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F Längle

Publications and source records attributed to F Längle.

At least 19 recordsLinked to original sources

[MRT of the liver. Clinical significance of nonspecific and liver-specific MRT contrast agents].

The liver is a common site for various benign and malignant focal lesions. The initial modality for assessing liver lesions is ultrasound or CT. MRI with its superior soft tissue contrast offers multiple advantages over other imaging modalities. Contrast agents have been developed that increase the detection rate and provide more specific information in comparison to unenhanced techniques. In the mean time three classes are available for MR imaging of the liver: extracellular gadolinium chelates, hepatobiliary and reticulo-endothelia, superparamagnetic agents. We describe in this review the most common focal lesions, their diagnostic possibilities, and the imaging protocols. Clinical use of these contrast agents facilitates detection and differential diagnosis of focal liver lesions that may help to avoid invasive procedures such as biopsy for lesion characterization.

Chelating Agents↗

Early cancer of the stomach arising after successful treatment of gastric MALT lymphoma in patients with autoimmune disease.

BACKGROUND: Extranodal marginal zone B-cell lymphoma of the mucosa associated lymphoid tissue (MALT lymphoma) arises in lymphoid tissue acquired through chronic antigenic stimulation as exemplified by Helicobacter pylori. Secondary development of gastric cancer, however, is thought to be a rare event. The detection of a signet ring cell carcinoma during follow-up endoscopy after successful therapy of MALT lymphoma in a patient with Sjögren's syndrome prompted us to analyse the frequency of subsequent gastric cancer in patients with underlying autoimmune disease (AD). METHODS: Patients with early stage MALT lymphoma and an underlying AD were evaluated for the occurrence of a secondary gastric cancer during the course of follow-up. Data analysed included the type of AD, stage of MALT lymphoma, H. pylori status, treatment for MALT lymphoma and response, follow-up, the presence of a secondary cancer, and time to development of cancer. In all patients, histologic samples were reassessed for the extent of gastritis, presence of intestinal metaplasia or focal atrophy at the time of lymphoma diagnosis. RESULTS: A total of eight patients with overt AD at the time of diagnosis of MALT lymphoma were identified. All patients were women aged between 56 and 77 years; 5 had Sjögren's syndrome, 2 had autoimmune thyroiditis (1 along with psoriasis) and 1 suffered from polymyalgia rheumatica. All patients had early stage MALT lymphoma restricted to the mucosa and submucosa at the time of diagnosis, and the presence of H. pylori was found in all cases. Two of these patients achieved complete remission (CR) of the lymphoma following H. pylori eradication, while six were judged unresponsive and underwent chemotherapy, resulting in CR in all cases. One patient died from stroke while being in CR for 2 months following chemotherapy. Two patients (25%) developed early cancer limited to the gastric mucosa while being in CR from lymphoma for 9 and 27 months, respectively, and underwent partial gastrectomy. Final staging of gastric cancer revealed pT1pN0M0 in both cases. Of the remaining 5 cases, 1 patient had a local lymphoma relapse 18 months after CR and was salvaged with radiotherapy. In the remaining 4 patients, no evidence of lymphoma recurrence or a second malignancy has been found so far by regular follow-up every 3 months for a time-span between 52 and 63 months after initial diagnosis. CONCLUSION: Patients with concurrent MALT lymphoma and an underlying autoimmune condition show not only an impaired response to H. pylori eradication but might also be at increased risk for the development of gastric cancer. In view of this, such patients should be followed closely by regular endoscopies after remission of MALT lymphoma.

Adenocarcinoma↗

Intermittent weekly high-dose capecitabine in combination with oxaliplatin: a phase I/II study in first-line treatment of patients with advanced colorectal cancer.

BACKGROUND: The aim of this phase I study was to determine the maximum-tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of an intermittent weekly capecitabine regimen in combination with oxaliplatin. Furthermore, we intended to explore its safety at the recommended dose, and to assess its principal antitumor activity in patients with advanced colorectal cancer. PATIENTS AND METHODS: Thirty patients with measurable metastatic colorectal cancer who previously were unexposed to palliative chemotherapy were enrolled on to this disease-oriented phase I trial. They were treated with a fixed dose of oxaliplatin (85 mg/m(2) administered as a 2-h intravenous infusion on day 1) plus escalating doses of capecitabine (given at two divided daily doses from days 1 to 7), repeated every 2 weeks. The dose of oral fluoropyrimidine was escalated in consecutive cohorts of three to six patients from 2500 to 4000 mg/m(2)/day. After having defined the toxic dose, nine additional patients were entered at the MTD/recommended dose to confirm its safety profile, and assure suitability for future phase II/III studies. RESULTS: In the phase I part of the study, 21 patients were enrolled, and a total of 222 courses were administered through four dose levels of capecitabine combined with oxaliplatin 85 mg/m(2). Gastrointestinal toxicities, predominantly diarrhea, were the principal DLTs. Other severe adverse events included grade 3 asthenia, acute neurological symptoms and skin toxicity. The combination was not myelosuppressive, eliciting only sporadically grade 3/4 neutropenia and/or thrombocytopenia. There was no alopecia, and only a few patients experienced mild symptoms of hand-foot syndrome. Externally reviewed objective responses were noted in 15 of all 30 evaluable patients (overall response rate, 50%; 95% confidence interval 31% to 69%) including three complete remissions and median progression-free survival was 8.8 months (range 7-14+ months). CONCLUSIONS: Overall results of this study indicate that the administration of clinically relevant single-agent doses of both capecitabine and oxaliplatin is feasible and seems to result in promising therapeutic activity in patients with advanced colorectal cancer. On the basis of the toxicological profile of the combination regimen shown in the present study, oxaliplatin 85 mg/m(2) as a 2-h intravenous infusion every 2 weeks administered in combination with capecitabine 3500 mg/m(2)/day x7 in two divided doses is recommended for further evaluations.

Administration, Oral↗

[Surgery for non-colorectal and non-neuroendocrine liver metastases].

INTRODUCTION: Hepatic resection has been shown to prolong survival in selected patients with colorectal liver metastases. Due to slow tumor growth patients with neuroendocrine liver metastases tend to have a good prognosis and benefit from chemo-embolisation and symptomatic treatment. The role of surgery in treating non-neuroendocrine and non-colorectal liver metastases is discussed controversially, due to the limited knowledge on this subject. The aim of our study was, therefore, to evaluate our own experiences with hepatic surgery for non-neuroendocrine, non-colorectal liver metastases. METHODS: A retrospective review of 72 patients (median age 60.9 years) who underwent 73 hepatic resections for non-neuroendocrine, non-colorectal liver metastases between 1980 and 2000 at a single tertial referral center was carried out. RESULTS: Hepatic resection was combined with surgery for the primary tumor in 30 cases (41.1%). Hospital mortality was 4.2%. 35 patients (47.9%) developed complications. The mean hospital stay was 17.5 days. In 64.4% of the cases a potentially curative resection was reached. Overall actuarial survival was 52.1% at 1 year, 25.3% at 3 years and 9.9% at 5 years. The respective median overall survival times were 7.1 months (gastric cancer metastases; n = 15), 4.9 months (cholangiocellular cancer metastases; n = 9), 5.6 months (gall bladder, bile duct cancer metastases; n = 8), 35.4 months (kidney cancer metastases; n = 8), 14.4 months (breast cancer metastases; n = 4), 15.3 months (pancreas and other adenocarcinoma metastases; n = 11), 49.9 months (sarcoma metastases; n = 10) and 32.9 months (other metastases; n = 7). CONCLUSIONS: In isolated hepatic metastases originating from sarcoma and hypernephroma radical resection can prolong survival. However, surgery cannot improve the prognosis in patients with liver metastases originating from the pancreas, gallbladder and the biliary tract. In selected patients with liver metastases from gastric and breast cancer long term survival seems possible after resection.

Adenocarcinoma↗

Malignancy in slow motion: diagnosis of biochemically apparent, but otherwise occult persistent disease 21 years after resection of a carcinoid tumour of the terminal ileum.

Carcinoid tumors may relapse after a long time span following initial diagnosis, and relapse might be clinically inapparent despite biochemical indications due to a low sensitivity of conventional methods. We present the case of a patient who had biochemical indication for hidden disease persistence for more than two decades. In 1978, a 39-year-old man underwent surgery for a carcinoid tumour of the ileum measuring 3.5 cm with multiple local lymph-node metastases. After surgery, however, serotonin- and urinary 5-hydroxy-indole-acetic-acid (5-HIAA) remained markedly elevated, and persisted over more than 20 years at levels between 600 and 950 ng/ml for serum serotonin (normal range 40-400 ng/ml) and 29-35 mg/24 h for 5-HIAA (normal range 2-9 mg/24 h). Despite this, regular radiological follow-up, including sonography and CT-scan, did not reveal the location of suspected malignancy until 1999, when the patient was re-admitted to our hospital for a hypertensive episode. CT-scanning of the abdomen showed a singular lesion within the liver, which was verified as recurrence of the carcinoid by fine needle biopsy. Somatostatin receptor scintigraphy using (111)In-DTPA-D-Phe1-Octreotide revealed a second lesion within the liver along with local recurrence at the anastomosis, which was verified by surgery. While the propensity for late relapse of ileal carcinoids has repeatedly been demonstrated, a case with biochemical signs of disease persistence over a time span of 21 years before final diagnosis is unusual. In addition, our case reflects the low sensitivity of conventional radiological evaluation for localization of carcinoid tumours as compared to somatostatin receptor scanning.

Adult↗

Successful treatment of a patient suffering from severe acute potassium dichromate poisoning with liver transplantation.

BACKGROUND: Oral ingestion of potassium dichromate produces a complex spectrum of complications. It has an extremely poor prognosis and usually leads to rapid death. METHODS: We report the case of a 16-year-old male patient who was admitted to hospital after oral ingestion of potassium dichromate with suicidal intention. RESULTS: The patient's condition deteriorated, and he became comatose within 5 days in spite of immediate attempts at detoxification. Because of irreversible liver failure, which occurred within 2 days after admission, and because of cerebral edema, the decision to perform a liver transplantation was made. On day 6 after admission, a compatible donor liver was transplanted. The course of liver transplantation and the patient's subsequent recovery were uneventful. CONCLUSION: The rationale for the delayed transplantation was to avoid damage of the new organ because of high serum chromium levels. Despite severe organ damage, the chromium content of the liver was increased. To the authors' knowledge, this is the first case report of acute toxic liver failure, caused by potassium dichromate poisoning, treated successfully by means of liver transplantation.

Acute Disease↗

Organ survival after primary dysfunction of liver grafts in clinical orthotopic liver transplantation.

In a retrospective analysis of 632 orthototopic liver transplant procedures performed between 1982 and 1997, the incidence of primary dysfunction (PDF) of the liver and its influence on organ survival were studied. Graft function during the first 3 postoperative days was categorized into four groups: (1) good (GOT max < 1000 U/l, spontaneous PT > 50%, bile production > 100 ml/day); (2) fair (GOT 1000-2500 U/l, clotting factor support < 2 days, bile < 100 ml/day); (3) poor (GOT > 2500 U/l, clotting factor support > 2 days, bile < 20 ml/day); (4) primary non-function (PNF; retransplantation required within 7 days). The aim of this study was to evaluate graft survival comparing organs with PDF (poor function) and PNF vs organs with initial good or fair function. After a median follow-up of 45 months, initially good and fair function of liver grafts resulted in a significantly better long-term graft survival compared with grafts with initially poor function or primary non-function (if re-transplanted) (P < 0.01). The Cox model revealed primary function as a highly significant factor in the prediction of long-term graft survival (P < 0.0001). We conclude that these results confirm the hypothesis that primary graft function is of major importance for the long-term survival of liver transplants. Patients with a poor primary function have the worst survival prognosis, which leads to the interpretation that these patients may be candidates for early retransplantation.

Adolescent↗

Radical surgical therapy of abdominal cystic hydatid disease: factors of recurrence.

A series of 74 consecutive patients (48 women, 26 men) were operated for abdominal hydatid disease between June 1949 and December 1995. The patients ranged in age from 15 to 81 years (median 49 years). In 69 cases only the liver was affected; two patients had concomitant extrahepatic disease (one spleen, one spleen and lung), and 3 had cysts in the spleen only. Cysts were multiple in 11 patients and calcified in 24. Conservative surgical procedures were used for 22 cysts in 20 patients [open partial (n = 3), open total (n = 6), closed total cystectomy (n = 9), marsupialization (n = 2), drainage (n = 2)] and radical surgical procedures for 72 cysts in 54 patients [pericystectomy (n = 41), wedge liver resection or hemihepatectomy (n = 25), splenectomy (n = 5), radical resection of a lung cyst (n = 1)]. Altogether 37 patients (50%) were given perioperative antihelmintic chemotherapy with mebendazole (18 patients) or albendazole (19 patients). Operative mortality rates were 5.0% after conservative surgery and 1.8% after radical surgery. Morbidity rates were 25.0% following conservative surgery and 24.1% following radical surgery. Antihelmintic therapy was well tolerated by all but five patients. All side effects were entirely reversible. Among the 74 patients, 60 (81.0%) were available for long-term follow-up (median 7.2 years; range 2.0-47.0 years). Recurrence of disease was seen in 9 of 60 patients at an interval of 3 months to 20 years from the first operation. The rate of recurrence was significantly lower after radical surgical procedures (p = 0.03) and after closed removal of the cyst (p = 0.04).

Adolescent↗

Glue embolization of a ruptured celiac trunk pseudoaneurysm via the gastroduodenal artery.

Percutaneous transcatheter embolization of splanchnic artery aneurysms is a minimally invasive and alternative therapy to conventional surgical intervention. Due to a high-grade stenosis at the origin of the celiac trunk, a retrograde approach to the celiac trunk pseudoaneurysm via the gastroduodenal artery was necessary. To prevent undesirable embolization into the peripheral left gastric artery initial occlusion of the central portion of the left gastric artery was performed with microcoils using a Tracker catheter. Complete occlusion of the celiac trunk itself and the short adjacent segments of the celiac artery was achieved by using a mixture of N-butyl-2-cyanoacrylate and ethiodized oil as the embolizing agent.

Aneurysm, False↗

The role of intra-abdominal pressure on splanchnic and pulmonary hemodynamic and metabolic changes during carbon dioxide pneumoperitoneum.

BACKGROUND AND METHODS: To find an intra-abdominal pressure (IAP) range for laparoscopic procedures that elicits only moderate splanchnic and pulmonary hemodynamic and metabolic changes, including hepatic and intestinal tissue pH and superficial hepatic blood flow, we installed an IAP of 7 and 14 mm Hg each for 30 minutes in 10 healthy pigs (30 +/- 4 kg). RESULTS: In parallel with the increase of IAP, the mean transmural pulmonary artery pressure increased (from 25 +/- 3 to 27 +/- 4 at 7 mm Hg IAP and 30 +/- 6 mm Hg at 14 mm Hg IAP, p < 0.05); the pulmonary artery-to-pulmonary capillary wedge pressure gradient also increased (from 17 +/- 2.7 to 21 +/- 3 mm Hg at 7 mm Hg IAP and 24 +/- 4.2 mm Hg at 14 mm Hg IAP, p < 0.01), and the arterial oxygenation decreased (p < 0.005). Relevant changes at an IAP of 14 mm Hg were observed in right atrial pressure during inspiration (from 7 +/- 2 to 12 +/- 3 mm Hg, p < 0. 0001) and in abdominal aortic flow (from 1.43 +/- 0.4 to 1.19 +/- 0. 3 L/min, p < 0.01). However, transmural right atrial pressure and cardiac output remained essentially unchanged. Portal and hepatic venous pressure increased in parallel with the IAP (portal: from 12 +/- 3 to 17 +/- 3 at 7 mm Hg IAP and 22 +/- 3 mm Hg at 14 mm Hg IAP, p < 0.01; hepatic venous: from 8 +/- 3 to 14 +/- 6 at 7 mm Hg IAP and 19 +/- 6 mm Hg at 14 mm Hg IAP, p < 0.005), but the transmural portal and hepatic venous pressures decreased (p < 0.01), indicating decreased venous filling. Portal flow was maintained at 7 mm Hg but decreased at 14 mm Hg from 474 +/- 199 to 395 +/- 175 mL/min (p < 0. 01), whereas hepatic arterial flow remained stable. Hepatic superficial blood flow decreased during insufflation and increased after desufflation. Tissue pH fell together with portal and hepatic venous pH (intestinal: from 7.323 +/- 0.05 to 7.217 +/- 0.04; hepatic: from 7.259 +/- 0.04 to 7.125 +/- 0.06, both p < 0.01) at 14 mm Hg. CONCLUSION: The hemodynamic and metabolic derangement in the pulmonary and splanchnic compartments are dependent on the extent of carbon dioxide pneumoperitoneum. The effect of low IAP (7 mm Hg) on splanchnic perfusion is minimal. However, higher IAPs (14 mm Hg) decrease portal and superficial hepatic blood flow and hepatic and intestinal tissue pH.

Abdomen↗

[Liver transplantation in acute liver failure].

Acute hepatic failure is characterized by jaundice and hepatic encephalopathy within eight weeks after the onset of disease. Although acute hepatic failure is a rare occurrence, its rapid progression and high mortality (50 to 90%, depending on the etiology of disease) necessitate immediate intervention. In the absence of causal therapy, orthotopic liver transplantation is currently the only definitive and effective means of treating acute hepatic failure in Europe, acute hepatic failure accounts for 11% of all liver transplantations. At the University department of transplantation surgery in Vienna a total of 27 patients with acute hepatic failure underwent 31 liver transplantations in the last 10 years (1.1.1987 to 31.12.1996). Twenty (74%) of the 27 patients survived the acute event and were discharged from hospital in good general condition after a median postoperative stay of 25 days (range 14-81 days). Seven patients (26%) died between the first and 34th postoperative day (median 26 days) in the intensive care unit, although all potential modern options of intensive care and surgery were used. The causes of death were irreversible cerebral edema (n = 3), multiple organ failure due to bacterial sepsis (n = 3) and uncontrollable haemolysis (n = 1). With a 3-year graft survival rate of 70% the 3-year patient survival rate was 74%. A retrospective analysis of our patients revealed that the postoperative graft function and the incidence of re-transplantation were significant prognostic factors (p < 0.05) for survival following orthotopic liver transplantation for acute hepatic failure. In the absence of further prognostically relevant preoperative indices and in consideration of the potentially fulminant progression of disease, we strongly recommend that any patient, in whom acute hepatic failure is suspected, is immediately transferred to a specialized center with experience both in the conservative treatment of acute hepatic failure and emergency liver transplantation.

Adolescent↗

Management of lymphoceles after kidney transplantation.

Post-transplant lymphoceles (LC) may lead to impaired graft function. Treatment modalities include fine-needle aspiration, percutaneous drainage, and surgical internal drainage. Recently, laparoscopic fenestration has been performed with good results, but experience is still limited. Between January 1991 and August 1996, 919 kidney transplantations were performed in 876 patients at our department. There were 745 first, 133 second, 30 third, 9 fourth, and 2 fifth operations. Sixty-three symptomatic LCs were detected in 62 patients (6.8%) after 39 +/- 31 days. In 44% of the cases, graft function was impaired; in 29% hydronephrosis was documented and in 6% infection of the LC. Forty-five of the 62 patients with LC (73%) had histologically proven rejection. Thirty-five of the 63 LCs were drained percutaneously, 20 LCs were internally drained by open surgery, and 8 LCs were drained by laparoscopy. In 14 of the 47 patients (30%) with primary percutaneous drainage, LC recurred; infection occurred in 17%. Twelve of these patients underwent surgery. One surgical redrainage was necessary after open fenestration. No conversion or complication was noted in the laparoscopy group. We conclude that surgery for post-transplant lymphoceles is safe and effective. We favor the laparoscopic technique in selected patients.

Adult↗

Stage-dependent therapy of rectal carcinoid tumors.

Although malignant behavior of rectal carcinoid tumors is rare, the risk of metastases and death does exist. Adaptation of therapy according to the estimated malignancy seems necessary. To develop a stage-dependent therapy, 31 patients with rectal carcinoid tumors measuring 5 to 50 mm in diameter were analyzed retrospectively. Malignancy was estimated according to tumor size, infiltration depth, and histopathology. There were 18 tumors within the mucosa and submucosa (T1), 7 tumors with muscularis propria invasion (T2), and carcinoid tumor penetrating the full rectal wall (T3) or spreading to surrounding tissue (T4) in 6 patients. Altogether 20 patients (65%) were treated with a minimally invasive intervention: endoscopic polypectomy (EP) in 12 and transanal excision (TE) in 8 patients. In 11 patients (35%) aggressive surgical procedures--anterior resection (AR) in 4 and abdominoperineal resection (APR) in 7--were performed. After a mean +/- SD follow-up of 86.0 +/- 61.3 months, tumor recurrence was not seen in any of the 20 patients with minimally invasive treatment, and all were still alive. No severe complications associated with surgical procedures were detected. In contrast, 5 of the 10 patients with advanced tumor stage died from their disease despite aggressive surgery (AR, APR). In conclusion, depending on tumor stage, treatment of rectal carcinoids includes EP, TE, or extended resection. Minimally invasive techniques are safe treatments for small to medium-size T1/T2 rectal carcinoids. Extended surgery cannot improve the overall survival of those with advanced tumors (T3/T4, N1, M1) but can be beneficial for preventing local complications.

Adult↗

Improvement of cardiac output and liver blood flow and reduction of pulmonary vascular resistance by intravenous infusion of L-arginine during the early reperfusion period in pig liver transplantation.

BACKGROUND: The release of liver arginase after orthotopic liver transplantation (OLT) causes a deficiency of L-arginine and nitrite in the plasma. This deficiency is possibly related to pulmonary hypertension and reduced hepatic blood flow, which are commonly observed in the immediate reperfusion period. The aim of this study was to evaluate the impact of L-arginine supplementation on metabolic and hemodynamic parameters during liver reperfusion after OLT in pigs. METHODS: Thirteen pig OLTs (control group, n=6; arginine group, n=7) were performed by a standard technique. Cold ischemic time was 20 hr. L-Arginine was infused at a dosage of 500 mg/kg body weight into the donor pigs (30 min before liver explantation) and also into the recipients (over a period of 3 hr from the beginning of the reperfusion period). At the end of the experimental study, the pigs were killed with an overdose of potassium. RESULTS: In the control group, liver revascularization increased plasma arginase concentrations (+615%) and reduced plasma levels of L-arginine (-87%), nitrite (-82%), and nitrate (-53%). Infusion of L-arginine increased plasma levels of L-arginine from 94+/-21 micromol/L to 1674+/-252 micromol/L (P<0.001), L-ornithine from 46+/-8 micromol/L to 2215+/-465 micromol/L (P<0.001), and L-citrulline from 58+/-8 micromol/L to 116+/-34 micromol/L (P<0.001), but had no effect on plasma levels of nitrite and nitrate. Administration of L-arginine in the donor pigs did not produce any systemic or organ-specific hemodynamic alterations. Infusion of L-arginine into the recipient pigs improved cardiac performance (increase in heart rate [+61%, P=0.017] and cardiac index [+53%, P=0.005], reduction in pulmonary capillary wedge pressure [-54%, P=0.014]). Moreover L-arginine infusion increased oxygen consumption (+65%, P=0.003), reduced pulmonary vascular resistance index (P=0.001), stimulated portal venous blood flow (P=0.014), and elevated body temperature during the reperfusion period (P=0.007). CONCLUSIONS: From these data, we conclude that the infusion of L-arginine during OLT improves the hemodynamic performance of the heart, lung, and liver.

Animals↗

Is inadequate thrombopoietin production a major cause of thrombocytopenia in cirrhosis of the liver?

BACKGROUND/AIMS: Thrombocytopenia secondary to cirrhosis of the liver and portal hypertension is a well-known complication of advanced stage liver disease, but theories about the underlying pathogenetic mechanisms, mostly centering on splenic sequestration and destruction of platelets, have failed to solve the problem so far. METHODS: Peripheral platelet count and thrombopoietin levels in human plasma were measured in 28 patients with cirrhosis of the liver. Seven of those patients underwent orthotopic liver transplantation and five patients portal decompression by transjugular intrahepatic portosystemic shunt. Thrombopoietin plasma levels were followed for 14 days after the interventions. RESULTS: No measurable thrombopoietin was detectable in the plasma of 28 thrombocytopenic patients with cirrhosis of the liver, in contrast to thrombocytopenic patients without liver disease. Seven of these patients with cirrhosis underwent orthotopic liver transplantation, resulting in a rise of thrombopoietin levels within 2 days after transplantation. The rise in platelet number followed with a mean lag of 6 days, and shortly thereafter, thrombopoietin levels returned to levels below the limit of detection. Five patients with thrombocytopenia, who underwent only decompression of portal hypertension, showed no rise in either thrombopoietin levels or platelet count. CONCLUSIONS: Thrombocytopenia associated with liver disease may at least in part be attributable to inadequate thrombopoietin production in the failing liver.

Humans↗

Arginase release following liver reperfusion. Evidence of hemodynamic action of arginase infusions.

Immediately after hepatic reperfusion in human orthotopic liver transplantation, high amounts of arginase are released from the graft, thereby influencing nitric oxide metabolism. This metabolic alteration may be one component of the ischemia-reperfusion syndrome in OLT with its hemodynamic disturbances (e.g., systemic hypotension, pulmonary hypertension). The aim of this study was to compare hemodynamic and metabolic changes following OLT in the pigs with those obtained under arginase infusions in catheterized, anesthetized pigs. Following liver revascularization in the pigs, plasma arginase concentrations increased from 48 +/- 19 IU/L to 2613 +/- 944 IU/L, resulting in a drop in plasma levels of L-arginine (-87%) and in a drop in nitrite (-82%) and nitrate (-53%) concentrations. Of the measured organ-specific hemodynamic alterations, the mean pulmonary arterial pressure increased from 17 +/- 2 mmHg to 30 +/- 5 mmHg, whereas the flow/pressure index of the portal vein decreased about 60%. A primed continuous infusion of arginase (25,000 IU) increased plasma arginase levels to a maximum of 3,690 +/- 962 IU and evoked a decrease of L-arginine, but did not alter plasma nitrite or nitrate levels. The administration of arginase in healthy pigs did not influence cardiac output, mean arterial pressure, heart rate, or total peripheral resistance, but led to an increase of mean pulmonary arterial pressure from 19 +/- 3 to 48 +/- 5 mmHg and to a reduction of arterial hepatic blood flow from 229 +/- 65 ml/min to 154 +/- 41 ml/min. From this we conclude that high levels of liver arginase cause hemodynamic alterations in the lung and the liver. We hypothesize that the pulmonary hypertension and the reduced hepatic blood flow found during the immediate reperfusion period after OLT are possibly related to the increased arginase release due to the hepatic damage of the graft.

Animals↗