Phase I trial of doxorubicin-containing low temperature sensitive liposomes in spontaneous canine tumors.

PURPOSE: To determine the maximum tolerated dose, dose-limiting toxicities, and pharmacokinetic characteristics of doxorubicin encapsulated in a low temperature sensitive liposome (LTSL) when given concurrently with local hyperthermia to canine solid tumors. EXPERIMENTAL DESIGN: Privately owned dogs with solid tumors (carcinomas or sarcomas) were treated. The tumors did not involve bone and were located at sites amenable to local hyperthermia. LTSL-doxorubicin was given (0.7-1.0 mg/kg i.v.) over 30 minutes during local tumor hyperthermia in a standard phase I dose escalation study. Three treatments, given 3 weeks apart, were scheduled. Toxicity was monitored for an additional month. Pharmacokinetics were evaluated during the first treatment cycle. RESULTS: Twenty-one patients were enrolled: 18 with sarcomas and 3 with carcinomas. Grade 4 neutropenia and acute death secondary to liver failure, possibly drug related, were the dose-limiting toxicities. The maximum tolerated dose was 0.93 mg/kg. Other toxicities, with the possible exception of renal damage, were consistent with those observed following free doxorubicin administration. Of the 20 dogs that received > or = 2 doses of LTSL-doxorubicin, 12 had stable disease, and 6 had a partial response to treatment. Pharmacokinetic variables were more similar to those of free doxorubicin than the marketed liposomal product. Tumor drug concentrations at a dose of 1.0 mg/kg averaged 9.12 +/- 6.17 ng/mg tissue. CONCLUSION: LTSL-doxorubicin offers a novel approach to improving drug delivery to solid tumors. It was well tolerated and resulted in favorable response profiles in these patients. Additional evaluation in human patients is warranted.     

高效液相色谱法测定人血浆中阿莫西林浓度及药代动力学

高效液相色谱法测定人血浆中阿莫西林浓度及药代动力学谭力周继红罗楠袁倚盛（南京军区南京总医院中心仪器分析科，南京２１０００１）阿莫西林（ａｍｏｘｉｃｉｌｉｎ）为β内酰胺类抗生素，其抗菌谱广，口服受食物影响小，对大多数病人耐受性良好，因而在临床上得以广泛...     

抗胆碱药3-(2-苯基-2-环戊基-2-羟基-乙氧基)奎宁环烷的立体化学和构效关系

研究了强效抗胆碱药dl-3-(2-苯基-2-环戊基-2-羟基-乙氧基)-奎宁环烷的四个光学异构体的两种不对称合成方法,用HPLC检测了异构体含量,讨论了构效关系。     

A prospective investigation of pulmonary embolism in women and men.

OBJECTIVE. The aim of this study was to compare, in women and men suspected of pulmonary embolism, the frequency, risk factors, diagnosis, and presentation of pulmonary embolism as well as the accuracy of the ventilation/perfusion scan (V/Q scan) as a diagnostic tool. DESIGN. Data were collected during a prospective study (the Prospective Investigation of Pulmonary Embolism Diagnosis) to establish the accuracy of the V/Q scan compared with pulmonary angiograms. SETTING. Six tertiary medical centers in Massachusetts, Michigan, Connecticut, Pennsylvania, and North Carolina. PARTICIPANTS. Patients suspected of pulmonary embolism for whom a request was made for a V/Q scan or pulmonary angiogram (496 women and 406 men). RESULTS. Women 50 years old and under had a decreased frequency of pulmonary embolism compared with men of that age (16% vs 32%), but there was no difference in patients over 50 years old (Breslow-Day test, P less than .01). Risk factors for pulmonary embolism, the usefulness of the V/Q scan, and 1-year mortality were not different for women and men. Estrogen use in women was not associated with an increased frequency of pulmonary embolism, except in women using oral contraceptives who had undergone surgery within 3 months; four of five (80%) had emboli compared with four of 28 (14%) age-matched surgical patients not using estrogens (P less than .01). CONCLUSION. Women 50 years old and under (even young women using oral contraceptives) who were suspected of having pulmonary emboli and were enrolled in the Prospective Investigation of Pulmonary Embolism Diagnosis study had a smaller frequency of pulmonary embolism than men of that age, The risk factors for pulmonary embolism were the same for women and men, except that women using oral contraceptives had an increased risk of pulmonary embolism following surgery. Although the V/Q scan was a useful tool in the preliminary evaluation for pulmonary embolism in these women, a pulmonary angiogram was often needed for accurate diagnosis.