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.     

A review of the updated European Best Practice Guidelines for the Management of Anaemia in Patients with Chronic Renal Failure

The management of anaemia of Chronic Kidney Disease (CKD) has progressed significantly during the last decade. Research studies show that effective treatment of anaemia in adult patients with CKD can reduce cardiovascular complications slow progression of renal failure, and improve quality of life. To ensure adult patients receive optimum care, evidence-based practice and recognised guidelines and management strategies are needed to help reduce variations in clinical practice. In 1999 a working party of European Nephrologists developed the European Best Practice Guidelines (EBPG) for Management of Anaemia in Patients with Chronic Renal Failure to address this issue. Since the publication of the guidelines in 1999, over 3,000 papers relating to anaemia in CKD, have been published, many of which have significant implications for the practice of anaemia management. To ensure that the most up to date scientific evidence is available to those who manage anaemia in CKD the guidelines were revised in 2004. These guidelines, look at the anaemia management of adults with CKD and do not include guidelines for children.     

Developing nodes of Ranvier are defined by ankyrin-G clustering and are independent of paranodal axoglial adhesion

Nodes of Ranvier are excitable regions of axonal membranes highly enriched in voltage-gated sodium channels that propagate action potentials. The mechanism of protein clustering at nodes has been a source of controversy. In this study, developmental analysis of nodes of Ranvier in optic nerve axons reveals that early node intermediates are defined by ankyrin-G. Other node components, including beta IV spectrin, voltage-gated sodium channels, and the L1 cell adhesion molecule neurofascin, are subsequently recruited to sites of ankyrin-G clustering. The role of intact paranodes in protein clustering was examined in the dysmyelinating mouse mutant jimpy. Jimpy mice do not have intact paranodal axoglial contacts, which is indicated by a complete lack of neurexin/contactin-associated protein/paranodin clustering in paranodes. In the absence of intact paranodes, ankyrin-G was still able to cluster, although fewer ankyrin clusters were seen in jimpy optic nerves than in wild-type optic nerves. Recruitment of Na(v)1.2, Na(v)1.6, beta IV spectrin, and neurofascin to sites of ankyrin-G clustering is unimpaired in jimpy mice, indicating that node formation occurs independent of intact paranodal axoglial contacts.     

Left ventricular endomyocardial biopsy II: The value of light microscopy

Histological sections of left ventricular endomyocardial biopsies have been examined by light microscopy. The biopsies were taken from patients with congestive, hypertrophic, or restrictive cardiomyopathy and from patients with either aortic stenosis or regurgitation. In congestive cardiomyopathy no specific features were found and similar abnormalities were seen in aortic valve disease. In only one of six cases of asymmetric septal hypertrophy were the characteristic histological appearances noted. In four out of five patients with a restrictive type of cardiomyopathy, amyloid was demonstrated. The muscle fibres in aortic stenosis had a greater cross-sectional area than those in aortic regurgitation. A greater degree of fibrosis was present in aortic stenosis than in aortic regurgitation. In aortic stenosis the amount of fibrous tissue was inversely related to function.     

Lymphatic Obstruction and Protein‐losing Enteropathy in Patients with Congenital Heart Disease

Objective. Protein‐losing enteropathy (PLE) is a known complication of surgical procedures for congenital heart disease. The pathogenesis and pathophysiology of PLE remain poorly understood. However, lymphatic insufficiency appears central to the disease process. We sought to investigate the role of lymphatic obstruction and central venous catheter‐related central venous thrombosis in patients with congenital heart disease and PLE. Design. A case‐control study design was constructed consisting of patients with congenital heart disease and PLE and 2:1 matched controls having undergone the same definitive surgical procedure. Obstruction to lymphatic return was considered present if the thoracic duct was ligated, or if there was complete central venous obstruction at the usual site of thoracic duct drainage. Results. Obstruction to lymphatic return was identified in 4 of 16 cases (25%) and 1 of 32 controls (4%), P = .06. There was no association between PLE and central venous catheter use or duration, and no discriminating characteristics between cases and controls with respect to anatomy, pre‐Fontan hemodynamic variables, operative or perioperative factors, or hemodynamic variables at the time of PLE diagnosis. Mortality for patients with PLE was 25% compared with 9% in controls (P = not significant). Long‐term resolution of PLE was obtained in six patients (38%). Conclusion. There is a high prevalence of apparent lymphatic obstruction in patients with congenital heart disease and PLE, suggesting that physical lymphatic obstruction may play an important, and previously unrecognized role in the development of PLE in patients with complex congenital heart disease.     

Why portal hypertensive varices bleed and bleed: a hypothesis.

Continued bleeding or early rebleeding is associated with a poor prognosis in patients with variceal haemorrhage. It is not clear why bleeding stops in some patients and continues or restarts in others. It is suggested that secondary haemodynamic changes in the splanchnic circulation after a bleed may contribute to the risk of further bleeding. These changes include the effects of hypotension on portocollateral resistance, the effects of blood in the gut on splanchnic blood flow, and the effects of blood volume expansion on portal venous pressure during resuscitation. These factors, working in concert, cause a secondary rise in portal venous pressure, which may precipitate further bleeding. Treatment aimed at preventing these secondary haemodynamic changes may be beneficial. It is probable that somatostatin and octreotide could act in this way, which may explain their therapeutic efficacy.