IFN-alpha1,8 inhibits tumor-induced angiogenesis in murine angiosarcomas.

Interferon-alpha (IFN-alpha) has proved effective in the treatment of hemangiomas, hemangioblastomas, and Kaposi's sarcoma. To investigate the ability of IFNs to inhibit angiosarcoma, we used two transformed murine endothelial cell lines that form angiosarcomas in vivo. SVR and MS1-VEGF cell lines express oncogenic H-ras or vascular endothelial growth factor (VEGF), respectively. IFN-alpha1,8, which is active against murine and human cells, inhibited SVR and MS1-VEGF proliferation in vitro by 40% at 10(3) U/mL (p = 0.028). In vivo, IFN-alpha1,8 inhibited SVR tumor volume by 71% (p = 0.047) and MS1-VEGF volume by 79% (p = 0.003). Tumor-induced angiogenesis was decreased in SVR tumors by 52% (p = 0.005) and in MS1-VEGF tumors by 58% (p = 0.001). Sera from IFN-alpha1,8-treated mice bearing either SVR or MS1-VEGF tumors demonstrated a 5-fold increase in IP-10/CXCL10 (p = 0.001), an IFN-induced antiangiogenic protein. Both recombinant IP-10 and IFN-alpha1,8 inhibited human umbilical vein endothelial cell (HUVEC) vessel formation in the fibrin gel assay, a three-dimensional culture model of angiogenesis, by 56% at 25 ng/mL and 50% at 1.2 ng/mL, respectively (p < 0.001). An IP-10 blocking antibody restored vessel formation to 80% of untreated controls (p = 0.001). Given the magnitude of the in vivo response, these data suggested that the antitumor effects of IFN-alpha1,8 were likely mediated through angiogenesis inhibition rather than solely by direct inhibition of tumor cell proliferation.     

Blood and plasma donations among a cohort of intravenous drug users

We evaluated the blood and plasma donation histories of a cohort of 2921 intravenous drug users in Baltimore, Md, and correlated these histories with their human immunodeficiency virus (HIV) serologic status, numbers of CD4 lymphocytes in the peripheral blood, and stigmata of intravenous drug use (scarred veins). Of the 793 intravenous drug users (27.1%) who had donated blood or plasma, 652 (82.2%) donated after they had started using intravenous drugs. Most subjects donated at commercial plasma centers, where they were paid $10 to $15 per donation. Although the HIV-1 seroprevalence of the entire cohort was 24.1%, the HIV-1 seroprevalence among those reporting plasma or blood donations declined progressively with time, from 17.1% in those who last donated in 1985 to 3.6% in those who last donated in 1988-1989. Many of the 437 intravenous drug users who had donated plasma or blood since 1985, when screening for HIV-1 was initiated, had not been notified and counseled about their HIV test results. Current programs to exclude individuals with a history of intravenous drug use from the plasma donor pool should be reevaluated and improved.     

Phase II trial of piroxantrone in patients with recurrent and metastatic squamous cell carcinoma of the head and neck

Summary Twenty-two patients with recurrent or metastatic squamous cell carcinoma of the head and neck were treated with piroxantrone 150 mg/m² intravenously every 21 days. There were no objective responses. The 95% upper confidence bound for response is 15%. Primary toxicity was hematologic.     

Facilitated uptake of zinc into human erythrocytes. Relevance to the treatment of sickle-cell anaemia

The ability of a number of heterocyclic metal chelators to deliver zinc into red cells, to release the liganded zinc to haemoglobin and thereby cause a left shift in the oxygen dissociation curve of intact red cells has been investigated. Incubation of neutrally charged zinc-pyrone and zinc-pyridin-2-one complexes with red cells led to the rapid accumulation of zinc within cells, whereas unliganded zinc in the form of zinc acetate, zinc chloride or zinc sulphate accumulated only slowly. The rate at which zinc was delivered to red cells by pyrone and pyridin-2-one ligands increased with increasing lipid solubility of the ligands. The uptake of zinc into both normal adult and sickle red cells was associated with a dose-dependent increase in the oxygen affinity of haemoglobin. The degree of left shift in the oxygen dissociation curve following the incubation of red cells with zinc-pyrone and -pyridin-2-one complexes suggests that these complexes may find application as agents to increase the oxygen affinity of haemoglobin in sickle cell disease and thereby decrease the probability of intravascular sickling at low tissue oxygen tensions. Ethylmaltol appears to be a particularly useful agent due to its known low toxicity.     

Treatment of acne vulgaris. Guidelines for primary care physicians.

The spectrum of acne vulgaris is wide, ranging from minor comedones to devastating nodules and cysts. Appropriate therapy requires an understanding of the various types of lesions, their pathophysiology, and the rationale for treatment. Good patient rapport and communication are important, and close follow-up is necessary until the treatment regimen has stabilized. Timely referral to a dermatologist is essential when therapy is not effective. With effort, the treatment of acne can be quite rewarding for both patient and physician.     

32nd Annual Meeting of the Scandinavian Society for Psychopharmacology Copenhagen,Denmark April 10–12, 1991 Abstracts

32nd Annual Meeting of the Scandinavian Society for Psychopharmacology Copenhagen, Denmark April 10–12, 1991 Abstracts     

Changes in the biophysical properties and ultrastructure of lungs, and intrapulmonary fibrin deposition in experimental acute pancreatitis

Using an experimental model of acute pancreatitis in the rat, we have studied changes in the biophysical properties of lungs and intrapulmonary fibrin deposition in this condition. Acute pancreatitis is associated with a significant decrease in pulmonary compliance (p less than 0.01) and a significant increase in lung weight (p less than 0.01) compared with a control sham operation group. These changes are associated with a 24% increase in intrapulmonary 125I fibrinogen deposition (p less than 0.01), and an 18% increase in 125I fibrinogen deposition per gram of lung tissue (p less than 0.05) in acute pancreatitis, compared with a control sham operation group. The increased fibrinogen deposition is abolished by treatment with low dose heparin. Using the same animal model changes in pulmonary ultrastructure are shown using scanning electron microscopy. The results indicate that pulmonary abnormalities are associated with intrapulmonary fibrin deposition in experimental acute pancreatitis and these findings may be relevant to the well described respiratory complications of the condition in man.