Toxicity of mycophenolate mofetil in patients with inflammatory bowel disease

Trials of mycophenolate mofetil (MMF) in inflammatory bowel disease (IBD) suggest that it may be useful in patients intolerant of azathioprine. We examined the safety and efficacy of MMF in IBD patients intolerant of or unresponsive to azathioprine. Twelve patients [seven with Crohn's disease (CD); seven women; mean age 40 years, range 14-76 years] were treated with MMF 500 mg b.i.d. for a mean of 12.5 weeks. Intolerance was defined as the development of side effects that resolved on discontinuing MMF. Improvement was described as symptomatic improvement, decreased steroid use, or disease entering endoscopic remission. Four patients responded with symptomatic improvement and reduced steroids or mesalazine requirement. Three patients developed headache, nausea, or arthralgia. Three patients developed profuse bloody diarrhea, and in two cases with previously quiescent ulcerative colitis (UC), the source was shown to be ulcers in a drug-induced colitis with histologic features similar to those previously reported in four renal transplant patients on MMF. There is no clear evidence of efficacy of MMF in the treatment of IBD, and its use in this condition should be confined to a randomized controlled trial. Moreover, as patients with UC may be unduly prone to colonic injury, MMF may not be a suitable drug for its treatment.     

<Superscript>18</Superscript>F-FDG-PET/CT Imaging to Diagnose Septic Emboli and Mycotic Aneurysms in Patients with Endocarditis and Cardiac Device Infections

Purpose of review

This review analyzes recent studies evaluating the diagnostic value of ¹⁸F-FDG-PET/CT for the detection of peripheral emboli and secondary infectious foci in patients with infective endocarditis and cardiac device infections.

Recent findings

Detection of extracardiac septic localizations in patients with infective endocarditis and cardiac device infections is crucial, as it may impact the diagnosis, prognosis, and therapeutic management. Recent literature substantiated the clinical usefulness of ¹⁸F-FDG-PET/CT in this setting.

Summary

¹⁸F-FDG-PET/CT has proven its high diagnostic value for the detection of peripheral emboli in patients with infective endocarditis and cardiac device infections, substantially affecting patients’ outcome and treatment. A multimodal approach, combining the high sensitivity of ¹⁸F-FDG-PET/CT with morphological imaging seems promising.

     

Cyclooxygenase (COX) 1 and 2 in normal, inflamed, and ulcerated human gastric mucosa

BACKGROUND AND AIMS: Constitutive cyclooxygenase (COX) 1 is believed to mediate prostaglandin dependent gastric protection. However, gastric mucosa contains cells capable of expressing inducible COX-2. We therefore investigated COX-1 and COX-2 expression, localisation, and activity in normal and abnormal human gastric mucosa. METHODS: COX-1 and COX-2 distribution was investigated by light and electron microscopic immunohistochemistry and by western blot analysis, and their contribution to prostaglandin (PG)E(2) synthesis using selective enzyme inhibitors. RESULTS: There was strong parietal cell COX-1 and COX-2 immunoreactivity in all sections and isolated cells, with macrophage and myofibroblast reactivity in some sections. Immunostaining was specifically abolished by antigen absorption. Western blot analysis confirmed COX-1 and 2 expression. COX-1 and COX-2 immunostaining was increased in Helicobacter pylori gastritis, particularly the mid glandular zone and lamina propria inflammatory cells. This was associated with increased ex vivo PGE(2) synthesis (62.4 (13.5) pg/mg v 36.3 (15.5) pg/mg in uninflamed mucosa; p=0. 017) which was significantly inhibited by COX-1 but not COX-2 inhibition. Increased COX-2 immunostaining in macrophages, endothelial cells, and myofibroblasts (with reduced epithelial expression) was seen at the rim of ulcers. CONCLUSION: COX-2, as well as COX-1, is expressed by normal human gastric mucosa and is increased at the rim of ulcers. Although both are increased with H pylori, COX-1 contributes more than COX-2 to gastric PGE(2) production.     

Complexity and Distribution of Drivers in Relation to Duration of Persistent Atrial Fibrillation

Background

The underlying mechanisms sustaining human persistent atrial fibrillation (PsAF) is poorly understood.

Current status of lung transplantation

Lung transplantation is a well-established treatment option for selected patients with end-stage lung disease, leading to improved survival and improved quality of life. The last 20 years have seen a steady growth in number of lung transplantation procedures performed worldwide. The increase in clinical activity has been associated with tremendous progress in the understanding of cellular and molecular processes that limit both short- and long-term outcomes. This review gives a comprehensive overview of the current status of lung transplantation for the referring physician. It demonstrates that careful selection of potential recipients, optimisation of their condition prior to transplant, use of carefully assessed donor organs, excellent surgery and meticulous long-term follow-up are all essential ingredients in determining a successful outcome.     

Supraventricular bigeminy originating from the mitral annulus: What is the mechanism?

We present a case of a 67‐year‐old female with a previous history of pulmonary vein isolation for paroxysmal atrial fibrillation who presented with supraventricular bigeminy with a constant coupling interval. The supraventricular bigeminy originated from the anterior mitral annulus with initial mapping suggestive of a focal mechanism. However detailed mapping using an ultrahigh resolution mapping system (with the manual shifting of the annotation window) revealed very low amplitude potentials connecting the previous sinus beat with continuous activation along the mitral annulus. Our observations were indicative of a re‐entry mechanism underlying the supraventricular bigeminy.     

Mononuclear phagocyte system of human Peyer''s patches: an immunohistochemical study using monoclonal antibodies.

Macrophages in sections of human terminal ileal Peyer's patches were studied using a panel of monoclonal antibodies. Germinal centre macrophages were large and strongly positive for acid phosphatase and stained with antibodies RFD1, RFD9, UCHM1 and other macrophage-specific monoclonal antibodies, but not RFD7. In the macrophages of the dome region there was heterogeneity of size and staining for acid phosphatase. The majority of the RFD1 positive cells in this region appeared to be macrophages. However, no RFD9- or RFD7-positive cells were present. By contrast, RFD7-positive but RFD9-negative macrophages were present in the lamina propria. In the interfollicular areas there were cells with a dendritic morphology which were strongly HLA-DR, HLA-DQ and RFD1-positive, but which did not stain with the other macrophage specific monoclonal antibodies or for acid phosphatase. Some macrophages and lymphocytes in the germinal centre and dome regions expressed interleukin 2 and transferrin receptors. These cells were not present in the adjacent lamina propria.