Correction of hyperbilirubinemia in the glucuronyltransferase-deficient rat by intraportal hepatocyte transplantation.
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Biomedical subjects
Publications and source records attributed to G Lundgren.
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The splenic uptake of 51Cr-labelled autologous erythrocytes was studied by body surface counting in 20 hemodialysis patients. Evidence for splenic hypersequestration of erythrocytes was obtained in 7 patients. Splenectomy was performed in 6 of these and led to a reduction in transfusion requirements. One patient without evidence of splenic hypersequestration of red cells was also subjected to splenectomy but was not improved. The importance of following the splenic uptake of 51Cr for a sufficiently long time to detect a delayed uptake of 51Cr is pointed out.
In several countries, organs for transplantation cannot be removed from cadaver donors until cardiac arrest has occurred. A technique is described for removal of the kidneys and pancreas in which the whole abdominal contents are freed and reflected so that the retroperitoneal organs lie uppermost. The aorta is opened longitudinally and the relevant arteries are cannulated via their orifices. Cold perfusion of the three organs can usually be initiated 5-15 minutes after cardiac arrest and significant ischaemia is avoided. The full length of the vascular pedicles can be preserved and the dissection of the retroperitoneal organs is greatly facilitated.
Lymphocyte depletion by drainage of lymph via a thoracic duct fistula was accomplished in 51 renal transplant recipients as an adjunct method for immunosuppression. The duration of lymph flow varied between 2 and 53 days and the total drained lymph volume between 1 and 168 liters. The graft survival of these patients was compared to that of a control group of patients undergoing transplantation during a similar period. The followup period was 2-6 years. In patients receiving transplants from living related donors, no beneficial effect of lymphocyte depletion was demonstrated, probably because of the satisfactory graft survival among the control patients (84% at 1 year). However, in recipients of cadaveric kidneys, a significantly higher 1-year graft survival was achieved in the lymph-drained patients. Drainage for more than 30 days and of more than 20 liters improved the results. Additional suppression by thymectomy and institution of antilymphocyte globulin suggested that the best treatment would be a combination of both these measures with lymph drainage continuing for more than 30 days. Infection around the thoracic duct cannula occurred in 5 patients, necessitating removal of the cannula in 2. Two patients developed septicemia. In one of them the infection originated from an infected incisional wound and in the other probably from reinfusion of contaminated lymph plasma. Two other patients developed malignant tumors 23 and 58 months after transplantation, respectively. It is felt that lymphocyte depletion by lymph drainage is an effective supplementary method of immunosuppression to enhance graft survival in recipients of cadaveric renal transplants.
The role of compatibility at the HL-A and mixed lymphocyte culture (MLC) loci for graft survival was analysed in 45 recipients of intrafamilial kidneys. MLC tests performed after transplantation when the recipients were on maintenance immunosuppressive therapy did not show a reduced reactivity of the recipient lymphocytes as compared to tests performed before surgery. The results with the two-way MLC test was paradoxical: patients with functioning grafts had a higher mean stimulation than did those with nonfunctioning grafts. Subsequent clinical correlations were based on one-way MLC carried out before or after transplantation. The 1-year survival of grafts from HL-A compatible donors was 94% and that of graft from HL-A incompatible donors was 75%. When the comparison was between grafts from MLC-negative and MLC-positive donors the figures were 100 and 75%, respectively. If the cases were divided in those displaying a low relative reactivity (RR), indicating identity at the major (LD-1, HL A-D) MLC locus, towards their donors in MLC and those with a high RR, the graft survival was 100% versus 70% (P less than 0.05). The prognosis seemed to be worse the higher the relative reactivity. At 3 years all grafts from donors with negative reaction or low RR in the MLC were still functioning. Analysis of the few exceptional cases in which there was compatibility for either the HL-A or MLC locus but not for the other points to the major MLC locus as being most important for graft survival.
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Transplantation of human pancreatic islets to diabetic patients may require that donor islets be kept viable in vitro for extended time periods before transfer to the recipient. We have maintained isolated pancreatic islets obtained from the human cadaveric pancreas in tissue culture for 1-3 wk, after which we studied the structure and function of the islets. Electron micrographs of the cultured islets showed a satisfactory preservation of both beta-cells and alpha 2-cells. After culture for 1 wk, the islet oxygen uptake proceeded at a constant rate at a low glucose concentration (3.3 mM) and was significantly enhanced by raising the glucose concentration to 16.7 mM. Likewise, after culture for 1 wk, the islets responded with an increased insulin release when exposed to 16.7 mM glucose with or without added theophylline (10 mM). Islets cultured for 1-3 wk were able to incorporate [3H]leucine into proinsulin, as judged by gel filtration of acid-alcohol extracts. Glucagon release from the cultured islets was reduced significantly by 16.7 mM glucose alone, but stimulated by glucose (16.7 mM) plus theophylline (10 MM). It is concluded that viable pancreatic islets can be isolated from the pancreas of adult human donors and maintained in tissue culture for at least 1 wk without loss of the specific functions of the alpha 2- and beta-cells. It remains to be established whether such islets will survive and remain functionally competent after transplantation to human recipients.
Ninety-four subcutaneous arterio-venous fistulas were created for haemodialysis in 83 patients. Seventy-one patients eventually received well-functioning fistulas. The most common complication was thrombosis at the suture line. Thus, 8 primary fistulas clotted within 24 hours of surgery and 5 clotted later. Eleven patients were reoperated with a successful result in six. One patient developed arterial insufficiency in the hand with finger ulcerations, probably due to a radial steal syndrome. Four patients got extremely swollen hands and threatening gangraena because of thrombosis of the vein proximally to the anastomosis. Vital capillary microscopy in the patients with vascular insufficiency demonstrated profound changes of the nutritional capillaries which were not seen in control patients with well-functioning fistulas. After closure of the fistulas the edema disappeared and the ulcerations healed rapidly.
In patients receiving cadaveric kidneys and treated with antilymphocyte globulin (ALG) the one-year graft survival 59%. The corresponding figures with living related donors were 87% and 83%, respectively. Side effects of ALG, of which allergic reactions were the most common, prompted its withdrawal in 33% of the cases. All patients studied developed antibodies against horse gammaglobulin when tested with a passive haemagglutination inhibition technique. ALG seems to act upon the T-cells since the number of cells forming rosettes with sheep red blood cells was reduced.
Four patients with diabetes mellitus of juvenile onset but without uremia have been treated with segmental transplantation of the body and tail of pancreas. The indications were hyperlabile diabetes or progressive loss of vision. The grafts were procured from cadaveric donors four to 16 minutes after circulary arrest and were subsequently stored in the cold for approximately four hours. In one patient, the pancreatic duct was ligated, while in the other three, drainage was attained by suturing the transected end of the pancreas into a jejunal Roux-en-Y loop. Three of the grafts failed within six weeks as a result of irreversible refection, and one graft failed because of the early onset of venous thrombosis. The first sign of graft rejection was an increase in the postprandial blood sugar level, an increase in the fasting blood sugar level occurring several days later. Neither hyperamylasemia nor fever was observed. Radioisotope scans and angiograms were of great value in establishing the diagnosis of graft rejection. All of the patients survived after graft removal.
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