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Biomedical subjects

H C Thomas

Publications and source records attributed to H C Thomas.

At least 181 records · Page 10Linked to original sources
PubMed1990

Antiviral therapy: hepatitis B.

Antiviral therapy for chronic hepatitis B virus infection can result in clearance of replicating virus from the liver and prevention of progression to cirrhosis in a substantial proportion of patients. Adenosine arabinoside monophosphate, a potent inhibitor of HBV replication, is of limited usefulness because it causes significant neuromuscular toxicity. Acyclovir alone is relatively nontoxic, but is clinically ineffective in eliminating HBV from the liver. Lymphoblastoid or recombinant alpha-interferons are the best option at present and offer up to a 50% chance of long-term inhibition of HBV replication (with only minor side-effects) in patients who acquire the infection in adulthood. However alpha-interferon therapy alone is not effective when infection is acquired from birth. In this latter group of patients, prednisolone pre-treatment followed by alpha-interferon is currently under evaluation.

Antiviral Agents↗
PubMed1990

Hepatitis C virus antibodies in subjects with and without liver disease in the United Kingdom.

The prevalence of antibody to hepatitis C virus, evidence of previous or current infection with this agent of parenterally transmitted non-A, non-B hepatitis, was determined in 340 subjects residing in the United Kingdom. The antibody was detected in 3 per cent of unselected blood donors and in 60 per cent of patients with chronic post-transfusion non-A, non-B hepatitis. Evidence for infection was also found in 30 per cent of intravenous drug abusers, and in 75 per cent of haemophiliacs receiving commercial factor VIII concentrate. The infection is uncommon in renal units and amongst sexually promiscuous groups attending sexually-transmitted disease clinics. Although the seropositivity rate in primary biliary cirrhosis and chronic B and delta hepatitis was very low (0-2 per cent), in patients with autoimmune and alcoholic liver disease it was 14-16 per cent which, although lower than that quoted in studies from Spain and Italy, is considerably higher than would be expected by chance. The reason for the high incidence of non-A, non-B hepatitis in this latter group of patients is unclear.

Blood Donors↗
PubMed1990

Cloning and expression of an immunodominant region of the hepatitis delta antigen.

A cDNA clone prepared from hepatitis delta virus (HDV) RNA extracted from human serum was subcloned in the bacterial expression vector pPL31 to produce a fusion protein consisting of the first 98 amino acids of MS2 polymerase and of 64 amino acids from near the N-terminal region of hepatitis delta antigen (HDAg). The fusion protein was shown to be related to HDAg by a commercial sandwich immunoassay (Abbott) and immunoblotting with human anti-HDAg serum. Antiserum against the fusion protein was raised in rabbits and used to identify HDAg extracted from the serum and liver of an HDV-infected woodchuck and chimpanzee and from the serum of an HDV-infected human, by immunoblotting and immunohistology. A single, major polypeptide of 24K was detected in both serum and liver extracts, with a minor polypeptide of 26K sometimes present. Liver extracts also contained lower Mr polypeptides thought to be degradation products, the major species being 22.5K. The same pattern of staining was obtained with human anti-HDAg serum. Absorption experiments with the expressed protein and cross-competition experiments with the rabbit antiserum suggest that a major immunodominant region of HDAg is present near the N-terminal end of the antigen, between positions 1561 and 1368 on the genome. Both the expressed protein and rabbit antiserum were shown to be good diagnostic reagents.

Amino Acid Sequence↗
PubMed1990

Cloning and sequencing of RNA of hepatitis delta virus isolated from human serum.

The RNA of hepatitis delta virus (HDV) 1682 nucleotides long, has been cloned from a human serum isolate. Comparison with the three complete published sequences shows that a region of the HDV genome, between positions 620 and 1350, which contains sequences involved in replication and possibly pathogenicity, is highly conserved.

Animals↗
PubMed1990

Histological and immunohistochemical study of hepatitis B virus in human immunodeficiency virus infection.

Because the risk factors for human immunodeficiency virus (HIV) infection and hepatitis B (HBV) are similar and therefore coinfection is not uncommon, a detailed histological and immunohistochemical study of chronic hepatitis B infection in a group of 20 HIV positive Caucasian males (who did not have AIDS) and 30 HIV negative controls were undertaken. Using both the conventional histological classification and the Knodell histological activity index it was shown that HIV negative patients were more likely to have active disease and also more scarring than HIV positive patients. Hepatitis B surface antigen (HBsAg) expression was not significantly different between the two groups but expression of hepatitis Be antigen (HBeAg) and HBV-DNA polymerase was greater in those who were HIV positive. HIV positive patients are therefore more likely to have immunohistochemical markers of active viral replication, although histologically, liver disease is less severe. These findings have important implications for assessing the biopsy specimens in this group of patients and for treatment strategies aimed at improving their immune function.

Adult↗
PubMed1990

Haemorrhagic pancreatitis--a cause of death in severe potassium permanganate poisoning.

Severe potassium permanganate poisoning (more than 10 g of potassium permanganate) is invariably associated with massive systemic upset and death. Multiple organ damage has been recognized as an inevitable consequence of such an overdose, although pancreatitis has not been previously reported. Death due to cardiovascular collapse and profound hypotension is a common end point in those who reach hospital, but the pathogenesis is uncertain. We report a case of haemorrhagic pancreatitis following an overdose of potassium permanganate and suggest that this complication may be an unrecognized factor contributing to the extremely high mortality rate associated with this condition.

Acute Disease↗
PubMed1990

[Subclasses of antibodies to hepatitis B core antigen in chronic HBV infections: changes during treatment with interferons and predictors of response].

Response to interferon therapy in chronic hepatitis B virus (HBV) carrier is preceded by the appearance of IgM class anti-HBc (antibody to hepatitis B core antigen). The temporal relationship and magnitude of the IgM anti-HBc response is variable, suggesting that the antibody is not directly involved in hepatocyte lysis, but is merely a marker of a changed state of immunity to the nucleocapsid proteins induced by interferon. IgG 1, 2, 3 and 4 did not change during therapy. IgG anti-HBc of all subclasses was absent in two Chinese HBV carriers. Lower than normal titres of anti-HBc (P less than 0.001) were detected in human immunodeficiency virus antibody positive (anti-HIV) carriers. These data indicate the presence of altered immunity to the nucleocapsid antigens in these two types of chronic HBV carrier that are known to respond poorly to antiviral therapy.

Adult↗
PubMed1989

Mutation preventing formation of hepatitis B e antigen in patients with chronic hepatitis B infection.

Some patients with chronic hepatitis B virus (HBV) infection are HB e antigen (HBeAg) negative, have circulating HBV particles, and often have especially severe chronic hepatitis. To test the hypothesis that the absence of HBeAg production may be due to a change in the nucleotide sequence of the pre-core region of the genome, 18 Greek and 3 non-Greek patients positive for HB surface antigen underwent direct sequencing of HBV-DNA amplified from sera. In 7 out of 8 HBeAg negative patients, two mutations (guanosine to adenosine) were found in the terminal two codons of the pre-core region, giving the sequence TAGGACATG. The remaining patient had the first mutation only. The sequence TGGGGCATG was found in 4 of 5 of the HBeAg positive patients. The first mutation results in a translational stop codon that is predicted to result in failure to produce HBeAg. The rest of the pre-core region in the HBeAg negative patients was otherwise homologous to that of the HBeAg positive patients and to known sequences.

Amino Acid Sequence↗
PubMed1989

Randomised controlled trial of lymphoblastoid interferon alfa in Europid men with chronic hepatitis B virus infection.

OBJECTIVE: To confirm the findings of pilot studies that interferon alfa is an effective treatment of Europid men with chronic hepatitis B virus infection. DESIGN: Randomised controlled trial of three months treatment with interferon alfa followed by 12 months of observation. SETTING: Outpatient clinic of a tertiary referral centre. PATIENTS: 37 Treated men (six anti-HIV positive) and 34 untreated men (nine anti-HIV positive) who met the criteria for the trial. Four controls failed to complete follow up. INTERVENTIONS: The treated group received subcutaneous injections of 5-10 MU interferon alfa/m2 daily for five days, then 10 MU/m2 thrice weekly for 11 weeks. Follow up continued at monthly intervals for 12 months. Untreated controls were monitored over the same period. MAIN OUTCOME MEASURE: Hepatitis B e antigen and hepatitis B virus DNA state after 15 months of observation. RESULTS: 12 Of the 37 treated patients cleared hepatitis B e antigen and hepatitis B virus DNA, whereas only one of 30 untreated controls seroconverted over the same period--an increased response rate of 29% (95% confidence interval 13% to 45%). The life table estimate of response at 15 months was 35% in treated patients, an increase of 32% above controls (95% confidence interval 16% to 48%). The response rates in groups by predictive pretreatment variables were 12 of 31 anti-HIV negative patients (excess response 34%; 95% confidence interval 14% to 54%), 12 of 26 with chronic active hepatitis before treatment (excess response 46%; 27% to 65%), and 12 of 21 with a pretreatment serum aspartate aminotransferase activity greater than 70 IU/l (excess response 46%; 16% to 76%). The combination of these factors predicted response with a sensitivity of 100% and a specificity of 80%. Four of the 12 responders, who had all been infected for less than two years, also lost hepatitis B surface antigen. Treatment was well tolerated. CONCLUSIONS: Interferon alfa is effective in the treatment of a proportion of Europid men with chronic hepatitis B virus infection, who might be identified before treatment. Additional strategies are required to improve the rate of response.

Adolescent↗
PubMed1989

Randomised controlled trial of interferon alfa (lymphoblastoid interferon) in chronic non-A non-B hepatitis.

OBJECTIVE: To determine the effect of low dose interferon alfa (human lymphoblastoid interferon) on aminotransferase activities in chronic non-A non-B hepatitis. DESIGN: Prospective randomised controlled parallel group study of active treatment versus no treatment carried out over 16 weeks and preceded by baseline measurements at weeks 8 and 4 and time zero. SETTING: HEPATOLOGY outpatient clinics in secondary referral centres. PATIENTS: Fourteen adults with histologically proved chronic hepatitis and persistently raised aminotransferase activities for six months or more. INTERVENTIONS: Seven patients randomised to receive interferon alfa 5 megaunits (MU) daily for one week, reducing to 5 MU thrice weekly for seven weeks, then 3 MU thrice weekly for eight weeks. Controls not treated. END POINT: Control of hepatic enzyme activity in chronic non-A non-B hepatitis. MEASUREMENTS AND MAIN RESULTS: Serum aspartate aminotransferase activity remained raised in controls (mean increase in study period 23.4 U/l) but fell rapidly to normal in the treated group (mean decrease 106.4 U/l). In four cases values were normal by eight weeks and in five cases by 16 weeks. Only minor side effects were recorded (fever, myalgia), which became less common as treatment progressed. CONCLUSIONS: Continuous low dose interferon alfa reduces aspartate aminotransferase activity to normal in most patients with chronic non-A non-B hepatitis and may prevent progression to cirrhosis.

Adult↗
PubMed1989

Defective response to interferons in cells transfected with the hepatitis B virus genome.

The interferon responsiveness of two cell lines transfected with the hepatitis B virus genome was investigated. A cosmid vector containing multiple copies of the hepatitis B virus genome was transfected into FL5-1 cells; it reduced their sensitivity to interferons as measured by inhibition of the cytopathic effect of Sindbis virus challenge. Similar vectors transfected into HeLa cells reduced their sensitivity to interferon as measured by production of beta 2-microglobulin. This resistance to interferon in hepatitis B virus-transfected cells may be a trans-acting phenomenon related to nucleotide homology between hepatitis B virus DNA and sequences regulating the interferon-induced antiviral system. Alternatively, other mechanisms involving transcription or translation products of hepatitis B virus may be responsible. Hepatitis B virus-induced cellular resistance to the action of interferon may be important in maintaining the chronic carrier state.

Cell Line↗
PubMed1989

Studies of GB hepatitis agent in tamarins.

Three tamarins (Saguinus labiatus), two of which had previously been infected with hepatitis A virus and parenteral non-A, non-B hepatitis, were inoculated intravenously with the agent of GB hepatitis. All three animals developed alanine aminotransferase abnormalities 2 weeks after inoculation. Peak alanine aminotransferase levels were recorded 4 weeks postinoculation. These declined thereafter but continued to fluctuate at abnormal levels for 32 weeks. Liver biopsies showed liver cell swelling and inflammation with focal necrosis. Portal tracts and areas around central veins were heavily infiltrated with mononuclear cells. A fourth animal (no previous exposure to hepatitis viruses) inoculated with GB was killed on Day 15 postinoculation. Serum and extracts of liver and feces from this day were used as inocula for three other animals. Only the serum and liver extract transmitted GB hepatitis. The fecal specimen did not transmit and a fecal extract taken at a later date from another animal was also noninfectious. GB hepatitis virus is distinct from the viruses causing Type A and blood-borne non-A, non-B-hepatitis. Although the virus is present in serum and has previously been transmitted per os, it is not shed in feces.

Alanine Transaminase↗
PubMed1989

Which patients with chronic hepatitis B virus infection will respond to alpha-interferon therapy? A statistical analysis of predictive factors.

Twenty-one pretreatment variables were assessed for their significance in response prediction using data from 114 patients given alpha-interferon for chronic hepatitis B virus infection. In those patients who had received a minimum of 90 million units per m2 total dose over 12 weeks, a negative anti-human immunodeficiency virus antibody status (p less than 0.001), chronic active hepatitis on liver biopsy (p less than 0.005), high AST level (p less than 0.001), low hepatitis B virus DNA level (p less than 0.001) and a history of acute hepatitis (p less than 0.005) were all associated with an increased likelihood of response on univariate analysis. On stepwise logistic regression analysis, hepatitis B virus DNA, AST and a history of acute hepatitis predicted response independently (p less than 0.05). The most reliable combination of predictive factors was a negative anti-human immunodeficiency virus antibody status, with either a positive history of acute icteric hepatitis and AST greater than 45 IU per liter or no history of acute icteric hepatitis and AST greater than 85 IU per liter, which predicted response in 77% with a specificity of 79% (p less than 0.001). The loss of HBsAg in addition to HBeAg and hepatitis B virus DNA was more likely to occur in patients with chronic infection of less than 2 years duration (p less than 0.001).

Adult↗
PubMed1989

Pre-S proteins in hepatitis B.

Two reactive sequences of the pre-S regions of hepatitis B surface antigen were synthesized chemically and used in micro-ELISAs for the assay of pre-S1 and pre-S2 antigens in serum from patients with acute and chronic hepatitis B. Pre-S1 antigen correlated well with the presence of HBV-DNA and was no longer detectable on cessation of viral replication, after natural recovery and after successful treatment with alpha-interferon. Pre-S2 proteins were also lost after treatment with alpha-interferon. The results show that the assay of pre-S1 and pre-S2 proteins in serum provides additional useful markers for assessing patients with acute and chronic hepatitis B infection and for monitoring the response to treatment with interferon.

Amino Acid Sequence↗
PubMed1989

Immune response of patients with congenital coagulation disorders to hepatitis B vaccine: suboptimal response and human immunodeficiency virus infection.

Seventy-eight patients with congenital coagulation disorders were treated with hepatitis B vaccine either subcutaneously or intradermally. All the children (eight vaccinated subcutaneously and eight vaccinated intradermally) responded. Seventeen of 19 (90%) anti-HIV-negative adults vaccinated subcutaneously and 14/25 (56%) anti-HIV-negative adults vaccinated intradermally showed an immune response. At 24 months, the anti-HBs level was greater than 10 IU/l in all children vaccinated subcutaneously, 83% of children vaccinated intradermally, 77% of adults vaccinated subcutaneously, and 55% of adults vaccinated intradermally. Eight of 15 (53%) adult patients who were anti-HIV positive were also anti-HBc positive before vaccination and 6/8 (75%) failed to produce an amnestic response to vaccine. Subcutaneous vaccination with regular monitoring of anti-HBs levels and appropriate boosting is recommended.

Adolescent↗