Nifekalant versus lidocaine for in-hospital shock-resistant ventricular fibrillation or tachycardia

Objective

To compare the efficacy and safety of nifekalant, a pure class III anti-arrhythmic drug, and lidocaine in patients with shock-resistant in-hospital ventricular fibrillation (VF) or ventricular tachycardia (VT).

Patients and methods

Between August 2005 and March 2008, we conducted a prospective, two-arm, cluster observational study, in which participating hospitals were pre-registered either to the nifekalant arm or the lidocaine arm. Patients were enrolled if they had in-hospital VF or VT resistant to at least two defibrillation shocks. Congenital or drug-induced long QT syndrome was excluded. The primary end-point was termination of VF or VT with/without additional shock. The secondary end-points were return of spontaneous circulation (ROSC), 1-month survival and survival to hospital discharge. We also assessed the frequency of adverse events, including asystole, pulseless electrical activity and torsade de pointes.

Results

In total, 55 patients were enrolled. After nifekalant, 22 of 27 patients showed termination of VF or VT, as compared with 15 of 28 patients treated with lidocaine with/without additional shock (odds ratio (OR): 3.8; 95% confidence interval (CI): 1.1-13.0; P = 0.03). Twenty-three of 27 patients given nifekalant showed ROSC, as compared with 15 of 28 patients given lidocaine (OR: 5.0; 95% CI: 1.4-18.2; P = 0.01). There was no difference in 1-month survival or survival to hospital discharge between the nifekalant and lidocaine arms. There was a higher incidence of asystole with lidocaine (7 of 28 patients) than with nifekalant (0 of 27 patients) (P = 0.005). Torsade de pointes was not observed.

Conclusion

Nifekalant was more effective than lidocaine for termination of arrhythmia and for ROSC in patients with shock-resistant in-hospital VF or VT (umin-CTR No. UMIN 000001781).     

Cardiac disease in pregnancy

Cardiac disease in pregnancy remains the leading cause of maternal mortality. In this review article we discuss our approach to caring for pregnant women with cardiac disease, and how the physiological changes of pregnancy can impact pre-existing conditions. This is illustrated by case discussions and practice points. Multi-disciplinary, individualised care is paramount to optimising outcomes for pregnant women with cardiac disease and their babies.     

Ca2+ responses to interleukin 1 and tumor necrosis factor in cultured human skin fibroblasts. Possible implications for Reye syndrome.

Elevated concentrations of cytokines were found in the plasma of patients acutely ill with Reye syndrome (RS) but not in control subjects or recovered RS patients. To determine whether this disorder involves a genetically determined abnormal response to cytokines, the effects of tumor necrosis factor (TNF) and IL-1 on intracellular free Ca2+ were compared in cultured skin fibroblasts from control subjects and patients with RS. IL-1 and TNF caused rapid, transient, and concentration-dependent increases in cytosolic free Ca2+. The peak cytosolic free Ca2+ was greater and occurred at higher concentrations of IL-1 and TNF in patient cells than in cells from age-matched controls. In control cells, the Ca2+ transient diminished sharply with increasing amounts of IL-1 or TNF above the maximum stimulatory concentration. In contrast, in patient fibroblast this bell-shaped curve of concentration dependency was much less apparent. Bradykinin-stimulated Ca2+ transients were similar in the two groups and did not exhibit the bell-shaped concentration dependency. Thus, plasma cytokine levels are elevated in RS patients and the Ca2+ response to cytokines is increased in cells derived from these patients. We propose that the increased response reflects a genetic defect in cytokine receptor-modulated signal transduction.     

Traumatic atlantal anterior arch fracture with associated avulsion fracture of the transverse ligament attachment: a previously undescribed combined entity

A case of an atlantal anterior arch burst fracture combined with an avulsion fracture of the transverse ligament attachment is presented. Similar cases have dealt with either isolated transverse ligament ruptures and avulsions or with Jefferson fractures associated with transverse ligament ruptures and avulsions. This case probably represents an entity in the spectrum of injury patterns to the atlanto-axial articulation.     

Cloning and characterization of Aplysia neutral endopeptidase, a metallo-endopeptidase involved in the extracellular metabolism of neuropeptides in Aplysia californica

Cell surface metallo-endopeptidases play important roles in cell communication by controlling the levels of bioactive peptides around peptide receptors. To understand the relative relevance of these enzymes in the CNS, we characterized a metallo-endopeptidase in the CNS of Aplysia californica, whose peptidergic pathways are well described at the molecular, cellular, and physiological levels. The membrane-bound activity cleaved Leu-enkephalin at the Gly3-Phe4 bond with an inhibitor profile similar to that of the mammalian neutral endopeptidase (NEP). This functional homology was supported by the molecular cloning of cDNAs from the CNS, which demonstrated that the Aplysia and mammalian NEPs share all the same amino acids that are essential for the enzymatic activity. The protein is recognized both by specific anti-Aplysia NEP (apNEP) antibodies and by the [125I]-labeled NEP-specific inhibitor RB104, demonstrating that the apNEP gene codes for the RB104-binding protein. In situ hybridization experiments on sections of the ganglia of the CNS revealed that apNEP is expressed in neurons and that the mRNA is present both in the cell bodies and in neurites that travel along the neuropil and peripheral nerves. When incubated in the presence of a specific NEP inhibitor, many neurons of the buccal ganglion showed a greatly prolonged physiological response to stimulation, suggesting that NEP-like metallo-endopeptidases may play a critical role in the regulation of the feeding behavior in Aplysia. One of the putative targets of apNEP in this behavior is the small cardioactive peptide, as suggested by RP-HPLC experiments. More generally, the presence of apNEP in the CNS and periphery may indicate that it could play a major role in the modulation of synaptic transmission in Aplysia and in the metabolism of neuropeptides close to their point of release.     

Reactive oxygen species as a signal in glucose-stimulated insulin secretion

One of the unique features of beta-cells is their relatively low expression of many antioxidant enzymes. This could render beta-cells susceptible to oxidative damage but may also provide a system that is sensitive to reactive oxygen species as signals. In isolated mouse islets and INS-1(832/13) cells, glucose increases intracellular accumulation of H2O2. In both models, insulin secretion could be stimulated by provision of either exogenous H2O2 or diethyl maleate, which raises intracellular H2O2 levels. Provision of exogenous H2O2 scavengers, including cell permeable catalase and N-acetyl-L-cysteine, inhibited glucose-stimulated H2O2 accumulation and insulin secretion (GSIS). In contrast, cell permeable superoxide dismutase, which metabolizes superoxide into H2O2, had no effect on GSIS. Because oxidative stress is an important risk factor for beta-cell dysfunction in diabetes, the relationship between glucose-induced H2O2 generation and GSIS was investigated under various oxidative stress conditions. Acute exposure of isolated mouse islets or INS-1(832/13) cells to oxidative stressors, including arsenite, 4-hydroxynonenal, and methylglyoxal, led to decreased GSIS. This impaired GSIS was associated with increases in a battery of endogenous antioxidant enzymes. Taken together, these findings suggest that H2O2 derived from glucose metabolism is one of the metabolic signals for insulin secretion, whereas oxidative stress may disturb its signaling function.     

Spica cast application in the emergency room for select pediatric femur fractures

OBJECTIVES: This study was designed to evaluate the efficacy and safety of immediate spica casting in the emergency room (ER) and evaluate the effect of discharge from the emergency room on short- term complications. DESIGN: Retrospective review of patients treated with immediate spica casting in the ER between June 1, 1993 and July 30, 2001. SETTING: Major, pediatric, orthopaedic trauma and referral center. PATIENTS: A total of 145 pediatric femur fractures in children, younger than age 7 years, treated with immediate spica casting in the ER were reviewed to determine radiographic outcome and short-term complication rates. INTERVENTION: All patients underwent immediate spica cast placement in the ER under conscious sedation. Patients meeting specific criteria were discharged immediately from the ER. MAIN OUTCOME MEASUREMENTS: Radiographic acceptability of alignment at fracture union (angulation, shortening), loss of reduction, number of return visits to the emergency room, and clinical outcome at final follow-up. RESULTS: Average follow-up was 20 +/- 16 weeks (range, 1-9 months). Forty-eight patients (33%) were discharged from the ER. No clinical complications were noted at last follow-up. All children younger than age 2 years, and 86.5% of children ages 2 to 5 years, met acceptable malalignment parameters on final radiographs. There were 16 ER visits (11%) for cast problems. Re-reduction in the operating room was needed in 11 patients (8.9%); 6.9% of patients had a cast problem noted during follow-up visits. Only 9% of patients developed a major complication. Initial shortening was the only independent risk factor found to be associated with loss of reduction. Admission status had no significant effect on the number of ER visits or development of a complication. CONCLUSIONS: If there are no associated factors requiring admission (ie, child abuse or polytrauma), spica casting in the ER for pediatric femur fractures followed by immediate discharge can be safely performed with a low complication rate in children younger than age 6 years, nearly eliminating the need for general anesthesia.