Biomedical subjects
Publications and source records attributed to J P Cullison.
Capnocytophaga has been found to cause disease in the normal and the immunocompromised patient. Most often this organism is an opportunist that is difficult to isolate but easy to identify and a unique reminder that uncommon infection may respond to common antibiotics.
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Orthoclone OKT3 (muromonab-CD3), a murine monoclonal antibody that virtually eliminates circulating T cells and inhibits medullary lymphocyte function, has recently been found effective in reversing stubborn severe allograft rejection after heart transplantation. To determine the influence of OKT3 therapy on the development of infections in cardiac allograft recipients, we compared the frequency and severity of infection in 16 patients who underwent treatment for cardiac allograft rejection at our institution from July 1985 through November 1986. these included 11 patients on OKT3 therapy and 5 patients on a conventional immuno-suppressive regimen. With 2 exceptions late in the trial, OKT3 was used only as a rescue therapy, for patients who did not respond to standard adjunctive therapy consisting of high doses of corticosteroids or antithymocyte globulin, or both. The 5 patients who did not receive OKT3 responded to adjunctive therapy and were in general not as ill as the OKT3 recipients. Our protocol specified that patients in both groups be studied during the 6 weeks (42 days) immediately following transplantation. During this period of study, 6 patients in our 11 member OKT3 group experienced 25 infectious processes, 22 of which occurred in only 3 patients and 14 of which were considered life-threatening (2 of the 3 very ill patients died during the study period). These infections were found most often in the gastrointestinal and genitourinary tracts, involved both bacterial and nonbacterial pathogens, and developed about 2 weeks after the initiation of therapy. By comparison, 2 patients in our 5-member non-OKT3 group experienced 3 infectious processes during the study period, and these were not life-threatening. Because of the occurrence in the OKT3 group of 22 of the 25 infections in only 3 patients, these early results were skewed, but a trend was noted towards a higher incidence of bacterial infection in the OKT3 group. A larger and longer-term trial is under way to evaluate the trend.
Candida (Torulopsis) glabrata is usually a nonpathogenic fungus living saprophytically with normal flora. However, under special circumstances, the organism can become locally invasive and potentially disseminate. Laboratory identification is based on colonial appearance, absence of hyphae, and characteristic biochemical reactions. Treatment usually consists of amphotericin B with occasional reports of 5-fluorocytosine usefulness. It is apparent that Torulopsis represents yet another "evolving" disease with which the clinician must be familiar because successful treatment rests on successful diagnosis.
A 62-year-old man developed cytomegalovirus gastrointestinal infection associated with moderate cardiac rejection. The patient was successfully treated with a new therapeutic agent 9-(1,3-dihydroxy-2-proproxymethyl) guanine during maximal immunosuppression. The medication was well-tolerated, and the patient had an excellent response to therapy. We believe this has significant implications for cytomegalovirus-induced gastrointestinal disease in the heart transplant patient.
The suppression of heart allograft rejection in heart transplantation commonly employs cyclosporine, steroids, and azathioprine, or some combination thereof as baseline therapies. When severe or stubborn rejection is unaltered by these drugs, adjunctive immunotherapy is required. This article details our experience in treating difficult allograft rejections with a purified murine monoclonal antibody directed against the murine antihuman mature T cell (OKT3) lymphocyte. The inclusion criteria for use of OKT3 included severe histologically confirmed rejection (7 on a 0 to 10 scale), rejection refractory to other immunosuppressive agents (methylprednisolone, antithymocyte globulin), or contraindications toward the use of other immunosuppressive agents. From July 1985 through September 1986, 11 patients with severe rejection that was documented by histologic, biochemical, and clinical criteria were treated with intravenous OKT3. Of these patients, 10 had received orthotopic heart transplantations and one had undergone heterotopic transplantation. The mean duration of therapy was 14.4 days, with a single, average dose of 5 mg/day. Intended duration of therapy was 14 days per our protocol. Occasionally this was extended because of evidence of ongoing rejection or because of the potential toxicity of other immunosuppressive agents (i.e., cyclosporine nephrotoxicity in a patient with kidney failure). One patient demonstrated an equivocal response to the drug but experienced no side effects. In the remaining 10 patients a full course of treatment with OKT3 dramatically reversed the rejection and resulted in improved graft performance. On a standardized scale for histologic grading of rejection the average score decreased from 8.4 to 4.1 and stayed in the "mild" rejection range (0 to 4) thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)