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Biomedical subjects

K Wonigeit

Publications and source records attributed to K Wonigeit.

At least 145 records · Page 8Linked to original sources
PubMed1988

Cyclosporin A treatment in children with minimal change nephrotic syndrome and focal segmental glomerulosclerosis.

In a pilot study 23 children with nephrotic syndrome were treated with cyclosporin A (Cs) for 6-45 months. 8 children suffered from steroid dependent minimal change nephrotic syndrome (MCNS) and had experienced at least one course with cytotoxic drugs, but had relapsed thereafter. 2 children had diabetes mellitus type I with nephrotic syndrome and 13 children had steroid resistant focal segmental glomerulosclerosis (FSGS). Cs was started with 100 mg/m2/day in two doses and increased stepwise to obtain a Cs whole blood trough level of 200-400 ng/ml. In steroid dependent MCNS treatment with Cs reduced relapse rate significantly, and prednisone therapy could be stopped completely. After discontinuation of Cs, relapses reoccurred as frequently as before. Renal function remained unimpaired despite repeated Cs treatment courses up to 38 months. In cases of nephrotic syndrome with diabetes type I Cs treatment led to complete remission without changing the insulin requirement. However, after discontinuation of Cs relapses reoccurred. In steroid resistant FSGS 6 children benefited from Cs treatment: 4 went into complete remission, 2 into partial remission. The 2 children with complete remission relapsed but remained Cs responsive. The remaining 7 children with FSGS did not respond to Cs but continued the course of their disease, with two patients rapidly progressing to terminal renal failure. Side-effects of Cs treatment were mild. It is concluded that Cs is an effective agent in steroid dependent MCNS and can be used as an alternative drug in specific cases like steroid toxicity or diabetes mellitus. In steroid resistant FSGS a trial with Cs seems to be warranted since some cases do respond favorably. To avoid nephrotoxicity treatment with Cs should always be monitored closely by determination of blood levels and renal function.

Biopsy↗
PubMed1988

The engymetric determination of acute functional impairment in kidney graft function caused by cyclosporine A.

Engymetry offers a new means of continuously measuring nuclear radiation fields without any need of restricting the patient's mobility. In this study, kidney function was measured simultaneously and continuously for 6.6 h with engymetry, after application of a 12 h therapy dose of Cyclosporine A (CsA) of 4.0 +/- 1.8 mg per kg bodyweight (bw). 15 kidney transplanted patients participated in this study. 370 MBq 99Tcm-DTPA and 10 MBq 131I-OIH were injected during routine transplant scintigraphy. Renal function was monitored from the external disappearance curves of the tracers recorded by portable double radionuclide detectors. Renal impairment could be seen in the rising phase of CsA or coincided with the CsA maximum in 13 of the 15 patients. Under the impairment the half-life of 99Tcm-DTPA increased from 4.1 +/- 1.2 to 15.9 +/- 12.3 h (p less than 0.005) for 61 +/- 45 min and the half-life of 131I-OIH increased from 3.2 +/- 0.7 to 12.7 +/- 8.4 h (p less than 0.001) for 71 +/- 37 min. With noninvasive engymetry it is possible to detect renal functional impairment during long observation periods. Acute restriction in glomerular filtration and renal blood flow was discovered in human kidney graft recipients after the application of a low therapeutic CsA dose.

Acute Kidney Injury↗
PubMed1988

Analysis of sequential changes in major histocompatibility complex expression in human liver grafts after transplantation.

The expression of class I and class II major histocompatibility complex (MHC) antigens in human liver grafts was analyzed in 88 liver biopsies from 22 patients. For the staining of MHC antigens, a panel of monoclonal antibodies directed against monomorphic determinants of class I and class II molecules and an indirect immunoperoxidase method were used. In the reference biopsies, class I antigens were expressed on all cell types but only weakly on hepatocytes; class II was only expressed on Kupffer cells, interstitial cells, and endothelia. After transplantation, this pattern of MHC expression was markedly modified. Increased class I expression on hepatocytes and HLA-DR expression on bile ducts occurred in the absence of clinical rejection. During acute rejection, class I was strongly expressed and HLA-DR weakly expressed on hepatocytes; on bile ducts, HLA-DR expression was further increased. Cytomegalovirus hepatitis caused class I and HLA-DR induction on hepatocytes; strong induction of HLA-DR on bile ducts was also found in cholangitis. These findings have a number of implications for the pathophysiology of rejection of the transplanted liver.

Acute Disease↗
PubMed1988

High incidence of monoclonal immunoglobulins in patients after liver or heart transplantation.

Sera from 56 recipients of liver or heart transplants were investigated for monoclonal immunoglobulins (mIg) by immunofixation electrophoresis (IFE) at different times during 4 years after transplantation. Transient, changing, or stable mIgs were found in 18 patients. A significantly increased mIg incidence was observed in heart Tx patients, patients over 40 years of age, and those receiving azathioprine or antithymocyte globulin in addition to prednisolone and cyclosporine as immunosuppressive treatment. No correlations could be found between the presence of mIg and the number of rejection episodes or intercurrent infections. Such serum mIg represent monoclones of at least 1 x 10(9) cells of B lymphocyte lineage that apparently proliferate without adequate suppressive control. Since immunosuppressed allograft recipients are at risk of developing B cell lymphomas, such monoclones may be regarded as prelymphomas necessitating a careful follow-up in these patients.

Antibodies, Monoclonal↗
PubMed1988

Liquid-chromatographic measurement of cyclosporin A and its metabolites in blood, bile, and urine.

Using solid-phase extraction columns and "high-performance" liquid-chromatographic (HPLC) analysis, we could determine cyclosporin A and nine of its metabolites in blood, bile, and urine. To facilitate calculations of concentrations of cyclosporin A and its metabolites from the chromatograms, we used cyclosporin D as internal standard. For the HPLC analysis we used two sequential 250-mm analytical columns filled with reversed-phase octyl (C8) sorbent, eluting with a concave gradient of water, adjusted to pH 3.0 with phosphoric acid, and acetonitrile. Peaks were detected at 205 nm. For characterization of the chromatographic peaks, we isolated, by semi-preparative HPLC, 32 fractions representing peaks potentially related to cyclosporin A metabolites and re-injected them into the HPLC system under the same conditions as authentic cyclosporin A metabolites. Analytical recovery was 70-80%. The inter-assay CV for bile was 7.2%, for urine 12.3%. The method was used for routine monitoring of cyclosporin A and its metabolites.

Bile↗