High dose melphalan and total body irradiation with autologous marrow rescue in childhood acute lymphoblastic leukaemia after relapse

High dose melphalan (HDM 110-140 mg/m2) and total body irradiation (TBI, 10.5 Gy, single fraction) followed by infusion of autologous bone marrow (ABMT) was evaluated for toxicity and efficacy in 24 children with acute lymphoblastic leukaemia (ALL) in second (CR2) or third remission (CR3). Marrow was purged with Campath 1 in six children (four were children in CR3). All children had engraftment with a median of 30 days (range 18-70 days) to neutrophil count greater than 0.5 x 10(9)/l. Four children (16%) died from toxicity 1-4 months after autograft, two from pneumonitis, one from an intracerebral haemorrhage and one from sepsis. Apart from fever and mucositis the procedure was well tolerated. Nine of 17 children treated in CR2 remain in complete remission 6-72 months after ABMT (median 25 months). Seven of these have a follow-up of greater than 12 months. Three of the seven children treated in CR3 are alive 17, 22 and 29 months post ABMT. Seven children relapsed within 10 months (median 4 months) of the autograft. Only one relapse has occurred beyond 10 months. HDM and TBI followed by ABMT is a relatively well tolerated regimen and may contribute to survival in children with relapsed ALL.     

Thiamin and vitamin B6 intakes and erythrocyte transketolase and aminotransferase activities in morbidly obese females before and after gastroplasty.

To assess the need for postoperative vitamin supplements, intakes and nutritional status of thiamin (B1) and vitamin B6 were studied in 18 female gastroplasty patients who received a placebo or different levels of supplemental vitamins. Postoperative erythrocyte transketolase basal (BA) and thiamin pyrophosphate-stimulated (SA) activities and activity coefficients (AC) correlated significantly with B1 intake. Despite a decrease in apotransketolase, low thiamin intakes were associated with increased AC values during the first 3 months. With return to low B1 intakes following repletion during month 4, the AC values remained normal with low total activities. Both alanine (EALT) and aspartate (EAST) aminotransferase apoenzyme levels declined and AC values increased significantly during the first 3 months. Although the EALT-indices were more sensitive to changes in B6 intake than the EAST-indices, the EASTBA and SA correlated most consistently with the intake. Postoperative dietary intakes of both vitamins were inadequate for maintenance of normal activities of these erythrocyte enzymes. Although B1 intake of greater than or equal to 1.0 mg/day was adequate for maintenance of normal thiamin status in most subjects of this study, supplementation with greater than or equal to 1.5 mg/day is prudent even though it may not prevent the early postoperative loss of apotransketolase. Vitamin B6 intake at the current recommended dietary allowance (1.6 mg) was not adequate to maintain coenzyme saturation of the erythrocyte aminotransferases. Marginal intake of other nutrients may have affected the utilization of both thiamin and vitamin B6.     

A randomized trial of plasmapheresis and subsequent pulse cyclophosphamide in severe lupus: design of the LPSG trial.

A group of clinics cooperating as the Lupus Plasmapheresis Study Group (LPSG) is starting an international multicenter study of the treatment of severe systemic lupus erythematosus. The primary goal of this randomized and prospective trial is to establish whether treatment with plasmapheresis and subsequent pulse cyclophosphamide improves the outcome compared to treatment with pulse cyclophosphamide alone. The underlying rationale assumes that plasmapheresis: a) eliminates pathogenic autoantibodies and immune complexes and b) induces a compensatory activation of pathogenic lymphocyte clones through a feed-back between circulating antibodies and their respective antibody-producing clones. Synchronization of plasmapheresis with subsequent pulse cyclophosphamide should enhance the deletion of pathogenic clones during the period of greatest vulnerability. This overview reviews the first results of treatment approaches based on this concept and summarizes the design of the LPSG trial.     

Persistent Hypotension Associated with Hypermedullipinemia: A New Syndrome

A new syndrome is described in a patient with advanced renal insufficiency. This consists of severe and persistent hypotension causing weakness but associated with a clear mental status. Also present is evidence for decreased vascular reactivity. The hypotension was not orthostatic. The hypotension was associated with a circulating vasodepressor substance having the characteristics of medullipin I. The medullipin appears to have been derived from the remaining right kidney. Hypotension existed despite the presence of major prohypertensive mechanisms, including an endstage kidney, hyperreninemia and hyperaldosteronemia. It is likely that hypotension due to hypermedullipinemia is an entity occurring in the human being.     

Cardiology

This article describes recent developments in cardiology and cardiovascular disease that are likely to be relevant to primary healthcare professionals and their patients. The following subject areas are covered: Primary prevention: recent developments in pharmaco-logical interventions, drug interactions, and drugs that are likely to cause harm; cardiovascular risk estimation and shared decision making with patients; and new developments in 24-hour ambulatory blood pressure monitoring. Secondary prevention: new models of care, including nurse-led care for the provision of hypertension and secondary prevention clinics; new drugs for the treatment of angina and myocardial infarction; ambulatory electrocardiography for the diagnosis of arrhythmias in primary care; and new developments in the treatment of atrial fibrillation - direct thrombin inhibitors and implantable devices. Tertiary prevention: recent developments in cardiac rehabilitation; recent evidence concerning revascularisation procedures and appropriateness criteria for referral; and implantable defibrillators.     

Onychomycoses due to Microascus cirrosus (syn. M. desmosporus)

Microascus cirrosus is very rarely the aetiological agent of onychomycosis. We report two additional cases of toenail infections caused by this fungus.