ABSTRACT
Gaucher disease is an uncommon autosomal recessive disorder characterized by lysosomal storage of glucosyl ceramide, a material released during cell degradation. Patients with Gaucher disease often have significant hematologic, bone structural, and visceral problems which sometimes greatly affect their health and life style. Based on some extraordinary scientific discoveries over the past 45 years, a treatment system has evolved which consists of administration of an enzyme, which destroys the lysosome-stored material and to some extent restores the patients to good health. There are still some problems for these patients; however, and the purpose of the study is to define some of the clinical, sociologic, and psychologic problems with a specially designed questionnaire. Questionnaire data was collected for 128 patients from two institutions with complete anonymity, and the information compared against data from a National Health Interview Survey. The results show that many of the patients still have fairly extensive problems, which could possibly be helped by some alterations in treatment protocols.
Subject(s)
Gaucher Disease/complications , Adolescent , Adult , Aged , Aged, 80 and over , Bone Diseases/etiology , Child , Child, Preschool , Female , Gaucher Disease/genetics , Gaucher Disease/psychology , Gaucher Disease/therapy , Heart Diseases/etiology , Hematologic Diseases/etiology , Humans , Joint Diseases/etiology , Lung Diseases/etiology , Male , Middle Aged , Pregnancy , Pregnancy Complications/etiology , Surveys and Questionnaires , United StatesABSTRACT
The objective of this study was to evaluate the biomechanical properties of newly formed cartilaginous tissue synthesized from isolated chondrocytes. Cartilage from articular joints of lambs was either digested in collagenase to isolated chondrocytes or cut into discs that were devitalized by multiple freeze-thaw cycles. Isolated cells were incubated in suspension culture in the presence of devitalized cartilage matrix for 3 weeks. Multiple chondrocyte/matrix constructs were assembled with fibrin glue and implanted subcutaneously in nude mice for up to 6 weeks. Testing methods were devised to quantify integration of cartilage pieces and mechanical properties of constructs. These studies showed monotonic increase with time in tensile strength, fracture strain, fracture energy, and tensile modulus to values 5-10% of normal articular cartilage by 6 weeks in vivo. Histological analysis indicated that chondrocytes grown on dead cartilage matrix produced new matrix that integrated individual cartilage pieces with mechanically functional tissue.
Subject(s)
Cartilage, Articular/cytology , Cell Transplantation , Animals , Biomechanical Phenomena , Cartilage, Articular/injuries , Cartilage, Articular/physiology , Cell Culture Techniques/methods , Cells, Cultured , Coloring Agents , Fibrin Tissue Adhesive , Joints , Mice , Mice, Nude , Phenazines , Sheep , Transplantation, HeterologousABSTRACT
In vivo acetabular contact pressures were measured over 32 months in an elderly man with a pressure instrumented hemiarthroplasty. After death, left (hemiarthroplasty) and right (control) acetabula were explanted. Cartilage thickness and degeneration were quantified from magnetic resonance imaging and histological analysis. Highest repetitive in vivo contact pressures during gait (4.5 to 6.5 MPa) were measured in the superior dome of the acetabulum and decreased at a rate of approximately 1 MPa per year after implant (R2 = 0.48, P < .001). Contact pressure magnitudes measured during gait correlated positively with regional histology score (R2 = 0.34, P < .0001) and negatively with cartilage thickness (R2 = 0.35, P < .0001). Although histology scores were typical of early osteoarthritis (histological grade of 4-6), there were no significant differences in overall histology score for the left and right acetabula (P = .23). We conclude that acetabular cartilage degeneration was explained, in part, by repetitive stress, but the degeneration did not appear to be mediated solely by articulation with the metallic endoprosthesis.
Subject(s)
Cartilage, Articular/pathology , Hip Prosthesis , Aged , Aged, 80 and over , Arthroplasty, Replacement, Hip/methods , Gait , Humans , Magnetic Resonance Imaging , Male , Pressure , TransducersABSTRACT
Normal human and osteoarthritic cells were isolated from cartilage with clostridial collagenase. The cells were grown in media as a suspension culture in the presence of 35SO4. Osteoarthritic cartilage of moderate histologic grade (4-8) yielded chondrocytes which incorporated 35SO4 at a rate 3-4 times greater than did normal chondrocytes. The rate of incorporation, however, decreased to normal levels with chondrocytes isolated from mild (grade 0-3) or more advanced (grade 9-13) stages of the disease. These results corroborate those obtained in earlier studies using organ cultures and show that when osteoarthritic cells are isolated from their matrix environment, they continue to synthesize macromolecules at an increased rate. Analysis of the material synthesized by the isolated cells on sizing column demonstrated an inverse relationship between the size of the 35SO4 containing molecules and the severity of the disease.