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Biomedical subjects

Y E Cossart

Publications and source records attributed to Y E Cossart.

At least 19 recordsLinked to original sources
PubMed1995

Post-transfusion hepatitis revisited.

OBJECTIVE: To evaluate the risk of post-transfusion and postoperative non-A non-B hepatitis in Australia immediately before the introduction of screening for hepatitis C. DESIGN: Retrospective testing of blood samples from a prospective study of cardiac surgery patients. Samples were taken from transfusion recipients and non-transfused controls at regular intervals for 12 months after surgery during 1987-1989. For all donor, recipient and control samples, alanine aminotransferase (ALT) levels were measured and tests for antibody to hepatitis B (anti-HBc, anti-HBs) and, when available, to hepatitis C (anti-HCV) were performed. SETTING: Cardiac surgery units. PARTICIPANTS: Participants were included if they lived in the metropolitan area, and had not had a transfusion in the past year. MAIN OUTCOME MEASURES: Post-transfusion hepatitis (two consecutive samples showing raised ALT levels, > 90 IU/L with no other known cause); hepatitis C infection and carriage (antibody to hepatitis C). RESULTS: Post-transfusion hepatitis occurred in 1.1% of 736 recipients of blood not screened for hepatitis C (i.e., two cases per 1000 unscreened units given). No hepatitis occurred in 514 controls. Seven of the eight patients with post-transfusion hepatitis seroconverted to hepatitis C virus infection. Seven of the 26 anti-HCV-positive donations transmitted hepatitis C, six of these were positive by recombinant immunoblot assay (RIBA) (one by second generation testing only) and one was RIBA indeterminate. Nineteen were RIBA non-reactive; one transmitted hepatitis but the recipient did not develop anti-HCV, although hepatitis C RNA was detected in the donation. Serum ALT was raised in four of the six infective donations. CONCLUSIONS: Hepatitis C virus infection accounted for almost all cases of non-A non-B post-transfusion hepatitis. First generation anti-HCV tests detected about 85% of infective donations. Surrogate testing of donations by ALT or anti-HBc offers no additional advantage.

Alanine Transaminase↗
PubMed1995

Identification of E6/E7 transcription patterns in HPV 16-positive cervical cancers using the reverse transcription/polymerase chain reaction.

Studies indicate the presence of four different forms of human papillomavirus (HPV) E6/E7 mRNA resulting from differences in transcription patterns and post-transcriptional nuclear splicing. Through a retrospective analysis of 28 cervical cancer patients, correlations were sought between E6/E7 transcription patterns and histologic type, FIGO stage, and tumor aggression. A combined reverse transcription/polymerase chain reaction was used to study E6/E7 transcription patterns in fresh and/or fixed paraffin-embedded tissues of HPV 16-positive cervical cancers. Random cervical biopsies from nine women with no history of cervical disease were included as controls. Two sets of primers used in the investigations detected the full-length (FL) E6, E6*I, and E6*II mRNAs and the FL E6 and E6*I mRNAs, respectively; eight of the tumors were also analyzed using a third primer combination designed to identify the E6*III mRNA. At least two of the transcripts were detected in all of the tumors, whereas E6/E7 mRNAs were not identified in any of the control cervical biopsies. Overall, the transcription patterns were consistent, but the major E6*I mRNA was not detected in two of the tumors. No relationship was found between the E6/E7 transcription patterns and the histological type and differentiation of the tumors, nor with the FIGO stage and the clinical behavior of the disease. The study confirms that E6/E7 transcription is a constant feature of HPV 16-related carcinoma, but the findings indicate that there may be no clinical advantage in adding E6/E7 mRNA detection to the routine assessment of cervical tumors.

Adult↗
PubMed1995

Associations between oncogenic human papillomaviruses and local invasive patterns in cervical cancer.

The polymerase chain reaction (PCR) was used to detect human papillomavirus (HPV) DNA in Formalin-acetic acid alcohol (FAA)-fixed paraffin-embedded tissue from 40 patients whose primary cervical cancers showed a tentacular pattern of invasion at their advancing edges, and 40 patients (matched by age, International Federation of Obstetrics and Gynecology (FIGO) stage and histology type) whose tumors showed broad front invasion. The rate of HPV DNA positivity was the same in both the tentacular and the broad front tumors (83%), but the ratios of HPV 16 to HPV 18 in the two groups were markedly different (20:10 versus 27:4, respectively). HPV type 18 was detected more frequently in tentacular than broad front tumors (P = 0.03). The overall rates of recurrence and mortality were 15 and 9%, respectively (18 and 10% in the tentacular group compared with 13 and 8% in the broad front group). Univariate analysis showed statistically significant associations between HPV 18 and tumor recurrence (P = 0.04), but not between a tentacular pattern of invasion and tumor recurrence (P < 0.05). The findings to emerge from this survey indicate that the presence of particular HPV types may, in part, mediate the histological and clinical behavior of cervical cancers.

Adult↗
PubMed1995

Human papillomavirus deoxyribonucleic acid as a prognostic indicator in early-stage cervical cancer: a possible role for type 18.

OBJECTIVE: Our purpose was to determine the prognostic significance of human papillomavirus deoxyribonucleic acid in cervical cancers. STUDY DESIGN: The polymerase chain reaction was used to detect human papillomavirus deoxyribonucleic acid types 6, 11, 16, 18, 31, 33, 52, or 58 in tumors from 148 patients (equal numbers of whom were disease free or had relapses) surgically treated for stage IB or IIA cancers in a major Australian hospital. Cox regression modeling was used to assess the effect of human papillomavirus status on tumor recurrence, taking into account patient age, clinical stage, histologic node status, and type of tumor. RESULTS: Seventy of 74 (95%) of the recurring tumors and 62 of 74 (84%) of the nonrecurring tumors were human papillomavirus deoxyribonucleic acid positive. The rates of positivity of types 16 and 18 were 64% versus 31% in the recurrers and 65% versus 14% in the nonrecurrers. Human papillomavirus type 18 positivity was associated with a greater risk of recurrence than was type 16 positivity (hazard ratio 1.8; p = 0.03). Clinical stage, nodal metastasis, and young age (< or = 35 years) also had adverse effects on relapse (hazard ratio for each approximately 2). CONCLUSION: Human papillomavirus type 18 positivity is a risk factor for tumor recurrence in surgically treated cervical cancer.

Adult↗
PubMed1995

An autopsy survey of hepatitis B in Sydney.

AIM: 1) To determine the prevalence of hepatitis B in Sydney autopsies and 2) to determine the relationship between seroprevalence, hepatitis B risk factors and histological changes in the liver. METHODS: One hundred autopsy subjects were studied for evidence of past or present hepatitis B infection, using RIA to detect the HBV antigens and antibodies in the serum and peroxidase-antiperoxidase technique to detect HBsAg and HBcAg in the liver. Both serum and liver were examined for the presence of HBV DNA. RESULTS: Markers of hepatitis B virus infection were detected in either serum and/or liver of 29 subjects. Four subjects (4%) were seropositive for HBsAg. Eight subjects had been recently infected, 7 were chronically infected and 14 had recovered. CONCLUSION: The 29% prevalence of HBV infection is higher than expected. In four cases the serum was either free of HBV markers or showed conventional evidence of recovery, yet the liver still contained HBsAg. There were few histopathological changes despite the presence of HBsAg in the liver. The only epidemiological factors possibly predisposing to HBV infection were tattooing and drug abuse.

Australia↗
PubMed1994

Tuberculosis: medical students at risk.

In 1979 an outbreak of tuberculosis occurred in medical students at the University of Sydney. Eight of 35 Mantoux-negative students who attended the autopsy of an immunosuppressed patient with unsuspected active tuberculosis became infected and one developed clinical disease. A report of the incident was prepared for publication because it supported the then controversial University policy of recommending BCG vaccination to medical and dental students in a country where the reported prevalence of tuberculosis is very low. The report was never published, mainly in order to protect the privacy of the individual students involved, but also because it was felt by the administration of the time that it might undermine confidence in infection control procedures in the autopsy room. The original report, updated and reproduced here, suggested that tuberculosis might be an emerging nosocomial problem. This has been all too clearly realised since its re-emergence as an opportunistic infection in AIDS patients. Worldwide, the problem of antibiotic resistance in Mycobacterium tuberculosis provides an added risk of a return to the situation which prevailed early this century when tuberculosis was a major occupational risk for young health care workers. Infection often restricted career choices, even in those whose disease was relatively benign. Our purpose in bringing this incident to light after so many years is to point out the relevance of the extensive studies of the problem which were conducted in the 1930s and 1940s to the current situation and to suggest that health care students are vulnerable to airborne infections as well as those spread by inoculation injuries. In retrospect, our 1979 conclusions about prospects for preventing nosocomial tuberculosis appear optimistic.

Autopsy↗
PubMed1994

Needlestick injury in medical students.

OBJECTIVE: To determine the incidence of needlestick injuries and the prevalence of hepatitis B vaccination among medical students, dentistry students, and hospital staff. DESIGN AND SUBJECTS: Anonymous survey of final year medical students and dentistry students enrolled at Sydney University in 1992, and nursing staff and doctors employed in the wards and emergency department of Royal Prince Alfred Hospital, Sydney. RESULTS: During their clinical training, 22% of medical students and 72% of dentistry students had received one or more contaminated, penetrating "sharps" injuries. Of hospital staff, 50% of ward nurses, 71% of ward doctors, and 50% of emergency staff had received this type of injury during the previous two years. Students were significantly more likely to be vaccinated against hepatitis B than hospital staff (P < 0.001)--98% of medical students and 95% of dentistry students had received a full course of vaccination. The rate of vaccination among hospital staff ranged from 79% in emergency staff to 85% in ward nurses. CONCLUSIONS: Clinical students sustain needlestick injuries at a rate comparable with hospital personnel and therefore face a significant risk of exposure to transmissible pathogens, including hepatitis B virus, HIV, and hepatitis C virus. The rate of hepatitis B vaccination is high among clinical hospital staff and almost universal among medical and dentistry students.

Adult↗
PubMed1992

Prevalence and distribution of human papillomavirus type-16 DNA in pelvic lymph nodes of patients with cervical cancer and in women with no history of cervical abnormality.

The polymerase chain reaction (PCR) was used to investigate the prevalence and distribution of human papillomavirus (HPV)-16 DNA in paraffin sections of all pelvic lymph nodes removed from 14 patients with Stage Ib-cervical cancer at the time of resection of their primary tumours. The results were compared with those obtained from 8 women with no known history of cervical abnormality. In all, 22 cervical biopsies and 40 I lymph nodes (296 paraffin blocks) were examined. Nine of the 14 cervical cancer patients had primary tumours that were positive for HPV-16 DNA: only 3 of these had lymph nodes with histological evidence of metastasis, and HPV 16 DNA was detected in each of the corresponding paraffin blocks. HPV 16 DNA was also detected in varying proportions (8%-92%) of the histologically-negative lymph nodes from these women. There was no correlation between the HPV DNA-positive lymph nodes and their proximity to the primary tumour. HPV-16 DNA was not identified in any of the lymph nodes from the 5 women whose cancers were not HPV-16-related, or in those of women with no evidence of cervical abnormality. This preliminary survey suggests that HPV DNA is frequently transported from HPV-16-related cervical tumours to regional lymph nodes. However, its practical significance will not be clear until sufficient time has elapsed for correlation of the results with the clinical outcome.

Adult↗
PubMed1992

Detection of HPV DNA in archival specimens of cervical cancer using in situ hybridisation and the polymerase chain reaction.

An archival survey of 98 cervical cancer specimens dating from the 1920s to the 1980s was undertaken to determine whether changes had occurred in the prevalence of human papilloma-virus (HPV) DNA. HPV DNA was detected in paraffin sections of cancers fixed in 10% formalin by in situ hybridisation (ISH) using HPV 6, 11, 16, and 18 32P-labelled DNA probes under conditions of high stringency; and by the polymerase chain reaction (PCR) using 20-mer oligonucleotide primers to amplify 109 bases of the E6 region of HPV 16. In 30 instances results obtained from Southern blot hybridisations which had been carried out on specimens of fresh tissue from the same cancers collected during the 1980s were available for comparison. The rates of HPV DNA detection in cervical cancers ranged from 83% (by Southern or PCR) and 70% (by ISH) on specimens from the 1980s, to 50% and 63% (by ISH and PCR, respectively) on specimens from the 1920s. HPV 16 was by far the most common type, being identified by Southern or ISH in approximately 92% of HPV DNA-positive specimens. No significant change in the prevalence of HPV DNA, or of HPV types, in cervical cancers was found over the 65 year period examined.

Archives↗
PubMed1991

Detection of human papillomavirus type 16 E6/E7 transcripts in fixed paraffin-embedded cervical cancers by the polymerase chain reaction.

A simple, and sensitive method for the detection of human papillomavirus (HPV) 16 E6/E7 transcripts in RNA purified from formalin acetic alcohol (FAA)-fixed, paraffin embedded cervical cancer (CaCx) tissue is described. The entire procedure, including polymerase chain reaction (PCR) amplification of cDNA obtained from mRNA by reverse transcription, can be completed within a day. The results obtained compare favourably with those using total nucleic acids extracted from the same fixed material, and are consistent with results using RNA purified from corresponding fresh tumour tissue. Although developed for investigating the expression of HPV in tumours, this method should find general application in studies of gene expression and viral detection.

DNA, Single-Stranded↗
PubMed1991

Duck hepatitis B virus: a model to assess efficacy of disinfectants against hepadnavirus infectivity.

The efficacy of three proprietary glutaraldehyde disinfectants and their component bases was assessed using the duck hepatitis B virus (DHBV) model. Inactivation of infectivity of undiluted serum containing 10(6.8) ID50/ml DHBV was assessed after a mixture with an equal volume of disinfectant had stood at room temperature for 10 min. A dried spill of infectious serum was simulated using sterile filter paper disks, saturated with serum containing DHBV, dried and then exposed to test disinfectant for 10 min. Residual infectivity, and hence the reduction in virus titre, was determined by inoculation of dilutions of the treated samples into 1-day-old ducklings. A greater than 3 log10 reduction in virus titre could be demonstrated for the disinfectants as well as for some of their component bases. Disinfectant activity varied according to the method of viral presentation but a reduction of exposure time from 10 to 2.5 min did not diminish activity. The experimental protocol permits a comparative and quantitative assessment of the efficacy of both established and new disinfectants.

Animals↗
PubMed1991

Factors associated with clinical and sub-clinical anal human papillomavirus infection in homosexual men.

OBJECTIVES: (I) to determine the relative sensitivities of clinical examination, cytology and HPV DNA hybridisation for the detection of anal human papillomavirus infection; and (ii) to examine various factors which may influence presentation of anal human papillomavirus infection in homosexual men. METHODS AND RESULTS: 112 unselected homosexual men attending a Sydney STD clinic for routine screening underwent a complete anogenital and physical examination, during which blood samples (for haematological, serological and immunological investigations), rectal swabs (for culture of anal pathogens) and anal scrapes of the dentate line (for cytology and HPV DNA hybridisation) were collected. Papanicolaou-stained anal smears were examined for cytological abnormalities, including those indicative of HPV infection or anal intraepithelial neoplasia (AIN). HPV DNA was detected by high stringency dot hybridisations using radiolabelled HPV 6, 11, 16 and 18 DNA probes. Visible anal condylomata, situated either externally or in the anal canal, were present in 26% of these men; 46% had cytological evidence of HPV infection, and 19% of the smears showed evidence of mild to moderate dysplastic changes (AIN I-II). Detectable HPV DNA was present in 40% of the anal scrapes. By combining these results, a total of 73 men (65%) were found to have at least one of the indicators of HPV infection. These data, together with that relating to HIV antibody, immune status and past or present infection with other STDs, was correlated with information obtained from a questionnaire administered to the patients at the time of their clinical examination. CONCLUSIONS: In this study cytology was found to be slightly more sensitive than HPV DNA dot hybridisation for the detection of HPV infection in the anal canal, providing the full range of HPV-associated cytological changes were accepted as a basis for diagnosis. Clinical anal lesions were more likely to be detected in young men, men who had symptomatic HIV infection and those with a history of past anal wart infection. The latter group also had a higher incidence of cytologically apparent HPV infection in their anal smears. There was a significant association between the detection of HPV 16/18 and the presence of anal dysplasia, but there were no significant correlations between HPV infection or anal dysplasia and HIV antibody, immune function status, sexual practices or history of other STDs.

Adolescent↗
PubMed1991

Anal intercourse: a risk factor for anal papillomavirus infection in women?

OBJECTIVE: To determine whether anal intercourse is a risk factor for anal HPV infection in women. DESIGN: Results derived from clinical examination, anal cytology and HPV DNA hybridisation were correlated with data obtained from a questionnaire administered to the patients at the time of their clinical examination. SETTING: A sexually transmitted diseases (STD) clinic in Sydney, Australia. SUBJECTS: 31 women attending the clinic for HPV related problems. METHODS AND RESULTS: A thorough history was elicited from each woman followed by physical examination of the anogenital region. Cervical and anal scrapes were collected for cytology and HPV DNA hybridisation. Of the 15 women who practised anal intercourse, a total of 12 (80%) had either clinical or subclinical HPV infection. Seven had overt anal warts, situated either internally or externally in the anal canal; and further 5 women had evidence of subclinical HPV infection as determined by positive cytological and/or HPV DNA hybridisation results on their anal scrapes. The women who did not have a history of anal intercourse had a lower (7/16, 43%), but not statistically significant, rate of anal HPV infection: five had anal warts and two had subclinical evidence of infection. No correlations were found between anal HPV infection and genital (cervical, vulval or vaginal) HPV infection; nor between the HPV typing patterns of women in either group. CONCLUSION: The results obtained from these women do not indicate a close relationship between anal intercourse and the presence of detectable anal HPV infection.

Adult↗
PubMed1990

Low-dose intradermal vaccination of medical and dental students.

In 454 medical and dental students who were vaccinated against hepatitis B by means of a low dose (0.1 mL) of serum-derived vaccine, seroconversion rates of 27%, 70% and 89% were obtained after the first, second and third doses, respectively. These figures are comparable with the results that have been reported for the conventional intramuscular schedule, as were the final antibody titres. A fourth intradermal dose boosted the percentage of students who were protected from 82% to 87%. There was a significant variation in the response to different batches of vaccine. This study shows that the low-dose intradermal method is practicable and effective and can be used to achieve great economy in hepatitis B vaccination programmes. The possibility of adding hepatitis B to the present formula of triple antigen should be investigated as a way of extending hepatitis B vaccination to all infants in our community.

Administration, Cutaneous↗
PubMed1990

Postexposure treatment of experimental DHBV infection: a new therapeutic strategy.

The therapeutic efficacy of antiviral agents for postexposure prophylaxis to hepadnavirus infection has been studied using acyclovir and foscarnet in the duck hepatitis B virus (DHBV) model. A total of 112 Pekin-Aylesbury ducks were inoculated with DHBV at 11 days post-hatch. Three days later, groups of these birds were injected intraperitoneally twice daily for 10 days with acyclovir (25 mg/kg) or foscarnet (250 mg/kg) or phosphate-buffered saline. Serum samples were taken before, during, and up to 4 weeks post-treatment and were analysed for DHBV DNA by dot hybridization. Liver tissue obtained at sacrifice was examined for viral DNA and for histological changes. At completion of treatment with acyclovir, 21 of 22 ducks were not viremic, compared with 6 of 26 control birds (P less than 0.001). Four weeks after withdrawal of acyclovir, 12 of 20 ducks remained nonviremic, compared with 2 of 23 controls (P less than 0.01). In liver tissue, viral DNA was detected in 10 of 19 treated ducks, compared with 21/24 controls (P less than 0.01). Histological changes of hepatitis were present in more of the control birds than in the treated group. The results with foscarnet treatment were similar, although a smaller inoculum of DHBV was used and fewer control birds became infected. The administration of antiviral agents soon after exposure prevented productive infection in approximately 50% of birds. Therefore, the use of a safe antiviral agent such as acyclovir, which can be given orally, should be considered in post-exposure prophylaxis against human hepatitis B virus (HBV) infection.

Acyclovir↗