Sustained effects of ornipressin in hepatorenal syndrome.
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Biomedical subjects
Publications and source records attributed to G Mentha.
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BACKGROUND: Occasionally patients with adult polycystic liver disease (APLD) have symptoms. For these patients surgery may represent a valuable therapeutic option to relieve symptoms. METHODS: From September 1977 to August 1993 at our institution, 10 women with APLD were examined and surgically treated. They underwent a partial hepatic resection together with cyst fenestration. The surgical outcome and long-term follow-up were retrospectively analyzed. RESULTS: Postoperative morbidity consisted of one case of pneumonia, and one case of acute pancreatitis with deep vein leg thrombosis. One patient died after acute Budd-Chiari syndrome developed as a result of liver collapse after fenestration of a posterior cyst. In the long term six of nine patients were symptom free. Late surgical complications included acute cholecystitis (one patient), small bowel obstruction (one), and incisional hernia (two). CONCLUSIONS: A combined surgical approach of hepatic resection and cyst fenestration has proved feasible for patients with highly symptomatic APLD. Extensive fenestration of posterior cysts should be avoided; transverse hepatic resection (frontal hepatectomy) up to the costal margin is proposed. This therapy provides good results at long-term follow-up.
RATIONALE AND OBJECTIVES: We examined the effects of arterial ischemia on the phagocytic activity of the hepatic macrophage-monocytic phagocytic system (MMPS). METHODS: Six minipigs were studied before and 24 hr after complete arterial devascularization of the liver. Magnetic resonance (MR) imaging was performed at 1.5 T using superparamagnetic iron oxide (SPIO) particles (18 mumol Fe/kg body weight) as an MMPS-specific contrast agent. Hepatobiliary scintigraphy, measurements of serum liver enzymes, and histology also were obtained. RESULTS: On MR imaging, the postcontrast-to-precontrast ratios of the arterially devascularized livers were significantly higher than the corresponding baseline values (p < .01). The greatest difference (52%) between the baseline and the postoperative values was observed on gradient-echo (GE) images. Scintigraphy, laboratory analyses, and histology results indicate that the MR imaging findings were probably predominantly attributable to a reduction in phagocytic activity of the hepatic MMPS. CONCLUSION: SPIO particles have already proved useful for improving detection of liver neoplasms on MR imaging, but they also may provide a novel way of evaluating the function of the hepatic MMPS in liver diseases.
The synthesis of some class 1 acute-phase proteins (APP), including C-reactive protein (CRP) and serum amyloid A (SAA) protein is completely blocked by the IL-1 receptor antagonist (IL-1Ra), whereas the production of fibrinogen, a class 2 APP, is increased by IL-1Ra in hepatoma cells, but this has never been tested in human hepatocytes in primary culture. Since previous studies on the contributions of cytokine inhibitors in connective tissues diseases suggested that IL-1 and tumour necrosis factor-alpha (TNF-alpha) might play an important role in the regulation of CRP, we decided to examine in more detail the respective roles of IL-1 beta, IL-6, and TNF-alpha and their inhibitors in the production of APP by human primary hepatocytes versus the hepatoma cell line PLC/PRF/5. In the hepatoma cell line, IL-1 beta and/or TNF-alpha had synergistic effects with IL-6 on the production of CRP and SAA. In contrast, these cytokines were devoid of effect in normal hepatocytes. The production of fibrinogen was increased by IL-6 and decreased by IL-1 (and TNF-alpha) in both cell types. The secretion of CRP and SAA by primary hepatocytes incubated with a cytokine-rich mononuclear cell-conditioned medium was totally unaffected by IL-1Ra or anti-TNF-alpha antibodies. In contrast, the addition of IL-1Ra increased the production of fibrinogen by both hepatoma cells and primary hepatocytes incubated with the mononuclear cell-conditioned medium. We therefore conclude that IL-1 beta and TNF-alpha do not exert any significant effect on the synthesis of CRP and SAA by human primary hepatocytes.
Glucokinase and phosphoenolpyruvate carboxykinase are key enzymes of glucose metabolism in the rat liver. The former is considered to be instrumental in regulating glucose hepatic release/uptake according to the glycaemia level, and cytosolic phosphoenolpyruvate carboxykinase is a major flux-generating enzyme for gluconeogenesis. The level of expression of both enzymes and the regulation of their mRNAs in the human liver cell were investigated. Surgical biopsies of liver from patients undergoing partial hepatectomies and parenchymal hepatocytes derived from the biopsies were used to assay glucokinase, hexokinase and phosphoenolpyruvate carboxykinase activities. Hepatocytes were placed in culture and the actions of insulin, glucagon and cAMP on glucokinase and phosphoenolpyruvate carboxykinase mRNAs were studied. The main results are: (a) glucokinase accounts for 95% of the glucose phosphorylation activity of human hepatocytes, although this fact is masked in assays of total liver tissue; (b) glucokinase activity is set at a lower level in human hepatocytes than in rat hepatocytes, and vice-versa for the gluconeogenic enzyme phosphoenolpyruvate carboxykinase; and (c) as previously shown in rat liver, glucokinase and phosphoenolpyruvate carboxykinase mRNAs are regulated in a reciprocal fashion in human hepatocytes, insulin inducing the first enzyme and repressing the latter, whereas glucagon has opposite effects. These data have interesting implications with respect to metabolic regulation and intracellular hormone signaling in the human liver.
Type-I diabetes is considered an autoimmune disease, directed against pancreatic beta cells. Diabetes recurrence after pancreas transplantation is theoretically possible, and some cases have been reported after isotransplantation of segmental grafts in HLA-identical twins, where no rejection phenomenon is possible and where no immunosuppression was used. Diabetes recurrence has never been observed in a cadaveric allograft recipient, probably because immunosuppression efficiently blocks the autoimmune mechanism. Autoreactivity against beta cells exists life-long in type-I diabetes, and the immunosuppression used after transplantation becomes an advantage y preventing the recurrence of the disease.
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Tumor necrosis factor (TNF) is a powerful cytokine with an important role in the inflammatory acute phase response and in the activation of the immune system. It exerts its action through the adherence to cellular receptors, known as the TNF-R55 und TNF-R75. High levels of these receptors are present in the blood in a soluble form and binding circulating TNF can neutralise its systemic effects. Although the knowledge on the biology of TNF and TNF-sR is progressing rapidly, little is known on the action of this cytokine and of its soluble receptors in liver disease and liver transplantation. The literature on the subject is reviewed, and trends for future research are discussed.
For immediately vascularised xenografts, the presence of preformed antibodies associated with the activation of the complement induces a hyperacute humoral rejection in discordant combinations. For neovascularised xenografts, such as the islets of Langerhans, the absence of an initial vascularisation prevents the acute humoral rejection and there is some evidence to suggest that the rejection is cell mediated. To analyse the influence of species response to cellular transplantation, we compared the functional outcome and the immunohistochemical analysis of concordant and discordant xenotransplated islets with allotransplanted islets of Langerhans. In the concordant xenotransplantation experiment, rat (Sprague Dawley) purified islets (N = 600) were transplanted under the kidney capsule of streptozotocin diabetic mice. In the discordant experiment, purified human islets (N = 1000), in the allotransplantation model Balb mouse islets (N = 600) were transplanted under the kidney capsule of C57BL/6 mice. Daily blood glucose levels were monitored until rejection occurred (blood glucose > 11 mMol/L) and kidney biopsies were taken every second day for immunohistological examination. In allotransplanted mice, rejection occurred after a mean of 15 +/- 4 days, in concordant xenotransplanted mice after a mean of 10 +/- 3 days and in the discordant xenotransplanted mice after a mean of 8 +/- 1 days. The immunohistological analysis showed in both xenotransplantation models a deposit of IgM and C3 surrounding the grafted cells, starting at day 1 and persisting until rejection, associated with the presence of Mac-1 positive cells. The intensity of the humoral response was moderate to important in the concordant group, but very strong and unchanged until rejection in the disconcordant group. An invasion with CD4+ and CD8+ cells started between day 4 and 6 in both groups, progressively increasing until rejection. In the allotransplantation model, no humoral response was detectable and the cellular response started between day 10 and 12 after transplantation. We conclude, that a cellular response is involved in the rejection process of both concordant and discordant xenotransplanted islets of Langerhans. Compared to an allotransplantation model, the humoral response does not destroy the function of transplanted islets, but could trigger or accelerate the cell-mediated response.
Between 1 january 1992 and 31 december 1993, 32 liver transplantations were performed in 29 patients (5 transplants in 3 children and 27 transplants in 26 adults) at Geneva University Hospital. Despite 5 super-urgent transplantations (3 fulminant hepatitis, 1 end-stage Wilson disease and 1 primary nonfunction), all patients are still alive and all have lived more than 10 months. On 1 october 1994, all patients were at home and 93% were in good general condition. No patient of this series had been transplanted for cancer and all patients positive for hepatitis B surface antigen receive long-term administration of anti-HBs immune globulin: in this respect, the long-term mortality risk of the present series of patients seems to be very low. Although these results highlight that liver transplantation can be performed safely by a competent medico-surgical team, two significant difficulties have to be outlined. First, patients are likely to die on the waiting list due to unavailable grafts, especially in emergency cases. Second, the postoperative period of patients with decompensated end-stage liver disease at the time of liver transplantation is still one of high morbidity. These facts underline that chronic liver disease patient should be evaluated for liver transplantation prior to the terminal decompensated stage of the disease, when the candidate's invariably poor general condition precludes successful liver transplantation.
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Cytomegalovirus (CMV) belongs to the family of Herpes viridae and has become the single most important viral pathogen in clinical transplantation. This is an endemic and ubiquitous virus. After transplantation it is necessary to distinguish CMV infection (positive seroconversion and/or isolation of the virus in the blood, urine, sputum or tissues in the absence of clinical symptoms) from CMV disease, which is a clinical expression of viremia in association with a documented CMV infection. The overall incidence of CMV infection in transplant recipients is about 50% and the incidence of CMV disease ranges from 15 to 25% whatever the transplanted organ. In this study (52 liver transplantations in 48 patients), 12 patients had CMV infection and 10 patients developed CMV disease (24%). The onset of CMV disease was 33 +/- 7 days after transplantation. Cytomegalovirus hepatitis was observed 7 times, CMV pneumonia once and 2 CMV infections characterized by oscillating fever in association with a hematological syndrome. 8 patients were treated with intravenous gancyclovir (DHPG, 9-[1,3-dihydroxy-2-propoxymethyl]-guanine) for 15 days and 2 patients by reduction of their immunosuppressive therapy only. There were significantly more (p < 0.05) opportunistic infections and/or bacteremia in patients with CMV disease. The association of CMV IgG negative recipients and CMV IgG positive donors appeared to be a significant factor (p < 0.05) for CMV disease. The number of transfusions, the level of immunosuppression and the absence of prophylaxis did not influence the incidence of CMV disease. Despite prolonged hospitalization and increased morbidity, there were no deaths in patients who developed CMV disease, which is good evidence of the efficacy of gancyclovir.(ABSTRACT TRUNCATED AT 250 WORDS)
The incidence of recurrence of hepatitis B virus (HBV) following orthotopic liver transplantation (OLT) is as high as 80% when no attempt at prevention has been considered. HBV reinfection is associated with the reappearance of hepatitis B surface antigen (HBsAg) and HBV DNA in serum and, in most cases, with rapid severe graft damage. Immunoprophylaxis using polyclonal anti-HBs immunoglobulins reduces the risk of recurrence but this long-term therapy remains highly expensive. In this report, we use fresh frozen plasma (FFP) with high titers of anti-HBs immunoglobulins in an attempt to reduce HBV recurrence. From July 1987 to September 1993, 11 patients underwent OLT for HBV-related liver disease (18% of our OLT patients). FFP were administered to 6 patients continually for 7 to 46 months. Only one patient, under long-term immunosuppressive treatment before OLT, was reinfected 7 months after OLT. Rapid development of graft failure was observed with histologic manifestations of a fibrosing cholestatic hepatitis, leading to patient death after 12.5 months with concomitant bacterial infection. In this protocol, the rate of reappearance of HBsAg was 17%, a figure which can be favorably compared with other reports. All patients were subsequently tested for HCV and HIV and remained negative. In conclusion, FFP with high titers of anti-HBs immunoglobulins is at least as effective as polyclonal anti-HBs immunoglobulins in reducing the rate of HBV recurrence following OLT. The estimated cost of this new immunoprophylaxis method is less than 10% of the classical prophylaxis based on purified human polyclonal anti-HBs immunoglobulins.
Pruritus is a severe and troublesome symptom in patients with cholestasis and is often difficult to treat. Propofol was recently shown to be efficient in the treatment of pruritus secondary to spinal morphine administration. In a prospective, randomized, double-blind, cross-over and placebo controlled study, 20 patients received 1 dose of propofol (15 mg) and 1 dose of Intralipid (1.5 mg) during a 2-day study period. Pruritus was assessed by a visual analogue scale from 0 (no pruritus) to 10 (most severe pruritus imaginable). Treatment success was defined as a decrease in pruritus of at least 4 points on the scale in 80% of the patients receiving propofol and in 15% of those receiving intralipid (p < 0.05). Discomfort on injection was observed in 15% under propofol treatment. In conclusion this study shows that subhypnotic doses of propofol are effective for the short-term symptomatic relief of pruritus associated with liver disease. At the dose administered, side effects were rare and minor.
BACKGROUND: Rapid assessment of hepatic function early after reperfusion of the liver graft is of great importance, because it may allow for prompt detection of incipient hepatic graft failure. The current study was undertaken to determine whether the continuous recording of neuromuscular transmission could be used as an on-line assessment of hepatic function during liver transplantation when a muscle relaxant with high hepatic uptake is used. METHODS: We quantified and compared the effect of liver exclusion and graft reperfusion on the level of vecuronium-induced neuromuscular blockade in nine pigs studied twice within 3 days. During the 1st day (control session), an intravenous infusion of vecuronium was administered to maintain a constant 90-95% twitch depression during 180 min. The twitch response was then allowed to recover spontaneously to 75% of its prerelaxant value. Neuromuscular transmission was continuously measured on the right anterior leg using an acceleration transducer. During the same time period, the metabolic rate of 14C-labeled aminopyrine (a well-established quantitative test of the liver microsomal function) was determined by measuring the excretion of 14CO2 in expired air after administration of an intravenous bolus of 14C-labeled aminopyrine. Two days later, the pigs underwent a hepatic autotransplantation, during which vecuronium was administered to maintain a constant 90-95% twitch depression. After reperfusion of the liver graft, the vecuronium infusion rate was maintained at its anhepatic level, and the recovery index of the neuromuscular blockade (the time from 25% to 75% recovery of twitch height) was calculated. The aminopyrine breath test was performed during the last 30 min of the anhepatic phase, and during 3 h after reperfusion of the liver graft. RESULTS: During control studies, the mean infusion rate of vecuronium was 1.30 +/- 0.33 mg.kg-1.h-1 and the recovery index was 3.4 +/- 0.5 min. During liver dissection, the infusion rate of vecuronium was similar to the control value (1.18 +/- 0.16 mg.kg-1.h-1), then considerably decreased to 0.05 +/- 0.03 mg.kg-1.h-1 during the anhepatic phase. After reperfusion of the liver graft, the recovery index was markedly prolonged to 35.5 +/- 15.8 min, indicating a prolongation of the recovery of neuromuscular blockade by a factor of 10.4. Excretion of 14CO2 was equal to zero during the anhepatic phase and then increased to 0.19 +/- 0.11% during the 1st h after reperfusion of the liver graft, an excretion rate corresponding to 11.2% of control conditions. The relationship between individual changes in the recovery index of the neuromuscular blockade and 14CO2 excretion in expired air after reperfusion of the liver graft showed a strong significant correlation (r2 = 0.71). CONCLUSIONS: These results indicate that, compared with the control studies, there is a similar decrease in the recovery rate of vecuronium-induced neuromuscular blockade and in the metabolic rate of 14C-labeled aminopyrine during the progressive recovery of hepatic function immediately after unclamping of the liver vessels. Metabolism of 14C-labeled aminopyrine increased progressively during the reperfusion phase. Therefore, recording of neuromuscular transmission during liver transplantation could serve as a continuous and easy to perform assessment of liver graft function provided that a muscle relaxant with a high hepatic uptake is used for neuromuscular blockade.
The case of a diabetic 62-year-old man with a past history of myocardial infarction, developing a cardial arrest followed by successful cardiopulmonary resuscitation, is reported. In the late clinical course, the patient displayed abdominal signs related to mesenteric ischaemia. The pathophysiology of non-occlusive mesenteric ischaemia is discussed. Risk factors such as diabetes, cardiovascular disease, hemodialysis, the use of digoxine or alpha-adrenergic drugs are listed. Non-occlusive mesenteric ischaemia is not an infrequent complication of cardiac failure in high risk patients.
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