[Rivastigmine for Alzheimer disease; evaluation of preliminary results and of structured assessment of efficacy]. / Rivastigmine bij de ziekte van Alzheimer; evaluatie van de eerste ervaringen en van gestructureerde effectmeting.

OBJECTIVE: Evaluation of the initial experiences with rivastigmine in Alzheimer's disease. DESIGN: Retrospective. METHOD: Data were collected from patients with Alzheimer's disease who were treated with rivastigmine between 1 October 1998-30 November 1999 at the Memory Disorders Outpatients Clinic at the Academic Medical Centre or the Slotervaart Hospital, both in Amsterdam, the Netherlands. Before, and 6 months after treatment, the course of the disease was evaluated using clinimetric scales relating to cognitive functions, behavioural abnormalities and instrumental daily functions. The treatment results were considered to be 'favourable' if they corresponded with a disease course seen in less than 10% of untreated Alzheimer patients. RESULTS: During the study period, 53 patients were treated, 36 women and 17 men, with a mean age of 77 years (range: 57-89). Follow-up data were incomplete for four patients. Of the remaining patients, 27 (55%; 95% CI: 40-69) withdrew from treatment during the first 6 months, mainly because of gastrointestinal side-effects. Of the other 22 patients (45%; 31-60) 18 continued with rivastigmine treatment (18/49 = 37%; 23-52), and in three of these patients the disease course was favourable (3/49 = 6%; 1-17). CONCLUSION: In daily practice, over 50% of the patients were unable to tolerate rivastigmine. Structured evaluation of treatment efficacy was feasible in this population. Treatment with rivastigmine seemed to be beneficial in a small proportion of the patients.

Heterogeneity of proteoglycans extracted before and after collagenase treatment of human articular cartilage. I. Physical properties related to age.

Proteoglycans were isolated from young and mature human articular cartilage 4 different ways: by direct extraction with 4M guanidine hydrochloride (GuHCl); after digestion of the residue from this first extraction with collagenase, by extraction with 4M GuHCl; associatively with 0.5M GuHCl after digestion of the cartilage with collagenase; and dissociatively with 4M GuHCl after digestion of the cartilage with collagenase. The structural properties of these proteoglycans were compared. Proteoglycan aggregates and monomers isolated from second extractions and from young cartilage were of larger hydrodynamic size than proteoglycans isolated from first extractions and mature cartilage, respectively. The same applied to the chondroitin sulfate chain lengths of these proteoglycans. The proteoglycan fraction from second extractions of cartilage contained a larger proportion of monomers than the fraction from first extractions. Associative extraction of mature collagenase-digested cartilage yielded mainly proteoglycan monomers, whereas an appreciable amount of proteoglycan aggregate was also liberated from young collagenase-digested cartilage. Our results indicate that, because of their larger size, proteoglycans from second extractions of cartilage are more entrapped in the collagen network. These large proteoglycans can only be liberated from the matrix after extraction of the smaller proteoglycans, followed by digestion of the residue with collagenase. This indicates that proteoglycans overlap and entangle with the collagen and protect it from degradation by collagenase.

Heterogeneity of proteoglycans extracted before and after collagenase treatment of human articular cartilage. II. Variations in composition with age and tissue source.

Proteoglycans (A1 fractions) were extracted with 4M guanidine hydrochloride (GuHCl) from human articular cartilage samples of a wide age range. Distinctions were made between hip and knee, and upper and lower layers. The residues of these extractions were digested with purified collagenase, and a second extraction with 4M GuHCl was performed, which yielded appreciable amounts of proteoglycans. When proteoglycans from second extractions were compared with those from first extractions, the following changes were observed: an increase in chondroitin sulfate; a relative decrease in keratan sulfate; a decrease in protein content; and a decrease in the ratio of chondroitin 6-sulfate to chondroitin 4-sulfate. The same changes were found when nonaggregating proteoglycans were compared with proteoglycan aggregates, when proteoglycans from young cartilage were compared with those from mature cartilage, when proteoglycans from knee cartilage were compared with those from hip cartilage, and when proteoglycans from upper layers of cartilage were compared with those from deeper layers. It is suggested that the differences found between first and second extractions of cartilage, between upper and lower layers of cartilage, and between knee and hip cartilage are caused by variations in the relative amount of nonaggregating proteoglycans and/or variations in proteoglycan size.

Metabolic and secretory properties of peripheral and synovial granulocytes in rheumatoid arthritis.

The metabolic and secretory properties of peripheral and synovial granulocytes of patients with rheumatoid arthritis were investigated with serum- or immunoglobulin-treated zymosan as activators of cell metabolism. During isolation of the synovial cells precautions were taken to prevent in vitro phagocytosis of immune materials present in the synovial fluids. Oxygen uptake, extracellular release of lysosomal enzymes under resting and activated conditions, yield of the isolated granulocytes, and the granule enzyme content of peripheral and synovial cells did not differ significantly from those of peripheral granulocytes from healthy volunteers. In agreement with the biochemical results, intracellular inclusions could be detected in only a few synovial cells with a direct immunofluorescence technique. The possibility that formation of "ragocytes" may be an in vitro phenomenon is discussed.