Psychiatric and neuropsychological characterization of Pallister-Hall syndrome.

Pallister-Hall syndrome (PHS) is a rare, single-gene, malformation syndrome that includes central polydactyly, hypothalamic hamartoma, bifid epiglottis, endocrine dysfunction, and other anomalies. The syndrome has variable clinical manifestations and is inherited in an autosomal dominant pattern. We sought to determine whether psychiatric disorders and/or neuropsychological impairment were characteristic of PHS. We prospectively conducted systematic neuropsychiatric evaluations with 19 PHS subjects ranging in age from 7 to 75 years. The evaluation included detailed clinical interviews, clinician-rated and self-report instruments, and a battery of neuropsychological tests. Seven of 14 adult PHS subjects met diagnostic criteria for at least one DSM-IV Axis I disorder. Three additional subjects demonstrated developmental delays and/or neuropsychological deficits on formal neuropsychological testing. However, we found no characteristic psychiatric phenotype associated with PHS, and the frequency of each of the diagnoses observed in these subjects was not different from that expected in this size sample. The overall frequency of psychiatric findings among all patients with PHS cannot be compared to point prevalence estimates of psychiatric disease in the general population because of biased ascertainment. This limitation is inherent to the study of behavioral phenotypes in rare disorders. The general issue of psychiatric evaluation of rare genetic syndromes is discussed in light of this negative result.

Neuroimaging in delirium and related conditions.

Delirium is one of the most fascinating and poorly understood syndromes in medicine. To a large extent, attempts to study the pathophysiology of delirium have been hampered by the many different types of delirium and their variable symptom expression. The emergence of sophisticated brain imaging methodologies has made it possible to move beyond diagnostic considerations and investigate the neurobiology of specific symptom clusters observed in delirium and related conditions. In this review, neuroimaging findings of relevance to delirium are interpreted in relation to phenomenologically similar symptom states as well as clinical diagnoses. A promising approach in this regard is to combine neuroimaging techniques with symptom-provoking pharmacologic challenge paradigms. Such symptom-oriented neuroimaging studies hold particular promise for improving our understanding of the pathophysiology of delirium and its treatment.

Neuropsychiatric toxicity associated with cytokine therapies.

The cytokines interleukin-2 and interferon-alpha are potent biological agents used to treat malignancy, infectious diseases, and neurodegenerative disorders. While these medications show substantial therapeutic promise, the neuropsychiatric toxicity associated with these agents is often treatment-limiting. The pathophysiology of this toxicity is not well delineated, and adverse effects to the central nervous system are often misdiagnosed by clinicians. This report reviews the preclinical and clinical literature describing the morbidity associated with these agents and suggests appropriate clinical management strategies and future directions for research.

How does a virus bud?

How does a virus bud from the plasma membrane of its host? Here we investigate several possible rate-limiting processes, including thermal fluctuations of the plasma membrane, hydrodynamic interactions, and diffusion of the glycoprotein spikes. We find that for bending moduli greater than 3 x 10(-13) ergs, membrane thermal fluctuations are insufficient to wrap the viral capsid, and the mechanical force driving the budding process must arise from some other process. If budding is limited by the rate at which glycoprotein spikes can diffuse to the budding site, we compute that the budding time is 10-20 min, in accord with the experimentally determined upper limit of 20 min. In light of this, we suggest some alternative mechanisms for budding and provide a rationale for the observation that budding frequently occurs in regions of high membrane curvature.

Acute upper airway obstruction resulting from systemic diseases.

Acute upper airway obstruction is usually associated with inflammatory processes such as epiglottitis, and with laryngeal trauma and laryngeal tumors. Not uncommonly, systemic diseases such as Wegener's granulomatosis and sarcoidosis may manifest initially as upper airway obstruction requiring intubation or tracheostomy. We describe our experience in the diagnosis and management of cases of airway obstruction due to previously undiagnosed systemic diseases. We believe that physicians should be familiar with the airway manifestations of these systemic diseases when treating patients with airway distress of apparently unknown cause.