E A Jones

Academisch Medisch Centrum Universiteit van Amsterdam, Amsterdamo, North Holland, Netherlands

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Publications (118)1025.18 Total impact

  • E. A. Jones · A. J. Meijer · R. A. F. M. Chamuleau ·

  • 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. · 2.50 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. DOI:10.1023/A:1011662411913 · 2.64 Impact Factor
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    ABSTRACT: To use laboratory data and liver biopsies, prospectively obtained from hepatitis B surface antigen (HBsAg) and anti hepatitis B e antigen (anti-HBe) positive patients, for the assessment of: (1) the relation between biopsy length/number of portal tracts and sampling error; (2) the relation between the severity of piecemeal necrosis and the new grading terminology (minimal, mild, moderate, and severe chronic hepatitis); and (3) liver pathology, which has not been studied in patients with this specific serological profile. The study group (n = 174) included 104 patients with normal aminotransferase concentrations and no cases with clinically apparent cirrhosis. The specimen length and number of portal tracts were measured at light microscopy examination. Sampling error analysis was related to the discrepancies between aminotransferase concentrations versus histological grade. Detailed histological scorings were undertaken by the reference pathologist and compared with laboratory and hepatitis B virus (HBV) DNA precore sequence data. Sampling error seemed to be a constant feature, even for biopsies > or = 20 mm, but increased dramatically in biopsies < 5 mm long and/or containing less than four portal tracts. Between 25% and 30% of biopsies, graded as "mild" or "moderate" activity showed features of moderate and severe piecemeal necrosis, respectively. Ten per cent of the patients with normal aminotransferase values had stage III-IV hepatic fibrosis, and 20% had piecemeal necrosis. Only cytoplasmic, not nuclear, core antigen expression was a strong predictor of high hepatitis B viraemia. There was no association between precore stop codon mutations, grade/stage of liver disease, and hepatitis B core antigen (HBcAg) expression. The specimen available for light microscopical examination should be > 5 mm long and should contain more than four portal tracts. In addition, the new grading terminology might give the clinician an inappropriately mild impression of the severity of piecemeal necrosis. Furthermore, even in the presence of normal aminotransferase concentrations, considerable liver pathology can be found in 10-20% of HBsAg and anti-HBe positive individuals; such pathology is not associated with the occurrence of precore stop codon mutations.
    Journal of Clinical Pathology 08/2000; 53(7):541-8. · 2.92 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. · 1.98 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. · 2.25 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. DOI:10.1023/A:1020693026810 · 2.64 Impact Factor
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    ABSTRACT: Although exacerbations of previously quiescent HBV infection, associated with chemotherapy, have been attributed to enhanced immunological responses to hepatocytes harboring reactivated HBV, the recommended treatment, prednisolone, is often unsuccessful. A young HBsAg-positive, anti-HBe-positive carrier, who received chemotherapy for choriocarcinoma, developed icteric hepatitis. The serum HBV DNA level was 34,000 x 10(6) genomic equivalents per milliliter serum. Treatment with prednisolone alone did not prevent progression to overt hepatic failure. By three days after initiating lamivudine therapy, however, there was reversal of stage III hepatic encephalopathy. With further lamivudine treatment, substantial further improvement in hepatocellular function occurred and HBV-DNA levels became undetectable. When an immunocompromised patient develops an exacerbation of hepatitis B associated with high HBV DNA levels, treatment with prednisolone seems inappropriate, as hepatocytotoxic HBV replication may be stimulated further. In this situation inhibition of HBV replication, eg, by administering lamivudine, may be life-saving.
    Digestive Diseases and Sciences 11/1998; 43(10):2267-70. DOI:10.1023/A:1026622807373 · 2.61 Impact Factor
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    ABSTRACT: Hepatitis B surface antigen (HBsAg) and antibodies to hepatitis B e antigen (anti-HBe) commonly coexist, and laboratory tests are often requested to assess histological hepatitis activity. An optimum panel of tests has not been found and the usefulness of hepatitis B virus (HBV) DNA assays in this context has not been established. We assessed various blood tests to find which best predicted hepatitis activity. Routine plasma biochemical liver tests and serum HBV DNA (hybridisation and PCR assays) were assessed prospectively in 123 patients positive for HBsAg and anti-HBe. We scored histological hepatitis activity (hepatitis activity index) and determined whether chronic active hepatitis (chronic hepatitis with portal and periportal lesions) was present. We analysed the relation between laboratory data and the hepatitis activity index or risk of chronic active hepatitis by multiple regression and multiple logistic regression, respectively. The analyses provided models for predicting either the hepatitis activity index or the risk of chronic active hepatitis. Aspartate aminotransferase was the most important test in the two models. The contribution of HBV DNA and other assays, especially alanine-aminotransferase activity, were of no practical importance. Because screening by aspartate-aminotransferase activity could not be improved by the addition of other assays or HBV DNA, patients positive for HBsAg and anti-HBe could be screened for chronic active hepatitis with a single assay and counselling of patients can be improved if proper reference values are used.
    The Lancet 07/1998; 351(9120):1914-8. DOI:10.1016/S0140-6736(97)09391-4 · 45.22 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. · 3.66 Impact Factor
  • H. A. J. Molenaar · J Oosting · EA Jones ·
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    ABSTRACT: Pruritus is an inherently subjective perception that cannot be quantified. However, in trials of new therapies for pruritus, it is necessary to base assessments of therapeutic efficacy on objective quantitative criteria. This can be achieved by measuring the behavioural consequence of pruritus, scratching activity, and using an index of scratching activity as an efficacy endpoint. A portable device to monitor scratching activity in patients with pruritus is described. The key feature of this device is a piezo-element attached to a fingernail. Vibrations of the fingernail in the act of scratching induce electrical impulses in the piezo-element. Electrical signals from the device are filtered and measured. The measurements, which are not absolute, have nevertheless been shown to provide an objective index of scratching activity that is independent of arm and hand movements. An advantage of the device is that recordings can be made while the patient is in a normal, non-hospital environment, thereby obviating effects of change of environment (e.g. hospitalisation) on the intensity of pruritus. Application of the device enables data on scratching activity during periods of treatment with a test drug and with a placebo to be compared in individual patients.
    Medical & Biological Engineering & Computing 04/1998; 36(2):220-4. DOI:10.1007/BF02510746 · 1.73 Impact Factor
  • N. V. Bergasa · E. A. Jones ·

  • E. A. Jones · N. V. Bergasa ·

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    ABSTRACT: A 27-year-old woman with chronic renal failure, who had been treated with chronic ambulatory peritoneal dialysis and had developed sclerosing peritonitis, was admitted to the hospital with intra-abdominal sepsis. In spite of antibiotic therapy, sepsis recurred and was associated with intrahepatic cholestasis. In addition, over a period of about 4.5 weeks she developed hepatomegaly and portal hypertension unassociated with occlusion of the portal vein or one of its main extrahepatic branches. A wedge biopsy of the liver revealed extensive thick fibrosis of the liver capsule, intrahepatic cholestasis, diffuse swelling of hepatocytes, central veins that were difficult to visualize and small portal tracts. It is suggested that the sepsis was responsible for the intrahepatic cholestasis, swelling of hepatocytes and hepatomegaly. It is also suggested that the rigidity of the fibrotic liver capsule provided resistance to the development of hepatomegaly, with the result that intrahepatic pressure increased (compressing intrahepatic branches of the portal vein as well as portal tracts and central veins) and portal hypertension developed.
    European Journal of Gastroenterology & Hepatology 01/1998; 10(1):95-8. DOI:10.1097/00042737-199801000-00017 · 2.25 Impact Factor
  • N. V. Bergasa · E. A. Jones ·

  • Source
    A S Basile · EA Jones ·

    Hepatology 06/1997; 25(6):1303-5. DOI:10.1002/hep.510250636 · 11.06 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. DOI:10.1097/00042737-199703000-00014 · 2.25 Impact Factor
  • E A Jones · A S Basile ·

    Advances in Experimental Medicine and Biology 02/1997; 420:75-83. · 1.96 Impact Factor
  • Source
    E A Jones · C Yurdaydin ·

    Hepatology 02/1997; 25(2):492-4. DOI:10.1002/hep.510250239 · 11.06 Impact Factor

Publication Stats

5k Citations
1,025.18 Total Impact Points


  • 1996-2001
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Academic Medical Center
      Amsterdamo, North Holland, Netherlands
    • National Cancer Institute (USA)
      • Laboratory of Human Carcinogenesis
      베서스다, Maryland, United States
  • 2000
    • University of Amsterdam
      • Faculty of Medicine AMC
      Amsterdamo, North Holland, Netherlands
  • 1998
    • Beth Israel Medical Center
      • Division of Gastroenterology & Liver Disease
      New York City, New York, United States
  • 1993-1995
    • The Rockefeller University
      • Laboratory of the Biology of Addictive Diseases
      New York, New York, United States
  • 1977-1995
    • National Institutes of Health
      • • Laboratory of Neurosciences (LNS)
      • • Branch of Digestive Diseases (DDB)
      • • Branch of Metabolism
      베서스다, Maryland, United States
  • 1988-1992
    • The National Institute of Diabetes and Digestive and Kidney Diseases
      베서스다, Maryland, United States
    • Bethesda Neuroscience Clinic
      Maryland, United States
  • 1990
    • National Heart, Lung, and Blood Institute
      Maryland, United States
  • 1986
    • University of California, Berkeley
      Berkeley, California, United States
  • 1985
    • National Institute of Allergy and Infectious Diseases
      • Laboratory of Immunoregulation
      베서스다, Maryland, United States
    • The University of Calgary
      • Department of Medicine
      Calgary, Alberta, Canada
  • 1984
    • Icahn School of Medicine at Mount Sinai
      Borough of Manhattan, New York, United States
  • 1978-1984
    • National Institute of Child Health and Human Development
      베서스다, Maryland, United States
  • 1983
    • National Institute of Mental Health (NIMH)
      베서스다, Maryland, United States