Bone Marrow Transplantation as a Rare Cause of Pulmonary Arterial Hypertension.

The development of pulmonary arterial hypertension after bone marrow transplantation (BMT) is a rare but serious complication. In this case report, we presented the development of pulmonary arterial hypertension in a 22-year-old woman who underwent BMT due to aplastic anemia. Her symptoms on admission included shortness of breath, palpitations and fatigue. Pulmonary hypertension was classified with right heart catheterization as pul monary arterial hypertension. The patient's laboratory, echocardiographic and hemodynamic findings improved with pulmonary arterial hypertension-specific treatment. Pul monary arterial hypertension should be considered in the differ ential diagnosis of BMT patients with 'unexplained' hypoxemia or respiratory distress.

Delays in Diagnosis and Treatment in Patients Underwent Endobronchial Ultrasound-Transbronchial Needle Aspiration (EBUS-TBNA).

Objectives: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been recognized as the first method of choice in the diagnosis of mediastinal and hilar lesions. Although the procedure is commonly used, there is no study assessing its contribution to the duration required for diagnosis and treatment. In this study, we aimed to determine the extent of diagnosis and treatment delays when using the EBUS-TBNA procedure and to address the possible factors contributing to these delays. Materials and Methods: The demographic data, pathological diagnosis, need for additional procedures, symptoms, presenting complaints, and the time until the beginning of treatment were recorded retrospectively in all patients who had undergone EBUS-TBNA. Results: A total of 134 patients (mean age 60.7 ± 12 years, M/F: 78/56) were included. Delay of the patients was found in 60.4% (n = 81), delayed referral in 35.8% (n = 48), diagnosis delays in 84.3% (n = 113), treatment delays in 38.8% (n = 52), and total delay in 73.1% (n = 98) of the patients. A statistically significant association was found between referral delay and total delay with age groups (p=0.006) and between patient delay and the presence of symptoms (p=0.027). EBUS-TBNA was found to have the lowest effect among all delay parameters (ß: 0.104, p < 0.001) in the regression analysis. When diagnosis times' subgroups were compared, EBUS-TBNA was found to have the least effect (correlation coefficient: 0.134, p=0.004). Conclusion: We found that approximately ¾ of the patients had a delay and this is not acceptable in real terms. Considering that the patient burden is increasing day by day, it is necessary to make a radical change in health care or a change in strategy in order to prevent delays. EBUS-TBNA, which is in the diagnosis delay subgroup, is less invasive and accelerates the process.

Effects of varenicline on lung tissue in the animal model. / Efeitos da vareniclina no tecido pulmonar em modelo animal.

OBJECTIVE: This study aimed to investigate acute and chronic effects of varenicline on lung tissue in an experimental study. METHODS: A total of 34 rats were randomly allocated into study (varenicline) and control groups. The rats were divided into two groups (i) control group, (ii) varenicline group. Then, the rats in the each group were sub-divided equally in turn as acute (C1; V1) and chronic (C2; V2) ; all rats of acute and chronic groups were sacrificed under the anesthesia on the 45th day for acute group [C1 (n=5) and V1 (n=12)] and the 90th day for chronic group [C2 (n=5) and V2 (n=12)], respectively. Thus, biochemical and histopathological analysis were carried out. RESULTS: Thirty four rats completed the study, 24 were in varenicline group and 10 were in control group. In chronic exposure to varenicline, oxidant levels comprising of malondialdehyde (MDA), and myeloperoxidase (MPO) increased and superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GPx) levels, named as antioxidants, decreased significantly when compared to the control group. MDA and MPO levels were also significantly higher and SOD, CAT, GPx, GSH levels were also significantly lower in chronic varenicline group when compared to acute varenicline group. These findings were also supported by histopathological observations. CONCLUSION: This is the first study, which evaluated pulmonary effects of varenicline experimentally on an animal model. It was observed that chronic varenicline treatments cause inflammation and lung cell injury.

OBJETIVO: O objetivo deste estudo foi investigar os efeitos agudos e crônicos da vareniclina no tecido pulmonar em um estudo experimental. MÉTODOS: Um total de 34 ratos foi alocado aleatoriamente em grupos de estudo (vareniclina) e controle. Assim, os ratos foram divididos em dois grupos: (i) grupo controle e (ii) grupo vareniclina. A seguir, os ratos de cada grupo foram, por sua vez, subdivididos igualmente em agudos (C1; V1) e crônicos (C2; V2), e todos os ratos dos grupos agudos e crônicos foram sacrificados sob anestesia: no 45.º dia, para o grupo agudo [C1 (n=5) e V1 (n=12)], e no 90.º dia, para o grupo crônico [C2 (n=5) e V2 (n=12)], respectivamente. Em seguida, foram realizadas análises bioquímicas e histopatológicas. RESULTADOS: Trinta e quatro ratos completaram o estudo. Destes ratos, 24 estavam no grupo vareniclina e 10 no grupo controle. Na exposição crônica à vareniclina, os níveis de oxidante composto por malondialdeído (MDA) e mieloperoxidase (MPO) aumentaram, e os níveis de superóxido dismutase (SOD), catalase (CAT), glutationa (GSH) e glutationa peroxidase (GPx), nomeados como antioxidantes, diminuiram significativamente quando comparados com o grupo controle. Os níveis de MDA e MPO também foram significativamente mais elevados e os níveis de SOD, CAT, GPx e GSH foram significativamente mais baixos no grupo vareniclina crônico, quando comparado ao grupo vareniclina agudo. Estes achados também foram confirmados por observações histopatológicas. CONCLUSÕES: Este é o primeiro estudo que avaliou os efeitos pulmonares da vareniclina experimentalmente em um modelo animal. Observamos que o tratamento crônico da vareniclina causa inflamação e lesão pulmonar.

Efeitos da vareniclina no tecido pulmonar em modelo animal / Effects of varenicline on lung tissue in the animal model

RESUMO Objetivo O objetivo deste estudo foi investigar os efeitos agudos e crônicos da vareniclina no tecido pulmonar em um estudo experimental. Métodos Um total de 34 ratos foi alocado aleatoriamente em grupos de estudo (vareniclina) e controle. Assim, os ratos foram divididos em dois grupos: (i) grupo controle e (ii) grupo vareniclina. A seguir, os ratos de cada grupo foram, por sua vez, subdivididos igualmente em agudos (C1; V1) e crônicos (C2; V2), e todos os ratos dos grupos agudos e crônicos foram sacrificados sob anestesia: no 45.º dia, para o grupo agudo [C1 (n=5) e V1 (n=12)], e no 90.º dia, para o grupo crônico [C2 (n=5) e V2 (n=12)], respectivamente. Em seguida, foram realizadas análises bioquímicas e histopatológicas. Resultados Trinta e quatro ratos completaram o estudo. Destes ratos, 24 estavam no grupo vareniclina e 10 no grupo controle. Na exposição crônica à vareniclina, os níveis de oxidante composto por malondialdeído (MDA) e mieloperoxidase (MPO) aumentaram, e os níveis de superóxido dismutase (SOD), catalase (CAT), glutationa (GSH) e glutationa peroxidase (GPx), nomeados como antioxidantes, diminuiram significativamente quando comparados com o grupo controle. Os níveis de MDA e MPO também foram significativamente mais elevados e os níveis de SOD, CAT, GPx e GSH foram significativamente mais baixos no grupo vareniclina crônico, quando comparado ao grupo vareniclina agudo. Estes achados também foram confirmados por observações histopatológicas. Conclusões Este é o primeiro estudo que avaliou os efeitos pulmonares da vareniclina experimentalmente em um modelo animal. Observamos que o tratamento crônico da vareniclina causa inflamação e lesão pulmonar.

ABSTRACT Objective This study aimed to investigate acute and chronic effects of varenicline on lung tissue in an experimental study. Methods A total of 34 rats were randomly allocated into study (varenicline) and control groups. The rats were divided into two groups (i) control group, (ii) varenicline group. Then, the rats in the each group were sub-divided equally in turn as acute (C1; V1) and chronic (C2; V2) ; all rats of acute and chronic groups were sacrificed under the anesthesia on the 45th day for acute group [C1 (n=5) and V1 (n=12)] and the 90th day for chronic group [C2 (n=5) and V2 (n=12)], respectively. Thus, biochemical and histopathological analysis were carried out. Results Thirty four rats completed the study, 24 were in varenicline group and 10 were in control group. In chronic exposure to varenicline, oxidant levels comprising of malondialdehyde (MDA), and myeloperoxidase (MPO) increased and superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GPx) levels, named as antioxidants, decreased significantly when compared to the control group. MDA and MPO levels were also significantly higher and SOD, CAT, GPx, GSH levels were also significantly lower in chronic varenicline group when compared to acute varenicline group. These findings were also supported by histopathological observations. Conclusion This is the first study, which evaluated pulmonary effects of varenicline experimentally on an animal model. It was observed that chronic varenicline treatments cause inflammation and lung cell injury.

Anticoagulant therapy for acute venous thromboembolism.

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are currently defined as venous thromboembolism (VTE) since they share pathophysiological features and the treatment is similar in many respects. It has been determined that more than 90% of PE cases originate from DVT in the legs. PE, which is difficult to diagnose, has a mortality rate of 12% when untreated. The worldwide increase in obesity, cancer diseases, and average survival time also contribute to the increase in the incidence of VTE. Traditional treatment of VTE includes heparin, low-molecular-weight heparin, and warfarin. Despite availability for oral use, warfarin has a narrow therapeutic range and a wide range of food interactions. After many years of research, new oral anticoagulant agents (NOACs) are expected to overcome these handicaps in treatment. In this review, the use of NOACs in the treatment of VTE is investigated in the light of current guidelines.

Protective and therapeutic effect of apocynin on bleomycin-induced lung fibrosis in rats.

We aimed to investigate the preventive and therapeutic effect of apocynin (APO) on bleomycin (BLC)-induced lung injury in rats. Rats were assigned into groups as follows: control group; APO group, 20 mg/kg APO was given intraperitoneal for 29 days; BLC-1 and BLC-2 groups, a single intratracheal injection of BLC (2.5 mg/kg); APO+BLC-preventive group, 20 mg/kg APO was administered 12 h before the intratracheal BLC injection and continued for 14 days; BLC+APO-treatment group, 20 mg/kg APO was given on the 14th day after the intratracheal BLC injection and continued to sacrifice. The BLC-1 group was sacrificed on the 14th day of BLC administration to validate BLC-induced lung inflammation and fibrosis on the 14th of study initiation. All other groups were sacrificed on the 29th day after BLC administration. The semiquantitative histopathological assessment, tissue levels of malondialdehyde (MDA), superoxide dismutase, catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), total antioxidant capacity, total oxidant status (TOS), and oxidative stress index (OSI) were measured. An addition to the serum myeloperoxidase (MPO), the cell count and cytokines (IL-1ß, IL-6, and IL-8) of bronchoalveolar lavage (BAL) fluid were assayed. BLC-provoked histological changes were significantly detected compared to the control group. APO restored these histological damages in different quantity in the treatment and prevention groups. BLC caused a significant decrease in GSH, CAT, and GPX, which were accompanied with significantly the increased MDA, TOS levels, and OSI in the lung tissue concomitant with increased levels of the cellular account and proinflammatory cytokines in the BAL fluid. Otherwise, APO administration, both before and after BLC, reversed all biochemical markers and cytokine as well as histopathological changes induced by BLC. Interestingly, APO treatment reversed MPO activity in serum increased by BLC. In this study, both protective and therapeutic effects of APO against BLC-induced lung fibrosis were demonstrated for the first time.

Protective and therapeutic effect of molsidomine on bleomycin-induced lung fibrosis in rats.

We aimed to investigate the preventive and treatment effect of molsidomine (MOL) on bleomycin (BLC)-induced lung injury in rats. Rats were assigned into groups as follows: control group; MOL group, 10 mg/kg MOL was continued orally for 29 day; BLC group, a single intratracheal injection of BLC (2.5 mg/kg), MOL+BLC-preventive group, 10 mg/kg MOL was administered 1 day before the intratracheal BLC injection and continued for 14 days; BLC+MOL-treatment group 10 mg/kg MOL was given on 14th day after the intratracheal BLC injection and continued until sacrifice. All animals were sacrificed on 29th day after BLC administration. The semiquantitative histopathological assessment, tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), total antioxidant status (TAS), total oxidant status (TOS), myeloperoxidase (MPO), and oxidative stress index (OSI) were measured. BLC-provoked histological changes were significantly detected compared to the control group. MOL restored these histological damages in different quantity in the treatment and preventive groups. BLC administration significantly decreased levels of GSH and TAS when compared to controls and these reductions was significantly ameliorated by MOL given prophylactic setting. However, therapeutic MOL administration significantly increased the TAS level decreased by BLC. The levels of MDA, MPO, and TOS were significantly increased with BLM, and these augmentations of MDA and TOS were significantly reduced by MOL given prophylactic setting. Furthermore, the OSI was higher in the BLC group, and this increase was reversed by the MOL administration before and after BLC treatment. In this study, both protective and therapeutic effects of MOL against BLC-induced lung fibrosis were demonstrated for the first time.

QT dispersion in patients with pulmonary embolism.

BACKGROUND: Various ECG patterns have been associated with acute pulmonary embolism. However, there is no data regarding the association between QT interval measurements and pulmonary embolism. We aimed to investigate the association between QT dispersion and the severity of pulmonary embolism (PE). METHODS: One hundred twenty-nine pulmonary embolism patients (mean age 58 ± 16.5 years) with ECGs obtained within the first 24 hours of hospital admission were included in the study. Patients were classified into low, intermediate and high-risk groups. We retrospectively measured ECG scores; maximum and minimum corrected QT intervals (QTc(max) and QTc(min)) and corrected QT interval dispersion (QTcd) in each risk group of patients. RESULTS: There was an increasing ECG score through from low to high-risk PE [3 (Interquartile Range, IQR: 2), 5 (IQR: 6) and 10 (IQR: 7) p < 0.0001]. QT interval analysis showed that QTcd was higher in high-risk group than in low and intermediate-risk groups (59.5 ± 23.4, 69.2 ± 21, 95.9 ± 33.2, p <0.001 and p = 0.01, respectively). Patients who died after diagnosis had significantly higher QTcd values at baseline compared with the QTcd values of surviving patients (89.1 ± 45.5 to 65 ± 22.9, p = 0.001). The sensitivity of QTcd > 71.5 ms for prediction of mortality was 71% with a specificity of 73% (p = 0.001). We observed a strong correlation between QTcd and ECG score values (r = 0.69, p< 0.001). There was also a correlation between QTcd values and pulmonary artery pressure (PAP) (r = 0.27, p = 0.05). CONCLUSION: QTcd is significantly increased in high-risk PE patients compared to intermediate and low-risk patients. In addition, QTcd is significantly correlated with ECG score and PAP.

[Comparative evaluation of 113 cases with severe and mild forms of extrapulmonary tuberculosis]. / Ciddi ve hafif seyirli 113 akciger disi tüberküloz olgusunun karsilastirmali olarak degerlendirilmesi.

Tuberculosis, one of the oldest diseases of human beings, has still high mortality rates. In this prospective study, 113 HIV seronegative patients with extrapulmonary tuberculosis (EPT) who were admitted to our department between January 2001 and July 2006 have been evaluated and cases with severe or mild forms of EPT have been compared with respect to epidemiological and clinical features, laboratory results and treatment outcomes. The age range of the patients were 16-78 years old (mean age: 46.3 +/- 16.9 years), and 64 of them (56.6%) were female. Severe and mild forms of EPT were diagnosed in 49 (43.3%) and 64 (56.6%) of the patients, respectively. The most frequently involved organ was detected as lymph nodes (43.3%), followed by pleura and vertebrate involvements with the rates of 12.4%. There was an underlying disease in 35 (30.9%) of the patients (diabetes mellitus in 15%; chronic renal dysfunction in 11.5%; malignancy in 4.4%), history of passed tuberculosis infection in 13 (11.5%) and history of contact with a tuberculosis patient in 25 (22.1%). In direct microscopic examination, samples from 19 (16.8) patients were found positive for acid-fast bacilli, and samples cultivated in Lowenstein-Jensen media yielded mycobacterial growth in 25 (22.1%) patients. The diagnosis have been made histopathologically in 89 (78.7%) of the cases. In comparison of the patients with severe and mild forms of EPT, the severe form were detected more frequently in males (p= 0.01), the positivity rates of culture and acid-fast staining were higher in patients with severe form (p= 0.0004 and p= 0.001, respectively). The mortality rate was also found higher in patients with severe form (p= 0.046). The cases who were diagnosed as EPT have been treated by three or four antituberculosis drugs. Izoniazid (300 mg/day, 6-12 months), rifampicin (600 mg/day, 6-12 months), ethambutol (1500 mg/day, 2-4 months), pyrazinamide (2000 mg/day, 2-4 months) and streptomycin (1 g/day, 45-60 days) were used for the therapy. Side effects due to the therapy were observed in 13.3% of the cases (most frequently; gastrointestinal intolerance in 53.3% and hepatitis in 40%), however, there was no necessity to quit the therapy. Surgical treatment has been applied in 14 (12.4%) of the patients. As a result, the investigation of epidemiological and clinical characteristics of extrapulmonary tuberculosis on the large series of cases may be essential for early diagnosis and treatment in endemic countries such as Turkey.

Lung cancer and mesothelioma in towns with environmental exposure to asbestos in Eastern Anatolia.

OBJECTIVE: Our previous study demonstrated the presence of environmental tremolite and chrysotile asbestos fiber exposure in Hekimhan town in Malatya located in eastern Turkey. The aim of this study was to investigate whether environmental asbestos exposure increases the incidence of lung cancer and mesothelioma. METHOD: One hundred and forty-nine patients with mesothelioma and lung cancer living in the center or in the towns of Malatya were retrospectively analyzed. The Incidences of lung cancer and mesothelioma were calculated. RESULTS: The incidences of lung cancer and mesothelioma were 3.39/100,000 and 0.21/100,000, respectively, for the whole population of Malatya; while they were 8.23/100,000 and 1.45/100,000 in Hekimhan. The incidences were strikingly high (22.39/100,000 for lung cancer and 7.46/100,000 for mesothelioma) in Arguvan, another town in Malatya where an analysis for asbestos could not be performed. The overall incidence in Turkey was reported as 5.9/100,000 by the Health Ministry in 1994. The incidences of lung cancer were nearly 1.3-fold higher in Hekimhan and fourfold higher in Arguvan then in the general population of Turkey. CONCLUSION: The incidences of mesothelioma and lung carcinoma in Hekimhan were higher than those of the general population in Turkey, suggesting a role of environmental asbestos exposure in lung cancer and mesothelioma.