A randomised controlled study comparing conventional and magnetic guidewires in a two-dimensional branching tortuous phantom simulating angulated coronary vessels.

OBJECTIVES: To directly compare the magnetic navigation system (MNS) guidewires with conventional guidewires in branching tortuous phantoms with operators of varying MNS and percutaneous coronary intervention experience. BACKGROUND: Vessel tortuosity, angulation, and side branches remain limiting factors in coronary interventions. The MNS addresses these limitations by precisely directing the tip of a magnetised guidewire in vivo aided by two permanent adjustable external magnets. METHODS: Crossing and fluoroscopy times of six operators were evaluated in five tortuous Perspex(R) phantom vessels in three consecutive attempts. Standard guidewire (SG) usage was unrestricted. Two 2nd generation magnetic guidewires (MG) were used. Failure was noted if the cross was unsuccessful within 5 min. RESULTS: The magnetic navigation was vastly superior to SG techniques with increasingly tortuous phantoms. It dramatically decreased both the crossing and fluoroscopy times with maximal reduction from 201.7 +/- 111 to 36.4 +/- 13 sec, P < 0.001 and 204.7 +/- 24 to 47.2 +/- 19 sec, P < 0.001, respectively. The MNS had a 98.8% procedural success rate compared to 68% with SG techniques. Moreover it considerably limited the amount of wire usage from 5.5 to 1.3. Operators with prior MG experience performed significantly better than those without, except in the simplest phantom where the difference was nonsignificant (33.8 +/- 13 sec vs. 41.7 +/- 17 sec, P = 0.2). CONCLUSION: MNS significantly reduces both the crossing and fluoroscopy times in tortuous coronary phantom models achieving excellent success rates with dramatic reductions in guidewire usage. Operators with prior MNS experience had an advantage over the inexperienced.     

Immunosuppression: evolution in practice and trends, 1993–2003

Immunosuppression trends for solid organ transplantation have undergone a perceptible shift over the past decade. This period is of interest because it was during this time that the Food and Drug Administration (FDA) expanded the variety of medications to allow for alternatives in immunosuppressive management. An organ-by-organ review of SRTR data identifies several important trends. Antibody induction continues to be used for the majority of kidney (70%) , simultaneous pancreas-kidney (SPK, 79%) pancreas after kidney (PAK, 74%), and intestine recipients (74%). It is used for under half of thoracic organ recipients and remains uncommon for liver transplant recipients (20%). The type of antibody preparation utilized has shifted from muromonab-CD3 and horse ATG to rabbit ATG and monoclonal anti-IL-2 receptor antagonists. Calcineurin inhibitors continue to be used for maintenance immunosuppression for most recipients, although there has been a shift from cyclosporine to tacrolimus. A clear transition is apparent in the choice of antimetabolite from azathioprine to mycophenolate mofetil. Although corticosteroids continue to be used as maintenance immunosuppression for most recipients prior to discharge, there is evidence that efforts of steroid avoidance protocols are having an impact across all organs, as slight decreases in their use have been observed.     

Cyclosporine Interacts with Mycophenolic Acid by Inhibiting the Multidrug Resistance-Associated Protein 2

In mycophenolate mofetil (MMF)-treated organ transplant recipients, lower mycophenolic acid (MPA) plasma concentrations have been found in cyclosporine (CsA) compared with tacrolimus (Tac)-based immunosuppressive regimens. We previously demonstrated that CsA decreases exposure to MPA and increases exposure to its metabolite MPA-glucuronide (MPAG), possibly by interfering with the biliary excretion of MPAG. To elucidate the role of the multidrug resistance-associated protein (Mrp)-2 in the interaction between MMF and CsA, we treated three groups of 10 Mrp2-deficient rats (TR- rat) for 6 days with either vehicle, CsA (8 mg/kg) or Tac (4 mg/kg) by oral gavage. Hereafter, co-administration with MMF (20 mg/kg) was started in all groups and continued through day 14. The 24-h MPA/MPAG area under the concentration-time curve (AUC) was determined after single (day 7) and multiple MMF doses (day 14). On both study days, there were no significant differences in the mean MPA and MPAG AUC between CsA and Tac-treated animals. We conclude that the pharmacokinetics of MMF are comparable in Mrp2-deficient rats receiving either CsA or Tac as co-medication. This finding suggests that CsA-mediated inhibition of the biliary excretion of MPAG by the Mrp2 transporter is the mechanism responsible for the interaction between CsA and MMF.     

Primary spinal epidural non-Hodgkin's lymphoma. The contribution of nuclear magnetic resonance imaging, therapeutic approach and review of the literature.

Primary spinal epidural lymphoma (Stage I) is diagnosed predominantly late after a long prodromal phase of local back pain resulting in spinal cord compression. The use of CT and NMR images in the early stage of investigation and their analysis may help to diagnose these cases prior to the appearance of neurologic deficit. We report on 2 patients who presented with prolonged localized back pain with sudden symptoms of spinal cord compression. CAT scan and NMR imaging demonstrated the characteristic appearance of lymphoma. Decompressive laminectomy supported the diagnosis. Radiotherapy treatment to the region of the non-Hodgkin's lymphoma resulted in complete resolution. Thereafter, systemic chemotherapy with CHOP achieved a good response.     

Glutathione effects on vitamin D metabolism in control and streptozotocin diabetic rat

The circulating concentration of 1,25-dihydroxycholecalciferol [1,25-(OH)₂D₃] is a physiologic index of enzymatic activity of the renal 1-hydroxylase of 25-hydroxychole-calciferol (25-OH-D₃). Hydroxylation of 25-OH-D₃ and circulating 1,25-(OH)₂D₃ are decreased in the streptozotocin diabetic rat. We previously found that activity of another redox enzyme system, cytosolic superoxide dismutase, also decreased in streptozotocin diabetes, can be restored by treatment with glutathione. In the present experiment we tested the effect of glutathione treatment on vitamin D metabolism in control and diabetic rats. Enteral glutathione increased circulating 1,25-(OH)₂D₃ and decreased 25-OH-D₃ in both control and diabetic animals. These results suggest that exogenous glutathione increases 25-OH-D₃ 1-hydroxylation both under basal conditions in the normal animal and in diabetes-induced depression.     

Spatial Learning Deficits in Mice with a Targeted Glucocorticoid Receptor Gene Disruption

Previous studies in rats using the Morris water maze suggested that the processing of spatial information is modulated by corticosteroid hormones through mineralocorticoid and glucocorticoid receptors in the hippocampus. Mineralocorticoid receptors appear to be involved in the modulation of explorative behaviour, while additional activation of glucocorticoid receptors facilitates the storage of information. In the present study we used the water maze task to examine spatial learning and memory in mice homozygous and heterozygous for a targeted disruption of the glucocorticoid receptor gene. Compared with wild-type controls, homozygous and heterozygous mice were impaired in the processing of spatial but not visual information. Homozygous mutants performed variably during training, without specific platform-directed search strategies. The spatial learning disability was partly compensated for by increased motor activity. The deficits were indicative of a dysfunction of glucocorticoid receptors as well as of mineralocorticoid receptors. Although the heterozygous mice performed similarly to wild-type mice with respect to latency to find the platform, their strategy was more similar to that of the homozygous mice. Glucocorticoid receptor-related long-term spatial memory was impaired. The increased behavioural reactivity of the heterozygous mice in the open field points to a more prominent mineralocorticoid receptor-mediated function. The findings indicate that (i) the glucocorticoid receptor is of critical importance for the control of spatial behavioural functions, and (ii) mineralocorticoid receptor-mediated effects on this behaviour require interaction with functional glucocorticoid receptors. Until the development of site-specific, inducible glucocorticoid receptor mutants, glucocorticoid receptor-knockout mice present the only animal model for the study of corticosteroid-mediated effects in the complete absence of a functional receptor.