Effect of low molecular weight heparin on intra-abdominal metastasis in a laparoscopic experimental study

Background and aims Metastatization, adhesion, invasion, and growth of tumor cells involve a cascade of complex phenomena which may be affected. We investigated the effect of a low molecular weight heparin, reviparin, on intra-abdominal tumor growth and intra-abdominal metastasis in rats undergoing laparoscopy.Methods CC531 adenocarcinoma cells (5×10⁶ cells/ml) were administered intraperitoneally to 150 Wistar Albino Glaxo rats, with 15 groups of animals each. During laparoscopy 1 ml saline containing 0.0, 0.5, 2.0,; 4.0, and 10 mg reviparin/kg b.w. was introduced intraperitoneally (i.p.), daily subcutaneously (s.c.), or combined. After 21 days the animals were killed and underwent autopsy, and the tumor weight and the number of metastases on the liver surface were determined.Results Tumor weight was significantly reduced by 4.0 and 10.0 mg/kg b.w. but not by 0.5 or 2.0 mg/kg b.w. compared to controls. Decreased metastatization was observed in all treated groups. These effects were most pronounced after the s.c. or combined i.p. and s.c. administration, whereas after a sole i.p. administration only the highest dose of 10 mg/kg b.w. induced a significant inhibition of tumor growth.Conclusion Low molecular weight heparin given s.c. or in combination of i.p. lavage and s.c. injections significantly inhibits intra-abdominal tumor growth and intraperitoneal metastasis of CC531 adenocarcinoma cells in rats undergoing laparoscopy. This may offer additional therapeutic options for patients undergoing laparoscopic and also open cancer surgery.     

Skin reaction to adalimumab

The tumor necrosis factor alpha (TNFalpha) inhibitors etanercept and infliximab have shown good clinical results in the treatment of rheumatoid arthritis and other autoimmune disorders. With these novel fusion proteins, immune-mediated side effects, among them various cutaneous reactions, have been encountered. We report herein the case of an erythema multiforme-like skin reaction to treatment with the monoclonal anti-TNFalpha antibody adalimumab in a patient with rheumatoid arthritis. The reaction occurred after the sixth injection and affected the palms and soles as well as the injection site. Discontinuation of the adalimumab therapy resulted in rapid improvement of the condition. Although this patient was receiving concomitant immunomodulatory therapy with methotrexate and leflunomide, these medications were not discontinued when the reaction developed, and no other potential pathogenetic mechanisms were identified. We believe the reaction is most likely attributable to adalimumab.     

Gastrostomy insertion: comparing the options--PEG,RIG or PIG?

AIM: To compare percutaneous endoscopic gastrostomy (PEG) with radiologically inserted gastrostomy (RIG) and assess a hybrid gastrostomy technique (per-oral image-guided gastrostomy, PIG). MATERIALS AND METHODS: Fifty PEGs and 50 RIGs performed in three centres were prospectively compared and the endoscopic findings of 200 PEGs reviewed. A fluoroscopy-guided technique was modified to place 20 F over-the-wire PEG-tubes in 60 consecutive patients. RESULTS: Technical success was 98%, 100% and 100% for PEG, RIG and PIG, respectively. Antibiotic prophylaxis significantly reduced stoma infection for orally placed tubes (p=0.02). Ten out of 50 (20%) small-bore RIG tubes blocked. Replacement tubes were required in six out of 50 PEGs (12%), 10 out of 50 RIGs (20%), but no PIGs (p<0.001). No procedure-related complications occurred. The function of radiologically placed tubes was significantly improved with the larger PIG (p<0.001), with similar wound infection rates. PIG was successful in 24 patients where endoscopic insertion could not be performed. Significant endoscopic abnormalities were found in 42 out of 200 PEG patients (21%), all related to peptic disease. Insignificant pathology was found in 8.5%. CONCLUSION: PIG combines advantages of both traditional methods with a higher success and lower re-intervention rate. Endoscopy is unlikely to detect clinically relevant pathology other than peptic disease. PIG is a very effective gastrostomy method; it has better long-term results than RIG and is successful where conventional PEG has failed.     

Detection of prostate carcinomas with T1-weighted dynamic contrast-enhanced MRI. Value of two-compartment model

AIM: The suitability of dynamic parameters of the two-compartment model for detecting prostate carcinomas and its correlation with tumor microvascular density were evaluated. METHODS: The study included 43 patients with biopsy-proven prostate carcinoma: 28 were examined by 1.0-T MRI (Turbo-FLASH) and 15 by 1.5-T MRI (FLASH) with infusion of 0.1 mmol/kg Gd-DTPA. Signal time curves were parametrized with an open two-compartment model in amplitude and exchange rate constants (k(ep)).The microvascular density of resected prostate carcinomas was determined. RESULTS: The microvascular density in the tumors was significantly higher than in the adjacent healthy prostate tissue and correlated in both sequences with k(ep). Prostate carcinomas of the peripheral zone were demarcated by amplitude and k(ep). In the Turbo-FLASH sequence there was a significant difference between the tumor tissue and healthy peripheral zone in terms of k(ep) and in the FLASH sequence in terms of amplitude. CONCLUSION: Prostate carcinomas can be visualized with dynamic T1-weighted MR sequences using a two-compartment model. Moreover, the parameter k(ep) reveals the microvascular density in the tumor and can thus provide valuable clinical information for characterizing the tumors.     

Long-term graft survival with neoral and tacrolimus: a paired kidney analysis

Calcineurin inhibitors (CNI) are an important component of most immunosuppressive protocols utilized in renal transplantation. Both CNI available (cyclosporine and tacrolimus) have been used for many years. Studies comparing the efficacy of these two agents in terms of long-term graft or patient survival have thus far failed to show an advantage for either agent. This failure to show a difference could possibly be due to underpowering of clinical trials. The authors used the SRTR database to analyze 5-yr graft survival of the microemulsion formulation of cyclosporine (Neoral) as compared with tacrolimus. To minimize the donor variability and bias, a paired kidney analysis was used. Deceased donors from the years 1995-2002 were analyzed from the SRTR database. All paired kidneys during this period, where one kidney was allocated to a patient receiving initial Neoral therapy and its mate allocated to a patient receiving initial tacrolimus therapy were evaluated. Multivariate and univariate analysis were performed. Univariate analysis demonstrated equivalent graft survival for Neoral compared with tacrolimus (66.9% versus 65.9%, respectively). Multivariate analysis could not demonstrate a difference in risk for 5-yr patient survival or graft loss. Renal function was superior for tacrolimus at all time points, whereas the slope of 1/Cr over time did not differ for the two agents. In this paired kidney analysis, no difference in 5-yr renal allograft survival could be found between the two agents. Renal function was superior in the patients receiving initial tacrolimus therapy; however, slope of 1/Cr did not differ between the agents.     

Leptin concentrations in semen are correlated with serum leptin and elevated in hypergonadotrophic hypogonadism

Leptin seems to play a role in both food intake and energy balance as well as in the regulation of reproductive features. In order to investigate the regulation of testicular functions by leptin we analysed leptin concentrations in the semen of men with different andrological diseases. It was demonstrated that semen leptin concentrations were inversely correlated with serum testosterone levels and directly with serum leptin concentrations. Furthermore, semen leptin concentrations display only a fraction of serum leptin levels. Semen leptin levels of patients with azoospermia due to hypergonadotrophic hypogonadism, associated with increased follicle-stimulating hormone levels and of high-grade oligozoospermia, were significantly elevated (1.19 +/- 0.46 and 1.09 +/- 0.54 microg l(-1), respectively), while semen levels of leptin in patients with obstructive azoospermia (0.54 +/- 0.41 microg l(-1)) and low-grade oligozoospermia (0.54 +/- 0.34 microg ml(-1)) were comparable with those of normozoospermic men (0.21 +/- 0.21 microg l(-1)). Our data suggest that dysfunction of testicular epithelia as found in hypergonadotrophic hypogonadism and high-grade oligozoospermia with decreased testosterone levels causes elevated spermal leptin concentrations. However, the correlation of semen with serum leptin concentrations indicates that leptin is not actively transported but rather leaks through the blood-testis barrier.     

Lung density distribution in dynamic CT correlates with oxygenation in ventilated pigs with lavage ARDS

Background. Fast dynamic computed tomography (dCT) has beenused to assess regional dynamics of lung inflation and deflationprocesses. The aim of this study was to relate ventilation-inducedchanges in lung density distribution, as measured over severalrespiratory cycles by dCT, to oxygenation and shunt fractionin a lavage acute respiratory distress syndrome model. Methods. Six anaesthetized pigs underwent pressure-constantventilation (FI_O2=1.0, inspiratory:expiratory ratio=1:1) beforeand after induction of lung damage by saline lavage. Mean airwaypressure (P