Volume of graft and native lung after single-lung transplantation for emphysema

The most important stimulus for the enhanced synthesis of erythropoietin (Epo) is a lowered O2 tension in the tissue. However, the mechanism by which an impaired O2 supply is transduced into appropriate Epo production is still not fully understood. Recently, studies in human hepatoma cells (line HepG2) indicate that reactive O2 species are involved in the signal transduction from the cellular O2 sensor to the Epo gene. To clarify the role of reactive O2 species in the regulation of Epo synthesis in the kidney, the principal Epo-producing organ in vivo, we investigated the influence of potent pro- and antioxidants on Epo production in isolated perfused rat kidneys. Under normoxic conditions, the iron chelator desferrioxamine and the antioxidant vitamin A increased renal Epo production, mimicking hypoxic induction. In contrast, supplementation of the perfusion medium of hypoxically perfused kidneys with the prooxidant compounds H2O2 or pyrogallol caused a significant reduction of Epo synthesis. The inhibition of Epo formation by reactive O2 species could be completely antagonized by desferrioxamine and the hydroxyl radical-(OH*)-scavenger tetramethylthiourea. Vitamin A also antagonized the H2O2-dependent inhibition of hypoxically induced Epo synthesis. Interestingly, the addition of the antioxidant vitamin A to hypoxically perfused kidneys also induced Epo production significantly. Our data strongly support the idea that reactive O2 species, especially H2O2, are part of the signaling chain of the cellular O2-sensing mechanism regulating the renal synthesis of Epo.     

Canine lung transplantation after more than twenty-four hours of normothermic preservation

BACKGROUND: Consistent clinical results have not been achieved when lung preservation times exceed 6 hours. The aim of this study was to use an alternative normothermic autoperfusion technique for lung preservation and transplantation. METHODS: In six paired dogs, donor lungs were removed, along with the heart, liver, pancreas, duodenum, and both kidneys, and were preserved for 24 to 33 hours in a normothermic autoperfused multiple organ block. Orthotopic left lung transplantation was performed at the end of the preservation period. RESULTS: Lung function was good during the preservation period. With a gas mixture of 50% O2 + 3% CO2 + 47% N2 delivered to the multiorgan block, arterial oxygen tension ranged from 331 +/- 19 to 383 +/- 8 mm Hg; carbon dioxide tension ranged from 18 +/- 5 to 32 +/- 5 mm Hg; and pH ranged from 7.36 +/- 0.02 to 7.45 +/- 0.08. After transplantation, the dogs were kept anesthetized and ventilated for 24 hours with the same gas mixture. The opposite pulmonary artery was occluded 0 to 6 hours after transplantation. Arterial blood pressures were stable after surgery. Arterial oxygen tension was maintained between 205 +/- 39 and 320 +/- 57 mm Hg, and arterial carbon dioxide tension was maintained between 23 +/- 2 and 34 +/- 2 mm Hg. Lung tissue wet/dry weight ratio was 4.94 +/- 0.17 after preservation; this ratio did not differ from that found in normal controls (4.91 +/- 0.10). CONCLUSIONS: This study shows that the lungs were well preserved for more than 24 hours of preservation when the normothermic multiorgan block preparation was used. The transplanted left lung was able to support the anesthetized dog after the opposite pulmonary artery was occluded.     

Strategies for graft immunomodulation in islet transplantation

BACKGROUND: The cortex of patients with schizophrenia exhibits a deficit in neuropil, but the nature and extent of cellular abnormalities remain unclear. To gain further insight into this abnormality, neuronal and glial somal size were analyzed in postmortem brains from 9 patients with schizophrenia, 10 normal (control) patients, and 7 patients with Huntington disease, the latter representing a known neurodegenerative disorder. METHODS: A 3-dimensional image analyzer was used to measure the perimeters of 10722 neuronal and 19913 glial profiles in Brodmann areas 9 and 17. Neurons and glia were classified by size and layer to assess specific vulnerabilities with respect to cortical architecture and circuitry. RESULTS: The schizophrenic prefrontal cortex was characterized by a downward shift in neuronal sizes accompanied by 70% to 140% per layer increases in the density of small neurons. In layer III only, a significant reduction in mean neuronal size was associated with a significant decrease in the density of very large neurons in sublayer Illc. Neither neuronal size in occipital area 17 nor glial size in prefrontal or occipital cortexes were reduced. In cortex with Huntington disease, neuronal degeneration was evidenced by concurrence of reduced neuronal size, decreased density of large neurons, and dramatic elevation in density of large glia. CONCLUSIONS: Distinct cytometric abnormalities support the hypothesis that neuronal degeneration in the prefrontal cortex is not a prominent feature of the neuropathological changes in schizophrenia, although an ongoing process in Huntington disease. Rather, schizophrenia appears to involve more subtle abnormalities, with the largest corticocortical projection neurons of layer IIIc expressing the greatest somal reduction.     

Preconditioning with cromakalim improves long-term myocardial preservation for heart transplantation

Polymerase chain reaction (PCR) and ligase chain reaction (LCR) were compared for the diagnosis of Chlamydia trachomatis infections by testing urine specimens from 408 high school female students. After therapy, sequential urine specimens were tested to determine persistence of chlamydial DNA in urine. Baseline PCR of cervical specimens was positive in 53 (13.0%) students, and PCR and LCR of urine specimens were positive in 63 (15.4%) and 60 (14.7%), respectively. After discrepant analysis, 64 (15.7%) patients could be confirmed as truly infected. Follow-up urine specimens from 33 infected patients demonstrated that at 1-3 days after therapy, PCR and LCR were positive for 40% and 73.3%, respectively. Only at 15 days after therapy did all specimens test negative. Urine tests for Chlamydia organisms should not be used as a test of cure within 3 weeks after treatment. Use of urine assays for screening sexually active adolescents has the potential to significantly improve control of chlamydial infections.     

Extended preservation of ischemic pulmonary graft by postmortem alveolar expansion

BACKGROUND: If lungs could be retrieved for transplantation from non-heart-beating cadavers, the shortage of donors might be significantly alleviated. METHODS: Peak airway pressure, mean pulmonary artery pressure, pulmonary vascular resistance, and wet to dry weight ratio were measured during delayed hypothermic crystalloid flush in rabbit lungs (n = 6) at successive intervals after death comparing cadavers with lungs left deflated (group 1), inflated with room air (group 2) or 100% oxygen (group 4), or ventilated with room air (group 3), or 100% nitrogen (group 5), or 100% oxygen (group 6). RESULTS: There was a gradual increase in mean pulmonary artery pressure and pulmonary vascular resistance with longer postmortem intervals in all study groups (p = not significant, group 1 versus group 2 versus group 3). There was also a gradual increase in peak airway pressure and wet-to-dry weight ratio over time in all groups, which reflected edema formation during flush (airway pressure, from 14.5 +/- 1.0 cm H2O to 53.7 +/- 12.2 cm H2O, and wet-to-dry weight ratio, from 3.6 +/- 0.1 to 11.5 +/- 1.2, in group 1 at 0 and 6 hours postmortem, respectively; p < 0.05). Compared with group 1, however, the increase in groups 2 and 3 was much slower (airway pressure, 20.9 +/- 0.5 cm H2O and 18.8 +/- 1.2 cm H2O, and wet-to-dry weight ratio, 5.2 +/- 0.3 and 4.6 +/- 0.4 at 6 hours postmortem, respectively; p < 0.05 versus group 1 and p = not significant, group 2 versus group 3). Airway pressure and wet-to-dry weight ratio did not differ between groups 2 and 4 or between groups 3, 5, and 6. CONCLUSIONS: These data suggest that (1) pulmonary edema will develop in atelectatic lungs if hypothermic flush is delayed for 2 hours after death, (2) postmortem inflation is as good as ventilation in prolonging warm ischemic tolerance, (3) inflation with oxygen or ventilation with nitrogen or oxygen is no different from that with room air, and (4) therefore, prevention of alveolar collapse appears to be the critical factor in protecting the lung from warm ischemic damage independent of continued oxygen delivery.     

Determinants of graft survival after renal transplantation

We studied multiple determinants of graft survival at a single center and the effects of nonimmunologic graft loss on transplant survival. This retrospective study examined the results of 589 cadaver donor transplants performed between 1986 and 1992. Graft survival rates were calculated using Kaplan-Meier estimates for both overall graft survival (all causes of graft loss) and immunologic graft survival (function lost due to acute or chronic rejection and noncompliance). Cadaver graft survival was significantly poorer with an increasing degree of DR mismatch (P=0.02). An analysis of pretransplant variables showed graft loss risk was highest with greater DR mismatches, two B-antigen mismatch, higher donor serum creatinine, and younger recipient age. After transplantation, acute rejection was the most significant factor associated with long-term graft survival. Our data demonstrate a significant advantage for zero DR and one DR mismatch cadaver donor transplants, with excellent immunologic graft survival. This study suggests that a combination of immediate graft function, prevention of acute rejection by appropriate early immunosuppressive therapy, and acceptable DR match enhances cadaveric graft survival.     

Reversible graft dysfunction after cardiac transplantation]

Catalase (CAT) activity in ground beef and pork was determined on samples cooked from 60 to 71.1 degrees C. One-gram samples of ground round (4% fat), hamburger (24% fat), and commercial pork sausage (38%fat) were cooked in a controlled-temperature waterbath at 65, 68.3 and 71 degrees C. Chilled samples were immersed in direct contact with the cooking water; the test samples were removed every 15 s and immediately immersed in an ice-water bath (O to 1 degrees C) to quick-chill the samples to prevent temperature over-run. Samples retained high (HMB value 20+, over range) CAT activity through 90, 60, and 45 s at 65, 68.3, and 71 degrees C, respectively, before showing rapid activity decreases. Four USDA-FSIS approved meat patty heating processes (66.1 degrees C, 41 s; 67.2 degrees C, 26 s; 68.3 degrees C, 16 s; and 69.4 degrees C, 10 s) were analyzed for CAT activity in meat frozen prior to cooking was slightly lower (P < 0.05) than in degrees C meat. CAT activity decreased (P < 0.05) among meat treated at 66.1 degrees C for 41 s, at 67.2 degrees C for 26 s, and at 68.3 degrees C for 16 s, but the treatment at 68.3 degrees C for 16 s was not different (P < 0.05) from that at 69.4 degrees C for 10 s. These results show this rapid (20 to 25 min) CAT activity test could be used to establish activity values at specific end-point temperatures for model heat-processed ground beef or sausage products and may be useful to USDA FSIS process inspectors and food processors in quality assurance and HACCP (hazard analysis critical control points) programs for thermal input verification.     

Pneumocytes type II ultrastructural modifications after storage in preservation solutions for transplantation

Although lung transplantation represents a real therapeutic opportunity, the problem of preserving the organ for a prolonged period (> 10 h) still remains unsolved. Further studies are necessary to fully understand the behavior of different lung cell types during the ischemic period. As ultrastructural modifications of cells of lung samples stored in different means of preservation represent an index of the integrity and therefore of cellular viability, in the present work we have compared the time-related ultrastructural changes in human pneumocytes type II cells after hypothermic (10 degrees C) storage for 6 and 12 h in University of Wisconsin (UW) solution and in low potassium dextran (LPD) solution. An ultrastructural grading scale was used to quantify the damage and the results confirmed what was observed microscopically. Statistical analysis (t test) of the data showed that after 6 h in LPD solution, pneumocytes type II were less damaged than those stored in UW solution; these differences were statistically significant (p < 0.05). In our opinion, ultrastructural studies should be considered among the methods presently used to assess the effectiveness of different storage fluids.     

Post-traumatic ARDS--a potential indication for lung transplantation?

Posttraumatic adult respiratory distress syndrome (ARDS) still involves significant mortality, despite progress in management concepts. Current therapeutic strategies are briefly described, including kinetic therapy, high-frequency jet ventilation and extracorporeal membrane oxygenation. In addition, a spectacular case of the first successful lung transplantation for posttraumatic ARDS after failed ECMO (extracorporeal membrane oxygenation) support is reported. This young man with severe posttraumatic ARDS developed a potentially lethal bilateral pulmonary hemorrhage under treatment with ECMO, and on the basis of this bilateral pulmonary transplantation was considered to be indicated. The patient is alive and well 2 years after the procedure.     

Pediatric and adult lung transplantation for cystic fibrosis

OBJECTIVE: This paper was undertaken to review the experience at our institution with bilateral sequential lung transplantation for cystic fibrosis. METHODS: Since 1989, 103 bilateral sequential lung transplants for cystic fibrosis have been performed (46 pediatric, 48 adult, 9 redo); the mean age was 21 +/- 10 years. Cardiopulmonary bypass was used in all but one pediatric (age <18) transplant, and in 15% of adults. RESULTS: Hospital mortality was 4.9%, with 80% of early deaths related to infection. Bronchial anastomotic complications occurred with equal frequency in the pediatric and the adult populations (7.3%). One- and 3-year actuarial survival are 84% and 61%, respectively (no significant difference between pediatric and adult age groups; average follow-up 2.1 +/- 1.6 years). Mean forced expiratory volume in 1 second increased from 25% +/- 9% before transplantation to 79% +/- 35% 1 year after transplantation. Acute rejection occurred 1.7 times per patient-year, with most episodes taking place within the first 6 months after transplantation. The need for treatment of lower respiratory tract infections occurred 1.2 times per patient in the first year after transplantation. Actuarial freedom from bronchiolitis obliterans was 63% at 2 years and 43% at 3 years. Redo transplantation was performed only in the pediatric population and was associated with an early mortality of 33%. Eight living donor transplants (four primary transplants, four redo transplants) were performed with an early survival of 87.5%. CONCLUSION: Patients with end-stage cystic fibrosis can undergo bilateral lung transplantation with morbidity and mortality comparable to that seen in pulmonary transplantation for other disease entities.     

Anterior ridge preservation and augmentation using a synthetic osseous replacement graft

A 7-year retrospective study, reporting 3 cases, is presented in which particulate synthetic osseous replacement grafts were placed for ridge preservation and augmentation in the maxillary anterior region after extraction of periodontally hopeless teeth. The ability of an osseous replacement graft to prevent and correct the postextraction atrophy of the alveolar ridge, as well as its esthetic implications in fixed prosthetics, is discussed.     

Risk factors for delayed graft function in cadaveric kidney transplantation: a prospective study of renal function and graft survival after preservation with University of Wisconsin solution in multi-organ donors. European Multicenter Study Group

BACKGROUND: Delayed graft function (DGF) remains an important complication in renal transplantation. In this multicenter study, we investigated the influence of donor and recipient factors on the occurrence of DGF and DGF's effect on long-term graft survival. METHODS: A total of 547 transplanted kidney allografts, retrieved from multi-organ donors, were analyzed, and results were compared with literature on kidney-only donors. RESULTS: Median follow-up of patients without graft failure was 3.4 years. Twenty-four percent of the recipients developed DGF. In univariate analysis, the following factors significantly increased the incidence of DGF: (a) among the donor factors, mean creatinine level >120 micromol/L and prolonged cold ischemia time (CIT); and (b) among the recipient factors, previous transplant(s), no intraoperative use of mannitol, poor quality of reperfusion, absence of intraoperative diuresis, and pretransplant anuria or oliguria. After stepwise logistic regression, donor age, CIT, recipient's number of previous transplants, and intraoperative diuresis proved to be of independent prognostic value for the occurrence of DGF. Overall graft survival was 91%, 87%, and 72% at 3 months, 1 year, and 4 years after transplantation, respectively. In case of DGF, graft survival was approximately 10% lower when compared with cases with immediate graft function (P<0.001). No difference in incidence of DGF was found between grafts of multi-organ donors and kidney-only donors. CONCLUSIONS: DGF results in an approximately 10% higher rate of graft failure. DGF incidence can be reduced by the administration of mannitol during transplantation, which minimizes CIT and optimizes donor management. Grafts from multi-organ donors and kidney-only donors appear to be of equal quality.     

Potassium-reduced lung preservation solutions: a screening study

PROBLEM: The direct immunosuppressive and suppressive inducing capacities of supernatants from human trophoblastic choriocarcinoma cell lines (HCS) are well investigated in several former studies. The responsible factor is not yet determined. METHOD OF STUDY: We first confirmed those data and we purified a 3-5-kDa suppressor-inducer factor from HCS by using high performance liquid chromatography (HPLC) on both DEAE and gel filtration columns, followed by ultrafiltration. We then tested the activities of such isolated fractions on in vitro immune responses from human cells and in vivo by its effects in a murine local graft-versus-host (GVH) assay (popliteal lymph node assay, PLN). RESULTS: A single fraction induces both "direct suppression" in vitro as well as in vitro suppressor cell activation/development in human peripheral blood lymphocyte cultures as assessed by suppression of cells cultured in such a fraction containing culture medium of the mixed lymphocyte reaction. Furthermore the very same fraction suppresses in vivo murine allogeneic immune responses as assessed by a local GVH reaction (PLN assay). CONCLUSIONS: We have isolated a suppressive fraction, whose activities suggest that it might be of interest not only in reproductive immunology, but also in transplantation systems.     

Protein catabolism after lung transplantation and heart transplantation

Any surgical intervention is associated with an activation of protein catabolism, the extent of which is dependent on the severity of surgical trauma. There is a paucity of reports on protein catabolism after transplantation of chest organs (lung transplantation (LTX) and heart transplantation (HTX)). The aim of the present study was to quantify and compare the extent of postoperative protein catabolism and associated metabolic perturbations in patients after LTX and HTX. Eighteen consecutive patients after LTX and 15 consecutive patients after HTX who required postoperative intensive care for more than 4 days, constituted the study population. The nitrogen balance (assessed on the basis of the urea nitrogen production rate and nitrogen intake) was assessed retrospectively and correlated with insulin requirements, immunosuppression and the clinical course. Within the first 5 days the nitrogen balance became progressively negative in both groups, reaching a maximum on the 5th day. Thereafter the nitrogen balance of patients following LTX remained negative, whereas the nitrogen balance of patients following HTX tended to improve. The evolution of nitrogen balance significantly differed between both groups (p < 0.01). The mean nitrogen loss was -0.29 +/- 0.17g/kg BW/day after LTX versus -0.22 +/- 0.12g/kg BW/day after HTX. Smaller amounts of glucocorticoids were used for immunosuppression in patients after HTX than in patients after LTX; nevertheless, heart transplant recipients required higher doses of insulin to maintain normoglycemia. A regression analysis revealed that the duration of stay at the intensive care unit (p < 0.001) and the amount of glucocorticoids (p < 0.01) negatively affected the nitrogen balance, whereas an increased protein intake (p < 0.001) exerted a positive effect. Compared to other major surgical procedures, protein catabolism is excessively elevated in patients after thoracic transplantation. Immunosuppressive therapy with glucocorticoids contributes to protein degradation; the nitrogen balance after LTX is more negative than that after HTX because of higher glucocorticoid requirements following LTX. More aggressive nutritional intervention and especially an increased nitrogen intake might help to reduce protein losses in these patients.     

Biphasic spiral computed tomography versus digital subtraction angiography for evaluation of arterial thrombosis after orthotopic liver transplantation

Aseptic loosening of implant components is a common and important complication of both cemented and uncemented prosthetic joint replacements. Wear particles derived from organic polymer and metal implant biomaterials are commonly found within macrophages and macrophage polykaryons in the fibrous membrane between loose implant components and the host bone undergoing resorption. In order to determine whether biomaterial particle-containing, foreign-body macrophages may contribute to periprosthetic bone resorption, we cultured murine monocytes that had phagocytosed particles of biomaterials commonly employed in bone implant surgery [polymethylmethacrylate (PMMA), ultra-high molecular weight polyethylene (PE), titanium and chromium-cobalt] on bone slices and glass coverslips with UMR 106 osteoblast-like stromal cells in the presence of 1,25-dihydroxy-vitamin D3. Under these conditions, all biomaterial particle-containing, foreign-body macrophages differentiated into osteoclastic cells, i.e. tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells capable of extensive lacunar bone resorption. This study shows that particle phagocytosis by macrophages does not abrogate the ability of these cells to undergo osteoclast differentiation. These findings emphasise the importance of the foreign-body macrophage response to biomaterial wear particles in the pathogenesis of aseptic loosening.     

Predictors of patient and graft survival following liver transplantation for hepatitis C

End-stage liver disease secondary to hepatitis C virus (HCV) infection is the leading indication for liver transplantation in the United States. Recurrence of HCV infection is nearly universal. We studied the patients enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database to determine whether pretransplantation patient or donor variables could identify a subset of HCV-infected recipients with poor patient survival. Between April 15, 1990, and June 30, 1994, 166 HCV-infected and 509 HCV-negative patients underwent liver transplantation at the participating institutions. Median follow-up was 5.0 years for HCV-infected and 5.2 years for HCV-negative recipients. Pretransplantation donor and recipient characteristics, and patient and graft survival, were prospectively collected and compared. Cumulative patient survival for HCV-infected recipients was similar to that of recipients transplanted for chronic non-B-C hepatitis, or alcoholic and metabolic liver disease, better than that of patients transplanted for malignancy or hepatitis B (P = .02 and P = .003, respectively), and significantly worse than that of patients transplanted for cholestatic liver disease (P = .001). Recipients who had a pretransplantation HCV-RNA titer of > or = 1 x 10(6) vEq/mL had a cumulative 5-year survival of 57% versus 84% for those with HCV-RNA titers of < 1 x 10(6) vEq/mL (P = .0001). Patient and graft survival did not vary with recipient gender, HCV genotype, or induction immunosuppression regimen among the HCV-infected recipients. While long-term patient and graft survival following liver transplantation for end-stage liver disease secondary to HCV are generally comparable with that of most other indications, higher pretransplantation HCV-RNA titers are strongly associated with poor survival among HCV-infected recipients.