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K Paradis

Publications and source records attributed to K Paradis.

At least 37 records · Page 2Linked to original sources
PubMed1996

Leucocyte adhesion deficiency presenting as a chronic ileocolitis.

CD11/CD18 leucocyte glycoprotein deficiency is a rare, congenital adhesion molecule disorder which, in its severe form, is usually fatal. Leucocytes in affected subjects have abnormal migration and adherence, rendering patients susceptible to life threatening infections. The CD11/CD18 integrins, and other adhesion molecules, are considered essential to the normal inflammatory response. It has been postulated that adhesion molecules may be responsible for mediating in part, the inflammatory changes observed in inflammatory bowel diseases and related disorders. This report describes the first case of CD11/CD18 deficiency characterised by a chronic ileocolitis. Bone marrow transplantation completely resolved the gastrointestinal symptoms, supporting a role for neutrophil dysfunction in the pathogenesis of the gut lesions. This case suggests that specific blockade of CD11/CD18 integrins alone may not halt the chronic inflammatory response observed in immune mediated bowel disorders, and that abnormalities of leucocyte function must be included in the differential diagnosis of paediatric Crohn's disease.

Bone Marrow Transplantation↗
PubMed1996

Tyrosinemia: the Quebec experience.

Tyrosinemia, a genetic disorder of the liver and kidneys, is caused by reduced activity of fumarylacetoacetate hydrolase (FAH), the final enzyme in the degradation of tyrosine. The consequent presence of succinylacetone in urine or blood is pathognomonic of tyrosinemia and is used as a confirmatory test in the Quebec neonaral screening program. Due to a complex founder effect, the province of Quebec has an unusually high prevalence of tyrosinemia, particularly in the Saguenay-Lac Saint-Jean region (where the prevalence is 1 in 1850). Tyrosinemia has several different clinical presentations, ranging from acute liver failure with severe coagulopathy early in life, to slowly progressing cirrhosis with multiple nodules and variable renal dysfunction, to normal liver function with renal failure. Hepatocarcinoma has been found in approximately one third of cases. FAH complementary DNA has been cloned and mapped to chromosome 15q23-q25. The mutation observed in Quebec is a splice mutation at intron 12. This mutation is common and has been observed in other areas of the world as well, although more than 20 mutations causing tyrosinemia have now been described. Liver transplantation remains the definitive treatment. The author's team has carried out 28 liver transplantations (including 2 combined liver-kidney transplantations) in 25 children. The overall survival rate has been 92%; two children died as a result of primary nonfunction. The primary indications for transplantation were hepatic nodules (in 14 cases), neurological crises (6) and hepatic (3) or renal failure (2). An abnormal glomerular filtration rate (GFR) of less than 80 mL/min per 1.73 m2 was documented before transplantation in 54% of the cases. The rate normalized after liver transplantation in most patients, with rapid improvement in tubular function. However, patients with a severely low rate (less than 55 mL/min per 1.73 m2) before transplantation still had borderline renal function and poor growth after the transplantion, despite normal liver function. Therefore, for children with a consistently low GFR, careful consideration should be given to performing a combined liver-kidney transplantation, and a renal biopsy should form part of the pretransplantation evaluation.

Amino Acid Metabolism, Inborn Errors↗
PubMed1995

Hypertrophic cardiomyopathy associated with tacrolimus in paediatric transplant patients.

Reported side-effects of tacrolimus, a potent immunosuppressive agent, have not included cardiotoxicity. We describe 5 consecutive paediatric transplant recipients (3 small bowel with or without liver and 2 liver) who received tacrolimus. 2 developed congestive heart failure and hypertrophic obstructive cardiomyopathy which resolved after changing to cyclosporin. In the other 3 patients the cardiomyopathy regressed or improved with a lower dose of tacrolimus or after stopping the drug.

Blood Pressure↗
PubMed1995

Safety, tolerability, and pharmacokinetic actions of diltiazem in pediatric liver transplant recipients on cyclosporine.

Thirty-two children who had undergone liver transplantation were paired according to their posttransplantation duration, renal function, and diagnoses when possible and randomized either to continue nifedipine (NIF group) or switch to diltiazem (DIL group), in addition to continuing their usual immunosuppressive medications. The cases were followed prospectively regarding diltiazem tolerance, cyclosporine dose requirements, effect on cyclosporine kinetics, diltiazem kinetics, as well as effect on renal function. Diltiazem was well tolerated at a dose of 3 mg to 6.4 mg/kg/day (max 180 mg/day) with infrequent self-limited mild side effects. Cyclosporine daily dose was reduced by a mean of 36.7% and 38.3% at 3 and 6 months, respectively, in the DIL group to achieve target trough cyclosporine levels without modifying liver function. No significant difference in renal function was observed after 3 to 6 months in either group based on blood urea nitrogen and creatinine levels and glomerular filtration rate by the DTPA method. Diltiazem appears to be well tolerated in children and allows for substantial dose reductions of CSA without apparent effects on liver graft function.

Adolescent↗
PubMed1995

Characterization and response to interleukin 1 and tumor necrosis factor of immortalized murine biliary epithelial cells.

BACKGROUND & AIMS: Biliary epithelial cells are the target of numerous immune-mediated liver diseases, yet their role in pathogenesis remains unclear because of difficulties in obtaining pure preparations. The aim of this study was to establish pure clones of immortalized murine intrahepatic biliary epithelial cells. METHODS: The transgenic mouse harboring the SV40 thermosensitive immortalizing mutant gene TsA58 under the control of the major histocompatibility complex class I promoter was used to establish conditionally immortalized intrahepatic bile duct cells by countercurrent centrifugal elutriation and clonal dilution. RESULTS: Immortalized clones of cells expressing cytokeratin 19, which organized themselves into ductlike structures, were obtained. On electron-microscopic sections, cells were well differentiated and polarized. Cells proliferate in response to epidermal growth factor, interleukin 1 alpha, and tumor necrosis factor alpha. Using the reverse-transcriptase polymerase chain reaction technique, these cells were found to contain messenger RNA, which encodes for the interleukin 1 and tumor necrosis factor receptors. CONCLUSIONS: The availability of unlimited numbers of pure bile duct cells that behave in an identical fashion to biliary epithelial cells from "normal" mice will allow for more rigorous studies of the behavior and function of this epithelium.

Animals↗
PubMed1995

Vascular complications after pediatric liver transplantation.

From February 1986 to July 1994, 81 hepatic transplantations were performed in 73 children, with an overall patient survival rate of 83%. Forty-two patients received whole-liver grafts (WLG) and 39 had reduced-size grafts (RSG). The mean patient weight was 19.7 kg, with 29 patients weighing less than 10 kg. Seventeen vascular complications (21%) occurred in 13 children: 8 (10%) had hepatic artery thrombosis (HAT), 5 (6%) had portal vein thrombosis (PVT), 1 had both HAT and PVT (1%), and 3 (4%) had aortic conduit perforation (ACP). There was no significant difference in the incidence of HAT between RSG (5%) and WLG (14%) or between children weighing less than 10 kg (10%) and those weighing more than 10 kg (10%). The site of arterial reconstruction, end-to-end to the recipient common hepatic artery or end-to-side to the infrarenal aorta, had no significant effect on the occurrence of HAT (7% v 8%), but HAT occurred in 2 of 6 cases (33%) in which an aortic conduit was used. PVT documented in 5 cases (6%) was associated with technical complications (2), preduodenal portal vein (2), and a circulating cardiolipid antibody (1), and required thrombectomy, with no graft loss. Combined HAT and PVT was found in one patient 2 years postretransplantation for HAT. Although graft function is normal, portal hypertension persists. The aortic conduit, used in six patients, led to arterial perforation (3), HAT (2), and death (2). Of the 8 cases of HAT, 1 was diagnosed during autopsy and 7 occurred within 30 days and required retransplantation (6) or thrombectomy with rearterialization (1).(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical↗
PubMed1995

Cavernous transformation of the portal vein: patterns of intrahepatic and splanchnic collateral circulation detected with Doppler sonography.

OBJECTIVE: Cavernous transformation of the portal vein is defined as the formation of venous channels within or around a previously thrombosed portal vein. The purpose of this work was to study the hemodynamic consequences of cavernous transformation of the portal vein in a group of afflicted patients by use of Doppler sonography. We wished to study the evolution from portal vein thrombosis to the formation of cavernous transformation, the extent of resulting extrahepatic collateral channels, and the patterns of splanchnic collateral circulation. MATERIALS AND METHODS: Seventy-five patients (48 adults and 27 children) with cavernous transformation of the portal vein were studied with color and/or pulsed Doppler sonography. Blood flow in the extrahepatic portal vein, in its segmental branches, in the hepatic veins and artery, and in the splanchnic veins was examined. Collateral pathways were sought. For nine patients with acute thrombosis of the portal vein, serial examinations were performed during the formation of cavernous transformation. RESULTS: In nine patients, a fresh thrombus filled and distended the portal vein and became recanalized within a few days. Tortuous vessels appeared at the porta hepatis. These were characterized as veins or arteries with Doppler sonography. Soon the portal vein could no longer be identified within the mass of tortuous vessels. The cavernous transformation developed within 6-20 days of the acute thrombosis. A spongelike mass of collateral vessels around the main portal vein was seen in all but two patients. Intrahepatic extension of the cavernous transformation was seen in 57 patients (76%) and involved one or more intrahepatic portal veins. Two types of collateral circulation were observed: portosystemic, mainly through the left gastric and the perisplenic veins (the caput medusae, i.e., the paraumbilical-to-abdominal venous route, was never seen); and portoportal, from the periportal or pericholecystic venous channels to the intrahepatic portal veins. In nine patients, flow within unaffected intrahepatic branches of the portal vein was reversed as directed toward the cavernous transformation surrounding other, thrombosed intrahepatic segments of the portal vein. CONCLUSION: After thrombosis of the portal vein, portoportal venous channels may form not only at the porta hepatis but also within the liver. Intrahepatic blood may be shunted from one segmental portal vein to another. In addition, portosystemic collateral channels are formed, suggesting that, despite extensive hemodynamic adaptations, portal hypertension ensues.

Acute Disease↗
PubMed1994

A conformational model for the human liver microsomal glucose-6-phosphatase system: evidence from rapid kinetics and defects in glycogen storage disease type 1.

Rapid kinetics of glucose-6-phosphate (G6P) uptake and hydrolysis as well as of orthophosphate uptake were investigated in microsomes prepared from normal and glycogen storage disease type 1a (GSD 1a) human livers using a fast sampling, rapid filtration apparatus and were compared to those of rat liver microsomes. As shown before with rat microsomes, the production of [U-14C]glucose from 0.2 mmol/L [U-14C]G6P by untreated normal human microsomes was characterized by a burst in activity during the first seconds of incubation, followed by a slower linear rate. The initial velocity of the burst was equal to the rate of glucose production in detergent-treated microsomes. In untreated and detergent-treated GSD 1a microsomes, no glucose-6-phosphatase activity was observed. When untreated normal human or rat microsomes were incubated in the presence of 0.2 mmol/L [U-14C]G6P, an accumulation of [U-14C]glucose was observed, whereas no radioactive compound (G6P and/or glucose) was taken up by GSD 1a microsomes. Orthophosphate uptake was, however, detectable in both GSD 1a and normal untreated vesicles. These results do not support a rate-limiting transport of G6P in untreated normal human microsomes and further show that in this case of GSD 1a, no distinct G6P transport activity is present.

Adolescent↗
PubMed1993

Circulating tumor necrosis factor-alpha levels and lipid abnormalities in patients with cystic fibrosis.

Hyperlipidemia is prominent among the disturbances in intermediary metabolism that occur subsequent to infections by microorganisms. The response to such infections is known to involve several cell types and is mediated by cytokines. We hypothesized that metabolic lipid disturbances seen during infection in cystic fibrosis (CF) patients may partly be the result of excessive tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine known to cause a large spectrum of pathophysiologic alterations, including impaired lipid metabolism. Therefore, we determined the circulating concentration of TNF-alpha and analyzed its relationship to lipid and lipoprotein levels, as well as lipoprotein lipase activity, in 31 CF patients. Plasma TNF-alpha values were significantly (p < 0.01) elevated in patients with CF compared with controls. The CF subjects were found to have decreased plasma cholesterol (25%), LDL cholesterol (35%), and HDL cholesterol (19%) concentrations, whereas plasma triglycerides were significantly increased (p < 0.001). The apo A-I level was reduced (p < 0.005), whereas apo B levels were normal. Low levels of the major essential fatty acids were found in the plasma of the CF patients, and the triene/tetraene ratio confirmed their essential fatty acid deficiency. Postheparin lipolytic activity was lower in CF patients than in controls, and the decreased activity was accounted for primarily by a decline in hepatic lipase. A significant positive correlation (p < 0.001, r = 0.70) was found between TNF-alpha and plasma triglyceride levels. However, no association was noted between TNF-alpha and essential fatty acid, cholesterol, or lipoprotein cholesterol levels, or with lipoprotein lipase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

The immunosuppressive effect of ursodeoxycholic acid: a comparative in vitro study on human peripheral blood mononuclear cells.

Ursodeoxycholic acid is an efficient treatment for putatively immune-mediated liver diseases, but its mechanism of action is unknown. We studied human mononuclear cell proliferation as an in vitro model for cell-mediated immunity in the presence of ursodeoxycholic acid, its glycoconjugate and tauroconjugate and chenodeoxycholic acid at concentrations of 5, 25 and 50 mumol/L. Proliferation was inhibited in a dose-dependent manner compared with control values (15% to 54% depending on the bile acid, concentration and mitogen used), except at 5 mumol/L where inhibition was significant with only one mitogenic stimulus of the three used. With one mitogen (phorbolester) the inhibition was additive with that of cyclosporine. The number of cell-surface receptors studied was not modified by bile acids. Interleukin-2 production was decreased 35% to 60% by ursodeoxycholic acid and its conjugates. The proliferation of the interleukin-2-dependent cell line CTLL-2 was also inhibited. The immunosuppression was reversible except at a chenodeoxycholic acid concentration of 50 mumol/L. Because bile acids are able to partition into membranes and change their properties, we speculate that this allows them to interact with cell-surface receptors or signaling systems within the membrane or on its inner face, thus impairing their function. This would inhibit the numerous extracellular messages that lymphocytes need to proliferate.

Animals↗
PubMed1991

Infectious complications of pediatric liver transplantation.

Twenty-five pediatric orthotopic liver transplantations (OLTs) performed in 22 patients at Sainte-Justine Hospital were reviewed for infections complications. One patient died within 12 hours posttransplantation and is excluded. The patients had an average age of 6.1 years (range, 1.25 to 19 years) and an average weight of 20.4 kg (range, 11 to 55 kg). Two patients (9%) were cytomegalovirus (CMV) seropositive and 9 of 19 patients (48%) were Epstein-Barr virus (EBV) seropositive preoperatively. Five of the donors (20%) were CMV seropositive. The most common indications for OLT were biliary atresia (8) and tyrosinemia (7). There were 4 deaths, for an overall mortality rate of 19%. In 3 patients, deaths were related to infection (CMV hepatitis and duodenitis with aortoduodenal fistula, adult respiratory distress syndrome [ARDS] with Streptococcus viridans pneumonia, Escherichia coli cholangitis with progressive hepatic failure). Fifteen patients (72%) had 41 major infections, most of them bacterial, during the first month posttransplantation. These include pneumonia (25%), line sepsis (17%), cholangitis (14%), and tracheitis (14%). There was only one major viral infection, a CMV hepatitis that occurred in the first month posttransplantation. Three patients had fungal infections (8%) associated with hepatic artery thrombosis and recurrent cholangitis. All three patients required retransplantation. There was only one protozoal infection (Pneumocystis carinii pneumonia) causing life-threatening respiratory failure, from which patient recovered without sequelae. Infection still remains a serious complication of OLT. Bacterial infection is common and is usually associated with technical complications. The low rate of CMV infection is related to low incidence of CMV in the donor pool and the minimal use of strong immunosuppressants.

Adolescent↗