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Biomedical subjects

R D Altman

Publications and source records attributed to R D Altman.

At least 73 records · Page 4Linked to original sources
PubMed1993

Treatment of canine osteoarthritis with insulin-like growth factor-1 (IGF-1) and sodium pentosan polysulfate.

The potential therapeutic effects of insulin-like growth factor-1 (IGF-1) and sodium pentosan polysulfate (PPS) were evaluated in an anterior cruciate ligament-deficient canine model of osteoarthritis (OA). A control group of animals received no treatment or surgery (N). The remaining four groups of animals received anterior cruciate transection and either no treatment (OA), intra-articular IGF-1 (IGF-1), intra-muscular PPS (PPS), or a combination of intra-articular IGF-1 and intra-muscular PPS (IGF-1/PPS). All therapy was begun 3 weeks after surgery and continued for 3 weeks. At 6 weeks, articular cartilage from the femoral condyle was evaluated for anatomy, histology (Mankin grade) and biochemistry. Anatomically, only cartilage from dogs in the IGF-1/PPS group approximated that found in N. Mankin scores indicated less severe disease in both PPS and IGF-1/PPS groups compared with the OA group. Consistent with histology, the level of active neutral metalloproteinase was lower in cartilage from the PPS group compared with the OA group. Active and total neutral metalloproteinase, tissue inhibitor of metalloproteinases (TIMP), total collagenase, uronate and hydroxyproline contents were all near normal in the IGF-1/PPS group. In a model of mild OA, therapeutic intervention with IGF-1 and PPS appeared to successfully maintain cartilage structure and biochemistry. From these data, it is hypothesized that proteinase activity was successfully blocked by PPS, and that this allowed the observed growth factor induced effects. As we unravel the various factors that regulate cartilage metabolism, it is becoming apparent that combinations of agents will be needed to effectively control cartilage repair in OA. The addition of PPS to IGF-1 shows promise as a therapeutic intervention and introduces a new rational approach to therapy of OA.

Animals↗
PubMed1993

Cartilage repair and conservation in osteoarthritis. A brief review of some experimental approaches to chondroprotection.

Osteoarthritis is the most prevalent rheumatic disease. Inasmuch as osteoarthritis is predominantly idiopathic, current treatment is aimed not at a cure but palliative management. Research, however, has made considerable forward strides with respect to feasibility of new methods for diagnostic markers of early disease and disease progression, as well as methods to conserve articular damage. This article briefly describes the authors' experience with the use of one type of surgical repair and five different medicinal agents for cartilage conservation.

Animals↗
PubMed1993

The effects of methotrexate on normal and osteoarthritic lapine articular cartilage.

OBJECTIVE: The effects of methotrexate (MTX) on articular cartilage and its influence on the development of osteoarthritis (OA) lesions were tested in a lapine partial medial meniscectomy model. METHOD: Animals were divided into groups consisting of unoperated and operated rabbits that either received or did not receive MTX treatment. After 8 weeks knee articular condylar cartilage was examined for gross and histologic anatomy, active and total neutral metalloproteinases, tissue inhibitor of metalloproteinase (TIMP), DNA, uronic acid and hydroxyproline content. RESULTS: Carbon black retention and histologic scores revealed moderately severe changes in the OA animals with a tendency to less severe changes in OA animals receiving MTX. Unoperated animals receiving MTX had abnormal cartilage that displayed pitting and elevations in histologic score. Active and total neutral metalloproteinase and TIMP were elevated in both untreated and treated OA animals when compared to either unoperated or unoperated and treated animals. CONCLUSION: Articular cartilage with lesser amounts of neutral metalloproteinase and high amounts of TIMP levels often seen with other therapeutic modalities for OA, were not observed with MTX therapy. Our data suggest that MTX may have limited value in the treatment of OA.

Animals↗
PubMed1992

Interaction of cyclosporine A and nonsteroidal anti-inflammatory drugs on renal function in patients with rheumatoid arthritis.

PURPOSE: To determine the additive renal effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclosporine A (CYA) in patients with rheumatoid arthritis (RA) and to determine the effects of CYA on active RA. PATIENTS AND METHODS: Eleven patients with RA refractory to other agents were treated separately for 2-week periods with an NSAID (sulindac or naproxen), CYA (5 mg/kg/d), and NSAID plus CYA in combination (NSAID/CYA). The NSAID/CYA combination was continued for an additional 20 weeks. Clinical parameters of RA, electrolytes, renal function, and the renin-aldosterone system were evaluated at each interval to determine the potential interaction of these two agents. RESULTS: Combined therapy was effective in suppressing many measures of active RA in 9 of the 11 patients. Adverse drug reactions were common, but withdrawals were limited to hirsutism (one) and peripheral neuropathy (one). In about half of the patients, CYA or NSAID resulted in a decrease in the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), with a mild reduction in the filtration fraction. With NSAID or CYA, early morning renin-aldosterone system values were mildly suppressed, and their response to ambulation/intravenous (IV) furosemide was not blunted. When combined, NSAID/CYA caused more marked reductions of GFR and ERPF at 2 weeks, and this persisted at 20 weeks. The morning renin-aldosterone system values during administration of NSAID/CYA were suppressed, with an added blunted response to ambulation/IV furosemide. CONCLUSION: As previously suspected, the impairment of renal function when CYA and NSAID are combined is greater than that obtained with either agent alone. This hemodynamic effect was reversible and appeared to be, at least in part, due to renal vasoconstriction.

Adult↗
PubMed1992

Takayasu's arteritis syndrome associated with systemic lupus erythematosus.

Takayasu's arteritis (TA) rarely coexists with systemic lupus erythematosus (SLE). Eighteen cases of TA associated with SLE found by worldwide literature search are reviewed, and an additional unique case is reported in association with the presence of anti-cardiolipin antibody. Patients with TA and/or SLE have similar age of onset and female predominance. The absence of specific SLE markers in patients with TA who subsequently develop SLE suggests that the coexistence of these conditions may be coincidental. The antiphospholipid syndrome in patients with SLE may mimic the occlusive vasculitis of TA.

Adolescent↗
PubMed1992

Preliminary observations of chondral abrasion in a canine model.

Articular cartilage repair was followed for one year in skeletally mature dogs after destabilisation by anterior cruciate ligament transection of the stifle joint (CT), abrasion of the inferior medial condyle (ABR) to bleeding bone, or anterior cruciate transection followed by chondral abrasion (CT/ABR). ABR animals formed repair cartilage at the abrasion site (ABR and CT/ABR) at six months as determined by arthroscopy and at necropsy. CT and CT/ABR animals had an additional cartilage ulcer on the superior aspect of the medial condyle. The abraded site extended in CT/ABR condyles. Repair cartilage (ABR and CT/ABR) contained reduced amounts of proteoglycan as seen by histological loss of safranin O staining and reduced uronic acid content. Fibrocartilage was suggested by histological appearance, hypocellularity, and a higher hydroxyproline content. In contrast with ABR animals, the repair cartilage in the CT/ABR animals contained near normal amounts of hydroxyproline. Collagen profiles of abrasion site repair cartilage in ABR animals had more types I and V collagens, similar amounts of type VI collagen, and decreased amounts of types II, IX, and XI collagens than CT/ABR animals. The results of this study are consistent with abrasion chondroplasty leading to a repair cartilage. Despite extended ulcers, repair cartilage from the destabilised joint (CT/ABR) animals was more hyaline-like in its hydroxyproline content and collagen composition than repair cartilage from the stable joint (ABR animals). In these models additional measures appear to be needed as the defects induced by abrasion chondroplasty did not form a functional hyaline cartilage.

Animals↗
PubMed1992

Association of amino acid sequences in the HLA-DQB1 first domain with antitopoisomerase I autoantibody response in scleroderma (progressive systemic sclerosis).

Previous studies in Caucasians with progressive systemic sclerosis (PSS) have suggested associations of antitopoisomerase I (antitopo I) autoantibodies with either serologically defined HLA-DR2 or DR5. To better define class II HLA associations with the antitopo I response, 161 PSS patients (132 Caucasians and 29 American blacks) were studied for antitopo I autoantibodies by immunodiffusion and immunoblotting, and their HLA-DRB1, DRB3, DQA1, and DQB1 alleles were determined by restriction fragment length polymorphic analysis and DNA oligotyping. Among Caucasians with antitopo I, HLA-DR5(DRB1*1101-*1104), DRB3*0202 and DQw3 (DQw7,8,9) were significantly increased in frequency. In American blacks, however, only HLA-DQB1*0301(DQw7) was significantly increased. The presence of HLA-DQB1*0301(DQw7) and other HLA-DQB1 alleles bearing the uncharged polar amino acid residue tyrosine at position 30 of the outermost domain was found in all antitopo I-positive Caucasian PSS patients compared with 66% of antitopo I-negative PSS patients (pc = 0.007) and 70% of normal controls (pc = 0.008), as well as all antitopo I-positive black patients. The association with HLA-DQB1 was independent of HLA-DR5(DRB1*1101-*1104) or any other HLA-DRB1, DRB3, or DQA1 alleles. Alternative or additional candidate epitopes for this autoimmune response include alanine at position 38 and threonine at position 77 of these same DQB1 alleles. These data suggest that genetic predisposition to the antitopo I response in PSS is associated most closely with the HLA-DQB1 locus.

Alleles↗
PubMed1991

Amelioration of lapine osteoarthritis by treatment with glycosaminoglycan-peptide association complex (Rumalon).

The chondroprotective potential of glycosaminoglycan-peptide association complex (GP-C) was examined in the medial meniscectomy model of lapine osteoarthritis (OA). Prophylactic treatment with increasing doses of intramuscular GP-C (0.05-0.5 ml/kg) caused a significant reduction in OA lesion area and histologic scores, and the effect on disease activity appeared to be dose related. The DNA and uronic acid contents of OA tissue were unaffected by prophylactic treatment with GP-C. However, levels of hydroxyproline in OA cartilage increased to near control levels with prophylactic treatment. Cartilage levels of active and total metalloproteinases that digest proteoglycans were elevated in rabbits with OA; prophylactic treatment with low-dose GP-C (0.05 ml/kg) produced a significant reduction in active, but not total, enzyme. Cartilage levels of tissue inhibitor of metalloproteinases in animals with OA were comparable with control levels, but rose with increasing doses of GP-C. We also investigated GP-C as a therapeutic treatment in animals that had already developed OA lesions. Carbon black retention and histologic score returned to near-normal after therapeutic treatment with GP-C. Uronic acid and hydroxyproline levels were decreased in OA cartilage. Therapeutic treatment with GP-C had no statistically significant effect on uronic acid levels, but was associated with increased hydroxyproline content in the cartilage. The changes in metalloproteinase and metalloproteinase inhibitor were similar to those found in the studies of prophylactic treatment. The findings in this animal model may help explain some of the beneficial effects of GP-C in human OA.

Animals↗
PubMed1991

Predictors of survival in systemic sclerosis (scleroderma).

We conducted followup of 264 patients with definite systemic sclerosis (SSc) who were entered into the multicenter Scleroderma Criteria Cooperative Study (SCCS) during 1973-1977. At the end of the study (average 5.2 years of followup), 38% were known to be alive, 50% were dead (68% of these deaths definitely related to SSc), and 12% were lost to followup. Survival analyses of 484 demographic, clinical, and laboratory items recorded at entry into the SCCS (within 2 years of physician diagnosis of SSc) were performed. Survival declined linearly, and the cumulative survival rate was less than 80% at 2 years, 50% at 8.5 years, and 30% at 12 years after entry. Analysis using combinations of entry variables identifying organ system involvement confirmed that renal, cardiac, pulmonary, and gastrointestinal involvement in SSc predicted reduced survival; however, data on organ system involvement at study entry could not be used to consistently predict which organ system would ultimately be involved as the primary cause of death. By survival tree analysis, the individual entry variables best predicting reduced survival included older age (greater than 64 years), reduced renal function (blood urea nitrogen greater than 16 mg/dl), anemia (hemoglobin less than or equal to 11 gm/dl), reduced pulmonary diffusing capacity for carbon monoxide (less than or equal to 50% of predicted), reduced total serum protein level (less than or equal to 6 gm/dl), and reduced pulmonary reserve (forced vital capacity less than 80% with hemoglobin greater than 14 gm/dl or forced vital capacity less than 65% with hemoglobin less than or equal to 14 gm/dl). Cox proportional hazards model analysis confirmed these results. Different combinations of variables led to markedly different survival rates. The poorest prospects for survival were in patients with SSc who were less than or equal to 64 years old with a hemoglobin level less than or equal to 11 gm/dl, and in those greater than 64 years old with a blood urea nitrogen level greater than 16 mg/dl. These results may be useful in predicting individual patients at risk for shortened survival.

Age Factors↗
PubMed1991

Classification of disease: osteoarthritis.

Criteria for the classification of osteoarthritis (OA) have been developed to establish uniformity in the reporting of this disease. Different criteria sets were developed for OA of the knee, hand, and hip that can serve different investigative purposes. The use of checklists facilitates the use of the criteria sets.

Hand↗
PubMed1991

Subcutaneous cholesterol crystals mimicking calcinosis cutis in systemic sclerosis.

A patient is described with systemic sclerosis (SSc) and subcutaneous cholesterol crystals mimicking calcinosis cutis. Though not detectable radiographically, basic calcium phosphate crystals were identified by alizarin red staining of aspirate from one digit. The value of crystal identification by microscopy in cases of SSc with presumed calcinosis cutis, but without radiographic evidence of subcutaneous calcific deposits, is emphasized.

Calcinosis↗
PubMed1991

Criteria for classification of clinical osteoarthritis.

Criteria for classification of symptomatic osteoarthritis (OA) have been developed by a Subcommittee of the American College of Rheumatology. Criteria for symptomatic OA of the knee, hand and hip have been developed. Different sets of criteria were developed for different investigative purposes: (1) clinical (history and physical examination), (2) clinical and laboratory, and (3) clinical, laboratory and radiographic changes. It is recommended that criteria for classification of symptomatic OA be used in patients to be evaluated in clinical trials, population surveys, and in reports dealing with patients who have symptomatic OA of the knee, hand and hip.

Hand↗
PubMed1991

Treatment of osteoarthritis with tiaprofenic acid: biochemical and histological protection against cartilage breakdown in the Pond-Nuki canine model.

Experimental and cage matched control animals were sacrificed 12 weeks after production of ligamentous instability in the right knee, and biochemical studies were performed on eroded OA and normal articular cartilage. Significant protection was afforded by tiaprofenic acid administered orally at 15 mg/kg body weight. Chondroprotection was manifested by reduction of fast sedimenting proteoglycan aggregates, as well as retention of hyaluronate content, and favorable proteoglycan aggregate S value levels. This agent showed significant chondroprotective action under the conditions of these studies.

Administration, Oral↗
PubMed1990

Osteoarthritis. Differentiation from rheumatoid arthritis, causes of pain, treatment.

Osteoarthritis affects a majority of the elderly population in one form or another. It must be differentiated from rheumatoid arthritis because treatment of the two diseases is quite different. Once the diagnosis of osteoarthritis has been established, treatment should include a combination of physical, medicinal, psychological, and surgical measures to improve the patient's quality of life. The future may bring new approaches to interrupt pathogenetic factors in the disease.

Adult↗
PubMed1990

Osteoarthritis research: animal models.

Although limited in scope and detail, the current review has sought to highlight the contribution of animal models in the study of OA. Further use of these and other models should provide information that may lead to methods for the early detection and successful treatment of human OA.

Animals↗
PubMed1990

Design and conduct of clinical trials in osteoarthritis.

Clinical features of osteoarthritis (OA) require that general recommendations for the design and conduct of clinical trials be modified in order to apply these concepts to clinical trials in OA. A format has been devised for design of clinical trials in OA. In order to assess the applicability of this format, it has been compared to a published clinical trial: chondroprotective agents versus standard treatment of OA of the knee. The published study appeared reliably designed and conducted in a manner that provided an answer to most of the questions posed. The study appears to form a sound basis for additional studies.

Anti-Inflammatory Agents, Non-Steroidal↗