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Biomedical subjects

F W Albert

Publications and source records attributed to F W Albert.

At least 19 recordsLinked to original sources

Cyclosporine A sensitivity in vitro and P-glycoprotein expression in patients on dialysis and after kidney transplantation.

BACKGROUND: In allogeneic kidney transplantation the response to cyclosporine A (CsA) is important for graft outcome. Although CsA therapy is controlled by drug monitoring to ensure therapeutic CsA levels, the sensitivity to the effects of CsA varies among individuals. Since CsA is an antagonist of cytostatic drugs in P-glycoprotein (Pgp)-mediated transport, increased Pgp expression might contribute to an increased resistance to CsA. METHODS: The sensitivity of lymphocytes at three different concentrations of CsA was tested in a non-radioactive lymphocyte-transformation test and related to Pgp expression as determined by flow cytometry on mononuclear cells. Five groups, including healthy donors (CON; n = 25), patients on dialysis (DIAL; n = 25), patients before transplantation (PTX; n = 5) and after transplantation [short-term (ATX; n = 5) and long-term (LTX; n = 25)] were investigated. RESULTS: In LTX, the sensitivity to CsA at 400 and 1000 ng/ml was significantly different from CON and DIAL. Overall a higher sensitivity to CsA was seen in patients after transplantation. In ATX, sensitivity to CsA was significantly higher than in PTX at a concentration of 1000 ng/ml CsA. However, comparing all groups no significant changes in Pgp expression were noted. Analysing the relationship between CsA sensitivity and Pgp expression, no significant heterogeneity could be observed between the different groups. CONCLUSION: In conclusion, our data suggest that in vitro testing of CsA sensitivity prior transplantation and Pgp expression monitoring yield independent results and cannot substitute for each other as predictors of graft outcome. The differential role of each test for the evaluation of CsA sensitivity or resistance remains to be determined.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Antihypertensive drugs in renal failure.

As a risk factor, arterial hypertension favors the progression of renal failure and promotes cardiovascular complications, leading to early death. Progressive renal failure can be delayed or halted in glomerular diseases, and damage to other end organs can be avoided, by effective measures to lower blood pressure. Calcium antagonists and angiotensin-converting enzyme (ACE) inhibitors appear to be especially suitable as antihypertensive medications, because they may have specific renoprotective properties. Diuretics are required when a volume expansion caused by retention of salt and water occurs in more severe restriction of the glomerular filtrate. After ruling out contraindications and with cautious individualized dosages of antihypertensives (especially ACE inhibitors), deterioration of kidney function resulting from therapy is very rare.

Angiotensin-Converting Enzyme Inhibitors↗

Nilvadipine in hypertension with renal dysfunction.

The pharmacokinetics and pharmacodynamics of nilvadipine, a new dihydropyridine calcium antagonist, were examined in 16 patients divided into two different population groups. The first group of eight patients had arterial hypertension with limited renal function (creatinine clearance of 15-50 ml/min). The second group of eight patients had arterial hypertension with no concomitant renal dysfunction (creatinine clearance over 80 ml/min). Following a 1-week placebo washout period, all patients were given 8 mg of nilvadipine once daily for 10 days. The diastolic blood pressure (24-h postdose) fell in group I from a mean of 100.5 to 91.5 mm Hg and in group II from a mean of 106.7 to 88.2 mm Hg, which was significant in comparison to the placebo period. In neither group was there a significant change in heart rate, renin and aldosterone plasma levels, serum electrolytes, or sodium and potassium excretion. The pharmacokinetics of the unchanged nilvadipine were not significantly different between group I and group II. Neither group showed unchanged nilvadipine in urine. There was a slight increase in plasma levels of the inactive main metabolites M3 and M7; there was correspondingly less M3 found in the urine of group I patients. Nilvadipine appears to be an effective hypotensive agent at single daily doses of 8 mg. This dosage was well tolerated. The findings of this study did not suggest that lower doses need to be given to patients with limited renal function, at least not those with a creatinine clearance between 15 and 50 ml/min.

Adult↗

Studies on morphological outcome of cyclosporine-associated arteriolopathy after discontinuation of cyclosporine in renal allografts.

Cyclosporine (CSA)-associated arteriolopathy (CAA) is the second most frequent morphological diagnosis in renal allografts and its final outcome remains unclear. The present study was performed to clarify the morphological outcome of CAA by follow-up histological analysis after stopping CSA. Furthermore, the clinical management of patients showing CAA is discussed. Most of the patients came from our early experience with CSA between 1981-1983 when CSA doses and trough levels were high. Twenty recipients were divided into two groups according to the presence of CAA after stopping CSA: group A (n = 9) showed persistent CAA and group B (n = 11) showed no CAA. The majority of the patients, including five incomplete remission in group A, showed obvious improvement of CAA even if the arterioles were severely affected. Improvement of CAA was noted a few months after stopping CSA or after lower dose CSA therapy. There were no significant differences in CSA blood levels or duration of CSA therapy between the groups. The severity of preexistent CAA was significantly greater in group A. Only two patients who died from malignant tumor showed exacerbation of CAA. Eight patients died and eight grafts were lost, seven due to vascular rejection and one to hemolytic uremic syndrome-like CAA. Poor renal function was also noted in four cases with functioning graft owing to vascular rejection even though the improvement of CAA was evident. The complete regression of CAA and the remodelling of arterioles showing well preserved vascular patency were frequently found after stopping or reducing the dose of CSA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Contributions to biorheology during hemodialysis.

Thrombogenicity is the property of a foreign surface to induce clotting processes or formation of aggregates after contact with blood. Beside the sort of anticoagulation patient's prethrombotic state, rheological factors as well as physicochemical properties of foreign membranes decisively influence thrombogenicity. We examined the influence of chronic renal failure and different hemodialyzers and blood transfusion therapy during hemodialysis on hemorheological parameters. Different membranes cannot be discriminated by the used hemorheological parameters. We clearly could demonstrate the close relationship between the hemofiltration rate and an increase of viscosity. Blood transfusion therapy or elevated hematocrit in combination with increased hemofiltration rate have influence on the flow behaviour of blood, especially in disturbed microcirculation.

Biocompatible Materials↗

The development of a central register for side effects of biomaterials.

Examination of the interaction between biomaterials and tissues from a clinical realistic as well as scientific viewpoint to complement the highly advanced experimental and biochemical basis research is an undertaking that has suffered a considerable amount of neglect in the past. Attempts to realize internationally a Central Registry for documenting clinically relevant side effects will be reported in detail. Implementation of the registry involves the review of present literature (prospective clinical studies, retrospective studies and case reports). An "incompatibility incident report/questionnaire" has been developed according to the guidelines of the "Report on Pharmacological Side Effects" of the Pharmaceutical Commission of the German Medical Association. The aims of registering and evaluating these reports will be demonstrated and discussed in detail.

Biocompatible Materials↗

Platelet-tumor cell interaction.

Several reports have appeared with regard to the potential role of platelets in tumor cells metastasis. Our in vitro studies with colon tumor cells in normals and in patients give some evidence against platelet aggregation as the determinant factor in tumor cell invasion and metastasis. Dimethylhydrazine induced colon tumors in Wistar rats demonstrate characteristic features of tumor cell dissociation in the invasion line and changes in intercellular adhesion.

Actin Cytoskeleton↗

HLA-DR-MT matching improves graft survival rate in cadaver kidney transplantation. A prospective multicenter analysis of the South German Cooperative Study Group for Kidney Transplantation.

The influence of prospective HLA-DR matching on the graft survival rate was investigated in a multicenter analysis of 85 transplants. Simultaneously in a retrospective analysis of graft outcome the importance of matching for MT-antigens MT1, MT2 and MT3 as a newly defined B-cell alloantigen system was evaluated. HLA-DR antigens and MT-specificities were determined on B-cells enriched by nylon-wool filtration using locally well characterised HLA-DR antisera and the antiserum set of the 8th International Histocompatibility Workshop ("disease set") which allowed the definition of the HLA-DR specificities HLA-DR 1-9 and of the MT-antigens MT1-3. HLA-DR matching showed a significantly improved graft outcome only in HLA-DR identical donor-recipient combinations. In 11 of 60 patients with one HLA-DR compatibility additional matching for two MT-antigens, however, improved the two year graft survival rate from 60% to 91%. Altogether 17 patients were matched for two MT-specificities with their kidney donor and showed a superior prognosis of 94% at two years compared to 53% or 17% of recipients with one or zero MT compatibility. Graft outcome in this patient group was also superior to that of HLA-DR identical or HLA-AB identical grafts. These data suggested that the MT-system rather than the HLA-DR antigens may be of critical importance in cadaver kidney transplantation. In addition a favorable influence of pretransplant blood transfusions on less HLA-DR matched grafts was confirmed.

B-Lymphocytes↗

Influence of Lewis and other blood group systems in kidney transplantation.

In 167 first cadaver kidney recipients and their donors the blood groups ABO, Rhesus, Lewis, MN, Ss, P, Kell and Duffy were determined. The influence of incompatibility in each system as well as of simultaneous presence of several mismatches was analysed. Whereas one-year graft survival of Lewis-compatible grafts was 67 per cent (p = 0.02). The other blood groups showed no significant effect on graft outcome. Cumulative red cell incompatibilities, however, led to decreased survival rates. One-year graft survival in the group with greater than or equal to 4 incompatibilities was only 51 per cent versus 69 per cent in transplants with less than 4 incompatibilities (18% difference, p less than 0.01). When the Lewis system was excluded from analysis, the difference in survival rates was reduced to only six per cent. These data indicate that cumulative incompatibilities of red cell antigens have an unfavourable effect on graft survival. Of the different blood groups, the Lewis system is of major importance.

Blood Group Antigens↗