Formation and reversibility of S-linked conjugates of N-(1-methyl-3,3-diphenylpropyl)isocyanate, an in vivo metabolite of N-(1-methyl-3,3-diphenylpropyl)formamaide, in rats

The metabolic disposition of N-(1-methyl-3,3-diphenylpropyl) formamide was studied in rats. The water-soluble metabolites, N-acetyl-S-[N-(1-methyl-3,3-diphenylpropylcarbamoyl)]cysteine and S-[N-(1-methyl-3,3-diphenylpropylcarbamoyl)]glutathione, were identified in urine and bile, respectively, of rats doses with the secondary formamide. The structures of these metabolites were confirmed by comparison with synthetic standards and by using liquid chromatography mass spectrometry and fast atom bombardment mass spectrometry. Synthetic standards of these metabolites were obtained by reacting the N-(1-methyl-3,3-diphenylpropyl)isocyanate with glutathione or N-acetylcysteine in methanolic solutions. The isocyanate was obtained in high yield by reacting 1-methyl-3,3-diphenylpropylamine with trichloromethyl chloroformate. The S-linked conjugates released the isocyanate in mild alkali, but were stable under acidic conditions. The released isocyanate was characterized by comparison with the synthetic standard using GC/MS and HPLC. A mechanism is proposed for the base-catalyzed elimination of the isocyanate from the thiol conjugates.     

Acute Renal Allograft Rejection Following Pegylated IFN-α Treatment for Chronic HCV in a Repeat Allograft Recipient on Hemodialysis: A Case Report

Interferon alpha (IFN-alpha) can be effective therapy for patients with chronic kidney disease who have chronic hepatitis C (HCV). However, acute allograft rejection has been reported in association with IFN-alpha following kidney transplantation, and therefore IFN therapy is recommended prior to, rather than after, kidney transplantation whenever feasible. The special case of repeat allograft recipients who contract HCV after the first transplantation presents special difficulties. This report features the case of a repeat allograft recipient who presented with neutropenic fevers after 5 months of pegylated IFN-alpha therapy, initiated 6 months following the functional loss of his third graft and the reinitiation of hemodialysis (HD). Physical exam, radiographic and laboratory findings led to allograft nephrectomy. The pathologic findings supported a diagnosis of acute-on-chronic rejection. This represents a rare case of IFN-alpha induced rejection following allograft failure and return to HD in a repeat allograft recipient. It also calls attention to the need for a high index of suspicion for the development of allograft rejection, which may require allograft nephrectomy even after allograft 'failure'.     

Self-evaluation and its relationship to clinical evaluation

An exploratory study was undertaken in a three-year nursing diploma program to determine instructor and student perceptions of self-evaluation (SE) and its relationship to clinical evaluation. A cross-section of instructors (n = 9) participated in three rounds of a Delphi survey. From this validated data base a questionnaire was developed and distributed to a stratified sample of 145 students. Combined results were then analyzed and compared. Results indicated that both students and instructors perceive self-evaluation more positively than negatively and they see the main purpose as providing direction for learning. Contrary to the literature and perceptions of surveyed instructors, students did not perceive self-evaluation as a factor in promotion of professional growth. Although students value a participatory role in clinical evaluation, the process of self-evaluation generates anxiety and underrating of performance. The authors conclude that self-evaluation is a developmental skill requiring guidelines and practice, and offer recommendations for its use.     

Comparison of three oral sip-feed supplements in patients with cancer

This study set out to compare the long-term palatability of three oral sip-feed supplements. Sixty patients with various malignancies were randomized to receive one of three products—Build-Up, Fortimel and Fortisip. Participants were encouraged to take as much of the supplements each day for as long as they could manage. At the initial tasting, palatability and acceptability of the products was recorded and this was repeated throughout the trial period. Patients' reasons for discontinuing the trial were noted.
Build-Up was found to be the best-tolerated product of the three. It was taken for a significantly longer time than either Fortimel or Fortisip. There was an indication that Build-Up was more acceptable at the initial tasting than Fortisip but not Fortimel. A smaller proportion of patients stopped taking Build-Up due to flavour-related reasons compared to Fortisip but there was no significant difference between Build-Up and Fortimel. In all, 54% of the patients discontinued the trial for flavour-related reasons. Thirty-five per cent found that the sip-feeds they had been allotted unpalatable at the initial tasting, while 19% stopped the trial due to 'flavour fatigue'. Only 10% of the sample continued taking their allotted product for 90 days or more.