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).

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.

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.

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).

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.

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.

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.

Benefit of high-dose methylprednisolone in comparison with conventional-dose prednisolone during remission induction therapy in childhood acute lymphoblastic leukemia for long-term follow-up.

Eight-year event-free survival (EFS) was evaluated in 205 patients with acute lymphoblastic leukemia (ALL), to consider the efficacy of high-dose methylprednisolone (HDMP) given during remission induction chemotherapy between 1 and 29 days. The St Jude Total XI Study protocol was used after some minor modifications in this trial. Patients were randomized into two groups. Group A (n = 108) received conventional dose (60 mg/m(2)/day orally) prednisolone and group B (n = 97) received HDMP (Prednol-L, 900-600 mg/m(2) orally) during remission induction chemotherapy. Complete remission was obtained in 95% of the 205 patients who were followed-up for 11 years; median follow-up was 72 months (range 60-129) and 8-year EFS rate was 60% overall (53% in group A, 66% in group B). The EFS rate of group B was significantly higher than of group A (P = 0.05). The 8-year EFS rate of groups A and B in the high-risk groups was 39% vs 63% (P = 0.002). When we compared 8-year EFS rate in groups A and B in the high-risk subgroup for both ages together /=10 years, it was 44% vs 74%, respectively. Among patients in the high-risk subgroup with a WBC count >/=50 x 10(9)/l, the 8-year EFS was 38% in group A vs58% in group B. During the 11-year follow-up period, a total of 64 relapses occurred in 205 patients. In group A relapses were higher (39%) than in group B (23%) (P = 0.05). These results suggest that HDMP during remission-induction chemotherapy improves the EFS rate significantly for high-risk patients in terms of the chances of cure.

Discovery and biological evaluation of a new family of potent inhibitors of the dual specificity protein phosphatase Cdc25.

The Cdc25 dual specificity phosphatases have central roles in coordinating cellular signaling processes and cell proliferation, but potent and selective inhibitors are lacking. We experimentally examined the 1990 compound National Cancer Institute Diversity Set and then computationally selected from their 140 000 compound repository 30 quinolinediones of which 8 had in vitro mean inhibitory concentrations <1 microM. The most potent was 6-chloro-7-(2-morpholin-4-ylethylamino)quinoline-5,8-dione (NSC 663284), which was 20- and 450-fold more selective against Cdc25B(2) as compared with VHR or PTP1B phosphatases, respectively. NSC 663284 exhibited mixed competitive kinetics against Cdc25A, Cdc25B(2), and Cdc25C with K(i) values of 29, 95, and 89 nM, respectively. As compared with NSC 663284, the regioisomer 7-chloro-6-(2-morpholin-4-ylethylamino)quinoline-5,8-dione was 3-fold less active against Cdc25B(2) in vitro and less potent as a growth inhibitor of human breast cancer cells. Computational electrostatic potential mapping suggested the need for an electron-deficient 7-position for maximal inhibitor activity. Using a chemical complementation assay, we found that NSC 663284 blocked cellular Erk dephosphorylation caused by ectopic Cdc25A expression.

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".

Intrauterine device use and some issues related to sexually transmitted disease screening and occurrence.

The objective of this study was to compare sexually transmitted disease (STD) occurrence and STD complaints in women using intrauterine device (IUD) with women who are not using any modern contraceptive method in a family planning setting in Trabzon, Turkey. A great majority of all women in both groups were housewives and all indicated their husbands as the first and only lifetime sexual partner. The IUD user group (n = 211) did not differ significantly from the nonuser group (n = 155) in terms of mean age, years of schooling, first age at intercourse, frequency of sexual intercourse or practice of vaginal douching (p >0.05). STD signs and symptoms were not found to be significantly different among both groups, with the exception of vaginal discharge. IUD users complained more of abnormal vaginal discharge than nonusers (RR = 2.09, CI = 1.17-3.75, p = 0.007). Bacterial vaginosis was diagnosed with the Gram-staining of the vaginal smear and current IUD users were found to be 2.78 times more likely to be diagnosed with bacterial vaginosis as compared to nonusers (p <0.00). The diagnosis of trichomoniasis, N. gonorrhea, vulvovaginal candidiasis, and Chlamydia was not found to be associated with IUD use.

Congenital insensitivity to pain with anhidrosis.

Congenital insensitivity to pain with anhidrosis is one of a group of rare diseases termed hereditary sensory-motor neuropathies. Primary clinical features of this entity include congenital analgesia, inability to sweat, and mental retardation. Besides the rarity of these clinical entities, difficulty in evaluating the sensory disturbances, especially in small children, makes the diagnosis a clinical problem. In this article a 3-year-old boy, with consanguineous parents and no family history of the disorder, who was evaluated for two years because of ulcerating lesions on his knees, is presented. Physical examination revealed deep ulceration on his knees and scars from burns on his neck and scalp. Moderate mental retardation and analgesia were noted. There was symmetrical loss of pain and touch sensation on his hands and feet. Electromyographic examination showed absence of action potentials of the ulnar and sural nerves, decrease in the sensory and motor nerve conduction velocities, and amplitude of action potentials. The result of the application of pilocarpine showed anhidrosis. His skin and nerve biopsy specimens were also examined.

Megakaryocyte emperipolesis in a child with chronic neutropenia: an unusual coexistence.

The term emperipolesis defines the temporary presence of one cell within another's cytoplasm. In clinical use, megakaryocyte emperipolesis is the penetration of hematopoietic cells into the cytoplasm of megakaryocytes. The pathophysiological significance of megakaryocyte emperipolesis is uncertain. It has been described in association with neoplastic disorders, and in a few instances in idiopathic thrombocytopenic purpura, iron deficiency anemia, bleeding, and during the administration of recombinant human granulocyte colony-stimulating factor. However, megakaryocyte emperipolesis in a patient with chronic neutropenia has not been reported. In the current report, emperipolesis of hematopoietic cells within megakaryocytes in a boy with chronic neutropenia is described and the possible mechanisms are discussed.

Pseudomonas sepsis with neutrophagocytosis in a premature newborn.

Secondary hemophagocytic syndrome may develop during certain severe infections commonly due to viral infections, but is rarely associated with bacterial infections, and its appearance in a premature newborn is uncommon. We present a case of hemophagocytosis during Pseudomonas aeruginosa septicemia in a premature infant. After sepsis treatment with imipenem-cilastatin and aminoglycoside, remission of hemophagocytosis was achieved.

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.

Effect of exercise on lipid peroxidation.

PURPOSE: The effect of physical exercise on lipid peroxidation was investigated. METHOD: 27 healthy young adult male subjects were included in this study. Urine samples were collected before and after exercises. Urinary malondialdehyde and creatinine levels (Cr) were measured. RESULTS: Urinary malondialdehyde levels were increased by exercise. While pre-exercise malondialdehyde levels were 5.02 +/- 1.26 nmol/mg Cr, post-exercise levels were 6.13 +/- 1.84 nmol/mg Cr (p < 0.05). CONCLUSION: These findings indicated that physical exercise induced lipid peroxidation.

Prevalence of Beta Thalassemia Trait in Denizli.

Beta thalassemia, characterized by the deficiency or the absence of beta globulin production, is the most widespread inherited disorder in the world and is also common in Turkey. To determine the prevalence of carriers for beta thalassemia, we screened the couples before their marriage. For this aim, from 1994 to 1999, a total of 14.200 people were screened. The complete blood count and red blood cell indices (hemoglobin: Hb, hematocrite: Hct, median corpusculer volume: MCV, median corpusculer hemoglobin: MCHb, median corpusculer hemoglobin concentration: MHbC, concentration were measured by automated cell counter on the same day of collection. Then for the samples with MCV values of 78 fL or below, hemoglobin electrophoresis were employed. Testing for beta thalassemia was carried out by the conventional cellulose asetate electropheresis at pH 8.4. People who have elevated HbA2 (≥ 3.5%) were accepted as beta-thalassemia carrier or patient. We detected 3300 people with MCV levels of 78 fL or below and 311 cases of beta thalassemia carrier and 11 cases of beta thalassemia. The prevalence of carriers for beta thalassemia in Denizli was 2.2%. This result indicated that the people with anemia in our region should be investigated for the existence of hemoglobinopathy.

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.