Patterns, incidence and predictive factors for pain after interventional radiology

AIM: To evaluate prospectively the pattern, severity and predictive factors of pain after interventional radiological procedures. MATERIALS AND METHODS: All patients undergoing non-arterial radiological interventional procedures were assessed using a visual-analogue scale (VAS) for pain before and at regular intervals for 24 h after their procedure. RESULTS: One hundred and fifty patients (87 men, mean age 62 years, range 18-92 years) were entered into the study. Significant increases in VAS score occurred 8 h after percutaneous biliary procedures (+47.7 mm, SD 14.9 mm; p=0.001), 6 h after central venous access and gastrostomy insertion (+23.7 mm, SD 19.5 mm; p=0.001 and +28.4 mm, SD 9.7 mm; p=0.007, respectively) and 4h after oesophageal stenting (+27.8 mm, SD 20.2 mm, p=0.001). Non-significant increases in VAS pain score were observed after duodenal and colonic stenting (duodenal: +5.13 mm, SD 7.47 mm; p=0.055, colonic: +23.3 mm, SD 13.10 mm, p=0.250) at a mean of 5h (range 4-6h). Patients reported a significant reduction in pain score for nephrostomy insertion (-28.4mm, SD 7.11 mm, p=0.001). Post-procedural analgesia was required in 99 patients (69.2%), 40 (28.0%) requiring opiates. Maximum post-procedural VAS pain score was significantly higher in patients who had no pre-procedural analgesia (p=0.003). CONCLUSION: Post-procedural pain is common and the pattern and severity of pain between procedures is variable. Pain control after interventional procedures is often inadequate, and improvements in pain management are required.     

Waiting time on dialysis as the strongest modifiable risk factor for renal transplant outcomes: a paired donor kidney analysis

BACKGROUND: Waiting time on dialysis has been shown to be associated with worse outcomes after living and cadaveric transplantation. To validate and quantify end-stage renal disease (ESRD) time as an independent risk factor for kidney transplantation, we compared the outcome of paired donor kidneys, destined to patients who had ESRD more than 2 years compared to patients who had ESRD less than 6 months. METHODS: We analyzed data available from the U.S. Renal Data System database between 1988 and 1998 by Kaplan-Meier estimates and Cox proportional hazards models to quantify the effect of ESRD time on paired cadaveric kidneys and on all cadaveric kidneys compared to living-donated kidneys. RESULTS: Five- and 10-year unadjusted graft survival rates were significantly worse in paired kidney recipients who had undergone more than 24 months of dialysis (58% and 29%, respectively) compared to paired kidney recipients who had undergone less than 6 months of dialysis (78% and 63%, respectively; P<0.001 each). Ten-year overall adjusted graft survival for cadaveric transplants was 69% for preemptive transplants versus 39% for transplants after 24 months on dialysis. For living transplants, 10-year overall adjusted graft survival was 75% for preemptive transplants versus 49% for transplants after 24 month on dialysis. CONCLUSIONS: ESRD time is arguably the strongest independent modifiable risk factor for renal transplant outcomes. Part of the advantage of living-donor versus cadaveric-donor transplantation may be explained by waiting time. This effect is dominant enough that a cadaveric renal transplant recipient with an ESRD time less than 6 months has the equivalent graft survival of living donor transplant recipients who wait on dialysis for more than 2 years.     

The effect of renal insufficiency on mycophenolic acid protein binding.

Mycophenolate mofetil (MMF) is commonly used in solid organ transplant recipients. MMF is converted to mycophenolic acid (MPA) upon reaching the systemic circulation. Many acidic drugs have altered protein binding in renal failure, and it is possible that MPA protein binding may be decreased. The authors studied 23 renal transplant recipients: 8 transplant patients (7 kidney, 1 kidney/pancreas) with chronic renal insufficiency (CRI) and 15 renal transplant patients with preserved renal function. Plasma was obtained for kinetic profiles of total MPA, free MPA, and its glucuronide metabolite (MPAG). Plasma was obtained from 10 hemodialysis patients and 8 healthy control volunteers to assess in vitro differences in MPA protein binding. Average free fraction of MPA in patients with chronic renal insufficiency was more than double that of patients with normal renal function (5.8 +/- 2.7 vs. 2.5 +/- 0.4, p < 0.01). Free MPAAUC was almost doubled in the patients with chronic renal insufficiency versus controls (2.04 +/- .08 vs. 1.03 +/- 0.6, p < 0.01). MPA protein binding is decreased, and free MPA concentrations are increased in patients with chronic renal failure.     

The physiological and pathophysiological roles of eosinophils in the gastrointestinal tract

Eosinophils and the gastrointestinal tract interact in an intimate and enigmatic relationship. Under healthy conditions, the presence of eosinophils is limited almost exclusively to the digestive tract mucosa where they exert several effector and immunoregulatory functions. While their precise function in the gastrointestinal tract is not completely understood, it is likely that, together with different T cell subsets, eosinophils are involved in maintaining the immunologic homeostastis across the mucosal barrier under resting conditions. Eosinophils also play a role in several inflammatory conditions, such as intestinal infections, hypersensitivity reactions, primary eosinophilic inflammations and several other chronic intestinal disorders. Depending on the responsible trigger, their effects may be beneficial or detrimental. Here, we discuss the available information regarding the physiological and pathological functions of eosinophils within the gastrointestinal tract.     

Interleukin 12 is associated with reduced relapse without increased incidence of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

Interleukin (IL)-12 has antitumor effects in murine studies. To evaluate this clinically, we investigated whether high levels of circulating IL-12 in patients after allogeneic hematopoietic stem cell transplantation (HSCT) are associated with improved relapse-free survival. We prospectively studied 134 patients undergoing HSCT. Median follow-up was 1158 days (range, 70-1792 days). Plasma IL-12 levels were measured before transplantation and on days 0, +4, +7, and +14 after transplantation. The highest levels were seen on days +4 and +7 and were categorized by a cluster analysis of the logarithmically transformed IL-12 concentrations, which were then correlated with relapse-free survival. Forty-six patients had low levels of IL-12 (median, 2 pg/mL; range, 0-6.5 pg/mL), 49 patients had medium levels (median, 20.5 pg/mL; range, 7-75.5 pg/mL), and 25 patients had high levels (median, 181 pg/mL; range, 84-623 pg/mL). Patients with high IL-12 levels before transplantation had the highest increase after transplantation. With a multivariate Cox model for relapse onset, with the low IL-12 level as the reference, patients in the high-IL-12 group had an adjusted hazard ratio of 0.27 (95% confidence interval, 0.09-0.79), and medium group patients had a hazard ratio of 0.65 (95% confidence interval, 0.31-1.36). The incidences of relapse at 500 days by Kaplan-Meier analysis by IL-12 group were 23.0% (high group), 40.3% (medium group), and 48.8% (low group). There was no association between IL-12 levels and the risk of acute graft-versus-host disease (GVHD; P = .51) or chronic GVHD (P = .28). In conclusion, high IL-12 levels after HSCT are associated with improved relapse-free survival without increasing the risk for GVHD. Patients with high pretransplantation IL-12 levels have an increased likelihood of higher posttransplantation IL-12 levels, possibly because of a host-graft interaction, and this may predispose to better clinical outcomes.     

Excellent outcome of renal transplantation in patients with Fabry's disease

INTRODUCTION: Fabry's disease is an X-linked error of glycosphingolipid metabolism. Clinical manifestations of the disease are secondary to accumulation of glycosphingolipids in various tissues. Renal failure and vascular complications are common. There are conflicting reports regarding the outcomes of patients with Fabry's disease after renal transplantation. METHODS: We reviewed the United States Renal Data System Registry database from 1988 and 1998, and found 93 patients with Fabry's disease who had received a renal transplant. Case-matched patients were identified to serve as controls. RESULTS: Patients with Fabry's disease demonstrated equivalent 5-year patient and graft survival, compared with controls (83% and 75%, respectively, for those with Fabry's disease vs. 82% and 67% for controls). CONCLUSION: Despite their high risk for cardiovascular complications, patients with Fabry's disease have excellent outcomes after renal transplantation.     

Relationship of recipient age and development of chronic allograft failure

BACKGROUND: The elderly are the fastest growing segment of the end stage renal disease (ERSD) population. Older renal transplant recipients experience fewer acute rejection episodes than do younger patients. Despite this, death censored graft survival is no better in these older transplant recipients than in younger recipients. We examined the United States Renal Data System (USRDS) database to determine whether recipient age itself has an independent effect on the development of chronic allograft failure (CAF). METHODS: We analyzed 59,509 patients from the files of the USRDS. To determine whether age was an independent risk factor for CAF, the population was analyzed separately for Caucasians, African-Americans, and other ethnic groups. All renal transplant recipients from 1988 to 1997 were examined. Both univariate and multivariate analysis were performed using chronic allograft failure as the outcome of interest. RESULTS: Actuarial 8-year censored graft survival was significantly decreased in the older age groups 67% for ages 18-49 vs. 61.8% for ages 50-64 vs. 50.7% for ages 65+ (P<0.001). In the multivariate analysis, recipient age was a strong and independent risk factor for the development of chronic allograft failure in Caucasians (RR 1.29 for ages 50-64, RR 1.67 for ages older than 65). These findings were reinforced by an analysis that was restricted to living donor transplants without acute rejection. CONCLUSION: In Caucasians increased recipient age is an independent risk factor for the development of chronic renal allograft failure.     

A 6-month large-scale study into the safety of tamsulosin

AIMS: Tamsulosin is an alpha1-adrenoceptor antagonist for the treatment of symptomatic benign prostatic hyperplasia with a tolerability similar to that of placebo in short-term, placebo-controlled studies with limited patient numbers. The present study was designed to test the safety of tamsulosin treatment in a large cohort of men during a prolonged period of time, particularly with regard to comedications. METHODS: A multicentre, open-label phase IIIb study with 1784 patients receiving 0.4 mg o.d. tamsulosin for 6 months was performed according to good clinical practice guidelines. The analysis was performed on an intention-to-treat basis and powered to detect adverse events (AE) occurring in 0.15% of patients with 95% confidence. RESULTS: During a total drug exposure time of 811 patient years, 386 AE were recorded in 253 patients (14.2%; 95% confidence intervals [CI] 12.0-15.2%). Twenty-nine patients suffered 44 serious AE including five fatal events (CI 0.12-0.73%) due to myocardial infarction (n = 3) and to pneumonia and a car accident (one each), but all deaths were judged to be unlikely to be related to study medication. The frequency of AE in patients without any comedication (n = 1095) was 13.0% (CI 11.3-14.9%). In a logistic regression analysis beta-adrenoceptor blockers, converting enzyme inhibitors, antidiabetics and diuretics did not significantly affect the odds ratio for having AE. However, concomitant alpha-adrenoceptor antagonists (a protocol violation) and treatment with verapamil (which also has alpha-adrenoceptor antagonist activity) significantly enhanced the odds ratio for having AE to 3.87 (CI 1.52-9.85) and 3.17 (CI 1.52-6.58), respectively. Minor increases in the odds ratio, which did not reach statistical significance, were also observed for Ca2+ antagonists other than verapamil and for nitrates. CONCLUSIONS: We conclude that tamsulosin has a good safety profile relative to AE rates in the placebo arms of previous studies on tamsulosin even in the presence of most potentially complicating comedications. No major unexpected severe AE were recorded during our 6 months study.