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Biomedical subjects

J Landmann

Publications and source records attributed to J Landmann.

At least 73 records · Page 4Linked to original sources

Cyclosporin A and osteonecrosis of the femoral head.

A vascular osteonecrosis has occurred in 5 to 40 per cent of patients who have undergone transplantation of a kidney and generally has been considered to be a complication of the use of corticosteroids. Currently cyclosporin A is in general use for its immunosuppressive property, so that a lower dose of corticosteroids is needed. We analyzed the cases of a series of our patients who underwent transplantation of a kidney in order to find out if our present regimen, using cyclosporin A, influenced the prevalence of osteonecrosis of the femoral head. Of a total of 270 patients, osteonecrosis of the femoral head developed in fifteen of 174 who received conventional immunosuppressive therapy and in only one of ninety-six who received cyclosporin A (p less than 0.05). During the first two months after transplantation, the mean dose of prednisone was approximately 2.5 milligrams per kilogram of body weight per day in the group that received conventional immunosuppressive therapy and approximately 1.1 milligrams per kilogram of body weight per day in the group that received cyclosporin A (p less than 0.001). We concluded that the pathogenesis of the osteonecrosis in patients who underwent transplantation of a kidney was probably related to the higher doses of corticosteroids that were administered.

Azathioprine↗

Cotton-wool exudates not observed in recipients of renal transplants treated with cyclosporine.

Retinal cotton-wool patches, not previously observed in bone marrow recipients, have been reported in three patients who received Sandimmun (cyclosporine) as prophylaxis for graft-versus-host-disease after bone marrow transplantation. These patients all had acute lymphoblastic leukemia and had received, in addition to the standard conditioning regimen, central nervous system irradiation before transplantation. We were thus prompted to examine 55 renal transplant recipients (15 of them prospectively) who were receiving cyclosporine for evidence of similar fundal changes. No cotton-wool patches were found in any of the renal transplant recipients.

Adolescent↗

Development of a chronic canine model for measurement of absorption by substrate appearance in portal venous blood.

Research in absorption physiology requires animal models which closely resemble the in vivo situation. The description of a new canine model satisfying these requirements is the objective of this report. Dogs were instrumented with indwelling portal vein and carotid artery catheters, a catheter jejunostomy and an electromagnetic flow measuring probe around the portal vein enabling continuous flow recordings. Following intrajejunal infusion of nutritive substrates in the conscious animal, absorption was measured as the product of porto-arterial substrate difference and portal venous flow. The model was validated in five mongrel dogs: (1) Catheters and flow measuring device function over several months. (2) The sensitivity of the method was evaluated following intrajejunal infusion of l-glycine-l-tyrosine and its constituent amino acids. A significant portoarterial concentration difference of both amino acids enabling quantitative measurement of absorption resulted when the peptide was infused at 4 mmoles/hour (20 mM solution, 200 ml/h). (3) Infusion of complete nutritive formulas caused a significant increase in portal venous flow whereas neither saline nor the amino acids or the peptides investigated had a comparable effect. (4) A validation experiment by implantation of a second flow probe distal to the chronically implanted device provided evidence that granulomatous tissue forming around the probe does not alter the accuracy of the flow recording. In summary, this method permits for the first time quantitative measurement of absorption by appearance rates in portal venous blood instead of by disappearance from the intestinal lumen.

Amino Acids↗

Sialic acid in newborn and maternal lymphocytes: preterm deliveries.

Sialic acid was determined in newborn and maternal lymphocytes immediately after preterm deliveries of 34 and 35 weeks of gestation. The results were compared with those found in full-term deliveries. In contrast with full-term deliveries, in preterm deliveries a significant increase in sialic acid in maternal as compared to newborn lymphocytes was found. However, the mean cumulative value of sialic acid for maternal and newborn lymphocytes was similar in both groups. In addition to this, sialic acid concentrations seem to be sex-dependent and higher mean cumulative values for maternal and newborn lymphocytes could be found for male as compared to female newborns after full- as well as after preterm deliveries.

Female↗

Cyclosporine alone or in combination with prednisone in cadaveric renal transplantation.

One hundred recipients of first cadaveric kidney transplants were treated with three different immunosuppressive regimens: (1) conventional immunosuppression, (2) CsA alone, and (3) low-dose CsA in combination with low-dose prednisone, with rapid adjustment to give CsA whole blood trough levels of 300 to 800 ng/mL. One-year graft survival in the aza + pred group was 76%, and in the CsA alone group 75%. Graft survival at two and six months in the CsA-pred group was 94%. The dose of CsA in the CsA-pred group in the first two months posttransplant was only about half that given to the CsA-alone group. Surprisingly, the reduction in the CsA dose also reduced the number of methylprednisolone pulses given for treating rejection by greater than 50%. The incidence of nephrotoxicity and extrarenal side effects also fell considerably. Withdrawal of prednisone in the CsA-pred group after five months led to reversible rejection in two cases. In conclusion, (1) the rapid reduction in the CsA dosage is beneficial and has no drawbacks, and (2) our guidelines for withdrawing prednisone (timing of withdrawal, rate of reduction in dosage) still need further refinement.

Adult↗

Trends in access surgery for hemodialysis.

Vascular access for chronic hemodialysis is for both doctors and nurses on one side and patients on the other a permanent, challenging problem. In respect to patency and complication rate, the direct AV fistula represents the most satisfactory solution and therefore should be achieved whenever feasible. In addition to the classic Brescia-Cimino and the brachiocephalic fistula, the most distal location in the snuff-box on one end and a transposed basilic vein at the upper arm on the other offer most satisfactory angioaccess alternatives that must be used stepwise from the periphery to more proximal sites. Graft fistulas should clearly be reserved for the patient for whom all autologous possibilities (with the exclusion of the autologous saphenous vein graft) have been used. Only ePTFE grafts have a patency rate comparable with direct autologous fistulas at a much higher cost.

Adult↗

Cyclosporin A used alone or in combination with low-dose steroids in cadaveric renal transplantation.

The actual survival rate of 25 primary cadaveric kidney grafts in recipients treated initially with cyclosporin A (CyA) alone was 84%. The survival rate in 37 patients under conventional immunosuppression was 76%. The mean number of dialyses required in the first 4 weeks after transplantation was 1.2 per patient in both groups. At 15-28 months posttransplant, mean serum creatinine levels have remained stable at 175 mumol/l in the CyA group. The mean daily dose of steroids (including methylprednisolone i.v.) in the first two months was 2.07 mg/kg/d in patients under conventional immunosuppression and 0.76 mg/kg/d in the patients receiving CyA (p less than 0.001). The combination of CyA with low-dose steroids enabled the dose of CyA to be rapidly tapered off in once-weekly steps. CyA levels were monitored by determination of whole blood trough concentrations (target level: 300-800 ng/ml). At 60 days posttransplant the average dose of CyA was 6.0 +/- 0.5 mg/kg/d compared with an average daily dose of 11.4 +/- 0.9 as recommended for CyA alone in the protocol for the European multicentre study. This more rapid reduction in the CyA dose reduced nephrotoxicity (serum creatinine levels 174 +/- 14 as compared with 289 +/- 31 mumol/l) (p less than 0.05) and almost halved the number of methylprednisolone pulses given up to the end of the second month. We conclude from these results (1) that previously the dosage of CyA administered at this centre was probably too high, and (2) early adjustment of dose levels on the basis of blood concentrations and with low-dose prednisone cover appears to be safe and effective, but requires further verification.

Azathioprine↗