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Biomedical subjects

J Craske

Publications and source records attributed to J Craske.

At least 19 recordsLinked to original sources
PubMed1998

Survey of resistance of herpes simplex virus to acyclovir in northwest England.

Acyclovir (ACV) has been used for more than 15 years in the management of herpes simplex virus (HSV) and varicella-zoster virus (VZV) disease. The present survey was undertaken to assess the level of ACV resistance in the population. More than 2,000 HSV isolates from both immunocompetent and immunocompromised patients in northwest England were collected over a 2-year period and tested for sensitivity to ACV. These studies suggested a prevalence of resistance of approximately 0.1 to 0.6% in immunocompetent individuals, with no apparent difference in prevalence between treated and untreated groups. In line with previous studies, the prevalence of resistance in treated immunocompromised individuals was approximately 6%.

Acyclovir↗
PubMed1998

Nucleic acid vaccines against hepatitis viruses.

Direct DNA intramuscular or intradermal injection of plasmids containing viral genes under the control of viral promoters is an efficient means of stimulating both class I and class II-mediated antiviral responses. Viral hepatitis B and C are suitable candidates for this approach, particularly as therapeutic immunogens for chronically infected individuals. Several groups have shown that the S gene of HBV is expressed in murine muscle and stimulates a high titre and long-lasting anti-HBs response. Uniquely, CD8+ CTL responses are also induced to HBsAg. No vaccine exists for HCV. Therefore the structural genes (C + E1 + E2) have been cloned as a 2,831 bp fragment from a genotype la isolate into the vector pcDNA3. The resulting plasmid DNA was injected directly into the quadriceps muscle of three-week-old BALB/c mice. Intracellular-expressed E1 and E2 proteins thus represent the complete spectrum of native structural epitopes, including those dependent on glycosylation and protein folding. Mouse antisera were tested for reactivity against conserved sequences using overlapping 7-mer peptides. Two conserved, overlapping epitopes were identified in E2 spanning residues 581-591 and 590-603. This domain represents one of seven major E2 antigenic domains recognized by HCV human antibodies, one of three with antigenic homologies to related flavivirus proteins. Thus antigen is presented with high efficiency following DNA injection and offers the potential of high rates of seroconversion and virus clearance in those predisposed to virus-induced chronic liver disease.

Animals↗
PubMed1997

The prevalence of Enterocytozoon bieneusi in acquired immunodeficiency syndrome (AIDS) patients from the north west of England: 1992-1995.

Microsporidia are increasingly being recognised as important enteric pathogens in patients with advanced human immunodeficiency virus (HIV) disease, i.e. acquired immunodeficiency syndrome (AIDS). The aims of this study were to investigate the frequency of detection of microsporidia associated with diarrhoea in patients with advanced HIV disease in the north west of England, and to determine the species involved and their prevalence. During the period from April 1992 to the end of December 1995, chronic diarrhoea in 88 patients in the late stage of HIV disease was investigated. Duodenal biopsies, duodenal aspirates or jejunal biopsies were received from 38 patients, and stool samples from 63 patients, as part of the routine investigation of possible causes of diarrhoea in these patients. Biopsies and aspirates were examined by thin-section electron microscopy (EM), and stool samples were examined by epi-fluorescence microscopy after staining with Calcofluor. Putative stool positives were confirmed by transmission electron microscopy. CD4-lymphocyte counts were available from all patients who provided samples. Nine out of 63 patients (14.3%) were found to be excreting microsporidial spores on stool examination. The species was confirmed as Enterocytozoon bieneusi. The mean CD4-lymphocyte count for this group was 37 x 10(6)/L (normal range 517-1677 x 10(6)/L). Three out of 38 biopsy specimens (7.9%) were also found to be infected with this microsporidian. The mean CD4-lymphocyte count for this group was 72 x 10(6)/L. Encephalitozoon intestinalis was not found in any samples examined. The prevalence of microsporidial infection in AIDS patients in the north west of England appears to be similar to that of patients in London, but less than that reported in studies from other developed countries.

AIDS-Related Opportunistic Infections↗
PubMed1995

Hepatitis C-related chronic liver disease among asymptomatic blood donors in the north west of England.

In the first 19 months of screening, the North Western Regional Transfusion Centre (RTC) tested 224,000 consecutive blood donors for antibody to hepatitis C virus (anti-HCV) by second generation enzyme immunoassay (EIA). Of these, 366 repeatedly reactive samples were referred for confirmatory testing at Manchester Public Health Laboratory (PHL). There, the initial EIA was repeated, together with two further EIAs. All the referred samples were subjected to a confirmatory line immunoblot (RIBA-II). Reverse transcription followed by the polymerase chain reaction (RT-PCR), in order to detect viral RNA, was performed on selected samples. Among the donors, 61 accepted offers for medical review and were assessed for risk factors, clinical findings and results of standard liver function tests. Of these donors, 53 proceeded to liver biopsy. The overall prevalence of confirmed positive donors was 0.04%. Main risk factors identified included intravenous drug abuse in 31 (51%) donors and prior blood transfusion in 12 (20%) but a risk factor was not apparent in 11 (18%). Viraemia, detected by RT-PCR, could be predicted with a high degree of accuracy by means of the readily available and simpler screening and confirmatory tests (EIA and RIBA-II). Established chronic hepatitis was demonstrated in 90% of the liver biopsies. A trend towards worsening histological findings accompanied increasing concentrations of serum transaminase. Even so, many donors with normal transaminase values had abnormal biopsies including those showing chronic active hepatitis (CAH). These findings indicate that a substantial proportion of previously unrecognised asymptomatic persons with established chronic liver disease exists among North Western blood donors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Detection of human cytomegalovirus antigenaemia: a rapid diagnostic technique for predicting cytomegalovirus infection/pneumonitis in lung and heart transplant recipients.

BACKGROUND: New rapid diagnostic techniques offer the opportunity of early diagnosis of human cytomegalovirus (CMV) infection in immunocompromised patients at risk of developing CMV disease. The use of human CMV antigenaemia as a predictor of clinical CMV infection and disease in lung and heart transplant recipients was studied prospectively. METHODS: Twenty three heart and nine lung transplant recipients who survived 40 days were observed by standard CMV surveillance with serological testing, culture, and by sequential testing for CMV antigenaemia. CMV antigenaemia testing is a rapid and quantifiable technique in which a viral lower matrix protein is detected in cytospin preparations of peripheral blood polymorphonuclear leucocytes (PMNLs) by immunofluorescent staining. RESULTS: Eleven patients developed CMV infection and five developed CMV disease (four pneumonitis, one duodenitis). These clinical events occurred at a median of 65 days following transplantation. CMV antigenaemia occurred in 17 patients at a median of 35 days following transplantation. Detection of CMV antigenaemia had a sensitivity of 100%, a specificity of 93.7%, and a positive predictive value of 94.1% for CMV related illness. CMV antigenaemia was positive at a significant interval before the clinical event. High levels of CMV antigenaemia (> 50 CMV antigen positive cells/2 x 10(5) PMNLs) occurred in 11 patients and five of these developed disease. CMV antigenaemia of > 50 CMV antigen positive cells/2 x 10(5) PMNLs had a positive predictive value of 45.5% for disease but a negative predictive value of 100%. Patients with disease had higher levels of antigenaemia than those without disease. CONCLUSIONS: CMV antigenaemia is a rapid diagnostic technique which can identify patients likely to develop CMV disease, potentially allowing early treatment.

Antigens, Viral↗
PubMed1994

Hepatitis B outbreak in a drug trials unit: investigation and recommendations.

In autumn 1990 three young men developed acute hepatitis B. They belonged to a group of 24 young male volunteers who had taken part in a trial in a residential unit for drug trials in July and August 1990. A further case of acute hepatitis B and a carrier of hepatitis B e antigen (HBeAg) were detected by serological testing of the volunteers. Volunteers, in two groups of twelve, had occupied the unit at different times during the trial. The four cases occurred in the group that contained the HBeAg positive carrier. The carrier had also taken part in two trials on the unit in 1989. He was HBeAg positive then, but transmission of hepatitis B virus (HBV) did not occur. Although blood samples were taken in each of the three trials, intravenous cannulas were used only in the 1990 trial. It is likely that HBV was transmitted by blood to blood contact between volunteers when blood was sampled through cannulas during the trial. This outbreak might have been prevented. If an infection control policy had been applied to avoid hazardous practices, and volunteers had been screened for HBV before entry and the carrier excluded (as recommended by the Association of Independent Clinical Research Contractors), the outbreak would not have occurred. Volunteers for drug trials in residential units should be screened for HBV, human immune deficiency virus (HIV) and hepatitis C virus (HCV), and those found to be infected should not be accepted.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗
PubMed1993

An algorithm for confirming screen reactivity in blood donors in enzyme immunoassays for antibodies to hepatitis C virus.

Three commercial second generation enzyme immunoassays (EIA) and a second generation immunoblot assay (RIBA-II) for detecting antibodies to hepatitis C virus (HCV) were evaluated in a study of confirmatory testing using sera referred by six Regional Blood Transfusion Centres (RTC). Of a total of 490 samples, 203 were negative in the same EIA as that used by the RTC and of these 162 were negative in all three EIAs. The RIBA-II immunoblot test was performed on all samples and 359 were negative, 69 were indeterminate and 62 reactive. We found a close relationship between RIBA-II reactivity, the reactivity of a sample in all three EIAs and the mean of the test/cut-off ratios of all three EIAs performed on that sample. When this was evaluated by PCR for HCV RNA, we found an association between the mean test/cut-off ratio and the probability that an immunoblot reactive or indeterminate sample was PCR positive. A mean ratio of greater than 5.0 in a RIBA-II reactive sample was associated with a 100% probability (16/16 tested) of being PCR positive. These observations should be extended by testing RIBA-II negative samples by PCR so that simplified algorithms for anti-HCV testing can be developed.

Blood Donors↗
PubMed1991

Voluntary antenatal HIV testing--results of a pilot study.

Voluntary testing for antibody to human immunodeficiency virus (HIV) was offered to 4929 antenatal patients attending two hospitals in South Manchester during a 12 month period in 1989/90 in order to assess the feasibility of obtaining seroprevalence data by this method. Of these patients, 1728 (35%) agreed to a named test, 1396 (28%) to an unlinked anonymous test and the remaining 37% declined to be tested. The proportion of women tested increased from 22% to 88% over the period, and was similar in those with and without an identified risk factor for infection. One HIV antibody positive patient was found; she was tested anonymously and had no identified risk. The substantial cost in time and money required to establish the universal voluntary testing programme and the incomplete patient compliance confirm the importance of the unlinked anonymous surveys currently being established in the UK to monitor seroprevalence in sentinel populations.

AIDS Serodiagnosis↗
PubMed1991

Latent herpes simplex virus type 1 in normal and Alzheimer's disease brains.

A viral aetiology has long been suspected for Alzheimer's disease (AD) but until now, techniques have not been sufficiently sensitive to provide clear evidence for or against the presence of any viral genome in AD brain. We have used the very highly sensitive method of polymerase chain reaction to look for herpes simplex virus type 1 (HSV1) DNA, specifically the viral thymidine kinase (TK) gene, in autopsy brain specimens. DNA-samples from HSV-infected and uninfected Vero cells have been examined concurrently to provide standard "HSV-positive" and "HSV-negative" samples, the latter guarding also against false positives caused by cross-contamination. To preclude false negatives, we have checked the presence of the human gene, hypoxanthine phosphoribosyl transferase. In all specimens from 8 AD patients and 6 normal individuals (temporal, frontal and hippocampal), we have found viral TK sequences. In contrast, in preliminary studies on lymphocytes from normals and AD patients, we did not find TK sequences. It is postulated that factors such as number or expression of viral genes and host susceptibility might be related to incidence of AD.

Alzheimer Disease↗
PubMed1990

Comparison of false-positive reactions in direct-binding anti-HIV ELISA using cell lysate or recombinant antigens.

In a 2-year study of false-positive anti-HIV-1 tests in blood donors at Manchester and Lancaster Blood Banks, the reactions associated with a HIV-infected cell lysate antigen were compared with those using recombinant-antigen-based tests. In year 1 (cell lysate test) at Manchester BTS 0.21% of 119.178 donations were repeatedly reactive, compared with 0.53% of 119,004 donations in year 2 (recombinant antigen). Reactive sera were tested at Manchester PHL by three different immunoassays. Referred specimens were classified as anti-HIV positive (95-100% reactive in all the assays), equivocal or negative (negative results in all three immunoassays). Two donors were confirmed to be anti-HIV positive over the 2-year period. Most sera were negative by confirmatory immunoassays in years 1 and 2. In year 1, a study of 60 referred sera with sex- and age-matched controls showed high correlation between a reactive anti-HIV-1 screening test and indeterminate anti-HIV-1 patterns on Western blot showing reactions with HIV gag-coded proteins. In year 2, less than 10% of referred sera were reactive by Western blot, and there was no correlation between a reactive screening anti-HIV test, the strength of signal in the test or a reactive Western blot. Follow-up showed that donors whose sera were reactive in years 1 and 2 by the anti-HIV-1 screening test formed almost two different populations. Four donors with equivocal anti-HIV-1 confirmatory tests had anti-HIV 'envelope' reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Western↗
PubMed1989

An open study of interferon in HIV-antibody-positive men.

Alpha-2a-recombinant interferon (Roferon A) was given subcutaneously in a dose of 3 mega units twice weekly for 15-18 months to 14 HIV-antibody-positive, p24-antigen-negative men with minimal HIV-related disease. Interferon was well-tolerated and safe. Although there was either improvement or lack of deterioration initially in 22 out of 26 HIV disease markers, including lymphadenopathy, thrombocytopenic purpura and nail fungal infection, there were 11 instances of HIV disease indicators appearing during the study. At 15 months, six patients were withdrawn from the study because of clinical and immunological deterioration.

Adult↗