Efficacy and safety of enalapril versus extended-release nifedipine for the treatment of mild-to-moderate essential hypertension: a multicenter 22-week study. Multicenter Cooperative Study Group

The antihypertensive effects and tolerability of single daily doses of enalapril and extended-release nifedipine (nifedipine-ER) were compared in an open-label, randomized, parallel-group, 22-week treatment study involving 230 men and women (mean age, 55 years). Following a 3-week washout period, mean +/- SD blood pressure levels were 153 +/- 17/99 +/- 4 mmHg in the enalapril group (n = 117) and 157 +/- 17/100 +/- 5 mmHg in the nifedipine-ER group (n = 113). Beginning at 5 mg once daily for enalapril and 30 mg once daily for nifedipine-ER, the dosage was titrated every 4 weeks for 16 weeks, up to a maximum of 40 mg for enalapril and 120 mg for nifedipine-ER. The treatment goal (satisfactory response) was to lower trough sitting diastolic blood pressure to < 90 mmHg or by at least 10 mmHg to a level of < 100 mmHg. At a mean daily dose of 16 mg of enalapril and 57 mg of nifedipine-ER, more than three quarters of each treatment group achieved a satisfactory response. The mean reductions in trough sitting blood pressure levels at the end of 22 weeks of treatment were 15/11 mmHg for enalapril and 21/13 mmHg for nifedipine-ER. The difference between treatments was significant only for the change in systolic blood pressure (P < 0.05). However, enalapril was better tolerated than nifedipine-ER. The numbers of patients with adverse experiences and withdrawals from the study because of an adverse experience were significantly lower for enalapril than for nifedipine-ER (P < 0.05). The incidence of abnormal laboratory findings was small and considered of no clinical importance in either group. These data suggest that enalapril and nifedipine-ER had approximately equal efficacy as once-daily antihypertensive treatments, but enalapril was better tolerated.     

Barnidipine, a novel calcium antagonist for once-daily treatment of hypertension: a multicenter, double-blind, placebo-controlled, dose-ranging study. Dutch Barnidipine Multicenter Study Group

The antihypertensive effects and tolerance of once-daily barnidipine, a novel dihydropyridine calcium antagonist, were evaluated. A total of 190 patients with a sitting diastolic blood pressure (DBP) of 95-114 mmHg were investigated in this multicenter, double-blind, placebo-controlled, dose-ranging study. After a 4-week single-blind placebo run-in period, patients were randomized to placebo or barnidipine (10 mg, 20 mg, or 30 mg modified release capsules) once daily for 6 weeks. Nonresponders (sitting DBP > or =90 mmHg and a decrease of < 10 mmHg) were treated for an additional 6 weeks with a dose increase of 10 mg. At each clinic visit, sitting and standing blood pressure and heart rate were measured approximately 24 hours after the last dose of study drug was taken. Compared with placebo, barnidipine lowered blood pressure, with a trend toward a dose-response relationship over the dose range 10-30 mg. A dose increment of 10 mg in nonresponders resulted in additional reductions in blood pressure. At the end of the active treatment period, the responder rates were 41% and 57% for 10 mg and 20 mg barnidipine, respectively. Heart rate in both sitting and standing positions was not affected by barnidipine. Treatment with barnidipine was well tolerated, and the incidence of adverse events was dose related and consistent with vasodilatation. In conclusion, barnidipine (10-30 mg) administered once daily is well tolerated and reduces blood pressure in patients with mild to moderate hypertension.     

Effectiveness and tolerability of slow release lanreotide treatment in active acromegaly: six-month report on an Italian multicenter study. Italian Multicenter Slow Release Lanreotide Study Group

The objective of the study was to determine the tolerability and effectiveness of the slow release (SR) somatostatin analog lanreotide in active acromegaly. Fifty-seven patients, unselected in terms of their previous responsiveness to octreotide therapy, were included in a prospective, open label study carried out at 6 Italian endocrinological centers. The effects of 6 months of SR lanreotide, given at first every 14 days at a dosage of 30 mg, im, were recorded. In some patients (33%), drug dosage was adjusted by increasing the dose (to 60 mg, im) and/or shortening the time interval (every 10 days) of SR lanreotide administration. Fifty patients completed the 6-month period of therapy; 2 subjects dropped out because of adverse events, and 5 dropped out because of ineffectiveness after changes in drug administration. The first SR lanreotide injection produced more than 50% suppression of GH levels from the basal value in 93% of patients. Thirteen days later, baseline GH levels were reduced by over 50% in 25% of patients. Mean GH values were normalized in 85% of patients after 6 months, whereas insulin-like growth factor I (IGF-I) levels were normalized in 38% of patients. No correlation was found between pretreatment GH levels and GH response to SR lanreotide or between changes in GH and IGF-I during therapy. During treatment, there was a significant reduction in the percentage of patients complaining of joint pain, hyperhydrosis, and paresthesias. Changes in soft tissue swelling were documented by significant decreases in finger measurements. Diarrhea and abdominal pain were the most frequent side-effects when therapy was started; these progressively decreased. After the first month of therapy, moderate, mild, and no side-effects were reported by 3%, 40%, and 53% of patients. A nonsignificant increase occurred in asymptomatic gallstones and amylase levels. Minimal changes were noted in carbohydrate tolerance, consisting of a slight increase in glycosylated hemoglobin, a rise in glucose and a decrease in pre- and postprandial insulin levels. No effects on PRL, free cortisol, TSH, or free thyroid hormone levels were noted. No significant change in the percentage of visual field abnormalities was noted. Decreases in pituitary tumor size occurred in 3 of 17 patients reevaluated after 6 months of therapy. The 6-month period of SR lanreotide therapy was compared, on an anamnestic basis, with a 6-month or longer period of sc octreotide therapy (median, 300 micrograms/day) in 34 patients. There were no differences in effectiveness or tolerability between the 2 somatostatin analogs. These data indicate that SR lanreotide at a dose of 30 mg, im, every 14 days is an effective treatment in most unselected acromegalic patients. When administered to a group of poorly responsive patients, an increase in drug dose (60 mg im) and/or a shortening of the drug interval (10 days) seem to improve the GH/IGF-I response. Tolerability to SR lanreotide therapy is high. The use of a new sustained release formulation of somatostatin analog is clearly advantageous in improving patient compliance with medical treatment for acromegaly.     

Results of the multicenter natural interferon-alpha treatment for chronic hepatitis C: correlation between total dose, administration periods and efficacy of therapy. Keio Natural IFN-alpha study group

From January 1993 to December 1995, intraarterial catheter guided urokinase infusion was used as an initial approach in the management of 29 episodes of infrainguinal graft thrombosis (12 venous and 17 prosthetic grafts) in 27 patients. The infusion catheter was embedded inside the occluding clot which was infiltrated by 225.000 U urokinase from distal to proximal. Local low-dose urokinase (1.000 U/kg/hr) was continued for a mean of 39 hours. By this regimen, prompt relief of ischaemia was achieved in 69% (20/29) of cases. Complete recanalization was obtained in 79% of cases. In six cases, the graft remained totally (n = 3) or partially (n = 3) occluded. Two of these patients benefited from secondary surgery, two improved clinically by conservative treatment, and two required amputation. In the 23 successful cases, thrombolysis unmasked an underlying flow-limiting stenosis in 83% (19/23), that was subsequently corrected by percutaneous balloon angioplasty (n = 15), by surgery (n = 3), or by a combination of both (n = 4). One early rethrombosis resulted in an amputation. The immediate limb-salvage rate was 89% (26/29). Surgical intervention was avoided in 17 cases (58%). The main hospital stay was 13 days. The short-term follow-up (mean of 17 months) reveals a high early rethrombosis rate (8/23 or 35%) within one year. Four of these repeated graft failures evolved to amputation. At one year, the overall limb salvage rate dropped to 79%. Thrombolytic management of infrainguinal occluded bypass grafts gives excellent initial technical results (79%), minimizing the need for major surgical revision. It is however characterized by a high procedure-related morbidity (21%). These immediate favourable results are not longstanding. Diffuse graft disease, limited outflow and high recurrence rate of anastomotic stenoses after balloon angioplasty explain poor long-term results after thrombolysis of failed grafts.     

A study of laboratory based faecal occult blood testing in Melbourne, Australia. The Faecal Occult Blood Testing Study Group

The effects of chromium (Cr) supplementation on diet-induced insulin resistance produced by feeding a high-fat, low-Cr diet were studied in rats to ascertain the role of Cr in insulin resistance. Wistar male rats were maintained for 16 weeks after weaning on a basal diet containing 40% lard, 30% sucrose, and 25% casein by weight and adequate vitamins and minerals without added Cr (-Cr). Fasting levels of insulin, glucose, and triglycerides and the responses during an intravenous glucose tolerance test (IVGTT) were compared as indices of insulin resistance and the effectiveness of dietary Cr. IVGTTs and blood sampling for data analyses were performed over a 40-minute period after IV glucose injection (1.25 g/kg body weight) in overnight-fasted animals under pentobarbital anesthesia (40 mg/kg body weight). All animals were normoglycemic (-Cr, 109 +/- 3 mg/dL; +Cr, 119 +/- 5), with fasting insulin levels elevated in the -Cr group (65 +/- 10 microU/mL) versus the +Cr group (31 +/- 4 microU/mL). Increases in plasma triglycerides in the -Cr group were not significant. Following glucose injection, the rate of glucose clearance was lower in the -Cr group (1.74 +/- 0.22 v2.39 +/- 0.11%/min), and 40-minute glucose areas in the -Cr group tended to be higher than in the +Cr group. The insulin response to glucose injection was 20% higher in the -Cr group. Forty-minute plasma triglyceride areas were lower in +Cr rats (875 +/- 62 v 1,143 +/- 97 mg/dL.min in -Cr rats). These data demonstrate that the insulin resistance induced by feeding a high-fat, nutrient-stressed diet is improved by Cr.     

Long-term effects of finasteride in patients with benign prostatic hyperplasia: a double-blind, placebo-controlled, multicenter study. PROWESS Study Group

OBJECTIVES: To compare the long-term effects of finasteride (5 mg/day) and placebo in patients with moderate symptoms of benign prostatic hyperplasia (BPH). METHODS: Patients aged 50 to 75 years, with at least two urinary symptoms indicating moderate BPH, and an enlarged prostate, were followed in a 2-year double-blind, randomized, placebo-controlled multicenter study. The effects of finasteride versus placebo were assessed by total symptom score (modified Boyarsky), obstructive symptom score, maximal urinary flow rate, prostate volume, and urologic end points (acute urinary retention, BPH-related surgical intervention). RESULTS: Of the 3270 men enrolled, 3168 contributed data to the safety analysis, and 2902 to the efficacy evaluation. Significantly greater improvement with finasteride compared to placebo was observed at 12 and 24 months for total symptom score (mean -2.9 versus -1.9 at 12 months, P < or =0.001; -3.2 versus -1.5 at 24 months, P < or =0.001), obstructive symptom score (mean -1.9 versus -1.3 at 12 months, P < or =0.001; -2.1 versus -1.1 at 24 months, P < or =0.001), maximal urinary flow rate (mean +1.2 versus +0.6 mL/s at 12 months, P = 0.010; +1.5 versus +0.7 mL/s at 24 months, P = 0.002), and prostate volume (mean -14.2 versus +5.4% at 12 months, P < or =0.01; -15.3 versus +8.9% at 24 months, P < or =0.001). Greater improvements in placebo-adjusted total symptom score occurred in men with large prostates than in men with small prostates (mean -2.4 versus -1.1 at 12 months; -3.2 versus -1.3 at 24 months, placebo-adjusted data, P = 0.053). Fifteen of 1450 men (1.0%) in the finasteride group experienced an acute urinary retention event, compared with 37 of 1452 (2.5%) in the placebo group, and the corresponding figures for surgery were 51 of 1450 (3.5%) and 86 of 1452 (5.9%), respectively. The hazard rate for occurrence, computed using the log-rank statistic, decreased by 57% for acute urinary retention and by 40% for surgery accompanied by finasteride therapy compared to placebo. CONCLUSIONS: Finasteride causes long-term symptomatic improvement and reduces the risk of acute urinary retention or surgery. Men with enlarged prostates benefit most from finasteride treatment.     

Evidence-based interventions in school psychology: Conceptual foundations of the Procedural and Coding Manual of Division 16 and the Society for the Study of School Psychology Task Force.

We present the conceptual, philosophical, and methodological basis for the Procedural and Coding Manual for Review of Evidence-Based Interventions (hereafter called the Procedural and Coding Manual), which is available on the World Wide Web (http://www.sp-ebi.org). First, we discuss some key conceptual issues and areas of potential controversy surrounding the content and organization of the Procedural and Coding Manual. Second, we discuss our research framework for coding evidence-based interventions (EBIs), taking into account the dimensional classification approach adopted by the Task Force on Evidence-Based Interventions in School Psychology. We contrast this coding scheme with the approach embraced by the Committee on Science and Practice of the Society of Clinical Psychology, Division 12, American Psychological Association. Third, we present our methodological framework for reviewing EBIs, including quantitative group-based and single-participant designs, qualitative research designs, and theory-guided confirmatory program evaluation models. Finally, we introduce the concept of a coding system to be implemented by practitioners to develop a knowledge base on what works in practice and help bridge the gap between research and practice. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Sulfasalazine in the treatment of juvenile chronic arthritis: a randomized, double-blind, placebo-controlled, multicenter study. Dutch Juvenile Chronic Arthritis Study Group

AIMS: To determine whether left ventricular volumes and ejection fractions calculated from single plane two-dimensional echocardiograms using the algorithm (0.85A2L) correlate with those calculated using the biplane Simpson's method, and whether small changes in volumes and ejection fraction occurring post-infarction could be detected from single-plane as well as from biplane two-dimensional echocardiograms. METHODS AND RESULTS: Serial two-dimensional echocardiograms were obtained in 371 patients from the DEFIANT II trial a mean of 2 days, 1 week and 6 months post-infarction. Single plane volumes from the apical four chamber and apical long axis correlated closely with biplane Simpson's left ventricular volumes. Both single-plane left ventricular volumes significantly over-estimated biplane Simpson's volumes. Biplane Simpson's ejection fractions were consistently slightly under-estimated from the single-plane images. Differences between biplane Simpson's and single-plane volumes increased independently with increasing left ventricular size and distortion. The small changes in left ventricular volumes and ejection fraction over time were as reliably detected from single plane as from biplane images. CONCLUSION: Single-plane left ventricular volumes over-estimate biplane Simpson's volumes and under-estimate ejection fraction, and these discrepancies are amplified in dilated hearts with abnormal shape.     

Oral dolasetron mesylate for prevention of postoperative nausea and vomiting: a multicenter, double-blind, placebo-controlled study. The Oral Dolasetron PONV Prevention Study Group

Parafunctional activities are assumed to play an important role in temporomandibular disorders (TMD), but experimental data in support of this hypothesis are lacking. This study examined the role of parafunctional clenching on various measures of TMD pain. Five subjects participated in daily 17-minute electromyogram biofeedback training sessions structured in three phases. Subjects were instructed to maintain temporalis and masseter muscle activity below 2 microV in the first (decrease) phase of training (10 sessions), above 10 microV in the second (increase) phase (1 to 8 sessions), and below 2 microV in the third (decrease) phase (10 to 15 sessions). Preliminary screening examinations showed that none of the subjects had TMD. Two subjects reported intolerable pain during increase training, and both were diagnosed with a TMD during this phase. No subject was diagnosed with TMD pain during either decrease training phase. The authors conclude that chronic, low-level parafunctional clenching may be a factor in the cause of TMD pain.     

Reduction of adhesions after uterine myomectomy by Seprafilm membrane (HAL-F): a blinded, prospective, randomized, multicenter clinical study. Seprafilm Adhesion Study Group

OBJECTIVE: To assess the safety and efficacy of Seprafilm (HAL-F), Bioresorbable Membrane, (Genzyme Corporation, Cambridge, MA) in reducing the incidence, severity, extent, and area of uterine adhesions after myomectomy. DESIGN: Prospective, randomized, blinded, multicenter study. Adhesion reduction was assessed by an independent, blinded, gynecologic surgeon who reviewed videotapes of each patient's second-look laparoscopy. SETTING: Nineteen institutions across the United States. PATIENT(s): One hundred twenty-seven women undergoing uterine myomectomy with at least one posterior uterine incision > or = 1 cm in length. INTERVENTION(s): Patients were randomized to treatment with Seprafilm or to no treatment at the completion of the myomectomy. MAIN OUTCOME MEASURE(s): The incidence, severity, extent, and area of uterine adhesions at second-look laparoscopy. RESULT(s): The incidence, measured as the mean number of sites adherent to the uterine surface, was significantly less in treated patients (4.98 +/- 0.52 [mean +/- SEM] sites) than in no treatment patients (7.88 +/- 0.48 sites) as were the mean uterine adhesion severity scores (1.94 +/- 0.14 versus 2.43 +/- 0.10; treatment versus no treatment, respectively), mean extent scores (1.23 +/- 0.12 versus 1.68 +/- 0.10), and mean area of adhesions (13.2 +/- 1.67 versus 18.7 +/- 1.66 cm2). No adverse events occurred that were judged to be related to the use of Seprafilm. CONCLUSION(s): In this multicenter study, treatment of patients after myomectomy with Seprafilm significantly reduced the incidence, severity, extent, and area of postoperative uterine adhesions. Additionally, Seprafilm treatment was not associated with an increase in postoperative complications.     

Sensitivity to change of generic quality of life instruments in patients with rheumatoid arthritis: preliminary findings in the generic health OMERACT study. OMERACT/ILAR Task Force on Generic Quality of Life. Life Outcome Measures in Rheumatology. International League of Associations for Rheumatology

In order to investigate intraspecific differences in Loxosceles intermedia spider venom we compared some biological properties of male and female venoms. Females produced higher amounts of venom than males. Furthermore, female venom presented more potent dermonecrotic and complement-dependent activities than male venom. Interestingly, the F35 toxin, a dermonecrotic and complement-dependent haemolytic factor, was also present in greater amounts in female venom, as demonstrated by ELISA. Therefore, the higher production and increased toxicity of venom in female specimens as compared to males may contribute to the variability observed in the severity of envenoming caused by L. intermedia spiders.     

Combined hormono/chemotherapy as primary treatment for metastatic prostate cancer: a randomized, multicenter study of orchiectomy alone versus orchiectomy plus estramustine phosphate. The Dutch Estracyt Study Group

OBJECTIVES: Based on the theory that hormone-resistant cells are present in all metastatic patients, early administration of chemotherapy appears to be logical and its use is supported by experimental studies. Therefore, trials with combined hormonal and cytotoxic treatment as primary therapy should be conducted. In the present trial, the efficacy and tolerance of estramustine phosphate (EMP) as a chemotherapeutic agent in addition to hormonal treatment (orchiectomy) was studied in patients with metastatic and nonmetastatic prostate cancer not previously treated. EMP was chosen because it produces few serious adverse reactions and no cumulative toxicity. METHODS: Four hundred nineteen patients were included in a 1.5-year period starting in January 1989. Patients with locally advanced prostate cancer or with bone metastases were randomized to orchiectomy (O) or orchiectomy followed by EMP (O + E), given until progression. RESULTS: Analysis of the total group showed no significant difference in time to progression between the treatment groups. Because the course of the disease is different in patients with either T4 tumor only or with lymph node metastases only (M0) as compared with patients with bone metastases (M1) and because the number of progressions in the M0 patients was low, corresponding analyses were performed for these subgroups as well. In the M1 patients, there was a tendency for a longer time to progression in the O + E group than in the O group, but there was no indication of a difference between the groups with regard to survival. In the M0 patients, there was no indication of any difference in results between the treatments. Multivariate analysis of prognostic factors showed pain, alkaline phosphatase, metastasis status, and tumor stage to be significant factors. There was a relation between age and drug treatment in that a significant beneficial effect of EMP in terms of prolonged progression-free interval as well as survival was evident in younger patients (aged less than 73 years) with metastatic disease. Tumor stage was also of importance for the drug effect; T0 to T3 patients who received EMP survived longer than those who were treated with orchiectomy only. The most common adverse reaction was nausea in the O + E group, which led to discontinuation of the drug in 7 patients. Cardiovascular problems are not uncommon in this age group, and there was a higher incidence of cardiovascular events, predominantly cardiac failure, in the O + E group, leading to treatment interruption in 16 patients. CONCLUSIONS: Our results indicate that future studies of hormono/chemotherapy should focus on younger patients with bone metastases.     

Evaluation of efficacy of traditional Chinese medicines in the treatment of childhood bronchial asthma: clinical trial, immunological tests and animal study. Taiwan Asthma Study Group

Traditional Chinese medicines (TCM) have been used to treat bronchial asthma for several centuries and a certain degree of clinical benefit has been observed; however, scientific substantiation is lacking. A multicenter, double-blind and placebo-controlled study was therefore conducted to evaluate the clinical efficacy in terms of symptom score, medication score, morning and evening PEFRs, and changes of immunoregulatory function, such as distribution of lymphocyte subsets and in vivo and in vitro production of lymphokines (IFN-gamma and IL-4) and inflammatory mediators (histamine, PGE2 and LTC4). Furthermore, the protective effect of TCM on the late asthmatic reaction (LAR) was evaluated by using asthmatic guinea pigs. Three hundred and three asthmatic children were classified by Chinese doctors, according to a standardized questionnaire designed on the basis of basic logic of Chinese medicine, into three groups of specific constitution (group A, B and C). Group A consisted of 32 herb A-treated patients and 34 placebo-treated; group B, 74 herb B-treated and 64 placebo-treated; and group C, 55 herb C-treated and 44 placebo-treated. The study period was six months. The results were: 1) Both treatment group and placebo group showed an improvement in all clinical parameters, thus demonstrating a placebo effect. However, the improvement was usually greater in the former than the latter, although only the difference in PEFR was significant; 2) Herb A could increase total T cell and decrease B cell; 3) Herb A and B enhanced production of PGE2 but not LTC4, IFN-gamma and IL-4; 4) There was a general tendency for in vivo and in vitro production of histamine to decrease at the end of study in both treatment group and placebo group; however, the decrease was significantly greater in the former than the latter; 5) In asthmatic guinea pigs, 10-day's pretreatment with Chinese herbs could reverse the decrease of sGaw, suppress eosinophilia in bronchoalveolar lavage fluid (BALF), prevent the eosinophil infiltration of airways, increase PGE2 production and decrease LTC4 production in serum and BALF. Thus, traditional Chinese medicines did show a certain degree of clinical efficacy. The decreased production of histamine and LTC4, increased production of PGE2 that were found in both asthmatic children and asthmatic guinea pigs, and prevention of occurrence of LAR by suppressing eosinophil infiltration of airways and preserving airway conductance that were observed in asthmatic guinea pigs after allergen challenge might be used to account partly for the effectiveness.     

CAMPATH-1H monoclonal antibody in therapy for previously treated low-grade non-Hodgkin's lymphomas: a phase II multicenter study. European Study Group of CAMPATH-1H Treatment in Low-Grade Non-Hodgkin's Lymphoma

PURPOSE: CAMPATH-1H is a human immunoglobulin G1 (IgG1) anti-CD52 monoclonal antibody (MAb) that binds to nearly all B-cell and T-cell lymphomas. We report here the results of a multicenter phase II trial of CAMPATH-1H in patients with advanced, low-grade non-Hodgkin's lymphoma (NHL) who were previously treated with chemotherapy. PATIENTS AND METHODS: Fifty patients who had relapsed (n=25) after or were resistant (n = 25) to chemotherapy were treated with CAMPATH-1H 30 mg administered as a 2-hour intravenous (i.v.) infusion three times weekly for a maximum period of 12 weeks. RESULTS: Six patients (14%) with B-cell lymphomas achieved a partial remission (PR). Patients with mycosis fungoides appeared to respond more frequently (50%; four of eight patients, which included two complete remissions [CRs]). Lymphoma cells were rapidly eliminated from blood in 16 of 17 patients (94%). CR in the bone marrow was obtained in 32% of the patients. Lymphoma skin lesions disappeared completely in four of 10 patients and partial regression was obtained in three patients. Lymphadenopathy and splenomegaly were normalized in only 5% and 15% of patients, respectively. Lymphopenia (< 0.5 x 10(9)/L) occurred in all patients. World Health Organization (WHO) grade IV neutropenia occurred in 14 patients (28%). Opportunistic infections were diagnosed in seven patients and nine patients had bacterial septicemia. Death related to infectious complications occurred in three patients. CONCLUSION: CAMPATH-1H had a significant but limited activity in patients with advanced, heavily pretreated NHL. The most pronounced effects were noted in the blood and bone marrow and in patients with mycosis fungoides. The risk for serious infectious complications needs to be considered for severely ill patients who are evaluated for CAMPATH-1H treatment.     

Risk factors for delayed graft function in cadaveric kidney transplantation: a prospective study of renal function and graft survival after preservation with University of Wisconsin solution in multi-organ donors. European Multicenter Study Group

BACKGROUND: Delayed graft function (DGF) remains an important complication in renal transplantation. In this multicenter study, we investigated the influence of donor and recipient factors on the occurrence of DGF and DGF's effect on long-term graft survival. METHODS: A total of 547 transplanted kidney allografts, retrieved from multi-organ donors, were analyzed, and results were compared with literature on kidney-only donors. RESULTS: Median follow-up of patients without graft failure was 3.4 years. Twenty-four percent of the recipients developed DGF. In univariate analysis, the following factors significantly increased the incidence of DGF: (a) among the donor factors, mean creatinine level >120 micromol/L and prolonged cold ischemia time (CIT); and (b) among the recipient factors, previous transplant(s), no intraoperative use of mannitol, poor quality of reperfusion, absence of intraoperative diuresis, and pretransplant anuria or oliguria. After stepwise logistic regression, donor age, CIT, recipient's number of previous transplants, and intraoperative diuresis proved to be of independent prognostic value for the occurrence of DGF. Overall graft survival was 91%, 87%, and 72% at 3 months, 1 year, and 4 years after transplantation, respectively. In case of DGF, graft survival was approximately 10% lower when compared with cases with immediate graft function (P<0.001). No difference in incidence of DGF was found between grafts of multi-organ donors and kidney-only donors. CONCLUSIONS: DGF results in an approximately 10% higher rate of graft failure. DGF incidence can be reduced by the administration of mannitol during transplantation, which minimizes CIT and optimizes donor management. Grafts from multi-organ donors and kidney-only donors appear to be of equal quality.     

The STOP-NIDDM Trial: an international study on the efficacy of an alpha-glucosidase inhibitor to prevent type 2 diabetes in a population with impaired glucose tolerance: rationale, design, and preliminary screening data. Study to Prevent Non-Insulin-Dependent Diabetes Mellitus

OBJECTIVE: To describe the rationale and design, and to discuss the preliminary screening data, of the Study to Prevent NIDDM (STOP-NIDDM Trial), an international study on the efficacy of the alpha-glucosidase inhibitor acarbose in preventing or delaying the development of type 2 diabetes in a population with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: A total of 1,418 subjects diagnosed with IGT according to the World Health Organization's criteria and having a fasting plasma glucose concentration > or =5.6 mmol/L were randomized in a double-blind fashion to receive either acarbose (100 mg t.i.d.) or placebo for a predictive median follow-up period of 3.9 years. The primary outcome is the development of type 2 diabetes diagnosed using a 75-g oral glucose tolerance test according to the new criteria. The secondary outcomes are changes in blood pressure, lipid profile, insulin sensitivity, cardiovascular events, and morphometric profile. RESULTS: Screening was performed in a high-risk population. As of 1 March 1997, 4,424 subjects had been screened, and data were available for 3,919 (88.5%) subjects. Of these subjects, 1,200 (30.6%) had glucose intolerance. Of the subjects with glucose intolerance, 521 (13.3%) had previously undetected type 2 diabetes, and 679 (17.3%) had IGT. Of the IGT population, 412 (60.7%) subjects were eligible for the study This population had the following characteristics: the mean age was 54.8 years, 52% of the subjects were female, 53% had more than one risk factor for type 2 diabetes, >90% had a family history of diabetes, 78.2% had a BMI > or =27 kg/m2, 47.5% had high blood pressure, 51.2% had dyslipidemia, and 22.8% of the women had a history of gestational diabetes. CONCLUSIONS: Screening of a high-risk population yields one eligible subject per every 10 volunteers screened. This study should definitely answer the question of whether acarbose can prevent or delay the progression of IGT to type 2 diabetes mellitus.