Upregulation of multi drug resistance genes in doxorubicin resistant human acute myelogeneous leukemia cells and reversal of the resistance

The major problem in the treatment of acute myeloid leukemia (AML) patients results from multidrug resistance to administered anticancer agents. Drug resistance proteins, MDR1 and MRP1, which work as drug efflux pumps, can mediate the multidrug resistance of human leukemia cells. In this study, the mechanisms of resistance to doxorubicin-induced cell death in human HL60 AML cells were examined. Continuous exposure of cells to step-wise increasing concentrations of doxorubicin resulted in the selection of HL60/DOX cells, which expressed about 10.7-fold resistance as compared to parental sensitive cells. The expression analyses of MRP1 and MDR1 drug efflux proteins in doxorubicin-sensitive and -resistant HL60 cells revealed that there was an upregulation of MRP1 gene in HL60/DOX cells as compared to parental sensitive cells. On the other hand, while there was no expression of MDR1 gene in parental cells, the expression of MDR1 gene was upregulated in HL60/DOX cells. HL60/DOX cells also showed cross-resistance to cytosine arabinoside (Ara-c). This resistance was reversed by a combination therapy of Ara-c and cyclosporine A. However, the expression levels of CD15 and CD16 surface markers were significantly decreased in HL60/DOX cells.     

Nonsteroidal Peptic Damage in Rheumatoid Patients Receiving Second-Line Drugs

Using endoscopy, we assessed the prevalence of peptic ulceration in 281 rheumatoid patients receiving nonsteroidal antiinflammatory drugs alone, or in combination with second-line agents. Ulcers were found in 33 of 96 patients who took nonsteroidals only (33/96, 34%), compared with 8/33 (24%) on hydroxychloroquine, 10/30 (33%) on penicillamine, 13/46 (28%) on sulphasalazine, but only 11/76 (14%) on intramuscular gold plus nonsteroidals (chi 2 = 7.95, 0.001 less than p less than 0.01, p less than 0.05 using Bonferroni correction). Second-line drugs do not seem to increase the prevalence of ulcers related to nonsteroidal antiinflammatory drugs; on the contrary, fewer ulcers were found in patients receiving gold therapy, and this might have therapeutic implications.     

Severe primary hypothyroidism manifesting with torsades de pointes

Hypothyroidism can manifest with myriad cardiac abnormalities, often consisting of a combination of morphologic and functional changes. Low voltage, sinus bradycardia, and slowed conduction are usually found on electrocardiography. We describe a patient with severe hypothyroidism who presented with presyncope, prolongation of the QT interval, and polymorphic ventricular tachycardia (torsades de pointes). No other cause for the malignant ventricular ectopy was evident. With levothyroxine therapy, the QT interval normalized and the ventricular tachycardia was abolished. In addition to its commonly known cardiac effects, myxedema can predispose to the potentially life-threatening arrhythmia of torsades de pointes. Conversely, in patients presenting with QT interval prolongation and polymorphic ventricular tachycardia, hypothyroidism should be considered in the differential diagnosis.     

Prognostic factors in small cell lung cancer

In order to find out prognostic factors and treatment results in small cell lung cancer (SCLC), 40 patients diagnosed in one year period were prospectively analysed. Following history and physical examination, patients were grouped according to ECOG performance scale and underwent Chest X-ray and thoracic computerized tomography (CT). Complete blood count, biochemical analyses, tumor markers were taken. Abdominal USG or CT, bone scintigraphy, cranial CT or MRI and bone marrow biopsy were made for detection of metastases. Limited stage patients received chemotherapy and thoracic RT, whereas cases with extensive disease received chemotherapy. Nineteen cases had limited and 21 had extensive disease. When laboratory findings between 2 stages were compared, LDH, SGOT and GGT were significantly higher in extensive stage (p= 0.005, 0.015, 0.001, respectively). Overall median survival was 6 +/- 1 months, cumulative survival in 6 and 12 months were 39% and 20.72%, respectively. Median survival was 10 +/- 2 months in limited stage and 3 +/- 1 months in extensive stage, with a statististically significant difference. Univariate analyses showed that incresed LDH, CA15-3, GGT and SGOT levels, hipoproteinemia and poor performance scale were poor prognostic signs (p= 0.024, 0.032, 0.047, 0.013, 0.021 ve 0.013, respectively), however multivariate analyses revealed no significant difference. Other blood tests, pleural effusion, age, mediastinal lymph node metastases and weight loss had no prognostic effect. Stage was found to be progniostic factor with both univariate and multivariate analyses (p= 0.045).     

The first documented case of brucellosis manifested with pancytopenia and capillary leak syndrome

Hematological complications have been frequently associated with acute brucellosis, but pancytopenia is less frequently seen. Also, capillary leak syndrome has been rarely reported in the literature. In this report, we present a case of brucellosis with pancytopenia leading to capillary leak syndrome. A 21-year-old man was admitted to hospital with complaints of a one-month history of weakness, sweats, and fever and he had hepatosplenomegaly and edema over the pretibial areas. Hemogram revealed pancytopenia and biochemical tests revealed moderate hypoalbuminemia, elevations of lactate dehydrogenase and aspartate aminotransferase. He was diagnosed as brucellosis and capillary leak syndrome. He was given doxycycline and rifampicin. The patient's symptoms were resolved after treatment.     

Leptin and TNF-alpha levels in patients with chronic obstructive pulmonary disease and their relationship to nutritional parameters

BACKGROUND: Leptin is a protein mainly secreted by adipocytes, and the major function of leptin was its role in body weight regulation. In humans, there was a strong correlation between leptin and nutritional parameters, such as body mass index (BMI) and fat mass (FM). Administration of recombinant leptin to OB/OB mice, which have a genetic defect in leptin production, reduces food intake, increases energy expenditure, and decreases body weight. It is suggested that increased levels of circulating leptin levels may contribute to anorexia and weight loss in pathologic conditions including chronic obstructive pulmonary disease (COPD). Recent studies have provided evidence for a link between leptin and proinflammatory cytokines such as TNF-alpha. OBJECTIVE: This study aimed to detect serum leptin and TNF-alpha levels in COPD patients without weight loss during stable disease and acute exacerbation, and to investigate relationships between leptin, TNF-alpha and nutritional parameters at different stages of the disease. MATERIAL AND METHODS: 26 stable COPD patients, 16 COPD patients with acute exacerbation and 15 control subjects participated in this study. To eliminate the effects of sex differences, all patients and controls were male. BMI, percent ideal body weight, percent FM, sum of skinfold thickness and serum leptin and TNF-alpha levels were measured in all participants. Leptin and TNF-alpha levels were measured by ELISA. RESULTS: Serum leptin and TNF-alpha levels were significantly higher in the patients experiencing exacerbation than in the stable patients and controls. Although leptin levels were lower and TNF-alpha levels were higher in the stable patient group than in the controls, these differences were not statistically different. Leptin levels were significantly correlated with the nutritional parameters in both control and stable groups. However, in patients with acute exacerbation, a correlation between leptin and nutritional parameters was not found. There was no significant relationship between TNF-alpha and nutritional parameters in the three groups. In addition, while there was no correlation between leptin and TNF-alpha levels in the stable and control groups, a significant positive correlation was observed in patients with exacerbation. CONCLUSION: In conclusion (1) elevated TNF-alpha levels may be related to increased inflammation in patients, (2) circulating TNF-alpha levels were associated with increased leptin levels and (3) although leptin and nutritional parameters were correlated in the stable COPD patients, the correlation was weaker compared to controls, and during an exacerbation it disappeared completely. Therefore, inappropriately increased levels of leptin and TNF-alpha noted during recurrent acute exacerbations in patients with COPD may lead to changes in nutritional parameters and body weight in the course of the disease.     

Improvement of Colonic Healing by Preoperative Rectal Irrigation With Short-Chain Fatty Acids in Rats Given Radiotherapy

BACKGROUND We investigated the effect of preoperative rectal irrigation with short-chain fatty acids on irradiated colonic anastomosis in rats.METHODS Sixty male Wistar rats were divided into four groups. Group I (control group, n = 15) underwent left colon resection and primary anastomosis. Group II (Short-chain fatty acids pretreatment group, n = 15) had short-chain fatty acids rectal irrigation for five days preoperatively. Group III (preoperative radiotherapy group, n = 15) underwent irradiation to the whole pelvis eight and four days before the operation, for a total dose of 20 Gy. Group IV (preoperative radiotherapy group + short-chain fatty acids pretreatment group, n = 15) had rectal irrigation with short-chain fatty acids for five days after the second irradiation. Within each group, animals were anesthetized to assess the clinical, mechanical, histologic, and biochemical parameters of anastomotic healing on either the third or seventh postoperative days.RESULTS The mean bursting pressure was significantly low in Group III on Day 3 and was significantly high in Group IV on Day 7 (P = 0.001, P = 0.021). The burst occurred at the anastomoses in all animals tested on the third postoperative day, and outside of the anastomoses in all animals tested on the seventh postoperative day. The histologic parameters of anastomotic healing, such as epithelial regeneration and formation of granulation tissue, were significantly improved by use of preoperative rectal irrigation with short-chain fatty acids on Day 7. The amount of total and salt-soluble collagen concentrations significantly increased in Group IV compared with the control group on Day 3 (P = 0.008, P = 0.004).CONCLUSION Some mechanical and histologic aspects of colonic anastomotic healing can be adversely affected by preoperative radiotherapy, but rectal irrigation with short-chain fatty acids may improve anastomotic healing.Supported by The Turkish Surgical Society, as funded by a grant from the Sanofi Pharma.     

Management of type 2 diabetes mellitus associated with pituitary gigantism

Pituitary gigantism, a condition of endogenous growth hormone (GH) hypersecretion prior to epiphyseal closure, is a rare condition. In the adult condition of GH excess, acromegaly, the occurrence of type 2 diabetes mellitus (T2DM) and diabetic ketoacidosis (DKA) have been reported, with resolution following normalization of GH levels. We report the case of a 16-year-old male with pituitary gigantism due to a large invasive suprasellar adenoma who presented with T2DM and DKA. Despite surgical de-bulking, radiotherapy and medical treatment with cabergoline and pegvisomant, GH and insulin-like growth factor-I (IGF-I) levels remained elevated. However, the T2DM and recurrent DKA were successfully managed with metformin and low-dose glargine insulin, respectively. We review the pathophysiology of T2DM and DKA in growth hormone excess and available treatment options.