Reaction of cytochrome P450 with cumene hydroperoxide: ESR spin-trapping evidence for the homolytic scission of the peroxide O-O bond by ferric cytochrome P450 1A2

ESR spin trapping was used to investigate the reaction of rabbit cytochrome P450 (P450) 1A2 with cumene hydroperoxide. Cumene hydroperoxide-derived peroxyl, alkoxyl, and carbon-centered radicals were formed and trapped during the reaction. The relative contributions of each radical adduct to the composite ESR spectrum were influenced by the concentration of the spin trap. Computer simulation of the experimental data obtained at various 5,5-dimethyl-1-pyrroline N-oxide (DMPO) concentrations was used to quantitate the contributions of each radical adduct to the composite ESR spectrum. The alkoxyl radical was the initial radical produced during the reaction. Experiments with 2-methyl-2-nitrosopropane identified the carbon-centered adducts as those of the methyl radical, hydroxymethyl radical, and a secondary carbon-centered radical. The reaction did not require NADPH-cytochrome P450 reductase or NADPH. It is concluded that the reaction involves the initial homolytic scission of the peroxide O-O bond to produce the cumoxyl radical. Methyl radicals were produced from the beta-scission of the cumoxyl radical. The peroxyl adduct was not observed in the absence of molecular oxygen. We conclude that the DMPO peroxyl radical adduct detected in the presence of oxygen was due to the methylperoxyl radical formed by the reaction of the methyl radical with oxygen. At a higher P450 concentration, a protein-derived radical adduct was also detected.     

One or two incisions for nephroureterectomy in transitional cell renal pelvis tumours

A retrospective study comprising 18 patients with transitional cell renal pelvis tumours (TCPT) was carried out to evaluate the results after two different surgical procedures for nephroureterectomy. The kidney was removed by a flank incision and the lower part of the ureter by either an incision in the lower part of the abdomen or intussusception of the ureter followed by transurethral resection of the ureteral orifice. Eight patients were subjected to nephroureterectomy by means of two incisions and another eight patients underwent a simple nephrectomy followed by ureteral intus-susception and transurethral resection. Two patients received other treatments. After nephroureterectomy with a separate incision for ureterectomy, the average hospital stay was 12 days, compared with 7.5 days in patients operated upon with only one abdominal incision. Recurrence of tumour or survival was not significantly different in the two groups.     

Parallel path consistency

Filtering algorithms are well accepted as a means of speeding up the solution of the consistent labeling problem (CLP). Despite the fact that path consistency does a better job of filtering than arc consistency, AC is still the preferred technique because it has a much lower time complexity. We are implementing parallel path consistency algorithms on multiprocessors and comparing their performance to the best sequential and parallel arc consistency algorithms.^(1,2) (See also work by Kerethoet al. ⁽³⁾ and Kasif⁽⁴⁾) Preliminary work has shown linear performance increases for parallelized path consistency and also shown that in many cases performance is significantly better than the theoretical worst case. These two results lead us to believe that parallel path consistency may be a superior filtering technique. Finally, we have implemented path consistency as an outer product computation and have obtained good results (e.g., linear speedup on a 64K-node Connection Machine 2).     

The transjugular stent implantation for the treatment of malignant portal and hepatic vein obstruction in cancer patients

BACKGROUND: The increase in portal vascular resistance is a significant complication of metastatic disease to the liver or locally advanced cancer, e.g., biliary cancer. PATIENTS AND METHODS: This paper describes the successful palliative treatment of two cancer patients with portal hypertension presenting with the symptoms of tense ascites, mesenteric congestion, and severe variceal bleeding. By creating a stenttract between a hepatic vein and a main branch of the portal vein and/or by placing an extendable stent into the portal vein, the transjugular intrahepatic portosystemic stent-shunt (TIPS) technique was used to decompress the portovascular system. RESULTS: The TIPS-technique offers a new, safe and effective palliation for malignant portal hypertension. In both patients, the symptoms of the portal hypertension disappeared after the procedure. This was accompanied by a significant improvement of the patients performance status allowing an early ambulation. CONCLUSION: Our findings demonstrate the feasibility and effectiveness of the TIPS procedure as a minimal invasive treatment for portal vein decompression in selected tumor patients.