRNA in PBLs were detected with real-time reverse transcriptase-polymerase chain reaction using LightCycler, with 2 sets of primers for the MEFV gene (exons 7-10 and exons 2-3) and with primers for CIAS1 and PSTPIP1 genes. Expression levels were compared with beta(2)-microglobulin as an internal control., Results: MEFV expression was reduced in FMF patients during asymptomatic periods as compared with the non-FMF controls (P < 0.001). We observed a further decrease in MEFV expression in FMF patients during periods of inflammation (P = 0.01). Reduced levels of MEFV mRNA were also noted during the preoperative period as compared with asymptomatic periods in control patients with acute appendicitis (P = 0.01). CIAS1 expression in PBLs from patients with FMF was also found to be lower than that in the control patients. However, CIAS1 expression did not change with acute inflammation., Conclusion: This study confirmed that reduced expression of the MEFV gene is associated with inflammation and that it may be one of the pathogenic mechanisms of the attacks of inflammation in FMF patients, along with disease-associated variations in pyrin.

Background: Endothelial nitric oxide synthase produces nitric oxide which is involved in many physiologic regulatory functions. Variable number of tandem repeats in intron 4 of endothelial nitric oxide synthase gene are reported to be associated with blood pressure regulation. Nitric oxide is involved in regulation of cardiomyocyte genes but it is not known If endothelial nitric oxide synthase 4 gene polymorphisms are related with left ventricular hypertrophy. We studied endothelial nitric oxide synthase 4a/b allele status in hypertensive and normotensive patients and echocardiographic parameters in a subgroup of hypertensive group., Methods: We performed a case-control study involving 110 Turkish hypertensive patients and 87 controls. All subjects were genotyped for endothelial nitric oxide synthase 4a/b polymorphism. Echocardiographic measurements were obtained in 94 of the hypertensive patients., Results: Endothelial nitric oxide synthase 4a/b genotype frequencies were 6.4%, 23.6%, 70% in hypertensives and 1.1%, 18.4%, 80.5% in controls for a/a, a/b, b/b, respectively. Left ventricular dimensions, mass and diastolic indices were not different across endothelial nitric oxide synthase 4 genotypes. Patients with 4a/a genotype had higher interventricular septal thickness than the other group; 14.83(1.6), 11.91(1.51), 12.21(1.56) for a/a, a/b, b/b, respectively and p = 0.0001., Conclusion: Endothelial nitric oxide synthase 4a/b gene polymorphism is not associated with hypertension in Turkish patients. 4a/a genotype was associated with higher interventricular septal thickness in hypertensive patients.

Background: Robots are sensor-based tools capable of performing precise, accurate and versatile actions. Initially designed to spare humans from risky tasks, robots have progressed into revolutionary tools for surgeons. Tele-operated robots, such as the da Vinci (Intuitive Surgical, Mountain View, CA), have allowed cardiac procedures to start benefiting from robotics as an enhancement to traditional minimally invasive surgery., Methods: The aim of this text was to discuss our experience with the da Vinci system during a 12 month period in which 61 cardiac patients were operated on. There were 59 coronary bypass patients (CABG) and two atrial septal defect (ASD) closures., Results: Two patients (3.3%) had to be converted to median sternotomy because of pleural adhesions. There were no procedure- or device-related complications., Conclusion: Our experience suggests that robotics can be integrated into routine cardiac surgical practice. Systematic training, team dedication and proper patient selection are important factors that determine the success of a robotic surgery programme., (Copyright 2006 John Wiley & Sons, Ltd.)

Acute leukemias (ALs) are heterogeneous diseases. Functional polymorphisms in the genes encoding detoxification enzymes cause inter-individual differences, which contribute to leukemia susceptibility. The CYP2D6, CYP1A1, CYP2E1, GSTT1, and GSTM1 polymorphisms in ALL (n = 156) and AML (n = 94) patients and 140 healthy controls were genotyped by PCR and/or PCR-RFLP using blood or bone marrow samples. No association was observed between the GSTT1 gene deletion and patients (OR = 0.8, 95% CI = 0.4-1.7 for AMLs and OR = 0.9, 95% CI = 0.5-1.6 for ALLs). Patients with ALL and AML had a higher prevalence of the GSTM1 deletions compared to controls but only the difference among adult AML patients (OR = 2.1, 95% CI = 1.0-4.2) was statistically significant. The CYP2D6*3 variant allele frequency was lower in the overall acute leukemia patients (0.6%) compared to controls (P = 0.03). CYP2D6*1/*3 genotype frequency also showed a protective association in AML patients (OR = 0.09, 95% CI = 0.01-1.7; P = 0.04). We also found a risk association for CYP2E1*5 in ALL and AML (OR = 3.6, 95% CI = 1.4-9.4 and OR = 3.9, 95% CI = 1.4-10.5, respectively). No association was found for the studied CYP2D6*4, CYP1A1*2A, and GSTT1"null" variants and the risk of acute leuke-mia (ALL or AML). This case-control study suggests a contribution of CYP2E1, CYP2D6, and GSTM1 "null" variants to the development of acute leukemias.

Background: The renin-angiotensin-aldosterone system (RAAS) plays an important role in blood pressure regulation, left ventricular and vascular structure. Some hypertensive patients develop left ventricular dilatation and heart failure symptoms while others are relatively less affected. The purpose of our study was to determine whether two major polymorphisms of RAAS are associated with echocardiographic left ventricular mass, function and dilatation in hypertensive patients with normal coronary arteries., Methods: A Turkish population of 88 patients with hypertension and normal coronary arteries were studied by echocardiography for left ventricular dimension, mass and function. Genotyping was performed for aldosterone synthase (CYP11B2) -344C/T polymorphism in 85, angiotensin-converting enzyme (ACE) I/D polymorphism in 88 patients. Left ventricular dimensions, mass and function indices, after adjustment for clinical covariates, were analysed by multiple regression according to genotypes., Results: None of the two genotypes studied predicted left ventricular dilatation, mass or function in hypertensive patients with normal coronary arteries., Conclusion: Neither ACE I/D nor CYP11B2 -344C/T polymorphisms were useful to predict left ventricular mass, function or dilatation in our hypertensive patients with normal coronary arteries.

Introduction: Endothelial-derived nitric oxide (NO), which is produced by endothelial nitric oxide synthase (eNOS) in response to increased blood flow, maintains the tumescence phase of erection. The eNOS gene is located on the seventh somatic chromosome and the polymorphism of this gene has been reported to cause changes in the structure of enzyme system, resulting in disturbance of its activity., Aim: The aim of this prospective study is to evaluate the relationship between polymorphism of eNOS gene and erectile dysfunction (ED)., Methods: Thirty patients with ED (mean age: 58.7 +/- 9.97, range: 39-74 years) and 25 voluntary controls (mean age: 56.44 +/- 7.58, range: 47-72 years) were enrolled to the study. Patients with ED were evaluated with International Index of Erectile Function (IIEF) questionnaire, routine blood tests for systemic vascular risk factors, and color Doppler ultrasonography while potency of the control group were only assessed with IIEF questionnaire. The presence of polymorphism of eNOS gene was determined in both groups by polymerase chain reaction in the fourth intron of the seventh somatic chromosome that encodes eNOS gene., Results: The incidences of diabetes mellitus and coronary artery disease were statistically higher in the ED group (P = 0.023 and 0.029, respectively) while mean IIEF score was significantly lower (P = 0.001). Evaluation with color Doppler ultrasonography revealed penile arterial insufficiency in six cases, cavernosal insufficiency in 19 cases, and mixed vascular insufficiency in five cases. The distributions of three eNOS genotypes (eNOS4b/b, eNOS4a/b, and eNOS4a/a) among ED patients and controls were similar (P > 0.05). However, eNOS4a/b genotype was statistically higher in diabetics (P = 0.042). Also, 80% of the patients with severe ED and 54.5% of the diabetic patients with ED had eNOS4a/b genotype., Conclusion: In our study, no correlation was detected between the polymorphism of eNOS gene and ED. However, 80% of the patients with severe ED and 54.5% of the diabetic patients with ED had eNOS4a/b genotype. Based on our data, it seems that diabetic patients with ED tend to have more eNOS4a/b genotype.

Purpose: The epidemiology of colorectal carcinoma is well known to differ among countries but the molecular characteristics are usually assumed to be similar. International differences in molecular pathology have not been studied extensively but have implications for the management of patients in different countries and of immigrant patients., Experimental Design: We evaluated the CpG island methylator phenotype pathway characterized by concordant methylation of gene promoters that often silences transcription of the genes, the microsatellite instability pathway, and K-ras and p53 gene status in 247 colorectal carcinomas from the three selected Middle Eastern countries of Egypt, Jordan, and Turkey., Results: Colorectal carcinoma from Egypt had the lowest frequencies of methylation. In multinomial logistic regression analysis, Jordanian colorectal carcinoma more frequently had methylation involving the p16 tumor suppressor gene (odds ratio, 3.5; 95% confidence interval, 1.2-10.6; P = 0.023) and MINT31 locus (odds ratio, 2.3; 95% confidence interval, 1.0-5.1; P = 0.041). The K-ras proto-oncogene was more frequently mutated in colorectal carcinoma from Turkey (odds ratio, 2.9; 95% confidence interval, 1.2-6.7; P = 0.016), but p53 overexpression was more common in both Jordanian and Turkish colorectal carcinoma than in Egyptian cases (odds ratio, 2.5; 95% confidence interval, 1.2-5.5; P = 0.019; and odds ratio, 3.6; 95% confidence interval, 1.8-7.1; P = 0.0003, respectively). The findings in Turkish colorectal carcinoma were most similar to those reported for Western cases., Conclusions: Colorectal carcinoma from Middle Eastern countries have differing gene methylation patterns and mutation frequencies that indicate dissimilar molecular pathogenesis, probably reflecting different environmental exposures. These molecular differences could affect prevention strategies, therapeutic efficacy, and transferability of clinical trial results.

On the basis of epidemiological studies, infection was suggested to play a role in the etiology of human cancer. While for some cancers such a role was indeed demonstrated, there is no direct biological support for the role of viral pathogens in the pathogenesis of childhood leukemia. Using a novel bioinformatic tool that alternates between clustering and standard statistical methods of analysis, we performed a 'double-blind' search of published gene expression data of subjects with different childhood acute lymphoblastic leukemia (ALL) subtypes, looking for unanticipated partitions of patients, induced by unexpected groups of genes with correlated expression. We discovered a group of about 30 genes, related to the interferon response pathway, whose expression levels divide the ALL samples into two subgroups; high in 50, low in 285 patients. Leukemic subclasses prevalent in early childhood (the age most susceptible to infection) are over-represented in the high-expression subgroup. Similar partitions, induced by the same genes, were found also in breast and ovarian cancer but not in lung cancer, prostate cancer and lymphoma. About 40% of breast cancer samples expressed the 'interferon-related' signature. It is of interest that several studies demonstrated mouse mammary tumor virus-like sequences in about 40% of breast cancer samples. Our discovery of an unanticipated strong signature of an interferon-induced pathway provides molecular support for a role for either inflammation or viral infection in the pathogenesis of childhood leukemia as well as breast and ovarian cancer.

Background: Expression of neuroectodermal markers is a key feature of small cell lung carcinoma (SCLC). Although immune responses against a number of these proteins have been associated with paraneoplastic neuronal disease (PND), most patients with SCLC have anti-neuroectodermal antibodies in the absence of PND. Whether these immune responses affect the clinical outcome in SCLC is critical in understanding the potential value of these proteins as cancer vaccine targets as well as in the pathogenesis of PND., Methods: The authors investigated the frequency of immunoglobulin G autoantibodies against Sry-like high-mobility group box (SOX)1, 2, 3 and Zinc-finger gene of the cerebellum (ZIC)2 proteins in stored serum samples from 90 patients utilizing the lambda-phage plaque assay. Data obtained from patient records were utilized to measure clinical correlates of seroreactivity., Results: Antibodies to SOX1 were present in 28% of patients and another 28% had anti-ZIC2 antibodies, classifying these as some of the most frequent antibody responses observed in SCLC. None had autoimmune paraneoplastic disease. Antibody titers were frequently as high as > or = 1:10(6) and were stable for < or = 6 months after diagnosis. Seroreactivity against either SOX1 or ZIC2 correlated with younger age, lower lactate dehydrogenase levels, and better response to initial therapy., Conclusions: The frequent and stable presence of SOX Group B and/or ZIC2 antibodies in SCLC, but not in healthy individuals examined, indicates they are serological markers of SCLC. However, the correlation between known clinical parameters of less aggressive disease and seroreactivity suggests that these antibodies are indicators of better prognosis in SCLC and warrants further studies to clarify the nature of the underlying immune responses., (Copyright 2005 American Cancer Society.)

The human ETS family gene TEL2/ETV7 is highly homologous to TEL1/ETV6, a frequent target of chromosome translocations in human leukemia and specific solid tumors. Here we report that TEL2 augments the proliferation and survival of normal mouse B cells and dramatically accelerates lymphoma development in Emu-Myc transgenic mice. Nonetheless, inactivation of the p53 pathway was a hallmark of all TEL2/Emu-Myc lymphomas, indicating that TEL2 expression alone is insufficient to bypass this apoptotic checkpoint. Although TEL2 is infrequently up-regulated in human sporadic Burkitt's lymphoma, analysis of pediatric B-cell acute lymphocytic leukemia (B-ALL) samples showed increased coexpression of TEL2 and MYC and/or MYCN in over one-third of B-ALL patients. Therefore, TEL2 and MYC also appear to cooperate in provoking a cadre of human B-cell malignancies.

Drugs and carcinogens are substrates of a group of metabolic enzymes including cytochrome p450 enzymes and gluthatione S-transferases. Many of the genes encoding these enzymes exhibit functional polymorphisms that contribute individual cancer susceptibility and drug response. Molecular studies based on these polymorphic enzymes also explain the aetiology of cancer and therapeutic management in clinics. We analysed the cytochrome p4501A1 (CYP1A1) and 2D6 (CYP2D6) variant genotype and allele frequencies by PCR-RFLP in Turkish individuals (n=140). The frequency of the CYP1A1*2A mutant allele was found to be 15.4%, and the CYP2D6*3 and *4 mutant allele (poor metabolizer) frequencies were 2.5% and 13.9%, respectively. This study presents the first results of CYP1A1 and CYP2D6 mutant allele distributions in the Turkish population and these data provide an understanding of epidemiological studies that correlate therapeutic approaches and aetiology of several types of malignancy in Turkish patients., (Copyright (c) 2005 John Wiley & Sons, Ltd.)

We investigated the peripheral blood gene expression profile of interferon induced transmembrane protein 1 (IFITM1) in sixty chronic myeloid leukemia (CML) patients classified according to new prognostic score (NPS). IFITM1 is a component of a multimeric complex involved in the trunsduction of antiproliferative and cell adhesion signals. Expression level of IFITM1 was found significantly different between the high- and low-risk groups (P = 9.7976 x 10(-11)) by real-time reverse transcription polymerase chain reaction (RT-PCR). Higher IFITM1 expression correlated with improved survival (P = 0.01). These results indicate that IFITM1 expression profiling could be used for molecular classification of CML, which may also predict survival.

Background: Children with cyanotic heart disease undergoing cardiac surgery in which cardiopulmonary bypass is used are at increased risk of postoperative bleeding. In this study, the authors investigated the possibility of reducing postoperative blood loss by using aprotinin and tranexamic acid alone or a combination of these two agents., Methods: In a prospective, randomized, blind study, 100 children undergoing cardiac surgery were investigated. In group 1 (n = 25) patients acted as the control and did not receive either study drugs. In group 2 (n = 25) patients received aprotinin (30.000 KIU.kg(-1) after induction of anesthesia, 30.000 KIU.kg(-1) in the pump prime and 30.000 KIU.kg(-1) after weaning from bypass). In group 3 (n = 25) patients received tranexamic acid (100 mg.kg(-1) after induction of anesthesia, 100 mg.kg(-1) in the pump prime and 100 mg.kg(-1) after weaning from bypass). In group 4 (n = 25) patients received a combination of the two agents in the same manner. Total blood loss and transfusion requirements during the period from protamine administration until 24 h after admission to the intensive care unit were recorded. In addition, hemoglobin, platelet counts and coagulation studies were recorded., Results: Postoperative blood loss was significantly higher in the control group (group 1) compared with children in other groups who were treated with aprotinin, tranexamic acid or a combination of the two agents (groups 2, 3 and 4) during the first 24 h after admission to cardiac intensive care unit (40 +/- 18 ml.kg(-1).24 h(-1), aprotinin; 35 +/- 16 ml.kg(-1).24 h(-1), tranexamic acid; 34 +/- 19 ml.kg(-1).24 h(-1), combination; 35 +/- 15 ml.kg(-1).24 h(-1)). The total transfusion requirements were also significantly less in the all treatment groups. Time taken for sternal closure was longer in the control group (68 +/- 11 min) compared with treatment groups 2, 3 and 4, respectively (40 +/- 18, 42 +/- 11, 42 +/- 13 min, P < 0.05). The coagulation parameters were not found to be significantly different between the three groups., Conclusions: Our results suggested that both agents were effective to reduce postoperative blood loss and transfusion requirements in patients with cyanotic congenital heart disease. However, the combination of aprotinin and tranexamic acid did not seem more effective than either of the two drugs alone.

Hypermethylator phenotype, a propensity of tumors to incur nonrandom concurrent methylation, has been described in several tumors, including acute myeloid leukemia (AML). More recent studies identified methylation of other tumor suppressor genes, DAP-kinase and SOCS1, singly in AML. We therefore assessed the methylation status of these genes concurrently with other known targets of methylation. We used methylation-specific PCR or COBRA to determine the extent of methylation of 10 genes in 28 AML samples from Turkey. In addition to DAP-kinase and SOCS1, we included ER, p15, and E-cadherin (reported to be frequently methylated) as well as p16, GSTP1, and HIC1 (reported as rarely methylated). We also included RARbeta and p73 for which only minimal data in AML is available. All samples were methylated at least in one locus and all except one demonstrated methylation of DAP-kinase, SOCS1, p15, and/or ER. DAP-kinase is the most frequently methylated gene in both pediatric (70%) and adult AML (55%). RARbeta is methylated in 18% and p73 in 10% of AMLs. Methylation of E-cadherin and RARbeta occurs preferentially in AMLs with high methylation index (MI), while epigenetic lesions in SOCS1, DAP-kinase, and p15 appear to be independent. MI may be age-dependent, with a peak in young adults. FAB M3 demonstrated a higher extent of methylation than M2/M4. This study provides an impetus for larger studies to define if the extent and pattern of methylation in subgroups of AML are clinically relevant.

Background: NAD(P)H:quinone oxidoreductase1 (NQO1) is a two-electron reductase that detoxifies quinones derived from the oxidation of phenolic metabolites of benzene. Exposure to benzene metabolites increases the risk of hematotoxicity and leukemia. NQO1 enzyme activity protects the cells against metabolites of benzene. C to T base substitution at nucleotide 609 of NQO1 cDNA (C609T) results in loss of enzyme activity. Low NQO1 activity may play a role in etiology of acute leukemia., Procedure: We analyzed NQO1 C609T gene polymorphism using the PCR-RFLP method in 273 patients with de novo acute leukemia (189 acute lymphoblastic leukemia (ALL), and 84 acute myeloid leukemia (AML) and 286 healthy volunteers to investigate the role of NQO1 polymorphism in the etiology of acute leukemia., Results and Conclusions: The frequency of homozygosity for NOQ1 C609T polymorphism was 3.5% in the healthy control population and 2.5% in pediatric acute leukemia. The NQO1 C609T allele frequency was not statistically different in the children with acute leukemia in comparison to the controls (odds ratio (OR), 0.76; 95% confidence interval (CI), 0.58-1.01; P = 0.06). The distribution of NQO1 genotypes among children with acute leukemia was not statistically different from the control group (P = 0.13). These findings do not support the role of NQO1 C609T polymorphism in the etiology of de novo pediatric acute leukemia., (Copyright 2004 Wiley-Liss, Inc.)

Myxomas are common cardiac tumors that are traditionally managed by complete excision through a median sternotomy approach with the use of cardiopulmonary bypass. We discuss a patient with left atrial myxoma and chronic atrial fibrillation who underwent surgical excision and combined irrigated radiofrequency ablation for atrial fibrillation through a Port Access approach. Minimally invasive operations constitute an expanding field for the treatment of many cardiac diseases and may be an alternative for the treatment of this pathology because of less surgical trauma and cosmetic superiority. In this case, both excision of the myxoma and radiofrequency ablation were feasible through this minimally invasive approach. The combination of direct and endoscopic views enabled both procedures to be performed safely and efficiently.

Among several newly identified oncogenes, dek and af4 are attractive targets for researchers interested with leukemia. In this study quantitative Real-Time RT-PCR technique was used to define alterations in expression of dek and af4 genes associated with acute promyelocytic leukaemia (APL) t (15; 17). RNA samples obtained from bone marrow aspirates of fourteen APL patients, cDNA portions were labelled with Syber Green 1 dye and LightCycler analysis have been performed. Expression changes in patients were found not significant in comparison to healthy donors for af4 (P = 0.192) and dek (P = 0.0895). We suggest that af4 gene may have a role in leukomogenesis restricted to lymphoblastic lineage; also further studies must carry on with a larger series of patients in order to understand the relationship between the dek gene and APL. Our study was the first attempt for analysing dek and af4 genes in APL t (15; 17) patients by quantitative Real-Time RT-PCR. This rapid and sensitive method could be used to screen these genes in different types of leukaemia.

Paternity tests are carried out by the analysis of hypervariable short tandem repeat DNA loci. These microsatellite sequences mutate at a higher rate than that of bulk DNA. The occurrence of germline mutations at STR loci posses problems in interpretation of resulting genetic profiles. We recently analyzed 59-159 parent/child allele transfers at 13 microsatellite loci. We identified 12 mutations in 7 microsatellite loci. No mutations were occurred in other 6 loci. The highest mutation rate was observed with 5 mutations at D8S1179 locus at different alleles. The event was always single repeat related. The mutation rate was between 0 and 1.5 x 10(-2) per locus per gamete per generation. The mutation event is very crucial for forensic DNA testing and accumulation of STR mutation data is extremely important for genetic profile interpretation.

All-trans retinoic acid (ATRA) treatment of the acute promyelocytic leukemia (APL) have subsequently resulted in cell apoptosis, but the molecular mechanism of this effect remains elusive. In order to understand a possible involvement of genes regulating apoptotic signal pathways, expression levels of bcl2, bax, dapk1, myc, bad, wt1, and mcl genes were analyzed during ATRA treatment in five APL patients with t (15;17) using Real- time PCR (LightCycler). Two samples from each patient were compared to each other: primary diagnostic sample and a sample taken at remission. Effect of the ATRA treatment was demonstrated by the concomitant induction of cd14 and il1beta genes in four patients. Also other apoptosis related genes were found down-regulated in general but especially the down regulated levels of wt1 and bax attract attention. Result suggested that ATRA dependent apoptosis of APL was under the control of both internal and external pathways without relationships to the amount of the blast populations. Ratio of bcl2 to bax may be more important for this regulation than the ratio of bcl2 to bad. Either bcl2 family or less known apoptosis related genes as wt1 will still be required to further studies in this setting.

Objective: The aim of this study was to assess the feasibility and effectiveness of irrigated radiofrequency (RF) modified Maze procedure through a port access approach during mitral valve surgery and evaluate early and mid-term results., Material and Method: During a 16 months time period, 67 patients with chronic atrial fibrillation (AF) eligible for port access mitral valve surgery were randomly assigned to either Group A, in which they underwent a combined procedure (N = 33) or Group B, in which a valve procedure alone was performed (N = 34). Both groups were similar in terms of age, sex, valve pathology, duration of AF left atrial diameter and left ventricle function (P > 0.05). Four had undergone previous operations., Results: Median follow-up was 10 months for both groups, 95% CI (9.18-10.8). One patient in each group died early postoperatively (3 and 2.9%). Two patients required reoperation for bleeding, one in each group (3 and 2.9%). There were two conversions to right thoracotomy. In Group A, freedom from AF was 100% at the end of the operation (76% sinus, 24% pacemaker) Six and twelve months freedom from AF was 87.2 and 93.6%, respectively. In Group B, freedom from AF at the end of operation was 41%. At the end of 6 and 12 months, freedom from AF was 9.4% (P = 0.0001). One patient in Group A required a permanent pacemaker (3%). During follow-up, one patient in Group A died of non-cardiac causes (3%). In Group B, there were two late deaths: one cardiac (2.9%) and one neurologic (2.9%). There were no thromboembolic events detected in Group A during follow-up, whereas two patients in Group B suffered this complication (6%, P = 0.081). At 12 months, functional capacity had improved for patients in both groups (P < 0.0001)., Conclusion: The combination of mitral valve surgery and irrigated RF Maze procedure was safe and efficient through a port access approach. There were no procedure related complications like esophageal or coronary artery injury. Early and mid-term results were favourable with 93.6% of patients free of AF at 1 year in comparison to the 9.4% of the control group. The data is not sufficient to reach any conclusions in terms of thromboembolic rates, despite favourable results for the RF Maze group. Nevertheless, in terms of feasibilty, sinus rhythm restoration and overall outcome, early results are encouraging and we advocate the use of the combined procedure through a port access approach.

Objective: Contribution of HLA-B51 to the genetic susceptibility for Behçet's disease is well documented and recent studies suggest involvement of other genes. Tumour necrosis factor (TNF) genes are located in the vicinity of the HLA-B locus. Polymorphisms in the promoter region of TNF-alpha gene has been found to be associated with altered TNF secretion, and it may have a prominent role in the increased inflammatory responses of Behçet's disease., Methods: The study group consisted of 99 Behçet's disease patients and 96 healthy matched controls. All patients fulfilled the International Study Group criteria for Behçet's disease. The TNF-alpha -308 and -376 promoter alleles were assigned by the digestion of each amplified PCR product with NcoI and TasI enzymes, respectively., Results: No significant difference was observed in the distribution of TNF-alpha promoter region polymorphisms between patients with Behçet's disease and controls. There was no association between the presence of uncommon -308A and -376A alleles and the manifestations or severity of Behçet's disease either. The TNF-alpha -308A allele and HLA-B*50 was found to be associated in this series of Turkish patients and controls., Conclusion: The role of TNF-alpha promoter region -308 and -376 polymorphisms in the pathogenesis of Behçet's disease is not supported by this data. The overexpression of TNF-alpha in Behçet's disease may be caused by other polymorphisms in the TNF gene or by post-transcriptional mechanisms.

Constantly expressed genes are used as internal controls in relative quantification studies. Suitable internal controls for such studies have not yet been defined for Pseudomonas aeruginosa. In this study, the genes ampC, fabD, proC, pbp-2, rpoD and rpoS of P. aeruginosa were compared in terms of expression stability by real-time quantitative RT-PCR. A total of 23 strains with diverse resistance phenotypes were studied. Stability of expression among the housekeeping genes was assessed on the basis of correlation coefficients, with the best-correlated pair accepted as being the most stable one. Eventually, proC and rpoD formed the most stable pair (r = 0.958; P < 0.001). Next, in four ciprofloxacin-selected nfxC-like mutants, levels of oprD, oprM and oprN mRNA were compared with those of their wild-type counterparts. The comparison was made after correcting the raw values by the geometric mean of the internal control genes proC and rpoD. The level of oprN mRNA was significantly up-regulated, while the oprD gene was down-regulated (although this difference was statistically insignificant), in the mutants. This expression pattern was consistent with that of the expected expression profile of nfxC-type mutants; this experiment therefore lends further support to the use of proC and rpoD genes simultaneously as internal controls for such studies.

Purpose: The t(12;21) translocation is the most common reciprocal chromosomal rearrangement in pediatric acute lymphoblastic leukemia (ALL). This translocation fuses two genes, TEL and AML1, and results in the production of the TEL-AML1 fusion protein. The authors investigated the incidence and prognostic significance of the TEL-AML1 fusion gene in patients with ALL in Turkey., Methods: The authors analyzed 219 children with ALL using the reverse transcription-polymerase chain reaction., Results: The TEL-AML1 fusion transcript was detected in 20.1% (44/219) of newly diagnosed children with ALL. -positive patients had precursor B-cell ALL and were 3 to 10 years old at diagnosis. -positive patients had a significantly lower rate of relapse compared with -negative patients. -positive patients have a higher overall survival rate than -negative patients., Conclusions: These data support that the presence of at diagnosis is an independent favorable prognostic indicator in patients with ALL in Turkey.

Heterogeneous mutations in the coagulation factor IX (FIX) gene result in a bleeding tendency known as haemophilia B. The haemophilia B mutation database has a total of 2353 patient entries, including 10 of the estimated 1000 Turkish patients. In this study, a more comprehensive analysis of the molecular pathology of haemophilia B in Turkey revealed one large deletion and 33 point mutations in the FIX gene of 34 unrelated patients. Haplotype analysis using six polymorphic sites showed that the mutations identified in a total of 45 patients occurred on 13 different haplotypes and that each mutation was family specific.

Background: The aim of this study was to compare intraoperative coronary graft flows performed on pump and off pump and to evaluate the effects of hemodilution on coronary graft flows in off-pump coronary artery bypass grafting (CABG) patients by using transit time flow measurements (TTFM)., Methods: Three hundred patients undergoing only CABG procedures were enrolled in a prospective randomized manner into 3 groups. Group 1 consisted of 100 patients undergoing operations with standard cardiopulmonary bypass techniques. Group 2 consisted of 100 patients scheduled for revascularizations using off-pump techniques. Group 3 consisted of 100 patients who underwent operations with offpump techniques under controlled hemodilution (hematocrit levels kept between 25% and 28%). TTFM were performed with the coronary Flometer system. Mean flows, pulsatility indices, and flow patterns were evaluated. Twenty-five patients in each group were randomly assigned for control angiography 6 days postoperatively. Thromboelastographic (TEG) measurements were performed for each patient before and after surgery to evaluate the patient's coagulation status., Results: The mean number of anastomoses was higher in group 1 than in groups 2 and 3 (P < .05). Mean arterial pressures and heart rates were similar between groups during measurements. Hematocrit values were higher in group 2 than in groups 1 and 3 (P < .05). Mean flows for left anterior descending coronary artery and right coronary artery territories were significantly lower in group 2 patients (P < .05). For the circumflex artery territory, mean flows did not reach statistically significant levels despite lower flows again in group 2. The pulsatility indices were similar in all 3 groups for all 3 coronary territories. Postoperative coronary angiographic results revealed similar graft patencies among the 3 groups (not significantly different). Postoperative TEG patterns failed to show a hypercoagulable state in off-pump patients., Conclusion: Off-pump CABG patients with hemodilution had significantly higher graft flows than off-pump CABG patients without hemodilution. Although we failed to show the existence of a hypercoagulable state for patients in the offpump group, an examination of the TTFM findings suggests that hemodilution may help to improve graft patency in offpump CABG patients during the early postoperative period.

Background: The aim of the study was to assess the feasibility and effectiveness of the irrigated radiofrequency modified maze procedure through a port-access approach during mitral valve surgery., Methods: Forty-three patients with atrial fibrillation (AF) and mitral valve disease underwent a combined procedure through a port-access approach. The indication was a history of continuous AF for more than 6 months in patients eligible for minimally invasive mitral valve surgery., Results: The incidence of early mortality was 1 patient (2.3%), and that of freedom from AF was 100% at the end of the operation (70% of patients with normal sinus rhythm, 30% with a pacemaker). One patient (2.3%) required permanent pacemaker implantation after surgery. One patient (2.3%) required reoperation for bleeding. There were no reoperations for failed valve repairs. The incidences of freedom from AF were 87% and 92% at 6 and 12 months, respectively. At 12 months, functional capacity had improved significantly (P < .05). There were no procedure-related complications. No thromboembolic events were detected during follow-up., Conclusion: The port-access approach provided a good access for both valve surgery and the radiofrequency maze procedure. The combination of direct and videoscopic vision allowed an adequate view and led to a safe and efficient combined procedure. Short- and intermediate-term follow-up results were favorable.

Recurrence of ductal patency is a rarely encountered complication in surgical repair of patent ductus arteriosus (PDA). An adult patient with ductal recurrency underwent closure of ductus by using cardiopulmonary bypass via transpulmonary approach. She had significant improvement of symptoms and no residual shunt or pseudoneurysm seven months after surgery.

We aimed to show conventional coronary sinus (CS) catheter could be used with transesophageal echocardiography (TEE) guidance through the limited surgical field in aortic valve surgery with 'J' sternotomy. This method was performed in 14 patients and completed successfully in 12. We believe that in minimally invasive aortic valve surgery, the insertion of the conventional retrograde cardioplegia catheter to the CS with routine way may not be possible but application of TEE guidance is cost-effective and easily applicable method without significant complications.

Purpose: The purpose is to develop a real-time multiplex reverse transcription-PCR assay for detection and quantification of leukemia-specific chimeric transcripts that identify the genetic subgroups of acute lymphoblastic leukemias (ALLs) proposed by the WHO classification., Experimental Design: Real-time multiplex assay for t(12;21), t(4;11), and t(1;19) with hypoxanthine phosphoribosyltransferase as internal standard used in tandem with a new real time quantitative-RT-PCR assay for the t(9;22). This new strategy was designed to yield an amplicon from each translocation with a distinct melting peak allowing dependable identification using only Sybr green I, without any need for expensive hybridization probes., Results: We validated this method with 92 primary ALLs and identified 4 E2A-PBX1, 4 mBCR-ABL and 10 TEL-AML1. When compared with conventional RT-PCRs and Southern blot analyses, 100% concordance was obtained. During the course of these studies, we found marked variations in the levels of the TEL-AML1 transcripts in individual patients. We, therefore, extended the study to accurately and reproducibly determine TEL-AML1 mRNA levels in 47 additional patients with t(12;21). The results indicated that the level of expression of TEL-AML1 varied among individual patients, and it was independent of the WBC count., Conclusions: Our new real-time multiplex assay can be used for rapid, simple, and reliable classification of pediatric ALL. Its reproducible quantification results should also facilitate studies on minimal residual disease. The observed variation in TEL-AML1 transcript levels is of interest because it could reflect biological and/or clinical heterogeneity in the behavior of these leukemias.

Allele and genotype frequencies for the nine loci D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317 and D7S820 were determined for 310 unrelated Turkish individuals.

Allele and genotype frequencies for the nine loci, HumCSF1PO, HumTHO1, HumTPOX, HumFES/FPS, HumF13B, HumVWA, D3S1358, D7S820 and D16S539 were determined using Silver STR III System on 223-598 unrelated Turkish individuals from different regions of the country.

Background: Early and mid-term results of stentless valves for the treatment of ascending aortic aneurysm (AAA) were evaluated in a retrospective manner., Material and Methods: During a four-year period, 26 patients with ascending aortic aneurysms and aortic valve insufficiency underwent a total root replacement procedure using a stentless "Freestyle" valve (Medtronic Inc., Minneapolis MN). Mean age was 71 +/- 4 years (range 66 to 79 years). Eight patients were in NYHA Class 2, 13 in Class 3, and 5 in Class 4. Cardiopulmonary bypass (CPB) was begun with femoral artery-right atrium (two-stage) cannulation in all cases but four, in which the right axillary artery was used. Myocardial protection was established by retrograde, cold-blood cardioplegia and direct antegrade blood cardioplegia from the right coronary ostium. The left ventricle outflow tract was constructed by using 2-0 ticron sutures and incorporating a pericardial strip in between. Coronary buttons were sewn to the xenograft with 6-0 polypropylene sutures. Meanwhile, the patient was cooled down to 18 degrees nasopharyngeal temperature and the distal anastomosis with the proximal arch was performed with a Dacron graft under total circulatory arrest (TCA), using 4-0 polypropylene sutures. During rewarming, the connection between the Freestyle valve and the Dacron graft was performed., Results: Ischemic time was 91 +/- 11 minutes and TCA time was 9 +/- 4 minutes. Operative mortality was zero, and there was one 30-day mortality (3.8%). At discharge, all 25 patients had a functional valve with low transvalvular gradients. Patients were followed for a mean period of 15 months, with one patient being lost to follow-up and one patient dying of non-cardiac causes. Follow-up was 97% complete, and echocardiographic control during the follow-up period revealed competent valves with gradients comparable to those at discharge. Two patients were screened with electron beam tomography (EBT) three years after the operation and there was no sign of wall or leaflet calcification. At the end of the 15 months (mean) follow-up, the functional capacity of the patients had improved significantly (p <0.05)., Conclusions: Our early results suggest that use of the Freestyle valve in conjunction with a Dacron tube graft can be a good alternative for patients over 65 years of age who present with ascending aortic aneurysm with aortic valve insufficiency.

CYP 2E1 is involved in metabolic activation of carcinogenic N-nitrosamines, benzene, urethane and other low molecular weight compounds. CYP2E1 gene is present in the population in various polymorphic forms. We detected the RFLP of the human CYP2E1 gene with the restriction endonuclease PstI, RsaI and DraI in a group of 153 Turkish individuals. According to the results of the PstI/RsaI analysis, 96.07% of the subjects were of the c1/c1 genotype, and 3.93% were of the c1/c2 genotype. In the DraI RFLP analysis, 84.30% DD genotype, 15.03% CD genotype and 0.66% CC genotype were determined. The data obtained may be useful in epidemiological studies of the influence of CYP2E1 polymorphism on carcinogenesis., (Copyright 2001 John Wiley & Sons, Ltd.)

To assess the clinical significance of AML1/ETO gene detected by nested reverse transcriptase polymerase chain reaction, the outcome of 7 patients with acute myeloblastic leukemia between 3 and 14 years of age were presented. All patients had complete remission (CR) at the end of induction (AML-MRC 10 protocol) and 4 underwent unpurged autologous, 2 allogeneic (from matched siblings) non-T-cell-depleted bone marrow transplantations (BMT) in first CR. One patient died due to allogeneic BMT-related complications, and 4 patients relapsed at 13, 17, 18, and 26 months. Only one patient achieved second CR. All relapsed patients died between 18 and 36 months with resistant disease (n = 3) or infection during salvage chemotherapy (n = 1). Two patients who had autologous BMT are alive and disease free at 44 and 50 months. Although statistical significance could not be shown, event-free survival and overall survival rates of AML1/ETO-positive patients (28.57 and 28.57%, respectively) at 3.5 years were even lower than those of AML1/ETO-negative patients. The results confirm some previous reports that AML1/ETO gene in children and adolescents is not a favorable prognostic factor.

The bronchoconstrictive effects of alveolar hypocapnia during weaning from cardiopulmonary bypass (CPB) were investigated in patients undergoing elective coronary artery revascularization. Thirty patients were randomly assigned into two equal groups. In both groups, mechanical ventilation was initiated for 3 min prior to weaning from CPB with the venous pressure low. This kept the pulmonary vascular bed empty, resulting in alveolar hypocapnia (ETCO2 < 2 kPa). Peak airway pressure (P(peak)) and plateau pressures (P(plateau)) were recorded. In group 1, 5% CO2 was added to the inspiratory gas mixture and the ETCO2 allowed to rise (ETCO2 > 3.3 kPa). The ventilation pressure measurements were recorded again after 3 min stabilization. In group 2, the venous pressure was increased to allow the pulmonary venous bed to fill and the ventilation pressures recorded after a 3 min period of stabilization. In group 1, the ventilatory pressures dropped significantly (p < 0.001) when the alveolar hypocapnia was reversed with added CO2 (P(peak) 19.71 +/- 5.7 to 12.31 +/- 2.8 cmH2O and P(plateau) 13.15 +/- 3.28 to 9.15 +/- 2.23 cmH2O). In group 2, a similar effect was achieved by allowing filling of the pulmonary vascular bed (P(peak) 17.46 +/- 4.72 to 11.92 +/- 3.03 cmH2O and P(plateau) 13.93 +/- 4.10 to 9.37 +/- 3.00 cmH2O). These results suggest that filling the pulmonary vascular bed prior to initiating ventilation, when weaning from CPB, prevents the otherwise deleterious effects of alveolar hypocapnia, resulting in raised bronchomotor tonus and raised airway pressures.

Purpose: Factor V Leiden mutation is a common genetic defect associated with a tendency to venous thrombosis. The aim of this study was to evaluate the prevalence of factor V Leiden in patients with retinal vein occlusion (RVO)., Methods: Blood samples were obtained from fifty RVO patients and were tested for factor V Leiden using DNA analysis. Twenty-three patients had central RVO (CRVO), twenty-five had branch RVO (BRVO) and two had CRVO in one eye and BRVO in the other eye., Results: DNA analysis showed that only 4 patients (8%) were heterozygous carriers of factor V Leiden. None of the patients were found to be homozygous. In the control group 11 (9.2%) were heterozygous carriers of factor V Leiden. The difference between the patients and the controls was not statistically significant., Conclusion: There was no clear association between RVO and factor V Leiden in this pool of patients. Factor V Leiden does not seem to play an important role in the development of RVO.

Objective: To evaluate the clinical significance of LH in the form of a mutant beta-subunit in women with polycystic ovary syndrome (PCOS)., Design: Prospective, controlled study., Setting: University hospital., Patient(s): Thirty healthy women and 30 women with PCOS., Intervention(s): Clinical, ultrasonographic, and hormonal findings were used to define PCOS. Nucleotide mutations within codons 8 and 15 in the LH beta-subunit gene (Trp8 => Arg and Ile15 => Thr) were analyzed with the use of polymerase chain reaction and subsequent restriction fragment length polymorphism., Main Outcome Measure(s): Serum levels of gonadotropins, androgens, E2, and prolactin were determined, and the results of restriction fragment length polymorphism were analyzed., Result(s): Five women in the control group and one woman in the PCOS group were found to be affected by the LHbeta gene mutations. No difference was observed in serum androgen and E2 levels between the affected women and 25 healthy women who were homozygous for the wild-type LH. However, women whose serum LH levels were < or = 5.1 mIU/mL had a higher risk of having mutant LH., Conclusion(s): The frequency of LH mutations in women with PCOS is similar to that in healthy women. The presence of the variant does not cause any significant change in serum levels of androgens and E2.

Evaluation of chimeric status following allogenic BMT is an important tool for monitoring the replacement of host cells with donor cells and for determining the risk of relapse. Polymorphic DNA sequences can be used as powerful markers in identification of donor/recipient genotype differences, even between close relatives. Polymerase chain reaction (PCR) amplification of three variable number of tandem repeat (VNTR) loci and five single-locus polymorphisms (SLP) was used to identify chimerism in 40 recipient-donor pairs. Mixed chimerism was present in 11 patients, and complete chimerism in 29. This PCR method is a rapid and sensitive assay to detect engraftment and evaluate relapse potential, and thus is very useful in the clinical management of BMT patients.