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Biomedical subjects

R Pichlmayr

Publications and source records attributed to R Pichlmayr.

At least 109 records · Page 6Linked to original sources
PubMed1996

Intraoperative ultrasound during ex situ liver resection.

This report describes the application of intraoperative ultrasound at the explanted liver during ex situ liver surgery. A 55-year-old woman underwent extracorporeal liver resection for multilocular metastases of a duodenal leiomyosarcoma. At surgery, routine intraoperative ultrasound (5-MHz probe) was performed before hepatectomy at the completely mobilized but still normally perfused liver. After hepatectomy ultrasound of the liver was repeated at the back table. By use of the ultrasonographic examination at the back table all the metastases seen with usual intraoperative ultrasound could be confirmed. In addition, one metastasis with a diameter of 6 mm was detected which had neither been suggested by peroperative computer tomography and sonography nor by intraoperative ultrasound or surgical exploration. In cases of extracorporeal liver surgery the combination of in situ and ex situ sonography may improve the identification of hepatic metastases.

Duodenal Neoplasms↗
PubMed1996

Tacrolimus (FK 506) biotransformation in primary rat hepatocytes depends on extracellular matrix geometry.

Established in vitro models for studies of hepatic drug biotransformation include the use of primary hepatocytes. In normal liver the space of Disse provides the possibility of bilateral attachment to extracellular matrix for each hepatocyte. This configuration is disrupted by the cell isolation procedure of normal liver tissue, which delivers suspensions of round shaped cells. In standard culture configurations this unphysiologic cell shape terminates in a morphological dedifferentiation and inability to biotransform drugs. This study analyses the relevance of extracellular matrix geometry in hepatocyte monolayer configurations for expression and activity of cytochrome P450 3A. This enzyme is involved in the biotransformation of a large number of pharmaceuticals including the immunosuppressants tacrolimus and sirolimus. Morphological analysis of primary rat hepatocytes cultured with and without overlay of collagen type I was performed by transmission and scanning electron microscopy. Expression and activity of cytochrome P450 3A was studied by Western blot and the use of two model drugs specific for this enzyme. To this purpose the immunosuppressive drugs tacrolimus and sirolimus were used. Metabolites were analyzed by HPLC and HPLC/MS. Two sided attachment to extracellular matrix induces profound changes of the hepatocellular morphology in vitro resulting in the reconstitution of a polyhedric cell shape. This phenomenon is paralleled by an enhanced expression of cytochrome P450 3A and corresponding metabolic activity. As shown for tacrolimus biotransformation, the model may be useful to study complex metabolic patterns. In addition this model may facilitate studies of the kinetics of hepatocellular drug biotransformation in a setting with prolonged stability.

Albumins↗
PubMed1996

High mortality from urothelial carcinoma despite regular tumor screening in patients with analgesic nephropathy after renal transplantation.

Patients with end-stage renal failure due to analgesic nephropathy have an increased risk of developing a urothelial carcinoma. To determine the impact of renal transplantation on the frequency of urothelial carcinomas, we analyzed 2072 patients who underwent 2371 renal transplantation between 1968 and 1993, including 78 (3.8%) with clinically proven analgesic nephropathy. Before and after transplantation a regular tumor screening was performed in patients with analgesic nephropathy by urine cytology and abdominal sonography. In 11 of the 78 patients with analgesic nephropathy (14.1%; age 51-66 years, 40-108 months after initiation of dialysis treatment, 5-77 months after transplantation), a urothelial carcinoma of the native urinary tract, especially the kidneys, was diagnosed. Therapy comprised nephroureterectomy (n = 6), transurethral resection (n = 6) and/or cystectomy (n = 2). Seven patients died due to tumor progression 16.3 (4-33) months postoperatively and one patient died due to a perioperative complication. Despite regular tumor screening after transplantation, the diagnosis of a urothelial carcinoma was made very late, leading to a high tumor-related mortality. As a consequence, we suggest that a bilateral nephroureterectomy should be performed prophylactically in patients with proven analgesic nephropathy. In addition, a cystoscopy with lavage cytology testing of the bladder should be performed twice a year.

Acetaminophen↗
PubMed1996

Tissue oxygen saturation of human hepatic grafts after reperfusion: paradoxical elevation in poor graft function.

The present study investigated the pathophysiology of primary nonfunction (PNF) of grafted livers with regard to hepatic tissue oxygenation. Hemoglobin oxygen saturation in hepatic tissue (H-So2) after reperfusion was determined using near-infrared spectroscopy. Graft tissue oxygen consumption was also estimated according to Fick's principle. Six grafts with PNF were compared with 40 functioning grafts. One PNF graft with extremely low and heterogeneous H-So2 after reperfusion was found to contain multiple intrahepatic portal thrombi. However, five other PNF grafts showed no lower and, on the contrary, more homogeneous H-So2 at the end of the operation. As a whole, mean H-So2 was negatively correlated and the coefficient of variation (CV) of H-So2 was positively correlated with graft tissue oxygen consumption at the end of the operation; grafts whose H-So2 showed a secondary decrease had better initial function. In later relaparotomy, the H-So2 of the five PNF grafts was significantly higher and more homogeneous than that of the functioning grafts. These results suggest that H-So2 level reflects tissue oxygen consumption as well as oxygenation, and that the dissociation of both factors can occur in hepatic graft reperfusion. Not only low and heterogeneous H-So2 but also high and homogeneous H-So2, suggesting some shunt mechanism, can be signs of poor graft function.

Adolescent↗
PubMed1996

[Indications for liver transplantation in severe amanita phalloides mushroom poisoning].

The clinical course of 12 patients with mushroom poisoning was evaluated in order to define the parameters considered to be relevant to the indication for liver transplantation. Eight patients recovered under conservative therapy; one patient died due to pre-existing, concomitant cardiopulmonary disease. In three patients transplantations had to be performed because of severe liver failure. On admission, the transplanted patients had a decreased Quick's test score and factor V value (< 10%). The peak of liver enzymes, serum bilirubin, serum creatinine, partial thromboplastin time and azotemia were not of any prognostic value. Main indications for liver transplantation were a very low initial Quick's test score and factor V value (both < 10%) and their inadequate response under substitution therapy. The development of encephalopathy and renal failure were further parameters indicating poor prognosis.

Adolescent↗
PubMed1996

[Urodilatin (INN: ularitide). A new peptide in the treatment of acute kidney failure following liver transplantation].

UNLABELLED: Acute renal failure (ARF) is a serious complication following liver transplantation. Many therapeutic regimens have been used so far but with limited success. Urodilatin (URO) is a new member of the atrial natriuretic peptide (ANP) family. When administered intravenously, URO induces strong diuresis and natriuresis with tolerable hemodynamic side effects. Preliminary non-controlled clinical studies demonstrate beneficial effects using URO as a therapeutic agent in patients suffering from ARF following heart and liver transplantation (HTx, LTx). These results prompted us to initiate this first controlled clinical trial to investigate whether URO infusion can improve renal function in patients with emerging ARF following LTx. METHOD: We initiated a randomized, double-blind, placebo-controlled study comparing five patients receiving i.v. URO infusion (20 ng/kg bw/min) with four placebo patients after informed consent was obtained. Optional inclusion criteria were oliguria/anuria ( < 0.5 ml/kg/h), refractory to conventional treatment including administration of furosemide and dopamine, increase of serum creatinine to a least 200% of preoperative values, and BUN levels > or = 25 mmol/l. The primary parameters for efficacy was the frequency of hemodialysis/hemofiltration. RESULTS: The frequency of hemodialysis/hemofiltration during URO or placebo infusion was significantly reduced (P = 0.03) in the URO-treated patients in comparison with placebo. BUN levels did not differ between two groups, but serum creatinine levels were consistently lower in the URO group. Diuresis tended to be stronger in the URO group, maintaining high levels despite a significant reduction in the administration of furosemide in comparison with placebo. CONCLUSION: We conclude that URO seems to be a new approach for the treatment of therapy-resistant postoperative ARF following LTx.

Acute Kidney Injury↗
PubMed1996

Enzymatic properties of transplanted glomerulosa cells.

There are several theories about the physiologic regeneration of adrenals and maintenance of physiologic steroid secretion after subtotal loss of adrenal cortical cells. According to the cell migration theory, adrenocytes from the zona glomerulosa migrate centripetally toward the medulla. This theory is opposed by the zonal theory according to which each zone resplenishes its cells independently. What these theories have in common is that they are based on data from the intact adrenal gland. We transplanted purified glomerulosa cells under the kidney's capsule of Lewis rats. The tissue was removed 30, 60, 90, and 150 days after transplantation to investigate the presence of two specific enzymes that are responsible for the secretion of aldosterone and corticosterone. Cytochrome p-450as is specific for glomerulosa cells producing aldosterone, and cytochrome p-45011beta is specific for fasciculata cells producing corticosterone. After sequencing the genetic code of these enzymes it became possible to demonstrate expression of the enzymes by in situ hybridization. The transplanted glomerulosa cells turned their enzymatic property to fasciculata cells expressing cytochrome p-45011beta. Our results suggest that glomerulosa cells are able to take over the physiologic function of a whole adrenal cortex in the absence of fasciculata cells, and that they are sufficient to maintain the function of the adrenal cortex.

Adrenal Medulla↗
PubMed1996

Serological pattern of hepatitis C virus recurrence after liver transplantation.

BACKGROUND/AIMS: Hepatitis C infection is characterized by a high incidence of liver cirrhosis, frequently requiring liver transplantation. After orthotopic liver transplantation, recurrence of hepatitis C virus infection is common, but often difficult to differentiate from allograft rejection. In this context the role and diagnostic value of hepatitis C virus-associated markers like the anti-GOR response have not yet been determined. In this study we analyzed the time course of hepatitis C virus recurrence in hepatitis C virus-infected patients who underwent liver transplantation because of end-stage cirrhosis or acute liver failure. METHODS: We evaluated the serological pattern and diagnostic significance of anti-HCV, anti-HCV-IgM, anti-HCV-core, anti-HCV-core 5-27, anti-GOR, anti-GOR-IgM and HCV-RNA in serial serum samples during hepatitis C virus recurrence with or without allograft rejection up to 5-64 months after orthotopic liver transplantation. For comparison, we also studied these markers in serial serum samples from previously uninfected patients who acquired hepatitis C virus-infection during or shortly after orthotopic liver transplantation. Hepatitis C virus-infected patients who had undergone orthotopic liver transplantation were identified by screening pre-transplant sera from 235 patients for the presence of anti-HCV (2nd generation ELISA) and serum HCV-RNA (reverse transcription polymerase chain reaction). RESULTS: Of 218 patients transplanted for end-stage liver cirrhosis, 65 (30%) were anti-HCV positive and 33 (15%) were HCV-RNA positive, while only one of 17 patients (6%) transplanted for acute liver failure was found to be anti-HCV positive without detectable HCV-RNA. Fifty-two hepatitis C virus-infected patients were studied serially before and after liver transplantation: 46 patients (89%) showed recurrent anti-HCV antibodies within 3 months and 51 patients (98%) within 42 months after orthotopic liver transplantation. Serum HCV-RNA was detected in 39 patients (75%) within 3 months and in 44 patients (85%) within 42 months after orthotopic liver transplantation. In the patients studied serially during hepatitis C virus-recurrence, anti-GOR antibodies displayed the same serological profile as hepatitis C virus antibodies, i.e. a decrease after orthotopic liver transplantation and slowly rising titers when HCV-RNA became detectable again. De novo infection with hepatitis C virus as studied in four patients produced a significant peak of anti-HCV titers accompanied or followed by an increase in anti-GOR titers, indicating that the immune response to GOR-autoantigen is triggered by the hepatitis C virus. No significant diagnostic difference between anti-GOR and anti-HCV was noted during hepatitis C virus recurrence and allograft rejection.

Amino Acid Sequence↗
PubMed1996

Surgical treatment in proximal bile duct cancer. A single-center experience.

OBJECTIVES: The authors evaluated the experience and results of a single center in surgical treatment of proximal bile duct carcinoma. SUMMARY BACKGROUND DATA: Whenever feasible, surgery is the appropriate treatment in proximal bile duct carcinoma. To improve survival rates and with special regard to liver transplantation, the extent of surgical radicalness remains an open issue. PATIENTS AND METHODS: Retrospective analysis of 249 patients who underwent surgery for proximal bile duct carcinoma via the following procedures: resection (n = 125), liver transplantation (n = 25), and exploratory laparotomy (n = 99). Survival rates were calculated according to the Kaplan-Meier method, uni- and multivariate analysis of prognostic factors, and log rank test (p < 0.05). RESULTS: Survival rates after resection and liver transplantation are correlated with international Union Against Cancer (UICC) tumor stage (resection: overall 5-year, 27.1%; stage I and II, 41.9%; stage IV, 20.7%; liver transplantation: overall 5-year, 17.1%; stage I and II, 37.8%; stage IV, 5.8%). Significant univariate prognostic factors for survival after liver resection were lymph node involvement (N category), tumor stage, tumor-free margins, and vascular invasion; for transplantation, they were local tumor extent, N category, tumor stage, and infiltration of liver parenchyma. For resection and transplantation, a multivariate analysis showed prognostic significance of tumor stage and tumor-free margins. CONCLUSION: Resection remains the treatment of choice in proximal bile duct carcinoma. Whenever possible, decisions about resectability should be made during laparotomy. With regard to the observation of long-term survivors, liver transplantation still can be justified in selected patients with stage II carcinoma. It is unknown whether more radical procedures, such as liver transplantation combined with multivisceral resections, will lead to better outcome in advanced stages. With regard to palliation, surgical drainage of the biliary system performed as hepatojejunostomy can be recommended.

Actuarial Analysis↗
PubMed1996

Evaluation of the Pro-Trac tacrolimus monoclonal whole-blood enzyme-linked immunosorbent assay for monitoring of tacrolimus levels in patients after kidney, heart, and liver transplantation.

In a prospective study, we evaluated a novel enzyme-linked immunosorbent assay (ELISA) (Pro-Trac) for determining tacrolimus (FK 506) concentrations in whole blood. Results obtained by the ELISA were compared with those obtained either by microparticle enzyme immunoassay (MEIA) or by high-performance liquid chromatography/mass spectrometry (HPLC-MS). The lower limit of quantitation of the ELISA was 0.5 microgram/L. The within-series coefficient of variation (CV) was < 11%. For spiked blood samples containing different concentrations of tacrolimus, interassay CV was 23.6% at 2.5 micrograms/L; however, at 15 and 60 micrograms/L, interassay CV was 44.9 and 50.8%, respectively. In crossover studies including blood samples from patients after liver, heart, or kidney transplantation, ELISA results correlated with those of the HPLC-MS (r = 0.73) as well as with those generated by MEIA (r = 0.82). The ELISA and MEIA showed 52.3 and 56.2% cross-reactivity with 15-O-demethyltacrolimus, respectively, but only 5.0 and 5.4% cross-reactivity with 13-O-demethyltacrolimus. We conclude that if assay precision in the upper range is improved, the Pro-Trac ELISA might be a valuable alternative to the MEIA for therapeutic drug monitoring of tacrolimus.

Chromatography, High Pressure Liquid↗
PubMed1996

Squamous cell carcinoma of the liver originating from a solitary non-parasitic cyst case report and review of the literature.

Squamous cell carcinoma of the liver arising from a non-parasitic cyst is a rare entity of a primary liver tumor with an unfavourable prognosis. We report a case of a patient with a cyst in the right lobe leading to upper abdominal symptoms and respiratory discomfort. Malignancy was not suspected from the clinical findings or repeated cytological examination of the cyst fluid. However, the blood stained brown color of the cyst fluid was unusual. Cyst recurrence after six attempts of conservative treatment with sonography guided drainage over a period for more than one year led to laparotomy with cyst unroofing. Because frozen section from the cyst wall revealed the unexpected finding of squamous cell carcinoma right hemihepatectomy was performed during the same operation. The patient is alive more than four years after surgery without cyst or tumor recurrence. The difficulties in establishing diagnosis are confirmed by the review of other reports. In the diagnosis and treatment of symptomatic non-parasitic liver cysts possible malignancy has to be considered. In case of proven carcinoma radical surgery with partial hepatectomy should be performed.

Aged↗