Accelerated radiochemotherapy in pancreatic cancer is not necessarily related to a pathologic pancreatic function decline in the early period

PURPOSE: To evaluate the functional effects of ionizing radiation in patients with unresectable pancreatic cancer in the early period after accelerated radiochemotherapy (ART). METHODS AND MATERIALS: To analyze the exocrine component, the amino acid consumption test and fecal elastase 1 were performed in 13 patients immediately before and 4-8 weeks after ART. Pancreatic duct morphology was evaluated before therapy. Weight loss and clinical steatorrhea were recorded. Endocrine parameters were examined according to standardized criteria. RESULTS: The relative change of the amino acid consumption test results and the median elastase concentration was 41.2% and 56.4%, respectively. Five patients still had normal test results after ART and 5 patients developed pathologic values. The median relative weight loss of the total body weight was 7.7% +/- 4.5%. No steatorrhea occurred. Of the 5 patients with normal values, 3 had a mean organ dose of <40 Gy. Of the 5 patients with pathologic values, 4 had a mean organ dose of >41 Gy. The endocrine function measurements remained unchanged. CONCLUSION: Although a nominal reduction of exocrine function parameters occurred in most patients, ART was not necessarily related to a pathologic level in the early period. Diabetes was not established. The functional impairment that was existent in the patient population presumably contributed to the weight loss. Pancreatic enzyme preparations may also play a role in maintaining an anabolic state during and after radiochemotherapy.     

Radiologic features poorly predict clinical outcomes in knee osteoarthritis

OBJECTIVES: To assess the impact of radiographic severity and progression on pain and disability. METHODS: Measurements of mean joint space width (JSW), narrowest join space (NJS) point and assessment of symptoms by the WOMAC questionnaire were performed at baseline and after three years in 212 subjects over 50 years with primary knee OA. RESULTS: At baseline, JSW and NJS were not significantly correlated with the scores recorded for the WOMAC global index or its pain, stiffness or function subscales. A statistically significant correlation was observed between the joint space narrowing over three years and the changes observed in the pain subscale of the WOMAC during the same period. The three-year changes in the global WOMAC index in patients within the lowest and the highest quartiles of mean joint space width at baseline showed, in both cases, a statistically (p<0.05) significant favorable difference between patients treated with glucosamine sulphate and those having received placebo. CONCLUSION: Radiographic and clinical progressions of the disease are significantly associated but the clinical relevance of the association is questionable.     

Nucleosomes in colorectal cancer patients during radiochemotherapy.

Apoptotic markers and tumor-associated antigens might be suitable to indicate the response to radiochemotherapy early. We analyzed the courses of nucleosomes, CEA, CA 19-9 and CYFRA 21-1 in 25 colorectal cancer patients during radiochemotherapy (4 postoperative, 13 preoperative, 8 local relapse therapy). Blood was taken before therapy, daily during the first week, once weekly during the following weeks, and at the end of the radiochemotherapy. After a temporary decline 6 h after the first irradiation, nucleosomes rose in most patients rapidly reaching a maximum during the first days which was followed by a subsequent decrease. In patients receiving postoperative therapy after complete resection of tumor, nucleosome levels generally were lower than in patients with preoperative or relapse therapy. Correspondingly, CEA, CA 19-9 and CYFRA 21-1 levels of postoperatively treated patients were the lowest whereas those with tumor relapse had the highest ones. During preoperative therapy, lower nucleosome concentrations were found in patients with response to therapy resulting in a smaller area under the curve of days 1-3 (AUC) than in those with progressive disease (p = 0.028). The other parameters did not indicate the response to therapy at the initial treatment phase. In conclusion, the course of nucleosomes (AUC) might be valuable for the early prediction of therapy response in preoperatively treated colorectal cancer patients.     

Aspiration von Babypuder

Ohne Zusammenfassung     

Tropisetron in the prevention of postoperative nausea and vomiting

STUDY OBJECTIVES: To evaluate the efficacy of tropisetron, a selective 5-HT(3) receptor antagonist, in preventing nausea and vomiting in high-risk inpatients undergoing various surgical procedures. DESIGN: Prospective, open, nonrandomized, observational, interventional study. SETTING: Postanesthesia care unit, and surgical wards of the University Hospital Center, Charleroi. PATIENTS: A total of 1,132 elective surgical inpatients (>15 years of age) in two separate surveys. The first prospective survey covered all surgical adult inpatients (n = 671) after various surgical procedures over a 3-month period. A new 3-month survey was performed to assess the effectiveness of the preventive measure and included another 461 patients. INTERVENTIONS: Risk factors associated with nausea and vomiting were recorded in the first survey and used to establish an antiemetic policy. This consisted in the administration of tropisetron 2 mg intravenously after anesthesia induction, if two patient-related risk factors associated with high-risk surgery and general anesthesia were present. MEASUREMENTS AND MAIN RESULTS: Nausea frequency and intensity, assessed every 4 hours using a visual analog scale (VAS), frequency and times of vomiting episodes and the need for rescue medication were recorded for 72 hours postoperatively. Nausea was experienced by 18.8% and vomiting by 9.8% of the patients in the first survey (211 high risk-patients of 671). In the second survey, 137 patients of 461, considered at high-risk received prophylactic tropisetron. The proportion of patients having nausea decreased to 11.1% (p,178 0.01) and vomiting episodes to 2.8% (p < 0.001). Twenty-six of the tropisetron-treated patients (19%) suffered subsequent postoperative nausea and vomiting (PONV). Patient satisfaction with tropisetron was high. CONCLUSION: Prophylactic tropisetron can reduce the incidence of PONV in selected high-risk inpatients undergoing various types of surgical procedures.     

Novel oligorhamnosides from the stem bark of Cleistopholis glauca

A reinvestigation of the stem bark of Cleistopholis glauca yielded 14 compounds, of which seven were either novel or had not been previously reported from this species. These were identified as the farnesane sesquiterpene methyl-(2E,6E)-10-oxo-3,7, 11-trimethyl-dodeca-2,6-dienoate (1); the azaanthracene alkaloid cleistopholine (4); two partially acetylated oligorhamnoside derivatives, 1-O-dodecanyl-2,3, 4-tri-O-acetyl-alpha-rhamnopyranosyl-(1-->3)-2, 4-di-O-acetyl-alpha-rhamnopyranosyl-(1-->3)-4-O-acetyl-alpha-rhamnopy ranosyl-(1-->4)-alpha-rhamnopyranoside (6) and 1-O-dodecanyl-2, 4-di-O-acetyl-alpha-rhamnopyranosyl-(1-->3)-2, 4-di-O-acetyl-alpha-rhamnopyranosyl-(1-->3)-4-O-acetyl-alpha-rhamnopy ranosyl-(1-->4)-alpha-rhamnopyranoside (8), for which the trivial names cleistetroside-7 and cleistetroside-6 were assigned, respectively; the dihydrobenzofuran neolignan rel-(2alpha, 3beta)-7-O-methylcedrusin (12); and the flavonoids dihydroquercetin (13) and quercetin (14). Structure assignments of all compounds were established by spectroscopic methods and comparison with published data. The chemosystematic significance of the occurrence of the isolated components is mentioned. Compounds 1, 6, and 8 are novel natural products.     

Pharmaceutical intervention in the JAK/STAT signaling pathway

Many cytokines exert their effect via the JAK/STAT signal transduction pathway. Due to the medical relevance of many of these cytokines, they are being exploited, either directly, or through antagonists, as therapeutics for a variety of serious diseases. Currently, these therapeutics consist almost entirely of protein products, with all of their attendant drawbacks. Delineation of the signaling mechanisms for the cytokines, however, has allowed the design and implementation of a variety of cell-based and biochemical screens for small molecule mimics or antagonists of these cytokines. Several successful assays will be described along with the advantages of each type of assay. Use of assays of this type should make it possible to discover numerous small molecule cytokine modulators with significant utility in the clinic. Oncogene (2000).