Studies on human factor VIII and its antibodies using radiolabelling and affinity chromatography

An immuno-affinity chromatography methods was used to isolated human factor VIII and its antibodies and the mechanism of the affinity system was investigated using iodine labelling. Rabbit antibodies to human factor VIII were insolubilised onto CNBr - activated Sepharose 2B which was used for the preparation of affinity columns. Both VIII:C and VIIIR:Ag were adsorbed onto such columns from factor VIII preparations. The subsequent application of immunoglobulin preparations containing human antibodies to factor VIII resulted in the adsorption of these antibodies onto the columns. Adsorbed material was eluted from the affinity columns with 0.2 M glycine - HCl, pH 2.3. When 125I-labelled factor VIII and 131I-labelled human antibodies to factor VII were used in this affinity system, the eluted material could be separated into three fractions by gel filtration on Bio-Gel A 1.5 m. Fraction 1 occurred at the void volume position, fraction 3 at a position corresponding to the elution position of IgG and fraction 2 at an intermediate position. 131I-labelled material was present in all three peaks. 125I-labelled material was present mainly in peak 1, with a little in peak 2. The results support the view that VIIIR:Ag, which binds heterologous antibodies, is non-covalently linked to a smaller subunit, VIII:C, which binds homologous antibodies.     

Cognition, function, and caregiving time patterns in patients with mild-to-moderate Alzheimer disease: a 12-month analysis

Placebo data were pooled from two 1-year, randomized, double-blind, placebo-controlled trials of sabeluzole in patients with mild-to-moderate Alzheimer disease (AD). Cognition was assessed using the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and activities of daily living (ADL) with the Disability Assessment in Dementia (DAD). Time spent assisting with ADL was estimated according to the caregiver for each DAD domain in the 2 weeks before assessment. Progressive annual decline was seen on ADAS-cog (5.6 +/- 7.3 [mean +/- SD]) and DAD (-12.4 +/- 17.8), with greater decline in moderate patients (Mini-Mental State Examination [MMSE] < or =18) than mild patients (MMSE >18). An MMSE score of 16 appeared to be a key transition point at which most instrumental ADL were lost and major losses of basic ADL began to occur over the next 12 months. Caregivers spent, on average, 14 hours more assisting with ADL over 2 weeks at the end of 1 year. The proportion of care provided by paid caregivers increased relative to the time spent by informal caregivers. Patients with mild-to-moderate AD experience predictable annual decline in cognition and daily functioning, with measurably increased caregiver time. Small changes in ADAS-cog are nevertheless associated with a substantial measurable effect on the daily lives of both patients and caregivers.     

Executive control of working memory in schizophrenia

There is considerable evidence that working memory impairment is a common feature of schizophrenia. The present study assessed working memory and executive function in 54 participants with schizophrenia, and a group of 54 normal controls matched to the patients on age, gender and estimated premorbid IQ, using traditional and newer measures of executive function and two dual tasks-Telephone Search with Counting and the Memory Span and Tracking Task. Results indicated that participants with schizophrenia were significantly impaired on all standardised measures of executive function with the exception of a composite measure of the Trail Making Test. Results for the dual task measures demonstrated that while the participants with schizophrenia were unimpaired on immediate digit span recall over a 2-min period, they recalled fewer digit strings and performed more poorly on a tracking task (box-crossing task) compared with controls. In addition, participants with schizophrenia performed more poorly on the tracking task when they were required to simultaneously recall digits strings than when they performed this task alone. Contrary to expectation, results of the telephone search task under dual conditions were not significantly different between groups. These results may reflect the insufficient complexity of the tone-counting task as an interference task. Overall, the present study showed that participants with schizophrenia appear to have a restricted impairment of their working memory system that is evident in tasks in which the visuospatial sketchpad slave system requires central executive control.     

Pseudo compartment syndrome of the calf in an athlete secondary to cystic adventitial disease of the popliteal artery

We report a patient with calf pain induced by sport and exercise, initially thought to represent compartment syndrome, in whom MRI and duplex ultrasound ultimately revealed cystic adventitial disease of the popliteal artery. Surgical de-roofing of the popliteal artery resulted in complete resolution of symptoms with return to sporting activities.