Reliability of information collected by proxy in family studies of Alzheimer's disease

The study evaluated the reliability of data obtained from proxy informants. The index subjects in this study were 81 nondemented participants in the Multi-Institutional Research in Alzheimer Genetic Epidemiology (MIRAGE) study. These index subjects and 159 proxy informants, identified by the index subjects, participated in the study. The kappa statistic with multiple raters per subject (for dichotomous variables) and the intraclass correlation coefficient (for continuous variables) were used to measure reliability. Among proxy respondents who provided answers, there was excellent agreement between proxy responses and the responses of the index subjects (0.7 < or = kappa < or =0.9), with the exception of questions about head injury (kappa = 0.4). A large proportion (>90%) of the proxy informants in this study were able to provide information on most items. Higher nonresponse rates (as high as 30%) were observed for medication history and women's health questions. This study supports the reliability of proxy responses for most categories of questions that are elicited in typical epidemiological studies, including the MIRAGE study.     

Experience with hyperselective vagotomy in patients with duodenal ulcer

Hyperselective vagotomy is a relatively recent surgical procedure used for the treatment of duodenal ulcer. We report excellent results in 98 consecutive patients during the last four years. After a mean follow-up period of 2.2 years, the results, according to the classification of Visick, are excellent in a large number of patients. There was a significant gain in body weight in a majority of the patients. The recurrence rate for an ulcer is only 4.5 per cent. There is a significant reduction of basal acid output of 63 per cent, maximal acid output of 46.8 per cent and postinsulin acid output of 73.7 per cent.     

Short stature with pigmentation

Four hypomelic children of abnormally short stature had slight intellectual defect, melanotic skin, and some facial features in common. 3 were followed to the age of 23-26 years, and they remained small and pigmented.     

Perinatal iron deficiency affects locomotor behavior and water maze performance in adult male and female rats

Iron deficiency during early growth and development adversely affects multiple facets of cognition and behavior in adult rats. The purpose of this study was to assess the nature of the learning and locomotor behavioral deficits observed in male and female rats in the absence of depressed brain iron levels at the time of testing. Adult female Wistar rats were fed either an iron-enriched diet (>225 mg/kg Fe) or an iron-restricted diet (3 mg/kg Fe) for 2 wk prior to and throughout gestation, and a nonpurified diet (270 mg/kg Fe) thereafter. Open-field (OF) and Morris water maze (MWM) testing began when the offspring reached early adulthood (12 wk). At birth, perinatal iron-deficient (PID) offspring had reduced (P < 0.001) hematocrits (-33%), liver iron stores (-83%), and brain iron concentrations (-38%) compared with controls. Although there were no differences in iron status in adults, the PID males and females exhibited reduced OF exploratory behavior, albeit only PID males had an aversion to the center of the apparatus (2.5 vs. 6.9% in controls, P < 0.001). Additionally, PID males required greater path lengths to reach the hidden platform in the MWM, had reduced spatial bias for the target quadrant, and had a tendency for greater thigmotactic behavior in the probe trials (16.5 vs. 13.0% in controls; P = 0.06). PID females had slower swim speeds in all testing phases (-6.2%; P < 0.001). These results suggest that PID has detrimental programming effects in both male and female rats, although the behaviors suggest different mechanisms may be involved in each sex.     

Cloning and expression of the gene involved in Sanfilippo B syndrome (mucopolysaccharidosis III B)

Sanfilippo B syndrome is caused by a deficiency of alpha-N- acetylglucosaminidase, a lysosomal enzyme involved in the degradation of heparan sulphate. Accumulation of the substrate in lysosomes results in degeneration of the central nervous system with progressive dementia often combined with hyperactivity and aggressive behaviour. In order to clone the deficient gene, we purified the enzyme from human placenta and obtained amino acid sequence information. Alignment of one of the CNBr generated internal peptides to sequence from the database revealed the chromosomal location of the gene in the 5' upstream flanking region of the gene for 17-beta-hydroxysteroid-dehydrogenase at 17q21.1. The available DNA sequence was used to clone the cDNA coding for alpha-N- acetylglucosaminidase and analyse its gene structure. The gene is fully contained in the 5' upstream flanking region of the gene for 17-beta- hydroxysteroid-dehydrogenase and interrupted by five introns. The cDNA clone has a length of 2575 bp and encodes a protein of 743 amino acids. Chinese hamster ovary cells transfected with the cDNA construct show alpha-N-acetylglucosaminidase activity about 17-fold over background. This will allow correction studies with NAG deficient Sanfilippo B cell lines and facilitate the development of enzyme replacement therapy for these patients.