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Biomedical subjects

E A Fagan

Publications and source records attributed to E A Fagan.

At least 37 records · Page 2Linked to original sources
PubMed1989

Viruslike particles in liver in sporadic non-A, non-B fulminant hepatitis.

In a patient who followed the typical clinical course of fulminant hepatitis attributable to "sporadic" non-A,non-B (NANB) hepatitis and who finally received treatment by orthotopic liver grafting, three, apparently separate, virus-like agents (26, 45, and 80 nm) and cytoplasmic, reticular tubular structures (CTS) were identified in collapsed and regenerating areas of liver using electron microscopy. The 80-nm particles present within vacuoles, together with the finding of intranuclear rods in association with the smaller particles (26 nm), are similar to those found in the nuclei of cells infected with several different arboviruses. The third type of particle, existing as 45-nm spheres and rods, is similar in morphology only to some form of polyoma virus, which, hitherto, has not been reported as affecting the liver. Unlike typical polyoma virus, replication of the virus "cores" (25-26 nm) was extranuclear and appeared to be occurring in vacuoles. Although analysis for serological markers against a representative panel for arboviruses, flaviviruses, phleboviruses, arenavirus, and nairovirus was negative, an insect vector was implicated in the clinical history.

Adult↗
PubMed1989

Toga-like virus as a cause of fulminant hepatitis attributed to sporadic non-A, non-B.

Virus-like particles (60-70 nm) with spiked surfaces budding into cell vacuoles and rod-shaped inclusions were detected in nuclei of hepatocytes from a British patient transplanted for sporadic non-A, non-B fulminant hepatitis (NANB-FHF), probably contracted in Kenya. Identical particles were seen in two successive grafts (days 2 and 10) at regrafting for recurrent FHF. Ultrastructural features resembled those of the RNA-containing arbovirus, Rift Valley fever virus, but serological markers against a representative panel for arboviruses (Togaviruses) and transmission in mice proved negative. The particles shared features with the different arboviruses seen in the hepatectomy specimen of a second patient with NANB-FHF, and in both patients an insect vector was implicated in the clinical history. The particles were identical in size to those of a third patient with NANB-FHF, who had remained in the United Kingdom. These findings, together with the recent report of isolation of an RNA-containing virus resembling the Togaviridae, in parenteral NANB, suggest that several exotic virus-like agents resembling the arboviruses may be involved in the aetiology of NANB, including in the sporadic forms of FHF in the United Kingdom.

Adolescent↗
PubMed1989

Adoptive immunotherapy administered via the hepatic artery and intralesional interleukin-2 in hepatocellular carcinoma.

We assessed the feasibility of using lymphokine-activated killer cells (adoptive immunotherapy) with infusions of interleukin-2 when given regionally in three patients with unresectable primary hepatocellular carcinoma (PHC). In 2 patients, 2 cycles, which included a bolus of LAK (10(7) to 10(8) cells followed by a 4-hourly infusion of IL-2 were administered via selective arterial catheterization of the hepatic artery. One further patient received 3 cycles of IL-2 alone by direct intralesional and perilesional injections. Minimal toxicity was observed and side effects such as fever were comparable to those observed with systemic infusions of IL-2 alone. Serial alpha-fetoprotein (AFP) levels initially fell but subsequently rose within 2 to 4 weeks of therapy. AFP levels had not reached pre-treatment values at 4 months in 2 patients, 1 of whom was alive and well at 15 months follow-up.

Carcinoma, Hepatocellular↗
PubMed1988

Sequential studies of pre-S2 antigenemia and anti-pre-S2 antibodies in relation to viral replication in acute hepatitis B followed from the early incubation phase.

To determine the time sequence of expression of pre-S2 peptide (120-150) during the presymptomatic phase of acute hepatitis B, we used a monoclonal antibody radioimmunoassay in five subjects followed from 30 to 70 days before the onset of liver damage. Pre-S2 peptide was present in serum at low levels from the early incubation phase and started to increase immediately after the first detection of HBV-DNA in serum, in parallel with the increase in HBsAg levels. During the symptomatic phase, levels of pre-S2 peptide declined rapidly; it was no longer detectable after recovery. Anti-pre-S2 antibodies were detected, in four patients, only in the recovery phase. These results demonstrate that expression of pre-S2 peptide occurs very early in the incubation phase of acute HBV infection and is cleared in parallel with HBsAg. Anti-pre-S2 antibodies seem to play no role in viral clearance in these patients.

Adolescent↗
PubMed1988

Clearance of pre-S2 antigen: a marker of successful interferon therapy in hepatitis B virus infection.

The relation between viral replication, the presence of HBsAg and pre-S2 in serum and eventual clinical outcome has been investigated in fourteen patients undergoing treatment with lymphoblastoid interferon for chronic hepatitis B virus (HBV) infection. In four patients permanent loss of pre-S2 was accompanied by loss of serum HBV-DNA in association with a marked elevation of serum aspartate aminotransferase activity and in each of these cases HBsAg was subsequently cleared from serum. In contrast there was no significant fluctuation in the concentration of either pre-S2 or HBsAg in four cases not responding to therapy although substantial or complete inhibition of viral replication had been observed during treatment. In the third group, permanent loss of HBV-DNA was observed but in these cases pre-S2 and HBsAg persisted in serum, albeit at lower concentrations, while in this group loss of HBV-DNA from serum was not accompanied by a flare in disease activity. These results suggest first, that assay of pre-S2 is a further measure of the response to interferon and second that in some cases interferon enhances immune recognition of both the pre-S2 and HBsAg polypeptides.

Adult↗
PubMed1988

Lack of reverse transcriptase activity in serum in sporadic post-transfusional and presumed epidemic or water-borne forms of severe non-A, non-B hepatitis.

Reverse transcriptase (RT) activity was not detected in any serum sample taken from 22 patients with mainly severe non-A, non-B hepatitis (NANBH), using two assays selected to cover the range of known human and animal retroviruses. The study included patients with fulminant and sub-acute hepatic failure, which was was attributed to sporadic, post-transfusional, and presumed epidemic or water-borne epidemiological forms of NANBH. Although we cannot exclude the possibility that some of the agents implicated in NANBH are retroviruses, our negative findings suggest that other agents may be involved at least in the severe forms of NANBH.

Adolescent↗
PubMed1988

Review of hepatitis non-A, non-B: the potential hazards in dental care.

Several of the common viral agents that can cause hepatitis have been detected in body fluids, including saliva and blood, which may both form important routes for transmission of disease. The viruses most commonly implicated include hepatitis A virus (HAV), hepatitis B virus (HBV), cytomegalovirus (CMV), and Epstein-Barr virus. Hepatitis delta virus (HDV) can be found in persons positive for hepatitis B surface antigen (HBsAg) and presumably follows the same routes of transmission as HBV. Herpes simplex and echo viruses can cause hepatitis on rare occasion. Other agents, not yet positively identified but collectively referred to as non-A, non-B are also believed to follow the same routes as HBV and/or HAV. The aim of this reviews is twofold. First, we will discuss hepatotropic viruses other than HBV that may be spread via saliva and blood and, therefore, should be considered along with HBV as a potential health hazard to dental personnel and also to dental patients. The second aim is to highlight the epidemiology and the risk of transmission of these viral infections. The potential hazards are discussed in relation to those associated with HBV and human immunodeficiency viruses (HIV), implicated in the acquired immunodeficiency syndrome (AIDS).

Dental Care for Persons with Disabilities↗
PubMed1987

Loss of HBsAg with interferon therapy in chronic hepatitis B virus infection.

46 male chronic hepatitis B virus (HBV) carriers with active viral replication were randomised, with stratification for histology and sexual preference, to receive six months' lymphoblastoid interferon or no therapy. After nine to eighteen months' follow-up, HBeAg was no longer detectable and anti-HBe was present in 6 of the 23 treated patients. HBsAg was not detectable in 5 of these patients and 3 had anti-HBs. All of the controls remained positive for HBeAg and HBsAg. Seroconversion from HBeAg to anti-HBe was preceded in all cases by a pronounced increase in serum aspartate aminotransferase levels of more than ten times the upper limit of normal at eight to twelve weeks; this response was exclusively associated with interferon therapy. These results suggest that loss of HBsAg and a hepatitis-like illness in the third month of therapy are direct effects of interferon treatment.

Adult↗
PubMed1987

Hepatitis B vaccine: immunogenicity and follow-up including two year booster doses in high-risk health care personnel in a London teaching hospital.

One hundred forty-four adult health care personnel (aged 18-62 years, median 33 years) considered at high risk of future HBV infection were vaccinated with a plasma-derived hepatitis B vaccine (20 micrograms HBVax at 0, 1, and 6 months) and followed-up for 2 years. Anti-HBs was present in only 6.9% prior to vaccination, and prescreening to detect this group would not have been cost-effective. At 9 months, 8.3% were nonresponders and a further 9% had anti-HBs levels less than 50 mIU/ml. Multivariate analysis showed that age was the single most important determinant of a poor response. In 47 of 52 individuals retested 2 years later, anti-HBs levels had fallen by 80% or more, and in four it had become undetectable. Response to a booster dose at this stage was excellent, with anti-HBs levels 3 months later much higher than at the end of the initial course. Additional booster doses of vaccine in two of the initial nonresponders at 14 and 22 months, respectively, also led to seroconversion. Although a significant proportion of health care workers in this study did not make a satisfactory response to the hepatitis B vaccine, later booster doses were very effective in subsequently increasing anti-HBs levels.

Adolescent↗
PubMed1987

Controlled clinical trial of acyclovir in chronic hepatitis B virus infection.

A randomised, controlled trial comparing acyclovir, 45 mg/kg/day as a continuous IV infusion for 28 days, with no other therapy, was carried out in 30 stable HBsAg carriers seropositive for HBeAg for more than 6 months. Twenty-eight had hepatitis B virus DNA-polymerase activity and/or hepatitis B virus DNA in serum at entry into the study. There were no significant adverse effects of therapy. At 12 months, seroconversion from HBeAg to anti-HBe had occurred in four of 15 treated patients, one of whom had also developed anti-HBs, compared with only one of 15 in the untreated group (95% confidence limits 12% and 51%). Seroconversion from HBeAg to anti-HBe was accompanied by return of serum liver function tests to normal and improved liver histology. The results of this study indicate that acyclovir is of no significant benefit in chronic HBeAg carriers with stable disease.

Acyclovir↗
PubMed1987

Microbial structures in a patient with sporadic non-A, non-B fulminant hepatitis treated by liver transplantation.

Double-shelled virus-like particles (60 nm) and long cytoplasmic tubular structures were found in the cytoplasm of hepatocytes from areas of collapsed and regenerating areas of hepatectomised liver in a 13-year-old boy who received a liver graft for fulminant hepatitis attributed to sporadic non-A, non-B hepatitis. The patient died on the ninth postoperative day from acute graft failure. Although virus-like particles were not found, instead, gram-negative rods were identified in the necrotic graft and the most likely cause of death was a gram-negative septicaemia with a Shwartzman-like reaction localized to the liver.

Adolescent↗
PubMed1987

Leucocyte hepatitis B virus DNA in acute and chronic hepatitis B virus infection.

In the present study we have investigated 53 patients with a spectrum of acute and chronic hepatitis B virus (HBV) infection for the presence of leucocyte HBV-DNA with the aid of molecular techniques. HBV-DNA was detected in peripheral blood mononuclear cells of 31 of 45 (69%) of chronic HBsAg carriers and 2 of 8 (25%) patients with acute hepatitis B. Although HBV-DNA was detected more frequently in leucocytes from those HBsAg carriers seropositive for HBeAg (79%), 50% of those with anti-HBe in serum had leucocytes positive for HBV-DNA independent of the presence of serum HBV-DNA. Examination of various leucocyte subpopulations showed the presence of HBV-DNA in polymorphonuclear leucocytes as well as T- and non-T-enriched mononuclear cell fractions. The HBV-DNA identified was predominantly 3.2-kilobase (kb), while higher molecular weight sequences were rarely detected, and lower molecular weight sequences indicative of active viral replication were not observed. These data indicate that although leucocytes do not actively support viral replication, they frequently harbour 3.2-kb HBV-DNA and may act as a reservoir for infection and, more importantly, since leucocytes contaminate several body secretions, may be involved in virus transmission.

Acute Disease↗
PubMed1987

Review of the herpesviruses and hepatitis A: the potential hazards in dental care.

There is now an increased awareness of the risk of transmission of viral infections via blood and saliva after the publicity given to the human immunodeficiency viruses responsible for the acquired immunodeficiency syndrome. The herpesviruses have been found in blood, in blood products, and in saliva, and information with respect to these routes of transmission is convincing. Although hepatitis A virus is spread predominantly by water contaminated with feces (fecal-oral route), the virus is also found in saliva. On these grounds alone, these viruses must be considered a potential hazard in dentistry. Information in regard to the actual risks of their transmission in the context of dental practice is not yet available, primarily because a high proportion of infections are asymptomatic. Serologic studies of their prevalence suggest that all are widespread in the population. They are particularly common in many of the groups known to be at high risk for hepatitis B virus and human immunodeficiency virus, including promiscuous homosexuals, bisexuals, and intravenous drug abusers. In addition, pregnant women and their babies are particularly at risk from the herpesviruses. It is important to identify members of these high-risk groups as a potential source of transmission of infection through dental practice and in addition, it is important to identify them because they are prone to chronic sequelae.

Dental Care for Persons with Disabilities↗
PubMed1987

Detection of hepatitis B virus DNA in spermatozoa, urine, saliva and leucocytes, of chronic HBsAg carriers. A lack of relationship with serum markers of replication.

Urine, saliva and semen from 18 chronic HBsAg carriers, material that might be concerned in the transmission of hepatitis B virus infection, was examined for the presence of HBV-DNA using molecular hybridisation. HBV-DNA was detected in samples from 14 patients: semen was positive in all of these, saliva in 12 and urine in 10. Autoradiographic studies indicated that HBV-DNA was present in the free form in all cases and in 10, higher molecular weight bands were also observed. While the latter suggested integration of HBV-DNA into host chromosome, resolution to 3.2 Kb following digestion with Eco RI in every case was more consistent with the HBV-DNA being free. In a further group of patients peripheral blood leucocytes were also found to contain HBV-DNA and were the likely source of HBV-DNA in saliva and urine, while in semen both spermatozoa and mononuclear cells contained HBV-DNA. Moreover, free HBV-DNA was identified in the semen of patients without markers of viral replication in serum indicating that sexual transmission could still occur and this is of importance in relation to current vaccination policies.

Carrier State↗
PubMed1986

Fulminant hepatitis B in successive female sexual partners of two anti-HBe-positive males.

In two separate families, consecutive, unrelated female sexual partners of a symptom-free, male, HBsAg-positive carrier died of fulminant hepatitis B. Although one man was HBeAg positive on the first occasion, both men were considered of low infectivity, being anti-HBe positive, negative for serum DNA polymerase activity, and negative for serum hepatitis B virus (HBV) DNA when their second partners presented with fulminant hepatitis B. By means of molecular hybridisation techniques, both men were found to have HBV DNA (3.2 kb) in seminal fluid, sputum, saliva, peripheral blood leucocytes, and liver.

Acute Disease↗