The evaluation of argon laser photocoagulation in a series of animal models of upper gastrointestinal bleeding

During the past five years we have evaluated argon laser photocoagulation in various canine models of upper gastrointestinal hemorrhage. In gastric erosions, the eight-watt argon laser was uniformly effective in stopping bleeding. In our standard acute ulcer model the seven-watt argon laser was effective in stopping bleeding from most ulcers and only occasionally produced deep injury. With the addition of a jet of CO2 exiting the laser catheter coaxial to the laser beam, the argon laser was 100% effective and no deep injury resulted. The application of the argon laser in a more physiologic canine bleeding model using a single bleeding vessel in an ulcer base is currently under study. The development of improved animal models of gastrointestinal bleeding should contribute to the identification of effective and safe endoscopic hemostatic methods.     

Afterload reduction in the management of postinfarction ventricular septal defect

The primary goal in the medical management of ventricular septal defect complicating myocardial infarction is to support cardiac function and control symptoms, if possible, for a period of 4 to 6 weeks. If the patient survives this period, surgical correction of the defect is technically easier and safer. In many cases, However, cardiac function is severly compromised, intractable biventricular failure develops,early operation is necessary and the likelihood of successful repair is diminished.     

Nonmitogenic anti-CD3F(ab')2 fragments inhibit lethal murine graft-versus-host disease induced across the major histocompatibility barrier

We have investigated the in vivo administration of nonmitogenic anti-CD3F(ab')2 fragments for the prevention of lethal graft-vs-host disease (GVHD) in irradiated recipients of fully allogeneic bone marrow cells plus splenocyte (BMS) inocula. Recipients of anti-CD3F(ab')2 fragments administered for 1 mo post-bone marrow transplantation (BMT) had 100% survival without clinical or histopathological evidence of GVHD. Controls given saline injections succumbed by 39 days post-BMT. Similar results were obtained in groups of recipient mice given BMS in which T cells were depleted by in vitro anti-Thy-1.2 plus C' treatment. Further studies were undertaken to define mechanistic differences in the two approaches. Using Ly-5 congenic sources of donor bone marrow and spleen, we determined that anti-CD3F(ab')2 fragments induced TCR modulation and T cell depletion. Mature splenic-derived CD4+ cells were depleted to a greater extent than CD8+ cells. Early post-BMT, recipients receiving injections with control saline had the highest number of CD4+ and CD8+ cells (which may cause GVHD) followed by recipients of anti-CD3F(ab')2 fragments, with the fewest CD8+ cells observed in the anti-Thy-1.2 + C' treated group. CD3+CD4-CD8- cells (which may suppress GVHD generation) were present in higher numbers early post-BMT in recipients given anti-CD3F(ab')2 fragments as compared to recipients given anti-Thy-1.2 + C'-treated BMS. In long term survivors, a mononuclear T cell containing infiltrate without evidence of destruction was observed in sites of GVHD (lung and liver), consistent with a "Quilty" effect, which was not observed in either of the other two groups. Although survivors were tolerant of donor skin grafts and rejected third party grafts, recipients given anti-CD3F(ab')2 fragments but not anti-Thy-1.2 + C'-treated BMS had vigorous anti-host proliferative responses. These results demonstrate that although in vitro anti-Thy-1.2 + C' treatment of BMS (which is highly depletionary) and in vivo administration of anti-CD3F(ab')2 fragments (which is modulatory and less depletionary) are both effective strategies for GVHD, the cellular events involved in achieving GVHD prevention are indeed different.