Mehmet Karadag

Self-Reported Snoring, Maternal Obesity and Neck Circumference as Risk Factors for Pregnancy-Induced Hypertension and Preeclampsia

Background: Physical and hormonal changes during pregnancy alter breathing patterns of pregnant women. It is possible that occult disordered breathing during sleep may be a risk factor for the development of pregnancy-induced hypertension (PIH) and preeclampsia. Objective: Our aim was to determine the incidence of self-reported snoring in pregnant women, and to investigate the relationship of snoring, obesity and neck circumference to PIH and preeclampsia. Methods: 469 pregnant women and 208 age-matched nonpregnant women were included in the study. Both groups were asked to complete a questionnaire. Maternal complications were retrieved from the medical records. Results: Habitual snoring was reported from 1.9% of nonpregnant women, 2.5% of pregnant women prior to pregnancy and 11.9% of those same women during the third trimester of pregnancy (p < 0.001). Age, smoking during pregnancy, and weight before delivery were independent risk factors for habitual snoring in pregnancy. PIH and preeclampsia developed in 20 and 10.9% of pregnant women with habitual snoring, as compared to 11 and 5.8% of non-snoring pregnant women (p = 0.045, p = 0.125, p = 0.415), respectively. In women who developed preeclampsia, weight before pregnancy, weight before delivery and neck circumference were significantly higher in univariate analysis. Neck circumference was an independent risk factor for PIH and preeclampsia according to logistic regression analysis. Conclusion: The incidence of snoring is significantly higher in pregnant women than in nonpregnant women. Snoring may indicate a risk of PIH. Neck circumference was an independent risk factor for both PIH and preeclampsia.

Circulating ICAM-1 and VCAM-1 Levels in Patients with Obstructive Sleep Apnea Syndrome

Background: Obstructive sleep apnea syndrome (OSAS)-induced hypoxic stress modulates circulating inflammatory mediators causing accelerated atherogenesis. Objectives: We hypothesized that OSAS-induced hypoxia might result in cardiovascular disease due to increased expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on the endothelial surface. Methods: Thirty-nine subjects with moderate-to-severe OSAS and 34 non-apneic controls matched for age, gender, body mass index (BMI), smoking history, and cardiovascular disease were included in this prospective study. Overnight polysomnography was performed. Circulating ICAM-1 and VCAM-1 levels in the serum were measured by enzyme-linked immunosorbent assay. Results: Circulating levels of both ICAM-1 (480.1 ± 216.7 vs. 303.4 ± 98.6 ng/ml, p < 0.0001) and VCAM-1 (1,156.6 ± 79.8 vs. 878.8 ± 71.1 ng/ml, p = 0.002) were significantly increased in the OSAS group compared to the control group. For an ICAM-1 cutoff level of 375 ng/ml, predictive sensitivity and specificity for OSAS were 69.2% (95% confidence interval, CI: 52.4–83.0%) and 82.4% (95% CI: 65.5–93.2%), respectively. For a VCAM-1 cutoff level of 859 ng/ml, predictive sensitivity and specificity for OSAS were 74.4% (95% CI: 57.9–86.9%) and 64.7% (95% CI: 46.5–80.2%), respectively. There was a significant positive correlation between circulating levels of ICAM-1 and ln of AHI (r = 0.276, p = 0.018). Multiple logistic regression analyses showed that OSAS was associated with high ICAM-1 and high VCAM-1 levels independent of age, gender, BMI, smoking status and cardiovascular disease. Conclusion: We conclude that OSAS can independently increase circulating levels of adhesion molecules.

Obstructive sleep apnea causes oxidative damage to plasma lipids and proteins and decreases adiponectin levels

PuposeObstructive sleep apnea (OSA) is associated with various metabolic disorders, and oxidative stress was suggested to play an important role. In the present study, we aimed to investigate serum adiponectin and oxidative stress markers, especially protein carbonyls, and to evaluate the correlation between these parameters and lipid, insulin and fasting glucose concentrations in OSA patients and controls.MethodBlood was drawn from healthy male volunteers following full-night polysomnographic evaluation. Subjects were classified as controls (n = 24), mild OSA group (n = 9) and moderate-severe OSA group (n = 17) according to their apnea–hypopnea indices (AHIs). Serum lipids, fasting glucose, adiponectin, malondialdehyde (MDA), protein carbonyl concentrations, and paraoxonase activities were measured in all subjects.ResultsResults of this study indicated that serum adiponectin concentrations were significantly decreased and MDA and protein carbonyl concentrations were significantly elevated in OSA patients compared to the controls. Protein carbonyl and MDA concentrations were significantly and positively correlated with AHI, while a significant negative correlation was found between adiponectin concentrations and AHI. Adiponectin levels were negatively correlated with MDA levels.ConclusionResults of this study, which is the first human study investigating and describing serum protein carbonyl concentrations in OSA patients, reveal that OSA causes increments in oxidative damage and decreases adiponectin levels. The recurrent hypoxia-reoxygenation attacks in OSA patients may activate oxidative stress, elevating sympathetic activity and leading to low levels of adiponectin.

Ghrelin, leptin, adiponectin, and resistin levels in sleep apnea syndrome: Role of obesity.

AIM: The aim of this study was to investigate the relationship among plasma leptin, ghrelin, adiponectin, resistin levels, and obstructive sleep apnea syndrome (OSAS). METHODS: Fifty-five consecutive newly diagnosed OSAS patients and 15 age-matched nonapneic controls were enrolled in this study. After sleep study between 8:00 AM and 9:00 AM on the morning, venous blood was obtained in the fasting state to measure ghrelin and adipokines. RESULTS: Serum ghrelin levels of OSAS group were significantly (P < 0.05) higher than those of the control group. No significant difference was noted in the levels of leptin, adiponectin, and resistin in OSAS group when compared to controls. There was a significant positive correlation between ghrelin and apnea–hypopnea index (AHI) (r = 0.237, P < 0.05) or the Epworth sleepiness scale (ESS) (r = 0.28, P < 0.05). There was also a significant positive correlation between leptin and body mass index (r = 0.592, P < 0.0001). No significant correlation was observed between leptin, adiponectin, resistin, and any polysomnographic parameters. CONCLUSION: Our findings demonstrated that serum ghrelin levels were higher in OSAS patients than those of control group and correlated with AHI and ESS. Further studies are needed to clarify the complex relation among OSAS, obesity, adipokines, and ghrelin.

Low Level of IGF-1 in Obesity May Be Related to Obstructive Sleep Apnea Syndrome

The aim of this study was to compare serum insulin-like growth factor (IGF-1) levels in patients with obstructive sleep apnea syndrome (OSAS) with those of nonapneic controls and to determine the risk factors of low IGF-1 levels in patients with OSAS. The study included 39 newly diagnosed moderate-to-severe OSAS patients and 36 nonapneic controls. Overnight polysomnography (PSG) was performed in all patients. The circulating levels of IGF-1 in the OSAS group were significantly lower than those of the control group (p < 0.05). There was a significant negative correlation between IGF-1 and logarithmic transformation (Ln) of the apnea-hypopnea index (AHI), duration of apnea-hypopnea, arousal index, average desaturation, and oxygen desaturation index (ODI). The result of stepwise regression analyses showed that OSAS (p = 0.001) was a risk factor for a low IGF-1 level, independent of age, gender, and body mass index (BMI). Our findings demonstrated that there was a significant negative correlation between IGF-1 and Ln AHI and that OSAS reduced the circulating levels of IGF-1.

The expression of common fragile sites and genetic predisposition to squamous cell lung cancers

The chromosomal aberration rates (including gaps and breaks) and expression frequency of fragile sites were determined in peripheral blood lymphocytes cultured with TC 199 medium from 8 patients with squamous cell lung cancer, 10 of their first-degree relatives, and 12 healthy control subjects. As a result of cytogenetic evaluation, both the chromosomal aberration rates and expression frequencies of common fragile sites observed in patients and their relatives were significantly higher than those in healthy control subjects. Our results showed that common fragile sites might be unstable factors in the human genome, and their expression might be affected by some genetic and environmental factors. As a result of this they might play an important role in genetic predisposition to lung cancer. The high expression of fra(3)(p14) in patients and their relatives may be a valid marker for genetic predisposition to lung cancer.

Association between serum neopterin, obesity and daytime sleepiness in patients with obstructive sleep apnea

OBJECTIVE Obesity and obstructive sleep apnea (OSA) and systemic inflammation may interact through biochemical pathways. Neopterin (NP) is a monocyte/macrophage activation marker produced by macrophages in response to interferon-gamma secreted by activated T-lymphocytes. This study examines the association between NP, obesity and OSA. PATIENTS AND METHODS The study included 22 newly diagnosed OSA (+) patients and 18 OSA (-) patients. Subjects with history of coronary artery disease, transplant patients, history of alcohol and drug abuse, history of HIV and any other significant medical illnesses such as active infections, autoimmune disease, malignancy, liver disease, pulmonary disease (COPD, asthma,...), neuromuscular disease, patients on immunomodulating therapy or HMG-CoA reductase inhibitors were excluded. RESULTS There were no significant differences in age, body mass index (BMI), and smoking habits of the OSA (+) patients and OSA (-) patients. Serum NP levels did not show any significant difference between the OSA (+) patients and OSA (-) patients, however, NP levels were positively correlated with BMI (r=0.320, p=0.044). There was no significant correlation between NP and any of the polysomnographic parameters. The result of stepwise regression analyses (r(2)=0.320, p<0.001) showed that high serum NP levels (p=0.004) and apnea-hypopnea index (AHI) were a risk factor for elevated Epworth sleepiness score, independent of BMI. CONCLUSION We suggest that serum NP levels correlate with BMI. There was a significant relationship between serum NP levels and excessive daytime sleepiness in OSA patients.

Catheter-Directed Therapy in Acute Pulmonary Embolism with Right Ventricular Dysfunction: A Promising Modality to Provide Early Hemodynamic Recovery

Background Catheter-directed therapy (CDT) for pulmonary embolism (PE) is considered as an alternative to systemic thrombolysis (ST) in patients with hemodynamically unstable acute PE who are considered at high bleeding risk for ST. We aimed to evaluate the efficacy and safety of CDT in the management of acute PE with right ventricular dysfunction (RVD). The primary outcomes were mortality, clinical success, and complications. Secondary outcomes were change in hemodynamic parameters in the first 24 hours following the procedure. Material/Methods Medical records of consecutive patients diagnosed as having acute massive or submassive PE with accompanying RVD treated by immediate CDT at our institution from January 2007 to January 2014 were reviewed. Patient characteristics, mortality, achievement of clinical success, and minor and major bleeding complications were analyzed in the overall study group, as well as massive vs. submassive PE subgroups. Change in hemodynamic parameters in the second, eighth, and 24th hours after the CDT procedure were also analyzed. Results The study included 15 consecutive patients (M/F=10/5) with a mean age of 54.2±16.6 years who underwent immediate CDT. Nine of the patients had submassive PE, and 6 had massive PE. In-hospital mortality rate was 13.3% (95% CI, 0.04–0.38). One major, but not life-threatening, bleeding episode was evident in the whole group. Hemodynamic parameters were stabilized and clinical success was achieved in 14/15 (93.3%; 95% CI, 70.2–98.8) of the patients in the first 24 hours. Notably, the hemodynamic recovery was significantly evident in the first 8 hours after the procedure. Conclusions CDT is a promising treatment option for patients with acute PE with RVD with no fatal bleeding complication. In experienced centers, CDT should be considered as a first-line treatment for patients with acute PE and RVD and contraindications for ST, with the advantage of providing early hemodynamic recovery.

Soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) is decreased in lung cancer patients showing progression: a pilot study.

Tumor growth and metastasis depend on angiogenesis, and the vascular endothelial growth factor (VEGF) is known to be one of the most important angiogenic factors although the knowledge about its receptors is limited. We, therefore, investigated the treatment-related changes both in the level of the soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) in the serum by ELISA and the expression of VEGFR-1 in cancer tissues by immunohistochemistry. The serum levels were studied in 38 lung cancer patients, and 55 control subjects (21 benign disease and 34 healthy subjects) before the chemotherapy. The treatment-related changes in serum sVEGFR-1 were evaluated in 15 patients 24 and 48 hours after treatment. In addition to serum analysis, the tissue expressions were evaluated in 32 patients before treatment. The treatment-related changes in tissue VEGFR-1 expressions were evaluated in only 12 patients 24 hours after treatment. We observed no significant difference in terms of serum sVEGFR-1 levels between malignant and nonmalignant groups (p > 0.05). There were no significant differences in the levels of sVEGFR-1 before and after treatment (p > 0.05). However, there was a significant difference between sVEGFR-1 levels in the groups (regressive, stable, progressive) classified according to the response to therapy (p = 0.043). A significant difference also was present between the expression levels of tissue VEGFR-1 in the same groups (p = 0.037). As a conclusion, we suggest that prechemotherapy sVEGFR-1 can be helpful for prediction of long-term response to therapy, but it should be studied in larger groups to elucidate its benefit in clinics.

Mutation analysis of the FHIT gene in bronchoscopic specimens from patients with suspected lung cancer

Aims and Background Lung cancer is a leading cause of cancer death worldwide. However, despite recent advances in molecular biology that have revealed various genetic changes in lung cancer, the prognostic outcome of lung cancer patients has improved only minimally. This situation has changed fundamentally with the identification of molecular abnormalities that are characteristic of premalignant changes, such as changes in tumor suppressor genes, loss of heterozygosity at crucial sites, and activation of oncogenes. Inactivation of the tumor suppressor gene Fragile Histidine Triad (FHIT) is a frequent genetic change in lung cancer. The aim of this study was to identify FHIT gene alterations in bronchoscopy specimens of patients with suspected lung cancer and to determine the molecular relevance, if any, of FHIT alterations in the development of cancer. Patients and Methods Sixty-two patients with suspected lung tumors were screened for variations within exons 5-9 of the FHIT gene using intronic primer pairs and single-strand conformation polymorphism and sequencing analysis. Results FHIT gene alterations were detected in 27 out of 62 bronchoscopic specimens (43.54%). All of these alterations were identified as T to A alteration at position IVS8-17. This intronic variant also was identified in approximately half of control cases (45%). Conclusions Our findings showed that the FHIT IVS8-17 T to A alteration identified in bronchoscopy specimens from patients with clinically suspected lung cancer is a polymorphism found in the Turkish population. We think that this polymorphism does not affect gene function because it is located in the intron portion of the gene and is present in many cancer patients as well as healthy subjects. We suggest that the FHIT gene may be turned off in lung carcinogenesis via other genetic or epigenetic mechanisms rather than mutations.