造血干细胞移植治疗儿童髓系白血病26例疗效分析

目的 了解造血干细胞移植对儿童急性髓系白血病(AML)和慢性粒细胞白血病(CML)的治疗效果.方法 髓系白血病患儿26例,平均年龄为9.8岁,其中CML 8例,AML18例.CML患儿中,第1次慢性期(CPl)6例,加速期(AP)1例,第2次慢性期(CP2)1例;AML患儿中,第1次缓解(CRl)9例,第2次缓解(CR2)7例,2例未缓解(NCR).26例中,2例接受HLA全相合同胞供者的外周血与骨髓干细胞联合移植;2例接受由HLA半相合母亲供者外周血干细胞分离出的CD34+细胞输注;2例接受脐血移植;其余20例接受外周血造血干细胞移植.每例移植有核细胞(6.8±6.0)×108/kg,CD34+细胞(4.0±5.8)×106/kg,CD3+细胞(2.6±3.8)×108/kg.所有患儿均采用白消安及环磷酰胺进行清髓性预处理.移植后采用环孢素A和甲氨蝶呤联用预防移植物抗宿主病(GVHD),接受无关供者造血干细胞移植者加用抗胸腺细胞球蛋白,6例CML患儿加用霉酚酸酯.若发生Ⅱ度以上GVHD,则给予甲泼尼龙或巴利昔单抗治疗.结果 除2例HLA半相合移植失败外,其余24例均获得造血功能重建.24例植入成功的患儿中,2例未发生急性GVHD(aGVHD),15例(62.5%,15/24)出现Ⅰ～Ⅱ度aGVHD,7例(29.2%,7/24)出现Ⅲ～Ⅳ度aGVHD(重度aGVHD).7例重度aGVHD均为CML患儿.26例平均随访20.5个月,其中原发病复发死亡者4例,治疗相关死亡者5例,尚有17例(65.4%,17/26)患儿无病存活.结论 异基因造血干细胞移植有助于提高髓系白血病患儿的存活率,只要加强预防,无关供者造血干细胞移植产生的GVHD是可以控制的.而对于高危患儿,无关供者造血干细胞移植的效果与亲缘相关供者移植相似.     

Mycophenolate mofetil for the prophylaxis of acute GVHD in HLA-mismatched bone marrow transplant patients

Mycophenolate mofetil (MMF), a new immunosuppressive drug successfully used in renal and heart transplant recipients, was used in combination with cyclosporin A (CsA), methotrexate (MTX) and prednisolone for the prophylaxis of acute graft-versus-host disease (aGVHD) after bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT) from human leukocyte antigen (HLA)-mismatched, unrelated (n = 9) and related donors (n = 4) in an open single-centre phase II study. Thirteen patients, transplanted from HLA-mismatched donors of 18-57 yr of age, received 1 g MMF daily, starting at day 10, in addition to CsA and prednisolone for aGVHD prophylaxis. All patients were engrafted between days 13 and 15. Four of the 13 patients experienced aGVHD grade I/II (n = 2) and grade III (n = 2). All patients except 3 were alive on day 100 post-transplantation. No severe adverse effects of MMF were recorded. In our pilot study, we demonstrated that MMF can be used safely for the prophylaxis of aGVHD.     

Combined immunosuppression with cyclosporine and methotrexate in dogs given bone marrow grafts from DLA-haploidentical littermates

We examined the effect of methotrexate (MTX) combined with cyclosporine (CSP) on the prevention of graft-versus-host disease (GVHD) in dogs. Ten recipients were prepared for grafting with 9 Gy of total-body irradiation and given marrow and buffy coat cells from littermate donors differing for one DLA haplotype (AA leads to AB or AB leads to AC). MTX (0.4 mg/kg) was given i.v. on days 1, 3, 6, and 11. CSP was given i.m. on days 0 to 7 and orally on days 8 to 100. The dose was 15 mg/kg/day on days 0 to 25, 10 mg/kg/day on days 26 to 50, 5 mg/kg/day on days 51 to 75, and 5 mg/kg every other day on days 75 to 100. All ten dogs had sustained engraftment. Three dogs died, one with pneumonia (day 57), one with pneumonia and GVHD (day 107), and one with convulsions (day 204). Seven dogs are surviving at 210 to 493 days, and all are complete chimeras; five are well and two have chronic GVHD that developed after immunosuppressive treatment had been stopped. These results with a combination of MTX and CSP as GVHD prophylaxis are superior to those obtained previously with MTX alone in dogs given marrow grafts from DLA-haploidentical littermates.     

Non-cross-resistant sequential combination chemotherapy consisting of cis-diammine-dichloroplatinum (II) mainly, based on synchronization theory, in human bladder cancer xenografts in athymic nude mice

We examined the chemotherapies with cis-diamminedichloroplatinum (II) (CDDP) alone and in combination, using the human bladder cancer xenografts (BT-8 and BT-11 strains) in athymic nude mice (BALB/C), to establish the most effective and useful method for urothelial cancer in clinical use. First, to assess the anti-tumor activities of single-drug and our devised VPM or CisCF combination chemotherapies, experiments were done using the BT-8 strain bladder cancer (transitional cell carcinoma and grade III). The schedule and dosage of each chemotherapy were as follows. Vincristine (VCR): 0.06 mg/kg, days 1-6, peplomycin (PEP): 0.9 mg/kg, days 1-6, methotrexate (MTX): 0.6 mg/kg, days 1-6, cytosine arabinoside (Ara-C): 3 mg/kg, days 1-6, 5-fluorouracil (5-FU): 30 mg/kg, days 1-6, adriamycin (ADM): 3 mg/kg, days 1-6, cyclophosphamide (CPM): 10 mg/kg, days 1-10, and CDDP: 2.5 mg/kg, days 1-6. These were for single-drug chemotherapies. The VPM combination consisted of VCR (0.06 mg/kg, days 1 and 4), PEP (0.3 mg/kg, days 1-6) and MTX (0.3 mg/kg, days 2, 3, 5 and 6), and the CisCF combination consisted of CDDP (2.5 mg/kg, days 1 and 4), Ara-C (3 mg/kg, days 1 and 4) and 5-FU (15 mg/kg, days 2, 3, 5 and 6). The control group was given normal saline of 0.1 ml/20 g body weight, intraperitoneally. All anti-cancer drugs were also given intraperitoneally. Secondly, to assess the anti-tumor activities of CDDP alone and various modes of combination chemotherapies with or without CDDP, the following experiments were done using the BT-11 strain bladder cancer (a mixed type of transitional cell carcinoma and squamous cell carcinoma). CDDP: 2.5 mg/kg, days 1-6. VPM X 2: VCR (0.04 mg/kg, days 1, 4, 8 and 11), PEP (0.2 mg/kg, days 1-4) and MTX (0.2 mg/kg, days 2, 3, 5, 6, 9, 10, 12 and 13). CisCF X 2: CDDP (2.5 mg/kg, days 1 and 8), Ara-C (3 mg/kg, days 1, 6, 8 and 13) and 5-FU (30 mg/kg, days 3, 4, 5, 10, 11 and 12). VPM-CisCF (I): VCR (0.04 mg/kg, days 1 and 4), PEP (0.2 mg/kg, days 1-7), MTX (0.2 mg/kg, days 2, 3, 5 and 6), CDDP (2.5 mg/kg, day 8), Ara-C (3 mg/kg, days 8 and 13), and 5-FU (30 mg/kg, days 10-12).(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of anticancer agents on rat prostate. Evaluation of organ weight, histological finding and 5 alpha-reductase activities

To evaluate the effect of anticancer chemotherapeutic antigens on rat prostate, ten kinds of anticancer agents corresponding to the dose generally used for humans were intraperitoneally injected to 63-day-old Wistar rats. The anticancer agents were administered as follows: Cyclophosphamide (CPM) was used at the dose of 8 mg/kg for 7 days. Methotrexate (MTX), actinomycin-D (ACD) and cis-platinum (CDDP), 163 micrograms/kg, 8 micrograms/kg and 833 micrograms/kg for 5 days, respectively. Nitrogen mustard (NM), bleomycin (BLM), peplomycin (PLM), adriamycin (ADM), vincristine (VCR), and vinblastine (VBL), 500 micrograms/kg, 250 micrograms/kg, 170 micrograms/kg, 2.5 mg/kg, 33 micrograms/kg and 83 micrograms/kg, twice in a week, respectively. The rats were killed on the fifth day after completion of the schedule. Then, the weight of the body, the prostate, the epididymis and the adrenal gland were measured. In addition, 5 alpha-reductase activities and histological findings in the prostate were examined. For determination of 5 alpha-reductase activities, cell-free homogenate obtained from the rat ventral prostate was incubated with C14-testosterone at 37 degrees C for 30 minutes in an atmosphere of 95% of O2 and 5% of CO2. Subsequently, the metabolites from testosterone were separated and purified with thin layer chromatography using the solvent system with benzene acetone, 4:1 (v/v). 5 alpha-Reductase activity was determined with the sum of dihydrotestosterone (DHT) and androstanediol converted from testosterone and indicated as pmol product/mg protein. The 5 alpha-reductase activity was employed as a biological marker for the degree of androgenic dependency in the prostate. The results were summarized as follows. CDDP significantly reduced the weight of the body (p less than 0.001, n = 7), but not the activity of 5 alpha-reductase. NM and VBL had a specific action to reduce the weight of the prostate (p less than 0.01, n = 8) without causing loss of body weight. NM and VBL showed no influence on 5 alpha-reductase activities. The activity of 5 alpha-reductase was markedly damaged by BLM (p less than 0.05, n = 6) and PLM (p less than 0.05, n = 5). However no significant reduction was recognized in the weight of the body and the prostate. CPM, MTX, ACD, ADM and VCR were ineffectual on the body and the prostate weight and 5 alpha-reductase activities. In the histological examination, atrophy and degeneration of the glandular epithelium were revealed in the prostate treated with NM, VBL and CDDP.(ABSTRACT TRUNCATED AT 400 WORDS)     

利用脊柱骨来源骨髓细胞建立急性移植物抗宿主病模型

目的探讨利用脊柱骨来源骨髓细胞建立小鼠异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,Allo-HSCT)急性移植物抗宿主病(aGVHD)模型的可行性。方法选择C57BL/6(H-2b)雄性小鼠为供体鼠,BALB/c(H-2d)雌性小鼠为受体鼠。制备供体鼠的脾细胞和脊柱骨来源骨髓细胞悬液。受体鼠采用药物加小剂量辐照的预处理方式,于移植前8d～移植前4d腹腔注射氟达拉滨(200mg/kg),接着移植前3d～移植前1d腹腔注射环磷酰胺(60mg/kg),最后在移植前进行全身照射(total-body irradiation,TBI),照射剂量为4Gy(戈瑞)。18只受体鼠经预处理后随机分为3组,每组6只:(1)骨髓移植组,只输入1×107个脊柱骨来源骨髓细胞;(2)aGVHD组,输注1×107个脊柱骨来源骨髓细胞和5×106个脾细胞,建立aGVHD模型;(3)空白对照组,不输入任何细胞。观察3组小鼠生存状态及存活率,取aGVHD组与骨髓移植组存活21d的受体鼠进行病理学检查,取aGVHD组移植后21～28d存活的小鼠的脾脏进行流式细胞术检测骨髓细胞嵌合度。结果骨髓移植组小鼠全部存活,可重建造血,单纯输注骨髓细胞不会诱发aGVHD。aGVHD组小鼠出现aGVHD表现,100%发生aGVHD相关死亡,中位生存期为18d;病理检查结果显示符合aGVHD病理表现,移植后21～28d存活的小鼠诊断为供受体混合嵌合状态,符合aGVHD诊断标准。结论用脊柱骨来源骨髓建立的aGVHD模型完全符合标准,且更加经济,适合大规模建模。     

The effect of N-acetylcysteine on pulmonary lipid peroxidation and tissue damage

BACKGROUND: We aimed to investigate the effect of N-acetylcysteine (NAC) on pulmonary lipid peroxidation and tissue damage in experimental obstructive jaundice (OJ) stimulated by lipopolysaccharide (LPS) in this study. MATERIALS AND METHODS: We randomized 40 rats into five groups. Group A: Sham (n = 8); group B: OJ (n = 8); group C: OJ + lipopolysaccharide (LPS; n = 8); group D: OJ + NAC + LPS (n = 8); group E: OJ + LPS + NAC (n = 8). OJ was performed by common bile duct ligation and division in all groups except the sham group. At the fifth day, the rats were jaundiced. At the fifth day of OJ, LPS was injected 10 mg/kg intraperitoneally to the rats and at the tenth day, the rats were sacrificed in group C. In group D; at the fifth day of OJ, NAC was started 100 mg/kg subcutaneously and the same dose NAC injection repeated every day for 5 days. At the tenth day of OJ, LPS was injected 10 mg/kg intraperitoneally to the rats and then after 6 h they were sacrificed. In group E; 10 mg/kg LPS was administered intraperitoneally at fifth day of OJ and after then NAC was started 100 mg/kg subcutaneously and the same dose NAC injection repeated every day for 5 days and at the tenth day, the rats were sacrificed. Tissue samples were harvested through a midline incision, and lungs were resected and examined histopathologically and immunohistochemically for tissue damage scoring. The blood was taken by cardiac puncture and malondialdehyde (MDA), myeloperoxidase (MPO), and levels of total antioxidant status were detected with biochemical methods to evaluate lung tissue damage. RESULTS: Increase in lung and serum MDA and MPO levels, as well as decrease in total antioxidant status, were observed in groups B and C when compared with the sham group (P = 0.0001, for each comparison). Furthermore, the lung tissue damage was observed in the same groups by histopathological examination when compared with sham group. There was significant decrease at serum and lung MPO and MDA levels after the NAC application in groups D and E, when compared with group C (P = 0.0001, for each comparison). Antioxidant status in groups D and E were increased in the presence of NAC (P = 0.0001, for each comparison). Lung histology was prevented relatively in group D when compared with groups B and C. CONCLUSION: Results of the study indicate that NAC has protective effect on pulmonary lipid peroxidation and tissue damage before and after LPS administration.     

Influence of different gases and intraperitoneal instillation of antiadherent or cytotoxic agents on peritoneal tumor cell growth and implantation with laparoscopic surgery in a rat model

BACKGROUND: A generally accepted approach to prevent tumor implantation with laparoscopic surgery does not exist. Alternative gases in combination with intraperitoneal instillation of different antiadherent or cytotoxic agents have not been evaluated. METHODS: The effect of taurolidine, heparin, and povidone-iodine on the growth of colon adenocarcinoma DHD/K12/TRb was measured in rats undergoing laparoscopy with carbon dioxide (n = 40), helium (n = 40), or xenon (n = 40). In the procedure, 10(4) tumor cells were administered intraperitoneally, and pneumoperitoneum was established over 30 min at 8 mmHg with the different gases. The rats additionally received intraperitoneal instillation with one of the following: 1 ml of Ringer's solution, 1 ml of 0.5% taurolidine, 1 ml 0.5% taurolidine with heparin (10 U/ml), or 1 ml 0.25% of povidone-iodine. Tumor growth was measured after 4 weeks. RESULTS: Median intraperitoneal tumor weight was lower in rats receiving taurolidine (CO(2): 10 mg; helium: 50 mg; xenon: 39.5 mg) or taurolidine with heparin (CO(2): 4 mg; helium: 4.5 mg; xenon: 46.5 mg) in all gas groups than in the control groups (CO(2): 427 mg; helium: 268 mg; xenon: 345 mg) (p < 0.001). Whereas povidone-iodine caused significantly lower tumor growth in the CO(2) group (56.5 mg) (p < 0.01), the combination of helium (145 mg) and xenon (457 mg) with povidone-iodine produced no reduction of tumor growth as compared with the control groups (helium: 268 mg; xenon: 345 mg). CONCLUSIONS: Taurolidine and taurolidine with heparin significantly inhibit intraperitoneal tumor growth, with different gases used for pneumoperitoneum. Only povidone-iodine caused significant decrease of tumor growth in combination with CO(2). The combination of xenon and povidone-iodine should not be used in patients with cancer because of increased tumor growth.     

Effect of glutamine on methotrexate efficacy and toxicity.

OBJECTIVE: To examine the effect of oral glutamine (GLN) on the efficacy and toxicity of methotrexate (MTX). SUMMARY BACKGROUND DATA: The use of high-dose chemotherapy regimens is limited by the severity of their toxicities. Oral GLN has been shown to decrease the gut toxicity seen with MTX treatment while enhancing its tumoricidal effect. METHODS AND RESULTS: Studies were done in laboratory rats and in breast cancer outpatients. Fischer 344 rats were randomized to 48 hours of prefeeding with GLN (1 g/kg/day) or an isonitrogenous amount of glycine. Rats were killed 24 hours after receiving a 20-mg/kg intraperitoneal dose of MTX. In the GLN group, there was a threefold increase in total MTX in the tumor as compared with the control group, and this increase was in both the diglutamated and pentaglutamated MTX. Inversely, there was a significant decrease in the total polyglutamated MTX in the gut in the GLN group. Given the results of this preclinical study, the authors performed a phase I trial. Nine patients diagnosed with inflammatory breast cancer received GLN (0.5 g/kg/day) during MTX neoadjuvant therapy, escalating from doses of 40 mg/m2 to 100 mg/m2 weekly for 3 weeks, followed by a doxorubicin-based regimen. No toxicity of oral GLN was detected. No patient showed any sign of chemotherapy-related toxicity. One patient had a grade I mucositis. Except for one, all patients responded to the chemotherapy regimen. Median survival was 35 months. CONCLUSIONS: These studies suggest that GLN supplementation is safe in its administration to the tumor-bearing host receiving MTX. By preferentially increasing tumor retention of MTX over that of normal host tissue, GLN may serve to increase the therapeutic window of this chemotherapeutic age.     

A study on the viscoelastic properties of the urinary bladder in dogs.

This experimental study was designed and carried out in order to investigate the participation of the collagen and muscular tissues on the viscoelastic properties of the bladder wall. Sixty-five adult male mongrel dogs were utilized. These animals were divided into 5 groups: control group (n = 10); dogs (n = 10) receiving 2.5 mg/kg atropine (cholinergic antagonist); dogs (n = 10) receiving 0.7 mg/kg verapamil (calcium extracellular inflow blocker); dogs (n = 10) receiving 0.1 mg/kg/min nitroprusside (intracellular calcium blocker), and dogs (n = 25) receiving EGTA (a calcium-chelating agent) at increasing doses from 90 to 450 mg/kg. Based on a mathematical model, we have demonstrated that: (1) the collagen component is responsible for the elastic properties; (2) the muscle component is responsible for the viscoelastic properties; (3) the viscoelastic properties have an active element which is affected by calcium total depletion, and (4) such viscoelastic properties are not dependent on cholinergic stimulation.     

Bombesin improves survival from methotrexate-induced enterocolitis.

OBJECTIVE: The authors determined whether bombesin could improve survival from methotrexate (MTX)-induced enterocolitis. SUMMARY BACKGROUND DATA: Bombesin prevents gut mucosal atrophy, which is produced by feeding rats an elemental diet. Administration of MTX produces a lethal enterocolitis in rats fed an elemental diet. METHODS: On treatment day 0, 60 rats were divided randomly into three groups and fed an elemental diet (Vivonex TEN, Sandoz, Minneapolis, MN) as the only source of nutrition. Groups were subdivided further to receive either saline or bombesin (10 micrograms/kg, subcutaneously, three times a day) beginning either on day 0 or day 14. Methotrexate (20 mg/kg, intraperitoneally) was given to all rats 14 days after the start of an elemental diet. RESULTS: Bombesin prevented the mucosal atrophy in the ileum produced by the elemental diet and significantly decreased mortality in rats given MTX (whether given as a pretreatment or at the time of MTX administration). CONCLUSION: Bombesin significantly improved survival in a lethal model of MTX-induced enterocolitis, possibly by maintaining gut mucosal structure. Administration of bombesin to patients receiving chemotherapy may be clinically useful in preventing the severe enterocolitis induced by various chemotherapeutic agents.     

Infectious complications following 72 consecutive enteric-drained pancreas transplants

New immunosuppressive protocols and advanced surgical technique resulted in an improved outcome of pancreatic transplantation (PTx) with infection remaining the most common complication. Seventy-two enteric-drained whole PTxs performed at the Innsbruck University Hospital between September 2002 and October 2004 were retrospectively analyzed. Prophylactic immunosuppression consisted of either the standard protocol consisting of single bolus antithymocyteglobulin (ATG) (Thymoglobulin, Sangstat or ATG Fresenius) induction (9 mg/kg), tacrolimus (TAC), mycophenylate mofetil (MMF) and steroids (38 patients) or a 4-day course of ATG (4 mg/kg) tacrolimus and steroids with MMF (n = 19), or Sirolimus (n = 15). Perioperative antimicrobial prophylaxis consisted of Piperacillin/Tazobactam (4.5 g q 8 h) in combination with ciprofloxacin (200 mg q 12 h) and fluconazole (400 mg daily). Ganciclovir was used for cytomegalovirus (CMV) prophylaxis if donor was positive and recipient-negative. Patient, pancreas, and kidney graft survival at 1 year were 97.2%, 88.8%, and 93%, respectively, with no difference between the groups. All retransplants (n = 8) and single transplants (n = 8) as well as all type II diabetics and nine of 11 patients older 55 years received standard immunosuppression (IS). The rejection rate was 14% and infection rate 46% with no difference in terms of incidence or type according to the three groups. Severe infectious complications included intra-abdominal infection (n = 12), wound infection (n = 7), sepsis (n = 13), respiratory tract infection (n = 4), urinary tract infection (n = 12), herpes simplex/human herpes virus 6 infection (n = 5), CMV infection/disease (n = 7), post-transplant lymphoproliferative disorder (PTLD, n = 3), invasive filamentous fungal infection (n = 4), Clostridial/Rotavirus colitis (n = 1), and endocarditis (n = 1). All four patients in this series died of infectious complications (invasive aspergillosis n = 2) (one with Candida glabrata superinfection), invasive zygomycosis (n = 1), PTLD (n = 1). Five grafts were lost (vascular thrombosis n = 3, pancreatitis n = 1, noncompliance n = 1). Infection represented the most frequent complication in this series and all four deaths were of infectious origin. Better prophylaxis and management of infections now should be the primary target to be addressed in the field of pancreas transplantation.     

Riluzole prevents ischemic spinal cord injury caused by aortic crossclamping

BACKGROUND: Recent studies support the involvement of glutamate neurotoxicity in the pathophysiology of spinal cord injury induced by aortic crossclamping. We investigated the effects of riluzole, a neuroprotective drug that blocks glutamatergic neurotransmission, in a rabbit model of spinal cord ischemia. METHODS: The infrarenal aortas of New Zealand White albino rabbits (n = 40) were occluded for 40 minutes. Experimental groups were as follows: sham operation group (n = 5), control group undergoing occlusion but receiving no pharmacologic intervention (n = 10), experimental group A (n = 10) receiving 8 mg/kg riluzole intravenously 30 minutes before ischemia, experimental group B (n = 10) receiving 4 mg/kg riluzole intravenously 30 minutes before ischemia and at the onset of reperfusion, and experimental group C (n = 10) receiving 8 mg/kg riluzole intravenously at the onset of reperfusion. Neurologic status was assessed at 6, 24, and 48 hours after the operation and then daily until the fifth day. All animals were killed at 24, 48, or 120 hours after the operation. Spinal cords were harvested for histopathologic studies, immunohistochemical studies for microtubule-associated protein 2, and search for morphologic features of apoptosis by the terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate-biotin nick-end labeling staining method. RESULTS: All animals in the control group became paraplegic. Except for 1 rabbit in group C, all riluzole-treated animals had better neurologic function. Luxol fast blue and terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate-biotin nick-end labeling staining methods demonstrated typical morphologic changes characteristic of necrosis and apoptosis in control animals. Riluzole prevented or attenuated ischemia-induced necrosis, apoptosis, and cytoskeletal proteolysis, depending on the dose and the timing of administration. CONCLUSION: Riluzole may have therapeutic utility during high-risk operations on the thoracoabdominal aorta.     

Wakefulness during cesarean section after anesthetic induction with ketamine, thiopental, or ketamine and thiopental combined

Thirty-six pregnant women (ASA class I or II) at term who underwent general anesthesia and cesarean section received either ketamine, 1 mg/kg (n = 12); thiopental, 4 mg/kg (n = 13); or a combination of ketamine, 0.5 mg/kg, and thiopental, 2 mg/kg (n = 11). A blood pressure cuff inflated to 250 mm Hg isolated one arm from the effects of succinylcholine so that awareness during anesthesia could be assessed by asking the patient to move her hand. Although only one patient receiving ketamine responded to commands during anesthesia, 46% of patients receiving either thiopental or the combination responded to commands intraoperatively. No patient hallucinated, the incidence of dreams was low (11%), and no postoperative dysphoria was noted. Three patients (8%) had postoperative recall of intraoperative awareness; one had received thiopental and two the combination. Maternal intraoperative cardiovascular responses among the groups were similar, as were umbilical blood gas values, newborn Apgar scores, and neonatal neurobehavioral test scores at 4 and 24 hr. Ketamine more effectively blocked maternal responsiveness to commands and strong stimuli during the first few minutes after anesthetic induction for cesarean section than did thiopental or a combination of thiopental and ketamine, each at a lower dose.     

A prospective comparison of murine monoclonal CD-3 (OKT3) antibody-based and equine antithymocyte globulin-based rejection prophylaxis in cardiac transplantation. Decreased rejection and less corticosteroid use with OKT3

To test the efficacy of murine monoclonal CD-3 antibody (OKT3) in early prophylaxis for cardiac allograft rejection, we conducted a 6-month trial, prospectively assigning 51 patients to receive either equine antithymocyte globulin-based (n = 25) or OKT3-based (n = 26) early prophylaxis. ATG patients received 8 days of ATG (10 mg/kg), with the first dose given preoperatively. OKT3 patients received 14 days of OKT3 (5 mg) beginning on the second postoperative day. Corticosteroid and azathioprine administration were similar during early prophylaxis. Cyclosporine was begun preoperatively in ATG patients and on the fourth postoperative day in OKT3 patients. In addition, patients in both groups were randomized to receive or not receive eight weekly administrations of vincristine (0.025 mg/kg). While infection rate (0.8 +/- 0.2 infections/patient in both groups [mean +/- SEM]) and mortality (1 patient in each group) did not differ, OKT3-based early prophylaxis delayed the first rejection episode (76 +/- 11 days vs. 36 +/- 8 days, P = 0.005) and decreased the risk of rejection during the 6-month follow-up (P less than 0.001, product-limit analysis). Overall, the OKT3 group manifested 1.5 +/- 0.2 episodes of rejection/patient compared with 2.2 +/- 0.2 episodes/patient in the ATG group (P = 0.036). Despite similar 6-month cumulative cyclosporine and azathioprine dosages, six month average corticosteroid administration was less in the OKT3 group (12.2 +/- 1.5 mg prednisone equivalent/m2/day versus 19.3 +/- 2.1 mg prednisone equivalent/m2/day, P = 0.008), fewer OKT3 patients subsequently required additional cytolytic therapy for rejection (2 [8%] versus 12 [48%], P = 0.001), and more patients in the OKT3 group were successfully weaned off maintenance corticosteroids (22 [88%] versus 11 [46%], P = 0.002). We conclude that, relative to an equine ATG-based protocol, OKT3-based early prophylaxis results in less rejection, permitting less chronic corticosteroid administration.     

A double-blind, randomized comparison of low-dose rocuronium and atracurium in a desflurane anesthetic

STUDY OBJECTIVES: To compare the neuromuscular and hemodynamic effects of rocuronium and atracurium when administered during a desflurane-based anesthetic. DESIGN: Randomized, double-blind clinical trial. PATIENTS: 51 adult ASA physical status I and II patients scheduled for general surgical operations. SETTING: University-based NCI-designated cancer center. INTERVENTIONS: Patients received either 0.45 mg/kg rocuronium (n = 28) or atracurium 0.5 mg/kg (n = 23). Induction of anesthesia was accomplished by 2 microg/kg fentanyl intravenously (IV) and 1.5 mg/kg propofol IV and maintained by a nitrous oxide/oxygen desflurane anesthetic. MEASUREMENTS AND MAIN RESULTS: A neuromuscular monitor was used at the adductor pollicis to monitor and record twitch response to train-of-four electrical stimulation. Baseline heart rate (HR) and blood pressure (BP) were measured and again at 2, 5, 10, and 15 minutes after muscle relaxant administration. Patients in the rocuronium group were found to have shorter times to 80%T(1)depression (109 +/- 53 vs. 135 +/- 47 sec), although those differences did not reach statistical significance (p = 0.07). Percent of the first twitch (T(1) ) was significantly lower in the patients receiving rocuronium at 60 seconds (53 +/- 24 vs. 73 +/- 27 sec; p = 0.006) and 90 seconds (25 +/- 22 vs. 47 +/- 29 sec; p = 0.003) than in the patients receiving atracurium. Duration was shorter in rocuronium-treated patients (25% T(1) recovery = 32 +/- 12 vs. 54 +/- 14 min; p < 0.001) than the patients receiving atracurium. Intubation scores were better at 60 seconds after muscle relaxant administration in the rocuronium group. No significant differences in HR or BP were seen between the patients in the two groups. CONCLUSIONS: Rocuronium at a dose of 0.45 mg/kg possesses a fairly rapid onset of neuromuscular blockade and has short:intermediate duration of action when used with a desflurane anesthetic. This quality makes it a desirable drug for operations of relatively short duration. Rocuronium at a dose of 0.45 mg/kg has a faster onset and shorter duration than atracurium, at 0.5 mg/kg, when used with a desflurane anesthetic.     

Correction of congenital hyperbilirubinemia in homozygous Gunn rats by xenotransplantation of hamster livers

The homozygous Gunn(j/j) rat is an animal model for Crigler-Najjarsyndrome in which the lack of the enzyme uridine diphosphoglucoronate-glucuronosyltransferase (UDP-GT) results in congenital unconjugated nonhemolytic hyperbilirubinemia. Because the binding of bilirubin to albumin in plasma varies from species to species, xenotransplantation (XTx) of liver afforded in this model the opportunity to study the interactions between xenoproteins of the donor and bilirubin of the recipient. For this purpose, orthotopic liver transplantation (OLTx) was performed from hamster to adult Gunn(j/j) rats. No immunosuppression (IS) was given to controls. (Group I, n=5) and to OLTx recipients of syngeneic (Gunn(j/j) rat) grafts (Group II, n=5), whereas tacrolimus (1 mg/kg/day × 15 days, IM) and cyclophosphamide (8 mg/kg/day × 7 days, IP) were administered to animals receiving hamster xenografts (Group III, n=l1). While untreated animals (Group I) died within 7 days (6.8±0.2 days) post-transplantation (Tx), the use however of IS resulted in prolonged (30.2±6.8 days) survival of xenogeneic recipients (Group III) who eventually succumbed to rejection. A precipitous decline in total serum bilirubin (TBili) from pre-operative levels of 5.3±1.0 mg/dL to 0.5±0.2 mg/dL was noted in both Group I and III animals, an observation that sustained itself only in the latter group during the course of their follow-up. The decrease in TBili was also associated with a contemporaneous increase in biliary concentration of conjugated bilirubin. No noticeable reversal of hyperbilirubinemia was however observed in OLTx recipients of syngeneic grafts (Group II). Taken together, these data suggest that hamster albumin and hepatocyte-associated xenoproteins and enzymes involved in the process of membrane transport and glucuronidation of bilirubin, functioned efficaciously after OLTx in Gunn(j/j), rats, resulting in the reversal of the inborn error of metabolism for the duration of follow-up.     

核黄素-月桂酸酯对化疗大鼠口腔黏膜的保护作用

目的:探讨核黄素-月桂酸酯(RFL)对大鼠化疗后口腔黏膜的保护作用.方法:70只大鼠,体重210～250 g,随机分4组:正常对照组(n=10)、甲氨喋呤(MTX)对照组(n=20)、RFL预防组(25 mg/kg,n=20)、RFL预防 甲酰四氢叶酸钙(CF,15 mg/kg,)组(n=20).化疗药选用MTX,皮下注射,3.0 mg·kg-1·d-1,连续给药3 d;RFL于第一次化疗前24 h给药;CF于化疗后24 h给药,连续给药3次.观察化疗后大鼠每日摄食量、体重、外周血白细胞的变化、口腔溃疡出现及愈合的时间、溃疡的分度.结果:MTX对照组和RFL预防组体重与进食量均于化疗第3～8日明显下降,分别于第5日和第6日降至最低,但RFL预防组每日摄食量和体重明显高于MTX对照组(P＜0.05或P＜0.01).与MTX对照组比较,RFL预防组口腔溃疡出现时间晚,愈合早,程度轻.RFL预防 CF组的体重、进食量和外周血白细胞均无明显变化,且未出现口腔溃疡.结论 RFL可有效减轻机体化疗后所致的口腔黏膜损伤.     

Prophylactic ketamine to prevent shivering in parturients undergoing Cesarean delivery during spinal anesthesia

Study ObjectiveTo compare the efficacy and safety of ketamine 0.25 mg/kg with ketamine 0.5 mg/kg to prevent shivering in patients undergoing Cesarean delivery.DesignProspective, randomized, double-blinded, placebo-controlled study.SettingOperating rooms and postoperative recovery rooms.Patients120 ASA physical status 1 and 2 pregnant women scheduled for Cesarean delivery during spinal anesthesia.MeasurementsPatient characteristics, anesthetic and surgical details, Apgar scores at 1 and 5 minutes, and side effects of the study drugs were recorded. Heart rate, mean arterial pressure, oxygen saturation via pulse oximetry, tympanic temperature, severity of shivering, and degree of sedation were recorded before intrathecal injection and thereafter every 5 minutes. Patients were randomized to three groups: saline (Group C, n=30), intravenous (IV) ketamine 0.25 mg/kg (Group K-0.25, n=30), or IV ketamine 0.5 mg/kg (Group K-0.5, n=30). Grade 3 or 4 shivering was treated with IV meperidine 25 mg and the prophylaxis was regarded as ineffective.Main ResultsThe number of shivering patients was significantly less in Group K-0.25 and in Group K-0.5 than in Group C (P = 0.001, P = 0.001, respectively). The tympanic temperature values of Group C were lower at all times of the study than in either ketamine group. Median sedation scores of Group K-0.5 were significantly higher than in Group K-0.25 or Group C at 10, 20, 30, and 40 minutes after spinal anesthesia.ConclusionsProphylactic IV ketamine 0.25 mg/kg was as effective as IV ketamine 0.5 mg/kg in preventing shivering in patients undergoing Cesarean section during spinal anesthesia.     

Following Universal Prophylaxis with Intravenous Ganciclovir and Cytomegalovirus Immune Globulin, Valganciclovir is Safe and Effective for Prevention of CMV Infection Following Lung Transplantation

We prospectively determined the safety and efficacy of valganciclovir for prevention of cytomegalovirus (CMV) in at-risk (donor positive/recipient negative [D+/R-] or R+) lung transplant recipients. We also determined the length of prophylaxis required to significantly decrease both CMV infection and disease. Consecutive lung transplant recipients surviving >30 days (n = 90) received combination prophylaxis with intravenous (i.v.) ganciclovir (GCV) 5 mg/kg/day and cytomegalovirus immune globulin (CMV-IVIG) followed by valganciclovir (450 mg twice-daily) to complete 180, 270 or 365 days of prophylaxis. This group was compared to a historical group (n = 140) who received high-dose oral acyclovir following i.v. GCV and CMV-IVIG. CMV disease was significantly lower in patients receiving valganciclovir compared to acyclovir (2.2% vs. 20%; p < 0.0001). Freedom from CMV infection and disease was significantly greater (p < 0.02) in patients receiving 180, 270 or 365 days of prophylaxis (90%, 95% and 90%, respectively) compared to those receiving 100-179 days (64%) or < 100 days (59%). No patient receiving valganciclovir died during the study. Following prophylaxis with i.v. GCV and CMV-IVIG, valganciclovir is safe and effective for prevention of CMV infection and disease in at-risk lung transplant recipients. The required length of prophylaxis was at least 180 days.