Citations

Background Regional anesthesia is increasing in popularity for ambulatory surgical procedures. Concomitantly, the prevalence of obesity in the United States population is increasing. The objective of the present investigation was to assess the impact of body mass index (BMI) on patient outcomes after ambulatory regional anesthesia. Methods This study was based on prospectively collected data including 9,038 blocks performed on 6,920 patients in a single ambulatory surgery center. Patients were categorized into three groups according to their BMI (<25 kg/m2, 25-29 kg/m2, > or =30 kg/m2). Block efficacy, rate of acute complications, postoperative pain (at rest and with movement), postoperative nausea and vomiting, rate of unscheduled hospital admissions, and overall patient satisfaction were assessed. Linear and logistic multivariable analyses were used to obtain the risk-adjusted effect of BMI on these outcomes. Results Of all patients 34.8% had a BMI <25 kg/m2, 34.0% were overweight (BMI 25-29 kg/m2), and 31.3% were obese (BMI > or = 30 kg/m2). Patients with BMI > or =30 kg/m2 were 1.62 times more likely to have a failed block (P = 0.04). The unadjusted rate of acute complications was higher in obese patients (P = 0.001). However, when compared with patients with a normal BMI, postoperative pain at rest, unanticipated admissions, and overall satisfaction were similar in overweight and obese patients. Conclusions The present investigation shows that obesity is associated with higher block failure and complication rates in surgical regional anesthesia in the ambulatory setting. Nonetheless, the rate of successful blocks and overall satisfaction remained high in patients with increased BMI. Therefore, overweight and obese patients should not be excluded from regional anesthesia procedures in the ambulatory setting.

Background— Many ablative approaches in or near the orifice of the pulmonary vein (PV) have demonstrated success in eliminating atrial fibrillation. Despite current practice, there are no data regarding the in vivo efficacy and safety of an 8-mm catheter tip for ablation at the PV orifice. Methods and Results— Ten mongrel dogs were studied. Thermocouples were implanted in the atrial muscle of the PV orifice. Intracardiac echocardiography monitored catheter position, tip/tissue orientation, and microbubble formation. Ninety-four ablations were performed for 120 seconds. A temperature discrepancy >10°C between the catheter tip and tissue occurred during 47 (50%) of the ablations. Despite termination of energy delivery, the average tissue temperature remained within 1°C of the achieved steady state for 9 seconds. A temperature discrepancy >10°C was more common in the right superior PV, with oblique catheter positioning, when tissue temperatures were >60°C or 80°C, and with type 1 or type 2 microbubble formation. However, microbubbles were not present in 7 (13%, type 1) and 10 (40%, type 2) ablations with tissue temperatures >80°C. The maximum tissue temperature achieved with non–full-thickness lesions was 47.3±7.4°C vs 75.9±11.7°C ( P <0.0001) for full-thickness lesions. Conclusions— Marked discrepancies between catheter-tip and tissue temperatures occurred with higher temperatures, prolonged ablation times, and unfavorable catheter thermistor–tissue contact. Also, these data suggest a conservative approach to atrial ablation, because full-thickness lesions were obtained when tissue temperatures reached 50°C to 60°C and the tissue retained high heat levels despite termination of radiofrequency energy. Finally, microbubbles are inconsistent markers of tissue overheating.

AbstractB-cell chronic lymphocytic leukemia (CLL) is characterized by accumulation of clonal lymphocytes resistant to apoptosis. We evaluated the ability of the investigational antileukemic agent adaphostin to induce apoptosis in CLL B cells and synergize with fludarabine in vitro. Analysis by annexin V/propidium iodide (PI) staining revealed that the concentration of adaphostin required to induce 50% cell death (IC50) at 24 hours was 4.2 μM (range, 1.10-11.25 μM; median, 4.25 μM; n = 29) for CLL isolates and more than 10 μM for B and T cells from healthy donors. Immunoblots demonstrated adaphostin induced poly(adenosine diphosphate-ribose) polymerase (PARP) cleavage and cleavage of caspase-3 substrates, suggesting that adaphostin induces apoptosis. Adaphostin increased the level of reactive oxygen species (ROS) within CLL B cells, and the antioxidant N-acetylcysteine blocked both adaphostin-induced ROS generation and apoptosis. Adaphostin also caused a decrease in the level of the antiapoptotic protein Bcl-2. When adaphostin was combined with fludarabine (F-ARA-AMP), a synergistic effect on cell death was observed in all 10 CLL samples. These findings not only indicate that adaphostin induces apoptosis selectively in CLL B cells through a mechanism that involves ROS generation but also demonstrate its ability to augment the effects of fludarabine. Further preclinical development of adaphostin as a novel agent for the treatment of CLL appears warranted.

Abstract Objectives To characterize the presentation and outcome of patients with heart failure (HF) after myocardial infarction (MI) according to left ventricular ejection fraction (LVEF) and test the hypothesis that the outcome of HF did not change over time. Background Little is known about the presentation and outcome of HF post-MI and how these may have changed over time. Methods Using the Rochester Epidemiology Project, all residents of Olmsted County, Minnesota who experienced an incident MI between 1979 and 1998 were identified; MI and HF were validated using standardized criteria. Subjects were followed through their community medical record. Results Between 1979 and 1998, 1915 patients with incident MI and no prior history of HF were identified. Of these, 791(41%) experienced new onset HF as defined by Framingham criteria during 6.6±5.0 years of follow-up. Forty-seven percent were men, mean age was 73±12 years. Forty-four percent had impaired LVEF, 18% preserved LVEF and 38% had no LVEF measurement within 60 days after the HF event. Median survival after HF onset was 4 years and at 5 years after HF onset, only 45% were alive. Older age, male sex, comorbidity, hypertension and no LVEF assessment were associated with increased risk of death, however, patients with impaired LVEF had the worst outcome. Over time, survival did not improve (HR for year: 1.00; 95% CI 0.99, 1.02; P=0.919) even after adjustment for baseline characteristics. Conclusion In this geographically defined cohort of patients with MI, new onset HF after the MI was frequent. When measured, LVEF was most frequently reduced, consistent with systolic heart failure. Mortality was high and did not decline over time and death was independently associated with male sex, older age, hypertension and comorbidity. It also differed according to LVEF, which was inconsistently ascertained in this setting, potentially representing practice opportunities.

Objective. 2-Methylbutyryl-CoA dehydrogenase deficiency, also known as short/branched-chain acyl-CoA dehydrogenase (SBCAD) deficiency, is a recently described autosomal recessive disorder of l-isoleucine metabolism. Only 4 affected individuals in 2 families have been described. One patient developed athetoid cerebral palsy, and another had severe motor developmental delay with muscle atrophy. A sibling of the first patient is asymptomatic after prenatal diagnosis and early treatment. Family investigations in the second family revealed that the patient’s mother was also affected but asymptomatic. Methods. We report 8 additional patients identified by prospective newborn screening using tandem mass spectrometry. Results. Molecular genetic analysis performed for 3 of these patients revealed that all are homozygous for an 1165A&gt;G mutation that causes skipping of exon 10 of the SBCAD gene. Although there was no obvious consanguinity, all patients belong to the Hmong, an ancient ethnic group that originated in China and constitutes only 0.8% and 0.6% of the Minnesota and Wisconsin population, respectively. Dietary treatment was initiated in the neonatal period. Except for 1 patient who developed mild muscle hypotonia, all patients remain asymptomatic at ages ranging from 3 to 14 months of age. Conclusions. These cases suggest that SBCAD deficiency is another inborn error of metabolism detectable by newborn screening using tandem mass spectrometry. The continued efficacy of long-term dietary therapy instituted presymptomatically remains to be established.

ABSTRACT Human immunodeficiency virus type 1 (HIV-1), feline immunodeficiency virus (FIV), and Moloney murine leukemia virus (MoMLV) integrases were stably expressed to determine their intracellular trafficking. Each lentiviral integrase localized to cell nuclei in close association with chromatin while the murine oncoretroviral integrase was cytoplasmic. Fusions of pyruvate kinase to the lentiviral integrases did not reveal transferable nuclear localization signals. The intracellular trafficking of each was determined instead by the transcriptional coactivator LEDGF/p75, which was required for nuclear localization. Stable small interfering RNA expression eliminated detectable LEDGF/p75 expression and caused dramatic, stable redistribution of each lentiviral integrase from nucleus to cytoplasm while the distribution of MoMLV integrase was unaffected. In addition, endogenous LEDGF/p75 coimmunoprecipitated specifically with each lentiviral integrase. In vitro integration assays with preintegration complexes (PICs) showed that endogenous LEDGF/p75 is a component of functional HIV-1 and FIV PICs. However, HIV-1 and FIV infection and replication in LEDGF/p75-deficient cells was equivalent to that in control cells, whether cells were dividing or growth arrested. Two-long terminal repeat circle accumulation in nondividing cell nuclei was also equivalent to that of LEDGF/p75 wild-type cells. Virions produced in LEDGF/p75-deficient cells had normal infectivity. We conclude that LEDGF/p75 fully accounts for cellular trafficking of diverse lentiviral, but not oncoretroviral, integrases and is the main lentiviral integrase-to-chromatin tethering factor. While lentiviral PIC nuclear import is unaffected by LEDGF/p75 knockdown, this protein is a component of functional lentiviral PICs. A role in HIV-1 integration site distribution merits investigation.