Effects of oxotremorine on synthesis of acetylcholine in striatum and whole brain of mice killed by various techniques.
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Biomedical subjects
Publications and source records attributed to G Lundgren.
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Lead concentrations in 541 samples of umbilical cord blood from different parts of Sweden were determined. The mean concentration was 7.6 mug lead/100 ml (=0.367 mumol/l). The blood lead values were also determined for 297 mothers and a mean value of 8.7 mug/100 ml (=0.420 mumol/l) was found. There was a significant correlation between the blood lead level of the mother and the infant as studied in 253 pairs. The slope of the regression line was 0.5 r (r=0.6). Significantly lower blood values for both mother and infant were found in areas with low pollution as estimated from the lead content in moss. No seasonal variation could be ascertained. Hematocrit versus lead concentration was also studied. A flameless atomic absorption method was used with a standard deviation of 0.9 mug lead/100 ml. The storage time and sample treatment were also studied.
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.
By a flameless atomic absorption spectrophotometry procedure, using a graphite furnace, it was possible to assay the contents of zinc and managanese in micro-dissected pancreatic islets of several rodents. Interest was focused upon the islets of guinea-pigs, due to the fact that guinea-pig insulin lacks a histidine residue in the B10 position of the molecule which normally binds zinc (or other heavy metals) in the hexamer formation, probably involved in the storage of insulin. Both the zinc and manganese contents were too low in the guinea-pig islet parenchyma to be reasonably involved in the storage of insulin in the beta-granules. Instead, it was suggested that guinea-pig insulin, like hagfish insulin, might crystallize without access to zinc or other heavy metals. Low zinc and manganese contents were also observed in newborn and diabetic guinea-pigs. The islet zinc content was high in the Wistar rat, the Chinese hamster, and the spiny mouse. No significant amounts of manganese were found in any of these kinds of islet parenchyma.
The prevalence and duration of secondary hyperparathyroidism in 42 renal transplant recipients, and the sequelae of this condition, were studied. Immediately before transplantation, an elevated PTH-value was recorded in 76% of the patients, postoperatively there was a marked drop. Early after successful transplantation, 57% of the patients had hypercalcemia. At follow-up 3 years later, moderate hypercalcemia persisted in half of the patients but only 3 patients had significantly elevated PTH. The quality of renal graft function was not inferior in the hypercalcemic patients. Subperiosteal bone resorption and soft tissue calcifications were more common among the hypercalcemic patients. Our data suggest that secondary hyperparathyroidism can be managed conservatively in most renal transplant recipients. If progressive bone changes occur, surgical removal of parathyroid tissue should be considered.
In a series of 335 renal transplant recipients, 28 patients underwent parathyroidectomy due to secondary hyperparathyroidism. Twenty patients were operated on prior to renal transplantation, 8 subsequent to it. Solitary adenomas were found in 6 cases, diffuse hyperplasia in 22. Fifteen of the patients with diffuse hyperplasia underwent total parathyroidectomy with autotransplantation of parathyroid fragments into the sternocleidomastoid muscle, subtotal parathyroidectomy was performed in 7. Four hypercalcaemic patients underwent parathyroid surgery because of deteriorating transplant function but without improvement. Following parathyroidectomy, 21 patients became hypocalcaemic. 15 of these patients had undergone total parathyroidectomy and autotransplantation. Dihydrotachysterol substitution was accompanied by toxic symptoms in three patients on dialysis and by deteriorating renal function in two transplanted patients. Therefore, subtotal parathyroidectomy is recommended as the surgical procedure of choice in the treatment of secondary hyperparathyroidism before, as well as after renal transplantation.
The incidence of steroid diabetes mellitus was studied retrospectively in 84 renal transplant recipients with grafts which had functioned longer than 3 months. The observation time ranged between 3 and 36 months (mean 17 months). Overt diabetes necessitating treatment was found in 24 patients (29%). Another 14 patients had transient elevations in blood glucose. The incidence of steroid diabetes was found to correlate with increasing age and body weight and with the number of rejection episodes. In the majority of the patients with manifest diabetes it was diagnosed within three months after transplantation.
The significance of HLA-matching for the survival of cadaver kidneys, transplanted between January 1970 and June 1976 to 170 uraemic patients has been assessed. When the patients were divided into groups according to degree of HLA compatibility it was found that the groups so obtained were comparable neither with regard to the quality of the transplants nor to the immunosuppressive therapy given. This was due to multiple changes in policy in 1973. When the case material was divided into patients treated before and after 1973, comparable groups were obtained within each series. The only correlation found was that, in the chronologically later groups, 2 year survival rate of transplants with E-G match (3--4 incompatibilities) was inferior to that of transplants with C-D match (1-2 incompatibilities).
A controlled study of the effect of antihuman lymphocyte globulin (AHLG) on patient and kidney transplant survival has been performed. The AHLG was administered as an adjuvant to the routine immunosuppressive drugs in either high (30 mg/kg) or low (15 mg/kg) doses, control patients received no AHLG. The clinical condition of the recipients and the quality and the degree of immunological compatibility of the transplants were comparable. During the period of the study, the results of all first-time cadaver-kidney transplantations to non-diabetic uraemic patients were included. The actuarial graft survival rates at 12 months for the three groups (high dose, low dose and control) were 67%, 49% and 35%. The corresponding patient survival rates were 91%, 66% and 65% respectively. The difference between the results in the high dose AHLG and in the control group was significant (p less than 0.05).
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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.