Mouse models of holoprosencephaly

PURPOSE OF REVIEW: Holoprosencephaly (HPE) is the most common anomaly of forebrain development in humans. The pathogenesis of HPE results in a failure of the brain hemispheres to separate during early development. Here we review experimental models of HPE in which some of the genes known to cause HPE in humans have been disrupted in the mouse. RECENT FINDINGS: To date, mutations that cause HPE have been identified in seven genes. Three of these genes encode members of the Sonic hedgehog (SHH) signaling pathway, which regulates the development of ventral structures throughout the neuraxis. Two other HPE mutations affect signaling by Nodal ligands, which also play important roles in neural patterning. The roles of the two other known HPE genes are not yet clear. Analysis of genetically altered mice has revealed that mutations in other members of the SHH and Nodal signaling pathways also result in HPE phenotypes. SUMMARY: Studies of HPE in the mouse have provided a framework for understanding key developmental events in human brain development and may provide new candidate genes for human HPE. Despite this progress, fundamental mysteries remain about how molecules that pattern ventral brain regions ultimately disrupt the formation of the cerebral hemispheres in dorsal regions.     

Radiologically guided balloon dilation of gastrointestinal strictures. Part I. Technique and factors influencing procedural success

Radiologically guided balloon catheters were used to dilate 94 gastrointestinal strictures in 92 patients over a 6-year period. Fifty strictures were esophageal and 44 nonesophageal (22 gastroenterostomies, 11 antral-pyloric strictures, four colorectal strictures, four enteroenterostomies, and three miscellaneous strictures). Factors influencing the success of stricture intubation included patient age, stricture location (esophageal vs. nonesophageal and proximal vs. distal esophageal), and association with a surgical anastomosis. Malignancy was associated with greater postdilation irregularity and a smaller increase in stricture diameter, as measured radiographically. Procedural failures occurred in 8% of cases (2% of esophageal and 30% of nonesophageal lesions). Two small, asymptomatic mucosal tears were seen after dilation (one esophageal and one colonic); no other procedural complications occurred. Following successful dilation, 16 patients (17%; six with esophageal and ten with non-esophageal strictures) had recurrence of symptoms during short-term (30-day) follow-up.     

Stability and change in milder psychiatric disorder over 7 years in a birth cohort.

BACKGROUND: Relatively little is known regarding stability or change over time in milder psychiatric disorder identified in epidemiological studies. METHODS: Data were analysed on 2890 subjects from the 1946 British birth cohort study. Psychiatric disorder was identified at age 36 years using the Present State Examination Index of Definition and 7 years later at age 43 using a symptom scale, employing a threshold to give identical 6% prevalence of disorder. Predictors were derived from recent social data and information collected earlier in childhood and younger adulthood. RESULTS: Over 7 years, there was considerable movement between case and non-case status. Only 1.7% of the sample satisfied case criteria at both points. Approximately two-thirds of cases at age 36 had fallen below case levels at age 43 and two-thirds of cases at age 43 were new cases. Most onsets and remissions were between definite case and non-case levels, rather than around the threshold. The strongest predictors of onset and remission were recent demographic, social and life stress variables, and earlier reported nervous disorder, with contributions from parental social background, and life history variables in adolescence. CONCLUSIONS: There is considerable change over 7 years in milder psychiatric disorder, with around two-thirds of it episodic or fluctuating and one-third chronic. Recent social variables are strong predictors of change or chronicity, with some lasting contributions from childhood social setting and earlier life history.