Pathologic analysis of right-lobe graft failure in adult-to-adult live donor liver transplantation

Live donor adult liver transplantation (LDALT) utilizing right-lobe grafts is now acceptable as an alternative to cadaveric orthotopic liver transplantation (OLT). However, some LDALTs fail and require urgent OLT or result in recipient death. Our aim was to determine the basis of LDALT failure. Liver specimens from 49 LDALT recipients were evaluated and the findings correlated with clinical outcome. Ten patients (20.4%) had either early (< or = 1 month) or late (> 1 month) graft failure. Eight early failures, 7 of which occurred among our first 25 cases, were due to extensive liver parenchymal necrosis as a result of hepatic artery thrombosis (n=3), portal vein thrombosis (n=1), hyperperfusion syndrome (n=1), complete graft thrombosis (n=1) with Factor V Leiden on a regimen of therapeutic heparin (n=1), sepsis and concomitant graft dysfunction with venous outflow tract injury (n=1), and venous outflow tract thrombosis and parenchymal thermal injury with sepsis (n=1). Preoperative, intraoperative, or postoperative severe vessel wall injury was evident in 6/8 early failures. Two patients had late graft failure, 1 from recurrent hepatitis C and 1 with sepsis/multisystem organ failure. There were no significant differences in graft size, rejection episodes, or operative or ischemic times between patients with and without graft failure. In conclusion, LDALT failed in 10/49 (20%) of our patients, with 8/10 occurring within 1 month post-LDALT owing to vascular/thrombotic complications experienced during the early phase of our institutional experience. Perioperative vessel wall injury appeared to be a major factor in predicting early graft loss.     

Spontaneous alpha peak frequency predicts working memory performance across the age span.

Working memory capacity has been consistently shown to decline with increasing age. Mechanisms underlying this decline are poorly understood. One index that has been found to predict performance on memory tests is alpha peak frequency, the peak of spectral alpha power of the EEG. Activity in the alpha band has been also associated with higher cognitive functions including attention and anticipation and has been shown to slow with age. Few studies, however, have examined whether there might be a relationship between WM decline and alpha peak frequency. The present study specifically investigated this relationship. Digit span was used as the index of WM function. The study made use of 550 normal subjects aged between 11 and 70 years in the Brain Resource International Database. The data were acquired from six laboratories located in the USA (2), Europe (2) and Australia (2). Forward and reverse digit span were found to be lower in older relative to younger age groups. Spontaneous alpha peak frequency slowed with age and more so at anterior than posterior sites. Frontal alpha peak frequency was found to be a significant predictor of reverse digit span, with each 1 Hz increase in frequency associated with a 0.21 increase in reverse digit span score and this was independent of age, indicating a positive relationship between alpha peak frequency and working memory performance.     

Car seat test for preterm infants: comparison with polysomnography

Objectives

To monitor preterm infants in a cot and a car seat and compare an observed car seat trial with polysomnography (PSG).

Design

Non‐randomised controlled trial.

Setting

Regional neonatal unit.

Patients

Preterm infants before discharge.

Interventions

Nap PSG respiratory and sleep variables were measured including gastro‐oesophageal pH. Nurse observations included respiratory distress, apnoea measured by apnoea alarm, oxygen saturation and heart rate. Infants were studied supine in a cot and then in a car seat. Nursing observations were compared with PSG during the car seat trial only. Criteria for failure of the PSG and observed tests were predefined.

Main outcome measures

Difference in respiratory instability between cot and car seat. Concurrence regarding failure of the car seat trial between nurse‐observed data and PSG.

Results

20 infants (median gestation 33 weeks (range 28–35 weeks; median postmenstrual age (PMA) at study 36.5 weeks (range 35–38 weeks)) were studied. There were sufficient car seat data on 18 infants for comparison. There were fewer central apnoeas and arousals in the cot than the car seat (p = 0.047 and p = 0.024, respectively). Airway obstruction was not more common in the car seat. Younger PMA at time of study predicted failure in both car seat (p = 0.022) and cot (p = 0.022). The nurse‐observed test had low sensitivity for predicting PSG failure but more accurately predicted airway obstruction on PSG.

Conclusions

Immature infants exhibit respiratory instability in cots and car seats. A car seat test does not accurately detect all adverse events during sleep in the seat.Since concerns were first raised about the vulnerability of preterm infants during transportation,1,2 several studies have attempted to quantify the respiratory compromise experienced by these infants while in car seats.3,4,5,6,7,8,9,10,11,12,13 Many of these studies had methodological limitations as not all measured the sleep state, or used a supine position for comparison or airflow measures to detect obstructive apnoea, or allowed for differences in postmenstrual age (PMA) at study.Although car seat trial before discharge has been incorporated into many neonatal discharge practices it has not been universally accepted as the gold standard test for assessing risk of respiratory compromise in a car seat after discharge.14,15,16 Despite many neonatal nurseries implementing variations of the practice,14 criteria defining how premature infants should be monitored, how long to monitor or what constitutes failure of the test are lacking.15,17,18 Neonatal unit car seat testing programmes therefore vary in equipment type, quality, time and outcome data.14The present study aimed to examine respiratory variables during active and quiet sleep in preterm infants ready for discharge and compare variables recorded supine in a cot with those recorded supine in a car seat, in particular, to determine whether more obstructive events occurred after transfer to the car seat. A second aim was to compare car seat testing before discharge with concurrent polysomnography (PSG) recording to determine if a nurse‐observed test was a sensitive enough predictor of respiratory instability, and in particular airway obstruction, found on PSG.     

Receptors and ligands involved in viral induction of type I interferon production by plasmacytoid dendritic cells

Virus infection is sensed by the innate immune system which then rapidly initiates biosynthesis of type I interferon (IFN). The IFN signaling systems produce a broadly effective innate antiviral response by creating an antiviral state in both an autocrine and paracrine manner in cells and by activating innate and adaptive immunity. Plasmacytoid dendritic cells (pDCs) have the unique ability to produce very high levels of type I IFN following viral infection in vivo. Most recent research has focused on oligonucleotide-mediated induction of type I IFN production, implicating viral genome and replication intermediates as the stimulus for this response. However there are additional viral ligands which can potentially induce type I IFN production in pDCs, such as envelope glycoproteins, viral glycolipids, tegument, capsid or nuclear proteins. This area of viral immunology, which has been neglected in the literature, will be discussed here.     

Mixture models of serum iron measures in population screening for hemochromatosis and iron overload

Homozygosity for the C282Y mutation of the hemochromatosis gene on chromosome 6p (HFE) is a common genetic trait that increases susceptibility to iron overload. The authors describe and apply methodology developed for the analysis of phenotypic and genotypic data from 46,136 non-Hispanic Caucasians, a subset of the multi-ethnic cohort enrolled in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. For analysis of the distribution of transferrin saturation (TS), mixtures of normal distributions were considered and the expectation-maximization (EM) algorithm was applied for parameter estimation. Maximized log-likelihoods were compared, and significance was assessed by resampling. Sensitivity, specificity, and predictive values from the modeled subpopulations were compared with the actual observed genotypes for C282Y and H63D mutations in the HFE gene. A strong association between HFE genotype and TS subpopulations was found in these data collected from different geographic regions, confirming the external validity of the statistical approach when applied to population-based data. It was concluded that mixture modeling of phenotypic data may provide a clinical guide for screening with gender-specific thresholds to identify potential samples for genetic testing.     

Right-lateralized pain processing in the human cortex: an FMRI study

Neuroimaging studies of human pain have revealed a widespread "pain matrix" distributed across both hemispheres of the brain. It is not resolved whether the pain matrix is biased toward one hemisphere, although behavioral and clinical data suggest that pain is perceived differently on the two sides of the body, and several neuroimaging studies suggest that pain processing in some regions of cortex may be lateralized toward the right hemisphere. The current study used fMRI in nine subjects to determine whether acute pain is preferentially processed in one cortical hemisphere. All cortical areas that were activated during the painful simulation were investigated, and several analytic approaches were used to directly compare activated regions to similar regions in the opposite hemisphere. Results indicated that four regions of the cortical pain matrix were activated either contralaterally (somatosensory cortex) or bilaterally (mid/posterior insula, anterior insula, and posterior cingulate). In addition, activation in five cortical regions during acute pain stimulation was localized either exclusively in the right hemisphere or was strongly lateralized to the right. These five areas were in the middle frontal gyrus, anterior cingulate, inferior frontal gyrus, medial/superior frontal gyri, and inferior parietal lobule. The location of some of these regions is consistent with the idea that there may be a right-lateralized attentional system to alert an organism to an infrequent, but behaviorally relevant, stimulus such as pain.     

Competitive ELISA employing monoclonal antibodies specific for coronafacoyl amino acid conjugates

Coronatine (COR) is composed of two structural components, coronafacic acid (CFA) and the amino acid coronamic acid (CMA), linked by an amide bond. Monoclonal antibodies (MAbs) were prepared against COR and incorporated into competitive ELISAs. MAbs were secreted by hybridoma cells which had been prepared from mice immunized with COR and conjugated, through the free carboxyl group on CMA, to ovalbumin, the available amino groups of which had been increased by derivatization with propyl diamine via free carboxyl groups. COR and coronafacoyl valine could be quantified at 6.800 ng ml^‐1(0.34–40 ng/assay) using peroxidase‐labelled MAb 8H3G2 in an indirect competitive ELISA. The corresponding limit of detection was 1 ng ml～’. Reduction and subsequent acetylation of the ketone oxygen of the CFA moiety of COR reduced the affinity of MAb 8H3G2 some 250 times, whereas methylation of the free carboxyl group on COR slightly enhanced the affinity four‐fold. These and other results suggest that CFA and the amide bond are important structural features of the epitope recognized by MAb 8H3G2.     

Prevalence of hypothalamic-pituitary-adrenal axis suppression in children treated for asthma with inhaled corticosteroid

OBJECTIVE:

To determine the prevalence of hypothalamic-pituitary-adrenal (HPA) axis suppression in asthmatic children on inhaled corticosteroids (ICS).

METHODS:

Clinical and demographic variables were recorded on preconstructed, standardized forms. HPA axis suppression was measured by morning serum cortisol levels and confirmed by low-dose adrenocorticotropic hormone stimulation testing.

RESULTS:

In total, 214 children participated. Twenty children (9.3%, 95% CI 5.3% to 13.4%) had HPA axis suppression. Odds of HPA axis suppression increased with ICS dose (OR 1.005, 95% CI 1.003 to 1.009, P<0.001). All children with HPA axis suppression were on a medium or lower dose of ICS for their age (200 μg/day to 500 μg/day). HPA axis suppression was not predicted by drug type, dose duration, concomitant use of long-acting beta-agonist or nasal steroid, or clinical features.

CONCLUSION:

Laboratory evidence of HPA axis suppression exists in children taking ICS for asthma. Children should be regularly screened for the presence of HPA axis suppression when treated with high-dose ICS (>500 μg/day). Consideration should be given to screening children on medium-dose ICS.