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Biomedical subjects

E Elias

Publications and source records attributed to E Elias.

At least 91 records · Page 5Linked to original sources
PubMed1995

Hereditary haemorrhagic telangiectasia and secondary biliary cirrhosis.

We report the case of a 65-year-old woman with a 10-year history of biliary disease and a 3-year history of anaemia, lethargy, angina and recurrent ascending cholangitis; she had hereditary haemorrhagic telangiectasia (HHT) with aneurysms in the splanchnic circulation, and was assumed to have secondary biliary cirrhosis with portal hypertension and hypertrophic obstructive cardiomyopathy. Her portal hypertension was caused by secondary biliary cirrhosis induced by intrahepatic gallstones; this was associated with left ventricular hypertrophy and a high cardiac output, caused by increased splanchnic circulation, and with aneurysms in the superior mesenteric and pancreaticoduodenal arteries, which were visualized by angiography. We conclude that HHT can produce abnormal abdominal vascular anatomy, which affects haemodynamic performance and makes it difficult to manage a patient with portal hypertension caused by secondary biliary cirrhosis. HHT has been shown to be associated with intrahepatic biliary stones and might have a causal role. When assessing patients with this type of condition for liver transplantation, particular attention should be paid to haemodynamic and circulatory abnormalities.

Aged↗
PubMed1995

Failure to incriminate hepatitis B, hepatitis C, and hepatitis E viruses in the aetiology of fulminant non-A non-B hepatitis.

Sporadic non-A, non-B hepatitis is the most common indication for liver transplantation in patients presenting with fulminant and subacute liver failure. This study used serological, histological, and molecular biological techniques to examine specimens from 23 consecutive patients transplanted for sporadic non-A, non-B hepatitis. No evidence was found of hepatitis C virus, hepatitis E virus, or 'cryptic' hepatitis B virus infection.

Adolescent↗
PubMed1995

Fetal mortality associated with cholestasis of pregnancy and the potential benefit of therapy with ursodeoxycholic acid.

Cholestasis of pregnancy is associated with increased fetal morbidity and mortality and should be treated actively. The significance attached to pruritus in pregnancy is often minimal, but it is a cardinal symptom of cholestasis of pregnancy, which may have no other clinical features. Eight women with previous cholestasis of pregnancy were referred to The Liver Unit within a 12 month period for advice concerning future pregnancies. Thirteen pregnancies had been affected by cholestasis of pregnancy and 12 had been treated expectantly with resultant perinatal morbidity or mortality in 11 (one normal delivery), including; eight stillbirths, two premature deliveries with fetal distress (one died in perinatal period), and an emergency caesarean section for fetal distress. The other pregnancy was treated actively and delivery was uncomplicated. Subsequently, three of these cases with recurrent cholestasis of pregnancy were referred while pregnant. In each, cholestasis developed with severe pruritus, gross increase of serum bile acids, and deranged liver tests. Each was treated with the choleretic agent ursodeoxycholic acid, with rapid clinical improvement and resolution of deranged biochemistry. In conclusion, cholestasis of pregnancy continues to be treated expectantly despite its association with increased morbidity and mortality and evidence suggesting improved prognosis with active treatment and the potential of reducing the associated perinatal mortality. In an uncontrolled series of three patients with cholestasis of pregnancy, ursodeoxycholic acid seemed to provide safe and effective therapy.

Adult↗
PubMed1995

The effects of ethanol, 3,5,3'-triiodothyronine (T3) and oestradiol (E2) on thyroid hormone nuclear receptor expression in human hepatocyte primary cultures.

The possibility that ethanol regulated the expression of thyroid hormone receptor mRNA levels was explored in a model involving human hepatocyte primary culture. Ethanol (20, 50 and 100 mM for 24 h was found to have no effect on the steady-state levels of either triiodothyronine (T3) receptor alpha 1 or alpha 2 mRNAs. In contrast both T3 (1, 10 and 100 nM) and oestradiol (0.1, 1 and 10 ng/ml) treatments affected either one or both of these mRNA levels in a complex manner, showing that the model was capable of responding to other stimuli. Triiodothyronine receptor beta 1 mRNA was not assayed. The hypermetabolic effects of long-term ethanol consumption in humans appears not to be due to the direct effect of ethanol on the regulation of these receptors.

Culture Techniques↗
PubMed1995

Markedly increased tissue concentrations of 7-dehydrocholesterol combined with low levels of cholesterol are characteristic of the Smith-Lemli-Opitz syndrome.

The Smith-Lemli-Opitz syndrome is an autosomal recessive birth defect (frequency 1:20,000-1:40,000) that results in profound mental retardation, physical deformities, and failure to thrive. It is characterized biochemically by low plasma cholesterol and greatly elevated levels of two dehydrocholesterols, one of which is the cholesterol precursor 7-dehydrocholesterol. To determine whether the block in cholesterol biosynthesis affects tissue sterols, we assayed several organs from two affected individuals, a female who died at 27 hours and a 20-week male fetus. Cholesterol concentrations in abdominal wall, adrenal gland, and kidney from two or three unaffected fetuses, who served as controls, averaged 2.0, 1.5, and 1.4 mg/g wet weight, compared to 0.08, 0.44, and 0.14, respectively, for the homozygous fetus. Cerebral cortex cholesterol concentrations were 2.2 mg/g for two 20-22-week fetal controls but only 0.21 and 0.09 mg/g, respectively, for the homozygous child and fetus. Similarly, tissue cholesterol levels were abnormally low in the homozygous child being less than 1 mg/g in liver, adipose, thymus, muscle, and adrenal and 6.2 mg/dl in plasma. Dehydrocholesterols could not be detected by conventional means in any controls but were elevated enough in tissues from affected individuals to make total sterol concentrations nearly normal. These results suggest that a defect in 3 beta-hydroxysterol delta 7-reductase leads to both a profound lack of cholesterol and its replacement by dehydrocholesterols. Such a combination may be lethal in the most severely affected individuals.

Abnormalities, Multiple↗
PubMed1994

Recovery despite impaired cerebral perfusion in fulminant hepatic failure.

We report 4 patients with fulminant hepatic failure who developed prolonged intracranial hypertension (> 35 mm Hg for 24-38 h) that was refractory to standard therapy and associated with impaired cerebral perfusion pressure (< 50 mm Hg for 2-72 h). All survived with complete neurological recovery. Refractory elevation of intracranial pressure and reduced cerebral perfusion pressure are generally thought to contra-indicate liver transplantation in hepatic failure and are indications to withdraw support. Our observations challenge this concept.

Adult↗
PubMed1994

Endothelial activation and circulating vascular adhesion molecules in alcoholic liver disease.

Alcoholic hepatitis is characterized by hepatocyte necrosis associated with infiltration of the liver parenchyma by neutrophils. The mechanisms responsible for recruiting neutrophils to the liver are unknown. We report high circulating levels and tissue expression of the endothelial adhesion molecule E-selectin in alcoholic hepatitis. Because expression of E-selectin is involved in neutrophil transmigration into inflamed tissue, it may play a crucial role in the recruitment of neutrophils to the liver in alcoholic hepatitis. By contrast, we detected high levels of vascular cell adhesion molecule-1, the endothelial counter-receptor for the lymphocyte adhesion molecule very late antigen-4, in alcoholic cirrhosis, which is associated with a predominantly mononuclear cell infiltrate. Both diseases were associated with high levels of circulating intercellular adhesion molecule-1, which is released by activated lymphocytes, providing further evidence of immune activation in alcoholic liver disease.

Cell Adhesion↗
PubMed1994

Schistosoma haematobium infection patterns in the Rahad Irrigation Scheme, Sudan.

Patterns of infection of urinary schistosomiasis (Schistosoma haematobium) were studied in 4 highly endemic village areas in the Rahad Irrigation Scheme, Sudan. The prevalence of S. haematobium infection in the total study population of 4725 individuals was 30%, and the age-prevalence and age-intensity figures increased rapidly to reach their maxima in the younger age groups. The overall prevalence of infection among males (31.7%) was slightly higher than among females (28.7%), and the two sexes differed in their age-specific prevalence patterns. The pattern of intensity of infection in males and females was rather similar. Marked differences in prevalence and intensity of S. haematobium infection were recorded between the four village areas, and the infection level in camp inhabitants exceeded markedly that in village inhabitants. Specific problems related to low school attendance rates, limited use of treatment opportunities provided at health centers and less than optimal efficacy of the focal snail control approach taken may be kept responsible for the fact that the control programme implemented in the Scheme has not achieved transmission control.

Adolescent↗
PubMed1994

Antibiotic-associated acute vanishing bile duct syndrome: a pattern associated with severe, prolonged, intrahepatic cholestasis.

We report cases of amoxycillin- and flucloxacillin-induced liver damage associated with an acute vanishing bile duct syndrome. Ductopenia was present at the time of first liver biopsy, 3 weeks and 3 months after administration of the two drugs, respectively. Ductopenia apparently occurred as the primary lesion, with no evidence of accompanying portal tract inflammation. Subsequent biopsies showed a persistent paucity of ducts, accompanied by increasing features of chronic cholestasis. Biochemical dysfunction persists at 2 year's follow-up and late prognosis remains guarded.

Abscess↗
PubMed1994

The adverse influence of pregnancy upon sulphation: a clue to the pathogenesis of intrahepatic cholestasis of pregnancy?

Sulphation of oestrogens and monohydroxy bile acids is important in attenuating their cholestatic potential. Thus, impairment of sulphation could lead to retention of cholestatic compounds and precipitate intrahepatic cholestasis in susceptible individuals. We tested the hypothesis that such a mechanism may be involved in the pathogenesis of intrahepatic cholestasis of pregnancy. In vivo and in vitro assessment of sulphation capacity was performed in patients with cholestasis of pregnancy, compared with control females on and off the oestrogen-containing oral contraceptive pill and control individuals during normal pregnancy and post partum, to assess the influence of high oestrogen states upon this metabolic pathway. During in vivo studies utilising paracetamol as a metabolic probe, the proportion of paracetamol sulphate and sulphate: glucuronide ratio were decreased in those with elevated oestrogens, whether the rise in oestrogens was endogenous, in pregnancy (paracetamol sulphate p < 0.05; paracetamol sulphate:glucuronide ratio p < 0.01), or exogenous, with the contraceptive pill (paracetamol sulphate p = 0.2; paracetamol sulphate:glucuronide ratio p < 0.001). In vitro, platelet sulphotransferase activity was measured, utilising phenol as substrate. Sulphotransferase activity decreased during pregnancy compared with repeat measurements post partum (p < 0.005) and compared with non-pregnant individuals (p < 0.05). In conclusion, we have shown that elevated oestrogens are associated with significant impairment in sulphation capacity. An imbalance of sulphation with glucuronidation provoked by high circulating oestrogen levels may be contributory in the pathogenesis of cholestasis of pregnancy.

Acetaminophen↗
PubMed1994

Plasma cysteine and sulphate levels in patients with cirrhosis of the liver.

1. Fasting levels of plasma cysteine, plasma sulphate and the plasma cysteine/sulphate ratio were measured in patients with primary biliary cirrhosis and compared with those in patients with other liver disease, general intensive therapy unit patients and healthy subjects. 2. Plasma cysteine was significantly elevated in patients with primary biliary cirrhosis (median 0.364 nmol/mg of protein, P < 0.0001) and patients with other liver disease (median 0.445 nmol/mg of protein, P < 0.0001), compared with healthy control subjects (median 0.125 nmol/mg of protein) and increased progressively with the severity of liver disease. Plasma cysteine was also elevated in intensive therapy unit patients (median 1.564 nmol/mg of protein) compared with healthy control subjects (P < 0.0001) and patients with other liver disease (P < 0.0001). 3. Plasma sulphate was reduced significantly only in patients with primary biliary cirrhosis (median 0.822 nmol/mg of protein) compared with healthy control subjects (median 1.37 nmol/mg of protein, P < 0.05). There was no significant difference in plasma sulphate between disease groups. 4. The plasma cysteine/sulphate ratio was significantly elevated in patients with primary biliary cirrhosis (median 0.448, P < 0.0001) and patients with other liver diseases (median 0.394, P < 0.0001) compared with healthy control subjects (median 0.095). The ratio was also elevated in intensive therapy unit patients (median 1.650, P < 0.0001) compared with healthy control subjects and liver disease groups (P < 0.0001). 5. In conclusion, cysteine rises in primary biliary cirrhosis and other forms of liver disease. This effect is not specific to liver disease, since cysteine is elevated in an heterogeneous group receiving intense care.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Serious paracetamol poisoning and the results of liver transplantation.

Paracetamol poisoning is the most common cause of fulminant liver failure in the United Kingdom. An accurate assessment of prognosis at the time of referral will allow the appropriate application of liver transplantation in this setting. The outcome of 92 patients consecutively admitted to a specialist liver unit with severe poisoning has been examined. In patients who did not have a transplant, a fatal outcome was seen for 26/82 (32%), and was associated with late presentation, coma grade, prothrombin time prolongation, metabolic acidosis, and renal dysfunction. Cerebral oedema, and sepsis were responsible for most deaths. Prognostic criteria defined at King's College Hospital seemed to predict the outcome of patients who did not have a transplant managed on the Birmingham liver unit. Seventeen patients were listed for transplantation, 10 had liver transplantation, and seven of 10 survived. Seven were listed but not transplanted, and one of seven survived. Psychological rehabilitation of patients who had a transplant has not proved difficult. These results suggest a role for liver transplantation in the management of selected patients with paracetamol poisoning.

Acetaminophen↗
PubMed1994

Viral hepatitis in Nigeria--sickle-cell disease and commercial blood donors.

Hepatitis virus infection is a major cause of morbidity and mortality in sub-Saharan Africa. The high prevalence of hepatitis B virus (HBV) infection in this region is thought to be due to horizontal transmission during childhood. Hepatitis C virus (HCV) infection is also quite prevalent in Africa, but the epidemiology of this infection has yet to be defined. We examined the prevalence of HBV and HCV serological markers in 220 patients attending sickle-cell anaemia clinics in Benin City, Nigeria, in 228 healthy locals, and in 104 local commercial blood donors, to test the hypothesis that patients requiring blood transfusion from unscreened commercial blood donors (in this area of high prevalence for viral hepatitis) are at great risk for the acquisition of post-transfusion hepatitis. Overall, the frequency of hepatitis viraemia in blood donors was high (14% of donors were either HbsAg or anti-HCV positive). Evidence of previous exposure to HBV was common in all three study groups. Risk of HBV infection for sickle-cell patients was not clearly increased by blood transfusion. HCV exposure, however, appears related to transfusion requirement, and all Western-blot-confirmed anti-HCV-positive sicklers had a history of blood transfusion. Screening of blood products in sub-Saharan Africa is unlikely to reduce prevalence of HBV, but may minimize the risks of HCV transmission.

Adolescent↗
PubMed1993

Species-specific induction of cytochrome P-450 4A RNAs: PCR cloning of partial guinea-pig, human and mouse CYP4A cDNAs.

PCR was used to demonstrate the presence of a conserved region and to clone novel members of the cytochrome P-450 4A gene family from guinea pig, human and mouse cDNAs. This strategy is based on the sequences at nucleotides 925-959 and at the haem binding domain (nucleotides 1381-1410) of the rat CYP4A1 gene. Murine Cyp4a clones showed high sequence identity with members of the rat gene family, but CYP4A clones from human and guinea pig were equally similar to the rat/mouse genes, suggesting that the rat/mouse line had undergone gene duplication events after divergence from human and guinea-pig lines. The mouse Cyp4a-12 clone was localized to chromosome 4 using interspecific backcross mapping, in a region of synteny with human chromosome 1. The assignment of the human CYP4A11 gene to chromosome 1 was confirmed by somatic cell hybridization. An RNAase protection assay was shown to discriminate between the murine Cyp4a-10 and Cyp4a-12 cDNAs. Treatment of mice with the potent peroxisome proliferator methylclofenapate (25 mg/kg) induced Cyp4a-10 RNA in liver, and to a lesser extent in kidney; there was no sex difference in this response. Cyp4a-12 RNA was present at high levels in male control liver and kidney samples, and was not induced by treatment with methylclofenapate. However, Cyp4a-12 RNA was present at low levels in control female liver and kidney RNA, and was greatly induced in both organs by methylclofenapate. Guinea pigs were exposed to methylclofenapate (50 mg/kg), but there was no significant induction of the guinea-pig CYP4A13 RNA. These findings are consistent with a species difference in response to peroxisome proliferators between the rat/mouse and the guinea pig.

Amino Acid Sequence↗
PubMed1993

Primary biliary cirrhosis. Histological evidence of disease recurrence after liver transplantation.

Histological evidence of primary biliary cirrhosis (PBC) recurring after orthotopic liver transplantation (OLT) was looked for in a 'blinded' study of 353 biopsies from 188 patients, 12-100 months post-transplant. Biopsies (172) were obtained from 83 patients transplanted for PBC and 181 biopsies from 105 patients with other liver diseases. Sixteen biopsies from 13 PBC patients (16%) had features suggestive of recurrent disease. The main diagnostic findings were: mononuclear portal inflammatory infiltration (n = 16), portal lymphoid aggregates (n = 14), portal epithelioid granulomas (n = 14) and bile duct damage (n = 15). This combination of changes was not seen in any biopsy from the non-PBC group. Additional features supporting a diagnosis of recurrent disease were ductopenia (n = 7), bile ductular proliferation (n = 7), portal fibrosis (n = 6) and copper deposition (n = 5). Thirteen biopsies from 12 patients were classified as stage I or II histologically. The other patient developed progressive damage in three serial biopsies resulting in an early micronodular cirrhosis, 5 years post-transplant. These observations provide further evidence that PBC recurs after OLT. More studies are required to determine the natural history and clinical significance of the predominantly early histological changes documented so far.

Adolescent↗
PubMed1993

Managing severe alcoholic hepatitis complicated by renal failure.

We examined the management and outcome of 15 patients admitted consecutively to a specialist Liver Unit with severe alcoholic hepatitis complicated by renal failure. Fourteen patients were managed conservatively. Of these, 11/14 underwent renal dialysis for a mean of 24 days. Three patients, including two requiring dialysis, recovered renal function. Despite intensive care, 12/14 patients died. Death was frequently associated with bacterial and fungal sepsis. One patient underwent liver transplantation with prompt post-operative recovery of renal function. He was discharged from hospital 16 days later, and remains abstinent from alcohol with normal liver function after one year. Most patients with renal failure complicating severe alcoholic hepatitis will die, despite intensive care including renal dialysis. Selected patients may be suitable for liver transplantation.

Adult↗