Weight loss in Huntington disease increases with higher CAG repeat number.

OBJECTIVE: Huntington disease (HD) is a hereditary neurodegenerative disorder caused by an expanded number of CAG repeats in the huntingtin gene. A hallmark of HD is unintended weight loss, the cause of which is unknown. In order to elucidate the underlying mechanisms of weight loss in HD, we studied its relation to other disease characteristics including motor, cognitive, and behavioral disturbances and CAG repeat number. METHODS: In 517 patients with early stage HD, we applied mixed-effects model analyses to correlate weight changes over 3 years to CAG repeat number and various components of the Unified Huntington's Disease Rating Scale (UHDRS). We also assessed the relation between CAG repeat number and body weight and caloric intake in the R6/2 mouse model of HD. RESULTS: In patients with HD, mean body mass index decreased with -0.15 units per year (p < 0.001). However, no single UHDRS component, including motor, cognitive, and behavioral scores, was independently associated with the rate of weight loss. Patients with HD with a higher CAG repeat number had a faster rate of weight loss. Similarly, R6/2 mice with a larger CAG repeat length had a lower body weight, whereas caloric intake increased with larger CAG repeat length. CONCLUSIONS: Weight loss in Huntington disease (HD) is directly linked to CAG repeat length and is likely to result from a hypermetabolic state. Other signs and symptoms of HD are unlikely to contribute to weight loss in early disease stages. Elucidation of the responsible mechanisms could lead to effective energy-based therapeutics.

An improved metabolic calibrator for stress test equipment: protocol for its clinical utilization.

In previous articles, the technical specifications, validation and clinical applicability of a new metabolic calibrator for stress test apparatuses were described. However no indication was given of a basic protocol for the current clinical practice. Here we present an organised check system to satisfy this aim. A method for the exhaustive evaluation of the technical reliability of the metabolic instruments is presented together with the proposal of a uniform simulation approach to organise checks on-line of the apparatuses' ability to follow correctly the various test phases (protocol). Examples of recordings of checks using the standardised approach are shown. The method seems to be very effective. Every operation is computer directed.

Mastoiditis: a case-based review.

Mastoiditis was a common complication of otitis media in the preantibiotic era. Because its incidence has decreased dramatically in recent years, its diagnosis can be delayed or missed, particularly in infants and young children. This delay can result in significant morbidity and increased costs, owing to longer inpatient treatment and surgical intervention. We offer a current, case-based review of the pathogenesis, presentation, and treatment of mastoiditis.

Detection of immunocytochemically stained rare events using image analysis.

The detection of rare-event cells circulating in peripheral blood using automated image analysis was evaluated using a model system consisting of cells from a breast cancer cell line (SKBR3) seeded in a mononuclear cell suspension. Slides of cells with optimal morphology were prepared according to an optimized preparation procedure based on centrifugal cytology in combination with formalin fixation. SKBR3 cells were immunocytochemically stained for cytokeratin using the cam 5.2 monoclonal antibody and labelled with alkaline phosphatase using CAS-red as substrate. Because, for optimal segmentation of cell images, plain differences in absorption wavelength are required, the red immunostaining was combined with a green nuclear counter-staining based on ethyl green. Slides were automatically screened for cytokeratin-positive SKBR3 cells resulting in a lowest detectable frequency of one positive cell per 1.87 x 10(6) negative cells. A comparison between manual screening and automated screening for cytokeratin-positive cells showed a high level of correlation (0.9998). For the definition of the total number of objects per slide, two counting procedures were evaluated. Results were close to the visual score with a coefficient of variation of 0.47% for the counting procedure used in this study. It is concluded that optimization of preparation and staining procedures for the detection of rare-event cells using automated image analysis results in optimal image contrast and, consequently, in an increase in sensitivity for detecting rare events.