E A Jones

The National Institute of Diabetes and Digestive and Kidney Diseases, Maryland, United States

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Publications (155)1289.24 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Six patients with chronic type B hepatitis were treated with adenine arabinoside 5'-monophosphate at a dosage of 10 to 15 mg per kg per day for 10 days. All demonstrated an immediate and marked decrease in serum hepatitis B virus DNA and DNA polymerase, and 5 of the 6 became negative for both markers by the end of the period of therapy. One patient remained negative for hepatitis B virus DNA and DNA polymerase when therapy was discontinued. This patient subsequently exhibited clinical, serum biochemical, and histological remission in disease activity concurrent with seroconversion from hepatitis B e antigen to antibody. In the remaining five patients, serum hepatitis B virus DNA and DNA polymerase returned to pretreatment values soon after therapy was stopped, and these patients demonstrated no significant changes in clinical, biochemical, serological, or histological features of the disease. Side effects of the therapy were mild and transient. These results suggest that a 10-day course of adenine arabinoside 5'-monophosphate is not adequate to induce permanent amelioration of infection and disease activity in the majority of patients with chronic type B hepatitis.
    Hepatology 01/2011; 2(6):784-8. · 11.19 Impact Factor
  • E A Jones, J Neuberger, N V Bergasa
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    ABSTRACT: Increased opioidergic neurotransmission in the brain appears to contribute to the pruritus that complicates cholestasis and certain non-cholestatic chronic liver diseases. Opiate antagonists have been shown to decrease scratching activity in patients with the pruritus of cholestasis. Initiation of oral administration of an orally bioavailable opiate antagonist may precipitate a florid opioid-withdrawal-like reaction in patients with pruritus complicating cholestasis. Such reactions can be minimized, or avoided completely, by cautiously infusing naloxone before giving small oral doses of an orally bioavailable opiate antagonist. The infusion rate of naloxone should initially be very low; it should be increased gradually and stopped when a rate known to be associated with opioid antagonist effects has been attained. Oral therapy with an opiate antagonist can then be initiated.
    QJM: monthly journal of the Association of Physicians 09/2002; 95(8):547-52. · 2.46 Impact Factor
  • James Neuberger, E. Anthony Jones
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    ABSTRACT: A woman with stage III (pre-cirrhotic) primary biliary cirrhosis was referred for liver transplantation because of intractable pruritus. Oral administration of 50 mg naltrexone precipitated a severe opioid withdrawal-like reaction. Subsequently, when oral naltrexone therapy was reintroduced following a cautious infusion of naloxone, no reaction occurred and the pruritus resolved completely. Liver transplantation should not be considered for apparently intractable pruritus of cholestasis before an adequate trial of opiate antagonist therapy.
    European Journal of Gastroenterology & Hepatology 12/2001; 13(11):1393-4. · 2.15 Impact Factor
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    ABSTRACT: The P300 complex was derived from the electroencephalogram (EEG) as subjects mentally counted infrequent large checkerboard visual stimuli, presented randomly among frequent small checkerboard stimuli. Use of low contrast (10%) stimuli and four midline scalp electrodes, facilitated separation of cognitive and sensory components and enabled the P300 complex to be resolved into three distinct components--N200, P3a, and P3b. In 20 healthy adult subjects normative data were established and the P3a and P3b components were shown to depend on cognitive function. In 19 age-matched cirrhotic patients without overt hepatic encephalopathy (HE) the EEG and visual evoked potentials (VEPs) were normal, but latencies of P3a and/or P3b were prolonged in 9. Prolonged latencies were not associated with an abnormal number connection test. Ten additional age-matched cirrhotic patients without overt HE, who were alcohol, drug, and caffeine free, were randomized to receive flumazenil (1 mg) and placebo intravenously, double-blind. After flumazenil or placebo, latencies of P3a and P3b and psychometric test results did not change significantly. These findings suggest that in cirrhotic patients without overt HE (i) impaired cognitive sensory function may occur in the absence of abnormalities of a standard psychometric test, the EEG, or VEPs, and (ii) increased latencies of P3a and P3b may constitute a component of subclinical HE, which is not mediated by increased brain levels of central benzodiazepine receptor agonist ligands.
    Metabolic Brain Disease 07/2001; 16(1-2):43-53. · 2.40 Impact Factor
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    ABSTRACT: Ambulant patients with cirrhosis and no clinical evidence of encephalopathy were screened for impaired brain function by neuroelectrophysiological testing dependent on cognitive function. Infrequent large checkerboard visual stimuli were randomly interleaved with frequent small ones to elicit P300 event-related potentials (ERPs). Three ERP components, N200, P3a and P3b, were derived from the electroencephalogram (EEG) by computer averaging. The use of 10% contrast and a minimum of four precisely placed scalp electrodes were found to be necessary for optimal separation of ERPs from sensory evoked potentials. Visual ERPs, onset/offset and pattern-reversal visual evoked potentials (VEPs), the spontaneous EEG and the time taken to complete a standard number connection test (NCT) were obtained from 20 normal adult subjects and 19 age-matched patients with histologically-confirmed cirrhosis and no clinical evidence encephalopathy. The latencies and amplitudes of evoked potentials and the alpha rhythm of the EEG were determined. In 6 of the 19 patients the latencies of P3a and/or P3b exceeded the corresponding mean for controls + 2 standard deviations of that mean. In 4 other patients the NCT was prolonged. In all of the patients the N200, VEPs and alpha rhythm of the EEG were normal. In conclusion: (i) Optimal isolation of ERPs is critically dependent on stimulus contrast and electrode placement; (ii) ERPs appear to be more sensitive than primary sensory evoked potentials or the EEG in detecting impaired brain neuroelectrophysiological function; and (iii) Cirrhotic patients without overt encephalopathy in whom P3a and/or P3b latencies are prolonged may have subclinical hepatic encephalopathy.
    Metabolic Brain Disease 10/2000; 15(3):179-91. · 2.40 Impact Factor
  • Nora V Bergasa, Jay K Mehlman, E.Anthony Jones
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    ABSTRACT: Pruritus is experienced by about 80% of patients with primary biliary cirrhosis. It can have a marked negative impact on the quality of life of patients, and it can be an indication for liver transplantation. There is evidence to suggest that the pruritus of cholestasis is mediated, at least in part, by endogenous opioids. A central component has been proposed. Behavioural data have shed light on the pathogenesis of this form of pruritus. Fatigue affects the majority of patients with primary biliary cirrhosis. It interferes with work performance and family life. An idea is emerging that suggests that fatigue in primary biliary cirrhosis also may be mediated centrally. Research tools need to be developed to study fatigue objectively in patients with primary biliary cirrhosis.
    Baillière&#x027 s Best Practice and Research in Clinical Gastroenterology 09/2000; 14(4):643-55. · 3.28 Impact Factor
  • E A Jones, N V Bergasa
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    ABSTRACT: The site of the pathogenic events responsible for initiating the pruritus of cholestasis has been assumed to be the skin. This assumption cannot be excluded but is not supported by convincing data. Empirical therapies such as anion exchange resins and rifampicin often appear to be partially efficacious. Recent evidence suggests that altered neurotransmission in the brain may contribute to this form of pruritus. In particular, the hypothesis that increased central opioidergic tone is involved is supported by three observations: opiate agonists induce opioid receptor-mediated scratching activity of central origin, central opioidergic tone is increased in cholestasis and opiate antagonists reduce scratching activity in cholestatic patients. Apparent subjective ameliorations of pruritus following intravenous administration of ondansetron to cholestatic patients suggest that altered serotoninergic neurotransmission may also contribute to this form of pruritus.
    Canadian journal of gastroenterology = Journal canadien de gastroenterologie 02/2000; 14(1):33-40. · 1.97 Impact Factor
  • E Anthony Jones
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    ABSTRACT: A woman with chronic hepatitis C and profound fatigue became symptomfree when treated long-term with ondansetron 4 mg twice daily. Altered central serotoninergic neurotransmission may contribute to fatigue complicating chronic liver disease.
    The Lancet 08/1999; 354(9176):397. · 39.21 Impact Factor
  • E A Jones, N V Bergasa
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    ABSTRACT: The pathogenesis of the pruritus that complicates cholestasis in patients with primary biliary cirrhosis (PBC) is uncertain. The limited and inconsistent efficacy of conventional empiric therapies, such as anion exchange resins and rifampicin, has led to inconclusive trials of invasive experimental therapies, such as plasmapheresis, charcoal haemoperfusion and partial external diversion of bile. However, some double-blind, placebo-controlled trials that used a subjective primary efficacy end-point (the perception of pruritus) have suggested that certain drugs that affect the metabolism of many compounds, for example rifampicin, may be efficacious. The potential mechanisms by which such drugs may mediate a beneficial effect have not been determined. There is a paucity of data to indicate whether peripheral events, such as the accumulation of bile acids in interstitial fluid of the skin, initiate the neural events which mediate this form of pruritus. Recent findings suggest that central events in the brain, specifically an increase in neurotransmission/ neuromodulation mediated by endogenous opioid agonists (increased opioidergic tone), may be implicated. This hypothesis is supported by three lines of evidence. (1) Opioid receptor ligands with agonist properties (e.g. morphine) mediate pruritus. (2) Endogenous opioid-mediated neurotransmission/neuromodulation in the central nervous system (CNS) is increased in cholestasis. (3) Controlled trials have shown that opiate antagonists induce ameliorations of the behavioural consequence of the pruritus of cholestasis (scratching activity). In such trials, measurements of scratching activity independent of limb movements constituted an objective quantitative primary efficacy end-point. Potent opiate antagonists, that are bioavailable when given by mouth, such as nalmefene and naltrexone, may have a place in the long-term management of pruritus in patients with PBC. Evidence that increased serotoninergic neurotransmission also contributes to the pruritus is at present less strong than that implicating an involvement of the opioid system, and further investigation is needed to determine whether specific serotonin receptor subtype ligands have a place in the treatment of pruritus in patients with PBC. There is some evidence which suggests that increased serotoninergic neurotransmission in the CNS contributes to fatigue of central origin, but whether there is a causal relationship between altered serotoninergic neurotransmission and the profound fatigue that occurs in many patients with PBC is currently uncertain.
    European Journal of Gastroenterology & Hepatology 07/1999; 11(6):623-31. · 2.15 Impact Factor
  • Source
    E. Anthony Jones, Nora V. Bergasa
    Hepatology 05/1999; 29(4):1003-6. · 11.19 Impact Factor
  • E A Jones, A S Basile
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    ABSTRACT: The ammonia and GABAergic neurotransmission hypotheses of the pathogenesis of hepatic encephalopathy (HE) have appeared to be unrelated and perhaps mutually exclusive. Observations in animal models of fulminant hepatic failure, that are consistent with increased GABAergic inhibitory neurotransmission contributing to the manifestations of HE, include: (i) abnormal visual evoked potential waveforms that resemble those induced by GABA(A)/benzodiazepine (BZ) receptor complex agonists; (ii) GABA(A)/BZ receptor complex antagonist-induced ameliorations of encephalopathy; (iii) increased resistance to drugs which decrease GABAergic tone; and (iv) hypersensitivity of CNS neurons to depression by GABA(A)/BZ receptor complex agonists. Mechanisms of increased GABAergic tone in HE may include the following: (i) increased brain concentrations of natural BZs; and (ii) increased GABA concentrations in synaptic clefts, possibly due to increased blood-brain-barrier permeability to GABA and a decrease in GABA(B) receptor density. Both neuroelectrophysiological and behavioral data indicate that ammonia concentrations in the range 0.75-2 mM induce increased excitatory neurotransmission. In contrast, recently, ammonia concentrations in the range 0.15-0.75 mM, i.e. concentrations that commonly occur in plasma in precoma HE, have been shown: (i) to increase GABA-induced chloride current in cultured neurons; and (ii) to enhance synergistically the binding of GABA(A)/BZ receptor agonists. In addition, increased ammonia concentrations enhance synthesis of neurosteroids in astrocytes, and some neurosteroids potently augment GABAergic neurotransmission. Thus, the modestly elevated concentrations of ammonia, that commonly occur in liver failure, may contribute to the manifestations of HE by enhancing GABAergic inhibitory neurotransmission. This concept appears to unify the ammonia and GABAergic neurotransmission hypotheses.
    Metabolic Brain Disease 01/1999; 13(4):351-60. · 2.40 Impact Factor
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    ABSTRACT: The effect of blockade of the enzyme ornithine decarboxylase by difluoromethylornithine (DFMO) on hepatocellular necrosis and survival in rats treated with thioacetamide (TAA) was investigated. In one experiment, the effect of DFMO on survival of rats with TAA-induced acute hepatocellular necrosis was determined. In another experiment, blood and liver specimens were obtained from DFMO or saline-treated rats 24 h after the administration of TAA for determinations of serum alanine aminotransferase (ALT) and liver content of polyamines and microsomal cytochrome P-450 and for assessment of hepatic histology. Liver polyamines were determined by reversed-phase HPLC and microsomal cytochrome P-450 content by dithionite-difference spectroscopy of CO-treated homogenates. The severity of hepatocellular necrosis was scored blindly. TAA-treated rats that received DFMO survived longer than saline-treated controls (P < 0.01). Serum ALT and liver putrescine concentrations were lower and the histological severity of acute hepatocellular necrosis was less in DFMO-treated rats with TAA-induced hepatocellular necrosis than in saline-treated controls (P < 0.05, P < 0.01 and P < 0.05, respectively). Total cytochrome P-450 levels were similar in DFMO and saline-treated rats with TAA-induced hepatocellular necrosis. DFMO increases survival in TAA-induced fulminant hepatic failure by decreasing the severity of acute hepatocellular necrosis. The beneficial effects of DFMO do not appear to be mediated by its effects on polyamine metabolism, but may be attributable to an effect of DFMO on thioacetamide metabolism or on an alternative pathway of ornithine metabolism.
    European Journal of Gastroenterology & Hepatology 07/1998; 10(6):503-7. · 2.15 Impact Factor
  • N V Bergasa, E A Jones
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    ABSTRACT: Pruritus is a distressing symptom experienced by a large proportion of patients with cholestasis. The cause of this form of pruritus is unknown, and therapy tends to be empirical and unsatisfactory. This article discusses the emerging role of the brain and neurotransmitter systems in the pathogenesis of the pruritus of cholestasis and emphasizes the importance of the application of quantitative methodology in clinical trials of therapies for the pruritus of cholestasis.
    Clinics in Liver Disease 06/1998; 2(2):391-405, x. · 2.70 Impact Factor
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    ABSTRACT: The aims of this study were to determine whether long-term oral administration of the opiate antagonist nalmefene is associated with any beneficial effects in patients with pruritus secondary to cholestatic liver disease and to assess the safety of long-term administration of this drug to these patients. Fourteen patients with unrelieved chronic pruritus of cholestasis were studied. Scratching activity, independent of limb movements, was recorded continuously for 24-hour periods before and during treatment with an initial ameliorating dose of nalmefene. Simultaneously, during these periods, visual analogue scores (VASs) of pruritus were recorded every 4 hours while patients were awake. The dose of nalmefene, which initially was 2 mg orally twice daily, was increased during the study, usually until a satisfactory clinical response was achieved. Five patients experienced a transient opioid withdrawal-like reaction that did not preclude continuing with nalmefene therapy. Serum biochemical indices of cholestasis did not change appreciably during treatment. Thirteen patients reported amelioration of the perception of pruritus on nalmefene. In 5 patients, exacerbations of pruritus occurred approximately 4 weeks after an initial ameliorating dose had been reached; these exacerbations were managed by increasing the dose. Baseline mean values for VAS and scratching activity were higher than corresponding means during nalmefene therapy in 13 (P = .002) and 12 (P = .013) patients, respectively. Possible tolerance to nalmefene occurred in 3 patients. Three patients experienced marked exacerbation of pruritus after nalmefene therapy was suddenly discontinued. Blood levels of nalmefene were consistent with normal pharmacokinetics of the drug. These results suggest that nalmefene may have a favorable risk-to-benefit ratio when it is administered orally long-term to patients with the pruritus of cholestasis.
    Hepatology 03/1998; 27(3):679-84. · 11.19 Impact Factor
  • N. V. Bergasa, E. A. Jones
    American Journal of Medical Genetics - AMER J MED GENET. 01/1998;
  • N. V. Bergasa, E. A. Jones
    American Journal of Medical Genetics - AMER J MED GENET. 01/1998;
  • E. A. Jones, N. V. Bergasa
    American Journal of Medical Genetics - AMER J MED GENET. 01/1998;
  • Source
    A S Basile, E A Jones
    Hepatology 07/1997; 25(6):1303-5. · 11.19 Impact Factor
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    ABSTRACT: To assess the feasibility of developing a model of overt portal-systemic encephalopathy (PSE) in rats with a surgically constructed portacaval anastomosis (PCA). The ability of increasing the load of nitrogenous substances in the gastrointestinal tract and/or further decreasing hepatocellular function to induce overt encephalopathy in rats with a PCA was determined. The load of nitrogenous substances in the gastrointestinal tract was increased by feeding a pure horse-meat diet or by gavaging with blood. Partial hepatectomy and the induction of cirrhosis were used to decrease hepatocellular function further. The severity of encephalopathy was assessed using a neurobehavioural scale. Overt encephalopathy was not induced in rats by a PCA alone, by a PCA plus a horse-meat diet, by a PCA plus induction of cirrhosis, or by a PCA plus a 50% hepatectomy. Predominantly mild, but overt, encephalopathy was induced in rats with a PCA alone by gavaging with blood and a higher incidence of more severe overt encephalopathy was induced in rats with a PCA combined with either cirrhosis or partial hepatectomy by gavaging with blood. Although these models of PSE were associated in some instances with plasma ammonia concentrations about 25 times higher than normal, no seizures were observed. A syndrome that resembles overt PSE in humans can be induced in the rat with a PCA by further reducing hepatocellular function and also gavaging with blood. Although the rat with a PCA has been. extensively used as a model in studies relating to the pathogenesis of PSE, a syndrome resembling overt PSE in humans cannot readily be induced in rats with a PCA.
    European Journal of Gastroenterology & Hepatology 04/1997; 9(3):293-8. · 2.15 Impact Factor
  • Source
    E A Jones, C Yurdaydin
    Hepatology 03/1997; 25(2):492-4. · 11.19 Impact Factor

Publication Stats

5k Citations
1,289.24 Total Impact Points


  • 1987–2011
    • The National Institute of Diabetes and Digestive and Kidney Diseases
      Maryland, United States
  • 1996–2002
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Academic Medical Center
      Amsterdam, North Holland, Netherlands
  • 2001
    • Queen Elizabeth Hospital Birmingham
      Birmingham, England, United Kingdom
  • 1999
    • Academic Medical Center (AMC)
      Amsterdamo, North Holland, Netherlands
  • 1998
    • Beth Israel Medical Center
      • Division of Gastroenterology & Liver Disease
      New York City, New York, United States
  • 1972–1998
    • National Institutes of Health
      • • Laboratory of Neurosciences (LNS)
      • • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
      • • Branch of Digestive Diseases (DDB)
      • • Laboratory of Clinical Investigation (LCI)
      • • Branch of Metabolism
      Maryland, United States
  • 1988–1996
    • Case Western Reserve University
      • • MetroHealth Medical Center
      • • Division of General Internal Medicine and Geriatrics
      Cleveland, OH, United States
    • Bethesda Neuroscience Clinic
      Maryland, United States
  • 1995
    • The Rockefeller University
      • Laboratory of the Biology of Addictive Diseases
      New York City, NY, United States
  • 1994
    • The University of Calgary
      • Gastrointestinal Research Group
      Calgary, Alberta, Canada
    • Ankara University
      • Department of Gastroenterology
      Ankara, Ankara, Turkey
  • 1990
    • National Heart, Lung, and Blood Institute
      Maryland, United States