Biomedical subjects
Publications and source records attributed to J Domergue.
We report the first case of leiomyosarcoma of the middle and upper part of the vena cava successfully treated by surgical resection, complete vena cava replacement and disobliteration of the hepatic veins under veno-venous bypass and liver hypothermic perfusion as described in "ex situ, in vivo liver surgery".
In this paper we report three cases of solitary pancreatic metastasis from renal cell carcinoma (RCC), treated surgically. Various features and the surgical approach of these metastases are discussed with references to the 33 previous published cases collected in the literature. Having eliminated widespread distant metastases, it is reasonable to restrict surgical resection of the pancreas to selected patients having a single synchronous or metachronous metastasis, or those having several unilateral metastatic foci. At any rate a careful long-term follow-up for patients with a past history of RCC is mandatory.
PURPOSE: To assess computed tomography (CT) with iodized oil for depiction of small hepatocellular carcinoma (HCC) before liver transplantation. MATERIALS AND METHODS: Thirty-five consecutive cirrhotic patients underwent CT with iodized oil to determine the presence, number, size, and location of possible nodules. All patients underwent liver transplantation within 4 months after CT. Explanted livers were cut in 8-mm slices that corresponded to axial CT scan planes. Comparison between CT staging and pathologic findings was made. RESULTS: Pathologic studies showed 17 HCC nodules (diameter, 0.9-4.0 cm) in nine of the 35 livers. CT depicted nine of these 17 nodules. Lesion-by-lesion analysis revealed a sensitivity of 53%; CT falsely depicted three additional nodules not confirmed with pathologic findings. Patient-by-patient analysis revealed an 89% sensitivity and an 88% specificity. CONCLUSION: CT with iodized oil, when assessed lesion by lesion, has a low sensitivity. These results must be considered when liver resection is proposed for HCC.
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We have investigated the effect of cytokines, including interleukin-6 (Il-6), interleukin-1 alpha (Il-1 alpha), and tumor necrosis factor-alpha (TNF-alpha), on the inducible expression of cytochrome P450s (CYP) CYP1A1, CYP1A2, and CYP3A4 in human hepatocytes in primary culture. The ability of these cultures to mimic the acute phase response when stimulated with cytokines was evaluated using immunoblotting to measure the production of albumin, ferritin, fibrinogen, and ceruloplasmin. The cytokines exhibited specific patterns of action on the production of these proteins. Albumin was depressed by all the cytokines. In contrast to Il-6 and Il-1 alpha, TNF-alpha reduced the production of fibrinogen and ceruloplasmin but stimulated the production of ferritin. When cells were treated with the CYP inducer alone, large increases in the expression of CYP1A1 and CYP1A2 by beta-naphthoflavone and of CYP3A4 by rifampicin were observed at messenger RNA (mRNA) and protein levels, by ribonuclease protection and immunoblotting, respectively. When the cells were treated with the inducer plus cytokines, the induction of mRNA was greatly reduced. Again, specific patterns of action were revealed: Il-6 had the most potent effect on CYP3A4, whereas TNF-alpha was the most potent with CYP1A genes. In all cases, changes at the protein levels paralleled changes at the mRNA levels. In cells preinduced with beta-naphthoflavone or rifampicin, the decay with time of the levels of the CYP1A2 or CYP3A4 proteins, after the removal of the inducer, was not affected by cytokines. We conclude that cytokines strongly repress the inducibility of CYP1As and CYP3A4 genes at a transcriptional or a posttranscriptional level, but affect neither the rate of translation of CYP mRNAs nor the rate of degradation of the CYP proteins in these cultures.
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We report a case of pancreatic fistula attributable to posttraumatic rupture of the main duct that was undiagnosed before ERCP and was cured instantaneously by endoscopic placement of an endoprosthesis in the pancreatic duct after failure of conventional medical treatment.
We report herein the case of a patient who developed fatal acute graft-versus host disease (GvHD) after liver transplantation (LT). GvHD occurred 18 days after LT and was characterized by skin epidermolysis, diarrhea and leucopenia. Skin biopsy showed epidermal dyskeratosis with epithelial necrosis, a lesion consistent with GvHD. Despite immunosuppressive therapy, the patient died within 24 days. In our observation, GvHD occurred although five HLA compatibilities were identified between the donor and the recipient, an apparently favorable and uncommon situation. This case further supports the qualification that LT may be complicated by GvHD and strongly suggests that minor rather than major histocompatibility antigens are the main target of allogenic interactions of GvHD. The involvement of chimerism in GvHD is controversial and requires further investigation.
The aim of this work was to identify the form(s) of human cytochrome P450 (P450) involved in the hepatic biotransformation of lansoprazole to its two main metabolites, i.e., the sulfone and the hydroxy derivative. In liver microsomes, the production of the sulfone of lansoprazole correlated with the level of P450 3A4, cyclosporin oxidase, and the production of the hydroxy derivative, as well as of omeprazole sulfone. The production of hydroxylansoprazole moderately correlated with the level of P450 3A4, cyclosporin oxidase, and (S)-mephenytoin 4'-hydroxylase. The production of the sulfone and of the hydroxy derivative of lansoprazole was significantly inhibited by anti-P450 3A4 antibodies, by cyclosporin and ketoconazole, and by tolbutamide. Anti-P450 2C8 and 2C3 antibodies moderately inhibited the biotransformation of lansoprazole, whereas they completely inhibited (S)-mephenytoin 4'-hydroxylase activity under the same conditions. In primary cultures of human hepatocytes, the biotransformation of lansoprazole and the oxidation of cyclosporin were strongly increased by rifampicin and phenobarbital, whereas (S)-mephenytoin 4'-hydroxylation was not. beta-Naphthoflavone did not induce the formation of the sulfones but stimulated the production of hydroxylansoprazole. Among several forms of cDNA-expressed human P450s, 3A4 generated significant amounts of the sulfones of lansoprazole and omeprazole and 2C18 was active for the production of hydroxylansoprazole but inactive in the 4'-hydroxylation of (S)-mephenytoin. We conclude that P450 3A4 is the major enzyme involved in the production of the sulfone of lansoprazole and that this P450, as well as P450 2C18 and/or another 2C-related form, could contribute to the production of hydroxylansoprazole.
The most common sites of hydatid disease (HD) are represented by the liver and the lungs. In 10% of cases, HD arises in unusual viscera: mainly spleen (0.9 to 8%) and also kidney, bones, heart, brain, peritoneum (0.5 to 5%). Other exceptional location was described in less than 1% of all cases of hydatid cysts. Ultrasonography and CTscan are highly suggestive of HD, while serologic tests are variable. The cysto-pericystectomy is the gold standard procedure but sometimes unsuitable for particular sites. In that cases a conservative approach (partial pericystectomy) is mandatory to preserve the organ function. The place of adjuvant medical treatment remains questionable.
The aim of this study was to identify the form(s) of cytochrome P450 (CYP) responsible for the biotransformation of zolpidem to its alcohol derivatives which, after rapid conversion to carboxylic acids, represents the main way of metabolism in humans. In human liver microsomes, zolpidem was converted to alcohol derivatives. Production of these correlated with the level of CYP3A4 and with cyclosporin oxidation and erythromycin N-demethylation activities, but not with the level of CYP1A2 nor with ethoxyresorufin O-deethylation or S-mephenytoin 4'-hydroxylation activities. Liver microsomes from CYP2D6-deficient patients exhibited normal activity. Production of alcohol derivatives was significantly inhibited by anti-CYP3A antibodies and by ketoconazole. Antibodies directed against other CYP forms (including CYP1A1, CYP1A2, CYP2A6, CYP2B4, and CYP2C8), and CYP-specific substrates or inhibitors (including propranolol, coumarin, mephenytoin, sulfaphenazole, quinidine, aniline, and lauric acid) produced a moderate or no inhibitory effect. cDNA-expressed CYP3A4 and CYP1A2 generated significant amounts of one of the alcohol derivatives, whereas CYP2D6 generated both of them in similar amounts. In human hepatocytes in primary culture, zolpidem was extensively and almost exclusively converted to one of the carboxylic acid derivatives, the main species identified in vivo. Treatment of cells with inducers of CYP1A (beta-naphthoflavone) and CYP3A (rifampicin and phenobarbital) greatly increased the rate of production of this metabolite. We conclude that the formation of alcohol derivatives of zolpidem is rate-limiting and principally mediated by CYP3A4. Both CYP1A2 and CYP2D6 participate in alcohol formation; but, because of their low relative level of expression in the human liver, their contribution is minor.
OBJECTIVES: To evaluate the medical (sexual dysfunction, psychological adjustment, stoma care) and social (working life, family life, leisure) consequences of definitive ileostomies or colostomies. METHOD: From February 1992 to May 1992, 1082 live patients (978 colostomies and 104 ileostomies) who had undergone surgery at least 6 months earlier were assessed in a multicentre national inquiry. RESULTS: More than 20% of the patients had not been informed before surgery of the possibility of a definitive stoma. In half of the cases, the stoma was well accepted psychologically and patient's primary reactions improved with time, especially in patients with ileostomy (p < 0.01) and patients under 60 years of age (p < 0.001). Patients were satisfied with their stoma appliance in 94% of the cases. Only 31% with colostomy performed irrigations. Life style was altered in 43% of the patients, especially those with ileostomies (p < 0.001). Sexual activity was disturbed in 55% of the colostomy patients and working life in 63% of the ileostomy patients. One-fourth of the patients were often followed by an enterostomal therapist and one-third were members of ostomate associations. CONCLUSIONS: Ileostomy appears to be more disabilitating than colostomy due to patient age and, unlike colostomy, the impossibility of irrigation. These findings emphasize the contribution of enterostomal therapy and the justified role of ostomate associations.
From January 1990 to December 1992, 129 patients presenting complicated cholelithiasis were included in a prospective study to assess the feasibility and efficiency of laparoscopic cholecystectomy. There were 84 females (65%) and 45 males (35%). Mean age was 60 years (range from 23 to 88). There were 90 acute cholecystitis (70%), 14 empyema (11%), 14 cholecystitis on scleroatrophic gallbladder (11%), and 11 mucocele (9%) cases. Laparoscopic cholecystectomy has been successfully performed in 106 cases (82%) (group I). In this group of patients, morbidity and mortality were 4.7% and 0.9% (n = 1), respectively. Mean hospital stay was 4.7 days after uneventful postoperative course. Two patients required reoperation for complications (1.8%). Twenty-three patients (18%) required enforced conversion to laparotomy after unsuccessful laparoscopic procedure (group II). Mean hospital stay was significantly higher in group II (10.8 days, P = 0.0001). There was no difference between the two groups according to sex, previous surgery, or indications. Laparoscopic cholecystectomy may be attempted and successfully realized in complicated cholelithiasis without morbidity increase. Main advantages of this procedure are a shorter hospital stay and a better recovery period.
We report a carcinosarcoma (CS) of the gallbladder in an 83-year-old woman. Ultrasonography found an enlarged gallbladder with thickened walls, a 3-cm gallstone, and a polypoid mass in the fundus. Pathological examination revealed neoplastic tissue composed of sarcomatous and glandular components. Twelve months later, the patient is alive. We review 24 other cases in the literature to outline the characteristics of this tumor.
Laparoscopic intestinal anastomosis is not very reliable and needs to be evaluate in an experimental model in animals before being performed in man. The purpose of this study was to evaluate the feasibility, efficacy and safety of manual anastomosis comparatively to the standard stapling suture. Twenty female pigs weighing 20 +/- 5 kg. were used for this study. A 5 cm ileal segment resection was performed under laparoscopy. The animals were assigned to 2 groups. Group I: 10 animals underwent end-to-end hand-swen anastomosis with Polyglactin 910, dec 1.5. Group II: 10 animals underwent side-to-side anastomosis using the Endo stapler. Operating time and anastomosis time were compared using the Mann-Whitney test for statistical analysis. On the 15th postoperative day, the animals were sacrificed and the anastomoses were evaluated. There was no operating death in the 2 groups. The operative time was significantly longer in group I than in group II (p < 0.01), with 180 +/- 40 min vs 49 +/- 25 min respectively. This difference was due to the anastomosis time of 130 +/- 40 min vs 16 +/- 6 min respectively (p < 0.01). There was 1 postoperative death related to fistula and peritonitis in group I and none in group II. The post-operative follow-ing showed 5 anastomotic leakages (4 in group I and 1 in group II) and 2 relative stenoses in group I. This study shows the simplicity and rapidity of performing stapling intestinal anastomosis under laparoscopy. Hand-sewn anastomosis is technically more difficult to perform under laparoscopy and requires a greater experience.
The ability of several gastric antiulcer drugs including lansoprazole, cimetidine and ranitidine to affect the expression of human liver microsomal cytochromes P450 comparatively to omeprazole, reported previously to be a CYP1A inducer, was evaluated in primary cultures of human hepatocytes. Poly (A)+ RNA and microsomes extracted from the cells were analyzed in Northern and Western blots with specific cDNA probes and antibodies, and assayed for form-specific monoxygenase activities. Lansoprazole induced both CYP1A1 and CYP1A2 as omeprazole and did not apparently bind to the aryl hydrocarbon receptor with high affinity. Omeprazole sulfone was not an inducer of CYP1A. Omeprazole, omeprazole sulfone and lansoprazole induced CYP3A in approximately 50% of tested cultures, whereas 100% of tested cultures responded to omeprazole and to rifampicin in terms of CYP1A and CYP3A induction, respectively. Finally, cimetidine and ranitidine were not inducers. We conclude that omeprazole and lansoprazole constitute a new class of mixed inducers of CYP1A and CYP3A in human hepatocytes in primary culture and that the induction of CYP3A in response to these molecules could be polymorphic in humans.
The aim of this work was to determine whether the extensive metabolism of cyclosporine, acquired in a donor by treatment with an inducer of cytochrome P450 3A (P450 3A) (cyclosporine oxidase), was transmissible to the recipient by orthotopic liver transplantation. For this purpose, male Wistar rats were divided into five groups including: control animals (group C), animals treated with dexamethasone (an inducer of P450 3A, 50 or 300 mg/kg/day, for 4 days, group D), animals transplanted with the livers of control rats (group G) or with the livers of dexamethasone-induced rats (group GD), and animals treated with beta-naphthoflavone (an inducer of P450 1A, group B). All animals received a single i.v. dose of 10 mg/kg cyclosporine 24 hr after either the last dose of inducer or the transplantation. For each group of animals, the area under the curve (AUC) of cyclosporine was calculated from the curves of blood cyclosporine levels (by radioimmunoassay) against time; liver microsomes were assayed for cyclosporine oxidase activity by HPLC, erythromycin demethylase and P450 3A level by western blot with specific anti-P450 3A antibodies. The decrease in the AUC in groups D and GD with respect to C and G was correlated with increased level of P450 3A (4-5-fold with respect to control) as well as of microsomal cyclosporine oxidase. In addition, cyclosporine oxidase activity of liver microsomes was specifically inhibited by anti-P450 3A antibodies and troleandomycin. The animals in group B did not exhibit increased metabolism of cyclosporine either in vivo or in vitro. We conclude that: (1) cyclosporine is predominantly oxidized in the rat liver by a form of P450 from the 3A subfamily; (2) the extensive metabolism of cyclosporine acquired by donor rats after treatment with dexamethasone is transmissible to the recipients through orthotopic liver transplantation.