A presenilin 1 mutation (L420R) in a family with early onset Alzheimer disease,seizures and cotton wool plaques,but not spastic paraparesis

Over 100 mutations in the presenilin‐1 gene (PSEN1) have been shown to result in familial early onset Alzheimer disease (EOAD), but only a relatively few give rise to plaques with an appearance like cotton wool (CWP) and/or spastic paraparesis (SP). A family with EOAD, seizures and CWP was investigated by neuropathological study and DNA sequencing of the PSEN1 gene. Aβ was identified in leptomeningeal vessels and in cerebral plaques. A single point mutation, p.L420R (g.1508T > G) that gives rise to a missense mutation in the eighth transmembrane (TM8) domain of PS1 was identified in two affected members of the family. p.L420R (g.1508T > G) is the mutation responsible for EOAD, seizures and CWP without SP in this family.     

Impaired helix 12 dynamics due to proline 892 substitutions in the androgen receptor are associated with complete androgen insensitivity

Human Molecular Genetics (2006) 15, 921–931;     

Physiologic mechanism and preoperative prediction of new-onset dysphagia after laparoscopic Nissen fundoplication

The aim of this study was to determine whether preoperative physiologic factors can account for and be used to predict the development of postoperative dysphagia after laparoscopic Nissen fundoplication. One hundred sixty-three patients with gastroesophageal reflux disease underwent laparoscopic Nissen fundoplication with a median follow-up of 14 months (range 6 to 81 months). Preoperative dysphagia was present in 37% (60 of 163) and was relieved in all but five patients (92%). Female sex (P = 0.01) and the presence of a stricture (P = 0.02) were the only preoperative variables associated with the presence of preoperative dysphagia. Eight percent (8 of 103) of patients without preoperative dysphagia developed new-onset dysphagia, and of these 63% (5 of 8) had a normal lower esophageal sphincter (LES) (pressure >6 mm Hg; length >2 cm; abdominal length >1 cm). New-onset dysphagia was significantly more common in patients with a normal LES (22% [5 of 23] vs. 4% [3 of 80], P = 001). Patients with a normal LES had almost a sixfold increase in the risk of developing dysphagia as those with an abnormal LES (relative risk = 5.8). Only a preoperative normal LES (P = 0.02) or mean LES pressures (P = 0.04) were positively associated with the development of postoperative dysphagia. The severity of this dysphagia also showed a strong positive trend of increasing with mean preoperative LES pressures (P = 0.07). Finally, preoperative LES pressure significantly correlated with postoperative LES pressure (r = 0.48, P = 0.01) and with mean residual LES (nadir) pressure (r = 0.33, P = 0.05) offering insight into the mechanism of this dysphagia. In conclusion, preoperative LES parameters play a role in the development of dysphagia after laparoscopic Nissen fundoplication. Patients with a normal LES or high mean LES pressures are at increased risk for developing this complication and should be informed of this before laparoscopic Nissen fundoplication. Presented at the Forty-Second Annual Meeting of The Society for Surgery of the Alimentary Tract, Atlanta, Ga., May 20–23, 2001.