Phase II trial of paclitaxel and granulocyte colony-stimulating factor in patients with pancreatic carcinoma: a Southwest Oncology Group study

PURPOSE: Pancreatic cancer is difficult to treat, with most patients surgically unresectable at the time of diagnosis. Radiotherapy and chemotherapy can offer palliation, but more effective therapy is needed. This trial evaluated the effects of an aggressive schedule of paclitaxel given with granulocyte colony-stimulating factor (G-CSF) to patients with advanced pancreatic cancer. PATIENTS AND METHODS: All patients were required to have a histologic diagnosis of pancreatic adenocarcinoma with measurable disease and no prior chemotherapy or radiation therapy. Patients had to have performance status of 0 to 2, pretreatment absolute granulocyte count > or = 1,500/microL, and platelet count greater than or equal to the institutional lower limit of normal. Following pretreatment with dexamethasone, diphenhydramine, and cimetidine, patients received paclitaxel at a dose of 250 mg/m2 by 24-hour infusion on day 1, repeated every 21 days. G-CSF was given at a dose of 5 microg/kg/d on days 3 to 18 or until two consecutive absolute neutrophil counts (ANCs) > or = 10,000/microL were obtained. Doses of paclitaxel were modified depending on nadir counts. RESULTS: Forty-five patients were entered onto this study, with six ineligible. For the 39 eligible patients, there was one complete response (CR) and two partial responses (PRs), five stable/no responses, 23 increasing disease, two early deaths, and six patients whose assessment was inadequate to determine response. The response rate was therefore three of 39 or 8% (95% confidence interval [CI], 2% to 21%). The median survival time for the 39 eligible patients was 5 months. The most common toxicities were anemia, leukopenia/granulocytopenia, malaise/fatigue, nausea/vomiting, alopecia, thrombocytopenia, paresthesias, and liver function abnormalities. There was one death due to sepsis. CONCLUSION: Single-agent paclitaxel in this dose and schedule has minimal activity in pancreatic adenocarcinoma patients.     

The putative tumor suppressor gene on chromosome 5q for hepatocellular carcinoma is distinct from the MCC and APC genes

We have previously shown that the tumor suppressor gene for hepatocellular carcinoma (HCC) without cirrhosis may be located on chromosome 5q35-qter. In this study, we analyzed nine cases of primary HCC without cirrhosis using probes from the MCC and APC genes, which are in the region 5q21-22. None of the informative cases had allele loss detected by these probes, whereas the probe lambda MS8 for the region 5q35-qter showed allele loss in six out of six informative cases. The results confirm that the putative tumor suppressor gene for HCC without cirrhosis on chromosome 5q is distinct from the MCC and APC genes.     

Gel-entrapment of perfluorocarbons: a fluorine-19 NMR spectroscopic method for monitoring oxygen concentration in cell perfusion systems

Oxygenation is a major determinant of the physiological state of cultured cells. 19F NMR can be used to determine the oxygen concentration available to cells immobilized in a gel matrix by measuring the relaxation rate (1/T1) of perfluorocarbons (PFC) incorporated into the gel matrix. In calcium alginate gel beads without cells the relaxation rate (1/T1) of the trifluoromethyl group of perfluorotripropylamine (FTPA) varies linearly with oxygen concentration, with a slope of 1.26 +/- 0.15 x 10(-3) s-1 microM-1 and an intercept of 0.50 +/- 0.04 s-1. During perfusion with medium equilibrated with 95%/5% O2/CO2, changes in PFC T1s indicate that the average oxygen concentration was reduced from 894 +/- 102 microM in the absence of cells to 476 +/- 65 microM and 475 +/- 50 microM in the presence of 0.7 x 10(8) EMT6/Ro and RIF-1 murine tumor cells per milliliter of gel, respectively. The presence of 0.2 microliters of FTPA/ml of gel had no effect on the energy status of the cells as indicated by 31P NMR spectra. To calculate oxygen gradients within the beads from the average PFC T1 of the sample, a mathematical model was used assuming that oxygen is the limiting nutrient for cell metabolism and that the cellular oxygen consumption rate is independent of oxygen concentration. Data for EMT6/Ro cells were fit using experimentally determined perfusion parameters together with literature values for cell volume and oxygen consumption rate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Are there structural and functional modules in the vertebrate olfactory bulb?

Each of twelve volunteers, at 2 week intervals, received 1 g of antipyrine, a test drug, and were exposed for 4 h either to toluene (375 mg/m3) or xylene (435 mg/m3) singly or in combination with ethanol (0.45 g/kg body wt. before the onset of exposure and 0.15 g/kg thrice every 1 h during exposure to maintain a steady level of ethanol in blood approximately 11 mmol/dm3). No significant differences were found in salivary antipyrine half-life (T1/2 approximately 12 h); and clearance (ClAP approximately 0.83 cm3/s) between control and groups exposed to solvents and/or ethanol. Nevertheless, a tendency to increase the metabolic rate of antipyrine in xylene-exposed group (T1/2 approximately 6.8 h; ClAP approximately 1.40 cm3/s) and counteraction of ethanol (T1/2 approximately 15 h; ClAP approximately 0.63 cm3/s) should be noted. The stimulation of lipid peroxidation in the serum as a biological effect of combined exposure to ethanol and toluene/xylene was observed.     

Prospective, randomized trial comparing blood and oxygenated crystalloid cardioplegia in reoperative coronary artery bypass grafting

OBJECTIVES: Reoperative coronary artery bypass grafting presents unique challenges for myocardial preservation. The purpose of this study was to compare oxygenated blood cardioplegia with oxygenated crystalloid cardioplegia during reoperative coronary artery bypass grafting using transesophageal echocardiography to assess regional wall motion of the left ventricle before and after cardiopulmonary bypass. METHODS: Sixty-one patients undergoing reoperative coronary artery bypass grafting were prospectively randomized to receive oxygenated blood cardioplegia or oxygenated crystalloid cardioplegia delivered with a combined antegrade-retrograde technique. Transgastric short axis views of the left ventricle were made with transesophageal echocardiography during the operation before cardiopulmonary bypass and immediately after cardiopulmonary bypass. Regional wall motion was graded by a blinded observer, and before cardiopulmonary bypass scores were compared with after cardiopulmonary bypass scores. RESULTS: No significant differences were found in the change in regional wall motion score from before cardiopulmonary bypass to after cardiopulmonary bypass between the blood and crystalloid cardioplegia groups. CONCLUSIONS: This study found blood and crystalloid cardioplegia to be equally efficacious for myocardial preservation during reoperative coronary artery bypass grafting.     

A circuit approach to field computation

Many design objectives can be expressed more directly in terms of circuit parameters, such as capacitance and inductance, than in terms of the field vectors E and B. A simple, although radical, change is suggested to provide a closer link between the field and circuit views. The electric potential φ and magnetic vector A are defined, in energy terms, as the primary field quantities, and they are visualized as measures of the capacitance and inductance, respectively. E and B become auxiliary symbols denoting derivatives, so that the customary roles of the potentials and field vectors are reversed. Some of the practical advantages of the change are examined and are illustrated by example     

Laparoscopic cholecystectomy in pancreas transplant recipients

Laparoscopic cholecystectomy is the treatment of choice for symptomatic cholelithiasis. Since its introduction in 1987, this procedure has been employed with increasing frequency as its safety has been documented in numerous studies. Absolute contraindications to laparoscopic cholecystectomy have become relative contraindications, and patients previously felt to be at excessive risk for laparoscopic cholecystectomy are viewed as patients who may benefit from laparoscopic cholecystectomy. The use of this procedure in patients with comorbid medical conditions has the potential to decrease patient morbidity. Patients who have previously undergone solid organ transplantation and require immunosuppressive therapy are a group of patients who may benefit from laparoscopic cholecystectomy. We report four patients who have previously undergone combined renal and pancreas transplantation who underwent successful laparoscopic cholecystectomy.