College of Medicine and Health

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A shuttle vector system for the rapid detection of recombination in murine cells.
(Oxford University Press, 1993-11-25) Fanning, Liam J.; McCarthy, Tommie V.
Haemophilia
(1997-04) Cahill, Mary R.; Colvin, B. T.
Although the nature of haemophilia has been understood for thousands of years, knowledge of its molecular genetics is recent. These X-linked bleeding disorders have diverse underlying DNA defects and, in 1992, DNA inversion within the X chromosome was found to explain half of the most serious cases of haemophilia A. The life-span and quality of-life for patients with haemophilia had improved steadily throughout the early 1980s but the principal cause of death remained intracranial haemorrhage until the epidemic of HIV infection due to contaminated factor concentrates. Infection with hepatitis C virus is almost universal for patients treated with clotting factors before 1985. No curative treatment is available for hepatitis C at present. Knowledge of the transmission of viruses in concentrates has led to important developments in processing techniques to eliminate them. Recombinant technology has produced factor VIII and, more recently, factor IX concentrate which is likely to be very safe. Development of inhibitors to factor concentrates (especially factor VIII) remains one of the most serious complications of haemophilia. The variety of treatments available testifies to the lack of a single universally efficacious one. The use of prophylactic treatment has been conclusively demonstrated to result in a preservation of joint function in severely affected patients who might otherwise develop significant joint problems. The many facets of the care of patients with severe haemophilia, ranging from dental care to genetic counselling, can be advantageously co-ordinated in a haemophilia comprehensive care centre.
Inflammation, aspirin, and the risk of cardiovascular disease
(Massachusetts Medical Society, 1997-08) Cahill, Mary R.; Perry, Ivan J.
Parasuicide and general practice: a pilot study
(Irish Medical Organisation, 1997-09) Kelleher, Michael J.; Burke, U.; Byrne, S.; Corcoran, Paul; Fitzsimons, M. M.; Keeley, Helen S.; Williamson, Eileen; Health Research Board; Department of Health, Ireland; Mid-Western Health Board, Ireland; Southern Health Board, Ireland
General Practitioners from Cork City and its environs were sent a questionnaire regarding their experience of parasuicide in the previous twelve months. Replies were received from 133 of the 185 GPs. 189 individuals, accounting for 212 episodes of parasuicide, were seen by 78 doctors, indicating a lower level of repetition than that found in hospital-referred cases. Almost a third of doctors saw no cases, just over one fifth saw one episode and the same proportion dealt with two. A small number of general practitioners saw many cases. Regarding management, 128 (60%) were referred to Casualty, 31 of whom were also referred for psychiatric care. Thirty percent were referred directly for psychiatric care. While only fourteen were retained within general practice without referral, 40% of the GPs felt that, ideally, acts of parasuicide should be retained with more specialised advice being obtained. Furthermore, 88.1% believed that management of parasuicide should form part of an integral part of post-graduate or continued general practitioner medical training. Clearly, GPs are willing to play a more active role in the management of parasuicide.
Variation in suicide rates between Health Board areas
(Irish Medical Organisation, 1998-04) Kelleher, Michael J.; Corcoran, Paul; Keeley, Helen S.; Health Research Board; Department of Health, Ireland; Mid-Western Health Board, Ireland; Southern Health Board, Ireland
This paper examines variations in suicide in the eight Health Boards of the Republic of Ireland for the years 1976 to 1995. It is found that while all have experienced a rise in male suicide, it has been much less pronounced in the Eastern Health Board which is somewhat surprising when one considers Dublin’s much-publicised problems with homelessness and hard drug misuse. Since the mid-eighties, female rates have been somewhat higher in the southern half of the country, comprising the Southern, Mid-Western and South-Eastern Health Boards. This variation may reflect a difficulty with contacting services for psychological distress in rural areas, either because of stigma or simple practical problems associated with transport. The development of appropriate services, especially in rural areas, should be at the top of the agenda of any Resource Officer to be appointed subsequent to the Final Report of the Task Force.
Neonatal resuscitation training in Ireland integrating teaching and research: a quality of care initiative in health services research
(University College Cork, 2001) Ryan, C. Anthony; Perry, Ivan J.
Resuscitation training is a vital area of education that could have a significant impact on patient outcome. This is especially true in the newborn period where inexperienced, inadequate or inappropriate resuscitation responses could affect the entire life span of a newborn infant. In addition, neonates are more often subject to asphyxia and are far more likely to be in need of resuscitation than any other age group. The World Health Organization (1995) estimates that every year there are one million neonatal deaths attributable to birth asphyxia. Due to the unique aetiology and pathophysiology of neonatal arrests, successful resuscitation requires the application of knowledge and skills that require special training. The purpose of resuscitation training is to transfer the science of resuscitation into classroom performance, with the objective of transferring knowledge and skills into clinical practice. The ultimate goal of the process is to improve neonatal survival and decrease handicap. While it is the responsibility of the Health Services to provide the necessary training for its employees, it is the function of Universities to design, develop, evaluate and promote effective educational programmes that improve patient care.
Home birth in Ireland 1993 - 1997: a review of community midwifery practice
(TM&D Press Ltd., 2002) O'Connell, Rhona; Cronin, Mary
To date little is known about the practices of domiciliary midwives and the outcomes of home birth in Ireland. The purpose of this review is to provide some background information on the situation for women seeking a home birth and to document the outcomes of home births in Ireland between 1993 -1997. Design: Descriptive analysis of prospective data collected from domiciliary midwives regarding women who requested a home birth between 1993 and 1997. Participants: The questionnaire was distributed to 15 domiciliary midwives; this included all the domiciliary midwives known to the authors to be practising in Ireland at that time. Findings: During this period, 585 women planned to give birth in their home with the assistance of midwives, 500 women achieved this. The spontaneous vaginal delivery rate for women who commenced their labour at home was 96.9% (n = 554). These women gave birth without medications or other interventions. 544 (93%) of the women breastfed their babies and 538 (92%) were still breastfeeding at 6 weeks. This is the first review of domiciliary midwifery practice in Ireland in recent years. They obtained data from 11 independent midwives on 585 women who planned home births. Findings showed high rates of spontaneous vaginal delivery and breastfeeding. There were 500 babies born at home with three perinatal deaths, including one undiagnosed breech delivery, one infant with abnormal lungs on post-mortem and one infant with Potter's Syndrome who was stillborn.
The Irish paradigm on the natural progression of hepatitis C virus infection: an investigation in a homogeneous patient population infected with HCV 1b (Review)
(Spandidos Publications, 2002-02-01) Fanning, Liam J.
The aetiological agent of chronic hepatitis C is the hepatitis C virus. The hepatitis C virus is spread by parenteral transmission of body fluids, primarily blood or blood products. In 1989, after more than a decade of research, HCV was isolated and characterised. The hepatitis C viral genome is a positive-sense, single-stranded RNA molecule approximately 9.4 kb in length, which encodes a polyprotein of about 3100 amino acids. There are 6 main genotypes of HCV, each further stratified by subtype. In 1994, a cohort of women was identified in Ireland as having been iatrogenically exposed to the hepatitis C virus. The women were all young and exposed as a consequence of the receipt of HCV 1b contaminated anti-D immunoglobulin. The source of the infection was identified as an acutely infected female. As part of a voluntary serological screening programme involving 62,667 people, 704 individuals were identified as seropositive for exposure to the hepatitis C virus; 55.4% were found to be positive for the viral genome 17 years after exposure. Of these women 98% had evidence of inflammation, but suprisingly, a remarkable 49% showed no evidence of fibrosis. Clinicopathology and virological analysis has identified associations between viral load and the histological activity index for inflammation, and, between inflammation and levels of the liver enzyme alanine aminotransferase. Infection at a younger age appears to protect individuals from progression to advanced liver disease. Molecular analyses of host immunogenetic elements shows that particular class II human leukocyte associated antigen alleles are associated with clearance of the hepatitis C virus. Additional class II alleles have been identified that are associated with stable viraemia over an extended period of patient follow-up. Although, investigation of large untreated homogeneous cohorts is likely to become more difficult, as the efficacy of anti-viral therapy improves, further investigation of host and viral factors that influence disease progression will help provide an evidence based approach were realistic expectations regarding patient prognosis can be ascertained.
The relation between maternal work, ambulatory blood pressure, and pregnancy hypertension
(BMJ Publishing Group Ltd., 2002-05) Higgins, John R.; Walshe, Joseph J.; Conroy, Rónán M.; Darling, Michael R. N.; Wellcome Trust, United Kingdom; Friends of the Rotunda Hospital, Dublin
Study objective: The purpose of the study was to determine the relations between maternal work, ambulatory blood pressure in mid-pregnancy, and subsequent pregnancy outcome. Design: Data were studied on 933 healthy normotensive primigravidas who had been enrolled into a study on the predictive value of ambulatory blood pressure measurement performed between 18 and 24 weeks gestation. They were classified into three groups depending on whether they were at work (working group, n=245), not working (not working group, n=289), or normally employed but chose not to work (ENK group, n=399), on the day monitoring was performed. Setting: The Rotunda Hospital (a large maternity hospital), Dublin, Ireland. Main results: Adjusted for age, body mass index, smoking, drinking, and marital status, women at work had higher mean daytime systolic (p<0.01) and diastolic (p<0.01) and 24 hour systolic pressures (p=0.03) compared with those not working. The rate of subsequent development of pre-eclampsia was significantly higher (odds ratio 4.1, 95% CI 1.1 to 15.2, p=0.03) among those at work compared with those not working. The association between pre-eclampsia and maternal work remained significant (odds ratio 5.5, 95% CI 1.1 to 27.8, p=0.04) even after allowing for the confounding factors of age, smoking, body mass index, and marital status. When daytime systolic and diastolic blood pressure were added to the regression analysis the risk ratios for pre-eclampsia remained high but did not quite reach statistical significance (odds ratio 4.7, 0.90 to 24.8, p=0.066). Birth weight and placental weight were not predicted by work status or blood pressure. Conclusions: A significant independent relation was found between maternal work and ambulatory blood pressure levels in mid-pregnancy. In addition, it was found that maternal work was significantly associated with the subsequent development of pre-eclampsia.
Established cardiovascular disease and CVD risk factors in a primary care population of middle-aged Irish men and women
(Irish Medical Organization, 2002-11) Perry, Ivan J.; Collins, A.; Colwell, N.; Creagh, D.; Drew, C.; Hinchion, Rita; O'Halloran, T. David; Servier Laboratories (Ireland) Ltd; Bristol-Myers Squibb, United States; Pfizer Ireland; Zeneca Pharma
Contemporary Irish data on the prevalence of major cardiovascular disease (CVD) risk factors are sparse. The primary aims of this study were (1) to estimate the prevalence of major cardiovascular disease risk factors, including Type 2 Diabetes Mellitus, in the general population of men and women between the ages of 50 and 69 years; and (2) to estimate the proportion of individuals in this age group at high absolute risk of cardiovascular disease events on the basis of pre-existing cardiovascular disease or as defined by the Framingham equation. Participants were drawn from the practice lists of 17 general practices in Cork and Kerry using stratified random sampling. A total of 1018 people attended for screening (490 men, 48%) from 1473 who were invited, a response rate of 69.1%. Cardiovascular disease risk factors and glucose intolerance are common in the population of men and women aged between 50 and 69 years. Almost half the participants were overweight and a further quarter met current international criteria for obesity, one of the highest recorded prevalence rates for obesity in a European population sample. Forty per cent of the population reported minimal levels of physical activity and 19% were current cigarette smokers. Approximately half the sample had blood pressure readings consistent with international criteria for the diagnosis of hypertension, but only 38% of these individuals were known to be hypertensive. Eighty per cent of the population sample had a cholesterol concentration in excess of 5 mmol/l. Almost 4% of the population had Type 2 Diabetes Mellitus, of whom 30% were previously undiagnosed. A total of 137 participants (13.5%) had a history or ECG findings consistent with established cardiovascular disease. Of the remaining 881 individuals in the primary prevention population, a total of 20 high-risk individuals (19 male) had a risk of a coronary heart disease event 30% over ten years according to the Framingham risk equation, giving an overall population prevalence of 2.0% (95% CI 1.3 - 3.0). At a risk level 20% over ten years, an additional 91 individuals (8.9%) were identified. Thus a total of 24.4% of the population were at risk either through pre-existing CVD (13.5%) or an estimated 10-year risk exceeding 20% according to the Framingham risk equation (10.9%). Thus a substantial proportion of middle-aged men are at high risk of CVD. The findings emphasise the scale of the CVD epidemic in Ireland and the need for ongoing monitoring of risk factors at the population level and the need to develop preventive strategies at both the clinical and societal level.
Principlism or narrative ethics: must we choose between them?
(BMJ Publishing Group, Institute of Medical Ethics, 2003-12) McCarthy, Joan
This paper addresses a current debate in the bioethics community between principlists, who consider that principles are at the heart of moral life, and narrativists, who see communication at its core. Using a case study entitled "The forgetful mourner" to introduce the tensions between each of these positions, I go on to explain the central tenets of both principlism and narrative ethics. Rather than focus on their respective weaknesses, which many theorists do, I emphasise instead, the contribution that each approach can make to understanding moral life and the process of ethical decision making in health care situations. My ultimate aim is to identify the, sometimes overlapping, skills that both principlism and narrative ethics require on the part of health professionals who deploy them. I conclude that a good principlist has narrativist tendencies and a good narrativist is inclined toward principlism.
Mechanisms of adherence of a probiotic Lactobacillus strain during and after in vivo assessment in ulcerative colitis patients
(Co-Action Publishing, 2004-07) Dunne, Colum P.; Kelly, Peter; O'Halloran, Sile; Soden, Declan; Bennett, Mary; von Wright, Atte; Vilpponen-Salmela, Terttu; Kiely, Barry; O'Mahony, Liam; Collins, J. Kevin; O'Sullivan, Gerald C.; Shanahan, Fergus; European Regional Development Fund; Department of Agriculture and Food, Ireland; Health Research Board; Science Foundation Ireland; European Commission; Higher Education Authority
In a pilot-scale, open-label study to determine the ability of well-characterized probiotic Lactobacillus salivarius UCC118 cells to adhere to human epithelial cells in situ , the bacterial strain was administered to ulcerative colitis patients at approximately 109 CFU/day for 12 days. Microbiological analysis of biopsy specimens demonstrated that the ingested bacteria effectively adhered to both inflamed and non-inflamed mucosa of the large bowel in significant numbers. In previous reports, we have described the ability of the lactobacilli to adhere to enterocytic epithelial cells in vitro. In this study, we found that the bacteria adhered at higher levels to differentiated rather than undifferentiated epithelial monolayers; and that stationary phase lactobacilli were found to adhere to eukaryotic HT-29 and Caco-2 epithelial cells at greater levels than log phase bacterial cells. Pretreatment of the Lactobacillus cells with proteolytic enzymes abolished attachment, indicating the potential involvement of surface/exposed protein(s) as bacterial adhesin(s). SDS-PAGE (denaturing) techniques determined that the proteolytic treatment resulted in degradation of a cell wall-associated protein of approximately 84 kDa. The proteinaceous factor was purified by both anion-exchange chromatography and by gel extraction after SDS-PAGE electrophoresis, and under in vitro assay conditions proved capable of adherence and significant inhibition of bacterial attachment to enterocytic epithelial cells. Key words: probiotic, Lactobacillus, adhesin, cell-borne, proteinaceous.
Abnormal patterns of tongue-palate contact in the speech of individuals with cleft palate
(Informa Healthcare, 2004-08) Gibbon, Fiona E.; Scottish Office Department of Health; Lloyds TSB Foundation for Scotland; MacRobert Trust, Scotland
Individuals with cleft palate, even those with adequate velopharyngeal function, are at high risk for disordered lingual articulation. This article attempts to summarize current knowledge of abnormal tongue-palate contact patterns derived from electropalatographic (EPG) data in speakers with cleft palate. These data, which have been reported in 23 articles published over the past 20 years, have added significantly to our knowledge about cleft palate speech. Eight abnormal patterns of tongue-palate contact are described and illustrated with data from children and adults with repaired cleft palate. The paper also discusses some of the problems in interpreting EPG data from speakers with abnormal craniofacial anatomy and emphasizes the importance of quantifying relevant aspects of tongue-palate contact data. Areas of research requiring further investigation are outlined.
The role of the dopaminergic neurotrophin growth/differentiation factor-5 in the developing rat ventral midbrain
(University College Cork, 2004-10) O'Keeffe, Gerard W.; Sullivan, Aideen M.; Irish Research Council for Science Engineering and Technology
Growth differentiation factor-5 (GDF-5) is a member of the transforming growth factor-β superfamily, a family of proteins that play diverse roles in many aspects of cell growth, proliferation and differentiation. GDF-5 has also been shown to be a trophic factor for embryonic midbrain dopaminergic neurons in vitro (Krieglstein et al. 1995) and after transplantation to adult rats in vivo (Sullivan et al. 1998). GDF-5 has also been shown to have neuroprotective and neurorestorative effects on adult dopaminergic neurons in the substantia nigra in animal models of Parkinson’s disease (Sullivan et al. 1997, 1999; Hurley et al. 2004). This experimental evidence has lead to GDF-5 being proposed as a neurotrophic factor with potential for use in the treatment of Parkinson’s disease. However, it is not know if GDF-5 is expressed in the brain and whether it plays a role in dopaminergic neuron development. The experiments presented here aim to address these questions. To that end this thesis is divided into five separate studies each addressing a particular question associated with GDF-5 and its expression patterns and roles during the development of the rat midbrain. Expression of the GDF-5 in the developing rat ventral mesencephalon (VM) was found to begin at E12 and peak on E14, the day that dopaminergic neurons undergo terminal differentiation. In the adult rat, GDF-5 was found to be restricted to heart and brain, being expressed in many areas of the brain, including striatum and midbrain. This indicated a role for GDF-5 in the development and maintenance of dopaminergic neurons. The appropriate receptors for GDF-5 (BMPR-II and BMPR-Ib) were found to be expressed at high levels in the rat VM at E14 and BMPR-II expression was demonstrated on dopaminergic neurons in the E13 mouse VM. GDF-5 resulted in a three-fold increase in the numbers of dopaminergic neurons in cultures of E14 rat VM, without affecting the numbers of neurones or total cells. GDF-5 was found to increase the proportion of neurons that were dopaminergic. The numbers of Nurr1-positive cells were not affected by GDF-5 treatment, but GDF-5 did increase the numbers of Nurr1- positive cells that expressed tyrosine hydroxylase (TH). Taken together this data indicated that GDF-5 increases the conversion of Nurr1-positive, TH-negative cells to Nurr1-positive, TH-positive cells. In GDF-5 treated cultures, total neurite length, neurite arborisation and somal area of dopaminergic were all significantly increased compared to control cultures. Thus this study showed that GDF-5 increased the numbers and morphological differentiation of VM dopaminergic neurones in vitro. In order to examine if GDF-5 could induce a dopaminergic phenotype in neural progenitor cells, neurosphere cultures prepared from embryonic rat VM were established. The effect of the gestational age of the donor VM on the proportion of cell types generated from neurospheres from E12, E13 and E14 VM was examined. Dopaminergic neurons could only be generated from neurospheres which were prepared from E12 VM. Thus in subsequent studies the effect of GDF-5 on dopaminergic induction was examined in progentior cell cultures prepared from the E12 rat VM. In primary cultures of E12 rat VM, GDF-5 increased the numbers of TH-positive cells without affecting the proliferation or survival of these cells. In cultures of expanded neural progenitor cells from the E12 rat VM, GDF-5 increased the expression of Nurr1 and TH, an action that was dependent on signalling through the BMPR-Ib receptor. Taken together, these experiments provide evidence that GDF-5 is expressed in the developing rat VM, is involved in both the induction of a dopaminergic phenotype in cells of the VM and in the subsequent morphological development of these dopaminergic neurons
Prevalence and lifestyle determinants of the metabolic syndrome
(Irish Medical Organization, 2004-11) Villegas, Raquel; Creagh, D.; Hinchion, Rita; O'Halloran, D.; Perry, Ivan J.
Participants with the metabolic syndrome are at risk of developing type 2 diabetes and coronary heart disease. The aim of this study was to determine the role of lifestyle risk factors in the development of the metabolic syndrome with particular reference to physical activity, smoking and alcohol consumption. We performed a cross sectional study of the prevalence of CVD risk factors and glucose intolerance, including type 2 diabetes involving a group of 1473 men and women were sampled from 17 general practice lists in the South of Ireland. A total of 1018 attended for screening, giving a response rate of 69%. Participants completed a detailed health and lifestyle questionnaire and provided fasting blood samples for analysis of glucose, insulin and lipids. The metabolic syndrome was defined according to the current WHO criteria. The prevalence of the metabolic syndrome was 21.0% (95% C.I. 18.7% to 24.1%). In multivariate analyses with the metabolic syndrome as the dependent variable we observed a significant, independent inverse association with physical activity level (OR=0.60; 95%CI, 0.39-0.90 for medium and OR=0.51; 95%CI, 0.28-0.93) for high level of activity relative to the low level of activity group). Ex-drinkers had a higher prevalence of the syndrome in multivariate analysis relative to occasional drinkers, (OR=2.38; 95%CI, 1.08-5.26). Prevalence of the metabolic syndrome was not significantly associated with current alcohol consumption or with smoking status. These data highlight the importance of physical inactivity in the aetiology of the metabolic syndrome.
Ascertaining women’s preferred mode of address and preferred choice of title during pregnancy and childbirth
(Irish Medical Organisation, 2005-02) Horgan, Richard P.; Guha, S.; O'Sullivan, K.; Higgins, John R.
To determine how women in pregnancy would like to be addressed and to ascertain their preferred choice of title during pregnancy. A questionnaire was administered to 925 antenatal women. Midwifery and medical staff (183) were invited to respond to a similar questionnaire.The response rate was 71.2% from the survey of pregnant women. The vast majority (82.1%) preferred to be addressed by their first name. Women were in favour of being called ’patient’ (32.8%) as their first choice. The staff survey yielded a response rate of 77%. The majority (81.8%) of health professionals preferred to address women by their first name. ’Mother’ (28.7%) was the most popular first choice. We conclude that women in pregnancy do have a preference on how they would like to be addressed and this is predominantly by first name. Health professionals also prefer to call pregnant women by their first name. The term ’patient’ was the most popular first choice of title of women in pregnancy but the term ’mother’ was the preferred choice of the health professionals. Medical staff were more likely to choose ’patient’ than midwives.
Writing to patients: 'putting the patient in the picture'
(Irish Medical Organization, 2005-02) O'Reilly, Máire; Cahill, Mary R.; Perry, Ivan J.; Health Research Board
We have explored consultant, general practitioner and patient attitudes towards the proposal that following an outpatient consultation, consultants should consider communicating directly with patients in the form of a summary letter, with a copy to the referring general practitioner or other professionals as appropriate. We conducted in-depth interviews with a purposive sample of 20 consultants, 16 patients and 12 general practitioners. The consultants and general practitioners were both involved in the care of participating patients. Patients highlighted the likely value of summary letters including, increased knowledge, improvement recall of the clinical encounter, and reassurance. Clinicians were concerned that patients would not understand letters from consultants. Additional concerns included the impact of letter on consultant-general practitioner relationship and medico-legal issues. These findings reflect fundamental differences in expectations about the nature and quality of communications between doctors and their patients.
Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 7-2005. A 59-year-old woman with an incidentally discovered adrenal nodule.
(Massachusetts Medical Society, 2005-03-10) Dluhy, R. G.; Maher, Michael M.; Wu, C. L.
Reactions to treatment debriefing among the participants of a placebo controlled trial
(BioMed Central Ltd., 2005-04-22) Di Blasi, Zelda; Crawford, Fay; Bradley, Colin P.; Kleijnen, Jos; Medical Research Council, United Kingdom; Chief Scientist Office, Scotland
BACKGROUND: A significant proportion of trial participants respond to placebos for a variety of conditions. Despite the common conduct of these trials and the strong emphasis placed on informed consent, very little is known about informing participants about their individual treatment allocation at trial closure. This study aims to address this gap in the literature by exploring treatment beliefs and reactions to feedback about treatment allocation in the participants of a placebo-controlled randomized clinical trial (RCT). METHODS: Survey of trial participants using a semi-structured questionnaire including close and open-ended questions administered as telephone interviews and postal questionnaires. Trial participants were enrolled in a double-blind placebo-controlled RCT evaluating the effectiveness of corticosteroid for heel pain (ISRCTN36539116). The trial had closed and participants remained blind to treatment allocation. We assessed treatment expectations, the percentage of participants who wanted to be informed about their treatment allocation, their ability to guess and reactions to debriefing. RESULTS: Forty-six (73%) contactable participants responded to our survey. Forty-two were eligible (four participants with bilateral disease were excluded as they had received both treatments). Most (79%) participants did not have any expectations prior to receiving treatment, but many 'hoped' that something would help. Reasons for not having high expectations included the experimental nature of their care and possibility that they may get a placebo. Participants were hopeful because their pain was so severe and because they trusted the staff and services. Most (83%) wanted to be informed about their treatment allocation and study results. Over half (55%) said they could not guess which treatment they had been randomized to, and many of those who attempted a guess were incorrect. Reactions to treatment debriefing were generally positive, including in placebo responders. CONCLUSION: Our study suggests that most trial participants want to be informed about their treatment allocation and trial results. Further research is required to develop measure of hope and expectancy and to rigorously evaluate the effects of debriefing prospectively.
Divergent and convergent evolution after a common-source outbreak of hepatitis C virus.
(© 2005 Rockefeller University Press, 2005-06) Ray, Stuart C.; Fanning, Liam J.; Wang, Xiao-Hong; Netski, Dale M.; Kenny-Walsh, Elizabeth; Thomas, David L.; Health Research Board
The genomic sequences of viruses that are highly mutable and cause chronic infection tend to diverge over time. We report that these changes represent both immune-driven selection and, in the absence of immune pressure, reversion toward an ancestral consensus. Sequence changes in hepatitis C virus (HCV) structural and nonstructural genes were studied in a cohort of women accidentally infected with HCV in a rare common-source outbreak. We compared sequences present in serum obtained 18–22 yr after infection to sequences present in the shared inoculum and found that HCV evolved along a distinct path in each woman. Amino acid substitutions in known epitopes were directed away from consensus in persons having the HLA allele associated with that epitope (immune selection), and toward consensus in those lacking the allele (reversion). These data suggest that vaccines for genetically diverse viruses may be more effective if they represent consensus sequence, rather than a human isolate.

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