The career development program in maternal and child health.
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Biomedical subjects
Publications and source records attributed to S Dooley.
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A sensitive nonradioactive ribunuclease protection assay is described which we have used to study c-myc gene transcription and promoter usage in GLC4, a human small cell lung carcinoma cell line with amplified gene. For in vitro transcription we used digoxygenine (DIG)-rUTP instead of [alpha-32P]CTP or [alpha-32P]UTP and after polyacrylamide gel electrophoresis the protected probes were transferred to a nylon membrane from Boehringer Mannheim using electroblotting. Subsequently the membrane was analyzed by chemiluminescent detection. Results were obtained after 1 h of exposure and were comparable with those using radioactivity.
BACKGROUND: Hepatitis C infection (HCV) has an estimated seroprevalence of 1-2% in women of child-bearing age and vertical transmission rate of 5-15%. AIMS: To characterise the current trends of HCV in an Irish antenatal population. METHODS: Infants of HCV seropositive women, born 1994 to 1999, were referred to the Paediatric Infectious Diseases service. Maternal details were collected retrospectively. RESULTS: 296 HCV seropositive women were studied. 244 (82%) were infected through intravenous drug use (IVDU), 25 (8%) through heterosexual contact and 13 (7%) via blood products. Nine women had no identifiable risk factors. Coinfection with other blood borne viruses was uncommon (4.7% HIV, 3.4% hepatitis B). Of 84 women tested for HCV-RNA, 46 (55%) were positive. Eighty three (26%) delivered prematurely; the caesarean section rate was 11%. CONCLUSIONS: HCV is increasingly detected in antenatal clinics. Heterosexual contact is a mode of spread. Maternal HCV viraemia can be variable in pregnancy. Further study of HCV in pregnancy is needed to define the impact of pregnancy on HCV, accurately predict infant outcome and selectively target interventions to women at greatest risk of transmission.
BACKGROUND: Hepatitis C (HCV) is a common cause of morbidity among patients who attend general practitioners (GPs) in Ireland for methadone maintenance treatment. AIMS: To describe the development and content of guidelines for the management of HCV among current or former opiate users in the Eastern Regional Health Authority area attending GPs for methadone treatment. METHODS: The guidelines were produced in five stages: identification of key stakeholders; development of evidence-based draft guidelines; discussion of content; determination of 'Delphi'-facilitated consensus and review by a sample of GPs for whom the guidelines would be intended. RESULTS: The guidelines contain advice for GPs on all aspects of care of patients at risk of HCV, including general and preventative care, care of other bloodborne and hepatotoxic viruses, and the factors to be considered and appropriate evaluation prior to referring a patient for assessment at a hepatology unit. CONCLUSIONS: GPs have an important role to play in the care of patients at risk of, or infected with, HCV.
BACKGROUND: Hepatitis C virus (HCV) can be transmitted vertically from mother to infant, either late in pregnancy or at delivery. AIMS: To determine the outcome of infants born to HCV infected women, to characterise epidemiology and to design an appropriate infant monitoring schedule. METHODS: Three hundred and fourteen infants, born to 296 HCV positive women between 1994 and 1999 were monitored for a median of 18 months (range 1-52). RESULTS: Forty per cent of infants were small for age and 46% had neonatal abstinence syndrome (NAS). Of 173 infants of defined status, 11 were infected (vertical transmission rate [VTR] 6.4%, 95% CI 2.8-10). Infected infants were diagnosed at a median of three months (range 0.5-10). Liver transaminases elevation was documented in 8% of uninfected infants. A negative HCV PCR test before one month of age did not exclude infection but all infected patients had detectable HCV RNA when next tested (range 2-10 months). CONCLUSIONS: 94% of infants born to HCV antibody positive women are not HIV infected. Liver transaminase elevation in exposed infants is not always indicative of infection. A minimum monitoring schedule of testing (PCR and antibody) at six to eight weeks, six and 18 months allows early diagnosis while detecting late seroconversions.
BACKGROUND/AIMS: Profibrogenic TGF-beta signaling in hepatic stellate cells is modulated during transdifferentiation. Strategies to abrogate TGF-beta effects provide promising antifibrotic results, however, in vivo data regarding Smad activation during fibrogenesis are scarce. METHODS: Here, liver fibrosis was assessed subsequent to bile duct ligation by determining liver enzymes in serum and collagen deposition in liver tissue. Activated hepatic stellate cells were identified by immunohistochemistry and immunoblots for alpha smooth muscle actin. Cellular localization of Smad3 and Smad7 proteins was demonstrated by immunohistochemistry. RTPCR for Smad4 and Smad7 was conducted with total RNA and Northern blot analysis for Smad7 with mRNA. Whole liver lysates were prepared to detect Smad2/3/4 and phospho- Smad2/3 by Western blotting. RESULTS: Cholestasis induces TGF-beta signaling via Smad3 in vivo, whereas Smad2 phosphorylation was only marginally increased. Smad4 expression levels were unchanged. Smad7 expression was continuously increasing with duration of cholestasis. Hepatocytes of fibrotic lesions exhibited nuclear staining Smad3. In contrast to this, Smad7 expression was localized to activated hepatic stellate cells. CONCLUSIONS: Hepatocytes of damaged liver tissue display increased TGF-beta signaling via Smad3. Further, negative feedback regulation of TGF-beta signaling by increased Smad7 expression in activated hepatic stellate cells occurs, however does not interfere with fibrogenesis.
In February 1996, four serologically confirmed cases of hepatitis A virus (HAV) occurred in one household. Investigation showed that the source was a family member with sub-clinical HAV who attended a Unit for Learning Disabilities. Reports of two further cases in the institution followed and control measures were instigated. Contacts were unwilling to accept human normal immunoglobulin (HNIG). Following salivary antibody and serological testing, hepatitis A vaccine was offered to the non-immune. An investigation found that sub-clinical infection was significantly associated with being less than 5 years old (RR = 6.07, p < 0.005) and being in one particular classroom (RR = 6.21, p < 0.0005). None of the staff in the institution became infected. In all, 31 cases of hepatitis A (18 clinical and 13 subclinical cases) occurred. This paper (a) describes an outbreak of hepatitis A (b) refers to the use of a salivary antibody test (assay performance to be published elsewhere) (c) identifies factors associated with the acquisition of HAV and (d) endeavours to assess the effectiveness of the vaccine to contain the outbreak.
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