E A Jones

University of Amsterdam, Amsterdamo, North Holland, Netherlands

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Publications (116)1034.4 Total impact

  • No preview · Article · Jan 2003
  • 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.
    No preview · Article · Sep 2002 · QJM: monthly journal of the Association of Physicians
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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.
    Full-text · Article · Aug 2000 · Journal of Clinical Pathology
  • 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.
    No preview · Article · Feb 2000 · Canadian journal of gastroenterology = Journal canadien de gastroenterologie
  • 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.
    No preview · Article · Jul 1999 · European Journal of Gastroenterology & Hepatology
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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.
    No preview · Article · Jul 1998 · The Lancet
  • 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.
    No preview · Article · Jun 1998 · Clinics in Liver Disease
  • 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.
    No preview · Article · Apr 1998 · Medical & Biological Engineering & Computing

  • No preview · Article · Jan 1998
  • N. V. Bergasa · E. A. Jones
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    ABSTRACT: Pruritus is a symptom experienced by 80% of patients with primary biliary cirrhosis (PBC)1 and 20–60% of jaundiced patients2. The presence of pruritus or the degree to which it is experienced does not correlate with routine serum biochemical indices of cholestasis. It can be mild to severe and it does not tend to be easily relieved by scratching.
    No preview · Article · Jan 1998
  • E. A. Jones · N. V. Bergasa

    No preview · Article · Jan 1998
  • N. V. Bergasa · E. A. Jones

    No preview · Article · Jan 1998
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    A S Basile · EA Jones

    Full-text · Article · Jun 1997 · Hepatology
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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.
    No preview · Article · Apr 1997 · European Journal of Gastroenterology & Hepatology
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    E A Jones · C Yurdaydin

    Full-text · Article · Feb 1997 · Hepatology
  • K D Mullen · EA Jones

    No preview · Article · Sep 1996 · Seminars in Liver Disease
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    ABSTRACT: The expression of cytokine mRNA species was determined in liver biopsies from six normal subjects, 18 patients with PBC and 14 patients with hepatitis B e antigen (HBeAg)-positive CHB using a reverse transcriptase-polymerase chain reaction (RT-PCR) technique. cDNA, obtained by reverse transcription using oligo d(T) primers, was amplified by PCR using primers specific for the coding region of seven different cytokines (IL-1, IL-2, IL-4, IL-5, IL-6, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha)). The abundance of some cytokines (IL-2, IL-4, IL-5 and IFN-gamma) was also estimated by semiquantitative RT-PCR, using as standards dilutions of synthetic cytokine mRNA transcripts, that could be distinguished electrophoretically from respective native cytokine mRNAs. Hepatic inflammation was assessed by a semiquantitative histologic score and by amplification of mRNA for T cell receptor (TCR)-alpha. mRNAs for IL-1 and IL-6 were detected in only one control liver. In CHB, mRNAs for IL-1, IL-2, IL-4, IL-5 and IFN-gamma were detected in 43%, 60%, 80%, 20%, and 54% of biopsies, respectively. mRNA for IFN-gamma and IL-4, but not IL-1, tended to be associated with severe inflammation. In five biopsies semiquantitative analyses revealed increased levels of mRNA for TCR-alpha and, when transcripts were detectable, high levels of mRNA for IFN-gamma and IL-4. In PBC, mRNA for IFN-gamma was detected in 60% of biopsies, but no mRNAs for IL-1, IL-2, IL-4, IL-5, or IL-6, or for TNF-alpha, were detected. Semiquantitative analyses revealed that absolute levels of mRNA for IFN-gamma tended to correlate with the severity of hepatic inflammation. The results suggest that: (i) there may be fundamental differences in the roles that cytokines play in the hepatic inflammatory processes of PBC and CHB; and (ii) while hepatic IFN-gamma mRNA expression is not specific for PBC, IFN-gamma may play a prominent role in the immunopathogenesis of PBC.
    Preview · Article · Sep 1996 · Clinical & Experimental Immunology
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    EA Jones · N V Bergasa

    Preview · Article · Jun 1996 · Gut
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    ABSTRACT: The p53 tumor suppressor gene is commonly mutated in human hepatocellular carcinoma (HCC). The most frequent mutation in HCC in populations exposed to a high dietary intake of aflatoxin Bl (AFB1) is an AGGarg→AGTser mis-sense mutation in codon 249 of the p53 gene. We analyzed HCCs from Monterrey, Mexico, for the codon 249ser hotspot mutation. We also analyzed the serum AFB1-albumin adduct levels of the donors and family members to measure the current AFB1 exposure in this population. Moreover, the presence of hepatitis B and/or C viral infection (HBV or HCV) was analyzed serologically in the patients. Tumor cells were microdissected from tissue sections and exon 7 p53 sequences were amplified by polymerase chain reaction from genomic DNA and sequenced directly. The serological tests for anti-p53 antibodies, HBV or HCV were done by ELISA. Immunohistochemical analysis of p53 protein was done using a polyclonal rabbit antisenim (CM-1). Eight of 21 cases were positive by p53 immunohistochemistry. Of the 16 cases sequenced for exon 7 of p53 three codon 249 AGGarg→AGTser mutations were found. Serum antibodies recognizing p53 protein were found in one of 18 patients. Positive serology for HBV and/or HCV was found in 12 of 20 cases. The serum AFB1-albumin adduct levels in this population ranged from 0.54 to 4.64 pmol aflatoxin/mg albumin. These results indicate that dietary AFB1 and hepatitis viruses are etiological agents in the molecular pathogenesis of HCC in this geographic region of Mexico.
    Full-text · Article · Jun 1996 · Carcinogenesis
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    ABSTRACT: To determine whether endogenous opioids contribute to the pruritus of cholestasis by studying the effect of the opiate antagonist naloxone on the perception of pruritus and on scratching activity in patients with this form of pruritus. Double-blind, placebo-controlled, crossover trial with four periods. Clinical research referral center. 29 pruritic patients with liver diseases of various causes. Each patient received as many as two naloxone and two placebo solution infusions consecutively in random order. Each infusion lasted 24 hours. During the infusions, visual analog scores of pruritus were recorded every 4 hours while patients were awake; scratching activity independent of limb movements was recorded continuously. One patient had a mild reaction consistent with a naloxone-precipitated syndrome similar to opiate withdrawal. A significant 24-hour rhythm of scratching activity was seen in 7 of 11 patients for whom complete 96-hour data were collected. The mean of a visual analog score of the perception of pruritus (maximum, 10.0) recorded during naloxone infusions was 0.582 lower than that recorded during placebo infusions (95% CI, 0.176 to 0.988; P < 0.01). Furthermore, the ratio of the geometric mean hourly scratching activity during naloxone infusions to that during placebo infusions was 0.727 (CI, 0.612 to 0.842; P < 0.001) and was greater than 1.0 in only five patients. Naloxone administration is associated with amelioration of the perception of pruritus and reduction of scratching activity in cholestatic patients. Because of the opioid receptor specificity of the action of naloxone, these findings support the hypothesis that a mechanism underlying the pruritus of cholestasis is modulated by endogenous opioids and suggest that opiate antagonists may have a role in the management of this complication of cholestasis.
    No preview · Article · Sep 1995 · Annals of internal medicine

Publication Stats

5k Citations
1,034.40 Total Impact Points


  • 2000
    • University of Amsterdam
      • Faculty of Medicine AMC
      Amsterdamo, North Holland, Netherlands
  • 1996-2000
    • 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
  • 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
  • 1972-1995
    • National Institutes of Health
      • • Laboratory of Neurosciences (LNS)
      • • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
      • • Branch of Digestive Diseases (DDB)
      • • Branch of Metabolism
      베서스다, Maryland, United States
  • 1984-1992
    • The National Institute of Diabetes and Digestive and Kidney Diseases
      베서스다, Maryland, United States
    • Icahn School of Medicine at Mount Sinai
      Borough of Manhattan, New York, United States
  • 1990
    • National Heart, Lung, and Blood Institute
      Maryland, United States
  • 1986
    • University of California, Berkeley
      Berkeley, California, United States
  • 1985-1986
    • The University of Calgary
      • Department of Medicine
      Calgary, Alberta, Canada
    • National Institute of Allergy and Infectious Diseases
      • Laboratory of Immunoregulation
      베서스다, Maryland, United States
  • 1983
    • National Institute of Mental Health (NIMH)
      베서스다, Maryland, United States