Search PubMed⌕ Search

Biomedical subjects

L Kelly

Publications and source records attributed to L Kelly.

At least 19 recordsLinked to original sources
PubMed2006

A multicentre longitudinal observational study of changes in self reported health status in people with Parkinson's disease left untreated at diagnosis.

BACKGROUND: The issue of when to start treatment in Parkinson's disease (PD) remains controversial. Some favour treatment at diagnosis while others opt for a "wait and watch" policy. The effect of the latter policy on the self reported health status of people with PD is unknown. AIMS: To record self reported health status through longitudinal use of a validated PD specific questionnaire (PDQ-39) in untreated PD patients in multiple centres in the UK. To compare patients who were left untreated with those who were offered treatment during follow-up. METHODS: A multicentre, prospective, "real life" observational audit based study addressing patient reported outcomes in relation to self reported health status and other sociodemographic details. RESULTS: 198 untreated PD were assessed over a mean period of 18 months. During two follow-up assessments, the self reported health status scores in all eight domains of the PDQ-39 and the overall PDQ-39 summary index worsened significantly (p<0.01) in patients left untreated. In a comparative group in whom treatment was initiated at or soon after diagnosis, there was a trend towards improvement in self reported health status scores after treatment was started. CONCLUSIONS: This study addresses for the first time self reported health status, an indicator of health related quality of life, in untreated PD. The findings may strengthen the call for re-evaluation of the policy to delay treatment in newly diagnosed patients with PD.

Aged↗
PubMed2006

A stastistical system for detecting Salmonella outbreaks in British livestock.

Worldwide, early detection systems have been used in public health to aid the timely detection of increases in disease reporting that may be indicative of an outbreak. To date, their application to animal surveillance has been limited and statistical methods to analyse human health data have not been viewed as being applicable for animal health surveillance data. This issue was investigated by developing an early detection system for Salmonella disease in British livestock. We conclude that an early detection system, as for public health surveillance, can be an effective tool for enhanced surveillance. In order to implement this system in the future and extend it for other data types, we provide recommendations for improving the current data collection process. These recommendations will ensure that quality surveillance data are collected and used effectively to monitor disease in livestock populations.

Animals↗
PubMed2005

A 93 year old man with the PRSS1 R122H mutation, low SPINK1 expression, and no pancreatitis: insights into phenotypic non-penetrance.

BACKGROUND: The cationic trypsinogen (PRSS1) R122H mutation causes autosomal dominant hereditary pancreatitis (HP) with multiple attacks of acute pancreatitis, but the penetrance, frequency, and severity of attacks are highly variable. HP twins study suggests that modifier genes influence severity but not penetrance. AIM: To investigate potential trypsin associated factors in subjects with the PRSS1 R122H mutation and phenotypic non-penetrance. METHODS: Two subjects from HP families (including a 93 year old subject with PRSS1 R122H without pancreatitis), one with chronic pancreatitis and one with a normal pancreas, were studied. Relative expression of: (a) the PRSS1 R122 and H122 alleles; and (b) the PRSS1 and SPINK1 genes in pancreatitis were determined using complementary methods. RESULTS: PRSS1 wild-type (R122) and mutant (H122) allele expression was equivalent in multiple (> 3) samples from the phenotypically affected and non-penetrant subjects with R122H genotypes using allele specific quantitative reverse transcription-polymerase chain reaction (RT-PCR) and intron spanning nested RT-PCR followed by cDNA sequencing. Compared with PRSS1 mRNA levels, SPINK1 mRNA levels were low in normal appearing tissue but markedly increased in samples with chronic inflammation, independent of PRSS1 genotype. CONCLUSION: Attacks of acute pancreatitis in HP subjects appear to be independent of the relative expression of the mutant PRSS1 H122 allele or SPINK1 gene expression. The marked increase in SPINK1 gene expression with inflammation is consistent with its regulation as an acute phase protein.

Aged, 80 and over↗
PubMed2005

Quantitative assessment of the risks of reducing the routine swabbing requirements for the detection of Taylorella equigenitalis.

The transmission of contagious equine metritis (CEM) on stud farms in Britain, Ireland and other European countries is prevented by following the recommendations in the Horserace Betting Levy Board's Code of Practice on CEM. A quantitative risk assessment was undertaken to estimate the likely impact of removing the recommendation, from the 2002 code, to culture endometrial or cervical swabs microaerophilically for the presence of Taylorella equigenitalis, the causative organism. The scientific literature was reviewed for evidence about the anatomical distribution of T. equigenitalis at different times after infection and it was found that, in chronically infected mares, the organism was detectable in the clitoral swabs of nearly 93 per cent, but in the cervical swabs of only 31 per cent. In contrast, in acutely infected mares, the organism was detectable in the clitoral swabs of nearly 69 per cent, but in the cervical swabs of 84 per cent. By using these results, a quantitative risk assessment was undertaken, assessing the likely effects of removing the recommendation that swabs from the cervix of low-risk mares should be cultured for T. equigenitalis. The results were sensitive to the prevalence of the infection, but when it was low, there appeared to be few benefits in continuing to culture cervical swabs routinely. However, such swabs are vital when the disease is suspected.

Algorithms↗
PubMed2005

The roles of proteolysis and nuclear localisation in the toxicity of the polyglutamine diseases. A review.

The polyglutamine disorders consist of a group of nine neurodegenerative diseases with overlapping phenotypes, but which affect distinct neuronal subsets, causing neuronal dysfunction and death. In the majority of these, the causative proteins share no homology to other known proteins, or to each other apart from the polyglutamine tract. The polyglutamine tracts themselves are toxic over a disease-specific threshold, and this common feature has suggested a common pathogenesis. The pathogenic mechanism(s) of this group of diseases is hotly debated, with proteolytic cleavage and nuclear accumulation both popular hypotheses. Such cleavage is thought to release toxic fragments containing an expanded polyglutamine tract, and may itself facilitate entry of cytoplasmic polyglutamine proteins to the nucleus. Numerous downstream effects including accumulation and apoptotic activation, misfolding, aggregation, and sequestration of other proteins including transcription factors and chaperones may then be initiated. It is uncertain whether all of the polyglutamine proteins undergo cleavage in vivo. Even in those in which proteolysis has been demonstrated, it remains unclear to what extent this also occurs in the wild-type proteins, or whether it is dependent on, or increased by, the expanded polyglutamine tract. Similarly, in at least one of these disorders (spinocerebellar ataxia type 6), nuclear localisation has not been demonstrated. The contradictory evidence for the production and role of proteolytic fragments and for nuclear localisation in toxicity, reviewed in this article, suggests that neither may be uniformly necessary steps in the pathogenesis of this group of diseases, and that, for all their apparent similarities, the exact pathogenic mechanisms may not be identical in each.

Animals↗
PubMed2005

A mathematical model of the growth of sea lice, Lepeophtheirus salmonis, populations on farmed Atlantic salmon, Salmo salar L., in Scotland and its use in the assessment of treatment strategies.

Sea lice are a persistent problem for farmed and wild salmonid populations. Control can be achieved through the use of veterinary medicines. A model was developed to describe the patterns of sea lice infection on salmon farms in Scotland and to predict the likely effect of various treatment strategies. This model takes into account development rates and mortality using compartments representing life history stages and external infection pressure. The national sea lice infection pattern was described using parameters representing stage survival, background infection levels and egg viability rates. The patterns observed across farms varied greatly and the model gave broad agreement to observed trends with different parameters being required in the model for sites using hydrogen peroxide and cypermethrin treatments. The parameter estimates suggest that the background infection pressure on sites where cypermethrin was administered was higher than for those using hydrogen peroxide. Both models had comparable magnitudes of sensitivity with survival from one stage to another being the most sensitive parameter, followed by feedback rates at which gravid females produce eggs, with background infection levels the least sensitive. The effect of different cypermethrin treatment strategies was assessed using the model. Increasing treatments in a production cycle gave more effective control. However, the model showed that timing of treatments is most important if sea lice are to be effectively controlled.

Animals↗
PubMed2005

Effect of IL-2 on hepatitis C virus RNA levels in patients co-infected with human immunodeficiency virus receiving HAART.

The effect of interleukin-2 (IL-2) on the plasma levels of hepatitis C RNA (HCV-RNA) has varied in published reports. We measured the impact of IL-2 on plasma HCV RNA levels in 54 human immunodeficiency virus (HIV)/HCV coinfected patients enrolled in a randomized trial of 512 participants designed to compare the virologic and immunologic effects of cycled IL-2 plus antiretroviral therapy (ART) vs ART alone in the treatment of HIV in patients with CD4 cell counts > or =300 cells/mm(3). The mean decreases in average HCV RNA levels (copies/mL, log (10)) were 0.28 log in the IL-2 group (n = 26) and 0.04 log in the ART alone group (n = 28) at 12 months (P = 0.18). The changes in HCV RNA level were not associated with baseline or nadir CD4 cell counts, baseline aspartate aminotransferanse, CD4 cell response to IL-2, or changes in plasma HIV RNA values. Compared with those participants who only had HIV, the HIV/HCV co-infected patients did not have a significantly different CD4 cell response to IL-2 therapy. Intermittent IL-2 therapy does not produce a significant sustained decrease in plasma HCV RNA levels among patients co-infected with HIV/HCV who are on highly active ART.

Adult↗
PubMed2005

Improving functional annotation of non-synonomous SNPs with information theory.

Automated functional annotation of nsSNPs requires that amino-acid residue changes are represented by a set of descriptive features, such as evolutionary conservation, side-chain volume change, effect on ligand-binding, and residue structural rigidity. Identifying the most informative combinations of features is critical to the success of a computational prediction method. We rank 32 features according to their mutual information with functional effects of amino-acid substitutions, as measured by in vivo assays. In addition, we use a greedy algorithm to identify a subset of highly informative features. The method is simple to implement and provides a quantitative measure for selecting the best predictive features given a set of features that a human expert believes to be informative. We demonstrate the usefulness of the selected highly informative features by cross-validated tests of a computational classifier, a support vector machine (SVM). The SVM's classification accuracy is highly correlated with the ranking of the input features by their mutual information. Two features describing the solvent accessibility of "wild-type" and "mutant" amino-acid residues and one evolutionary feature based on superfamily-level multiple alignments produce comparable overall accuracy and 6% fewer false positives than a 32-feature set that considers physiochemical properties of amino acids, protein electrostatics, amino-acid residue flexibility, and binding interactions.

Analysis of Variance↗
PubMed2005

A comparison of four serologic assays in screening for Brucella exposure in Hawaiian monk seals.

A survey for Brucella spp. antibodies was undertaken on 164 serum samples from 144 Hawaiian monk seals (Monachus schauinslandi) from the northwestern Hawaiian Islands collected between 1995 and 2002. The buffered antigen plate agglutination test (BPAT), the indirect enzyme immunoassay (I-ELISA), the competitive enzyme immunoassay (C-ELISA), and the fluorescence polarization assay (FPA) were compared with regard to their ability in detecting antibodies to Brucella spp. in the serum samples. Overall, antibodies were detected in 28 (17.1%) animals, using the BPAT test, 25 (15.2%) by the C-ELISA, and 19 (11.6%) in the I-ELISA and the FPA test, using thresholds established for cattle. No evidence of gross pathology consistent with clinical brucellosis was noted in any of the seropositive animals tested. Although further work would be necessary to validate these tests for use with monk seals it appears that both the C-ELISA and the FPA tests would be appropriate as diagnostic screening tests for detection of antibodies to Brucella spp. in this species.

Agglutination Tests↗
PubMed2005

The safety assessment of foods from transgenic and cloned animals using the comparative approach.

The comparative approach to food safety assessment is based on the idea that the safety of a new food can largely be determined by its comparison to the benchmark of commonly consumed foods already in the food supply (also called the 'conventional counterpart'). Any differences between the new food and its conventional counterpart are evaluated to determine their relevance to human health and safety. In this way it is possible to conclude whether a new food is 'as safe as' conventional food already in the food supply. This approach, first developed primarily for use in the safety assessment of food from transgenic plants, is now generally accepted for food from both transgenic and cloned animals as well. This article outlines the basic principles behind the comparative approach, discusses some of the potential food safety concerns associated with transgenic and cloned animals, and describes important elements of the comparative approach and how these might be applied to assessing the safety of food from animals.

Animals↗
PubMed2004

Serological relationship between cattle exposed to Brucella abortus, Yersinia enterocolitica O:9 and Escherichia coli O157:H7.

Sera from cattle naturally infected with Brucella abortus (n = 160), vaccinated with B. abortus S19 (n = 88) or immunized with Yersinia enterocolitica O:9 (n = 25) or Escherichia coli O157:H7 (n = 80) were collected. The sera were compared for antibody content to the same bacteria by indirect enzyme immunoassay (IELISA), fluorescence polarization assay (FPA) and competitive enzyme immunoassay (CELISA). Cattle sera (n = 523) collected randomly from across Canada were tested in the same tests. Sera from the B. abortus infected group reacted positively in the brucellosis IELISA (IELISA(Br)), CELISA and FPA (FPA(Br)) and the Y. enterocolitica IELISA (IELISA(Ye)) while the Y. enterocolitica FPA (FPA(Ye)) detected antibody in 93.8% and the E. coli IELISA (IELISA(Ec)) 86.9% and the E. coli FPA (FPA(Ec)) 48.1%. About 70% of the sera from B. abortus S19 vaccinated animals reacted in the three IELISAs, 45% in the CELISA, and 37.7% in the FPA(Ec), 21.6% in the FPA(Br) and 5.7% in the FPA(Ye). Sera from E. coli O:157 exposed cattle reacted mainly in the IELISA(Ec) and FPA(Ec) although surprisingly 87.5% reacted in the IELISA(Ye) and only 3.8% in the IELISA(Br). No reactions were observed with these sera in the FPA(Br) and FPA(Ye) but one serum gave a low positive reaction in the CELISA. All sera from Y. enterocolitica O:9 exposed cattle reacted in the IELISA(Br) and IELISA(Ye) and 80% in the IELISA(Ec). In the CELISA, 44% gave a positive reaction and 64% were positive in the FPA(Br), 28% in the FPA(Ye) and 12% in the FPA(Ec). Of the 523 Canadian sera, about 50% reacted in the E. coli tests with only minor reactions in the Y. enterocolitica O:9 and B. abortus assays. From the data, the cross reaction between E. coli O157:H7, Y. enterocilitica O:9 and B. abortus is dependent on the test used. Thus, extensive cross reaction was observed with the IELISA with much less reactivity in the FPA and the CELISA.

Animals↗
PubMed2004

A quantitative risk assessment for the importation of brucellosis-infected breeding cattle into Great Britain from selected European countries.

Great Britain (GB) has been "Officially Brucellosis Free" (OBF) since 1991; because this disease has both public-health and international-trade implications, it is in the country's interest to maintain this freedom. A quantitative risk-assessment model was developed to determine the annual risk of importing brucellosis-infected breeding cattle into GB from Northern Ireland and the Republic of Ireland. (These countries exported the largest number of cattle into GB and were not brucellosis free during the development of the assessment in 2000.) We predicted that we can expect to import brucellosis from Northern Ireland every 2.63 years (1.89, 4.17) and from the Republic of Ireland, every 3.23 years (2.13, 5.88). The estimates of risk are sensitive to the assumed proportion of animals missed during routine surveillance that originate from OBF herds and the uncertainty associated with the surveillance test sensitivities. As a result of the assessment, the Department for Environment, Food and Rural Affairs (Defra) introduced post-calving testing for all cattle imported into British herds.

Animals↗
PubMed2004

A simulation model of brucellosis spread in British cattle under several testing regimes.

Brucellosis is a widespread, economically devastating and highly infectious zoonosis. In cattle, infection predominantly is caused by Brucella abortus, and is usually detected in pregnant females through abortions. Great Britain (GB) has been declared free from brucellosis (officially brucellosis free (OBF)) since 1993 and as such is required by European Union (EU) regulations to test > or =20% of both beef and dairy cattle >24 months old routinely. Currently, however, GB serologically tests more cattle than required and the issue of reducing the level of testing has come under consideration. We developed a simulation model to determine the rate of spread of brucellosis under a variety of testing regimes. For dairy herds, we found that reducing the level of testing would have a major effect on the rate of spread of infection, should it be imported. For beef herds, reducing the level of testing would have much less effect. We also found that abortion notification is a very-important additional means of surveillance. As a result of our predictions, policy-makers decided not to reduce the level of testing and actively to promote abortion notification.

Abortion, Veterinary↗
PubMed2004

Quantitative estimates of the risk of new outbreaks of foot-and-mouth disease as a result of burning pyres.

The risk of dispersing foot-and-mouth disease virus into the atmosphere, and spreading it to susceptible holdings as a result of burning large numbers of carcases together on open pyres, has been estimated for six selected pyres burned during the 2001 outbreak in the UK. The probability of an animal or holding becoming infected was dependent on the estimated level of exposure to the virus predicted from the concentrations of virus calculated by the Met Office, Bracknell. In general, the probability of infection per animal and per holding decreased as their distance from the pyre increased. In the case of two of the pyres, a holding under the pyre plumes became infected on a date consistent with when the pyre was lit. However, by calculating their estimated probability of infection from the pyres it was concluded that it was unlikely that in either case the pyre was the source of infection.

Animals↗
PubMed2004

Animal growth promoters: to ban or not to ban? A risk assessment approach.

The use of antibiotics for animal growth promotion has been controversial because of the potential transfer of antibiotic resistance from animals to humans. Such transfer could have severe public health implications in that treatment failures could result. We have followed a risk assessment approach to evaluate policy options for the streptogramin-class of antibiotics: virginiamycin, an animal growth promoter, and quinupristin/dalfopristin, a antibiotic used in humans. Under the assumption that resistance transfer is possible, models project a wide range of outcomes depending mainly on the basic reproductive number (R(0)) that determines the potential for person-to-person transmission. Counter-intuitively, the benefits of a ban on virginiamycin were highest for intermediate values of R(0), and lower for extremely high or low values of R(0).

Animal Husbandry↗
PubMed2004

Optimizing bacterial expression of catalytically active human cytochromes P450: comparison of CYP2C8 and CYP2C9.

1. Methods for the co-expression in Escherichia coli of human cytochrome P450 (CYP) 2C8 and CYP2C9 with NADPH-cytochrome P450 reductase (OxR) to produce a catalytically active system were compared. 2. Approaches assessed were expression of a CYP:OxR fusion construct, bicistronic plasmids, simultaneous transformation with CYP and OxR plasmids, and separate expression of CYP and OxR with reconstitution of activity by mixing the bacterial membranes. Two N-terminal modifications (Delta3-20 and 17alpha-leader) of the individual P450s were additionally investigated. 3. Each approach gave efficient expression of CYP2C8 and CYP2C9, but the bicistronic constructs under the expression conditions used gave low OxR expression and low catalytic activity. CYP expression was higher with the Delta3-20 construct for CYP2C9 and with the 17alpha-presequence construct for CYP2C8. 4. Using torsemide as substrate, all methods gave catalytically active systems with K(m) values similar to human liver microsomes. Mixing bacterial membranes containing separately expressed CYP and OxR reconstituted a catalytically active system with the Delta3-20 construct for CYP2C9 but not for CYP2C8, and with neither of the 17alpha- presequence constructs. OxR co-expressed with CYP in the same membrane interacted with CYP to reconstitute activity more effectively than addition of exogenous OxR membranes. 5. Expression construct and OxR co-expression strategy should be individualized for CYP isoforms.

Aryl Hydrocarbon Hydroxylases↗