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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
PubMed2001

Risk of hepatitis C virus infection in multiply transfused premature neonates.

BACKGROUND: Reports from around the world indicate that multiply transfused patients are at increased risk of hepatitis C virus (HCV) infection, with reported rates of between 4% and 44%. Such reports are mostly of haematological and renal patients. As recipients of blood products in the newborn period, premature infants share this risk, but there is little information regarding their risk. AIM: To assess the risk of HCV infection in children who, as premature neonates, received multiple blood products prior to the introduction of screening of donated blood for HCV. METHODS: Premature infants born between January 1985 and January 1990 who had attended our high-risk follow-up clinic were selected on the basis of the number of transfusions of blood, platelets or fresh frozen plasma they received in the newborn period. Ethical approval to offer HCV testing to parents was obtained from the Central Sydney Area Health Service Ethics Review Committee. Parents of infants who received three or more transfusions were then contacted by mail with the approved letter explaining the study, and offered HCV testing. Detection of anti-HCV antibodies was undertaken using second, and later third generation enzyme immunoassay kits. Samples which were found to be 'indeterminate' were tested using a Wellcozyme HCV western blot assay (Murex Diagnostics Ltd, Datford, UK). Hepatitis C virus-ribonucleic acid (RNA) was detected using an 'in-house' polymerase chain reaction (PCR) assay. Alanine transaminase (ALT) was also measured, with values above 55 U/L considered abnormal. RESULTS: Consent was obtained for 45 children (25 males, 20 females). The mean (+/- SEM) gestational age and weight of the children at birth was 26.7 +/- 0.2 weeks and 938 +/- 27 g, respectively. The children received 198 transfusions of blood products, an average of 4.4 U per child. All of the infants except for one were negative for anti-HCV antibodies. One infant was 'indeterminate' (low positive on third generation test but negative on second generation test), but proved negative subsequently on both western blot and PCR testing. HCV-RNA was not detected in any of the infants on PCR testing. All of the samples had normal ALT values, the mean being 16 U/L (range 8-52). CONCLUSION: None of the children consenting to this study had evidence of current HCV infection. Because of the sample size, we were not able to estimate the true risk of infection from this study, except that the upper limit for the risk is about 1/200 per transfused blood sample.

Blood Transfusion↗
PubMed2000

Analysis of mutations in the URR and E6/E7 oncogenes of HPV 16 cervical cancer isolates from central China.

High rates of cervical cancer have been reported from parts of China and this may reflect a predominance of cervical infection with particularly aggressive human papillomavirus (HPV) variants. This PCR-based investigation of cervical tumours from Sichuan province in central China demonstrated an HPV positivity rate of 88%. HPV 16 was most common (21/34, 61%), followed by HPV 18 (3/34, 9%), while types 33, 45, 58 and 59 were each identified in one specimen. Sequencing of up to 1349 bases of the 21 HPV 16-positive isolates, encompassing the enhancer/promoter of the upstream regulatory region (URR) and the E6 and E7 genes, revealed distinct patterns of genomic stability and variability. An overall mutation rate of 5% was seen in the URR. One isolate had a large deletion of 436 bases in the enhancer; while varying combinations of 21 point mutations were identified in the remainder, impacting several YY1, NF1, TEF-1 and Oct-1 sites. More sequence variations were found in E6 compared to E7 (81% vs. 52% of isolates showing at least one mutation), some of which resulted in changes to the translated amino acids. Since the E6/E7 genes encode the oncogenic proteins essential for malignant transformation, and as their expression is controlled by the URR, it is possible that some of the identified mutations altered the oncogenicity of the virus: either directly by changing amino acid sequences of the E6 or E7 oncoproteins, or indirectly through alterations to transcription factor binding sites in the URR.

China↗
PubMed2000

Squamous carcinoma of the head and neck: molecular mechanisms and potential biomarkers.

Squamous cell carcinoma (SCC) of the head and neck remains a major health problem worldwide. Recent advances in cell biology suggest that cancer results from the accumulation of specific genetic mutations, many of which have now been identified. These mutations can cause the activation of genes that promote cellular proliferation or inhibit cell death (oncogenes), or they may inactivate genes that inhibit proliferation or promote cell death (tumour suppressor genes). Although there is no known set sequence of events leading to the formation of SCC of the head and neck, there is evidence that many of the genomic mutations implicated in other forms of cancer have an aetiological role in these tumours. Certain viruses, notably Epstein-Barr virus and some types of human papillomaviruses, are causally related to some head and neck cancers. There is now the prospect of using molecular markers to achieve earlier diagnosis and to aid in the prediction of both tumour behaviour and likely responses to particular treatment modalities.

Biomarkers, Tumor↗
PubMed2000

Hepatitis C in injecting drug-using women during and after pregnancy.

BACKGROUND: A high proportion of female injecting drug users (IDU) have evidence of hepatitis C virus (HCV) infection. We undertook a prospective study of patients attending a clinic for pregnant IDU to determine the impact of pregnancy on the course of HCV infection and whether pregnancy is affected by HCV infection. METHODS: One hundred and thirty-one IDU were recruited and followed up with liver function tests, HCV serology and HCV-RNA tests. RESULTS: Of 131 patients, 125 had HCV antibodies (anti-HCV positive) at delivery, and of these 62% were HCV-RNA positive. The anti-HCV-negative women were younger and had a shorter duration of drug use than the anti-HCV-positive women. There were no differences between viraemic and non-viraemic women with respect to age, ethnicity, duration of injecting drug use, methadone maintenance dose, hepatitis B exposure or reported high-risk behaviour. Alanine aminotransferase (ALT) levels were higher and the proportion with ALT > 55 IU/L higher in viraemic women. Viraemia persisted in all 55 women who were viraemic at term. Eleven had an ALT flare post-partum that was unrelated to viral load and was clinically unsuspected. Four had concurrent elevated gamma-glutamyltranspeptidase and were considered to be drinking alcohol at hazardous levels. Four of 23 women who were HCV-RNA negative at term became positive during follow up. CONCLUSIONS: Pregnancy does not adversely affect the course of hepatitis C. A modest rebound in ALT levels, but not HCV-RNA, occurs after delivery in some viraemic women. This supports the theory that immune mechanisms rather than direct viral cytopathology are involved in hepatocyte injury during HCV infection. Hepatitis C infection did not influence pregnancy complications and outcomes.

Adult↗
PubMed1999

Varicella vaccination of health-care workers.

The objective of this open study was to evaluate the response of non-immune health-care workers to two doses of live attenuated varicella vaccine given two months apart. One hundred subjects (58 females; aged 17-49 yr, mean 22.8 yr) received two doses of varicella vaccine. Blood samples for antibody estimation were taken before vaccination, 2 months after the first dose and 6 weeks after the second dose. Reactions were recorded daily in diaries by the vaccinees and controlled by telephone contacts by the investigators. Ninety-four of 99 vaccinees (94.9%, 95% CL 88.6, 98.3) had detectable antibodies after the first dose [titers 4-1024, geometric mean titer (GMT): 53.2 (95% CL 42.4, 66.8)]. After the second dose, all vaccinees had antibodies (100%, 95% CL 96.6, 100.0) [titers 32-2048, GMT: 235.6 (95% CL 199.0, 278.8)]. Mild reactions limited to the injection site occurred in 1 in 4 subjects after each dose. Vesicular rashes occurred in one subject after the 1st dose and in 3 subjects after the 2nd dose, 1 subject was febrile (38.2 degrees C) after the 1st dose. Eighty-one subjects were retested 12 months after the second vaccination. Three had become seronegative (one developed mild varicella 2 months later). Two had boosted their titers (one after mild clinical varicella 1 month earlier, the other after close contact with clinical cases). The GMT of the group had fallen to 83.6 (95% CL 65.4, 106.8). The identification and vaccination of seronegative health-care workers is safe and efficient, and will benefit the workers themselves and the communities in which they work.

Adolescent↗
PubMed1999

Evaluation of disinfection and sterilization of reusable angioscopes with the duck hepatitis B model.

PURPOSE: Nosocomial transmission of viral hepatitis and retrovirus infection has been reported. The expected risk is greatest for the hepatitis B virus (HBV). The duck HBV (DHBV) has similar biologic and structural characteristics to HBV and has been adopted as a suitable model for disinfectant testing. METHODS: Angioscopic examination of the external jugular vein was performed on DHBV-infected ducks. After use, the instrument was air dried for 3 minutes. Samples were obtained by flushing the channel with 5 mL of phosphate buffered saline solution. The samples were collected immediately after drying (control), after flushing with 5 mL of water, after glutaraldehyde disinfection for 5, 10, and 20 minutes, and after ethylene oxide gas sterilization. Angioscopes were either precleaned or uncleaned before disinfection/sterilization. Residual infectivity was assessed with inoculation of samples into the peritoneal cavity of day-old ducks (n = 231). RESULTS: DNA analysis results of liver samples showed that all 38 control ducks became infected. The frequency of DHBV infection was reduced to 93% (14 of 15) by flushing the angioscope with 5 mL of sterile water. No transmission occurred after the use of any of the properly precleaned and disinfected/sterilized angioscopes. However, after the use of the uncleaned angioscopes, the transmission rate was 90% (9 of 10) and 70% (7 of 10) after 5 and 10 minutes of contact time, respectively, in 2% glutaraldehyde. Even after the recommended 20 minutes of contact time, there was still 6% (2 of 35) transmission. After ethylene oxide sterilization, two of the recipient ducklings (2 of 35) were infected with DHBV. CONCLUSION: There was no disease transmission after reuse of disposable angioscopes adequately cleaned before disinfection or sterilization. However, if the angioscopes are inadequately cleaned, DHBV can survive despite glutaraldehyde disinfection or ethylene oxide sterilization. This contrasts with previous in vitro and in vivo data with solid surgical instruments. It is postulated that the presence of a narrow lumen or residual protein shielding within the lumen may compromise effective inactivation of hepadnaviruses on angioscopes, with the potential risk for patient-to-patient transmission.

Angioscopes↗
PubMed1999

Inactivation of duck hepatitis B virus by a hydrogen peroxide gas plasma sterilization system: laboratory and 'in use' testing.

Human hepatitis B virus (HBV) is an important cause of nosocomial infections and can be transmitted by contaminated instruments. However, tests of the efficacy of sterilization of materials and equipment contaminated by HBV are difficult to perform because the virus cannot be cultured in the laboratory. In this study, we aimed to evaluate the capability of a low temperature, hydrogen peroxide gas plasma sterilizer (Sterrad, Advanced Sterilization Products, Irvine California,) to inactivate duck hepatitis B virus (DHBV). In laboratory efficacy studies using DHBV dried on to glass filter carriers and exposed to one-half of the hydrogen peroxide gas plasma sterilization process, there was a 10(7) or greater decrease in the viral titer, with no infectivity detected on the carriers after treatment. In-use studies were performed using a laparoscope that was experimentally contaminated with DHBV to mimic the possible transmission of infection between successive patients. Following exposure to the hydrogen peroxide gas plasma sterilization process no transmission of DHBV infection from the laparoscope occurred despite obvious visual soiling with blood (N = 8) while the transmission rate for the unprocessed laparoscope (positive control) was 100% (26/26), and that for instruments after a water wash was 63% (7/11). In conclusion the hydrogen gas plasma sterilization process completely inactivates DHBV a representative of the hepadna group of viruses.

Animals↗
PubMed1998

Molecular epidemiology and variation of hepatitis B in recent immigrant families to Australia.

Natural variation in hepatitis B virus (HBV) was studied in asymptomatic carriers originating from countries of high endemicity. HBV DNA was detected by dot blot and/or polymerase chain reaction (PCR) in 34 of the 184 members of 22 new immigrant families who agreed to be tested after one of their children had been found to have current or past hepatitis B in a school survey. PCR products from both the S and distal-X pre-C regions were sequenced. One vaccinated child had the classical "escape" mutation at amino acid position 126 in the S-gene and two other children and two adults had other substitutions at amino acid positions 133, 120, 165, and 159. Mutations were more frequent in the distal-X pre-C region and included two pre-C mutants and 13 other amino acid substitutions. The strains originating in the various countries were placed in almost identical groups by phylogenetic analysis using each amplicon, and determination of subtype by antigenic analysis gave the same result as sequencing. The S-data allowed recognition of three dominant strains within genotype B, while the distal-X pre-C data provided better discrimination between family groups. No change was found when the sequence of samples obtained for the study was compared with those collected from 14 of the children two years earlier. There was some evidence of horizontal spread in addition to vertical transmission. Reports of mutations of HBV in patients with severe or unusual clinical features should be interpreted with caution until the prevalence of the mutant in asymptomatic carriers has been determined.

Adolescent↗
PubMed1998

Cholestatic hepatitis after liver transplantation is associated with persistently high serum hepatitis C virus RNA levels.

Viral recurrence is universal after transplantation for hepatitis C infection. This may lead to difficulties in differentiating allograft dysfunction caused by chronic rejection from hepatitis C virus (HCV) recurrence. Cases of severe cholestatic hepatitis have also been reported in conjunction with reinfection of the graft with HCV. Patients receiving transplants for HCV-related liver disease were studied before and after transplantation by HCV RNA quantitation of serial serum samples. Four major clinical patterns of HCV recurrence could be distinguished posttransplantation: group 1, asymptomatic hepatitis with no significant symptoms; group 2, cholestatic hepatitis with centrilobular ballooning; group 3, hepatitis leading to chronic allograft rejection; and group 4, persistently normal serum aminotransferase levels. Pretransplantation viral load was shown to be an important indicator of disease severity because the group 2 patients had significantly higher pretransplantation viral loads than patients in group 1 (P = 0.01) and group 4 (P = 0.005). The group 2 patients also had persistently significantly higher posttransplantation viral loads than the patients in group 1 (P = 0.01) and group 4 (P = 0.02), whereas patients who developed chronic allograft rejection showed marked decreases in serum HCV RNA before retransplantation. Patients from group 4 had the lowest viral loads after transplantation. These results show that persisting graft cholestasis due to HCV is associated with persistently high HCV RNA levels compared with other etiologies of graft dysfunction. Prospective studies are needed to determine whether such quantitation may be diagnostically helpful in distinguishing the different patterns of HCV-related graft dysfunction observed after liver transplantation.

Adult↗
PubMed1998

Detection of persistent vegetative bacteria and amplified viral nucleic acid from in-use testing of gastrointestinal endoscopes.

Hospital-acquired infection attributed to inadequate decontamination of gastrointestinal endoscopes prompted an in use evaluation of recommended procedures. Specimens were obtained from the internal channels of 123 endoscopes before, during and after decontamination by flushing with saline and brushing with a sterile brush, and examined for vegetative bacteria by broth and plate culture. Four endoscopy units were tested; the chemical disinfectants used were: 2% glutaraldehyde in Centres 1 and 2 (automated) and Centre 3 (manual); peracetic acid in Centre 4 (automated). Samples from patients in Centre 1 with known chronic hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV-1) infection were also examined for viral nucleic acid by ultracentrifugation, nucleic acid extraction, reverse transcription (for RNA) and polymerase chain reaction (PCR). No persistent vegetative bacteria were found following standard manual cleaning and disinfection for 20 min in 2% glutaraldehyde in Centres 2 and 3 (N = 37). At Centre 1, while plate culture yielded no growth, 34% of samples (10/29) grew vegetative bacteria in broth culture after cleaning and disinfection for 20 min in 2% glutaraldehyde. Investigation revealed an error in manual cleaning; no bacteria were detected in 37 samples taken after this was corrected. At Centre 4, despite the use of peracetic acid as a sterilant, three out of 20 (15%) of post decontamination samples grew bacteria; one contained persistent bacteria. HBV and HCV PCR analysis detected viral nucleic acid in three out of four and four out of six samples from viraemic patients undergoing endoscopy in Centre 1 during the period of improper manual washing. After proper cleaning was instituted, samples from nine out of nine HCV viraemic patients were negative. HIV RNA was detected in five of 14 samples taken from endoscopes after use on HIV positive patients but all post decontamination samples were negative. Detection of bacteria in washes from endoscope channels is a useful warning of a breakdown in decontamination practice. Inadequate brushing of internal channels may result in persistent HCV and HBV viral nucleic acid, the significance of which is not clear. These results reinforce the importance of adequate manual cleaning of endoscopes before chemical disinfection.

Bacteria↗
PubMed1997

Sequence variation in the upstream regulatory region of HPV 18 isolates from cervical cancers.

This study describes sequence variation in both the enhancer and promoter segments of the upstream regulatory region (URR) of 28 human papillomavirus (HPV) type 18 isolates from cervical cancers, 25 from women treated at an Australian center and three from overseas included for comparison. No large-scale changes were found in either region. Fourteen substitutions were identified in the enhancer region with the number in individual isolates ranging from one to eight. Four substitutions impacted cellular transcription factor binding sites but there were no obvious associations with clinicopathological variables. The promoter segment was found to be more highly conserved than the enhancer, but four of the five point mutations identified involved cellular transcription factor binding motifs including a substitution of C for T at nt 104 which affected 21 samples. This change was found to impact upon a previously unrecognized Yin Yang (YY1) binding site. Electrophoretic mobility shift assays (EMSA) showed that this substitution significantly reduced protein-DNA binding and evidence was sought for its possible clinical implications. Of the 24 women with less than Stage III disease and known clinical outcome, tumor recurrence was observed in all of the 6 women whose isolates had the "prototype" T at nt 104, whereas only 8 of the 18 cancers with the mutation at this YY1 site recurred. This is the first report on URR variation in HPV 18 isolates from the South Pacific region. The study also provides initial data on diversity in the promoter region and preliminary evidence suggesting that a specific point mutation in this region may be clinically significant.

DNA, Viral↗
PubMed1997

Transmission of hepatitis C virus to infants of human immunodeficiency virus-negative intravenous drug-using mothers: rate of infection and assessment of risk factors for transmission.

The risk of perinatal transmission of hepatitis C virus (HCV) from a cohort of 95 human immunodeficiency virus (HIV)-negative intravenous drug users (IVDU) is described, 89 of whom were positive for antibodies to HCV (anti-HCV). Infection, defined as the presence of HCV RNA in a serum sample collected from an infant at any time during follow-up, was detected in six of 63 (9.5%) infants born to HCV antibody-positive viraemic mothers. No mother who was HCV RNA negative at delivery transmitted HCV to her infant. Hepatitis C virus antibodies became undetectable in uninfected infants by 15 months, but persisted in all HCV-infected infants throughout follow-up. An abnormal alanine aminotransferase (ALT) level was observed on at least one occasion in all HCV-infected infants and in six occasions in uninfected infants. Two of the six HCV-infected infants became HCV RNA negative during follow-up by 27 and 29 months. Both of these infants had a large ALT elevation (mean peak ALT 398U l-1) at around 12 months of age. Analysis of a range of potential risk factors revealed that maternal HCV RNA load was important in predicting transmission, but suggested that other factors play a role in perinatal transmission from mother to child. No difference was found between mothers who transmitted HCV to their infants and those who did not for HCV genotype, duration of drug use, duration of methadone use, methadone dose, history of alcohol abuse, past hepatitis B virus (HBV) infection, mode of delivery, maternal and gestational age, birth weight and incidence of breast-feeding. Mothers who transmitted HCV to their infants had a longer duration between membrane rupture and delivery than the mothers who did not transmit (P = 0.03). HCV RNA was not detected in breast milk and colostrum samples from 38 viraemic mothers, including two who transmitted HCV to their infant.

Alanine Transaminase↗
PubMed1997

Horizontal transmission of hepatitis B in a children's day-care centre: a preventable event.

Using molecular finger-printing, we provided evidence that, in a children's day-care centre, a known hepatitis B virus (HBV) hepatitis B e antigen (HBeAg) carrier transmitted HBV to another child (the index case). The chronic HBV carrier had an exudative skin lesion and a history of biting. We sought to identify other at-risk children and prevent further transmission. Blood samples were collected and tested serologically for HBV. Of the 90 other children, 78 (87 per cent) were tested and none had serological evidence of HBV infection; 73 (81 per cent) were of Caucasian background; 38 (49 per cent) had a history of HBV immunisation with serological confirmation. Therefore, 1 (2.4 per cent, 95 per cent confidence interval 1.0 to 12.8 per cent) of the 41 known susceptible contacts became infected. The risk of horizontal HBV transmission in a children's day-care centre is low but not negligible. Staff and children should be vaccinated when a child in a day-care centre is a known HBV carrier.

Australia↗
PubMed1997

Human papillomavirus and host variables as predictors of clinical course in patients with juvenile-onset recurrent respiratory papillomatosis.

This study provides the first systematic evaluation of papillomavirus type and viral mutation occurring during the course of juvenile-onset recurrent respiratory papillomatosis. One hundred ninety-nine consecutive papillomas excised from 47 children between 1981 and 1996 at The New Children's Hospital in Sydney, Australia, were tested for human papillomavirus (HPV) DNA by PCR. PCR products from the viral upstream regulatory region (URR) enhancer were sequenced, and variation was related to clinical variables. Forty-four of the 47 children had HPV-induced papillomas, with type 11 accounting for 24 (55%) and type 6 accounting for 19 (43%); one (2%) was positive for either type 6 or 11. Overall, 183 (98%) of the 186 samples with amplifiable DNA were HPV positive. There was no change in HPV type over time and no statistically significant association between HPV type and disease aggressiveness. One novel, large-scale URR duplication was identified in an HPV type 11 isolate in the last of a series of six papillomas examined and the first from the bronchus. However, the duplication was not found in HPV type 11 isolates from the associated pulmonary carcinoma and its metastases in other organs. Three of 14 URR point mutations coincided with transcription factor binding sites, but there were no obvious associations with clinical course. Chi-square and multiple linear regression analyses of clinicopathological variables revealed early age at diagnosis (less than 4 years) as an independent predictor of aggressive disease (P < 0.001). A bimodal distribution of the age at diagnosis was noted, with peaks at 2 and 11 years of age.

Adolescent↗