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J Hardwigsen

Publications and source records attributed to J Hardwigsen.

At least 19 recordsLinked to original sources
PubMed2003

Evaluation of glycogen loss in human liver transplants. Histochemical zonation of glycogen loss in cold ischemia and reperfusion.

To find a prognosis model of human liver transplant, we evaluate 62 surgical biopsies for the loss of glycogen and its variations in relation to cold ischemia, reperfusion, lobular zonation and donor's ages. We applied univariate, multivariate and discriminant analysis and logistic regression. There was a clear lobular zonation of glycogen during cold ischemia and at reperfusion. During cold ischemia, the mean loss was 48% in periportal zones and 74% in pericentrilobular zones. At reperfusion, it was in the range of 60% in periportal zones and 95% in pericentrilobular zones. It was observed in 64% of the grafts for an ischemia time less than 10 hr and in 82% of the grafts for an ischemia time of 10 hr or more. It was increased by 90% at reperfusion with pericentral predominance. Donors' age was an aggravating factor of glycogen loss beyond 28 years of age. In conclusion, in periportal zones, mean global glycogen depletion was about 54% during cold ischemia and reperfusion. It decreased by 90% at reperfusion with pericentral predominance. Logistic regression has allowed modelization of cold ischemia and reperfusion.

Adolescent↗
PubMed2001

Modified AdCTLA-4 vector blocks alloimmune response in vitro.

BACKGROUND: Gene transfer of the costimulatory blockade molecule CTLA-4Ig into cold-preserved rat liver allografts results in indefinite allograft survival. Despite local delivery, this mode of immunomodulation is associated with systemic immunosuppression. In an effort to restrict immunosuppression to the graft, we have constructed a novel adenoviral vector, AdCTLA-4ex-TAG, in which the Ig sequence of CTLA-4Ig DNA has been deleted to destabilize the gene product to promote rapid extrahepatic degradation while maintaining its immunosuppressive activity within the graft milieu. METHODS: (1) Vector construction. CTLA-4 extracellular binding domain (CTLA-4ex) was prepared by PCR-based cloning methods and fused in frame to a genetic element encoding an epitope TAG allowing identification of the transgene product CTLA-4exTAG. CTLA-4exTAG was subcloned into a shuttle vector enabling isolation of AdCTLA-4exTAG. (2) In vitro transfection: AdCTLA-4exTAG was transfected into MH(1)C(1) cells and then supernatant was recovered for Western blot analysis. (3) In vitro alloimmune response was characterized by CFSE proliferation assay. (4) Extrahepatic effect of AdCTLA-4exTAG was characterized by the ability to control tumor growth after implantation of a regressive, immune sensitive cancer cell line (REGb) in the skin of BDIX rats after liver transduction with AdCTLA-4exTAG. RESULTS: Expression and secretion of the recombinant protein were documented by Western blot after infection of the MH(1)C(1) cell line() with AdCTLA-4exTAG. Addition of infected MH(1)C(1) cell supernatant resulted in abrogation of alloimmune response as shown by markedly diminished division of CD4(+) T cells in a CFSE proliferation assay. Extrahepatic tumor regressed normally after liver transduction with AdCTLA-4exTAG. CONCLUSIONS: These results show efficient in vitro expression of CTLA-4exTAG after transfection with AdCTLA-4exTAG. The modified protein retains its ability to abrogate in vitro alloimmune response. Efficient control of extrahepatic tumor growth after liver-directed delivery of AdCTLA-4exTAG suggests that the immunosuppressive effect of this vector is restricted to the liver. These results set the ground for the utilization of this novel adenoviral vector in the transplant setting.

Abatacept↗
PubMed2001

Effect of ischemia-reperfusion on bile canalicular F-actin microfilaments in hepatocytes of human liver allograft: image analysis by confocal laser scanning microscopy.

We studied and quantified the effect of ischemia-reperfusion on hepatic F-actin on bile canalicular and basolateral membranes in human liver allografts by means of confocal laser scanning microscopy imaging. The phalloidin-FITC staining of F-actin was normal in liver hepatocytes before reperfusion but decreased significantly after reperfusion (by 25% of controls). These results indicate that hepatic F-actin alteration is produced during the reperfusion phase. This modification, probably induced by reactive oxygen species, could impair bile canalicular contraction and tight junction permeability and consequently bile secretion in the postoperative period.

Actin Cytoskeleton↗
PubMed2001

Resection of the inferior vena cava for neoplasms with or without prosthetic replacement: a 14-patient series.

OBJECTIVE: To review the outcome of resection of the suprarenal or infrarenal inferior vena cava (IVC) and possible indications for prosthetic replacement. SUMMARY BACKGROUND DATA: Involvement of the IVC has long been considered a limiting factor for curative surgery for advanced tumors because the surgical risks are high and the long-term prognosis is poor. Prosthetic replacement of the IVC is controversial. METHODS: The authors retrospectively reviewed a 7-year series of 14 patients who underwent en bloc resection including a circumferential segment of the IVC. The tumor was malignant in 12 patients and benign in 2. The resected segment of the IVC was located above the kidneys in eight patients and below in six. Resection was performed without extracorporeal circulation in all patients. RESULTS: In all but one patient, IVC resection was associated with multivisceral resection, including extended nephrectomy (n = 8), major hepatic resection (n = 3), digestive resection (n = 3), and infrarenal aortic replacement (n = 2). Prosthetic replacement of the IVC was performed in eight patients cases and was more common after resection of a suprarenal (6/8) than an infrarenal segment of the IVC (2/6). One patient died of multiorgan failure. Major complications occurred in 29% of patients. Symptomatic complications of prosthetic replacement occurred in one patient (acute postoperative thrombosis, successfully treated by surgical disobstruction). Graft-related infection was not observed. Marked symptoms of venous obstruction developed in three of the six patients who did not undergo venous replacement. In patients undergoing surgery for malignant disease, the estimated median survival was 37 months and the actuarial survival rate was 67% at 1 year. CONCLUSION: Multivisceral resection including a segment of IVC is justified to achieve complete extirpation in selected patients with extensive abdominal tumors. Prosthetic replacement of the IVC may be required, particularly in cases of suprarenal resection. It is a safe procedure with a low complication rate and good functional results.

Adult↗
PubMed2000

Oxidative metabolism of bupivacaine into pipecolylxylidine in humans is mainly catalyzed by CYP3A.

Bupivacaine is used to provide prolonged anesthesia and postoperative analgesia. The human cytochrome P450 (CYP) involved in bupivacaine degradation into pipecolylxylidine (PPX), its major metabolite, has, to our knowledge, never been described. Microsome samples were prepared from six human livers and incubated in the presence of bupivacaine. The concentrations of PPX in the microsomal suspensions were assessed, and K(m) and V(max) values were calculated. Bupivacaine incubations were then performed with specific CYP substrates and inhibitors. For each sample of hepatic microsomes, the correlation between the rate of PPX formation and the corresponding erythromycin N-demethylase activity was analyzed. Finally, an immunoinhibition study using an anti-rabbit CYP3A6 antibody and assays with cDNA-expressed human CYP were conducted. The apparent K(m) and V(max) values of bupivacaine were, respectively, 125 microM and 4.78 nmol/min/mg of microsomal protein. The strongest inhibition of bupivacaine metabolism was obtained for troleandomycin (-95% at 50 microM), a specific CYP3A inhibitor. The correlation between PPX formation and erythromycin N-demethylase activity showed an R value of 0.99 whereas anti-rabbit CYP3A6 antibody inhibited the degradation of bupivacaine into PPX by 99%. Finally, CYP1A2 and CYP2E1 cDNA-expressed forms of human CYP did not allow PPX formation, CYP2C19 and CYP2D6 produced only small amounts whereas CYP3A4 most efficiently metabolized bupivacaine into PPX. These results demonstrated that bupivacaine degradation into PPX was mediated in humans by CYP3A.

Anesthetics, Local↗
PubMed2000

Quantitative analysis of glycogen content in hepatocytes of human liver allograft after ischemia and reperfusion.

In order to examine glucose metabolism in liver grafts after cold ischemia and reperfusion, the heterogeneous lobular distribution pattern of glycogen content was studied using histochemical quantitative analysis. In most of the cases, this heterogeneous pattern of glycogen was observed after preservation and reperfusion. However, a 42% reduction of glycogen content, expressed as the ratio between stained surface and total surface of liver biopsies, was observed in biopsies after reperfusion. Moreover, both periportal and centrilobular hepatocytes showed a significant decrease in mean optical density after reperfusion (18% and 25%, respectively). The comparison of our results to early postoperative liver function tests and cold ischemia times showed no significant correlation (p<0.05).

Adolescent↗
PubMed1999

[Hepatocellular carcinoma in a non-cirrhotic liver. Presentation of series of 77 operated patients].

OBJECTIVE: To present epidemiologic profile of this supposedly rare condition, its diagnostic management and the results of surgical treatment in a population of the mediterranean border. PATIENTS AND METHODS: Between 1987 and 1999, the records of patients operated on for hepatocellular carcinoma and in whom cirrhosis was not present on pathological examination of liver parenchyma were collected. Data were collected prospectively. RESULTS: Mean age was 57.6 years. There were 61 men (79%) and 16 women but sex ratio was 1/1 for patients under 50. Hepatitis B and/or C serology was positive in 22 patients (29%). At presentation, 56 patients (73%) suffered of symptoms and there was evidence of tumor at clinical examination in 30 (39%). Sensitivity of alpha-fetoprotein measurement was 55%, and 58% for preoperative percutaneous biopsy. Twelve had exploratory laparotomy only, 61 underwent partial liver resection and 4 were transplanted. Resection was presumed curative in 56 cases (73%). There was one single tumor mass in 41 cases (53%) and its mean size was 10.3 cm. Liver fibrosis was present in 24 cases (29%). After curative resection, 5-year survival rate was 46%, and favorable prognostic factors were: alpha-fetoprotein within normal range, single tumor mass or tumor size less than 10 cm. CONCLUSION: Hepatocellular carcinoma arising on noncirrhotic liver is not a rare occurrence. It is usually encountered at an advanced stage of the disease. Nonetheless, it remains extirpable in many cases with low postoperative mortality and long term results are better than those of resections for hepatocellular carcinoma on cirrhotic liver.

Actuarial Analysis↗
PubMed1999

Morbidity of major hepatic resections: a 100-case prospective study.

OBJECTIVE: To assess the morbidity and its main risk factors after major hepatic resection. DESIGN: Retrospective study of prospectively collected data. SETTING: University hospital, France. SUBJECTS: 100 consecutive patients who underwent major hepatic resections, 1989-95. INTERVENTIONS: Major hepatic resection, defined as resection involving 3 or more segments according to Couinaud's classification, in all cases. MAIN OUTCOME MEASURES: All complications that affected outcome or prolonged hospital stay. Risk factors identified by univariate and multivariate analysis. RESULTS: 45 patients developed at least 1 complication and 7 died. The most common complications were: pleural effusion (n = 21), hepatic failure (n = 12), and ascites (n = 9). Univariate analysis showed that the following variables were significantly related to the morbidity: age >55 years, American Society of Anesthesiologists (ASA) grade II or more, bilirubin >80 micromol/L, alkaline phosphatase activity more than double the reference range, malignant tumours, abnormal liver parenchyma, simultaneous surgical procedures, operative time >4 hours, and perioperative blood transfusion > or =600 ml. The extent of resection did not correlate with postoperative complications. Multivariate analysis showed that volume of blood transfusion > or =600 ml and simultaneous surgical procedures were the most important independent risk factors for complicated outcome. CONCLUSIONS: The morbidity associated with major hepatic resections remains high, and the main determinants of outcome are intraoperative surgeon-related factors.

Adult↗
PubMed1999

Effect of ischemia-reperfusion on the heterogeneous lobular distribution pattern of glycogen content and glucose-6-phosphatase activity in human liver allograft.

In order to examine glucose metabolism in liver grafts after cold ischemia and reperfusion, the heterogeneous lobular distribution pattern of glycogen content and glucose-6-phosphatase activity was studied using histochemical methods. The characteristic heterogeneous lobular distribution pattern of glycogen and glucose-6-phosphatase was maintained after preservation and reperfusion. However, it appeared that glycogen content decreased in both periportal and centrilobular hepatocytes after reperfusion. The glycogen decrease was higher in periportal hepatocytes. Glucose-6-phosphatase activity was maintained after reperfusion in most of the cases in periportal hepatocytes. In centrilobular hepatocytes, more cases showed a decrease in enzyme activity. It is suggested that ischemia-reperfusion mainly affects the glycogen content in both periportal and centrilobular hepatocytes and that centrilobular glucose-6-phosphatase activity is more sensitive to ischemia-reperfusion injury than periportal hepatocytes.

Adolescent↗
PubMed1998

Intravenous leiomyomatosis with caval involvement: report of a case with radical resection and venous replacement.

Intravenous leiomyomatosis is a rare, histologically benign neoplasm that may be malignant in its specific tendency to intravascular extension. A case of intravenous leiomyomatosis with extension into the entire inferior vena cava in a 41-year-old woman is described. The patient was diagnosed with syncope 3 years after hysterectomy and was treated with a 1-stage procedure including venous replacement.

Adult↗
PubMed1998

Inflammatory process complicating giant hemangioma of the liver: report of three cases.

Three cases of giant hemangioma of the liver associated with clinical and laboratory signs of inflammatory process, including low-grade fever, weight loss, abdominal pain, accelerated erythrocyte sedimentation rate, anemia, thrombocytosis, and increased fibrinogen level with normal white blood cell count are described. One patient presented with slight cholestatic jaundice because of tumor-related bile duct compression, but the other two patients had normal liver function tests, except for a slight increase in gammaglutamyl transferase. Clinical and laboratory abnormalities disappeared after surgical excision. Inflammatory manifestations have rarely been reported during giant liver hemangioma. Intratumoral inflammation necrosis or bleeding could explain the symptoms but histological signs of inflammation were not detected in two of three surgical specimens. The release of immune mediators by liver endothelial cells lining the hemangioma is an alternative explanation. The incidence of inflammatory process complicating giant hemangioma is probably underestimated because our three cases were observed within a span of only 3 years.

Adult↗
PubMed1998

[Liver transplantation in the adult: who and when to transplant?].

INTRODUCTION: The shortage of cadaveric organ donors imposes a severe limit to the number of liver transplantations. A selection is thus necessary among patients: should the sickest be selected, or those who supposedly have the best chance to survive and recover? Optimizing the timing of transplantation during the course of the disease (not too early, but not too late) is another issue. CURRENT KNOWLEDGE AND KEY POINTS: Suitable candidates for transplantation are patients suffering from an irreversible, symptomatic liver disease. The goals of therapy are: firstly, to favorably modify the natural outcome of the disease; and secondly, in an acceptable risk taking manner. Major criteria for indication in the most common liver diseases can be summarized as follows: a) for chronic parenchymal liver diseases, a Child-Pugh score of 9 or 10, or less if complications have already occurred, is a mandatory and often sufficient criterion; b) for cholestatic liver diseases, a serum bilirubin level higher than 100-150 mumol/L is generally required; c) apart from "small" hepatocellular carcinomas on cirrhotic parenchyma (less than three tumors of less than 5 cm in diameter), most cancers are considered contraindications; d) acute liver failure requires early referral to a liver transplant center for potential emergency indication. FUTURE PROSPECTS AND PROJECTS: In an organ shortage situation which is likely to perdure, early consultative contact between the patient and the liver transplant team will allow improvement in the access to transplantation procedure.

Adult↗
PubMed1998

Surgical resection of locally recurrent colorectal adenocarcinoma.

BACKGROUND: Recurrence rates after curative resection of colorectal adenocarcinoma remain steady at 50 per cent. Thirty per cent of the deaths are linked to locoregional recurrence. The aim of this study was to evaluate the results of resection for locoregional recurrence. METHODS: This retrospective review analyzed a series of 120 patients who underwent resection of colonic (56) or rectal (64) locoregional recurrence. Sixty-nine resections were considered as curative. Sixty-one recurrences required extended resection. There were nine synchronous hepatic resections. RESULTS: The hospital mortality rate was 7 per cent and the morbidity rate was 40 per cent. The overall 5-year survival rate was 27 per cent. Survival was significantly higher: (1) after curative resection (44 versus 0 per cent after palliative resection, P < 0.0001); (2) in women (44 versus 11 per cent for men, P = 0.0036); and (3) after resection for intramural recurrence (45 versus 19 per cent for extramural recurrence, P = 0.0024). Multifactorial analysis showed that curability of the resection was the most important prognostic parameter. CONCLUSION: The results in this highly selected group seem to justify an attempt at reresection whenever possible. Long-term results may be improved by using adjuvant treatment.

Adenocarcinoma↗
PubMed1998

Immunoexpression of E-cadherin and beta-catenin correlates to survival of patients with hepatocellular carcinomas.

Expression of E-cadherin (E-cad) and -catenin ( -cat) was investigated immunohistologically in 91 cases of excised hepatocellular carcinomas. Immunodectection was altered in 56% of tumours for E-cad and in 30.8% for -cat. Downregulation of E-cad and -cat correlated with the size of tumours, and high nuclear grade, but only E-cad alteration correlated with the mitotic index. Alterations of E-cad and -cat expression correlated with survival. Although E-cad and -cat immunodetections were independent prognostic factors, their prognostic value was lower than that of current clinicopathological parameters.

Adult↗