Reversible renal failure during treatment with captopril.
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Biomedical subjects
Publications and source records attributed to G Lundgren.
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A 51-year-old patient with aplastic anaemia in whom a successful allogeneic bone-marrow transplantation had been performed developed acute graft-versus-host disease in spite of prophylactic administration of methotrexate. There was severe liver injury but no involvement of the skin or intestines. When prednisone therapy was introduced the fever and the eosinophilia disappeared and liver damage was rapidly reversed. There was no haematological impairment. It would seem warranted to consider a wider use of prednisone in the treatment of acute GVHD in human recipients of allogeneic bone-marrow.
The effect of physostigmine salicylate (0.5 mg/kg, i.p.) alone and in combination with atropine sulfate (25 mg/kg, i.p.) on levels of acetylcholine (ACh) and choline (Ch) and turnover of ACh has been studied in whole brain and striatum of mice. The animals were killed by focussed microwave irradiation and the turnover of ACh was studied after i.v. injection of deuterium labelled Ch by employing mass fragmentography. Physostigmine increased the levels of ACh in whole brain from 24.5--28.0 nmol/g(P less than 0.001) whereas there was no significant increase in striatum. The levels of Ch were also increased. The turnover rate of ACh was decreased in whole brain from 15.4 to 8.4 and in striatum from 52.9 to 24.4 nmol/g . min. Physostigmine given before or after atropine did not completely block the ACh lowering effect of atropine. When atropine was given before physostigmine the turnover rate of ACh in whole brain was increased to 24.2 nmoles/g . min. The results seem to indicate that there is no clear cut relation between the turnover rate and level of ACh in vivo. The increase of the turnover rate induced by atropine is masked unless a cholinesterase inhibitor is given to protect the newly synthesized labelled ACh released by atropine.
The phagocytic and metabolic functions of the reticuloendothelial system (RES) were determined, by measuring the plasma clearance rate of 125I-labelled microaggregated human serum albumin and the increase in plasma metabolites of this test substance, in patients with chronic renal failure and in renal transplant recipients at different times after transplantation. All transplant recipients received triple immunosuppressive therapy consisting of azathioprine, corticosteroids, and antilymphocyte globulin. The intravascular clearance of microaggregated albumin was significantly depressed in patients when tested at 1 to 12 days (P less than 0.001), 1 to 4 months (P less than 0.02), and 6 to 9 months (P less than 0.001) after transplantation compared to pretransplantation. The 1- to 3-year transplant survivors had a normal RES phagocytosis. Furthermore, the metabolic RES function in all groups of transplant recipients except the group of patients tested at 1 to 4 months after transplantation was significantly impaired compared to pretransplantation. Administration of antilymphocyte globulin and extremely high daily doses of steroids were probably responsible for the significant depression in the RES functions recorded immediately post-transplantation. The further development of the phagocytic ability of the RES was shown to be correlated to the cumulative dose of steroids given over the last 12 months. The azathioprine regime seemed to have no influence on the RES functions.
Renal graft survival was better for the patients receiving blood transfusions or treated with dialysis before transplantation. Graft survival was more strongly correlated with pretransplant dialysis than with blood transfusion.
In our view, renal transplantation in the uremic diabetic patient is justified. Recipients should be selected with caution. Patients with both loss of vision and heart disease will only rarely benefit from renal transplantation. Living related donor should be preferred if possible.
In Gaucher disease there is a deficiency of the lysosomal enzyme, cerebroside-beta-glucosidase, as a result of which cerebroside (glucosylcereamide) accumulates in various organs. In northern Sweden 22 patients with a juvenile form of this disease have been identified. In one such patient, a girl of 10 years, we have attempted enzyme replacement by renal transplantation. After this operation the hepatic glucocerebroside content fell significantly. In another child afflicted with Gaucher disease in whom splenectomy was performed for severe splenomegaly and hypersplenism there was a progressive increase in the level of this lipid. These findings suggest that enzyme replacement was achieved by transplantation of a normal organ.
Following renal transplantation, hepatic glucocerebroside deposits in a child with Gaucher disease were reduced. This suggests that enzyme replacement had been achieved.
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Sixty-two living related kidney donors were nephrectomized during a 10-year period. The overall complication rate was 40%, most complications being minor. Among the major complications was one patient with pulmonary embolism and three patients with hepatitis. One female donor suffered a psychoneurotic reaction following rejection of the donated kidney and she is still away from work, more than 2 years later. The other 61 donors were back to work within 2 to 18 (mean 8) weeks. The mean serum creatinine livels increased from 0.95 preoperatively to 1.15 mg/100 ml at the followup examination, which took place between 6 months and 9 years after nephrectomy. The mean increase in serum creatinine was higher in donors above 50 years of age (P less than 0.02). The mean creatinine clearance of the whole group decreased from 111 to 90 ml/min. The mean increase in size of the remaining kidney was 22%. Donor nephrectomy is a safe procedure with few serious complications and the prognosis for the recipient is excellent. Therefore, we consider transplantation from a family member to be the treatment of choice in terminal uremia.
Listeria encephalitis has occurred recently in 5 renal transplant recipients at the Transplantation Unit in Stockholm. Symptoms from the central nervous system, such as coma, hemiparesis and cranial nerve paresis, dominated the clinical picture. Listeria monocytogenes was isolated from the blood of all the patients, from the cerebrospinal fluid in two, from the urine in one and post mortem from the brain in one patient. Pleocytosis never exceeded 200 leucocytes/mm3 and the glucose ratio was normal or near normal. Complement fixation test for Listeria was negative in all 5 patients. Four patients expired in spite of treatment with large doses of penicillin and other antibiotics to which the isolated strains were sensitive in vitro. At autopsy, inflammation and necrosis were observed in the brain, especially the brain stem, and there was mild lymphocytic infiltration of the meninges. The surviving patient was treated with a combination of chloramphenicol and ampicillin.
The effect of adenosine on cholinergic neuroeffector transmission was studied in the isolated guinea pig ileum. Adenosine caused a dose-dependent and inverse frequency-dependent inhibition of contraction responses to transmural nerve stimulation. Blockade of adrenergic neurotransmission did not alter the inhibitory effect of adenosine. Adenosine also inhibited contraction responses to serotonin, angiotensin and high potassium, but not the responses to acetylcholine, histamine or direct electrical stimulation of the smooth muscle cells. Adenosine had little effect on basal outflow of acetylcholine but inhibited markedly and reversibly the release of acetylcholine induced by nerve stimulation. Acetylcholine was determined with gas chromatography-mass spectrometry. The results provide direct evidence that adenosine inhibits cholinergic neuroeffector transmission in the gut by a prejunctional action on acetylcholine release. This may be of functional importance since adenine compounds are released during stimulation of intestinal nerves.
Serial graft angiographies and scintigraphies were obtained in 4 human pancreatic allograft recipients. Important information was obtained both of graft morphology and function. Graft rejection was accompanied by characteristic abnormalities, including arterial irregularities and prolonged contrast medium passage time. On scintigraphy, rejection was associated with reduced isotope uptake.
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In hagfish islet parenchyma, consisting practically only of insulin-producing B-cells and agranular B-cell precursors, the contents of glutathione (GSH) and total protein-free thiols (NPSH) were determined on micro-dissected islet lobules. GSH was found to be of the same order of magnitude (22-25 mg/100 g wet weight) as in the islet parenchyma of a previously studied teleost fish and of some mammals, including man. However, the NPSH was found to be considerably higher in the islet lobules of the hagfish than in the teleostean islet parachyma. As in both teleost fish and mammals, GSH made up most of the NPSH in the hagfish erythrocytes, myocardium, and skeletal musculature. This discrepancy between hagfish islet parenchyma and other tissues indicates that the non-GSH portion of NPSH may be of particular significance for the insulin-producing B-cells. By means of flameless atomic absorption spectrophotometry the contents of zinc, cobalt, and manganese were determined in micro-dissected hagfish islet lobules. Neither zinc, nor cobalt, occurred in significantly higher concentrations in the islet parenchyma than in the liver or the skeletal musculature. Only manganese was found in somewhat higher amounts in the islet lobules than in the other tissues, but the contents were still low. The results indicate that none of the three heavy metals play any important role in the synthesis, storage, or release of insulin in the hagfish. The significance of this in relation to the prevailing hypotheses regarding the pathogenesis of alloxan diabetes is discussed.