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Biomedical subjects

A G Fam

Publications and source records attributed to A G Fam.

At least 19 recordsLinked to original sources

HLA antigens in North American patients with Takayasu arteritis.

OBJECTIVE: To determine the frequency of HLA class I and II antigens in Caucasian North American patients with Takayasu arteritis (TA). METHODS: Seventy-three class I antigens and 13 class II antigens were examined in 21 Caucasian North American patients with TA, and their frequencies were compared with findings in 243 healthy, untreated controls. HLA typing was performed by microlymphocytotoxicity assay. RESULTS: We found no statistically significant positive association of TA with DR2, DR4, DQw3, or any of the other class I or class II antigens studied. A negative association between TA and DR1 was noted. There was no significant association between any of the HLA antigens and the severity of the disease or the presence of complications. CONCLUSION: The negative association between TA and the DR1 antigen suggests that this antigen may be protective against the development of the disease.

Adolescent

Desensitization to allopurinol in patients with gout and cutaneous reactions.

PURPOSE: To determine the efficacy and safety of slow oral desensitization in the management of allopurinol-related pruritic cutaneous eruptions. PATIENTS AND METHODS: Nine patients with renal insufficiency and chronic tophaceous gouty arthritis, who had to interrupt their allopurinol therapy because of an allergic-type pruritic maculopapular eruption, were enrolled in an allopurinol oral desensitization protocol using a schedule of gradually increasing doses. RESULTS: Cautious reinstitution of allopurinol was successfully accomplished in all nine patients, but four individuals required dose adjustment because of development of a mild, recurrent, macular rash early during the protocol at allopurinol doses of less than or equal to 5 mg/d. Transient, postdesensitization cutaneous reactions occurred in two patients, one of whom also had an early rash. CONCLUSION: Oral desensitization to the minor rashes induced by allopurinol is a feasible and acceptably safe approach to therapy, particularly for those with renal insufficiency in whom no substitute urate-lowering drug is available.

Administration, Oral

Acute calcific periarthritis in scleroderma.

Three patients with limited cutaneous scleroderma (CREST syndrome) and acute calcific periarthritis are presented. "Chalky" bursal effusion in one patient demonstrated masses of calcium hydroxyapatite crystals. In contrast to idiopathic acute calcific periarthritis, resorption of periarticular calcifications after resolution of acute attacks occurs both less frequently and incompletely in scleroderma associated acute calcific periarthritis.

Acute Disease

Calcium pyrophosphate crystal deposition disease and other crystal deposition diseases.

A number of cells, chemotactic factors, and inflammatory mediators are implicated in the complex mechanisms underlying crystal-mediated inflammation. Interleukin-8, released from mononuclear cells that have been exposed to urate and other crystals, is a potent chemotaxin and activator of neutrophils. Experimental and clinical observations suggest that joint movements, local biomechanical factors, and previous joint damage may play a role in influencing the intensity of microcrystalline synovitis and the distribution of articular and periarticular crystal deposits in both calcium pyrophosphate dihydrate crystal deposition disease and gout. There are rare reports of extra-articular calcium pyrophosphate dihydrate crystal deposition in tendons, bursae, dura mater, and ligamentum flavum (with radiculomyelopathy) and of massive "tumoral," tophuslike, periarticular calcium pyrophosphate dihydrate crystal deposits. Synovial fluid levels of ATP, the main substrate for nucleoside triphosphate pyrophosphohydrolase ectoenzyme, which cleaves ATP-releasing inorganic pyrophosphate, are higher in patients with calcium pyrophosphate dihydrate crystal deposition disease than in those with other arthritides, and the levels correlate with inorganic pyrophosphate concentrations. Further reports of acute calcific periarthritis of the first metatarsophalangeal joint (hydroxyapatite pseudopodagra) in young women have been described. The mitogenic response of fibroblasts to stimulation with basic calcium phosphate crystals is accompanied by induction and secretion of collagenase and neutral proteases, implicating a role for the crystals in the pathogenesis of both synovial proliferation and joint damage in chronic basic calcium phosphate crystal-associated arthropathy. Subcutaneous cholesterol crystal deposition with tophus formation is extremely rare and has been described in a patient with scleroderma and calcinosis cutis.

Arthritis

A comparison of five preparations of synthetic monosodium urate monohydrate crystals.

We conducted preliminary crystallographic investigations and biologic studies on 5 synthetically grown preparations of monosodium urate monohydrate (MSUM) crystals including one preparation of urate spherulites. The 5 crystal preparations exhibited wide variations in morphology, size, surface area, and ultrastructure, but only a few changes in their biologic effects. When injected intraarticularly, urate spherulites were less phlogistic than most acicular forms. Since crystal-cell interactions and inflammatory responses are influenced by crystal size, morphology, and surface characteristics, standardization of methods of preparing MSUM crystals is, therefore, important, particularly when analyzing and comparing results from different research laboratories.

Crystallization

Ankylosing spondylitis antirheumatic drug trials. I. Effects of standardization procedures on observer dependent outcome measures.

We designed a study to assess the effects of standardization procedures on reducing interobserver variability for outcome measures given in the current Food Drug Administration and European League Against Rheumatism guidelines and others selected from the rheumatology literature. Over 2 days, 6 rheumatologists independently examined 7 patients with ankylosing spondylitis (AS) in predetermined order before and after standardizing their examination techniques. An important and beneficial effect of the standardization procedure was observed on the majority of outcome variables. Such reductions in observer variability have the potential to diminish sample size requirements for AS antirheumatic drug studies.

Adult

Ankylosing spondylitis antirheumatic drug trials. II. Tables for calculating sample size for clinical trials.

The calculation of sample size requires knowledge of the standard deviation (SD) of index variables. Unfortunately, there are no published lists of standard deviations and it is exceedingly difficult to locate variance estimates based on relevant populations. We used standardized procedures to determine in 60 patients with ankylosing spondylitis (AS) the SD of key outcome measures recommended in current Food Drug Administration and European League Against Rheumatism guidelines for AS clinical trials. We anticipate that these tables will be useful to clinical researchers in selecting outcome measures as well as for calculating sample size requirements for future clinical studies in AS.

Analysis of Variance

Ankylosing spondylitis antirheumatic drug trials. III. Setting the delta for clinical trials of antirheumatic drugs--results of a consensus development (Delphi) exercise.

Defining the minimum clinically important difference or delta to be detected in a clinical trial depends on a number of factors including the research hypothesis, patient characteristics, the nature of the intervention and the trial design. In 2 previous studies, we have developed standardized procedures for conducting outcome measurement based on current Food and Drug Administration and European League Against Rheumatism guidelines for clinical trials in ankylosing spondylitis, and thereafter, determined the standard deviation for these outcome measures. In the final component of this series of studies, we have employed a Delphi technique to establish estimates for delta, and calculated the sample size requirements under 2 different conditions of Type I and Type II error probabilities.

Anti-Inflammatory Agents

Synovial fluid immunocytology in the diagnosis of leukemic synovitis.

We describe a patient with leukemic synovitis complicating acute lymphoplastic leukemia. Leukemic cells were identified in the synovial fluid by an indirect immunofluorescent technique using monoclonal antibodies against early B cell antigens. Since focal leukemic lesions may be missed in synovial biopsy specimens, immunocytological analysis of joint fluids may facilitate early diagnosis of leukemic arthritis.

Adult

Clinically unsuspected inclusion body myositis.

We describe a patient with inclusion body myositis presenting as chronic, therapy resistant polymyositis. Our report highlights the slow evolution of inclusion body myositis in some patients, and emphasizes the diagnostic importance of examining one or more muscle biopsy specimens by both frozen section and electron microscopy.

Biopsy

Effect of joint motion on experimental calcium pyrophosphate dihydrate crystal induced arthritis.

We studied the effects of joint movement and immobilization on acute and chronic calcium pyrophosphate dihydrate (CPPD) crystal induced arthritis in lapine knee joints. Exercised CPPD injected joints, in both acute (single 10 mg CPPD intraarticular (IA), duration: 5 h) and chronic (repeated 10 mg CPPD IA, duration: 20 and 42 days) experiments, demonstrated a more intense histologic synovitis compared to cast immobilized knees (p = 0.0001). In chronic experiments, both CPPD injected and noninjected immobilized knees showed greater cartilage histopathologic-histochemical abnormalities (p less than 0.004) and significant reduction in cartilage hexosamine content (p less than 0.005), compared to exercised joints. CPPD injected knees, both exercised and immobilized, demonstrated an initial phase of increased cartilage biosynthetic activity (35S incorporation) at 20 days, compared to noninjected knees (p = 0.02), followed by a decline at 42 days (p less than 0.005). Our data indicate that joint movement enhances acute and chronic experimental CPPD crystal induced synovitis. Articular cartilage is more adversely affected by joint immobilization than by chronic crystalline inflammation. An optimum balance between exercise and rest seems necessary for patients with arthritis so that cartilage can be preserved but pain from active inflammation also controlled.

Animals

Hydroxyapatite pseudopodagra. A syndrome of young women.

Six women with acute calcific periarthritis of the first metatarsophalangeal joint (hydroxyapatite pseudopodagra) are described, and 10 previously reported cases (8 female patients and 2 male patients) are reviewed. The onset was characterized by acute pain, swelling, erythema, tenderness, and limitation of movement of the first metatarsophalangeal joint, symptoms indistinguishable from those of gouty podagra, which is associated with transient amorphous calcific deposits in the vicinity of the joint. Based on these results it appears that hydroxyapatite pseudopodagra is a disorder that predominantly affects premenopausal women.

Acute Disease