Physiological aspect of apoptosis-regulating microRNAs expressions during fasting.

OBJECTIVE: Fasting is an activity that requires a certain calorie restriction without consuming food or drinks for a certain period of daytime. However, fasting triggers many complex events, including activating cellular stress response pathways, autophagy promotion, apoptosis pathways, and a change in hormonal balance. Among the many events affecting the regulation of apoptosis, the expression of microRNAs (miRNAs) plays an important role. Therefore, we aimed to investigate the levels and importance of miRNA expression in fasting. PATIENTS AND METHODS: The expressions of 19 miRNAs regulating different pathways from saliva samples, isolated by matching healthy university students (n = 34) as group 1 (fasting for 17 consecutive hours) and group 2 (testing 70 minutes after meal consumption), were examined using the real-time PCR method. RESULTS: In fasting, modulation of apoptotic pathways by miRNAs triggers anti-pathogenic effects, and the adaptation of abnormal cells in the body decreases. For this reason, vital diseases, such as cancer, can be treated by preventing the proliferation and growth of cancerous cells by increasing programmed cell death due to the downregulation expression mechanism of miRNAs. CONCLUSIONS: Our study aims to improve the knowledge about the mechanisms and functions of miRNAs in various apoptosis pathways during fasting and may be a model for further future physiological and pathological studies.

A Novel Variant in Triple A Syndrome.

Triple A syndrome is an autosomal recessive inherited multisystem disorder that was first described in 1978. Triple A syndrome has a high genotypic and phenotypic heterogeneity and has been linked with mutations in the AAAS gene, which has been identified on chromosome 12q13. A 14 years old male patient applied to outpatient clinic complaining of weakness and darkening of skin color since 4 months. On physical examination hyperpigmentation was observed on both the skin and mucosa. The morning cortisol level was 1.8 µg/dL and ACTH was >1250 ng/L. Schirmer test showed absence of tears. In the patient's esophagoscopy, mucosal paleness and stenosis of the cardia were observed. Molecular genetic analysis of AAAS gene confirmed the diagnosis of triple A syndrome caused by homozygous mutation: c.1368_1372delGCTCA (p.Gln456HisfsTer38). This variant is considered to be a possible pathogenic because it causes a frame shift that changes the protein structure. As a result of the genetic analysis of the patient's parents, the AAAS gene was detected as heterozygous in both parents for the c.1368_1372delGCTCA mutation. To the best of our knowledge, this is the first report of homozygous mutation: c.1368_1372delGCTCA (p.Gln456HisfsTer38).

Genotype-phenotype correlation, gonadal malignancy risk, gender preference, and testosterone/dihydrotestosterone ratio in steroid 5-alpha-reductase type 2 deficiency: a multicenter study from Turkey.

BACKGROUND: Studies regarding genetic and clinical characteristics, gender preference, and gonadal malignancy rates for steroid 5-alpha-reductase type 2 deficiency (5α-RD2) are limited and they were conducted on small number of patients. OBJECTIVE: To present genotype-phenotype correlation, gonadal malignancy risk, gender preference, and diagnostic sensitivity of serum testosterone/dihydrotestosterone (T/DHT) ratio in patients with 5α-RD2. MATERIALS AND METHODS: Patients with variations in the SRD5A2 gene were included in the study. Demographic characteristics, phenotype, gender assignment, hormonal tests, molecular genetic data, and presence of gonadal malignancy were evaluated. RESULTS: A total of 85 patients were included in the study. Abnormality of the external genitalia was the most dominant phenotype (92.9%). Gender assignment was male in 58.8% and female in 29.4% of the patients, while it was uncertain for 11.8%. Fourteen patients underwent bilateral gonadectomy, and no gonadal malignancy was detected. The most frequent pathogenic variants were p.Ala65Pro (30.6%), p.Leu55Gln (16.5%), and p.Gly196Ser (15.3%). The p.Ala65Pro and p.Leu55Gln showed more undervirilization than the p.Gly196Ser. The diagnostic sensitivity of stimulated T/DHT ratio was higher than baseline serum T/DHT ratio, even in pubertal patients. The cut-off values yielding the best sensitivity for stimulated T/DHT ratio were ≥ 8.5 for minipuberty, ≥ 10 for prepuberty, and ≥ 17 for puberty. CONCLUSION: There is no significant genotype-phenotype correlation in 5α-RD2. Gonadal malignancy risk seems to be low. If genetic analysis is not available at the time of diagnosis, stimulated T/DHT ratio can be useful, especially if different cut-off values are utilized in accordance with the pubertal status.

Pituitary Insufficiency and Hyperprolactinemia Associated with Giant Intra- and Suprasellar Carotid Artery Aneurysm.

Pituitary insufficiency secondary to internal carotid artery (ICA) aneurysm is a very rare condition. Its prevalence is reported as 0.17% (Heshmati et al., 2001). We present a case of pituitary insufficiency and hyperprolactinemia secondary to suprasellar giant intracranial aneurysm. A 71-year-old man was admitted to our clinic with symptoms of hypopituitarism, hyperprolactinemia, and visual field defect. His pituitary MRI and cerebral angiography revealed a giant saccular aneurysm filling suprasellar cistern arising from the ophthalmic segment of the right ICA. Endovascular treatment was performed on the patient to decrease the mass effect of aneurysm and improve the hypophysis dysfunction. After treatment, his one-year follow-up showed the persistence of hypophysis insufficiency, decrease of prolactin (PRL) level, and normal visual field. An intracranial aneurysm can mimic the appearance and behavior of a pituitary adenoma. Intracranial aneurysms should be taken into consideration in the situation of hypopituitarism and hyperprolactinemia. It is important to distinguish them because their treatment approach is different from the others.

Frequency of eosinophilic esophagitis in patients with esophageal symptoms: a single-center Turkish experience.

Eosinophilic esophagitis (EoE) is a chronic, immune/antigen-mediated esophageal disease characterized with symptoms related to esophageal dysfunction and eosinophil-predominant inflammation. There has been a dramatic increase in the diagnosis of this disease in recent years. The primary objective of this study was to determine the frequency of EoE in adult patients who were evaluated by gastroenterologists in our clinic with esophageal symptoms. Between November 2010 and May 2011, 311 adult patients who were evaluated in our clinic with esophageal symptoms were enrolled prospectively. All patients underwent endoscopy and had biopsies taken. Gastroesophageal reflux disease was excluded by either proton pump inhibitory treatment or 24-hour ambulatory pH monitorization. The diagnosis was confirmed by one independent pathologist. Frequency of EoE in patients with esophageal symptoms was 2.6% (n = 8; four men and four women). Mean age at diagnosis was 40.2 ± 8 years. Heartburn was the predominant symptom in patients (75% of the patients), and 87.5% (n = 7) of patients had more than one symptom at diagnosis. Nearly 38% of the patients (n = 3) had a history of allergic disease. Endoscopic findings were as follows: transient/fixed esophageal rings (25%), white exudates (25%), and normal appearance (50%). Median number of circulating eosinophils was 208 (93-659)/mm(3) . Median number of intraepithelial eosinophils in proximal-middle 1/3 part and distal 1/3 part of esophagus were 0 (0-50)/hpf and 37 (16-50)/hpf, respectively. In conclusion, EoE is not rare in Turkey, and it should be considered in the differential diagnosis of patients with esophageal symptoms.

Long-term results of hepatitis B immunoglobulin and lamuvidine for hepatitis B prophylaxis after liver transplantation.

PURPOSE: Recurrence of hepatitis B virus after a liver transplantation (OLT) is a risk factor affecting graft and patient survivals. Short-term hepatitis B virus reactivation rates after OLT range between 3% and 15%. Using combination prophylaxis, the outcomes of OLT among patients with liver disease related to hepatitis B virus have improved to levels comparable to those whose disease is not related to hepatitis B virus. MATERIALS AND METHODS: Since September 2001, we performed 288 OLT in 282 patients including 74 who had liver failure related to hepatitis B virus among whom 58 were followed for >12 months and analyzed retrospectively. Our protocol included lamivudine (100 mg orally per day beginning the day after surgery) and hepatitis B immunoglobulin (10,000 IU IV during the anhepatic phase, 2000 IU/d IV during the first week after surgery, 2000 IU IV/month from postoperative months 1 to 12). Using our protocol, the anti-hepatitis B surface antibodies (HBsAb) serum titer was maintained up to 100 IU/mL. The female:male ratio was 11:47. The mean age of patients was 43±12.8 years. RESULTS: Five patients died of causes unrelated to hepatitis B virus. At the time of death, their hepatitis B surface antigens were negative, and serum titers of anti-HBsAb were 45, 35.3, 56.4, 79.6, and 123 IU/mL. Mean follow-up was 46.5±18.9 months (range, 12-79). The hepatitis B surface antigen became positive in 4 patients; the remaining 49 had no evidence of hepatitis B surface antigen. In 18 patients, serum titer of anti-hepatitis B surface antigen was 0; in the remaining 31 patients, it was 69.2±133 IU/mL. CONCLUSION: Our combination protocol with hepatitis B immunoglobulin and lamivudine is a safe, cost-saving, and effective treatment for hepatitis B virus prophylaxis after liver transplantation.

Screening for Corynebacterium diphtheriae and Corynebacterium ulcerans in patients with upper respiratory tract infections 2007-2008: a multicentre European study.

Diphtheria is now rare in most European countries but, when cases do arise, the case fatality rate is high (5-10%). Because few countries continue to routinely screen for the causative organisms of diphtheria, the extent to which they are circulating amongst different European populations is largely unknown. During 2007-2008, ten European countries each screened between 968 and 8551 throat swabs from patients with upper respiratory tract infections. Six toxigenic strains of Corynebacterium diphtheriae were identified: two from symptomatic patients in Latvia (the country with the highest reported incidence of diphtheria in the European Union) and four from Lithuania (two cases, two carriers); the last reported case of diphtheria in Lithuania was in 2002. Carriage rates of non-toxigenic organisms ranged from 0 (Bulgaria, Finland, Greece, Ireland, Italy) to 4.0 per 1000 (95% CI 2.0-7.1) in Turkey. A total of 28 non-toxigenic strains were identified during the study (26 C. diphtheriae, one Corynebacterium ulcerans, one Corynebacterium pseudotuberculosis). The non-toxigenic C. ulcerans strain was isolated from the UK, the country with the highest reported incidence of cases due to C. ulcerans. Of the eleven ribotypes detected, Cluj was seen most frequently in the non-toxigenic isolates and, amongst toxigenic isolates, the major epidemic clone, Sankt-Petersburg, is still in circulation. Isolation of toxigenic C. diphtheriae and non-toxigenic C. diphtheriae and C. ulcerans in highly-vaccinated populations highlights the need to maintain microbiological surveillance, laboratory expertise and an awareness of these organisms amongst public health specialists, microbiologists and clinicians.

A severely mental and motor retarded boy with monosomy 9pter-->p22 trisomy 10q26-->qter due to paternal reciprocal translocation 46,XY,t(9;10)(p23;q26).

We report on a twenty-two months old male patient with hypotonia, mental and motor retardation and trigonocephaly. Standard GTG banding chromosomal analysis (from metaphyses of a periferal blood lymphocyte culture) showed 46,XY, der(9) monosomy 9pter-->p22, trisomy 10q26--> qter karyotype. This unbalanced translocation resulted from the father's t(9,10) (p22;p26) karyotype. Deletions of the terminal part of 9p and partial trisomy of chromosome 10q are rare chromosomal disorders. To our knowledge, this is the first case report in the literature of a deletion of 9pter-->p22.3 and a duplication of 10q26-->qter. We assume that the clinical anomalies are due to der(9) monosomy 9pter-->p22, trisomy 10q-->26qter.

Analysis of the SRY gene in a girl with 45,X/46,XY genotype.

Analysis of the SRY gene in a girl with 45,X/46,XY genotype: We present a Turner syndrome patient with a 45, X/46, XY mosaicism. A seven-year-old patient was admitted to our laboratory for evaluation of Turner Syndrome. On physical examination, short stature, a webbed neck, a broad chest with widely spaced nipples, syndactyly on toes, horse shoe kidney and typical findings of aortic coarctation were present. The chromosome karyotype of the patient was 45 X/46 XY. Molecular analysis of the blood lymphocytes confirmed the presence of the SRY gene of the patient. We report here the clinical and cytogenetic findings in a patient with an unusual sex chromosome mosaicism.

Turner syndrome and 45,X/47,XXX mosaicism.

The occurrence of double aneuploidy is a relatively rare phenomenon. We report on a 17-year-old woman with short stature, minimal pubic and axillar hair and short hands. In cultured lymphocyte a double aneuploidy mosaicism was detected, consisting of a cell line with trisomy for X chromosome and a cell line with monosomy for the X-chromosome and no cell line with a normal karyotype. To our knowledge, this is the first case of mosaic 45,X/47,XXX in Turkey.

Relationship between polymorphism in the manganese superoxide dismutase gene and breast cancer.

Manganese superoxide dismutase (MnSOD) acts as an antioxidant and protects cells from the harmful effects of reactive oxygen species. We investigated the relationship between the MnSOD Ala-9Val polymorphism and breast cancer. Genotypes of 250 cases and 330 controls were determined by use of PCR-RFLP. Compared with the MnSOD Val/Val genotype, the MnSOD Val/Ala or MnSOD Ala/Ala genotype was not significantly associated with the overall risk for breast cancer. The risk increased in women with MnSOD Ala allele-containing genotypes as well as higher level of education (Ala/Ala: OR, 6.00; 95% CI, 1.02-35.33), BMI >or= 25 kg/m(2) (Val/Ala: OR, 1.74; 95% CI, 1.10-2.76), late age at first pregnancy (Val/Ala: OR, 1.52; 95% CI, 1.01-2.42), and premenopausal status (Val/Ala: OR, 1.78; 95% CI, 1.03-3.10). In conclusion, the MnSOD Ala-9Val polymorphism may contribute to an increased risk for breast cancer development, particularly in the presence of a higher level of education, high BMI, late age at first pregnancy, and premenopausal status.

A male case with double aneuploidy (48,XXY,+21).

The co-occurrence of two numerical chromosomal abnormalities in same individual (double aneuploidy) is relatively rare and the clinical presentations are variable depending on the predominating aneuploidy or a combination effect of both. Furthermore, double aneuploidy involving both autosomal and sex chromosomes is seldom described. We describe a male patient with typical clinical features of Down Syndrome and his karyotype revealed 48,XXY,+21. The phenotypic characteristics of this child have been discussed in the light of the published reports on double aneuploidies of XXY and trisomy 21.

Legionnaire's disease: a nosocomial outbreak in Turkey.

Six nosocomial cases of Legionella pneumophila occurred over a two-week period, with one further case being diagnosed retrospectively after 30 days. Strains isolated from the hospital water system were clonally related to a single sputum isolate. A sero-epidemiological investigation into legionella exposure amongst staff and inpatients was undertaken at the eight-year-old Inonu University Medical Centre in Turkey, which has 600 beds and central air conditioning. There is no disinfection programme for the hospital water system. A total of 500 serum samples (400 hospital staff and 100 inpatients) were screened for antibody to L. pneumophila by enzyme-linked immunosorbent assay (ELISA). Seroreactive cases were confirmed by a four-fold antibody rise in ELISA, a high indirect immunofluorescent assay (IFA) antibody titre or a positive urinary antigen test. ELISA showed that 24 (6%) of the 400 hospital staff and seven (7%) of the 100 inpatients had antibody titres higher than the cut-off value. ELISA-seroreactive cases were followed for two to four weeks. Of these subjects, seven (three patients and four staff) showed a four-fold rise in antibody titre by ELISA, six (three patients and three staff) had a high IFA titre, three patients with pneumonia had a positive urinary antigen test, and one of these patients also had a positive sputum culture. In addition, 22 water distribution systems were screened for the presence of L. pneumophila by culture. L. pneumophila was isolated from 15 sites. Pulsed-field gel electrophoresis typing indicated that all strains isolated from water systems were identical and clonally related to the strain isolated from sputum. Superheating and flushing of water systems were undertaken with legionella being re-isolated from four sites. Repeated superheating and flushing eliminated legionella completely. This study demonstrated that rapid detection of L. pneumophila and adequate superheating and flushing of water systems are effective for elimination and reduction of spread of this organism.

An investigation of effects of toluene and cigarette smoking on some blood parameters and lymphocyte life span.

As toluene is an organic solvent, its cytotoxic effect on the cell is known. Similarly, it has been demonstrated that many of the chemical agents that enter the body through smoking have cytotoxic and genotoxic effects on the cells. In this study, the effects of these two toxic agents, both separately and in combination, on leukocyte counts, lymphocyte counts and mitotic index values were investigated. The study was carried out on blood samples of 100 males, divided into four groups: 25 non-smokers and 25 smokers, 25 toluene-exposed non-smokers and 25 no toluene-exposed smokers. The blood cell values of the blood samples were determined automatically on the hemogram apparatus. In addition slides of the blood samples were prepared according to the chromosome analysis procedure and the mitotic index values were determined through microscopy. The possible effects of smoking and toluene on lymphocyte life span was considered by correlating mitotic index values with lymphocyte counts in the same way for each of the subgroups. Results revealed that leukocyte counts and mitotic index values were higher in the smokers than the non-smokers whether or not they had been exposed to toluene. In addition the results indicate that lymphocyte life span may be shortened due to cigarette smoking and toluene exposure.

Effects of X-rays and cigarette smoking on leukocyte, lymphocyte and mitotic index values and SCE rates: the relationship between mitotic index and lymphocyte count.

Many previous studies revealed that smoking increases leukocyte and lymphocyte counts while exposure to X-rays decreases these counts. However the relationships between lymphocyte life span and smoking as well as X-rays were not well documented. The primary aim of this study was to determine relationships between smoking X-rays (in combination and individually) and life span of lymphocytes. Blood samples from 200 healthy individuals, half of which were X-ray exposed individuals, were collected. Half of X-ray exposed and of non-X-ray exposed individuals were smokers. There were equal numbers of male and female participants. Two lymphocyte cultures, one for the sister chromatid exchange (SCE) analysis and the other for the determination of mitotic index values were prepared using one part of the blood samples collected from the individuals. From the other part of the blood sample leukocyte and lymphocyte counts were determined with a haemogram device. Evaluation of the findings suggested that leukocyte count, lymphocyte count, mitotic index were relatively lower for the X-ray exposed individuals. In addition these values were higher for smokers than nonsmokers in general. The highest SCE rates were recorded for smoking radiology technicians. The most important finding is that lymphocyte life span is relatively low in smokers and in X-ray exposed males.

Legionnaires' disease and pneumonia. Beware the temptation to underestimate this "exotic" cause of infection.

Legionnaires' disease is an often overlooked but common cause of community-acquired pneumonia. The clinical presentation is nonspecific, although fever higher than 39 degrees C (102.2 degrees F), gastrointestinal symptoms, and hyponatremia should raise the index of suspicion. In this article, Drs Akbas and Yu describe specialized laboratory tests needed for definitive diagnosis and discuss therapeutic options.

Legionella as a cause of severe pneumonia.

Legionella pneumophila has been found to be a common cause of community-acquired pneumonia in patients who required intensive care unit (ICU) admission. In many studies, the clinical manifestations for Legionnaires' disease were more severe and the mortality was higher when compared with pneumonias of other etiology. However, this may be due to delay in diagnosis and suboptimal antibiotic therapy, rather than enhanced virulence of L. pneumophila. A syndromic approach using high fever, diarrhea, mental status changes, hyponatremia, etc., may be useful in suggesting the correct diagnosis in patients with severe pneumonia, but this remains to be validated. The availability of Legionella diagnostic microbiology testing in-house (rather than being sent to an outside reference laboratory) maximizes the ability to correctly diagnose Legionnaires' disease. All patients with community-acquired pneumonia admitted to an ICU should undergo Legionella testing using the urinary antigen and culture on selective media. Moreover, we recommend routine cultures of the hospital water supply once a year (regardless of whether a case of nosocomial Legionnaires' disease has ever been diagnosed). If Legionella is found in the water supply, all patients with nosocomial pneumonia should undergo diagnostic tests for Legionella; empiric anti-Legionella antibiotics should be administered pending definitive diagnosis.

A quantitative study of genital skin flora and urinary colonization in spinal cord injured patients.

This study was performed to define the relation between colonization of genital skin flora and bacteriuria in spinal cord injured patients with neurogenic bladder dysfunction. Twenty-seven female and 23 male spinal cord injured patients were included in the study. Patients were evaluated regarding their type of bladder management, educational status, level and degree of the spinal cord lesion. Quantitative cultures were obtained from the perineum labium/dorsum of penis, external meatus of urethra, and urine. We investigated whether the organisms isolated from urine were also present in one or more skin sites in every patient. In total 54 identical bacterial isolates were observed both from urine and one or more skin sites in 43 of the patients. Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, and Proteus stuartii were the most common bacterial isolates. The distribution of identical colonization of genital skin flora with urine were as follows: 30 in urethra, one in perineum, four in urethra and perineum, nine in urethra and labium/dorsum of penis, and 10 in both three skin sites. Identical colonization of both perineum and labium/dorsum of penis with urine were significantly higher in female patients than those of males (P = 0.037, P = 0.003, respectively). No significant difference was found in the presence/distribution of colonization with respect to type of bladder management, educational status, and neurologic status. These results demonstrate the importance of the urethra, perineum, and labium/dorsum of penis as a source of bacteria causing urinary infection in spinal cord injured patients.

Sample adequacy in detecting Chlamydia trachomatis.

OBJECTIVE: Chlamydia trachomatis is an important etiological agent in female genital infection and may result in infertility. In recent years rapid diagnostic methods have become widely used as alternatives to cell culture. Our objective was to evaluate the technique of direct fluorescence assay (DFA) in estimating the presence of C. trachomatis. METHODS: Specimens taken from 40 infertile and 20 fertile women were examined by DFA for the presence of C. trachomatis. RESULTS: Six of forty (15%) infertile women were found to be positive whereas no positive specimens were detected in the control group. When the specimens were grouped into those which were adequate or inadequate, 19 and five specimens, respectively, were adequate in the infertile and healthy groups. If only adequate specimens are included in estimating the presence of Chlamydia, the percentage is 31.6%. CONCLUSIONS: In order to use DFA as a more reliable and rapid diagnostic test of C. trachomatis in female genital infection, false-negativity must be eliminated. Specimens must be collected adequately and concentrated in order to achieve optimal diagnostic success.