The Effects of O6-methyl Guanine DNA-methyl Transferase Promotor Methylation and CpG1, CpG2, CpG3 and CpG4 Methylation on Treatment Response and their Prognostic Significance in Patients with Glioblastoma.

This retrospective study examined the prognostic significance and treatment effect of promoter methylation of O6- methyl guanine methyl transferase (MGMT) and meth-ylation of CpG 1, CpG2, CpG3 and CpG4 in glioblastoma (GB) patients received postoperative radiotherapy (PORT), with or without adjuvant temozolomide (TMZ). One hundred patients with GB who received PORT with concomitant TMZ plus adjuvant TMZ or PORT alone, were included. The MGMT promoter methylation of CpG1, CpG2, CpG3 and CpG4 islands were examined. Overall, MGMT-methylation emerged as a significant prognostic factor for better overall survival (OS) and progression-free survival (PFS) [odds ratio (OR): 0.609, 95% confidence interval (95% CI): 0.395-0.939, p = 0.02; OR: 0.662,95% CI: 0.430-1019, p = 0.5, respectively]. The methylation of each CpG1, CpG2, CpG3 and CpG4 islands was found to have no significant effects on OS and the methylation of each CpGl, CpG2 and CpG4 islands had no significant effect on PFS (p <0.05 for all). On the other hand, the methylation of CpG3 had a positive prognostic effect on PFS (OR: 2.1, 95% CI: 0.99-4.67, p = 0.04). In the group that only received radiotherapy (RT), CpG1 and CpC3 methylations were found to have a positive prognostic significance in terms of PFS (OR: 266, 95% CI: 1.05-6.75, p -0.03 for CpG1; OR: 2.4, 95% CI: 1.01-5.92, p = 0.04 for CpG3). The MGMT promoter methylation represents an important biomarker for predicting response to therapy. Individual islands, particularly CpG3, deserves further investigation as a prognostic marker. Further studies need to be done with larger sample sizes to clarify the results.

Low dosages of vitamin A may cause a decrease in the total neuron number of fetal hippocampal rat cells.

OBJECTIVES: We investigated the effect of low, medium and high doses of oral vitamin A, on the number of fetal hippocampal neurons. BACKGROUND: High doses of vitamin A during pregnancy may cause embryonic malformations. There are reports about dosages that don't cause macroscopic malformations, but may cause mental and behavioral disorders. Still, quantitative morphological studies explaining this topic are lacking. METHODS: We administered oral vitamin A to pregnant rats on the 10th-12th days of pregnancy at doses of 10000, 20000, 30000, 40000, 50000, 100000 and 200000 IU/kg. We collected the fetuses on the 19th day and removed their brains. After staining with cresyl violet and immunolabeling with Tunel and Ki67 antibody, we examined the hippocampi with stereological methods. RESULTS: Vitamin A decreased hippocampal neuron numbers beginning from 20000 IU/kg. While the number of Ki67 positive cells increased with the dosage, the increase of apoptotic cells begun at the dose of 50000 IU/kg. CONCLUSION: Our study demonstrates that vitamin A, beginning from the dosage of 20000 IU/kg, is decreasing the total hippocampal neuron numbers during the critical period of embryonic brain development and that apoptosis may not be the only factor in this outcome (Tab. 1, Fig. 3, Ref. 27).

Protein modelling to understand FGB mutations leading to congenital hypofibrinogenaemia.

INTRODUCTION: Congenital hypofibrinogenaemia is a quantitative fibrinogen disorder characterized by proportionally decreased levels of functional and antigenic fibrinogen. Mutations accounting for quantitative fibrinogen disorders are relatively frequent in the conserved COOH-terminal globular domains of the γ and Bß chains. The latter mutations are of particular interest since the Bß-chain is considered the rate-limiting chain in the hepatic production of the fibrinogen hexamer. AIM: The aim of this study was to study the molecular pattern of four patients with congenital hypofibrinogenaemia. METHODS: Four novel fibrinogen Bß-chain mutations leading to congenital hypofibrinogenaemia were identified in four women with heterogeneous symptoms. The human fibrinogen beta chain precursor protein sequence (P02675) was obtained from the UniProt database. The resulting models were analysed using swisspdbviewer 4.1.0. RESULTS: Three patients were heterozygous for different missense mutations located in the highly conserved ß nodule: c.882G>C:Arg294Ser (Arg264Ser), c.1298G>T:Trp433Leu (Trp403Leu) and c.1329C>G:Asn443Lys (Asn413Lys). Modelling analyses predicted major structural modifications likely to result in impaired fibrinogen secretion. One patient was heterozygous for an intron 7 donor splice mutation (c.1244 + 1G>A), leading to the complete abolishment of the donor site. CONCLUSIONS: Protein modelling of new causative mutations and comparison of molecular, biochemical and clinical data continue to yield valuable information on the development and course of fibrinogen disorders as well as on the choice of the most appropriate treatments.

Specific mosaic KRAS mutations affecting codon 146 cause oculoectodermal syndrome and encephalocraniocutaneous lipomatosis.

Oculoectodermal syndrome (OES) and encephalocraniocutaneous lipomatosis (ECCL) are rare disorders that share many common features, such as epibulbar dermoids, aplasia cutis congenita, pigmentary changes following Blaschko lines, bony tumor-like lesions, and others. About 20 cases with OES and more than 50 patients with ECCL have been reported. Both diseases were proposed to represent mosaic disorders, but only very recently whole-genome sequencing has led to the identification of somatic KRAS mutations, p.Leu19Phe and p.Gly13Asp, in affected tissue from two individuals with OES. Here we report the results of molecular genetic studies in three patients with OES and one with ECCL. In all four cases, Sanger sequencing of the KRAS gene in DNA from lesional tissue detected mutations affecting codon 146 (p.Ala146Val, p.Ala146Thr) at variable levels of mosaicism. Our findings thus corroborate the evidence of OES being a mosaic RASopathy and confirm the common etiology of OES and ECCL. KRAS codon 146 mutations, as well as the previously reported OES-associated alterations, are known oncogenic KRAS mutations with distinct functional consequences. Considering the phenotype and genotype spectrum of mosaic RASopathies, these findings suggest that the wide phenotypic variability does not only depend on the tissue distribution but also on the specific genotype.

Are Physicians Healthy When They Are Aged and Retired? A Survey of the Ankara Chamber of Medicine and the Turkish Geriatrics Society.

In literature, there is a lack of knowledge about clinical and lifestyle characteristics of retired physicians. Aim of the study is to describe the health profile of older physicians registered to the Ankara Chamber of Medicine (Ankara, Turkey). Two hundred and seventy four registered physicians agreed to participate to a survery. Most of them (76.6%) were men. Mean age was 74.9 (standard deviation 6.3) years. More than 85% of the participants presented at least one chronic disease. High scores were reported for the role-physical component of the SF-36, differently from the general health section of it scoring low. The results of the present survey pose the basis for collaborative efforts from the Ankara Chamber of Medicine and the Turkish Geriatrics Society collaboratively to improve the design and development of services for local older physicians.

Our experience with McKusick-Kaufman syndrome patients.

AIM: McKusick-Kaufman syndrome (MKKS) is a rare autosomal recessive disorder. Less than one hundred cases have been reported in the English literature to date. We report three different aged children with a large hydrometrocolpos and postaxial polydactyl. PATIENTS AND RESULTS: These children had various degrees of associated renal disorders. Bardet Biedl syndrome (BBS) is characterized by retinal dystrophy or retinitis pigmentosa, postaxial polydactyl, obesity, nephropathy, mental disturbances or mental retardation. Typically MKKS is diagnosed in young children especially in neonates whereas the diagnosis of BBS is delayed until the teenage years. CONCLUSION: All MKKS cases should be re-evaluated for Retinitis pigmentosa, other signs of BBS and for disorders that may worsen with time (Ref. 12).

NADH-cytochrome b5 reductase in a Turkish family with recessive congenital methaemoglobinaemia type I.

The development of cyanosis at birth, the so-called blue baby syndrome, alerts paediatricians to the presence of congenital heart disease. In rare cases where the arterial blood gas analysis is normal the cyanosis is a consequence of methaemoglobinaemia. There are three distinct origins of methaemoglobinaemia; the presence of a haemoglobin variant, environmental toxicity and deficiency of cytochrome b5 reductase (cb(5)r). Two children born to two sets of first-degree related parents were cyanotic from birth. Differential diagnosis eliminated cardiac and pulmonary abnormalities. Measurement of methaemoglobin levels confirmed recessive congenital methaemoglobinaemia (RCM) and treatment with ascorbic acid was commenced. In the absence of neurological defects, type I disease was diagnosed. Sequence analysis of CYB5R3 revealed two different missense mutations (one which is novel, Ile85Ser) in the two families. Neither of the mutations was located in the FAD or the NADH binding sites of cb(5)r, thus supporting a diagnosis of type I disease.

Determination of malondialdehyde, reduced glutathione levels and APOE4 allele frequency in late-onset Alzheimer's disease in Denizli, Turkey.

OBJECTIVES: The aim of the present study was to determine the Apolipoprotein E (APOE) 4 allele frequency of patients with late-onset Alzheimer's disease (AD) and to determine the effects of oxidant-antioxidant balance on AD. DESIGN AND METHODS: PCR-RFLP was undertaken in 62 cases with AD and 56 aged-matched controls. Activities of reduced glutathione (GSH) and malondialdehyde (MDA) concentration were measured in same groups. RESULTS: Patients with at least one E4 allele genotype were significantly different in patients with AD (21%) than controls (9%) (p=0.01). Serum MDA levels were significantly different between AD patients and Control group (p=0.0001). There was no significant difference in serum GSH levels between AD patients and C groups. CONCLUSION: These results confirmed that the APOE4 allele occurs frequently in late onset AD compared with normal controls. Also elevated MDA levels are likely an essential factor in the pathogenesis and neuronal damage of AD.

Adolescent peers and anti-smoking activities

In this paper, we aim to evaluate and discuss the details of a five days' peer education training program, including creative drama techniques, which was then used to carry out anti-smoking activities among a group of 10th grade adolescents at a high school in Ankara, Turkey. Participatory methods/approaches were used during the training of the peers. Interactive (ice-breakers, feedback of the peers about each day of the training, role play, brain storming discussions, case studies, video recording, etc) and creative drama techniques were the two major training methods used during the process. Although the smoking prevalence in the study school did not significantly decrease after the intervention, this method contributed to increasing students' awareness of anti-smoking issues. Change in the knowledge and attitudes of the students in the study school were significantly different from the change in the control school. This study was also an opportunity for the peer leaders to be part of an enjoyable educational activity. The findings of the study suggest that peer counselors, well trained, and with on-going supervision, can have a positive effect on [quot ]knowledge[quot ] and [quot ]attitudes[quot ] about smoking among their friends. Changing behaviors may require a longer time. Peer counseling programs in which the intervention component lasts at least 6 months are recommended to be carried out among similar groups. (AU)

The usefulness of glycosylated hemoglobin (HbA1C) in discriminating between iron deficiency and thalassemia.

This study assessed whether glycosylated hemoglobin could be used as an index to distinguish between iron-deficiency anemia and thalassemia minor. Glycosylated hemoglobin was measured by high-pressure liquid chromatography in 40 ss -thalassemia minor patients, 20 iron-deficiency anemia patients, and 38 healthy controls, all nondiabetic. Median glycosylated hemoglobin was lower in ss -thalassemia minor than in the iron-deficiency and control groups (p = .000). There was no difference between iron-deficiency patients and healthy controls (p = .095). Glycosylated hemoglobin was not different in iron-replete and iron-deficient traits (p > .05). A cutoff value of 5% has provided a sensitivity of 95% and specificity of 75.7% for distinguishing between these two entities. Positive and negative predictive value were 96.6 and 67.9%. These values were superior to the traditional discriminants' values calculated on the same individuals. Glycosylated hemoglobin could be useful in discriminating between iron-deficiency anemia and thalassemia minor. Further studies are needed, but the point that it can also be used when both conditions exist simultaneously seems to be clinically important.

Asthma-like symptoms prevalence in five Turkish urban centers.

BACKGROUND: Asthma, which is a chronic inflammatory disorder of the airways characterized by the infiltration of inflammatory cells, is a common cause of morbidity in adults. It is almost the third leading cause of preventable hospitalization in the developed countries and accounts for approximately millions of visits to emergency departments. METHODS: In this study, we aimed to determine asthma prevalence in five urban centers in Turkey. Three of the cities were located in the middle-west region of the Anatolia one of them as located across the Mediterranean cost and the last one was in the north part of the country. Data of totally 2353 participants was collected by the trained interviewers, who visited the households and administered the questionnaire to the household members at or over the age of 15 years. RESULTS: The prevalence of asthma was found to be 6.6 % and the difference of asthma prevalence between the urban centers was statistically non-significant (p = 0.059).

Asthma-like symptoms prevalence in five Turkish urban centers

Background: Asthma, which is a chronic inflammatory disorder of the airways characterized by the infiltration of inflammatory cells, is a common cause of morbidity in adults. It is almost the third leading cause of preventable hospitalization in the developed countries and accounts for approximately millions of visits to emergency departments. Methods: In this study, we aimed to determine asthma prevalence in five urban centers in Turkey. Three of the cities were located in the middle-west region of the Anatolia one of them as located across the Mediterranean cost and the last one was in the north part of the country. Data of totally 2353 participants was collected by the trained interviewers, who visited the households and administered the questionnaire to the household members at or over the age of 15 years. Results: The prevalence of asthma was found to be 6.6 % and the difference of asthma prevalence between the urban centers was statistically non-significant (p = 0.059)

No disponible

A prospective analysis of sexual functions during pregnancy.

The aim of the study was to evaluate the sexual functions during pregnancy using the Female Sexual Function Index (FSFI) questionnaire. Pregnancies were recorded in a prospective cohort study comprising 40 healthy pregnant women. Pregnant women who had a stable relationship with their partner were enrolled in the study when were first diagnosed to be pregnant. During their antenatal visits, subjects were asked to complete the FSFI questionnaire and other information about their sexual life in each trimester. Each FSFI domain score was calculated and mean scores in each domain were compared according to the trimesters of pregnancy. Data of 37 subjects for the first, 36 for the second and 34 for the third trimesters of pregnancy were eligible for the analysis. The mean age was 25.5+/-4.5 y; mean parity was 0.4+/-0.7 and mean gravity was 1.6+/-0.9. The frequency of intercourse attempts during the last 4 weeks was 8.6+/-3 before pregnancy, and 6.9+/-2.5, 5.4+/-2.6 and 2.5+/-1.4 in the first, second and third trimesters of pregnancy, respectively. In all domains of FSFI, significant decline in domain scores was determined during pregnancy. The comparison of satisfaction and pain domain scores between first and second trimesters showed significant differences. All of the domain scores significantly decreased in the third trimester of pregnancy. Our results showed that sexual functions are significantly decreased during pregnancy and worsen as the pregnancy progresses. Childbearing couples should be given information about the sexual problems and fluctuations in the patterns of sexuality during pregnancy.

Self-evaluations of tuberculosis patients about their illnesses at Ankara Atatürk Sanatorium Training and Research Hospital, Turkey.

Tuberculosis (TB) is one of the leading causes of morbidity and mortality and almost one-third of the world is infected with this disease. In Turkey, it remains an important public health concern. In many of the studies, social aspects of TB are underestimated. In this study, self-evaluations of TB inpatients between the ages of 18 and 65 were assessed between July 29 and August 01, 2002 at Ankara Atatürk Sanatorium Training and Research Hospital, which is one of the major reference hospitals for TB in Turkey. This was a cross-sectional epidemiological study in which the participation rate was 88.2%. Mean age of the total 97 participants was 41.3 (SD = 13.6) and 80.4% of patients were male. Patients expressed "unhappiness and stress (23.7%)" to be the major cause of their illness. From the patients' point of view, the three major difficulties incorporated in their lives due to TB were "financial problems (27.9%)", "loneliness (9.3%)", and "hospitalization (9.3%)". Relationships between the patients and their social environments were also assessed in five categories: "closest friend at work, closest friend in life, parents, children, and spouse".

Supernumerary nipples in children with hematologic disorders.

The authors report on supernumerary nipples and various hematologic disorders in 7 patients [factor X deficiency (n = 1), factor XI deficiency (n = 2), acute lymphoblastic leukemia (n = 3), and acute myeloblastic leukemia (n = 1)]. They would like to draw attention to the association of supernumerary nipples with hematological disorders, which has not been published before and is considered to be added to the anomalies associated with supernumerary nipples.

Temporary dysplastic hematological features due to iron deficiency in a case of Poland syndrome.

Poland syndrome has been sporadically associated with hematological conditions, primarily acute leukemias. The authors report a child with this syndrome coexisting with temporary hematological dysplasia due to iron deficiency. Further hematological evaluation failed to demonstrate malignancy. Because of its premalignant nature, in patients with Poland syndrome, hematological dysplastic features should be an indication for further investigation. However, in addition to the well-known hematological malignancies, treatable causes may be responsible.

Capture-recapture methods for estimation of fertility and mortality in a rural district of Turkey.

The study used capture-recapture methods to determine if information on births, deaths and family planning use obtained from two data sources provides the same or more complete information than that available from a single source. Five different data sources used were: village heads (mukhtars), community health volunteers, primary health care centres, maternal and child care units and local administrative units (health group presidencies) in 10 selected villages in a rural area of Turkey from May to October 1999. Although the numbers of deaths and births were estimated, no estimation of the number of women using any family planning method could be made. The study highlights some data collection problems of the surveillance system in Turkey and recommends that the routine surveillance systems be strengthened.

Capture-recapture methods for estimation of fertility and mortality in a rural district of Turkey

The study used capture-recapture methods to determine if information on births, deaths and family planning use obtained from two data sources provides the same or more complete information than that available from a single source. Five different data sources used were: village heads [mukhtars], community health volunteers, primary health care centres, maternal and child care units and local administrative units [health group presidencies] in 10 selected villages in a rural area of Turkey from May to October 1999. Although the numbers of deaths and births were estimated, no estimation of the number of women using any family planning method could be made. The study highlights some data collection problems of the surveillance system in Turkey and recommends that the routine surveillance systems be strengthened

Primary hemophagocytic lymphohistiocytosis in Turkish children.

Nineteen children with hemophagocytic lymphohistiocytosis (HLH) were studied in the Department of Pediatric Hematology, Hacettepe University. Patients were divided into two groups. Group 1: Thirteen patients were classified as having a genetic etiology (7 familial, 6 presumed familial) on the basis of an affected sibling and consanguinity. There was a history of consanguineous marriage in 13 of the families. Seven of them had a history of a sibling with HLH. Group 2: Six patients were diagnosed with sporadic HLH. The age at presentation for familial patients was 0.7-84 months (mean 21.9 +/- 24.9 months), and for sporadic cases it was 2.5-48 months (mean 22.7 +/- 19.8 months). The clinical and laboratory data of these two groups were similar at diagnosis. Thirteen cases were diagnosed premortem by bone marrow aspiration. Splenic biopsy was performed in 2 patients. Four patients were diagnosed by postmortem examination. Elevated LDH levels were found in all patients tested. No significant differences for clinical and laboratory data were found between the two groups.