Mycophenolic acid concentrations in long-term heart transplant patients: relationship with calcineurin antagonists and acute rejection

BACKGROUND: When used in conjunction with steroids and cyclosporin, mycophenolate mofetil (MMF) has been shown to significantly reduce mortality and incidence of rejection in the first year after heart transplantation. It also appears that in this early post-transplantation period, the monitoring of immunosuppressive therapies may be warranted. The current study was undertaken to determine if such monitoring is still useful more than 1 yr after heart transplantation. METHODS: Twenty-six patients who had survived the first year after orthotopic heart transplantation and had been on MMF therapy for more than 3 months were prospectively followed. At the time of their routine endomyocardial biopsy blood samples were taken to monitor immunosuppressive therapy. Most patients had two samples taken, on average 109 d apart. RESULTS: There were 22 episodes of asymptomatic rejection documented on a total of 48 biopsies. Of these, only two were of ISHLT (International Society for Heart and Lung Transplantation) grade 3A the remainder being of ISHLT grades 1 or 2. There was no relation between immunosuppressive regimen (tacrolimus and MMF or cyclosporin and MMF) and rejection. There was no relation between monitored immunosuppressive levels and rejection. Patients with the combination of MMF and tacrolimus had significantly higher plasma mycophenolic acid levels despite significantly lower daily MMF dose. CONCLUSION: There does not appear to be a benefit in continued monitoring of plasma mycophenolic acid levels beyond the first year of heart transplantation. There were significant differences in plasma mycophenolic acid levels depending on the type of calcineurin inhibitor concomitantly used.     

Evaluation of intermittent pneumatic compression systems

The operational characteristics of eight intermittent pneumatic compression systems were evaluated. Considerable differences between the pressure/time curves were found when different pumps were compared. The pressure attained in the garments varied from 6 to 124 mmHg and the rate of inflation from less than 1 to 9 mmHg per second.     

The clinicopathological features, treatment and survival of gastric adenocarcinoma in Omani Arab patients

Background: Gastric carcinoma (GC) is the second most frequent cancer worldwide and the most common cancer in the Sultanate of Oman. The surgical and medical management of GC varies worldwide, and variable ethnic differences in clinicopathological features and survival have been observed. The aim of this work was to study clinicopathological features, management and survival trends of GC in Oman and to assess the impact of aggressive management trends on survival. Methods: A retrospective study of gastric adenocarcinoma cases, treated at three main hospitals in Oman over a 12‐year period, was undertaken. The study was divided into period I (1993–1998) and period II (1999–2004), based on the evolution of cancer services. Results: A population of 339 patients was included in the study (M : F ratio 1.9 : 1). GC was mainly a disease of elderly males with mean ages of 60.3 and 59.3 years for periods I and II, respectively. The most prevalent types of GC observed during periods I and II were distal (60.7% vs. 57.7%), ulcerating (64.3% vs. 63.7%) and intestinal (80.9% vs. 78.4%), with no significant differences between them. The main histopathology was adenocarcinoma with an increase in the signet cell variant (4% to 12.1%, P, 0.03) during period II. Advanced stages III and IV constituted 71.1% and 76.5% of all patients in periods I and II, respectively (P, 0.9). More D2 lymph node dissections and increased use of adjuvant chemo‐radiotherapy and palliative chemotherapy were noted during period II. Median survival time for the entire cohort was 12.3 months (95% CI 9.7–14.4) with a 5‐year overall survival rate of 16.5%. The 5‐year overall survival for periods I and II was 14% and 19% (P, 0.27), respectively. Conclusion: GC in Oman is seen predominantly in elderly males who display predominately distal, ulcerative lesions with an intestinal‐type histology. GC continues to present in advanced stages, with poor prognosis. This fact underscores the need for early diagnosis to achieve a better outcome. There is a need to employ early detection policies of gastric cancer in developing countires as aggressive treatment does not alter the outcome of advanced presentaion.     

Preparation for regional anaesthesia induces changes in thrombelastography

The effects of crystalloid and colloid infusions on coagulation measured by thrombelastography (TEG) present a confused picture. The influence of environmental factors may explain the disparity between previous studies. We studied two groups of 20 women presenting at term for elective Caesarean section. In the first group, TEG analysis was performed before and after infusion of Gelofusine 500 ml over 15 min. The second group was treated in the same way except that subjects did not receive fluid. We found significant changes in r and k values in both groups, suggesting enhanced coagulation. As hypercoagulable changes were also seen in the group that did not receive fluid preload, the hypothesis that moderate haemodilution causes hypercoagulability must be questioned. The influence of environmental factors can explain differences reported between in vivo and in vitro studies.      

Structure-activity studies of novobiocin analogs as modulators of the cytotoxicity of etoposide (VP-16)

We have previously reported that the antibiotic novobiocin enhanced the toxicity of the anticancer agent etoposide (VP-16) to several drug-sensitive and -resistant tumor cell lines. The increase in VP-16 cytotoxicity produced by novobiocin was not due to the combined effects of these agents on topoisomerase II, but to inhibition by novobiocin of VP-16 efflux, which in turn led to increased accumulation of VP-16 and increased formation of potentially lethal VP-16-stabilized topoisomerase II-DNA covalent complexes. We have now identified novobiocin analogs that are essentially equivalent to novobiocin as inhibitors of the activity of topoisomerase II, but that are more potent than novobiocin (a) as modulators of the cytotoxicity of VP-16 to WEHI-3B leukemia and A549 lung carcinoma cells and (b) in increasing VP-16 accumulation in these cell lines. Thus, removal of the sugar moiety of novobiocin to form novobiocic acid enhanced the potency of the antibiotic as a modulator of VP-16, whereas the substituted coumarin ring alone (U-7587) was devoid of VP-16 modulatory activity. Modifications of the side chain of novobiocin significantly influenced modulatory activity, with cyclonovobiocic acid, which was formed from novobiocic acid by acid-catalyzed cycloaddition, being the most active in enhancing the cytotoxicity of VP-16. The increased potency of novobiocic acid and cyclonovobiocic acid as modulators of VP-16 activity was achieved with no change from novobiocin in the capacity of these analogs to inhibit the catalytic activity of mammalian topoisomerase II, indicating a change in the specificity of these analogs.