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Biomedical subjects

K Wagner

Publications and source records attributed to K Wagner.

At least 271 records · Page 15Linked to original sources
PubMed1987

Prevention of posttransplant acute tubular necrosis by the calcium antagonist diltiazem: a prospective randomized study.

In a prospective randomized trial we evaluated the influence of the calcium antagonist diltiazem (Dil) on the development of acute tubular necrosis (ATN) in cadaveric kidney transplantation. Dil was added to Eurocollin's solution (20 mg/l) at donor nephrectomy. The graft recipient received a preoperative bolus injection of Dil (0.28 mg/kg) which was followed by an infusion of Dil (0.0022 mg/min/kg) for 2 days. Thereafter, Dil was applied orally. Immunosuppressive therapy consisted of ciclosporin (CS) and low-dose steroids. There were no significant differences between the groups with respect to donor characteristics, HLA matching and ischemic periods. In the control group (n = 22), 9 patients (41%) developed ATN compared to 2 patients (10%) in the Dil group (p less than 0.05). In the control group, 3.5 +/- 0.4 HD per patient were necessary compared to 0.6 +/- 0.2 in the Dil group (p less than 0.05). Although CS blood levels were significantly higher in the Dil group (1st week 1,150 vs. 728 ng/ml; p less than 0.01), the GFR of grafts with primary function was significantly higher in the Dil group (day 7:39 vs. 24 ml/min; p less than 0.05). A significant reduction of the CS dose by 30% (p less than 0.01) led to comparable CS levels. In the Dil group, significantly fewer rejection episodes occurred during the first month. Our data indicate that the application of the calcium antagonist Dil lowered the incidence of posttransplant ATN. In addition, there is a possibility that Dil not only ameliorates ischemic damage in the kidney, but also reduces CS nephrotoxicity.

Acute Kidney Injury↗
PubMed1987

Hematopoietic effects of continuous intravenous infusion of mice with growth factors produced by the WEHI-3 cell line.

A method for continuous intravenous infusion of unanesthetized adult C3H/HeJ or Wx/Wv anemic mice was designed using cage immobilization and a tail vein catheter connected to a model 940 Harvard infusion pump. Infusates included: WEHI-3 cell line dialyzed, 5 times concentrated conditioned medium containing multi-colony-stimulating factor (C-SF) interleukin 3 (IL-3); purified murine IL-3; bacterial endotoxin; serum-free medium, or normal saline. Mice were monitored at days 5-7 after infusion for complete peripheral blood counts and production of granulocytes in vitro by explanted marrow in long-term bone marrow cultures. We observed a stimulatory effect of WEHI-3 conditioned medium infusion that was not attributable to endotoxin and produced significant increases in peripheral blood WBC count and neutrophils, colony-forming units in spleen and numbers of granulocyte/macrophage colony-forming unit culture responsive to both C-SF-1 (L cell C-SF) and multi-C-SF in vitro. This infusion method should prove valuable for test of the in vivo effects of purified growth factors and molecularly cloned hematopoietins.

Animals↗
PubMed1987

Constitutive expression of the granulocyte-macrophage colony-stimulating factor gene in acute myeloblastic leukemia.

Expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene was studied by Northern blot analysis in normal human hematopoietic cells and a series of leukemias. GM-CSF messenger (m)RNA was detected in activated T cells, but not in normal bone marrow cells, monocytes, or nonactivated T cells. In contrast, leukemic cells from 11 of 22 cases of acute myeloblastic leukemia expressed GM-CSF transcripts. Biologically active CSF was detected in supernatant conditioned by 6 of these 11 leukemias. Expression of the GM-CSF gene was not detected in "common" (pre-B cell) acute lymphoblastic leukemia (11 cases tested) or chronic myeloid leukemia (4 cases tested). These results show that the GM-CSF gene is constitutively expressed in a subset of patients with AML, and further suggest that expression of this gene could contribute to the abnormal growth properties characteristic of AML.

Antigen-Antibody Reactions↗
PubMed1987

The role of subtalar motion and ankle contact pressure changes from angular deformities of the tibia.

It is a well known entity that fractures of the tibia heal with some component of angular deformity. Ankle and subtalar joints may compensate for small degrees of angular deformities, but the exact amount of malunion that can be accepted without development of late sequalae has yet to be determined. Two recent studies from this institution have concluded that contact changes at the tibiotalar joint tend to be greater with distal third tibial fracture deformities compared to proximal and middle with the ankle in neutral, 5 degrees dorsiflexion, and 20 degrees of plantar flexion. Anterior and posterior bow deformities produced a greater change in contact area of the tibiotalar joint than with valgus or varus deformities. This phenomena may be possibly explained by the subtalar motion in the horizontal plane which averages 23 degrees. Thus, it was the primary purpose of this paper to determine the exact role, if any, in subtalar motion on tibiotalar contact in angular deformities of the tibia. To achieve this objective the subtalar joint was transfixed thereby eliminating its perceived compensatory movement. Six cadaveric lower extremities were disarticulated at the knee joint and stripped of soft tissue preserving capsular and ligamentous structures. A custom universal joint was used to create various angulatory deformities at proximal, middle, and distal third levels of the tibia.(ABSTRACT TRUNCATED AT 250 WORDS)

Ankle Joint↗
PubMed1987

Prevention of delayed graft function in cadaver kidney transplants by diltiazem: outcome of two prospective, randomized clinical trials.

Calcium entry blockers have a protective effect on experimental postischemic acute renal failure (ARF). Since delayed graft function (DGF) in cadaver kidney transplants is in part due to an ischemic damage to the kidney, we initiated two prospective, randomized clinical trials of human kidney transplants. Study I (control: n = 22; diltiazem: n = 20): Diltiazem (D) was added to Eurocollin's solution at a dose of 20 mg/l. If the donor had been treated with D, the graft recipient got a bolus injection of 0.28 mg/kg D and a continuous infusion of 0.002 mg/min/kg D for the first two days. A dose of 60 mg D was then given orally twice daily. Study II (control: n = 11; diltiazem: n = 10): We used the same regimen without donor pretreatment. All patients had immunosuppression with cyclosporine A (CsA) and low-dose steroids. Primary graft function (PGF) was defined as vital kidney function without hemodialysis (HD) during the first week. In both studies the incidence of PGF was higher in the D groups (I: 90% vs. 59%, p less than 0.05; II: 70% vs. 55%). In the control groups, 3.6 +/- 0.4 (I) and 4.9 +/- 0.7 (II) HD per patient was necessary, compared to 0.6 +/- 0.2 (I), p less than 0.05) and 1.9 +/- 0.4 (II) HD in the treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1987

Screening for monoclonal antibodies with covalently linked antigen.

Microtitre plates prepared for ELISA are treated for the maximum adsorption of gamma-globulins (at pH 9). The adsorption of other soluble proteins (e.g. antigens) is sometimes less effective and therefore requires a higher amount of protein for the primary coat of wells. In order to reduce the amount of pure antigen required for the screening of mAb-producing hybridomas, we improved the sensitivity of our screening ELISA technique by coupling the antigen covalently to the surface of the microtiter wells. The antigen (urokinase) was coupled by the glutaraldehyde or carbodiimide procedures respectively using "aminoplates" (Nissho Iwai, Japan). The glutaraldehyde method led to at least a five fold increase of the sensitivity compared to coventional adsorption. Reduced requirement of antigen for the assay is thus achieved by a simple procedure.

Animals↗
PubMed1987

Effect of dialyzer membranes on in vitro generation of eicosanoids.

Eicosanoids are potent substances released from blood cells after contact with foreign materials. Eicosanoid generation, in addition to complement fragment formation, may be a valuable indicator of the biocompatibility of dialyzer membranes. In the present in vitro study, eicosanoid generation induced by several different flat dialyzer membranes [polyacrylonitrile (PAN), cuprammonium cellulose (CC), and polycarbonate (PC)] was evaluated and compared using blood from non-uremic healthy volunteers. Generation of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) was greatest with PC followed by PAN and CC. The formation of C3a des arg with PAN was less than with either CC or PC. Our results suggest that dialyzer membranes affect complement activation and eicosanoid generation differently; biocompatibility as expressed by a low level of complement fragment formation does not necessarily translate into biocompatibility when considering eicosanoid generation.

Acrylic Resins↗
PubMed1987

The effects of GM-CSF and G-CSF in promoting growth of clonogenic cells in acute myeloblastic leukemia.

A small subset of leukemic cells from most patients with acute myeloblastic leukemia (AML) have properties of stem cells and can be assayed by colony formation in agar or methylcellulose. Colony formation generally requires the addition of exogenous growth factors, but the exact factors required are incompletely defined. The AML colony-promoting activities of two recombinant human colony-stimulating factors (GM-CSF and G-CSF) were investigated by using blasts from 48 patients with AML. In nine cases, no colonies formed with either CSF. In seven cases colonies formed only in response to G-CSF and in 11 cases only in response to GM-CSF. In 21 cases colonies formed in response to either GM-CSF or G-CSF, and in 12 of these cases there was an additive effect between the two CSFs in determining maximum colony size. For cases responding to both GM- and G-CSF, the total number of colonies formed in response to the combination of both CSFs was almost always less than additive compared with the number of colonies formed in response to the individual CSFs. Further, the AML-CFU responding to either GM-CSF or G-CSF could not be distinguished by surface markers or by the cytochemical staining pattern of the colonies. These results suggest that there is considerable overlap between the GM-CSF- and G-CSF-responsive AML-CFU subpopulations in most cases. For five of seven cases, the combination of GM-CSF and G-CSF could replace a leukocyte feeder layer in providing maximum growth stimulation. These results indicate that GM-CSF and G-CSF are active growth factors for AML cells and are frequently additive in promoting maximum colony size.

Adult↗
PubMed1987

Cross flow diafiltration of serum with basal medium suitable for growth of hybridomas, sterilization and protein reduction.

Fetal Calf Serum (FCS) was extensively extracted by cross flow diafiltration (Pellicon, Millipore) and sterilized using the basal growth medium (DMEM) for the extraction. Ultrafiltration membranes of 10(5) and 3 X 10(5) Dalton cut off were used respectively. The diafiltrates were used for hybridoma cultivation and the results of growth and mAb-production were compared with standard medium (DMEM + 5% FCS). Slightly reduced mAb-titers were achieved. These were, however, compensated by decreased concentration of contaminating protein and higher specific mAb/protein ratio as examined by SDS-PAGE and enzyme linked immuno electro transfer blot (EITB).

Animals↗
PubMed1986

[Protective effect of the calcium antagonist diltiazem on acute kidney failure following kidney transplantation. The results of a prospective randomized study].

UNLABELLED: In a prospective randomised study the effect of the calcium antagonist diltiazem on primary transplant failure following cadaver kidney transplantation was studied. The transplants were perfused with a solution containing 20 mg/l diltiazem, the graft recipient received diltiazem as a bolus injection of 0.28 mg/kg pre-operatively, followed by a continuous infusion of 0.0022 mg/kg X min for 48 hours. Thereafter diltiazem was applied orally (twice 60 mg/d). Glomerular filtration rate and renal blood flow were measured by single-shot techniques (inulin, PAH). For immunosuppression ciclosporin A and low-dose methylprednisolone were given. Nine patients (41%) in the control group (n = 22) but only two (10%) in the diltiazem group (n = 20) developed primary transplant failure (P less than 0.05). Glomerular filtration rate in transplants with primary function was significantly higher in the diltiazem group (day 4: 29 +/- 0.8 vs. 20 +/- 0.8; day 7: 39 +/- 1.4 vs. 24.9 +/- 0.7 ml/min, P less than 0.05) although ciclosporin blood levels were significantly higher in this group (week 1: 1150 vs. 728 ng/ml, P less than 0.01). The rate of rejection episodes was significantly higher in controls than in patients on diltiazem (0.5 +/- 0.05 vs. 0.1 +/- 0.02 rejection episodes per patient in the first postoperative month, P less than 0.05). CONCLUSION: Diltiazem has a protective effect against primary transplant failure following cadaver kidney transplantation. Furthermore, it might reduce the nephrotoxicity of ciclosporin A.

Acute Kidney Injury↗
PubMed1986

The influence of long-term infusion of the calcium antagonist diltiazem on postischemic acute renal failure in conscious dogs.

The influence of long-term infusion of the calcium-entry blocker diltiazem on postischemic acute renal failure was investigated in conscious dogs monitored by implanted instruments. In 18 uninephrectomized beagle dogs on a salt-rich diet, an electromagnetic flow probe and an inflatable plastic cuff were placed around the renal artery. Acute renal failure was induced by inflating the cuff for 180 min in the conscious animal. Group A (n = 5, control) received an intraaortic injection of 0.9% NaCl (5 ml/day) from the 3rd day before until the 7th day after ischemia and group B (n = 6, posttreatment) an intra-aortic injection of diltiazem (5 micrograms X min-1 X kg-1) beginning at the end of ischemia until the 7th day. Group C (n = 7, pre- and posttreatment) received diltiazem from the 3rd day before until the 7th day after ischemia. In group A, renal blood flow dropped from 149 +/- 16 (preischemic) to 129 +/- 29 ml X min-1 on the 1st day after ischemia. In contrast, renal blood flow increased on the 1st postischemic day in both treatment groups by 29 +/- 15% (group B, P 0.05) and 14 +/- 13% (group C). In the following days, there was no significant difference in renal blood flow between groups A, B and C. In group B, the reduction of the glomerular filtration rate was similar to that in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗