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J Domergue

Publications and source records attributed to J Domergue.

At least 19 recordsLinked to original sources
PubMed1992

Omeprazole, an inducer of human CYP1A1 and 1A2, is not a ligand for the Ah receptor.

Omeprazole is a benzimidazole derivative which induces both P450 1A1 and 1A2 in human liver in vitro and in vivo. Northern blot analysis of polyA RNA prepared from primary cultures of human hepatocytes indicates that both 1A1 and 1A2 messages are induced by beta-naphthoflavone and omeprazole. Co-treatment of cells with these inducers and with actinomycin D or cycloheximide results in no accumulation of both mRNA or superinduction of 1A1 mRNA, respectively. 9S enriched fraction of cytosol was prepared either from human hepatocytes in culture or from human liver tissue and analyzed by sucrose density gradient sedimentation for its capacity to bind 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), omeprazole or omeprazole sulfone (a metabolite of omeprazole in man). Whereas 2 microM TCDD displaced almost totally [3H]TCDD from the Ah receptor, both omeprazole and omeprazole sulfone did not, even at 5000-fold molar excess. In addition, when [14C] omeprazole was incubated with 9S enriched fraction of human liver or hepatocyte cytosol, no interaction could be detected in sucrose density gradient. These experiments suggest that omeprazole is not a ligand for the human liver Ah receptor.

Adult↗
PubMed1992

Effects of imidazole derivatives on cytochromes P450 from human hepatocytes in primary culture.

The expression of several forms of cytochrome P450 including P450 1A2, 2D6, 2E1, and 3A was investigated in human hepatocytes maintained in primary culture for 96 h in the absence or presence of 50 microM of various imidazole derivatives. These included ketoconazole, clotrimazole, miconazole, fluconazole, secnidazole and metronidazole. In addition, the typical inducers rifampicin and beta-naphthoflavone were used for comparison. Western and Northern blot analysis of microsomes and RNA prepared from these cultures as well as de novo synthesis experiments revealed that, among the imidazole derivatives tested, only clotrimazole was a strong rifampicin-like inducer of P450 3A. The expression of the other forms of P450 tested was not affected by the treatments. Analysis of the inhibition of 13 monoxygenase activities, including ethoxyresorufin and phenacetin O-deethylases, coumarin 7 alpha-, lauric acid 11- and 12-, mephenytoin 4-, debrisoquin 4-, and aniline hydroxylases, benzphetamine, aminopyrine, mephenytoin and erythromycin demethylases, and cyclosporin oxidase (representative of 10 different forms of P450 in human liver microsomes) revealed that ketoconazole was a strong and selective in vitro inhibitor of P450 3A (cyclosporin oxidase) with a Ki less than 1 microM. Clotrimazole and miconazole were also strong inhibitors of P450 3A-mediated activities in contrast to the other imidazole derivatives.

Blotting, Northern↗
PubMed1992

[Cyclosporin A metabolism and induction of cytochrome P-450 in orthoptic hepatic transplantation in rats].

The aim of our study were 1) to establish that cyclosporin (CsA) metabolism was correlated with the rate of cytochrome P4503A (cyt.) in Wistar rats induced with dexamethasone (Dex.), 2) to demonstrate that the induction of cyt. with Dex. in liver "rat donor" was transmissible to "recipient rat" after liver transplantation. Sixty rats were divided in 5 groups. In group T, a single dose of CsA (10 mg/kg) was administered intravenously in 10 rats; in group D, 10 rats were treated with Dex (300 mg/kg daily for 4 days) and then received CsA as above; in group BN 5 rats were treated with beta-naphthoflavone. Thirty five rats underwent a liver transplantation either from "non induced donors" (group G, n = 11) or from "induced donors with Dex." (group GD, n = 24) followed by CsA injection the next day. For each rat, CsA plasma levels were determined by radioimmunoassay in 6 samples. Liver microsomes cyt. from samples of the liver of donor rats (group G and GD) or after sacrifice (group T, D, BN) were quantitated by immunoblot analysis and estimated from densitometric analysis of the blot. Mean maximal plasma concentration (Cmax) were 2,822 +/- 997 ng/ml in group T, 1,447 +/- -458 ng/ml in group D, 2,685 +/- 1,383 ng/ml in group G, 1,337 +/- 713 ng/ml in group GD and 3,094 +/- 685 ng/ml in group BN. Considering the Cmax and the ASC (area under curve), there was a significant difference between all groups and separately between groups T and D, G and GD.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Mitotic responsiveness of cultured adult human hepatocytes to epidermal growth factor, transforming growth factor alpha, and human serum.

The present study was undertaken to evaluate the ability of human hepatocytes to respond in culture to various mitotic agents including epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), or serum from patients with fulminant hepatitis. Human hepatocytes were maintained in culture on collagen-coated plates in a chemically and hormonally defined serum-free medium at low cell density. Twelve hours after plating, cultures were treated with increasing amounts of EGF (1-100 ng/mL), TGF-alpha (1-100 ng/mL), or human serum (1%-10%) for 0-96 hours. Proliferative response was assessed by determining against time the rate of DNA synthesis by [3H]thymidine incorporation in DNA, the labeling index, the expression of cyclin A, the amount of DNA, and the number of cells. The rate of DNA synthesis reached a maximum after 48 hours of treatment with 20 ng/mL EGF, 40 ng/mL TGF-alpha, or 5%-10% of human serum (fulminant hepatitis); the average increase with respect to untreated cells was 4.35 times with EGF, 5.4 times with TGF-alpha, and 4-6 times with serum from patients with fulminant hepatitis. The maximum expression of cyclin A coincided with the maximum of DNA synthesis. After 72 hours of treatment with EGF or human serum (fulminant hepatitis), the amount of DNA increased by 75%-100% (P less than 0.001) and the number of cells by 50% (P less than 0.001). These results show that adult human hepatocytes respond to mitogens, as expected from previous studies on animal hepatocytes, and provide experimental basis for future investigations in the field of human liver regeneration.

Adult↗
PubMed1992

[Celioscopic cholecystectomy in simple and complicated cholelithiasis. Apropos of 392 cases].

In a study including 392 patients we compared two groups of patients according to the indication for laparoscopic cholecystectomy: group I: 293 patients treated for simple cholelithiasis (n = 291) or gallbladder polyps (n = 2). Group II: 99 patients operated for complicated cholelithiasis. For each patient, 14 pre, intra and postoperative parameters were analysed and compared. Mean operative time was 80 minutes. Primary and secondary laparotomies were necessary in 5.8% and 1.3% of cases respectively. Biliary injury was the most frequent complication (1.3%). Mean hospital stay was 4.5 days. In terms of mean age, operative time, intraoperative incidents and complications, and primary laparotomy. There was a significant difference between the two groups (p less than 0.001). There were 4 secondary laparotomies in group II and one in group I. These results suggests that laparoscopic cholecystectomy is a safe technique with a low mortality rate (0.25%). The comparative study proves that this technique, first indicated for simple cholelithiasis, is also applicable to the majority of complicated cholelithiasis.

Acute Disease↗
PubMed1992

Effect of corticosteroids on the expression of cytochromes P450 and on cyclosporin A oxidase activity in primary cultures of human hepatocytes.

Prednisone, prednisolone, and methylprednisolone are currently administered in association with cyclosporin A in the postoperative treatment of transplant patients. The aim of this work was to evaluate the effects of these corticosteroids on the expression of several forms of cytochromes P450 (P450), including P450 1A2, 2D6, 2E1, and 3A, and on cyclosporin A oxidase activity in human liver. For this purpose, human hepatocytes prepared from lobectomies were maintained in culture in a serum-free medium, in collagen-coated dishes, for 96-144 hr, in the absence or presence of 50-100 microM corticosteroids, rifampicin, or dexamethasone. To mimic more closely the current clinical protocol, hepatocyte cultures were also co-treated with corticosteroids and cyclosporin A or ketoconazole (a selective inhibitor of P450 3A). Cyclosporin A oxidase activity, intracellular retention of cyclosporin A oxidized metabolites within hepatocytes, accumulation of P450 proteins and corresponding messages, and de novo synthesis and half-lives of these P450 were measured in parallel in these cultures. Our results, obtained from seven different hepatocyte cultures, showed that 1) dexamethasone and prednisone, but not prednisolone or methylprednisolone, were inducers of P450 3A, at the level of protein and mRNA accumulation, as well as of cyclosporin A oxidase activity, known to be predominantly catalyzed by these P450; 2) although corticosteroids are known to be metabolized in human liver, notably by P450 3A, partial or total inhibition of this P450 by cyclosporin or ketoconazole, respectively, did not affect the inducing efficiency of these molecules; 3) corticosteroids did not affect the half-life of P450 3A or the accumulation of other forms of P450, including 1A2, 2D6, and 2E1; 4) chronic treatment of cells with cyclosporin did not affect P450 3A accumulation; 5) corticosteroids were all competitive inhibitors of cyclosporin A oxidase in human liver microsomes, with Ki values of 61 +/- 12, 125 +/- 25, 190 +/- 38, and 210 +/- 42 microM for dexamethasone, prednisolone, prednisone, and methylprednisolone, respectively; and 6) chronic treatment of cells with corticosteroids did not influence the excretion of oxidized metabolites of cyclosporin from the cells. These results support most of clinical reports dealing with mutual interactions between cyclosporin A and corticosteroids.

Adrenal Cortex Hormones↗
PubMed1991

[Heterotopic hepatic transplantation. Apropos of a case treated in the terminal stage of decompensated alcoholic cirrhosis].

Heterotopic liver transplantation is an exceptional indication for acute or chronic liver disease. The authors report a case of auxiliary liver transplantation performed for end-stage alcoholic cirrhosis. The patient was contra-indicated for orthotopic transplantation because of poor general and nutritional status. The HLT was indicated because of intractable ascites, liver insufficiency and chronic encephalopathy. The operation was performed according to the technique described by Fortner. Liver function tests returned to normal within 3 days and the only postoperative complication were gastro-intestinal bleeding due to CMV viral infection. Liver function was assessed by HIDA scintigram which showed blood intake by the graft and atrophy of the native liver. The patient was discharged after 3 months. The follow-up is 17 months. At the 15th month control, liver CT showed multiple hypodense nodules biopsied and corresponding to metastasis from a probable pancreatic carcinoma. ERCP and morphologic explorations did not show the primary tumor. The authors discuss the indications of HLT, the rules of successful performance of HLT and the problem of the graft involvement by metastases.

Hemodynamics↗
PubMed1991

[A prospective and comparative study of 262 laparoscopic cholecystectomies].

A prospective, comparative study is made of 262 patients (195 males, 67 females) subjected to laparoscopic cholecystectomy. Two groups were considered: simple cholelithiasis (SC) (187 cases), and complicated cholelithiasis (CC) (75 cases: 63 acute cholecystitis, 8 hydrocholecystitis, 4 pancreatitis). Mean age was 51 among the SC cases, and 57 in the CC patients. Mean operating time was 67 and 96 minutes for the SC and groups, respectively. Preoperative complications were more frequent in the CC group (51.4%) than in the SC patients (24%)--immediate laparotomies being performed in 2 and 25% of the SC and CC patients, respectively. Mortality was zero, with similar morbidity in both groups. Mean hospitalization time was 4.9 and 3.4 days for the CC and SC groups, respectively.

Age Factors↗
PubMed1991

[Treatment of exocrine pancreas tumors].

A review of the literature over the last five years reveals that the results of treatment of pancreatic carcinoma have barely improved over the last thirty years, except in terms of the operative mortality which has markedly improved over the last decade. Pancreatectomy still constitutes the only, although slight, chance of cure. It must be reserved to the rare macroscopically curable cases, i.e. small tumours of the head of the pancreas, apparently confined to the pancreas. Palliative treatments should preferably be surgical. Endoscopic biliary drainage should only be performed in inoperable cases. Adjuvant radiotherapy and chemotherapy must be integrated into curative and palliative strategies. These various therapeutic modalities can only be evaluated by means of prospective studies and controlled trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Intrahepatic bile duct cystadenocarcinoma: case report and imaging diagnosis.

The authors report the 30th case in the literature of cystadenocarcinoma of the liver and the second case arising in the caudate lobe. This case illustrates the 2 main questions raised by this tumor: the importance of differentiating benign and malignant cystadenoma and bile duct cyst on sonographic and scanographic aspects and the surgical management of these tumors of the liver, especially in this malignant centrohepatic case.

Bile Duct Neoplasms↗
PubMed1990

[Ileal pouch in the treatment of ulcerative rectocolitis and familial polyposis. Analysis of morbidity in a series of 30 cases].

Between 1984 and 1989, 30 patients underwent total coloproctectomy with J ileal pouch and ileo-anal anastomosis. They corresponded to 29 cases of ulcerative colitis and one case of familial polyposis. The authors report their own experience and the related morbidity and functional results. There were 23% fistulae, 6.6% pouchitis, 10% stenoses, 8.7% pelvic abscesses, 10% bowel obstructions, 6.6% fistulae after ileostomy closure. Only one pouch had to be removed for severe pouchitis. Functional results were partly related to post-operative complications: 50% of patients had normal continence, 57% at least 6 stools per day, 81% had one stool per night, 15% had soiling. Morbidity is discussed for the various types of complications.

Adenomatous Polyposis Coli↗
PubMed1990

The thumb and index finger as principal surgical instruments to secure the inferior vena cava between the liver and the diaphragm in routine operations of the liver.

Presented herein is a simple and safe technique to secure the IVC in its segments above the liver and below the diaphragm through a simple incision in the abdomen. After complete division of the hepatic ligaments, the index finger is passed through the upper recessus of the lesser sac, behind the vein, and just above the caudate lobe, meeting the right thumb on the right side of the vein. A tissue string is then passed, and the IVC is secured. The experience of the authors with more than 100 consecutive hepatectomies has shown this technique to be a reliable approach to secure the IVC during routine hepatic operations.

Diaphragm↗