Search PubMed⌕ Search

Biomedical subjects

R D Altman

Publications and source records attributed to R D Altman.

At least 91 records · Page 5Linked to original sources
PubMed1990

Neutrophil activation: an alternative to prostaglandin inhibition as the mechanism of action for NSAIDs.

Experimental findings suggest that inhibition of neutrophil activation rather than suppression of prostaglandin formation may represent the principal mechanism of action of antiinflammatory drugs. This theory would account for the effectiveness of prostaglandin preserving agents, such as the nonacetylated salicylate salsalate, in the treatment of rheumatic disease. Results of the controlled clinical trials described in other papers contained in this supplement indicate that salsalate is equally effective as aspirin and the newer NSAID naproxen in relieving the signs and symptoms of rheumatoid arthritis. The damage to the gastric mucosa associated with NSAID use is believed to be attributable to impairment of mucosal defense mechanisms resulting from the inhibition of gastroprotective prostaglandins. Confirmation of neutrophil activation as the mechanism of action of NSAIDs would explain the efficacy of salsalate in light of its lower incidence of gastrointestinal side effects in controlled clinical trials with aspirin and naproxen. Establishment of such a mechanism would also suggest that the other adverse effects related to prostaglandin inhibition, such as hypersensitivity reactions, platelet dysfunction, and a reduction in renal function, are not necessary correlates of effective antiinflammatory therapy.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1990

Elevated plasma histamine levels in systemic sclerosis (scleroderma).

Systemic sclerosis is characterized by excessive deposition of collagen and other matrix proteins in the skin and internal organs. One hypothesis supports fibroblast stimulation for production of excess amounts of collagen by factors present in the blood or released by cells composing inflammatory tissue infiltrates. Increased numbers of mast cells are present in the involved skin of patients with systemic sclerosis, and histamine has been thought to be a possible mediator of fibrosis in this and other fibrotic conditions. We therefore measured plasma histamine levels in 32 patients with systemic sclerosis and found elevated levels in 18 patients (56%). Elevated plasma histamine levels were more common in patients with diffuse disease (74%), in contrast to limited disease (31%). The degree of clinical activity and the duration of disease could not be correlated with histamine levels.

Adult↗
PubMed1989

Prophylactic treatment of canine osteoarthritis with glycosaminoglycan polysulfuric acid ester.

The prophylactic effect of glycosaminoglycan polysulfuric acid ester (GAGPS) on cartilage lesions was studied using the Pond-Nuki model of canine osteoarthritis. Starting 2 days after anterior cruciate transection, GAGPS or saline was administered intraarticularly twice weekly for 4 weeks. After 4 weeks, gross and histologic medial femoral condylar lesions had developed to a lesser degree in GAGPS-treated dogs than in saline-treated dogs. The uronic acid and hydroxyproline levels in cartilage were significantly higher in the GAGPS-treated dogs than in the saline-treated dogs. Levels of active and latent collagenase in the cartilage of GAGPS-treated dogs were lower than in the cartilage of saline-treated dogs. With GAGPS treatment, swelling of the cartilage, an indicator of collagen network integrity, remained near control levels. Although increased synthesis of proteoglycan and collagen may account for some of these results, we propose that one mechanism of action of GAGPS is its ability to decrease collagen degradation, either by decreasing the synthesis of collagenase or by directly inhibiting the production of collagenase in cartilage.

Animals↗
PubMed1989

Therapeutic treatment of canine osteoarthritis with glycosaminoglycan polysulfuric acid ester.

The therapeutic effect of glycosaminoglycan polysulfuric acid ester (GAGPS) was studied using the Pond-Nuki model of canine osteoarthritis. The clinical setting was simulated by permitting 4 weeks ambulation without treatment, following anterior cruciate transection. Animals were then injected with GAGPS, 4 mg/kg intramuscularly, twice weekly during weeks 4-8. Control animals received intramuscular saline. The study was terminated 4 weeks after completion of the GAGPS or saline regimen (i.e., 12 weeks postoperatively). Cartilage from the medial femoral condyle was analyzed for collagen integrity (swelling properties), hydroxyproline, uronic acid, active and total proteoglycan (PG)-degrading metalloproteinase, PG-degrading serine proteinase, and histopathology (Mankin score). Condylar cartilage from animals treated with GAGPS demonstrated less cartilage swelling, less total and active metalloproteinase, and lower histopathologic scores than were found in cartilage from saline-treated animals. GAGPS was able to suppress PG-degrading enzyme activity and maintain a more normal-appearing cartilage. It is proposed that GAGPS suppressed PG breakdown by decreasing synthesis of metalloproteinase or by directly inhibiting metalloproteinase in cartilage, rather than by increasing synthesis of PG by chondrocytes.

Animals↗
PubMed1988

Salicylates in the treatment of arthritic disease. How safe and effective?

Despite the adverse effects of aspirin, many physicians still consider it to be the drug of choice for initial treatment of arthritic disorders. Nonsteroidal antiinflammatory drugs (NSAIDs) are better tolerated than aspirin but have similar, although milder, side effects. The nonacetylated salicylates appear to have fewer adverse effects than either aspirin or the NSAIDs and therefore may warrant greater consideration as first-line therapy for arthritis.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1988

Plasma somatomedin-C levels in systemic sclerosis.

We have measured the plasma levels of somatomedin-C (SM-C) or insulin-like growth factor I (IGF-I) in 13 patients with progressive systemic sclerosis (PSS) and age and sex matched healthy controls. We found the plasma SM-C levels to be within normal limits in all the patients. Thus, if somatomedin-C plays a role in the pathogenesis of PSS, it is more likely to be at the fibroblast receptor level or in the synthetic response of fibroblasts to SM-C.

Adult↗
PubMed1988

Future therapeutic trends in osteoarthritis.

Since cartilage contains no nerve endings, symptoms of osteoarthritis (OA) are indirect. Therapy of OA, to date, has been directed at the symptoms of pain, signs of inflammation and loss of function. A major advance has been surgical joint replacement. This benefit however, is often limited by the joint area involved and to the survival of the endoprosthesis. Orthopedic new approaches to therapy of OA include removal of abnormal tissue to stimulate repair (e.g., burring, abrasion) and grafting (e.g., osteochondral grafts, perichondrium, periosteum) to the subchondral bone. Controlled activity (e.g., passive motion) has been studied alone and with the above. Can a medication retard or reverse the degradative process of OA? Several medications are being examined for potential "chondroprotective" characteristics. Some of these agents are not new: oversulfated glycosaminoglycans (Arteparon) derived from cartilage and glycosaminoglycan peptides (Rumalon) derived from cartilage and bone marrow extracts may be prototypes of this approach to therapy. Other agents demonstrating potential benefit in retarding cartilage degradation may include non-steroidal anti-inflammatory agents, tiaprofenic acid, sodium pentosan sulfate and low dose corticosteroids. This concept of "chondroprotection" provides us a new approach to a disease in need of a new approach.

Animals↗
PubMed1988

Ketoprofen versus indomethacin in patients with acute gouty arthritis: a multicenter, double blind comparative study.

Fifty-nine patients with acute gouty arthritis entered into a 7-day multicenter, double blind trial of ketoprofen versus indomethacin. Patients were randomly assigned to receive 100 mg of ketoprofen (n = 29 patients) or 50 mg of indomethacin (n = 30 patients) 3 times a day. More than 90% of the patients in each group reported pain relief within the 1st day of treatment. By Day 5, 7 patients in the ketoprofen group and 6 in the indomethacin group discontinued treatment because of complete or substantial pain relief. At the end of the study, most patients in both groups were rated as having marked improvement both by the investigators and by self-assessment. Three patients in each group withdrew prematurely because of drug related gastrointestinal disorders. Ketoprofen compared favorably for efficacy and safety with indomethacin in the treatment of gouty arthritis.

Administration, Oral↗
PubMed1987

Overview of osteoarthritis.

Osteoarthritis is a disease characterized by defects in articular cartilage with involvement of the tissues about the joint. The disease is frequent in the population over the age of 40 and is a major public health problem. Development of disease is due to cartilagenous, bony, synovial, mechanical, and other factors operating independently, as well as in combination. Therapeutic programs should be an integration of physical measures, medicinal agents, psychosocial interventions, and surgery. Therapy should be directed at the pathophysiologic causes of the patients' symptoms.

Humans↗
PubMed1987

Radiographic assessment of progression in osteoarthritis.

We evaluated methods of grading radiologic progression of osteoarthritis (OA). Sets of radiographs were assessed separately by 8 readers who were blinded to the time sequence. Included were radiographs of patients with OA of the hands (24 pairs), hips (40 pairs), and knees (32 pairs). Most films were taken 12-60 months apart. The relative contribution of individual joints (such as particular interphalangeal joints), of observations (such as narrowing or spurs), and of a single joint compartment (such as the medial or lateral compartment of the knee) toward evidence of OA progression was evaluated, as well as the reliability and concordance of scoring, and the sensitivity in detecting change. In assessing OA of the hand, the greatest sensitivity was achieved by reading a single posteroanterior bilateral hand radiograph for narrowing, spurs, and erosions, and scoring 10 joints (second and third distal interphalangeal, second and third proximal interphalangeal, and trapeziometacarpal joints, bilaterally), using a scale of 0-3. In OA of the hip, a single anteroposterior radiograph assessed for joint space narrowing and cyst formation yielded the greatest sensitivity. In OA of the knee, an anteroposterior radiograph, with weight-bearing, assessed for narrowing, spurs, and sclerosis in both the medial and lateral compartments yielded the greatest sensitivity. These techniques will be useful to the investigator in designing experimental studies and to the clinician in determining the rate of disease progression in an individual patient.

Aged↗
PubMed1987

Criteria for the classification of osteoarthritis of the knee and hip.

The Osteoarthritis (OA) Criteria Subcommittee of the American Rheumatism Association set out to develop (a) a classification of OA that includes recognised subsets; and (b) subsets of OA identified by a combination of clinical and laboratory features. For the purposes of classification, OA should be specified if of unknown origin (idiopathic, primary) or if related to a known medical condition or event (secondary). Clinical criteria for classification of idiopathic OA of the knee were developed through a multicentre study group involving 130 patients with OA and 107 comparison patients. Comparison diagnoses included rheumatoid arthritis (RA) and other painful conditions of the knee exclusive of referred or para-articular pain. Variables from the history, physical examination, laboratory test results and radiographs were used to develop sets of criteria that serve different investigative purposes: clinical examination (sensitivity 89%; specificity 88%); clinical examination and laboratory tests (sensitivity 88%; specificity 93%); clinical examination, laboratory tests and radiographs (sensitivity 94%; specificity 88%). In contrast to prior classification criteria, the proposed criteria utilise decision trees or algorithms. Clinical criteria for classification of idiopathic OA of the hip are under development. Comparison groups are comprised of patients with other rheumatic diseases (e.g. RA), periarticular pain (e.g. trochanteric bursitis) and referred pain (e.g low back pain). From a method of opinion sampling, OA of the hip may be suggested by a combination of clinical criteria including the following: age greater than 40 years, weight-bearing pain, pain relieved by sitting, antalgic gait, decreased painful range of motion, a normal erythrocyte sedimentation rate (ESR) and a negative rheumatoid factor test.

Algorithms↗
PubMed1987

Low back pain in Paget's disease of bone.

Clinical and laboratory evaluation with bone scan, radiography, and computed tomography were performed on 25 patients with severe Paget's disease of bone and low back pain. Back pain was classified as caused by Paget's disease in only three patients. The remaining 22 patients had coexistent Paget's disease and osteoarthritis. There was difficulty separating the cause of back pain in those patients with coexistent Paget's disease and osteoarthritis, even when the diseases were present at different levels of the spine. The pathogenesis of Paget's disease appears to precipitate osteoarthritis and several low back syndromes. Suppressive therapy with disodium etidronate (EHDP) for Paget's disease was of benefit in eight of 22 patients (36%) with identifiable osteoarthritis. It is suggested that EHDP and perhaps other suppressive agents for Paget's disease receive limited use in patients with back pain unless a defined pagetic lesion appears related to the clinical syndrome in the absence of identifiable osteoarthritis.

Back Pain↗
PubMed1987

Synthetic human calcitonin in refractory Paget's disease of bone.

Fourteen patients with symptomatic and active Paget's disease of bone who had demonstrated resistance to parenteral synthetic salmon calcitonin, oral disodium etidronate, or both in combination were treated with parenteral synthetic human calcitonin. Eleven patients (79%) demonstrated clinical and chemical improvement for up to five years. Two patients received additional benefit with combined synthetic human calcitonin and etidronate disodium.

Aged↗
PubMed1987

The effect of glycosaminoglycan polysulfuric acid ester on articular cartilage in experimental arthritis: effects on collagenolytic enzyme activity and cartilage swelling properties.

Some of the effects of the semi-synthetic glycosaminoglycan polysulfuric acid ester (GAGPE) were investigated on the osteoarthritis-like lesions in the Pond-Nuki dog model, in respect to histological grade of anatomical lesions, collagenolytic enzyme activity, and a parameter of collagen network integrity. Prophylactic treatment by intra-articular injections twice weekly for 4 weeks caused amelioration of canine cartilage erosions. Preliminary evidence for suppression of collagenolytic enzyme activity, as well as protection of a tight collagen network studied in the canine cartilage was obtained.

Animals↗
PubMed1987

Development of clinical criteria for osteoarthritis.

Clinical criteria for the classification of osteoarthritis (OA) in the knee have been developed and the use of algorithms has been proposed. Criteria for the classification of OA in the hand and hip are still being developed.

Hand↗
PubMed1986

Osteoarthritis. Aggravating factors and therapeutic measures.

Clinical criteria for diagnosis of osteoarthritis are not yet formally established; at present, diagnosis is usually made through physical and radiologic examination and evaluation of synovial fluid. Severe trauma and possibly repeated microtrauma, excessive activity, inactivity, and obesity are believed to aggravate symptoms. Treatment objectives are to reduce pain and improve, or at least preserve, function. Antiinflammatory agents provide relief for many patients, although gastrointestinal reactions may accompany their use. Antispasmodics may be helpful for pain caused by muscle spasm, and intraarticular injections of depocorticosteroids are useful for inflammation. Agents that provide analgesia are an appropriate part of the therapeutic program. Patients should be taught to protect weakened joints through use of orthotics, strengthening exercises, and proper body movement and posture. A supportive physician who encourages a healthy life-style and positive outlook will see better physical as well as emotional results with these patients.

Adrenal Cortex Hormones↗