Transplantation of porcine fetal pancreas to a diabetic patient.
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Biomedical subjects
Publications and source records attributed to J Tollemar.
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During liver transplantation, extracorporeal veno-venous bypass (VVBP) from the lower to the upper part of the body is used to prevent the negative circulatory effects otherwise seen on clamping the inferior caval vein during the actual change of livers. Extracorporeal circulation can sometimes be complicated by hemolysis. Therefore, we wanted to determine whether the technique used during liver transplantation might also cause hemolysis. This was measured as plasma hemoglobin using a spectrophotometric method including tetramethylbenzidine. Of 11 patients tested, 5 showed an increase in plasma hemoglobin during the use of VVBP; in no case, however, was this clinically significant. Three patients showed short peaks of hemoglobin during bypass. In two patients the rise continued after bypass and they required higher pump speed than the six patients without hemolysis (mean +/- SD 1900 +/- 150 RPM vs 1700 +/- 60 RPM, respectively). Pump flow, time of VVBP, and numbers of transfusions during the transplantation did not differ between the groups. We conclude that VVBP used during liver transplantation may cause hemolysis, but with low frequency and low clinical significance. We further conclude that the spectrophotometric method used is reliable and sensitive enough to determine the degree of hemolysis.
The mean total serum amylase levels in patients was 3.2 +/- 0.5 mukat/l (+/-SE) before total body irradiation (TBI) prior to bone marrow transplantation of which 50% was due to pancreatic isoamylase and 50% salivary isoamylase. Total serum amylase increased to a maximum of 100.3 +/- 12.3 mukat/l on the first day after TBI and most of this increase was due to an increase in salivary isoamylase (90.0 +/- 12.1 mukat/l). In association with this, all patients had clinical symptoms of parotitis. An increase in pancreatic isoamylase was found in 27% of the patients; however, none of them had clinical symptoms of pancreatitis. Serum amylase levels returned to normal within 5 days after TBI but then decreased to subnormal values, remaining below the normal range for 3 weeks. Pancreatic isoamylase returned to pre-irradiation levels 1.5 months after TBI, while salivary isoamylase remained low for the rest of the observation time. TBI of 7.5 Gy at 26 cGy/min gave significantly lower salivary amylase at 2 days after TBI compared with 10 Gy at 4 cGy/min: 32 +/- 4 versus 76 +/- 13 mukat/l (P less than 0.05). At 2.5 and 6 months after TBI significantly higher total amylase levels were recorded for patients treated with 7.5 Gy of TBI compared with 10 Gy: 2.5 +/- 0.4 and 2.7 +/- 0.3 versus 2.0 +/- 0.5 and 0.8 +/- 0.3 mukat/l, respectively (P less than 0.01, P less than 0.05, respectively). Acute or chronic GVHD did not affect acinar cells in this investigation.
One hundred and twenty-six patients were treated for 137 episodes of fungal infection with liposomal amphotericin B (AmBisome) at 43 investigational centres. Among the patients were 72 with malignancies, 17 organ transplant recipients, 20 patients with immunological disorders and 17 others. AmBisome treatment was instituted after toxicity from previous amphotericin B treatment in 49 cases, nephrotoxicity or renal insufficiency in 40 and failure of previous antifungal treatment in 41. One hundred and eight episodes were clinically evaluable; among these 52 were caused by Candida spp. and 34 by Aspergillus spp. Ninety-nine patients were treated for at least eight days with a maximum dose of 0.7-5 mg/kg/day. Among 64 cases with proven invasive fungal infection 58% were cured. Fungi were eradicated in 35 of 54 (65%) mycologically evaluable cases. The cumulative dose was 3.2 +/- 3.2 (mean +/- S.D.) in cases where fungi were eradicated in comparison with 3.3 +/- 2.3 g in cases where fungi persisted. The eradication rate was 83% for Candida spp. compared with 41% for Aspergillus spp. (P less than 0.01). Among 24 cases with presumptive invasive fungal infections 14 (58%) were cured. Candida spp. were eradicated in seven of ten of these cases. Among 11 cases with superficial fungal infections eight were cured and three improved. Candida spp. were eradicated in four of five patients. It is concluded that AmBisome is an effective antifungal agent in a majority of patients with invasive or superficial fungal infections.
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In adult leukemic marrow recipients of HLA identical sibling marrow, 23 patients were randomized to T cell depletion and 25 received cyclosporin (CSA) and four doses of methotrexate (MTX) to prevent graft-versus-host disease (GVHD). Anti-CD8 and anti-CD6 antibodies plus complement depleted 95.3 +/- 5.8% (mean +/- SE) CD3 cells. All patients engrafted except one who died early. Patients receiving T cell-depleted marrow had a faster time to 0.2 x 10(9) WBC/l (p less than 0.001), but required more erythrocyte units (p = 0.03). Platelet transfusions, infections and time in hospital did not differ. The incidence of grade II-III acute GVHD was 23% following T cell depletion and 12% for those receiving CSA + MTX. Chronic GVHD occurred in 51% and 23% in the two groups, respectively (p = 0.06). Recipients of T cell-depleted marrow who developed grade I-III acute GVHD received more T cells compared to those without acute GVHD (p = 0.02). The major cause of death in both groups was relapse, the cumulative incidence of which, at 4 years, was 39% in the recipients of T cell-depleted marrow and 54% in the CSA + MTX group. The 3-year actuarial leukemia-free survival was 42% and 44% in the two respective groups.
Blood lymphocyte responses to Candida protein antigen (CP, Candida mannan mitogen (CM) and Staphylococcus aureus protein A (SPA) were followed in 133 bone marrow transplant (BMT) recipients. Lymphocyte proliferative responses to CP and SPA normalized within 6-12 months. The response to CM was only decreased in non-colonized patients during the first 2 months post-BMT and had already returned to normal by 1 month in colonized patients. During the forthcoming years all three lymphocyte stimulatory tests responses reached donor levels. There was a tendency for low lymphocyte reactivity to CP, high reactivity to CM and equal reactivity for SPA among recipients of T cell-depleted marrows as compared to patients with conventional graft-versus-host disease (GVHD) prophylaxis. After BMT, patients who were colonized with Candida recovered and increased their lymphocyte response to CP and CM within 1-3 months, while non-colonized patients required more than 6 months to regain normal stimulatory capacity. Patients who developed grades II-IV acute GVHD had significantly higher pretransplant lymphocyte responses to both CP (p = 0.02) and CM (p = 0.02) than patients with grades 0-I acute GVHD. There was also a trend for patients who later had a confirmed invasive Candida infection to have high responses to CP before BMT (p = 0.07). After BMT, stimulation by CM, CP and SPA was not affected by acute or chronic GVHD or cytomegalovirus. In conclusion, proliferative capacity to Candida is restored early after BMT and superficial fungal colonization seem to be of importance for this maturation.
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A 9-month-old boy with a suggested candidemia was treated with liposomal amphotericin B (AmBisome, Vestar) after a liver transplant due to an inherited glycogenosis (Pompe's disease). This is believed to be the youngest patient in which this new therapeutic agent has been utilized.
At Huddinge Hospital 275 patients underwent allogeneic bone marrow transplantation. Among children in first remission of acute leukemia or chronic phase CML (early leukemia), with HLA-identical marrow the 8-year leukemia-free survival was 77%. This was better than 38% in children undergoing transplantation in second to fourth remission (p less than 0.0009). In adults with early leukemia, the 8-year leukemia-free survival was 47% compared to 21% for intermediate-risk adults (p = 0.007). Among 25 patients with severe aplastic anemia receiving marrow from HLA-identical siblings, the actuarial 10-year survival was 78%. In 14 patients with various metabolic disorders, of whom half received marrow from HLA-mismatched donors, the actuarial 7-year survival was 71%. Forty-three patients were given marrow from HLA-mismatched donors and had an increased incidence of acute graft-versus-host disease (GvHD) and death due to GvHD compared to recipients of HLA-identical bone marrow. The major causes of death among our patients were relapse of leukemia, death due to GvHD, cytomegalovirus (CMV) pneumonitis, bacterial infection and invasive fungal infections. By preventing GvHD with T-cell depletion or methotrexate (MTX) combined with cyclosporine (CsA) acute GvHD decreased, but the incidence of relapse increased compared to patients treated with MTX or CsA alone. This resulted in improved survival in patients older than 30 years, but a nonsignificant decrease in leukemia-free survival in younger patients. There was an association between herpes virus immunity in the recipient and GvHD. CMV pneumonitis increased following GvHD and decreased in patients treated with MTX combined with CsA. Invasive fungal infections may be treated or prevented using amphotericin B encapsulated in liposomes with few side effects.
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