bluuebunny/crossref_metadata_2025 huggingface dataset:
Woodchuck Gamma Interferon Upregulates Major Histocompatibility Complex Class I Transcription but Is Unable To Deplete Woodchuck Hepatitis Virus Replication Intermediates and RNAs in Persistently Infected Woodchuck Primary Hepatocytes
Authors: Lu Mengji , Lohrengel Beate , Hilken Gero , Kemper Thekla , Roggendorf Michael
Published: July 2002

Gamma interferon (IFN-γ) is an important mediator with multiple functions in the host defense against viral infection. IFN-γ, in concert with tumor necrosis factor alpha (TNF-α), leads to a remarkable reduction of intrahepatic replication intermediates and specific mRNAs of hepatitis B virus (HBV) by a noncytolytic mechanism in the transgenic mouse model. Thus, it is rational to evaluate the potential value of IFN-γ for the treatment of chronic HBV infection. In the present study, we expressed recombinant woodchuck IFN-γ (wIFN-γ) in Escherichia coli and mammalian cells. wIFN-γ protected woodchuck cells against infection of murine encephalomyocarditis virus in a species-specific manner. It upregulated the mRNA level of the woodchuck major histocompatibility complex class I (MHC-I) heavy chain in permanent woodchuck WH12/6 cells and regulated differentially the gene expression. However, the level of the replication intermediates and specific RNAs of woodchuck hepatitis virus (WHV) in persistently WHV-infected primary woodchuck hepatocytes did not change despite a treatment with 1,000 U of wIFN-γ per ml or with a combination of wIFN-γ and woodchuck TNF-α. Rather, hepatocytes derived from chronic carriers had an elevated level of the MHC-I heavy-chain mRNAs, most probably due to the exposure to inflammatory cytokines in vivo. Treatment with high doses of wIFN-γ led to an abnormal cell morphology and loss of hepatocytes. Thus, wIFN-γ regulates the gene expression in woodchuck hepatocytes but could not deplete WHV replication intermediates and mRNAs in persistently infected hepatocytes. The cellular response to wIFN-γ may be changed in hepatocytes from chronically WHV-infected woodchucks. It should be clarified in the future whether the continuous exposure of hepatocytes to inflammatory cytokines or the presence of viral proteins leads to changes of the cellular response to wIFN-γ.
Genetic Analysis of Sequences in the 3′ Nontranslated Region of Hepatitis C Virus That Are Important for RNA Replication
Authors: Friebe Peter , Bartenschlager Ralf
Published: July 2002

The genome of the hepatitis C virus (HCV) is a plus-strand RNA molecule that carries a single long open reading frame. It is flanked at either end by highly conserved nontranslated regions (NTRs) that mediate crucial steps in the viral life cycle. The 3′ NTR of HCV has a tripartite structure composed of an about 40-nucleotide variable region, a poly(U/UC) tract that has a heterogeneous length, and a highly conserved 98-nucleotide 3′-terminal sequence designated the X tail or 3′X. Conflicting data as to the role the sequences in the 3′ NTR play in RNA replication have been reported. By using the HCV replicon system, which is based on the self-replication of subgenomic HCV RNAs in human hepatoma cell line Huh-7, we mapped in this study the sequences in the 3′ NTR required for RNA replication. We found that a mutant with a complete deletion of the variable region is viable but that replication is reduced significantly. Only replicons in which the poly(U/UC) tract was replaced by a homouridine stretch of at least 26 nucleotides were able to replicate, whereas RNAs with homopolymeric guanine, adenine, or cytosine sequences were inactive. Deletions of individual or all stem-loop structures in 3′X were not tolerated, demonstrating that this region is most crucial for efficient RNA replication. Finally, we found that none of these deletions or substitutions within the 3′ NTR affected RNA stability or translation, demonstrating that the primary effect of the mutations was on RNA replication. These data represent the first detailed mapping of sequences in the 3′ NTR assumed to act as a promoter for initiation of minus-strand RNA synthesis.
Efficient Integration of Recombinant Adeno-Associated Virus DNA Vectors Requires a p5-
rep
Sequence in
cis
Authors: Philpott Nicola J. , Giraud-Wali Catherine , Dupuis Carolyn , Gomos Janette , Hamilton Henry , Berns Kenneth I. , Falck-Pedersen Erik
Published: July 2002

The initial aim of this study was to combine attributes of adeno-associated virus (AAV) and adenovirus (Ad) gene therapy vectors to generate an Ad-AAV hybrid vector allowing efficient site-specific integration with Ad vectors. In executing our experimental strategy, we found that, in addition to the known incompatibility of Rep expression and Ad growth, an equally large obstacle was presented by the inefficiency of the integration event when using traditional recombinant AAV (rAAV) vectors. This study has addressed both of these problems. We have shown that a first-generation Ad can be generated that expresses Rep proteins at levels consistent with those found in wild-type AAV (wtAAV) infections and that Rep-mediated AAV persistence can occur in the presence of first-generation Ad vectors. Our finding that traditional rAAV plasmid vectors lack integration potency compared to wtAAV plasmid constructs (10- to 100-fold differences) was unexpected but led to the discovery of a previously unidentified AAV integration enhancer sequence element which functions in
cis
to an AAV inverted terminal repeat-flanked target gene. rAAV constructs containing left-end AAV sequence, including the p5-
rep
promoter sequence, integrate efficiently in a site-specific manner. The identification of this novel AAV integration enhancer element is consistent with previous studies, which have indicated that a high frequency of wtAAV recombinant junction formation occurs in the vicinity of the p5 promoter, and recent studies have demonstrated a role for this region in AAV DNA replication. Understanding the contribution of this element to the mechanism of AAV integration will be critical to the use of AAV vectors for targeted gene transfer applications.
Restriction of Measles Virus RNA Synthesis by a Mouse Host Cell Line:
trans
-Complementation by Polymerase Components or a Human Cellular Factor(s)
Authors: Vincent Séverine , Tigaud Isabelle , Schneider Henriette , Buchholz Christian J. , Yanagi Yusuke , Gerlier Denis
Published: July 2002

The mouse epithelial MODE-K cell line expressing human CD46 or CD150 cellular receptors was found to be nonpermissive for measles virus (MV) replication. The virus binding and membrane fusion steps were unimpaired, but only very limited amounts of virus protein and RNA synthesized were detected after the infection. In a minigenome chloramphenicol acetyltransferase assay, MODE-K cells were as able as the permissive HeLa cells in supporting MV polymerase activity. The restriction phenotype of MODE-K cells could be alleviated by providing, in
trans
, either N-P-L or N-P functional protein complexes but not by P-L complexes or individual N, P, and L proteins. Several human × mouse (HeLa × MODE-K) somatic hybrid clones expressing human CD46 were isolated and found to be either nonpermissive or permissive according to their human chromosomal contents. The MV-restricted phenotype exhibited by the MODE-K cell line suggests that a cellular factor(s) can control MV transcription, possibly by stabilizing the incoming virus polymerase templates.
Feline Calicivirus: Recovery of Wild-Type and Recombinant Viruses after Transfection of cRNA or cDNA Constructs
Authors: Thumfart Jörg Oliver , Meyers Gregor
Published: July 2002

The RNA genome of the vaccine strain 2024 of feline calicivirus was cloned as cDNA and analyzed by nucleotide sequencing. A full-length DNA copy of the viral genome was established and proved to be a source of infectious cRNA after in vitro transcription and RNA transfection. Virus could also be recovered when the DNA construct was introduced into cells containing phage T7 RNA polymerase that was provided by vaccinia virus MVA-T7. After insertion of the sequence encoding the green fluorescent protein into the structural protein-encoding region of the infectious cDNA clone, a defective replicon was recovered that was able to replicate autonomously and was packaged into virus particles when the structural proteins were provided in
trans
.
The S4 Genome Segment of Baboon Reovirus Is Bicistronic and Encodes a Novel Fusion-Associated Small Transmembrane Protein
Authors: Dawe Sandra , Duncan Roy
Published: July 2002

We demonstrate that the S4 genome segment of baboon reovirus (BRV) contains two sequential partially overlapping open reading frames (ORFs), both of which are functional in vitro and in virus-infected cells. The 15-kDa gene product (p15) of the 5"-proximal ORF induces efficient cell-cell fusion when expressed by itself in transfected cells, suggesting that p15 is the only viral protein required for induction of syncytium formation by BRV. The p15 protein is a small, hydrophobic, basic, integral membrane protein, properties shared with the p10 fusion-associated small transmembrane (FAST) proteins encoded by avian reovirus and Nelson Bay reovirus. As with p10, the BRV p15 protein is also a nonstructural protein and, therefore, is not involved in virus entry. Sequence analysis indicates that p15 shares no significant sequence similarity with the p10 FAST proteins and contains a unique repertoire and arrangement of sequence-predicted structural and functional motifs. These motifs include a functional N-terminal myristylation consensus sequence, an N-proximal proline-rich motif, two potential transmembrane domains, and an intervening polybasic region. The unique structural properties of p15 suggest that this protein is a novel member of the new family of FAST proteins.
PrP
c
Expression Influences the Establishment of Herpes Simplex Virus Type 1 Latency
Authors: Thackray Alana M. , Bujdoso Raymond
Published: July 2002

PrP
c
is a glycophosphatidylinositol-linked cell-surface protein expressed principally by neural tissue. The normal function of this protein is unestablished, although a role in either transmembrane signaling, cell-cell adhesion, or copper metabolism has been proposed. In this study we have investigated the effect of the neurotropic virus herpes simplex virus type 1 (HSV-1) in strains of mice which express different levels of PrP
c
. Viral gene expression under the control of the HSV-1 early promoter IE110, detected either by in situ hybridization for RNA transcripts or by β-galactosidase (β-Gal) activity from an inserted
lacZ
gene, showed that the magnitude of HSV replication was retarded in PrP
−/−
mice. This was reflected in the lower level of acute viral titers in tissues from these virus-inoculated mice. However, HSV-inoculated PrP
−/−
mice contained higher levels of latent virus in both peripheral and central nervous tissue than those seen in mice which express PrP
c
. Our observations show that lack of PrP
c
expression favors the establishment of HSV latency whereas HSV replication proceeds more efficiently in neuronal tissue that expresses this protein. The data further suggest that PrP
c
may be involved in a metabolic pathway that culminates in apoptosis of neurons that have been infected by neurotropic viruses.
Inhibition of In Vitro Leukocyte Proliferation by Morbilliviruses
Authors: Heaney J. , Barrett T. , Cosby S. L.
Published: July 2002

Immune suppression associated with morbillivirus infections may influence the mortality rate by allowing secondary bacterial infections that are lethal to the host to flourish. Using an in vitro proliferation assay, we have shown that all members of the genus
Morbillivirus
inhibit the proliferation of a human B-lymphoblast cell line (BJAB). Proliferation of freshly isolated, stimulated bovine and caprine peripheral blood lymphocytes is also inhibited by UV-inactivated rinderpest (RPV) and peste-des-petits ruminants viruses. As for measles virus, coexpression of both the fusion and the hemagglutinin proteins of RPV is necessary and sufficient to induce immune suppression in vitro.
Dengue Type 3 Virus in Plasma Is a Population of Closely Related Genomes: Quasispecies
Authors: Wang Wei-Kung , Lin Su-Ru , Lee Chao-Min , King Chwan-Chuen , Chang Shan-Chwen
Published: July 2002

Using reverse transcription-PCR and clonal sequencing of the dengue virus envelope gene derived from the plasma samples of six patients, we reported for the first time that dengue virus circulates as a population of closely related genomes. The extent of sequence diversity varied among patients, with the mean pairwise proportions of difference ranging from 0.21 to 1.67%. Genome-defective viruses were found in 5.8% of the total number of clones analyzed. Our findings on the quasispecies nature of dengue virus and the defective virus in vivo have implications with regard to the pathogenesis of dengue virus.
Synthesis, Bioassay and NMR Study of Methyleneoxy Isosters of Oxytocin and Vasopressin
Authors: Mařík Jan , Buděšínský Miloš , Slaninová Jiřina , Hlaváček Jan
Published: July 2002

Syntheses of pseudodipeptides H-Tyrψ[CH2O]Ile-OH and H-Tyrψ[CH2O]Phe-OH were carried out using the intramolecular Williamson reaction of O-benzyltyrosinol with ethyl chloroacetate followed by N-protection and aldol reaction of the corresponding morpholin-3-one in position C2 with butanone or benzaldehyde, elimination of the hydroxy group to give derivatives with a double bond either as the E/Z (1 : 1) diastereomeric mixture in the case of the former derivative or as the Z-isomer only in the case of the latter one. Stereoselective hydrogenation and hydrolysis of both the lactams yielded the corresponding pseudodipeptides lacking the carbonyl group as a hydrogen bond donor. The introduction of the pseudodipeptides into positions 2 and 3 of oxytocin and vasopressin caused total absence of all biological activities in the formed analogues. The results of the bioassay and NMR study confirmed the importance of the H-bond between the backbone carbonyl of the Tyr2 and NH proton of the Asn5 residues for stabilization of the β-turn in the cyclic hexapeptide part of both the hormones and for their biological activity.
Incidence and nature of the most common rugby injuries sustained in Argentina (1991–1997)
Authors: Bottini E , Poggi E J T , Luzuriaga F , Secin F P
Published: July 2002

Objective—To study the incidence of the most commonly sustained injuries in Argentine rugby and analyse them according to type, position and age of the players, and phase and time of play.

Methods—A prospective registry of injuries was constructed in different provincial unions of Argentina. Data were collected during a whole weekend each year from 1991 to 1997. χ2with Yates correction test, contingency tables, odds ratios (OR), and 95% confidence intervals (CI) were calculated (Epi Info Version 6.04a).

Results—A total of 924 injuries were registered in 1296 rugby games, involving 38 933 players. The mean (SD) incidence per weekend was 2.4 (0.2)% (95% CI 2.22 to 2.53), and the number of injuries per season was 24 188. Overall, senior players suffered more injuries than those in younger divisions (OR = 1.53; 95% CI 1.34 to 1.76; p<0.0001). The most common type of injury was pulled muscles of the lower limbs (11.7%, p<0.0001). Overall, the knee was the most susceptible to injury (14.1%, p<0.0001). Senior players suffered more pulled muscles of the lower limbs (OR = 2.99; 95% CI 2.01 to 4.46; p<0.0001), ankle ligament distension (OR = 1.69; 95% CI 1.12 to 2.53; p = 0.01), knee trauma (OR = 1.69; 95% CI 1.06 to 2.68; p = 0.02), bleeding wounds on the face (OR = 3.86; 95% CI 2.24 to 6.70; p<0.0001), and knee ligament distension (OR = 2.14; 95% CI 1.16 to 3.96; p = 0.01). Younger players had a greater risk of suffering muscular or ligament injuries of the cervical column (OR = 3.0; 95% CI 1.05 to 10.08; p = 0.04). The forwards had a higher risk of injury (OR = 1.41; 95% CI 1.23 to 1.61; p<0.0001). The most commonly injured player was the flanker (15.5%, p<0.01), and the most common mechanism was in open play (33%). More injuries were sustained in the second half (OR = 1.17; 95% CI 1.03 to 1.34; p = 0.01).

Conclusions—Injuries are the cause of significant morbidity among rugby players in Argentina. A more thorough investigation and a greater understanding of the mechanisms are crucial in order to update the rugby laws and reduce this high injury incidence.
Injury and injury rates in Muay Thai kick boxing
Authors: Gartland S , Malik M H A , Lovell M E
Published: July 2002

Objective—To determine the type and number of injuries that occur during the training and practice of Muay Thai kick boxing and to compare the data obtained with those from previous studies of karate and taekwondo.

Methods—One to one interviews using a standard questionnaire on injuries incurred during training and practice of Muay Thai kick boxing were conducted at various gyms and competitions in the United Kingdom and a Muay Thai gala in Holland.

Results—A total of 152 people were questioned, 132 men and 20 women. There were 19 beginners, 82 amateurs, and 51 professionals. Injuries to the lower extremities were the most common in all groups. Head injuries were the second most common in professionals and amateurs. Trunk injuries were the next most common in beginners. The difference in injury distribution among the three groups was significant (p≤0.01). Soft tissue trauma was the most common type of injury in the three groups. Fractures were the second most common in professionals, and in amateurs and beginners it was sprains and strains (p≤0.05). Annual injury rates were: beginners, 13.5/1000 participants; amateurs, 2.43/1000 participants; professionals, 2.79/1000 participants. For beginners, 7% of injuries resulted in seven or more days off training; for amateurs and professionals, these values were 4% and 5.8% respectively.

Conclusions—The results are similar to those found for karate and taekwondo with regard to injury distribution, type, and rate. The percentage of injuries resulting in time off training is less.
Two cases of peroneus brevis tendon tear
Authors: Minoyama O , Uchiyama E , Iwaso H , Hiranuma K , Takeda Y
Published: July 2002

A longitudinal tear of the peroneal tendon is thought to be the result of repetitive peroneal subluxation. However, this report documents two cases of longitudinal split of the peroneus brevis tendon that had no peroneal tendon subluxation. Primary suture was performed. Subluxation of the peroneal tendons was not identified surgically in either case.
Heterotopic gastric mucosa together with intestinal metaplasia and moderate dysplasia in the gall bladder: report of two clinically unusual cases with literature review
Authors: Xeropotamos N , Skopelitou A S , Batsis Ch , Kappas A M
Published: July 2002

We report the clinicopathological findings of two patients with ectopic gastric mucosa within the gall ladder. The first patient, a 78 year old man, was asymptomatic. He was admitted to hospital for a colon adenocarcinoma. Intraoperatively, a firm nodule was palpable in the gall bladder. Histological examination of the resected specimen revealed a body type gastric mucosa in the submucosa, adjacent to which were extensive pyloric gland and intestinal metaplasia with mild to moderate dysplasia. The remaining gall bladder mucosa demonstrated changes of chronic cholecystitis. The second patient was a 62 year old woman with symptoms of chronic cholecystitis. The preoperative diagnosis was consistent with this diagnosis with a “polyp” at the junction of the neck and cystic duct. Cholecystectomy was performed and the histological examination of the resected specimen showed that the “polyp” consisted of heterotopic gastric mucosa with glands of body and fundus type. In the remaining mucosa, chronic cholecystitis was evident. To the best of our knowledge, this is the first report of a clinicopathological presentation of heterotopic gastric mucosa, pyloric gland type, and intestinal metaplasia with dysplastic changes in the gall bladder. As heterotopic tissue may promote carcinogenesis of the gall bladder, close attention should be paid to any occurrence of such lesions in this anatomical region.
The cardiac response to exercise in cirrhosis
Authors: Wong F , Girgrah N , Graba J , Allidina Y , Liu P , Blendis L
Published: July 2002

BACKGROUND

Impaired exercise capacity and oxygen consumption are common in cirrhosis.

AIM

To explore the relationship between possible myocardial dysfunction and exercise tolerance in cirrhosis.

METHODS

Cardiac responses to exercise, using radionuclide angiography and graded upright cycle ergometry with oxygen consumption, were assessed before and after exercise in 39 cirrhotics patients and compared with 12 age and sex matched healthy volunteers. Baseline cardiac chamber dimensions and wall thickness, ejection fraction, and diastolic function were measured using two dimensional echocardiography is all subjects.

RESULTS

Baseline diastolic dysfunction with prolonged isovolumic relaxation times (p=0.02), left atrial enlargement, and left ventricular wall thickening were present in all cirrhotics (p=0.02), despite increased mean ejection fraction. With graded exercise, cirrhotics achieved 71 (4)% (p=0.03) (pre-ascitics) and 46 (3)% (p<0.001) (ascitics) of predicted work loads, respectively, without significant increases in ejection fraction. The smaller absolute and percentage increases in cardiac output (p=0.003) in the cirrhotics were associated with significantly reduced oxygen consumption (p=0.003) and anaerobic threshold (p<0.001), and correlated significantly with work and metabolic parameters.

CONCLUSIONS

Impaired exercise capacity in cirrhosis is associated with myocardial thickening and ventricular stiffness leading to decreased diastolic function, inotropic and chronotropic incompetence under conditions of stress, with metabolic consequences. This picture is compatible with the condition now known as cirrhotic cardiomyopathy.
Mast cells: the forgotten cells of renal fibrosis
Authors: Roberts I S D , Brenchley P E C
Published: July 2002

Background/Aims—Mast cells, when activated, secrete a large number of fibrogenic factors and have been implicated in the development of fibrotic conditions of the liver, lung, and skin. There is evidence that renal fibrosis is closely linked with a chronic inflammatory cell infiltrate within the interstitium, but a potential role for mast cells in this process has yet to be defined. Therefore, the numbers of mast cells in normal and fibrotic kidneys with various pathologies were investigated.

Methods—Mast cells were quantified in renal transplants showing acute and chronic rejection and cyclosporin toxicity, kidneys removed for chronic pyelonephritis, and renal biopsies from patients with IgA nephropathy, membranous nephropathy, and diabetic nephropathy. Mast cells were stained using two methods: acid toluidine blue detected less than 30% of the mast cells revealed by immunohistochemistry for mast cell tryptase.

Results—Mast cells were scarce or absent in normal kidney (median, 1.6 mast cells/mm2) but numerous throughout the cortex and medulla in all specimens that showed fibrosis. They were almost entirely confined to the renal interstitium. Mast cells were present in large numbers in biopsies from patients with membranous nephropathy (median, 21.7 mast cells/mm2) and diabetic nephropathy (median, 29.2 mast cells/mm2), which were selected on the basis of showing chronic injury. In 24 unselected IgA nephropathy biopsies there was a close correlation between numbers of mast cells and the extent of interstitial fibrosis (r = 0.771; p < 0.0001). In renal transplant biopsies, mast cells were associated with allograft fibrosis in chronic rejection (median, 27.1 mast cells/mm2) and chronic cyclosporin toxicity (median, 10.6 mast cells/mm2) but not acute rejection (median, 2.7 mast cells/mm2) or acute cyclosporin toxicity (median, 2.0 mast cells/mm2). There was no detectable increase in mast cell numbers during acute rejection in those transplants that subsequently progressed to chronic rejection. In some biopsies the mast cells were largely intact, but in most cases some or all were degranulated.

Conclusions—An increased number of mast cells is a consistent feature of renal fibrosis, whatever the underlying pathology, and the number of mast cells correlates with the extent of interstitial fibrosis. This suggests that mast cells might play a pathogenetic role in the fibrotic process.
Paying research subjects: participants' perspectives
Authors: Russell Margaret L , Moralejo Donna G , Burgess Ellen D
Published: July 2002

Objective—To explore the opinions of unpaid healthy volunteers on the payment of research subjects.

Design—Prospective cohort.

Setting—Southern Alberta, Canada.

Participants—Medically eligible persons responding to recruiting advertisements for a randomised vaccine trial were invited to take part in a study of informed consent at the point at which they formally consented or refused trial participation. Of 72 invited, 67 (62 trial consenters, 5 trial refusers) returned questionnaires at baseline and 54 at follow-up.

Outcome measures—Proportions of persons who agreed or disagreed with three close-ended statements on the payment of research subjects; themes and categories identified by content analysis of responses to an open-ended question.

Results—A minority (43.3%) agreed with paying either patient or healthy volunteer participants. Opinions did not change over time. Participants' comments addressed: benefits and drawbacks to research participation; benefits and drawbacks to paying research participants; conditions under which payment of research subjects would be acceptable, and the nature of acceptable recognition. Acceptable conditions were to improve problematic recruitment, to reimburse costs, and to recognise participants, particularly for their time investment. Both non-monetary and monetary recognition of volunteers were thought to be appropriate.

Conclusions—Most unpaid volunteers disagreed with paying research participants. The themes arising from their comments are similar to those that have been raised by ethicists and suggest that recognising the time and effort of participants should receive greater emphasis than presently occurs.(Journal of Medical Ethics2000;26:126–130)
The decision making process regarding the withdrawal or withholding of potential life-saving treatments in a children's hospital
Authors: Street Karen , Ashcroft Richard , Henderson John , Campbell Alastair V
Published: July 2002

Objectives—To investigate the factors considered by staff, and the practicalities involved in the decision making process regarding the withdrawal or withholding of potential life-sustaining treatment in a children's hospital. To compare our current practice with that recommended by the Royal College of Paediatrics and Child Health (RCPCH) guidelines, published in 1997.

Design—A prospective, observational study using self-reported questionnaires.

Setting—Tertiary paediatric hospital.

Patients and participants—Consecutive patients identified during a six-month period, about whom a formal discussion took place between medical staff, nursing staff and family regarding the withholding or withdrawal of potentially life-sustaining treatments. The primary physician and primary nurse involved in the discussion were identified.

Method—Two questionnaires completed independently by the primary physician and nurse.

Results—Twenty-two patients were identified (median age 1 year; range 1 day—34 years). In 20 cases treatment was withdrawn or withheld, in two cases treatment was continued. Nursing staff considered family wishes and family perceptions of patient suffering as significantly more important factors in decision making than medical staff, who considered prognostic factors as most important. In only two cases were the patient's expressed wishes apparently available. In most cases staff considered the patient's best interests were served and the process would not be enhanced by the involvement of an independent ethics committee. The exceptions were those cases in which treatment was continued following disagreement between parties.

Conclusions—Our current practice is consistent with that recommended by the RCPCH. The contribution of the patient, provision of staff counselling and general practitioner (GP) involvement were identified as areas for improvement.
What makes a problem an ethical problem? An empirical perspective on the nature of ethical problems in general practice
Authors: Braunack-Mayer Annette Joy
Published: July 2002

Whilst there has been considerable debate about the fit between moral theory and moral reasoning in everyday life, the way in which moral problems are defined has rarely been questioned. This paper presents a qualitative analysis of interviews conducted with 15 general practitioners (GPs) in South Australia to argue that the way in which the bioethics literature defines an ethical dilemma captures only some of the range of lay views about the nature of ethical problems. The bioethics literature has defined ethical dilemmas in terms of conflict and choice between values, beliefs and options for action. While some of the views of some of the GPs in this study about the nature of their ethical dilemmas certainly accorded with this definition, other explanations of the ethical nature of their problems revolved around the publicity associated with the issues they were discussing, concern about their relationships with patients, and anxiety about threats to their integrity and reputation. The variety of views about what makes a problem a moral problem indicates that the moral domain is perhaps wider and richer than mainstream bioethics would generally allow.
Conditions and consequences of medical futility—from a literature review to a clinical model
Authors: Löfmark R , Nilstun T
Published: July 2002

Objectives: To present an analysis of “futility” that is useful in the clinical setting.

Design: Literature review.

Material and methods: According to Medline more than 750 articles have been published about medical futility. Three criteria (language, time period, and the authors expressed their own opinions) singled out 43 of them. The authors' opinions about futility were analysed using the scheme: “If certain conditions are satisfied, then a particular measure is futile” and “If a particular measure is futile, then certain moral consequences are implied”.

Results: Regarding conditions, most authors stated that judgments about futility should be made by physicians. The measure was usually some kind of medical treatment, and the goals related to quality of life, physiological improvement, or prolongation of life. The probability of success in reaching the goal was in most cases described in semiquantitative terms. Regarding consequences, the authors stated that health care professionals may (sometimes ought or should) withhold or withdraw a futile measure, most often after a dialogue with the patient (29 articles), but sometimes without informing the patient (nine articles), or with one-way information (four articles). Over time more and more articles recommend that the patient should be involved in joint decision making. Based on this literature review a clinical model was developed.

Conclusions: The model, requiring that conditions and consequences should be made explicit, may, in “futility situations”, facilitate both the collection of the necessary information and make the moral implications visible. It also makes communication about measures considered to be futile possible without using such ambiguous terms as “futile”.
Update on the genotoxicity and carcinogenicity of cobalt compounds
Authors: Lison D , De Boeck M , Verougstraete V , Kirsch-Volders M
Published: July 2002

OBJECTIVE

To integrate recent understandings of the mechanisms of genotoxicity and carcinogenicity of the different cobalt compounds.

METHOD

A narrative review of the studies published since the last IARC assessment in 1991 (genotoxicity, experimental carcinogenesis, and epidemiology).

RESULTS

Two different mechanisms of genotoxicity, DNA breakage induced by cobalt metal and especially hard metal particles, and inhibition of DNA repair by cobalt (II) ions contribute to the carcinogenic potential of cobalt compounds. There is evidence that soluble cobalt (II) cations exert a genotoxic and carcinogenic activity in vitro and in vivo in experimental systems but evidence in humans is lacking. Experimental data indicate some evidence of a genotoxic potential for cobalt metal in vitro in human lymphocytes but there is no evidence available of a carcinogenic potential. There is evidence that hard metal particles exert a genotoxic and carcinogenic activity in vitro and in human studies, respectively. There is insufficient information for cobalt oxides and other compounds.

CONCLUSION

Although many areas of uncertainty remain, an assessment of the carcinogenicity of cobalt and its compounds requires a clear distinction between the different compounds of the element and needs to take into account the different mechanisms involved.
Cumulative exposure to dust causes accelerated decline in lung function in tunnel workers
Authors: Ulvestad B , Bakke B , Eduard W , Kongerud J , Lund M B
Published: July 2002

OBJECTIVES

To examine whether underground construction workers exposed to tunnelling pollutants over a follow up period of 8 years have an increased risk of decline in lung function and respiratory symptoms compared with reference subjects working outside the tunnel atmosphere, and relate the findings to job groups and cumulative exposure to dust and gases.

METHODS

96 Tunnel workers and a reference group of 249 other heavy construction workers were examined in 1991 and re-examined in 1999. Exposure measurements were carried out to estimate personal cumulative exposure to total dust, respirable dust, α-quartz, oil mist, and nitrogen dioxide. The subjects answered a questionnaire on respiratory symptoms and smoking habits, performed spirometry, and had chest radiographs taken. Radiological signs of silicosis were evaluated (International Labour Organisation (ILO) classification). Atopy was determined by a multiple radioallergosorbent test (RAST).

RESULTS

The mean exposure to respirable dust and α-quartz in tunnel workers varied from 1.2–3.6 mg/m3(respirable dust) and 0.019–0.044 mg/m3(α-quartz) depending on job task performed. Decrease in forced expiratory volume in 1 second (FEV1) was associated with cumulative exposure to respirable dust (p<0.001) and α-quartz (p=0.02). The multiple regression model predicted that in a worker 40 years of age, the annual decrease in FEV1would be 25 ml in a non-exposed non-smoker, 35 ml in a non-exposed smoker, and 50–63 ml in a non-smoking tunnel worker (depending on job). Compared with the reference group the odds ratio for the occurrence of new respiratory symptoms during the follow up period was increased in the tunnel workers and associated with cumulative exposure to respirable dust.

CONCLUSIONS

Cumulative exposures to respirable dust and α-quartz are the most important risk factors for airflow limitation in underground heavy construction workers, and cumulative exposure to respirable dust is the most important risk factor for respiratory symptoms. The finding of accelerated decline in lung function in tunnel workers suggests that better control of exposures is needed.
Particulate matter and daily mortality and hospital admissions in the west midlands conurbation of the United Kingdom: associations with fine and coarse particles, black smoke and sulphate
Authors: Anderson H R , Bremner S A , Atkinson R W , Harrison R M , Walters S
Published: July 2002

OBJECTIVES

There is considerable evidence linking ambient particles measured as particulate matter with aerodynamic diameter <10 μm (PM10) to daily mortality and hospital admissions but it is not clear which physical or chemical components of the particle mixture are responsible. The relative effects of fine particles (PM2.5), coarse particles (PM2.5–10), black smoke (mainly fine particles of primary origin) and sulphate (mainly fine particles of secondary origin) were investigated, together with ozone, SO2, NO2, and CO, on daily mortality and hospital admissions in the west Midlands conurbation of the United Kingdom.

METHODS

Time series of health outcome and environmental data were obtained for the period 1994–6. The relative risk of death or hospital admission was estimated with regression techniques, controlling for long term time trends, seasonal patterns, influenza epidemics, effects of day of the week, and temperature and humidity. Models were adjusted for any remaining residual serial correlation and overdispersion. The sensitivities of the estimates for the effects of pollution to the inclusion of a second pollutant and seasonal interactions (warm or cool) were also examined.

RESULTS

Daily all cause mortality was not associated with any gaseous or particulate air pollutant in the all year analysis, although all measures of particles apart from PM2.5–10showed significant positive effects of the warm season. Neither respiratory nor cardiovascular admissions (all ages) were associated with any air pollutant, and there were no important seasonal interactions. However, analysis of admissions by age found evidence for various associations—notably between PM10, PM2.5, black smoke, SO2,and ozone (negative) and respiratory admissions in the 0–14 age group. The coarse fraction, PM2.5-10differed from PM2.5in having smaller and less consistent associations (including several large significant negative associations) and a different lag distribution. The results for black smoke, an indicator of fine primary carbonaceous particles, were very similar to those for PM2.5, and tended to be more robust in two pollutant models. The effects of sulphate, an indicator of secondary particles, also showed some similarities to those of PM2.5.

CONCLUSIONS

Clear effects of air pollution on mortality and hospital admissions were difficult to discern except in certain age or diagnostic subgroups and seasonal analyses. It was also difficult to distinguish between different measures of particles. Within these limitations the results suggest that the active component of PM10resides mostly in the fine fraction and that this is due mainly to primary particles from combustion (mainly vehicle) sources with a contribution from secondary particles. Effects of the coarse fraction cannot be excluded.
Proctocolitis in breast fed infants: a contribution to differential diagnosis of haematochezia in early childhood
Authors: Pumberger W , Pomberger G , Geissler W
Published: July 2002

Dietary protein induced proctocolitis in exclusively breast fed infants is rarely taken into consideration as a cause of rectal bleeding or blood streaked stool in the neonatal period and early infancy. Eleven babies are presented in whom it is believed that bleeding through the rectum was due to proctocolitis as a result of allergy triggered by cows’ milk protein transferred to the infants via the breast milk. Colonoscopy was performed in five infants, revealing benign eosinophilic proctocolitis. Standard treatment was the exclusion of the allergen from the mother’s diet. Resolution of visible rectal bleeding took place within 72 to 96 hours after elimination of the offending protein from the mother’s diet.
Ability to learn inhaler technique in relation to cognitive scores and tests of praxis in old age
Authors: Allen S C , Ragab S
Published: July 2002

Clinical observations have shown that some older patients are unable to learn to use a metered dose inhaler (MDI) despite having a normal abbreviated mental test (AMT) score, possibly because of dyspraxia or unrecognised cognitive impairment. Thirty inhaler-naive inpatients (age 76–94) with an AMT score of 8–10 (normal) were studied. Standard MDI training was given and the level of competence reached was scored (inhalation score). A separate observer performed the minimental test (MMT), Barthel index, geriatric depression score (GDS), ideational dyspraxia test (IDT), and ideomotor dyspraxia test (IMD). No correlative or threshold relationship was found between inhalation score and Barthel index, GDS, or IDT. However, a significant correlation was found between inhalation score and IMD (r = 0.45, p = 0.039) and MMT (r = 0.48, p = 0.032) and threshold effects emerged in that no subject with a MMT score of less than 23/30 had an inhalation score of 5/10 or more (adequate technique requires 6/10 or more), and all 17/18 with an inhalation score of 6/10 or more had an IMD of 14/20 or more.

The three patients with a MMT >22 and inhalation score <6 had abnormal IMD scores. Inability to learn an adequate inhaler technique in subjects with a normal AMT score appears to be due to unrecognised cognitive impairment or dyspraxia. The MMT is probably a more useful screening test than the AMT score in this context.
Subacute sclerosing panencephalitis
Authors: Garg R K
Published: July 2002

Subacute sclerosing panencephalitis (SSPE) is a progressive neurological disorder of childhood and early adolescence. It is caused by persistent defective measles virus. Brain biopsies or postmortem histopathological examination show evidence of astrogliosis, neuronal loss, degeneration of dendrites, demyelination, neurofibrillary tangles, and infiltration of inflammatory cells. Patients usually have behavioral changes, myoclonus, dementia, visual disturbances, and pyramidal and extrapyramidal signs. The disease has a gradual progressive course leading to death within 1-3 years. The diagnosis is based upon characteristic clinical manifestations, the presence of characteristic periodic EEG discharges, and demonstration of raised antibody titre against measles in the plasma and cerebrospinal fluid. Treatment for SSPE is still undetermined. A combination of oral isoprinosine (Inosiplex) and intraventricular interferon alfa appears to be the best effective treatment. Patients responding to treatment need to receive it life long. Effective immunisation against measles is the only solution presently available to the problem of this dreaded disease.
Smoking cessation in China: findings from the 1996 national prevalence survey
Authors: Yang Gonghuan , Ma Jiemin , Chen Aiping , Zhang Yifang , Samet Jonathan M , Taylor Carl E , Becker Karen
Published: July 2002

OBJECTIVES

To describe patterns of smoking and smoking cessation in China within the context of the stages of change model, using data from the 1996 national prevalence survey.

DESIGN

A cross sectional survey was carried out using the 145 preselected disease surveillance points, which provide a representative sample for the entire country. A standardised questionnaire on smoking was interviewer administered.

SETTING

The country of China.

SUBJECTS

122 220 people aged 15–69 years.

MAINTENANCE MEASURES

Smoking cessation patterns, as defined by smoking status (current or former) and stage of change (precontemplation, contemplation, and action).

RESULTS

The sample included 45 995 ever smokers of whom 4336 had quit. About 72% of current smokers reported not intending to give up their smoking behaviour, and about 16% of current smokers said they intended to do so, but have not taken any action. Of all ever smokers, the percentage of former smokers was 9.5%, and 12% of current smokers had quit at least once, but relapsed by the time of the survey. The patterns were similar in men and women with regard to the stated intent to quit. Among males, the percentage of former smokers increased with age but the percentage intending to quit was constant at about 15% across age strata. The most common reason for quitting was illness. Participants with a university education were more likely to have made an attempt to quit.

CONCLUSIONS

The percentage of smokers contemplating quitting was low in China in 1996. The study shows that smokers in China must be mobilised to contemplate quitting and then to take action.

Key points

72% of current smokers in China did not intend to give up smoking in 1996

About 10% of ever smokers in China have stopped smoking

The relapse rate equals the rate of quitting

Key professional groups (health workers and teachers) have similar cessation patterns to the general population

The most common reason for quitting was illness

Smokers in China should be mobilised to contemplate quitting and then to take action
Sources of tobacco for youths in communities with strong enforcement of youth access laws
Authors: DiFranza Joseph R , Coleman Mardia
Published: July 2002

AIM

To determine how youths obtain tobacco in communities with strong enforcement of tobacco sales laws.

SETTING

Ten communities in Massachusetts with merchant compliance rates at or above 90%.

METHODS

Paper surveys and focus group discussions with 68 adolescent smokers.

RESULTS

Parents and friends are the primary sources of tobacco for new smokers. When stealing from parents can no longer satisfy the need for cigarettes, young adolescents ask strangers to buy them tobacco. For high school age smokers, teenage store clerks are a major source. Teenage clerks sell to other teenagers, steal tobacco, and help their friends steal from their employers. Friends who are 18 years of age or over are a second major source for older adolescents. Parents often purchase tobacco for older adolescents.

CONCLUSION

Recommended actions include raising the minimum age for the purchase of tobacco to 21 years, and prohibiting individuals less than 21 years of age from selling tobacco.
Colonization during early succession of restored freshwater marshes
Authors: Kellogg Chev H , Bridgham Scott D
Published: July 2002

Little is known about the importance of initial colonization in the successional development of restored wetlands. We compared plant communities of two lightly planted restorations (water levels restored + planted and seeded), three hydrologic restorations (water levels restored), and two undrained sites. Measurements typically used in monitoring (richness, diversity, aboveground biomass) indicated that 23 years after restoration, restored wetlands showed only small differences from the plant community structure of undrained wetlands in the saturated zone. In contrast, analysis of vegetation based on species composition indicated differences in vegetation communities among all wetland types. Plant communities of planted restorations and reference sites were dominated by emergent species, while hydrologic restorations had a more variable plant community. These results indicate a small effect of initial planting and seeding at low densities and show that colonization is rapid during early succession of restored marshes. It was not clear whether either restoration method would eventually result in vegetation communities similar to reference sites. These results indicate that current monitoring periods of 35 years are insufficient to allow time for an accurate assessment of the successional development in each wetland.Key words: dispersal, germination, monitoring, plant biomass, plant community, wetland.
Experimental study of the friction of ice over concrete under simplified icestructure interaction conditions
Authors: Fiorio Bruno , Meyssonnier Jacques , Boulon Marc
Published: July 2002

Cyclic friction tests between laboratory grown columnar ice and micro-concrete plates were performed at 10°C to study iceconcrete friction under conditions similar to those observed in icestructure interactions. This paper presents the results obtained in terms of friction coefficients. Effects of time and contact conditions are analysed, and conclusions about the effective physical mechanisms of friction are drawn. These conclusions are validated by a simple model of the iceconcrete contact.Key words: ice, structure, concrete, contact, interaction, friction, law, model, viscoplasticity, roughness.