bluuebunny/crossref_metadata_2025 huggingface dataset:
Children with speech and language disability: caseload characteristics
Authors: Broomfield Jan , Dodd Barbara
Published: May 2004

Background: There has been no previous incidence survey of children referred to a speech and language therapy service in the UK. Previous studies of prevalence of specific communication difficulties provide contradictory data from which it is difficult to plan speech and language therapy service provision. Reliable data are needed concerning the nature and severity of impairments as well as the age and source of referral and the effects of cultural and socio‐economic profiles of the population served.

Aims: To describe referrals received between January 1999 and April 2000 by the paediatric speech and language therapy service of Middlesborough Primary Care Trust, an area of social deprivation.

Methods & Procedures: All referrals were offered an initial assessment appointment within 8 weeks of referral. Standardized tests and quantitative measures of communication difficulties, determined by age, were undertaken. Population and case history information was also gathered.

Outcomes & Results: The incidence rate of referrals who attended for assessment in a single year was calculated as 16.3% for primary communication disability and 14.6% for speech/language disability. Of the 1100 referrals, 14.9% failed to attend and 9.8% had normal functioning. The distribution of disorder type was dysfluency 5.3%, voice or nasality disruption 2.0%; receptive language difficulties 20.4%, expressive language difficulties 16.9% and speech difficulties 29.1%. A further 0.7% had special educational needs and 0.9% had speech and language impairment but refused consent. The majority of referrals were between 2 and 6 years old, more boys than girls were referred, and socio‐economic status matched that of the local population. Both gender and socio‐economic status affected diagnosis.

Conclusions: Based on the Middlesborough data, the estimated national incidence rate of referrals who attend for assessment and who have speech and language disability is 85 000–90 000 children per year (14.6% of births). While findings from only one Primary Care Trust must be treated cautiously, they provide paediatric speech and language therapy services managers with information that might guide service planning.
Using a parental checklist to identify diagnostic groups in children with communication impairment: a validation of the Children's Communication Checklist—2
Authors: Norbury Courtenay Frazier , Nash Marysia , Baird Gillian , Bishop Dorothy V. M.
Published: May 2004

Background: The Children's Communication Checklist (CCC 1998) was revised in 2003 (CCC‐2) to provide a general screen for communication disorder and to identify pragmatic/social interaction deficits. Two validation studies were conducted with different populations of children with language and communication impairments.

Methods & Procedures: In Study 1, the questionnaire was given to families of 87 children attending full‐time special education for specific language impairment, pragmatic language impairments or autistic spectrum disorders. In addition, the teachers of half the sample completed CCC‐2 forms for the same children, providing evidence for interrater agreement. In Study 2, the sample was increased to include 24 children with similar diagnoses in educational contexts in Scotland and 27 children referred for clinical evaluation at a neurodevelopment centre.

Outcomes & Results: The CCC‐2 distinguished children with communication impairments from non‐impaired peers. Furthermore, the social‐interaction deviance composite (SIDC) of the CCC‐2 identified children with disproportionate pragmatic and social difficulties in relation to their structural language impairments. This measure also had good interrater agreement (r=0.79).

Conclusions: CCC‐2 provides a useful screening measure for communication impairment and can be helpful in identifying children who should be referred for more detailed assessment of possible autistic spectrum disorder. However, the present data highlight substantial overlap amongst groups with ‘distinct’ diagnoses. It is suggested that it is unrealistic to use the CCC‐2 to make categorical distinctions on this continuum of disorder.
Applying verbal autopsy to determine cause of death in rural Vietnam
Authors: Dao Lan Huong  , Hoang Van Minh  , Byass Peter
Published: May 2004

Aims: Verbal autopsy (VA) is an attractive method for ascertaining causes of death in settings where the proportion of people who die under medical care is low. VA has been widely used to determine causes of childhood and maternal deaths, but has had limited use in assessing causes in adults and across all age groups. The objective was to test the feasibility of using VA to determine causes of death for all ages in Bavi District, Vietnam, in 1999, leading to an initial analysis of the mortality pattern in this area. Methods: Trained lay field workers interviewed a close caretaker of the deceased using a combination closed/open-ended questionnaire. Results: A total of 189 deaths were studied. Diagnoses were made by two physicians separately, with good agreement (κ=0.84) and then combined to reach one single underlying cause of death for each case. The leading causes of death were cardiovascular and infectious diseases (accounting for 20.6% and 17.9% of the total respectively). Drowning was very prevalent in children under 15 (seven out of nine cases of drowning were in this age group). Discussion: One month seemed an acceptable minimum recall period to ensure mourning procedures were over. A combination VA questionnaire was an appropriate instrument provided it was supported by adequate training of interviewers. Two physicians were appropriate for making the diagnoses but predefined diagnostic methods for common causes should be developed to ensure more replicable results and comparisons, as well as to observe trends of mortality over time. The causes of death in this study area reflect a typical pattern for developing countries that are in epidemiological transition. No maternal deaths and a low infant mortality rate may be the result of improvements in maternal and child health in this study area. Using the VA gave more precise causes of death than those reported at death registration. Although the validity of the VA method used has not been fully assessed, it appeared to be an appropriate method for ascertaining causes of death in the study area.
A probabilistic approach to interpreting verbal autopsies: methodology and preliminary validation in Vietnam
Authors: Byass Peter , Dao Lan Huong  , Hoang Van Minh
Published: May 2004

Aims: Verbal autopsy (VA) has become an important tool in the past 20 years for determining cause of death in communities where there is no routine registration. In many cases, expert physicians have been used to interpret the VA findings and so assign individual causes of death. However, this is time consuming and not always repeatable. Other approaches such as algorithms and neural networks have been developed in some settings. This paper aims to develop a method that is simple, reliable and consistent, which could represent an advance in VA interpretation. Methods: This paper describes the development of a Bayesian probability model for VA interpretation as an attempt to find a better approach. This methodology and a preliminary implementation are described, with an evaluation based on VA material from rural Vietnam. Results: The new model was tested against a series of 189 VA interviews from a rural community in Vietnam. Using this very basic model, over 70% of individual causes of death corresponded with those determined by two physicians, increasing to over 80% if those cases ascribed to old age or as being indeterminate by the physicians were excluded. Discussion: Although there is a clear need to improve the preliminary model and to test more extensively with larger and more varied datasets, these preliminary results suggest that there may be good potential in this probabilistic approach.
Ser-123 of the large antigen of hepatitis delta virus modulates its cellular localization to the nucleolus, SC-35 speckles or the cytoplasm
Authors: Tan Keng-Poo , Shih Ko-Nien , Lo Szecheng J.
Published: May 2004

Hepatitis delta virus (HDV) is a defective virus and requires hepatitis B virus (HBV) to supply envelope proteins (HBsAg) for maturation and secretion. It is known that two proteins produced by HDV, the small (SDAg) and large (LDAg) antigens, are located in the nucleolus, speckles and the cytoplasm and are involved in genome replication and virion packaging. However, little is known about how they are targeted to the specific sites where they act. A green fluorescence protein fused to LDAg (GFP–LD) has been shown previously to translocate from the nucleolus to SC-35 speckles in the presence of the casein kinase II inhibitor dichlororibofuranosyl benzimidazole. In this study, we determined which amino acids of GFP–LD were responsible for the translocation from the nucleolus to SC-35 speckles and created three GFP–LD derivatives, GFP–LDS2A, GFP–LDS123A and GFP–LDS2/123A. Fluorescence microscopy studies showed that Ser-123 mutants had a high tendency to target SC-35 speckles in both transfected HeLa and HuH-7 cells and suggested that Ser-123, but not Ser-2, plays a role in modulating LDAg translocation to the nucleolus or to SC-35 speckles. This study also demonstrated that HBsAg plays a role in facilitating the transportation of LDAg from the nucleus to cytoplasm. Compared with GFP–LD and GFP–LDS2A, mutants of Ser-123 were less efficiently transported to the cytoplasm and resulted in a lower level of secretion. In contrast, little or no isoprenylation mutant was observed in the cytoplasm of HuH-7 cells expressing HbsAg, suggesting that the isoprenylation of LDAg plays a role in export from the nucleus. Thus, the current study demonstrated that both cis and trans elements modulate HDAg translocation to various subcellular sites.
Susceptibility of mouse primary cortical neuronal cells to coxsackievirus B
Authors: Ahn Jeonghyun , Choi Jene , Joo Chul Hyun , Seo Ilseon , Kim DongHou , Yoon Seung Yong , Kim Yoo Kyum , Lee Heuiran
Published: May 2004

Coxsackievirus B (CVB) is often associated with aseptic meningitis and encephalitis, but the six serotypes of CVB vary in their relative disease severity. To elucidate the detailed mechanisms of CVB-induced cytopathological effects, the morphological and biochemical characteristics caused by the CVB serotypes in mouse primary cortical neuronal cells were investigated. By 24 h post-infection, all CVB serotypes except CVB2 induced severe cytotoxic alterations, including a loss of neurites. Both fluorescence and transmission electron microscopy revealed CVB-induced morphological changes indicative of apoptosis, including heavily condensed nuclei, subsequent chromatin condensation into the periphery of the nuclei and oligonucleosomal DNA fragmentation. It was also found that infection with all six CVB serotypes led to productive virus replication, which was completed prior to an apoptotic signal. The caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone significantly inhibited nuclear changes associated with virus-induced apoptosis, but had less effect on virus-associated cytopathic effects and no effect on virus production. In contrast, the transcription inhibitor actinomycin D profoundly inhibited all three virus-induced events. Taken together, these findings demonstrate that all six CVB serotypes can efficiently replicate in mouse cortical neuronal cells and that productive replication of these CVBs, except for CVB2, induces multiple cytopathological effects, including apoptotic alterations.
Steatosis and intrahepatic lymphocyte recruitment in hepatitis C virus transgenic mice
Authors: Alonzi Tonino , Agrati Chiara , Costabile Barbara , Cicchini Carla , Amicone Laura , Cavallari Claudio , Rocca Carlo Della , Folgori Antonella , Fipaldini Cristina , Poccia Fabrizio , Monica Nicola La , Tripodi Marco
Published: May 2004

To assess the effects of constitutive hepatitis C virus (HCV) gene expression on liver, transgenic mice carrying the entire HCV open reading frame inserted in theα1 antitrypsin (A1AT) gene were generated. Expression of A1AT/HCV mRNA was found to be mainly limited to perivascular areas of the liver as indicated byin situhybridization analysis. HCV core protein was detected in Western blots of liver extracts, whereas the expression of E2, NS3 and NS5 proteins was revealed by immunostaining of liver samples using HCV-specific antisera. Histological analysis of HCV transgenic mice showed that these animals develop extensive steatosis, but very little necrosis of liver tissue. Moreover, a consistent T cell infiltrate and a slight hepatocyte proliferation were observed. Phenotypic analysis of cells infiltrating the liver indicated that recruitment and/or expansion of residing CD8+, NK, NKT andγδT cells occurred in transgenic animals. Among these cells, a large fraction of CD8+T lymphocytes released mainly IL-10 and, to a lesser extent, IFN-γupon mitogenic stimulationin vitro. Furthermore, both intrahepatic lymphocytes and splenocytes did not produce cytokines in response to HCV antigens. Thus, these data indicate that constitutive expression of HCV proteins may be responsible for intrahepatic lymphocyte recruitment in absence of viral antigen recognition. This response is likely to be driven by virus-induced cellular factors and may play a significant role in the immunopathology of chronic HCV infection and liver disease.
Mapping of domains responsible for nucleocapsid protein–phosphoprotein interaction of henipaviruses
Authors: Chan Y. P. , Koh C. L. , Lam S. K. , Wang L.-F.
Published: May 2004

Hendra virus (HeV) and Nipah virus (NiV) are members of a new genus, Henipavirus, in the family Paramyxoviridae. Each virus encodes a phosphoprotein (P) that is significantly larger than its counterparts in other known paramyxoviruses. The interaction of this unusually large P with its nucleocapsid protein (N) was investigated in this study by using recombinant full-length and truncated proteins expressed in bacteria and a modified protein-blotting protein-overlay assay. Results from our group demonstrated that the N and P of both viruses were able to form not only homologous, but also heterologous, N–P complexes, i.e. HeV N was able to interact with NiV P and vice versa. Deletion analysis of the N and P revealed that there were at least two independent N-binding sites on P and they resided at the N and C termini, respectively. Similarly, more than one P-binding site was present on N and one of these was mapped to a 29 amino acid (aa) C-terminal region, which on its own was sufficient to interact with the extreme C-terminal 165 aa region of P.
Recent isolates of parapoxvirus of Finnish reindeer (Rangifer tarandus tarandus) are closely related to bovine pseudocowpox virus
Authors: Tikkanen Maria K. , McInnes Colin J. , Mercer Andrew A. , Büttner Mathias , Tuimala Jarno , Hirvelä-Koski Varpu , Neuvonen Erkki , Huovilainen Anita
Published: May 2004

Cases of papular stomatitis in Finnish reindeer have been reported for many years. The causative agent was thought to beOrf virus(ORFV), one of theParapoxviridae, although this assumption was based mainly on clinical symptoms, pathology and electron microscopy. Here sequence analyses of the viral DNA isolated from a recent outbreak of disease in 1999–2000 are presented in comparison to that isolated from earlier outbreaks in 1992–1994. The results show that the virus isolated from the 1999–2000 outbreak is most closely related toPseudocowpox virus, whereas those from previous years grouped with ORFV. The present study describes a method for genetic characterization and classification of parapoxviruses (PPVs) and provides for the first time an extended phylogenetic analysis of PPVs isolated from Finland, established members of the genusParapoxvirusand selected members of the subfamilyChordopoxvirinae.
Complete genome sequences of all members of the species Human enterovirus A
Authors: Oberste M. Steven , Peñaranda Silvia , Maher Kaija , Pallansch Mark A.
Published: May 2004

The speciesHuman enterovirus A(HEV-A) in the familyPicornaviridaeconsists of coxsackieviruses (CV) A2–A8, A10, A12, A14 and A16 and enterovirus 71. Complete genome sequences for the prototype strains of the 10 serotypes whose sequences were not represented in public databases have been determined and analysed in conjunction with previously available complete sequences in GenBank. Members of HEV-A are monophyletic relative to all other human enterovirus species in all regions of the genome except in the 5′ non-translated region (NTR), where they are known to cluster with members of HEV-B. The HEV-A prototype strains were about 66 to 86 % identical to one another in deduced capsid amino acid sequence. Antigenic cross-reactivity has been reported between CVA3-Olson and CVA8-Donovan, between CVA5-Swartz and CVA12-Texas-12 and between CVA16-G-10 and EV71-BrCr. Similarity plots, individual sequence comparisons and phylogenetic analyses demonstrate a high degree of capsid sequence similarity within each of these three pairs of prototype strains, providing a molecular basis for the observed antigenic relationships. In several cases, phylogenies constructed from the structural (P1) and non-structural regions of the genome (P2 and P3) are incongruent. The incongruent phylogenies and the similarity plot analyses imply that recombination has played a role in the evolution of the HEV-A prototype strains. CVA6-Gdula clearly contains sequences that are also present in CVA10-Kowalik and CVA12-Texas-12, suggesting that these three strains have a shared evolutionary history despite their lack of similarity in the capsid region.
Shift in Japanese encephalitis virus (JEV) genotype circulating in northern Vietnam: implications for frequent introductions of JEV from Southeast Asia to East Asia
Authors: Nga Phan Thi , Parquet Maria del Carmen , Cuong Vuong Duc , Ma Shao-Ping , Hasebe Futoshi , Inoue Shingo , Makino Yoshihiro , Takagi Masahiro , Nam Vu Sinh , Morita Kouichi
Published: May 2004

This study analyses the evolutionary relatedness of 16 Japanese encephalitis virus (JEV) isolates (nine from Vietnam and seven from Japan) to previously published JEV strains using E gene sequence data. Vietnamese and Japanese strains isolated between 1986 and 1990 were found to cluster in genotype 3. However, more recent Vietnamese and Japanese strains isolated between 1995 and 2002 grouped within genotype 1, now a dominant though previously unreported genotype in Vietnam. In addition, in this study, strains isolated between 1995 and 2002 were more closely related to those isolated in the 1990s than to the older genotype 1 strains. Recently, the introduction of JEV genotype 1 into Japan and Korea has also been reported. Hence this genotype shift phenomenon may be occurring throughout all East Asia. Further studies on JEV ecology are needed to clarify the mechanism of JEV genotype 1 spread to new territories.
Identification of novel hepatitis C virus-specific cytotoxic T lymphocyte epitopes by ELISpot assay using peptides with human leukocyte antigen-A*2402-binding motifs
Authors: Hakamada Taku , Funatsuki Kiyomi , Morita Hiroki , Ugajin Takuhiro , Nakamura Ikuo , Ishiko Hiroaki , Matsuzaki Yasushi , Tanaka Naomi , Imawari Michio
Published: May 2004

The human leukocyte antigen (HLA)-A*2402 is common in Asians. The authors attempted to identify epitopes for HLA-A*2402-restricted, hepatitis C virus (HCV)-specific CD8+ T cells by an enzyme-linked immunospot (ELISpot) assay using peripheral blood CD8+ T cells from HLA-A*2402-positive hepatitis C patients and synthetic HCV peptides based on HLA-A*2402-binding motifs and the amino acid sequence of type 1b HCV. Ten novel epitopes were identified in five of seven HLA-A*2402-positive patients with acute or short-term chronic HCV infection (<3 years), but in none of four with longer-term chronic infection (>10 years). Only one of the ten epitopes proved to be definitely HLA-A*2402-restricted. Another epitope was identified in one of two HLA-A*2402-negative acute hepatitis C patients. In two of the six patients with positive CD8+ T cell responses, the targeted epitopes were multiple. The same epitope was targeted in two patients. When patients with unresolved acute HCV infection were treated with alpha interferon, peripheral blood HCV-specific CD8+ T cells decreased with resolution of the hepatitis. In conclusion, CD8+ T cell responses to HCV infection are heterogeneous. One definite HLA-A*2402-restricted and ten probably non-HLA-A*2402-restricted epitopes were identified. Patients with short-term HCV infection are suitable for searching for novel HCV epitopes, but peripheral blood HCV-specific CD8+ T cells decrease markedly after loss of antigenic stimulation.
Determination and analysis of the complete genomic sequence of avian hepatitis E virus (avian HEV) and attempts to infect rhesus monkeys with avian HEV
Authors: Huang F. F. , Sun Z. F. , Emerson S. U. , Purcell R. H. , Shivaprasad H. L. , Pierson F. W. , Toth T. E. , Meng X. J.
Published: May 2004

Avian hepatitis E virus (avian HEV), recently identified from a chicken with hepatitis–splenomegaly syndrome in the United States, is genetically and antigenically related to human and swine HEVs. In this study, sequencing of the genome was completed and an attempt was made to infect rhesus monkeys with avian HEV. The full-length genome of avian HEV, excluding the poly(A) tail, is 6654 bp in length, which is about 600 bp shorter than that of human and swine HEVs. Similar to human and swine HEV genomes, the avian HEV genome consists of a short 5′ non-coding region (NCR) followed by three partially overlapping open reading frames (ORFs) and a 3′NCR. Avian HEV shares about 50 % nucleotide sequence identity over the complete genome, 48–51 % identity in ORF1, 46–48 % identity in ORF2 and only 29–34 % identity in ORF3 with human and swine HEV strains. Significant genetic variations such as deletions and insertions, particularly in ORF1 of avian HEV, were observed. However, motifs in the putative functional domains of ORF1, such as the helicase and methyltransferase, were relatively conserved between avian HEV and mammalian HEVs, supporting the conclusion that avian HEV is a member of the genus Hepevirus. Phylogenetic analysis revealed that avian HEV represents a branch distinct from human and swine HEVs. Swine HEV infects non-human primates and possibly humans and thus may be zoonotic. An attempt was made to determine whether avian HEV also infects across species by experimentally inoculating two rhesus monkeys with avian HEV. Evidence of virus infection was not observed in the inoculated monkeys as there was no seroconversion, viraemia, faecal virus shedding or serum liver enzyme elevation. The results from this study confirmed that avian HEV is related to, but distinct from, human and swine HEVs; however, unlike swine HEV, avian HEV is probably not transmissible to non-human primates.
Cytokine production by virus-specific CD8+ T cells varies with activation state and localization, but not with TCR avidity
Authors: Kristensen Nanna Ny , Madsen Andreas Nygaard , Thomsen Allan Randrup , Christensen Jan Pravsgaard
Published: May 2004

The ability of virus-specific CD8+T cells to produce cytokines was studied in mice infected with lymphocytic choriomeningitis virus and vesicular stomatitis virus. Intracellular staining was used to visualize cytokine-producing CD8+and CD4+T cells. Overall, virus-specific CD8+T cells produce a similar range of cytokines (IFN-γ, TNF-α, IL-2, GM-CSF, RANTES, MIP-1αand MIP-1β) as CD4+T cells, but the relative distribution of cytokine-producing subsets is different. Moreover, cytokine-producing CD8+T cells were found to dominate numerically at all time-points tested. Co-staining for more than one cytokine revealed that while all cytokine-producing CD8+T cells synthesized IFN-γ, additional cytokines were produced by partly overlapping subsets of this population. The frequency of cells producing more than one cytokine was higher in a tertiary site (peritoneum) and generally increased with transition into the memory phase; however, GM-CSF producing cells were only present transiently. Concerning factors predicted to influence the distribution of cytokine-producing subsets, IFN-γand IL-12 did not play a role, nor was extensive virus replication essential. Notably, regarding the heterogeneity in cytokine production by individual cells with similar epitope specificity, variation in TCR avidity was not the cause, sincein vivo-activated TCR transgene-expressing cells were as heterogeneous in cytokine expression as polyclonal cells specific for the same epitope.
Tomato yellow leaf curl Sardinia virus can overcome transgene-mediated RNA silencing of two essential viral genes
Authors: Noris Emanuela , Lucioli Alessandra , Tavazza Raffaela , Caciagli Piero , Accotto Gian Paolo , Tavazza Mario
Published: May 2004

To evaluate RNA silencing for the control of geminivirus infection, two classes of post-transcriptionally silenced (PTS) plants were tested using Tomato yellow leaf curl Sardinia virus (TYLCSV) Rep-210-transgenic plants, a sense×antisense hybrid and two multicopy sense lines. In both classes, PTS plants accumulated low or undetectable amounts of Rep-210 protein and mRNA but high amounts of Rep-210 small interfering RNAs. PTS plants were susceptible to TYLCSV when challenged by agroinoculation or using high viruliferous whitefly (Bemisia tabaci) pressure, although some plants were resistant at low whitefly pressure. Delayed infections were also observed, indicating that TYLCSV could overcome transgene silencing of rep and of the nested C4 gene. TYLCSV infection boosted transgene silencing but this did not lead to recovery. The data suggest that if the virus reaches a threshold level of expression/replication in the initially infected cells then virus spreading can no longer be prevented.
Standards for the assay of Creutzfeldt–Jakob disease specimens
Authors: Minor P. , Newham J. , Jones N. , Bergeron C. , Gregori L. , Asher D. , van Engelenburg F. , Stroebel T. , Vey M. , Barnard G. , Head M. ,   the WHO Working Group on International Reference Materials for the Diagnosis and Study of Transmissible Spongiform Encephalopathies
Published: May 2004

Assays for the agent of Creutzfeldt–Jakob disease (CJD) include measurement of infectivity in different animal systems, such as wild-type or transgenic mice, and detection of PrPSc by different methods and formats. The various assays could be best calibrated against each other by use of uniform readily available materials, and samples of four human brains, two from sporadic CJD patients, one from a variant CJD patient and one from a non-CJD patient, have been prepared as 10 % homogenates dispensed in 2000 vials each for this purpose. Results of in vitro methods, particularly immunoblot assays, were compared in the first collaborative study described here. While dilution end-points varied, the minimum detectable volume was surprisingly uniform for most assays and differences in technical procedure, other than the sample volume tested, had no detectable systematic effect. The two specimens from sporadic CJD cases contained both type 1 and type 2 prion proteins in approximately equal proportions. The materials have been given the status of reference reagents by the World Health Organization and are available for further study and assessment of other in vitro or in vivo assay procedures.
The C terminus of the movement protein of Brome mosaic virus controls the requirement for coat protein in cell-to-cell movement and plays a role in long-distance movement
Authors: Takeda Atsushi , Kaido Masanori , Okuno Tetsuro , Mise Kazuyuki
Published: May 2004

The 3a movement protein (MP) plays a central role in the movement ofBrome mosaic virus(BMV). To identify the functional regions in BMV MP, 24 alanine-scanning (AS) MP mutants of BMV were constructed. Infectivity of the AS mutants in the host plantChenopodium quinoashowed that the central region of BMV MP is important for viral movement and both termini of BMV MP have effects on the development of systemic symptoms. A green-fluorescent-protein-expressing RNA3-based BMV vector containing a 2A sequence fromFoot-and-mouth disease viruswas also constructed. Using this vector, two AS mutants that showed more efficient cell-to-cell movement than wild-type BMV were identified. The MPs of these two AS mutants, which have mutations at their C termini, mediated cell-to-cell movement independently of coat protein (CP), unlike wild-type BMV MP. Furthermore, a BMV mutant with a truncation in the C-terminal 42 amino acids of MP was also able to move from cell to cell without CP, but did not move systemically, even in the presence of CP. These results and an encapsidation analysis suggest that the C terminus of BMV MP is involved in the requirement for CP in cell-to-cell movement and plays a role in long-distance movement. Furthermore, the ability to spread locally and form virions is not sufficient for the long-distance movement of BMV. The roles of MP and CP in BMV movement are discussed.
Methylprednisolone reduces airway microvascular permeability but not airway resistance induced by N‐formylmethionine leucyl‐phenylalanine in the rabbit
Authors: MATHESON Melissa , MCCLEAN Melissa , RYNELL Ann‐Christine , BEREND Norbert
Published: May 2004

Objective:  The aim of this study was to determine the effect of corticosteroids on the increase in airway microvascular permeability (MVP) and airway resistance induced by N‐formylmethionine leucyl‐phenylalanine in the rabbit.

Methodology:  After pretreatment with methylprednisolone (for 1 day or 1 week) rabbits were nebulized with N‐formylmethionine leucyl‐phenylalanine and MVP was assessed using the Evans blue dye technique (on the trachea, bronchi and bronchioles), while airway resistance was measured using a volume displacement plethysmograph.

Results:  There were no significant differences in airway resistance between the steroid treated group and the control group for either steroid treatment regime. The degree of extravasation of Evans blue dye was significantly inhibited in the bronchioles after both the 1‐day and 1‐week treatment with methylprednisolone. There were no significant differences in MVP in the trachea or bronchi between the treated groups and the control groups.

Conclusion:  These results show that methylprednisolone can significantly reduce N‐formylmethionine leucyl‐phenylalanine‐induced MVP without affecting airway resistance.
The effect of chest wall restriction on exercise capacity
Authors: COAST J. Richard , CLINE Camala C.
Published: May 2004

Objective:  Subjects with restrictive pulmonary disease exhibit a decreased exercise capacity compared to non‐diseased subjects, as do subjects in certain workplace situations, for example when wearing bullet‐proof vests. The purpose of this study was to examine the effects of varying degrees of chest wall restrictive loading on exercise performance. We have designed and validated a chest wall restrictor that mimics the elastic loading occurring in some disease states and some occupational situations.

Methodology:  In this study, 18 subjects performed five graded maximal cycling tests while wearing the device at four different inflation pressures (0, 20, 40, and 60 mmHg).

Results:  Maximal values of oxygen uptake (V̇O2max), minute ventilation (V̇Imax), tidal volume (VT at max) and breathing frequency (fB at max) were monitored, as was the time to maximal exercise (TTM). V̇O2, V̇I, VT, and fB were also measured at three submaximal loads. The results showed that V̇O2max, V̇Imax, TTM, and VT at max were significantly decreased, while fB at max was maintained. At submaximal loads, the ventilatory parameters VT, and fB were altered with load, but V̇I and V̇O2 were not affected by load.

Conclusions:  These results indicate that the wearing of this device decreases variables associated with maximal exercise, and that the decreases are related to the degree of chest wall restriction. Furthermore, submaximal exercise ventilation was minimally altered, with an increase in fB and a decrease in VT associated with increasing restrictive loads. Submaximal oxygen uptake was not affected by breathing restriction.
Post‐hyperventilation hypoxaemia is due to alteration of ventilation and perfusion matching
Authors: NOLAN Stephen R. , SAXENA Manox , BURGESS Keith R. , SIMMEL Rein , BRAUDE Stanley
Published: May 2004

Objective:  The aim of this study was to investigate the mechanisms of post‐hyperventilation hypoxia.

Methodology:  Seven healthy male volunteers, aged 29.1 ± 1.4 years, underwent two 10‐min periods of voluntary hyperventilation to pulmonary end tidal CO2 values of 20 mmHg (severe hyperventilation), or 30 mmHg (moderate hyperventilation). Post‐hyperventilation, the arterial oxygen saturation, VE and arterial blood gas values were measured. Sleep was excluded by EEG monitoring.

Results:  Maximal hypoxaemia occurred in proportion to severity of hyperventilation; at approximately 5 min post‐hyperventilation Pao2 fell to 64 ± 7 mmHg (severe hyperventilation) and 72 ± 6 mmHg (moderate hyperventilation) from 97 ± 3 mmHg at baseline. Hypoxaemia persisted beyond the time of normalization of Paco2 and HCO3. On another occasion, a N2 washout test was performed after severe hyperventilation, which excluded bronchoconstriction.

Conclusion:  Relative hypoventilation may partly explain post‐hyperventilation hypoxaemia, but by excluding bronchoconstriction and periodic breathing, we have demonstrated that most of the hypoxaemia must have been due to alteration of pulmonary blood flow distribution causing a fall in V/Q ratio.
Respiratory function testing: The impact of respiratory scientists on the training and support of primary health care providers
Authors: BURTON Mark A. , BURTON Deborah L. , SIMPSON Maree D. , GISSING Peter M. , BOWMAN Scott L.
Published: May 2004

Objective:  In rural Australia access to doctors is limited, access to respiratory physicians even more so and these are the traditional sources of lung function testing.The aim of this study was to assess the feasibility of training and supporting existing rural primary healthcare providers in lung function testing as a screening and monitoring mechanism due to the shortage of healthcare professionals capable of providing such a service.

Methodology:  As pharmacists are readily accessible healthcare professionals, they were trained in spirometry measurement and supported with ongoing quality assurance by respiratory scientists. Spirometers were provided to the pharmacists. People purchasing respiratory medications or responding to advertising about the service were tested after giving informed consent. Spirometic assessments were assessed for accuracy and reproducibility. Participants’ spirometry results were reviewed and those with abnormal test results were referred to their doctor.

Results:  Pharmacists were able to competently develop the skills necessary for providing spirometry measurement as a screening and monitoring technique. The level of competence exceeded that reported in previously published studies. Pharmacists were able to successfully identify spirometry results within the normal range.

Conclusions:  Training and supporting accessible healthcare professionals to provide lung function testing increases access in areas of need and has implications for respiratory morbidity and mortality in such settings.
Management of malignant pleural effusions
Authors: LEE Y. C. Gary , LIGHT Richard W.
Published: May 2004

Abstract:  Malignant pleural effusion is a common clinical problem. Evacuation of the pleural fluid and prevention of its reaccumulation are the main aims of management. Pleurodesis should be attempted early, although considerable practice variations exist in the way it is performed. There is a lack of consensus among respiratory physicians worldwide on the optimal method and agent for pleurodesis. Talc remains the most commonly used pleurodesing compound in most countries. While talc produces a higher success rate than other compounds, it generates more side‐effects. The association between talc and ARDS continues to be debated. Ambulatory small‐bore pleural catheter drainage followed by intrapleural instillation of a pleurodesing agent is increasingly accepted as an alternative to conventional in‐patient pleurodesis. Development of novel methods to control pleural fluid formation should be made a high priority in future pleural research.
The relative survival of COPD patients on long‐term oxygen therapy in Australia: A comparative study
Authors: CRANSTON Josephine M. , NGUYEN Anh‐Minh , CROCKETT Alan J.
Published: May 2004

Objective: The survival of patients with COPD on long‐term oxygen therapy (LTOT) has been studied using both univariate and multivariate procedures. There has been only one previous report of relative survival. Relative survival takes into account the risk of death due to increasing age. The objective of this study was to determine the relative survival of a group of South Australian patients prescribed home oxygen therapy for COPD.

Methodology: A method proposed by Hakulinen was used to determine relative survival. The results were compared with the relative survival of a similar group of French COPD patients.

Results: A total of 505 COPD patients (249 males, 256 females) were included in the survival analysis. Relative survival corrected for life expectancy was 78.1%, 56.7%, 23.1% and 1.1% at 1, 2, 5 and 10 years, respectively, which was less than that reported in a recent French study of comparable patients. Our patients were similar with respect to age, severity of hypoxaemia and oxygen usage to those in the French study.

Conclusions: Using relative survival analysis, Australian LTOT patients with COPD have worse outcomes than some European patients. Factors contributing to the excess mortality in South Australian COPD patients need to be investigated.
Occult pneumomediastinum in a SARS patient presenting as recurrent chest pain and acute ECG changes mimicking acute coronary syndrome
Authors: TSE Tak‐Sun , TSUI Kin‐Lam , YAM Loretta Y‐C. , SO Loletta K‐Y. , LAU Arthur C‐W. , CHAN Kwok‐Keung , LI Shu‐Kin
Published: May 2004

Objective:  Severe acute respiratory syndrome (SARS) is a newly emergent disease due to a novel coronavirus, which caused outbreaks worldwide.

Methodology:  We report a SARS patient who had developed recurrent chest pain and acute T‐wave inversion over the precordial leads on electrocardiography (ECG).

Results:  She developed progressive subcutaneous emphysema a few days later. Her CXR showed features suggestive of pneumomediastinum, which was confirmed by high‐resolution CT scan of the thorax.

Conclusion:  Pneumomediastinum should be considered in SARS patients as a possible cause of chest pain and ECG changes that mimic acute coronary syndrome.
Effect of low‐dose theophylline on airway inflammation in COPD
Authors: KOBAYASHI Motoko , NASUHARA Yasuyuki , BETSUYAKU Tomoko , SHIBUYA Eiji , TANINO Yoshinori , TANINO Mishie , TAKAMURA Kei , NAGAI Katsura , HOSOKAWA Takeshi , NISHIMURA Masaharu
Published: May 2004

Objective:  Recent studies have shown that theophylline may exert anti‐inflammatory effects on neutrophils. We undertook to assess the effect of theophylline on airway inflammation in COPD.

Methodology:  We performed a 4‐week randomized double‐blind, placebo‐controlled study in 11 theophylline‐naive patients with mild to moderate COPD. After a 1‐week run‐in period, six subjects were administered 400 mg/day theophylline (Theodur; Nikken Chemicals Co. Ltd, Tokyo, Japan) for 4 weeks, while five subjects were administered a placebo. Induced sputum was obtained before and after the run‐in period and then after 2 and 4 weeks of treatment. Cell differential count and levels of interleukin‐8, matrix metalloproteinase‐9, neutrophil elastase (NE), myeloperoxidase (MPO), α1‐antitrypsin (α1‐AT), leukotriene B4 and tissue inhibitor of metalloproteinases‐1 (TIMP‐1) were assessed.

Results:  No variable was significantly different during the run‐in period or with placebo treatment. In contrast, theophylline treatment significantly decreased NE and MPO levels at 4 weeks, although the cell differential count did not change appreciably as a result of treatment.

Conclusion:  These results suggest that 4 weeks of theophylline treatment attenuates neutrophil‐associated inflammation in the airways of mild to moderate COPD patients. However, the clinical benefits remain to be determined.
Clinical features of Q fever pneumonia
Authors: OKIMOTO Niro , ASAOKA Naoko , OSAKI Kohichi , KURIHARA Takeyuki , YAMATO Kenji , SUNAGAWA Takako , FUJITA Kazue , OHBA Hideo , NAKAMURA Junichi , NAKADA Keiichi
Published: May 2004

Abstract:  The aim of the study was to assess the clinical features of Q fever pneumonia in Japan. Four cases of Q fever pneumonia (a female aged 21 and males aged 53, 74 and 87 years) who were diagnosed using the PanBio ELISA test kit, were assessed and their clinical features are described. The frequency of Q fever pneumonia among our cases of community‐acquired pneumonia was 1.4% (4/284). A 21‐year‐old female had a typical case of the disease with (i) a history of owning a cat, (ii) onset with fever and dry cough, (iii) multiple soft infiltrative shadows on CXR, (iv) a normal white blood cell count, and (v) good response to clarithromycin. The pneumonias in the other three cases were considered mixed infections with bacteria such as Streptococcus pneumoniae and Haemophilus influenzae. Their clinical features included the following: (i) an elderly person with an underlying disease, (ii) onset with fever and purulent sputum, (iii) coarse crackles on auscultation, (iv) infiltrative shadows and pleural effusion on CXR, (v) increased white blood cells with elevated BUN and hyponatraemia, and (vi) modest responses to combined therapy with carbapenem and minocycline. Our observations suggest that two types of pneumonia caused by Coxiella burnetti exist; one with the usual features of atypical pneumonia, and the other presenting with the clinical features of bacterial pneumonia in the elderly due to mixed bacterial infection.
Laparoscopic live‐donor nephrectomy: modifications for developing nations
Authors: Kumar A. , Chaudhary H. , Srivastava A. , Raghavendran M.
Published: May 2004

Authors from Lucknow describe their experience with laparoscopic live‐donor nephrectomy, and describe modifications they have used to make the procedure cost‐effective for developing nations. As the urological world is increasingly realising, this approach to renal transplantation is increasing the number of live‐donor kidneys being offered for the many patients with end‐stage renal failure. In this considerable series, the authors are strongly of the opinion that this is the best approach to live donor nephrectomy, and that their modifications are helpful in its use in developing nations.

OBJECTIVE

To describe modifications to laparoscopic live‐donor nephrectomy (LLDN) to make it more cost‐effective for developing countries; LLDN was developed as a better alternative to conventional donor nephrectomy, with advantages of an earlier return to normal activities and smaller scars, but is not popular in developing countries because of high cost of disposable items.

PATIENTS AND METHODS

From January 2000 to January 2002, 148 LLDNs were performed, of which two used a hand‐assisted technique, 17 the standard technique, 79 a modified laparoscopically assisted cost‐saving approach and 50 by the modified technique. In the latter approach the kidney was delivered through a 6–8 cm anterior subcostal flank incision. In last 50 patients we further modified the technique, clipping the hilum using endoclips and delivering the kidney by holding the lateral pararenal fat through a 5 cm iliac fossa incision.

RESULTS

The mean age, operative duration, warm ischaemia time, blood loss, analgesic requirements, pain score and hospital stay were comparable among the various techniques used. Re‐exploration was required in four patients (bleeding in two, trocar‐induced bowel injury in two). Immediate complications after surgery occurred in 20% of patients. Using endoclips, the cost was considerably reduced, from $400 to $290. The iliac fossa incision was aesthetically pleasing and more acceptable to patients.

CONCLUSION

These modifications are relevant in the context of a developing nation, as they provide all the benefits of LLDN at reduced cost and with better cosmetic results.
Bupivacaine provides rapid, effective periprostatic anaesthesia for transrectal prostate biopsy
Authors: Rabets J.C. , Jones J.S. , Patel A.R. , Zippe C.D.
Published: May 2004

OBJECTIVE

To examine the effectiveness of the longer acting agent bupivacaine in providing periprostatic anaesthesia during transrectal ultrasonography (TRUS)‐guided biopsy, as the periprostatic injection of lidocaine has been shown to significantly alleviate the pain of this procedure.

PATIENTS AND METHODS

Seventy‐five patients were randomized to receive a periprostatic injection with either bupivacaine, a lidocaine/bupivacaine (1/1) combination, or no local anaesthesia. Immediately before biopsy 5 mL of the anaesthetic was injected under TRUS guidance into the periprostatic nerves bilaterally. After taking a 10‐core biopsy the patients were given a visual analogue scale (VAS; 0–10) to assess their pain during the procedure.

RESULTS

The mean VAS scores were 2.04 in the bupivacaine group and 4.46 in the control (no local anaesthetic) group (P < 0.001).

CONCLUSIONS

Bupivicaine provides significant, immediate periprostatic anaesthesia for TRUS biopsy.
Characterization of bone metastases in patients with renal cell cancer
Authors: Adiga G.U. , Dutcher J.P. , Larkin M. , Garl S. , Koo J.
Published: May 2004

OBJECTIVE

To characterize the clinical features of bone metastases in patients with renal cell carcinoma (RCC) treated with interleukin‐2 therapy. Bone lesions contribute to significant morbidity and mortality, and although present in up to half of patients with RCC, their behaviour and response to therapy have not been well characterized.

PATIENTS AND METHODS

We evaluated skeletal metastases in 19 patients with bone lesions who received either moderate‐ or high‐dose interleukin‐2 therapy. Data on bone disease, including location and number of bone lesions, need for bone‐specific therapies and use of pain medications, were noted. The response of bone lesions to interleukin‐2 was compared with the response of other systemic metastatic sites.

RESULTS

Skeletal metastases resulted in significant morbidity by causing pain (75%) and other complications requiring surgical and/or radiotherapeutic intervention (94%) before beginning interleukin‐2 therapy. In most patients the response of bone lesions to interleukin‐2 was similar to that in their other systemic sites. Treatment with interleukin‐2 had no significant effect on the requirement for pain medication for bone pain. However, it may have prevented skeletal complications requiring surgery or radiotherapy. None of the patients had hypercalcaemia; there was no significant association between bone metastases and elevated alkaline phosphatase levels.

CONCLUSIONS

Skeletal metastases are a significant contributor to morbidity among patients with RCC. Bone lesions respond similarly to interleukin‐2 therapy as other systemic sites. Bisphosphonates appear promising for these predominantly osteolytic lesions.