bluuebunny/crossref_metadata_2025 huggingface dataset:
First steps towards evaluating clinical supervision in nursing and health visiting. I. Theory, policy and practice development. A review
Authors: BUTTERWORTH TONY , BISHOP VERONICA , CARSON JEROME
Published: December 2007

The subject of clinical supervision for nurses and health visitors in the UK is considered in this paper.

The paper highlights recent debates in thinking and rapid developments in practice.

The original concept of clinical supervision, its theoretical propositions and development, recent policy influences and current strategies for evaluation are debated.
An investigation into the attitudes and practices of intensive care nurses towards verbal communication with unconscious patients
Authors: BAKER C. , MELEY V.
Published: December 2007

This study attempted to investigate the attitudes and practices of intensive care nurses towards verbal communication with unconscious patients. A sample of five staff nurses working in an intensive care unit in Northern Ireland formed the basis for the study.

The research design was non‐experimental and descriptive‐exploratory in nature, incorporating 4‐hourly observational periods and structured interviews.

Qualitative and quantitative analysis indicated that intensive care nurses spend on average 5% of their time verbally communicating with unconscious patients. Most of this communication involves informing the patient of immediate procedural matters or providing reassuring statements.

Most intensive care nurses claim that verbal communication with unconscious patients is very important, and some ambiguity is apparent as to the unconscious patient's level of awareness. Major factors influencing communication are the patient's level of consciousness, the amount of physical care being given and the presence of relatives.
Community mental handicap nursing services in Northern Ireland: a profile of clients and selected working practices
Authors: PARAHOO KADER , BARR OWEN
Published: December 2007

The aim of this survey of community mental handicap nursing in Northern Ireland (NI) was, among other things, to construct a profile of clients of the service as well as to describe selected working practices.

A 25‐item questionnaire was developed and administered to all 50 community nurses working with people with learning disabilities in NI. The number of responses was 36, giving a rate of 72%.

Fifty‐six per cent of the clients were female. Young to middle‐aged adults made up the largest portion of the caseload. Over 80% of the clients had no history of hospital admission.

Caseload size also differed according to the years of service, gender and grade of the nurses. The main reason for visiting clients as reported by respondents was to give physical care.
An evaluation of staff training in psychological techniques for the management of patient aggression
Authors: WHITTINGTON RICHARD , WYKES TIL
Published: December 2007

Training for staff working with violent patients is frequently recommended, sometimes implemented, but rarely objectively evaluated.

In this longitudinal study 47 nurses attending a training day to learn strategies for coping with violent psychiatric patients were compared with 108 non‐attending control group subjects.

The rate of assaults on staff on wards taking part in the study was 31% lower after implementation of the training and wards sending a majority of staff to the training experienced a particularly significant reduction in assaults.

The effectiveness of this 1‐day training package is discussed.
The evolving role of the clinical nurse specialist within the comprehensive breast cancer centre
Authors: POOLE KAREN
Published: December 2007

The collaborative functioning of a specialist multidisciplinary team is a fundamental prerequisite in the establishment of designated breast cancer units throughout the UK. It is, therefore, opportune for clinical nurse specialists to examine carefully their unique contribution to the care of women with breast disease.

This article explores the contemporary developments in service provision and identifies potential areas for nursing development.

It is only when the role of the breast care nurse is explicitly defined can research begin to determine the effectiveness of nursing practice in terms of women's health.
Readability of printed educational materials used to inform potential and actual ostomates
Authors: COEY LAURENCE
Published: December 2007

This paper is primarily concerned with the use of readability formulas to determine the reading ease of printed education materials (PEMs) given to ostomy patients. Whilst the particular clinical focus is stoma care nursing, the content is relevant to all nurses who use printed text to inform their patients. PEMs have significant advantages in conveying information compared with verbal presentations alone.

Methods to calculate readability using the Flesch, FOG and SMOG readability formulas are described. Presentation factors that affect readability are briefly reviewed, including use of ‘white space’, font size and paper colour. The problem of functional illiteracy and the need for indirect assessment of patient literacy are discussed.

PEMs in use are often found to be difficult to read. Stress is identified as a potential factor in further reducing a patient's ability to deal with information.

Three commercially available PEMs are evaluated for ease of reading and their score on the FOG index indicates that only about 40% of the UK population would understand them.

Nurses are advised to evaluate the readability of their PEMs and to assess indirectly the literacy of their patients, so that they can more sensitively match PEMs to patient ability and need.
Coping with rheumatoid arthritis. How can specialist nurses influence it and promote better outcomes?
Authors: NEWBOLD DAVID
Published: December 2007

Psychological stressors are said to be an important influence on the outcome of chronic illnesses such as rheumatoid arthritis (Engel, 1977).

Helping patients to cope with stressors is identified as a central concept in the delivery of nursing care (Khan et al., 1994). It is thus reasonable to suggest that rheumatology nurses may be key players in the process of coping with rheumatoid arthritis.

But in order for rheumatology nurses to be effective players in this process, they need to discourage coping behaviour(s) linked to poor outcomes, and/or promote an overall behaviour pattern linked to a better outcome. Literature showing the link between different coping behaviours and outcome is examined, and cognitive restructuring is emphasized as one method nurses could use.

Having identified coping behaviour which is optimal in terms of future outcome, further study of different forms of coping‐based educational intervention is suggested, to reveal how such patterns of behaviour can be taught by nurses in the most effective way
Endotracheal suctioning: an example of the problems of relevance and rigour in clinical research
Authors: WAINWRIGHT STEVEN P. , GOULD DINAH
Published: December 2007

Endotracheal suctioning is a routine but potentially dangerous procedure. The literature documenting approaches to minimizing the cardiopulmonary complications of endotracheal suctioning is reviewed. Hyperoxygenation, hyperventilation, hyperinflation and the use of adaptors are all evaluated. The effects of endotracheal suctioning on haemodynamics and oxygen transport are also examined. The traditional dualist approach to the respiratory and cardiovascular systems is contrasted with the recent emphasis on oxygen transport by the cardiopulmonary system.

The trade‐off between the rigour of laboratory studies (which can be well controlled but are difficult to generalize) and the relevance of clinical research (which is more easily generalized but which often lacks internal validity) is discussed. Although research studies have become both more methodologically and conceptually sophisticated, definitive recommendations for a safe and effective suctioning procedure still remain elusive.
Future imperatives: developing health visiting in response to changing demands
Authors: DOLAN BRIAN , KITSON ALISON
Published: December 2007

This paper is based on work undertaken by the National Institute for Nursing to establish mechanisms to enable purchasers to be more explicit about purchasing health visiting services by the commissioning health authority.

The paper describes work undertaken to identify current issues, through selected reviews of the literature, the use of questionnaires, interviews with key stakeholders and, as a result, the development of an ‘ideal model for practice’ for health visitors.

The development of possible outcome measures for health visiting practice is also considered in the context of changing health‐care demand and delivery which is both a feature and the future of community care.
A situational analysis of an HIV/AIDS clinical area
Authors: GRIGG ELIZABETH
Published: December 2007

The following paper is an account of a situational analysis in a human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) ward. Initially it was intended to test a number of hypotheses extracted from the literature, and, using previous experience from participant observation, apply them to this particular clinical area.

Becoming established (‘getting in’) in the new unit to be studied (situation) took 6 months and, although it was eventually possible to test the original hypotheses, the process of ‘getting in’ became the main point of analysis.

Taking into account the situation of ‘getting in’, the conversations with the nursing staff and the background information, it is concluded that the HIV/AIDS predicament is and will continue to provide a major challenge for nurses and nurse educators.
Beyond expertise: theory, practice and the reflexive practitioner
Authors: ROLFE GARY
Published: December 2007

This paper reconsiders Benner's book From Novice to Expert, in which the expert is portrayed as a reflective practitioner who works intuitively, drawing almost unconsciously on a repertoire of context‐specific paradigm cases.

In the light of more recent writings on informal, practice‐based theory, it is suggested that there is a sixth level beyond expertise which is characterized by mindful practice and informal theory building. At this level, the practitioner constructs informal theory out of practice, applies that theory back into practice, and reflexively modifies the theory as a result of the changed clinical situation.

Seen in this way, theory and practice are two parts of the same process, and the theory‐practice gap is closed.
Towards a defence of nursing routine and ritual
Authors: BILEY FRANCIS C. , WRIGHT STEPHEN G.
Published: December 2007

Healing routines and rituals have been an essential part of life since time immemorial. Rather than dismiss modern healing rituals because, in many instances, they appear to have no empirically proven manifest function, an argument is proposed in defence of routine and ritual, suggesting that there is an urgent need to explore their meaning or latent function.
Critical incidents, crucial issues: insights into the working lives of registered nurses
Authors: PERRY LIN
Published: December 2007

The critical incident technique has been used in nursing in a number of ways: in developing understanding of the nursing role, as a quality assurance strategy, as an assessment and evaluation tool, and as an aid in the fostering of reflective practice.

This article describes how the technique, used as a theoretical course assessment for a group of students studying long ENB courses, could be used to shed light upon issues regarded as crucial in the daily working lives of this group of registered nurses, and upon the reflective skills which they were able to employ.
A conceptual framework for advanced practice: an action research project operationalizing an advanced practitioner/consultant nurse role
Authors: MANLEY KIM
Published: December 2007

A preliminary conceptual framework for an advanced practice/consultant nurse role is presented which links the role to its context and outcomes.

The conceptual framework was developed in the process of analysing data from a 3‐year action research study involving the operationalization of an advanced practice/consultant nurse role in a Nursing Development Unit.

The skills and knowledge base of consultancy, underpinned by a strong nursing foundation, augmented by strong leadership and combined with the educator and researcher functions, are presented as the attributes of the advanced practitioner/consultant nurse.

The facilitation of a transformational culture is highlighted as central to the skills and processes used within the role.

Implications for the preparation and accreditation of the advanced practitioner/ consultant nurse are highlighted.
Where do I stand? Legal implications of telephone triage
Authors: COLEMAN ANDREW
Published: December 2007

The introduction of telephone triage in many accident and emergency (A&E) departments is seen as a way to give clients information immediately on demand, to assess and prioritize the need for treatment and to direct the client to the most appropriate service available.

This article aims to examine the medico‐legal aspects of telephone triage and the nurse's responsibility to the caller and themselves.

It will involve looking at triage as a nursing function and how the nurse may minimize the threat of liability by beginning to understand the legal implications of giving advice by telephone.

The article will also discuss the use of detailed documentation and communication skills and will aim to show how important these are in the protection of nurses in a court of law.
Nursing staff's perceptions and experiences of primary nursing practice in intensive care 4 years on
Authors: MANLEY KIM , HAMILL JANE‐MARIE , HANLON MARTHA
Published: December 2007

This study explores the perceptions of staff who have been practising primary nursing for more than 4 years in intensive care.

It considers what primary nursing is, what its benefits, disadvantages, and role impact are and other issues within an intensive care setting from the staff's perceptions and experiences.

Although many of the perceived advantages and disadvantages are similar to experiences from other areas of nursing, there are some differences.

The differences seem to relate to the way primary nursing is practised within the research setting – each primary nurse works with the same small team of associates, which is perceived as providing added benefits in terms of personal support and development of junior staff.

The changes in role are seen to reflect other models in the literature which focus on becoming more patient centred and on working therapeutically.

A number of future issues are addressed.
Advocacy in nursing – perceptions of practising nurses
Authors: MALLIK MAGGIE
Published: December 2007

This paper reports on a qualitative study which examined the interpretation of patient advocacy by practising nurses.

Focus group interviews, which allowed respondents to recount and share their particular ‘stories’ of patient advocacy, were used to collect data.

Results indicate that a triadic model of advocacy predominated which involved the nurse in a conflict/potential conflict situation. The patient's requests, the patient's fear, the patient's vulnerability or threats to the patient's human rights provoked an advocacy response in the perceptive nurse. The nurse was sustained in the role through patient recognition, the nurse–patient relationship, emotional strength, moral justification and knowledge/expertise legitimacy.

The nurse used direct and indirect means to protect the patient against incompetent/inappropriate practice and/or represent patient/family choice, the advocacy activity resulting in positive or negative outcomes.

In conclusion it is argued that if the triadic conflict model of advocacy outlined by this research is to be sustained by practising nurses, the potential risks involved should be recognized. Professionalization of the role may be the only way forward if the ethical code (United Kingdom Central Council, 1992) continues to make patient advocacy a mandatory activity for the professional nurse.
Defining ‘competency’ in nursing (Part I): a policy review
Authors: BRADSHAW ANN
Published: December 2007

How the nursing profession in England defines the basic competency of the registered general nurse is crucial for the safety of the patient and the protection of the nurse. It is also essential for determining advanced practice, extended practice and specialist practice in nursing.

An historical overview of documentation from the United Kingdom Central Council for Midwifery and Health Visiting, the English National Board for Nursing, Midwifery and Health Visiting and the Royal College of Nursing shows a profound change in educational policy during the 1980s regarding the interpretation of nursing competency.

The effects of this policy change on the current methods developed to define, teach and test nursing competency are examined.

Preliminary conclusions show shortcomings and uncertainty in the present preparation and evaluation of nursing competency.
Changes in practice nursing: professionalism, segmentation and sponsorship
Authors: DENT MIKE , BURTNEY ELIZABETH
Published: December 2007

In the wake of recent government policies and legislation, practice nursing has undergone major changes. Not least of these has been the rapid growth in the number of practice nurses.

In addition, their work role has grown greatly over recent years.

This has given rise to the question of whether their professional development now justifies their status as autonomous nurse practitioners.

This and related issues are explored in the empirical part of this paper, which focuses on the changes in the work and responsibilities of practice nurses in two industrial towns in the English Midlands.
A study of nurses' views about the prevention of nosocomial urinary tract infections
Authors: BRIDGER JANE C.
Published: December 2007

This study sought to discover the contribution of nursing practice to the prevention of hospital‐acquired or nosocomial urinary tract infections (NUTIs), the most commonly occurring nosocomial infection.

Seventy‐five per cent of such infections are associated with urethral catheters.

The practices of nurses who are caring for patients on a 24 h basis would appear to be fundamental to achieving any reduction in the incidence of NUTIs.

This qualitative study utilized unstructured interviews to explore the views of 12 registered nurses about three key issues: first, what care do nurses give with the aim of preventing catheter‐associated NUTIs; secondly, what improvements in practice would further prevent catheter‐associated NUTIs; thirdly, what do nurses see as constraints to the prevention of catheter‐associated NUTIs?

The nurses identified many of the measures that were cited in the literature as effective for preventing NUTIs; however, in reality, they stated that their practice differed because of a lack of time to give care and to update themselves.

The consequences of under‐staffing were that junior and temporary staff (whose competence in preventing NUTIs was questioned) worked unsupervised.

Those interviewed identified feelings of powerlessness in effecting preventative measures, and identified not only the role of medical staff in influencing NUTIs but also their inconsistent approach to care.

All these forces effectively limited the nurses' ability to prevent NUTIs.

The study is concluded with recommendations for changes in practice and further research.
An attempt to give nursing home residents a voice in the quality improvement process: the challenge of frailty
Authors: MITCHELL PATRICIA , KOCH TINA
Published: December 2007

Advanced frailty and confusion of many nursing home residents present a particular conundrum to researchers committed to resident participation. While the research is set in Australia, the challenge of frailty is common to researchers working with compromised older persons.

This study was conducted in an Australian 32 bed nursing home. As researchers we took on the roles of facilitators and negotiators within a quality improvement process using the approach of fourth generation evaluation.

The overall aim of the project was to provide all stakeholders, including residents and their significant others, with a voice in the negotiations and decisions that impact on their lives.

The focus of this paper is our attempt to gain the perspective of residents and significant others.
Evaluation of a new night nursing service for elderly people suffering from dementia
Authors: WATKINS MARY , REDFERN SALLY J.
Published: December 2007

A new night hospital nursing service was developed for older people with dementia.

A case study approach to evaluation was adopted using a structure‐process‐outcome quality assurance cycle.

The effects and attendance of patients are reported and discussed.

Discussion relating to care provision for the future is presented.

The effects on carers of patients' attendance are briefly discussed.
Integrated Care Pathways: effective tools for continuous evaluation of clinical practice
Authors: Kitchiner Denise , Davidson Campbell , Bundred Peter
Published: December 2007

The critical examination of clinical practice should be an integral part of patient care. It includes the development and implementation of guidelines, together with continuous evaluation of clinical process and outcomes to improve the quality of care provided. Clinical audit has not been successful in achieving this. The use of Integrated Care Pathways facilitates the introduction of guidelines and the continuous evaluation of clinical practice. Improvements are achieved by frequently revising the pathways to reflect current, local best practice.

Integrated Care Pathways define the expected course of events in the care of a patient with a particular condition, within a set time‐scale. A pathway is divided into time intervals during which specific goals and expected progress are defined, together with appropriate investigations and treatment. A pathway reflects the activities of a multidisciplinary team and can incorporate established guidelines and evidence‐based medicine. It is usually unique to the institution in which it was developed. The pathway forms part of the clinical record of every patient. All variations from the pathway are documented, and the reasons for the variations analysed. Solutions are developed to address the causes of potentially avoidable variation, and the pathway is revised to incorporate these improvements. Integrated Care Pathways provide a powerful audit tool, as all aspects of the process and outcome of clinical practice can be constantly monitored. Variations from set standards are minimized, and improvements are rapidly incorporated into routine practice and subsequently re‐evaluated.
Qualitative research in health care: II. A structured review and evaluation of studies
Authors: Boulton Mary , Fitzpatrick Ray , Swinburn Clare
Published: December 2007

A hand search of the original papers in seven medical journals over 5 years was conducted in order to identify those reporting qualitative research. A total of 210 papers were initially identified, of which 70 used qualitative methods of both data collection and analysis. These papers were evaluated by the researchers using a checklist which specified the criteria of good practice. Overall, 2% of the original papers published in the journals reported qualitative studies. Papers were more frequently positively assessed in terms of having clear aims, reporting research for which a qualitative approach was appropriate and describing their methods of data collection. Papers were less frequently positively assessed in relation to issues of data analysis such as validity, reliability and providing representative supporting evidence. It is concluded that the full potential of qualitative research has yet to be realized in the field of health care.
Decision making in HIV testing among a group with low HIV risk
Authors: Coyle Adrian , Knapp Maria , O'Dea Edmond
Published: December 2007

Relatively little is known about how individuals (apart from gay and bisexual men) decide to have an HIV test and how, once they have presented for testing, they make decisions about proceeding through the testing trajectory. This paper reports on a qualitative study in which 55 mainly heterosexual respondents with low HIV risk were interviewed about their experiences of decision making around HIV testing. Reasons for deciding to be tested centred on a desire for reassurance and the circumstances of the respondents' current relationship. The most common relationship reason focused on a desire to confirm HIV status before beginning sexual relations or engaging in unprotected sex with a partner. Although some respondents recognized that other individuals had influenced their decision to be tested, few said that pretest counselling had been influential in this respect. Instead, it was said to have promoted feelings of ‘ownership’ of a decision which had already been taken prior to counselling. The potential effects of HIV testing on HIV risk behaviour were also examined and a non‐significant increase in unprotected sex was reported between the month before the test and the month after. The implications of these findings for the provision of HIV testing services are explored.
Is the patient's right to die evolving into a duty to die?: Medical decision making and ethical evaluations in health care
Authors: Sprung Charles L. , Eidelman Leonid A. , Steinberg Avraham
Published: December 2007

When patient or family requests for continued life‐sustaining treatments conflict with doctor recommendations, different conclusions as to what is beneficial for the patient may arise. Past practices usually accepted patient or family requests based on the principle of autonomy or that the doctor's primary responsibility is to the individual patient. Many patients die in intensive care units after doctors forego life‐prolonging interventions. Health care changes and cost containment have led to a change in the classical ethical model of the patient‐doctor relationship such that concerns for societal requirements increasingly overrule those for individual patient needs. The ability to keep patients alive with little likelihood of recovery and the recognition of escalating health costs have led to calls for the needs of society and distributive justice to be taken into account. A tendency to justify a duty to die for these patients has arisen. Recent legal decisions in cases with conflicts between families and health care providers and institutions over foregoing life‐sustaining therapies have decided for the families against doctors and hospitals, compelling institutions and their staff to act contrary to their ethical views. Value judgments of doctors are sometimes confused with medical indications for therapy. Doctors have defined therapies as futile or non‐beneficial based on their own values and even withdrawn life‐sustaining treatments without patient or family input. In some cases, the right to die is leading to the duty to die even against patient or surrogate wishes. Such observations indicate the need for rigorous analyses of medical decision making in this context and for ethical evaluations in health care in general.
Evidence‐based medicine: a Kuhnian perspective of a transvestite non‐theory
Authors: MD Joaquim S. Couto
Published: December 2007

Evidence‐based medicine (EBM) has been presented by its protagonists as a new paradigm for medical practice. In this article that claim is analysed through the theory of scientific development proposed by Thomas S. Kuhn in 1962. Traditional medical paradigms are discussed, as well as the assumptions of the supposedly ‘new’ paradigm of EBM. The value of the results of randomized clinical trials (RCTs) for the elaboration of clinical guidelines is analysed within the context of the assumptions of EBM and the paradigm concept of Thomas S. Kuhn. It is argued that the results of RCTs, whenever contradicted by fundamental medical theory, constitute inadmissible evidence for the development of clinical guidelines. The supremacy of results of clinical trials over traditional medical paradigms, advocated by the protagonists of EBM, is rejected. Fundamental contradictions of EBM are also exposed: the fact that there is no evidence to support the utility of EBM and its call for a new type of authoritarianism in medicine. Finally, it is suggested that ‘epidemiology‐based medical practice’ is a better, rhetoric‐free designation for what is currently termed evidence‐based medicine*. It is concluded that EBM is not what it claims to be and that its assumptions are simply irrational.
A false dichotomy. Commentary on ‘Clinical guidelines: ways ahead’ (C. W. R. Onion and T. Walley, Journal of Evaluation in Clinical Practice 4, 287–293, this issue)
Authors: MRCGP Jeremy M. Grimshaw MBChB PhD , MRCGP M. Stuart Watson MBChB MSc , MFPHM Martin Eccles MBBS MD FRCP FRCGP
Published: December 2007

The dichotomy between ‘scientific’ and ‘practical’ approaches to guideline development is false and divisive. Instead we should concentrate on developing mechanisms to develop and implement valid guidelines to improve patient care. The development of valid guidelines requires considerable expertise and is time consuming and expensive. It is most efficiently done at a regional or national level. The implementation of valid guidelines requires local action including the identification and modification of valid guidelines and a coordinated evidence‐based implementation strategy (Grimshaw & Eccles 1998).
Performance management using health outcomes: in search of instrumentality
Authors: MFPHM H.T.O. Davies PhD Hon
Published: December 2007

The past decade has seen the growing use of performance data in the hope of bringing about quality improvements in health care. Most recently, an emphasis on health outcomes (and especially mortality rates) has led to much activity around collecting and publishing such data. Two major problems intervene. What meanings can be ascribed to reported health outcomes? And what impacts are they likely to have on clinical performance? Much empirical work supports the assertion that reported outcomes may be poor indicators of service quality. In addition, the impact of these data may be small or even detrimental unless great care is made to connect the reporting with explicit quality‐improving actions.
Trainee teachers’ attitudes to inclusive education for children with Down's syndrome
Authors: Wishart J. G. , Manning G.
Published: December 2007

The attitudes of 231 trainee teachers towards inclusive education for children with Down's syndrome were surveyed in two UK colleges of education, one in Scotland and one in Northern Ireland. While the right to educational integration for children with special educational needs was widely endorsed, considerable reservations were expressed about its implementation in practice. Only 13% of respondents indicated that they would welcome the opportunity to teach in an integrated setting and 96% felt that their professional training did not prepare them to meet this challenge. Many underestimated potential levels of achievement in children with Down's syndrome and over half wrongly associated the condition with very short life expectancy.
Recessive (true) microcephaly: a case report with neuropathological observations
Authors: McCreary B. D. , Rossiter J. P. , Robertson D. M.
Published: December 2007

The clinical and pathological features of a severely retarded 77‐year‐old man with recessive (true) microcephaly are reported. This case demonstrates that this major developmental error can be consistent with normal longevity.
Ring chromosome 22 and mood disorders
Authors: Sovner R. , Stone A. , Fox C.
Published: December 2007

The case of a 21 ‐year‐old man with severe developmental disabilities, ring chromosome 22 and rapid‐cycling bipolar illness is presented. This is the first reported occurrence of mood disorder in a person with ring chromosome 22. Previously published case reports describing behavioural problems associated with this chromosome disorder suggest that severe hyperactivity is typical and that affected individuals may have an excited mood state. These symptoms are consistent with atypical bipolar disorder and raise the possibility that ring chromosome 22 increases the risk for atypical bipolar disorder.
Hepatitis δ virus attaches to human hepatocytes via human liver endonexin II, a specific HBsAg binding protein
Authors: de Bruin W. , Leenders W. , Kos T. , Hertogs K. , Depla E. , Yap S. H.
Published: December 2007

SUMMARY. Recently we identified human liver endonexin II (EII) as a specific hepatitis B surface antigen (HBsAg) binding protein. To investigate whether EII is also able to interact with the HBsAg envelope of the hepatitis δ virus (HδV). immunoprecipitation experiments were performed. HδV particles could be co‐precipitated by polyclonal rabbit anti‐EII, but not by rabbit anti‐glutathiontransferase (GSTφ) antibodies from an HδV‐enriched fraction containing EII or GSTφ. These findings suggest that HδV particles were co‐precipitated by anti‐EII as a consequence of the binding between HBsAg present in the HδV envelope and EII. Furthermore, binding of HδV particles to human hepatocytes could be inhibited by incubation of the liver cells with rabbit anti‐EII IgG or the HδV particles with anti‐idiotypic (anti‐HBsAg) antibodies, developed spontaneously in rabbits immunized with EII. These findings support the assumption that small HBsAg present in the HδV envelope is important for the attachment to the hepatocytes and that EII plays an important role in this process.
Alterations of the RB tumour suppressor gene in hepatocellular carcinoma and hepatoblastoma cell lines in association with abnormal p53 expression
Authors: Farshid M. , Hsia C. C. , Tabor E.
Published: December 2007

SUMMARY. Alterations in the expression of the RB tumour suppressor gene were found by Western immunoblot in three of seven hepatocellular carcinoma and hepatoblastoma cell lines. Abnormalities were detected by single‐strand conformation polymorphism (SSCP) within exons 17–21 in RB cDNA from two of these three cell lines and within exons 20–21 in the third cell line. In these three cell lines with abnormal RB expression, abnormal expression of the p53 tumour suppressor gene was also found, apparently the product of a mutant gene. Thus, mutations within the RB gene (or splice‐site mutations with exon‐skipping) and apparent mutations of the p53 gene together may have contributed to the development of three of these tumours or to the establishment of these cell lines.
Immunogenicity of a ‘pre‐S2 plus S’ hepatitis B vaccine in healthy adults
Authors: Katkov W. N. , Watkins E. , DeMelia H. C. , Dienstag J. L.
Published: December 2007

SUMMARY. The product of the pre‐S plus S gene of hepatitis B virus appears to be more immunogenic in mice than the S‐gene product (HBsAg) alone. Therefore, we tested the immunogenicity in healthy adults of a hepatitis B vaccine containing the ‘middle protein’ gene product of pre‐S2 plus S (pre‐S vaccine). We compared the immunogenicity of three doses of the pre‐S vaccine with that of a commercially available recombinant hepatitis B vaccine (Recombivax‐HB®): 87 seronegative adults were randomized to receive 12 μg (group 1), 24 μg (group 2), or 48 μg (group 3) of the pre‐S vaccine or 10μg of Recombivax‐HB (group 4) by deltoid injection at 0, 1 and 6 months. Antibody to HBsAg (anti‐HBs) appeared after booster vaccination in 94% of vaccinees. Immunogenicity was best in recipients of 48 μg of the pre‐S vaccine and Recombivax‐HB, and geometric mean titres (GMT) for the pre‐S vaccine were higher than those for Recombivax‐HB only at the pre‐S vaccine dose of 48 μg (group 3). Antibody to pre‐S2 developed in 75% of the pre‐S2 vaccine recipients (not in Recombivax‐HB recipients) within 7 months. These findings indicate that the pre‐S vaccine is immunogenic in healthy adults but that a dose of 48 μg of the current formulation is required to equal or exceed the immunogenicity of currently available, recombinant S‐only vaccine. Studies in non‐responders to S‐only vaccines will be necessary to define an immunological advantage of the pre‐S vaccines, and additional assessments will be necessary to determine whether anti‐pre‐S2 enhances protective efficacy.
Detection and quantitation of hepatitis B virus DNA: comparison of two commercial hybridization assays with polymerase chain reaction
Authors: Aspinall S. , Steele A. D. , Peenze I. , Mphahlele M. J.
Published: December 2007

Summary. Serum hepatitis B virus (HBV) DNA is now the most important and reliable marker for monitoring hepatitis B viral replication. Quantitative detection of HBV DNA in serum is based on commercial standardized molecular hybridization test systems. We compared two hybridization assays, the Digene Hybrid Capture assay (Digene Diagnostics, Beltsville, MD) and the Abbott HBV DNA assay (Abbott Laboratories, North Chicago, EL, USA) with the polymerase chain reaction (PCR) technique, for detection and quantitative measurement of serum HBV DNA. Forty‐two patients with various HBV serological marker profiles were included in this study. The patients were divided into four groups according to their HBV DNA values after HBV DNA determination in the serum by the Abbott assay. For each patient HBV DNA was then determined by the Digene assay and by PCR. In the case of Digene and PCR there was a 97.6% correspondence in the outcome of the two methods, whereas in the Abbott assay and PCR there was only 69% correspondence. The McNemar test of symmetry showed no statistically significant difference between the Digene assay and PCR, whereas there was a significant difference (P < 0.01) in the Abbott assay and PCR. For low positive HBV DNA values between 1.5 and 20 pg ml‐1 the Abbott assay yields inconclusive results. Differences observed between the two hybridization assays underline the need for standardization of HBV DNA quantitation.
Post‐hepatitis syndrome revisited
Authors: Berelowitz G. J. , Burgess A. P. , Thanabalasingham T. , Murray‐Lyon I. M. , Wright D. J. M.
Published: December 2007

Summary. To examine the role of acute hepatitis A and B infection in the aetiology of chronic fatigue syndrome and psychiatric morbidity we studied 40 patients with acute viral hepatitis A or B consecutively admitted to an infectious diseases unit and studied at least 6 months after recovery. Liver function tests (LFT) had returned to normal in each case. Forty‐seven patients with other infectious diseases, of which 12 were presumed viral, admitted immediately after each hepatitis patient during the same period acted as controls. The main outcome measures were scores on a fatigue and muscle pain questionnaire, general health questionnaire (GHQ12) and supplementary questions. The hepatitis cases scored significantly higher fatigue scores, GHQ‐12 scores and muscle pain scores. Length of time since recovery from illness, age and sex were not confounding factors. Hepatitis cases were also less energetic, had greater weight change, had altered alcohol tolerance, had less exercise tolerance and felt less fit than the control group and compared with their premorbid state. Hence fatigue is more common after recovery in patients hospitalized for hepatitis A and B up to 30 months post‐infection compared with matched controls hospitalized for other infectious diseases. Hepatitis A and B infection is a risk factor for post‐infection fatigue, intermittent fatigue, as well as for psychiatric morbidity.
The fluctuations of hepatitis C virus RNA and IgM anti‐HCV (core) serum levels correlate with those of alanine aminotransferases during the hepatitis relapses of patients treated with interferon
Authors: Negro F. , Abate M. L. , Mondardini A. , Baldi M. , Leandro G. , Lombardi S. , Wolfe L. , Ryff J. C. , Verme G. , Brunetto M. R. , Bonino R
Published: December 2007

Summary. Variations in the serum levels of hepatitis C virus (HCV) RNA, IgM antibody against the HCV ‘core’ structural protein (c22) and alanine aminotransferase (ALT) were measured in 23 patients with chronic hepatitis C who underwent therapy with interferon‐α2a (IFNα2a). Low pretreatment levels of viraemia and undetectable IgM anti‐core were significantly associated with a long‐term response to treatment. In patients with hepatitis relapses after the end of treatment, HCV RNA levels increased before or at the same time as ALT in 29 out of 34 cases (85%). ALT flares occurred before or simultaneously with IgM anti‐core elevations in 18 out of 20 cases (90%). Therefore, post‐treatment hepatitis C exacerbations show the same sequence of events seen as in hepatitis B exacerbations (increases of viraemia followed by those of ALT and IgM anti‐‘core’). These findings underscore the diagnostic and prognostic usefulness of monitoring anti‐HCV‐positive patients with quantitative assays for HCV markers.
Plasma glutathione concentration in patients with chronic hepatitis C virus infection
Authors: Lim H. L. , Myers B. M. , Hamilton B. A. , Davis G. L. , Lau J. Y. N.
Published: December 2007

Summary. It has recently been proposed that a depletion of glutathione (GSH) may be a contributing factor to viral persistence and resistance to interferon‐α (IFN‐α) therapy in chronic hepatitis C virus (HCV) infection. The aim of this study was: (1) to compare plasma GSH levels in patients with chronic HCV infection and normal healthy controls; and (2) to correlate GSH levels with liver histology and serum HCV RNA levels. Twenty‐four patients with compensated chronic hepatitis C and 2 7 healthy subjects were studied. Serum and heparinized plasma were prospectively prepared and frozen within 1 h of collection. Plasma glutathione and glutathione peroxidase (GP) levels were measured spectrophotometrically. The serum HCV RNA level was quantitated by the branched chain DNA signal‐amplification assay. Plasma GSH levels were not decreased in patients with chronic HCV infection but were actually greater than in controls (control 1.2 7 ± 0.12 μg ml‐1, HCV 1.62 ± 0.11 μg ml‐1, P < 0.05). There was also no difference in plasma GP activity between these two groups (control 0.233 ± 0.007 U ml‐1, HCV 0.230 ± 0.007 U ml‐1). Among the patients with chronic HCV infection, there was no correlation between either plasma GSH or GP levels and the serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST), serum HCV RNA level, or liver histology. This study demonstrates that chronic HCV infection does not decrease the plasma GSH and GP levels.
Sequence analysis of the hepatitis C virus (HCV) core gene suggests the core protein as an appropriate target for HCV vaccine strategies
Authors: HitOmi Y. , McDonnell W. M. , Killeen A. A. , Askari F. K.
Published: December 2007

Summary. Hepatitis C virus (HCV) is a major health problem with a prevalence of 1% in the United States population, and a significant percentage of infected patients progress to chronic liver disease and cirrhosis. Interferon therapy has demonstrated that the immune system can be modulated to alter the acute course of the disease, but long‐term treatments remain elusive. Prevention of hepatitis C infection is therefore an important strategy to mitigate the impact of this disease. Initial attempts at vaccination have focused on recombinant envelope vaccines, which have shown an ability to protect against very low titre challenges of HCV in chimps. The need for vaccines capable of protecting against higher titre challenges has led to the search for alternative vaccine strategies. The most highly conserved structural protein in the HCV genome is the core protein, and vaccine strategies targeting the core protein have been proposed to increase vaccine efficacy. The variability of HCV core sequences and genotypes in the Ann Arbor patient population are not known, and the present study was undertaken to assess the theoretical feasibility of developing a HCV core vaccine by excluding promiscuous core (C) gene variability as a mechanism of vaccine failure. Results of nucleotide and deduced amino acid sequence analysis from 13 of 14 patients studied reveal a 93% nucleotide and 96.4% amino acid core sequence homology in the C gene regions studied. Genotype analysis revealed four of 14 to be type 1a and nine of 14 to be type 1b with one infection not being sufficiently characterized to determine genotype. These results demonstrate a sufficiently high degree of conservation of HCV core sequences in our patient population to permit design of a vaccine directed against core protein.
Long‐term effects of interferon‐α in five HIV‐positive patients with chronic hepatitis B
Authors: di Martino V. , Lunel F. , Cadranel J.F. , Hoang C. , Parlier Y. , Charpentier Y. Le , Opolon P.
Published: December 2007

Summary. Chronic hepatitis B viral infection is common in human immunodeficiency virus (HIV) carriers, but the effectiveness of interferon therapy is still unknown. We report the results of a long‐term pilot study of five patients, who were infected with HIV and chronic hepatitis B, treated by interferon. Five males co‐infected with HIV and hepatitis B virus (HBV) (mean age 2 7 years) were given a 6‐month course of interferon (IFN)‐α2b 5 million units (MU) three times weekly. On initiating the treatment, their CD4 lymphocyte count was 340–553 mm‐3, their CDC stage was IIa‐III; all had histologically proven chronic hepatitis, with Knodell's score ranging from 6–10, and active HBV replication (HBV DNA and hepatitis B e antigen (HBeAg) were detectable). There was no associated hepatitis δ virus (HδV) or hepatitis C virus (HCV) infection. Follow‐up was for 53 months on average (24–74 months). After the treatment, hepatitis B e antibody (HBeAb) and hepatitis B s antibody (HBsAb) sero‐conversion was observed in one patient, HBeAb seroconversion alone in two patients, HBV DNA was absent from serum in three patients, and HBV DNA significantly decreased in one patient. The serum alanine aminotransferase (ALT) activity was normal in four patients. Histological improvement was obtained in four patients. The HIV stage remained unchanged in all patients during the whole follow‐up. These preliminary results suggest that interferon can be successfully used in immunocompetent HIV carriers with chronic hepatitis B as well as in HIV‐negative patients.
Ligase chain reaction (LCR®) assay for semi‐quantitative detection of HBV DNA in mononuclear leukocytes of patients with chronic hepatitis B
Authors: Trippler M. , Hampl H. , Goergen B. , Spies U. , Knolle P. , Grimm B. , Büschenfelde K‐H. Meyerzum , Gerken G.
Published: December 2007

Summary. A ligase chain reaction (LCR®)‐based approach to detect hepatitis B virus (HBV) DNA in peripheral blood mononuclear cells (PBMC) is described. Using this new amplification technique, we determined semi‐quantitatively the amount of a short HBV S‐gene fragment in PBMC lysates of 25 patients with different forms of chronic hepatitis (group A (n= 8), hepatitis B s antigen (HBsAg)+/hepatitis B e antigen (HBeAg)+; group B (n= 9), HBsAg+/HBeAg‐; group C (n= 8), HBsAg‐/HBeAg‐). The LCR results were compared with the findings obtained with polymerase chain reaction (PCR) amplification of three distinct HBV gene regions (preS1/2, S and C) and related to the serological profiles of the patients. Depending on the primer pair used for PCR amplification, sensitivity of HBV LCR in PBMC was equivalent or slightly superior to PCR. The highest positivity rate for HBV DNA was observed in the HBeAg+ and HBV DNA seropositive group (8/8) and was lower in the other patient groups B (4/9) and C (1/8). Interestingly, HBV gene sequences could also be detected in the lymphocytes of an HBsAg negative patient and in two patients from group B who were both negative for serum viral particles by PCR. The rapid LCR® procedure represents a reliable alternative to PCR for the sensitive detection of HBV DNA in PBMC samples. In combination with the automated IMx™‐system the new amplification technique may be routinely used for screening for HBV in whole blood samples and thus may help to better evaluate the risk of HBV reinfection in liver transplant recipients.