Pediatric patients with eosinophilic esophagitis: an 8-year follow-up

BACKGROUND: Eosinophilic esophagitis (EE) is a gastrointestinal disorder that is increasingly diagnosed in pediatric patients. OBJECTIVE: We aimed to define, in pediatric patients with EE, their demographic and atopic characteristics, the histopathology of all segments of the gastrointestinal tract, and the effect of therapeutic interventions on the natural history. METHODS: We conducted a retrospective analysis of a database of pediatric patients with EE followed over a period of 8 years. RESULTS: In 89 pediatric patients with EE, male sex (78.6%), white race (94.4%), young age at diagnosis, mean +/- SD, 6.2 +/- 4.8 years, and atopy with sensitization to environmental and food allergens in 79% and 75%, respectively, were prevalent. Patients had EE of the proximal and distal esophagus, and 77% had in addition either mucosal eosinophilia or noneosinophilic histopathology in the stomach, duodenum, and colon. EE was chronic, with a duration of mean +/- SD, 0.91 +/- 0.84 years, until first resolution, and was recurrent; of 66% of the patients who had resolution, 79% later relapsed. CONCLUSION: Eosinophilic esophagitis in the pediatric population is a chronic and relapsing condition, associated with atopy and sometimes with subsequent histopathology in segments of the gastrointestinal tract other than the esophagus. CLINICAL IMPLICATIONS: Physicians evaluating pediatric patients with chronic gastrointestinal symptoms should consider the diagnosis of EE, particularly in young white male patients with atopy. Once diagnosed and treated, the physicians should follow the patients over a period of several years because the course of the disease is protracted, other gastrointestinal segments may be affected, and relapses are common.     

Predicting clinical ischaemia during awake carotid endarterectomy: use of the SJVO2 probe as a guide to selective shunting

Stroke is a major cause of disability within the western world. About 20% of strokes are a consequence of atheromatous narrowing of the origin of the internal carotid artery. Carotid endarterectomy has been shown to be an effective treatment for those with symptomatic and severe stenosis, provided the risk of death and peri-operative stroke is less than 7%. The aim of this study was to investigate the clinical value of jugular venous oxygen saturation (SJVO2) monitoring in identifying patients who develop cerebral ischaemia whilst undergoing an awake carotid endarterectomy by comparison with a simple neurological assessment. Each patient underwent a standard awake carotid endarterectomy. Peri-operatively a SJVO2 catheter was inserted, and the jugular oxygen saturation was correlated with the presence or absence of cerebral ischaemia. Data from 34 patients were analysed using time-series plots and by calculating a receiver operator characteristic (ROC) curve. The optimal sensitivity and specificity for this technique were found to be 1.0 and 0.8, respectively, when a 25% change in SJVO2 was used as a threshold. Although a small observational study, we have shown that percentage change in SJVO2 correlates well with the development of clinically apparent cerebral ischaemia. This technique may improve the safety of carotid endarterectomy under general anaesthesia when used with other more established monitoring methods.     

Mouse spinal cord in cell culture. I. Morphology and intrinsic neuronal electrophysiologic properties.

1. Reliable methods for establishing fetal mouse spinal cord (SC) and dorsal root ganglion (DRG) cells in long term (greater than 1 mo) dissociated cell cultures are described. These cells have been studied by morphologic and intracellular electrophysiologic techniques. 2. Cells studied electrophysiologically can be relocated after preparation for electron microscopy and examined in thin sections. The electron microscope shows that the surface membranes of these cells were directly accessible to the culture medium. The surfaces of SC cells were studded with synaptic boutons, whereas the DRG cell surfaces generally had none. 3. Current-voltage relationships and linear electrotonic properties of the neurons are described. Delayed and anomalous rectification were seen in both cell types. The length of SC cell dendrites was about one characteristic electrotonic length, while little or no contribution of the relatively sparse DRG cell processes was seen in the transient responses of the DRG cells. 4. Postspike and posttetanic hyperpolarizations in DRG cells were due to a surface membrane conductance increase; this was probably primarily an increase in K+ conductance. Post-activation hyperpolarization in SC cells was primarily due to activation of an electrogenic Na+ pump.     

Can the apparent adaptation of dopamine neurons’ mismatch sensitivities be reconciled with their computation of reward prediction errors?

According to modern reinforcement learning theories, midbrain dopamine (DA) neurons are part of an adaptive system within which learned expectations filter reward-related signals to enable computation of reward prediction errors (RPEs). Recent electrophysiological data on DA neuron responses to probabilistic reward schedules inspired the idea that DA neurons might be adapting their mismatch sensitivities to reflect variances of expected rewards. Taken literally as a mathematical hypothesis, this idea contradicts reinforcement learning theory, and most computational models of basal ganglia learning. Here, we report a qualitative mathematical derivation of the implications of a generic class of circuit models for learning to compute RPEs. This analysis and concordant circuit simulations, both of which predict DA neuron responses on probabilistic schedules, support a reinterpretation of the electrophysiological data that is fully compatible with the examined class of RPE models. This reinterpretation implies a novel and readily testable prediction.