Biomedical subjects
Publications and source records attributed to B F Germain.
Two patients are described in whom a progressive systemic sclerosis-like illness developed several years after silicone augmentation mammoplasty. Both had removal of breast implants, followed by marked-to-complete recovery from clinical abnormalities. This entity is increasingly recognized and has become known as human adjuvant disease.
Nabumetone is a new nonsteroidal anti-inflammatory agent. Therapy with nabumetone 1,000 mg given at bedtime was compared with naproxen 250 mg given twice daily in a prospective double-blind study of patients with rheumatoid arthritis. Both drugs were found to be efficacious in a comparable fashion. Both drugs were well tolerated in terms of patient withdrawal rates, which were 5 and 8 percent, respectively. Gastrointestinal side effects were the most commonly encountered problem. Nabumetone holds promise as an important new therapeutic approach in arthritis.
A six-month, multicenter, double-blind study compared the efficacy and safety of two therapeutic regimens in 332 patients with osteoarthritis. The patients received either 1,000 mg of nabumetone as a single bedtime dose or 900 mg of aspirin in four divided doses. At the end of the study, patients in both treatment groups showed significant improvement from baseline for all five parameters; no statistically or clinically significant differences were observed between the groups. The safety data did reveal clinically and statistically significant differences between the groups. Aspirin-treated patients experienced a greater frequency of withdrawal from the study because of adverse experiences (34 percent versus 13 percent), a greater incidence of having at least one treatment-related adverse experience (73 percent versus 52 percent), a greater percentage of patients with at least one moderate or severe treatment-related adverse experience (47 percent versus 22 percent), and a greater percentage of patients with treatment-related adverse experiences affecting the gastrointestinal system (43 percent versus 32 percent) or the inner ear (32 percent versus 10 percent). The results of this study demonstrated that nabumetone, 1,000 mg at bedtime, is as efficacious as aspirin, 900 mg four times daily, produces fewer adverse effects, and is indicated in the treatment of osteoarthritis.
Eight patients with long-standing rheumatoid arthritis and cutaneous vasculitis ulcerations resistant to conventional therapy were treated successfully with a low-dose intermittent regimen of oral methotrexate. Objective clinical response was prompt and complete resolution was observed at about 12 weeks of therapy. The drug was well tolerated. Mild gastrointestinal side effects were the most common untoward reaction. We conclude that methotrexate therapy is an effective agent for some of the extraarticular manifestations of rheumatoid arthritis including vasculitis, and further clinical evaluation should be a consideration.
The efficacy of piroxicam 20 mg/qd was compared with that of sulindac 200 mg twice a day in 49 patients with rheumatoid arthritis. Both nonsteroidal anti-inflammatory agents showed statistically significant improvement in efficacy variables including duration of morning stiffness, disease activity as judged by the examiner and by the patient, patient assessment of feeling, total joint pain, total joint swelling, and performance of daily activities. The overall frequency of adverse reactions was similar with both treatment regimens, and required discontinuance in three patients in each treatment group. However, the number of moderate/severe adverse reactions in the sulindac-treated patients was greater than that in the piroxicam-treated patients, and there was a trend toward the differences between the two groups being statistically significant (P = .06). Both drugs were effective in the treatment of rheumatoid arthritis and resulted in comparable improvement in efficacy variables.
A patient with progressive systemic sclerosis who presented with a painless, destructive joint disease consistent with a neuropathic arthropathy is described. Roentgenogram of the cervical spine revealed marked osteolysis of C1 and C2 which allowed the odontoid process to migrate upward, compress and produce atrophy of the cervical spine cord. We suggest that these changes were responsible for the development of the neuropathic joints.
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We report 3 male patients with a unique eosinophilic myositis of unknown etiology who appear to have a benign course. The most striking feature in 2 patients was relapsing myalgias with lower extremity predilection and tendency for spontaneous recovery. Laboratory studies showed peripheral eosinophilia, elevated CPK, and EMG consistent with a myositic pattern. Muscle biopsies showed myositis characterized by focal necrosis and degeneration with an inflammatory infiltrate predominantly composed of histiocytes and eosinophils. Skin and fascia were normal.
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Light and electron microscopic studies were performed on the synovial membranes from the large joints of 12 patients with psoriatic arthritis. The most significant histopathologic findings were vascular changes that were characterized by endothelial cell swelling accompanied by inflammatory cell infiltration and marked thickening of the vessel wall. Fibrosis of the subsynoviocyte tissue was also prominent, especially in patients with chronic disease. Villi were not prominent, and the lining layer was not thickened. Both type A and B cells were seen; none had significant abnormalities. No electrondense deposits were observed. These findings lend further support to the theory that microvascular changes play a significant role in the pathogenesis of psoriasis and its related arthritis.
We studied sera from 20 patients with polymyalgia rheumatica (PMR)/giant cell arteritis (GCA), 15 patients with systemic lupus erythematosus (SLE), 15 patients with the CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangietasia) and 33 age and sex matched controls for cytotoxicity against human endothelial cells using a 51Cr release assay. We observed increased levels of endothelial cytotoxic activity in the PMR/GCA sera compared with controls (P less than 0.001). This cytotoxicity was predominantly found in the GCA group, where 7 out of 10 patients (70%) demonstrated significant cytotoxicity. Sequential studies showed that the cytotoxic activity returned to normal when the disease was under control. Although 7 SLE and 3 CREST sera had significant cytotoxic activity, as a group they did not differ from controls (P less than 0.05). Pre-incubation with soybean trypsin inhibitor suppressed the cytotoxic activity in the positive sera suggesting the cytotoxicity is mediated via a protease mechanism. Our results demonstrate the presence of a cytotoxic factor in the serum of patients with PMR/GCA which may play an important role in the pathogenesis of the vascular lesions observed in these disorders.
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