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Background and objective: Extrapulmonary sarcoidosis is common, and is almost always associated with concomitant thoracic involvement. Extrapulmonary manifestations vary on the basis of gender, age at presentation and ethnicity. The aim of this study was to investigate extrapulmonary involvement in patients with sarcoidosis in Turkey. Methods: This study was conducted by Turkish Thoracic Society Clinical Problems Study Group. New cases of sarcoidosis between 1 June 2004 and 31 May 2006 were recorded on electronic case record forms sent to all potential investigators and information about extrapulmonary involvement was collected. Results: One hundred and nineteen of 293 patients (83 female, 36 male, mean age = 45 ± 12 years) had extrapulmonary involvement in this study (40.6%). The median time to diagnosis was 6 months and this was longer than patients with just thoracic sarcoidosis (P = 0.001). Extrapulmonary symptoms were present in 181 (61.8%) patients, and skin lesions, arthralgia and back pain were the commonest (33.4%, 20.8% and 16.4%, respectively). Incidence of organ involvement was independent of age with the exception of ocular involvement, which was higher in those under the age of 40 years (P = 0.007). Conclusions: Skin and peripheral lymph node involvement were the most common sites of extrapulmonary involvement and ocular involvement was more common in those under the age of 40 years in patients with sarcoidosis in a Turkish population.

Objective: We aimed to assess the resting energy expenditure in bipolar I disorder, manic episode patients. Method: Forty-two bipolar I disorder, manic episode patients that were treated in the inpatient psychiatry clinic of Trakya University Hospital and had met the necessary study criteria were included along with 27 controls. DSM-IV criteria and the Bech-Rafaelsen Mania Rating Scale were used to evaluate patients’ diagnosis and severity of the manic episodes. The indirect calorimetry device was used to measure resting energy expenditure values. Results: Resting energy expenditure values of manic patients were found to be higher than those of the controls. Controls showed significant correlations between body mass index and resting energy expenditure, but manic patients did not exhibit similar correlations. There was also no relation between Bech-Rafaelsen Mania Rating Scale scores and resting energy expenditure values in manic patients. Conclusions: We found significantly increased resting energy expenditure values in bipolar I disorder, manic episode patients. These findings suggest a possible clinical use of resting energy expenditure for evaluation of bipolar I disorder manic episode and also suggest resting energy expenditure as a possible biological marker.

An elevated plasma D-dimer level indicates the activation of coagulation and fibrinolysis. In the present study, we investigated the association of pre-treatment haemostatic parameters (D-dimer, fibrinogen and prothrombin fragment 1+2) with clinicopathological parameters and outcome in patients with lung cancer.Plasma levels of D-dimer and other parameters were measured in 78 evaluable patients with lung cancer (60 non-small cell lung cancers, 18 small cell lung cancers). At diagnosis, 35 patients (44.9%) were locally advanced stage (IIIA/B) and 43 patients (55.1%) had metastatic disease (IV). Multivariate statistical analysis was carried out using Cox's proportional hazards model. The receiver operating characteristic curve was used to determine the cut-off values for D-dimer, fibrinogen and prothrombin fragment 1+2.The median survival for all patients was 264 days (95% confidence interval 200-328 days). A significant association between the plasma levels of D-dimer and the response to chemotherapy was observed (P=0.03). With the univariate analysis, tumour stage, pre-treatment plasma levels of D-dimer, fibrinogen, platelet count, lactate dehydrogenase concentration and Karnofsky performance status were predictive for survival. With the multivariate analysis (Por =0.1), the plasma level of D-dimer (P0.001), tumour stage (P=0.01) and Karnofsky performance status (P=0.02) were identified as independent predictive factors. The median survival times were 405 days (95% confidence interval 165-644 days) and 207 days (95% confidence interval 146-267 days, P0.001), respectively, for patients with a low D-dimer level (or =0.65 microg/ml) and a high D-dimer level (0.65 microg/ml).Elevated plasma levels of D-dimer in patients with lung cancer are associated with decreased survival and a poor response to treatment. Pre-treatment for the D-dimer level may be useful in the prediction of survival and the response to treatment.

The mechanisms of dyspnea and exercise intolerance have not been fully elucidated. We aimed to investigate the clearance rate of technetium-99m diethyltriaminepentaaceticacid (Tc-99m DTPA) from lungs in hyperthyroid patients without clinical evidence of lung disease and to explore the interactions between their Tc-99m DTPA radioaerosol lung scintigraphy, spirometric measurements, and the levels of thyroid hormones.We studied 19 hyperthyroid patients and 16 sex- and age-matched controls. Thyroid hormone levels were assessed. Spirometric lung function tests, diffusing capacity of the lung for carbon monoxide (DLCO) and the clearance rate of Tc-99m DTPA were performed in all participants. Ratio of DLCO value to the alveolar ventilation (DLCO/VA) and the means of half-time (T1/2) of Tc-99m DTPA clearance rate, which were used to evaluate alveolar-capillary membrane permeability, were calculated.There were no statistical differences between spirometric parameters (VC, FVC, FEV1/FVC, FEF 25-75) of the two groups (p0.05). Although the mean FEV1 level was significantly lower in the hyperthyroid patients than the control subjects (p0.01), in five patients FEV1 was only less than 80 percent of the predicted value. No significant difference in the means of DLCO, DLCO/VA or T1/2 values of Tc-99m DTPA clearance was observed between the two groups (p0.05). In hyperthyroid patients, there was a positive relation between DLCO/VA, DLCO/VA % and T1/2 values of Tc-99m DTPA clearance (p0.01, r = 0.732, p0.01, r = 0.742, respectively). The lung volumes and the levels of thyroid hormones did not show a significant relationship to T1/2 values of Tc-99m DTPA clearance in hyperthyroid group (p0.05).We conclude that increased thyroid hormones have no effect on permeability of alveolar-capillary membrane in hyperthyroid patients.

WOS: 000266684100017, PubMed ID: 19181507, Epidemiological characteristics of sarcoidosis differ according to geographical distribution. The aim of our study was to disclose epidemiological characteristics in our country. The data was collected from investigators, who sent information on newly-diagnosed patients via internet. In 2 years 198 female and 95 mate patients were enrolled to the study (f/m:2.08). Mean age of patients was 44 +/- 13 years (17-90). Mean age of mate patients was 38 12 while mean age of female patients was 48 13 (p < 0.001). 73.4% of patients were nonsmokers (85.4% of females; 48.4% of mates; (p < 0.001)). About 50% of our 293 patients were housewives. Familial sarcoidosis was found in 3 patients' first degree relatives. Estimated annual incidence of sarcoidosis for Turkey was calculated as 4 per 100,000 person. According to our study, 2/3 of sarcoidosis patients were women; mean age of patients was 45 and the disease began 10 years later in female patients. 80% of patients were nonsmokers; negative relation between sarcoidosis and smoking was evident especially in women. Familial sarcoidosis frequency was lower compared to other studies in the literature. There was no occupational exposure history in our patients. Our incidence rate, is similar with the results of other European studies. (C) 2008 Elsevier Ltd. All rights reserved.

Coskun, Abdurrahman/0000-0002-1273-0604 WOS: 000265263400004 PubMed: 19365167 Background: Pregnancy-associated plasma protein-A (PAPP-A) has insulin-like growth factor (IGF)-dependent IGFBP-4 protease activity and plays an important role in amplifying local IGF-1 activity in wound healing, vascular repair. and bone remodeling. We postulated that PAPP-A may contribute to the availability and activity of IGFs, which affect lung cancer. Therefore, we determined the levels of PAPP-A in patients with lung cancer and their possible clinical significance. Methods: The study population consisted of 83 patients with lung cancer and 33 healthy subjects as a control group. Serum PAPP-A levels were determined using an ultrasensitive enzyme-linked immunosorbent assay. Results: The serum PAPP-A levels were higher in patients with lung cancer [median (interquartile range) 10.7 (7.6-14.2) ng/mL] than in the control group [6.2 (5.2-9.8) ng/mL, P < 0.001]. There was a significant negative correlation between the serum PAPP-A levels and Karnofsky performance status (r = -0.330; P < 0.001) and a positive correlation with patient age (r = 0.358; P < 0.001). Conclusion: PAPP-A is a proatherosclerotic metalloproteinase that is also thought to be an inflammatory marker. We found that the serum PAPP-A levels increased in patients with lung cancer and postulated that PAPP-A levels may be a prognostic factor in such cases.

The study was prospectively designed to assess the correlation between a new clinical model empirically developed for acute pulmonary embolism (PE) and ventilation/perfusion (V/P) scan results. One hundred sixty consecutive patients with suspected acute PE underwent clinical evaluation before V/P scintigraphy. The clinical probability of PE was categorized according to a structured clinical model empirically developed as low, intermediate, or high, and the results were compared with those of V/P scintigraphy. Forty, 61, and 59 patients were classified as low, intermediate, and high clinical probability, respectively. Seventy-five percent (30/40) of the patients with low clinical probability were also of low scintigraphic probability or had a normal result (rs: 0.39, p=0.000); 28% (17/61) of the patients with intermediate clinical probability demonstrated intermediate scintigraphic probability (rs: 0.20, p=0.012); and 68% (40/59) of the patients with high clinical probability were also of high scintigraphic probability (rs: 0.43, p=0.000). Overall, the correlation of two scoring systems was statistically significant (rs: 0.39, p=0.000). Unilateral leg swelling (p=0.027), syncope or near syncope (p=0.002), amputation of a hilar artery (p=0.007), and electrocardiographic signs of right ventricular overload (p=0.000) prevailed in patients with high scintigraphic probability. “Syncope-near syncope or hemodynamic collapse” PLUS “electrocardiographic signs of right ventricular overload or hypoxemia” combination had the most significant correlation with a high scintigraphic probability (rs: 0.31; p=0.000). In conclusion, the new clinical model empirically developed was significantly successful to provide comparable results with V/P scan. This consistency was particularly prominent in patients with low or high clinical probability for PE.

While the increased prevalence of venous thromboembolic events (VTE) is fully recognized in lung cancer, its pathogenesis is not fully understood. Profiling of surrogate markers of thrombosis and inflammation provides an opportunity to understand the pathogenesis of VTE. More recently, ProteinChip Array technology has provided a novel approach to profile unique biomarkers in cancer patients. Protease activation in these patients results in the generation of unique biomarkers, which can be identified and monitored during the course of patient management. In a prospective, randomized, controlled study patients with inoperable lung cancer (n=100) were randomized to receive A) chemotherapy, radiation and warfarin (INR 1.5–2.5) or B) chemotherapy, radiation without warfarin (n=50). Blood samples were drawn prior to and after the second treatment cycle in both groups A and B. All samples were also analyzed for such inflammation markers as the tumor necrosis factor alpha (TNFa), CD 40 ligand (CD 40L), C-reactive protein (CRP), interleukin 1 beta (IL-1B), asymmetric dimethylarginine (ADMA) and nitric oxide (NO). In addition, prothrombin fragment F1.2 (F1.2), thrombin antithrombin complex (TAT) and functional microparticles were also measured. Proteomic profiling is widely used to identify unique biomarkers in various hemotologic disorders. Albumin was used as control proteins throughout the study. The baseline blood levels of the inflammatory markers and coagulation activation marker were increased in both the warfarin treated and control group. After the second treatment cycle, the warfarin treated group exhibited varying levels of decrease in all of the surrogate markers of coagulation activation and inflammation (13 – 15%). On the other hand, none of the warfarin treated group showed a marked increase in the TNFα, CD40L, NO, F1.2 and TAT (18–30%). No change in the IL-1B was noted in this group. However, CRP levels were markedly reduced (46%). Most of the baseline samples in both groups showed a unique biomarker peak at 11.9 kDa. The prevalence of this unique biomarker peak was decreased after the second cycle of chemotherapy and after the final course of chemotherapy, it was totally diminished. No significant differences in the down regulation of this unique biomarker were obvious in both groups. Since inflammatory markers showed a decrease (13–50%) in the warfarin treated group, whereas the non-warfarin treated group exhibited an increase (18–30%) in all markers except IL-1B, CRP and ADMA, anticoagulation down regulates these mediators. Markers of thrombin generation were also down regulated in the warfarin treated group. The identification of the unique biomarker at 11.9 kDa in both groups and its gradual down regulation eventually leading to diminution in both groups, suggests that chemotherapy and radiation treatment appear to regulate this biomarker. The levels of various inflammatory markers are upregulated in lung cancer suggesting a pathogenic role of this process in lung cancer. Warfarin down regulated the inflammatory process in contrast to the non-warfarin treated group. However, the unique biomarker at 11.9 kDa appears to be regulated by chemotherapy and radiation. The clinical relevance of these observations requires additional investigations.

7705 Background: Venous thromboembolic events (VTE) are associated with lung cancer and significantly contributes to the increased mortality in these patients. While the increased prevalence of VTE is fully recognized in lung cancer, its pathogenesis is not fully understood at this time. Even the patients undergoing therapeutic interventions are at high risk to develop VTE. Profiling of surrogate markers of thrombosis and inflammation provides an opportunity to understand the pathogenesis of thrombosis in these patients. Methods: In a prospective, randomized, controlled study patients with inoperable lung cancer (n=100) were randomized to receive chemotherapy, radiation and warfarin (INR 1.5–2.5) or chemotherapy, radiation without warfarin (n=50). Blood samples were drawn prior to and after the second treatment cycle with warfarin. All samples were analyzed for such inflammation markers as the tumor necrosis factor alpha (TNF a), CD 40 ligand (CD 40L), C-reactive protein (CRP), interleukin 1 beta (IL-1β), asymmetric dimethylarginine (ADMA) and nitric oxide (NO). In addition, prothrombin fragment F1.2 (F1.2) and thrombin antithrombin complex (TAT) were also measured. Results: The results are summarized in the following table . All of the surrogate markers of inflammation showed a decreased trend (13–50%) in the warfarin treated group, whereas the non-warfarin treated group exhibited an increase (18–46%) in all markers except CRP and ADMA. The markers of thrombin generation were down regulated in the warfarin treated group. Conclusions: The levels of various inflammatory markers are upregulated in lung cancer suggesting a pathogenic role of this process in lung cancer. Warfarin down regulated the inflammatory and thrombogenic processes in contrast to the non-warfarin treated group. The clinical relevance of these observations require additional analysis. No significant financial relationships to disclose. [Table: see text]

17050 Background: Venous thromboembolic events (VTE) are associated with lung cancer and significantly contributes to the increased mortality in these patients. While the increased prevalence of VTE is fully recognized in lung cancer, its pathogenesis is not fully understood. Even the patients undergoing therapeutic interventions are at high risk to develop VTE. These patients provide a unique clinical setting to investigate the pathogenesis of lung cancer associated thrombosis. Methods: In a prospective, randomized, controlled study patients with inoperable lung cancer (n = 100) were randomized to receive chemotherapy, radiation and warfarin (INR 1.5–2.5) or chemotherapy, radiation without warfarin (n = 50). Blood samples were drawn prior to and after the second treatment cycle with warfarin. All samples were analyzed for tumor necrosis factor alpha (TNF α), CD 40 ligand (CD 40L), C-reactive protein (CRP), interleukin 1 beta (IL-1β), asymmetric dimethylarginine (ADMA) and nitric oxide (NO). Results: Summarized in the table given below. All of the surrogate markers of inflammation showed a decreased trend (13–50%) in the warfarin treated group, whereas the non-warfarin treated group exhibited an increase (18–46%) in all markers except CRP and ADMA. Conclusions: The levels of various inflammatory markers are upregulated in lung cancer suggesting a pathogenic role of this process in lung cancer. Warfarin down regulated the inflammatory process in contrast to the non-warfarin treated group. The clinical relevance of these observations require additional analysis. [Table: see text] No significant financial relationships to disclose.