Electrophysiologically guided pulmonary vein isolation during sustained atrial fibrillation

INTRODUCTION: Sustained atrial fibrillation (AF) is frequently encountered during pulmonary vein (PV) isolation. The aim of this study was to evaluate the feasibility and safety of PV isolation during sustained AF. METHODS AND RESULTS: Thirty-seven patients (30 men, age 54 +/- 10 years) underwent Lasso-guided isolation of 87 PVs during sustained AF. Baseline PV electrogram patterns were classified into one of two types: organized, with consistent PV activation sequence; or disorganized, with constant variation of PV activation sequence. In disorganized activity, radiofrequency ablation was performed circumferentially around the Lasso while the earliest PV potential was targeted during organized activity. Complete left atrial (LA) to PV block during AF was identified by abolition or dissociation of all sharp potentials recorded within the vein. PV isolation then was verified during sinus rhythm. Baseline activation patterns of PV potential were organized in 32 PVs (37%) [more frequently in inferior veins than superior veins (53% vs 26%, P = 0.01)] and disorganized in 55 PVs (63%). In 59 of 87 PVs, isolation was begun and completed during AF. Radiofrequency ablation organized PV activation sequence in 75% prior to isolation. LA-PV block was confirmed during sinus rhythm in 54 (92%) of 59 PVs. In 28 of 87 PVs, sinus rhythm was restored before complete LA-PV block. Complete isolation was achieved in all 87 PVs without complications. CONCLUSION: PV isolation can be effectively and safely performed during sustained AF, preceded in most cases by organization of PV electrogram activity. This strategy may be the preferred alternative to multiple intraprocedural cardioversions.     

Effects of redox cycling compounds on DT diaphorase activity in the liver of rainbow trout (<Emphasis Type="Italic">Oncorhynchus mykiss</Emphasis>)

Background  

DT diaphorase (DTD; NAD(P)H:quinone oxidoreductase; EC 1.6.99.2) catalyses the two electron reduction of quinones, thus preventing redox cycling and consequently quinone dependent production of reactive oxygen species. In rat and mouse, a wide range of chemicals including polyaromatic hydrocarbons, azo dyes and quinones induces DTD. Bifunctional compounds, such as β-naphthoflavone (β-NF) and benzo(a)pyrene (B(a)P), induce DTD together with CYP1A and phase II enzymes by a mechanism involving the aryl hydrocarbon receptor (AHR). Monofunctional induction of DTD is mediated through the antioxidant response element and does not lead to the induction of AHR dependent enzymes, such as CYP1A. The aim of this study was to investigate the effects of prooxidants (both bifunctional and monofunctional) on the activity of hepatic DTD in rainbow trout (Oncorhynchus mykiss) in order to evaluate DTD suitability as a biomarker. We also investigated the effect of β-NF on hepatic DTD activity in perch (Perca fluviatilis), shorthorn sculpin (Myoxocephalus scorpius), eelpout (Zoarces viviparus), brown trout (Salmo trutta) and carp (Cyprinus carpio). In addition, the effect of short term exposure to prooxidants on catalase activity was investigated.     

Churg‐Strauss syndrome with poor‐prognosis factors: A prospective multicenter trial comparing glucocorticoids and six or twelve cyclophosphamide pulses in forty‐eight patients

Objective

To compare long and short durations of adjunctive cyclophosphamide for the treatment of severe Churg‐Strauss syndrome (CSS).

Methods

In this prospective multicenter therapeutic trial, 48 patients with CSS with at least 1 poor‐prognosis factor at baseline were treated with glucocorticoids and either 12 or 6 intravenous cyclophosphamide pulses.

Results

At 8 years, complete remission rates and severe side effects of therapy were comparable for both groups. The overall difference in relapses was not significant between the 12‐pulse and the 6‐pulse regimens (P = 0.07), but when considering only the number of mild relapses this difference became statistically significant (P < 0.02). Although the total number of inclusions was not reached, the study was stopped prematurely in response to the superiority of the 12‐pulse regimen.

Conclusion

We concluded that 12 cyclophosphamide pulses were better able to control severe CSS than a 6‐pulse regimen. The optimal duration of therapy remains to be determined.     

beta-Arrestin2, interacting with phosphodiesterase 4, regulates synaptic release probability and presynaptic inhibition by opioids

Most mu-opioid receptor agonists recruit beta-arrestin2, with some exceptions such as morphine. Surprisingly, however, the acute analgesic effect of morphine is enhanced in the absence of beta-arrestin2. To resolve this paradox, we examined the effects of morphine and fentanyl in acute brain slices of the locus coeruleus and the periaqueductal gray from beta-arrestin2 knockout mice. We report that, in these mice, presynaptic inhibition of evoked inhibitory postsynaptic currents was enhanced, whereas postsynaptic G protein-coupled K(+) (Kir3/GIRK) currents were unaffected. The frequency, but not amplitude, of miniature inhibitory postsynaptic currents was increased in beta-arrestin2 knockout mice, indicating a higher release probability compared to WT mice. The increased release probability resulted from increased cAMP levels because of impaired phosphodiesterase 4 function and conferred an enhanced efficacy of morphine to inhibit GABA release. Thus, beta-arrestin2 attenuates presynaptic inhibition by opioids independent of mu-opioid receptor-driven recruitment, which may make beta-arrestin2 a promising target for regulating analgesia.     

Eccrine squamous syringometaplasia and cytomegalovirus infection

BACKGROUND: Eccrine squamous syringometaplasia has been reported in some cases as an Herpeviridae complication. We report a case of eccrine squamous syringometaplasia associated with a severe cytomegalovirus infection in an immunocompromised patient, and we discuss about potential viral or drug triggering factors. METHODS: A 22 years-old man was hospitalized in an intensive care unit for rejection of a renal graft associated with a disseminated cytomegalovirus infection. A papular and papulopustular eruption appeared on the trunk and the limbs. RESULTS: Histological examination of a skin sample showed eccrine squamous syringometaplasia, with evidence of cytomegalovirus genomic sequences using PCR. Two weeks later, the patient developed toxic epidermal necrolysis, with fatal issue. CONCLUSIONS: Eccrine squamous syringometaplasia is a rare condition, without specific clinical features. Numerous local affections have been reported to induce eccrine syringometaplasia (ulcer, scar, pyoderma gangrenosum, drug injection.), drugs (cytotoxic agents, non steroidal anti inflammatory therapies) and in cases of infection due to cytomegalovirus or herpes simplex virus. The potential implication of cytomegalovirus or foscarnet as triggering factors in our case is discussed. This observation and other similar reported cases lead to the conclusion that eccrine squamous syringometaplasia may be an underestimated complication of cytomegalovirus infections in immunocompromised patients.     

Gangrène de membre à la suite d’un traitement traditionnel de fractures par attelle en bambou chez l’enfant à l’Hôpital régional de Kaolack (Sénégal)

Little published data exist on the morbidity and mortality associated with poor trauma care in developing countries. This report highlights our experience with iatrogenic limb gangrene related to fracture management by traditional bonesetters. Children with bonesetter’s gangrene were identified from a prospectively recorded paediatric surgery database at the Regional Hospital of Kaolack in Central Senegal. 21 children were treated for bonesetter’s gangrene during a 18-month period (January 2007 up to June 2008). The average age was 10 years (range, 5 to 15 years). Bonesetter’s gangrene was more common in boys (90.5%) and occurred almost exclusively in children from rural areas where access to health care was limited. 16 children underwent proximal extremity amputation. Complications included one case of tetanus. Bonesetter’s gangrene is a preventable complication that results from a failure of child health planners to recognize the importance of basic trauma care. Management of fractures should be considered an essential component of child health programs in developing countries.     

A Phenotypic Approach for IUIS PID Classification and Diagnosis: Guidelines for Clinicians at the Bedside

The number of genetically defined Primary Immunodeficiency Diseases (PID) has increased exponentially, especially in the past decade. The biennial classification published by the IUIS PID expert committee is therefore quickly expanding, providing valuable information regarding the disease-causing genotypes, the immunological anomalies, and the associated clinical features of PIDs. These are grouped in eight, somewhat overlapping, categories of immune dysfunction. However, based on this immunological classification, the diagnosis of a specific PID from the clinician’s observation of an individual clinical and/or immunological phenotype remains difficult, especially for non-PID specialists. The purpose of this work is to suggest a phenotypic classification that forms the basis for diagnostic trees, leading the physician to particular groups of PIDs, starting from clinical features and combining routine immunological investigations along the way. We present 8 colored diagnostic figures that correspond to the 8 PID groups in the IUIS Classification, including all the PIDs cited in the 2011 update of the IUIS classification and most of those reported since.