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Biomedical subjects

G Lundgren

Publications and source records attributed to G Lundgren.

At least 109 records · Page 6Linked to original sources

Bone marrow transplantation for aplastic anemia and acute leukemia at Huddinge Hospital.

Eight patients with aplastic anemia were transplanted with marrow from HLA-identical donors. Two patient rejected their grafts and died while 5 patients (71%) show no ill effects 3 months, 10 months, and more than 1, 2 and 4 years after the transplantation. Three of the patients who received unirradiated donor buffy coat after transplantation developed chronic graft-versus-host disease (GVHD) which, however, resolved following treatment with Prednisolone and Azathioprine. One patient with end-stage acute myeloid leukemia, who was transplanted with marrow from an identical twin, died 6 days after the transplantation of bleedings and sepsis. Eight patients with acute non-lymphoblastic leukemia (ANL) were transplanted, while in remission, with marrow from HLA-identical siblings. One patient died of interstitial pneumonia 3 months after transplantation, while another patient recovered from GVHD of the gut at 5 months after the transplantation. Seven out of 8 patients with ANL (88%) are home and well between 2 and 12 months after the transplantation.

Acute Disease↗

The influence of HLA-DR match on cadaveric renal graft survival. Experience from Stockholm.

The influence of HLA-DR match on graft and patient survival was analyzed in 124 cadaveric kidney transplant recipients treated between January 1977 and September 1980. The material consisted of 90 primary transplant and 34 retransplants. The mean patient age was 49 years, 72 were males and 52 females. Eighteen of the recipients were diabetics. Sera against the HLA-DR antigens 1-5, 7 and DRw8 were available, for DRS only during the later half of the period. When the case material was divided according to the number of donor-recipient HLA-DR antigens shared, a significant improvement in graft survival was found if one antigen was shared as compared to none shared. When 2 antigens were shared graft survival was excellent but there were only 7 such cases. When division was performed according to the number of existing HLA-DR incompatibilities, a significant improvement in graft survival was noted when there were no incompatibilities as compared with 2 incompatibilities. The distribution of foreign HLA-A, B antigens was even between the DR match groups and did therefore not constitute a bias. We conclude that matching for the HLA-DR antigens has a major beneficial effect on cadaveric kidney graft survival.

Actuarial Analysis↗

Fulminating anti-A autoimmune hemolysis with anuria in a renal transplant recipient: a therapeutic role of plasma exchange.

In this communication we present a case of fulminating anti-A autoimmune hemolysis with anuria occurring during the postoperative course after a successful renal transplantation. The patient was treated with repeated plasma exchange in an effort to remove antibodies directed against the red cells and also to eliminate the products of hemolysis known to cause acute renal failure. Subsequently the hemolysis receded and the patient regained graft function. Repeated plasma exchange, in addition to immunosuppression, appeared to have contributed to the ultimate recovery of the patient.

Acute Kidney Injury↗

Plasma C-peptide and serum insulin antibodies in diabetic patients receiving pancreatic transplants.

Plasma C-peptide and serum insulin antibody levels were determined in 5 diabetic patients undergoing vascularized pancreatic transplantation. The grafts functioned well at first and exogenous insulin could be withdrawn, but one to 7 weeks later the grafts were rejected. After the transplantation there was an increase in the fasting plasma C-peptide level, and B-cell stimulation with glucose or glucagon evoked a C-peptide response. Healing of ischaemic damage was reflected in an increase in the C-peptide level. During graft rejection the C-peptide level fell. Measurement of plasma C-peptide levels provides a direct index of the B-cell function of the pancreatic graft. After transplantation the insulin antibody level fell exponentially, with an apparent half life of 10-11 days, whereas the level of total IgG was variable. The results indicate that formation of insulin antibodies ceases immediately on removal of the immunogenic stimulus, that is, on withdrawal of xenogeneic insulin.

Adult↗

Improved renal graft survival in transfused uremics. A result of a number of interacting factors.

In a series of 229 first-time recipients of cadaveric renal grafts the graft survival was better for the patients that had received 4 or more units of blood, than for those patients that had never received blood; on the other hand, for the patients 1 to 3 units the survival was not better. A relationship between blood transfusion and graft survival was found only for patients receiving kidneys with two or less HLA-A and B incompatibilities. Among the patients receiving 20 or more units of blood, one-half became long-term HBsAg carriers and 60% developed HLA antibodies. A larger proportion of these patients had received grafts with a good HLA-A,B match. The graft survival was better for patients that had been on regular dialysis before the transplantation than those that had not. The choice of dialysis method was also significant, the survival being better for patients that had been on peritoneal dialysis than those on hemodialysis. It would appear that blood transfusion and dialysis treatment had an additive effect on graft survival.

Antibodies↗

Cadaveric renal transplantation in patients of 60 years and above.

Between 1971 and 1977, 34 patients aged 60 years and above were treated with cadaveric renal transplantation in Stockholm. The survival figures were nearly the same as for patients of the same age group that had undergone long-term dialysis, with 2-year survival rates of 49 and 45%, respectively. Comparison with a younger group of transplant patients, ages 16 to 49, showed poorer patient and graft survival figures for the older patients, with 49 and 38%, respectively, after 2 years against 70 and 56% for the younger group. Complications were more frequent among the older patients, especially in regard to serious infections, heart conditions, and steroid diabetes. Irreversible rejection, on the other hand, was less common in the older group. On the basis of these findings, we intend continuing to offer renal transplantation to patients of 60 years and above. It would, moreover, seem worthwhile to try to reduce the dose of prednisolone in these patients.

Adolescent↗

Experience with pancreatic transplantation in Stockholm.

Eight attempts at segmental pancreatic transplantation were made in 6 diabetic patients. While the indications for transplantation differed all the patients were severely incapacitated by the disease. None was uremic. The body and tail of the pancreas from cadaveric donors was used, the grafts were revascularized to the recipient's iliac vessles. Six of the grafts provided control of blood glucose for 7-51 days. Five of the grafts then failed owing to rejection, and one had to be removed while still functioning, because of arterial bleeding. Important lessons have been learned concerning both surgical and immunological aspects of this form of treatment : 1) Ducto-jejunostomy should be used to provide exocrine pancreatic drainage. 2) HLA-DR typing for donor-recipient selection and thoracic-duct drainage as an adjunctive immunosuppressive measure should be used to reduce the incidence of graft rejection. 3) An elevation of the postprandial blood glucose concentration is a first sign of rejection and should cause treatment. 4) Graft rejection can be reversed by conventional steroid medication.

Adult↗

Pre- and postjunctional effects of prostaglandin E2, prostaglandin synthetase inhibitors and atropine on cholinergic neurotransmission in guinea pig ileum and bovine iris.

The effects of prostaglandin E2, arachidonic acid, prostaglandin synthetase inhibitors and atropine on cholinergic neuromuscular transmission were examined in isolated guinea pig ileum longitudinal muscle and bovine iris sphincter muscle. Prostaglandin E2 and arachidonic acid markedly enhanced contraction responses induced by nerve stimulation. In addition, prostaglandin E2, enhanced contraction responses to acetylcholine and direct muscle stimulation, approximately to the same extent as those to nerve stimulation. Prostaglandin synthetase inhibitors (indomethacin, meclofenamic acid and eicosatetraynoic acid) very effectively reduced contraction responses to nerve stimulation or acetylcholine, and they annulled the stimulant effect of arachidonic acid. Basal and nerve-induced efflux of acetylcholine from the eserinized tissues, as measured by mass fragmentography, was unaltered by prostaglandin E2, but diminished slowly during indomethacin. Subsequent prostaglandin administration caused a slight increase of nerve-induced release of acetylcholine. Atropine markedly increased overflow of acetylcholine form stimulated preparations of both types. This indicates that muscarinic receptors, causing diminished acetylcholine release in eserinized tissue, may be present also at postganglionic terminals. During atropine, an effect of prostaglandin E2 on acetylcholine release could still not be seen. Thus, using physicochemical determination of acetylcholine, we could not verify earlier reports, employing bioassay, claiming enhanced release of transmitter during prostaglandin E2 treatment. However, it seems likely that prostaglandin E2 takes part in the regulation of contractility and tone of the smooth muscle cells.

Acetylcholine↗

Segmental pancreatic transplantation with duct ligation or drainage to a jejunal Roux-en-Y loop in nonuremic diabetic patients.

The results of seven segmental pancreas transplantations in diabetic patients, using a jejunal Roux-en-Y loop for drainage of digestive enzymes, are presented. An initial case with pancreatic duct ligation is also included. The patients ranged in age from 30 to 45 yr, with duration of diabetes from 8 to 24 yr, and were incapacitated but not uremic. Immunosuppression was attempted with azathioprine, prednisone, and antilymphocyte globulin, and, in one patient, thoracic duct drainage was added. The pancreas tolerated at least 16 min of warm ischemia and at least 4 h of cold storage; flushing with a balanced electrolyte solution was optimal. Six of the grafts provided control of blood glucose for 7--51 days, and, in one patient, an intravenous glucose tolerance test was normal at 7 and 21 days. Five of the grafts failed due to rejection 7--51 days after transplantation, and one was removed at 14 days, while still functioning, due to bleeding. In one case, early detection of rejection by a rise in post-prandial blood glucose was treated and reversed by corticosteroid administration. Two failed in the immediate postoperative period from vascular thrombosis. Drainage of pancreatic secretions from a fistula was a common problem.

Adult↗

Transplantation of fetal pancreatic microfragments via the portal vein to a diabetic patient.

Human fetal pancreas preserved in culture was used as a donor organ in a 45-yr-old man with diabetes of 14-yr duration complicated by severe retinopathy and nephropathy. Renal failure had been successfully treated by a cadaveric renal transplant 2 yr earlier. Six fetal pancreases, obtained within 30 min of delivery after prostaglandin-induced abortion at 14--20 wk of gestation, were minced and placed in tissue culture for 3 h at the earliest and 15 days at the longest duration. The cultures were harvested 2--3 h before transplantation. Approximately 3 ml of tissue was infused into a right portal vein branch. Azathioprine was continued at 2 mg/kg and prednisolone increased from 10 mg to 100 mg/day on the day of transplantation and gradually reduced to 25 mg/day. Only two doses of antilymphocytic globulin were given because of a severe reaction. During the 40 days since transplantation, insulin requirements have not changed, but C-peptide has appeared in the urine, suggesting function of the transplanted tissue.

C-Peptide↗

The effect of immunosuppressive therapy on the phagocytic and metabolic functions of the reticuloendothelial system in renal transplant recipients.

The object of this study was to examine the bearing that immunosuppressive therapy may have on the phagocytic and metabolic functions of the reticuloendothelial system (RES). The phagocytic and metabolic activities of the RES were determined in renal graft recipients before transplantation and at intervals afterwards. The activities were measured as the plasma clearance rate of 125I-labelled microaggregated human serum albumin and the increase in the plasma metabolites of this test substance. The intravascular clearance of microaggregated albumin was significantly depressed at 1-12 days (P less than 0.001), 1.4 months (P less than 0.02) and 6-9 months (P less than 0.01) after transplantation compared to the levels before operation. RES phagocytosis was normal in the 1-3 year group. Furthermore, in all except the 1-4 month group the metabolic activity was significantly reduced. The significant impairment of the RES functions immediately after transplantation was probably due to administration of antilymphocyte globulin and extremely high doses of steroids. After antilymphocyte globulin had been withdrawn the phagocytic capacity of the RES was correlated to the total dose of steroids given over the 12 months prior to the test. The azathioprine regime seems to have had no influence on the RES functions.

Adult↗

Steroid diabetes--a sign of overtreatment with steroids in the renal graft recipient?

The development of steroid diabetes was studied in a consecutive series of 114 patients receiving a cadaveric renal graft. All were first-time transplantations. For acceptance in the series the graft should have functioned for at least 2 weeks after the transplant operation. The median age of the patients was 52 years. The follow-up period was at least one year. The criterion for a diagnosis of steroid diabetes was an elevated fasting blood glucose concentration of more than 8 mmoles/l. Fifty-two of the patients (46 per cent) developed steroid diabetes. Thirty-four (65 per cent) of them required insulin therapy or peroral anti-diabetic drugs. The mean age of these patients was higher than for those not afflicted by this complication. The first-year mortality was significantly higher, 42 against 13 per cent, respectively (p less than 0.01). The level of significance was not notably affected by correction for age at transplantation. Severe infection was the cause of a large proportion of the deaths in the diabetes group. The findings suggest that the development of steroid diabetes can serve as a warning signal for excessive dosage of corticosteroids, and help to identify patients that are particularly sensitive to immunosuppressive therapy with large doses of steroids.

Adolescent↗