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D Steinhilber

Publications and source records attributed to D Steinhilber.

49 records · Page 3Linked to original sources
PubMed1989

5-Lipoxygenase inhibition by antifungal azole derivatives: new tools for immunosuppression?

The effect of novel azole derivatives (itraconazole and fluconazole) on 5-lipoxygenase activity was examined using human polymorphonuclear leukocytes (PMNL) as the enzyme source. The novel imidazole derivative itraconazole proved to be a potent inhibitor (IC50 2 X 10(-6) M) of 5-lipoxygenase activity. In contrast, fluconazole, an antifungal agent with bistriazole structure, had no effect on the Ca2+ ionophore A 23187-induced formation of 5-lipoxygenase metabolites in PMNL.

Antifungal Agents↗
PubMed1988

Determination of picogram amounts of lipoxin A4 and lipoxin B4 by high-performance liquid chromatography with electrochemical detection.

A new method for the determination of lipoxins with electrochemical detection after high-performance liquid chromatography is described. The half-wave potentials of lipoxin A4 and lipoxin B4 at a glassy carbon electrode and a mobile phase of methanol-water (65:35 v/v) and 1 mM trifluoroacetic acid was found to be +1.14 V versus an Ag/AgCl reference electrode. The use of trifluoroacetic acid instead of sulphuric acid and lithium perchlorate led to a background current of 6-8 nA at +1.20 V. The detection limits for both lipoxins, based on a signal-to-noise ratio of 3:1 were found to be 5-10 pg (15-30 fmol). The new method was applied to an extract of human polymorphonuclear granulocytes, preincubated with 15-hydroxyeicosatetraenoic acid and stimulated with Ca2+ ionophore A23187.

Chemical Phenomena↗
PubMed1988

L-ascorbic acid modulates 5-lipoxygenase activity in human polymorphonuclear leukocytes.

Leukotriene B4 (LTB4), a metabolite of the arachidonic acid pathway mediated by 5-lipoxygenase, is released by stimulated polymorphonuclear neutrophils (PMNL) and has been postulated to be an important mediator of the inflammatory response. Extracellular L-ascorbate at concentrations in the range of 0.5-5.0 mM effectively inhibits the biosynthesis of LTB4 and 5-hydroxyeicosatetraenoic acid (5-HETE) stimulated by the calcium ionophore A 23187. The ionophore-activated LTB4 production is reduced after incubation of PMNL with opsonized zymosan as a phagocytic stimulus. Extracellular L-ascorbate at concentrations above 0.1 mM reverses the zymosan-induced deactivation of 5-lipoxygenase, resulting in significantly higher LTB4 and 5-HETE yields. The inhibitory effect of zymosan preincubation on LTB4 production is independent of calcium or free arachidonic acid in the incubation medium. Interaction of L-ascorbate with the catabolism of LTB4 was excluded by measuring the trihydroxy metabolites which were unchanged. Furthermore, the formation of glutathione derivatives of leukotriene A4 can be excluded due to the lack of glutathione transferase activity in PMNL. In order to link the intracellular function of L-ascorbate with the serum level, the ascorbate uptake has been studied in more detail. The L-ascorbate transport into PMNL is stereospecific and can best be described by kinetics consisting of a saturation part, Km and Vmax being 39 microM and 0.28 nmol/10(8) cells.min, respectively, plus passive diffusion, the diffusion coefficient P being 1.75 microliter/10(8) cells.min. Furthermore, the uptake is inhibited by the isomers D-ascorbic acid and D-erythorbic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Arachidonate 5-Lipoxygenase↗
PubMed1986

Renal transplantation in end stage renal disease patients with existing urinary diversion.

From 1971 to 1984 renal transplantation was performed in 20 patients with end stage renal disease who presented with an existing form of urinary diversion. These patients were evaluated with a cystometrogram, voiding cystourethrogram and cystoscopy. In some cases bladder function was studied further by cycling through a suprapubically placed catheter. The bladder was considered unstable in 13 patients and undiversion was done at transplantation. The period of prior diversion ranged from 3 to 20 years (mean 12.7 years). There were no surgical complications postoperatively and normal bladder function returned in all patients. Currently, 8 patients have a functioning renal allograft 16 months to 9 years after transplantation (mean 4.2 years). Seven patients were considered to have a nonusable bladder owing to severe neurogenic disease or refractory contracture. In these patients transplantation was done into a pre-fashioned intestinal conduit (5) or cutaneous ureterostomy (2). Currently, 4 patients have a functioning renal allograft 16 months to 6.2 years after transplantation (mean 3.8 years). Transplantation candidates who present with an existing form of urinary diversion should be evaluated carefully, since many will have a usable bladder. Regardless of whether the bladder is usable, transplantation can be performed safely with no increased surgical or immunological risk.

Adult↗
PubMed1986

A prospective analysis of the accuracy and cost-effectiveness of digital subtraction angiography for living-related renal donor evaluation.

From 1982 to 1984, we conducted a prospective study to evaluate the usefulness of i.v. renal digital subtraction angiography (DSA) for living-related donor (LRD) evaluation. Twenty-eight LRDs were evaluated with the traditional approach of intravenous pyelography (IVP) and standard catheter arteriography (SCA) (group 1). During the same period, 33 LRDs underwent renal DSA and IVP from a single i.v. contrast injection (group 2). If renal arterial imaging with DSA was considered satisfactory, no further radiographic studies were done (group 2-A, n = 23). If renal arterial imaging with DSA was not satisfactory, SCA was then obtained (group 2-B, n = 10). DSA alone accurately defined the number and location of renal arteries in 21 of 23 patients from group 2-A, and in 5 of 10 patients from group 2-B. The major limitation of DSA was in patients with multiple renal arteries; accurate imaging was obtained in only 7 of these 13 patients (54%). In group 2 overall, preoperative renal imaging was not accurate in 2 of 33 patients (6%); in both cases, an unsuspected polar artery was found at nephrectomy. The mean cost per patient of all radiographic renal imaging studies was $953.00 for group 2 and $1721.00 for group 1. These data suggest that the approach of preferentially evaluating LRDs with DSA-IVP, and obtaining SCA only if DSA yields poor visualization, is more cost-effective but not as accurate as the traditional policy of obtaining SCA and IVP in all cases.

Angiography↗
PubMed1986

Detrimental effect of cyclosporine on initial function of cadaver renal allografts following extended preservation. Results of a randomized prospective study.

We report herein the results of a randomized prospective trial comparing maintenance cyclosporine (CsA)-prednisone immunosuppression to a regimen of azathioprine-prednisone-antilymphocyte globulin (ALG) in cadaver renal transplant recipients. Fifty-six patients were entered into this study with 31 assigned to the ALG group and 25 to the CsA group. These two groups were well matched for most major determinants of graft outcome and the mean renal preservation time was 37 hr in each group. The incidence of acute tubular necrosis (ATN) was high in both groups (58% ALG, 72% CsA, NS). There were five cases of primary nonfunction in the CsA group and only one in the ALG group (P = .05). Of the kidneys that functioned, the mean serum creatinine nadir (1.5 vs. 2.2 mg/dl, P = .06) and the mean number of days to reach the serum creatinine nadir (24.2 vs. 43.3 days, P = .03) were both less in the ALG group. The actuarial one-year graft survival rate in the ALG and CsA groups is 78% and 48%, respectively (P less than .05). This difference is mainly due to the large number of primary nonfunctioning grafts in the latter group, which we attribute to the effect of CsA's nephrotoxicity superimposed on renal ischemia incurred prior to transplantation. These data emphasize that, in order to realize the full benefit of CsA in cadaver transplantation, renewed emphasis must be placed on minimizing ischemic renal damage.

Adolescent↗
PubMed1985

Pregnancy after donor nephrectomy.

The use of living-related kidney donors has been a routine practice in most major transplant centers in the United States for more than 20 years. Concern has arisen regarding the potential for developing hypertension and progressive renal dysfunction after renal donation. Pregnancy results in hyperfiltration and might be an added risk for the development of hypertension, proteinuria, or renal insufficiency in donors. From 1963 until 1984, the Cleveland Clinic Foundation performed 1031 renal transplants, 355 from living donors. Of these 355 living donors, 191 were female, and of these, 23 successfully conceived after kidney donation. Prenatal and delivery records of all 23 were reviewed. There were 39 pregnancies in 23 women with 32 viable births. Conception ranged from 2 weeks to more than 9 years postnephrectomy. Mean blood pressure at the time of donor evaluation was 120/75 mm Hg (SD: +/- 11/8 mm Hg). Mean blood pressure during pregnancy was 114/68 mm Hg (SD: +/- 7/6 mm Hg). One plus proteinuria was detected in 2 women during the third trimester and trace proteinuria was seen in 7 pregnancies; this proteinuria disappeared after delivery. Thirteen of twenty women who carried to term were reevaluated 2-14 years after donor nephrectomy. All parameters studied were normal. Mean length of follow-up after donor nephrectomy was 7.9 years. These data suggest that, after donor nephrectomy, women can have a normal pregnancy without significant problems related to the kidney donation. Also, hyperfiltration associated with the combination of unilateral nephrectomy and pregnancy does not lead to significant hypertension, proteinuria, change in glomerular filtration rate, or abnormalities of the urinary sediment.

Adult↗