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Biomedical subjects

Pierre Bernard

Publications and source records attributed to Pierre Bernard.

16 recordsLinked to original sources

Management of digestive bleeding related to portal hypertension in cirrhotic patients: A French multicenter cross-sectional practice survey.

AIM: To investigate the conformity of management practices of gastrointestinal hemorrhage in cirrhotic patients with relevant guidelines. METHODS: A questionnaire on the management of digestive bleeding was completed for all consecutive cirrhotic patients admitted to 31 French hospitals. RESULTS: One hundred and twenty-six bleeding events were recorded. It was the first bleeding episode in 79 patients (63%), of whom 40 (51%) had a prior diagnosis of cirrhosis and 25 (32%) had previously undergone an endoscopy. The bleeding episode was a recurrence in 46 patients (37%). The median time between onset and admission was 4 h, but exceeded 12 h in 42% of cases. There was an agreement between centers for early vasoactive drug administration (87% of cases), association with ligation (42%) more often than sclerosis (21%) at initial endoscopy, and antibiotic prophylaxis (64%). By contrast, prescription of beta-blockade alone or in combination (0 to 100%, P = 0.003) for secondary prophylaxis and lactulose (26% to 86%, P = 0.04), differed among centers. CONCLUSION: In French hospitals, management of bleeding related to portal hypertension in cirrhotic patients is generally in keeping with the consensus. Broad variability still remains concerning beta-blockade use for secondary prophylaxis. Screening for esophageal varices, the use of antibiotic prophylaxis and patients information need to be improved.

Adrenergic beta-Antagonists↗

High dose daily interferon-alpha induction and secondary adjunction of ribavirin in treatment-naive patients with chronic hepatitis C. A multicentric, randomised, controlled trial.

OBJECTIVES: To evaluate in naive patients with chronic hepatitis C 1- the efficacy and safety of one month interferon alpha (IFN-alpha) induction regimen; 2- the potential virological benefit of a secondary adjunction of ribavirin among HCV RNA negative patients after 20 weeks of IFN therapy, with or without an initial 4-week IFN induction. MATERIAL AND METHODS: 151 naive HCV-RNA positive patients presenting with biopsy- proven chronic hepatitis C and elevated ALT were randomised in a 2: 1 ratio in two arms: IFN-alpha 3 MU thrice a week (tiw) for 24 weeks (non-induced patients); IFN-alpha 6 MU daily for two weeks, then 3 MU daily for two weeks then 3 MU tiw for 20 weeks (induced patients). At week 24, HCV-RNA negative patients were randomised to receive in addition or not ribavirin 1-1.2 g daily for 24 additional weeks. Induction efficacy was assessed on the early viral response (EVR) defined as undetectable HCV RNA at week 4 then week 20. Ribavirin efficacy was assessed on the proportion of maintained complete response until the end of follow-up, 24 weeks after discontinuation of treatment. Data were analysed on an intent-to-treat basis. RESULTS: Efficacy of IFN-alpha induction: 104 patients were randomised to the non-induction group, 47 to the induction group. Gender, age, genotype distribution and HCV viral load at baseline did not differ significantly between the two groups. There was one treatment discontinuation because of adverse events in induced patients versus four in non-induced patients (P > 0.05). The 4 week EVR was significantly greater in induced patients in patients with HCV genotype 1, 4 or 5 (47% vs 12%, P=0.0002) only. There was no impact of induction in patients with HCV genotype 2 or 3. Efficacy of ribavirin: at week 24, 28 and 26 HCV-RNA negative patients were randomised to addition of ribavirin or not, respectively. Patients randomised to secondary additive ribavirin were more often HCV-RNA negative at the end of follow-up than patients treated with IFN-alpha alone: 18/28 (64%) vs 10/26 (39%); P=0.06. Among patients randomised to bitherapy, the relapse rate was significantly lower in patients with genotype 2 or 3 (0/12 vs 6/13, P=0.01) and not in those with genotype 1, 4 or 5 (5/11 vs 3/6, P=0.99). CONCLUSION: A 4 week IFN-alpha induction significantly increases the EVR rate in patients with HCV genotype 1, 4 or 5. Late secondary adjunction of ribavirin to IFN-alpha for 6 months in HCV-RNA negative patients after 6 months of IFN-alpha significantly decreases the relapse rate in patients with HCV genotype 2 or 3, but not in patients with genotypes 1, 4 or 5.

Adult↗

[Human immunodeficiency virus (HIV) infection in pregnancy: antiretroviral treatment (ART) and mode of delivery].

Antiretroviral therapy (ART) administered to pregnant women infected with HIV diminishes the rate of perinatal viral transmission. This is true for mono-, bi-, or tri-therapy (HAART), with the greatest effects being seen in the latter case. Nevertheless, when these therapies are employed, potential risks to the mother and fetus must be considered. These risks include hyperglycemia, lactic acidosis, mitochondrial toxicity, cutaneous rash, hepatitis, hypertension, and premature labor. Elective caesarean section reduces the perinatal transmission of HIV in patients with or without monotherapy, but has not shown a benefit in patients on tri-therapy (HAART). This article reviews the evidence for and against antiretroviral therapy and elective caesarean section in the setting of HIV in pregnancy and proposes treatment guidelines for these patients.

Anti-HIV Agents↗

The outcome of 400 consecutive liver grafts using the aortic perfusion-only technique.

The goal of this study is to establish the effect of cadaveric liver retrieval, using the technique of aortic perfusion only, on liver graft function, and to identify associated potential risk factors for graft dysfunction. The authors reviewed the outcome of 400 consecutive, orthotopic, cadaveric liver transplantation retrieved by the technique of aortic perfusion only. Relevant parameters pertaining to the donor, recipient, procurement, graft and peri-operative variables are analyzed to assess their influence on graft function. The univariant analysis revealed that donor age, body mass index, blood pressure, and vasopressor dependence influence graft function. Furthermore, predictors of dysfunction included prolonged anhepatic phase, transplantation duration and partial grafts. In addition, multivariant analysis revealed significant association between obesity of donors, partial graft, and dysfunction. The technique of aortic perfusion only, is a simple and reproducible procedure. The post-transplantation outcomes appear to be similar to those reported for the traditional liver procurement technique.

Adult↗

Preoperative evaluation of intraductal papillary mucinous tumors performed by pancreatic magnetic resonance imaging and correlated with surgical and histopathologic findings.

PURPOSE: To evaluate the effectiveness of magnetic resonance imaging (MRI) in predicting the location, type of ductal involvement, and malignant transformation of intraductal papillary mucinous (IPM) pancreatic tumors made in a preoperative routine exam. MATERIALS AND METHODS: A total of 24 patients with histologic confirmation of IPM tumor (IPMT) were included in this study. The MR images obtained in operation patients were retrospectively assessed. Two radiologists who were unaware of the initial interpretations of the images independently analyzed the MRI studies and characterized the type of lesions, location, and signs of malignant transformation. Interobserver agreement was determined with weighted kappa statistics. After consensus of both radiologists, the observer performances for the MRI interpretations were compared with surgical and histologic results using weighted kappa statistics and Fisher test. RESULTS: At macroscopic examination, lesions were of combined type in 17 cases and of branch duct type in seven cases. At histologic analysis, three cases were classified as benign, three as borderline tumors, and 18 as carcinomas (eight in situ, 10 invasive). The lesions were located mainly in the head or uncinate process (N = 16) or were diffuse or multifocal (N = 2). Excellent agreement was found between the interpreters (0.90) in the evaluation of ductal involvement, good in the evaluation of lesion location (0.80) and in the diagnosis of malignant transformation (0.74). The correlation between MRI and histopathologic results was excellent in the evaluation of ductal involvement (0.90, sensitivity = 100%, specificity = 94%) and moderate in the evaluation of lesion location (0.57, sensitivity = 87%, specificity = 56%) and in the diagnosis of malignant transformation (0.60, sensitivity = 83%, specificity = 83%). CONCLUSION: MRI is an effective method of characterizing IPMT in preoperative practice. The predictive sign of IPM pancreatic tumor malignancy at MRI included only the presence of solid mass or mural nodules.

Adenocarcinoma, Mucinous↗

Peritoneovenous shunt as a bridge to liver transplantation.

Intractable ascites carries great morbidity. The aim of this study was to determine the efficacy of peritoneovenous shunt (PVS) in patients listed for liver transplantation (LT). Between January 1999 and January 2004, PVS was inserted in 36 (30 males and 6 females) cirrhotic patients, 50.3 years of median age (range: 30-66), who failed multiple large-volume paracenteses and diuretic therapy, when listed for LT. Data were collected until LT or the present time, and were compared to an historical cohort (1997-1998) as control. No operative death occurred. Four patients died before LT in a median delay of 9 months after PVS insertion. PVS provided palliation for intractable ascites in 30 patients (83%). Renal function significantly improved (glomerular filtration rate (GFR) improved from 0.642 to 0.987 mL/s, p<0.05). Eighteen patients were transplanted in a median delay of 6 months (range: 3-12 months) after PVS insertion. When compared to the historical cohort of 18 patients, the occurrence of post-LT acute renal failure was significantly lower in the PVS group (3/18 vs. 13/18, p<0.05). Our results suggest that PVS might be beneficial in patients with refractory ascites waiting for LT and could prevent postoperative acute renal failure.

Adult↗

Characterization of human CD55 and CD59 transgenic pigs and kidney xenotransplantation in the pig-to-baboon combination.

New transgenic pigs expressing combinations of regulators of complement activation and other molecules are needed to resist xenograft hyperacute rejection (HAR) and to further analyze and treat xenograft rejection. Double transgenic pigs for human CD55 (hCD55) and human CD59 (hCD59) using the promoter of the human elongation factor 1 alpha gene were generated, and their kidneys were transplanted into nonimmunosuppressed baboons. hCD55 and hCD59 were mainly expressed by the endothelial cells, and these cells showed increased resistance to complement-mediated lysis. Baboons receiving kidneys from hCD55hCD59 pigs survived for 5 and 6 days, and displayed alterations in coagulation. Thrombocytopenia and platelet microthrombi were present within the kidneys. Nontransgenic kidneys showed HAR in less than 2 days. Kidneys from pigs expressing hCD55hCD59 displayed protection against HAR in the absence of immunosuppression. Rejection was associated with coagulopathy leukocyte infiltration and a rebound of anti-alpha Gal antibodies.

Animals↗

Association of rapamycin and co-stimulation blockade using anti-B7 antibodies in renal allotransplantation in baboons.

BACKGROUND: Co-stimulation blockade has already been shown to induce transplantation tolerance in rodents, but until now has failed in large animal models. We therefore sought to investigate whether the addition of rapamycin to a co-stimulation blockade regimen could induce tolerance in baboon recipients of a renal allograft and to characterize the immunological characteristics of rejection. METHODS: Two baboons were used for a pharmacological and toxicological analysis and received anti-B7.1 and anti-B7 antibodies every other day for 60 days. Three groups of baboons underwent classical heterotopic renal allotransplantation; the first group received no treatment (control group; n = 2), the second received a combination of anti-CD80 and anti-CD86 monoclonal antibodies (mAbs) (B7 group; n = 4), and the third received the anti-B7 antibody treatment as above with an additional treatment of rapamycin (B7-Rapa; n = 4). Graft survival as well as immunological analyses were performed. RESULTS: Anti-B7 mAb monotherapy prolonged allograft survival in three out of four of the animals, one of whom survived rejection free for 87 days but died from a pulmonary embolism; the fourth animal died without rejection. The addition of rapamycin to the regimen did not prolong survival further; three of the four animals underwent early rejection whereas the fourth survived long term but eventually rejected at day 114. Whereas alloimmunization only occurred in this latter animal, rejection was always characterized by a substantial lymphocyte and monocyte infiltration, associated with a strong pro-inflammatory/cytotoxic mRNA accumulation in the anti-B7-treated animals, but to a lesser extent in the B7-Rapa group. T cells extracted and cloned from a biopsy taken at a stable post-transplant time showed a lower frequency of anti-donor alloreactivity in vitro than those extracted from a rejected tissue. Nevertheless, these non-responding clones failed to show regulatory activity in vitro. CONCLUSIONS: We thus confirm that blocking the CD28/B7 pathway by anti-B7 mAbs could prolong graft survival in baboons, but the addition of rapamycin was insufficient to induce tolerance.

Animals↗

The effect of immunoglobulin immunadsorptions on delayed xenograft rejection of human CD55 transgenic pig kidneys in baboons.

Delayed xenograft rejection (DXR) remains a major obstacle in discordant xenotransplantation. As strategies of complement inhibition and xenogeneic natural antibody (Ab) removal have been shown to give prolonged xenograft survival, we endeavored to determine whether combining these two strategies would lead to an additive effect in terms of graft survival. The study was initiated with two groups, A and B, where group A received normal kidneys and group B received hCD55 transgenic kidneys. Both groups underwent pre-transplant (day-1) total immunoglobulin (Ig) immunoadsorption (IA) and received an immunosuppression of cyclophosphamide, cyclosporine A, mycophenolate mofetil and corticosteroids. Two subsequent groups (C and D) receiving hCD55 transgenic pig kidneys were then performed with an 'optimized' immunosuppression (Cyclophosphamide starting 1 day earlier) but only group D recipients were immunoadsorbed. Biopsies taken during the post-transplantation period were analyzed for Ab deposition, compliment activation and cellular infiltration. No hyperacute rejection was observed. In the initial immunoadsorbed groups A and B, all baboons underwent DXR, which started surprisingly early (day 5 in most cases. In the subsequent two groups, the immunoadsorbed group D baboons also underwent DXR, again as early as day 5. In contrast, group C baboons did not show any signs of DXR on their day 6 biopsy or at their time of death. Analysis of graft biopsies from the kidneys undergoing rejection or with stable function showed strong deposition of anti-Gal IgM in all cases whereas strong complement C5b-9 deposits were only observed in biopsies at rejection. Cellular infiltration consisted mostly of monocytes/macrophages, was more pronounced in biopsies taken at rejection and was associated with a pro-inflammatory environment involving interleukins 1alpha, 6 and 8. Our findings suggest non-specific Ig (anti-Gal and non-Gal Ig of all isotypes) IA or even incomplete IA in immunosuppressed baboon recipients of transgenic pig kidneys is detrimental to graft survival by being associated with an Ab and compliment driven rejection. We speculate that the IA were insufficient in terms of Ig depletion or frequency inducing an Ab rebound or that this total Ig depletion also removed components facilitating graft survival.

Animals↗

Portomesenteric disconnection for small-for-size grafts in liver transplantation: Preclinical studies in pigs.

This study reviews the evaluation and results of a new liver transplantation technique for small-for-size grafts with portomesenteric disconnection. Twenty Large-White pigs underwent heterotopic liver transplantation after a mesocaval shunt, ligation of the superior mesenteric vein downstream from the shunt, and ligation of the recipient portal vein near the native liver. The donor-to-recipient weight ratio was 24%, and the graft-to-recipient weight ratio was 0.6%. In five control pigs, no mesocaval shunt was performed. The mesocaval shunt provided diversion of 60% of the splanchnic blood flow. The median survival of study pigs was 39 days (range, 8 to 98). Median serum bilirubin levels at 1 week were 12 micromol/L (range, 4 to 59). At autopsy, graft weight was increased to 2.7 times the initial weight and histologic findings were normal. In the control group, all pigs died quickly of acute splanchnic congestion. Portomesenteric disconnection was effective to achieve survival of small-for-size grafts in pig liver transplantation.

Animals↗

Intraductal papillary-mucinous tumors of the pancreas: predictive criteria of malignancy according to pathological examination of 53 cases.

BACKGROUND: One of the main problems in the management and treatment of intraductal papillary-mucinous tumors is the lack of a reliable predictive factor for malignancy. HYPOTHESIS: Surgical treatment could be adapted to macroscopic criteria (presence of mural nodules and diameter of the pancreatic duct and of the lesion) or to tumor location (main duct, branch duct, or combined lesions) associated with benign or malignant forms. DESIGN: Retrospective study. SETTING: Two university and tertiary referral centers. PATIENTS: Fifty-three consecutive patients who underwent pancreatic resection for intraductal papillary-mucinous tumors between January 1, 1985, and December 31, 2000. RESULTS: Macroscopic analyses of tumors showed 6 main duct lesions, 12 branch duct lesions, and 35 combined lesions. A carcinoma was present in 33 cases (62%): 22 (41%) were invasive and 11 (21%) were noninvasive; 9 (17%) were borderline tumors and 11 (21%) were benign. Carcinoma and invasive carcinoma forms were less frequent in branch duct lesions (P<.001 and P =.009, respectively). Mural nodules were more frequent in carcinomas (P =.006) and invasive carcinomas (P<.001), with a positive predictive value of malignancy of 81%. The diameter of lesions (branch duct lesion > or =30 mm) or main duct (main pancreatic duct > or =15 mm in combined or main pancreatic duct lesions) did not correlate with malignancy. CONCLUSIONS: No carcinoma occurred in branch duct types smaller than 30 mm without mural nodules. Limited resection may be appropriate only in this type of tumor.

Adenocarcinoma, Mucinous↗

Cavaterm thermal balloon endometrial ablation versus hysteroscopic endometrial resection to treat menorrhagia: the French, multicenter, randomized study.

STUDY OBJECTIVE: To compare the efficacy and safety of Cavaterm thermal balloon endometrial ablation with hysteroscopic endometrial resection. DESIGN: Multicenter randomized trial (Canadian Task Force classification I). SETTING: Departments of obstetrics and gynecology in French university hospitals. PATIENTS: Fifty-one women with menorrhagia unresponsive to medical treatment. INTERVENTIONS: Women were randomized to thermal destruction of the endometrium or to hysteroscopic endometrial resection. Women completed preoperative, 6-, and 12-month postoperative pictorial charts to determine Higham blood loss scores and a satisfaction questionnaire. Operative time, discharge time, complication rate, and resumption of normal activities were evaluated for each group. MEASUREMENTS AND MAIN RESULTS: Amenorrhea rates were 36% (95% CI 19%-56%) and 29% (95% CI 8%-51%) in the Cavaterm and the endometrial resection groups at 12 months, respectively (ns). Both treatments significantly reduced uterine bleeding. The median decrease in Higham score at 12 months was significantly higher in women treated by Cavaterm (377, range 108-1300) than in women treated by resection (255, range -82 to 555) (p=.006). A subsequent hysterectomy for recurrent bleeding was performed in 2 women, both previously treated by resection. The rate of women reporting good or excellent satisfaction was 89% (95% CI 72%-98%) in the Cavaterm group and 79% (95% CI 54%-94%) in the resection group at 12 months. Discharge time was significantly lower in women treated by Cavaterm, although postoperative pain at 1 hour was higher. There were no major complications in either group. CONCLUSIONS: Cavaterm thermal balloon ablation was as effective as hysteroscopic endometrial resection to treat menorrhagia, both resulting in a significant reduction in menstrual blood loss and high patient satisfaction.

Adult↗

A new, liquid-based cytology technique.

OBJECTIVE: To evaluate a new liquid-based cytology technique, Papspin (Thermo Shandon, Pittsburgh, Pennsylvania, U.S.A.). STUDY DESIGN: Three thousand cervical samples were examined. Each cervix was sampled with a Cervex Brush (Roche, Oss, the Netherlands), used first for a Pap smear and afterwards for a Papspin. One cytospin was prepared from each vial. RESULTS: An identical rate of epithelial cell abnormalities (3.8%) was detected with the two methods. Diagnostic concordance was observed in 86% of the 114 cases. Differences in diagnoses occurred in 168 of 3,000 cases (5.6%) concerning fungal infection (22 cases), epithelial cell abnormalities (24 cases) and minimal differences within the nonneoplastic Bethesda category (122 cases). Endocervical cells were absent from 158 Papspins (5.3%) and 66 Pap smears (2.2%), while they were present in the respective Pap smear or Papspin. Seven Papspins were considered "satisfactory, but limited by ..." (SBLB) as compared to 33 Pap smears given the absence of endocervical cells. CONCLUSION: Discordances concerning epithelial cell abnormalities were observed in 24 of 3,000 cases (0.8%). Fungal infections were more easily diagnosed on Papspin. The absence of endocervical cells in 5.3% of Papspins is due to a bias of methodology. Quality improvement was evident on Papspin for SBLB specimens. HPV testing could be performed with good results.

Adolescent↗