bluuebunny/crossref_metadata_2025 huggingface dataset:
Overexpression of Interleukin-2 by a Recombinant Herpes Simplex Virus Type 1 Attenuates Pathogenicity and Enhances Antiviral Immunity
Authors: Ghiasi Homayon , Osorio Yanira , Perng Guey-Chuen , Nesburn Anthony B. , Wechsler Steven L.
Published: October 2002

The expression of interleukin-2 (IL-2) has been implicated in the modulation of the outcome of ocular infection with herpes simplex virus type 1 (HSV-1); however, its effects remain controversial. To clarify the role of IL-2, we constructed a recombinant HSV-1 (HSV-IL-2) that expresses two copies of the murine IL-2 gene under the control of the latency-associated transcript (LAT) promoter of HSV-1 in a LAT-negative virus. In tissue culture, the replication of the HSV-IL-2 was 100-fold lower than that of the wild-type virus at a low multiplicity of infection (MOI). Addition of recombinant anti-IL-2 polyclonal antibody markedly enhanced HSV-IL-2 replication in tissue culture. In the 7-day period after ocular infection of BALB/c mice, the replication of HSV-IL-2 was significantly lower than that of wild-type virus in tear cultures, whole eyes, and brain, but was equivalent to wild-type replication in the trigeminal ganglia. Ocular challenge of BALB/c mice with HSV-IL-2 alone, at an MOI that resulted in only 13% survival when parental virus was used, was associated with 90% survival. This decrease in virulence was further shown to be attributable to the expression of IL-2 by coinfection of mice with HSV-IL-2 and the parental virus. This resulted in a decrease in virulence of the parental virus (5% survival when administered alone versus 50% survival on coinfection with HSV-IL-2). The survival of HSV-IL-2-infected mice was compromised by depletion of either IL-2, CD4+, or CD8+T cells (50% survival) and abolished completely by depletion of both T-cell subtypes. Moreover, depletion of CD4+T cells, CD8+T cells, or both increased the titers of HSV-IL-2 in the tears, eyes, trigeminal ganglia, and brains of infected mice, so that titers were equivalent to or higher than that of the parental virus. These results suggest that IL-2 expression by recombinant HSV-1 reduces virulence and that depletion of IL-2 or T cells increases virulence in HSV-1-infected mice.
Homomultimerization of the Coxsackievirus 2B Protein in Living Cells Visualized by Fluorescence Resonance Energy Transfer Microscopy
Authors: van Kuppeveld Frank J. M. , Melchers Willem J. G. , Willems Peter H. G. M. , Gadella, Theodorus W. J.
Published: October 2002

The 2B protein of enteroviruses is the viral membrane-active protein that is responsible for the modifications in host cell membrane permeability that take place in enterovirus-infected cells. The 2B protein shows structural similarities to the group of lytic polypeptides, polypeptides that permeate membranes either by forming multimeric membrane-integral pores or, alternatively, by lying parallel to the lipid bilayer and disturbing the curvature and symmetry of the membrane. Our aim is to gain more insight into the molecular architecture of the 2B protein in vivo. In this study, the possible existence of multimers of the coxsackie B3 virus 2B protein in single living cells was explored by fluorescence resonance energy transfer (FRET) microscopy. FRET between fusion proteins 2B-ECFP and 2B-EYFP (enhanced cyan and yellow fluorescent variants of green fluorescent protein) was monitored by using spectral imaging microscopy (SPIM) and fluorescence lifetime imaging microscopy (FLIM). Both techniques revealed the occurrence of intermolecular FRET between 2B-ECFP and 2B-EYFP, providing evidence for the formation of protein 2B homomultimers. Putative models for the mode of action of the membrane-active 2B protein and the formation of membrane-integral pores by 2B multimers are discussed.
Nuclear Localization of Human Immunodeficiency Virus Type 1 Preintegration Complexes (PICs): V165A and R166A Are Pleiotropic Integrase Mutants Primarily Defective for Integration, Not PIC Nuclear Import
Authors: Limón Ana , Devroe Eric , Lu Richard , Ghory Hina Z. , Silver Pamela A. , Engelman Alan
Published: October 2002

Retroviral replication requires the integration of reverse-transcribed viral cDNA into a cell chromosome. A key barrier to forming the integrated provirus is the nuclear envelope, and numerous regions in human immunodeficiency virus type 1 (HIV-1) have been shown to aid the nuclear localization of viral preintegration complexes (PICs) in infected cells. One region in integrase (IN), composed of Val-165 and Arg-166, was reportedly essential for HIV-1 replication and nuclear localization in all cell types. In this study we confirmed that HIV-1V165Aand HIV-1R166Awere replication defective and that less mutant viral cDNA localized to infected cell nuclei. However, we present three lines of evidence that argue against a specific role for Val-165 and Arg-166 in PIC nuclear import. First, results of transient transfections revealed that V165A FLAG-tagged IN and green fluorescent protein-IN fusions carrying either V165A or R166A predominantly localized to cell nuclei. Second, two different strains of previously described class II IN mutant viruses displayed similar nuclear entry profiles to those observed for HIV-1V165Aand HIV-1R166A, suggesting that defective nuclear import may be a common phenotype of replication-defective IN mutant viruses. Third, V165A and R166A mutants were defective for in vitro integration activity, when assayed both as PICs isolated from infected T-cells and as recombinant IN proteins purified fromEscherichia coli.Based on these results, we conclude that HIV-1V165Aand HIV-1R166Aare pleiotropic mutants primarily defective for IN catalysis and that Val-165 and Arg-166 do not play a specific role in the nuclear localization of HIV-1 PICs in infected cells.
Prevalence and Quantitation of Species C Adenovirus DNA in Human Mucosal Lymphocytes
Authors: Garnett C. T. , Erdman D. , Xu W. , Gooding Linda R.
Published: October 2002

The common species C adenoviruses (serotypes Ad1, Ad2, Ad5, and Ad6) infect more than 80% of the human population early in life. Following primary infection, the virus can establish an asymptomatic persistent infection in which infectious virions are shed in feces for several years. The probable source of persistent virus is mucosa-associated lymphoid tissue, although the molecular details of persistence or latency of adenovirus are currently unknown. In this study, a sensitive real-time PCR assay was developed to quantitate species C adenovirus DNA in human tissues removed for routine tonsillectomy or adenoidectomy. Using this assay, species C DNA was detected in Ficoll-purified lymphocytes from 33 of 42 tissue specimens tested (79%). The levels varied from fewer than 10 to greater than 2 × 106copies of the adenovirus genome/107cells, depending on the donor. DNA from serotypes Ad1, Ad2, and Ad5 was detected, while the rarer serotype Ad6 was not. When analyzed as a function of donor age, the highest levels of adenovirus genomes were found among the youngest donors. Antibody-coated magnetic beads were used to purify lymphocytes into subpopulations and determine whether viral DNA could be enriched within any purified subpopulations. Separation of T cells (CD4/8- expressing and/or CD3-expressing cells) enriched viral DNA in each of nine donors tested. In contrast, B-cell purification (CD19-expressing cells) invariably depleted or eliminated viral DNA. Despite the frequent finding of significant quantities of adenovirus DNA in tonsil and adenoid tissues, infectious virus was rarely present, as measured by coculture with permissive cells. These findings suggest that human mucosal T lymphocytes may harbor species C adenoviruses in a quiescent, perhaps latent form.
Vγ4+T Cells Promote Autoimmune CD8+Cytolytic T-Lymphocyte Activation in Coxsackievirus B3-Induced Myocarditis in Mice: Role for CD4+Th1 Cells
Authors: Huber S. A. , Sartini D. , Exley M.
Published: October 2002

T cells expressing the Vγ4 T-cell receptor (TCR) promote myocarditis in coxsackievirus B3 (CVB3)-infected BALB/c mice. CD1, a major histocompatibility complex (MHC) class I-like molecule, is required for activation of Vγ4+cells. Once activated, Vγ4+cells initiate myocarditis through gamma interferon (IFN-γ)-mediated induction of CD4+T helper type 1 (Th1) cells in the infected animal. These CD4+Th1 cells are required for activation of an autoimmune CD8+αβ TCR+effector, which is the predominant pathogenic agent in this model of CVB3-induced myocarditis. Activated Vγ4+cells can adoptively transfer myocarditis into BALB/c mice infected with a nonmyocarditic variant of CVB3 (H310A1) but cannot transfer myocarditis into either uninfected or CD1−/−recipients, demonstrating the need for both infection and CD1 expression for Vγ4+cell function. In contrast, CD8+αβ TCR+cells transfer myocarditis into either infected CD1−/−or uninfected recipients, showing that once activated, the CD8+αβ TCR+effectors function independently of both virus and CD1. Vγ4+cells given to mice lacking CD4+T cells minimally activate the CD8+αβ TCR+cells. These studies show that Vγ4+cells determine CVB3 pathogenicity by their ability to influence both the CD4+and CD8+adaptive immune response. Vγ4+cells enhance CD4+Th1 (IFN-γ+) cell activation through IFN-γ- and CD1-dependent mechanisms. CD4+Th1 cells promote activation of the autoimmune CD8+αβ TCR+effectors.
Biology of Ovine Adenovirus Infection of Nonpermissive Cells
Authors: Kümin Daniel , Hofmann Christian , Rudolph Michael , Both Gerald W. , Löser Peter
Published: October 2002

Nonhuman adenoviruses, including those of the genus
Atadenovirus
, have the potential to serve as vectors for vaccine and gene therapy applications in humans, since they are resistant to preexisting immunity induced by human adenoviruses in the majority of the population. In this study, we elucidate the outcome of infection by ovine adenovirus type 7 isolate 287 (OAdV) of several nonovine cell types. We show here that OAdV infects a wide range of nonovine cells but is unable to complete its replication cycle in any of them. In nonovine, nonfibroblast cells, viral replication is blocked at an early stage before the onset of, or early in, DNA replication. Some fibroblasts, on the other hand, allow viral DNA replication but block virus production at a later stage during or after the translation of late viral proteins. Late viral proteins are expressed in cells where viral DNA replication takes place, albeit at a reduced level. Significantly, late proteins are not properly processed, and their cellular distribution differs from that observed in infected ovine cells. Thus, our results clearly show that OAdV infection of all nonovine cells tested is abortive even if significant viral DNA replication occurs. These findings have significant positive implications with respect to the safety of the vector system and its future use in humans.
Isolation of an Intertypic Poliovirus Capsid Recombinant from a Child with Vaccine-Associated Paralytic Poliomyelitis
Authors: Martín Javier , Samoilovich Elena , Dunn Glynis , Lackenby Angie , Feldman Esphir , Heath Alan , Svirchevskaya Ekaterina , Cooper Gill , Yermalovich Marina , Minor Philip D.
Published: October 2002

The isolation of a capsid intertypic poliovirus recombinant from a child with vaccine-associated paralytic poliomyelitis is described. Virus 31043 had a Sabin-derived type 3-type 2-type 1 recombinant genome with a 5′-end crossover point within the capsid coding region. The result was a poliovirus chimera containing the entire coding sequence for antigenic site 3a derived from the Sabin type 2 strain. The recombinant virus showed altered antigenic properties but did not acquire type 2 antigenic characteristics. The significance of the presence in nature of such poliovirus chimeras and the consequences for the current efforts to detect potentially dangerous vaccine-derived poliovirus strains are discussed in the context of the global polio eradication initiative.
Varicella-Zoster Virus (VZV) ORF17 Protein Induces RNA Cleavage and Is Critical for Replication of VZV at 37
o
C but Not 33
o
C
Authors: Sato Hitoshi , Callanan Lawrence D. , Pesnicak Lesley , Krogmann Tammy , Cohen Jeffrey I.
Published: October 2002

Varicella-zoster virus (VZV) open reading frame 17 (ORF17) is homologous to herpes simplex virus (HSV) UL41, which encodes the viral host shutoff protein (vhs). HSV vhs induces degradation of mRNA and rapid shutoff of host protein synthesis. An antibody to ORF17 protein detected a 46-kDa protein in VZV-infected cells. While HSV vhs is located in virions, VZV ORF17 protein was not detectable in virions. ORF17 protein induced RNA cleavage, but to a substantially lesser extent than HSV-1 vhs. Expression of ORF17 protein did not inhibit expression from a β-galactosidase reporter plasmid, while HSV type 1 vhs abolished reporter expression. Two VZV ORF17 deletion mutants were constructed to examine the role of ORF17 in virus replication. While the ORF17 VZV mutants grew to peak titers that were similar to those of the parental virus at 33°C, the ORF17 mutants grew to 20- to 35-fold-lower titers than parental virus at 37°C. ORF62 protein was distributed in a different pattern in the nuclei and cytoplasm of cells infected with an ORF17 deletion mutant at 37°C compared to 33°C. Inoculation of cotton rats with the ORF17 deletion mutant resulted in a level of latent infection similar to that produced by inoculation with the parental virus. The importance of ORF17 protein for viral replication at 37°C but not at 33°C suggests that this protein may facilitate the growth of virus in certain tissues in vivo.
Hepatitis C Virus Nonstructural 5A Protein and Interferon Resistance: a New Model for Testing the Reliability of Mutational Analyses
Authors: Sarrazin Christoph , Herrmann Eva , Bruch Katharina , Zeuzem Stefan
Published: October 2002

Presumably due to the capability of the hepatitis C virus (HCV) to evade the antiviral effects of alpha interferon, treatment is ineffective in more than half of chronically genotype HCV type 1 (HCV-1)-infected patients. Previous approaches to correlate the number of amino acid mutations within regions of HCV nonstructural (NS)-5A protein with virologic treatment response provided conflicting results. In the present study, we developed a new mathematical model to investigate NS5A sequences of HCV-1-infected patients. The mean number of all mutations within the complete NS5A protein was significantly higher in virologic responders compared to nonresponders (
P
= 0.008 and
P
= 0.0001 for amino acid residues predicted on the surface of the NS5A protein). Differences did not achieve statistical significance for NS5A regions that are currently assumed to be functionally relevant (e.g., the interferon sensitivity-determining region, the RNA-activated protein kinase-binding domain, etc.). Analyses of smoothed mutational frequencies showed that the number of mutations in other NS5A regions correlated with virologic response. Such a correlation was observed for both genuine and randomly generated NS5A sequences. The existence of local accumulations of mutations within genuine NS5A isolates that truly correlated with treatment response was defined by a refined test procedure. Upon considering the predicted residue accessibility, we identified the main focus of mutations correlating with treatment response to be the sequence from amino acids 2350 to 2370. Thus, evaluation of NS5A mutations in correlation with treatment response is improved by consideration of functional and predicted conformational amino acid properties. As shown by simulations with randomly generated sequences, multiple analyses of simple counts of local NS5A amino acid mutations and correlation with treatment response are insufficient. For improvement of mutational analysis, a refined specific functional data test procedure is proposed.
Synthesis of 12-Hydroxy and 12-Dioxane Derivatives of the closo-1-Carbadodecaborate(1-) Ion. Variations on the Plešek's Cobalt Bis(dicarbollide) Pattern
Authors: Grüner Bohumír , Císařová Ivana , Čáslavský Josef , Bonnetot Bernard , Cornu David
Published: October 2002

Synthesis of two new B(12) substituted derivatives of the closo-[1-CB11H12]- anion (1) is reported. The zwitterionic derivative containing dioxane ring {12-[O(CH2CH2)2O]+-1-CB11H11-}0 (2) was obtained in moderate yield using reaction of anion 1 with dioxane as solvent, induced by dimethyl sulfate. The anion [12-(HO)-1-CB11H11]- (3) was obtained in high yield upon treatment of the parent anion with 80% H2SO4 at high temperature. Both compounds containing reactive functionalities were designed to serve as useful synthons for a variety of synthetic purposes. The compounds were characterized by 11B and 1H high-field NMR, IR spectroscopy, mass spectrometry, melting points and TLC. Molecular structure of compound 2 was determined by single crystal X-ray diffraction analysis.
C-Halogenation of the closo-[CB11H12]- Anion
Authors: Janoušek Zbyněk , Hilton Cameron L. , Schreiber Peter J. , Michl Josef
Published: October 2002

A synthesis is described of the four C-halogenated 1-X-CB11H11- anions (X = I, Br, Cl, F) using N-halosuccinimides and N-fluorobis(benzenesulfonyl)amine as halogenating agents. The procedure yields only the desired product next to unreacted starting material. Regularities in the 11B and 13C NMR chemical shifts of singly halogenated icosahedral carboranes are summarized.
Investigations of Electronic Interactions Between closo-Boranes and Triple-Bonded Substituents
Authors: Kaszynski Piotr , Pakhomov Serhii , Young Victor G.
Published: October 2002

Intramolecular electronic interactions were investigated in five series of 12-, 10-, and 6-vertex closo-boranes and hydrocarbons (benzene, acetylene, bicyclo[2.2.2]octane, and cubane) substituted with triple-bonded groups Y≡Z (C≡CR, C≡N, C≡O, and N≡N). Structural data (single crystal X-ray crystallography), spectroscopic properties (UV, IR, and NMR), chemical behavior (dediazoniation reactions), and electronic structure calculations (hybridization and π bond order) are all in agreement that the degree of electronic conjugation between the cluster and the Y≡Z substituent is lowest for the 12-vertex closo-borane and highest for the 6-vertex analog.
Fluorination of Graphite at High Temperatures
Authors: Gupta Vinay , Nakajima Tsuyoshi , Ohzawa Yoshimi
Published: October 2002

Graphite powder (57-74 μm) was fluorinated at 380 °C for 1 h-2 weeks. The composition of the products ranged from CF0.055 to CF0.659. X-Ray diffractometry showed the formation of graphite fluoride, (C2F)n with a trace of CxF phase with planar layers in addition to unreacted graphite which finally disappeared. Raman spectroscopy clearly revealed the existence of a fluorinated phase with planar layers with sp2 structure.
Why men with prostate cancer want wider access to prostate specific antigen testing: qualitative study
Authors: Chapple Alison , Ziebland Sue , Shepperd Sasha , Miller Rachel , Herxheimer Andrew , McPherson Ann
Published: October 2002

Objectives:
To explore the attitudes of men with confirmed or suspected prostate cancer to testing for prostate specific antigen.

Design:
Qualitative interview study with a purposive sample.

Setting:
Great Britain.

Participants:
52 men with suspected or confirmed prostate cancer, recruited through general practitioners, urologists, patient support groups, and charities.

Results:
Almost all men remembered their prostate specific antigen test but recalled being given little information beforehand. Arguments in favour of increased access to testing included the belief that early diagnosis would reduce mortality, improve quality of life, and save the NHS money. Men also thought that a national screening programme should be available because symptoms can be ambiguous, screening for cancer is responsible health behaviour, and screening would encourage men to be tested. Four men who opposed a screening programme had gathered information alerting them to uncertainty about the benefits of treatment, and two regretted that they had been tested. Others thought that access to testing is restricted in the United Kingdom because of a lack of government backing, concerns about the accuracy of the test, and a lack of resources.

Conclusions:
The few men in this study who subscribed to the argument that evidence of the benefits of treatment is a prerequisite for a screening programme did not want to see screening introduced. Men who proposed an alternative set of principles for testing gave reasons that did not all relate to overoptimism about the benefits of early diagnosis. People who plan services and people who respond to requests for testing need to understand men's perspectives and concerns.
Natural experiment examining impact of aggressive screening and treatment on prostate cancer mortality in two fixed cohorts from Seattle area and Connecticut
Authors: Lu-Yao Grace , Albertsen Peter C , Stanford Janet L , Stukel Therese A , Walker-Corkery Elizabeth S , Barry Michael J
Published: October 2002

Objective:To determine whether the more intensive screening and treatment for prostate cancer in the Seattle-Puget Sound area in 1987-90 led to lower mortality from prostate cancer than in Connecticut.

Design:Natural experiment comparing two fixed cohorts from 1987 to 1997.

Setting:Seattle-Puget Sound and Connecticut surveillance, epidemiology, and end results areas.

Participants:Population based cohorts of male Medicare beneficiaries aged 65-79 drawn from the Seattle (n=94 900) and Connecticut (n=120 621) areas.

Main outcome measures:Rates of screening for prostate cancer, treatment with radical prostatectomy and external beam radiotherapy, and prostate cancer specific mortality.

Results:The prostate specific antigen testing rate in Seattle was 5.39 (95% confidence interval 4.76 to 6.11) times that of Connecticut, and the prostate biopsy rate was 2.20 (1.81 to 2.68) times that of Connecticut during 1987-90. The 10 year cumulative incidences of radical prostatectomy and external beam radiotherapy up to 1996 were 2.7% and 3.9% for Seattle cohort members compared with 0.5% and 3.1% for Connecticut cohort members. The adjusted rate ratio of prostate cancer mortality up to 1997 was 1.03 (0.95 to 1.11) in Seattle compared with Connecticut.

Conclusion:More intensive screening for prostate cancer and treatment with radical prostatectomy and external beam radiotherapy among Medicare beneficiaries in the Seattle area than in the Connecticut area was not associated with lower prostate cancer specific mortality over 11 years of follow up.
Back, neck, and shoulder pain in Finnish adolescents: national cross sectional surveys
Authors: Hakala Paula , Rimpelä Arja , Salminen Jouko J , Virtanen Suvi M , Rimpelä Matti
Published: October 2002

Objectives:To study changes in pain of the back and neck in adolescents between 1985 and 2001 and pain of the neck, shoulder, and lower back between 1991 and2001.

Design:Biennial nationwide postal surveys, 1985-2001, and annual classroom surveys, 1996-2001.

Setting:Finland.

Participants:62 677 12, 14, 16, and 18 year olds and 127 217 14-16 year olds.

Main outcome measures:Pain in the back and neck, neck and shoulder, or lower back, at least weekly.

Results:Prevalence of pain in the back and neck was greater in the 1990s than in the 1980s and increased steadily from 1993 to 1997. Pain of the neck and shoulder and pain of the lower back was much more common in 1999 than in 1991 and in 2001 than in 1999. Pain was more common among girls and older groups: pain of the neck and shoulder affected 24% of girls and 12% of boys in 14 year olds, 38% of girls and 16% of boys in 16 year olds, and 45% of girls and 19% of boys in 18 year olds; pain in the lower back affected 8% of girls and 7% of boys in 14 year olds, 14% of girls and 11% of boys in 16 year olds, and 17% of boysand 13% of girls in 18 year olds.

Conclusion:Pain in the neck, shoulder, and lower back is becoming morecommon in Finnish adolescents. This pain suggests a new disease burden of degenerativemusculoskeletal disorders in future adults.
Association between psychological symptoms in adults and growth in early life: longitudinal follow up study
Authors: Cheung Y B , Khoo K S , Karlberg J , Machin D
Published: October 2002

Objectives:To test the hypothesis that birth weight for gestational age and weight gain in early childhood have a long term association with psychological distress in adults.

Design:Longitudinal study of 1958 birth cohort followed to age 42 years.

Setting:Population based birth cohort study.

Participants:9731 cohort members with valid perinatal, postnatal, and adult data.

Main outcome measures:Malaise inventory scores measured at ages 23, 33, and 42 years. Generalised estimating equations approach used to analyse repeated measures.

Results:Psychological distress score was inversely related to birthweight z score and weight gain from birth to the age of 7 years. A unit increase in birthweight z score or childhood weight gain was associated with a mean reduction in psychological distress score of 0.10 (95% confidence interval 0.05 to 0.15) and 0.06 (0.02 to 0.10), respectively. Birth weight and weight gain were also inversely related to the odds of having a high level of psychological distress, with odds ratios being 0.90 (0.85 to 0.95) and 0.93 (0.89 to 0.98), respectively.

Conclusions:Psychological health in adults is related to fetal growth and growth in early childhood.
Home based exercise programme for knee pain and knee osteoarthritis: randomised controlled trial
Authors: Thomas K S , Muir K R , Doherty M , Jones A C , O'Reilly S C , Bassey E J
Published: October 2002

Objectives:
To determine whether a home based exercise programme can improve outcomes in patients with knee pain.

Design:
Pragmatic, factorial randomised controlled trial of two years' duration.

Setting:
Two general practices in Nottingham.

Participants:
786 men and women aged—45 years with self reported knee pain.

Interventions:
Participants were randomised to four groups to receive exercise therapy, monthly telephone contact, exercise therapy plus telephone contact, or no intervention. Patients in the no intervention and combined exercise and telephone groups were randomised to receive or not receive a placebo health food tablet.

Main outcome measures:
Primary outcome was self reported score for knee pain on the Western Ontario and McMaster universities (WOMAC) osteoarthritis index at two years. Secondary outcomes included knee specific physical function and stiffness (scored on WOMAC index), general physical function (scored on SF-36 questionnaire), psychological outlook (scored on hospital anxiety and depression scale), and isometric muscle strength.

Results:
600 (76.3%) participants completed the study. At 24 months, highly significant reductions in knee pain were apparent for the pooled exercise groups compared with the non-exercise groups (mean difference -0.82, 95% confidence interval
-1.3 to -0.3). Similar improvements were observed at 6, 12, and 18 months. Regular telephone contact alone did not reduce pain. The reduction in pain was greater the closer patients adhered to the exercise plan.

Conclusions:
A simple home based exercise programme can significantly reduce knee pain. The lack of improvement in patients who received only telephone contact suggests that improvements are not just due to psychosocial effects because of contact with the therapist.
Quality improvement report
Improving design and conduct of randomised trials by embedding them in qualitative research: ProtecT (prostate testing for cancer and treatment) study
Commentary: presenting unbiased information to patients can be difficult
Authors: Donovan Jenny , Little Paul , Mills Nicola , Smith Monica , Brindle Lucy , Jacoby Ann , Peters Tim , Frankel Stephen , Neal David , Hamdy Freddie
Published: October 2002

Problem:
Recruitment to randomised trials is often difficult, and many important trials are not mounted because recruitment is thought to be “impossible.”

Design:
Controversial ProtecT (prostate testing for cancer and treatment) trial embedded within qualitative research.

Background and setting:
Screening for prostate cancer is hotly debated, and evidence from trials about the effectiveness of treatments (surgery, radiotherapy, and monitoring) is lacking. Mounting a treatment trial is controversial because of past failures and concerns that differences in complications of treatment but not survival make randomisation unacceptable to patients and clinicians, particularly for a trial including monitoring.

Strategy for change:
In-depth interviews explored interpretation of study information. Audiotape recordings of recruitment appointments enabled scrutiny of content and presentation of study information by recruiters. Initial qualitative findings showed that recruiters had difficulty discussing equipoise and presenting treatments equally; they unknowingly used terminology that was misinterpreted by participants. Findings were used to determine changes to content and presentation of information.

Effects of change:
Changes to the order of presenting treatments encouraged emphasis on equivalence, misinterpreted terms were avoided, the non-radical arm was redefined, and randomisation and clinical equipoise were presented more convincingly. The randomisation rate increased from 40% to 70%, all treatments became acceptable, and the three arm trial became the preferred design.

Lessons learnt:
Changes to information and presentation resulted in efficient recruitment acceptable to patients and clinicians. Embedding this controversial trial within qualitative research improved recruitment. Such methods probably have wider applicability and may enable even the most difficult evaluative questions to be tackled.
Epidemiology of unintentional drowning and near-drowning in Denmark in 1995: Table 1
Authors: Lindholm Peter , Steensberg Jens
Published: October 2002

Objectives—To determine the pattern of accidental drowning and near-drowning in Denmark.

Design—Prospective study of all cases of accidental drowning and near-drowning during one year.

Setting—Denmark, 1995.

Subjects—All patients brought to Danish hospitals after incidents of unintentional near-drowning or cooling in water and all fatal cases.

Main outcome measures—Number of near-drowned patients reported prospectively by hospital departments supplemented by cases reported after requests based on the National Patient Register. Number of drownings reported by public health medical officers (as medical examiners), institutes of forensic medicine, and hospitals.

Results—Sixty three (38%) of 167 unintentionally immersed persons died: eight (17%) of 47 children and 55 (46%) of 120 adults. The annual incidence of serious immersion events in children leading to hospital contact was 5.2/100 000; mortality was 0.7/100 000. For adult males the annual incidence of serious unintentional immersions was 4.3/100 000 and for females 1.2/100 000. For foreigners the risk was three to four times higher than for Danes.

Conclusions—More attention should be paid to the risk of drowning in children, adult males, and foreigners.
Adult-worn child carriers: a potential risk for injury
Authors: Frisbee Stephanie J , Hennes Halim
Published: October 2002

Objectives—To examine and describe types of injuries associated with adult-worn child carriers and illustrate the need for careful use of these products by parents.

Methods—A literature search for the terms infant carriers, backpack carriers, infant slings, baby carriers, and baby slings was conducted. Information was also obtained and tabulated from the three Consumer Product Safety Commission databases: the National Electronic Injury Surveillance System (NEISS), the In-Depth Investigations File, and the Injury/Potential Injury Incident File.

Results—No reports of injuries were found in the medical literature. In the NEISS database, 51 injuries were reported between January 1990 and September 1998. Of these injuries, 38 (74.5%) were head traumas and eight (15.7%) were facial trauma. Of the 51 injuries, 11 (22%) required hospitalization.

Conclusions—Based on the data presented in this paper, injuries associated with the use of adult-worn child carriers appear to come from three general sources: product appropriateness and design, product condition, and product use. It is important for health care providers to assist in the dissemination of information regarding the safe use of these products to parents in an effort to prevent injuries.
Violence and its injury consequences in American movies: a public health perspective
Authors: McArthur David , Peek-Asa Corinne , Webb Theresa , Fisher Kevin , Cook Bernard , Browne Nick , Kraus Jess
Published: October 2002

Objectives—The purpose of this study was to evaluate the seriousness and frequency of violence and the degree of associated injury depicted in the 100 top grossing American films of 1994.

Methods—Each scene in each film was examined for the presentation of violent actions upon persons and coded by means of a systematic context sensitive analytic scheme. Specific degrees of violence and indices of injury severity were abstracted. Only actually depicted, not implied, actions were coded, although both explicit and implied consequences were examined.

Results—The median number of violent actions per film was 16, with a range from 1 to 110. Intentional violence outnumbered unintentional violence by a factor of 10. Almost 90% of violent actions showed no consequences to the recipient's body, although more than 80% of the violent actions were executed with lethal or moderate force. Fewer than 1% of violent actions were accompanied by injuries that were then medically attended.

Conclusions—Violent force in American films of 1994 was overwhelmingly intentional and in four of five cases was executed at levels likely to cause significant bodily injury. Not only action films but movies of all genres contained scenes in which the intensity of the action was not matched by correspondingly severe injury consequences. Many American films, regardless of genre, tend to minimize the consequences of violence to human beings.
Evaluation of the Waitakere Community Injury Prevention Project
Authors: Coggan Carolyn , Patterson Pam , Brewin Marilyn , Hooper Rhonda , Robinson Elizabeth
Published: October 2002

Objective—To evaluate the Waitakere Community Injury Prevention Project (WCIPP).

Methods—Process and outcome evaluations were conducted over a three year period. Process activities included analysis of project documentation, participant observation, key informant interviews, and two post-implementation case studies. A quasiexperimental design was used for the outcome evaluation. Three primary sources of data were collected and analysed: injury statistics; a pre-post telephone survey (n=4000); and a pre-post organisation survey (n=144).

Results—Process evaluation provided a comprehensive account of the operation and activities of the WCIPP. Findings stress the pivotal role of the coordinators and highlight the value of incorporating a multicultural approach. A positive impact on changes to Waitakere City Council safety policies and practices was also evident. Outcome evaluation findings demonstrated significant reductions in rates of Waitakere child injury hospitalisations (p<0.05), while comparison communities showed an increase in child hospitalisation rates. In addition, compared with pre-intervention and comparison data, significantly more Waitakere residents were aware of injury prevention safety messages (p=0.0001) and had acquired appropriate child safety items (p=0.0001).

Conclusion—The community injury prevention model appears to be an effective strategy for injury prevention. The support provided by the council for the WCIPP has provided a benchmark for the role of local governments in injury prevention.
Prevention of spinal cord injuries caused by diving: evaluation of the distribution and usage of a diving safety video in high schools
Authors: Bhide Vinay M , Edmonds Virginia E , Tator Charles H
Published: October 2002

Objective—To determine and assess the distribution and use ofSudden Impact, a video designed by Think First and SportsSmart Canada, to help prevent spinal cord injury caused by careless shallow water diving among teenagers in the high risk group (15–24 years old).

Design—Survey of 92 public secondary schools in Toronto, Canada.

Subjects—The heads of the physical and health education departments of the 92 secondary public schools in the Metropolitan Toronto region.

Results—The response rate was 64% (59 schools), of which 76% (45) had actually received the video. Forty one schools (91%) of those that received the video reported using it. Eighty per cent of responding schools showed it to grade 11 students. Eighty per cent of schools with swimming pools used the video compared with only 42% of schools without swimming pools.

Conclusions—There is a need for improvements in the system of distribution to ensure greater use of material such as this video. These may include direct distribution to principals, continuing contact with the schools, or mandatory inclusion of diving safety into the school curriculum.
An evaluation of the effectiveness of the Injury Minimization Programme for Schools (IMPS)
Authors: Frederick Katrina , Bixby Elizabeth , Orzel Marie-Noelle , Stewart-Brown Sarah , Willett Keith
Published: October 2002

Objective—To evaluate the effect of an injury prevention programme (Injury Minimization Programme for Schools, IMPS) on children's primary and secondary prevention, and basic life support, knowledge, attitudes, skills, and behaviour.

Design—Prospective non-randomised matched control.

Setting—Radcliffe NHS Trust and primary and middle schools in Oxfordshire, UK.

Subjects—1200 year 6 children (10 and 11 years old); 600 received IMPS, a primary and secondary injury prevention programme taught in the school and hospital environments; 600 children in the control group received no planned intervention.

Main outcome measures—Safety knowledge, measured using a quiz. Resuscitation skills and behaviour observed and assessed using a simulated emergency scenario. Attitude and hypothetical behaviour towards safety assessed by the “draw and write” technique.

Results—Before intervention, both groups had similar levels of knowledge. Five months after the intervention, significantly more IMPS trained children demonstrated a greater increase in knowledge in administering first aid and the correct procedure for making a call to the emergency services. They also demonstrated better basic life support techniques—for example, mouth-to-mouth and cardiac compressions. They identified more subtle dangers, were more likely to seek help, and tell others that their behaviour was dangerous.

Conclusion—The results demonstrate the benefits of the IMPS programme on injury prevention knowledge, attitudes, and behaviours.
Motor vehicle crashes in Pakistan: the emerging epidemic
Authors: Hyder Adnan A , Ghaffar Abdul , Masood Tayyeb I
Published: October 2002

Setting—Motor vehicle injuries are increasingly being recognized as a growing public health issue in the developing world. Pakistan is a developing country in South Asia where motor vehicle use has increased since independence in 1947.

Objective—This paper explores the magnitude and impact of injuries from motor vehicle crashes in Pakistan.

Methods—An exhaustive review of published and gray literature, together with a detailed analysis of government data from 1956.

Results—The data indicate a persistent increase in the numbers of motor vehicle crashes, injuries, and fatalities. Changes in the reporting of rates are important to note in evaluating the data. Commercial vehicles contribute disproportionately to these motor vehicle injuries.

Conclusions—There is a need to further the recognition of injuries as a public health issue in this country. Specific exploration of the epidemiological data; intersectoral collaboration between health, law, police and transport; and the development of appropriate information systems, will contribute to an appropriate response by Pakistan.
Decreasing incidence of burn injury in a rural state
Authors: Clark D E , Dainiak C N , Reeder S
Published: October 2002

Objectives—To determine changes in the incidence of burn injury since the regionalization of burn care and intensification of fire prevention initiatives that occurred in Maine during the 1970s.

Methods—Death certificate data from Maine and the United States for deaths due to fire or burns were obtained for 1960–98. Hospitalization and burn registry data were obtained for Maine from 1973–98. Frequencies and incidence rates were compared over time and, where possible, between Maine and the United States.

Results—During 1960–79, annual burn mortality in Maine averaged 5.1/100 000, with random variation. After this, the rate declined steadily to an average annual level of 1.4/100 000 during 1993–96. For the entire United States, average annual mortality declined from 4.2/100 000 during 1961–64 to 1.5/100 000 during 1993–96. Reduction in mortality has been principally due to prevention of dwelling fires. Hospitalization for burns in Maine was 34.8/100 000 during 1973–76 and declined to 10.6/100 000 during 1995–98.

Conclusions—Burn prevention measures have dramatically reduced the incidence of death and hospitalization resulting from burns in Maine.
Misuse of booster seats
Authors: Morris S D , Arbogast K B , Durbin D R , Winston F K
Published: October 2002

Objective—To describe several aspects of booster seat use and misuse in a sample of children attending child safety seat clinics.

Methods—Booster seat practices were assessed at 76 child safety seat clinics held between April 1997 and January 1999 in Pennsylvania and southern New Jersey. At each assessment, a child passenger safety team evaluated the booster seat and identified modes of misuse.

Results—Altogether 227 booster seats were observed. Sixty eight per cent (68%) of shield boosters and 20% of belt positioning boosters were misused. Thirty two per cent of the children using a shield booster weighed more than 40 lb (18.1 kg); 68% of children in shield boosters and 63% in belt positioning boosters weighed less than 40 lb.

Conclusions—This study identified a relatively high rate of booster seat misuse. Shield boosters were more likely to be misused than belt positioning booster seats. Significant numbers of children weighing more than 40 lb were using possibly dangerous shield boosters. The majority of children in this study were less than 40 lb. In this weight range, a convertible child restraint system provides better protection than a booster seat. Booster seat use should only be initiated once the child has completely outgrown their convertible child restraint system.
Social differences in traffic injury risks in childhood and youth—a literature review and a research agenda: Figure 1
Authors: Laflamme L , Diderichsen F
Published: October 2002

Objectives—The paper reviews the scientific literature concerning social differences in traffic injuries in childhood in order to highlight the current state of knowledge and to draw the main lines of a research agenda.

Method—A conceptual framework is used that identifies the mechanisms through which social context, social position, and various exposures may interact in the determination of health inequalities. It is used as a frame for presenting the evidence accumulated so far concerning social differences in traffic injury in childhood, including pedestrian, cyclist, and vehicle passenger injuries.

Results—For most types of traffic injuries, mortality and morbidity are often higher among children from lower social positions and in more deprived socioeconomic areas. Whether the greater occurrence of injuries in deprived areas is a phenomenon attributable to the areas themselves, or merely a reflection of a wider pattern of injuries affecting lower socioeconomic groups, is unclear. There is evidence of an interaction effect between age and gender, and also between socioeconomic status and gender.

Conclusions—The mechanisms leading to social inequalities in traffic injuries in childhood deserve greater scrutiny in future research. Further theoretical developments and empirical investigation will help define intervention needs and enable more effective targeted, long term prevention.
An overview of the injury severity score and the new injury severity score
Authors: Stevenson M , Segui-Gomez M , Lescohier I , Di Scala C , McDonald-Smith G
Published: October 2002

Objective—The research was undertaken to describe the injury severity score (ISS) and the new injury severity score (NISS) and to illustrate their statistical properties.

Design—Descriptive analysis and assessment of the distribution of these scales.

Methods—Three data sources—the National Pediatric Trauma Registry; the Massachusetts Uniform Hospital Discharge Data Set; and a trauma registry from an urban level I trauma center in Massachusetts—were used to describe the distribution of the ISS and NISS among injured patients.

Results—The ISS/NISS was found to have a positively skewed distribution and transformation did not improve their skewness.

Conclusion—The findings suggest that for statistical or analytical purposes the ISS/NISS should not be considered a continuous variable, particularly if ISS/NISS is treated as a continuous variable for correlation with an outcome measure.
Injury in young people with intellectual disability: descriptive epidemiology
Authors: Sherrard J , Tonge B J , Ozanne-Smith J
Published: October 2002

Objectives—To assess the public health importance of injury in a representative sample of young people with intellectual disability relative to the general population.

Setting—This study forms part of the Australian Child and Adolescent Development (ACAD) program examining emotional and behavioural problems in a cohort of young people with intellectual disability (IQ<70). The program has collected extensive biopsychosocial data from carers of subjects at two time intervals, 1990 (n=579) and 1996 (n=465).

Method—Carer report of medically attended injury to subjects was collected for the first time during 1996 (age 5–29 years) and supplemented with medical record injury data from hospitals and general practitioners for 147 of the ACAD sample and 110 supplementary subjects. These data were compared with general population injury data to assess relative epidemiological differences.

Results—Annual injury mortality and morbidity rates were 150/100 000 and 55.6/1000 persons, with age standardised mortality and morbidity ratios of 8 and 2 respectively. Males and females had similar injury rates. The rate for injury hospitalisations was twice that of the general population. Falls were more common and transport injury and intentional injury less common causes of injury morbidity compared with general population. The patterns of cause, circumstances, and severity of injury in young people with intellectual disability have more similarities with younger children than with their same age group in the general population.

Conclusion—This study should alert clinicians and others to the increased risk for injury and possible further handicap in this population. It is essential that injury prevention programs be implemented and evaluated for their effectiveness in reducing the substantial additional burden of suffering, care and cost resulting from injury to young people with intellectual disability.