Clinical and radiographic response in a minority of patients with recurrent malignant gliomas treated with high-dose tamoxifen.

Previous work has demonstrated the importance of the Protein Kinase C (PKC) signal transduction system in regulating the growth rate of malignant gliomas in vitro. Tamoxifen inhibits PKC in a minority of malignant gliomas within the micromolar concentration range in vitro, a property distinct from its estrogen receptor blockade effect. Tamoxifen was administered orally in very high dosages to 11 patients (9 males:2 females, age range 26-73, mean 45 years) with malignant gliomas (anaplastic astrocytoma or glioblastoma multiforme) who had failed treatment with external beam radiation therapy (and additional chemotherapy in 2). The dosage administered was estimated to be that necessary to achieve tissue concentrations within the low micromolar range, shown necessary to inhibit PKC in these tumors in vitro, and is approximately 5 times that used for standard antiestrogen therapy. Tumor reduction on radiographic images (MRI and PET [18FdG uptake]) with clinical improvement occurred in 3 patients; halting of tumor progression clinically and radiographically occurred in an additional patient. Of the remaining seven patients, three patients had marked and rapid progression of their disease despite treatment (dead after 3, 4, and 6 months respectively). Complications of treatment included a deep venous thrombosis requiring anticoagulation in one patient, nausea in one patient, and "hot-flashes" in a third patient. Tumor biopsy and measurement of tamoxifen and its active metabolite within the tumor of one patient (non-responder) showed levels within the middle of the in vitro therapeutic range. Follow-up of alive patients ranges from 4-18 months (mean 10 months). These encouraging preliminary results in a minority of these patients suggests some potential for this type of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Regression of reactive systemic amyloidosis due to ankylosing spondylitis following the administration of colchicine.

We describe a patient in whom nephrotic syndrome due to renal amyloidosis occurred 4 years into the course of severe ankylosing spondylitis with peripheral joint and extraarticular involvement. Treatment with colchicine was accompanied by reversal of proteinuria, and histologic regression of amyloid deposits was documented from bone marrow obtained from the femoral heads during total hip arthroplasties staged 1 year apart.

Serum levels of interleukin-2 receptor and activity of rheumatic diseases characterized by immune system activation.

Levels of interleukin-2 receptors (IL-2R), as measured by a double-antibody "sandwich" enzyme-linked immunosorbent assay technique, were markedly elevated in the serum of patients with systemic lupus erythematosus, rheumatoid arthritis, and bacterial endocarditis, but not in patients with acute gout. Serum levels of IL-2R correlated strongly with clinical and laboratory indicators of disease activity in patients with lupus and in those with rheumatoid arthritis. This relationship was confirmed by sequential determinations in individual patients. Serum IL-2R values correlated with disease activity better than did the Westergren erythrocyte sedimentation rate. Our findings indicate that serum levels of IL-2R may serve as a reliable serologic indicator of disease activity in inflammatory diseases characterized by immune system activation.

Renal involvement in mixed connective tissue disease: a longitudinal clinicopathologic study.

Eleven of 30 patients with MCTD, followed for a mean of 10 years, developed immune complex nephropathy (five membranous, two mesangial, one mixed, and one sclerosing) with NS in nine of 11. Another patient had membranous nephropathy at autopsy. Patients with renal disease tended to have more systemic manifestations than those without. NS was at times of abrupt onset, recurrent, and/or persistent. Anti-RNP and serum complement were not helpful in predicting nephritis. Seventy-two percent of nephropathy and 62% of NS episodes resolved or improved after corticosteroid therapy. Five patients became hypertensive, two developed chronic renal failure and required chronic dialysis, and one needed acute dialysis twice. One patient progressed to focal proliferative crescentic nephritis with necrotizing arteritis. Three patients with nephropathy died, two of pulmonary hypertension with acute cor pulmonale and one of overwhelming sepsis. Nephropathy is relatively common in MCTD, is associated with substantial morbidity, and with the risk of hypertension and chronic renal failure.

T lymphocyte subsets in systemic lupus erythematosus. Correlations with corticosteroid therapy and disease activity.

The contribution of immune regulation to the etiology of systemic lupus erythematosus (SLE) is poorly understood. Using the monoclonal antibodies OKT4 and OKT8, we quantitated, by flow cytometry, T inducer/helper and T cytotoxic/suppressor cells in patients with SLE. Serologically active patients, who had clinical manifestations such as arthritis or rash and were not receiving prednisone, were characteristically lymphopenic due to a marked reduction in OKT4+ cells. Prednisone therapy produced the same phenomenon. Untreated patients, who were serologically inactive, demonstrated no abnormalities. These studies have thus revealed two presumably independent factors that can produce similar immunoregulatory aberrations.

Salmonella dublin arthritis: an initial case presentation.

Salmonella dublin is a rare pathogen in man usually causing an enteric fever syndrome. We report a 32-year-old black male who developed septic polyarthritis with Salmonella dublin. The clinical features are similar to those seen with other Salmonella serotypes reported to cause arthritis. The initial presentation is suggestive of a reactive arthritis that is immunologically mediated.

Esophageal dysfunction in patients with mixed connective tissue diseases and systemic lupus erythematosus.

We sought to correlate esophageal symptoms with esophageal motility abnormality in 17 patients with mixed connective tissue disease (MCTD) and in 14 patients with systemic lupus erythematosus (SLE). Heartburn and regurgitation were common symptoms (11/17) in patients with MCTD, and most of the (10/11) exhibited significant manometric abnormalities. Additionally, impairment of esophageal peristalsis was found in four of the remaining asymptomatic patients. Severe esophageal aperistalsis was noted in nine MCTD patients. Patients with SLE also frequently reported esophageal symptoms (8/14), but significant motility abnormalities were seen in only three cases. In both patient groups good correlation between Raynaud's phenomenon and esophageal aperistalsis was found. Our results reveal that, although esophageal symptoms are commonly present in patients with both MCTD and SLE, severe esophageal motility abnormalities are more often found in patients with MCTD than in those with SLE.

Wegener's granulomatosis. Electron microscopic and immunofluorescent studies.

We report a case of classic Wegener's granulomatosis. Direct immunofluorescent study showed finely granular deposits of IgG and IgM in some of the alveolar walls, and of IgM in the maxillary sinus arteries. Electron-microscopic study of the lung and maxillary sinus showed intravascular fibrin, but failed to demonstrate electron-dense deposits in the blood vessel walls. Our patient also had circulating cryoglobulins, consisting of IgG, IgM, Clq, and C3, and evidence of circulating immune complexes as demonstrated by the Clq-binding test. These findings suggest that circulating immune complexes may play an important role in the pathogenesis of the respiratory lesions of Wegener's granulomatosis.