Fibrin sealant: clinical use and the development of the University of Virginia Tissue Adhesive Center

The utilization of fibrin sealants to augment hemostasis, seal tissues, and facilitate targeted delivery of drugs is increasing. In 1985, a hospital-based program was established to provide autologous and allogeneic cryoprecipitate that serves as a fibrin sealant when combined with bovine thrombin. To date, more than 4,000 patients have been treated with this product at our institution, with an efficacy rate greater than 90%. Collaboration among surgical services and the blood bank fostered multispecialty expertise with this product that led, in 1997, to the establishment of the University of Virginia Tissue Adhesive Center. The Tissue Adhesive Center is a multidisciplinary center whose physician director and nursing and administrative support staff facilitate basic research, laboratory investigation, and preclinical and clinical trials with collaborators throughout the university. The Tissue Adhesive Center also provides educational programs and clinical consultation, and tracks and participates in peer review of sealant use. The licensure of a commercially produced, virally inactivated, pooled-plasma fibrin sealant in May 1998 provided an alternative source of adhesive. Utilization of the commercial product surpassed use of the blood bank product in April 1999. At present, use of the commercial product is approximately 3 times that of the blood bank-produced sealant. This report reviews the clinical uses of fibrin sealant, its regulatory history, the production of fibrin sealants, the evolution of a blood bank fibrin sealant program, the development of the Tissue Adhesive Center, and the utilization of commercial and blood bank-produced sealant at our university hospital.     

Presence of virus-specific DNA sequences in murine type C viruses.

Total nucleic acids prepared from a number of murine retroviruses have been shown to contain virus-specific DNA in addition to genomic RNA. This virus-specific DNA has been shown to be at least partially double stranded and to be present within the virus core particle. The DNA isolated from the virus is greatly enriched in virus-specific DNA relative to that from virus infected cells.     

Infection of chicken erythrocytes with influenza and other viruses.

Chicken erythrocytes can be infected by the fowl plague (Rostock) strain (FP/R) of influenza type A, Newcastle disease virus (NDV), and Semliki Forest virus (SFV). Only NDV and SFV produced infectious progeny, albeit at low levels. Infection by FP/R was monitored by de novo synthesis of viral proteins, and the proteins synthesized could be identified by comparison with infected chicken fibroblast cells. FP/R synthesized far greater amounts of viral protein than did NDV or SFV.     

Activation of the respiratory burst in murine phagocytes by certain guanine ribonucleosides modified at the 7 and 8 positions: possible involvement of a pertussis toxin-sensitive G-protein

The capacity of certain guanine ribonucleosides (modified at the 7 and/or 8 positions) to enhance the respiratory burst of murine peritoneal phagocytes was evaluated. The results show that 8-mercaptoguanosine, 8-bromoguanosine, 7-methyl-8-oxoguanosine and 7-thia-8-oxoguanosine, when injected intraperitoneally into mice, induced peritoneal phagocytes to generate reactive oxygen species as early as 1 h after injection. In vivo administration of the nucleosides induced higher levels of phagocyte activation than in vitro treatment with the same nucleosides. However, the addition of interferon alpha/beta in vitro significantly increased the magnitude of phagocyte activation by the nucleosides, suggesting an important role for cytokines/lymphokines in the nucleoside-induced phagocyte activation in vivo. Furthermore, pre-treatment of phagocytes in vitro with Bordetella pertussis toxin, before treatment with the guanosines, inhibited their capacity to induce the respiratory burst. These observations establish these low-molecular-weight compounds as interesting probes for the study of stimulus-response coupling in phagocytes.     

Treatment Options in Severe Psychotic Depression

In our sample of 15 hospitalized patients with severe psychotic depression, six responded to therapy with tricyclic antidepressants combined with neuroleptics. Of the nine nonresponders, eight showed an excellent clinical response to electroconvulsive therapy (ECT). The clinical outcome after 6 months of treatment was similar in both groups. We recommend that protracted, complicated trials of pharmacotherapy be reevaluated in psychotic depression. A prospective comparative study of ECT and pharmacotherapy is needed to define the optimal treatment for psychotic depression.