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J Cremer

Publications and source records attributed to J Cremer.

108 records · Page 6Linked to original sources

[Hyperimmunoglobulin treatment in CMV infections following heart transplantation].

Clinically manifest cytomegalovirus (CMV) infections, with and without pulmonary involvement, occurred in two patients after heart transplantation. The diagnosis was confirmed immunologically. After administration of CMV hyperimmunoglobulin and prophylactic antibiotics and a reduction of immunosuppressives, rapid clinical improvement ensued so that both patients were discharged from hospital after seven and ten days, respectively.

Adolescent↗

Regulation of enzymes of lysine biosynthesis in Corynebacterium glutamicum.

The regulation of the six enzymes responsible for the conversion of aspartate to lysine, together with homoserine dehydrogenase, was studied in Corynebacterium glutamicum. In addition to aspartate kinase activity, the synthesis of diaminopimelate decarboxylase was also found to be regulated. The specific activity of this enzyme was reduced to one-third in extracts of cells grown in the presence of lysine. Aspartate-semialdehyde dehydrogenase, dihydrodipicolinate synthase, dihydrodipicolinate reductase, and diaminopimelate dehydrogenase were neither influenced in their specific activity, nor inhibited, by any of the aspartate family of amino acids. Homoserine dehydrogenase was repressed by methionine (to 15% of its original activity) and inhibited by threonine (4% remaining activity). Inclusion of leucine in the growth medium resulted in a twofold increase of homoserine dehydrogenase specific activity. The flow of aspartate semialdehyde to either lysine or homoserine was influenced by the activity of homoserine dehydrogenase or dihydrodipicolinate synthase. Thus, the twofold increase in homoserine dehydrogenase activity resulted in a decrease in lysine formation accompanied by the formation of isoleucine. In contrast, repression of homoserine dehydrogenase resulted in increased lysine formation. A similar increase of the flow of aspartate semialdehyde to lysine was found in strains with increased dihydrodipicolinate synthase activity, constructed by introducing the dapA gene of Escherichia coli (coding for the synthase) into C. glutamicum.

Amino Acids↗

Pneumocystis carinii pneumonia following heart transplantation.

Pneumocystis carinii pneumonia represents a rare complication that is associated with a high mortality following heart transplantation. The cases of two heart transplant recipients who developed Pneumocystis pneumonia within the first 3 postoperative months are reported. Both patients had severe clinical symptoms of the disease; the diagnosis was confirmed by bronchoalveolar lavage, and the patients were treated with a combination of trimethoprim and sulfamethoxazole. Both patients recovered and are well at the time of this report.

Adult↗

Surgical therapy of a coronary artery fistula draining into the left atrium.

Coronary artery fistulas (CAFs) are rare vascular anomalies. We describe a case of CAF draining into the left atrium, combined with an atrial septum defect (ASD) and azygos continuity in a 3-year-old girl. Surgical therapy included closure of the ASD combined with closure of the CAF through a left atrial approach. Even though CAF can be treated by interventional means, surgical correction may be required in the presence of associated cardiac abnormalities.

Atrial Appendage↗

Some aspects of changed histopathologic appearance of acute rejection in cardiac allografts after prophylactic application of OKT3.

The histopathologic findings of therapy-requiring acute rejection in the cardiac allograft observed in endomyocardial biopsy specimens taken from patients under prophylactic administration of OKT3 show certain differences in comparison with the classic description of acute rejection. These differences are characterized above all by a distinctly reduced cellularity of the infiltrates, with a relative decrease of T cells, as well as edema and retrogressive changes, up to necroses of myocytes with marked fragmentation; some patients also have increased vascular reactions. Furthermore, an earlier occurrence of and an increased frequency of changes corresponding to the so-called lymphoma-like lesions ("Quilty" effect) were observed in patients who received immunosuppressive prophylaxis with OKT3. The changed histopathologic findings of therapy-requiring acute rejection under prophylactic application of OKT3 may, to a certain extent, explain the discrepant results reported by different transplant groups with respect to the frequency of rejection episodes and the time when the first episode of therapy-requiring rejection occurs after heart transplantation.

Antibodies, Monoclonal↗

Donor heart-related variables and early mortality after heart transplantation.

Impaired donor heart function after heart transplantation results in the necessity for prolonged catecholamine and ventilatory support of the patient. Subsequently the risk of multiorgan impairment, infection, and rejection will be increased. In this retrospective analysis we tried to identify donor-related risk factors in patients who died early after transplantation. Of 174 patients undergoing heart transplantation from October 1985 through October 1988, 22 (12.6%) died early. Of the total, 39 cases were evaluated retrospectively for donor-related logistic and metabolic factors. All donors were analyzed with respect to the early mortality for age, weight, height, maximum dopamine concentration, thyroid hormone levels, and the duration from brain death until explantation and ischemia. Thirty patients were survivors (group A); nine patients died early (group B). By multiple regression analysis a significant influence (group A vs group B) of donor age, dopamine support, and ischemic time on early mortality could be demonstrated, whereas donor weight and height, hormone levels of triiodothyronine and thyroxine, and duration of brain death showed no correlation. From this limited experience we conclude that use of hearts from older donors with higher catecholamine support and longer ischemic times will result in an increased early mortality. In contrast, no influence of prolonged brain death times and metabolic factors could be demonstrated.

Adult↗

Treatment of rejection after heart transplantation: what dosage of pulsed steroids is necessary?

Histologically proved rejection after heart transplantation is commonly treated with intravenous steroids, 1 gm/day for 3 days. This regimen may result in severe side effects, however, both metabolic and infectious. In a total of 663 rejection episodes, we treated 397 with conventional steroid therapy, 1000 mg per day for 3 days (group 1), 199 with 500 mg/day for 3 days (group 2), and 67 with 250 mg/day for 3 days (group 3). Response to treatment was assessed by control biopsy after 1 week and graded as ongoing, resolving, or resolved rejection. The efficacy of the three regimens showed no significant differences between the groups as determined by the results of the subsequent biopsy. Ongoing rejection, resolving rejection, and resolved rejection, respectively: group 1-3.3%, 66.5%, 30.2%; group 2-8.0%, 66.8%, 25.2%; group 3-4.5%, 73.1%, 22.4%. We conclude that comparable effects, even with a considerable reduction of pulsed steroids, may be obtained in the treatment of cardiac allograft rejection, if triple-drug immunosuppression is used for maintenance therapy. It seems likely that steroid side effects may be decreased without jeopardizing the graft.

Adult↗

Oxygen free radical scavengers to prevent pulmonary reperfusion injury after heart-lung transplantation.

Oxygen free radical scavengers, such as superoxide dismutase (SOD) and catalase (CAT), have been shown to reduce effectively myocardial reperfusion injury. No such data have been reported for cold global pulmonary ischemia, which is required in heart-lung transplantation. Heterotopic heart-left lung allotransplantation was performed in 18 dogs after single-flush perfusion of the lungs with Euro-Collins solution (60 ml/kg), cardioplegic arrest, and 6 hours of cold global ischemia. Six dogs served as controls. In six other dogs prostacyclin (PGI2) was administered both into the pulmonary artery (20 ng/kg/min) and to the Euro-Collins solution (15 mg/L) before explantation (group A). Grafts in six other dogs were preserved with Euro-Collins solution plus SOD (40,000 U/L) and CAT (100,000 U/L)(group B). In addition, SOD (1 mg/kg) and CAT (1.5 mg/kg) were given intravenously during the first 20 minutes of reperfusion. There was no significant difference in cardiac output, right and left atrial pressures, nor pulmonary arteriolar resistance among the groups. In contrast, left atrial oxygen pressure (PO2) values were best in group B. At all times, PO2 values in animals in groups A and B exceeded those in control animals. Compared with control animals with Euro-Collins solution preservation alone, animals with both PGI2 and SOD/CAT preservation had significantly improved pulmonary function after heart-lung transplantation. Better oxygenation in the SOD/CAT group (group B) suggests an important impact of oxygen free radicals during reperfusion.

Animals↗

Cytoimmunologic monitoring in early and late acute cardiac rejection.

The absolute concentration of circulating lymphoblasts and prelymphoblasts has been shown repeatedly to closely correlate with acute cardiac rejection in heart transplant recipients. Little information, however, is available with respect to the reliability of this measurement in the late postoperative course. Fifty-two heart transplant recipient operated on from October 1985 through September 1986 were studied with cytoimmunologic monitoring for lymphocyte activation in peripheral blood. Immunosuppressive therapy consisted of azathioprine, cyclosporine, and steroids. Endomyocardial biopsies were obtained at regular intervals. Cytoimmunologic monitoring was performed daily during hospitalization and together with endomyocardial biopsy at outpatient visits. A total of 768 endomyocardial biopsies and 1077 mononuclear concentrates for study of lymphocyte activation were obtained. Concentration of activated cells showed a significant increase during acute rejection. Cytoimmunologic monitoring had an overall sensitivity of 76% and a specificity of 79%. Within 90 days after transplantation cytoimmunologic monitoring showed a sensitivity of 84%, which decreased to 71% beyond 3 months. We therefore conclude that cytoimmunologic monitoring, a noninvasive adjunct for diagnosis of acute allograft rejection, cannot replace routine endomyocardial biopsy, particularly in view of a significant loss in sensitivity in the late postoperative course.

Adolescent↗

Distinct expression of cell-cell and cell-matrix adhesion molecules on endothelial cells in human heart and lung transplants.

BACKGROUND AND METHODS: Intercellular reactions and cell-matrix interactions are mediated by a number of specific adhesion molecules. For the intravascular reactivity of leukocytes and thrombocytes the endothelial expression of adhesion ligand molecules is of main importance. This condition may be of special relevance for the organ-specific manifestation of immune reactions in heart and lung transplants. The question was investigated as to whether organ-specific differences exist on arterial, venous, and capillary endothelial lining cells in heart and lung transplants and whether this condition is modified during transplant rejection. Transplant biopsy specimens of 24 heart transplant recipients (n = 303) and lung transplant recipients who underwent retransplantation for rejection (n = 4), as well as normal heart (n = 7) and lung tissue (n = 4), were studied. Cell-cell adhesion molecules (intercellular adhesion molecule-1 (CD54) and -2; LFA-3; CD31; vascular cellular adhesion molecule-1; neural cellular adhesion molecule; E-/P-selectin; CD44) and cell-matrix adhesion molecules (very late antigen-1 through -6; CD51) were studied on cryostat sections by means of standard immunohistology. RESULTS: (1) Arterial, venous, and capilary endothelia in lung and heart tissue show a distinct pattern of cell-cell and cell-matrix adhesion molecules: capillary and venous endothelia are in contrast to arterioles negative for vascular cellular adhesion molecule-1 and P-selectin. Arterial endothelia of the lung, in contrast to veins and capillaries, express no receptors for laminin (very late antigen-2 and very late antigen-6). (2) With transplant rejection, an induction of a number of adhesion molecules was noted on all endothelial lining cells in heart and lung transplants (intercellular adhesion molecule-1[CD54], intercellular adhesion molecule-2, lymphocyte function antigen-3, very late antigen-2, and very late antigen-6). Capillaries of the lung, in contrast to heart capillaries, displayed no inducibility of vascular cellular adhesion molecule-1 and E-selectin. In heart transplants, differences between capillaries and arteriovenous endothelia were found for virus-like agent-2 and -3. CONCLUSIONS: These results show a distinct expression of a both cell-cell and cell-matrix adhesion molecules on arterial, venous, and capillary endothelia of heart and lung transplants. This expression may influence the local regulation of leukocyte and thrombocyte adhesion during transplant rejection. Especially lung capillaries show a lack of inducibility for vascular cellular adhesion molecule-1 and E- and P-selectin required for the induction phase of leukocyte adhesion. This lack was not found in heart transplants. This observation may explain differences in intravascular adhesion and infiltration between vessel compartments in hearts and lungs and could be of relevance for therapeutic interventions to modify leukocyte and thrombocyte adhesion, as during transplant rejection and reperfusion damage.

Biopsy↗