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Biomedical subjects

R Pichlmayr

Publications and source records attributed to R Pichlmayr.

At least 289 records · Page 16Linked to original sources

Application of adjusted survival curves to renal transplant data.

An important means in the analysis of survival time data is the estimation and graphical representation of survival probabilities. In this paper unifactorial parametric and non-parametric survival curve estimators and two types of adjusted survival curves based on a parametric multifactorial approach are applied to renal transplant data. It is shown that the resulting survival curves can differ substantially. The unifactorial survival curves yield biased results in case of serious disequilibrium in the data. This drawback of the unifactorial methods has been overcome by the use of adjusted survival curves which take possible distortions in the data set into account. The benefits of adjusted survival curves in assessing potentially prognostic factors are elucidated by the application to data from renal transplantation.

Humans↗

[Aorto-iliac reconstruction after kidney transplantation with in situ transplant perfusion with HTK solution].

A case report of a 57 year old male is presented, who underwent kidney transplantation in 1987. Subsequently he developed arterial occlusive disease. A bifurcated prosthesis was implanted and the graft preserved by in-situ-perfusion with HTK-solution (Custodiol). The graft artery was anastomosed in an end to side fashion to the prosthesis. The postoperative course was uncomplicated with unimpaired renal function. We conclude that in-situ-perfusion with cold HTK-solution represents a simple method for kidney graft protection during reconstructive vascular procedures.

Aorta, Abdominal↗

[Solitary angiomyolipoma of the liver].

Today in the age of ultrasonography focal hepatic lesions are diagnosed more often, which are difficult to be classified. Metastases are leading numerically among the malignant tumors, hemangiomas among the benign. We report on a rare case of a hemangiomyolipoma of the liver and the diagnostic difficulties. The final diagnosis was made only after hemihepatectomy.

Adult↗

[Cervical interventions on the airway and esophagus in infiltrating thyroid cancer].

In 1989 und 1990 a resection within the region of the cervical airways and/or oesophagus was performed for an infiltrating tumor in 9 out of 95 patients (9.5%) suffering from thyroid carcinoma and in one patient with lymph node metastases from a carcinoma of the uterine cervix. There was no operative mortality. One patient died six weeks after resecting the anterior wall of the trachea of an intratracheal arterial bleeding due to radiation therapy. In one case the reconstruction of the trachea was performed with autologous material, in three patients alloplastic material was used. The oesophagus was reconstructed preferably by means of free microvascular jejunum autografts (n = 4), using a colon interposition in another two patients. In locally advanced differentiated and medullary thyroid carcinoma curative operations of the cervical hollow organs using microsurgical techniques can be performed with an acceptable operative risk and good functional results. They may markedly improve the otherwise limited prognosis of the disease.

Combined Modality Therapy↗

[Experimental damage of the epithelial layer of the ileum by dietary fats: transmission electron microscopy findings and their comparison with cell pathology in Crohn disease].

Regarding the unknown pathogenesis of Crohn's disease repeatedly the importance of diet has been accentuated. Epidemiological, biochemical and animal experimental results have focused on a possible relationship between the consumption of chemically processed, partial hydrogenated fats and the development of regional enteritis. In this context an experimental animal model in pigs was designed to analyze, whether transmission electron microscopic alterations of ileal mucosa could be induced by forage of chemically processed fats. By creation of a retroperistaltic ileal segment the contact time between chyme and intestinal mucosa was prolonged. Our underlying question was to what extent disorders of the intestinal barrier function could be compared to Crohn's disease. Present study concentrates on the epithelial-cell-layer. It was shown that in comparison to the control animals the lamina epithelialis mucosae of all animals after fat-feeding was characterized by: sublethal lesion of the enterocytes/crypt-epithelial cells (shortening and alteration of the microvilli, degeneration of mitochondria, formation of autophagocytic vacuoles); goblet cell hyperplasia and increased production of mucus; focal appearance of intraepithelial lymphocytes as well as presence of polymorphonuclear granulocytes in the epithelium; widening of the intercellular-space locally up to total loss of the functional structure of the epithelial-cell-layer. In total the picture can be evaluated as an inflammatory process of the ileal mucosa. It can be concluded, that chemically processed fats as used in the described experimental conditions could induce this process. The feature of mucosal damage shows obvious similarities to ultrastructural findings in Crohn's disease if compared.

Animals↗

[Acute posttraumatic lung failure. Its treatment through pressure-limited respiration and continuous postural change].

Nine patients (4 women and 5 men; mean age 31 [20-48] years) with severe posttraumatic adult respiratory distress syndrome (ARDS) were treated with continuous postural change (kinetic bed) and pressure-limited ventilation. Seven patients survived; only one patient died as a result of pulmonary insufficiency. As compliance was markedly reduced (less than 20 ml/cm H2O), low stroke volumes (up to 380 ml) and high respiratory rate (up to 45/min) were employed to keep airway peak pressure below 40 mmHg. Kinetic treatment lasted for a mean of 14 (2-28) days; artificial ventilation was maintained for 31 (9-49) days. Practical problems of the method are the intensive nursing care required for the kinetic bed and the risk of decubitus ulcers, as well as disconnection of infusion tubing. The results indicate that kinetic treatment with pressure-limited ventilation constitutes a low-risk and, in many cases, effective treatment of severe ARDS.

Adult↗

[What is the role of nutrition in Crohn disease? A contribution to the importance of dietary therapy in regional enteritis].

The clinical appearance of Crohn's disease (CD) is especially marked by nutritional deficits and insufficiencies. For a long time the goal of nutritional care was reduced to the readjustment of the nutritional status. The development and clinical use of controlled parenteral nutrition (TPN) and enteral nutritive solutions (EN) did not only emphasize this therapeutical issue, but furthermore showed positive effects on the conservative as well as on the surgical treatment concepts. Therefore today artificial nutritional support is a firm part of therapy in acute, active phases or in the contact of surgical management of CD. This is especially valid in children, where complications in general and growth failure in particular can be reduced. EN is the preferred feeding method in most of the cases, due to a lower complication rate and reduced cost when compared to TPN. The question regarding the importance of nutritional support as primary therapy has also been investigated. The results differ extensively, but point towards the conclusion that patients with solitary small bowel disease do profit from this therapeutical concept. Nevertheless it is unclear, how TPN or EN interfere in the pathophysiology or -biochemistry in this process. A question about reduction e.g. of allergic components of daily diet did stimulate new theories regarding the hypothesis of a possible causal relationship between diet and the pathogenesis of CD. Investigations on dietary habits and daily dietary therapy did not reveal an overall accepted dietary guideline. Nevertheless it seems obvious that dietary counselling has a positive effect on the disease process. It does appear, that today in the acute, active phase as well as in the long term management of Crohn's disease nutritional-care is an important therapeutical method.

Crohn Disease↗

Ciclosporin metabolite pattern in blood and urine of kidney graft patients in relation to liver function.

Ciclosporin, an immunosuppressant, is metabolized by the liver cytochrome P450 system. Changes in the pattern of its metabolites in blood and urine in patients with disturbed liver function have been studied. Forty seven kidney graft patients receiving 2.9 mg/kg/d ciclosporin b.i.d., and no additional medication that would interfere with ciclosporin metabolism, were allocated to three groups according to liver function: I with normal liver function (n = 19), II with elevated liver enzyme activity or bilirubin concentration in serum (n = 20), and III with cholestasis (n = 8). Ciclosporin and 17 metabolites were determined in blood and 24 h-urine. In blood the trough concentrations of metabolites M19 and M1A were significantly higher in group III than in groups I and II. The total quantity of metabolites excreted in 24 h-urine was significantly different for H230, M4N69 and M1A (group III greater than I = II). Renal excretion of the daily dose of ciclosporin in patients in group I was 2.7%, group II 3% and group III 5.7%. In group III compared to group I the ciclosporin metabolite pattern was shifted to a relatively higher concentration of M19 in blood and of H 230, M19 and M1A in urine. Since high ciclosporin metabolite concentrations appear to be associated with nephrotoxicity, the metabolite pattern in patients with impaired liver function should be monitored.

Alanine Transaminase↗

Ciclosporin metabolite pattern in blood and urine of liver graft recipients. I. Association of ciclosporin metabolites with nephrotoxicity.

Blood ciclosporin (Cs) metabolite pattern in 58 liver grafted patients was routinely monitored by HPLC from the first Cs dose after transplantation until discharge from hospital. Eighteen patients with normal kidney function were allocated to Group I and 14 patients in Group II suffered Cs nephrotoxicity during their clinical course. There were no significant differences between both groups in blood Cs level, kidney function before transplantation, liver function or co-administration of other potentially nephrotoxic drugs. A correlation matrix involving both groups showed a significant correlation between the blood concentration of metabolite M1c9 and serum creatinine and urea, and an inverse correlation with creatinine clearance. During a nephrotoxic episode the blood concentrations of metabolites M1c9 and M1A were significantly elevated in patients in Group II. Analysis of the time course revealed significantly higher blood levels of M19 and M1c9 in Group II patients compared with those in Group I for the first 10 days after transplantation. Serum creatinine and urea concentrations remained significantly elevated, the creatinine clearance being significantly reduced throughout the period of observation. The elevated blood concentrations of ciclosporin metabolites M1c9 and M19 during nephrotoxic episodes suggest that these metabolites are associated with ciclosporin nephrotoxicity. It could not be decided if the elevated metabolite concentrations were the result of and/or the reason for impaired kidney function.

Adult↗

Ciclosporin metabolite pattern in blood and urine of liver graft recipients. II. Influence of cholestasis and rejection.

The pattern of metabolites of ciclosporin in blood and 24 h-urine of 58 liver graft recipients was routinely monitored by HPLC from transplantation until discharge from hospital. Liver function and ciclosporin metabolite pattern in patients with an uncomplicated clinical course and in those with cholestasis or acute rejection were compared. During cholestasis M19 and M1A, and during acute rejection M19, in blood were significantly elevated compared to the control group. Blood M19 was significantly correlated with bilirubin concentration and gamma-glutamyl transferase activity in serum, and M1A with the serum bilirubin concentration. Analysis of the metabolite pattern over the observation period showed higher concentrations of M19 and M1A in blood from patients with cholestasis and acute rejection than in the control group; concentrations were lower in the rejection group than in the cholestasis group. The metabolite pattern in 24 h-urine showed similar alterations in ciclosporin metabolite pattern to those in blood. Cholestasis and rejection shift the ciclosporin metabolite pattern in blood and urine to higher concentrations of M19 and M1A, whereas the concentrations of other metabolites and ciclosporin were not significantly affected.

Cholestasis↗

Contribution of cyclosporin metabolites to immunosuppression in liver-transplanted patients with severe graft dysfunction.

The aim of this study was to analyse the immunosuppressive contribution of cyclosporin metabolites in liver-grafted patients. Therefore the immunosuppressive potency of 17 metabolites, alone and in combination, was tested in human mixed lymphocyte cultures, and the results were correlated with metabolite blood levels in liver-grafted patients. Of the 17 metabolites tested only six highly lipophilic metabolites showed a detectable immunosuppressive activity of up to 10% of the activity of cyclosporin; the effect of combining metabolites was additive. For calculation of the in vivo activity, blood levels of seven major cyclosporin metabolites were determined in liver-grafted patients with normal liver function (group A, 43 episodes) and with severe hyperbilirubinaemia (group B, 66 episodes). Both patient groups had comparable levels of parent drug (122.9 +/- 17.4 vs. 111.1 +/- 23.5 ng/ml by HPLC) and similar blood levels of the highly lipophilic metabolites 17, 1 and 18. By contrast, blood levels of the less lipophilic metabolites 8, 9, 26 and 203-218 were substantially increased in group B (P less than 0.05). High overall metabolite blood levels in group B were also indicated by a non-specific monoclonal RIA (520 +/- 199 ng/ml for group A vs. 1318 +/- 407 ng/ml for group B). Despite the very high levels in group B, however, the overall contribution of the metabolites to immunosuppression was similar in both groups (12.6 +/- 5.0% for group A vs. 13.8 +/- 5.6% for group B). These findings indicate that, despite a marked accumulation of cyclosporin metabolites in patients with severe cholestatic liver dysfunction, their immunosuppressive contribution remains low.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclosporins↗

[In situ protection of the liver with Bretschneider HTK solution].

Liver resections are usually performed under occlusion of the hepatoduodenal ligament (Pringle manoeuvre) in order to limit operative blood loss. The maximal ischemic tolerance, although individually different, is generally accepted to be 60 min. Resections of centrally located tumors require precise preparation, sometimes combined with vascular reconstructions. In such cases a prolonged ischemic time is inevitable. A save prolongation of the ischemic tolerance could be useful for extensive liver resections. In an experimental study in pigs ischemic tolerance of the liver was studied under hypothermic protection with the HTK solution of Bretschneider during 2 and 3 h. Deterioration of liver function was compared with a warm ischemia during 2 h. Results showed significantly less serum transaminase activities and better hepatic blood flow (ICG test) after an ischemia under protection with the HTK solution compared to a warm ischemia during 2 h. A prolonged ischemia during 3 h under protection with the HTK solution was well tolerated. First clinical applications of hypothermic hepatic protection during resection were successful.

Animals↗