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2.  Combined effects of body composition and ageing on joint torque, muscle activation and co-contraction in sedentary women 
Age  2014;36(3):9652.
This study aimed to establish the interplay between body mass, adiposity, ageing and determinants of skeletal muscle strength. One hundred and two untrained healthy women categorised by age into young (Y) (mean ± SD, 26.7 ± 9.4 years) vs. old (O) (65.1 ± 7.2 years) were assessed for body fat, lean mass, plantar flexion and dorsiflexion maximum voluntary isometric contraction (MVC) torque, muscle activation capacity and antagonist muscle co-contraction. MVC torque normalised to body mass in the obese group was 35 and 29 % lower (p < 0.05) in Y and 34 and 31 % lower (p < 0.05) in O, compared with underweight and normal weight individuals, respectively. Y with ≥40 % body fat had significantly lower activation than Y with <40 % body fat (88.3 vs. 94.4 %, p < 0.05), but O did not exhibit this effect. Co-contraction was affected by ageing (16.1 % in O vs. 13.8 % in Y, p < 0.05) but not body composition. There were significant associations between markers of body composition, age, strength and activation capacity, with the strongest correlation between muscle strength and total body mass (r2 = 0.508 in Y, p < 0.001, vs. r2 = 0.204 in O, p < 0.01). Furthermore, the age-related loss in plantar flexion (PF) MVC torque was exacerbated in obese compared to underweight, normal weight and overweight individuals (−0.96 vs. −0.54, −0.57 and −0.57 % per year, p < 0.05). The negative impact of adiposity on muscle performance is associated with not only muscular but also neural factors. Overall, the effects of ageing and obesity on this system are somewhat cumulative.
PMCID: PMC4082607  PMID: 24744050
Activation; Adiposity; Ageing; Lean mass; Muscle strength; Obesity
3.  Emphysema Predicts Hospitalisation and Incident Airflow Obstruction among Older Smokers: A Prospective Cohort Study 
PLoS ONE  2014;9(4):e93221.
Emphysema on CT is common in older smokers. We hypothesised that emphysema on CT predicts acute episodes of care for chronic lower respiratory disease among older smokers.
Materials and Methods
Participants in a lung cancer screening study age ≥60 years were recruited into a prospective cohort study in 2001–02. Two radiologists independently visually assessed the severity of emphysema as absent, mild, moderate or severe. Percent emphysema was defined as the proportion of voxels ≤ −910 Hounsfield Units. Participants completed a median of 5 visits over a median of 6 years of follow-up. The primary outcome was hospitalization, emergency room or urgent office visit for chronic lower respiratory disease. Spirometry was performed following ATS/ERS guidelines. Airflow obstruction was defined as FEV1/FVC ratio <0.70 and FEV1<80% predicted.
Of 521 participants, 4% had moderate or severe emphysema, which was associated with acute episodes of care (rate ratio 1.89; 95% CI: 1.01–3.52) adjusting for age, sex and race/ethnicity, as was percent emphysema, with similar associations for hospitalisation. Emphysema on visual assessment also predicted incident airflow obstruction (HR 5.14; 95% CI 2.19–21.1).
Visually assessed emphysema and percent emphysema on CT predicted acute episodes of care for chronic lower respiratory disease, with the former predicting incident airflow obstruction among older smokers.
PMCID: PMC3974731  PMID: 24699215
4.  Inter-unit comparisons are flawed 
Archives of Disease in Childhood  2002;87(6):559-560.
PMCID: PMC1755821  PMID: 12456572
6.  Calibration of the paediatric index of mortality in UK paediatric intensive care units 
Archives of Disease in Childhood  2001;84(2):125-128.
AIM—To test a paediatric intensive care mortality prediction model for UK use.
METHOD—Prospective collection of data from consecutive admissions to five UK paediatric intensive care units (PICUs), representing a broad cross section of paediatric intensive care activity. A total of 7253 admissions were analysed using tests of the discrimination and calibration of the logistic regression equation.
RESULTS—The model discriminated and calibrated well. The area under the ROC plot was 0.84 (95% CI 0.819 to 0.853). The standardised mortality ratio was 0.87 (95% CI 0.81 to 0.94). There was remarkable concordance in the performance of the paediatric index of mortality (PIM) within each PICU, and in the performance of the PICUs as assessed by PIM. Variation in the proportion of admissions that were ventilated or transported from another hospital did not affect the results.
CONCLUSION—We recommend that UK PICUs use PIM for their routine audit needs. PIM is not affected by the standard of therapy after admission to PICU, the information needed to calculate PIM is easy to collect, and the model is free.

PMCID: PMC1718658  PMID: 11159286
7.  Early filtration and mortality in meningococcal septic shock? 
Archives of Disease in Childhood  2000;83(6):508-509.
Following the introduction of a policy of early therapeutic filtration for presumed meningococcal septicaemic shock, the overall mortality has decreased.

PMCID: PMC1718580  PMID: 11087288
8.  Hepatic histology in hepatitis C virus carriers coinfected with hepatitis G virus 
Gut  1998;42(1):103-106.
Background—A novel flavivirus has been described recently and designated hepatitis G virus (HGV). The virus is transmitted by the parenteral route but it is uncertain whether it is associated with chronic liver disease because liver biopsy is difficult to justify in this group. 
Aims—To examine histological features of liver biopsy in patients infected with hepatitis C virus (HCV) according to the presence or absence of HCV and HGV RNA. 
Methods—One hundred and thirty one consecutive HCV carriers undergoing staging liver biopsy were studied retrospectively. In each, HCV RNA and HGV RNA were detected by reverse transcription polymerase chain reaction on serum samples collected at the time of biopsy. The presence of each RNA was correlated with histological features blind to the RNA results; individual histological features of inflammation or fibrosis were scored separately. 
Results—Nineteen patients were positive for both HGV and HCV RNA in serum, 91 were positive for HCV RNA alone, two were positive for HGV RNA alone, and 19 were negative for both RNA species. Neither age nor sex differed between the groups; a greater proportion of intravenous drug users were HGV RNA positive, but this was not statistically significant. There was no effect of HGV coinfection on the stage of fibrosis or any other histological parameter except steatosis; patients with HCV and HGV RNA had a higher mean score for fat than those patients with HCV RNA alone (p<0.05). 
Conclusions—HGV coinfection has no important effects on histological features in chronic HCV carriers. It is unlikely that HGV infection causes chronic liver disease. 

Keywords: hepatitis C virus; hepatitis G virus; RNA; histology
PMCID: PMC1726944  PMID: 9505894
9.  Contributory and Exacerbating Roles of Gaseous Ammonia and Organic Dust in the Etiology of Atrophic Rhinitis 
Pigs reared commercially indoors are exposed to air heavily contaminated with particulate and gaseous pollutants. Epidemiological surveys have shown an association between the levels of these pollutants and the severity of lesions associated with the upper respiratory tract disease of swine atrophic rhinitis. This study investigated the role of aerial pollutants in the etiology of atrophic rhinitis induced by Pasteurella multocida. Forty, 1-week-old Large White piglets were weaned and divided into eight groups designated A to H. The groups were housed in Rochester exposure chambers and continuously exposed to the following pollutants: ovalbumin (groups A and B), ammonia (groups C and D), ovalbumin plus ammonia (groups E and F), and unpolluted air (groups G and H). The concentrations of pollutants used were 20 mg m−3 total mass and 5 mg m−3 respirable mass for ovalbumin dust and 50 ppm for ammonia. One week after exposure commenced, the pigs in groups A, C, E, and G were infected with P. multocida type D by intranasal inoculation. After 4 weeks of exposure to pollutants, the pigs were killed and the extent of turbinate atrophy was assessed with a morphometric index (MI). Control pigs kept in clean air and not inoculated with P. multocida (group H) had normal turbinate morphology with a mean MI of 41.12% (standard deviation [SD], ± 1.59%). In contrast, exposure to pollutants in the absence of P. multocida (groups B, D, and F) induced mild turbinate atrophy with mean MIs of 49.65% (SD, ±1.96%), 51.04% (SD, ±2.06%), and 49.88% (SD, ±3.51%), respectively. A similar level of atrophy was also evoked by inoculation with P. multocida in the absence of pollutants (group G), giving a mean MI of 50.77% (SD, ±2.07%). However, when P. multocida inoculation was combined with pollutant exposure (groups A, C, and E) moderate to severe turbinate atrophy occurred with mean MIs of 64.93% (SD, ±4.64%), 59.18% (SD, ±2.79%), and 73.30% (SD, ±3.19%), respectively. The severity of atrophy was greatest in pigs exposed simultaneously to dust and ammonia. At the end of the exposure period, higher numbers of P. multocida bacteria were isolated from the tonsils than from the nasal membrane, per gram of tissue. The severity of turbinate atrophy in inoculated pigs was proportional to the number of P. multocida bacteria isolated from tonsils (r2 = 0.909, P < 0.05) and nasal membrane (r2 = 0.628, P < 0.05). These findings indicate that aerial pollutants contribute to the severity of lesions associated with atrophic rhinitis by facilitating colonization of the pig’s upper respiratory tract by P. multocida and also by directly evoking mild atrophy.
PMCID: PMC95687  PMID: 10066654
11.  Pathological complications of non-survivors of newborn extracorporeal membrane oxygenation 
The pathology was reviewed of the early deaths identified from the first 50 neonates treated with extracorporeal membrane oxygenation (ECMO) during its introduction to the UK. Fifteen neonates died during or shortly after ECMO between August 1989 and June 1992. Data on 12 are presented (three did not have a postmortem examination). The clinical diagnoses at referral for ECMO were as follows: persistent pulmonary hypertension of the newborn (six infants), primary congenital pneumonia (one infant), community acquired pneumonia (two infants), birth asphyxia (one infant), respiratory distress syndrome (one infant), and meconium aspiration syndrome (one infant). In our group, at necropsy, five had significant haemorrhage (three intracranial, one pulmonary, one pericardial and intraventricular). Three of five infants with evidence of haemorrhage also had signs of sepsis. Six infants had evidence at necropsy of systemic sepsis, five showed evidence of severe anoxic brain injury, and four infants had cerebellar haemorrhages. Three infants had evidence of myocardial ischaemia. It is difficult to discriminate between the relative influence of the primary diagnosis, the mode of treatment, and the severity of presentation in the genesis of this pathology. It is likely that the extent and severity of some of the findings represent a pathological progression that would have been interrupted by the death of the patient, had ECMO not been instituted.
PMCID: PMC1061089  PMID: 7979484
12.  Extracorporeal life support in paediatrics. 
Extracorporeal membrane oxygenation (ECMO) is a life support technique based on modifications of heart-lung bypass technology. It is used to support severe but potentially reversible pulmonary or cardiopulmonary failure. There is increasing use of the technique for neonates and a return of interest in its use for adults. The number of non-neonatal paediatric patients receiving pulmonary support with ECMO worldwide is, however, small, and survival rates average less than 50%. Initial experience in 15 patients aged 3 months to 5 years with a high survival and low morbidity is reported.
PMCID: PMC1029191  PMID: 8435019
13.  UK experience in neonatal extracorporeal membrane oxygenation. 
Archives of Disease in Childhood  1992;67(7 Spec No):822-825.
Extracorporeal membrane oxygenation (ECMO) is a life support technique capable of supporting pulmonary, cardiac, or cardiopulmonary function. It has proved most successful in neonatal respiratory failure. We report the initial UK experience with a survival rate of 80% in 15 neonates (gestations 36-41 weeks, birth weights 2690-3990 g) whose condition exceeded American criteria for ECMO treatment for a prolonged period before referral. Ages at referral varied from 11 to 240 hours and the duration of bypass required varied from 30 to 240 hours respectively.
PMCID: PMC1590433  PMID: 1519983
14.  Neonatal hyperoxaemia. 
PMCID: PMC1793646  PMID: 1575565
15.  Naturally acquired Pasteurella multocida infection in rabbits: clinicopathological aspects. 
A cohort of 41 New Zealand White rabbits, 35 to 60 days old, from twelve litters were followed for twelve weeks for development of pasteurellosis. Eleven of 19 rabbits in five litters acquired Pasteurella multocida infection. The incubation period was difficult to determine as P. multocida infection was detected both before and after the onset of rhinitis. The response of rabbits to infection varied from subclinical infection to death from systemic pasteurellosis. Atrophy of the maxilloturbinates of the nares was detected in rabbits with chronic rhinitis associated with P. multocida infection.
PMCID: PMC1263457  PMID: 1889034
16.  The roots of violence. 
BMJ : British Medical Journal  1988;297(6660):1352-1353.
PMCID: PMC1835077  PMID: 3146361
17.  Characterization of the restricted component of Epstein-Barr virus early antigens as a cytoplasmic filamentous protein. 
Journal of Virology  1986;58(3):748-756.
Four monoclonal antibodies produced against the restricted component of the Epstein-Barr virus (EBV) early antigen (EA-R) precipitated a polypeptide with an approximate molecular weight of 85,000. Three of these antibodies prepared against the native 85,000-molecular-weight protein (85K protein) reacted by immunofluorescence with acetone-fixed smears but not methanol-fixed smears of EBV-producing cells activated with tumor-promoting agent and sodium butyrate. The fourth monoclonal antibody which was produced against the denatured 85K protein reacted with both acetone-fixed cells and methanol-fixed cells. Blocking of direct immunofluorescence by the different monoclonal antibodies established that these monoclonal antibodies were directed against three different epitopes expressed on the 85K protein. The cytoplasmic staining pattern produced by each antibody was granular during the first 24 to 28 h after induction, developed into filamentous structures about 36 h after induction, and then began to aggregate after 48 h. Similar structures were observed in human placental cells transfected by EBV DNA and stained with three of the monoclonal antibodies. These results suggest that the EA-R polypeptide is assembled into filaments during the EBV lytic cycle. The significance of this in regards to replication has yet to be determined. Biochemical characterization of this major EA-R component did not reveal any major differences in this protein isolated from different cell lines.
PMCID: PMC252980  PMID: 2422401
18.  Rheumatoid arthritis synovial membrane contains a 62,000-molecular-weight protein that shares an antigenic epitope with the Epstein-Barr virus-encoded associated nuclear antigen. 
Journal of Clinical Investigation  1986;77(5):1539-1547.
A monoclonal antibody, selected for reactivity with the Epstein-Barr virus (EBV)-encoded antigen EBNA-1, exhibited strong reactivity with the synovial lining cells in joint biopsies from 10 of 12 patients with rheumatoid arthritis (RA) and adherent cells eluted from these tissues. No staining of RA synovial membrane frozen tissue sections or eluted synovial-lining cells was obtained with monoclonal antibodies directed against other EBV-encoded antigens (anti-p160, anti-gp200/350) or with monoclonal antibodies directed against antigens encoded by cytomegalovirus, herpes simplex viruses, or human T cell leukemia virus type I. Among 12 osteoarthritis and normal synovial biopsies only rare reactive cells were noted. Characterization of the antigen(s) in RA synovium by the Western immunoblotting technique revealed a 62,000-molecular-weight (mol-wt) protein, in contrast to the 70,000-85,000-mol-wt EBNA-1 antigen found in EBV-transformed cells. The structural basis for the cross-reactivity of the RA synovial membrane 62,000-mol-wt protein and the EBNA-1 antigen appears to reside in the glycine-alanine rich region of these molecules. A rabbit antibody directed against a synthetic peptide (IR3-VI-2) derived from the glycine-alanine-rich region of EBNA-1 reacted with the 70,000-85,000-mol-wt EBNA-1 antigen in EBV-infected cells and with the 62,000-mol-wt molecule in RA synovial membrane extracts. Since strong antibody responses to EBNA-1 are known to exist in RA patients, these results suggest that immune responses to a cross-reactive antigen may play a role in the pathogenesis of RA.
PMCID: PMC424557  PMID: 2422209
19.  Comparison of standard tube and shell vial cell culture techniques for the detection of cytomegalovirus in clinical specimens. 
Journal of Clinical Microbiology  1985;21(2):217-221.
A monoclonal antibody was used to detect an early antigen of cytomegalovirus (CMV) by fluorescence 16 h after inoculation of MRC-5 monolayers in 1-dram (ca. 3.7-ml) shell vials and low-speed centrifugation. Of 770 specimens (urine, blood, lung tissue, sputum) processed in shell vials, 124 (16%) were positive for the virus at 16 h postinfection. CMV was isolated in standard tube cell cultures (average time, 9 days) from only 88 specimens, but there were no instances (with the exception of 2 blood specimens) in which CMV was recovered from tube cultures but not from shell vials. Additional specimens from 18 patients were positive in the shell vial assay but negative in the conventional tube cell culture assay. Other specimens from 14 of the 18 patients yielded CMV in conventional tube cell cultures. Of the 4 patients from whom CMV was not recovered from other specimens by conventional tube cell culturing, all had evidence of recent CMV infections, as indicated by a fourfold or greater rise in antibody titer. The specificity of the shell vial assay for the detection of CMV is supported by assays of other specimens from the same patients yielding the virus or serological evidence indicating recent infections, the known enhancement of CMV detection after centrifugation of the shell vials, and the distinct and easily recognizable fluorescence confined to the nuclei of CMV-infected cells. Our data indicate that the shell vial cell culture assay for the detection of CMV is as specific as and more sensitive than conventional tube cell culturing for the diagnosis of CMV infections.
PMCID: PMC271616  PMID: 2982911
20.  Molecular cloning of the six mRNA species of infectious hematopoietic necrosis virus, a fish rhabdovirus, and gene order determination by R-loop mapping. 
Journal of Virology  1985;53(2):469-476.
Plasmids carrying cDNA sequences to the mRNA species of infectious hematopoietic necrosis virus were constructed and cloned into Escherichia coli. Characterization of 21 cloned plasmids by hybridization to mRNA blots identified sets of plasmids with homology to each of the six viral mRNA species. R-loop mapping with these cDNA plasmids determined that the gene order on the infectious hematopoietic necrosis virus genome is (3')N-M1-M2-G-NV-L(5').
PMCID: PMC254659  PMID: 3838192
21.  Characterization of a major protein with a molecular weight of 160,000 associated with the viral capsid of Epstein-Barr virus. 
Journal of Virology  1985;53(1):107-113.
A monoclonal antibody designated V3 was produced against a late protein associated with the Epstein-Barr virus-induced viral capsid antigen complex. The antibody reacted with discrete patches in the nuclei of infected cells as well as with virus particles, as shown by immunofluorescence and ultrastructural immunoperoxidase staining. The molecular weight of the protein precipitated by this monoclonal antibody was ca. 160,000. All anti-viral capsid antigen antibody-positive sera tested in an enzyme-linked immunosorbent assay reacted with this purified protein. The synthesis of the antigen was inhibited by phosphonoacetic acid but was not affected by tunicamycin, indicating that this was a late nonglycosylated viral protein. No differences were noted between the protein isolated from the P3HR-1 and B-95-8 cell lines as determined by immunoprecipitation and peptide mapping. By isoelectric focusing, this protein had a pI on the basic side ranging from 7.5 to 9.0.
PMCID: PMC254985  PMID: 2981328
22.  Identification and characterization of a cellular protein that cross-reacts with the Epstein-Barr virus nuclear antigen. 
Journal of Virology  1984;52(3):833-838.
A 62,000-dalton (62K) cell protein reacts with antisera to the 72K polypeptide of the Epstein-Barr virus nuclear antigen (EBNA) in immunoblots. This protein was initially detected in EBNA-negative as well as EBNA-positive cell lines with anti-EBNA-positive human sera. A monoclonal antibody raised against the 72K EBNA and an antiserum from a rabbit immunized with the glycine-alanine domain of EBNA also reacted with the cellular protein. The cellular protein was partially purified from Epstein-Barr virus genome-positive and -negative cell lines. Absorption experiments identified a shared antigenic determinant between the 72K EBNA and 62K cellular protein. A comparison of the 62K protein and EBNA by protease digestion did not reveal similar peptides.
PMCID: PMC254603  PMID: 6208381
23.  Rapid detection of cytomegalovirus in MRC-5 cells inoculated with urine specimens by using low-speed centrifugation and monoclonal antibody to an early antigen. 
Journal of Clinical Microbiology  1984;19(6):917-919.
A commercially available monoclonal antibody directed against an early nuclear protein of cytomegalovirus was used with low-speed centrifugation for the rapid detection of this virus from urine specimens inoculated onto MRC-5 cells. A total of 19 of 162 (11.7%) urine specimens inoculated were positive by both immunofluorescence and peroxidase-antiperoxidase procedures (sensitivity, 100%), whereas only 18 of the samples produced cytopathic effects in conventional cell culture (specificity, 94.7%). All specimens were positive by immunofluorescence and peroxidase-antiperoxidase procedures at 36 h postinfection, whereas an average of 9 days was required for cytopathic effects to develop in cell cultures.
PMCID: PMC271213  PMID: 6088574
24.  Small bowel function in acute lymphoblastic leukaemia. 
Archives of Disease in Childhood  1984;59(5):460-465.
Small bowel function before, during, and after treatment for acute lymphoblastic leukaemia was studied in 26 children. A significant impairment of D-xylose absorption was found during treatment. Permeability studies showed a significant decrease in mannitol and a significant increase in lactulose concentrations; five of 20 children tested had evidence of lactose malabsorption, three of whom were symptomatic. Intestinal function abnormalities were greater in children whose methotrexate treatments were separated by 7 day than by 16 day intervals. Only five (19%) children had no abnormal tests. Abnormalities of small bowel function may be treatment induced and this has implications for morbidity from gastrointestinal symptoms, impairment of the mucosal barrier, and malabsorption of both nutrients and drugs leading to malnutrition and suboptimal drug concentrations.
PMCID: PMC1628499  PMID: 6428327
25.  Proteins tightly bound to HeLa cell DNA at nuclear matrix attachment sites. 
Molecular and Cellular Biology  1983;3(9):1567-1579.
DNA-protein complexes have been isolated from HeLa cell nuclei and nuclear matrix preparations. Two proteins, 55 and 66 kilodaltons in size, remain bound to HeLa DNA after treatment at 80 degrees C in 2% sodium dodecyl sulfate and purification by exclusion chromatography on Sepharose 2B-CL in the presence of 0.3% sodium dodecyl sulfate. These proteins appear to be tightly bound but not covalently linked to the DNA, and they are distributed over the DNA with an average spacing of 40 kilobase pairs. This spacing distribution remains essentially constant throughout the cell cycle. The proteins are bound to the residual 2% of HeLa cell DNA which remains attached to the nuclear matrix after extensive nuclease digestion, a condition which reduces the average size of the DNA to approximately 150 base pairs. Our results suggest that these tightly bound proteins are involved in anchoring cellular DNA to the nuclear matrix. These tightly bound proteins are identical by partial peptide mapping to proteins found tightly bound to the DNA of mammalian, plant, and bacterial cells (D. Werner and C. Petzelt, J. Mol. Biol. 150:297-302, 1981), implying that these proteins are involved in the organization of chromosomal domains and are highly conserved in both procaryotic and eucaryotic cells.
PMCID: PMC370010  PMID: 6355827

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