Transthoracic and transesophageal echocardiographic evaluation of the aortic root and subvalvular structures in ankylosing spondylitis.

OBJECTIVE: During the preclinical phase of cardiac involvement in ankylosing spondylitis (AS), examination, electrocardiography, and transthoracic echocardiography (TTE) may lack the sensitivity to detect cardiac abnormalities. Since transesophageal echocardiography (TEE) allows a closer view of the aortic root and subvalvular structures we investigated whether preclinical abnormalities of the aortic root and subvalvular structures could be detected. METHODS: Clinical and echocardiographic (TTE and TEE) evaluation of 29 male patients with AS and 13 age matched controls. RESULTS: No patient with AS had a high degree heart block. Aortic root dimensions were comparable between the study groups, but the anterior aortic wall was thinner in patients with AS than controls, 0.25 and 0.41 cm, respectively (p = 0.016). The posterior aortic wall was thicker and subjectively more echogenic than the anterior wall in 17/29 patients with AS compared to 4/13 controls. Aortic valve insufficiency was detected with TEE in 10/29 patients with AS. In 8/9 patients with AS studied with TEE, the subaortic structures were thickened and/or of increased echogenicity. This abnormal echo extended into the membranous septum. CONCLUSION: Abnormal subvalvular echoes consistent with fibrosis of the aortic root and membranous interventricular septum were detected with TEE but not TTE. The use of TEE may allow earlier diagnosis of cardiac involvement in AS.

Clinical correlations of osteoarthritis associated with a single-base mutation (arginine519 to cysteine) in type II procollagen gene. A newly defined pathogenesis.

OBJECTIVE: To investigate the occurrence and clinical correlation of the arg519-to-cys mutation in the type II procollagen gene in patients with osteoarthritis (OA). METHODS: Sixty-six subjects from 7 families with a strong family history of generalized OA and 13 patients with erosive OA were evaluated clinically and radiologically. Blood samples from 58 subjects in the familial OA group and from all 13 patients with erosive OA were obtained for DNA analysis. Exon 31 of COL2A1, which spans residue 519, was amplified by polymerase chain reaction. RESULTS: The arg519-to-cys mutation was detected in 2 of the 7 families with generalized OA. In these 2 families, the mutation was present in the 2 probands and in 19 other clinically affected family members, as well as in 3 (so-far) clinically unaffected family members (ages 25, 14, and 11 years). It was absent in 18 clinically unaffected members tested. The mutation was associated with a distinctive pattern of early-onset, aggressive, generalized OA with a mild spinal chondrodysplasia. Inheritance was autosomal dominant. No mutation was found in any of the patients with erosive OA. CONCLUSION: The arg519-to-cys mutation defines a new pathogenic factor in generalized OA with characteristic clinical and radiologic features. The demonstration of a mutation in 3 of 8 families with OA studied thus far suggests a significant incidence of genetically related clinical OA.

Neuropathologic findings in multi-infarct dementia associated with anticardiolipin antibody. Evidence for endothelial injury as the primary event.

OBJECTIVE: There are few reports describing histopathologic changes associated with the antiphospholipid antibody syndrome. We describe a patient with multi-infarct dementia and antiphospholipid antibody syndrome, in whom a brain biopsy was performed. METHODS: Biopsy material from the left frontal cortex, including meninges, cortex, and underlying subcortical white matter, was investigated. Microscopic examination and special staining were performed. RESULTS: Microscopic examination showed lumenal occlusion by thrombi, and marked endothelial hyperplasia of small meningeal and cortical arterioles. CONCLUSION: These findings suggest that the pathogenesis of this cerebral vasculopathy is noninflammatory and is associated with reactive endothelial hyperplasia and thrombosis of small arterioles.

Prosthesis-induced synovitis simulating villonodular synovitis.

Prosthetic arthroplasties are performed frequently in arthritic patients. The usual causes of prosthetic failures are loosening, infection, subluxation, or fracture. A 65-year-old man with total knee arthroplasty illustrates the complication of prosthetic synovitis developing 5 years after metal-polyethylene arthroplasty. Double contrast arthrography revealed nodular synovial filling defects. Arthrotomy and hematoxylin-and-eosin-stained histological sections of the synovium showed nonpigmented villonodular synovitis (VS). Giant cells and polyethylene particles were observed by polarized light within the synovium.

Pneumocystis carinii pneumonia following corticosteroid therapy for giant cell arteritis.

Pneumocystic carinii pneumonia (PCP) is a well-recognized complication of immunodeficiency disorders. PCP has been reported in patients with connective tissue diseases, but most were on cytotoxic drugs. We report a case of PCP occurring in a patient with giant cell arteritis who was receiving high dose prednisone. To our knowledge this complication has not been previously reported.

Low-dose weekly oral methotrexate therapy for inflammatory arthritis.

The efficacy and toxicity of low-dose, weekly oral methotrexate (MTX) therapy for inflammatory arthritis was evaluated. Fifty-nine patients with a diagnosis of inflammatory arthritis who had failed to respond to or developed toxicity to gold, penicillamine, or hydroxychloroquine therapy were treated with MTX 10-20 mg administered orally or intravenously once a week in divided doses. Various tests to assess arthritis were performed upon each patient's entrance into the study and at specified intervals throughout the 24-month study period. The mean duration of methotrexate therapy was 15.5 months. Patients showed significant improvement in number of swollen joints, duration of morning stiffness, amount of pain, and amount of activity during the study period. Of the 35 patients who had had roentgenographic studies of their hands performed initially and after one year of MTX therapy, 23 had no evidence of new joint erosions after one year. Biopsies of hepatic tissue from 20 patients showed no progressive changes when compared with pretreatment biopsies. Gastrointestinal symptoms, mucocutaneous lesions, or small increases in liver enzyme concentrations were observed in 31 patients; three patients developed pulmonary toxicity and had to be withdrawn from the study. MTX is an effective agent for the treatment of inflammatory arthritis in patients who do not respond to therapy with nonsteroidal anti-inflammatory drugs or slow-acting antirheumatic drugs. Short-term weekly oral MTX therapy does not appear to result in clinically important liver disease.

A review of selected investigational nonsteroidal antiinflammatory drugs of the 1980s.

We reviewed the literature on 7 investigational nonsteroidal antiinflammatory drugs (NSAIDs): fenbufen, flurbiprofen, tiaprofenic acid, diclofenac, fenclofenac, etodolac and proquazone. These drugs all appear to be at least as effective as currently marketed NSAIDs. Toxicity reported with these newer agents is similar to that seen with other drugs in this class, with gastrointestinal complaints being most commonly reported. The frequency of gastritis and the extent of gastrointestinal microbleeding are less than what occur with aspirin therapy. Fenclofenac may affect thyroid function tests, an effect not noted with other NSAIDs. Proquazone and fenclofenac may have some effect on immunologic function similar to those of slow-acting antirheumatic drugs. These drugs decrease immunoglobulins, rheumatoid factor and C-reactive protein. The place for these drugs in the management of rheumatic diseases has yet to be defined. They may prove to be more beneficial than currently marketed drugs for some patients.

Streptococcal myositis.

Two patients had streptococcal myositis. Both patients developed extensive muscle necrosis and overwhelming sepsis after trivial skin trauma. Death occurred within 48 hours of hospital admission despite aggressive surgical and medical treatment. Review of the literature is included to highlight the fulminant nature of this unusual infection and to contrast streptococcal myositis with other soft-tissue streptococcal infections.

Use of biofeedback training in treatment of Raynaud's disease and phenomenon.

To assess biofeedback training in Raynaud's, we retrospectively reviewed 23 patients' records. Eleven had Raynaud's disease and 12 had Raynaud's phenomenon; 9 had recurrent digital ulcers. Patients demonstrated lower baseline digital temperatures than controls (p less than or equal to 0.001), patients with Raynaud's and scleroderma manifesting the lowest. After biofeedback training all patients elevated baseline temperatures. Patients with scleroderma and systemic lupus erythematosus had the greatest elevations. Improvement, both subjective (57%) and ulcers (44%), persisted one year after treatment. Four of 7 patients were capable of elevating digital temperatures within 5 min, 18 months after their last training session. These findings support biofeedback training as beneficial therapy in Raynaud's.

Fibrous myopathy in association with pentazocine.

Cutaneous complications of chronic parenteral narcotic use have been described. A 61-year-old man had severe joint restriction secondary to fibrous replacement of proximal muscles. Parenteral pentazocine lactate use was implicated in the cause of his condition.

Budd-Chiari syndrome and renal failure in Behcet disease. Report of a case and review of the literature.

A case of Behcet syndrome associated with three rare complications is presented. The patient initially presented with asymmetric polyarticular arthritis, subcutaneous nodules, conjunctivitis, and episcleritis. Necrotizing vasculitis and renal failure subsequently evolved. Despite immunosuppressive therapy, Budd-Chiari syndrome with high grade hepatic obstruction developed. A Denver shunt procedure failed to alter the terminal course. At postmortem examination, skin lesions, carditis, hepatic vein thrombosis, gastric ulcerations, and focal proliferative glomerulonephritis were found. The immunoglobulins and complement present in skin and renal tissue suggest an immune complex pathogenesis.

Second course gold therapy in the treatment of rheumatoid arthritis.

Twenty-three rheumatoid arthritis patients who had previously received gold therapy were selected for second course gold. Eleven patients had developed complete remission during the first course of gold therapy. Four of these had a complete response to second course gold. Of the 10 nonresponders and 2 partial responders to first course gold, none responded to second course gold. We conclude that individuals in whom first course gold is unsuccessful respond poorly to repeated gold treatments. In addition, only 36% of the patients who initially had a complete response sustained complete remission with second course gold.

Reduction in oral penicillamine absorption by food, antacid, and ferrous sulfate.

Plasma levels of penicillamine, urinary recovery of penicillamine and its oxidized metabolites, and urinary excretion of copper were examined after single 500-mg oral doses of penicillamine to six healthy men. Penicillamine was given after an overnight fast, a standard breakfast, and after antacid and ferrous sulfate. Following the fasting dose, the mean peak plasma level of 3.05 micrograms/ml developed at 3.8 hr and the drug was cleared from plasma with a t1/2 of 2.1 hr. Penicillamine levels were reduced to 52%, 35%, and 66% of those from the fasting dose after food, ferrous sulfate, and antacid. The rates of penicillamine appearance and disappearance from plasma were essentially treatment independent. There were good correlations between urinary recovery of total penicillamine (r = 0.875), between urinary copper excretion (r = 0.758) and the penicillamine plasma concentration AUCs. The availability of oral penicillamine is very susceptible to interactions with other substances. Further studies may be necessary to assess the full clinical significance of these interactions.

Influence of food on the bioavailability of penicillamine.

The relative bioavailability of D-penicillamine was determined after single 500 mg oral doses of commercial tablets to healthy male volunteers under fasting and nonfasting conditions. In fasted individuals the mean maximum penicillamine level in plasma of 3.05 mcg/ml occurred at 3.8 h, and the area under the 0-12 h plasma curve was 14.7 mcg/h/ml. In nonfasted individuals the mean maximum penicillamine level of 1.52 mcg/ml occurred at 2.3 h, and the area under the 0-12 h plasma curve was reduced to 7.16 mcg/h/ml. Thus under these conditions food reduced systemic penicillamine availability by 1/2, but did not reduce the apparent absorption rate.