Incidence and risk factors of prolonged mechanical ventilation and causes of reintubation after liver transplantation.
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Adolescent↗
Biomedical subjects
A R Müller
Publications and source records attributed to A R Müller.
Five-year follow-up of tacrolimus as primary immunosuppressant after liver transplantation.
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Adolescent↗
Angiotensin II-induced calcium signalling in neurons and astrocytes of rat circumventricular organs.
The subfornical organ and organum vasculosum laminae terminalis represent neuroglial circumventricular organ structures bordering the anterior third cerebral ventricle. Owing to the absence of the blood-brain barrier, the cellular elements of the subfornical organ and the organum vasculosum laminae terminalis can be reached by circulating messenger molecules transferring afferent information. As demonstrated for the control of extracellular fluid composition, the circulating hormone angiotensin II acts on these sensory circumventricular organs to induce drinking, elevated peripheral resistance and neurohypophyseal hormone release via interaction with membrane-spanning receptor proteins. To characterize the cell-specific distribution of angiotensin II receptors within the circumventricular organs, primary cell cultures derived from the subfornical organ or organum vasculosum laminae terminalis of five- to six-day-old rat pups were used to measure alterations in intracellular calcium at the single cell level. Neurons and astrocytes were identified by immunocytochemical staining for specific marker proteins. Bath application of angiotensin II (10(-10)-10(-6) M) dose-dependently induced calcium transients in neurons (19.6%) and astrocytes (15.7%), and angiotensin II threshold concentrations to elicit intracellular calcium signalling proved to be one order of magnitude higher in astrocytes as compared to neurons (10(-9) M). At angiotensin II concentrations higher than 10(-7) M, pronounced desensitization of the angiotensin II receptor occurred. Employing the angiotensin II receptor antagonists losartan (DUP-753; AT1-receptor) and PD-123319 (AT2-receptor), exclusive expression of the AT1 receptor subtype coupled to intracellular calcium concentration signalling could be demonstrated for neurons and astrocytes. In all cells examined, the angiotensin II-evoked increase in intracellular calcium concentrations could be fully suppressed in the absence of extracellular calcium. Co-activation by angiotensin II and other agents (vasopressin, its fragment 8-arginine-vasopressin(4-9), oxytocin, endothelin) was indicated for subfornical organ neurons and organum vasculosum laminae terminalis astrocytes.
Angiotensin II↗
Detection of sequences of TT virus, a novel DNA virus, in German patients.
Recently a novel DNA virus, designated TT virus (TTV), that possibly accounts for some of the cases of liver disease of unknown aetiology, was identified in Japanese patients. Using specific primer pairs for conserved regions, we detected TTV DNA by PCR in 16/84 (19%) German patients awaiting orthotopic liver transplantation because of decompensated liver cirrhosis (of diverse causes); in 4/25 (16%) patients with non-A-G hepatitis; in 1/7 patients with autoimmune hepatitis; and in one intravenous drug user. Sequence analysis showed that in contrast to the findings in Japanese patients only about 37% of our TTV sequences belonged to genomic group 1 but about 58% belonged to group 2, including several sequences belonging to a further subgroup tentatively designated group 2c. Further studies to clarify whether the novel virus has hepatitis-inducing capacity or other clinical significance are needed.
Amino Acid Sequence↗
[L-arginine administration improves mucosal structure in the early phase of reperfusion of small intestine transplants].
L-arginine and molsidomine application prior to reperfusion significantly reduced the preservation and reperfusion-related injury after small bowel transplantation. The architecture of the mucosa was best preserved after treatment with L-arginine and methylprednisolone. The macroscopic appearance of the mucosa was improved (less watery and less thin than after reperfusion of non-treated recipients). The histological appearance was improved. But the most prominent changes were observed by antilaminin staining showing an almost normal architecture of the basement membrane compared with compressed and thickened basement membrane structures in non-treated recipients. This was accompanied by a decrease in CD44-expression within the villi cores and crypts 20 minutes and 24 hours after reperfusion. The release of hyaluronic acid into the plasma was also lower after treatment with L-arginine and molsidomine in combination with methylprednisolone than in non-treated recipients. These improvements may result from increased NO-production by L-arginine which may scavenge superoxid anions. The latter are known intermediates that cause significant injury at the endothelial level and at the extracellular matrix including the basement membrane.
Animals↗
A liver with polycystic liver disease as graft for orthotopic liver transplantation.
Donor organ shortage calls for widening of criteria for organ transplantation. In exceptional cases, even livers with macroscopic alterations may be accepted for transplantation. The case of a patient who received a liver graft from a donor with previously unknown adult polycystic degeneration is reported. The liver showed only small bilobar cysts with less than 10% of hepatic replacement and was successfully used for orthotopic liver transplantation. Two years after transplantation the patient is in good clinical condition and has returned to work.
Cysts↗
Ontogenesis of the alpha2-adrenergic receptor system in the hypothalamo-limbic system of the Pekin duck.
The development of the central nervous alpha2-adrenergic system in the duck was studied by semiquantitative autoradiography at the ontogenetic stages embryonic days 20 (E20) and 27 (E27) and postnatal days 3 (P3) and 14 (P14) by using the monoradioiodinated alpha2-agonist clonidine ([125I]CLO) as radioligand. All structures endowed with alpha2-adrenoceptors in the adult animal were specifically labeled with [125I]CLO by E20. A detailed analysis of the binding capacity for [125I]CLO was performed for parts of several functional systems: hypothalamic structures (nucleus inferior hypothalami, nucleus magnocellularis preopticus, nucleus paraventricularis), limbic system (habenula, nucleus septalis lateralis, nucleus striae terminalis), circumventricular organs (organum pineale, organum subfornicale, plexus choroidei ventriculi tertii and ventriculi lateralis), visual system (hyperstriatum accessorium, nucleus reticularis superior, tectum opticum), and associative cortex (hyperstriatum ventrale). Except for the nucleus inferior hypothalami and the plexus choroideus ventriculi lateralis, all structures showed a perinatal (E27-P3) maximum of alpha2-adrenoceptor-binding capacity with a subsequent decline to values of prehatching stages. This uniform expression pattern of alpha2-adrenoceptors indicates that the days around hatching are a critical period for the development of the adrenergic system in the brain of the duck.
Animals↗
Angiotensin II receptor subtypes in the duck subfornical organ: an electrophysiological and receptor autoradiographic investigation.
The pharmacology of angiotensin II (AngII) receptors was investigated in the brain of ducks using receptor autoradiographic and electrophysiological methods. Using 125I[Val5]AngII as a ligand, specific binding was observed in sections of the duck adrenal gland and in several brain areas involved in body fluid homeostasis. Displacement studies using the same antagonists as used for classifying mammalian AngII receptor subtypes revealed that the rank order of potencies in competition with AngII receptors in the adrenal gland and in the subfornical organ was: AngII > CGP-42112A > losartan > PD-123319. Electrophysiological recordings from spontaneously active neurons of duck SFO slices revealed that the majority of neurons could be excited by AngII (10(-7) M). The excitatory effect of AngII could be partially inhibited by CGP-42112A (10(-5) M), which proved to be more effective than equimolar losartan and far more effective than PD-123319. These data suggest that the neuronal AngII receptors in the SFO are pharmacologically distinct from the mammalian AT1- and AT2-receptors. Further, central AngII receptors of ducks share common pharmacological characteristics with AngII receptors in the duck adrenal gland and peripheral organs of other bird species.
Angiotensin II↗
[Liver transplantation as school for visceral surgery--experiences for perioperative management].
Liver transplantation is one of the most extensive operations in visceral surgery. Preexisting cardiopulmonary abnormalities, disturbances of glucose, hormone, and electrolyte metabolism and cirrhosis-associated diseases, including hypersplenism with thrombopenia and severe coagulopathy, require advanced surgical skills. Optimal perioperative intensive care management is necessary because of the patient's immunosuppressed condition. In principle, patient management after liver transplantation is similar to that performed after major visceral surgery. However, special attention should be paid to initial liver perfusion and function. Like for sepsis in visceral surgery, in liver transplantation monitoring of cytokines and other mediators is important. New approaches for bioartificial liver support in patients with acute liver failure have primarily been developed as a bridging system to liver transplantation, but they may also be of value for patients with septic liver failure or liver failure after major liver resections.
Artificial Organs↗
AVP-fragment peptides induce Ca2+ transients in cells cultured from rat circumventricular organs.
To investigate receptors for the naturally occurring fragments of [Arg8]vasopressin (AVP), Ca2+ measurements were performed in cells cultured from the subfornical organ (SFO) and the organum vasculosum of the lamina terminalis (OVLT). AVP(4-9) and AVP(4-8) applied in nanomolar concentrations triggered rises in the intracellular Ca2+ concentration in neurons and astrocytes cultured from both circumventricular organs (CVOs) which are located in the lamina terminalis of the rat brain. The determination of the investigated cell type was confirmed by immunocytochemistry with cell type-specific antibodies. The functional data from single cultured cells and receptor autoradiographic studies on tissue slices favour the existence of specific receptors for AVP fragments which are different from those for the parental AVP.
Animals↗
Characterization of vasopressin receptors in cultured cells derived from the region of rat brain circumventricular organs.
The aim of the present study was to characterize vasopressin receptors within the two circumventricular organs located in the lamina terminalis of the rat brain, namely the organum vasculosum of the lamina terminalis and the subfornical organ. Cells derived from both structures were isolated, cultured and intracellular Ca2+ concentrations were measured in single fura-2 loaded neurons and astrocytes after application of vasopressin and various vasopressin analogues. Subsequent to Ca2+ measurements, the identification of neurons and astrocytes was verified using immunocytochemistry with cell type-specific antibodies. High proportions of subfornical organ (34%) and organum vasculosum laminae terminalis (28%) neurons exhibited increased intracellular Ca2+ concentration after exposure to 1-1000 nM vasopressin. Within single cells, the response was dose-dependent. Similar results were obtained in subfornical organ (62%) and organum vasculosum laminae terminalis (38%) astrocytes with minor differences in the transient amplitude and pattern distribution when compared with neurons. Since omission of extracellular Ca2+ preserved vasopressin responsiveness, it is likely that intracellular stores were the main source of mobilized Ca2+. The preincubation of neurons and astrocytes with the V1 receptor-specific antagonist d(CH2)5[Tyr(Me)2]8-arginine vasopressin (10-100 nM) selectively and reversibly blocked the vasopressin-mediated response. Oxytocin-induced Ca2+ transients (0.32-1000 nM), which were observed in 32% (63%) or organum vasculosum laminae terminalis and in 54% (42%) of subfornical organ neurons (astrocytes), were not affected by the V1-specific antagonist. These data indicate the presence of a V1-like vasopressin receptor and an oxytocin receptor in cultured neurons and astrocytes from both circumventricular organ structures. In addition, the exposure to the highly selective V2 receptor agonist, 1-desamino,8-D-arginine vasopressin, evoked Ca2+ transients almost exclusively in organum vasculosum laminae terminalis neurons (eight of 18 tested). Only 1 (n = 14) subfornical organ neuron and none of the astrocytes tested (n = 26) responded to 1-desamino,8-D-arginine vasopressin. Since 1-desamino,8-D-arginine vasopressin acting via "classical" V2 receptors is not expected to affect the intracellular Ca2+ concentration, these data indicate the tissue and cell type-specific expression of a 1-desamino,8-D-arginine vasopressin-sensitive vasopressin receptor in neurons of the organum vasculosum laminae terminalis. In summary, the results indicate a heterogeneity of neurohypophyseal peptide receptor subtypes in the primary cell culture of both circumventricular structures.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Liver transplantation in hepatitis B surface antigen positive patients with postoperative long-term immunoprophylaxis.
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Adult↗
Primary culture of circumventricular organs from the rat brain lamina terminalis.
A primary culture system of cells derived from two circumventricular organs (CVO) of the rat brain was established. The subfornical organ (SFO) and the organum vasculosum of the lamina terminalis (OVLT) were dissected from the rostral wall of the third ventricle and its cells taken into culture after mechanical dissociation. The cells were cultured in a modified microculture chamber system ensuring relatively high cell density despite their low absolute number. When animals were injected with Evans blue prior to cell preparation, the macroscopically visible penetration of the dye into the parenchyma of the CVOs could be used as guidance during tissue isolation and labelled cells could be identified in culture. Cultured CVO neurones and astrocytes were identified using antibodies against cell type specific marker proteins. The histochemical NADPH-diaphorase staining was used for the detection of nitric oxide synthase in tissue sections of both CVOs and in their cultured neurones. In addition, angiotensin II (ANG II)-evoked elevations of the intracellular Ca2+ concentration ([Ca2+]i) in single cultured OVLT neurones were measured. The described methods will be useful for further characterization of CVO neurones and astrocytes.
Amino Acid Oxidoreductases↗
Progressive multifocal leukoencephalopathy after orthotopic liver transplantation.
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Female↗
Ontogenesis of the angiotensin II (ANGII) receptor system in the duck brain.
The ontogenetic development of the central nervous angiotensin II (ANGII) receptor system in the duck was studied at embryonic days E20 and E27 and at postnatal days P3 and P14 by computerized semiquantitative autoradiography employing the receptor antagonist 125I[1Sar,8Ile]ANGII as radioligand. For circumventricular structures involved in the sensing of brain-intrinsic (AV3V region) or blood-borne (subfornical organ, SFO) ANGII, binding sites for 125I[1Sar,8Ile]ANGII were first detectable at E27, with a steady rise in binding density up to P14. The choroid plexus of the lateral (PCVL) and third (PCVIII) cerebral ventricles responsible for cerebrospinal fluid (CSF) production were endowed with maximal ANGII receptor densities at E20 with subsequent reduction to constant medium (PCVIII) or low (PCVL) values. Besides the choroid plexus, the magnocellular paraventricular nucleus (PVN) was the only structure presenting ANGII specific binding sites at E20, although at low density. As for the SFO and AV3V region, labelling of ANGII binding sites in the PVN increased continuously during development to high values at P14. Nuclear components of the limbic system (archistriatum, amygdala and habenular complex) did not reveal specific labelling by the radioligand at E20 with constant, moderate binding densities evaluated for E27, P3 and P14. In the duck brain, functionally related structures exhibited a homogeneous ontogenetic development of their ANGII receptor system.
Angiotensin II↗
Evaluation of preservation conditions and various solutions for small bowel preservation.
The aim of the study was to delineate the most optimal preservation conditions for small bowel grafts. Established preservation solutions such as EuroCollins, University of Wisconsin, histidine-tryptophane-ketoglutarate-Brettschneider, phosphate-buffered sucrose (PBS 140), and 3 new solutions--extracellular fluid (ECF), lactobionate fructose, and a modified lactobionate fructose solution--were compared with saline to determine the most optimal solution for the intestine. Recipient survival, standard histology, and glutaminase activity were used to assess the degree of injury encountered after 12 hr of preservation followed by transplantation. To evaluate the various preservation conditions, ECF was used at pH 6.8 (original ECF). Grafts were preserved most optimally when a vascular washout after the cold storage period was omitted and when topical rewarming of the graft with 37 degrees C saline before reperfusion was performed. Graft survival was not significantly different after preservation with any solution tested (50-83%). Highest graft survival (83%) was achieved with lactobionate fructose and PBS140. Histologic evaluation 20 min after reperfusion revealed minor differences between most groups; a slight advantage was observed for PBS140-preserved grafts. Mucosal glutaminase activity of PBS140-preserved grafts was significantly higher 20 min after reperfusion compared with any other solution evaluated, indicating a superior graft function. These data indicate that different preservation conditions have a great impact on postoperative graft survival and that PBS140 might be preferable to any of the other preservation solutions tested.
Adenosine↗
Mucosal glutaminase activity and histology as parameters of small bowel preservation injury.
The present study in Lewis rats was designed to assess the predictive value of the mucosal enzyme activities of glutaminase, maltase, and xanthine oxidase and of histology as parameters to delineate the degree of small bowel preservation injury. Small bowel grafts were flushed with saline or a modified phosphate-buffered sucrose (PBS) solution, stored at 8 degrees C for 1, 6, or 12 hr, and transplanted heterotopically. Tissue samples for determination of mucosal enzyme activities were taken after the cold storage period, 20 min after reperfusion and 2 and 7 days postoperatively. Biopsies for light microscopic evaluations were obtained at the same time points, but not after cold storage. Glutaminase activity was well maintained after cold storage, regardless of the duration of preservation. Enzyme activities measured 20 min after reperfusion decreased with increasing duration of preservation (saline: R2 = 32.8%; P < 0.01; PBS: R2 = 52.3%; P < or = 0.001) and with increasing histologic preservation injury. Glutaminase activities were predictive for survival of grafts preserved with the PBS solution (R2 = 49.6%; P < or = 0.001; sensitivity 92%; specificity 100%), while the activities of maltase and of xanthine oxidase failed to do so. The degree of histologic preservation injury seen in graft specimens obtained 20 min after reperfusion was a good predictor of graft survival with a sensitivity of 90% for saline-preserved grafts and 92% for PBS-preserved grafts and a specificity of 88 and 67%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Mucosal recipient-type mononuclear repopulation and low-grade chronic rejection occur simultaneously in indefinitely surviving recipients of small bowel allografts.
Lewis rat recipients of long-term, surviving, orthotopic Brown-Norway rat intestinal allografts, initially treated with cyclosporin A (CyA) or FK 506, were evaluated for their functional capacity and morphology over 1 year after the immunosuppressive therapy had been discontinued. Functional parameters such as nitrogen and fat balances, maltose absorption, blood chemistry, hematologic studies, and the weight gained by the allografted animals did not differ from those of syngeneically grafted or age-matched normal animals. Immunohistochemical studies showed that the lamina propria of the allografts was repopulated with recipient MHC class II+ mononuclear cells and that a normal distribution of T helper, T suppressor/killer, and IgA+ plasma cells had occurred. However, fibrous replacement of the mesenteric lymph nodes and Peyer's patches were detected in all, and an inflammatory obliterative arteriolopathy developed in the mesenteric vasculature of half of the allografted animals. No such findings were observed in recipients of syngeneic grafts. These results demonstrate that the limited use of potent immunosuppressive agents immediately after transplantation averts rejection and is followed by recipient-type mucosal lymphocytic repopulation. Simultaneously, a clinically not recognizable chronic rejection evolves. This suggests that the timely diagnosis of chronic rejection may not be possible with the use of standard tests of gut function and random mucosal biopsies alone.
Animals↗