Search PubMedSearch

Biomedical subjects

S D Ladefoged

Publications and source records attributed to S D Ladefoged.

At least 19 recordsLinked to original sources

Transfusion-associated graft-versus-graft and potential graft-versus-host disease in a renal allotransplanted patient.

Transfusion-associated graft-versus-host disease (GVHD) is a rare but often fatal condition. We report on a case in which a 54-year-old man with polycystic kidneys shortly after receiving a male cadaver donor kidney developed severe intractable rejection and symptoms of GVHD. In situ hybridization with a Y chromosome- "specific" DNA probe and combined in situ hybridization and immunohistochemistry with monoclonal antibodies defining cellular phenotypes were performed on biopsy and tissue specimens taken at rejection episodes and from the lost allograft. The vast majority of infiltrating leukocytes in the morphologically rejecting kidney parenchyma were of female origin and consisted mainly of T lymphocytes and macrophages. This could only be explained by engraftment of leukocytes received in connection with transfusion of female whole blood in association with the transplantation. The patient developed symptoms of GVHD, and graftectomy was performed due to life-threatening cytomegalovirus infection. This case of combined "graft"-versus-graft disease and GVHD indicates that precautions in the administration of blood transfusion to severely immunosuppressed patients should be taken. We recommend the use of gamma-irradiated and lymphocyte-depleted blood products.

Graft Rejection

1 alpha-Hydroxycholecalciferol adsorption to peritoneal dialysis bags: influence of time, glucose concentration, temperature, and albumin.

The present study examines the adsorptive phenomenon of 1 alpha-hydroxycholecalciferol (1 alpha-OHD3) to peritoneal dialysis bags. One minute after injection of 1 alpha-OHD3 into the dialysis bags, a significant adsorption to the bags was observed in experiments where albumin was not added. A higher temperature (37 degrees versus 23 degrees C) in bags containing 13.6 mg glucose/ml resulted in less adsorption (P < 0.05). Adding albumin to bags at 37 degrees C with a glucose concentration of 13.6 mg/ml, reduced the adsorptive phenomenon significantly (P < 0.01). Bags tested at 37 degrees C with a glucose concentration of 38.6 mg/ml resulted in a significantly higher 1 alpha-OHD3 adsorption than bags containing 13.6 mg glucose/ml (P < 0.01). It is concluded that adsorption of 1 alpha-OHD3 to dialysis bags is affected by time, albumin, temperature and glucose concentrations. Substantial amounts of 1 alpha-OHD3 is retained by the peritoneal dialysis system when albumin is not added.

Adsorption

Intravenous versus subcutaneous administration of recombinant human erythropoietin in patients on haemodialysis and CAPD.

The most effective route of administration of rHuEpo is still a matter of discussion. Prospectively we studied subcutaneous (s.c.) versus intravenous (i.v.) administration in three comparable groups of patients; HD-s.c. (n = 9), HD-i.v. (n = 11), and CAPD-s.c. (n = 9). All the groups initially received 50 units/kg three times weekly. During the first 8 weeks dose adjustments were made only if target haemoglobin exceeded 11.3 g/dl (7 mM). Target haemoglobin was reached after 84 (42-98) days in the i.v. group and 42 (14-77) and 42 (28-56) respectively in the HD-s.c. and CAPD groups. The difference was statistically significant (P less than 0.05). Even the cumulative doses to reach target haemoglobin were significantly less in the two s.c. groups. To maintain haemoglobin at about 11.3 g/dl, weekly doses were as follows: HD-i.v. 125 U/kg (86-168), HD-s.c. 63 U/kg (20-85), and CAPD 72 U/kg (31-100). The total observation time after the target haemoglobin level was reached, was median 130 (114-264) days. The difference between the i.v. group and the two s.c. groups was statistically significant, (P less than 0.05) whereas there was no difference between the s.c. groups. We conclude that s.c. administration of rHuEpo is more effective in induction as well as in maintenance therapy and that s.c. administration is equally efficient in HD and CAPD patients.

Adolescent

An assessment of the flow rate within peritoneal dialysis catheters, using a standardized in vitro technique.

A variety of peritoneal dialysis catheters are used in clinical practice. The catheters are mainly described by their design, French number (circumference in mm) and length. However, this description does not provide information about the catheters inflow and outflow rates. We have therefore, studied flow rates of 18 adult catheters, using a uroflowmeter. Inflow rates were measured with the inflow bag 100 cm and 145 cm above the tip of the catheter, and outflow rates were measured with the flow transducer located 35 cm and 80 cm below the tip of the catheter, imitating situations where patients are sitting in a chair or laying in a bed during fluid exchanges. Ten measurements were made for each catheter at all heights. We found that catheter designs do affect flow rates. Straight catheters had statistic significantly faster inflow and outflow rates compared to curled catheters (p < 0.001). Moreover, curled catheters had statistic significantly faster flow rates than Swan Neck catheters (p < 0.001). The length and internal diameter of the catheter was found to be the determining factor for the differences in flow rates.

Catheterization

Cellular inflammatory infiltrates and renal cell turnover in kidney allografts: a study using in situ hybridization and combined in situ hybridization and immunohistochemistry with a Y-chromosome-specific DNA probe and monoclonal antibodies.

The generation and targeting of inflammatory cells in acutely rejecting kidney allografts are only partly understood. In order to investigate the origin of infiltrating mononuclear cells and the renal cell turnover, percutaneous renal biopsies (45) and lost renal allografts (4) from 40 sex-mismatched transplant patients clinically suspected of developing acute rejection were analysed by in situ hybridization (ISH) and combined ISH and immunohistochemistry (IMH). A biotinylated Y-chromosome-specific DNA probe was used for ISH. Monoclonal antibodies against leukocytes (leukocyte common antigen (CD45), T lymphocytes (CD43), B lymphocytes (L26) and myeloid/histiocytic cells (mac 387] were employed using a three-stage immunoperoxidase technique followed by ISH on the same specimens. The ISH method was very sensitive when differentiating male from female cells (p less than 0.01). Posttransplant mononuclear infiltrates were shown to be of recipient origin and dominated by T lymphocytes and myeloid/histiocytic cells. Tubular and glomerular cells remained of donor origin even after 10 months. There was no evidence of revascularization by recipient endothelial cells.

Antibodies, Monoclonal

Overall renal and tubular function during infusion of amino acids in normal man.

1. Amino acids have been used to test renal reserve filtration capacity. Previous studies suggest that amino acids increase glomerular filtration rate (GFR) by reducing distal tubular flow and tubuloglomerular feedback activity. 2. Glomerular function and the renal tubular handling of sodium during infusion of amino acids was studied in 12 normal volunteers. 3. Clearance of sodium (CNa) was unchanged. Effective renal plasma flow increased slightly, but significantly, by 9% (P less than 0.05). GFR was increased by 13% (P less than 0.001). Clearance of lithium (CLi) (used as an index of proximal tubular outflow) increased by 38% (P less than 0.001). Calculated absolute proximal reabsorption (GFR-CLi) remained unchanged. Fractional proximal reabsorption [1-(CLi/GFR)] was decreased by 10% (P less than 0.001). Calculated absolute distal sodium reabsorption [(CLi-CNa) x PNa, where PNa is plasma sodium concentration] increased by 40% (P less than 0.001). Plasma renin concentration did not change significantly. 4. The results suggest that amino acids increase GFR by a primary effect on renal haemodynamics or, less likely, by reducing the signal to the tubuloglomerular feedback mechanism. The increase in proximal tubular outflow was compensated for in the distal tubules, so that the sodium excretion rate remained unchanged.

Absorption

Renal tubular reabsorption of sodium and water during infusion of low-dose dopamine in normal man.

1. Using the renal clearance of lithium (CLi) as an index of proximal tubular outflow of sodium and water, together with simultaneous measurements of effective renal plasma flow, glomerular filtration rate (GFR) and sodium clearance (CNa), renal function and the tubular segmental reabsorption rates of sodium and water during dopamine infusion (3 micrograms min-1 kg-1) were estimated in 12 normal volunteers. 2. CNa increased by 128% (P less than 0.001). Effective renal plasma flow and GFR increased by 43% (P less than 0.001) and 9% (P less than 0.01), respectively. CLi increased in all subjects by, on average, 44% (P less than 0.001). Fractional proximal reabsorption [1-(CLi/GFR)] decreased by 13% after dopamine infusion (P less than 0.001), and estimated absolute proximal reabsorption rate (GFR-CLi) decreased by 8% (P less than 0.01). Absolute distal sodium reabsorption rate [(CLi-CNa) x PNa, where PNa is plasma sodium concentration] increased (P less than 0.001), and fractional distal sodium reabsorption [(CLi-CNa)/CLi] decreased (P less than 0.001). 3. It is concluded that natriuresis during low-dose dopamine infusion is caused by an increased outflow of sodium from the proximal tubules that is not fully compensated for in the distal tubules.

Absorption

Detection of CMV DNA and CMV antigen in renal allograft biopsies by in situ hybridisation and immunohistochemistry.

One hundred kidney allograft biopsies from 85 patients and tissue specimens from 31 failed allografts were analysed by immunohistochemistry (IMH) with a monoclonal antibody against a cytomegalovirus (CMV) antigen and by in situ hybridisation (ISH) with a biotinylated CMV DNA probe. Six clinically and serologically CMV-infected patients with AIDS served as positive controls. Biopsies from six seronegative donor kidneys and autopsy specimens from five clinically and serologically negative patients served as negative controls. Adequate serology in 56 patients showed 50% to be actively CMV infected. No statistically significant difference was found between the frequency of acute rejection in the seropositive and the seronegative patients. Four seropositive transplanted patients contained CMV DNA or CMV antigen in the biopsies and in the grafts. Both methods gave a negative result in 15 patients with glomerulopathy. Expression of MHC class I and II antigens in 17 of the biopsies demonstrated no relation to positive serology or local demonstration of CMV. In conclusion, (1) CMV was not renotropic, (2) there was no correlation between (a) CMV and acute rejection, (b) CMV and glomerulopathy, or (c) CMV and MHC class I and II antigen expression. The study suggests that CMV does not play a major role in rejection.

Antigens, Viral

[Cimetidine and creatinine clearance].

Cimetidine lowers secretion of creatinine in the renal tubuli in healthy individuals and persons with chronic renal disease. The conditions in patients with renal transplants have hitherto been unknown. The renal clearance of endogenic creatinine (CKrea) was investigated prior to and after an intravenous bolus injektion of cimetidine (5 mg/kg) in nine patients with renal transplants. The rate of glomerular filtration (GFR) was determined by clearance investigation of 125I-thalamate (CTh). CKrea fell 29% from 65 ml/min (median) to 46 ml/min (p less than 0.01), whereas GFR remained unchanged. The fractionated creatinine clearance (CKrea/CTh) fell therefore from 1.43 (median) to 1.03 (p less than 0.01). It is concluded that cimetidine reduces creatinine secretion in patients with renal transplants and this should be borne in mind when the function of the graft is assessed solely with CKrea.

Adult

[Primary hyperoxaluria].

Primary hyperoxaluria is a recessive hereditary disturbance of glyoxylate metabolism caused by deficiency of the liver enzyme, alanine glyoxylate transaminase. The main symptoms are recurrent renal stones, nephrocalcinosis and renal failure. In the advanced state, the disease is frequently complicated by osseous disease, vascular insufficiency and cardiac arrhytmias caused by deposits of calcium oxalate in the tissue. The prognosis is poor. No specific medical treatment exists. Dialysis is not effective and the results of renal transplantation is poor. Combined liver and renal transplantation correct the metabolic defect and the excretion of oxalate is normalised. Combined transplantation must be regarded as the optimal treatment of renal failure caused by PHO. The transplantation should be undertaken preferably before the creatinine clearance falls below 10-20 ml/min in order to avoid tissue deposits of calcium oxalate and excessive urinary excretion of oxalate during immediate post-transplantation period.

Adult

[Results and complications of balloon dilatation of renal artery stenosis in patients with renovascular hypertension].

During the years 1981 to 1987, 32 patients with renovascular hypertension due to renal artery stenosis were submitted to percutaneous transluminal renal angioplastic (PTRA) in four hospitals in Copenhagen. Nineteen of the interventions were technically successful and six of these patients (32%) no longer required medicine, eight (42%) were able to manage on reduced medication while the circumstances where five were concerned (26%) remained unchanged. Serious complications occurred in 16% and the mortality was 6%. The results of this treatment correspond to those reported elsewhere but the frequency of complications is high. It is concluded that the procedure should be centralized, possibly as a national function.

Adult

The effects of cimetidine on creatinine excretion, glomerular filtration rate and tubular function in renal transplant recipients.

The renal clearance of endogenous creatinine (CCr), sodium (CNa) and lithium (CLi) was determined before and after a single intravenous bolus of cimetidine in nine renal transplant recipients. The glomerular filtration rate (GFR) was measured with 125I-iothalamate clearance (CTh). The initial CCr of 65 ml/min (median) was reduced to a nadir of 46 ml/min (p less than 0.01) during the first 2 h after infusion of cimetidine. GFR remained unchanged, and thus the fractional clearance of creatinine (CCr/CTh) was reduced from 1.43 (median) to 1.03 (p less than 0.01). CNa and the fractional excretion of sodium decreased throughout the study (p less than 0.05); CLi was unchanged. In conclusion cimetidine, when measured during 1-h clearance periods, interferes with tubular creatinine secretion in the denervated kidney of transplant recipients without affecting the glomerular filtration rate or proximal tubular flow. This suggests that on-going cimetidine treatment must be taken into account when graft function is evaluated by the CCr alone.

Absorption