Clinical studies of biochemical modulation of 5-fluorouracil by leucovorin in patients with advanced colorectal cancer by the North Central Cancer Treatment Group and Mayo Clinic

The North Central Cancer Treatment Group (NCCTG) and Mayo Clinic are collaborating in an ongoing, prospective, randomized clinical trial of new approaches to the chemotherapy of advanced metastatic colorectal cancer. Single agent 5-fluorouracil (FUra) given by intensive-course rapid intravenous administration serves as a control. Included among the experimental treatments are two regimens consisting of FUra plus leucovorin (folinic acid). One of these regimens uses folinic acid at a dose level of 200 mg/m2 daily for 5 days based on earlier studies by Machover et al. (4). The second regimen uses folinic acid at 1/10 the dose level (20 mg/m2 daily for 5 days), since this lower dose of folinic acid has been shown to produce peak serum levels equivalent to the concentration of folinic acid required in culture medium to produce optimal inhibition of L1210 cells by FUra in vitro, and because of the great expense of folinic acid when given at the higher dose levels. As of January 1986, 78 patients had been randomized to receive treatment with FUra alone or one of the FUra-folinic acid regimens. The toxicity of the folinic acid regimens has been clinically tolerable, with stomatitis and, to a lesser extent, diarrhea being dose-limiting. Hematologic toxicity has been very mild. There is suggestive evidence that folinic acid given at the higher dose level in combination with FUra at a constant dose produces more severe effects on the oropharyngeal mucosa. Preliminary tumor response and survival data remain blinded in accordance with NCCTG policy. Further patient accrual and follow-up are required to assess the therapeutic effect of these folinic acid regimens compared to FUra given alone.     

Hepatic Artery Chemoembolization for Hepatocellular Carcinoma in Patients Listed for Liver Transplantation

We retrospectively analyzed all listed patients having hepatic artery chemoembolization (HACE) for hepatocellular carcinoma (HCC) stage T2 or less. Outcomes were transplantation, waiting list removal, death, and HCC recurrence. Twenty patients (mean age 55.7 years; 15 males) were identified. Twelve (60%) were transplanted, seven (35%) were removed from the list and one (5%) remains listed. Fourteen (70%) are alive. All 12 transplanted patients are alive (mean 2.94 years); one of seven removed from the list is alive (mean 1.45 years). Survival was significantly higher for those transplanted or listed vs. removed from the list (100% vs. 14.3%, p = 0.0002). No HCC's recurred. Three patients (15%) were removed from the list after prolonged waiting times before MELD. Hepatic artery chemoembolization induced deterioration and removal from the list of one (5%) patient. Survival for those transplanted was excellent(100%), but overall survival was significantly lower (61.3%) at a mean 5.48 years. Hepatic artery chemoembolization for listed patients with 相似文献   

Possible Idiopathic Thrombocytopenic Purpura Associated with Natural Alpha Interferon Therapy for Chronic Hepatitis C Infection

We report the case of a 41-yr-old male with chronic hepatitis C who developed severe thrombocytopenia on interferon alfa-n3 therapy. The patient was enrolled in a multi-center trial of interferon alfa-n3 in the treatment of chronic hepatitis C. In the 10th wk of therapy, he presented with gingival bleeding and a petechial rash. Complete blood count demonstrated WBC 5,800/mm³, Hgb 16.3 g/dl, Hcl 45.5%, and platelet count 6,000/mm³. Interferon was withdrawn, and he was admitted to intensive care and was treated with platelet transfusion, intravenous steroids, and intravenous immunoglobulin. His platelet counts returned to 157,000/mm³ in 7 days and remained normal on a tapering dose of prednisone. Bone marrow biopsy/aspirate demonstrated numerous megakaryocytes. Stored plasma was negative for development of specific high-titer anti-platelet antibody. We suggest that the clinical findings and response to therapy are consistent with interferon-induced idiopathic throm-bocytopenic purpura.     

Mirizzi syndrome Type IV: A rare entity

Mirizzi's syndrome, characterized by obstructive jaundice due to an extrinsic compression of common hepatic duct by an impacted gallstone in the cystic duct or the neck of the gallbladder, is a rare complication of gallstone disease. The present case describes Mirizzi's syndrome classified as Type IV in a 50‐year‐old man with obstructive jaundice. Abdominal computed tomography scan demonstrated a dilated intrahepatic biliary tree and a tumoral mass at the porta hepatis, suggesting cholangiocarcinoma. Endoscopic retrograde cholangiopancreatography also suggested cholangiocarcinoma involving the entire circumference of the common hepatic duct in porta hepatis. The diagnosis of Mirizzi's syndrome Type IV was confirmed during cholecystectomy, withdrawal of gallstone and Roux‐en‐Y hepaticojejunostomy.     

Randomized trial to evaluate the addition of tamoxifen to cyclophosphamide, 5-fluorouracil, prednisone adjuvant therapy in premenopausal women with node-positive breast cancer

A randomized clinical trial was performed to determine if the addition of hormonal therapy with tamoxifen to a combination chemotherapy regimen was superior to the chemotherapy alone for adjuvant treatment of premenopausal women after mastectomy for node-positive breast cancer. The chemotherapy regimen utilized consisted of cyclophosphamide (C), 5-fluorouracil (F), and prednisone (P), and the doses employed were: C, 150 mg/m2 IV days 1 to 5; F, 300 mg/m2 IV days 1 to 5; and P, 10 mg orally three times daily on days 1 to 7. A total of ten courses of therapy, given every 6 weeks, was planned. Tamoxifen (T) was given at a dose of 10 mg twice daily and was stopped 6 weeks after the last course of CFP. Four hundred patients are fully eligible and evaluable. With a median observation time of 5.3 years, the proportion of recurrences on each arm were: CFP, 95 of 202 (47%); CFPT, 77 of 198 (39%). The relapse-free survival distribution for CFPT was superior to that for CFP, at a borderline level of significance (two-sided P = 0.06). When significant prognostic factors were considered in covariate analysis, CFPT was not significantly better than CFP (P = 0.43). This marked change in level was due to imbalance in several factors not considered in stratification. Currently, 31% of CFP and 25% of CFPT patients have died, and although there is a slight separation of the survival curves in favor of CFPT, the difference is not significant (P = 0.21). Analysis within receptor subsets also showed no significant advantage for the addition of tamoxifen. This study does not establish a significant advantage for the concurrent administration of tamoxifen with the CFP regimen. It does, however, clearly demonstrate the importance of examination of clinically important prognostic factors, even those not utilized in stratification, and consideration of these factors in covariate analysis if imbalances are present.     

柱切换HPLC法研究米托蒽醌毫微粒冻干静脉注射剂的药代动力学

建立了血浆中米托蒽醌的柱切换高效液相色谱测定法,测定和比较了米托蒽醌溶液型注射剂和毫微粒冻干静脉注射剂在家兔体内的血药曲线,并研究比较了二者的药代动力学参数。米托恩醌毫微粒冻干注射剂使米托蒽醌在血中浓度大为降低,血中分布容积增大了近5倍,体内平均驻留时间延长了2倍多。表明米托蒽醌毫微粒有明显的体内长效作用,结合其体内分布试验研究结果,表明其具有明显肝靶向分布作用。     

Sleep deprivation in the rat: III. Total sleep deprivation

Ten rats were subjected to total sleep deprivation (TSD) by the disk apparatus. All TSD rats died or were sacrificed when death seemed imminent within 11-32 days. No anatomical cause of death was identified. All TSD rats showed a debilitated appearance, lesions on their tails and paws, and weight loss in spite of increased food intake. Their yoked control (TSC) rats remained healthy. Since dehydration was ruled out and several measures indicated accelerated use rather than failure to absorb nutrients, the food-weight changes in TSD rats were attributed to increased energy expenditure (EE). The measurement of EE, based upon caloric value of food, weight, and wastes, indicated that all TSD rats increased EE, with mean levels reaching more than twice baseline values.     

Association of marginal folate depletion with increased human chromosomal damage in vivo: demonstration by analysis of micronucleated erythrocytes

Recent studies have demonstrated that in the absence of spleen function, frequencies of micronuclei (Howell-Jolly bodies) in peripheral blood rbcs can be used to measure in vivo cytogenetic damage. Among 20 subjects studied greater than or equal to 6 months after splenectomy, 1 had a frequency of micronucleated rbcs more than an order of magnitude higher than rates for the others. Initial data suggested that this subject was mildly folate-depleted, and a therapeutic trial with folate rapidly reduced the frequency of micronucleated rbcs to normal values. These observations suggest a need to evaluate further the contribution of mild levels of folate depletion to spontaneous chromosomal damage. The approach used here provides a sensitive index of clastogenic damage and offers unique opportunities for investigating the determinants of cytogenetic damage in humans.