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K Reemtsma

Publications and source records attributed to K Reemtsma.

At least 73 records · Page 4Linked to original sources
PubMed1988

Respiratory complications of cardiac transplantation.

The authors evaluated all respiratory complications of cardiac transplantation in a 10-year study of 94 consecutive recipients. Mean follow-up time was 20 +/- 17 months. The initial 20 patients were treated with azathioprine and prednisone, while the subsequent 74 patients received cyclosporine and prednisone. In the azathioprine group, respiratory infections accounted for 24 of 60 (40%) infections. Two-thirds of the respiratory infections occurred in the first 3 postoperative months and were generally localized processes (focal pneumonitis, nodule(s), abscess, or empyema). Gram-positive and gram-negative bacteria (8/30) and aspergillus (8/30) were the predominant pathogens. Respiratory failure occurred in 29% of infectious episodes. In the cyclosporine group, there were significantly fewer respiratory infections. There was also a reduction in the number of nonrespiratory infections; hence, the percentage of total infections due to respiratory causes, 26 of 50 (52%), was not significantly different. In contrast, however, nearly two-thirds of the respiratory infections in cyclosporine-treated patients occurred after the first 3 postoperative months, and were usually diffuse processes. Despite diffuse disease, respiratory failure was observed with similar frequency (19%). Pneumocystis carinii (9/31) and cytomegalovirus (CMV) (7/31) were the predominant pathogens. CMV pneumonitis tended to occur earlier than that due to P. carinii (2.9 +/- 1.9 mo vs. 9.8 +/- 11.2 mo, respectively), but there was considerable overlap. In comparison with infectious processes, there were 50% fewer noninfectious respiratory complications in both groups. These were primarily pleural (46%) or thromboembolic (18%) disorders. Four of five pulmonary emboli occurred in patients with intercurrent cardiorespiratory illness, and were detected only at autopsy. The authors conclude that respiratory infections account for one-half of all infections observed in cardiac transplant recipients, despite the reduced infection rate associated with the use of cyclosporine. Furthermore, respiratory infections in cyclosporine-treated patients exhibit different clinical and etiologic features than those seen in azathioprine-treated patients. Finally, occult thromboemboli may be difficult to recognize in cardiac transplant recipients because of the high incidence of coexisting cardiorespiratory disease.

Adult↗
PubMed1988

Effect of ultraviolet-B-irradiated donor-specific blood transfusions and peritransplant immunosuppression with cyclosporine on rat cardiac allograft survival.

We have previously demonstrated that pretreatment of ACI recipients with ultraviolet-irradiated donor-specific blood transfusion (UV-DST) leads to permanent cardiac allograft survival without further host immunosuppression (ACI rats are weak responders to Lewis lymphocytes in mixed-lymphocyte reaction). This study examines the effect of UV-DST and the timing of transfusions on ACI cardiac allograft survival in Lewis recipients with and without the addition of peritransplant cyclosporine (CsA) (20 mg/kg i.m.) given on days 0, +1, and +2 in relation to the time of transplantation. The mean survival time (MST) of ACI cardiac allografts in Lewis recipients was significantly increased to 33.6 +/- 5.7 days (P less than 0.001) by CsA treatment alone as compared to 6.5 +/- 0.5 days survival in control. When DST was given on day -3 combined with CsA, graft survival was increased to 42.0 +/- 9.3 days (P less than 0.01), as compared to 5.8 +/- 1.3 days when DST alone was used. When DST was irradiated with ultraviolet B (UV-DST) and administered on day -3 combined with peritransplant CsA, the MST was increased to 68.83 +/- 16.1 days as compared to an MST of 10.0 +/- 1.0 days in controls treated with UV-DST alone. When UV-DST was given on day -7 and combined with peritransplant CsA immunosuppression, the results were similar. However, when UV-DST was peritransplant CsA course, 4 of 6 recipients maintained their ACI heart allografts indefinitely (greater than 300 days) in contrast to the effect of UV-DST alone (MST of 13.5 days). Third-party (W/F) UV-irradiated blood transfusions were ineffective in prolonging ACI cardiac allografts in Lewis rats, regardless of whether the transfusions were given alone or in combination with peritransplant immunosuppression with CsA. In conclusion, these results demonstrate that UV-DST combined with a brief peritransplant immunosuppression with CsA induces prolonged heart allograft survival in a histoincompatible, strong responder host, and that such effect is donor specific. The use of UV-DST combined with peritransplant CsA immunosuppression offers a promising approach to achieving organ transplant unresponsiveness, and decreased sensitization to the donor blood elements, which eventually may have important clinical implications.

Animals↗
PubMed1988

Induction of donor-specific unresponsiveness to rat cardiac allograft by donor leukocytes and cyclosporine.

Many recent reports have emphasized the importance of donor antigens in the induction of allograft tolerance. This study examines the effect of pretransplant infusion of 10(8) donor leukocytes (DL) combined with peritransplant cyclosporine (CsA) on W/F cardiac allograft survival in Lewis rats. Peritransplant recipient treatment consisted of CsA 20 mg/kg given i.m. on days 0, +1, and +2 relative to heart transplantation. Lewis recipients, 5-8 per group, were pretreated with 10(8) DL with or without peritransplant CsA. A single DL transfusion on day -3 or day -7 prior to transplantation significantly prolonged the mean survival time (MST) of W/F hearts from 7.0 +/- 0.9 days in controls to 12.2 +/- 4.5 days and 12.4 +/- 1.0 days (P less than 0.01), respectively. Two DL infusions on days -7 and -3 or on days -14 and -7 prolonged the MST to 10.6 +/- 1.3 days (P less than 0.02) and 16.4 +/- 2.8 days (P less than 0.001), respectively. The administration of peritransplant CsA alone significantly prolonged W/F heart allograft survival to 43.1 +/- 2.7 days. When pretransplant DL transfusion on day -3 was combined with CsA treatment, 4/8 animals maintained their grafts indefinitely (greater than 100 days). Similarly, DL infusion on day -7 with peritransplant CsA led to indefinite graft survival in 3/5 animals. Administration of DL on days -7 and -3 combined with CsA resulted in indefinite graft survival (greater than 100 days) in 4/6 animals. Transfusion of DL on day -3 alone or in combination with peritransplant CsA, had no effect on a third-party (ACI) heart allograft survival prolongation compared with appropriate controls. To define the underlying mechanisms responsible for donor-specific unresponsiveness in this model, pooled sera and unseparated spleen cells were passively transferred from recipients of long-term cardiac allografts to syngeneic rats receiving donor-type (W/F) or third-party (ACI) cardiac allografts. Transfer of serum (1 ml on days 0, and 1, 0.5 ml on days +2, +3, and +4) from ungrafted recipients of DL on days -14 and -7 led to significant donor graft survival of 9.8 +/- 0.4 days (P less than 0.02) in unmodified hosts. Similarly, passive transfer of serum obtained at 20 and 100 days after transplantation significantly prolonged the MST of donor-type hearts in syngeneic untreated hosts to 11.3 +/- 0.8 and 10.0 +/- 1.1 days, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Mechanisms of immunologic unresponsiveness induced by ultraviolet-irradiated donor-specific blood transfusions and peritransplant cyclosporine.

Recipient pretreatment with UV-B irradiated donor-specific blood transfusions (UV-DST) combined with peritransplant cyclosporine on days 0, +1, and +2 leads to permanent cardiac allograft survival in the ACI-to-Lewis rat strain combination. This study investigates the mechanisms of immunologic unresponsiveness induced by UV-DST and CsA by examining several in vitro and in vivo parameters in long-term cardiac allograft recipients. The results of the in vitro studies demonstrate that thoracic duct lymphocytes (TDL) of treated and allografted Lewis rats respond less in a mixed lymphocyte reaction to donor splenic lymphocytes (SpL) by 69%, 75%, and 73% (P less than 0.001) at 30, 50, and 100 days after transplantation, respectively, compared with controls, while the response to a third-party (W/F) SpL is unimpaired. In coculture experiments, the TDL from treated recipients specifically suppressed the response of unmodified Lewis TDL to ACI SpL by 59% and 40% (P less than 0.01) at 30 and 50 days after transplantation, respectively, while responses to W/F SpL were suppressed by only 3-6%. The sera obtained from ungrafted rats transfused with UV-DST suppressed the MLR between unmodified Lewis TDL and ACI SpL by 31% (P less than 0.05) while the sera from UV-DST and CsA-treated and allografted rats specifically suppressed the MLR by 75%, 80% (P less than 0.001) and 37% (P less than 0.01) at 10, 30, and 50 days after transplantation, respectively. In vivo adoptive transfer of 10(4) donor-type dendritic cells (DC) into recipients of beating cardiac allografts at 40 or 60 days after transplantation led to rapid and acute allograft rejection, while the adoptive transfer of 10(8) unseparated SpL obtained at 50 days after transplantation from treated Lewis recipients to syngeneic naive hosts led to a modest but significant prolongation of ACI test cardiac allografts. The transfer of serum from treated and allografted recipients at 10, 30, and 50 days after transplantation led to specific and significant prolongation of test grafts in syngeneic naive hosts. These findings suggest that the mechanisms underlying the in vivo immunologic unresponsiveness induced by pretreatment with UV-DST and peritransplant CsA include inactivation without elimination of class II-antigen presenting cells (APC), generation of specific serum suppressor factor(s) and/or antiidiotypic antibody, and induction of donor-specific suppressor cells.

Animals↗
PubMed1988

Utility of airway endoscopy in the diagnosis of respiratory complications of cardiac transplantation.

We evaluated 39 episodes (in 32 patients) of pulmonary parenchymal infiltrates following cardiac transplantation with fiberoptic bronchoscopy (FOB) in a prospective study of 94 consecutive recipients. Initial FOB established the diagnosis in 24/39 (62 percent) instances. Subsequent examinations included repeat FOB (five), open lung biopsy (five), needle aspiration (two), and autopsy (nine), establishing 49 diagnoses. Specific pathogens were identified in 45 instances, neoplasm in two, and idiopathic interstitial pneumonitis in two. Bronchoalveolar lavage alone yielded diagnoses in 63 percent and transbronchial biopsy and bronchial washings/brushings in 46 and 43 percent, respectively. Transbronchial biopsy suggested idiopathic interstitial pneumonitis in 17 instances, but four had spontaneous clearing, and open lung biopsy or autopsy showed alternative diagnoses (particularly CMV and Aspergillus) in 11. The main complication of FOB was moderate (25 to 100 ml) hemorrhage after transbronchial biopsy (10 percent); no severe episodes occurred despite elevated pulmonary vascular pressures. In this population of immunocompromised hosts: (1) bronchoalveolar lavage is the most sensitive bronchoscopic technique for detecting infection; (2) transbronchial biopsy is not useful in detecting CMV or Aspergillus infection; (3) pulmonary hypertension is associated with some risk of moderate but not severe hemorrhage after transbronchial biopsy.

Adult↗
PubMed1988

Permanent rat cardiac allograft survival induced by ultraviolet B-irradiated donor lymphocytes and peritransplant cyclosporine.

This study examines the effect of pretreatment with 10(8) ultraviolet B-irradiated donor leukocytes (UV-DL) with or without peritransplant cyclosporine (CyA) treatment (20 mg/kg on days 0, +1, and +2 relative to transplantation) on rat cardiac allograft survival across major histocompatibility loci. A single UV-DL pretreatment on day -3 or -7 (before transplantation) significantly prolonged survival of heart allografts from Wistar-Furth rats (W/F) in Lewis recipients from 6.8 +/- 0.8 days to 18.4 +/- 2.1 and 17.6 +/- 1.5 days (p less than 0.001), respectively. Multiple UV-DL infusions on days -14 and -7 increased the mean survival time to 20.0 +/- 0.9 days (p less than 0.001). Similarly, UV-DL infusion on day -3 or -7 significantly prolonged the mean survival time of heart allografts from ACI rats in Lewis rats. A single or multiple UV-DL infusions combined with peritransplant CyA led specifically to permanent W/F cardiac allograft survival (more than 200 days) in all recipients. Similarly, UV-DL infusion combined with peritransplant CyA led to indefinite survival of ACI cardiac allografts in two thirds of Lewis recipients. Adoptive transfer of splenocytes from long-term recipients of cardiac allografts, which specifically prolonged donor test grafts in syngeneic hosts, suggests that unresponsiveness to cardiac allografts is, in part, dependent on suppressor cells. This study emphasizes the importance of UV irradiation of DLs in the modulation of alloreactivity and the induction of donor-specific unresponsiveness in adult animals.

Animals↗
PubMed1987

Prolongation of primate cardiac xenograft survival with cyclosporine.

Cardiac xenotransplantation in nonprimates using traditional immunosuppression (azathioprine and prednisone) or cyclosporine has been unsuccessful or has required doses of immunosuppressants not tolerated by man. This study sought to determine if primate hearts could be transplanted successfully across genus boundaries using a dose of cyclosporine applicable to human transplantation. The hearts of outbred cynomolgus monkeys (Macaca fascicularis) were heterotopically transplanted into the necks of outbred baboons (Papio anubis). Hyperacute rejection did not occur and there were no cyclosporine-induced malignancies or nephrotoxicity. A 12-fold prolongation of mean cardiac xenograft survival to 77 days was accomplished using parenteral cyclosporine and steroids. The histology of rejection was notable for the appearance of reversible rejection on the 30-day biopsies. The histopathologic and immunologic data support the role of both cell-mediated and humoral mechanisms in primate cardiac xenograft rejection. Neither mixed lymphocyte cultures or cytotoxic antibody assays were predictive of graft loss, but there was a significant increase in their respective levels at the time of cessation of graft function. Thus, significant prolongation of primate cardiac graft survival across a genus boundary was accomplished using a dose of cyclosporine similar to that used in human transplantation.

Animals↗
PubMed1987

Patent foramen ovale complicating heart transplantation. A window on posttransplantation hemodynamics.

A patient developed refractory hypoxemia and right-to-left shunt across a patent foramen ovale after orthotopic cardiac transplantation. The right-to-left shunt was produced by volume overload of the donor right ventricle during the period of early postoperative myocardial depression and resolved with preload reduction and diuresis. Increased preload of the right heart needs to be considered in the early postoperative management after cardiac transplantation. The foramen ovale of the donor and recipient should be evaluated at operation by visual and probe examination and securely closed if either is patent, since this pattern of hemodynamic changes is common following cardiac transplantation.

Adult↗