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E A Roberts

Publications and source records attributed to E A Roberts.

At least 73 records · Page 4Linked to original sources
PubMed1993

The role of transjugular liver biopsy in fulminant liver failure: relation to other prognostic indicators.

Early and accurate diagnosis and prognosis of patients with fulminant liver failure is of critical importance for optimum management. We investigated the role of transjugular liver biopsy in the management of patients with fulminant liver failure and assessed its value in comparison with the recently proposed King's College criteria. Sixty-one patients with fulminant liver failure, ages 2 to 82 yr, were retrospectively analyzed. The main outcome measures were survival vs. death or progression to orthotopic liver transplantation. Transjugular liver biopsy was successful in 60 of 61 patients, with a mean core tissue length of 2.1 cm. There were eight minor complications, all of which were managed conservatively. Biopsy specimens were evaluated for degree of fibrosis, percentage of hepatocellular necrosis and presence of bile duct proliferation, hepatocellular mitotic figures and binucleate hepatocytes for each of the 54 specimens available for analysis. In 34 of 54 patients (63%), the presumed clinical diagnosis was confirmed by transjugular liver biopsy. In 11 patients the procedure served to clarify clinical uncertainty, whereas in 9 of 54 (16.7%) the diagnosis was altered after transjugular liver biopsy. The percentage of necrosis was the only histological parameter that appeared to have significant discriminatory prognostic value, with only 2 of 19 survivors having greater than 70% necrosis. Twenty-one of these biopsy specimens were reviewed by two pathologists, and their degree of correlation for the various features was assessed. Almost perfect concordance was found between the two pathologists on the percentage of hepatocellular necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗
PubMed1992

Transjugular liver biopsy in children.

Transjugular liver biopsy is widely used in adult patients with liver disease when transthoracic needle liver biopsy is contraindicated by severe coagulopathy or ascites. It has not been used extensively in children. We report our experience with 30 consecutive transjugular liver biopsy procedures performed in 27 young patients at the Hospital for Sick Children in Toronto. Patient weights ranged from 14 to 91 kg (median = 42 kg); most patients had not yet attained adult size. A 9F catheter was used except in very small children, for whom we developed a 7F biopsy needle catheter. Most procedures were done with patients under general anesthesia. Specimens were obtained in all patients, and the procedure was tolerated well. A major complication occurred only once: perforation of the inferior vena cava, which was later repaired at liver transplantation. Minor complications included subcapsular extravasation of contrast agent in five patients and a small intrahepatic hematoma in one. Results of transjugular liver biopsy changed the diagnosis in 30% of patients and added valuable information about the disease process in most patients. Transjugular liver biopsy was an important component of emergency assessment for liver transplantation. Our results indicate that transjugular liver biopsy can be performed safely in children with liver disease if a skilled interventional radiologist and a well-equipped angiography suite are available. Histological studies in these patients enhance our understanding of the natural history of pediatric liver diseases.

Acute Disease↗
PubMed1992

Modification of the daily photoreceptor membrane shedding response in vitro by antioxidants.

The shedding of rod outer segment disc membrane was investigated in a commonly used frog eyecup preparation, with respect to length of time in vitro. It was found that the amplitude, but not the timing, of the "dawn" (ie, when the lights are turned on) shedding response was increased threefold if the time in vitro was increased from 1.5-2 hr to 12-13 hr before dawn. After the overnight incubation, morphologic deterioration of the photoreceptors was not apparent by light or electron microscopy. The addition of the antioxidants, vitamin C or alpha-tocopherol (vitamin E), inhibited the increase in shedding, suggesting that it was induced by oxidation. These results help define conditions necessary for the maintenance of normal retinal metabolism in vitro. They also suggest a link between the amplitude of the dawn disc membrane shedding response and oxidation.

Animals↗
PubMed1991

Ah receptor mediating induction of cytochrome P450IA1 in a novel continuous human liver cell line (Mz-Hep-1). Detection by binding with [3H]2,3,7,8-tetrachlorodibenzo-p-dioxin and relationship to the activity of aryl hydrocarbon hydroxylase.

The Ah receptor regulates induction of cytochrome P450IA1 and mediates certain toxicities of polyhalogenated aromatics such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). It has been characterized previously in continuous cell lines, notably the mouse hepatoma line Hepa 1, the human squamous cell carcinoma line A431, and the human liver cell line Hep G2. The present work extends our knowledge of the Ah receptor in continuous human liver cell lines. Ah receptor can be detected in Mz-Hep-1, a hepatitis B virus-negative cell line derived from a Thorotrast-induced hepatocellular carcinoma. The mean concentration of Ah receptor in Mz-Hep-1 cells was 341 +/- 22 fmol/mg cytosol protein (mean +/- SEM, nine separate determinations). This is equivalent to approximately 30,000 sites per cell. The concentration of Ah receptor in Mz-Hep-1 cells is similar to that in Hepa 1 cells and approximately three times higher than that in Hep G2 cells. The Mz-Hep-1 Ah receptor sedimented in continuous sucrose gradients at approximately 9 S. Specificity of binding by [3H]TCDD was demonstrated by competitive binding of non-radiolabeled 2,3,7,8-tetrachlorodibenzofuran, 3-methylcholanthrene (MC), and dibenz[a,h]anthracene in 50-fold molar excess. Phenobarbital, which is not a substrate for P450IA1, did not compete with [3H]TCDD for binding to Mz-Hep-1 Ah receptor. Dexamethasone and estradiol also did not compete with [3H]TCDD for binding, suggesting non-identity of Ah receptor with glucocorticoid or estrogen receptor. In separate experiments, glucocorticoid receptor was identified in Mz-Hep-1 cells. By Scatchard plot analysis, the apparent equilibrium dissociation constant (Kd) for binding of [3H]TCDD to Mz-Hep-1 Ah receptor was estimated to be 4.4 nM, compared to 0.8 nM in Hepa 1 cells. By Woolf plot analysis the Kd was 5.4 nM, compared to 1.2 nM in Hepa 1 cells. The [3H]TCDD.Ah receptor complex extracted from nuclei of Mz-Hep-1 cells incubated with [3H]TCDD in culture at 37 degrees sedimented at approximately 6 S under conditions of high ionic strength. Aryl hydrocarbon hydroxylase (AHH) activity was detectable in Mz-Hep-1 cells after pretreatment with inducing chemicals. Mz-Hep-1 cells have the highest concentrations of Ah receptor in any continuous human liver cell line thus far investigated. The Mz-Hep-1 Ah receptor is similar physicochemically to that described in murine systems. AHH activity is inducible in Mz-Hep-1 cells.

Animals↗
PubMed1991

3'-end formation at the phage lambda tR1 rho-dependent transcription termination site.

The rho-dependent transcription terminator tR1 of bacteriophage lambda stops RNA synthesis downstream of the major rightward promoter, PR, shortly after the cro gene. Terminated transcripts produced in a purified in vitro transcription system display a heterodisperse set of 3' termini, occurring in clusters located at +290-300, 308-312, 340-345, 385-390, and 440-450 nucleotides from the transcription start site [Morgan, W.D., Bear, D.G., & von Hippel, P.H. (1983) J. Biol. Chem. 258, 9553-9564]. However, transcripts from the same promoter in vivo have been reported to end primarily at +310-312 [Court, D., Brady, C., Rosenberg, M., Wulff, D. L., Behr, M., Mahoney, M., & Izumi, S. (1980) J. Mol. Biol. 138, 231-254]. In order to understand the nature of this discrepancy, we have carried out a comparative analysis of lambda PR transcription products produced in translationally active S30 cell extracts, in a purified in vitro system and in vivo. RNAs from the cell extracts coupled to translation show primarily three PR-derived transcripts beginning at one predominant 5' end and terminating at +263, 308, and 318. Sites +263 and +308 appear to be RNA processing sites. S1 nuclease mapping studies of RNAs produced in vivo show one 5' end and two 3' termini ending at +263 and 311; the +263 site is the predominant 3' end. When transcripts produced in a purified in vitro transcription system are incubated in the S30 cell extract under various conditions, the RNAs are degraded to two primary products with lengths of 263 and 308-311 nt.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteriophage lambda↗
PubMed1991

Neonatal hepatitis syndrome with paucity of interlobular bile ducts in cystic fibrosis.

A male infant presenting with neonatal hepatitis syndrome, characterized by conjugated hyperbilirubinemia and very mild liver function test abnormalities, at 2 weeks of age was found to have no excretion of radioisotope into the intestinal tract on hepatobiliary scan. Liver biopsy revealed severe interlobular bile duct paucity. Other features of Alagille's syndrome were not present; other conditions frequently associated with interlobular bile duct paucity were also excluded. Subsequently, the infant was found to have cystic fibrosis. Cystic fibrosis is thus another disease that may be associated with paucity of interlobular bile ducts presenting as neonatal hepatitis syndrome, and this represents a different pathogenesis of cholestatic jaundice in neonates with cystic fibrosis besides those previously recognized.

Alkaline Phosphatase↗
PubMed1990

Characterization of the Ah receptor mediating aryl hydrocarbon hydroxylase induction in the human liver cell line Hep G2.

The Ah receptor, a soluble cytoplasmic receptor that regulates induction of cytochrome P450IA1 and mediates toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), was detected and characterized in the continuous human liver cell line Hep G2. The mean concentration of specific binding sites for TCDD was 112 +/- 26 (SEM) fmol/mg cytosol protein as determined in eight separate cytosol preparations in the presence of sodium molybdate. This is equivalent to 14,000 binding sites per cell, approximately 40% of the sites per cell found in the mouse hepatoma line Hepa-1. The cytosolic Ah receptor from Hep G2 cells sedimented at 9 S and was specific for those halogenated and nonhalogenated aromatic compounds known to be agonists for the Ah receptor in rodent tissues and cells. Specific binding in the 9 S region was detected with both [3H]TCDD and 3-[3H]methylcholanthrene. 3-[3H]Methylcholanthrene did not bind to any component besides that at approximately 9 S. Phenobarbital, dexamethasone, and estradiol did not compete with [3H]TCDD for binding to the Hep G2 Ah receptor. Specific binding of [3H]triamcinolone acetonide to glucocorticoid receptor could also be demonstrated in Hep G2 cytosol. The apparent equilibrium dissociation constant (Kd) for binding of [3H]TCDD to Hep G2 Ah receptor was 9 nM by Woolf plot analysis, about an order of magnitude weaker than the affinity of [3H]TCDD for the mouse Hepa-1 Ah receptor or for the C57BL/6 murine hepatic Ah receptor. [3H]TCDD.Ah receptor complex, which was extracted from nuclei of Hep G2 cells incubated with [3H]TCDD at 37 degrees C in culture, sedimented at approximately 6 S under conditions of high ionic strength. Aryl hydrocarbon hydroxylase (AHH) activity was significantly induced after 24 h of incubation with polycyclic aromatic hydrocarbons: the EC50 for AHH induction was 5.3 microM for benz(a)anthracene and 1.3 microM for 3-methylcholanthrene. Modification of the preparative technique for cell cytosol, especially inclusion of 20 mM sodium molybdate in homogenizing and other buffers, was necessary to detect cytosolic Hep G2 Ah receptor. Hep G2 cells appear to conserve drug-metabolizing activity associated with cytochrome P450IA1 as well as the receptor mechanism which regulates its induction.

Aryl Hydrocarbon Hydroxylases↗
PubMed1990

Cytomegalovirus infections in pediatric liver transplantation.

From 1986 to 1989, 26 consecutive pediatric liver transplant recipients were followed up at The Hospital for Sick Children, Toronto, Canada. The patients were reviewed to assess the incidence of infection with cytomegalovirus, the severity of disease, and the relationship of recipient and donor serostatus to cytomegalovirus disease. Overall, the incidence of infection was 54% (14/26). Over 90% of patients who were seropositive or whose donors were seropositive developed evidence of cytomegalovirus infection after transplantation. Forty-three percent (6/14) of those with cytomegalovirus infections developed severe, fatal cytomegalovirus disease, despite treatment with immunoglobulins and ganciclovir (Syntex Laboratories Inc, Palo Alto, Calif) or foscarnet sodium (Astra, Pharmaceutical Products Inc, Westborough, Mass). Of all posttransplant deaths, two thirds were associated with severe cytomegalovirus infection. Cytomegalovirus-related deaths occurred in three of four seronegative patients with seropositive donors and three of six seropositive patients with seropositive donors. Therefore, a seropositive donor appeared to be a major risk factor for severe cytomegalovirus disease.

Adolescent↗
PubMed1990

Phenobarbital hepatotoxicity in an 8-month-old infant.

Severe hepatotoxicity from phenobarbital occurred in an infant boy who had a complicated illness with chronic bilateral subdural hematomas and sepsis. Skin rash began after 2 weeks of treatment, and signs of hepatocellular failure developed 3 weeks after phenobarbital had been started. Signs of severe liver disease included elevated aminotransferases, conjugated hyperbilirubinemia, significant coagulopathy, hepatosplenomegaly and ascites. Other features of this adverse drug reaction were unremitting fever, leukocytosis with eosinophilia and atypical lymphocytosis, and proteinuria. Sepsis, viral hepatitis, and metabolic liver disease were excluded. The child was on no other medication and had been previously well. In-vitro rechallenge of the patient's lymphocytes with cytochrome P-450 generated metabolites of phenobarbital showed extensive cytotoxicity compared to control. These data support the hypothesis that a defect in drug detoxification was responsible for the child's susceptibility to this drug hepatotoxicity.

Carbamazepine↗
PubMed1990

Liver disease in neonatal lupus erythematosus.

We report the cases of neonatal lupus erythematosus associated with significant hepatic involvement in three living infants and in one infant who died 3 hours after delivery. The three living infants had neonatal cholestasis as a major component of their clinical findings. Pathologic changes included giant cell transformation, ductal obstruction, and extramedullary hematopoiesis. Liver involvement has been noted incidentally in children with neonatal lupus erythematosus, but it has generally been attributed to hemodynamic compromise as a result of congenital heart block or systemic toxic reactions. We speculate that neonatal hepatitis proceeding to hepatic fibrosis may occur in neonatal lupus erythematosus, analogous to the occurrence of "idiopathic" congenital heart block. The neonatal hepatitis associated with neonatal lupus erythematosus is a form distinguishable from the "idiopathic" group. Liver involvement may be more common than was previously recognized, and prospective studies to look for maternal autoantibodies in idiopathic neonatal liver disease should be undertaken.

Antibodies, Antinuclear↗
PubMed1990

Liver cell dysplasia and early liver transplantation in hereditary tyrosinemia.

Two cases of hereditary tyrosinemia presented with ascites and coagulopathy in infancy. Both patients underwent liver transplantation at the age of 25 and 36 mo, respectively. Both cases had normal liver function 37 and 24 mo later. The native liver in each case showed mixed micro- and macronodular cirrhosis with hepatocellular dysplasia, including both the large and small cell varieties. One of the subjects had also shown dysplasia in a prior liver biopsy. We compared the hepatic morphology with that from two other cases from our autopsy files. One of these (a female, 9 mo old) showed dysplasia, and the other (her male sibling, 4 yr old) had a liver cell carcinoma with lung metastases. These observations confirm prior reports that neoplastic transformation occurs early in the natural history of hereditary tyrosinemia despite meticulous dietary management and other supportive treatment. With the detection of liver cell dysplasia, efforts should be intensified to find an appropriate donor. Liver transplantation cures the hepatic disease and should be performed before malignancy develops.

Amino Acid Metabolism, Inborn Errors↗
PubMed1989

Liver transplantation in children: the initial Toronto experience.

The Hospital for Sick Children's initial 2-year experience with pediatric liver transplantation is reviewed. Patients are divided into high- and low-risk groups according to certain criteria. The high-risk group includes patients under 10 kg in weight, those with extrahepatic biliary atresia (EHBA), those with portal vein atresia or thrombosis, and those in hepatic coma. All others were considered low risk. Twenty-nine patients were assessed for transplantation: 18 were transplanted and 6 (21% of total referred) died while on the waiting list. Eighteen patients received 23 transplants. Of the 18 recipients, nine had EHBA, four had fulminant hepatic failure, two had tyrosinemia, one had glycogen storage disease, one had Indian childhood cirrhosis, and one had idiopathic cirrhosis. Seven of the 13 patients in the high-risk group survived (55% survival) with 1 to 23 month follow-up. Survival was significantly higher (80%) in the low-risk group (P less than 0.05). Four patients were retransplanted and two survived. Early deaths occurred from prolonged warm ischemia, recurrent portal vein thrombosis, and brain death in a patient who had been transplanted in hepatic coma. Late deaths occurred from cytomegalovirus (CMV) disease (2 patients), acute rejection (1 patient), and myocardial infarction (1 patient). The incidence of primary nonfunction was 4.3% (1 of 23) and of arterial thrombosis was 13% (3 of 23). Survival in patients transplanted for EHBA (67%) was slightly higher than it was for the rest of the group, although not as good as it was in the low-risk group.(ABSTRACT TRUNCATED AT 250 WORDS)

Biliary Atresia↗
PubMed1989

Resting energy expenditure is increased in infants and children with extrahepatic biliary atresia.

To determine if liver dysfunction in children affects energy and macronutrient homeostasis, we performed 13 metabolic studies in 11 patients (age, 17.8 +/- 5.9 months [mean +/- SEM]) with extrahepatic biliary atresia (EHBA). Nutritional balance, indirect calorimetry, anthropometry, and biochemical liver function tests were utilised. Sixty-four percent of the energy losses were in the form of stool fat. Energy expenditure (68 kcal/kg/d) was 29% higher than normal (P less than 0.0025). Only one third of the metabolisable energy intake (37 kcal/kg/d) was stored in the body for new tissue synthesis. In spite of the bountiful protein intake for age, the increased protein oxidation (2g/kg/d) resulted in a virtually zero mean nitrogen balance. In addition, four patients oxidised endogenous protein as well. The respiratory quotient was 0.96, and did not change significantly between pre- and post-meal measurements, suggesting a predominant utilisation of carbohydrate for energy metabolism. Net lipid oxidation was severely diminished. We found that the higher the serum aspartate aminotransferase level (previously named SGOT), the lower the net fat oxidation, and the higher the conversion of glucose to fat. These data suggest that markedly increased energy expenditure contributes to the malnutrition of patients with EHBA. We characterised for the first time how severe liver disease in infants and children affects carbohydrate, fat, and protein metabolism, thus inducing protein-energy malnutrition.

Basal Metabolism↗
PubMed1989

Ultraviolet irradiation for hepatic rickets.

An infant with chronic cytomegalovirus hepatitis and a child with atypical Alagille's syndrome had vitamin D deficiency rickets due to malabsorption. Both received ultraviolet irradiation. This treatment corrected biochemical abnormalities and healed the rickets. In the infant use of a sunlamp at home maintained normal 25 hydroxy-vitamin D for over a year. Our study shows that ultraviolet irradiation is an effective treatment of hepatobiliary rickets.

Child↗
PubMed1989

Ah receptor in spleen of rodent and primate species: detection by binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin.

In many species systemic toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is manifested by a generalized wasting syndrome accompanied by a variety of specific organ changes including atrophy of the thymus and spleen. TCDD toxicity in most tissues is thought to be mediated by the Ah receptor. Although the spleen is a prime target for TCDD toxicity, the possible presence of Ah receptor in the spleen has not previously been investigated. Specific binding of [3H]TCDD to Ah receptor in spleen cytosols was assessed by velocity sedimentation on sucrose gradients. Ah receptor was detected in spleen cytosols from adult Rhesus monkeys (mean +/- SEM, 36 +/- 8 fmol/mg cytosol protein), fetal Rhesus monkeys (9 +/- 6), Sprague-Dawley rats (20 +/- 5), C57BL/6J mice (18 +/- 2), New Zealand white rabbits (19 +/- 2), and Hartley guinea pigs (15 +/- 2). Ah receptor was not detectable in spleen cytosol from genetically "nonresponsive" DBA/2J mice or from Golden Syrian hamsters, a species resistant to toxicity of TCDD. Molecular properties of Ah receptor from spleen were similar to those of the receptor from liver of the same species. The high Ah receptor content in spleen cytosols from those species that are most susceptible to TCDD toxicity is consistent with the view that the Ah receptor mediates TCDD toxicity in spleen as well as in other tissues.

Animals↗
PubMed1989

Biochemical and clinical response of fulminant viral hepatitis to administration of prostaglandin E. A preliminary report.

The effect of PG on patients with fulminant and subfulminant viral hepatitis (FHF) was studied. 17 patients presented with FHF secondary to hepatitis A (n = 3), hepatitis B (n = 6), and non-A, non-B (NANB) hepatitis (n = 8). 14 of the 17 patients had stage III or IV hepatic encephalopathy (HE). At presentation the mean aspartate transaminase (AST) was 1,844 +/- 1,246 U/liter, bilirubin 232 +/- 135 mumol/liter, prothrombin time (PT) 34 +/- 18, partial thromboplastin time (PTT) 73 +/- 26 s, and coagulation Factors V and VII 8 +/- 4 and 9 +/- 5%, respectively. Intravenous PGE1 was initiated 24-48 h later after a rise in AST (2,195 +/- 1,810), bilirubin (341 +/- 148), PT (36 +/- 15), and PTT (75 +/- 18). 12 of 17 responded rapidly with a decrease in AST from 1,540 +/- 833 to 188 +/- 324 U/liter. Improvement in hepatic synthetic function was indicated by a decrease in PT from 27 +/- 7 to 12 +/- 1 s and PTT from 61 +/- 10 to 31 +/- 2 s, and an increase in Factor V from 9 +/- 4 to 69 +/- 18% and Factor VII from 11 +/- 5 to 71 +/- 20%. Five responders with NANB hepatitis relapsed upon discontinuation of therapy, with recurrence of HE and increases in AST and PT, and improvement was observed upon retreatment. After 4 wk of intravenous therapy oral PGE2 was substituted. Two patients with NANB hepatitis recovered completely and remained in remission 6 and 12 mo after cessation of therapy. Two additional patients continued in remission after 2 and 6 mo of PGE2. No relapses were seen in the patients with hepatitis A virus and hepatitis B virus infection. Liver biopsies in all 12 surviving patients returned to normal. In the five nonresponders an improvement in hepatic function was indicated by a fall in AST (3,767 +/- 2,611 to 2,142 +/- 2,040 U/liter), PT (52 +/- 25 to 33 +/- 18 s), and PTT (103 +/- 29 to 77 +/- 44 s), but all deteriorated and died of cerebral edema (n = 3) or underwent liver transplantation (n = 2). These results suggest efficacy of PGE for FHF, and further investigation is warranted.

Adolescent↗