Thyrotropin receptor antisera for the detection of immunoreactive protein species in retroocular fibroblasts obtained from patients with Graves' ophthalmopathy.

Autoimmunity against the TSH receptor (hTSH-R) is known to be the proximate cause of thyroidal activation in Graves' disease, but has not been definitively linked to extrathyroidal manifestations of this disorder, such as ophthalmopathy and pretibial myxedema. In an effort to increase our knowledge concerning mechanisms responsible for Graves' ophthalmopathy, we used antiserum directed against a highly immunogenic portion of the hTSH-R (amino acids 352-367; P1) to assess the presence of this receptor or immunologically related protein in cultured human retroocular fibroblasts obtained from patients with Graves' ophthalmopathy. Immunoenzymatic and immunofluorescent studies revealed specific staining of both cytoplasmic and cell membrane-associated protein in discrete vesicles. To further evaluate the immunoreactive species present in these cells, immunoblotting experiments were performed using hTSH-R-specific antisera (anti-P1) and sera obtained from patients with Graves' disease. Several protein bands were identified using both anti-P1 and Graves' disease patient sera, including species at mol wt of 95, 71, and 18 kilodaltons, the possible significance of which is discussed. The results support the hypothesis that immunity against the hTSH-R or related proteins contributes to the ophthalmopathy of Graves' disease.

FAM chemotherapy +/- aminoglutethimide in the treatment of pancreatic carcinoma.

Human pancreas contains receptors for estrogens and androgens as well as aromatase activity. FAM chemotherapy was administered to 14 patients with pancreatic cancer (seven at Stage IV). The median survival of these patients was 24.4 +/- 4.8 weeks. FAM chemotherapy plus aminoglutethimide/hydrocortisone (AG/HC) (250 mg bid AG + 20 mg bid HC) was administered to 14 patients (seven at stage IV). The median survival of this group was 17.3 +/- 2.9 weeks (P = 0.74 vs FAM alone). We conclude that addition of AG/HC does not add to the survival of patients with carcinoma of the pancreas treated with chemotherapy.

Perirectal infections in acute leukemia. Improved survival after incision and debridement.

During a 6-year period, 16 (7.9%) of 202 patients with acute leukemia of both the lymphocytic and nonlymphocytic types developed perirectal infections. All patients were febrile and severely neutropenic (14 patients had absolute neutrophil counts of less than 100/mm3). Lesions were painful and indurated but lacked fluctuance. Urinary retention, peritoneal signs, and extension of the infection to the genitalia were common. Eleven patients had bacteremia, and an average of 2.1 enteric bacteria were recovered from samples of abscess fluid or blood. Perirectal lesions were operatively incised and debrided (10 patients), unless spontaneous drainage occurred (5 patients). These 15 patients became pain-free in less than 48 hours and afebrile in 2 to 8 days. Drained lesions healed in all. Thirteen of fifteen patients left the hospital, whereas 2 died in the hospital of unrelated causes. The only patient whose lesion was not drained died of continuous bacteremia. Early incision and debridement contributed to our patients' improved survival.

Comparison of the effects of mezlocillin, carbenicillin, and placebo on normal hemostasis.

Mezlocillin was compared with carbenicillin and 0.9% NaCl as placebo in a double-blind manner to determine its effect in vivo on hemostasis in normal volunteers. Eighteen subjects were randomized to receive mezlocillin, 4 g every 6 h; carbenicillin, 7.5 g every 6 h; or placebo, 50 ml every 6 h, each given for 20 intravenous doses unless the template bleeding time after 10 doses was greater than 15 min. Template bleeding times were determined before the dose 1 and 1 h after doses 10 and 20. Five of six (83%) subjects receiving carbenicillin developed template bleeding time prolongation to greater than 21 min, and two of six (33%) subjects receiving mezlocillin and one of six (17%) subjects receiving carbenicillin had mild template bleeding time prolongations of less than 13 min. Coagulation studies (prothrombin time, partial thromboplastin time, and thrombin time) were normal in all subjects, and blood salicylate levels were negative. Thus, in standard therapeutic doses, mezlocillin was less likely than carbenicillin to prolong the template bleeding time above normal (P = 0.04) and, when prolongation occurred with mezlocillin, it was mild. These data support the selective use of mezlocillin in patients at increased risk for bleeding and who require therapy with an antipseudomonal penicillin.