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Biomedical subjects

E Elias

Publications and source records attributed to E Elias.

At least 55 records · Page 3Linked to original sources
PubMed1999

Managing Budd-Chiari syndrome: a retrospective review of percutaneous hepatic vein angioplasty and surgical shunting.

BACKGROUND: The role of percutaneous hepatic vein angioplasty in the management of Budd-Chiari syndrome has not been well defined. Over a 10 year period at our unit, we have often used this technique in cases of short length hepatic vein stenosis or occlusion, reserving surgical mesocaval shunting for cases of diffuse hepatic vein occlusion or failed angioplasty. AIMS: To review the outcome of angioplasty and surgical shunting to define their respective roles. PATIENTS: All patients treated by angioplasty or surgical shunting for non-malignant hepatic vein obstruction over a ten year period from 1987 to 1996. METHODS: A case note review of pretreatment features and clinical outcome. RESULTS: Angioplasty was attempted in 21 patients with patent hepatic vein branches and was successful in 18; in three patients treatment was unsuccessful and these patients had surgical shunts. Fifteen patients were treated by surgical shunting only. Mortality according to definitive treatment was 3/18 following angioplasty and 8/18 following surgery; in most cases this reflected high risk status prior to treatment. Venous or shunt reocclusion rates were similar for both groups and were associated with subtherapeutic warfarin in half of these cases. Most surviving patients in both groups are asymptomatic although one surgical patient has chronic hepatic encephalopathy. CONCLUSION: With appropriate case selection, many patients with Budd-Chiari syndrome caused by short length hepatic vein stenosis or occlusion may be managed successfully by angioplasty alone. Medium term outcome is good following this procedure provided that anticoagulation is maintained. Further follow up is required to assess for definitive benefits but we suggest that this should be included as a valid initial approach in the algorithm for management of Budd-Chiari syndrome.

Adolescent↗
PubMed1999

Selection of hepatitis B surface "escape" mutants during passive immune prophylaxis following liver transplantation: potential impact of genetic changes on polymerase protein function.

CASE REPORT: A patient is described who developed hepatitis B virus (HBV) reinfection five months following liver transplantation. Failure of hepatitis B immunoglobulin prophylaxis was associated with the emergence of mutations. HBV gene sequencing identified nucleotide substitutions associated with amino acid changes, one within the major hydrophilic region (MHR) of the HBV surface antigen at amino acid position 144 and one outside the MHR. Because of the overlapping reading frames of surface and polymerase genes, the latter surface antigen change was associated with an amino acid change in the polymerase protein. The patient developed significant allograft hepatitis and was treated with lamivudine (3TC) 100 mg daily. Rapid decline of serum HBV DNA was observed with loss of HBV e antigen and HBV surface antigen from serum. There was normalisation of liver biochemistry, and liver immunohistochemistry showed a reduction in HBV core and disappearance of HBs antigen staining. CONCLUSION: Surface antigen encoding gene mutations associated with HBIg escape may be associated with alteration of the polymerase protein. The polymerase changes may affect sensitivity to antiviral treatment. Selection pressure on one HBV reading frame (for example, HBIg pressure on HBsAg, or nucleoside analogue pressure on polymerase protein) may alter the gene product of the overlapping frame. Such interactions are relevant to strategies employing passive immune prophylaxis and antiviral treatment.

Aged↗
PubMed1999

Analysis of hepatitis B virus quasispecies changes during emergence and reversion of lamivudine resistance in liver transplantation.

This report describes nucleotide sequence analysis of part of the polymerase gene of hepatitis B virus (HBV) during the development of lamivudine-resistant HBV in five patients who received lamivudine treatment in conjunction with liver transplantation. Samples from patients were analysed before, during and after drug treatment in conjunction with serum HBV quantification by PCR. Lamivudine resistance was found to be associated with L526M and M550V changes in two patients and M550I change in three patients. Other changes associated with lamivudine resistance in some patients were V509I, A546V, S565A and A568T. The effects on HBV surface antigen are also described. Some patients were subsequently treated with famciclovir and/or ganciclovir with variable outcomes. In two out of three patients who stopped lamivudine treatment, reversion (partial or complete) to wild-type virus was observed after about 5 months. In contrast, a complex mixture of mutant viruses emerged in a third patient who stopped lamivudine treatment.

Antiviral Agents↗
PubMed1998

Glycogen storage disease type II: identification of four novel missense mutations (D645N, G648S, R672W, R672Q) and two insertions/deletions in the acid alpha-glucosidase locus of patients of differing phenotype.

Glycogen storage disease type II (GSDII), an autosomal recessive myopathic disorder, results from deficiency of lysosomal acid alpha-glucosidase. We searched for mutations in an evolutionarily conserved region in 54 patients of differing phenotype. Four novel mutations (D645N, G448S, R672W, and R672Q) and a previously described mutation (C647W) were identified in five patients and their deleterious effect on enzyme expression demonstrated in vitro. Two novel frame-shifting insertions/deletions (delta nt766-785/insC and +insG@nt2243) were identified in two patients with exon 14 mutations. The remaining three patients were either homozygous for their mutations (D645N/D645 and C647W/C647W) or carried a previously described leaky splice site mutation (IVS1-13T-->G). For all patients "in vivo" enzyme activity was consistent with clinical phenotype. Agreement of genotype with phenotype and in vitro versus in vivo enzyme was seen in three patients (two infantile patients carrying C647W/C647W and D645N/+insG@nt2243 and an adult patient heteroallelic for G648S/IVS1-13T-->G). Relative discordance was found in a juvenile patient homozygous for the non-expressing R672Q and an adult patient heterozygous for the minimally expressing R672W and delta nt766-785/+insC. Possible explanations include differences in in vitro assays vs in vivo enzyme activity, tissue specific expression with diminished enzyme expression/stability in fibroblasts vs muscle, somatic mosaicism, and modifying genes.

Adult↗
PubMed1998

Combination alpha-interferon and lamivudine therapy for alpha-interferon-resistant chronic hepatitis B infection: results of a pilot study.

BACKGROUND/AIMS: Alpha-interferon achieves seroconversion in about one third of naive patients. Attempts to achieve seroconversion in patients who have previously failed alpha-interferon have proved disappointing. Combination chemotherapy (alpha-interferon with a nucleoside analogue) might provide a treatment alternative for these patients. We have undertaken a phase 2 study in 20 patients who had previously failed at least one course of alpha-interferon. The study was designed to assess the safety, tolerability and efficacy of the combination. METHODS: All patients were treated for 16 weeks with alpha-interferon in combination with 12 or 16 weeks of Lamivudine (3'TC). Patients were followed for 16 weeks post-treatment. Pharmacokinetic studies were performed to identify/exclude significant pharmacokinetic drug interaction. RESULTS: The combination was well tolerated, and side-effects of the combination were indistinguishable from the recognised side-effects of alpha-interferon. Pharmacokinetic studies performed on days 1 and 29 did not show any significant interaction. All patients achieved HBV DNA clearance during treatment, but 19 relapsed at the end of treatment. HBeAg/anti-HBe seroconversion was observed for four patients, but was sustained for a single patient (who also had sustained DNA clearance). CONCLUSIONS: Combination therapy with alpha-interferon and lamivudine given for 16 weeks appears safe and is well tolerated. However, for this group of patients who had previously failed interferon monotherapy, the efficacy of combination interferon/lamivudine therapy appears disappointing, and other treatment strategies should be investigated.

Adult↗
PubMed1997

Synthesis, physical and biological properties of lithocholyl-lysyl-fluorescein: a fluorescent monohydroxy bile salt analogue with cholestatic properties.

We have synthesised and characterised a fluorescent monohydroxy bile salt analogue, lithocholyl-lysyl-fluorescein and compared its physical and biological properties with those of lithocholate, glycolithocholate, sulpholithocholate, lithocholic acid glucuronide and taurocholate. The synthetic method used excess N-epsilon-CBZ-L-lysine methyl ester hydrochloride and lithocholic acid via N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinolone (EEDQ) to give lithocholyl-lysine. Lithocholyl-lysyl-fluorescein (LLF) was then prepared using equimolar amounts of lithocholyl-lysine and fluorescein isothiocyanate (FITC) in bicarbonate buffer. LLF retained an apple green fluorescence, similar to that of fluorescein. Unlike lithocholate, the critical micellar concentrations (CMCs) of LLF, glycolithocholate (GLC), lithocholic acid glucuronide (LG) and sulpholithocholic acid (SLC) were similar. HPLC retention times (tRs) of LLF and GLC were similar with a ratio of LLF/GLC of 1.05. In contrast, the tR of SLC (6.52 min) but not of LG (21.2 min) was more comparable to that of taurocholate (5.73 min). In rats under pentobarbital anaesthesia, the plasma half-life (t(1/2alpha)) (min) was 4.5 +/- 1.3 (n = 6) for LLF, 2.9 +/- 0.4 (n = 5) for [14C]sulpholithocholate (14C-SLC) and 4.3 +/- 0.3 (min) for [14C]lithocholic acid glucuronide (14C-LG). Plasma clearances of 14C-SLC, LLF and 14C-LG were 15.5 +/- 2.2 (n = 6), 18.1 +/- 4.2 (n = 6) and 17.8 +/- 0.5 ml/min/kg (n = 6) (P = 0.15), respectively. Biliary excretion in bile-fistula rats gave cumulative 20 min biliary output as a percentage of injected dose as follows: LLF, 71.6 +/- 0.8% (n = 10); 14C-SLC, 75.5 +/- 2.8% (n = 6) and 14C-LG, 61.7 +/- 0.5% (n = 6) (P = NS). Peak biliary excretion rates, given as % dose/2 min, were 10.2 +/- 0.3 for LLF, 13.5 +/- 0.6 for 14C-SLC and 12.8 +/- 0.4 for 14C-LG. In another group of bile-fistula rats, a 3.0 micromol/500 microl saline i.v. bolus of LLF caused a 15.4 +/- 1.9% decrease in bile flow and, similarly, sodium lithocholate in a solution of albumin caused a 17.9 +/- 1.8% (P = NS) diminution in bile flow. Despite the similar cholestatic properties of LLF and lithocholate, LLF was more soluble than lithocholate, with a relative retention time on HPLC similar to that of GLC. LLF is a divalent 'unipolar' anionic fluorescent monohydroxy bile salt analogue with physical, biological and cholestatic properties that are similar to those of lithocholate, glycolithocholate and their derivatives and thus offers a potentially useful probe for studying mechanisms of monohydroxy bile salt-induced cholestasis at the hepatocellular level.

Animals↗
PubMed1997

Enhanced (cytomegalovirus) viral replication associated with septic bacterial complications in liver transplant recipients.

BACKGROUND: Complications of the biliary anastomosis are the principal cause of clinically serious bacterial sepsis in liver transplant recipients. Reported series suggest an association of bacterial and fungal infection with cytomegalovirus (CMV) infection, although the mechanism of this association is unclear. METHODS: We examined the association of serious bacterial sepsis with CMV replication in a cohort of 106 consecutive liver transplant recipients. Sequentially collected buffy coats were examined with a polymerase chain reaction (PCR) assay that has been shown to have good predictive value for the development of CMV infection. For selected patients, CMV-specific IgM response and serum tumor necrosis factor-alpha (TNF-alpha) were also measured. RESULTS: Ten of 13 patients with serious bacterial sepsis developed buffy coat PCR positivity, compared with 26 of 93 patients without bacterial sepsis (chi-square, P<0.001). Ten of 10 septic recipients with a seropositive liver donor developed PCR positivity. For 9 of 10 recipients, bacterial sepsis developed before PCR positivity. Bacterial sepsis was associated with high serum levels of TNF-alpha. Immune response to CMV (reflected by the appearance CMV-specific IgM) was apparently affected by bacterial sepsis, and IgM response was not observed for the three septic patients who died during the study period. CONCLUSIONS: We conclude that CMV replication is encouraged by serious bacterial sepsis. Replication may be promoted by high antecedent levels of TNF-alpha, and/or by poor immune response to CMV in the context of serious bacterial infection.

Antibodies, Viral↗
PubMed1997

Patterns of viremia in liver transplant recipients with symptomatic cytomegalovirus infection.

Cytomegalovirus (CMV) titer in blood seems to be the principal determinant of clinical symptoms in immunosuppressed patients. We have developed an assay for quantitation of CMV DNA in serum. The assay requires the coamplification by polymerase chain reaction (PCR) of extracted serum DNA with 1000 molecules of mutated internal standard DNA, and then an ELISA detection system. We examined 133 paired buffy coats and sera from 15 patients with symptomatic infection. Sera were examined by quantitative PCR, and buffy coats were examined by qualitative PCR (with a detection threshold of approximately 40 copies per 150,000 cells). Serum viral titers peaked during the seventh week after transplant (median day 40, range 26-58) at about the time of symptom onset. Mean viral titer measured during the seventh week was 1.2 x 10(5) copies per milliliter of serum (standard error 6.5 x 10(4). Buffy-coat PCR results were generally concordant with results of serum PCR (overall concordance 103/133=77.4%). Serum CMV titer fell, as symptoms resolved with reduction of immunosuppression and specific antiviral therapy. High titers and poor response to antiviral therapy were observed in the context of excessive immunosuppression and bacterial sepsis. Measurement of serum CMV titer may be useful for the management of immunosuppressed transplant recipients, and provides a tool for the better understanding of factors that enhance or inhibit viral replication.

Antibodies, Viral↗
PubMed1997

Enhanced (cytomegalovirus) viral replication after transplantation for fulminant hepatic failure.

Fulminant hepatic failure (FHF) is an established indication for liver transplantation. A pretransplant diagnosis of FHF may be a risk factor for subsequent development of cytomegalovirus (CMV) infection, although the mechanism of this association is not understood. FHF is associated with very high levels of tumor necrosis factor alpha (TNF-alpha), and TNF-alpha may directly promote viral replication. We have used the polymerase chain reaction (PCR) to examine sequentially collected buffy coats from 106 consecutive adult liver transplant recipients. PCR evidence of CMV replication was found for 13 of 18 patients who underwent transplantation for FHF (c.f. 23/88 non-FHF patients; P < .01). Ten of 12 patients who received transplants transplanted for fulminant seronegative hepatitis were buffy-coat PCR-positive, sometimes during the first posttransplant week. TNF-alpha was measured by enzyme-linked immunosorbent assay in selected sera, and results were examined in the context of a quantitative PCR assay. Serum TNF-alpha levels increased and decreased in concert with viral titers. High levels of TNF-alpha were not found in the early posttransplant period. We conclude that FHF (in particular, seronegative hepatitis) is associated with enhanced CMV replication in the posttransplant period. Results also suggest that viral replication may be enhanced before transplantation. These patients may be at special risk for development of symptomatic CMV infection.

Cytomegalovirus↗
PubMed1997

Ethylmalonic adipic aciduria--a treatable hepatomuscular disorder in two adult brothers.

An adult male presented at 28 years of age with muscle weakness and liver dysfunction. His brother had died suddenly 2 years earlier after presenting with Reye's syndrome. Urine organic acid analysis and muscle and cultured fibroblast fatty acid oxidation studies confirmed a diagnosis of ethylmalonic/adipic aciduria-an inherited defect of fatty acid oxidation. The patient responded favourably to treatment with a low fat/high carbohydrate diet supplemented with riboflavin. This case highlights the importance of considering inborn errors of metabolism, in particular fatty acid oxidation defects, in adults with liver disease, muscle disease or Reye's syndrome.

Adipates↗
PubMed1997

Plasma clearance of cholyl-lysyl-fluorescein: a pilot study in humans.

BACKGROUND/AIMS: Cholyl-lysyl-fluorescein is a fluorescent analogue of the natural bile acid, cholyl glycine. In vivo and in vitro studies showed that this analogue has many biological characteristics similar to cholyl glycine. In this study we analysed cholyl-lysyl-fluorescein plasma clearance in six healthy volunteers as a potential quantitative liver function test. METHODS: The compound in water for injection was administered as an i.v. bolus in the dose of 0.02 mg/kg b.w. RESULTS: The plasma elimination curve showed rapid, intermediate and slow phases of clearance. Half-life (T1/2 time) for the first (t1/2 1st phase), second (t1/2 2nd phase) and third (t1/2 3rd phase) phases of elimination was 1.7+/-0.9 min, 6.7+/-1.6 min and 68+/-17 min, respectively. Ninety-minute plasma retention (% dose/l plasma) was 2.2%. Cholyl-lysyl-fluorescein volume of distribution and residual fluorescence after 60 min were similar to the data obtained by others for natural or radiolabelled bile acids. In five out of six healthy volunteers a 25-fold higher dose of cholyl-lysyl-fluorescein (0.5 mg/kg b.w.) was injected to estimate the safety margins of the compound. This dose was eliminated at a disappearance rate similar to that of the dose of 0.02 mg/kg b.w. and did not cause any adverse reactions. Serum liver tests measured before and after injection did not change significantly. CONCLUSIONS: This study showed that cholyl-lysyl-fluorescein clearance is similar to the clearance of endogenous natural bile acids and may potentially offer a new, dynamic test of liver function.

Adult↗
PubMed1997

Obstructive sleep apnoea syndrome (OSAS) as a complication of carcinoid syndrome treated successfully by hepatic artery embolization.

Obstructive sleep apnoea syndrome (OSAS) appears to be an extremely rare complication of carcinoid syndrome and has not yet been reported in the literature. We describe a 75-year-old patient with a history of bronchial carcinoid who besides typical carcinoid syndrome symptoms developed sleep disturbance and day lethargy caused by massive facial and nasal tissue oedema. Sleep apnoea was confirmed by sleep study. Abdominal ultrasound and computed tomography (CT) scan showed the presence of multiple liver metastases. Because the patient did not respond to octreotide therapy, embolization of the hepatic artery was performed. After this procedure we observed dramatic improvement of the patient's life quality, and rapid disappearance of facial swelling and sleep apnoea symptoms. We conclude that hepatic artery embolization appeared to be an effective method of abolishing obstructive sleep apnoea associated with carcinoid syndrome.

Aged↗
PubMed1997

Poor prognosis and limited therapeutic options in patients with Budd-Chiari syndrome and portal venous system thrombosis.

OBJECTIVES: Therapeutic options in Budd-Chiari syndrome (BCS) are highly dependent on the site and extent of hepatic vein thrombosis. The aim of this study was to evaluate the effect of additional portal venous system thrombosis on the clinical presentation, treatment and outcome in patients with BCS. PATIENTS: Clinical notes of 51 patients with BCS admitted to our centre were evaluated. We identified 13 patients (25%) with BCS and additional portal venous system thrombosis. Ten patients were female and three male with a mean age at presentation of 42 years (range 32-67). RESULTS: An underlying haematological aetiology was identified in 10 of the 13 patients. Only four patients (31%) were anticoagulated before referral to our centre. In addition to hepatic vein thrombosis seven patients had portal vein thrombosis (PVT), three had PVT, splenic vein (SV) and superior mesenteric vein (SMV) thrombosis and three had either SV, SMV or inferior vean cava (IVC) thrombosis. The presentation was acute in three patients, subacute in six and chronic in four with a high incidence of encephalopathy (6/13; 46%). Treatment included liver transplantation (four), mesoatrial shunt (one) and balloon dilatation of hepatic veins (two). Six patients were treated medically as all other options were considered too risky or technically impossible. Nine of 13 patients (70%) died either after surgery or before any treatment could be instituted (median survival 1 month), compared to 14/38 (37%) in patients with isolated hepatic vein thrombosis (median survival 6.3 years). CONCLUSION: We conclude that patients with BCS and portal venous system thrombosis constitute a unique group with limited therapeutic options and poor prognosis. The importance of early recognition and anticoagulation of patients with BCS is emphasized.

Adolescent↗
PubMed1997

Prevalence of the factor V Leiden mutation in hepatic and portal vein thrombosis.

BACKGROUND: The factor V Leiden (FVL) mutation has been shown to be the most frequent cause of hereditary thrombophilia. The prevalence of the mutation in patients with Budd-Chiari syndrome (BCS) and portal vein thrombosis (PVT) has not been fully elucidated. AIMS: To investigate the association between the FVL mutation and BCS and PVT. PATIENTS: Thirty patients with BCS, 32 patients with PVT, and a control group of 54 patients with liver disorders and no history of thrombosis. METHODS: The factor V gene was analysed for the presence of the FVL mutation by a polymerase chain reaction (PCR) technique. The presence of the mutation was confirmed by DNA sequencing. RESULTS: Seven (23%) patients with BCS, one (3%) patient with PVT, and three (6%) patients in the control group were identified as having the FVL mutation. There of the BCS patients had coexisting hypercoagulable states. The prevalence of the FVL mutation was significantly higher in patients with BCS compared with patients with PVT and controls (p < 0.04). The FVL mutation was the second most common aetiology associated with BCS. CONCLUSION: The FVL mutation is an important factor in the pathogenesis of BCS and screening for the disorder must be included in the investigation of patients presenting with this condition. In contrast, the FVL mutation is not a major predisposing factor in the pathogenesis of PVT.

Adolescent↗