Phase I trial of a melanoma vaccine with gp100(280-288) peptide and tetanus helper peptide in adjuvant: immunologic and clinical outcomes.

A melanoma vaccine composed of HLA-A2-restricted peptide YLEPGPVTA (gp100(280)), with or without a modified T-helper epitope from tetanus toxoid AQYIKANSKFIGITEL, has been evaluated in a Phase I trial to assess safety and immunological response. The vaccines were administered s.c. in either of two adjuvants, Montanide ISA-51 or QS-21, to 22 patients with high-risk resected melanoma (stage IIB-IV). Local and systemic toxicities were mild and transient. We detected CTL responses to the gp100(280) peptide in peripheral blood in 14% of patients. Helper T-cell responses to the tetanus helper peptide were detected in 79% of patients and had a Th1 cytokine profile. One patient with a CTL response to gp100 had a recurrence in a lymph node 2 years later; her nodes contained CD8+ cells reactive to gp100(280) (0.24%), which proliferated in response to peptide. The overall survival of patients is 75% (95% confidence interval, 57-94%) at 4.7 years follow-up, which compares favorably with expected survival. Four of 14 patients who completed at least six vaccines subsequently developed metastases, all of which were solitary and surgically resectable. They remain alive and clinically free of disease at last follow-up. Data from this trial demonstrate immunogenicity of the gp100(280) peptide and suggest that immune responses may persist long-term in some patients. The frequency and magnitude of the CTL response may be improved with more aggressive vaccination regimens. Although this Phase I study was not intended to evaluate clinical benefit, the excellent survival of patients on this protocol suggests the possibility of a benefit that should be assessed in future studies.     

High dose cyclophosphamide plus recombinant human granulocyte-colony stimulating factor (rhG-CSF) in the treatment of follicular, low grade non-Hodgkin's lymphoma: CALGB 9150

The main objectives of this study were to determine the feasibility of administering high doses of cyclophosphamide plus recombinant human granulocyte-colony stimulating factor (rhG-CSF) every 14-21 days to patients with follicular small cleaved cell lymphoma. For each patient, the treatment was not considered feasible if fewer than four cycles of cyclophosphamide chemotherapy could be administered on schedule (i.e. at least every 29 days) or (1) hospitalization of the patient for longer than three days was necessary for neutropenic fever (38 degrees C) or bacteriologically documented infection in > 50% of the cycles, or (2) grade > or = 2 hemorrhage in association with thrombocytopenia of grade > or = 3 severity occurred in > 50% of the cycles or (3) non-hematologic toxicity (excluding nausea/vomiting and alopecia) of grade > or = 3 occurred in > 50% of cycles. The goal was to have a treatment program feasible in 75% or more of the treated patients. The secondary objectives were to determine the toxicities, the complete and partial response rates, and the time to treatment failure (TTF). The trial also attempted to assess the effectiveness of this treatment program in eradicating Bcl-2 rearrangements by PCR, and to assess complete remission duration in relationship to PCR results in patients who respond to this chemotherapy program. Patients were required to have histologically documented non-Hodgkin's lymphoma of the subtypes follicular, predominantly small cleaved cell (IWF-B) or follicular mixed, (IWF-C). Patients were required to have Stage IV disease including histologic evidence of bone marrow involvement. Measurable disease was required and patients were also required to have one of the following risk factors: > or = 2 extranodal sites, node or nodal group > or = 5 cm. Submission of fresh bone marrow for molecular genetic studies for the presence of Bcl-2-Ig fusion DNA was mandatory in previously untreated patients. Patients had to be between 18 and physiologic age 55 years (carefully selected patients over age 55 years were also eligible), expected survival > 2 years, performance status 0-1, and have adequate renal, hepatic and bone marrow function, and a cardiac ejection fraction > or = 50%. Cyclophosphamide 4.5 g/m2 i.v. was given with mesna every 14 days with rhG-CSF support. Twenty-nine patients were accrued to this trial. The median follow-up time is 5.0 years, with a range of 2.5-6.7 years. The overall response rate was 75% (9 CRs 37.5%, 9PRs 37.5%). The median duration of survival is 5.53 years. The 1-year estimated probability of freedom from treatment failure was 50% and of survival at 1 year was 92%. No strong association was observed between TTF and age, symptomatic stage, histology performance status, number of extranodal sites or baseline Bcl-2 status. At 3 years the survival of all patients was 78% and failure free survival was 17%. 15 (62%) of the 24 eligible previously untreated patients met the criteria for feasibility specified in the protocol. The 95% CI for the feasibility rate is (44 and 82%). Twenty-two of the 24 (92%) previously untreated patients had specimens submitted for testing for Bcl-2 rearrangements. Thirteen of the 22 (59%) were found to have rearrangements at baseline. Post-treatment specimens were submitted for seven of the 13 patients. Four of the seven converted to Bcl-2 negative following treatment. Eight of 13 Bcl-2 positive patients (62%) had a clinical response to treatment. The 95% exact binomial CI for the total response rate in this subgroup is (28 and 88%). This study demonstrates that repetitive doses of cyclophosphamide at 4.5 g/m2 every two weeks with rhG-CSF support can be administered to selected younger patients with advanced follicular lymphoma with morphologic involvement of the bone marrow with acceptable non-hematologic toxicity.     

Small bowel intussusception: what is the role of laparoscopy?

Small bowel intussusception in adults is a rare surgical disease which almost always occurs as a complication of either benign or malignant lesion of the bowel that is working as a leading point. In adults, the surgical approach consists of the resection of the bowel involved to ensure the excision of the lesion below. The authors report a case of ileocecal intussusception occurred in a young woman, 35 years old, observed for abdominal pain and signs of small bowel occlusion. She underwent surgical resection of the ileocecal segment with laparoscopic approach. The authors discuss the feasibility of the laparoscopic approach in this rare surgical disease and its benefits in terms of patient's postoperative comfort and outcome.     

The influence of duration of Kleinert immobilization on the functional recovery of primarly reconstructed flexor tendons in children and adult patients

Flexor tendon repair in the hand is very often complicated by the formation of peritendinous adhesions that result in loss of normal tendon gliding, digital stiffnes and functional disability. While stability is critical for a successful tendon repair, mobility is also important, as motion of the repaired tendon decreases the formation of postoperative adhesions and increases the strength of the repair. Immobilization and its duration, can ensure the integrity of the repair but can also lead to scaring, stiffness, and joint contractures. This study included 20 children and 39 adult patients, in the period from January 2000 to April 2003., with flexor tendon ruptures of the hand. Tendons were primary repaired using direct tennoraphy, and postoperately patients were treated with Kleinert dynamic imobilization. The aim of this study was to investigate the influence of the duration of the dynamic immobilization on successful postoperative functional recovery, separately in children and adult patients. Research in this area has been directed at achieving the optimal balance between stability and mobility, without compromising one for the other.     

大鼠红细胞流变性变化及抗运动疲劳效应与补服肉碱和糖的作用

目的:观察单独和配合补充肉碱和糖对大鼠红细胞流变性及抗运动疲劳能力的影响。方法:实验于2005-09/11于河北师范大学体育学院运动生理学实验室完成。①选用SD雄性大鼠72只,按随机数字表法分为4组:安静组(n=6)、安静补服组(n=18)、安慰运动组(n=12)和补服运动组(n=36)。安静补服组和补服运动组均给予3种药物形式:左旋肉碱(由沈阳东宇精细化工有限公司生产)、葡萄糖(济南利民制药有限公司生产)、肉碱和葡萄糖。安静补服组和补服运动组每天上午8∶30给予自来水溶解的肉碱和/或糖补剂,安静组和安慰运动组给予相同量的自来水。连续补充7d,补服量:肉碱组、葡萄糖组、肉碱 葡萄糖组分别为650mg/(kg·d),7g/(kg·d),325mg/(kg·d) 3.5g/(kg·d)。②在实验第8天,将安静组取血4mL。安慰运动组和补服运动组进行无负重游泳至力竭,然后取血。采用北京泰诺德新技术研究所生产的BV-100型无摩擦式血液流变仪测全血高切黏度(180s-1)、全血高切还原黏度(180s-1)、全血低切黏度(3s-1)、全血低切还原黏度(3s-1)、刚性指数及聚集指数。③计量资料进行正态分布、方差齐性检验后,再进行方差分析。结果:大鼠72只均进入结果分析。①红细胞流变性指标变化:安静补服组各组虽大部分红细胞流变性指标有改善,但与安静组相比,差异无显著性意义(P>0.05)。安慰运动组运动后5min全血高切黏度和全血高切还原黏度明显高于安静组(P<0.01),运动24h后全血高、低切黏度和红细胞聚集指数明显高于安静组(P<0.01)。一次力竭运动后5min各补服运动组全血低切黏度明显低于安慰运动组(P<0.01)。各组间红细胞刚性指数和红细胞聚集指数差异不明显(P>0.05)。各补服运动组间相比,补服肉碱组的全血低切还原黏度最高(P<0.01)。各补服运动组运动后24h全血低切还原黏度和红细胞聚集指数明显低于安慰运动组(P<0.05～0.01),补服肉碱和肉碱 葡萄糖运动组全血低切还原黏度和全血低切黏度、红细胞聚集指数明显高于补服葡萄糖运动组(P<0.05～0.01)。②抗疲劳作用:补服肉碱、葡萄糖、肉碱 葡萄糖运动组大鼠游泳时间分别为(334.5±27.81),(321.0±51.83),(326.5±39.9)min,均长于安慰运动组[(252.5±42.69)min,P<0.01];各补服运动组间差异不明显(P>0.05)。结论:单独补充或合用肉碱和糖均有利于力竭运动后大鼠红细胞流变性指标的改善,导致其运动能力的提高。     

Enhancement of t lymphocyte functions by Fc fragments of immunoglobulins. I. Augmentation of allogeneic mixed lymphocyte culture reactions requires I-A- or I-B-subregion differences between effector and stimulator cell populations

Fc fragments derived from human Ig were found to be capable of enhancing T cell-mediated, antigen-induced proliferative and mixed lymphocyte culture responses. Maximum enhancement occurred when suboptimal amounts of antigen or suboptimal numbers of stimulator cells were employed. Augmentation of the allogeneic mixed lymphocyte culture reaction requires an I-A and/or I-B subregion difference between effector and stimulator cell populations. Although a significant proliferative response was observed with K- or D- region differences, Fc fragments were unable to enhance the response. The T cell population acted upon by Fc fragments in the potentiation of these responses bears the Lyt-1(+)23(-) phenotype.