Extracorporeal treatment for digoxin poisoning: systematic review and recommendations from the EXTRIP Workgroup

Background: The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup was formed to provide recommendations on the use of extracorporeal treatments (ECTR) in poisoning. Here, we present our results for digoxin. Methods: After a systematic literature search, clinical and toxicokinetic data were extracted and summarized following a predetermined format. The entire workgroup voted through a two-round modified Delphi method to reach a consensus on voting statements. A RAND/UCLA Appropriateness Method was used to quantify disagreement, and anonymous votes were compiled and discussed in person. A second vote was conducted to determine the final workgroup recommendations. Results: Out of 435 articles screened, 77 met inclusion criteria. Only in-vitro, animal studies, case reports and case series were identified yielding a very low quality of evidence for all recommendations. Based on data from 84 patients, including six fatalities, it was concluded that digoxin is slightly dialyzable (level of evidence?=?B), and that ECTR is unlikely to improve the outcome of digoxin-toxic patients whether or not digoxin immune Fab (Fab) is administered. Despite the lack of robust clinical evidence, the workgroup recommended against the use of ECTR in cases of severe digoxin poisoning when Fab was available (1D) and also suggested against the use of ECTR when Fab was unavailable (2D). Conclusion: ECTR, in any form, is not indicated for either suspected or proven digoxin toxicity, regardless of the clinical context, and is not indicated for removal of digoxin-Fab complex.     

Angiotensin converting enzyme gene insertion-deletion polymorphism is associated with juvenile rheumatoid arthritis

OBJECTIVE: To investigate the incidence of angiotensin converting enzyme (ACE) gene insertion-deletion (I/D) polymorphism genotypes in children with juvenile rheumatoid arthritis (JRA), a heterogeneous chronic disease with autoimmune pathology. ACE gene I/D polymorphism influences the plasma and tissue levels of ACE and has an involvement in inflammatory mechanisms. METHODS: The incidence of ACE gene I/D polymorphism genotypes was determined in 82 children with JRA from Kuwait and compared to that in 48 ethnically matched healthy controls using polymerase chain reaction. RESULTS: A considerably higher incidence of II genotype was observed in the JRA patients compared to controls (p < 0.003). In contrast, no statistically significant difference was detected in the incidence of DD and ID genotypes in JRA patients and controls (p = 0.276 and 0.460, respectively). The incidence of ACE gene polymorphism genotypes was also studied in clinical subclasses of JRA patients and controls. There was no significant difference in the incidence of DD and ID genotypes in either of the 3 JRA subclasses (oligoarticular, polyarticular, and systemic) when compared to controls. However, the incidence of II genotype was found to be significantly higher in all the 3 JRA subclasses compared to controls. The strongest association between II genotype and JRA subclasses was detected in systemic JRA, followed by oligoarticular and polyarticular JRA. This was also reflected in a higher prevalence of I-allele in the systemic JRA cases (13/26, 50%) compared to the D-allele (11/26, 42%). In contrast, D-allele of the ACE gene was more prevalent in oligoarticular and polyarticular JRA cases, than the I-allele (61% and 58%, respectively). CONCLUSION: Our data suggest a significant association of the I-allele of the ACE gene I/D polymorphism with the 3 clinical subclasses of JRA in children, and the highest association was observed in systemic JRA cases.     

Hemolytic-uremic syndrome following bone marrow transplantation in adults for hematologic malignancies

One hundred and sixty eight adult patients with B-cell non-Hodgkin's lymphoma (NHL) and other hematologic malignancies who underwent autologous or allogeneic bone marrow transplantation (BMT) were investigated for the subsequent development of hemolytic-uremic syndrome (HUS). All patients were conditioned with cyclophosphamide and total body irradiation. When examined at 3-month intervals for the first year post-BMT, all patients had uniform measurements of hematocrit (Hct) and serum creatinine. Sixteen patients who initially exhibited Hct and creatinine values that were normal range for the BMT populations developed a sudden decrease in Hct and increase in creatinine between 3 and 11 months post-BMT and fulfilled the clinical and laboratory criteria for HUS. None of these patients had known active cytomegalovirus infection, graft-versus-host disease, or cyclosporine administration. The degree of decrease in Hct and creatinine elevation ranged from solely laboratory abnormalities to a clinically significant syndrome. Twelve of the 16 patients developed acute clinical complications of congestive heart failure, hypertension (HTN), or peripheral edema. Twelve patients required red blood cell support, whereas only four patients required platelet transfusions. Both hemolytic anemia and thrombocytopenia have resolved in virtually all cases. At a mean follow up of 18 months postdiagnosis, creatinine elevations have persisted along with HTN. All patients have survived without life-threatening long-term sequelae. With the increasing use of BMT as a curative modality for patients with hematologic malignancies, it becomes important to prospectively monitor patients for the development of HUS and its potential long-term impact on renal function.     

Sleep apnoea caused by rheumatoid arthritis

Sleep apnoea syndrome (SAS) is a rarely documented, but possibly lethal, complication of the instability of the cervical spine in rheumatoid arthritis. Five patients with SAS of a central or peripheral origin are presented, and the problems of recognizing and diagnosing the syndrome are discussed. We hope that clinicians will become more aware of the existence and the different aetiologies of SAS, thus improving early recognition and appropriate treatment. Adequate treatment has proven to increase survival in peripheral SAS and seems to be successful in doing so in central SAS.      

Induction Therapy for Lupus Nephritis: the Highlights

Purpose of Review

Lupus nephritis is a frequent complication of systemic lupus erythematosus and is more common and severe in children. This is a disease of the immune system characterized by T cell, B cell, and complement activation, as well as immune complex formation and deposition. The introduction of steroids and later cyclophosphamide transformed lupus nephritis from a fatal to a treatable condition. However, the standard therapies currently used for treatment carry significant toxicity and chronic kidney disease still remains a far too frequent outcome. To address these issues, we will review current and emerging induction therapies in LN.

Recent Findings

Several clinical trials have been undertaken to test more effective and safer drugs, often targeting mechanistic disease pathways.

Summary

At present, it is difficult to identify an induction regimen that is more effective and less toxic than the standard of care; however, we believe continuing efforts in drug development will bring breakthrough agents to clinics.

     

Cariporide potentiates the effects of epinephrine and vasopressin by nonvascular mechanisms during closed-chest resuscitation

BACKGROUND: The efficacy of vasopressor therapy during closed-chest resuscitation is limited and decreases over time. We previously reported that sodium-hydrogen exchanger isoform-1 inhibition during ventricular fibrillation (VF) using cariporide ameliorates ischemic contracture and enhances the efficacy of chest compression. We currently investigated whether cariporide could potentiate pressor responses to epinephrine and vasopressin. METHODS: VF was induced and left untreated for 12 min in two series of 16 rats each. Chest compression was then started and the depth adjusted within the initial 2 min to attain an aortic diastolic pressure between 26 and 28 mm Hg. In one series, rats received boluses of epinephrine (150 microg/kg); in the other series, rats received boluses of vasopressin (0.8 U/kg) to maintain the aortic diastolic pressure > 25 mm Hg. Within each series, rats were randomized to receive a 3 mg/kg bolus of cariporide or 0.9% NaCl immediately before starting chest compression. Defibrillation was attempted at 20 min of VF (8 min of chest compression). RESULTS: Cariporide prompted higher and more sustained coronary perfusion pressures in both the epinephrine group (37 +/- 5 mm Hg vs 29 +/- 7 mm Hg, p < 0.05) and the vasopressin group (36 +/- 5 mm Hg vs 28 +/- 6 mm Hg +/- SD, p < 0.02) even though fewer additional vasopressor doses were required. After resuscitation, cariporide-treated rats had less ventricular ectopic activity, better hemodynamic function, and improved survival scores. In separate experiments, in situ perfusion of the aorta excluded a vascular-mediated effect of cariporide. CONCLUSION: Cariporide enhanced the hemodynamic efficacy of vasopressor agents and improved resuscitation outcomes probably as a result of enhanced forward blood flow without effect on the peripheral vasculature.     

Is seroprevalence of HTLV-I/II among blood donors in Lebanon relevant?

Human T-cell lymphotropic virus type I (HTLV-I) is associated with certain hematologic and neurologic disorders. Seroprevalence studies demonstrated that the distribution of HTLV-I is heterogeneous worldwide and not specific to 1 region. Because blood is one of the major routes of transmission of the virus, blood banks of several countries routinely screen all blood donations for HTLV-I. The aim of the present study was to assess the seroprevalence rate of HTLV-I/II antibodies among Lebanese blood donors. Between August 2001 and March 2002, consecutive blood samples of 3529 blood donors were collected at blood banks of 4 major hospitals in Lebanon. Initial enzyme-linked immunosorbent assay (ELISA) screening resulted in 23 (0.7%) positive samples, of which 12 (0.3%) were reconfirmed positive by ELISA. Further analysis by Western blot resulted in 2 (0.06%) positive samples, of which 1 tested positive for HTLV-I by PCR (0.028%). Although its very low prevalence among Lebanese blood donors does not support routine screening of Lebanese blood donors for HTLV-I, screening of blood donors from other nationalities may be exercised, especially those from HTLV-I endemic areas.     

N‐methyl‐D‐aspartate (NMDA) receptor involvement in central nervous system prostaglandin production during the relapse phase of chronic relapsing experimental autoimmune encephalomyelitis (CR EAE)

Our previous studies have established that major changes in central nervous system (CNS) prostaglandin (PG) levels occur during the relapse phase of chronic relapsing experimental autoimmune encephalomyelitis (CR EAE), an animal model of the human demyelinating disease multiple sclerosis. PG production is controlled through a series of enzymic pathways that, in EAE, are influenced by neuroantigen‐driven autoimmune events. In non‐immune‐based models of CNS disease, endogenous glucocorticoids have been proposed as instigators of PG synthesis via activation of the N‐methyl‐D‐aspartate (NMDA) receptor. Glucocorticoids have an important regulatory role in the pathogenesis EAE and the NMDA receptor is intimately involved in many of the characteristic neuroinflammatory processes that govern the disease. Therefore, the alterations in prostanoid concentrations during the relapse stage of CR EAE may ultimately be governed by glucocorticoid‐induced NMDA receptor activation. The current investigation has examined the proposed glucocorticoid–NMDA receptor link by determining the effects of the receptor antagonist, (+) MK‐801, on CNS PGE ₂ and PGD ₂ levels in Biozzi mice with relapse symptoms of CR EAE. Prostanoid concentrations in the cerebral cortex were not altered by drug administration, and in cerebellar tissues, a vehicle effect negated any drug‐induced changes. However, the level of PGD ₂ in spinal cords from (+) MK‐801‐dosed mice was significantly lower, compared to controls, but PGE ₂ concentrations remained unchanged. The results suggest that glucocorticoid–NMDA receptor‐linked events are not primarily responsible for PG generation in the brain but may influence prostanoid production in discrete areas of the CNS.