(Diagnosis, Diagnostics, Immunodiagnosis, Immunodiagnostics, Pathogenesis, Vaccines & Drugs)



Back to Reference




1254. Agarwala S.  Mitra DK. Biliary atresia--the current management. [Review] [29 refs] Indian Journal of Pediatrics.  63(6):719-24, 1996 Nov-Dec.


Despite extensive research, controversies still exist regarding the etiology, pathology and management of biliary atresia. It is now thought to be a progressive panductal inflammatory obliterative process and not a developmental anomaly. The histologic changes are indistinguishable from neonatal hepatitis but some changes have prognostic significance. The clinical presentation is that of infantile obstructive cholangiopathy-waxing and waning icterus, clay coloured stools and high coloured urine from early neonatal period. The diagnosis is suggested by the absence of intestinal excretion on HIDA scan and confirmed on  operative cholangiogram. Of utmost importance towards the final prognosis is early detection, prompt confirmation and surgical treatment before 2 months of age. Even with early treatment the result of bilioenteric drainage procedures have been discouraging in the long term. Portoenterostomy (PE) done in older children has been largely unsuccessful all over the world. The poor results of PE prompted the search for alternative treatment and liver transplantation (LT) has emerged as a viable treatment option both as a primary procedure and after failed PE. Although the technical know-how and infrastructure are available, LT in children has still not been done in India because of various economic and  social constraints. It is hoped that all physicians and surgeons dealing with such patients would also consider this treatment modality.  [References: 29]




1255.  Anonymous. WHO Expert Committee on Biological Standardization. World Health Organization Technical Report Series.  889:i-vi, 1-111, 1999.


This report presents the recommendations of a WHO Expert Committee commissioned to coordinate activities leading to the adoption of international requirements for the production and control of vaccines and other biologicals and the establishment of international biological reference materials. The report starts with a discussion of general issues brought to the Committee's attention and provides information on the status and development of reference materials for various antibodies, antibiotics, antigens, blood products and related substances, cytokines and growth factors and other substances for which the Committee has discerned a need for international reference materials. The second part of the report, of particular relevance of manufacturers and national control authorities, contains guidelines for the production and control of  synthetic peptide vaccines, requirements for tick-borne encephalitis vaccine (inactivated), guidelines for thromboplastins and plasma used to control oral anticoagulant therapy, an amendment to the requirements for hepatitis B vaccine made by recombinant DNA techniques and a report on the standardization and calibration of cytokine immunoassays.


1256. Arbuthnot P.  Capovilla A.  Kew M. Putative role of hepatitis B virus X protein in hepatocarcinogenesis: effects on apoptosis, DNA repair, mitogen-activated protein kinase and JAK/STAT pathways [see comments]. [Review] [130 refs] Journal of Gastroenterology & Hepatology.  15(4):357-68, 2000 Apr.


Chronic infection with hepatitis B virus (HBV) is a major risk factor for the development of hepatocellular carcinoma (HCC). The pathogenesis of  HBV-induced malignant transformation is, however, incompletely understood. HBx, the protein encoded by the X open reading frame, is a transcriptional activator that has been implicated in hepatocarcinogenesis. HBx inhibits the function of the tumour suppressor protein p53 in what is thought to be an early event in hepatocyte transformation before the later accumulation of inactivating p53 point mutations. HBx inhibits apoptosis but also exerts pro-apoptotic effects. The effects of HBx on apoptosis may be important not only for the development of HCC but also for the establishment of HBV infection. Further implication of HBx in hepatocyte transformation has been the demonstration that it inhibits the repair of damaged hepatocyte DNA. This effect may be mediated by interaction with p53 or through binding to the damaged DNA binding protein (DDB), which plays an accessory role in nucleotide excision repair. In addition, HBx activates cell signalling cascades involving mitogen-activated protein kinase (MAPK) and Janus family tyrosine kinases (JAK)/signal transducer and activators of transcription (STAT) pathways. The implications of these modulating effects of HBx are not fully understood, but they are likely to have wide-ranging effects on hepatocyte proliferation, apoptosis and the regulation of cell growth checkpoints. The cellular functions ascribed to HBx are unusually diverse, and defining the biologically important role of HBx during HBV replication will go some way to understanding the sequelae of chronic HBV infection. [References: 130]


1257. Assy N.  Minuk GY. Serum aspartate but not alanine aminotransferase levels help to predict the histological features of chronic hepatitis C viral infections in adults. American Journal of Gastroenterology.  95(6):1545-50, 2000 Jun.


OBJECTIVES: The aims of this study were to assess the predictive values of age, gender, route of transmission, extent of steatosis, alcohol consumption, and serum aminotransferase values on the histological findings in patients with chronic hepatitis C viral infections. METHODS:  We retrospectively reviewed the charts and liver biopsy findings from 79  adult patients with serological evidence of chronic hepatitis C viral  infections. RESULTS: The mean (+/- SD) age of the patient population was  43.5 +/- 10.8 yr; 47 patients (60%) were male. The routes of transmission  were considered to be parenteral drugs in 44 patients (56%), previous  blood transfusions in 25 (32%), and miscellaneous parenteral and  nonparenteral routes in 10 (13%). The mean histological activity core of  the group as described by Desmet et al. was 3.5 +/- 0.8 (maximum possible  score, 18) and the fibrosis score 1.5 +/-0.4 (maximum possible score, 4),  indicating relatively mild disease in the majority of cases. The extent of  inflammation correlated with fibrosis (r = 0.72). By multivariate stepwise  regression analyses, serum aspartate aminotransferase (AST) values emerged  as the most important predictive variable of histological activity (r =  0.62). When overall histological activity was further divided into portal  inflammation, piecemeal necrosis, and lobular activity, correlations were  found between AST values and portal inflammation (r = 0.58) and piecemeal  necrosis (r = 0.61) but not lobular activity (r = 0.1). A correlation was  also observed between AST values and the extent of hepatic fibrosis (r =  0.64). On the other hand, serum ALT values did not correlate with  histological activity but did correlate weakly with the extent of hepatic  fibrosis (r = 0.39 and 0.51, respectively). There were no significant  correlations between age, gender, route of transmission, steatosis, or  alcohol consumption with the extent of histological activity or fibrosis.  CONCLUSIONS: Serum AST values correlate well with two of three features of  hepatic inflammation and with the extent of hepatic fibrosis. These  findings suggest that, among other factors, serum AST values should be  considered in decisions regarding the need for liver biopsy and treatment in patients with chronic hepatitis C viral infections.



1258. Bautista AP. Impact of alcohol on the ability of Kupffer cells to produce chemokines and its role in alcoholic liver disease. [Review] [50 refs] Journal of Gastroenterology & Hepatology.  15(4):349-56, 2000 Apr.


Chemokines are implicated in the pathogenesis of alcoholic liver disease in humans and in experimental models of alcohol intoxication. The major sources of these chemokines are Kupffer cells which represent more than 80% of tissue macrophages in the body. Kupffer cells are highly responsive to the effects of ethanol, endotoxin and human immunodeficiency virus (HIV)-1 glycoprotein120. These agents, either independently or in combination, may exacerbate the production of chemokines. Chemokines are agents that are highly chemotactic to mononuclear cells and granulocytes. The levels of these chemokines in sera and tissue are elevated in patients with alcoholic hepatitis, alcoholic cirrhosis, diseased livers, viral hepatitis, and in experimental models of chronic alcohol intoxication. Alcohol-induced influx of endotoxin from the gut into the portal  circulation is suggested to play an important role in the activation of Kupffer cells which leads to enhanced chemokine release. The up-regulation of chemokines during alcohol consumption is selective. During the early phase of alcoholic liver disease, C-X-C or alpha-chemokines predominate. This is also associated with neutrophilic infiltration of the liver. In the later stage, up-regulation of C-C or beta-chemokine production and migration of mononuclear cells into the liver are observed, and this may lead to liver cirrhosis. Selective up-regulation of chemokine synthesis and release may involve differential modulation of the transcription factors required for chemokine gene expression. Increased cytokine release following alcohol consumption may also regulate chemokine secretion in Kupffer cells via paracrine and autocrine mechanisms and vice versa. In addition, infection with HIV-1 may further compromise the liver to more damage. During HIV-1 infection, a pre-existing liver disease superimposed on chronic alcohol consumption may also exacerbate HIV-1 replication and lymphocytic infiltration in the liver, because of the ability of HIV-1 gp120 to stimulate chemokine production by Kupffer cells and stimulate  migration of inflammatory leucocytes in the liver. [References: 50]



1259. Bock HL.  Kruppenbacher JP.  Bienzle U.  De Clercq NA.  Hofmann F. Clemens RL. Does the concurrent administration of an inactivated hepatitis A vaccine  influence the immune response to other travelers vaccines?. Journal of Travel Medicine.  7(2):74-8, 2000 Mar-Apr.


BACKGROUND: Travelers seeking protection from hepatitis A also often need   protection against other infections, prevalent at their destinations. METHODS: A total of 396 volunteers received not only a hepatitis A vaccine but also either a vaccine against polio, hepatitis B, diphtheria, tetanus, yellow fever, Japanese encephalitis, typhoid fever or rabies according to their individual needs. We investigated the potential influence of the hepatitis A vaccination on the immune response to the other travelers vaccines that were administered concurrently. RESULTS: With seroprotection rates of 100% for yellow fever, Japanese encephalitis and rabies immunization and tetanus boosters our data demonstrate that the concurrent administration of hepatitis A vaccine does not compromise the immune response of these vaccines. Also for oral typhoid, hepatitis B and diphtheria vaccination we did not detect a negative influence of  concurrent hepatitis A vaccine administration as compared with respective  vaccinations when given alone. Prior to vaccination, more than one third  of our subjects lacked protective antibody levels against diphtheria and only 44% of initially seronegative travelers seroconverted to an anti-diphtheria titer > or = 0.01 mIU/mL, supporting a need for an additional dose. Furthermore, only two thirds of the vaccinees tested prior to vaccination were protected against polio type 3, and the seroconversion rate following the administration of oral polio vaccine, was lower for viral type 3 (80%), as has been previously demonstrated in settings without concurrent other vaccinations. CONCLUSION: No negative  effect of concurrent travelers vaccinations on the immune response of a  hepatitis A vaccine has been detected in a previous report, and, likewise our data suggest no impairment of the antibody response of these travelers vaccines by the concurrent administration of the hepatitis A vaccine.



1260. Calabrese F.  Pontisso P.  Pettenazzo E.  Benvegnu L.  Vario A.  Chemello  L.  Alberti A.  Valente M. Liver cell apoptosis in chronic hepatitis C correlates with histological but not biochemical activity or serum HCV-RNA levels. Hepatology.  31(5):1153-9, 2000 May.


In hepatitis C virus (HCV) infection, mechanisms responsible for liver cell damage are still poorly understood and both necrosis and apoptosis may be operative. By using terminal deoxynucleotydil transferase-mediated  d-UTP-biotin nick-end labeling (TUNEL) we have evaluated and quantified  apoptosis in liver biopsy specimens from 61 patients with chronic  hepatitis C. All patients had detectable apoptotic cells in the liver.  Presence of increased apoptotic activity was confirmed in selected cases  by electron microscopy and by DNA gel electrophoresis. The amount of liver  cell apoptosis expressed as apoptotic index, ranged between 0.01% to 0.54%  and showed a positive correlation with histological activity grading (P  <.0005) and with the amount of infiltrating CD8-positive cells (P =. 01).  Apoptosis did not correlate with transaminase levels or with HCV load and  genotype. These results support the concept that immune-mediated apoptosis  may play a role in the pathogenesis of chronic hepatitis C and indicate  that this type of reaction may occur in the absence of significant alanine  transaminase (ALT) elevation, thus explaining the lack of correlation  between biochemical activity and liver histological damage.


1261. Carrigan DR. Adenovirus infections in immunocompromised patients. [Review] [05 refs] American Journal of Medicine.  102(3A):71-4, 1997 Mar 17.


Adenovirus infections have been reported in as many as one-fifth of bone marrow transplant (BMT) recipients and patients with acquired immunodeficiency syndrome (AIDS), and in a lesser, though still prominent, proportion of organ transplant recipients. The relative contributions of primary infections versus reactivations from latency in immunocompromised patients remain unclear. Compared with adult BMT recipients, pediatric BMT recipients appear to be infected by adenovirus more frequently and earlier in the post-transplant period. The diagnosis of adenovirus infection is complicated by the existence of > 40 viral serotypes, although certain subgroups are more likely to be involved in certain patient populations. Adenoviruses are responsible for a broad range of clinical diseases that may be associated with high mortality, including pneumonia, hepatitis, encephalitis, hemorrhagic cystitis, and gastroenteritis. The clinical and histopathologic features of adenovirus disease may resemble those of cytomegalovirus disease, potentially complicating the diagnosis. Risk  factors for clinical adenovirus disease include the number of sites from which the virus is cultured and, in BMT recipients, the presence of moderate to severe acute graft-versus-host disease. [References: 05]



1262. Ciocca M. Clinical course and consequences of hepatitis A infection.  Vaccine.  18 Suppl 1:S71-4, 2000 Feb 18.


Hepatitis A virus (HAV) is a small, non-enveloped RNA virus belonging to the Picornaviridae, for which only one serotype has been identified. Transmission is usually through the faecal-oral route by person-to-person contact. The most common risk factors are household or sexual contact with a sufferer, attendance or working at a day-care centre, international travel, and association with food or waterborne outbreaks; 55% of cases have no identifiable risk factors. HAV infection may be symptomatic or asymptomatic, and shows three phases. Virus is shed during the incubation phase, anti-HAV IgM appears during the symptomatic phase and can be used for diagnosis, and anti-HAV IgG appears at the same time but persists lifelong. Unusual clinical manifestations of hepatitis A include  cholestatic, relapsing and fulminant hepatitis. Hepatitis A accounts for  93% of cases of acute hepatitis in Argentina, including 7% of atypical  clinical cases. Hepatitis A is the major cause of fulminant hepatitis, and  has been reported to account for 10% of liver transplants in children in  France and 20% in Argentina. One-year survival after liver transplantation  is 64%. Prevention must be considered as the main means of averting this  severe illness.



1263.   Dalekos GN.  Kistis KG.  Boumba DS.  Voulgari P.  Zervou EK.  Drosos AA.   Tsianos EV. Increased incidence of anti-cardiolipin antibodies in patients with  hepatitis C is not associated with aetiopathogenetic link to anti-phospholipid syndrome. European Journal of Gastroenterology & Hepatology.  12(1):67-74, 2000 Jan.


OBJECTIVE: Chronic infection with hepatitis C virus (HCV) has been found to be associated with various diseases known as extra-hepatic manifestations of HCV. Recently, HCV has been implicated as a cause of the antiphospholipid syndrome (APLS). We conducted a study in a well-characterized area for epidemiological and prospective studies in the  north-western part of Greece in order to address whether an  aetiopathogenesis exists between HCV and APLS. DESIGN: Seventy-five  patients with chronic hepatitis C were investigated for the presence of  anti-cardiolipin antibodies (anti-CL) and for a past medical history  supportive to the diagnosis of APLS. In addition, 24 patients with  well-defined APLS (primary or secondary) and 12 patients with systemic  lupus erythematosus (SLE) were tested for the presence of markers of HCV  infection (anti-HCV and HCV RNA). The SLE patients were anti-CL-positive  but none of them had developed any of the known clinical features of APLS.  In addition, 267 healthy subjects were investigated for the presence of  anti-CL. METHODS: IgG and IgM anti-CL were determined by a quantitative  isotype-specific solid phase enzyme-linked immunosorbent assay set up in  our laboratory. Anti-HCV was determined using a third-generation enzyme  immunoassay and a confirmatory third-generation recombinant immunoblot assay. Active virus replication was defined by the detection of HCV RNA  using a combination assay based on a reverse transcriptase polymerase  chain reaction and a DNA enzyme immunoassay. RESULTS: Of the HCV patients,  37.3% had IgG and/or IgM anti-CL (P<0.00005 compared to healthy controls  (2.25%)). However, the mean titres of each specific isotype were  significantly lower in HCV patients compared with those found in the APLS  patients (P<0.05 for IgM and P<0.001 for IgG isotypes). The mean titres of  IgG anti-CL were also significantly lower in HCV patients compared with  those found in the SLE patients (P<0.01). All patients with APLS or SLE (n  = 36) tested negative for HCV infection markers. In addition, neither  thrombotic events nor thrombocytopenia were associated with a positive  anti-CL test in HCV patients. CONCLUSIONS: A significant proportion of HCV  patients (37.3%) had detectable anti-CL of low titre. However, this finding was not associated with the development of APLS. On the other hand, none of the APLS patients was positive for HCV. Taken together, our data rather failed to reveal an aetiopathogenetic link between HCV and APLS. For this reason, testing for HCV in patients with APLS or follow-up for the possibility of the development of APLS in HCV patients cannot be suggested, at least in Greek patients. More prospective studies of longer duration are required in order to address whether HCV is involved or not  in the aetiopathogenesis of APLS.


1264. De Meyer S.  Depla E.  Maertens G.  Soumillion A.  Yap SH. Characterization of small hepatitis B surface antigen epitopes involved in  binding to human annexin V. Journal of Viral Hepatitis.  6(4):277-85, 1999 Jul.


Previously, we have shown that small hepatitis B surface antigen (SHBsAg) binds specifically to human annexin V (hAV) and that hAV plays a key role in the initial steps of hepatitis B virus (HBV) infection. We have also demonstrated the spontaneous development of anti-idiotypic antibodies (antibodies to HBsAg Ab2) in rabbits immunized with hAV. As Ab2 is able to inhibit the binding of hAV to SHBsAg, Ab2 might contain epitope(s) mimicking a region of hAV for binding to SHBsAg. Identification of this epitope will therefore reveal a SHBsAg sequence involved in hAV binding. Using a panel of synthetic peptides covering the region of SHBsAg located on the outer surface of the virus, binding studies showed that the region incorporating amino acids (aa) 125-131 of SHBsAg is important for binding to Ab2 and consequently also for binding to hAV. Further experiments  revealed that not only this region, but also the region incorporating aa 158-169, is involved in the binding of SHBsAg to hAV. As these regions are located in the structural vicinity according to the topological model of HBsAg proposed by Chen et al., our findings suggest that these regions are parts of a conformational epitope of SHBsAg for binding to hAV. Because of the crucial role of hAV in HBV infection, further studies on the HBsAg epitopes for hAV binding may lead to the development of a new generation of vaccines or molecules for prevention and for treatment of patients with chronic hepatitis B.


1265. Degos F.  Christidis C.  Ganne-Carrie N.  Farmachidi JP.  Degott C.   Guettier C.  Trinchet JC.  Beaugrand M.  Chevret S. Hepatitis C virus related cirrhosis: time to occurrence of hepatocellular carcinoma and death. Gut.  47(1):131-6, 2000 Jul.


BACKGROUND: In patients with hepatitis C virus (HCV) infection and cirrhosis, long term outcome and the incidence of hepatocellular carcinoma (HCC) are still debated. DESIGN: From January 1987 to January 1997, 416 patients (240 male, median age 57 years) with uncomplicated Child-Pugh A HCV related cirrhosis were followed in two Paris area centres from diagnosis of cirrhosis until death or reference date (1 June 2024). The analysis used a three state disability model generalising the Cox model. RESULTS: Of the 416 patients, 60 developed HCC with a five year rate of 13.4% (95% confidence interval (CI) 9.0-17.8%) and 83 died (including 34 with HCC), with a five year death rate of 15.3% (95% CI 12.6-18.0%). By multivariable analysis, time to HCC relied on age (hazard ratio (HR) 1.05 per year; p=0.0005), male sex (HR 2.13; p=0.01), oesophageal varices (HR  2.36; p= 0.008), decreased platelet count (HR 0.99; p=0. 03), and  bilirubin level (HR 1.01; p=0.003), while death after HCC was mainly  related to tobacco consumption (HR 1.04; p=0.0006). In contrast, death  free of HCC was dependent on age (HR 1.04; p=0.01), oesophageal varices (HR 2.75; p=0.001), low platelet count (HR 0.99; p=0.006), and albumin level (HR 0.90; p=0.0001). CONCLUSION: The incidence of HCC and mortality should be higher in these patients than previously stated, and prognostic factors of HCC and death are closely related age and symptoms of portal hypertension.



1266. El Mir S.  Triebel F. A soluble lymphocyte activation gene-3 molecule used as a vaccine adjuvant elicits greater humoral and cellular immune responses to both particulate and soluble antigens. Journal of Immunology.  164(11):5583-9, 2000 Jun 1.


The lymphocyte activation gene-3 (LAG-3) product is a MHC class II ligand that has been used in vivo to stimulate MHC class II+ APCs to increase tumor-specific immune responses. We investigated whether LAG-3 could also play an adjuvant role in vivo for the induction of humoral and CD4 or CD8 cell-mediated immune responses when immunizing mice with a particulate (hepatitis B surface Ag) or soluble (OVA) Ag. In both cases, coadministration of 1 microg of a soluble fusion protein between murine LAG-3 and the Fc fraction of a murine IgG2a mAb (mLAG-3Ig) as a vaccine adjuvant induced or increased CTL responses to the corresponding MHC class I-restricted peptide. In addition, splenocytes of mice vaccinated with either the particulate or soluble Ag plus mLAG-3Ig exhibited a  significantly greater proliferative response than did splenocytes of mice  immunized with Ag and a control Ig molecule. Similarly, these splenocytes  had a greater Th1- but not Th2-type cytokine response. Finally, mice  immunized with Ag plus mLAG-3Ig produced higher titers of Abs than mice  immunized with Ag and a control Ig molecule. Thus, these data provide  evidence of a novel means of improving the immunogenicity of subunit  vaccines.


1267. Fattori D.  Urbani A.  Brunetti M.  Ingenito R.  Pessi A.  Prendergast K.   Narjes F.  Matassa VG.  De Francesco R.  Steinkuhler C. Probing the active site of the hepatitis C virus serine protease by fluorescence resonance energy transfer. Journal of Biological Chemistry.  275(20):15106-13, 2000 May 19.


A serine protease domain contained within the viral NS3 protein is a key player in the maturational processing of the hepatitis C virus polyprotein and a prime target for the development of antiviral drugs. In the present work, we describe a dansylated hexapeptide inhibitor of this enzyme. Active site occupancy by this compound could be monitored following fluorescence resonance energy transfer between the dansyl fluorophore and protein tryptophan residues and could be used to 1) unambiguously assess active site binding of NS3 protease inhibitors, 2) directly determine equilibrium and pre-steady-state parameters of enzyme-inhibitor complex formation, and 3) dissect, using site-directed mutagenesis, the contribution of single residues of NS3 to inhibitor binding in direct  binding assays. The assay was also used to characterize the inhibition of the NS3 protease by its cleavage products. We show that enzyme-product inhibitor complex formation depends on the presence of an NS4A cofactor peptide. Equilibrium and pre-steady-state data support an ordered mechanism of ternary (enzyme-inhibitor-cofactor) complex formation, requiring cofactor complexation prior to inhibitor binding.


1268.   Flint M.  McKeating JA. The role of the hepatitis C virus glycoproteins in infection. [Review] [95 refs] Reviews in Medical Virology.  10(2):101-17, 2000 Mar-Apr.


HCV encodes two glycoproteins, E1 and E2, that are believed to be exposed on the surface of virions. These molecules are likely to be involved in  viral interactions with the host immune response and responsible for mediating viral entry into target cells. They are obvious major components for prototype vaccine studies. Recently, E2 has been reported to bind to the tetraspan molecule CD81, which represents a putative receptor for HCV. Here, we discuss the role the HCV gps may play during infection, the contribution of E2 gp variation to HCV evasion from the immune response and possible implications of the E2-CD81 interaction for HCV pathogenesis. Copyright 2000 John Wiley & Sons, Ltd. [References: 95]


1269. Greaves M.


  Chronic urticaria. [Review] [64 refs]


  Journal of Allergy & Clinical Immunology.  105(4):664-72, 2000 Apr.


  Chronic urticaria remains a major problem in terms of etiology,

  investigation, and management. It is important to identify patients in

  whom physical urticaria is the principal cause of disability. Once

  confirmed by appropriate challenge testing, no further investigation is

  required. Urticarial vasculitis (UV) is a major differential diagnosis of

  "idiopathic" urticaria (CIU). I perform biopsy of most patients in this

  category because UV cannot be considered confirmed in the absence of

  histologic evidence. Patients with confirmed UV need to be thoroughly

  investigated for paraproteins, lupus erythematosus hepatitis B and C, and

  inflammatory bowel disease. Of patients with CIU, a few (<5%) prove to

  have food additive reactivity confirmed by placebo-controlled challenge

  testing. There is no convincing evidence of the involvement of

  Helicobacter pylori or parasite infestation as a cause of chronic

  urticaria, although H pylori could have an indirect role. Recently it has

  become clear that 27% to 50% of patients with CIU have functional

  autoantibodies directed against the alpha-chain of the high-affinity IgE

  receptor or less commonly against IgG. These antibodies, whose involvement

  has now been independently confirmed in several centers, are identified by

  autologous serum skin testing and confirmed by histamine release studies

  or immunoblotting. Their removal (by intravenous Ig or plasmapheresis) or

  treatment by cyclosporine has proved highly beneficial in severely

  affected patients. However, the routine treatment of all CIU patients,

  irrespective of etiology, remains the judicious use of H(1)

  antihistamines. [References: 64]


1270. Hass PL.


  Differentiation and diagnosis of jaundice. [Review] [29 refs]


  AACN Clinical Issues.  10(4):433-41, 1999 Nov.


  Bilirubin metabolism is a complex and fascinating example of the body's

  ability to discard, renew, and recycle vital elements. Jaundice is the

  warning sign for derangements in this system. As is true of pain, jaundice

  is a powerful impetus for visiting a healthcare provider. Usually

  associated with hepatitis by a nonclinician, the origins of jaundice can

  range from benign to fatally malignant. Patients may have any number of

  idiopathic or nosocomial conditions that can contribute to an icteric

  state. This review delineates the steps of bilirubin metabolism,

  enumerates the sources of bilirubin derangement, and examines elements of

  patient condition and therapeutics that can contribute to

  hyperbilirubinemia and jaundice. [References: 29]


1271. Haviv YS.  Sharkia M.  Galun E.  Safadi R.


  Pancreatitis following hepatitis A vaccination.


  European Journal of Medical Research.  5(5):229-30, 2000 May 23.


  We describe a 23-year-old male patient who presented with epigastric

  abdominal pain, 8 days following vaccination with inactivated hepatitis A

  virus (Haverix(R)). Clinical and laboratory data confirmed the diagnosis

  of pancreatitis. Repeat polymerase chain reaction (PCR) for hepatitis A

  replication was negative. A comprehensive evaluation ruled out other

  etiologies for pancreatitis. IgM Hepatitis A antibodies did not develop

  even after 3 months. Pancreatitis following Hepatitis A is a well-known

  complication of the viremia, but the exact mechanism is controversial. We

  suggest that the pancreatitis may have been a cellular immunlogical

  reaction to one of the antigens of hepatitis A virus vaccine, or it might

  have been caused by the release of mediators of anaphylaxis such as

  histamine and leucotriens, induced by HAV antigens, resulting in

  pancreatitis without development of humoral immunization.


1272. Huang CJ.  Chen YH.  Ting LP.


  Hepatitis B virus core protein interacts with the C-terminal region of

  actin-binding protein.


  Journal of Biomedical Science.  7(2):160-8, 2000 Mar-Apr.


  Hepatitis B viral core protein is present in the nucleus and cytoplasm of

  infected hepatocytes. There is a strong correlation between the

  intrahepatic distribution of core protein and the viral replication state

  and disease activity in patients with chronic hepatitis. To understand the

  role of core protein in the pathogenesis of HBV, we used a yeast

  two-hybrid system to search for cellular proteins interacting with the

  carboxyl terminus of core protein, as this region is involved in a number

  of important functions in the viral replication cycle including RNA

  packaging and DNA synthesis. A cDNA encoding the extreme C-terminal region

  of human actin-binding protein, ABP-276/278, was identified. This

  interaction was further confirmed both in vitro and in vivo. In addition,

  the extreme C-terminal region of ABP-276/278 interacted with the nearly

  full-length HBV core protein. Since this region is present in both the

  core and the precore proteins, it is likely that both core and precore

  proteins of HBV can interact with the C-terminal region of ABP-276/278.

  The minimal region of ABP-276/278 which interacted with the HBV core

  protein was the C-terminal 199 amino acid residues which correspond to

  part of the 23rd repeat, the entire 24th repeat and the intervening hinge

  II region in ABPs. The potential functional outcome of ABP interaction in

  HBV replication and its contribution to the pathological changes seen in

  patients with chronic HBV infection are discussed.


1273. Kessel A.  Rosner I.  Zuckerman E.  Golan TD.  Toubi E.


  Use of antikeratin antibodies to distinguish between rheumatoid arthritis

  and polyarthritis associated with hepatitis C infection.


  Journal of Rheumatology.  27(3):610-2, 2000 Mar.


  OBJECTIVE: To investigate whether antikeratin antibodies (AKA) could be

  useful in the differential diagnosis of patients with rheumatoid arthritis

  (RA) compared to patients with hepatitis C virus (HCV) associated

  polyarthritis, who are seropositive for rheumatoid factor (RF). METHODS:

  AKA were assayed in 3 different groups of patients; all were RF

  seropositive: Group 1: 25 patients with HCV associated polyarthralgia or

  arthritis. Group 2: 33 patients with RA. Group 3: 13 patients with

  autoimmune disorders other than RA. Fifteen healthy individuals served as

  controls. RESULTS: AKA were detected in 20/33 patients with RA (60.6%)

  compared to only 2/25 patients (8%) with HCV associated arthritis (p <

  0.0001). AKA were observed in 2/13 patients of Group 3 (15.3%). These

  results were also statistically different from those of patients with RA

  (p = 0.008). AKA were not found in the sera of the healthy controls.

  CONCLUSION: AKA is a useful marker to differentiate patients with RA from

  those with hepatitis C arthritis.


1274. Kimura Y.  Hayashida K.  Ishibashi H.  Niho Y.  Yanagi Y.


  Antibody-free virion titer greatly differs between hepatitis C virus



  Journal of Medical Virology.  61(1):37-43, 2000 May.


  Hepatitis C virus (HCV) virions have been shown to be bound to antibodies

  in patients with chronic HCV infection. The sera from patients infected

  with genotype 1b HCV contained more antibody-free virions than those from

  patients with genotype 2a/2b HCV. When compared at the same levels of

  serum HCV RNA, free virion titers of genotype 2a/2b-infected patients were

  much lower than those of genotype 1b-infected patients, indicating that a

  larger fraction of HCV virions are bound to antibodies in the former than

  in the latter. The gene segments encoding the hypervariable region (HVR)

  1, a principal neutralization epitope, of HCV were amplified from the

  patients' sera by reverse transcription-polymerase chain reaction. The

  majority of genotype 2a/2b-infected patients had very similar HVR 1

  sequences to one another, whereas patients infected with genotype 1b HCV

  had highly heterogeneous sequences. Differences in the amount of

  antibody-free virion and HVR1 sequence variability between genotypes may

  have an implication in HCV pathogenesis. Copyright 2000 Wiley-Liss, Inc.


1275. Lakshman M.  Nichter M.


  Contamination of medicine injection paraphernalia used by registered

  medical practitioners in south India: an ethnographic study.


  Social Science & Medicine.  51(1):11-28, 2000 Jul.


  While considerable attention has been directed at the important role of

  intravenous drug use in the spread of human immunodeficiency virus (HIV)

  and hepatitis B, little research to date has been conducted on the role of

  medicine injections in disease transmission. This is the case despite the

  fact that (a) the number of medicine injections is several orders of

  magnitude greater than injections of illegal drugs and (b) the networks of

  people potentially affected by contaminated medicine injection

  paraphernalia is far wider. In this article we examine the medicine

  injecting practices of a random sample of 40 registered medical

  practitioners (RMP) who have not had formal training in allopathic

  medicine (do not have MBBS or MD degrees) in Tamil Nadu, India. Attention

  is drawn to: (a) the lack of vigilance practitioners exercise in

  maintaining hygienic needles and syringes, (b) their perceptions of what

  constitutes acceptable hygienic procedure and (c) how patients respond in

  contexts where they are able to purchase disposable needles and syringes

  directly from practitioners or from the open market prior to visiting a

  practitioner. Study results are a cause for alarm and indicate widespread

  contamination of injection paraphernalia as well as common reuse of

  disposable needles. The study was confined to RMPs and the researchers

  strongly suggest that future studies of MBBS trained doctors practising in

  the public and private sectors be carried out. A structured observation

  instrument developed to record needle and syringe contamination during the

  process of injection administration is provided.


1276. Lakshmi G.  Reddy RP.  Kumar KK.  Bhavani NV.  Dayanand M.


  Study of the safety, immunogenicity and seroconversion of a hepatitis-B

  vaccine in malnourished children of India.


  Vaccine.  18(19):2009-14, 2000 Apr 3.


  Sixty rural children who were seronegative for HBV markers received three

  doses of 10 microgram of a new Hepatitis-B vaccine, Revac-B (1 ml of

  vaccine contains 20 microgram recombinant surface antigen) that was

  formulated from hepatitis-B surface antigen expressed in a recombinant

  strain of Saccharomyces cerevisiae. Vaccines were administered on a 0, 30

  and 60-day schedule. Levels of anti-HBs titres were determined on the

  30th, 60th and 90th days following the initial injection. None of the

  participants in the trial had serious adverse reactions and the

  frequencies of minor side effects were minimal. No clinically important

  adverse effects which could be considered as directly related to the

  vaccination were recorded. The volunteers showed a very good immune

  response and were seroprotected on the 30th day after the first dose of

  vaccination. The present study revealed that the new vaccine, Revac-B is

  highly immunogenic and is well tolerated.


1277. Lima AR.  Lima MS.  Soares BG.  Churchill R.  Farrell M.


  Carbamazepine for cocaine dependence. [Review] [6 refs]


  Cochrane Database of Systematic Reviews [computer file].  (2):CD002023,



  BACKGROUND: Cocaine dependence has become a substantial public health

  problem, developing a significant number of medical, psychological and

  social problems, including the spread of infectious diseases (e.g. AIDS,

  hepatitis and tuberculosis), crime, violence and neonatal drug exposure.

  Although there is no consensus regarding how to treat cocaine dependence,

  effective pharmacotherapy has a potentially major role to play as part of

  a broader treatment milieu. The anti-convulsant carbamazepine, a tricyclic

  medication that is widely used to treat a variety of neurological and

  psychiatric disorder, has also been used for treatment of cocaine

  dependence, although its effectiveness has not been established.

  OBJECTIVES: To determine whether carbamazapine (CBZ) is effective on the

  treatment of cocaine dependence. SEARCH STRATEGY: Electronic searches of

  Cochrane Library, EMBASE, MEDLINE, PsycLIT, Biological Abstracts and

  LILACS; scan of reference list of relevant articles; personal

  communication; conference abstracts; unpublished trials from

  pharmaceutical industry; book chapters on treatment of cocaine dependence.

  SELECTION CRITERIA: The inclusion criteria for all randomised controlled

  trials were that they should focus on the use of carbamazepine drugs

  versus placebo on the treatment of cocaine dependence. Trials including

  patients with additional diagnosis such as opiate dependence were also

  eligible. DATA COLLECTION AND ANALYSIS: The reviewers extracted the data

  independently and Odds Ratios, weighted mean difference and number needed

  to treat were estimated. Qualitative assessments of the methodology of

  eligible studies were carried out using validated checklists. The

  reviewers assumed that people who died or dropped out had no improvement

  and tested the sensitivity of the final results to this assumption. Where

  possible analysis was carried out according to the "intention to treat"

  principles. MAIN RESULTS: 5 studies were included in the review, with 455

  people randomised. No differences were found regarding positive urine

  sample for cocaine metabolites. Scores on Spielberg State Anxiety

  Inventory slightly favoured carbamazepine, but didn't reach statistical

  significance. Dropouts were high in both groups up to 70% in the placebo

  group. Less dropout occurred in the Carbamazepine group (RR 0.87 95%CI

  0.71-1.06). When no retention in treatment was due to side effects no

  differences were found. The number of participants presenting at least one

  side effect, reported in Kranzler (1995), was higher in the carbamazepine

  group (RR 4.33 95% CI 1.45-12.91). REVIEWER'S CONCLUSIONS: There is no

  current evidence supporting the clinical use of CBZ in the treatment of

  cocaine dependence. Larger randomised investigation must be considered

  taking into account that these time-consuming efforts should be reserved

  for medications showing more relevant and promising evidence. [References:



1278. Linder N.  Handsher R.  German B.  Sirota L.  Bachman M.  Zinger S.

  Mendelson E.  Barzilai A.


  Controlled trial of immune response of preterm infants to recombinant

  hepatitis B and inactivated poliovirus vaccines administered

  simultaneously shortly after birth.


  Archives of Disease in Childhood Fetal & Neonatal Edition.  83(1):F24-7,

  2000 Jul.


  AIM: The study was conducted to evaluate the immunogenicity of an early,

  extra dose of enhanced inactivated poliovirus vaccine (IPV) administered

  simultaneously with recombinant hepatitis B vaccine (HBV) to preterm

  infants shortly after birth. METHODS: Three groups were studied. Fifty

  preterm infants received IPV intramuscularly within 24 hours of birth, in

  addition to routine recommended childhood immunisations. Fifty two preterm

  infants and 35 full term infants received routine immunisations only

  (routine vaccination timing: HBV at birth, 1 and 6 months of age; IPV at 2

  and 4 months; oral polio vaccine (OPV) at 4 and 6 months;

  diphtheria-tetanus-pertussis (DTP) at 2, 4, and 6 months; and Haemophilus

  influenzae B vaccine at 2 and 4 months). Blood samples were taken at

  birth, 3 and 7 months of age from all infants, and at 1 month of age from

  preterm infants only. RESULTS: At birth, a lower percentage of both study

  and control preterm infants had antipoliovirus type 3 titres >/= 1:8 than

  full term infants. At 1 and 3 months of age significantly more early IPV

  infants had antipoliovirus type 3 titres >/= 1:8 than routinely vaccinated

  preterm infants (p < 0.05). At 7 months of age there were no significant

  differences in percentage of antipoliovirus titres >/= 1:8 or geometric

  mean times (GMTs) between the early IPV group and the routinely vaccinated

  preterm group. At 3 and 7 months of age, the percentage of positive

  antihepatitis B titres (>/= 1:10) and the GMT of the early IPV preterm

  group did not differ significantly from those of preterm controls. There

  was no significant difference in percentage of positive antihepatitis B

  titres between the early IPV group and full term controls at any time.

  GMTs for hepatitis B antibodies were significantly lower in the early IPV

  preterm group than in full term controls at 3 and 7 months of age.

  CONCLUSIONS: Administration of an additional dose of IPV simultaneously

  with routine HBV to preterm infants shortly after birth provides early

  protection from poliovirus and hepatitis B infection, and does not

  interfere with poliovirus antibody production at the age of 7 months.


1279. Lindgren S.  Nilsson S.  Nassberger L.  Verbaan H.  Wieslander J.


  Anti-neutrophil cytoplasmic antibodies in patients with chronic liver

  diseases: prevalence, antigen specificity and predictive value for

  diagnosis of autoimmune liver disease. Swedish Internal Medicine Liver

  Club (SILK) [see comments].


  Journal of Gastroenterology & Hepatology.  15(4):437-42, 2000 Apr.


  BACKGROUND: Anti-neutrophil cytoplasmic antibodies (ANCA) against

  proteinase 3 are diagnostic of Wegener's granulomatosis, but ANCA occur

  also in patients with other inflammatory disorders, such as ulcerative

  colitis, primary sclerosing cholangitis (PSC) and autoimmune hepatitis. As

  their predictive value for autoimmune liver disease remains unknown, we

  analysed the prevalence and antigen specificity of ANCA in patients with

  various chronic liver diseases (CLD). METHODS: We studied sera from 100

  patients with primary biliary cirrhosis (PBC), from 76 with PSC and from

  279 with various CLD, consecutively drawn during a 5-year period at the

  time of liver biopsy. The ANCA were detected by indirect

  immunofluorescence (IIF) while the antigen specificity was characterized

  by ELISA by using lactoferrin, neutrophil elastase, cathepsin G and BPI

  (bactericidal/permeability increasing protein) as antigens. RESULTS: In

  PBC, ANCA were detected by IIF in 39 patients (39%). The antigen

  reactivity by ELISA was lactoferrin in seven, elastase in 15, BPI in 20

  and cathepsin G in four patients. Four patients had reactivity against

  more than one antigen. In PSC, IIF demonstrated ANCA in 49 patients (65%).

  The antigen reactivity was lactoferrin in 17, elastase in 14, BPI in 20

  and cathepsin G in four patients. Twelve patients showed reactivity

  against more than one antigen. In CLD, ANCA were observed in sera from 55

  patients (20%). Nineteen of 45 patients (42%) with autoimmune liver

  disease were ANCA positive versus 36/234 (15%) with non-autoimmune liver

  disease (P = 0.0002). Among IIF-positive patients, antibody reactivity

  against lactoferrin was noted in 14, elastase in 28, BPI in 25 and

  cathepsin G in five patients. Twenty-one patients had reactivity against

  more than one antigen. Elastase and BPI antibodies occurred more

  frequently in patients with autoimmune compared to non-autoimmune liver

  disease (P < 0.01). CONCLUSIONS: Anti-neutrophil cytoplasmic antibodies

  are prevalent in patients with chronic liver diseases, but although they

  occur more frequently in patients with autoimmune liver disease their

  specificity and sensitivity for autoimmune liver disease is low. The

  predominant antigens are lactoferrin, elastase and BPI, but the

  correlation between IIF findings and ELISA reactivity against these

  antigens is weak.



1280. Lodha R.  Bagga A.


  Traditional Indian systems of medicine. [Review] [52 refs]


  Annals of the Academy of Medicine, Singapore.  29(1):37-41, 2000 Jan.


  INTRODUCTION: A number of traditional systems of medicine exist in India

  of which Ayurveda is the most popular. Despite being in use for more than

  3000 years, few properly designed trials have scientifically examined the

  clinical potential of Ayurvedic and other medications. METHODS: We

  reviewed the MEDLINE database to identify clinical trials conducted using

  traditional Indian medicines. Single case reports were excluded. RESULTS:

  Ayurvedic preparations have been successfully used for the treatment of

  bronchial asthma, ischaemic heart disease and hyperlipidaemia.

  Formulations containing curcumin were reported to reduce inflammation and

  disability in double-blind clinical trials on patients with rheumatoid

  arthritis. A number of products are reported to be useful in patients with

  acute viral hepatitis. A multicentric study by the Indian Council of

  Medical Research showed that a preparation from Pterocarpus marsupium was

  effective in reducing levels of blood glucose and glycosylated haemoglobin

  in patients with non-insulin-dependent diabetes mellitus. In another

  multicentric trial, patients with fistula-in-ano were randomised to

  surgery or application of medicated seton (Ksharsootra). Surgical

  treatment led to a faster cure but recurrence rates were lower with

  medicated seton. Administration of extract from Bacopa monnieri, to

  children with mental retardation, was reported to significantly improve

  short-term and long-term memory. CONCLUSIONS: Evidence-based studies on

  the efficacy and safety of traditional Indian medicines are limited. The

  essential ingredient in most formulations is not precisely defined. High

  quality studies are necessary to evaluate and compare the value of

  traditional Indian drugs to modern medicine. [References: 52]



1281. MacLennan JM.  Shackley F.  Heath PT.  Deeks JJ.  Flamank C.  Herbert M.

  Griffiths H.  Hatzmann E.  Goilav C.  Moxon ER.


  Safety, immunogenicity, and induction of immunologic memory by a serogroup

  C meningococcal conjugate vaccine in infants: A randomized controlled

  trial [see comments].


  JAMA.  283(21):2795-801, 2000 Jun 7.


  CONTEXT: Neisseria meningitidis is a common cause of meningitis and

  septicemia in infants worldwide. Whether a meningococcal C conjugate

  vaccine protects infants against the serogroup C strain is unknown.

  OBJECTIVES: To determine whether a meningococcal C conjugate vaccine is

  safe and immunogenic and induces immunologic memory in infants. DESIGN:

  Single-center, double-blind, randomized controlled trial in 1995 and 1996.

  SETTING: Community, Oxfordshire, England. PARTICIPANTS: One hundred

  eighty-two healthy infants. INTERVENTIONS: Participants were randomly

  assigned to receive vaccination with 0. 5-mL doses of 1 of 2 lots of

  meningococcal C conjugate vaccine (groups 1 and 2; n=60 in each group) or

  a hepatitis B control vaccine (group 3; n=62), administered with routine

  immunizations at 2, 3, and 4 months of age. Approximately half of each

  group received meningococcal C conjugate vaccine and half received plain

  meningococcal polysaccharide vaccine (MPS) at 12 months of age. MAIN

  OUTCOME MEASURES: Serum antibodies to meningococcal C polysaccharide,

  assayed by enzyme-linked immunosorbent assay, and serum bactericidal

  activity (SBA), at 2, 3, 4, 5, 12, and 13 months of age; local and

  systemic reactions, recorded for 6 days after each vaccination, compared

  by intervention group. RESULTS: Meningococcal C conjugate vaccine was well

  tolerated. After 3 doses, children in groups 1 and 2 achieved

  significantly higher meningococcal C IgG geometric mean concentrations (21

  and 17 U/mL, respectively, vs 0.20 U/mL; P<.001) and SBA titers (629 and

  420, respectively, vs 4.1; P<. 001) than controls. At 12 months, antibody

  concentrations had decreased in all groups but remained significantly

  higher in children vaccinated with meningococcal C conjugate vaccine (SBA,

  24 and 16 in groups 1 and 2, respectively, vs 4.2 in group 3; P<.001).

  Following vaccination with MPS at 12 months of age, SBA in the

  meningococcal C conjugate vaccine group was significantly higher than in

  controls (SBA, 789 vs 4.5; P<.001). CONCLUSIONS: Our data indicate that

  meningococcal C conjugate vaccine is safe and immunogenic and results in

  immunologic memory when given with other routinely administered vaccines

  to infants at 2, 3, and 4 months of age. JAMA. 2000;283:2795-2801


1282. Mahoney RT.  Ramachandran S.  Xu Z.


  The introduction of new vaccines into developing countries II. Vaccine

  financing. [Review] [38 refs]


  Vaccine.  18(24):2625-35, 2000 Jun 1.


  The development of new vaccines for important childhood diseases presents

  an unparalleled opportunity for disease control but also a significant

  problem for developing countries: how to pay for them. To help address

  this problem, the William H. Gates Foundation has established a Global

  Fund for Children's Vaccine. In this paper, we discuss the allocation of

  this and other similar funds, which we call Global Funds. We propose that

  allocation of the Global Funds to individual countries be guided in part

  by a Vaccine Procurement Baseline (VPB). The VPB would set a minimum of

  0.01% of gross national product (GNP) as an amount each developing country

  would devote to its own vaccine procurement. When this amount is not

  sufficient to procure the vaccines needed by a developing country, the

  Global Funds would meet the shortfall. The amount required of donors to

  maintain the Global Funds would be about $403 million per year for both

  existing EPI vaccines as well as for a hypothetical group of five new

  vaccines costing $0.50 per dose and requiring three doses per child.

  Including program costs, poor developing countries currently spend about

  0.13% of GNP on EPI immunizations. In contrast, the United States, as one

  example donor country, spends about 0.035% of GNP for childhood

  immunization including several new vaccines. This paper analyzes the

  Global Funds requirements for hepatitis B and Haemophilus influenzae type

  b (Hib) vaccines. After a ramp-up period, needier countries would

  eventually require about $62 million for hepatitis B and $282 million for

  Hib at current prices. Various additional criteria could be used to

  qualify countries for participation in the Global Funds. [References: 38]


1283. Matsuo I.  Ikuno N.  Omagari K.  Kinoshita H.  Oka M.  Yamaguchi H.  Kohno

  S.  Mackay IR.


  Autoimmune reactivity of sera to hepatocyte plasma membrane in type 1

  autoimmune hepatitis [see comments].


  Journal of Gastroenterology.  35(3):226-34, 2000.


  Type 1 autoimmune hepatitis (AIH-1) is an organ-specific autoimmune liver

  disease for which no tissue-specific autoantigen has yet been identified.

  We examined the reactivity by sensitive immunoblotting with enhanced

  chemiluminescence (IB-ECL) of 43 sera from patients with AIH-1 and 182

  sera from patients with other diseases on hepatocyte plasma membrane

  derived from rat or human liver (RHPM, HHPM) and separated by aqueous

  two-phase partition. The sera studied were from patients with AIH-1,

  primary biliary cirrhosis, chronic viral hepatitis, and systemic lupus

  erythematosus (SLE); and from normal subjects. Specificity of reactivity

  by IB-ECL was sought: (i) by testing sera on human or rat liver membrane;

  (ii) by testing sera on liver or kidney membrane; (iii) by serial

  titration of reactive sera; and (iv) by testing reactive sera from AIH-1

  before and after successful treatment with prednisolone. The results were

  that in AIH-1 there were multiple reactive components which were not

  species-specific, since they were detected with both RHPM and HHPM, but

  were mostly tissue-specific for liver. There was no significant

  correlation between antinuclear antibodies (ANA) titer and the frequencies

  of sera reactivities against RHPM. Most of these reactive components were

  demonstrable at a lesser frequency in other liver diseases and in SLE.

  There was a striking decrease in reactivity by IB-ECL of AIH-1 sera with

  liver membrane after clinical remission, further suggesting that

  differences between AIH-1 and other inflammatory liver diseases and SLE

  are predominantly quantitative rather than qualitative. However, our study

  did point to candidate liver membrane antigens with molecular sizes of

  136, 116, 81, and 49 kDa, additional to components previously described by

  others. The molecular identification of these prominent reactants with

  AIH-1 sera could prove informative for ascertaining pathogenesis.


1284. Milkiewicz P.  Mutimer D.  Hubscher SG.  Elias E.


  Autoimmune liver disease in patients with neoplastic diseases.


  European Journal of Gastroenterology & Hepatology.  11(5):569-73, 1999



  BACKGROUND: Development of de novo autoimmune liver disease has not been

  well documented in patients with malignant diseases. METHODS/RESULTS: In

  this paper we report on a series of six patients with neoplastic disorders

  who acquired liver disease with autoimmune features. Five patients had

  suffered from haematological neoplasms and one from colonic cancer. In two

  patients, liver disease was detected at the time of presentation with

  malignancy. In the remaining four, all of whom were successfully treated

  for malignancies, features of liver disease presented at intervals 24-72

  months after the cancer diagnosis. Twelve liver specimens (11 biopsies and

  one hepatectomy specimen) were obtained at time intervals of 1-76 months

  after initial presentation of neoplastic disease. Biopsies from three

  patients showed features of hepatitis (one acute, one sub-acute, one

  chronic). Two patients had histological features suggestive of an overlap

  syndrome (one autoimmune hepatitis/primary biliary cirrhosis, one

  autoimmune hepatitis/primary sclerosing cholangitis). The sixth patient

  had features of autoimmune cholangiopathy. All but one responded well to

  steroid therapy with complete clinical and biochemical remission obtained

  4 weeks to 8 months after steroid introduction. We discuss briefly

  possible aetiologies of autoimmune liver disease in these patients.

  CONCLUSIONS: Autoimmune liver disease may be precipitated by therapy for

  neoplastic disease or malignant disease itself. The unusually

  heterogeneous clinicopathological findings in this group as well as the

  response to treatment support the concept of a wide spectrum of

  manifestations of autoimmune liver disease. The results may also suggest

  that autoimmune liver disease may be possibly added to the list of

  paraneoplastic syndromes. Further prospective studies are required to

  confirm a causal association and to determine whether the mechanisms

  involved are disease- or treatment-related.


1285. Modahl LE.  Lai MM.


  Hepatitis delta virus: the molecular basis of laboratory diagnosis.

  [Review] [203 refs]


  Critical Reviews in Clinical Laboratory Sciences.  37(1):45-92, 2000 Feb.


  Infection with hepatitis delta virus (HDV), a satellite virus of hepatitis

  B virus (HBV), is associated with severe and sometimes fulminant

  hepatitis. The traditional methods for the diagnosis of HDV infection,

  such as detection of serum anti-HD antibodies, are sufficient for the

  clinical diagnosis of delta infection. However, such techniques lack the

  sensitivity and specificity required to more accurately characterize the

  nature of HDV infection and to assess the efficacy of therapies. Recent

  improvements in molecular techniques, such as HDV RNA hybridization and

  RT-PCR, have provided increased diagnostic precision and a more thorough

  understanding of the natural course of HDV infection. These advances have

  enhanced the clinician's ability to accurately evaluate the stage of HDV

  infection, response to therapy, and occurrence of reinfection after

  orthotopic liver transplant. This review focuses on the recent advances in

  the understanding of the molecular biology of HDV and in the laboratory

  diagnosis of HDV infection. [References: 203]



1286. Muratori L.  Parola M.  Ripalti A.  Robino G.  Muratori P.  Bellomo G.

Carini R.  Lenzi M.  Landini MP.  Albano E.  Bianchi FB.


  Liver/kidney microsomal antibody type 1 targets CYP2D6 on hepatocyte

  plasma membrane [see comments].


  Gut.  46(4):553-61, 2000 Apr.


  BACKGROUND: Liver/kidney microsomal antibody type 1 (LKM1) is the marker

  of type 2 autoimmune hepatitis (AIH) and is detected in up to 6% of

  patients with hepatitis C virus (HCV) infection. It recognises linear and

  conformational epitopes of cytochrome P450IID6 (CYP2D6) and may have liver

  damaging activity, provided that CYP2D6 is accessible to effector

  mechanisms of autoimmune attack. METHODS: The presence of LKM1 in the

  plasma membrane was investigated by indirect immunofluorescence and

  confocal laser microscopy of isolated rat hepatocytes probed with 10 LKM1

  positive sera (five from patients with AIH and five from patients with

  chronic HCV infection) and a rabbit polyclonal anti-CYP2D6 serum. RESULTS:

  Serum from both types of patient stained the plasma membrane of

  non-permeabilised cells, where the fluorescent signal could be visualised

  as discrete clumps. Conversely, permeabilised hepatocytes showed diffuse

  submembranous/cytoplasmic staining. Adsorption with recombinant CYP2D6

  substantially reduced plasma membrane staining and LKM1 immunoblot

  reactivity. Plasma membrane staining of LKM1 colocalised with that of

  anti-CYP2D6. Immunoprecipitation experiments showed that a single 50 kDa

  protein recognised by anti-CYP2D6 can be isolated from the plasma membrane

  of intact hepatocytes. CONCLUSIONS: AIH and HCV related LKM1 recognise

  CYP2D6 exposed on the plasma membrane of isolated hepatocytes. This

  observation supports the notion that anti-CYP2D6 autoreactivity may be

  involved in the pathogenesis of liver damage.


1287. No Abstract

1288. Obermayer-Straub P.  Strassburg CP.  Manns MP.


  Target proteins in human autoimmunity: cytochromes P450 and UDP-

  glucuronosyltransferases. [Review] [112 refs]


  Canadian Journal of Gastroenterology.  14(5):429-39, 2000 May.


  Cytochromes P450 (CYPs) and UDP-glucuronosyltransferases (UGTs) are

  targets of autoantibodies in several hepatic and extrahepatic autoimmune

  diseases. Autoantibodies directed against hepatic CYPs and UGTs were first

  detected by indirect immunofluorescence as antiliver and/or kidney

  microsomal antibodies. In autoimmune hepatitis (AIH) type 2, liver and/or

  kidney microsomal (LKM) type 1 autoantibodies are detected and are

  directed against CYP2D6. About 10% of AIH-2 sera further contain LKM-3

  autoantibodies directed against family 1 UGTs. Chronic infections by

  hepatitis C virus and hepatitis delta virus may induce several autoimmune

  phenomena, and multiple autoantibodies are detected. Anti-CYP2D6

  autoantibodies are detected in up to 4% of patients with chronic hepatitis

  C, and anti-CYP2A6 autoantibodies are detected in about 2% of these

  patients. In contrast, 14% of patients with chronic hepatitis delta virus

  infections generate anti-UGT autoantibodies. In a small minority of

  patients, certain drugs are known to induce immune-mediated, idiosyncratic

  drug reactions, also known as 'druginduced hepatitis'. Drug-induced

  hepatitis is often associated with autoantibodies directed against hepatic

  CYPs or other hepatic proteins. Typical examples are tienilic acid-induced

  hepatitis with anti-CYP2C9, dihydralazine hepatitis with anti-CYP1A2,

  halothane hepatitis with anti-CYP2E1 and anticonvulsant hepatitis with

  anti-CYP3A. Recent data suggest that alcoholic liver disease may be

  induced by mechanisms similar to those that are active in drug-induced

  hepatitis. Autoantibodies directed against several CYPs are further

  detected in sera from patients with the autoimmune polyglandular syndrome

  type 1. Patients with autoimmune polyglandular syndrome type 1 with

  hepatitis often develop anti-CYP1A2; patients with adrenal failure develop

  anti-CYP21, anti- CYP11A1 or CYP17; and patients with gonadal failure

  develop anti-CYP11A1 or CYP17. In idiopathic Addison disease, CYP21 is the

  major autoantigen. [References: 112]


1289. Pessayre D.  Mansouri A.  Haouzi D.  Fromenty B.


  Hepatotoxicity due to mitochondrial dysfunction. [Review] [47 refs]


  Cell Biology & Toxicology.  15(6):367-73, 1999.


  Mitochondria are involved in fatty acid beta-oxidation, the tricarboxylic

  acid cycle, and oxidative phosphorylation, which provide most of the cell

  energy. Mitochondria are also the main source of reactive oxygen species

  in the cell and are involved in cell demise through opening of the

  mitochondrial permeability transition pore. It was therefore to be

  expected that mitochondrial dysfunction could be a major mechanism of

  drug-induced liver disease. Microvesicular steatosis (which may cause

  liver failure, coma, and death) is the consequence of severe impairment of

  mitochondrial beta-oxidation. Endogenous compounds (such as cytokines or

  female sex hormones) or xenobiotics (including toxins such as ethanol and

  drugs such as aspirin, valproic acid, ibuprofen, or zidovudine) can

  inhibit beta-oxidation directly or through a primary effect on the

  mitochondrial genome or the respiratory chain itself. In some patients,

  infections and cytokines, or inborn errors of beta-oxidation enzymes or

  the mitochondrial genome, may favor the appearance of drug-induced

  microvesicular steatosis. Nonalcoholic steatohepatitis may develop under

  conditions causing prolonged, microvesicular, and/or macrovacuolar

  steatosis. In this condition, chronic impairment of mitochondrial

  beta-oxidation (causing steatosis) and the respiratory chain (increasing

  the production of ROS) lead to lipid peroxidation, which, in turn, may

  cause the diverse lesions of steatohepatitis, namely, necrosis,

  inflammation, Mallory's bodies, and fibrosis. Finally, mitochondria are

  involved in several forms of drug-induced cytolytic hepatitis, through

  inhibition or uncoupling of respiration or through a drug-induced or

  reactive metabolite-induced mitochondrial permeability transition. The

  latter effect commits hepatocytes to either apoptosis or necrosis,

  depending on the number of organelles that have undergone the permeability

  transition. [References: 47]



1290. Ray RB.  Meyer K.  Ray R.


  Hepatitis C virus core protein promotes immortalization of primary human



  Virology.  271(1):197-204, 2000 May 25.


  Hepatitis C virus (HCV) core protein has many intriguing properties as a

  viral factor and is implicated in cell growth regulation. In this study,

  the cell growth regulation potential of HCV core protein was investigated

  by introduction of the core genomic region into primary human hepatocytes,

  a natural host for virus replication and tropism. Core-transfected primary

  human hepatocytes displayed altered cell morphology resembling that of

  low-differentiated epithelial cells. Those cells retained an immortalized

  phenotype and exhibited continuous growth after more than 50 passages over

  2 years. Stable hepatocyte transfectants exhibited albumin secretion and

  HCV core protein expression. Telomerase activity, a characteristic of

  immortalized or transformed cells, was evident in the transfected

  hepatocytes immediately after senescence. Anchorage-independent growth of

  the immortalized hepatocytes provided further evidence for a transformed

  phenotype. Results from these studies suggest that the HCV core protein

  promotes primary human hepatocytes to an immortalized phenotype, which may

  predispose cells over an extended period of time to undergo a transforming

  event. Thus, HCV core protein appears to contribute to virus-mediated

  pathogenesis in a persistently infected host. Copyright 2000 Academic



1291. Roberts EA.


  Autoimmune hepatitis. [Review] [39 refs]


  Indian Journal of Pediatrics.  62(5):525-31, 1995 Sep-Oct.


  Autoimmune hepatitis can present as either acute or chronic disease in

  children. Clinical and laboratory features, including association with

  extrahepatic autoimmune syndromes and prompt response to immunosuppressive

  treatment, circulating autoantibodies and hypergammaglobulinemia, suggest

  an immune etiology. However, the disease mechanism remains uncertain.

  Different types of autoimmune hepatitis are defined on the basis of which

  autoantibodies are present: anti-smooth muscle (type 1), anti-liver/kidney

  microsomal (type 2), or anti-soluble liver antigen (type 3). Diseases

  which may be clinically similar to autoimmune hepatitis must be excluded

  before the diagnosis of autoimmune hepatitis is established: Wilson's

  disease, primary sclerosing cholangitis, chronic hepatitis B or C, and

  drug-induced liver disease are among the most important entities.

  Corticosteroids alone or with azathioprine constitute the usual treatment

  for autoimmune hepatitis. Although some children achieve a complete

  remission, or even recovery, and can stop immunosuppressive treatment,

  others required low-dose prednisone treatment indefinitely. [References:



1292. Safary A.  Beck J.


  Vaccination against hepatitis B: current challenges for Asian countries

  and future directions. [Review] [40 refs]


  Journal of Gastroenterology & Hepatology.  15(4):396-401, 2000 Apr.


  AIMS: To review the current status of hepatitis B immunization programmes

  as well as future issues concerning hepatitis B immunization in Asian

  countries. METHODS: Pertinent literature was identified via in-house and

  MEDLINE (1980-99) searches and references cited in published articles.

  Articles within the Proceedings of the IX Triennial International

  Symposium on Viral Hepatitis and Liver Disease provided valuable

  state-of-the-art resource data. RESULTS: Chronic hepatitis B infection is

  responsible for 75-90% of primary hepatocellular carcinoma, one of the 10

  most common cancers worldwide. Hepatitis B and its chronic sequelae can

  potentially be eradicated through vaccines that have been shown to be

  95-99% efficacious in preventing development of the disease or the carrier

  state in immunized infants. Approximately 75% of the world's hepatitis B

  carriers live in Asian countries wherein wide variations in immunization

  strategies exist. Vaccination programmes in hyperendemic Asian countries

  have elicited decreases in the incidence of acute and chronic infections

  as well as a decrease in chronic carriers in the unvaccinated population.

  Decreases in the incidence of hepatocellular carcinoma have been recorded

  in Taiwan and Singapore after at least 10 years of universal hepatitis B

  immunization programmes. CONCLUSIONS: In Asian countries currently without

  nationwide hepatitis B programmes, utilization of the existing vaccination

  infrastructure for administration of other World Health Organization

  Expanded Programme on Immunization vaccines will provide the most

  economical and efficient means of administration of the hepatitis B

  vaccine. [References: 40]



1293.  Shamsuzzaman SM.  Haque R.  Hasin SK.  Hashiguchi Y.


  Evaluation of indirect fluorescent antibody test and enzyme-linked

  immunosorbent assay for diagnosis of hepatic amebiasis in Bangladesh.


  Journal of Parasitology.  86(3):611-5, 2000 Jun.


  Serum samples of 31 amebic liver abscess (ALA) patients, 8 amebic

  hepatitis (AH) patients, and 60 controls were tested for anti-amebic IgG

  by enzyme-linked immunosorbent assay (ELISA) and indirect fluorescent

  antibody tests (IFAT). Sera of 29 (93.6%) ALA and 6 (75%) AH patients and

  2 (3.3%) control subjects were positive by IFAT. Anti-amebic antibody

  titer above the cutoff point (= 0.168; x + 2 SD of control sera) was

  observed in sera of 27 (87%) ALA, 4 (50%) AH, and 1 (1.7%) control by

  ELISA. All the 8 pus samples were positive for anti-amebic antibodies by

  IFAT and ELISA. Sensitivity of ELISA was 87% for ALA, with a positive

  predictive value of 0.96, and 50% for AH cases, with a positive predictive

  value of 0.80. The sensitivity of IFAT was 93.6% for ALA, with a positive

  predictive value of 0.94, and 75% for AH, with a positive predictive value

  of 0.75. When pus samples were tested, the sensitivity was 100% for both

  tests. The specificity was 98.3% for ELISA and 96.7% for IFAT. Although

  not significant, IFAT was found more sensitive than ELISA (P>0.05).


1294. Sharara AI.


  Diagnosis and management of chronic hepatitis C. [Review] [32 refs]


  Journal Medical Libanais - Lebanese Medical Journal.  47(6):339-42, 1999



  Chronic HCV infection is a major cause of chronic liver disease, cirrhosis

  and hepatocellular carcinoma worldwide. The disease is indolent or

  subclinical in the majority of patients but alcohol consumption and older

  age at infection may be associated with an accelerated course. Current

  diagnostic modalities are highly sensitive and specific in confirming the

  diagnosis and may help predict response to therapy. Treatment with

  interferon is effective in clearing the virus in a small number of

  patients but the addition of ribavirin results in an enhanced overall

  chance of viral eradication. The development of an effective vaccine to

  HCV is presently encumbered by the presence of multiple viral genomic

  subtypes and the high rate of spontaneous viral mutation leading to

  limited efficacy of neutralizing antibodies. [References: 32]


1295. Strickland DK.  Riely CA.  Patrick CC.  Jones-Wallace D.  Boyett JM.

  Waters B.  Fleckenstein JF.  Dean PJ.  Davila R.  Caver TE.  Hudson MM.


  Hepatitis C infection among survivors of childhood cancer.


  Blood.  95(10):3065-70, 2000 May 15.


  Preliminary reports have suggested that survivors of childhood cancer and

  aplastic anemia who are infected with the hepatitis C virus (HCV) have a

  low risk for progression to significant liver disease. Among our surviving

  patients who were transfused between 1961 and March 1992, 77 (6.6% of

  surviving patients tested thus far) have evidence of HCV infection,

  whereas 4 surviving patients who were transfused after March 1992 are

  HCV-infected. One patient chronically infected with HCV died of liver

  failure, and 2 patients died of hepatocellular carcinoma. To characterize

  the risk for these and other complications, 65 patients are enrolled in a

  longitudinal study of HCV infection, of whom 58 (89.2%) had circulating

  HCV RNA at the time of protocol enrollment, with genotypes 1A and 1B most

  commonly isolated. Most enrolled patients have few or no symptoms, carry

  out normal activities, and have normal liver function. To date, 35

  patients have undergone liver biopsy for abnormal liver function since the

  diagnosis of primary malignancy; central pathology review shows 28 (80%)

  have chronic active hepatitis, 25 (71%) have fibrosis, and 3 (9%) have

  cirrhosis. These preliminary data suggest that though most survivors of

  childhood cancer who are infected with HCV are clinically well, some are

  at risk for clinically significant liver disease. Identification of other

  HCV-infected patients and prospective monitoring of this cohort are

  ongoing to determine the risk for, and to identify factors associated with

  the progression of, liver disease.


1296. Takeda K.  Hayakawa Y.  Van Kaer L.  Matsuda H.  Yagita H.  Okumura K.


  Critical contribution of liver natural killer T cells to a murine model of



  Proceedings of the National Academy of Sciences of the United States of

  America.  97(10):5498-503, 2000 May 9.


  Natural killer T (NKT) cells constitute a distinct subpopulation of T

  cells with a unique antigen specificity, prompt effector functions, and an

  unusual tissue distribution. NKT cells are especially abundant in the

  liver, but their physiological function in this organ remains unclear. In

  the present study, we examined the possible contribution of NKT cells to a

  murine model of hepatitis induced by i.v. injection of Con A.

  CD1-deficient mice lacking NKT cells were highly resistant to Con

  A-induced hepatitis. Adoptive transfer of hepatic NKT cells isolated from

  wild-type mice, but not from FasL-deficient gld mice, sensitized

  CD1-deficient mice to Con A-induced hepatitis. Furthermore, adoptive

  transfer of hepatic mononuclear cells from wild-type mice, but not from

  CD1-deficient mice, sensitized gld mice to Con A-induced hepatitis. Upon

  Con A administration, hepatic NKT cells rapidly up-regulated cell surface

  FasL expression and FasL-mediated cytotoxicity. At the same time, NKT

  cells underwent apoptosis leading to their rapid disappearance in the

  liver. These results implicated FasL expression on liver NKT cells in the

  pathogenesis of Con A-induced hepatitis, suggesting a similar pathogenic

  role in human liver diseases such as autoimmune hepatitis.


1297. Tarao K.  Rino Y.  Takemiya S.  Tamai S.  Ohkawa S.  Sugimasa Y.  Miyakawa

  K.  Morinaga S.  Yoshida M.  Shibuya A.  Kokubu S.  Kakita A.  Endo O.


  Close association between high serum ALT and more rapid recurrence of

  hepatocellular carcinoma in hepatectomized patients with HCV-associated

  liver cirrhosis and hepatocellular carcinoma.


  Intervirology.  43(1):20-6, 2000.


  We investigated whether or not a high serum alanine aminotransferase (ALT)

  level is associated with a more rapid recurrence of hepatocellular

  carcinoma (HCC) in hepatectomized patients with hepatitis C virus

  (HCV)-associated liver cirrhosis (LC) (HCV-LC) and HCC. Thirty-three

  hepatectomized patients with HCV-LC and HCC of a single nodule who had no

  histologic evidence of portal or hepatic vein invasion and who had been

  followed up for more than 3 years were included in the study. They were

  subdivided into two groups according to their serum ALT levels, ALT being

  a well-known marker of inflammatory necrosis in the liver. Seventeen

  patients whose serum ALT levels showed several peaks or plateaus above 80

  international units (IU) were designated as the high ALT group, and 16

  patients whose serum ALT levels showed a sustained low level below 80 IU

  until the first recurrence were designated as the low ALT group, and the

  interval between hepatectomy and the first recurrence was observed. In the

  high ALT group, HCC recurred within 3 years in 70.6% of the patients. In

  contrast, it recurred in only 18.8% of the low ALT group within the same

  period (p < 0.05). There was a significant difference (p = 0.0201) between

  the two groups in the cumulative nonrecurrence rate. The mean interval in

  recurrent patients between hepatectomy and the first recurrence in the

  high ALT group (23.6 +/- 2.8 months; mean +/- SE) was significantly (p <

  0.02) shorter than that in the low ALT group (49.3 +/- 9.7 months). The

  expected interval between hepatectomy and recurrence was as short as 2.8

  +/- 0.5 years (mean +/- SE) in the high ALT group, compared with 5.8 +/-

  0.7 years in the low ALT group (p < 0.05). These results showed that the

  recurrence of HCC was accelerated in the high ALT group, suggesting that

  suppression of the rise in ALT level after hepatectomy by treatment with

  anti-inflammatory drugs may prolong the interval until recurrence by about

  2 years in hepatectomized patients with HCC and HCV-LC. Copyright 2000 S.

  Karger AG, Basel.



1298. Ulmer SC.


  Hepatocellular carcinoma. A concise guide to its status and management.

  [Review] [24 refs]


  Postgraduate Medicine.  107(5):117-24, 2000 May 1.


  Although common worldwide, hepatocellular carcinoma is relatively rare in

  the United States. However, for unknown reasons, the incidence is rising.

  Multiple causes exist, but chronic viral hepatitis in the setting of

  cirrhosis is probably the most common. Despite limitations, AFP

  measurement and multiple-phase abdominal CT are the most sensitive tests

  for diagnosis. Surgical resection and liver transplantation are at present

  the only treatment options that offer potential for long-term survival or

  cure in limited-stage hepatocellular carcinoma. Otherwise, the prognosis

  is poor, and 1-year survival is rare. Future efforts should focus on

  improving detection of early-stage disease and improving preventive

  measures to reduce viral hepatitis infection, transmission, and

  progression. [References: 24]


1299. Vyas GN.


  Immunobiology of persistent blood-borne viral infections. [Review] [17



  Developments in Biological Standardization.  102:9-17, 2000.


  Host-virus interactions have co-evolved to play an interactive role in the

  pathogenesis of viral infections and their disease outcome. Host responses

  to viral infections, including the cell-mediated and humoral immune

  responses, have been a subject of intensive research in virology and

  immunology. Definition of specific cellular receptors for cellular entry

  of the agents, the rates of their intracellular viral replication, the

  rates of turnover of circulating virions, persistence of viral infection

  possibly due to inadequate immune responses, and continued formation of

  circulating immune complexes provide the framework for our current

  understanding of the immunopathology of virally induced disease. Among the

  multiple blood-borne viruses (BBV) transmissible through transfusion,

  hepatitis B virus (HBV), hepatitis C virus (HCV), and human

  immunodeficiency viruses (HIV-1/-2) are relatively more important than

  several other viruses. Not only do they establish asymptomatic persistent

  infections with occasional oncogenic sequelae, but they also cause

  significant morbidity and mortality when transmitted through transfusion

  of blood and blood products. Molecular characterization of these agents

  and their in vitro inactivation and removal from blood have become key

  issues in contemporary transfusion safety since the advent of AIDS.

  Because many of the BBV are associated with white blood cells that have no

  therapeutic benefit in haemotherapy, simple filtration-removal of

  leukocytes from donated blood confers a dual benefit of immunological and

  virological safety in transfusion medicine. [References: 17]


1300. Walsh K.  Alexander G.


  Alcoholic liver disease. [Review] [45 refs]


  Postgraduate Medical Journal.  76(895):280-6, 2000 May.


  Alcohol is a major cause of liver cirrhosis in the Western world and

  accounts for the majority of cases of liver cirrhosis seen in district

  general hospitals in the UK. The three most widely recognised forms of

  alcoholic liver disease are alcoholic fatty liver (steatosis), acute

  alcoholic hepatitis, and alcoholic cirrhosis. The exact pathogenesis of

  alcoholic liver injury is still not clear but immune mediated and free

  radical hepatic injury are thought to be important. There is increasing

  interest in genetic factors predisposing to hepatic injury in susceptible

  individuals. Diagnosis is based on accurate history, raised serum markers

  such as gamma-glutamyltransferase, mean corpuscular volume, and IgA and

  liver histology when obtainable. Abstinence is the most important aspect

  of treatment. Newer drugs such as acamprosate and naltrexone are used to

  reduce alcohol craving. Vitamin supplements and nutrition are vital while

  corticosteroids have a role in acute alcoholic hepatitis where there is no

  evidence of gastrointestinal haemorrhage or sepsis. Liver transplantation

  has excellent results in abstinent patients with end stage liver disease

  but there are concerns about recidivism after transplant. [References: 45]



1301. Ward BJ.


  Vaccine adverse events in the new millennium: is there reason for concern?

  [see comments]. [Review] [62 refs]


  Bulletin of the World Health Organization.  78(2):205-15, 2000.


  As more and more infectious agents become targets for immunization

  programmes, the spectrum of adverse events linked to vaccines has been

  widening. Although some of these links are tenuous, relatively little is

  known about the immunopathogenesis of even the best characterized

  vaccine-associated adverse events (VAAEs). The range of possible use of

  active immunization is rapidly expanding to include vaccines against

  infectious diseases that require cellular responses to provide protection

  (e.g. tuberculosis, herpes viral infections), therapeutic vaccines for

  chronic infections (e.g. human immunodeficiency virus (HIV) infection,

  viral hepatitis B and C), and vaccines against non-infectious conditions

  (e.g. cancer, autoimmune diseases). Less virulent pathogens (e.g.

  varicella, rotavirus in the developed world) are also beginning to be

  targeted, and vaccine use is being justified in terms of societal and

  parental "costs" rather than in straightforward morbidity and mortality

  costs. In the developed world the paediatric immunization schedule is

  becoming crowded, with pressure to administer increasing numbers of

  antigens simultaneously in ever simpler forms (e.g. subcomponent, peptide,

  and DNA vaccines). This trend, while attractive in many ways, brings

  hypothetical risks (e.g. genetic restriction, narrowed shield of

  protection, and loss of randomness), which will need to be evaluated and

  monitored. The available epidemiological and laboratory tools to address

  the issues outlined above are somewhat limited. As immunological and

  genetic tools improve in the years ahead, it is likely that we shall be

  able to explain the immunopathogenesis of many VAAEs and perhaps even

  anticipate and avoid some of them. However, this will only happen if the

  human and financial resources needed for monitoring and studying vaccine

  safety stay in step with the accelerating pace of vaccine development.

  Failure to make such a commitment would put all immunization programmes at

  risk. [References: 62]


1302. Widera G.  Austin M.  Rabussay D.  Goldbeck C.  Barnett SW.  Chen M.

  Leung L.  Otten GR.  Thudium K.  Selby MJ.  Ulmer JB.


  Increased DNA vaccine delivery and immunogenicity by electroporation in



  Journal of Immunology.  164(9):4635-40, 2000 May 1.


  DNA vaccines have been demonstrated to be potent in small animals but are

  less effective in primates. One limiting factor may be inefficient uptake

  of DNA by cells in situ. In this study, we evaluated whether cellular

  uptake of DNA was a significant barrier to efficient transfection in vivo

  and subsequent induction of immune responses. For this purpose, we used

  the technique of electroporation to facilitate DNA delivery in vivo. This

  technology was shown to substantially increase delivery of DNA to cells,

  resulting in increased expression and elevated immune responses. The

  potency of a weakly immunogenic hepatitis B surface Ag DNA vaccine was

  increased in mice, as seen by a more rapid onset and higher magnitude of

  anti-hepatitis B Abs. In addition, the immunogenicity of a potent HIV gag

  DNA vaccine was increased in mice, as seen by higher Ab titers, a

  substantial reduction in the dose of DNA required to induce an Ab

  response, and an increase in CD8+ T cell responses. Finally, Ab responses

  were enhanced by electroporation against both components of a combination

  HIV gag and env DNA vaccine in guinea pigs and rabbits. Therefore,

  cellular uptake of DNA is a significant barrier to transfection in vivo,

  and electroporation appears able to overcome this barrier.


1303. Wies I.  Brunner S.  Henninger J.  Herkel J.  Kanzler S.  Meyer zum

  Buschenfelde KH.  Lohse AW.


  Identification of target antigen for SLA/LP autoantibodies in autoimmune

  hepatitis [see comments].


  Lancet.  355(9214):1510-5, 2000 Apr 29.


  BACKGROUND: Autoantibodies are a hallmark of autoimmune hepatitis, but

  most are not disease specific. Autoantibodies to soluble liver antigen

  (SLA) and to liver and pancreas antigen (LP) have been described as

  disease specific, occurring in about 30% of all patients with autoimmune

  hepatitis, but no standardised assays are available. Methods We tested

  2000 serum samples from patients with various liver diseases and controls

  for SLA autoantibodies by inhibition ELISA. Serum samples positive for SLA

  antibodies were used for immunoscreening of cDNA expression libraries.

  Identified clones were tested against a panel of serum samples positive

  for SLA and LP autoantibodies and control serum samples, and the epitope

  mapped by deletion mutants and exonuclease digestion. FINDINGS: SLA and LP

  autoantibodies were identical. Of 2000 serum samples screened, 35 were

  positive for SLA autoantibodies. These positive samples came from patients

  with autoimmune hepatitis; three from patients with an overlap syndrome

  (primary biliary cirrhosis and secondary autoimmune hepatitis). Expression

  cloning and absorption experiments identified a 422 aminoacid protein

  present in two splice variants as the sole target antigen. Aminoacids

  371-409 were critical for immune recognition. INTERPRETATION: The

  identified cDNA encodes the primary target antigen of SLA/LP

  autoantibodies. The SLA/LP antigen has a previously unknown aminoacid

  sequence, and presumably codes for an unindentified enzyme, suggested to

  be UGA-suppressor tRNA-associated protein. SLA/LP autoantibodies are

  disease specific and recognise a dominant epitope, suggesting a specific

  antigen-driven immune response. Identification of the SLA/LP target

  antigen will allow establishment of a reliable, widely available

  diagnostic assay. Furthermore, its role in the pathogenesis of autoimmune

  hepatitis can now be studied.



1304. Ying C.  De Clercq E.  Neyts J.


  Lamivudine, adefovir and tenofovir exhibit long-lasting anti-hepatitis B

  virus activity in cell culture.


  Journal of Viral Hepatitis.  7(1):79-83, 2000 Jan.


  In this work, we investigated the anti-hepatitis B virus (HBV) activity of

  lamivudine, adefovir, tenofovir, penciclovir and lobucavir after

  short-term (i.e. 24 or 48 h) or continuous (9 days) exposure of the

  HBV-containing cell line, HepG2 2.2.15, to these drugs. Lamivudine

  maintained significant anti-HBV activity when added for only 24 or 48 h to

  the cell cultures compared to when the drug was present for the whole

  period (9 days) on the cells, i.e. 50% effective concentration (EC50)

  values for the inhibition of HBV DNA synthesis were 0.07 +/- 0.02

  microgram ml-1 after 24 h of incubation, 0.02 +/- 0.01 microgram ml(-1)

  after 48 h of incubation and 0.0016 +/- 0.001 microgram ml(-1) after 9

  days of incubation. Similarly, the nucleoside phosphonate analogues,

  adefovir and tenofovir, retained significant anti-HBV activity when added

  for only a short period of time to the cells. The EC50 values were 12 +/-

  1 microgram ml(-1) (24 h) and 1.0 +/- 0.2 microgram ml(-1) (48 h) vs 0.003

  +/- 0.001 microgram ml(-1) (9 days) for adefovir, and 6.5 +/- 1.1

  microgram ml(-1) (24 h) and 0.8 +/- 0.1 microgram ml(-1) (48 h) vs 0.03

  +/- 0.02 microgram ml(-1) (9 days) for tenofovir. In contrast, penciclovir

  and lobucavir lost most of their anti-viral activity when present on the

  cells for 48 h or less.


1305. Zucca E.  Roggero E.  Maggi-Solca N.  Conconi A.  Bertoni F.  Reilly I.

  Castelli D.  Pedrinis E.  Piffaretti JC.  Cavalli F.


  Prevalence of Helicobacter pylori and hepatitis C virus infections among

  non-Hodgkin's lymphoma patients in Southern Switzerland.


  Haematologica.  85(2):147-53, 2000 Feb.


  BACKGROUND AND OBJECTIVE: Several recent studies have reported a high rate

  of previous hepatitis C virus (HCV) infection in patients with

  non-Hodgkin's lymphoma (NHL). However, it appears that there are marked

  geographical differences in the prevalence of HCV among NHL patients.

  There is further controversy concerning a possible pathogenetic link

  between HCV and certain histologic lymphoma subtypes, in particular MALT

  lymphomas, and it has recently been speculated that HCV might be involved

  in the multistep process of gastric lymphoma genesis, in addition to the

  well established role of chronic Helicobacter pylori infection. The aim of

  this study was to investigate the prevalence of HCV and H. pylori

  infections in patients with B-cell NHL in Southern Switzerland. DESIGN AND

  METHODS: One hundred and eighty newly diagnosed HIV-negative B-cell NHL

  patients, consecutively seen at a referral oncology center in Southern

  Switzerland between 1990 and 1995 were prospectively studied. A

  microparticle enzyme immunoassay was used to detect antibodies to HCV.

  Serologic determination of HCV genotype was done by the Murex method. The

  quantitative detection of IgG anti-H. pylori was performed by the Biorad

  GAP test. RESULTS: Infection with HCV was detected in 17/180 patients

  (9.4%; 95% C.I., 6%-15%). This prevalence is significantly higher than

  that observed in a large survey of 5424 new blood donors from the same

  area tested in 1992-97 (0.9%; 95% C.I., 0.7-1.2). Neither histologic

  subtypes nor specific extranodal presentations of NHL were associated with

  a higher prevalence of HCV. HCV serotype 2 (corresponding to genotypes

  2a-c) was the most common. HCV infection was significantly associated with

  a shorter progression-free survival at both univariate and multivariate

  analysis. Anti-Helicobacter antibodies were detected in 81/180 patients

  (45%; 95% C.I., 38%-53%) and H. pylori infection was significantly

  associated with the development of primary lymphomas of the stomach.

  INTERPRETATION AND CONCLUSIONS: A high prevalence of HCV infection was

  detected in NHL lymphoma patients and was associated with a shorter time

  to lymphoma progression. HCV infection was not correlated with primary

  gastric presentation or with MALT-type histology. Our findings further

  support the key role of H.pylori infection in the pathogenesis of primary

  gastric lymphoma of MALT-type. The possible role of HCV in the

  pathogenesis of NHL should be further investigated.



1686. Authors

  Aizawa Y.  Shibamoto Y.  Takagi I.  Zeniya M.  Toda G.


  Analysis of factors affecting the appearance of hepatocellular carcinoma

  in patients with chronic hepatitis C. A long term follow-up study after

  histologic diagnosis.


  Cancer.  89(1):53-9, 2000 Jul 1.


  BACKGROUND: Hepatocellular carcinoma (HCC) occurs more frequently in

  patients with hepatitis C virus (HCV)-related chronic liver disease than

  those with hepatitis B virus-related disease. It is important to assess

  the factors affecting the development of HCC. METHODS: A long term

  follow-up study involving patients with chronic HCV was performed

  retrospectively. A total of 153 patients diagnosed between June 1981 and

  November 1990 with chronic HCV with or without cirrhosis by liver biopsy

  were enrolled in a long term follow-up study (average, 99.4 months) and

  the cumulative incidence rate of HCC and factors affecting the appearance

  of HCC were examined. RESULTS: The 5-year cumulative incidence rate was

  9%, the 10-year cumulative incidence rate was 23%, and the 15-year

  cumulative incidence rate was 42%. The annual rate of incidence increased

  as the follow-up period progressed. The authors selected ten variables and

  investigated their effect on the incidence rate of HCC, including age,

  gender, habitual heavy drinking, positivity of antibody against hepatitis

  B virus surface antigen, treatment with interferon (IFN) during the

  follow-up period, maximum and minimum serum alanine aminotransferase

  levels during the follow-up period, histologic staging, grading, and

  irregular regeneration of hepatocytes. Of the 10 variables, age (> 50

  years), habitual heavy drinking, and histologic staging were determined to

  be independent risk factors according to multivariate Cox proportional

  hazards regression analysis. IFN therapy by itself was not found to be an

  independent factor affecting the appearance of HCC. CONCLUSIONS: In

  patients with chronic HCV, the annual incidence rate of HCC appeared to

  increase as the follow-up period progressed. According to the results of

  the current study, the factors that independently affected the development

  of HCC were age, habitual heavy drinking, and histologic staging.

  Copyright 2000 American Cancer Society.


1687. Authors

  Berenguer M.  Prieto M.  Rayon JM.  Mora J.  Pastor M.  Ortiz V.  Carrasco

  D.  San Juan F.  Burgueno MD.  Mir J.  Berenguer J.


  Natural history of clinically compensated hepatitis C virus-related graft

  cirrhosis after liver transplantation.


  Hepatology.  32(4 Pt 1):852-8, 2000 Oct.


  The natural history of clinically compensated hepatitis C virus (HCV)

  cirrhosis after liver transplantation is unknown. This information is

  relevant to transplant centers to improve the management of these patients

  and decide the optimal timing for retransplantation. The aims of the study

  were (1) to describe the natural history of patients with HCV-cirrhosis

  transplants in a center with annual liver biopsies, and (2) to determine

  predictors for clinical decompensation, retransplantation, and mortality

  rates. A total of 49 patients with HCV-graft cirrhosis, 39 clinically

  compensated at histologic diagnosis of cirrhosis (post-liver

  transplantation cirrhosis) were included and followed up for 1 year (15

  days-3.5 years). All patients tested were infected with genotype 1b.

  Predictive variables included histologic activity index (HAI) at

  post-liver transplantation cirrhosis, liver function tests, age, sex, and

  maintenance immunosuppression. Eighteen of 39 patients developed at least

  1 episode of decompensation after a median of 7.8 months (4 days-2.6

  years; 93% ascites). The cumulative probability of decompensation was 8%,

  17%, and 42% at 1, 6, and 12 months, respectively. Graft and patient

  survival rates were 100%, 85%, and 71% and 100%, 92%, and 74% at 1, 6, and

  12 months, respectively. Patient survival rates dropped significantly once

  decompensation developed (93%, 61%, and 41% at 1, 6, and 12 months,

  respectively). Variables associated with decompensation,

  retransplantation, and mortality rate included a high Child-Pugh score

  (>A), low levels of albumin at post-liver transplantation cirrhosis, and a

  short interval between liver transplantation and post-liver

  transplantation cirrhosis. The natural history of clinically compensated

  HCV-graft cirrhosis is shortened when compared with immunocompetent

  patients. If retransplantation is considered, it should be performed

  promptly once decompensation develops.


1688. Authors

  Blatt LM.  Mutchnick MG.  Tong MJ.  Klion FM.  Lebovics E.  Freilich B.

  Bach N.  Smith C.  Herrera J.  Tobias H.  Conrad A.  Schmid P.

  McHutchison JG.


  Assessment of hepatitis C virus RNA and genotype from 6807 patients with

  chronic hepatitis C in the United States.


  Journal of Viral Hepatitis.  7(3):196-202, 2000 May.


  Hepatitis C virus (HCV) RNA status and HCV genotype have become important

  tools in the diagnosis and monitoring of therapy in chronic HCV infection.

  To establish a database with respect to HCV genotype and serum HCV RNA

  concentrations in chronic hepatitis C patients in the United States, we

  analysed 6807 chronic hepatitis C patients who had HCV RNA and HCV

  genotype tests conducted at a central laboratory. The HCV RNA

  concentration cut-off for the lower 25th percentile of this population

  (low titre) was 0.9 x 106 copies ml-1. The median HCV RNA concentration

  was 3.5 x 106 copies ml-1 and the cut-off for the upper 25th percentile

  (high titre) was 5 x 106 copies ml-1. Male patients had a median HCV RNA

  concentration of 3.9 x 106 copies ml-1, which was significantly higher

  than the median HCV RNA level for females (2.75 x 106 copies ml-1; P <

  0.001). HCV genotype 1 was detected in 73% of patients; genotype 2 in 14%;

  genotype 3 in 8%; mixed genotype in 4%; and genotypes 4, 5 and 6 with a

  frequency of < 1%. Patients from the Northeast, Southeast and Midwest had

  significantly (P < 0.001) more infections with genotype 1 than patients

  from the Western and Southern regions. African-American patients were more

  likely to be infected with genotype 1 when compared with Caucasian,

  Hispanic or Asian Pacific Islanders (P < 0.001). Patients infected with

  HCV genotype 1 and mixed HCV genotypes had significantly higher serum HCV

  RNA concentrations when compared with HCV genotypes 2 and 3 (P < 0.001 for

  all comparisons).



1689. Authors

  Caniatti LM.  Tugnoli V.  Eleopra R.  Tralli G.  Bassi R.  De Grandis D.


  Cryoglobulinemic neuropathy related to hepatitis C virus infection.

  Clinical, laboratory and neurophysiological study.


  Journal of the Peripheral Nervous System.  1(2):131-8, 1996.


  Peripheral neuropathy is frequently reported in mixed cryoglobulinemia. As

  a close relationship has been established between mixed cryoglobulinemia

  and hepatitis C virus (HCV), the clinical, neurophysiological, and

  serologic findings of five patients affected by neuropathy,

  cryoglobulinemia and HCV infection were investigated. HCV infection was

  ascertained by the presence in the serum of anti-HCV antibodies detected

  by enzyme-linked immunosorbent assay(ELISA), and of HCV RNA assessed by

  polymerase chain reaction (PCR). Initial symptoms included paresthesias

  and painful dysesthesias in the legs. Later on, the patients developed a

  mainly asymmetric axonal polyneuropathy or a multifocal neuropathy

  associated with signs of systemic vasculitis. In this case series we

  report the short-term prognosis, as well as the response to interferon

  (IFN) alpha and conventional treatment. The presence of HCV RNA supports

  the hypothesis that a persistent HCV infection might be involved in the

  pathogenesis of mixed cryoglobulinemia and cryoglobulinemia-associated



1690. Authors

  Chattopadhyay D.  Sen MR.  Aryya NC.


  Immunohistopathological reactions for liver-specific membrane lipo-protein

  in experimental autoimmune hepatitis.


  Indian Journal of Pathology & Microbiology.  42(3):291-7, 1999 Jul.


  Antibody to the hepatocyte membrane protein, was induced in inbred strain

  C57BL/6 and C3H mice by immunisation with 100,000 g supernatant of

  syngeneic liver homogenate in CFA. Three weekly intraperitoneal injection

  of 200 ul of liver homogenate with CFA for continuous 4 weeks gave the

  best possible result. Histopathological changes were characterised mainly

  by perivascular inflammatory infiltrates and hepatocyte necrosis which

  mimicked human autoimmune hepatitis. In one of the immunological

  parameters, antibody to hepatocyte membrane protein (LSP) has been

  demonstrate by ouchterlony method in the test serum of those animals, who

  had received weekly doses of liver antigen. Thus in experimental

  autoimmune liver disease, semi-purified syngeneic liver fluid (S-100)

  leads to hepatic destruction and to an inflammatory process with several

  features in common with human chronic aggressive hepatitis. The presence

  of antibody against syngeneic liver antigen (S-100) in the test sera

  emphasizes that hepatocyte membrane protein does have an important role in

  liver tissue pathogenesis and disease process in experimental model. In

  this study we tried to prove that hepatocyte membrane protein may act as a

  target antigen in developing experimental autoimmune hepatitis.


1691. Authors

  Cote PJ.  Toshkov I.  Bellezza C.  Ascenzi M.  Roneker C.  Ann Graham L.

  Baldwin BH.  Gaye K.  Nakamura I.  Korba BE.  Tennant BC.  Gerin JL.


  Temporal pathogenesis of experimental neonatal woodchuck hepatitis virus

  infection: increased initial viral load and decreased severity of acute

  hepatitis during the development of chronic viral infection.


  Hepatology.  32(4 Pt 1):807-17, 2000 Oct.


  Acute hepatitis B virus (HBV) infections either resolve or progress to

  chronicity. Identification of early deviations in host-virus responses

  associated with these outcomes can further differentiate cause-effect

  mechanisms that initiate and maintain chronicity. Neonatal woodchucks were

  infected experimentally with the woodchuck hepatitis virus (WHV) at 3 days

  of age. At 8 or 14 weeks of age (i.e. , the early- or mid-acute stage of

  infection), whole blood and large surgical biopsies of the liver were

  obtained from infected animals and uninfected controls. These were stored

  for later correlating histopathologic responses and viral load with the

  subsequently determined outcome of infection. As of 1 year postinfection,

  half of the surgically treated infected woodchucks had developed

  self-limited infections, while the other half developed chronic

  infections. The self-limited outcome was characterized by decreased viral

  load in acute-phase liver and plasma and a generally robust acute hepatic

  inflammatory response. Comparisons at the same early time points revealed

  that the chronic outcome was characterized by increasing initial viral

  load in liver and plasma, and a detectable, but diminished, acute hepatic

  inflammation. These cotemporal comparisons indicate that there is an early

  host-response deviation during the acute phase of a developing chronic

  infection. Continued analysis of the tissues banked from this study will

  facilitate further temporal characterization of acute-phase mechanisms

  that determine resolution versus chronicity in WHV infection.

  Understanding such mechanisms may be useful in the rational design of

  therapy for established chronic HBV infection.


1692. Authors

  de La Rosa JM.  Escobedo M.


  Tuberculosis and other infectious diseases in the adolescent immigrant.

  [Review] [23 refs]


  Adolescent Medicine.  11(2):453-66, 2000 Jun.


  Adolescent medicine physicians are frequently the initial contact for

  adolescents newly arriving in the U.S. and it is important that they

  recognize the needs of their patients. The adolescent immigrant may be

  encountered in a school-based health setting, private practice, community

  health center, or other health care settings. This article begins with a

  review of the categories of immigrants comprising the adolescent

  population. It gives an extensive review of tuberculosis among

  Mexican-American adolescents, detailing history, epidemiology, diagnosis,

  social factors, and treatment modalities. It further delineates the impact

  of Mexican tuberculosis control strategies on the practice of medicine in

  the U.S., and outlines preventive, diagnostic, and therapeutic strategies

  that should be followed in the adolescent immigrant. This article also

  reviews viral hepatitis in its multiple forms and its impact on the

  adolescent immigrant. It concludes by delineating prevention practices

  required for the adolescent immigrant and summarizes the interventions an

  initial contact physician should undertake upon encountering such

  adolescents. [References: 23]



1693. Authors

  Egner W.


  The use of laboratory tests in the diagnosis of SLE. [Review] [149 refs]


  Journal of Clinical Pathology.  53(6):424-32, 2000 Jun.


  ANA IIF is an effective screening assay in patients with clinical features

  of SLE and will detect most anti-ssDNA, anti-dsDNA, ENAs, and other

  autoantibodies. False positives are common. The clinical importance cannot

  be extrapolated from the ANA titre or pattern, although higher titres (>

  1/160) are more likely to be important. HEp-2 cells are the most sensitive

  substrate for ANA detection, but this must be balanced against an

  increased incidence of insignificant positivity. ANA positive samples

  should be subjected to more specific assays for the diagnosis of SLE. A

  combination of ENA (Ro/La/Sm/RNP) and dsDNA assays will detect most

  patients with SLE as long as the characteristics of the assays used are

  well understood. ESR and CRP measurements provide useful additional

  information. Sjogren's syndrome and MCTD will produce overlapping serology

  with SLE, and anti-dsDNA titres are sometimes seen in autoimmune hepatitis

  and rheumatoid arthritis. All results should be reported in the light of

  the clinical details, by an experienced immunologist. A suggested

  diagnostic protocol is outlined in fig 1. The type of assay used crucially

  influences the predictive value of the tests. ELISA technology dominates

  routine laboratory practice, but tends to produce more false positive and

  true weak positive results, which may reduce the PPV of the test. This can

  be minimised by using IgG specific conjugates and careful assay

  validation. The NPV for SLE [figure: see text] is high for most assays but

  the PPV varies. Where necessary, laboratories should use crithidia or Farr

  dsDNA assays to confirm dubious ELISA dsDNA results, and ID/IB to confirm

  dubious ENA results. For monitoring, a precise, quantitative assay is

  required. It is unclear whether the detection of IgM or low affinity

  antibodies has a role here. A combination of anti-dsDNA, C3, C4, CRP, and

  ESR assays provides the most useful clinical information. Anti-ssDNA

  assays are likely to be useful, and are potentially more robust than

  anti-dsDNA assays, but require more validation. Local validation of

  individual assays and EQA participation is essential. Not all assays that

  apparently measure the same antibody specificities have equal clinical

  relevance, even within a single technology. Insufficient international or

  national reference preparations are currently available for many antibody

  specificities to enable effective standardisation. Quality assurance

  schemes reveal large differences in units reported by different assays for

  some analytes, even when calibrated against an IRP or equivalent reference

  preparation. Serial results can therefore only be compared from the same

  laboratory at present. Most autoantibodies increase during active disease,

  but few prospective data are currently available to justify treatment on

  the basis of rising titres. Further randomised prospective studies are

  required to examine the importance of antibody isotype and affinity in the

  monitoring of SLE by individual assay methods. The most important aspect

  of the appropriate use of laboratory assays is to become familiar with the

  limitations of the technology currently in use in your local laboratory,

  and to consult with your clinical immunologist in cases of doubt,

  preferably before commencing serological screening. [References: 149]


1694. Authors

  Griga T.  Tromm A.  Muller KM.  May B.


  Overlap syndrome between autoimmune hepatitis and primary sclerosing

  cholangitis in two cases.


  European Journal of Gastroenterology & Hepatology.  12(5):559-64, 2000



  The overlap syndrome between autoimmune hepatitis and primary sclerosing

  cholangitis is a rare condition and only few cases have been published,

  partly associated with ulcerative colitis, but not with Crohn's disease.

  We report an autoimmune hepatitis/primary sclerosing cholangitis overlap

  syndrome in a female patient with Crohn's disease. In addition, a second

  case of overlap syndrome is reported in a man without inflammatory bowel

  disease. A 24-year-old woman was referred with a 10-month history of

  diarrhoea and biochemical changes including elevated serum levels of

  alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase

  and immunoglobulin G. Enzyme linked immunosorbent assay showed that

  antinuclear autoantibodies were elevated. Immunofluorescence for

  perinuclear-staining antineutrophil cytoplasmatic antibodies was positive.

  Diagnostic criteria of definite autoimmune hepatitis according to the

  International Autoimmune Hepatitis Group were fulfilled. Liver biopsy

  simultaneously showed criteria of autoimmune hepatitis and primary

  sclerosing cholangitis. Endoscopic retrograde cholangiography demonstrated

  features of primary sclerosing cholangitis. Colonoscopy and colonoscopic

  biopsies indicated an active Crohn's disease affecting the terminal ileum

  and the ascending and transverse colon. Furthermore, we report the case of

  a 28-year-old man with known primary sclerosing cholangitis for the

  previous 6 years, and who developed jaundice and a marked increase of

  aspartate aminotransferase, alanine aminotransferase and immunoglobulin G,

  leading to the diagnosis of definite autoimmune hepatitis. A review of the

  literature revealed only 16 cases of an autoimmune hepatitis/primary

  sclerosing cholangitis syndrome in patients without inflammatory bowel

  disease or in association with ulcerative colitis. We report two

  additional cases, one case showing an association with Crohn's disease.


1695. Authors

  Hayashi S.  Ohtake H.  Koike M.


  Laparoscopic diagnosis and clinical course of chronic schistosomiasis



  Acta Tropica.  77(1):133-40, 2000 Oct 23.


  Laparoscopic findings of nine patients with chronic schistosomiasis

  japonica were analyzed and compared to hepatic ultrasonograms, computed

  tomography (CT) scans and histological findings from the same patients. In

  all nine patients laparoscopy revealed yellowish, small speckles,

  approximately 50 microm in diameter, sparse or clustered over the liver

  surface, which were later found to represent subcapsular calcified ova of

  Schistosoma japonicum. While the liver surface was almost smooth in mild

  schistosomiasis, multiple whitish markings and irregular, relatively wide,

  groove-like septums were seen in more advanced cases. In severe

  schistosomiasis block-like formations of variable size, separated by

  groove-like depressions, made the liver surface appear like a tortoise

  shell. In moderate or severe schistosomiasis ultrasonography revealed

  spotted high echoes and CT scans demonstrated network patterns and lineal

  calcified spots. The liver surface of chronic schistosomiasis japonica

  without re-infection appeared stable without change over time but with a

  tendency to improve. Hepatocellular carcinoma was initially recorded in

  two of the nine patients and follow-up revealed a further two with the

  same diagnosis. However, all these four cases also had chronic hepatitis C

  (HCV). Hepatocellular carcinoma was not detected in patients without viral

  hepatitis, indicating that hepatic viral infection is more important than

  schistosomiasis in promoting the development of hepatocellular carcinoma.


1696. Authors

  Heile JM.  Fong YL.  Rosa D.  Berger K.  Saletti G.  Campagnoli S.  Bensi

  G.  Capo S.  Coates S.  Crawford K.  Dong C.  Wininger M.  Baker G.

  Cousens L.  Chien D.  Ng P.  Archangel P.  Grandi G.  Houghton M.

  Abrignani S.


  Evaluation of hepatitis C virus glycoprotein E2 for vaccine design: an

  endoplasmic reticulum-retained recombinant protein is superior to secreted

  recombinant protein and DNA-based vaccine candidates.


  Journal of Virology.  74(15):6885-92, 2000 Aug.


  Hepatitis C virus (HCV) is the leading causative agent of blood-borne

  chronic hepatitis and is the target of intensive vaccine research. The

  virus genome encodes a number of structural and nonstructural antigens

  which could be used in a subunit vaccine. The HCV envelope glycoprotein E2

  has recently been shown to bind CD81 on human cells and therefore is a

  prime candidate for inclusion in any such vaccine. The experiments

  presented here assessed the optimal form of HCV E2 antigen from the

  perspective of antibody generation. The quality of recombinant E2 protein

  was evaluated by both the capacity to bind its putative receptor CD81 on

  human cells and the ability to elicit antibodies that inhibited this

  binding (NOB antibodies). We show that truncated E2 proteins expressed in

  mammalian cells bind with high efficiency to human cells and elicit NOB

  antibodies in guinea pigs only when purified from the core-glycosylated

  intracellular fraction, whereas the complex-glycosylated secreted fraction

  does not bind and elicits no NOB antibodies. We also show that

  carbohydrate moieties are not necessary for E2 binding to human cells and

  that only the monomeric nonaggregated fraction can bind to CD81. Moreover,

  comparing recombinant intracellular E2 protein to several E2-encoding DNA

  vaccines in mice, we found that protein immunization is superior to DNA in

  both the quantity and quality of the antibody response elicited. Together,

  our data suggest that to elicit antibodies aimed at blocking HCV binding

  to CD81 on human cells, the antigen of choice is a mammalian

  cell-expressed, monomeric E2 protein purified from the intracellular



1697. Authors

  Hilleman MR.


  Vaccines in historic evolution and perspective: a narrative of vaccine



  Journal of Human Virology.  3(2):63-76, 2000 Mar-Apr.


  The sciences of vaccinology and immunology were created only two centuries

  ago by Jenner's scientific studies of prevention of smallpox through

  inoculation with cowpox virus. This rudimentary beginning was expanded

  greatly by the giants of late 19th- and early 20th-century biomedical

  sciences. The period from 1930 to 1950 was a transitional era, with the

  introduction of chick embryos and minced tissues for propagating viruses

  and rickettsiae in vitro for vaccines. Modern vaccinology began about 1950

  as a continuum following notable advances made during the 1940s and World

  War II. Its pursuit has been based largely on breakthroughs in cell

  culture, bacterial polysaccharide chemistry, molecular biology, and

  immunology which have yielded many live and killed viral and bacterial

  vaccines plus the recombinant-expressed hepatitis B vaccine. The present

  paper was presented as a lecture given at a Meeting of the Institute of

  Human Virology entitled A Symposium on HIV-AIDS and Cancer Biology,

  Baltimore, Maryland, on August 30, 2023 and recounts, by invitation, more

  than 55 years of vaccine research from the venue of personal experience

  and attainment by the author. The paper is intentionally brief and

  truncated with focus only on highlights and limited referencing. Detailed

  recounting and referencing are given elsewhere in text references 1 and 2.

  This narration will have achieved its purpose if it provides a background

  of understanding and guidelines that will assist others who seek to engage

  in creation of new vaccines.


1698. Authors

  Hwang SJ.  Luo JC.  Lai CR.  Chu CW.  Tsay SH.  Lu CL.  Wu JC.  Chang FY.

  Lee SD.


  Clinical, virologic and pathologic significance of elevated serum

  gamma-glutamyl transpeptidase in patients with chronic hepatitis C.


  Chung Hua i Hsueh Tsa Chih - Chinese Medical Journal.  63(7):527-35, 2000



  BACKGROUND: Elevated serum gamma-glutamyl transpeptidase (GGT) is often

  seen in patients with chronic hepatitis C virus (HCV) infection and is

  associated with a poor response to interferon treatment. The pathogenesis

  of these phenomena is unclear. Therefore, we assessed the prevalence of

  elevated serum GGT in Chinese patients with chronic hepatitis C and

  evaluated the clinical, biochemical, virologic and histologic features of

  this phenomenon. METHODS: One hundred and twelve patients with

  biopsy-proven chronic hepatitis C were enrolled. Patients who were

  habitual alcohol drinkers, alcoholics or had diabetes mellitus were

  excluded. RESULTS: Forty-three (38.4%) of 112 patients had elevated serum

  GGT (> 60 U/l). Patients with elevated serum GGT had significantly higher

  serum levels of alanine and aspartate aminotransferases, alkaline

  phosphatase and total bilirubin, significantly higher histologic scores of

  liver lobular necro-inflammation and fibrosis when compared to patients

  with normal serum GGT. Elevated serum GGT was not correlated to serum HCV

  RNA titer or HCV genotype. Multivariate logistic regression analysis

  showed that a histologic fibrotic score > or = 2 was the only

  significantly independent predictor associated with elevated serum GGT.

  Fifty-seven of 112 patients completed a six-month course of interferon

  treatment. Patients with elevated serum GGT had a significantly lower

  sustained response rate to interferon when compared to patients with

  normal serum GGT (8% vs 30%, p = 0.042). CONCLUSIONS: Elevated serum GGT

  in chronic hepatitis C patients was frequently associated with more severe

  hepatic fibrosis or cirrhosis and may, in part, account for poor response

  to interferon therapy.


1699. Authors

  Imperiale TF.  Said AT.  Cummings OW.  Born LJ.


  Need for validation of clinical decision aids: use of the AST/ALT ratio in

  predicting cirrhosis in chronic hepatitis C.


  American Journal of Gastroenterology.  95(9):2328-32, 2000 Sep.


  OBJECTIVE: A value of > or = 1 for the ratio of aspartate

  amino-transferase to alanine aminotransferase (the AST/ALT ratio or AAR)

  has been shown to have a positive predictive value of 100% for the

  diagnosis of cirrhosis in patients with chronic hepatitis C. If validated

  on separate cohorts, an AAR > or = 1 might obviate the need for liver

  biopsy in some patients with hepatitis C. METHODS: We attempted to

  validate the AAR by abstracting demographic and clinical data from a

  database of consecutive patients with hepatitis C who had a liver biopsy

  between 1993 and 1998. We used definitions, methods of data collection,

  and analyses comparable to those of the published study. A

  hepatopathologist blindly reviewed 49 liver biopsies for histological

  grade and stage. RESULTS: The current cohort of 177 patients and the

  previous cohort of 139 patients were comparable in mean age (42.3 vs 43.8

  yr), percentage of men (63 vs 67), percentage with an AAR > or =1 (20 vs

  17), and Child-Pugh distribution, but differed in substantial use of

  ethanol (11% vs 3.6%; p = 0.01) and in the prevalence of cirrhosis (23% vs

  34%, p = 0.06). Respective sensitivities of the AAR were 56% and 53%. An

  AAR > or =1 had a positive predictive value of 64% (95% confidence

  interval 48-78%) for the current cohort. Thirteen of 36 patients (36%)

  with an AAR > or =1 were incorrectly identified as having cirrhosis. Of

  these 13 patients, 6 had a normal AST and ALT, 5 had a minimally elevated

  AST or ALT, and 1 had advanced fibrosis without cirrhosis. CONCLUSIONS:

  These results suggest that an AAR > or =1 may not be as useful for

  predicting cirrhosis in chronic hepatitis C as previously thought, and

  emphasizes the need for validation of clinical decision aids on

  independent patient cohorts.


1700. Authors

  Jacobs RJ.  Margolis HS.  Coleman PJ.


  The cost-effectiveness of adolescent hepatitis A vaccination in states

  with the highest disease rates.


  Archives of Pediatrics & Adolescent Medicine.  154(8):763-70, 2000 Aug.


  BACKGROUND: The Advisory Committee on Immunization Practices has

  recommended routine childhood hepatitis A vaccination in states and

  communities where the incidence of disease exceeds the national average,

  but most adolescents are currently unprotected from infection. OBJECTIVE:

  To estimate clinical and economic consequences of vaccinating adolescents

  against hepatitis A in the 10 states with the highest disease rates.

  DESIGN: Decision analysis was used to assess cost-effectiveness from

  societal and health system perspectives. Parameter estimates were obtained

  from national surveillance data, a study of hepatitis A cases, and an

  expert panel. MAIN OUTCOME MEASURES: Reduction in disease incidence; costs

  of vaccination, treatment, and work loss; years of life saved (YOLS); and

  costs per YOLS. RESULTS: In states with the highest disease rates,

  vaccination of adolescents against hepatitis A would reduce the lifetime

  risk of symptomatic infection from 3.3% to 0.7% and prevent loss of 2117

  years of life. Vaccination of a single birth cohort would cost $30.9

  million, yet treatment and work loss costs would decline $14.2 million and

  $23.8 million, respectively. Hepatitis A vaccination would cost the health

  system $7902 per YOLS or $13,722 per discounted YOLS. Results are most

  sensitive to variation in the discount rate and assumptions regarding

  long-term vaccine protective efficacy. CONCLUSIONS: Hepatitis A

  vaccination of adolescents in states with high disease rates would reduce

  costs to society. Although health system costs would increase,

  cost-effectiveness is comparable to other recommended vaccines and

  superior to many commonly used medical interventions. Arch Pediatr Adolesc

  Med. 2000;154:763-770


1701. Authors

  Jeffers L.


  Hepatocellular carcinoma: an emerging problem with hepatitis C.


  Journal of the National Medical Association.  92(8):369-71, 2000 Aug.


  Hepatocellular carcinoma (HCC) is emerging as a major problem in the

  United States, primarily due to the development of liver cancer in

  patients with cirrhosis secondary to the hepatitis C virus. The diagnosis

  of HCC in patients with underlying cirrhosis can be achieved at an early

  stage if appropriate diagnostic measures are pursued by primary care

  physicians and gastroenterologists. African Americans are particularly

  vulnerable in developing HCC since their response to current therapy for

  chronic hepatitis C is less than optimal.



1702. Authors

  Kaakkola S.


  Clinical pharmacology, therapeutic use and potential of COMT inhibitors in

  Parkinson's disease. [Review] [109 refs]


  Drugs.  59(6):1233-50, 2000 Jun.


  When peripheral decarboxylation is blocked by carbidopa or benserazide,

  the main metabolic pathway of levodopa is O-methylation by

  catechol-O-methyltransferase (COMT). Entacapone and tolcapone are new

  potent, selective and reversible nitrocatechol-type COMT inhibitors.

  Animal studies have demonstrated that entacapone mainly has a peripheral

  effect whereas tolcapone also inhibits O-methylation in the brain. In

  human volunteers, both entacapone and tolcapone dose-dependently inhibit

  the COMT activity in erythrocytes, improve the bioavailability and

  decrease the elimination of levodopa, and inhibit the formation of

  3-O-methyldopa (3-OMD). Entacapone is administered with every scheduled

  dose of levodopa whereas tolcapone is administered 3 times daily. The

  different administration regimens for these agents are based on their

  different pharmacokinetic and pharmacodynamic profiles. Both entacapone

  and tolcapone enhance and extend the therapeutic effect of levodopa in

  patients with advanced and fluctuating Parkinson's disease. They prolong

  the duration of levodopa effect. Clinical studies show that they increase

  the daily ON time by an average 1 to 3 hours, improve the activities of

  daily living and allow daily levodopa dosage to be decreased.

  Correspondingly, they significantly reduce the daily OFF time. No

  comparative studies between entacapone and tolcapone have been performed.

  Tolcapone also appears to have a beneficial effect in patients with

  nonfluctuating Parkinson's disease. The main adverse effects of the COMT

  inhibitors are related to their dopaminergic and gastrointestinal effects.

  Enhancement of dopaminergic activity may cause an initial worsening of

  levodopa-induced adverse effects, such as dyskinesia, nausea, vomiting,

  orthostatic hypotension, sleep disorders and hallucinations. Levodopa dose

  adjustment is recommended to avoid these events. Tolcapone is associated

  with diarrhoea in about 16 to 18% of patients and entacapone in less than

  10% of patients. Diarrhoea has led to discontinuation in 5 to 6% of

  patients treated with tolcapone and in 2.5% of those treated with

  entacapone. Urine discoloration to dark yellow or orange is related to the

  colour of COMT inhibitors and their metabolites. Elevated liver

  transaminase levels are reported in 1 to 3% of patients treated with

  tolcapone but very rarely, if at all, in patients treated with entacapone.

  The descriptions of acute, fatal fulminant hepatitis and potentially fatal

  neurological reactions, such as neuroleptic malignant syndrome and

  rhabdomyolysis, in association with tolcapone led to the suspension of its

  marketing authorisation in the European Community and Canada. In many

  other countries, the use of tolcapone is restricted to patients who are

  not responding satisfactorily to other therapies. Regular monitoring of

  liver enzymes is required if tolcapone is used. No such adverse reactions

  have so far been described for entacapone and no laboratory monitoring has

  been proposed. COMT inhibitors added to levodopa therapy are beneficial,

  particularly in patients with fluctuating disease. They may be combined

  with other antiparkinsonian drugs, such as dopamine agonists, selegiline

  and anticholinergics without adverse interactions. They provide a new

  treatment possibility in patients with Parkinson's disease who have

  problems with their present levodopa therapy. [References: 109]


1703. Authors

  Kallinowski B.  Knoll A.  Lindner E.  Sanger R.  Stremmel W.  Vollmar J.

  Zieger B.  Jilg W.


  Can monovalent hepatitis A and B vaccines be replaced by a combined

  hepatitis A/B vaccine during the primary immunization course?.


  Vaccine.  19(1):16-22, 2000 Aug 15.


  A combined hepatitis A/B vaccine (Twinrix Adult) has been licensed in

  Germany since 1997. We investigated possible differences in immunogenicity

  and safety when changing over from vaccinations with monovalent vaccines

  made by different manufacturers to vaccinations with the combined

  hepatitis A/B vaccine in an open, randomized, multicenter trial. We

  therefore compared four different schemes changing over from concomitant

  vaccinations with monovalent vaccines against hepatitis A and B (Havrix

  1440+Engerix-B or Vaqta+Gen H-B-Vax) to combined vaccination against

  hepatitis A+B with three injections of the combined hepatitis A/B vaccine

  (0, 1, and 6 month schedule). Local and general symptoms were mostly mild

  in all five groups. With complete three-dose course using the combined

  vaccine or an early changeover from monovalent vaccines to the combined

  vaccine, higher overall anti-HBs seroprotection rates and geometric mean

  concentrations (GMCs) against hepatitis B could be achieved as early as

  after 2 months as compared to those groups switching later to the combined

  vaccine. This study demonstrated for the first time that switching from

  monovalent hepatitis A and B vaccinations to the combined hepatitis A and

  B vaccination has no negative influence on the tolerability and improves

  the immunogenicity.


1704. Authors

  Konomi N.  Yamaguchi M.  Naito H.  Aiba N.  Saito T.  Arakawa Y.  Abe K.


  Simultaneous detection of hepatitis B, C, and G viral genomes by multiplex

  PCR method.


  Japanese Journal of Infectious Diseases.  53(2):70-2, 2000 Apr.


  We established a multiplex polymerase chain reaction (PCR) method for

  simultaneous detection of hepatitis B, C, and G viral genomes. The levels

  of concordance with the data obtained by conventional single PCR method

  were 100% for single infection, 98 to 100% for double infections, and 92%

  for triple infections. This method is not only suited to rapid,

  large-scale epidemiological screening and clinical diagnosis of those

  virus infections occurring alone or in combination, but is also time- and



1705. Authors

  Kumar KS.  Malet PF.


  Nonalcoholic steatohepatitis. [Review] [38 refs]


  Mayo Clinic Proceedings.  75(7):733-9, 2000 Jul.


  Nonalcoholic steatohepatitis (NASH) is a liver disease that, until

  recently, has been underrecognized as a common cause of elevated liver

  enzymes. This distinct clinical entity is characterized by liver biopsy

  findings similar to those seen in alcoholic hepatitis but in the absence

  of alcohol consumption sufficient to cause such changes. Patients with

  NASH are often middle-aged and obese, with coexisting diabetes or

  hyperlipidemia, but NASH also occurs in younger lean, otherwise healthy

  individuals and even in children. Although NASH is generally a benign

  disorder, it may be progressive, leading to cirrhosis and complications of

  portal hypertension. Liver biopsy remains the gold standard for diagnosis.

  Therapy for NASH remains poorly defined, although weight reduction and

  ursodeoxycholic acid may have a beneficial effect. [References: 38]


1706. Authors

  Leung W.  Hudson MM.  Strickland DK.  Phipps S.  Srivastava DK.  Ribeiro

  RC.  Rubnitz JE.  Sandlund JT.  Kun LE.  Bowman LC.  Razzouk BI.  Mathew

  P.  Shearer P.  Evans WE.  Pui CH.


  Late effects of treatment in survivors of childhood acute myeloid leukemia.


  Journal of Clinical Oncology.  18(18):3273-9, 2000 Sep 15.


  PURPOSE: To investigate the incidence of and risk factors for late

  sequelae of treatment in patients who survived for more than 10 years

  after the diagnosis of childhood acute myeloid leukemia (AML). PATIENTS

  AND METHODS: Of 77 survivors (median follow-up duration, 16. 7 years), 44

  (group A) had received chemotherapy, 18 (group B) had received

  chemotherapy and cranial irradiation, and 15 (group C) had received

  chemotherapy, total-body irradiation, and allogeneic bone marrow

  transplantation. Late complications, tobacco use, and health insurance

  status were assessed. RESULTS: Growth abnormalities were found in 51% of

  survivors, neurocognitive abnormalities in 30%, transfusion-acquired

  hepatitis in 28%, endocrine abnormalities in 16%, cataracts in 12%, and

  cardiac abnormalities in 8%. Younger age at the time of diagnosis or

  initiation of radiation therapy, higher dose of radiation, and treatment

  in groups B and C were risk factors for the development of academic

  difficulties and greater decrease in height Z: score. In addition,

  treatment in group C was a risk factor for a greater decrease in weight Z:

  score and the development of growth-hormone deficiency, hypothyroidism,

  hypogonadism, infertility, and cataracts. The estimated cumulative risk of

  a second malignancy at 20 years after diagnosis was 1.8% (95% confidence

  interval, 0.3% to 11.8%). Twenty-two patients (29%) were smokers, and 11

  (14%) had no medical insurance at the time of last follow-up. CONCLUSION:

  Late sequelae are common in long-term survivors of childhood AML. Our

  findings should be useful in defining areas for surveillance of and

  intervention for late sequelae and in assessing the risk of individual

  late effects on the basis of age and history of treatment.


1707. Authors

  Louie M.  Louie L.  Simor AE.


  The role of DNA amplification technology in the diagnosis of infectious

  diseases. [Review] [81 refs]


  CMAJ.  163(3):301-9, 2000 Aug 8.


  Nucleic acid amplification and detection methods developed in the past

  decade are useful for the diagnosis and management of a variety of

  infectious diseases. The most widely used of these methods is the

  polymerase chain reaction (PCR). PCR assays can detect rapidly and

  accurately the presence of fastidious and slow-growing microorganisms,

  such as Chlamydia, mycoplasmas, mycobacteria, herpesviruses and

  enteroviruses, directly from clinical specimens. Commercial PCR assays for

  the diagnosis of tuberculosis and genital C. trachomatis infection are now

  routinely used in many diagnostic laboratories. Assays have also been

  developed that can detect antimicrobial resistance and are used to

  identify the cause of infection by organisms that cannot be cultivated.

  The value of viral load measurement by nucleic acid amplification in the

  management of patients with HIV infection or hepatitis C has also been

  well established. However, evaluations of this technology for rapid

  microbial diagnosis have generally been limited by small samples, and the

  cost of these assays may be as high as Can$125 per test. As nucleic acid

  amplification methods continue to evolve, their role in the diagnosis and

  management of patients with infectious diseases and their impact on

  clinical outcomes will become better defined. [References: 81]


1708. Authors

  Manoussakis MN.  Moutsopoulos HM.


  Sjogren's syndrome: autoimmune epithelitis.


  Best Practice & Research in Clinical Rheumatology.  14(1):73-95, 2000 Mar.


  Sjogren's syndrome (SS) is a chronic autoimmune disorder of the exocrine

  glands of unknown aetiology, which is typically associated with focal

  lymphocytic infiltrates of glandular tissues and autoantibody responses

  against the Ro(SSA) and La(SSB) ribonucleoproteins. In almost one-third of

  patients disease involves various extraglandular sites, whereas

  approximately 5% of patients may also develop malignant B-cell lymphoma.

  In addition, features of SS are frequently encountered (5-20%) in patients

  with several other autoimmune rheumatic diseases, and in several respects

  these 'secondary' forms may be distinct from SS found alone (primary-SS),

  as well as from each other. The correct diagnosis and management of SS may

  require consideration from various specialists. Differential diagnosis

  includes adverse effects of drugs, sarcoidosis, lipoproteinaemias,

  age-related atrophy, chronic graft-versus-host disease, lymphomas,

  amyloidosis and infection by human immunodeficiency virus or hepatitis C

  virus. Based on the sequential application of the validated European

  classification criteria for SS, a practical algorithm for diagnosis is

  presented. Despite progress in the understanding of the broad

  clinicopathological spectrum of the entity, its treatment remains largely

  empirical and symptomatic. To date, the decision for systemic therapeutic

  intervention is primarily based on the severity of extraglandular



1709. Authors

  Matheson AJ.  Goa KL.


  Diphtheria-tetanus-acellular pertussis vaccine adsorbed (Triacelluvax;

  DTaP3-CB): a review of its use in the prevention of Bordetella pertussis

  infection. [Review] [50 refs]


  Paediatric Drugs.  2(2):139-59, 2000 Mar-Apr.


  DTaP3-CB (Triacelluvax) is an acellular pertussis (aP) vaccine containing

  3 antigens from purified Bordetella pertussis bacteria combined with

  diphtheria and tetanus toxoids (DT). In addition to purified filamentous

  haemagglutinin and pertactin, DTaP3-CB contains pertussis toxin which has

  been genetically rather than chemically detoxified. As shown in

  randomised, double-blind clinical trials in infants, DTaP3-CB elicits an

  immune response similar to or greater than that of whole cell (DTwP)

  vaccines. Results of a large multicentre study comparing DTaP3-CB with 12

  acellular and 1 DTwP vaccine indicate that DTaP3-CB, like all acellular

  vaccines, induces variable immune responses to different pertussis

  antigens; however, antibody titres to pertussis toxin are normally higher

  after immunisation with the genetically detoxified vaccine than with other

  3- or 4-component vaccines. When given as a fourth or fifth booster dose,

  DTaP3-CB produced a significant immune response in infants primed with 3

  doses of either a DTaP or DTwP vaccine. Virtually all infants immunised

  with DTaP3-CB had a serological response to diphtheria and tetanus

  toxoids. Data from 2 very large efficacy studies indicate that DTaP3-CB

  has high and long lasting protective efficacy against culture-confirmed

  pertussis which is greater than that of a 2-component vaccine (DTaP2-SB)

  and the whole cell DTwP-CON vaccine after a 3-, 5- and 12-month

  immunisation schedule and after a 2-, 4- and 6-month schedule with the

  DTwP-CON vaccine. However, the DTwP-CON whole cell vaccine has been noted

  for its low immunogenicity in 1 study and low efficacy and immunogenicity

  in another study. On the other hand, DTaP3-CB vaccine has similar efficacy

  to DTaP3-SB (after immunisation at 2, 4 and 6 months), DTaP5-CON and

  DTwP-EVANS against culture-confirmed pertussis with > or =21 days cough in

  infants immunised according to a 3-, 5- and 12-month schedule. Infants

  immunised with DTaP3-CB experienced significantly fewer adverse events

  such as pain, redness, swelling and irritability than infants given DTwP.

  DTaP3-CB has a similar tolerability profile to other acellular vaccines

  and is associated with similar rates of local tenderness, irritability,

  fever (> or =40 degrees C) and persistent crying. Comparative trials have

  shown that infants immunised with DTaP3-CB had a lower incidence of pain

  at the site of injection and fever (> or =38 degrees C) compared with

  other acellular vaccines, although this may have little clinical

  significance. Concomitant administration of DTaP3-CB with hepatitis B,

  oral polio or Haemophilus influenzae type B vaccines did not affect the

  immunogenicity of these other paediatric vaccines. CONCLUSION: Data from

  clinical trials with DTaP3-CB vaccine indicate that this vaccine induces

  high and long lasting efficacy. It is at least as efficacious as most

  whole cell vaccines and generally similar in efficacy to the most

  efficacious acellular pertussis vaccines containing 3 or more pertussis

  antigens. DTaP3-CB is better tolerated than whole cell vaccines and has a

  similar tolerability profile to other acellular vaccines; the possible

  lower risk of severe adverse events remains to be confirmed. The low

  reactogenicity of DTaP3-CB is likely to make it well tolerated and

  therefore well accepted for the immunisation of infants, thereby enabling

  wider implementation of vaccination programmes. [References: 50]


1710. Authors

  Matsumura H.  Moriyama M.  Goto I.  Tanaka N.  Okubo H.  Arakawa Y.


  Natural course of progression of liver fibrosis in Japanese patients with

  chronic liver disease type C--a study of 527 patients at one



  Journal of Viral Hepatitis.  7(4):268-75, 2000 Jul.


  Patients with chronic hepatitis C infection show a gradual progression of

  fibrosis to liver cirrhosis and hepatocellular carcinoma (HCC). We studied

  whether the progression of liver fibrosis differed among Japanese subjects

  who were infected with different hepatitis C virus (HCV) genotypes. In 527

  patients we examined whether there was a relationship between gender, age,

  history of blood transfusion, interval between date of blood transfusion

  and date of liver biopsy or date of diagnosis of HCC, serum alanine

  aminotransferase level, platelet count or HCV genotype, with the extent of

  liver fibrosis, classified into four stages (F1-F4). Moreover, we compared

  the mean rate of liver fibrosis progression per year in patients with each

  HCV genotype. Patients who had a higher fibrosis score tended to be older,

  have a lower platelet count and a longer interval since blood transfusion

  than those who had a lower fibrosis score. The mean rate of liver fibrosis

  progression was 0.12 +/- 0.15 stages per year after the blood transfusion.

  However, the progression rate of liver fibrosis in patients who had

  received a blood transfusion when they were > or = 30 years of age was

  0.19 +/- 0.22, while the progression rate of liver fibrosis in the

  patients who had received a blood transfusion when they were < 30 years

  was 0.09 +/- 0.09. In conclusion, chronic hepatitis C is a progressive

  disease, and patients with genotype 1b, 2a and 2b have a similar rate of

  progression of liver fibrosis. Particular attention should be paid to

  patients who are infected with HCV when > or = 30 years of age, because

  intrahepatic fibrosis rapidly progresses in these patients.


1711. Authors

  Matsuoka S.  Uchiyama K.  Kuniyasu Y.  Niio Y.  Shima H.  Doai K.  Oishi

  S.  Nojiri Y.  Ogata H.


  Abnormal pulmonary accumulation of indium-111 chloride in pneumocystis

  carinii pneumonia as detected by bone marrow scintigraphy.


  Clinical Nuclear Medicine.  25(5):361-3, 2000 May.


  PURPOSE: Unusual pulmonary uptake of In-111 chloride in a patient with

  Pneumocystis carinii pneumonia and autoimmune hepatitis is described.

  METHOD: In-111 chloride bone marrow scintigraphy was performed to evaluate

  the bone marrow activity associated with pancytopenia in a 56-year-old

  woman with autoimmune hepatitis. RESULTS: An In-111 chloride bone marrow

  scan showed increased pulmonary uptake predominantly in both upper lung

  fields. P. carinii pneumonia was seen to be developing as an

  immunocompromised complication after treatment for autoimmune hepatitis.

  CONCLUSION: When In-111 chloride bone marrow scintigraphy shows increased

  uptake in the lungs of immunocompromised patients, a combined

  opportunistic inflammatory disease such as P. carinii pneumonia should be

  considered in the diagnosis.



1712. Authors

  Meral A.  Sevinir B.  Gunay U.


  Efficacy of immunization against hepatitis B virus infection in children

  with cancer.


  Medical & Pediatric Oncology.  35(1):47-51, 2000 Jul.


  BACKGROUND: The purpose of this study was to evaluate the impact of

  hepatitis B prophylaxis in preventing hepatitis B infection in children

  with malignancy. PROCEDURE: Between May, 1993, and September, 1998, a

  total of 151 children (95 boys, 56 girls), 29 (19%) with lymphoma, 58

  (39%) with leukemia, and 64 (42%) with solid tumor, were screened for

  hepatitis B virus (HBV). The mean age was 7. 5 +/- 2.5 years. Children

  with negative serology received active and/or passive immunization. HBsAg

  and anti-HBs were positive prior to vaccination in 16 (10%) and 17 (11%)

  children, respectively. One hundred eighteen children (78%) of one hundred

  fifty-one with negative serology were included in the vaccination program.

  The vaccine dose was 40 &mgr;g. Children with solid tumor and lymphoma

  received recombinant hepatitis B vaccine at diagnosis, repeated at months

  1, 2, and 12. Hyperimmunglobulin was administered monthly in children with

  leukemia during the intensive chemotherapy period. They were then

  vaccinated following the third month of maintenance therapy with the

  schedule described above. Anti-HBs titers were measured every 3 months,

  and titers above 10 mlU/ml were accepted as protective. RESULTS: Anti-HBs

  positivity after the first three doses was 77% in solid tumors, 88% in

  acute leukemia, and 48% in lymphomas. Anti-HBs positivity with respect to

  diagnosis in children completing the vaccination schedule was 94% in solid

  tumor, 90% in leukemia, and 74% in lymphoma (P > 0.05). Thirty-three

  percent of children have not received the fourth dose as yet. In total 78%

  of the children developed protective antibody titers with or without the

  fourth dose, and none was infected with HBV during 3 years of follow-up.

  Ten (39%) of twenty-six children who remained unresponsive to immunization

  were infected with HBV. CONCLUSIONS: These data reveal that HBV

  prophylaxis is necessary and that our vaccination schedule is effective in

  preventing HBV infection in these children. Copyright 2000 Wiley-Liss,



1713. Authors

  Merican I.


  Screening for hepatocellular carcinoma.


  Medical Journal of Malaysia.  51(1):12-7, 1996 Mar.


  Hepatocellular carcinoma (HCC) is one of the commonest cancers in Asian

  males. In Malaysia, it is one of the ten most common cancers amongst the

  male population. Most of our patients with HCC present to us rather late

  and almost all die within 4 months of diagnosis. HCC occurs more commonly

  in patients with cirrhosis associated with hepatitis B and C infections.

  Screening for HCC can lead to early detection of small tumours (< 5 cm)

  that are more amenable to surgical resection, resulting in improved

  survival rates. The average 5-year survival rate for those who have

  undergone surgical resection is 68% (range, 22-73%). Better results are

  obtained with the smaller tumours (< 2 cm in diameter). Patients with

  chronic hepatitis B and C infection especially those who are > 45 years of

  age, who have concomitant cirrhosis or have a family history of HCC should

  be examined every 3-6 months with periodic serum alpha-fetoprotein (AFP)

  measurements and abdominal ultrasound examinations. Abdominal ultrasound

  is useful in the detection of small tumours. While mass screening for HCC

  is not cost-effective in countries of low incidence of HCC, screening of

  high risk groups may be justified in countries with a high endemicity of

  HBV infection. Screening for HCC in Japan, Taiwan and China appears to

  yield better results than those in the West. Nonetheless, primary

  prevention with mass hepatitis B vaccination and blood donor screening for

  anti-HCV is expected to make a much greater impact in the control of HCC

  in the years to come.


1714. Authors

  Milkiewicz P.  Saksena S.  Hubscher SG.  Elias E.


  Wilson's disease with superimposed autoimmune features: report of two

  cases and review. [Review] [17 refs]


  Journal of Gastroenterology & Hepatology.  15(5):570-4, 2000 May.


  We describe two females, 15 and 23 years old, respectively, who presented

  with classical features of Wilson's disease (WD) and several features of

  autoimmune hepatitis (AIH). The first patient was initially diagnosed as

  AIH and treated with prednisolone which caused clinical improvement, with

  an increase of serum albumin from 22 to 30 g/L, and a decrease of

  aspartate aminotransferase from 103 to 47 U/L. Subsequent diagnosis of WD

  and introduction of penicillamine gave excellent improvement and complete

  normalization of liver function tests. The second patient, at first also

  diagnosed as having AIH, was treated with steroids and azathioprine with

  initial improvement, but subsequent deterioration. The diagnosis of WD was

  made 2 years after initial diagnosis of AIH, as the patient reached

  end-stage liver disease and required a transplant. Therefore,

  d-penicillamine treatment was not attempted. We conclude that, in patients

  with AIH, a thorough screening for WD is necessary, particularly when the

  response to steroid therapy is poor. Conversely, in patients suffering

  from WD with superimposed features of AIH, a combination of steroids and

  penicillamine may be of benefit. [References: 17]


1715. Authors

  Minutello M.  Zotti C.  Orecchia S.  Di Martino E.  Bastianoni I.  Ypma E.

  Ruggenini Moiraghi A.  Podda A.


  Dose range evaluation of a new inactivated hepatitis A vaccine

  administered as a single dose followed by a booster.


  Vaccine.  19(1):10-5, 2000 Aug 15.


  A total of 242 healthy adults were immunised with a first dose of an

  investigational inactivated hepatitis A vaccine. Three concentrations (3,

  6 and 12 EU [ELISA units]) of the experimental vaccine were used and

  compared to a licensed reference vaccine. The aim was to determine the

  antigenic concentration of the study vaccine inducing the highest

  seroconversion rate and anti-Hepatitis A virus (HAV) antibody response at

  2 weeks after the primary immunisation. A booster dose was given at month

  6. At 15 days after the primary immunisation the seroconversion rates in

  subjects vaccinated with the 6 and 12 EU vaccines were 78 and 94%,

  respectively. At 30 and 180 days after the primary immunisation the

  percentages of seropositivity were 100% for both groups. The antibody

  response to the 12 EU study vaccine was similar to that to the reference

  vaccine. The percentages of seropositivity at 15 and 180 days after the

  primary immunisation were 94 vs 93%, and 100 vs 93% in the experimental

  and reference vaccine respectively. Thus, because it induces early and

  lasting seroconversion, the 12 EU study vaccine seems to be the most

  effective as a high potency HAV vaccine.


1716. Authors

  O'Beirne J.  Patch D.  Holt S.  Hamilton M.  Burroughs AK.


  Alcoholic hepatitis-the case for intensive management. [Review] [18 refs]


  Postgraduate Medical Journal.  76(898):504-7, 2000 Aug.


  Alcoholic hepatitis is a common condition with a high mortality. Although

  treatment options for established alcoholic hepatitis are limited, many of

  the complications of this condition are preventable. This case report and

  discussion illustrate the important role of early diagnosis and

  intervention in this patient group. Important management points are

  stressed to aid physicians who may encounter this condition rarely.

  [References: 18]


1717. Authors

  Ohta A.  Sekimoto M.  Sato M.  Koda T.  Nishimura S.  Iwakura Y.  Sekikawa

  K.  Nishimura T.


  Indispensable role for TNF-alpha and IFN-gamma at the effector phase of

  liver injury mediated by Th1 cells specific to hepatitis B virus surface



  Journal of Immunology.  165(2):956-61, 2000 Jul 15.


  We report the development and characterization of a novel model of severe

  hepatitis induced against hepatitis B virus surface Ag (HBsAg). HBsAg was

  successfully targeted into the liver in soluble form. Using this unique

  property of HBsAg, we established a liver injury model induced by

  HBsAg-specific Th1 cells. Severe liver injury was induced in C57BL/6 mice

  by injection of HBsAg together with HBsAg-specific Th1 cells.

  Histochemical examination demonstrated extensive necroinflammatory hepatic

  lesions in these animals. Application of this liver injury model to mutant

  or gene knockout mice enabled us to define the effector mechanisms of Th1

  cells in fulminant hepatitis. When Fas-deficient lpr mice were used as

  recipients, a similar degree of liver injury was induced as in wild-type

  mice. Moreover, HBsAg-specific Th1 cells obtained from perforin-/- mice

  could induce severe liver injury in both wild-type and lpr mice. These

  results indicated that neither Fas ligand nor perforin are essential for

  Th1-mediated liver injury in this model. Pretreatment with anti-TNF-alpha

  mAb prevented liver injury, whereas severe liver injury was induced in

  TNF-alpha-/- mice. Moreover, IFN-gamma receptor-deficient mice were

  resistant to Th1-mediated liver injury. Therefore, TNF-alpha and

  IFN-gamma, which were produced by HBsAg-specific Th1 cells during the

  effector phase, appeared to be indispensable in the pathogenesis of

  fulminant hepatitis.


1718. Authors

  OiConnor JA.


  Acute and chronic viral hepatitis. [Review] [30 refs]


  Adolescent Medicine.  11(2):279-92, 2000 Jun.


  Viral hepatitis is the most common cause of acute and chronic hepatitis.

  The term viral hepatitis generally refers to infections resulting from one

  of the hepatotrophic viruses: hepatitis A, B, C, D, and E. The last 10

  years have brought many important advances in understanding the

  epidemiology, pathogenesis, molecular biology, and immunoprophylaxis of

  infections caused by hepatotrophic viruses. Development of sensitive and

  specific immunoassays has enabled detection of specific agents. This has

  allowed for identification of infected patients and monitoring response to

  therapy. Additionally, serologic markers have allowed for isolation of

  contaminated blood products and a reduction in the spread of disease. The

  remaining challenge is the application of this knowledge to the treatment

  and prevention of viral hepatitis. This article explores the risk factors,

  epidemiology, microbiology, clinical and laboratory diagnosis, treatment,

  and prevention of the hepatotrophic viral infections. [References: 30]


1719. Authors

  Par A.


  Diagnosis and management of chronic hepatitis C. [Review] [33 refs]


  Canadian Journal of Gastroenterology.  14 Suppl B:83B-88B, 2000 Jul-Aug.


  This mini-review is devoted to the main questions of diagnosis, treatment

  and prevention of chronic hepatitis C (CHC). Diagnosis of CHC is based on

  virological, biochemical and histological findings. The etiology of CHC

  should be proven by the presence of antibody to hepatitis C virus

  (anti-HCV) and detection of viral nucleic acid (HCV RNA), using

  qualitative and quantitative polymerase chain reaction or branched chain

  DNA techniques. Serum aminotransferase levels can reflect the biochemical

  activity of liver disease, while biopsy is very important in the grading

  and staging of the pathological process. The generally accepted treatment

  of CHC is interferon (IFN); however, recently, the combination of IFN with

  the oral nucleoside analogue ribavirin has become the therapy of choice,

  not only for relapsers but also for naive patients. Prevention of

  hepatitis C by vaccination is not yet available. Screening blood donors

  and members of high risk groups, as well as ensuring good public health

  measures, are imperative to inhibit the spread of HCV. [References: 33]


1720. Authors

  Roca B.  Gomez CJ.  Arnedo A.


  Adherence, side effects and efficacy of stavudine plus lamivudine plus

  nelfinavir in treatment-experienced HIV-infected patients.


  Journal of Infection.  41(1):50-4, 2000 Jul.


  OBJECTIVES: To evaluate adherence, side effects and efficacy of a modality

  of highly active antiretroviral therapy (HAART) in HIV-infected patients.

  METHODS: In a cohort, prospective study, 65 previously treated patients

  received stavudine plus lamivudine plus nelfinavir. Fifty-three

  participants (81%) had a history of intravenous drug use. Patients were

  evaluated at 3-month intervals. The association of adherence with

  demographic variables, hepatitis C virus infection, number of stopped

  antiretroviral regimens, HIV RNA level, CD4 cell count, and adverse

  effects to drugs was assessed. RESULTS: After a median follow-up of 12

  months, 30 participants (46%) showed adequate adherence in all visits. An

  association was observed between adherence and female sex: 18 of 47 men

  (38%) vs. 12 of 18 women (67%) presented adequate adherence in all visits

  (P=0. 0416). An association was also observed between adherence and low

  baseline HIV RNA level (P=0.0229). Discontinuation of treatment took place

  because of refusal to take medication in 11 participants (17%) and because

  of side effects in seven participants (11%). Undetectable HIV RNA level

  was achieved in 26 patients (40%) at 3 months and in lower percentages at

  months 6, 9 and 12. CONCLUSIONS: Overall adherence to the employed HAART

  regimen was poor. Female sex and low baseline HIV RNA were associated with

  better adherence. Refusal to take medications and side effects were the

  main reasons to stop therapy. At 3 months' follow-up, virological efficacy

  was achieved in 40% of patients. Copyright 2000


1721. Authors

  Roeckel IE.


  Commentary: Iron metabolism in hepatitis C infection. [Review] [11 refs]


  Annals of Clinical & Laboratory Science.  30(2):163-5, 2000 Apr.


  Hepatitis C virus (HCV) infections have started to decline, but up to

  10,000 deaths each year are the consequence of chronic liver disease,

  following the infection. Laboratory testing identifies HCV-infected

  individuals using positive recombinant immunoblot assays to detect the

  presence of the antibody; the diagnosis is confirmed by detecting HCV RNA

  in serum. HCV-infected patients who have large accumulations of hepatic

  iron have not responded well to interferon therapy, compared to patients

  with normal hepatic iron stores. Physicians who treat patients infected

  with HCV should be aware of the detrimental effect of excess liver iron on

  interferon therapy. The degree of hepatic iron overload should be assessed

  and the reason for the excess iron should be investigated. Phlebotomy is

  the most practical method for iron removal and is well tolerated by

  patients with HCV infection. [References: 11]


1722. Authors

  Rosen HR.  Gretch D.  Kaufman E.  Quan S.


  Humoral immune response to hepatitis C after liver transplantation:

  assessment of a new recombinant immunoblot assay.


  American Journal of Gastroenterology.  95(8):2035-9, 2000 Aug.


  OBJECTIVE: The immune control of infection with hepatitis C virus (HCV) is

  poorly understood; vigorous antibody responses to viral proteins seem to

  coexist with the virus and thus whether they are neutralizing remains

  controversial. HCV-related liver failure is the leading indication for

  orthotopic liver transplantation (OLT) worldwide. Attenuated antibody

  responses in immunosuppressed patients and decreased reliability compared

  to assessment of HCV RNA has hampered the use of antibody testing

  post-OLT. The goals of this current analysis were twofold: to determine

  the sensitivity of a prototype strip immunoblot assay (RIBA 3.0, Chiron

  Diagnostics) for the diagnosis of HCV post-OLT; to determine if there was

  a correlation between antibody response and severity of histological

  recurrence. METHODS: The study was comprised of 76 HCV-positive

  individuals divided into three patient groups: liver allograft recipients

  with evidence of mild or no histological recurrence (n = 52), liver

  allograft recipients with evidence of severe HCV recurrence and allograft

  cirrhosis (n = 12), and nontransplant patients being enrolled in an

  induction interferon trial (n = 12). All transplant patients had

  histological follow-up of at least 1 yr. RESULTS: Sixty of the 64 (94%)

  HCV-positive OLT recipients had 1+ reactivity to two or more recombinant

  antigens; three of the patients who lacked a detectable response had

  minimal histological recurrence and one had severe recurrence. All

  nontransplant patients demonstrated 4+ reactivity to at least two

  antigens, and 55/64 (86%) OLT recipients demonstrated this same level of

  reactivity. Seven of the nine patients lacking this high level of

  reactivity had evidence of minimal recurrence. Furthermore, the mean (+/-

  SEM) level of antibody reactivity for c100 (p = 0.04) and NS5 (p = 0.01)

  were significantly lower for patients with mild recurrence after OLT,

  compared to the other groups. The level of antibody reactivity was

  unrelated to HCV genotype or viral load. CONCLUSIONS: The recently

  developed RIBA 3.0 assay for detection of antibodies to HCV appears to be

  highly sensitive for the diagnosis of HCV post-OLT. In general, the level

  of antibody reactivity was comparable in the transplant patients and in

  nonimmunosuppressed controls. The pathogenic implications of the

  relatively diminished humoral response in patients with mild recurrence

  post-OLT are discussed.


1723. Authors

  Roubalova K.  Suchankova A.  Vitek A.  Sajdova J.


  Presence of herpes simplex virus (HSV) in peripheral leukocytes of patient

  who developed active HSV infection after bone marrow transplantation.


  Journal of Clinical Virology.  17(1):37-42, 2000 Jun.


  BACKGROUND: Despite of prophylactic antiviral therapy, latent HSV may be

  reactivated in bone marrow transplant (BMT) recipients and cause serious

  disease. Rapid diagnosis of HSV infection is needed to prompt institution

  of appropriate therapy. OBJECTIVES: We report a case of the allogenic BMT

  recipient, who developed ulcerative esophagitis which progressed to

  generalized HSV infection and graft versus host reaction (GVHR).We

  consider several diagnostic approaches to detection of active HSV

  infection in this patient. STUDY DESIGN: Polymerase chain reaction (PCR)

  was used to detect HSV DNA in esophageal biopsy specimens and peripheral

  leukocytes (PBL). Isolation of HSV in tissue culture was performed to

  prove infectious virus in swabs from mucocutaneous lesions or in PBL.

  RESULTS: Using PCR, HSV DNA was detected in peripheral leukocytes of the

  patient who had developed generalized HSV infection accompanied with

  hepatosplenomegaly and hepatitis. At that time, a fully infectious

  ACV-resistant HSV was isolated from his PBL. On the other hand, HSV DNA

  was not detected in PBL of other BMT-recipients with skin- or

  organ-localized infection. CONCLUSIONS: Presence of HSV-DNA in PBL of BMT

  recipients can signalize generalized HSV infection. Isolation of HSV from

  PBL by cocultivation with human fibroblasts can be used as an alternative

  diagnostic approach in these patients.


1724. Authors

  Schmitt HJ.  Knuf M.  Ortiz E.  Sanger R.  Uwamwezi MC.  Kaufhold A.


  Primary vaccination of infants with diphtheria-tetanus-acellular

  pertussis-hepatitis B virus- inactivated polio virus and Haemophilus

  influenzae type b vaccines given as either separate or mixed injections

  [see comments].


  Journal of Pediatrics.  137(3):304-12, 2000 Sep.


  OBJECTIVE: The aim of this open, multicenter, randomized trial was to

  evaluate the immunogenicity and reactogenicity of a candidate combined

  diphtheria-tetanus-acellular pertussis-hepatitis B virus-inactivated polio

  virus (DTaP-HBV-IPV) vaccine when given as either a mixed or as separate

  concomitant injections with Haemophilus influenzae type b (Hib) vaccine.

  STUDY DESIGN: A total of 359 subjects were randomized to receive either

  DTaP-HBV-IPV/Hib (mixed administration - 180 subjects) or DTaP-HBV-IPV +

  Hib (separate administration in opposite limbs - 179 subjects) at 2, 3,

  and 4 months of age. RESULTS: After vaccination, seroprotective antibody

  concentrations against diphtheria, tetanus, hepatitis B, and polio viruses

  and a high (> or = 97%) pertussis vaccine response were seen in almost all

  study participants. All subjects except one in the mixed administration

  group had postvaccination Hib anti-PRP antibody concentrations > or = 0.15

  microg/mL. Of subjects in the mixed and separate group, 77.2% (geometric

  mean antibody concentration, 2. 62 microg/mL) and 88.6% (geometric mean

  antibody concentration, 4.45 microg/mL) had Hib anti-PRP concentrations >

  or = 1 microg/mL, respectively. The addition of the Hib component to the

  5-component vaccine did not increase the incidence of local or general

  reactions. CONCLUSION: Both administrations of the candidate vaccine were

  found to be safe, immunogenic, and well tolerated. Although anti-PRP

  geometric mean antibody concentrations and the percent of subjects

  achieving the 1 microg/mL seroprotective level were lower after the mixed

  administration, they were in the range seen with monovalent Hib vaccines

  or with other DTaP-based/Hib combinations licensed in some European

  countries. Therefore both administrations have the potential to simplify

  childhood immunization.


1725. Authors

  Seeto RK.  Fenn B.  Rockey DC.


  Ischemic hepatitis: clinical presentation and pathogenesis.


  American Journal of Medicine.  109(2):109-13, 2000 Aug 1.


  BACKGROUND: The pathophysiology of ischemic hepatitis, otherwise known as

  "shock liver," is poorly understood, although it is believed to be the

  result of a reduction in systemic blood flow as typically occurs in shock.

  The aim of this study was to investigate the importance of this phenomenon

  as well as other clinical features in patients with ischemic

  hepatitis.METHODS: We identified a cohort of 31 patients (case group) who

  met the most commonly accepted definition of ischemic hepatitis (an acute

  reversible elevation in either the serum alanine or aspartate

  aminotransferase level of at least 20 times the upper limit of normal,

  excluding known causes of acute hepatitis or hepatocellular injury, in an

  appropriate clinical setting). We also evaluated the clinical features and

  serum aminotransferase levels in a cohort (the control group) of 31

  previously healthy patients who sustained major nonhepatic trauma at San

  Francisco General Hospital, a major trauma center. Both groups of patients

  had documented systolic blood pressures <75 mm Hg for at least 15 minutes.

  Clinical and hemodynamic (invasive and noninvasive) data were

  recorded.RESULTS: Despite the marked reduction in blood pressure, no

  patient in the control group developed ischemic hepatitis. The mean (+/-

  SD) peak serum aspartate aminotransferase level in the control group was

  only 78 +/- 72 IU, in contrast with a mean peak of 2,088 +/- 2,165 IU in

  the case group. All 31 patients with ischemic hepatitis had evidence of

  underlying organic heart disease, 29 (94%) of whom had right-sided heart

  failure.CONCLUSIONS: Systemic hypotension or shock alone did not lead to

  ischemic hepatitis in any patient. The vast majority of patients with

  ischemic hepatitis had severe underlying cardiac disease that had often

  led to passive congestion of the liver. These data lead us to propose that

  right-sided heart failure, with resultant hepatic venous congestion, may

  predispose the liver to hepatic injury induced by a hypotensive event.


1726. Authors

  Seltsam A.  Shukry-Schulz S.  Salama A.


  Vaccination-associated immune hemolytic anemia in two children.


  Transfusion.  40(8):907-9, 2000 Aug.


  BACKGROUND: Two children in whom acute autoimmune hemolytic anemia (AIHA)

  developed after vaccination were studied. CASE REPORTS: The children were

  a 20-month-old girl and a 21-month-old boy. The diagnosis of AIHA was made

  in accordance with established criteria (hemolysis, positive DAT, and lack

  of other reasons for the hemolysis). Serologic tests were performed

  according to standard technique. RESULTS: The girl experienced two attacks

  of hemolysis. The first episode occurred 2 weeks after oral polio

  vaccination, and the second episode was observed 7 months later, when she

  received a simultaneous vaccination against mumps, rubella, and measles.

  The DAT was strongly positive with anti-C3d. No autoantibodies were

  detectable in either episode. The boy experienced acute hemolysis a few

  days after a simultaneous revaccination against

  diphtheria-pertussis-tetanus, Haemophilus influenzae, hepatitis B, and

  polio. The DAT using anti-IgG was strongly positive, and the DAT performed

  with anti-C3d was weakly positive. CONCLUSION: Vaccination-induced AIHA

  resembles those forms of AIHA related to infectious diseases, and it may

  occur more frequently than has been reported.


1727. Authors

  Stevens AB.  Coyle PV.


  Hepatitis C virus: an important occupational hazard?. [Review] [74 refs]


  Occupational Medicine (Oxford).  50(6):377-82, 2000 Aug.


  Infection with Hepatitis C virus (HCV) is estimated to affect 3% of the

  world's population and is an important cause of liver disease. It is most

  commonly transmitted by percutaneous exposure. Although current evidence

  does not suggest an increased prevalence of HCV infection among healthcare

  workers, transmission of infection following occupational exposure has

  been demonstrated. An average transmission rate of 1.8%, following

  percutaneous injury, has been reported. The risk of transmission is higher

  from patients with viraemia, as measured by a positive polymerase chain

  reaction for HCV RNA. After exposure to HCV, healthcare workers should be

  actively followed up, initially using a test to detect viral RNA. This may

  facilitate earlier diagnosis and treatment. Recent reports in the UK, of

  transmission of infection to patients from HCV infected healthcare

  workers, have prompted a review of the appropriateness of HCV infected

  individuals undertaking exposure prone procedures. [References: 74]


1728. Authors

  Strassburg CP.  Manns MP.


  Autoimmune tests in primary biliary cirrhosis. [Review] [80 refs]


  Best Practice & Research in Clinical Gastroenterology.  14(4):585-99, 2000



  Primary biliary cirrhosis (PBC) is characterized by an immune mediated,

  irreversible destruction of the small intrahepatic bile ducts leading to

  progressive liver cirrhosis and frequently to liver failure. The course of

  the disease is variable and an early diagnosis is desirable to identify

  individuals with rapidly progressing disease, to initiate adequate

  therapeutic measures and to evaluate the necessity of liver

  transplantation. Serological tests represent the single most important

  diagnostic feature of PBC because liver histology, biochemistry, or

  clinical syndrome alone are not reliable in this respect. The molecular

  definition of the autoantigen targets of antimitochondrial antibodies

  (AMA) has resulted in the development of reproducible and effective

  serological testing strategies. AMA directed against the ketoacid

  dehydrogenase complex are highly disease-specific but not directed against

  liver-specific target structures. Despite a high disease specificity,

  their usefulness for predicting the course of disease, the timing of liver

  transplantation, or disease recurrence after transplantation is limited.

  The realization that about 5% of patients with PBC do not display AMA has

  led to the identification of PBC-specific antinuclear autoantibodies

  directed against the nuclear pore complex and other targets. The overlap

  of PBC with autoimmune hepatitis and primary sclerosing cholangitis

  represents a diagnostic challenge in which autoantibody determinations

  play a central role and contribute to the administration of suitable

  treatment options. Copyright 2000 Harcourt Publishers Ltd. [References:



1729. Authors

  Tanaka E.  Ohue C.  Aoyagi K.  Yamaguchi K.  Yagi S.  Kiyosawa K.  Alter



  Evaluation of a new enzyme immunoassay for hepatitis C virus (HCV) core

  antigen with clinical sensitivity approximating that of genomic

  amplification of HCV RNA.


  Hepatology.  32(2):388-93, 2000 Aug.


  The aim of this study was to analyze the clinical performance of a new

  enzyme immunoassay (EIA) for hepatitis C virus (HCV) core antigen in

  comparison with the reverse transcription polymerase chain reaction

  (RT-PCR). A total of 310 patients with acute or chronic hepatitis C, and

  132 HCV-negative controls were studied. Chemiluminescence EIA with

  monoclonal anti-HCV core antigen was used, and qualitative and

  quantitative commercial RT-PCRs and an in-house nested RT-PCR were

  performed. Compared with nested RT-PCR, the core antigen assay showed 97%

  sensitivity and 100% specificity in 75 patients with chronic hepatitis C

  and 132 controls. HCV core antigen was positive in 16 (94%) of 17 patients

  with acute hepatitis C at initial consultation. In 3 persons prospectively

  followed, core antigen was detected in the first available (1-3 weeks)

  post-transfusion sample. In 167 anti-HCV-positive individuals, 129 (77%)

  were viremic; core antigen was detected in 126 (98%) compared with 129

  (100%) for nested RT-PCR and 121 (94%) for the commercial RT-PCR. In 48

  patients with chronic hepatitis C treated with interferon alfa, the

  concentration of core antigen before treatment was significantly (P <.002)

  lower in patients with sustained response than in nonresponders. All

  responders had a sustained loss of core antigen, whereas all nonresponders

  remained core antigen positive. The concentrations of HCV core antigen and

  HCV RNA correlated significantly (n = 48, r =.627, P <.001). In

  conclusion, the HCV core antigen assay is useful for the diagnosis of

  acute and chronic hepatitis C, and for predicting and monitoring the

  effect of interferon alfa treatment.


1730. Authors

  Tanaka H.  Tsukuma H.  Kasahara A.  Hayashi N.  Yoshihara H.  Masuzawa M.

  Kanda T.  Kashiwagi T.  Inoue A.  Kato M.  Oshima A.  Kinoshita Y.  Kamada



  Effect of interferon therapy on the incidence of hepatocellular carcinoma

  and mortality of patients with chronic hepatitis C: a retrospective cohort

  study of 738 patients.


  International Journal of Cancer.  87(5):741-9, 2000 Sep 1.


  The effect of interferon on the long-term clinical outcome of patients

  with chronic hepatitis C remains unclear. This study included 594 patients

  with chronic hepatitis C who received interferon-alpha therapy (Interferon

  group) and 144 patients with chronic hepatitis C who did not receive

  interferon (Control group). The patients in the Interferon group were

  classified into the following three groups based on the response of the

  serum aminotransaminase level of the patient during and after completion

  of the therapy protocol: sustained responders (n = 175), transient

  responders (n = 165), and non-responders (n = 254). The age, sex, serum

  aminotransaminase level, platelet count, histological staging, hepatitis C

  virus (HCV) subtype, and HCV concentration at baseline were adjusted with

  the Cox proportional hazards model. The length of follow-up for assessment

  of the risk for developing hepatocellular carcinoma (HCC) was 57.2 +/-

  13.9 months in the Interferon group and 67.7 +/- 28.7 months in the

  Control group. Multivariate analysis showed that interferon therapy

  decreased the risk for developing HCC by 48% compared with that in the

  Control group (P = 0.064). The older the age, being male, having a low

  platelet count, and higher histological stage were independent factors

  associated with the development of HCC. The hazard rate ratio for

  development of HCC in the sustained responders, transient responders, and

  non-responders was 0.16 (95% confidence interval [CI]: 0.04-0.62), 0.27

  (95% CI: 0. 09-0.79), and 0.74 (95% CI: 0.37-1.48), respectively. During

  follow-up, 18 patients in the Interferon group died (10 from liver-related

  diseases) and 17 patients in the Control group died (10 from liver-related

  diseases). No sustained responder or transient responder in the Interferon

  group died of liver-related disease. The cumulative survival rates of the

  Interferon and Control groups were nearly identical during the first 5

  years following diagnosis. Thereafter, the cumulative survival rate of the

  Control group declined, resulting in an 8-year survival rate in the

  Interferon and Control groups of 97% and 81%, respectively (P = 0. 061).

  Similar trends were seen in the survival analysis of those who had died of

  liver disease: the 8-year survival rates of the Interferon and Control

  groups were 98% and 88%, respectively (P = 0. 32). Our study demonstrated

  that interferon therapy significantly lowered the incidence of HCC among

  patients with chronic hepatitis C who showed sustained normalization and

  among patients who showed transient normalization of the serum

  aminotransferase level after completion of interferon therapy. The

  survival analyses and determination of cause of death suggested that

  interferon therapy improves the long-term survival of chronic hepatitis C

  patients who respond to this therapy, possibly by decreasing mortality

  from liver-related diseases. Copyright 2000 Wiley-Liss, Inc.



  Teixeira R.  Pastacaldi S.  Papatheodoridis GV.  Burroughs AK.


  Recurrent hepatitis C after liver transplantation. [Review] [112 refs]


  Journal of Medical Virology.  61(4):443-54, 2000 Aug.


  Cirrhosis due to hepatitis C is now the commonest indication for liver

  transplantation in Western Europe and in the United States. Graft

  reinfection is almost universal. The natural history of recurrent

  hepatitis C ranges from minimal damage to cirrhosis in a few months or

  years. Different virus and host immune factors are involved in the

  pathogenesis of hepatitis and are determinants of the outcome. The

  association between immunosuppression and severity of HCV recurrence is

  conflicting and remains to be evaluated fully. The treatment of recurrent

  HCV disease with IFN or ribavirin, as monotherapy, is ineffective.

  Preliminary results from combination therapy, however, are encouraging.

  Currently, a reasonable approach would be to treat patients with

  histological and clinical disease progression. New approaches for the

  prophylaxis of recurrent hepatitis C are under evaluation but whether this

  treatment will influence the severity of liver disease or the outcome of

  recurrence is still unknown. Copyright 2000 Wiley-Liss, Inc. [References:



1732. Authors

  Thobe N.  Pilger P.  Jones MP.


  Primary hypothyroidism masquerading as hepatic encephalopathy: case report

  and review of the literature. [Review] [13 refs]


  Postgraduate Medical Journal.  76(897):424-6, 2000 Jul.


  A 74 year old woman with hepatitis C of long duration was admitted to

  hospital in hyperammonaemic coma. Despite aggressive treatment of hepatic

  encephalopathy, there was no clinical improvement. As part of her

  evaluation for other causes of altered mental status, she was found to be

  profoundly hypothyroid. Treatment with thyroid replacement hormone was

  accompanied by prompt normalisation of her mental status and

  hyperammonaemia. Hypothyroidism may exacerbate hyperammonaemia and

  portosystemic encephalopathy in patients with otherwise well compensated

  liver disease. Hyopthyroidism should be considered in the differential

  diagnosis of encephalopathy in patients with liver disease. [References:



1733. Authors

  Wang F.  Yoshida I.  Takamatsu M.  Ishido S.  Fujita T.  Oka K.  Hotta H.


  Complex formation between hepatitis C virus core protein and



  Biochemical & Biophysical Research Communications.  273(2):479-84, 2000

  Jul 5.


  The core protein (Core) of hepatitis C virus (HCV) has been known to play

  an important role in hepatocarcinogenesis. By using glutathione

  S-transferase (GST) pull-down assay, we show here that Core formed a

  complex with p21Waf1/Cip1/Sdi1 (p21) cell cycle regulator. The

  deletion-mapping analysis revealed that a portion near the N-terminus of

  Core (amino acids 24-52) and a C-terminal portion of p21 (amino acids

  139-164) were involved in the complex formation. The complex formation was

  not impaired by point mutations of p21 at residues 147, 149, and 150,

  which have been reported to abrogate interaction of p21 with proliferating

  cell nuclear antigen (PCNA), discriminating the Core-binding sequence from

  the PCNA-binding sequence. Due to the close vicinity of the binding sites,

  however, Core and PCNA competed with each other when interacting with p21.

  The distinct interaction between Core and p21 may provide a new aspect to

  the studies of HCV pathogenesis. Copyright 2000 Academic Press.


1734. Authors

  Woo PC.  Tsoi HW.  Leung HC.  Wong LP.  Wong SS.  Chan E.  Yuen KY.


  Enhancement by ampicillin of antibody responses induced by a protein

  antigen and a DNA vaccine carried by live-attenuated Salmonella enterica

  serovar Typhi.


  Clinical & Diagnostic Laboratory Immunology.  7(4):596-9, 2000 Jul.


  Live-attenuated Salmonella species are effective carriers of microbial

  antigens and DNA vaccines. In a mouse model, the immunoglobulin M (IgM)

  and total antibody levels directed toward the lipopolysaccharide of

  Salmonella enterica serovar Typhi were significantly enhanced at day 21

  after oral immunization with live-attenuated serovar Typhi (strain Ty21a)

  when ampicillin was concomitantly administered (P < 0.05 and P < 0.005,

  respectively). The heat-killed Ty21a-stimulated lymphocyte proliferation

  indices for the ampicillin group at day 21 were significantly higher than

  those for the normal saline (NS) group (P < 0.005, P < 0.001, and P <

  0.01) for all three doses of antigen (10(4), 10(5), and 10(6) heat-killed

  Ty21a per well, respectively). The 50% lethal doses for mice from the

  ampicillin and NS groups immunized with Ty21a with pBR322 after wild-type

  serovar Typhi challenge on day 24 were 3.4 x 10(7) and 5.0 x 10(6) CFU,

  respectively. The fecal bacterial counts for the ampicillin group at days

  1, 3, and 5 were significantly lower than those for the NS group (P <

  0.01, P < 0.01, and P < 0.05, respectively), and there was a trend toward

  recovery of Ty21a in a larger number of mice from the ampicillin group

  than from the NS group. Furthermore, the IgG2a levels directed toward

  tetanus toxoid were significantly enhanced at days 7 and 21 after oral

  immunization with Ty21a that carried the fragment c of tetanus toxoid when

  ampicillin was concomitantly administered (P < 0.05 and P < 0.005,

  respectively), and the IgM and total hepatitis B surface antibody levels

  were significantly enhanced at days 7 (P < 0.005 and P < 0.05,

  respectively) and 21 (P < 0.01 and P < 0.05, respectively) after oral

  immunization with Ty21a that carried the DNA vaccine that encodes

  hepatitis B surface antigen when ampicillin was concomitantly

  administered. The present observation may improve the efficacy of the

  protein antigens and DNA vaccines carried in live-attenuated bacteria, and

  further experiments should be carried out to determine the best

  antibiotics and dosage regimen to be used, as well as the best carrier

  system for individual protein antigens and DNA vaccines.


1735. Authors

  Yamaguchi N.  Tokushige K.  Yamauchi K.  Hayashi N.


  Humoral immune response in Japanese acute hepatitis patients with

  hepatitis C virus infection.


  Canadian Journal of Gastroenterology.  14(7):593-8, 2000 Jul-Aug.


  The humoral immune response to acute infection by hepatitis C virus (HCV)

  is not yet perfectly clear in terms of immunoglobulin (Ig) response,

  diversity of HCV antigen, and the relation with hepatitis severity and

  antibody response. Serum IgM and IgG anti-HCV levels in patients with HCV

  and either acute hepatitis (AH) or fulminant hepatitis (FH) were

  investigated; the diversity of HCV antigen was investigated by RIBA test

  III. Of 22 AH patients, 12 (54.5%) were positive for IgM anti-HCV, mainly

  reacting to HCV core protein. The mean interval until the appearance of

  IgM anti-HCV after onset was 24.1+/-26.2 days. IgG anti-HCV mainly reacted

  to both core and NS-3 antigen, appearing 42.6+/-42.1 days after onset.

  From a serial study of 15 AH patients, it was considered that in seven AH

  patients (46. 7%), the IgM response would precede the IgG response. In

  another two AH patients, IgM anti-HCV was not detected during the acute

  disease phase. Of 48 chronic hepatitis patients with HCV-RNA, 40 patients

  were positive for IgM anti-HCV. Therefore, IgM anti-HCV was useful for

  diagnosis in some of the AH patients, but it was difficult to use for

  distinguishing between acute and chronic infection. All four FH patients

  with HCV-RNA were positive for both IgM and IgG antibody to HCV at onset.

  Their antibody titres were higher than those of AH patients. These results

  suggested that, as in FH due to HBV, FH due to HCV could induce strong and

  rapid humoral immunity.


1736. Authors

  Zeuzem S.


  Gut-liver axis. [Review] [301 refs]


  International Journal of Colorectal Disease.  15(2):59-82, 2000 Apr.


  The gut and the liver are the key organs in nutrient absorption and

  metabolism. Bile acids, drugs, and toxins undergo extensive enterohepatic

  circulation. Bile acids play a major role in several hepatic and

  intestinal diseases. Endotoxins deriving from intestinal Gram-negative

  bacteria are important in the pathogenesis of liver and systemic diseases.

  Chronic liver diseases can influence gastrointestinal motility, which

  together with other factors may contribute to bacterial overgrowth and in

  patients with ascites to an increased risk of spontaneous bacterial

  peritonitis. Patients with end-stage liver disease frequently develop

  portal hypertension leading to varices, gastric vascular ectasia, and

  portal hypertensive gastroenteropathy. Several liver and biliary

  abnormalities are observed in patients with inflammatory bowel disease

  (primary sclerosing cholangitis, autoimmune hepatitis, cholelithiasis).

  The primary defect in hemochromatosis is located in the intestine, causing

  an inappropriate increase in iron absorption, and the liver is the site of

  earliest and heaviest iron deposition. Elevated transaminases are observed

  in many patients with celiac disease, and steatohepatitis frequently

  develops in patients with jejunoileal bypass and short bowel syndrome.

  Furthermore, the liver is the primary organ for metastasis of intestinal

  cancer. Many viral, bacterial, fungal, and parasitic diseases affect the

  intestine as well as the liver and the biliary tract. [References: 301]






2189. Bilezikci B.  Haberal AN.  Demirhan B.


  Hepatocyte growth factor in patients with three different stages of

  chronic liver disease including hepatocellular carcinoma, cirrhosis and

  chronic hepatitis: an immunohistochemical study.


  Canadian Journal of Gastroenterology.  15(3):159-65, 2001 Mar.


  BACKGROUND AND AIMS: The specific role of hepatocyte growth factor in

  liver disease is unknown. The presence and density of this factor in

  patients with three different stages of liver disease were investigated,

  with the aim of assessing its prognostic significance. PATIENTS AND

  METHODS: Liver specimens from patients with chronic hepatitis (n=20),

  cirrhosis (n=20), hepatocellular carcinoma (n=30) and normal livers (n=20)

  were immunohistochemically stained to determine the presence and density

  of hepatocyte growth factor. RESULTS: There were significantly more

  hepatocyte growth factor-positive Kupffer and Ito cells in all three

  diseased groups than in the control group. Also, there was significantly

  more positive staining in chronic hepatitis specimens than in specimens

  from the cirrhosis, hepatocellular carcinoma and control groups (P<0.05).

  The hepatoma cells in 10 of the hepatocellular carcinoma cases stained

  positive, but none of the hepatocytes in the chronic hepatitis, cirrhosis

  and normal liver specimens stained. It was only possible to assess

  nonmalignant hepatocytes adjacent to the hepatocellular carcinoma in the

  four resection specimens, and no staining for hepatocyte growth factor was

  observed in these areas. There was no statistical association between

  density of hepatocyte growth factor and histological activity index in

  chronic hepatitis, or between density of hepatocyte growth factor and

  grade of hepatocellular carcinoma. CONCLUSIONS: Similar to some previous

  reports, this study revealed that hepatoma cells can also express this

  growth factor. Immunohistochemical detection of hepatocyte growth factor

  may prove to be a useful method of diagnosing hepatocellular carcinoma in

  challenging cases.


2190. Chan AY.  Dieckhaus KD.  Ramsey WH.


  Cytomegalovirus hepatitis in a nontransplant patient with autoimmune

  hepatitis taking immunosuppressants.


  American Journal of Gastroenterology.  96(1):262-3, 2001 Jan.


2191. High KA.


  Gene transfer as an approach to treating hemophilia. [Review] [70 refs]


  Circulation Research.  88(2):137-44, 2001 Feb 2.


  Hemophilia is an X-linked bleeding diathesis caused by a deficiency of

  either factor VIII or factor IX. Present treatment for hemophilia involves

  intravenous infusion of either recombinant or plasma-derived clotting

  factor concentrates. Problems with this treatment method, including the

  expense, need for intravenous access, and risks of blood-borne disease

  transmission, have fueled an interest in developing a gene-transfer

  approach to treatment. On the basis of experience with protein concentrate

  therapy, it seems likely that even modest elevations in circulating levels

  of factor VIII or factor IX can prevent most of the mortality and much of

  the morbidity associated with the disease. Hemophilia has a number of

  advantages as a model system for working out strategies for gene transfer

  as an approach to the treatment of genetic diseases; these include wide

  latitude in choice of target tissue, a wide therapeutic window for levels

  of circulating factor, ease of determining therapeutic endpoints, and

  existence of excellent animal models of the disease. Preclinical studies

  over the last decade have recently culminated in the initiation of

  clinical trials of gene transfer for hemophilia A and B. Three trials,

  each using different vectors and target tissues, are presently underway,

  and two additional trials are in late planning stages. This report reviews

  the preclinical data underlying these strategies and the design of the

  ongoing and proposed clinical trials. [References: 70]


2192. Kato Y.  Nakata K.  Omagari K.  Kusumoto Y.  Mori I.  Furukawa R.  Tanioka

  H.  Tajima H.  Yano M.  Eguchi K.


  Clinical features of fulminant hepatitis in Nagasaki Prefecture, Japan.


  Internal Medicine.  40(1):5-8, 2001 Jan.


  OBJECTIVE: Fulminant hepatitis is a rare but fatal disease. In the present

  study, we examined the changes in etiology and prognosis of fulminant

  hepatitis in Nagasaki Prefecture, Japan between 1980 to 1999. METHODS:

  Eighty-one patients with fulminant hepatitis admitted to our hospitals

  from 1980 to 1999 were examined with respect to the etiology and

  prognosis. RESULTS: Fulminant hepatitis was due to hepatitis A virus in 2

  (12%) cases, hepatitis B virus in 18 (22%) cases, unknown etiology in 50

  (62%) cases, and drug-induced in 11(14%) cases. The number of cases in the

  first half of the study (1980-1989) was 47 and that of the latter half

  (1990-1999) was 34 cases. The incidence of fulminant hepatitis type B also

  decreased from 14 cases (30%) to 4 cases (12%) during these periods. The

  overall survival rate of fulminant hepatitis was 32%; it was equal in

  fulminant hepatitis type B, fulminant hepatitis of unknown etiology and

  fulminant drug-induced hepatitis. The survival rate of fulminant hepatitis

  type A was 100%, though only two cases were identified. Retrospectively,

  the survival rate in patients with a pre-encephalopathy period of < or =

  10 days and aged < or = 39 years was significantly higher than in patients

  > or = 40 years of age (p<0.01). There was no difference between the two

  age groups when pre-encephalopathy period was > or = 11 days. CONCLUSIONS:

  The incidence of fulminant hepatitis especially that of fulminant

  hepatitis type B in Nagasaki Prefecture has decreased in recent years. The

  survival rate is significantly higher in younger patients with a short

  pre-encephalopathy period.


2193. Malik AH.  Collins RH Jr.  Saboorian MH.  Lee WM.


  Chronic graft-versus-host disease after hematopoietic cell transplantation

  presenting as an acute hepatitis.


  American Journal of Gastroenterology.  96(2):588-90, 2001 Feb.


  A variety of illnesses involving the gut and liver follow hematopoietic

  cell transplantation (HCT). A 20 yr-old white male developed severe acute

  hepatitis 36 wk (day 252) after matched, unrelated, allogeneic HCT for

  chronic myelogenous leukemia (CML). Mild skin graft-versus-host disease

  (GVHD) had occurred at about 20 wk (day 140) after transplant. Liver

  biopsy showed bile duct injury and a diffuse lobular injury pattern most

  consistent with a GVHD variant and not reminiscent of drug-induced or

  viral hepatitis. No findings suggestive of herpesvirus, adenovirus, or

  varicella-zoster virus were found. High-dose steroids resulted in marked

  improvement of his liver enzyme levels. We report this patient as

  representing the acute hepatitic presentation of chronic GVHD of the



2194. Neubauer K.  Saile B.  Ramadori G.


  Liver fibrosis and altered matrix synthesis. [Review] [75 refs]


  Canadian Journal of Gastroenterology.  15(3):187-93, 2001 Mar.


  Liver fibrosis represents the uniform response of liver to toxic,

  infectious or metabolic agents. The process leading to liver fibrosis

  resembles the process of wound healing, including the three phases

  following tissue injury: inflammation, synthesis of collagenous and

  noncollagenous extracellular matrix components, and tissue remodelling

  (scar formation). While a single liver tissue injury can be followed by an

  almost complete restitution ad integrum, the persistence of the original

  damaging noxa results in tissue damage. During the establishment of liver

  fibrosis, the basement membrane components collagen type IV, entactin and

  laminin increase and form a basement membrane-like structure within the

  space of Disse. The number of endothelial fenestrae of the sinusoids

  decreases. These changes of the sinusoids are called 'capillarization'

  because the altered structure of the sinusoids resembles that of

  capillaries. At the cellular level, origin of liver fibrogenesis is

  initiated by the damage of hepatocytes, resulting in the recruitment of

  inflammatory cells and platelets, and activation of Kupffer cells, with

  subsequent release of cytokines and growth factors. The hepatic stellate

  cells seem to be the primary target cells for these inflammatory stimuli,

  because during fibrogenesis, they undergo an activation process to a

  myofibroblast-like cell, which represents the major matrix-producing cell.

  Based on this pathophysiological mechanism, therapeutic methods are

  developed to inhibit matrix synthesis or stimulate matrix degradation. A

  number of substances are currently being tested that either neutralize

  fibrogenic stimuli and prevent the activation of hepatic stellate cells,

  or directly modulate the matrix metabolism. However, until now, the

  elimination of the hepatotoxins has been the sole therapeutic concept

  available for the treatment of liver fibrogenesis in humans. [References:



2195. Sanyal A.


  Nonalcoholic steatohepatitis. [Review] [79 refs]


  Indian Journal of Gastroenterology.  20 Suppl 1:C64-70, 2001 Mar.


2196. Senyuz OF.  Yesildag E.  Emir H.  Tekant G.  Bozkurt P.  Sarimurat N.

  Soylet Y.


  Diagnostic laparoscopy in prolonged jaundice.


  Journal of Pediatric Surgery.  36(3):463-5, 2001 Mar.


  BACKGROUND: The early diagnosis of surgical jaundice in a neonate is an

  important step for the surgical success in extrahepatic biliary atresia.

  Diagnostic laparoscopy, as in many areas in surgery, is included in the

  conventional diagnostic methods of extrahepatic biliary atresia. METHODS:

  Since 1992, 24 infants with prolonged jaundice, in whom extrahepatic

  biliary atresia and neonatal hepatitis could not be differentiated with

  conventional diagnostic interventions, have been evaluated

  laparoscopically. RESULTS: A coarse, irregular, greenish-brown liver with

  some degree of fine angiomatous development and an atretic gallbladder are

  the findings of laparoscopic evaluation in an infant with extrahepatic

  biliary atresia. However, in neonatal hepatitis, the liver is smooth,

  sharp-edged, and chocolate brown in color, and simultaneously performed

  cholangiography should show the passage of the contrast material both into

  the proximal biliary tracts and the intestinal system. In this series, 10

  of 24 cases were proved to be neonatal hepatitis diagnosed by laparoscopy,

  so unnecessary laparotomy was avoided in 42% of the cases. CONCLUSION:

  When the diagnostic laparoscopy, in which the liver and the gallbladder

  are directly visualized, is combined with the cholangiographic

  examination, the most accurate and earlier diagnosis in an infant with

  prolonged jaundice can be achieved, and the important period of time for

  the surgical success in extrahepatic biliary atresia will be minimally



2197. Yoon SN.  Yoo BM.  Hwang KH.


  Hepatobiliary scintigraphy showing acute complete common bile duct

  obstruction in a patient with acute hepatitis.


  Clinical Nuclear Medicine.  26(2):151-2, 2001 Feb.



2198. Zen Y.  Katayanagi K.  Tsuneyama K.  Harada K.  Araki I.  Nakanuma Y.


  Hepatocellular carcinoma arising in non-alcoholic steatohepatitis.


  Pathology International.  51(2):127-31, 2001 Feb.


  The incidence and significance of hepatocellular carcinoma (HCC) in

  non-alcoholic steatohepatitis (NASH) has not been previously evaluated in

  detail. We recently experienced a case of NASH with multicentric HCC in a

  female patient. At the age of 58 years, the patient was diagnosed with

  non-insulin-dependent diabetes mellitus, treated by insulin therapy. The

  patient did not drink alcohol. She was negative for all serological

  markers of hepatitis B and C virus infection. Because of liver

  dysfunction, a needle biopsy was performed at the age of 62 years, and

  pathological findings, such as fatty change, Mallory's body, nuclear

  glycogen and pericellular fibrosis, suggested a diagnosis of NASH.

  Subsequently, four nodules were detected in the liver by imaging. Liver

  biopsies were performed from each nodule. One nodule was pathologically

  diagnosed as a pseudolymphoma, while three other nodules were moderately

  differentiated HCC (10 years after the diagnosis of non-alcoholic

  steatohepatitis), well-differentiated HCC (11 years later) and dysplastic

  nodule (11 years later), suggesting multicentric occurrence of HCC. This

  case suggests that HCC could be a late complication of NASH.



2735.    Abass F.  Thomas RD.  Rajkumar A.  Gupta N.  Puliyel JM. Controlling perinatally acquired hepatitis B. Indian Journal of Pediatrics.  68(4):365, 2001 Apr.

2736.    Ahmed A.  Samuels SL.  Keeffe EB.  Cheung RC. Delayed fatal hemorrhage from pseudoaneurysm of the hepatic artery after percutaneous liver biopsy. American Journal of Gastroenterology.  96(1):233-7, 2001 Jan.

2737.    Alper J. Searching for medicine's sweet spot. Science.  291(5512):2338-43, 2001 Mar 23.

2738.    Anonymous. From the Centers for Disease Control and Prevention. Impact of the 1999 AAP/USPHS Joint Statement on Thimerosal in Vaccines on Infant Hepatitis B Vaccination Practices. American Academy of Pediatrics/U.S. Public Health Service.  JAMA.  285(12):1568-70, 2001 Mar 28.

2739.    Anonymous. From the Centers for Disease Control and Prevention. Recommended childhood immunization schedule--United States, 2001. JAMA. 285(7):875-6, 2001 Feb 21.

2740.    Anonymous. Impact of the 1999 AAP/USPHS joint statement on thimerosal in vaccines on infant hepatitis B vaccination practices. MMWR - Morbidity & Mortality Weekly Report.  50(6):94-7, 2001 Feb 16.

2741.    Anonymous. Recommended childhood immunization schedule--United States, 2001. MMWR - Morbidity & Mortality Weekly Report.  50(1):7-10, 19, 2001 Jan 12.

2742.    Ascherio A.  Zhang SM.  Hernan MA.  Olek MJ.  Coplan PM.  Brodovicz K.  Walker AM.  Hepatitis B vaccination and the risk of multiple sclerosis. [see comments]. New England Journal of Medicine.  344(5):327-32, 2001 Feb 1.

2743.    Authier FJ.  Cherin P.  Creange A.  Bonnotte B.  Ferrer X.  Abdelmoumni A.  Ranoux D.  Pelletier J.  Figarella-Branger D.  Granel B.  Maisonobe T.  Coquet M.  Degos JD.  Gherardi RK. Central nervous system disease in patients with macrophagic myofasciitis. Brain.  124(Pt 5):974-83, 2001 May.

2744.    Bah E.  Parkin DM.  Hall AJ.  Jack AD.  Whittle H. Cancer in the Gambia: 1988-97.  British Journal of Cancer.  84(9):1207-14, 2001 May 4.

2745.    Bates I.  Bedu-Addo G.  Jarrett RF.  Schulz T.  Wallace S.  Armstrong A.  Sheldon J.  Rutherford T.  B-lymphotropic viruses in a novel tropical splenic lymphoma. British Journal of Haematology.  112(1):161-6, 2001 Jan.

2746.    Berger A.  Preiser W.  Doerr HW. The role of viral load determination for the management of human immunodeficiency virus, hepatitis B virus and hepatitis C virus infection. [Review] [39 refs]  Journal of Clinical Virology.  20(1-2):23-30, 2001 Jan.

2747.    Brecher LS.  Cymet TC. A practical approach to fibromyalgia. [Review] [45 refs]  Journal of the American Osteopathic Association.  101(4 Suppl Pt 2):S12-7, 2001 Apr.

2748.    Bryan JP.  McCardle P.  South-Paul JE.  Fogarty JP.  Legters LJ.  Perine PL. Randomized controlled trial of concurrent hepatitis A and B vaccination. Military Medicine.  166(2):95-101, 2001 Feb.

2749.    Caldwell SH.  Hespenheide EE.  von Borstel RW. Myositis, microvesicular hepatitis, and progression to cirrhosis from troglitazone added to simvastatin. Digestive Diseases & Sciences.  46(2):376-8, 2001 Feb.

2750.    Calleja JL.  Albillos A.  Rossi I.  Moreno R.  Domper F.  Martinez JL.  Escartin P. Time course of serum hepatitis C virus-RNA during chronic hepatitis C treatment accurately predicts the type of response. Alimentary Pharmacology & Therapeutics.  15(2):241-9, 2001 Feb.

2751.    Chan CH.  Hadlock KG.  Foung SK.  Levy S. V(H)1-69 gene is preferentially used by hepatitis C virus-associated B cell lymphomas and by normal B cells responding to the E2 viral antigen. Blood.  97(4):1023-6, 2001 Feb 15.

2752.    Chodick G.  Lerman Y.  Peled T.  Aloni H.  Ashkenazi S. Cost-benefit analysis of active vaccination campaigns against hepatitis A among daycare centre personnel in Israel.  Pharmacoeconomics.  19(3):281-91, 2001.

2753.    Christenson  JC.  Fischer  PR.  Hale  DC.  Derrick  D. Pediatric travel consultation in an integrated clinic.  Journal of Travel Medicine.  8(1):1-5, 2001 Jan-Feb.

2754.    Colombo M. Screening for cancer in viral hepatitis. [Review] [60 refs] Clinics in Liver Disease.  5(1):109-22, 2001 Feb.

2755.    Daar ES.  Lynn H.  Donfield S.  Gomperts E.  Hilgartner MW.  Hoots WK.  Chernoff D.  Arkin S.  Wong WY.  Winkler CA.  The Hemophilia Growth and Development Study.   Relation between HIV-1 and hepatitis C viral load in patients with hemophilia.  Journal of Acquired Immune Deficiency Syndromes.  26(5):466-72, 2001 Apr 15.

2756.    Davidovici B.  Karakis I.  Bourboulia D.  Ariad S.  Zong J.  Benharroch D.  Dupin N.  Weiss R.  Hayward G.  Sarov B.  Boshoff C. Seroepidemiology and molecular epidemiology of Kaposi's sarcoma-associated herpesvirus among Jewish population groups in Israel.  Journal of the National Cancer Institute.  93(3):194-202, 2001 Feb 7.

2757.    Doshi AV.  Desai D.  Bhaduri A.  Udwadia ZF. Lymphocytic interstitial pneumonitis associated with autoimmune hepatitis. Indian Journal of Gastroenterology.  20(2):76-7, 2001 Mar-Apr.

2758.    Dudas J.  Kovalszky I.  Gallai M.  Nagy JO.  Schaff Z.  Knittel T.  Mehde M.  Neubauer K.  Szalay F.  Ramadori G. Expression of decorin, transforming growth factor-beta 1, tissue inhibitor metalloproteinase 1 and 2, and type IV collagenases in chronic hepatitis.  American Journal of Clinical Pathology.  115(5):725-35, 2001 May.

2759.    Ericsson  CD. Travel medicine: key to improved adult vaccination against Hepatitis A and B. [letter; comment].  Journal of Travel Medicine.  8 Suppl 1:S1-2, 2001 Jan.

2760.    Faustini A.  Franco E.  Sangalli M.  Spadea T.  Calabrese RM.  Cauletti M.  Perucci CA. Persistence of anti-HBs 5 years after the introduction of routine infant and adolescent vaccination in Italy. Vaccine.  19(20-22):2812-8, 2001 Apr 6.

2761.    Fisher MA.  Eklund SA.  James SA.  Lin X. Adverse events associated with hepatitis B vaccine in U.S. children less than six years of age, 1993 and 1994. Annals of Epidemiology.  11(1):13-21, 2001 Jan.

2762.    Fracanzani AL.  Conte D.  Fraquelli M.  Taioli E.  Mattioli M.  Losco A.  Fargion S. Increased cancer risk in a cohort of 230 patients with hereditary hemochromatosis in comparison to matched control patients with non-iron-related chronic liver disease. Hepatology.  33(3):647-51, 2001 Mar.

2763.    Gilbert P.  Self S.  Rao M.  Naficy A.  Clemens J. Sieve analysis: methods for assessing from vaccine trial data how vaccine efficacy varies with genotypic and phenotypic pathogen variation. [Review] [65 refs] Journal of Clinical Epidemiology.  54(1):68-85, 2001 Jan.

2764.    Gout O. Vaccinations and multiple sclerosis. New England Journal of Medicine.  344(23):1794; discussion 1795, 2001 Jun 7.

2765.    Harcourt C.  van Beek I.  Heslop J.  McMahon M.  Donovan B. The health and welfare needs of female and transgender street sex workers in New South Wales. Australian & New Zealand Journal of Public Health.  25(1):84-9, 2001.

2766.    Herold C.  Heinz R.  Radespiel-Troger M.  Schneider HT.  Schuppan D.  Hahn EG. Quantitative testing of liver function in patients with cirrhosis due to chronic hepatitis C to assess disease severity. Liver.  21(1):26-30, 2001 Feb.

2767.    Hostetler L. Vaccinations and multiple sclerosis. New England Journal of Medicine.  344(23):1795, 2001 Jun 7.

2768.    Hsu HM.  Lee SC.  Wang MC.  Lin SF.  Chen DS. Efficacy of a mass hepatitis B immunization program after switching to recombinant hepatitis B vaccine: a population-based study in Taiwan.  Vaccine.  19(20-22):2825-9, 2001 Apr 6.

2769.    Imbert-Bismut F.  Ratziu V.  Pieroni L.  Charlotte F.  Benhamou Y.  Poynard T.  MULTIVIRC Group. Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study. Lancet.  357(9262):1069-75, 2001 Apr 7.

2770.    Iwata M.  Sasaki M.  Harada K.  Kaneko S.  Kobayashi K.  Adachi K.  Sasaki M.  Nakanuma Y. Intrahepatic cholangitis and arteritis after transcatheter arterial embolization in a patient with tumor-like lesion-associated autoimmune hepatitis. Pathology, Research & Practice.  197(1):59-63, 2001.

2771.    Jonsson JR.  Hong C.  Purdie DM.  Hawley C.  Isbel N.  Butler M.  Balderson GA.  Clouston AD.  Pandeya N.  Stuart K.  Edwards-Smith C.  Crawford DH.  Fawcett J.  Powell EE. Role of cytokine gene polymorphisms in acute rejection and renal impairment after liver transplantation. Liver Transplantation.  7(3):255-63, 2001 Mar.

2772.    Jungkind D. Automation of laboratory testing for infectious diseases using the polymerase chain reaction-- our past, our present, our future. [Review] [16 refs]  Journal of Clinical Virology.  20(1-2):1-6, 2001 Jan.

2773.    Kalkeri G.  Khalap N.  Garry RF.  Fermin CD.  Dash S. Hepatitis C virus protein expression induces apoptosis in HepG2 cells. Virology.  282(1):26-37, 2001 Mar 30.

2774.    Kita H.  Mackay IR.  Van De Water J.  Gershwin ME.  The lymphoid liver: considerations on pathways to autoimmune injury. [Review] [140 refs]  Gastroenterology.  120(6):1485-501, 2001 May.

2775.    Kulkarni R.  Scott-Emuakpor AB.  Brody H.  Weil WB.  Ragni MV.  Gera R.  Nondisclosure of human immunodeficiency virus and hepatitis C virus coinfection in a patient with hemophilia: medical and ethical considerations. Journal of Pediatric Hematology/Oncology.  23(3):153-8, 2001 Mar-Apr.

2776.    Lee CH.  Choi YH.  Yang SH.  Lee CW.  Ha SJ.  Sung YC. Hepatitis C virus core protein inhibits interleukin 12 and nitric oxide production from activated macrophages. Virology.  279(1):271-9, 2001 Jan 5.

2777.    Lerose R.  Molinari R.  Rocchi E.  Manenti F.  Villa E. Prognostic features and survival of hepatocellular carcinoma in Italy: impact of stage of disease. European Journal of Cancer.  37(2):239-45, 2001 Jan.

2778.    Liu ZX.  Govindarajan S.  Okamoto S.  Dennert G. Fas-mediated apoptosis causes elimination of virus-specific cytotoxic T cells in the virus-infected liver. Journal of Immunology.  166(5):3035-41, 2001 Mar 1.

2779.    Macdonald GA. Pathogenesis of hepatocellular carcinoma. [Review] [106 refs] Clinics in Liver Disease.  5(1):69-85, 2001 Feb.

2780.    Maddrey WC. Hepatitis B--an important public health issue. [Review] [33 refs]  Clinica y Laboratorio.  47(1-2):51-5, 2001.

2781.    Majumder M.  Ghosh AK.  Steele R.  Ray R.  Ray RB. Hepatitis C virus NS5A physically associates with p53 and regulates p21/waf1 gene expression in a p53-dependent manner.  Journal of Virology.  75(3):1401-7, 2001 Feb.

2782.    Marie I.  Levesque H.  Tranvouez JL.  Francois A.  Riachi G.  Cailleux N.  Courtois H.  Autoimmune hepatitis and systemic sclerosis: a new overlap syndrome?. Rheumatology (Oxford).  40(1):102-6, 2001 Jan.

2783.    Meng SD.  Gao T.  Gao GF.  Tien P. HBV-specific peptide associated with heat-shock protein gp96. Lancet.  357(9255):528-9, 2001 Feb 17.

2784.    Minkovitz CS.  Belote AD.  Higman SM.  Serwint JR.  Weiner JP. Effectiveness of a practice-based intervention to increase vaccination rates and reduce missed opportunities. Archives of Pediatrics & Adolescent Medicine.  155(3):382-6, 2001 Mar.

2785.    Oram RJ.  Daum RS.  Seal JB.  Lauderdale DS. Impact of recommendations to suspend the birth dose of hepatitis B virus vaccine.  JAMA.  285(14):1874-9, 2001 Apr 11.

2786.    Park GJ.  Mann SP.  Ngu MC. Acute hepatitis induced by Shou-Wu-Pian, a herbal product derived from Polygonum multiflorum. Journal of Gastroenterology & Hepatology.  16(1):115-7, 2001 Jan.

2787.    Perrillo RP. Acute flares in chronic hepatitis B: the natural and unnatural history of an immunologically mediated liver disease. [Review] [124 refs] Gastroenterology.  120(4):1009-22, 2001 Mar.

2788.    Post JJ.  Dolan KA.  Whybin LR.  Carter IW.  Haber PS.  Lloyd AR. Acute hepatitis C virus infection in an Australian prison inmate: tattooing as a possible transmission route. Medical Journal of Australia.  174(4):183-4, 2001 Feb 19.

2789.    Randhawa P.  Blakolmer K.  Kashyap R.  Raikow R.  Nalesnik M.  Demetris AJ.  Jain A. Allograft liver biopsy in patients with Epstein-Barr virus-associated posttransplant lymphoproliferative disease. American Journal of Surgical Pathology.  25(3):324-30, 2001 Mar.

2790.    Rayes N.  Seehofer D.  Hopf U.  Neuhaus R.  Naumann U.  Bechstein WO.  Neuhaus P.   Comparison of famciclovir and lamivudine in the long-term treatment of hepatitis B infection after liver transplantation.  Transplantation.  71(1):96-101, 2001 Jan 15.

2791.    Read SJ. Recovery efficiences on nucleic acid extraction kits as measured by quantitative LightCycler PCR. Molecular Pathology.  54(2):86-90, 2001 Apr.

2792.    Rinaldi M.  Ria F.  Parrella P.  Signori E.  Serra A.  Ciafre SA.  Vespignani I.  Lazzari M.  Farace MG.  Saglio G.  Fazio VM. Antibodies elicited by naked DNA vaccination against the complementary-determining region 3 hypervariable region of immunoglobulin heavy chain idiotypic determinants of B-lymphoproliferative disorders specifically react with patients' tumor cells. Cancer Research.  61(4):1555-62, 2001 Feb 15.

2793.    Schaffer JV.  Davidson DM.  McNiff JM.  Bolognia JL. Perinuclear antineutrophilic cytoplasmic antibody-positive cutaneous polyarteritis nodosa associated with minocycline therapy for acne vulgaris. Journal of the American Academy of Dermatology.  44(2):198-206, 2001 Feb.

2794.    Shor A. A pathologist's view of organisms and human atherosclerosis. Journal of Infectious Diseases.  183(9):1428-9, 2001 May 1.

2795.    Siddiqui F.  Mutchnick M.  Kinzie J.  Peleman R.  Naylor P.  Ehrinpreis M. Prevalence of hepatitis A virus and hepatitis B virus immunity in patients with polymerase chain reaction-confirmed hepatitis C: implications for vaccination strategy. American Journal of Gastroenterology.  96(3):858-63, 2001 Mar.

2796.    Smieja M.  Cronin L.  Levine M.  Goldsmith CH.  Yusuf S.  Mahony JB. Previous exposure to Chlamydia pneumoniae, Helicobacter pylori and other infections in Canadian patients with ischemic heart disease.  Canadian Journal of Cardiology.  17(3):270-6, 2001 Mar.

2797.    Soussan P.  Pol S.  Garreau F.  Brechot C.  Kremsdorf D. Vaccination of chronic hepatitis B virus carriers with preS2/S envelope protein is not associated with the emergence of envelope escape mutants.  Journal of General Virology.  82(Pt 2):367-71, 2001 Feb.

2798.    Sturkenboom MC.  Fourrier A.  Vaccinations and multiple sclerosis. New England Journal of Medicine.  344(23):1794; discussion 1795, 2001 Jun 7.

2799.    Tseng CT.  Miskovsky E.  Houghton M.  Klimpel GR. Characterization of liver T-cell receptor gammadelta T cells obtained from individuals chronically infected with hepatitis C virus (HCV): evidence for these T cells playing a role in the liver pathology associated with HCV infections.  Hepatology.  33(5):1312-20, 2001 May.

2800.    Ulrich RG.  Bacon JA.  Brass EP.  Cramer CT.  Petrella DK.  Sun EL. Metabolic, idiosyncratic toxicity of drugs: overview of the hepatic toxicity induced by the anxiolytic, panadiplon. [Review] [73 refs] Chemico-Biological Interactions.  134(3):251-70, 2001 May 16.

2801.    Viswanathan C. Are our donors safe?. Indian Journal of Pediatrics.  68(1):69-75, 2001 Jan.

2802.    Walewski JL.  Keller TR.  Stump DD.  Branch AD. Evidence for a new hepatitis C virus antigen encoded in an overlapping reading frame.  Rna.  7(5):710-21, 2001 May.

2803.    Webster G.  Barnes E.  Dusheiko G.  Franklin I.  Protecting travellers from hepatitis A. BMJ.  322(7296):1194-5, 2001 May 19.

2804.    Weisbord JS.  Koumans EH.  Toomey KE.  Grayson C.  Markowitz LE. Sexually transmitted diseases during pregnancy: screening, diagnostic, and treatment practices among prenatal care providers in Georgia. Southern Medical Journal.  94(1):47-53, 2001 Jan.

2805.    Whitehead MW.  Hainsworth I.  Kingham JG. The causes of obvious jaundice in South West Wales: perceptions versus reality. Gut.  48(3):409-13, 2001 Mar.

2806.    Wickens K.  Crane J.  Kemp T.  Lewis S.  D'Souza W.  Sawyer G.  Stone L.  Tohill S.  Kennedy J.  Slater T.  Rains N.  Pearce N.  A case-control study of risk factors for asthma in New Zealand children.  Australian & New Zealand Journal of Public Health.  25(1):44-9, 2001.

2807.    Zhu J.  Nieto FJ.  Horne BD.  Anderson JL.  Muhlestein JB.  Epstein SE.  Prospective study of pathogen burden and risk of myocardial infarction or death. Circulation.  103(1):45-51, 2001 Jan 2.


Back to Reference