Loss of heterozygosity at chromosomes 3p and 17p in primary non-small cell lung cancer

BACKGROUND: Loss of heterozygosity (LOH) of selected regions at chromosomes 3p and 17p in non-small cell lung cancer (NSCLC) and the association of these abnormalities with major clinical parameters and prognosis were studied. MATERIALS AND METHODS: The study group included 92 consecutive primary NSCLC tumours and four microsatellite markers from chromosome 3p and three markers from 17p were analyzed. RESULTS: LOH of at least one locus was found in 83% of all analyzed tumours. Most frequently deletion (58%) was found at locus D3S1481 (3p14.2). Sequence deletions of D17S520 (17p12) and TP53 (17p13.1) occurred in 52% of tumours. LOH occurrence at 3p and 17p was more frequent in squamous cell carcinomas compared to adenocarcinomas (89% vs. 75%), but this difference was not significant. CONCLUSION: No significant association was found between LOH on any analyzed loci and tumour stage (TNM) and grade (G). There was no correlation between LOH and survival.     

Obstetrical hysterectomy

OBJECTIVE: Obstetrical hysterectomy still remains life saving operation. The aim of study was to determinate the frequency, indications and complications after the operation in the hospital in Zielona Góra, Poland. MATERIALS AND METHODS: A retrospective review based on hospital data of 36 patients undergoing obstetrical hysterectomy over the period of 11 years was undertaken. RESULTS: The incidence of obstetrical hysterectomy during 1990-2001 et the Department of Obstetrics and Gynaecology in the district hospital in Zielona Góra was 1: 593 deliveries. Post partum hysterectomy occurred in 0.021% of normal deliveries and 1.03% of cesarean sections. The most common indications were placenta increta and placenta accreta /61.1%/, followed by uterine atony /13.8%/ and rupture of the uterus /11.1%. The most frequent complications were shock and lesion of the urinary bladder/both 5.6%/. The maternal mortality was 2.8%. CONCLUSIONS: 1. The most common indications for the obstetrical hysterectomy are: placenta's pathologies; uterine atony and rupture of the uterus. 2. Obstetrical hysterectomy is connected with high risk of complications and maternal mortality.     

Impaired gastric ulcer healing in diabetic rats: role of heat shock protein, growth factors, prostaglandins and proinflammatory cytokines

Gastric mucosa of diabetic rats is highly vulnerable to acute injury, but little is known about the influence of diabetic conditions on the healing of gastric ulcers. In this study, streptozotocin (70 mg/kg injected intraperitoneally) was used to induce diabetes mellitus in rats. Four weeks after streptozotocin injection, gastric ulcers were induced using the acetic acid method, and 10 days later, the healing rate and the gastric blood flow (GBF) were measured by planimetry and hydrogen (H(2))-gas clearance method, respectively. Six major groups of rats with gastric ulcers were used: (1) vehicle (saline); (2) streptozotocin alone; (3) insulin (4 IU/day intraperitoneally); (4) streptozotocin plus insulin; (5) pentoxifylline, an inhibitor of synthesis and release of tumor necrosis factor-alpha (TNF alpha); and (6) aspirin, a non-selective inhibitor of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), and rofecoxib, the highly selective COX-2. In the diabetic rats, a significant delay in ulcer healing ( approximately by 300%), accompanied by a decrease in the gastric mucosal blood flow was observed. The prolongation of the healing in diabetic animals was associated with an increase in gastric mucosal expression and release of TNFalpha, interleukin-1 beta (IL-1 beta), suppression of the vascular endothelial growth factor (VEGF), platelet endothelial cell adhesion molecule-1 (PECAM-1) and the mucosal overexpression of heat shock protein 70 (HSP 70). Administration of insulin reversed the delay in ulcer healing and significantly decreased the expression of IL-1 beta and TNF-alpha, while producing the rise in the expression of VEGF and PECAM. Pentoxifylline, an inhibitor of TNF-alpha, which by itself accelerated ulcer healing in non-diabetic rats, counteracted the increase in the area of gastric ulcer induced by streptozotocin, raised significantly gastric blood flow and suppressed the plasma TNF-alpha levels. Aspirin and rofecoxib, that significantly suppressed the mucosal prostaglandin E(2) generation in ulcer area, delayed significantly the rate of ulcer healing and decreased the GBF at ulcer margin in non-diabetic rats, and these changes were significantly augmented in diabetic animals. We conclude that: (1) Experimental diabetes dramatically impairs ulcer healing, depending upon the increased release of proinflammatory cytokines and the attenuation of angiogenesis that can limit the ulcer healing effects of locally produced HSP 70 and TNF-alpha. (2) Insulin reversed this impairment of ulcer healing in diabetic rats, mainly due to the enhancement of angiogenesis and reduction in expression of cytokines in the ulcer area. (3) Classic non-steroidal anti-inflammatory drugs such as aspirin prolonged ulcer healing under diabetic conditions due to suppression of endogenous prostaglandins and the fall in the microcirculation at the ulcer margin and these effects were mimicked by selective, so called "safe" COX-2 inhibitor, rofecoxib, suggesting that both COX isoforms are important sources of prostaglandins that are essential in the ulcer healing in diabetes.     

Dendritic cells as vectors for immunotherapy of cancer

Dendritic cells (DCs) initiate and regulate immune responses. Numerous studies in mice showed that tumor antigens-loaded DCs are able to induce therapeutic and protective anti-tumor immunity. The immunogenicity of antigens delivered on DCs has now been demonstrated in cancer patients and some clinical responses without any significant toxicity have been observed. Nevertheless, many parameters of DC vaccination need to be established including: (1) the type of DCs, their maturation stage and stimuli; (2) the quality and the breadth of induced immune responses; (3) host-related factors, such as the extent of metastatic disease and myeloablation; and (4) efficacy as measured by the clinical outcome.     

Antihistaminic activity of carane derivatives in isolated guinea pig ileum

Local anesthetics (LAs) inhibit membrane depolarization by reducing sodium and potassium conductance, and subsequent displacement of calcium ions from binding sites seems to occur. Histamine release appears to be a secretory process in which calcium couples the stimulus to the exocytosis of histamine-containing granules. Furthermore, LAs are structurally similar to histamine H₁-receptor antagonists. Thus, LAs can be considered antihistaminic drugs.Previous pharmacological investigations have shown strong local anesthetic, anti-inflammatory and analgesic activity of the carane derivative KP-23. As it has previously been demonstrated that KP-23R, S and its R, S-diasteroisomers have an inhibitory effect on guinea pig ileum contractions, the aim of the present study was to determine and compare the antihistaminic effects of KP-23R, S and its individual isomers KP-23R and KP-23S on isolated guinea pig ileum.     

Evaluation of a multiprofessional rehabilitation programme for persistent musculoskeletal-related pain: economic benefits of return to work

OBJECTIVE: The aim of this study was to evaluate the economic consequences of an 8-week multiprofessional rehabilitation programme for patients with persistent pain. SUBJECTS: A group of 67 patients following the programme and a comparison group of 322 patients. METHODS: The effect on return to work was estimated using 3 different methods: (i) a matched sample approach; (ii) regression analysis; and (iii) propensity score matching. The economic benefit of the programme was estimated as a reduction in production losses due to sick-leave. This benefit was compared with the actual cost of the programme. RESULTS: The benefit of the programme was estimated to be euro3,799-7,515 per treated patient and year. The total cost of the programme was estimated to be euro5,406 per patient. Based on these figures the total cost of the programme, including costs for patients remaining on sick-leave, had been recovered when the successfully rehabilitated patients had worked for 9-17 months. Any additional work after that yielded net economic benefits. CONCLUSION: Since other studies indicate that a large proportion of the patients working after one year also work after 3 and 6 years, we conclude that this multiprofessional rehabilitation programme for patients with persistent pain most likely generates substantial net economic gains.     

Comparative evaluation of simple indices using a single fasting blood sample to estimate beta cell function after islet transplantation

Six single fasting blood sample–based indices—Secretory Unit of Islet Transplant Objects (SUITO), Transplant Estimated Function (TEF), Homeostasis Model Assessment (HOMA)2‐B%, C‐peptide/glucose ratio (CP/G), C‐peptide/glucose creatinine ratio (CP/GCr), and BETA‐2 score—were compared against commonly used 90‐minute mixed meal tolerance test (MMTT) serum glucose and beta score to assess which of them best recognizes the state of acceptable blood glucose control without insulin supplementation after islet allotransplantation (ITx). We also tested whether the indices could identify the success of ITx based on the Igls classification of beta cell graft function. We analyzed values from 47 MMTT tests in 4 patients with up to 140 months follow‐up and from 54 MMTT tests in 13 patients with up to 42 months follow‐up. SUITO, CP/G, HOMA2‐B%, and BETA‐2 correlated well with the 90‐minute glucose of the MMTT and beta‐score (r 0.54‐0.76), whereas CP/GCr showed a modest performance (r 0.41‐0.52) while TEF showed little correlation. BETA‐2 and SUITO were the best identifiers and predictors of the need for insulin support, glucose intolerance, and ITx success (P < .001), while HOMA2‐B% and TEF were unreliable. Single fasting blood sample SUITO and BETA‐2 scores are very practical alternative tools that allow for frequent assessments of graft function.