[Granular cell tumor involving the appendix].
Explore the source record for details and available documents.
Appendiceal Neoplasms↗
Biomedical subjects
P Balladur
Publications and source records attributed to P Balladur.
Morphological and biochemical integrity of human liver slices in long-term culture: effects of oxygen tension.
We tested the effects of low (20% O2) and high (70% O2) oxygen tension on the morphological and biochemical integrity of human liver slices incubated for up to 72 h in supplemented Williams' E medium in a dynamic rotating culture system. High oxygen tension was more effective than low oxygen tension for preserving morphological integrity in long-term culture (48-72 h). After 72 h of culture with 70% O2, the lobular pattern was well preserved, and the survival of hepatocytes (approximately 80%) and other cell types was good. Immunohistochemical studies showed good preservation of the region-specific expression of CYP2EI and CYP3A4 isoenzymes for up to 72 h of incubation in 70% O2. As compared to 20% O2, the oxidized glutathione content and reactive oxygen species production were slightly increased in 70% O2, suggesting that minimal oxidative stress occurred with the high oxygen tension. In conclusion, despite slight oxidative stress associated with high oxygen tension, 70% O2 appeared more appropriate than 20% O2 for preserving the morphological and biochemical integrity of human liver slices cultured in a dynamic organ culture system for up to 72 h.
Adult↗
Small solitary littoral cell angioma associated with splenic marginal zone lymphoma and villous lymphocyte leukaemia in a patient with hepatitis C infection.
Explore the source record for details and available documents.
Female↗
Long-term follow-up after neoplastic seeding complicating percutaneous ethanol injection for treatment of hepatocellular carcinoma.
We describe a case of subcutaneous metastasis along the needle track after percutaneous ethanol injection (PEI) for treatment of hepatocellular carcinoma. After surgical resection and extrabeam radiation therapy the patient is alive without evidence of recurrence five years after PEI. One should pay attention to the abdominal wall around the needle track in interpreting CT or MR images of patients with previous PEI.
Abdominal Muscles↗
Indirect cytotoxicity of flucloxacillin toward human biliary epithelium via metabolite formation in hepatocytes.
Flucloxacillin, an isoxazolyl-penicillin, causes cholestasis and biliary epithelium injury. The aim of the study was to determine whether flucloxacillin, either directly or through metabolite formation, may induce cytotoxicity in hepatic or biliary cells. Cytotoxicity was assessed by lactate dehydrogenase release in primary cultures of human hepatocytes and of gallbladder-derived biliary epithelial cells (BEC). Metabolite production in microsome and cell preparations was analyzed by chromatography, nuclear magnetic resonance spectroscopy, and mass spectrometry. While flucloxacillin induced no direct cytotoxicity in any of the hepatocyte (n = 12) and BEC (n = 19) preparations, the conditioned media from cultured hepatocytes preincubated with flucloxacillin (50-500 mg/L) triggered a significant increase in lactate dehydrogenase release over controls in approximately 50% of BEC preparations (7/12), and this effect depended upon flucloxacillin concentration. Remaining BEC preparations exhibited no toxic response. Cytotoxicity in BEC preparations (9/13) was also induced by the supernatants of human liver microsomes and of recombinant human cytochrome P450 (CYP)3A4 preincubated with flucloxacillin (500 mg/L). Supernatants from both liver microsome and CYP3A4 preparations contained one major metabolite which was identified as 5'-hydroxymethylflucloxacillin. The production of this metabolite was inhibited following CYP3A4 inhibition by troleandomycin in human liver microsomes, and markedly enhanced following CYP3A induction by dexamethasone in rat liver microsomes. As opposed to BEC, cultured hepatocytes displayed significant CYP3A activity and produced low amounts of this metabolite. The purified metabolite (0.01-5 mg/L) exerted toxic effects in BEC but not in hepatocytes. In conclusion, hepatocytes mainly via CYP3A4 activity, generate flucloxacillin metabolite(s) including 5'-hydroxymethylflucloxacillin that may induce cytotoxicity in susceptible BEC. These metabolic events may contribute to the pathogenesis of drug-induced cholangiopathies.
Biliary Tract↗
An unexpected liver secondary.
Explore the source record for details and available documents.
Anastomosis, Surgical↗
Survival and functions of encapsulated porcine hepatocytes after allotransplantation or xenotransplantation without immunosuppression.
BACKGROUND: This study evaluated the survival and functions of encapsulated porcine hepatocytes after intraperitoneal allotransplantation and xenotransplantation without immunosuppression. METHODS: Isolated porcine hepatocytes were encapsulated in AN 69 polymer capsules (45.10(6)/capsule) and transplanted intraperitoneally in 12 rats and 12 pigs. Fifteen, 30, and 60 days after transplantation, capsules were removed and the viability and morphology of explanted hepatocytes were examined under light and electronic microscopy. The potential to produce albumin was assessed by evaluating the level of albumin messenger RNA, using semiquantitative reverse transcription-polymerase chain reaction. 6beta-Hydroxylase activity was measured by high-performance liquid chromatography. In addition, cytochrome P450 3A proteins were detected by Western blot only in allogeneic hepatocytes. RESULTS: Similar results were observed after allotransplantation and xenotransplantation. Histologic studies showed that hepatocytes were well-preserved and arranged in cords for up to 30 days. The expression of porcine albumin gene was maintained up to 15 days. 6beta-Hydroxylase activity was 2.5-fold lower at day 15 than in freshly encapsulated hepatocytes, which were not transplanted. In allogeneic hepatocytes, the expression of CYP 3A protein was detected up to 60 days after transplantation. CONCLUSIONS: Encapsulated porcine hepatocytes remain viable and functional for at least 15 days after allotransplantation and xenotransplantation without immunosuppression. The demonstration of maintained hepatic functions in transplanted porcine hepatocytes up to 15 days is a first step toward application in the treatment of acute liver failure.
Albumins↗
Semiautomatic macroencapsulation of fresh or cryopreserved porcine hepatocytes maintain their ability for treatment of acute liver failure.
We have previously demonstrated that fresh or cryopreserved xenogeneic hepatocytes manually macroencapsulated in AN69 polymer and transplanted intraperitoneally in rats were able to improve the survival rate after 95% hepatectomy without immunosuppression. In addition, we developed a semiautomatic device where porcine hepatocytes were coextruded with AN69 hydrogel in order to macroencapsulate large amounts of cells. The purpose of the present study was to 1) test whether transplanted porcine hepatocytes macroencapsulated in this device remained functional as evaluated by their ability to prevent death from acute liver failure, and 2) compare the efficiency of cryopreserved or freshly isolated hepatocytes. Fresh or cryopreserved porcine hepatocytes were macroencapsulated in the semiautomatic device by coextrusion in AN69 polymer in 2-m minitubes containing 6 x 10(7) cells. Acute liver failure was induced in rats by two-step 95% hepatectomy. At the time of completion of liver resection, rats were either not transplanted with minitubes (control group I, n = 13), or were implanted with two minitubes containing culture medium (control group II, n = 11), hepatocytes killed by heat treatment (control group III, n = 10), coextruded fresh hepatocytes (group IV, n = 11), or coextruded cryopreserved hepatocytes (group V, n = 11), without immunosuppression. The survival rate at day 7 was between 0% and 31% in the three control groups. By contrast, coextruded fresh hepatocytes significantly improved the survival rate (group IV, 82%) as did cryopreserved cells (group V, 91% survival). In surviving rats, minitubes were explanted after 20 days; either fresh or cryopreserved hepatocytes appeared morphologically viable and their ultrastructure was preserved. Their detoxification capacities evaluated by the activity of the cyt P450 CYP3A4 were partly maintained. In conclusion, porcine hepatocytes macroencapsulated by coextrusion using a semiautomatic device and transplanted without immunosuppression were able to prevent death from acute liver failure in rats. Cryopreserved cells were as efficient as fresh hepatocytes.
Animals↗
Transplanted cryopreserved encapsulated porcine hepatocytes are as effective as fresh hepatocytes in preventing death from acute liver failure in rats.
BACKGROUND: An implantable bioartificial liver (BAL) using xenogeneic isolated hepatocytes may be an alternative method to orthotopic liver transplantation for treatment of acute liver failure. The purpose of this study was to demonstrate that not only fresh but also cryopreserved porcine hepatocytes could be used in a BAL to prevent death after the onset of acute liver failure in rats. METHODS: Acute liver failure was induced by two-stage 95% hepatectomy. At the time of completion of liver resection, 100 rats were assigned to undergo or not undergo transplantation into the peritoneum of 4 meters of hollow fibers filled with 60 million either fresh or cryopreserved porcine hepatocytes, or syngeneic hepatocytes, or culture medium, or of 60 million nonencapsulated cryopreserved porcine hepatocytes without immunosuppressive therapy. Survival rates at 7 days were compared between the different groups. RESULTS: In the control groups of hepatectomized animals not receiving encapsulated hepatocytes, 69-79% of the rats died from acute liver failure. The mortality rate was reduced to 15% (2 of 13) in rats receiving fresh porcine hepatocytes (P<0.01), 25% (4 of 16) in rats transplanted with either cryopreserved or syngeneic hepatocytes (P<0.05). Survival rates were maintained when hollow fibers were explanted > or =4 days after hepatectomy. In surviving rats, the weight of the remnant native liver increased with time and returned to the initial weight after 1 month. CONCLUSIONS: The implantable BAL using xenogeneic porcine hepatocytes was able in preventing death from acute liver failure without immunosuppressive therapy. Encapsulated cryopreserved hepatocytes were as effective as fresh hepatocytes.
Animals↗
A reversible model of acute hepatic failure by temporary hepatic ischemia in the pig.
BACKGROUND: To evaluate new therapies for human fulminant hepatic failure, a suitable large animal model is needed. The purpose of this study was to develop a reversible surgical model of acute hepatic liver failure by transient ischemia in pigs. MATERIALS AND METHODS: Under general anesthesia, an end-to-side portacaval shunt was performed in 17 pigs and tape was laid around the hepatoduodenal ligament. Two days after construction of the functional portacaval shunt, 13 ambulant pigs underwent transient total liver ischemia by tightening of the tape around the hepatoduodenal ligament for 5.5 h. During ischemia, 10% glucose was continuously infused intravenously to prevent hypoglycemia. RESULTS: Ten animals (77%) died with hepatic coma after a mean duration of 22.5 +/- 1.9 h. The 3 remaining animals survived more than 5 days and were sacrificed. In dying animals, encephalopathy was observed 14 +/- 1.7 h after the onset of ischemia. During ischemia, similar progressive decrease of fibrinogen, platelets, prothrombin time, and factors V and VII activities was observed in dying and surviving animals. Just before death, mean prothrombin and factors V and VII activities were respectively 22 +/- 2, 21 +/- 4.4, and 24 +/- 5%. At 22 h, plasma ammonia and lactate levels were respectively 705 +/- 93 micromol/L and 10.5 +/- 0.4 mmol/L in dying animals and 249 +/- 75 micromol/L and 2.9 +/- 0.1 mmol/L in surviving animals (P < 0.01). Estimation of the percentage liver cells necrosed was 74 +/- 4.7% in the survivors and 86 +/- 5.5% in animals who died of hepatic coma (NS). CONCLUSIONS: This model is reproducible and reversible and should allow the quantitative evaluation of new technologies, such as bioartificial liver, for the support of hepatic failure in humans.
Acute Disease↗
Adenosarcoma arising in hepatic endometriosis.
We report a case of adenosarcoma arising in hepatic endometriosis. Both CT and MR scans demonstrated a huge heterogeneous mass containing septated, thick-walled cystic lesions. After enlarged right hepatectomy, the patient was asymptomatic with no abnormalities at liver and abdominal CT scan at 2-year follow-up.
Adenosarcoma↗
Semiautomatic macroencapsulation of large numbers of porcine hepatocytes by coextrusion with a solution of AN69 polymer.
We have previously demonstrated that allogenic and xenogenic hepatocytes macroencapsulated manually in AN-69 polymer and transplanted intra-peritoneally in rats remained viable for several weeks. However, this manual technique is inadequate to encapsulate several billions of hepatocytes which would be required to correct hepatic failure in big animals or humans. In the present study, we developed an original semiautomatic device in which isolated pig hepatocytes and the polymer solution containing 6% poly(acrylonitrile-sodium methallylsulfonate), 91% dimethylsulfoxide and 3% 0.9% NaCl solution were coextruded through a double-lumen spinneret. The extruded minitube (inner diameter: 1.8 mm, wall thickness: 0.07-0.1 mm) containing the encapsulated hepatocytes fell and coiled up in a 0.9% NaCl solution at 4 degrees C and was cut down in 4 m units containing about 120 million hepatocytes. This process allowed to encapsulate 50 million hepatocytes by minute with a preserved immediate cell viability (92 +/- 5%). To test prolonged cell viability after coextrusion, the minitubes were implanted intraperitoneally in rats. Three and seven days after implantation, they were explanted and analyzed. Cells were viable and well-preserved. Therefore, the semiautomatic device appears able to efficiently macroencapsulate in a limited time several billions of porcine hepatocytes which remain viable after transplantation in xenogenic conditions.
Acrylic Resins↗
An observational evaluation of the rate of awakening after isoflurane or desflurane used in daily clinical practice.
STUDY OBJECTIVE: To evaluate the rate of awakening after desflurane (D) or isoflurane (I) anesthesia when used during daily clinical practice. DESIGN: Observational prospective study. SETTING: University-affiliated metropolitan hospital. PATIENTS: 68 ASA physical status I and II patients (18-75 yrs) scheduled for abdominal surgeries. INTERVENTIONS: Patients scheduled for abdominal surgery of various duration received either D or I. No time was specified for discontinuation of the inhaled drugs at the end of the surgery. T0 for recovery parameters was stated as the end of the surgery. A p-value < 0.05 was considered as significant. Results are expressed as medians and ranges. MEASUREMENTS AND MAIN RESULTS: 68 patients (32 in D group and 36 in I group) were analyzed. Patient demographic data were similar between the two groups. Duration of surgery was 151 minutes (83-428 min) and 174 minutes (40-552 min) for I and D, respectively. Extubation occurred earlier after D (18 min [9-35 min]) as compared to I (32 min [7-77 min]). Time to reach the Aldrete score at 10 was faster after D (30 min [12-45]) as compared to I (46 min [15-110]). Unlike I, the rate of awakening after D was independent of the duration of surgery. The differences between D and I reached statistical significance in surgical procedures lasting more than 100 minutes. CONCLUSION: Used during routine conditions, D allows for faster recovery than I in surgical procedures lasting more than 100 minutes. The rate of awakening after D remained independent of the duration of the surgical procedure.
Abdomen↗
[Viability and differentiation of human hepatocytes immunoprotected by macroencapsulation and transplanted in rats].
OBJECTIVES: To determine the viability and differentiation of human hepatocytes immunoprotected by encapsulation and transplanted in rats without immunosuppression. METHODS: Freshly isolated human hepatocytes were encapsulated in hollow fibers and transplanted in the peritoneal cavity of immunocompetent rats. The fibers were explanted for analysis at D3, D7 and D14 following transplantation. Morphological features under light and electron microscopy and gene expression were compared to those of non-transplanted encapsulated hepatocytes (D0). Human cytochrome P450 3A and albumin mRNAs were quantified by Northern blot. Cytochrome P450 3A proteins were detected by Western blot and cytochrome P450 3A enzyme activity was assessed by measuring the formation of 6beta-hydroxytestosterone by high performance liquid chromatography. RESULTS: Transplanted hepatocytes were more than 60 % viable and exhibited morphological criteria of hepatocytic differentiation up to D7. Albumin and cytochrome P450 3A transcripts were also detected up to D14. At D3 and D7, albumin mRNA levels were of 30 %, compared to control D0 hepatocytes, while cytochrome P450 3A5 and cytochrome P450 3A4 mRNA levels were 65 % and 0 %, respectively. Cytochrome P450 3A immunoreactivity was detected by Western blot up to D14 and 6beta-hydroxylase activity was 17 % at D3 compared to D0, supporting with disappearance of cytochrome P450 3A4 mRNA. CONCLUSIONS: Human hepatocytes remain viable for a short period, following encapsulation and intraperitoneal transplantation in rat. Other experimental conditions need to be tested to prevent or delay a decrease in hepatocyte specific gene expression.
Animals↗
Phase I and phase II drug-metabolizing enzymes are expressed and heterogeneously distributed in the biliary epithelium.
Tissue expression of drug-metabolizing enzymes influences susceptibility to drugs and carcinogens. Because the biliary epithelium, exposed to bile-borne chemicals, may give rise to drug-induced cholangiopathies and to cholangiocarcinomas, we determined the pattern of expression of drug-metabolizing enzymes in this epithelium. We first demonstrated by blot analyses that biliary epithelial cells (BEC) isolated from human gallbladders display cytochrome P450 (CYP) 1A, 2E1, and 3A, microsomal epoxide hydrolase (mEH), alpha, mu, and pi glutathione S-transferase (GST), transcripts and proteins. We also identified CYP-associated steroid 6beta-hydroxylase activity in BEC. CYP and mEH expression was 5- to 20-fold lower in BEC than in autologous hepatocytes, and further differed by a higher ratio of CYP3A5/CYP3A4, and by CYP1A1 predominance over CYP1A2. alphaGST was highly expressed in both hepatocytes and BEC, while piGST was restricted to BEC. In approximately 50% of individuals, muGST was expressed in hepatocytes and at lower levels in BEC. By using the same antibodies as those used in immunoblots, we could show by immunohistochemistry that CYP2E1, CYP3A, mEH, alpha, mu, and piGST immunoreactivities are expressed and display a heterogeneous distribution in the epithelium lining the entire biliary tract except for small intrahepatic bile ducts that were devoid of CYP3A and alphaGST immunoreactivities. In conclusion, BEC contribute to phase II, and although to a lesser extent than hepatocytes, to phase I biotransformation. The distribution of drug-metabolizing enzymes in BEC suggest that they are heterogeneous in their ability to generate and detoxicate reactive metabolites, which may contribute to specific distributions of cholangiopathies.
Aryl Hydrocarbon Hydroxylases↗
Restorative proctocolectomy for distal ulcerative colitis.
BACKGROUND: Chronic distal colitis may cause troublesome symptoms and alter quality of life. When medical treatment fails to control symptoms, patients and doctors are often reluctant to consider surgical resection because of the relatively small portion of the large bowel affected by the disease. AIM: To assess the outcome of restorative proctocolectomy (RP) in patients with distal colitis who required surgery for chronic debilitating symptoms and failed medical management. PATIENTS/METHODS: From 1986 to 1996, of 263 patients receiving RP for ulcerative colitis, 27 (16 men) were operated on for distal ulcerative colitis limited to the rectum and sigmoid colon. Bowel function and quality of life were compared before and one year after RP. RESULTS: The mean (SD) duration of ulcerative colitis was 11 (6) years. RP was performed at a mean age of 46 (10) years. All the pouches were J-shaped, and a diverting loop ileostomy was always performed. Mean (SD) hospital stay was 25 (10) days. Seven complications occurred in six patients. Previously unknown severe dysplasia was discovered on the colectomy specimen in two patients. After RP there was a significant decrease in mean (SD) daytime stool frequency (8.2 (4) v 4.7 (2), p<0.05), night-time stool frequency (2 (2) v 1 (1), p = 0.05), and the number of patients with urgency to defecate (26/27 v 1/27, p<0.001). Sex life was improved in eight patients, social life in 26, and professional life in eight. Twenty six patients were satisfied with the results, and 25 wished that they had received surgery earlier in the course of their disease. CONCLUSION: RP can improve bowel function and quality of life in patients with disabling chronic symptoms of distal ulcerative colitis.
Adult↗
Endothelin-1 is synthesized and inhibits cyclic adenosine monophosphate- dependent anion secretion by an autocrine/paracrine mechanism in gallbladder epithelial cells.
Ion and fluid transport across the biliary epithelium contributes to bile secretion. Since endothelin (ET)-1 affects ion transport activities and is released by human gallbladder- derived biliary epithelial cells in primary culture, we examined the expression of ET peptides and ET receptors and the influence of ET-1 on ion transport in this epithelium ex vivo. In freshly isolated gallbladder epithelial cells, preproET-1, -2, and -3 mRNAs were detected by reverse transcription PCR and ET-1 isopeptide was identified by chromatography. The cells also displayed ET receptor mRNAs and high-affinity binding sites for ET-1, mostly of the ETB type. Electrogenic anion secretion across intact gallbladder mucosa was stimulated by forskolin, secretin, and exogenous ATP, as assessed by short-circuit current (Isc) increases in Ussing-type chambers. ET-1 inhibited forskolin- and secretin-induced changes in Isc, without affecting baseline Isc or ATP-induced changes. Accordingly, ET-1 significantly reduced the accumulation of intracellular cAMP elicited by forskolin and secretin in the epithelial cells, and this effect was abolished by pertussis toxin. This is the first evidence that ET-1 is synthesized and inhibits, via a Gi protein-coupled receptor, cAMP-dependent anion secretion in human gallbladder epithelium, indicating a role in the control of bile secretion by an autocrine/paracrine mechanism.
Anions↗
Surgical treatment of severe duodenal polyposis in familial adenomatous polyposis.
BACKGROUND: Patients with familial adenomatous polyposis (FAP) are at risk for adenomas and cancers in the duodenum but the ideal management of duodenal polyposis remains uncertain. METHODS: The outcome of surgical resection was analysed in 18 patients with FAP who had severe duodenal polyposis. RESULTS: Duodenotomy and clearance of duodenal adenomas was performed seven times in six patients. There were two duodenal leaks and, after a mean follow-up of 53 (range 36-72) months, duodenal adenomas recurred in all patients and five had severe polyposis. Pancreatoduodenectomy was performed in seven patients with severe duodenal polyposis. Histology of the specimens revealed two unsuspected duodenal carcinomas at an early stage. After a mean follow-up of 42 months all patients were alive and well, and there was no case of jejunal polyposis. Pancreatoduodenectomy was attempted in five patients with duodenal cancer and only one survived more than 4 years. CONCLUSION: Surgical excision of duodenal adenomas should be discussed before carcinoma occurs. Surgical polypectomy fails to guarantee a polyp-free duodenum and carries a risk of postoperative complications whereas pancreatoduodenectomy eliminates the risk of duodenal cancer with an acceptable morbidity rate. Pancreatoduodenectomy could be offered to some patients with large or multiple villous duodenal adenomas repeatedly showing severe dysplasia.
Adenoma↗