静脉输注地尔硫治疗冠状动脉搭桥术前不稳定性心绞痛

目的 :评价静脉输注地尔硫治疗冠状动脉搭桥 (CABG)术前不稳定性心绞痛的疗效和安全性。方法 :68例CABG术前不稳定性心绞痛病人停服肾上腺素 β受体阻滞剂、钙通道阻滞剂及抗血小板药物 ,静脉给予地尔硫 ,以 33～ 167μg·min- 1,持续微泵注入 72h以上。观察心绞痛症状、心电图、血压、心率及不良反应。结果 :65例 (96% )病人有效。与用药前相比 ,心绞痛发作平均次数减少 (5 .4±s 1.8)次·d- 1(P <0 .0 1) ,发作持续时间缩短 (7.6± 2 .5 )min(P <0 .0 1)。心肌耗氧指数降低。心电图异常者ST T明显改善 ,4 9例病人在病情稳定后 1wk内接受CABG。无严重不良反应。结论 :静脉输注地尔硫为CABG术前不稳定性心绞痛提供了一种较为安全有效的药物治疗手段     

Calcium-Induced Natriuresis: Physiologic and Clinical Implications

Assessment of the tubular reabsorption of calcium (Ca) by infusion is complicated by suppression of parathyroid hormone (PTH) secretion, and by activation of the serpentine Ca sensing receptor in the renal tubule, which inhibits Ca and sodium reabsorption, but little is known about the magnitude of the natriuretic effect of Ca in human subjects. Accordingly, we reanalyzed the relationship between serum Ca and urine Ca and sodium excretion expressed per unit of creatinine clearance (CaE and NaE), and per unit of time (UCa and UNa), during a standard Ca infusion, in 14 healthy volunteers and in 8 primary hyperparathyroid patients. In healthy subjects we observed a large effect of Ca infusion on NaE, which rose as high as 8 mmol/liter GFR. In patients with primary hyperparathyroidism both CaE and NaE during Ca infusion were significantly lower overall than in healthy subjects for comparable values of serum Ca (P < 0.05 by covariance analysis), due mainly to a decline or reversal of the slopes at the highest serum Ca levels. In both controls and primary hyperparathyroid subjects the variance of CaE as dependent variable was explained by both serum Ca and by NaE as independent variables (P < 0.001). We conclude that (1) The natriuretic effect of hypercalcemia was unexpected large and if maintained would lead to substantial depletion of extracellular fluid. (2) Patients with chronic hypercalcemia, including primary hyperparathyroidism, probably have mild sodium depletion, and are more susceptible to volume depletion. (3) Calcium reabsorption during Ca infusion is reduced by suppression of PTH secretion and increased by volume contraction due to sodium depletion. Discrimination between different basal levels of parathyroid function is successful because these effects usually cancel out. (4) The increase in tubular reabsorption of Ca due to volume contraction can initiate a vicious circle, of importance to the pathogenesis and treatment of severe hypercalcemia. Received: 11 May 1999 / Accepted: 13 January 2000     

磁导向载体阿霉素介入治疗原发性肝癌的临床研究

目的：观察磁导向载体阿霉素(MTC-DOX)肝动脉介入治疗原发性肝癌的有效性和安全性。方法：将Seldinger导管超选择插入肿瘤供血肝动脉，以脉冲给药的方式注入MTC-DOX，21天为一周期，连续用药2周期以上按照WHO标准进行评价。结果：不能手术的原发性肝癌患共11例入组，10例可以评价疗效，治疗后NC7例，PD3例，中位肿瘤进展时间(TTP)为182天，有3例临床症状减轻，有4例生活质量改善，1年生存率达到54．5％；11例可以评价毒性，毒副反应均较轻，主要为轻中度的肝区疼痛和发热，少数患有胃肠道反应和一过性转氨酶升高。结论：采用磁导向载体阿霉素介入治疗原发性肝癌靶向性特别好，疗效明显，同时毒性反应轻微，值得进一步研究。     

术前动脉灌注化疗结合手术治疗直肠癌疗效分析

目的 :总结和分析直肠癌术前介入灌注化疗 (Pre operativeArteraInfusionChemotherapy ,PAIC)的疗效及其优点 ,探讨直肠癌综合治疗的远期疗效。方法 :应用Seldinger方法经皮右侧股动脉穿刺 ,选择肠系膜下动脉或骼内动脉造影确定肿瘤位置后 ,注入化疗药物。术后一周进行直肠癌根治术。术后采用 5 氟尿嘧啶加甲酰四氢叶酸钙进行 6个疗程的化疗。以同期未行介入灌注治疗而手术的直肠癌患者作为对照组。结果 :PAIC组大多数患者症状、体征减轻 ,肿块缩小。介入灌注化疗前后病理检查发现肿瘤细胞有变性坏死 ,细胞核变性 ,胞浆凝固 ,间质炎细胞浸润及纤维增生等不同程度的改变。术后五年生存率 75 0 0 % ,对照组为 4 5 2 4 % ,对比差异有显著性意义 (P <0 0 5 )。结论 :术前介入灌注化疗作为直肠癌新辅助化疗方法之一是有效、安全的 ,并能提高直肠癌患者的术后长期生存时间。     

Multimodal therapy with intravenous biweekly leucovorin, 5-fluorouracil and irinotecan combined with hepatic arterial infusion pirarubicin in non-resectable hepatic metastases from colorectal cancer (a European Association for Research in Oncology trial).

BACKGROUND: The purpose of this study was to evaluate the tolerance and efficacy of combining i.v. irinotecan, 5-fluorouracil (5-FU) and leucovorin (LV) with hepatic arterial infusion (HAI) of pirarubicin in non-resectable liver metastases from colorectal cancer. PATIENTS AND METHODS: Thirty-one patients were included in a phase II trial with i.v. irinotecan/5-FU/LV administered every 2 weeks, combined with HAI pirarubicin 60 mg/m(2) on day 1 every 4 weeks. In most cases HAI was administered via a percutaneous catheter. RESULTS: The main grade 3/4 toxicity was neutropenia, encountered in 78% of the patients. When all patients were considered in the analysis, tumour response rate was 15 out of 31 [48%; 95% confidence interval (CI) 32% to 65%]. Liver resection was made possible in 11 patients (35%; 95% CI 21% to 53%). There were no toxic death. Median overall survival was 20.5 months, and median progression-free survival was 9.1 months. In patients with completely resected metastases, median overall survival was not reached and median progression-free survival was 20.2 months. CONCLUSION: The multimodality approach used in the present study was well-tolerated and yielded dramatic responses. An aggressive approach combining i.v. and HAI chemotherapy deserves further investigation.     

替尼泊甙-司莫司汀序列给药治疗恶性脑胶质瘤

目的 探讨替尼泊甙（VM26）与司莫司汀（MeCCNU）序列给药治疗恶性脑胶质瘤的疗效及其并发症的防治。方法 对145例经病理证实的恶性胶质瘤病人术后采用超选择性动脉内灌注加静脉滴注VM26及口服MeCCNU化疗,通过比较化疗前后影像学表现评价近期疗效。结果 本组145例病人治疗后完全缓解21例（14.5%）、部分缓解72例（49.6%）、无变化31例（21.4%）、恶化21例（14.5%）。1、2、3年存活率分别为90.3%、74.5%和22.8%。全部病人无严重并发症及毒性反应。结论 VM26-MeCCNU联合序列给药可延长脑胶质瘤病人生存时间,并发症及毒副作用少。     

Feasibility trial of high-dose 7-day continuous-infusion ifosfamide given on an outpatient basis

 High-dose ifosfamide (HD-IFX) has shown significant antitumor activity in advanced sarcoma and breast carcinoma. The use of uroprotective agents and the availability of ambulatory continuous-infusion pumps has allowed dose escalation in the administration of ifosfamide (IFX) on an outpatient schedule. We report the results of a phase II trial of IFX given at high doses to heavily pretreated patients. IFX was infused at 2 g/m² per day for a total of 7 days through a central venous access, with cycles being repeated every 21 days. Mesna was given concomitantly at equimolar doses. No hematopoietic support was used. A total of 27 heavily pretreated patients whose disease had progressed during conventional-dose chemotherapy were included (14 sarcomas, 10 breast carcinomas, and 3 bladder carcinomas). Reversible neutropenia and gastrointestinal toxicity were the most frequently encountered toxicities. Only two patients developed transient renal failure, and two others developed central nervous system toxicity. No treatment-related death was observed. Of 22 patients who were evaluable for response, 6 (27%) showed an objective response (OR), all ORs being partial responses (PRs) with a median duration of 6 months, and 12 patients had stable disease (SD; 55%) with a median duration of 3.5 months. The median overall survival (OS) was 6 months. Three patients underwent high-dose chemotherapy after showing a response to our IFX schedule. We conclude that continuous-infusion IFX given in an outpatient setting is a feasible and active regimen that produces, a manageable toxicity profile in heavily pretreated breast cancer and sarcoma patients. Early institution of this schedule in less advanced stages could improve the results obtained. Received: 30 June 1996 / Accepted: 20 January 1997     

Phase II study of continuous-infusion high-dose ifosfamide in advanced and/or metastatic pretreated soft tissue sarcomas

Background: Ifosfamide has important activity in pretreated soft tissue sarcomas (STS), and recent data support a clinically significant dose-response relationship for this agent. Administration by continuous infusion and hematopoietic support have rendered dose intensification regimens possible by reducing both hematologic and non-hematologic toxicities. The optimal dose and schedule of ifosfamide when given at high doses remain to be defined. In a previous phase I study, we demonstrated the feasibility of a continuous infusion (c.i.) high-dose ifosfamide (HDI) regimen in the ambulatory setting for patients with advanced solid tumors. The objective of the present phase II study was to assess the antitumor activity and toxicity of such a schedule in patients with advanced pretreated STS.Patients and methods: Thirty-eight patients with advanced and/or metastatic STS, all pretreated with an anthracycline with or without standard-dose ifosfamide, were treated. Ifosfamide was given by c.i. at a dose of 3.5 g/m²/day over four consecutive days, with equidose mesna uroprotection over five days. G-CSF was added at a dose of 200 µg/m²/day subcutaneously from day 6 to day 12. Cycles were repeated every three weeks in the outpatient setting.Results: A total of 159 cycles of therapy were given (median 4 per patient, range 3–6). Treatment compliance was generally satisfactory. The major toxicity was hematologic, with six febrile neutropenic episodes requiring hospitalisation and parenteral antibiotics. Acute renal failure occurred in one patient after three cycles of therapy; central nervous system toxicity was mild. An overall response rate of 39% was observed (95% confidence interval, 26% to 55%), with one complete and 14 partial remissions. All but one of the responder patients had previously received standard-dose ifosfamide. The median response duration was nine months (range 5–21+ months), and the overall median survival ranged from 6–30+ months (median 13 months).Conclusions: High-dose ifosfamide is an active regimen in anthracycline- pretreated STS. Future clinical trials should be aimed at evaluating the impact of different administration schedules on clinical response and outcome. The potential role of HDI as front-line chemotherapy as well as in the adjuvant treatment of STS needs to be investigated in randomized trials.     

动脉化疗在中晚期膀胱癌治疗中应用的初步报告

自1996年1月至今，我科为12例晚期膀胱癌患者施行了髂内动脉灌注化疗。结果：1例T4期降至T2期后给予膀胱部分切除；7例经手术＋动脉化疗，2年复查未发现复发现象；4例带瘤生存，病灶无进展。动脉化疗毒性反应较轻，疗效是肯定的，为中晚期膀胱癌开辟了一条新的治疗途径。     

Donor Lymphocyte Infusion for the Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation

The results of donor lymphocyte infusion (DLI) for treatment of relapse after bone marrow transplantation (BMT) are reviewed. Durable complete remission can be achieved at the molecular level for a majority (more than 70%) of patients with CML, when treated at early relapse. Results are less favourable for acute leukemias, although useful responses have been reported. Data are scarce though promising for myelodysplastic syndromes and multiple myeloma. Major treatment-associated toxicities are GVHD and bone marrow aplasia. The latter complication can be predicted by evaluating the level of residual donor-derived hematopoiesis. Modification of infused cells (CD8 negative selection or transduction with a suicide gene), addition of peripheral blood stem cells, and early implementation of escalating doses may counteract the complications and increase the response rate. Response rate is variably influenced by the presence of chronic GVHD after initial BMT, T-cell depleted BMT, underlying disease and stage at relapse, and the level of mixed chimerism. DLI is a direct demonstration of the graft-versus-leukemia effect (GVL). Because GVL after BMT is sometimes the predominant cause of cure, it may be advisable in such situations to redirect the conditioning regimens for BMT towards engraftment and less immediate cytotoxicity.