肝移植中应用巴利昔单抗诱导治疗的免疫抑制方案的疗效

目的 探讨肝移植中应用巴利昔单抗诱导治疗的免疫抑制方案的疗效。方法 2007年8月至2009年7月间139例成人肝移植受者接受含巴利昔单抗诱导的免疫抑制方案（诱导组）。以2006年1月至2006年12月间接受常规免疫抑制方案的106肝移植受者为对照组。术后随访12个月,记录两组受者排斥反应、代谢并发症的发生情况,以及患者的存活情况。结果 诱导组术后1个月内急性排斥反应、糖尿病、高血压及感染的发生率分别为7.9％、33.8％、21.6％和22.3％,对照组分别为15.1％、72.6％、40.6％和43.4％,差异有统计学意义(P＜0.05)。术后12个月内,诱导组急性排斥反应、移植后新发糖尿病、高血压以及高脂血症的发生率分别为10.8％、5.0％、4.3％和7.9％,而对照组分别为19.8％、9.4％、8.5％和14.2％,差异有统计学意义(P＜0.05)。诱导组和对照组术后1年的存活率分别为92.1％和88.7％(P＞0.05)。结论 免疫抑制方案中应用巴利昔单抗诱导治疗可以早期撤除皮质激素,并可降低急性排斥反应的发生率及减少使用皮质激素引起的不良反应。     

Retrospective analysis of efficacy and tolerability of tolterodine in children with overactive bladder

OBJECTIVE: To evaluate the efficacy and tolerability of tolterodine in children with an overactive bladder, treated in a single incontinence centre. MATERIALS AND METHODS: A retrospective analysis of a database of a total of two hundred and fifty-six patients (175 boys and 81 girls, age range 3 years to 17 years, mean age 8.33 years) with urodynamically confirmed bladder overactivity was performed. All children received tolterodine tartrate (dose range of 0.5-4 mg orally). In group I (n=205) tolterodine tartrate replaced anticholinergic drugs (AC) (oxybutinin chloride or oxyphencyclimin hydrochloride). A subgroup of patients switched because of intolerance due to serious adverse events (60.4%) or because of lack of improvement in micturition variables (39.6%). In group II tolterodine was prescribed as initial therapy (n=51). Tolerability was assessed by a standardised questionnaire on adverse events at every outdoor clinic visit. Efficacy assessment was based on micturition diary variables, mean change of maximum bladder capacity and number of incontinence episodes/24 h. RESULTS: The mean treatment time was 9.32 months with a range from 1.5 months to 23.4 months. The final dose was 0.1mg/kg orally daily divided into two doses. In group I central nervous system disorders (81%) were the most common adverse events, 26.2% showed flushing, 12.2% accommodation problems and 25.2% had gastrointestinal complaints (constipation, encopresis, abdominal pain). Withdrawal of the non-selective antimuscarinic drug resulted in total recovery from adverse events.Introduction of tolterodine in group I and II caused no serious adverse events. Nine patients (3.5%) reported side-effects and only two discontinued treatment. There were no reports of flushing, troubles of visual accommodation, hyperpyrexia. In group I we observed a mean decrease in urgency by 38.7%, a mean increase in maximal bladder capacity by 33.6% and the number of incontinence episodes decreased by 64.8%. In group II we observed equivalent values with a significant (p<0.001) change in maximal bladder capacity (49.7%), incontinence episodes (64.8%) and micturition episodes/24 h. CONCLUSIONS: The results of this retrospective analysis suggest that tolterodine is well tolerated in children and offers an effective treatment for urinary symptoms due to overactive bladder. Tolterodine is superior to non-selective antimuscarinic drugs, with respect to adverse events, allowing more compliance and more effective treatment in children.     

Limited-dose Daclizumab versus Basiliximab: a comparison of cost and efficacy in preventing acute rejection

The purpose of this study was to compare the efficacy and cost of the limited-dose Daclizumab regimen to that of the standard-dose Basiliximab regimen. Two antibody induction regimens were compared in patients aged 18 years and older who received renal transplants from January 2002 to September 2003 and completed interleukin (IL)-2R antibody induction with standard-dose Basiliximab (20 mg x 2 doses) or limited-dose Daclizumab (1 mg/kg x 2 doses). The primary outcome measure was the incidence of acute rejection. Secondary outcomes included cost, changes in serum creatinine level, and delayed graft function. Of the 46 patients randomized, 42 patients completed the 6-month follow-up. Mean serum creatinine level at time of discharge was originally higher in the limited-dose Daclizumab group than the standard-dose Basiliximab group (1.89 vs 1.57, respectively). By 1, 3, and 6 months, mean serum creatinine values were similar between both groups, with a trend toward lower mean serum creatinine values in the limited-dose Daclizumab group. The incidence of acute rejection was also similar between the groups (6% vs 7%). The average cost difference between the 2 regimens was approximately $715. This study suggests that a limited-dose Daclizumab regimen may be an efficacious and less costly alternative to the standard-dose Basiliximab regimen for antibody induction therapy following renal transplantation.     

Mycophenolate sodium: tolerability and efficacy in transplantation in the rat

Inhibition of inosine monophosphate dehydrogenase by mycophenolate compounds results in potent immunosuppression, as demonstrated by the efficacy of the marketed prodrug mycophenolate mofetil (MMF) in clinical allotransplantation. Side effects are well-known and include bone marrow depression and gastrointestinal intolerability. Mycophenolate sodium (MPS) is in clinical development as an enteric-coated formulation to alleviate this gastrointestinal adverse effect. Accompanying this development, MPS and MMF were evaluated in a tolerability study in rats and in efficacy studies in rat allo- and xenotransplantation models. The compounds were given either singly or in combination with cyclosporine A and were efficacious in the prevention of allo- or xeno-graft rejection, but with a rather narrow window between optimal immunosuppression and adverse side effects. For instance, the minimal effective dose to prevent rejection of a kidney or heart allograft or a hamster heart xenograft is a daily dose of 10-20 mg/kg MPS, at which dose the first adverse side effects can be observed: the compound at 40 mg/kg is not tolerated. This window is even narrower for MMF than for MPS, and in most models, a minimal effective MMF dose could not be established. The window between optimal immunosuppression and adverse side effects is larger when the compounds are given in combination with cyclosporine A: in all models investigated combinations were established yielding long-term survival without histologic signs of rejection and without signs of side effects. Thus, the combination of an IMPDH inhibitor (MPS, MMF) and a calcineurin inhibitor (cyclosporine A) enables fine-tuning in achieving optimal immunosuppression avoiding drug side effects.     

Basiliximab induction improves the outcome of renal transplants in children and adolescents

Thirty-two children and adolescents received their renal transplant at the Montefiore Medical Center, in New York, between October 1996 and May 2000. Twenty-four patients received basiliximab, in addition to tacrolimus and steroids (basiliximab group). The remaining eight patients received only tacrolimus and steroids (non-basiliximab group). The 1-year patient survival rate was 100% in both groups. The 1-year graft survival rate was 87.5% for the basiliximab group and 75% for the non-basiliximab group (P=0.45). The rates of acute rejection in the basiliximab and non-basiliximab groups were 26% and 43%, respectively (P=0.36). However, in recipients with ≤3 HLA mismatches, the rate of acute rejection was zero in the basiliximab group, and 40% in the non-basiliximab group (P=0.04). The beneficial effect occurred despite the fact that tacrolimus was maintained at below the target levels. There were no adverse events directly attributable to the administration of basiliximab. There were no cases of opportunistic infections or post-transplant lymphoproliferative disease. In summary, addition of basiliximab to tacrolimus and prednisone significantly decreased the rate of acute rejection in well-matched patients. Moreover, this effect was manifest at lower, and therefore less toxic, tacrolimus levels. Received: 19 December 2000 / Revised: 23 April 2001 / Accepted: 24 April 2001     

Propiverine versus tolterodine: efficacy and tolerability in patients with overactive bladder

OBJECTIVES: Propiverine and tolterodine were compared with respect to efficacy, tolerability and impact on the quality of life in the treatment of patients with idiopathic detrusor overactivity. METHODS: In a randomised, double-blind, multicentre clinical trial, patients with idiopathic detrusor overactivity were treated with 15 mg propiverine twice daily or 2mg tolterodine twice daily over a period of 28 days. The maximum cystometric capacity was determined at baseline and after 4 weeks of therapy. The difference of both values was used as the primary endpoint. Secondary endpoints were voided volume per micturition, evaluation of efficacy (by the investigator), tolerability, post void residual urine, and quality of life. RESULTS: The mean maximum cystometric capacity increased significantly (p < 0.01) in both groups. The volume at first urge and the frequency/volume chart parameters also showed relevant improvements during treatment. 42/100 patients in the propiverine group and 43/102 in the tolterodine group experienced adverse events. The most common adverse event, dry mouth, occurred in 20 patients in the propiverine group and in 19 patients in the tolterodine group. The scores for the quality of life improved comparably in both groups. CONCLUSION: The study demonstrates comparable efficacy, tolerability, and improvement in the quality of life of 15 mg propiverine twice-daily and 2mg tolterodine twice-daily in the treatment of the symptoms of idiopathic detrusor overactivity.     

Treatment of overactive bladder: long-term tolerability and efficacy of tolterodine

Previously available antimuscarinic therapies for overactive bladder are poorly tolerated due to a high incidence of adverse events, notably dry mouth. Tolterodine is a bladder-selective, antimuscarinic agent for the treatment of frequency, urgency, and urge incontinence that characterize overactive bladder. In a 9-month open-label study, the safety, tolerability, and clinical efficacy of tolterodine 2 mg twice daily was evaluated in 854 patients with overactive bladder symptoms who had completed one of four 12 week randomized, controlled trials of tolterodine. Safety and tolerability were assessed in terms of adverse events and clinical/laboratory variables. Efficacy was assessed using micturition diaries and patient perception of their bladder condition. In all, 70% of patients remained on treatment for 9 months. Dry mouth was the most frequently reported adverse event, occurring in 28% of patients (intensity: 19% mild, 7% moderate, 2% severe). A total of 9% of patients withdrew due to adverse events. Dosage reduction occurred in 13% of patients. Significant improvements (P < 0.0001) in micturitions per 24 h (−22%), urge incontinence episodes per 24 h (−76%) and volume voided per micturition (+22%) were observed after 9 months of treatment, with 65% of patients reporting an improvement in perception of their bladder problems. The incidence of adverse events and improvements in micturition diary variables during open-label treatment were comparable with those observed during a 12 week randomized treatment. It was concluded that tolterodine is well tolerated and maintains its clinical efficacy during 9 months of treatment. The high proportion of patients remaining on treatment indicates that tolterodine is an effective long-term treatment for overactive bladder.     

Basiliximab in lung transplantation: preliminary experience

BACKGROUND: Basiliximab is a chimeric anti-interleukin-2 monoclonal antibody that has shown safety and efficacy in the prophylaxis of acute organ rejection in renal, liver, heart, and kidney-pancreas transplantation (Tx). The aim of this study was to present our initial experience with the use of Basiliximab in lung Tx. METHODS: Basiliximab (2 doses of 20 mg on day 0 and day 4) was administered to 16 patients treated with cyclosporine, azathioprine, and steroids between September 13, 2001 and August 26, 2003, including 12 men and 4 women patients with a mean age of 56.5 years (range, 19-69). The indication for use in transplantations were: reduced renal function (n = 14), post-Tx acute renal failure (n = 1) and steroid-resistant acute rejection (n = 1). Eight double-lung and eight single-lung Tx were performed for emphysema (n = 6), idiopathic pulmonary fibrosis (n = 7), silicosis (n = 2), and cystic fibrosis retransplantation (n = 1). RESULTS: The incidence of acute rejection was 16.6% (2 patients). Infections included cytomegalovirus (CMV) 33.3% (n = 4), bacterial 16.6% (n = 2), and fungal 8.3% (n = 1). Two patients died in the postoperative period and another at 3 months. There was no reaction to the medicine, and no malignancies or Bronchiolitis Obliterans Syndrome (BOS) during a follow-up period of more than 1 year in 10 patients. CONCLUSION: Basiliximab appeared to reduce the incidence of acute organ rejection and showed a good safety profile in terms of infections and adverse events.     

Safety, tolerability and efficacy of acipimox in type II hyperlipidaemia

Twenty-one patients with type II hyperlipidaemia were treated with the nicotinic acid analogue, acipimox (Olbetam; Farmitalia), for 6 months. Total cholesterol decreased by 10% and the high-density lipoprotein: low-density lipoprotein cholesterol ratio increased by 13%. Triglycerides were unaltered. Two patients stopped the drug after developing gastro-intestinal side-effects. Acipimox therapy warrants ongoing use and further investigation.     

An evaluation of the efficacy and tolerability of oral tramadol hydrochloride tablets for the treatment of postsurgical pain in children

In this double-blinded, randomized, multicenter study, we examined analgesic efficacy and tolerability of tramadol in postoperative pediatric patients. Eighty-one postsurgical ASA physical status I and II patients ages 7-16 yr received oral tramadol (approximately 1 or 2 mg/kg) for postoperative analgesia when they were ready to transition from morphine patient-controlled analgesia to oral analgesics. Rescue analgesia consisted of morphine patient-controlled analgesia or an oral equivalent dose of oxycodone. Patients rated their pain just before the administration of tramadol and at regular intervals for 8 h afterwards using the Wong-Baker Faces Pain Rating Scale. The 2-mg/kg group required approximately half as much rescue analgesia as the 1-mg/kg group (P = 0.006). Parents rated the larger dose more favorably. Adverse events were generally mild to moderate in severity (vomiting [10%], nausea [9%], pruritus [7%], rash [4%]) and similar between the two treatment groups. There were no significant changes in hemodynamic variables, respiratory rate, or SpO(2) percentages between the two treatment groups or in all patients compared with pretreatment values. IMPLICATIONS: Oral tramadol 1-2 mg/kg is well tolerated and effective in postoperative children ready to transition from morphine patient-controlled analgesia. The group receiving 2 mg/kg required less rescue analgesic compared with those receiving 1 mg/kg.     

Achalasia in children and adults

Achalasia or primary megaloureter is a relatively rare disorder characterized by a functional obstruction of the distal ureter. The etiology and pathophysiology are presently obscure, and the diagnosis is established on clinical, radiographic, and surgical findings. Review of 22 cases in children and adults demonstrated a high incidence of associated congenital anomalies. Many of these patients had symptoms of infection or hematuria during infancy or early childhood. In adults the disease often is stabilized and can be treated without surgery. In childhood, operative intervention by excision of the anomalous segment and reimplantation of the ureter into the bladder with an antireflux procedure is the treatment of choice.     

Induction With Basiliximab in Renal Transplantation

Introduction

The use of monoclonal antibodies in renal transplantation for induction therapy has been associated with a marked reduction in acute rejection rates with an impact on graft and patient survivals.

Objective

We sought to evaluate the efficacy of renal transplant induction protocols using Basiliximab based on the rates of acute rejection episodes (ARE) and delayed graft function (DGF) of infectious complications in the first 6 months posttransplant, as well as patient and graft survivals.

Methods

We retrospectively evaluated all renal transplants performed between 2000 and 2008 that were primary grafts from cadaveric heart-beating donors, into recipients with a panel reactive antibody titer <5% and who were treated with an immunosuppression scheme based on cyclosporine, mycophenolate mofetil/mycophenolic acid plus corticosteroids, with (group 1) or without basiliximab (group 2).

Results

We enrolled 52 recipients in group 1 (induction with basiliximab) and 189 in group 2 (without basiliximab). The baseline characteristics were similar among the groups, except for time on dialysis which was longer in group 1 and the number of HLA matches, which was lower in group 1. The ARE rate was lower among group 1 (7.8% vs 27.8%; P = .001); rates of DGF and infectious complications were similar. There was no significant difference in graft and patient survivals.

Conclusion

In this study, induction with basiliximab was associated with a reduced rate rate of ARE, despite a lower number of HLA matches and a longer previous time on dialysis. The use of this induction modality was not associated with a greater rate of infectious complications.     

Splenic embolization in children: long-term efficacy

Eighteen partial splenic embolization procedures (PSEs) were performed in 17 children for hypersplenism (13) and/or esophageal variceal hemorrhage (12). The underlying disease was biliary atresia (BA) in nine children, portal vein thrombosis (PVT) in four, and biliary cirrhosis (BC) in four. From 20% to 90% of the spleen was embolized. Immediate morbidity was high, albeit minor, and the initial hospitalization was protracted for an average of 16 days. The children were followed from 4 to 81 months (average, 34.2). Four patients with BA patients subsequently had liver transplantation at an average of 20 months after PSE. In ten of 13 patients with hypersplenism, hematologic indexes returned to and remained normal throughout follow-up. The three exceptional patients (who had only 20%, 60% and 60% splenic embolization) developed recurrent mild hypersplenism, one of whom was reembolized and is free from hypersplenism 22 months later. Variceal hemorrhage was ameliorated in all 12 patients (average, 2.4 episodes of hemorrhage per year before PSE, 0.5 per year afterwards). Overwhelming postsplenectomy sepsis did not occur in an aggregate follow-up of 48.5 years. PSE is a legitimate treatment alternative for hypersplenism and for esophageal varices in children.