Noncardiac surgery in long-term implantable left ventricular assist-device recipients.

OBJECTIVE: The authors describe their experience with left ventricular assist-device (LVAD) recipients undergoing noncardiac surgery and delineate surgical, anesthetic, and logistic factors important in the successful intraoperative management of these patients. SUMMARY BACKGROUND DATA: Left ventricular assist-devices have become part of the armamentarium in the treatment of end-stage heart failure. As the numbers of patients chronically supported with long-term implantable devices grows, general surgical problems that are commonly seen in other hospitalized patients are becoming manifest. Of particular interest is the intraoperative management of patients undergoing elective noncardiac surgical procedures. METHODS: The anesthesia records and clinical charts were reviewed for eight ventricular assist-device recipients undergoing general surgical procedures between August 1, 1990 and August 31, 1994. RESULTS: A total of 12 procedures were performed in 6 men and 2 women averaging 52.7 years of age. Mean time elapsed from device implantation to operation was 68 +/- 35 days. Conventional inhalational and intravenous anesthetic techniques were well tolerated in these patients undergoing diverse surgical procedures. No perioperative mortality was observed. Five of eight patients went on to successful cardiac transplantation. CONCLUSIONS: Hemodynamic recovery after LVAD insertion has defined a new group of patients who develop noncardiac surgical problems often seen in other critically ill patients. Recognition of the unique potential problems that the LVAD recipient may encounter in the perioperative period--in particular patient positioning, device limitations, and fluid and inotropic management--will ensure an optimal surgical outcome for LVAD recipients undergoing noncardiac surgery.     

Inhibitory Effect of IL-1β on HBV and HDV Replication and HBs Antigen-Dependent Modulation of Its Secretion by Macrophages

Co-infection with the hepatitis B virus and hepatitis delta virus (HDV) leads to the most aggressive form of viral hepatitis. Using in vitro infection models, we confirmed that IL-1β, a crucial innate immune molecule for pathogen control, was very potent against HBV from different genotypes. Additionally, we demonstrated for the first time a strong and rapid antiviral effect induced by very low doses of IL-1β against HDV. In parallel, using co-culture assays, we demonstrated that monocytes exposed to HBV, and in particular to HBsAg, during differentiation into pro-inflammatory macrophages secreted less IL-1β. Altogether, our data emphasize the importance of developing combined antiviral strategies that would, for instance, reduce the secretion of HBsAg and stimulate the immune system to produce endogenous IL-1β efficient against both HBV and HDV.     

Nanomolar propofol stimulates glutamate transmission to dopamine neurons: a possible mechanism of abuse potential?

Anesthesiologists among physicians are on the top of the drug abuse list, and the mechanism is unclear. Recent studies suggest occupation-related second-hand exposure to i.v. drugs, including propofol, may play a role. Growing evidence indicates that propofol is one of the choices of drugs being abused. In this study, we show that propofol at minute concentrations increases glutamatergic excitatory synaptic transmission and discharges of dopamine neurons in the ventral tegmental area (VTA). We found that acute application of propofol (0.1-10 nM) to the VTA in midbrain slices of rats increased the frequency but not the amplitude of spontaneous excitatory postsynaptic currents (EPSCs) mediated by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. We observed that propofol increased the amplitude but decreased the paired-pulse ratio of EPSCs evoked by stimulation in the absence and the presence of gabazine (SR 95531), a GABA(A) receptor antagonist. Moreover, the propofol-induced facilitation of EPSCs was mimicked by 6-phenyl-4-azabicyclo[5.4.0]undeca-7,9,11-triene-9,10-diol (SKF38393), an agonist of dopamine D(1) receptor, and by 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine dihydrochloride (GBR 12935), a dopamine reuptake inhibitor, but blocked by (+/-)-7-bromo-8-hydroxy-3-methyl-1-phenyl-2,3,4, 5-tetrahydro-1H-3-benzazepine hydrochloride (SKF83566), a D(1) antagonist, or by depleting dopamine stores with reserpine. Finally, 1 nM propofol increased the spontaneous discharge rate of dopamine neurons. These findings suggest that propofol at minute concentrations enhances presynaptic D(1) receptor-mediated facilitation of glutamatergic synaptic transmission and the excitability of VTA dopamine neurons, probably by increasing extracellular dopamine levels. These changes in synaptic plasticity in the VTA, an addiction-related brain area might contribute to the development of propofol abuse and the increased susceptibility to addiction of other drugs.     

Short report: edematous Mycobacterium ulcerans infection (Buruli ulcer) on the face: a case report

We report a case of a four-year-old Angolan boy with the edematous form of Buruli ulcer on the face and scalp, who was treated at a rural hospital in the Bas-Congo Province, Democratic Republic of Congo. Treatment consisted of a series of surgical interventions and antimycobacterial chemotherapy (rifampin and ciprofloxacin) for two months. This case demonstrates the diagnostic and management difficulties of an edematous lesion of BU on the face and suggests an enhancement of healing and limitation of extent of excision by specific antibiotherapy. The outcome in this patient also underscores the importance of prompt referral of suspected cases and training of health professionals in the early diagnosis of BU.     

Population history and infrequent mutations: how old is a rare mutation? GUCY2D as a worked example

The mosaic pattern of haplotypes observed around a single mutation results from one or several founder events. The difficulties involved in calculating the age of the variant are greatly reduced by assuming a single event, but this simplification may bias analysis of the genealogy of the mutation. However, if it is assumed that more than one founder event occurred, the number of genealogies is very large and the likelihood of every possible tree could not be realistically calculated. A multipoint approach is required, given the number of independent variables needed to describe a complex bifurcating genealogy. Starting from the observation that a limited number of parameters is needed for calculation of the simplest models of bifurcating genealogies, we show that the probability density of a two-ancestor model genealogy can be simply described as an algebraic function in a closed form, two coalescence times being calculated simultaneously without compromising accuracy. Implementation in a Bayesian framework is facilitated by the simplicity of the function, which describes the reciprocal relationship between the region of complete linkage disequilibrium and the branch length of the tree. We illustrate the use of haplotype information about allele-sharing decay around a mutation as a genetic clock, using data for two GUCY2D mutations in Mediterranean populations.     

Using the Edinburgh postnatal depression scale to screen for perinatal anxiety

We replicated the factor structure of the anxiety subscale of the Edinburgh Postnatal Depression Scale (EPDS) in a large convenience sample of Western Australian women who participated in the beyondblue National Postnatal Depression Program. In addition, we determined an appropriate cut-off score for the anxiety subscale. Factor analyses conducted on the EPDS responses yielded depression and anxiety factors as identified in previous research. Two-factor solutions accounted for over 50% of the variance at two time frames: antenatally (N = 4,706) and at postnatal follow-up (N = 3,853). The anxiety and depression factors had similar factor structures antenatally and postnatally and were consistent with previous published findings. The concurrent validity of the anxiety subscale was demonstrated by its significant relationship to anxiety-related items on a psychosocial risk factors questionnaire. Anxiety dropped significantly from the antenatal to the postnatal time period. These findings confirm the anxiety subscale of the EPDS and point to its utility in screening for anxiety symptoms using a cut-off score ≥4 which captured the top quartile of the antenatal sample.     

Risk Prediction for Peripartum Cardiomyopathy in Delivering Mothers: A Validated Risk Model: PPCM Risk Prediction Model

BackgroundPeripartum cardiomyopathy (PPCM) causes significant morbidity and mortality in childbearing women. Delays in diagnosis lead to worse outcomes; however, no validated risk prediction model exists. We sought to validate a previously described model and identify novel risk factors for PPCM presenting at the time of delivery.Methods and ResultsAdministrative hospital records from 5,277,932 patients from 8 states were screened for PPCM, identified by International Classification of Disease-9 Clinical Modification codes (674.5x) at the time of delivery. Demographics, comorbidities, procedures, and outcomes were quantified. Performance of a previously published regression model alone and with the addition of novel PPCM-associated characteristics was assessed using receiver operating characteristic area under the curve (AUC) analysis. Novel risk factors were identified using multivariate logistic regression and the likelihood ratio test. In total, 1186 women with PPCM were studied, including 535 of 4,003,912 delivering mothers (0.013%) in the derivation set compared with 651 of 5,277,932 (0.012%) in the validation set. The previously published risk prediction model performed well in both the derivation (area under the curve 0.822) and validation datasets (area under the curve 0.802). Novel PPCM-associated characteristics in the combined cohort included diabetes mellitus (odds ratio [OR] of PPCM 1.93, 95% confidence interval [CI] 1.23–3.02, P = .004), mood disorders (OR 1.74, 95% CI 1.22–2.47, P = .002), obesity (OR 1.92, 95% CI 1.45–2.55, P < .001), and Medicaid insurance (OR 1.54, 95% CI 1.22-1.96, P < .001).ConclusionsThis is the first validated risk prediction model to identify women at increased risk for PPCM at the time of delivery. Diabetes mellitus, obesity, mood disorders, and lower socioeconomic status are risk factors associated with PPCM. This model may be useful for identifying women at risk and preventing delays in diagnosis.