Biomedical subjects
Publications and source records attributed to G Mantion.
We report two cases of amyloid goiter which clinical appearance had evoked a neoplastic lesion. The diagnosis was made by histologic examination. The nature of the amyloid precursor, determined by immunohistochemistry, has allowed to evoke primitive amyloidosis in one case and to attribute amyloid goiter to renal insufficiency in the second case.
OBJECTIVE: To study the possible influence of ursodiol (ursodeoxycholic acid), a hydrophilic bile acid, on cyclosporine (CsA) bioavailability. METHODS: Seven adult liver transplant recipients participated in a randomised cross-over pharmacokinetic study comparing ursodiol (600 mg) with placebo in single doses. Blood concentrations of CsA were measured by HPLC. RESULTS: There was no significant effect of ursodiol on CsA absorption: AUC was 5011 vs 5486 ng.h.ml-1, Cmax was 832 vs 871 ng.ml-1 and tmax was 2 vs 2 h, after ursodiol and placebo, respectively. CONCLUSION: Although a significant period effect was observed, we conclude that a single dose of ursodiol has little effect on CsA absorption in liver transplant patients and that an interaction in the intestinal lumen between these two drugs is unlikely.
Cyclosporin A (CsA) absorption is low and variable after liver transplantation, and during the intravenous-oral transition period CsA concentrations may not be maintained within the therapeutic range. Trough whole blood CsA concentrations were measured by high-performance liquid chromatography before and after the transition period in 27 liver transplant patients. Mean (SD) CsA concentrations decreased from 291 (92) to 198 (96) ng/ml (p < 0.001). When analyzed on individual charts, a decrease was observed in 15 of 27 patients and it was associated with a duration of 2 days or less (p < 0.01) and a total bilirubin value below 3.5 mg/dl (p < 0.05). Our results show that, despite therapeutic drug monitoring, CsA blood concentrations may decrease during the intravenous-oral transition period.
Liver transplantation (LT) is a therapeutic method in many, otherwise infaust diseases of the liver. During the recent decade the experimental therapeutic procedure has become a routine therapeutical method. The stage of clinical experiment was ultimated by the Washington Conference held on the consensus in LT indications (1983). Large centries (USA, England, Germany) yield 80-100 liver transplantations per year. The recent years have recorded a change in some principal opinions on LT. It is possible to state that liver transplantation is being abstained from cases with more extensive primary neoplamatic affliction of the liver. Conservative therapy in primary biliary cirrhosis of the liver by means of ursodeoxycholic acid has shifted the LT indication into the later stages of the disease. The opinions on the meaning of LT in alcoholic cirrhosis remain still unsettled. LT remains unambiquously indicated in life-endangering fulminant and subfulminant liver failures. Among the viral diseases, attention is paid to liver cirrhosis caused by infection by the hepatitis C virus. Cirrhosis due to hepatitis B has a better prognosis, owing to the complex antiviral therapy. Liver transplantation represents, beside the main indications, the therapy of first selection, e.g. also in Wilson's disease, alpha-1-antitrypsin deficiency, alveolar echinococcosis etc. (Tab. 1, Fig. 2, Ref. 54.)
In December 1994, The French Consensus Conference on the Treatment of Rectal Cancer stated that: "Preoperative irradiation improves local control in T3 and T4 resectable rectal cancer patients and is recommended". Recent data indicate that this approach not only reduces local failure but also increases overall survival. The therapeutic ratio depends on the total dose delivered and technical parameters. Inadequate radiotherapy techniques leeds to increased toxicity and masks the potential benefits of the treatment. Combined preoperative chemo-radiotherapy, a promising issue in rectal cancer patients, is now under evaluation in a large European phase III trial (EORTC 22921).
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Liver metabolism may be modified after liver transplantation according to the phenotype of the donor and may be influenced by posttransplantation complications. The CYP2D6 phenotype was assessed in 13 patients (group I) before and after liver transplantation using debrisoquine. CYP2D6 activity was also assessed in vitro on microsomes from the liver of the recipients and the donors, using dextromethorphan. Twelve patients were extensive metabolizers both before and after transplantation. One apparently poor metabolizer was transplanted with the liver of another poor metabolizer. The intrinsic clearance of dextromethorphan (CL(int)) measured on recipient liver microsomes was significantly lower than that on donor liver microsomes (p < 0.05). In extensive metabolizers, the debrisoquine metabolic ratio was correlated with CL(int) before (r = 0.78, p < 0.05) and after (r = 0.89, p < 0.0005) transplantation. Debrisoquine phenotype was measured repeatedly in nine additional patients (group II) up to 3 years after liver transplantation. Their phenotype was stable during the follow-up observation, although the variations observed may be clinically relevant. Therefore, no change in CYP2D6 phenotype (extensive/poor metabolizer) was observed because of the liver transplantation, and the debrisoquine log metabolic ratio was largely unaffected by the liver complications observed during the posttransplantation follow-up observation.
The glucuronoxylomannan component of the Cryptococcus neoformans capsular polysaccharide confers serotype specificity, and its detection in cerebrospinal fluid or serum by the latex agglutination test is used for diagnosis. Low-molecular-weight hydroxyethyl starches can be used as an alternative to albumin for vascular filling. This study reports the occurrence of a false-positive result with the Pastorex Cryptococcus test (Sanofi Diagnostics Pasteur, Marnes la Coquette, France) for a patient receiving hydroxyethyl starch characterized by a substitution ratio of 0.6 (Elohes, Biosedra, Sèvres, France).
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To assess the efficacy of liver transplantation in patients with alcoholic cirrhosis, we compared 2-year survival of 169 liver transplantation patients in 12 French centres with survival of two control groups treated conservatively. The matched group was 169 patients of similar age, cirrhosis severity, and bleeding history; the simulated group was 169 patients whose theoretical survival was determined in a cohort of 797 patients with alcoholic cirrhosis. The probability of survival to 2 years in transplanted patients was 73 (95% confidence interval 67-79%) versus 67% (59-75) in the matched and 67% (63-71) in simulated controls. When prognostic factors were taken into account, transplantation was associated with survival (r = 0.527; p = 0.069). Patients with severe liver disease (high-risk group) benefited most for 2-year survival: 64% (42-86) vs 41% (23-59) in the matched and 23% (19-27) in the simulated control groups (p < 0.01). There was no difference for patients at low and at medium risk. Liver transplantation increases the 2-year survival of patients with severe alcoholic cirrhosis. In patients with less severe disease, further studies should be done by non-randomised controlled studies with longer follow-up or by randomised trials.
OBJECTIVES: The aim of this prospective study was to evaluate and to compare the results of the circular fundoplication (Nissen) and the posterior hemifundoplication (Toupet) for the treatment of gastro-oesophageal reflux. METHODS: For each of the 71 included patients (Nissen, n:43; Toupet, n:28) the following data were collected: surgical complications, clinical symptoms, pH-metric and manometric data, before and 4 and 28 months after operation. RESULTS: Rates of perioperative complications were 26% and 7% in the Nissen and Toupet groups respectively. The Nissen induced more late complications (14%) than the Toupet (0%). At early postoperative evaluation (mean follow-up: 4 months), the rates of clinical and pH-metric recurrences were 2% and 2.5% respectively in the Nissen group and 4% and 9% in the Toupet group (NS). Thirty-seven percent of the patients in the Nissen group and 38% in the Toupet group experienced dysphagia (NS). Disturbances in oesophageal motility, which were present in both groups before surgery, were not significantly modified. At the late evaluation (mean follow-up 28 months), some symptoms of reflux were present in 8% and 17% of patients of the Nissen and Toupet groups respectively (NS). The pH-metric recurrence rate was 10% versus 44% in the Nissen and Toupet groups respectively (P < 0.01). Dysphagia was present in 39% of patients in the Nissen group versus 13% in the Toupet group (P < 0.02). Oesophageal motility remained unchanged in the Nissen group whereas it was significantly improved in the Toupet group where the peristaltic velocity rose from 3.2 cm/s before surgery to 4.4 cm/s after (P < 0.05), giving a value comparable to that of controls (4.2 cm/s). CONCLUSIONS: These results suggest that the short term effectiveness of both procedures is comparable. The effectiveness of the Nissen is more durable, but its morbidity is higher than for the Toupet. Moreover, oesophageal motility is significantly improved by the latter.
The liver tissue mRNA expression of protooncogenes c-fos, c-myc, c-Ha-ras, c-met and c-erb B1, and TGF alpha and TGF beta genes is sequentially and temporarily increased in the early stages after partial hepatectomy, ischaemia or other mitogenic stimuli. These gene expressions were studied in 38 samples of liver tissue from 24 patients who underwent orthotopic liver transplantation, at different evolution stages. Eleven samples were obtained from surgical liver biopsies before graft implantation at day 0 (Group A), 14 samples from percutaneous liver biopsies during the post-operative period from day 9 to day 48 (Group B) and 13 samples in the long-term follow-up period from day 102 to day 1,382 (Group C). Gene expression was studied using 32P-labeled cDNA and oligonucleotidic probe hybridization in slot blots. A GAPD gene was used as a control gene. All expression values of protooncogenes were related to those of the GAPD gene. After cold ischaema, the relative gene expression (quantity of specific mRNA/quantity of GAPD mRNA ratio) tended to diminish in most cases. The relative expressions of c-fos, c-myc, c-Ha-ras, c-met and TGF alpha gene were correlated at day 0. During and after the liver transplantation, an overexpression of c-fos, c-myc, c-Ha-ras, c-met and TGF alpha was observed in different pathological conditions such as cold ischaemia and conservation injury, acute rejection, and cytomegalovirus infection. In three cases the relative expression values of c-fos, c-myc and c-Ha-ras increased over long-term follow-up without any associated acute pathology. These results suggest the necessity of an intercellular mediation--by means of graft reperfusion--in induction of hepatocyte proliferation and regeneration of the transplanted liver.
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Orthotopic liver transplantation has been considered as one of the therapeutic tools in certain patients with hepatocellular carcinoma. In our liver Unit in Besançon, 17 patients with hepatocellular carcinoma were treated by orthotopic liver transplantation between March 1986 and December 1991. This series included 14 men and 3 women. The mean age was 51 years (range: 36-62). In 11 cases, hepatocellular carcinoma was multifocal and larger than 5 cm, in 6 cases, the tumor was encapsulated, and was well differentiated in 11 cases. Lymph node invasion was observed in 2 cases and the portal vein was invaded in 5 cases. Before orthotopic liver transplantation, alpha foetoprotein was increased in 10 cases. Kaplan-Meier actuarial survival was 76%, 53%, 40%, at one, two and three years, respectively, and remained unchanged at four years. There were 9 recurrences of hepatocellular carcinoma. There were 8 deaths, 4 due to a tumor recurrence. A tumor larger than 5 cm was the only parameter statistically associated with recurrence in this study.
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