The effect of sterilization on transforming growth factor beta isolated from demineralized human bone

Growth factors have been identified as the primary cause of osteoinduction in bone healing. Transforming growth factor beta (TGF- beta) has been shown to promote bone formation and is present in bone in high quantities. The aims of the present study were to isolate TGF- beta from human bone, demonstrate its biologic activity, and analyze the effects of conventional sterilization techniques on activity. Bone, obtained from femoral heads of five patients (mean age, 70 years) was ground, demineralized, and freeze-dried, and samples from each patient were divided into three groups: no treatment, sterilization with 1.60 to 1.94 Mrad of 60Co irradiation, and sterilization with ethylene oxide (ETO). Carrier-free recombinant TGF-beta control was also treated and was totally inactivated by ETO but not by irradiation (p < 0.01). TGF- beta activity in demineralized bone was not significantly diminished (p > 0.1) by either sterilization procedure, and substantial amounts of active TGF-beta were recovered in all bone samples: 1.04 +/− 0.77 ng per mg of protein in irradiated samples, 0.67 +/− 0.26 ng per mg in ETO- treated samples, and 1.04 +/− 0.33 in untreated samples, respectively (mean +/− SD). Although a recent report demonstrated that the osteoinductive activity of bone morphogenetic protein in bone powder is diminished considerably by ETO and by 2.5 Mrad of irradiation sterilization of bone powder, these data demonstrate that TGF-beta activity, with its osteoinductive properties, was not destroyed in more coarsely ground, demineralized bone by ETO or by lower doses of irradiation. These findings support the use of human bone allografts in clinical instances involving impaired bone formation.     

白介素与溃疡性结肠炎

近年来对白介素(interleukin,IL)和溃疡性结肠炎(ulcerative colitis,UC)的研究取得了很大进展,我们通过总结整理以前有关IL和UC的文献,概括出IL的产生和在UC发病及病理变化中的作用机制:IL-1直接介导了UC初期阶段炎症的发生:IL-8、IL-6直接促进炎性细胞过度分泌和/或抑制了炎性细胞的凋亡,IL-2分泌减少导致免疫系统内细胞间网络调节失衡, 使局部炎症介质和自由基释放,引起细胞毒作用,IL主要通过影响机体整体和/或局部免疫系统的功能介导UC的产生,并与UC的迁延难愈和反复发作有关．     

National Comparative Audit of Blood Use in Elective Primary Unilateral Total Hip Replacement Surgery in the UK

INTRODUCTION

Blood is a scarce and expensive product. Although it may be life-saving, in recent years there has been an increased emphasis on the potential hazards of transfusion as well as evidence supporting the use of lower transfusion thresholds. Orthopaedic surgery accounts for some 10% of transfused red blood cells and evidence suggests that there is considerable variation in transfusion practice.

PATIENTS AND METHODS

NHS Blood and Transplant, in collaboration with the Royal College of Physicians, undertook a national audit on transfusion practice. Each hospital was asked to provide information relating to 40 consecutive patients undergoing elective, primary unilateral total hip replacement surgery. The results were compared to indicators and standards.

RESULTS

Information was analysed relating to 7465 operations performed in 223 hospitals. Almost all hospitals had a system for referring abnormal pre-operative blood results to a doctor and 73% performed a group-and-save rather than a cross-match before surgery. Of hospitals, 47% had a transfusion policy. In 73%, the policy recommended a transfusion threshold at a haemoglobin concentration of 8 g/dl or less. There was a wide variation in transfusion rate among hospitals. Of patients, 15% had a haemoglobin concentration less than 12 g/dl recorded in the 28 days before surgery and 57% of these patients were transfused compared to 20% with higher pre-operative values. Of those who were transfused, 7% were given a single unit and 67% two units. Of patients transfused two or more units during days 1–14 after surgery, 65% had a post transfusion haemoglobin concentration of 10 g/dl or more.

CONCLUSIONS

Pre-operative anaemia, lack of availability of transfusion protocols and use of different thresholds for transfusion may have contributed to the wide variation in transfusion rate. Effective measures to identify and correct pre-operative anaemia may decrease the need for transfusion. A consistent, evidence-based, transfusion threshold should be used and transfusion of more than one unit should only be given if essential to maintain haemoglobin concentrations above this threshold.     

Incidence of nonsustained and sustained ventricular tachyarrhythmias in patients with an implantable cardioverter defibrillator

INTRODUCTION: Nonsustained ventricular tachycardia (NSVT) is a frequent phenomenon in some patients with heart disease, but its association with sustained ventricular tachycardias (ventricular tachycardia [VT]/ventricular fibrillation [VF]) is still not clear. The aim of this study was to determine whether NSVT incidence was associated with sustained VT/VF in patients with an implantable cardioverter defibrillator (ICD). METHODS AND RESULTS: Retrospective data analysis was conducted in 923 ICD patients with a mean follow-up of 4 months. NSVT and sustained VT/VF were defined as device-detected tachycardias. The incidence rates of NSVT and sustained VT/VF as well as ICD therapies were determined as episodes per patient. The NSVT index was defined as the product of NSVT episodes/day times the mean number of beats per episode, i.e., total beats/day. The NSVT index peak was defined as the highest value on or prior to the day with sustained VT/VF episodes. Patients (n = 393) with NSVT experienced a higher incidence of sustained VT/VF (17.2 +/- 63.0 episodes/patient) and ICD therapies (15.2 +/- 61.4 episodes/patient) than patients (n = 530) without NSVT (sustained VT/VF: 0.5 +/- 6.6 and therapies: 0.5 +/- 5.6; P < 0.0001). Approximately 74% of NSVT index peaks occurred on the same day or <3 days prior to sustained VT/VF episodes. The index was higher for peaks < or =3 days prior to the day with sustained VT/VF (94.3 +/- 140.1 total beats/day) than for peaks >3 days prior to the day with sustained VT/VF (32.7 +/- 55.9 total beats/day; P < 0.0001). CONCLUSION: ICD patients with NSVT represent a population more likely to experience sustained VT/VF episodes with a temporal association between an NSVT surge and sustained VT/VF occurrence.     

射频毁损治疗肝脏肿瘤

肝脏肿瘤包括肝原发性肿瘤和肝转移瘤,其治疗目前仍首选手术切除,但确诊时85％～95％的患者已失去手术切除时机,对难以手术治疗的患者已有多种介入治疗方法,如肝动脉栓塞化疗(TAE)、经皮无水酒精注射、微波、激光、冷冻、高功率超声聚焦等。射频毁损(radiofrequency ablation,RFA)是近年国外刚用于肝脏肿瘤治疗的新技术,具有安全性高、并发症少、患者易耐受、肿瘤复发可重复治疗等优点,具有良好的应用前景。 1 射频治疗仪及治疗机制 1868年法国的d'Arsonval发现高于10KHz的高变电流通过活体组织时,并不引起神经肌肉的应激,但局部产热造成组织毁损,自此射频毁损术在神经及心血管领域得以应用并     

Development of a marrow transplant regimen for acute leukemia using targeted hematopoietic irradiation delivered by 131I-labeled anti-CD45 antibody, combined with cyclophosphamide and total body irradiation

In an attempt to decrease the relapse rate after bone marrow transplantation (BMT) for advanced acute leukemia, we initiated studies using 131I-labeled anti-CD45 antibody (BC8) to deliver radiation specifically to hematopoietic tissues, followed by a standard transplant preparative regimen. Biodistribution studies were performed in 23 patients using 0.5 mg/kg trace 131I-labeled BC8 antibody. The BC8 antibody was cleared rapidly from plasma with an initial disappearance half-time of 1.5 +/- 0.2 hours, presumably reflecting rapid antigen- specific binding. The mean radiation absorbed doses (cGy/mCi131I administered) were as follows: marrow, 7.1 +/- 0.8; spleen, 10.8 +/- 1.4; liver, 2.7 +/- 0.2; lungs, 2.1 +/- 0.1; kidneys, 0.7 +/- 0.1; and total body, 0.4 +/- 0.03. Patients with acute myelogenous leukemia (AML) in relapse had a higher marrow dose (11.4 cGy/mCi) than those in remission (5.2 cGy/mCi; P = .001) because of higher uptake and longer retention of radionuclide in marrow. Twenty patients were treated with a dose of 131I estimated to deliver 3.5 Gy (level 1) to 7 Gy (level 3) to liver, with marrow doses of 4 to 30 Gy and spleen doses of 7 to 60 Gy, followed by 120 mg/kg cyclophosphamide (CY) and 12 Gy total body irradiation (TBI). Nine of 13 patients with AML or refractory anemia with excess blasts (RAEB) and two of seven with acute lymphocytic leukemia (ALL) are alive disease-free at 8 to 41 months (median, 17 months) after BMT. Toxicity has not been measurably greater than that of CY/TBI alone, and the maximum tolerated dose has not been reached. This study demonstrates that with the use of 131I-BC8 substantially greater doses of radiation can be delivered to hematopoietic tissues as compared with liver, lung, or kidney, which may improve the efficacy of marrow transplantation.