Biomedical subjects
Publications and source records attributed to D Scholz.
Application of OKT-3 as rescue therapy in steroid-resistant rejection was effective in 7 out of 9 patients early after cadaveric kidney transplantation. Under attention of instructions for use of OKT-3 the adverse first-dose reactions are rare. The problem of OKT-3 therapy is early use and its reuse.
This study reviews two newly developed battery-powered monitors for the accurate and invasive measurement of arterial blood pressure and body temperature. Their way of functioning is described in detail. Both devices allow a close monitoring of blood pressure, pulse rate and body temperature and a suitable intervention during the transport of critically ill patients and organ donors. Both monitors have high accuracy and stability, simplicity of operation and are robust. They are also relatively small and light. In addition, the devices are very suitable for measurement not only in humans but also in small animals like rats. The temperature monitor shows high accuracy in a range from -20 to 100 degrees C and is well suited for momentary and continuous temperature measurement in many other fields of application.
In 41 patients suffering from complications late after kidney transplantation the conventional immunosuppression was converted to Cyclosporin A. A complete normalization was obtained in the case of acquired immunoglobulin G deficiency and in persistent leukocytopenia. 6 patients suffering from life-threatening bacterial infections did survive after conversion with functioning allograft and 8 out of 9 late rejections were reversible. Conversion may be necessary in chronic hepatopathy and chronic rejection. A conversion to cyclosporin A is recommended because of control of complications in 78% (46/59) of the recipients.
The shortage of donor kidneys is the main cause of the even insufficient supply of patients suffering from end stage renal disease. In 1987 a transplant coordinator to the districts Berlin, Frankfurt and Potsdam with 3.1 Mio inhabitants was introduced. The functions of the coordinator and the approach to organ procurement are described in detail. In comparison with 1986 the number of explanted kidneys could doubled in 1988 (68 vs 143). The number of 46.3 explanted kidneys per million inhabitants is comparable with other areas or countries with excellent organ procurement system.
From a series of newly synthesized 3'-fluoro-modified nucleosides the C-5-chloro-substituted derivative of 2',3'-dideoxy-3'-fluorouridine (FddUrd) and the 4-thio analogue of 2',3'-dideoxy-3'-fluorothymidine (FddUrd) emerged as the most efficient and selective anti-HIV agents. Their antiviral doses (ED50) proved to be 700-and 480-fold below their toxic doses (CD50) in MT-4 cells. The 50% inhibitory dose of cell proliferation of the 5-chloro-substituted FddUrd and its parent agent FddUrd was found to be in the millimolar range for various other human cell-lines and for mouse CFU-GM. The 5'-triphosphate of FddUrd as well as of its 5-Chloro derivative are demonstrated to be two of the most active and selective inhibitors of the HIV-reverse transcriptase (IC50 = 0.07 +/- 0.01 and 0.04 +/- 0.006 microM).
The aim of our study was to establish the extent to which therapy of hypertrophic obstructive cardiomyopathy (HOCM) can influence the degree of hypertrophy. By means of two-dimensionally guided M-mode echocardiography, 120 patients with HOCM (age range 4-72 years, mean age 41 years) were observed over an average period of 49 +/- 41 months. Depending on the respective therapy, we formed four patient groups: group 1: 13 patients without any therapy (follow-up period 31 +/- 30 months); group 2: 27 patients receiving propranolol (follow-up period 47 +/- 34 months); group 3: 50 patients receiving verapamil (follow-up period 39 +/- 27 months), and group 4: 30 patients with myectomy (follow-up period 34 +/- 32 months). In group 4, as expected, the thickness of the interventricular septum (IVS) decreased postoperatively (from 24.2 +/- 4.5 to 19.8 +/- 6.7 mm, p less than 0.05), and the left ventricular posterior wall (LVPW) thickness also decreased later postoperatively (from 13.0 +/- 2.6 to 11.9 +/- 2.3 mm, p less than 0.05). The left ventricular diameters increased. In groups 2 and 3 treated with pharmacotherapy as in the untreated patients of group 1, on average there was no change in IVS and LVPW thickness nor in the left ventricular diameters (with the exception of increasing left ventricular end-diastolic diameter in the propranolol-treated group). In contrast to group 1, in occasional cases there were substantial decreases of IVS thickness (11% of the patients in group 2, 13% in group 3) or LVPW thickness (13% of the patients in group 2, 12% in group 3).(ABSTRACT TRUNCATED AT 250 WORDS)
We used purified bovine leukaemia virus (BLV) to test the inhibitory effects of suramin, HPA-23, and 3'-azidothymidine triphosphate (N3dTTP) on the reverse transcriptase activity. The 50% inhibitory concentrations (ID50) of the compounds were determined to be 2.8 mumol/l (suramin), 8.0 mumol/l (HPA-23), and 0.17 mumol/l (N3dTTP). Kinetic analyses of suramin and HPA-23 inhibition are discussed. The observed inhibitory effects emphasize the suitability of BLV as a model virus for investigations of retrovirus chemotherapy.
Report on 3 cases who had been non-diabetics at the time of cadaver kidney transplantation. After that within 1-5 years diabetes mellitus developed. The patients died 13-14 years after transplantation (9-12 years of diabetes duration). Autopsy revealed typical nodular glomerulosclerosis including diffuse mesangial widening, glomerular aneurysms, exudative lesions, capsular drops, arteriolosclerosis, and in 2 cases with hyalinosis of the vas efferens; moreover, chronic transplant glomerulopathy was found in all cases. Steroid therapy seemed to be responsible for the diabetic state, in 2 cases apparently in combination with disposition.
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In 56 kidney transplant recipients 93 specimens from transplant aspiration biopsy and peripheral blood were examined on the presence of cytomegalovirus (CMV) using the monoclonal antibody (mab) H 11. The used mab H 11 did react safe and exclusive in the acute infection period with the virus antigen. This antigen detection makes possible the laboratory diagnosis of a CMV infection 11 days (median value) prior to detection of specific IgM antibodies. In comparison with the cytological evaluation of fine needle aspiration biopsy the rejection process could be differentiated from infection.
Calves were immunised by means of a native Al(OH)3-absorbed gp51-preparation which had been obtained from a foetal lamb kidney cell line, following bovine leucosis virus (BLV) infection. 9 animals were immunised 3 times, using 300 micrograms gp51. 7 animals underwent test infection, using 2.5 x 10(3) or 2.5 x 10(4) BLV-infected lymphocytes. Serological and virological reactions of all animals, including 3 calves which had received only test infections, were followed up through 40 weeks by means of immunodiffusion test, enzyme-immuno-assay, gp51 antibody radio-immuno-assay, reverse transcriptase test, syncytial test, competitive p24 radio-immuno-assay, and by transmission of whole blood in animal experiments. The results obtained from virological testing showed that 1 animal had been protected by preceding immunisation. 4 in 7 immunised and test-infected animals exhibited transient BLV values, between the 7th and 16th weeks from infection. Typical leucosis infection had been induced to 2 animals. The above findings are discussed and are compared to similar results recorded by other working groups.
The aim of the present study was to evaluate the influence of a pretreatment of the heart and kidney donor with the photosensitizer 8-methoxypsoralen plus ex vivo longwave ultraviolet irradiation of the graft (PUVA) on survival time and immunogenicity of rat heart and kidney allografts. PUVA pretreatment significantly prolonged the survival of these transplants in allogenic recipients. Furthermore, a synergistic effect with conventional immunosuppression (azathioprine, cyclosporine) was demonstrated. Immunohistological studies using monoclonal antibodies showed a significant reduction of MHC class II antigen expression in heart cryostat sections after PUVA treatment. In clinical kidney transplantation the number of rejection episodes was significantly lower in the first 3 months in the PUVA-treated patient group.
Function and importance of biochemical research in kidney transplantation are presented. By selected examples of the own research work it is shown that fundamental and clinical-related research should be combined to a comprehensive scientific conception. A close cooperation with the clinician of the transplant center and other medical, scientific and technical disciplines are necessary to allow an effective biochemical research.
The envelope structure of human immunodeficiency virus type 1 (HIV-1) was examined using a computer image processor combined with an image rotation-averaging system. Our results indicate that the envelope of the HIV-1 particle is constructed of a T-7 laevo icosahedral surface net, and the knobs are distributed in the positions of pentamer-hexamer clustering, the total number being 72, which correspond to the results obtained by Gelderblom et al. and Ozel et al.
3'-fluorothymidine (FddThd) is well phosphorylated to the 5'-triphosphate in various relevant cell-lines. This results in fairly stable levels of this compound without accumulation of the 5'-monophosphate to the extent described for 3'-azidothymidine (AzT). The di- and triphosphate of FddThd seems unable to influence the ribonucleotide reductase in permeable cells. FddThd protects 50% of the MT-4 cells against the cytopathic effect of HIV at 3 nM, but reduces the number of uninfected viable cells to 50% at 1.1 microM. All other tested human cell-lines displayed a far less antiproliferative sensitivity to FddThd, comparable with that of AzT.
The pretreatment of both kidney and heart donor with the photosensitizer 8-methoxy-psoralen followed by in vitro longwave ultraviolet graft irradiation (PUVA therapy) significantly prolonged graft survival times in rats even across a strong major histocompatibility complex (MHC) barrier. Immunohistological studies using monoclonal antibodies (Mab) to rat MHC class I and II antigens showed a significant reduction of class II antigen expression after PUVA therapy in both Sprague-Dawley rat kidneys and hearts. Using MHC class I Mab there were no differences in distribution pattern in untreated as well as in PUVA treated organs. Thus, our results represent the first in vivo evidence that photochemotherapy-induced graft survival time prolongation is closely connected with its ability to reduce MHC class II antigen expression.
The concentrations of cholesterol in the high density lipoprotein (HDL) fraction and the HDL2 and HDL3 subclasses were compared in 333 male renal transplant recipients, 36 male patients on maintenance hemodialysis, and 43 healthy men. The subclasses were separated by a precipitation method using polyethylene glycol 6000 and dextran sulphate. In hemodialyzed patients, total HDL cholesterol and both subclasses were reduced. In renal transplant recipients, both total HDL cholesterol and HDL2 were normal, whereas HDL3 remained reduced, analogous to hemodialyzed patients. It can be concluded that a successful renal transplantation has a beneficial effect on HDL metabolism and thus on the development of atherosclerosis.
Twenty retransplant patients were serially screened for donor-reactive antibodies (DRA). DRA appeared exclusively in patients whose grafts permanently failed and these DRA shared some common features, namely early appearance (days 4-8 post-transplant), high titers (1:10 up to more than 1:400), and broad anti-HLA specificity. This preliminary data would suggest that regrafted patients with primary graft failure represent a distinct subgroup of particularly immune responsive individuals.