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Biomedical subjects

M Gillet

Publications and source records attributed to M Gillet.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effect of liver transplantation on hepatic glucose metabolism in a patient with type I glycogen storage disease.

BACKGROUND: In type I glycogenosis, mutation of the glucose-6-phosphatase gene results in absent glucose-6-phosphatase activity in liver cells leading to fasting hypoglycemia. Liver transplantation is expected to normalize glucose homeostasis. METHODS: Endogenous glucose production (6,6 2H2 glucose) was measured after an overnight fast and during exogenous 13C-labeled glycerol infusion in a patient with glycogenosis type I 24 months after liver transplantation and in a group of healthy subjects. RESULTS: Compared with healthy subjects, the glycogenosis patient had normal fasting glucose production and glucose and insulin concentrations after liver transplantation, but mildly elevated plasma glucagon concentrations. Gluconeogenesis from exogenous glycerol (13C glucose synthesis) was similar and did not lead to enhancement of glucose production in both healthy controls and the patient. CONCLUSIONS: Liver glucoregulatory function is restored by orthotopic liver transplantation in type I glycogenosis.

Adolescent↗
PubMed2000

Postprandial hepatic glycogen synthesis in liver transplant recipients.

BACKGROUND: The liver plays a central role in glucose homeostasis by releasing glucose in the fasting state and by taking up and converting into glycogen part of the glucose absorbed from the gastrointestinal tract after meal ingestion. METHODS: To determine whether the hepatic denervation that accompanies liver transplantation interferes with these functions, we assessed glucose tolerance to an oral glucose load in seven patients at 2-6 weeks after orthotopic liver transplantation, in six patients after kidney transplantation, and in six healthy controls. Hepatic glycogen synthesis was non-invasively assessed over the 4 hours after ingestion of a glucose load by monitoring hepatic uridine diphosphoglucose turnover with 13C galactose and acetaminophen. RESULTS: Liver and kidney transplant recipients had increased postprandial glucose concentrations but normal hepatic uridine diphosphoglucose turnover, indicating an unaltered hepatic glycogen synthesis. CONCLUSIONS: These results indicate that denervated liver transplants have an adequate glucoregulatory function. Postprandial hyperglycemia in liver transplant recipients is therefore not due to alterations of liver glucose metabolism.

Adult↗
PubMed2000

Angiogenesis of liver metastases: role of sinusoidal endothelial cells.

PURPOSE: Tumor-induced angiogenesis requires migration and remodeling of endothelial cells derived from pre-existing blood vessels. Vascular endothelial growth factor is the growth factor most closely implicated in the development of neovessels in colon cancer. However, vascular endothelial growth factor-specific receptors flt-1 and KDR mRNA expression are absent in normal sinusoid vessels surrounding vascular endothelial growth factor-producing secondary hepatic tumors. Thus, the potential role of sinusoidal endothelial cells in the mechanism of neovessel formation within liver metastatic carcinomas remains unclear. The purpose of this study was to determine whether sinusoidal endothelial cells are involved in tumor angiogenesis in a syngeneic model of liver metastases from colorectal cancer. METHODS: Sinusoidal endothelial cells were identified by fluorescence microscopy after uptake of acetylated low density lipoprotein labeled with a fluorescent probe (dioctadecylindocarbocyanine). One hundred microliters of dioctadecylindocarbocyanine acetylated low density lipoprotein were injected intraportally at the start of experiment in BD IX rats. Two days later, intraportal injection of 10(7) DHD K12, a chemically induced colon carcinoma cell line, was performed in syngeneic BD IX rats. Animals were killed one week later and the livers were processed for routine histologic examination and immunohistochemistry using the rat endothelial cell antigen-1 monoclonal antibody. RESULTS: In normal parenchyma fluorescence was associated with sinusoidal cells but not with endothelium of large blood vessels. Thus, specific acetylated low density lipoprotein uptake allowed histological differentiation of sinusoidal endothelial cells from other large-vessel endothelial cells present in the hepatic parenchyma. In tumor-bearing liver a spatial gradient of fluorescence was generated. Labeled cells accumulated at the periphery of the metastases. When tumors grow beyond 200 microm, neovessel formation was observed; there was an invasion of fluorescent-labeled cells from the periphery, which were arranged in a tubular formation within neoplasia. CONCLUSION: In liver metastases tumor vessels are lined with sinusoidal endothelial cells. Identification of a specific cell type involved in the formation of the stromal compartment of tumors has important implications. Sinusoidal endothelial cells express well-characterized surface receptors and differ morphologically and metabolically from large-vessel endothelia. They should be considered as attractive targets for future and existing antiangiogenic strategies directed against the stromal compartment of liver metastases.

Animals↗
PubMed2000

[Surgical treatment of hepatic alveolar echinococcosis].

INTRODUCTION: Alveolar hydatid disease is an uncommon parasitosis found in the northern hemisphere, caused by the larval stage of a tapeworm growing in the liver: Echinococcus multilocularis. It behaves like a malignant tumor, producing liver necrosis and invading the biliary tract, main vessels and surrounding structures. METHODS: Review of the different therapeutic approaches in hepatic alveolar echinococcosis over 21 years in an epidemic area. RESULTS: The various surgical approaches (all types of hepatectomy, palliative surgical procedures and liver transplantation) were combined with medical, endoscopic and radiological interventional treatment. Recently, asymptomatic forms were more frequently encountered. CONCLUSIONS: The wide use of ultrasonography and specific serological tests have led to early diagnosis, allowing more curative hepatectomies.

Echinococcosis, Hepatic↗
PubMed2000

Safety and immunogenicity profile of a recombinant outer-surface protein A Lyme disease vaccine: clinical trial of a 3-dose schedule at 0, 1, and 2 months.

OBJECTIVES: This study compared the tolerability of a Lyme disease vaccine administered intramuscularly at 0 and 1 months with that of a vaccine administered at 0, 1, and 2 months to determine (1) whether adding a third dose of vaccine 1 month after the second would affect the safety profile, and (2) whether a shortened vaccination schedule of 0, 1, and 2 months would provide an immune response similar to that obtained with vaccine administered at 0, 1, and 12 months. BACKGROUND: An efficacy trial of a Lyme disease vaccine had demonstrated safety and efficacy against definite (clinically manifested and laboratory-confirmed) Lyme disease after 3 doses at 0, 1, and 12 months and resulted in 90% of subjects having titers > or =1400 enzyme-linked immunosorbent assay units (EL.U)/mL (the proposed seroprotective level for 1 tick season). METHODS: This multicenter, open-label, prospective, randomized study assessed the safety and efficacy of different doses of a recombinant outer-surface protein A (OspA) vaccine in 956 volunteers aged 17 to 72 years from 3 Lyme disease-endemic sites. Blood samples were collected at months 0, 2, 3, 12, and 13 to assess total immunoglobulin-G anti-OspA titers. RESULTS: Most adverse events were transient and mild to moderate. The geometric mean antibody titer increased 2.8-fold from month 2 (1786 EL.U/mL to 4842 EL.U/mL), and approximately 90% of the volunteers had a titer > or =1400 and 99% had a titer > or =400 EL.U/mL (the mini- mum seroprotective level at any given time) after the third dose. An antibody kinetics model predicts that protection would last for a typical tick-transmission season. CONCLUSIONS: In volunteers aged 17 to 72 years, 3 doses of vaccine administered in 2 months was well tolerated, more immunogenic than 2 doses, and provided a higher probability of protection before exposure or travel to Lyme disease-endemic areas.

Adolescent↗
PubMed2000

Growth inhibition of liver metastases by the anti-angiogenic drug TNP-470.

OBJECTIVE: This study was undertaken in order to assess the efficacy of a potent angiogenesis inhibitor, TNP-470, on tumor growth in a syngeneic rodent model of liver metastases from colorectal cancer. BACKGROUND: New blood vessel formation is a prerequisite for primary and metastatic tumor growth. TNP-470, a synthetic derivative of fumagillin when subcutaneously transplanted into nude mice, inhibits endothelial cell proliferation and migration, as well as the growth of various human cancers. However, the antitumor effect of this drug has not been studied in models reproducing a natural metastatic environment. Since the liver provides an extensive vascular bed for secondary tumor growth, an anti-angiogenic strategy may therefore be less efficient for treating hepatic metastases than primary tumors. METHODS: 10(7) DHD K12 colon carcinoma cells were injected intrasplenically into syngeneic BD IX rats to produce diffuse liver metastases. TNP-470 (30 mg/kg/day) was administered on alternate days starting 4 days after tumor implantation. The animals were sacrificed after 4 weeks and their livers were processed for histologic examination. In both the treatment and control groups (n=7), tumor volume was determined using a computerized analytical system, and tumor microvessel density was measured by immunostaining with anti-von Willebrand Factor monoclonal antibody. RESULTS: In vitro, TNP-470 demonstrated a direct toxicity towards the DHD K12 cell line with an IC50 of 0.1 microg/ml. Metastases were present in all animals from both groups. Liver weight (15.2 g vs 11.7 g, p=0.01), and tumor volume (1218 mm3 vs 406 mm3, p=0.03) were significantly reduced in the TNP-470 group compared to the control group. Tumor microvessel density was not statistically different between the two groups (67 vs 63 microvessels/x200 field, p=0.41). CONCLUSION: TNP-470 inhibits the growth of liver metastases in a syngeneic rat model of colorectal cancer. The mechanism responsible for this effect remains unclear, but may involve a combination of anti-angiogenic and direct cytotoxic effects.

Angiogenesis Inhibitors↗
PubMed2000

Prognostic value of postoperative carcinoembryonic antigen concentration and extent of invasion of resection margins after hepatic resection for colorectal metastases.

OBJECTIVE: To evaluate the prognostic value of postoperative concentration of carcinoembryonic antigen (CEA) and extent of surgical margins after resection of liver metastases from colorectal cancer. DESIGN: Retrospective study. SETTING: Teaching hospital, Switzerland. SUBJECTS: 49 patients with hepatic metastases after primary colorectal cancer. INTERVENTIONS: Resection of hepatic metastases MAIN OUTCOME MEASURES: Assessment of prognostic value of variables by univariate and multivariate analysis. RESULTS: Median survival was 24 months (range 5-86 months). Resection margins were clear (> 1-cm) in 10, close (< 1-cm) in 25 and invaded in 9 patients. On univariate analysis, a postoperative concentration of CEA of <4ng/ml was correlated with prolonged survival (p < 0.001), but the width of the resection margin was not of prognostic importance. There was no correlation between width of resection margins and postoperative concentration of CEA (p = 0.5). On multivariate analysis, postoperative concentrations of CEA of 4 ng/ml or more were associated with increased risk of death (relative risk 7.3; 95% confidence interval (CI) 2.8-18.7, p < 0.001). CONCLUSION: Postoperative CEA offers better prognostic discrimination than the width of resection margins after resection of liver metastases from colorectal tumours. Some patients with invaded resection margins did survive for 3 years, but no patient did whose CEA concentration was 4 ng/ml or more. The definition of a potentially curative hepatic resection should include a postoperative CEA concentration of <4 ng/ml (within the reference range).

Carcinoembryonic Antigen↗
PubMed2000

Columnar cuff cancer after restorative proctocolectomy for familial adenomatous polyposis.

AIMS: Restorative proctocolectomy with ileoanal anastomosis is one of the treatments of choice for patients suffering from familial adenomatous polyposis (FAP). However, any residual rectal mucosa left behind after mucosectomy is at risk for the development of neoplasia. CASE REPORT: A 31 year old male patient with FAP underwent restorative proctocolectomy with a pelvic ileal pouch-anal anastomosis. Seven years later he presented with right inguinal and perianal pain. A diagnosis of invasive columnar cuff carcinoma was made. DISCUSSION: Islets of columnar epithelium may be left behind after restorative proctocolectomy, exposing the patient to later malignant change. This risk must be emphasised and prevented by regular surveillance of the anastomosis.

Adenocarcinoma↗
PubMed2000

Permanent access to the portal vein in rats: an experimental model.

A safe and reproducible method for placement of indwelling catheters into the portal venous system is a prerequisite for improved delivery of anticancer drugs to experimental liver metastases. Due to the lack of tumor models in large animals and the difficulty in establishing permanent access to the portal vein in rodents, this type of model has rarely been described in the laboratory setting. We propose a simple, minimally invasive method for repeated portal vein injections in rats. A vascular access device was used, which remained patent for periods of up to 3 months. Placement and support of the catheter tip in the portal vein was performed with a technique designed to avoid portal thrombosis and infections. Permanent portal vein access in a rodent model of liver metastases will be invaluable for the development of novel therapeutic strategies.

Animals↗
PubMed2000

Mechanisms of postprandial hyperglycemia in liver transplant recipients: comparison of liver transplant patients with kidney transplant patients and healthy controls.

Impaired glucose tolerance or diabetes mellitus are frequent complications after organ transplantation, and are usually attributed to glucocorticoid and immunosuppressive treatments. Liver transplantation results in total hepatic denervation which may also affect glucoregulation. We therefore evaluated postprandial glucose metabolism in a group of patients with liver cirrhosis before and after orthotopic liver transplantation. Seven patients with liver cirrhosis of various etiologies, 6 patients having received a kidney transplant, and 6 healthy subjects were studied. Their glucose metabolism was evaluated in the basal state and over 4 hours after ingestion of a glucose load with 6.6 (2) H glucose dilution analysis. The patients with liver cirrhosis were studied before, and again 4 weeks (range 2-6) and 38 weeks (range 20-76, n=6) after orthotopic liver transplantation. Basal glucose metabolism was similar in liver and kidney transplant recipients. Impaired glucose tolerance was present in both groups, but postprandial hyperglycemia was exaggerated and lasted longer in liver transplant patients. Postprandial insulinemia was lower in liver transplant recipients, while C-peptide concentrations were comparable to those of kidney transplant recipients, indicating increased insulin clearance. Glucose turnover was not altered in both groups of patients during the initial 3 hours after glucose ingestion, but was higher in liver transplant early after transplantation during the fourth hour. Postprandial hyperglycemia remained unchanged in liver transplant recipients 38 weeks after liver transplantation, despite substantial reduction of immunosuppressive and glucocorticoid doses. We conclude that liver transplant recipients have severe postprandial hyperglycemia which can be attributed to insulinopenia (secondary, at least in part, to increased insulin clearance) and a late increased glucose turnover. These changes may be secondary to hepatic denervation.

Adult↗
PubMed2000

Agenesis of the vermiform appendix.

Agenesis of the vermiform appendix is very rare. The incidence is estimated to be one in 100,000 laparotomies for suspected appendicitis. Several criteria have to be met before the investigator can conclude that the appendix is congenitally absent. This case is reported to bring this entity to the attention of surgeons who may encounter a similar situation during celioscopy. A 29-year-old patient was admitted through the emergency room with the chief complaint of abdominal pain. Acute appendicitis was suspected, and he was accordingly prepared for celioscopy. This report presents a patient with vermiform appendix agenesis diagnosed at celioscopy with concomitant mesenteric lymphadenitis. Agenesis of the vermiform appendix is very rare, and the diagnosis should not be made unless the ileocecal and retrocecal area are thoroughly explored.

Abdomen, Acute↗
PubMed1999

[Gene therapy and liver metastases].

Liver metastases occur in approximately 60% of patients with colorectal cancer. Liver resection is currently the only treatment that offers long-term survival. The 5-year survival rates range from 25 to 40%; however, less than 20% of patients are candidates for resection. The prognosis for the remaining patients is grim, since palliative chemotherapy and symptomatic care are the only available options. The ability to transfer therapeutic genes to target cells in vivo has opened up unprecedented possibilities for the management of metastatic liver cancer. A large number of genes with therapeutic potential have been cloned. Families of genes currently used can be classified as "suicide", cytokine, anti-angiogenic, tumour-suppressor, and oncogenes. Physico-chemical and, more commonly, viral vectors can be used to enhance gene transfer into tumours. The delivery systems for gene therapy continue to improve as minimally invasive techniques are combined with recent vector technology. Encouraging results, such as tumour destruction and long-term protective immunity against metastatic disease, have been obtained in different animal models. This article discusses several recent phase I and II clinical trials. The results of these combined laboratory and clinical studies are expected to define optimal means of incorporating gene therapy into the treatment of liver metastasis.

Colorectal Neoplasms↗
PubMed1999

[Monolobar Caroli's disease. Apropos of 12 cases].

BACKGROUND: Caroli's disease is the dilatation of the segmental intrahepatic bile ducts. It usually affects the entire liver but can occasionally involve only one lobe, commonly the left. This study included 12 cases of unilobular disease, nine localised in the left lobe and three in the right lobe, which were all treated by liver resection. PATIENTS AND METHODS: These 12 patients underwent surgery between 1974 and 1997. There were six men and six women (mean age: 51 years). The initial presentation and diagnosis were reported. The mean interval between the first symptoms and diagnosis was 12.5 years. Eight of the 12 patients had undergone 22 surgical or endoscopic procedures prior to liver resection. In the present series a preoperative ultrasonogram or CT scan established the diagnosis in all cases. Six patients did not have stones in the gallbladder. RESULTS: Surgical treatment consisted in seven left lobectomies, two left hepatectomies and three right hepatectomies (Couinaud's classification). A intrahilar cholangiojejunostomy was performed in five cases. Pathological examination showed cystic dilatation of the intrahepatic segmental and subsegmental bile ducts, measuring from a few millimetres to 4 cm, which contained calculi. Two cases were associated with congenital hepatic fibrosis. An intrahepatic focus of ectopic pancreatic tissue was seen in one case. There were no cases with cholangiocarcinoma. One patient developed a biliary fistula which required reoperation. All patients had an uneventful long term postoperative course except for one patient who died of colon carcinoma 3 years postoperatively. CONCLUSION: When associated with other malformations, most notably congenital hepatic fibrosis, this commonly diffuse disease is called Caroli's syndrome. The unilobar form, most usually involving the left lobe of the liver, is called Caroli's disease. Both monolobar and diffuse types are often characterised by recurrent bouts of cholangitis and, in over half of the cases, by common bile duct stones without gallbladder stones.

Adult↗
PubMed1999

Asbestosis.

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Asbestosis↗
PubMed1999

Hepatic nonoxidative disposal of an oral glucose meal in patients with liver cirrhosis.

Seven patients with liver cirrhosis and five healthy subjects were studied over 4 hours after ingestion of a glucose meal to determine whether alterations of hepatic nonoxidative glucose disposal participate in the pathogenesis of impaired glucose tolerance. Hepatic uridyl-diphosphoglucose (UDPG) turnover was calculated from the isotopic enrichment of urinary acetaminophen glucuronide during continuous infusion of 13C-galactose and used as an index of hepatic glycogen synthesis. Patients with cirrhosis had postprandial hyperglycemia and decreased glucose clearance, but hepatic UDPG turnover was not altered (1.84 +/- 0.29 mg/kg fat-free mass min v 1.76 +/- 0.15 in controls, nonsignificant). It is concluded that hepatic postprandial glycogen synthesis is unaltered in patients with advanced cirrhosis, demonstrating important hepatic functional reserve.

Adult↗
PubMed1999

Effect of major hepatectomy on glucose and lactate metabolism.

BACKGROUND: The liver plays an important role in glucose and lactate metabolism. Major hepatectomy may therefore be suspected to cause alterations of glucose and lactate homeostasis. METHODS: Thirteen subjects were studied: six patients after major hepatectomy and seven healthy subjects who had fasted overnight. Glucose turnover was measured with 6,6(2)H glucose. Lactate metabolism was assessed using two complementary approaches: 13C-glucose synthesis and 13CO2 production from an exogenous 13C-labeled lactate load infused over 15 minutes were measured, then the plasma lactate concentrations observed over 185 minutes after lactate load were fitted using a biexponential model to calculate lactate clearance, endogenous production, and half-lives. RESULTS: Three to five liver segments were excised. Compared to healthy controls, the following results were observed in the patients: 1) normal endogenous glucose production; 2) unchanged 13C-lactate oxidation and transformation into glucose; 3) similar basal plasma lactate concentration, lactate clearance, and lactate endogenous production; 4) decreased plasma lactate half-life 1 and increased half-life 2. CONCLUSIONS: Glucose and lactate metabolism are well maintained in patients after major hepatectomy, demonstrating a large liver functional reserve. Reduction in the size of normal liver parenchyma does not lead to hyperlactatemia. The use of a pharmacokinetic model, however, allows the detection of subtle alterations of lactate metabolism.

Adult↗