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Biomedical subjects

R Wiesner

Publications and source records attributed to R Wiesner.

At least 37 records · Page 2Linked to original sources
PubMed1996

[Between family-oriented help and child protection--interventions within the scope of the child and youth aid law: an unsolvable dilemma?].

The new child care and protection legislation (German Social Aid) emphasises the support of the parents' responsibility for education. In addition, it includes separate provisions and opportunities for counseling and supporting young children and adolescents in crisis situations. Finally, it requires the Youth Welfare Office to inform the Guardianship Court if a legal decision is required to avert a threat of the child's welfare. In the process of making the complex precise and responsible decision on the prognosis for the child, the experts from the Youth Welfare Office mus decide weather to respond to a threat to the child with family-oriented support, of with intervention concerning parental care that will usually lead to the separation of the child from its social setting.

Adolescent↗
PubMed1995

Urinary endothelin and renal vasoconstriction with cyclosporine or FK506 after liver transplantation.

Transplant immunosuppression using either cyclosporine (CsA) or FK506 leads to renal vasoconstriction. To examine the role of endothelin (ET) in this process, we measured plasma and urinary ET before and at intervals for two years after liver transplantation. Urinary prostacyclin (as 6-keto-PG-F1 alpha), thromboxane, glomerular filtration rate and renal plasma flow were also measured. Forty-four patients were treated with CsA-based regimens and 31 patients with FK506-based regimens. Prednisone doses after one year were lower with FK506 (5.5 +/- 0.5 vs. 10.5 +/- 0.5 mg/day) by study design. Circulating plasma ET remained above normal, but not different from pre-transplant levels. Urinary ET was elevated before transplant (24.6 +/- 3.4 ng/day vs. normal 16 +/- 1.5 ng/day, P < 0.05) and rose further after transplantation (48.5 +/- 13 ng/day, P < 0.05), remaining elevated for two years. 6-keto-PG-F1 alpha fell from 2567 +/- 338 ng/day to subnormal levels and remained suppressed (1158 +/- 128 ng/day, P < 0.01). Over the same period GFR fell (84 +/- 3 ml/min to 60 +/- 3 ml/min, P < 0.01) and renal vascular resistance index rose (11,119 +/- 561 to 23,279 +/- 1692 d.s.cm-5.m-2, P < 0.01). Similar changes were observed both with CsA and FK506-based immunosuppression. No changes in ET were attributable to dihydropyridine calcium channel blockers. These results demonstrate that urinary ET changes independently from plasma ET after transplantation. Elevated ET and suppression of endothelium-derived prostacyclin persist with intense renal vasoconstriction for at least two years after transplant.

Cyclosporine↗
PubMed1995

[Responsibility of youth assistance teams for rehabilitation of mentally handicapped young adults].

The change of responsibilities for the integration assistance of mentally handicapped young people from social welfare to youth care confronts the socio-pedagogical view with the child and youth psychiatric view. The advantages of the new order of responsibility, which is only a first step regarding the assignment of all handicapped young people to youth care, will only become visible if representatives of both disciplines are open for diverse procedures and work with children, youths, and parents as equals and as partners. The eighth, volume of the Social Welfare Law Book (Achtes Buch Sozialgesetzbuch, SGB VIII) supplies the necessary framework.

Adolescent↗
PubMed1994

Systemic and renal effects of nifedipine in cyclosporine-associated hypertension.

Cyclosporine induces hypertension and wide-spread vasoconstriction after transplantation in addition to reducing kidney function. We studied hemodynamic, renal, and hormonal effects of monotherapy with nifedipine XL (n = 37) in liver transplant recipients within a year after transplant (median, 4.4 months). Systemic hemodynamics were determined with thoracic electrical bioimpedance. Blood pressure before therapy was 172 +/- 4/108 +/- 2 mm Hg. Sixty-four percent of recipients achieved blood pressures less than 140/90 mm Hg mediated by a fall in systemic vascular resistance index (2427 +/- 245 dyne.s.cm-5.m-2 in responders versus 2905 +/- 281 in nonresponders, P < .01). Despite the fall in systemic vascular resistance, glomerular filtration rates were not changed during nifedipine therapy, as measured by both creatinine and iothalamate clearances. Urinary prostacyclin (6-ketoprostaglandin F1 alpha) was suppressed below normal from 2468 +/- 323 ng/d before transplant to 1103 +/- 99 ng/d (P < .01) after transplant and did not change during nifedipine therapy. Urinary thromboxane B2 and plasma renin activity also fell after transplant and remained low during nifedipine. These data demonstrate that nifedipine can reverse systemic vasoconstriction associated with hypertension after transplantation. Systemic effects were not transmitted to the kidney sufficiently to improve glomerular filtration rate or reverse hormonal changes within the kidney. Hence, vascular and functional regulation of the kidney was dissociated from the systemic circulation during nifedipine administration after transplantation.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Resolution of posttransplant hypertension after liver transplantation despite impaired glomerular filtration.

Hypertension developing after transplantation is characterized by widespread vasoconstriction including the kidney. Late resolution (mean, 29 +/- 4 months) of posttransplant hypertension has been observed in 15 (Group I) of 278 subjects monitored after liver transplantation. These studies were undertaken to define the systemic and renal changes associated with resolution, as compared with a group matched for age, sex, and time after transplant who remained hypertensive (Group II; N = 15) or a group who never developed hypertension (Group III; N = 23). Blood pressure during resolution paralleled changes in the systemic resistance index, which fell from 3,052 +/- 548 to 1,872 +/- 205 dyne/s.cm5/m2 (P < 0.01). GFR and RBF remained low, despite the resolution of hypertension, and renal vascular resistance did not change. Circulating endothelin levels remained above normal in all transplant recipients (Group I, 11.9 +/- 3.0 versus normal subjects, 7.0 +/- 1.1 pg/mL; P < 0.05), and urinary prostacyclin excretion was suppressed (880 +/- 120 versus 2,247 +/- 187 ng/day; P < 0.01). No hormonal differences were apparent between transplant groups. These results demonstrate the capacity for systemic vasodilation to occur after transplantation, independent of vascular tone in the kidney. They further suggest that renal vasoconstriction and impaired GFR alone are not sufficient to explain de novo hypertension after transplantation.

Adult↗
PubMed1993

Oxygenation of lipoproteins by mammalian lipoxygenases.

Oxidative modification converts low-density lipoprotein (LDL) into its atherogenic form and appears to be a necessary precondition for LDL uptake by macrophages during foam cell formation. Cellular lipoxygenases have been implicated in this process. We studied the interaction of purified mammalian lipoxygenases with human LDL in vitro and found that the arachidonate 15-lipoxygenases of rabbit and man are capable of oxygenating lipoproteins as indicated by oxygen uptake and by the formation of thiobarbituric-acid-reactive substances. Furthermore, oxygenated polyenoic fatty acids, such as 13-hydro(pero)xy-9Z,11E-octadecadienoic acid and 15-hydro(pero)xy-5,8,11,13(Z,Z,Z,E)-eicosatetraenoic acid were detected in the lipid compartment of various lipoproteins classes after lipoxygenase treatment. More than 90% of the oxygenated polyenoic fatty acids were found in the ester-lipid fraction, particularly in the cholesterol esters, whereas only small amounts of free hydro(pero)xy polyenoic fatty acids were detected. Lipoxygenase-catalyzed oxygenation of LDL is not restricted to the lipid compartment but also leads to a cooxidative modification of the apoproteins as indicated by changes in the electrophoretic mobility and by the formation of carbonyl derivatives of amino acid side chains. The possible biological significance of lipoxygenase-induced oxidative modification of lipoproteins in the pathogenesis of atherosclerosis is discussed.

Amino Acid Sequence↗
PubMed1993

Solid organ transplantation: results and implications of acyclovir use in liver transplants.

CMV infection is a major cause of morbidity and mortality following liver transplantation (LT). A prospective study of 218 LT recipients showed that 55% of patients developed CMV infection during the 1st year post-transplantation. Symptomatic CMV infection developed in 25% of all patients, being a major cause of death (21% of all deaths). Of 62 episodes of documented organ invasion, liver was the major site (38 episodes), followed by lung (20), gastrointestinal (4), and retina (4). The main patient group at risk (according to CMV serology of the recipient [(R)/donor(D)]) was the R-/D+: 77% of patients developed CMV infection, all of them with symptoms. The lowest group at risk was the R-/D-: 13% of patients developed CMV infection, half of whom developed symptoms. Time-dependent multivariate statistical analysis of risk factors indicated that the R-/D+ group was the main risk factor for CMV infection (P < .02) and symptomatic infection (P < .0001). To decrease the incidence and severity of CMV infection following LT, a randomized study is ongoing to evaluate the efficacy of ganciclovir (5 mg/kg/IV/q 12 hours for the first 14 days post-LT) followed by acyclovir (800 mg/po/qid for 14 weeks) GCV + ACV (group I), versus acyclovir (same dose for 16 weeks, starting immediately post-LT) ACV (group II). These treatment groups are compared to matched historical controls (C). Preliminary analysis of 83 LT recipients indicates that in group I the median date for the first evidence of CMV infection is delayed (82 days) as compared to group II and C (41 and 33 days, respectively) (P = .004).(ABSTRACT TRUNCATED AT 250 WORDS)

Acyclovir↗
PubMed1993

Systemic and renal hemodynamic differences between FK506 and cyclosporine in liver transplant recipients.

Immunosuppression after transplantation is complicated by hypertension and nephrotoxicity, reflecting widespread vasoconstriction associated with CsA. FK506 is a novel alternative immunosuppressive agent, structurally unrelated to CsA. These studies compared systemic and renal vascular changes developing in the initial 4 weeks after liver transplantation in patients treated with FK506 (plus PRED) and CsA (plus PRED and AZA). We studied arterial pressure, cardiac index (pulsed doppler ultrasound), and systemic resistance index (SVRI) before and weekly after liver transplant in 32 patients treated with CsA (2 mg/kg initial dose plus PRED; median dose at week 4, 30 mg/day) and 14 patients treated with FK506 (0.15 mg/kg/day initial dose and PRED; mean week 4 dose, 12.5). Renal plasma flow and glomerular filtration rate (GFR) were measured by clearance of para-amino hippurate and 125-iothalamate. Renin activity, aldosterone, and urinary prostanoids were measured by RIA. Pretransplant pressures and hemodynamics reflected low SVRI and increased cardiac index typical of end-stage liver disease. After transplantation, SVRI and pressures rose in both groups, but after week 2, SVRI was lower in patients treated with FK506. This was associated with less prevalent clinical hypertension during the subsequent 4 months (4/14 FK506 (28%) vs. 25/32 (78%) CsA, P < 0.01). By contrast, renal blood flow and GFR fell in both treatment groups similarly, whereas renal vascular resistance rose. Urinary 6-keto-PG-F1-alpha was suppressed in all transplant recipients, but to a greater degree in FK506-treated patients. This value correlated directly to post-transplant GFR (r = 0.48, P < 0.001). These data indicate that FK506-based immunosuppression differs from CsA by inducing less systemic vasoconstriction and hypertension. Renal vasoconstrictive effects were at least as great as those seen with CsA, however, and indicate that nephrotoxicity will remain a common feature to both regimens.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Changes in levels of mRNA encoding myosin heavy chain in porcine trachealis during ontogenesis.

We determined the steady-state level of mRNA for myosin heavy chain (MHC) from airway smooth muscle during maturation in domestic swine. Tissues were excised, and airway smooth muscle was dissected from three neonatal (NEO), three 2-wk-old swine (2ws), three 10-wk-old swine (10ws), and three adult swine. Total RNA was isolated, fractionated, and transferred to a nitrocellulose membrane (Northern blot). A single-stranded oligonucleotide of 63-nt was synthesized corresponding to the 3' coding region of the chicken gizzard MHC cDNA. This region appeared to be highly conserved (92% nucleotide sequence homology with the corresponding portion of rabbit uterine smooth muscle MHC cDNA). Northern blots, which were loaded with equivalent quantities of total RNA, were probed with gamma 32P-labeled synthetic oligonucleotide, and, under stringent washing conditions, the 5' end-labeled DNA was hybridized to a single band of the expected molecular weight. The mRNA for total myosin was quantified using autoradiograms of blots, and signal intensity was measured as integrated areas expressed as arbitrary densitometric units x mm (AU). The content of mRNA for MHC was substantially greater in NEO than in more mature animals; maximal area was 1.33 +/- 0.15 AU for NEO, 0.33 +/- 0.05 AU for 2ws, 0.30 +/- 0.04 AU for 10ws, and 0.34 +/- 0.08 AU for adult swine (P < 0.05, NEO versus 2ws, 10ws, and adult). Rehybridization of each blot with a 28S ribosomal RNA probe confirmed comparable total RNA loadings for all tissue samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1992

Renal hemodynamics, urinary eicosanoids, and endothelin after liver transplantation.

Patients with hepatic cirrhosis develop widespread abnormalities in kidney function and vasoactive hormones. These change rapidly after liver transplantation during immunosuppression with cyclosporine. The role of changing eicosanoid excretion and endothelin levels in regulating renal function after transplantation in humans remains uncertain. We studied 32 patients with regard to renal hemodynamics, glomerular filtration, urinary prostacyclin (6-keto-PG-F1-alpha), thromboxane (TBX2), and endothelin before and during the first four weeks after orthotopic liver transplantation. Arterial pressure rose from 106 +/- 2/61 +/- 2 to 146 +/- 4/81 +/- 2 mmHg, (P less than .001), while renal blood flow fell (686 +/- 38 to 453 +/- 24 ml/min/1.73 m2, P less than .05), as did GFR. Pretransplant excretion of 6-keto and TBX2 was above that of normal subjects and fell progressively after transplant, as did plasma renin activity and aldosterone. The 6-keto levels fell below normal after two weeks. The ratio of TBX2/6-keto remained elevated compared with normal subjects throughout the month after transplant (1.54 +/- 0.38 vs. 0.54 +/- 0.07, P less than .01). Endothelin levels rose during the first week (7.4 +/- 1.4 vs. 12.4 +/- 2.7 pg/ml, P less than .05), but fell back to baseline thereafter. These results indicate that high levels of urinary eicosanoids in patients with liver disease fall rapidly after liver transplantation during CsA immunosuppression. Unlike results in many experimental models, these data suggest that renal vasoconstriction in humans may be associated primarily with suppression in renal prostacyclin excretion rather than stimulation of thromboxane.

Adult↗
PubMed1992

Structure elucidation of oxygenated lipids in human atherosclerotic lesions.

Oxidative modification of low density lipoproteins and tissue lipids has been proposed to be involved in the pathogenesis of atherosclerosis. We examined human atherosclerotic lesions of various stages from fifteen victims of acute heart failure and detected substantial amounts of oxygenated fatty acids in the tissue ester lipids. The degree of lipid oxygenation correlated with the stage of advancement of the lesion. More than 85% of the oxygenated fatty acids were localized in the cholesterol esters, whereas phospholipids contained only small amounts. Structure elucidation of the oxygenation products indicated a nonspecific product pattern of various isomers of keto- and hydroxy-octadecadienoic acid. The data presented suggest an involvement of lipid peroxidation in the pathogenesis of atherosclerosis and indicate that the majority of the oxygenation products are formed via nonspecific, non-enzymatic reactions possibly initiated by the action of a 15-lipoxygenase.

Adult↗
PubMed1991

The oxygenation of cholesterol esters by the reticulocyte lipoxygenase.

The arachidonate 15-lipoxygenase from rabbit reticulocytes oxygenates cholesterol esters containing polyenoic fatty acids. Cholesterol esterified with saturated fatty acids is not oxygenated. The structures of the oxygenation products formed from various cholesterol esters have been identified by high pressure liquid chromatography, UV-spectroscopy and gas chromatography/mass spectroscopy. Oxygenated cholesterol esters have been detected in atherosclerotic plaques of human aortas.

Arteriosclerosis↗
PubMed1991

Azathioprine hepatotoxicity after liver transplantation.

We report the first two cases of apparent azathioprine hepatotoxicity occurring after liver transplantation. The two patients exhibited jaundice, elevated serum transaminase activities and histopathological features of sinusoidal congestion and centrilobular hepatocellular degeneration 17 and 61 days after transplantation. After withdrawal of azathioprine, liver test results improved immediately in both patients. Recurrence of liver injury after another challenge with azathioprine was seen in the first case. Previously, fatal venoocclusive disease occurring after kidney transplantation had been attributed to azathioprine. Irreversible venoocclusive disease and the reversible hepatotoxicity described in this report (i.e., sinusoidal congestion with centrizonal necrosis) most likely represent different stages of hepatic endotheliitis caused by azathioprine. Thus early diagnosis of azathioprine hepatotoxicity is of great importance.

Adult↗