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Biomedical subjects

K Rogers

Publications and source records attributed to K Rogers.

At least 19 recordsLinked to original sources

Wavelet-based feature extraction applied to small-angle x-ray scattering patterns from breast tissue: a tool for differentiating between tissue types.

This paper reports on the application of wavelet decomposition to small-angle x-ray scattering (SAXS) patterns from human breast tissue produced by a synchrotron source. The pixel intensities of SAXS patterns of normal, benign and malignant tissue types were transformed into wavelet coefficients. Statistical analysis found significant differences between the wavelet coefficients describing the patterns produced by different tissue types. These differences were then correlated with position in the image and have been linked to the supra-molecular structural changes that occur in breast tissue in the presence of disease. Specifically, results indicate that there are significant differences between healthy and diseased tissues in the wavelet coefficients that describe the peaks produced by the axial d-spacing of collagen. These differences suggest that a useful classification tool could be based upon the spectral information within the axial peaks.

Algorithms↗

A comparison of survival models for assessing risk of racehorse fatality.

Survival analysis was used to assess risk factors for fatal injuries on UK race courses. This allowed assessment of variation due to temporal horse-level effects, including previous racing intensity and historical distribution of race types, as well as race-level factors. Comparisons were made between measuring survival time as number of days and as number of races to injury from the first race. Two related models were presented for time as number of races to injury: a Cox regression model fitted using partial likelihood, with the Efron approximation to handling ties, and a discrete-time logit model fitted using maximum likelihood. The latter approach had the advantages of being computationally more efficient and enabling the testing of different functional forms for the dependence of hazard on time. Retrospective data were available from all race starts on the 59 courses in Britain from 1990 to the end of 1999, as analysed by . The analysis was conducted on the data for the 47,424 horses that had started racing in the UK: 538,895 starts with 1,228 fatal injuries. Horses starting racing abroad were excluded, but some included horses would have raced abroad at some stage during their racing career. The results for the selected models were broadly consistent with each other and with previously published studies. Steeplechase and hurdle races had a higher risk of fatal injury than flat races (relative hazards 1.5 and 1.7, respectively). Risk increased with the firmness of surface, age and race distance (reaching a plateau at 20 furlongs) and decreased with previous racing intensity (reaching a plateau after seven races run in the last 12 months). Horses running their first race of a new type were also found to be at higher risk (relative hazard 1.5). The main difference between the models for time as number of days and number of races concerned the role of age: age at race was identified as the more important factor in the latter model, whereas, age at first race was more significant in the former model.

Age Factors↗

The effects of halothane and isoflurane on cardiovascular function in laterally recumbent horses.

BACKGROUND: Experimental studies in adult horses have shown that general anaesthesia maintained with isoflurane is associated with less depression of cardiovascular function compared with halothane anaesthesia. Adverse effects of intermittent positive-pressure ventilation (IPPV) have also been demonstrated. Nevertheless, the haemodynamic effects of these agents and the effects of differing modes of ventilation have not been assessed during clinical anaesthesia in horses undergoing surgery. METHODS: The haemodynamic effects of isoflurane or halothane anaesthesia during spontaneous or IPPV were studied non-invasively in 32 laterally recumbent horses undergoing elective surgery. Indices of cardiac function and measurements of femoral arterial blood flow and resistance were recorded using transoesophageal and transcutaneous Doppler echocardiography, respectively. Arterial pressure was measured directly using a facial artery catheter. RESULTS: Cardiac index (CI) was significantly higher during isoflurane anaesthesia than during halothane anaesthesia and was also higher during spontaneous ventilation with isoflurane. CI decreased significantly over time and an inverse relationship was observed between CI and mean arterial pressure (MAP). Horses with higher MAP had a significantly lower CI. During isoflurane anaesthesia, femoral arterial blood flow was significantly higher in both pelvic limbs compared with halothane anaesthesia, and flow in the lower limb was significantly higher during spontaneous ventilation than during IPPV. No significant change in femoral blood flow was observed over time. CONCLUSION: The effects of anaesthetics and mode of ventilation on cardiovascular function recorded under surgical conditions in horses are similar to those reported under experimental conditions. However, in contrast with previous experimental studies, CI progressively decreased over time regardless of agent used or mode of ventilation employed.

Anesthesia, Inhalation↗

Left ventricular size and systolic function in Thoroughbred racehorses and their relationships to race performance.

Cardiac morphology in human athletes is known to differ, depending on the sports-specific endurance component of their events, whereas anecdotes abound about superlative athletes with large hearts. As the heart determines stroke volume and maximum O(2) uptake in mammals, we undertook a study to test the hypothesis that the morphology of the equine heart would differ between trained horses, depending on race type, and that left ventricular size would be greatest in elite performers. Echocardiography was performed in 482 race-fit Thoroughbreds engaged in either flat (1,000-2,500 m) or jump racing (3,200-6,400 m). Body weight and sex-adjusted measures of left ventricular size were largest in horses engaged in jump racing over fixed fences, compared with horses running shorter distances on the flat (range 8-16%). The observed differences in cardiac morphologies suggest that subtle differences in training and competition result in cardiac adaptations that are appropriate to the endurance component of the horses' event. Derived left ventricular mass was strongly associated with published rating (quality) in horses racing over longer distances in jump races (P < or = 0.001), but less so for horses in flat races. Rather, left ventricular ejection fraction and left ventricular mass combined were positively associated with race rating in older flat racehorses running over sprint (<1,408 m) and longer distances (>1,408 m), explaining 25-35% of overall variation in performance, as well as being closely associated with performance in longer races over jumps (23%). These data provide the first direct evidence that cardiac size influences athletic performance in a group of mammalian running athletes.

Adaptation, Physiological↗

Risk factors for epistaxis on British racecourses: evidence for locomotory impact-induced trauma contributing to the aetiology of exercise-induced pulmonary haemorrhage.

REASONS FOR PERFORMING STUDY: The proposed biological mechanisms for exercise-induced pulmonary haemorrhage (EIPH) are many and varied. Better knowledge of risk factors should lead to achievable measures to reduce the incidence. OBJECTIVES: To identify risk factors associated with epistaxis following racing in UK Thoroughbreds, to gain possible insights into the pathogenesis of the condition and to investigate the association between epistaxis and race finishing position. METHODS: The association of epistaxis occurring on UK racecourses between 1996 and 1998 with a wide range of race-, horse- and start-level variables was examined in multivariable mixed effect logistic regression analyses. Four multivariable analyses were conducted, one for all race types considered collectively and one each for flat, hurdle and steeplechase race types considered separately. RESULTS: Risk of epistaxis was significantly increased for hurdle and steeplechase race types compared to both flat and National Hunt flat races. In 3 of the 4 final models, there was a significant biological trend for increasing risk of epistaxis with increasing ground hardness ('going') and accumulated years spent racing. However, in flat races epistaxis was such a rare outcome (0.33 cases per 1000 starts) that this subset analysis had insufficient power to measure the detectable effect of 'going' as statistically significant. Horses with epistaxis were significantly more likely to have a poorer finishing position than those without blood at the nostrils. CONCLUSIONS: Findings were consistent with the theory that locomotory impact-induced trauma contributes to exercise-induced epistaxis. Further validation of this hypothesis through application of similar methods to endoscopically visible EIPH and through biomechanical studies is warranted. POTENTIAL RELEVANCE: Knowledge of significant risk factors should allow formulation of practical measures, such as track watering, to reduce the risks of EIPH and epistaxis in racehorses.

Animals↗

Disseminated Beauveria bassiana infection in a patient with acute lymphoblastic leukemia.

We describe a case of disseminated Beauveria bassiana infection in a patient with acute lymphoblastic leukemia. Her infection was successfully treated with amphotericin B and itraconazole. B. bassiana is rarely reported as a human pathogen. It is commonly found in soil and because of its pathogenicity to many insect species is incorporated into several pesticides.

Adult↗

Comparison of intradermal and serum testing for allergen-specific IgE using a Fcepsilon RIalpha-based assay in atopic dogs in the UK.

Atopic dermatitis in dogs is a common allergic skin disease that affects substantial numbers of dogs in the UK. The purpose of this study was to compare the results of an intradermal test (IDT) and an in vitro test in a large cohort of dogs. Dogs were intradermal tested with Greer allergens (Greer Labs Inc, Lenoir, NC, USA) using standard techniques. At the same time blood samples were drawn and submitted for evaluation by ELISA using the ALLERCEPT Definitive Allergen Panels for allergen-specific IgE, a commercial assay that uses a biotinylated recombinant extracellular domain of the high affinity Fc-epsilon receptor alpha chain protein (Fcepsilon RIalpha). The allergens used in the two tests included grass, tree and weed pollens, moulds, flea saliva/whole flea extract and house dust mite species. The optical density readings from the ELISA for each allergen were compared with the results of the IDT for 265 dogs. The prevalence of positive reactions in the ELISA was equal to or greater than the results of the IDT in the case of almost all of the allergens, but two notable exceptions were the house dust mites Dermatophagoides farinae and Dermatophagoides pteronyssinus. These two allergens were the most common positive reactions by IDT (prevalence D. farinae 78.9%, D. pteronyssinus 66.4%). The results of the two tests were significantly different (McNemar's test, P<0.05) for 16 of the 22 allergens. The sensitivities of the ELISA compared to the IDT (where there were more than 3 dogs with positive reactions in both tests) varied between 19.3 and 77.1% (D. pteronyssinus 19.3% and D. farinae 67.9%) and the specificities varied between 64.2 and 96.6% (D. pteronyssinus 96.6% and D. farinae 89.3%).

Allergens↗

Sequence and genetic arrangement of the UL region of the monkey B virus (Cercopithecine herpesvirus 1) genome and comparison with the UL region of other primate herpesviruses.

The complete DNA sequence of the unique long (U(L)) region of monkey B virus (BV) was determined. Based on sequence homology and the presence of transcriptional control element motifs, homologues of every open reading frame present in the U(L) region of the Human herpesvirus 1 (herpes simplex virus 1, HSV-1) and Human herpesvirus 2 (herpes simplex virus 2, HSV-2) genomes were identified in BV. The BV genes are arranged in the same order and orientation as in HSV. These results demonstrate that the BV U(L) region is entirely co-linear with that of HSV-1 and HSV-2.

Animals↗

Isolation of two phenylethanoid glycosides from Eremophila gilesii.

The leaves of Eremophila gilesii have been used traditionally to treat colds, headaches, sores, and chest pains. Our previous screening of Australian native plants showed that the methanol extract of the aerial parts of E. gilesii demonstrated notable inhibition of ADP-induced human platelet aggregation and serotonin release. Subsequent fractionation on the methanol extract led to the isolation of two phenylethanoid glycosides, verbascoside (1) and poliumoside (2). This is the first study reporting the presence of phenylethanoid glycosides in E. gilesii.

Australia↗

Heritability and epidemiology of canine hip-dysplasia score and its components in Labrador retrievers in the United Kingdom.

Hip-dysplasia (malformation of the coxofemoral joint) in dogs is a major health problem. Under the British Veterinary Association/Kennel Club's voluntary hip-dysplasia scheme, dog-owners/breeders submit radiographs from animals >1-year-old, to ensure adequate skeletal maturity. An overall hip score quantifies the degree of malformation in the hip joints of these animals, by summing the scores for nine components of the radiographs of both the left and right joints. The hip score data for 29,610 Labrador retrievers (registered with The Kennel Club, UK) were merged with the Kennel Club pedigree database for 472,435 Labrador retrievers. The merged data included the animal's identity, date of birth, sex and hip score and similar records for the dog's relatives, including the hip score if the relative had been tested. In recent years, breeding had been increasingly from tested parents. The mean hip score for male Labradors was significantly higher than that for females. Regression modelling showed a significant, positive dependence of the hip score of the offspring upon the hip scores of its sire, dam and grandparents. Genetic heritability (using data from 13,382 Labrador retrievers comprising 718 litters) was highly significant: 0.34 from the two parents, 0.41 from sire alone and 0.30 from dam alone. Using components data from 2038 offspring Labrador retrievers comprising 1248 litters, three similar estimates of heritability were significant for three major components (Norberg angle, cranial acetabular edge and subluxation); for other components, heritability was significant from the sire but not from the dam. Offspring hip score could be reduced substantially by using only parents with zero hip score.

Animal Husbandry↗

Canine neoplasia in the UK: estimates of incidence rates from a population of insured dogs.

Neoplasia is common in pet dogs but accurate figures for the incidence of tumours in this, as in other species, are sparse. The purpose of this study was to document the occurrence of tumours in a defined population of dogs. From a database of 130,684 insured dogs, claims relating to the investigation or treatment of tumours or tumour-like lesions during a 12-month period were accessed and followed up. A total of 2,546 claims were tumour related and were classified according to tumour site and type. Because the demographics of the insured population were skewed towards younger animals, a standard population, as described in the veterinary literature, was used in the calculation of tumour incidence rates. The skin and soft tissues were the most common sites for tumour development, with a standardised incidence rate of 1,437 per 100,000 dogs per year, followed by alimentary (210), mammary (205), urogenital (139), lymphoid (134), endocrine (113) and oropharyngeal (112). Canine cutaneous histiocytoma was the most common single tumour type, with a standardised incidence rate of 337 per 100,000 dogs per year, followed by lipoma (318), adenoma (175), soft tissue sarcoma (142), mast cell tumour (129) and lymphosarcoma (114). These data are unique and provide a valuable basis for future research into the aetiology and epidemiology of canine tumours.

Animals↗

Chromophore-enhanced 805 nm laser therapy for gastrointestinal neoplasia.

BACKGROUND: A new technique of 805 nm semiconductor diode laser-tissue interaction potentiation using indocyanine green (ICG) as an exogenous chromophore has been assessed for use in the palliation of advanced gastrointestinal malignancy. MATERIALS AND METHODS: The tissue effects of ICG potentiated 805 nm laser were assessed both in-vivo using rat stomach and colon, and in vitro using normal and neoplastic human gastric and colonic mucosa. RESULTS: Intravenous ICG did not potentiate the laser-tissue effects of the 805 nm laser in in-vivo studies. Local techniques of ICG application (submucosal injection +/- surface painting of 0.1% ICG solution) enhanced the total depth and diameter of laser induced thermal injury in all in-vitro tissues. Without ICG enhancement thermal tissue injury was minimal in normal gastric and colonic mucosa. CONCLUSION: Local techniques of ICG application enhance laser induced thermal injury in normal and neoplastic gastric and colonic mucosa. This may permit targeting of 805 nm laser-tissue effects with minimal collateral damage during endoscopic laser palliation of advanced gastrointestinal malignancy.

Colon↗

The effect of troglitazone biliary excretion on metabolite distribution and cholestasis in transporter-deficient rats.

We investigated whether lack of the canalicular multispecific organic anion transporter in transport-deficient (TR-) rats would result in plasma and urinary accumulation of troglitazone or its major metabolites and whether any accumulation would be associated with increased levels of bilirubin or bile acids. Administration of a single oral dose of troglitazone (200 mg/kg) to TR- rats resulted in 2- and 50-fold increases in plasma levels and 30- and 500-fold increases in urinary amounts of troglitazone sulfate and troglitazone glucuronide, respectively, compared with normal rats. No changes were found in the plasma concentrations and urinary amounts of troglitazone or troglitazone-quinone. Accumulation of troglitazone metabolites in plasma was accompanied by a 2-fold increase in the serum level of conjugated bilirubin in TR- rats, whereas no changes were observed in normal animals. Bile acids were detected in the urine of both TR- and normal rats, with an average 3-fold greater level found in the urine of TR- animals. Biliary metabolic profiles revealed a delay in the secretion of troglitazone sulfate and troglitazone glucuronide in TR- rats over the first 2- and 4-h periods, respectively. These results demonstrate the role of multidrug resistant associated protein-2 in biliary secretion of troglitazone glucuronide and troglitazone sulfate and suggest the presence of compensatory mechanisms responsible for transport of troglitazone metabolites and bilirubin-glucuronide at the basolateral and canalicular sites of hepatocytes.

Animals↗

Integrated sample collection and handling for drug discovery bioanalysis.

An integrated sample handling process for drug discovery bioanalysis is described. The streamlining of study design, sample collection and automatic bioanalytical sample processing is demonstrated. Specific details for the entire procedure regarding the time saved, ease of automation and integration are defined. Details of sample handling involved a sample collection map, sample collection formatting and volume, dilution schemes for high concentration samples, choice of biological fluid and evaluating the capabilities of two liquid-handling workstations. Numerous comparisons were conducted between the new approaches and the conventional sample handling approaches. The precision and accuracy obtained from the new integrated sample handling process were comparable to those obtained from a conventional approach, as were pharmacokinetic profiles and parameters. This new sampling process greatly improved the efficiency of drug discovery bioanalysis. The integration of pre-clinical protocol design, sample collection and bioanalysis processes was also achieved.

Animals↗

Three amino acid residues determine selective binding of FK506-binding protein 12.6 to the cardiac ryanodine receptor.

FK506-binding protein (FKBP12) has been found to be associated with the skeletal muscle ryanodine receptor (RyR1) (calcium release channel), whereas FKBP12.6, a novel isoform of FKBP, is selectively associated with the cardiac ryanodine receptor (RyR2). For both RyRs, the stoichiometry is 4 FKBP/RyR. Although FKBP12.6 differs from FKBP12 by only 18 of 108 amino acids, FKBP12.6 selectively binds to RyR2 and exchanges with bound FKBP12.6 of RyR2, whereas both FKBP isoforms bind to RyR1 and exchange with bound FKBP12 of RyR1. To assess the amino acid residues of FKBP12.6 that are critical for selective binding to RyR2, the residues of FKBP12.6 that differ with FKBP12 were mutated to the respective residues of FKBP12. RyR2 of cardiac sarcoplasmic reticulum, prelabeled by exchange with [35S]FKBP12.6, was used as assay system for binding/exchange with the mutants. The triple mutant (Q31E/N32D/F59W) of FKBP12.6 was found to lack selective binding to the cardiac RyR2, comparable with that of FKBP12.0. In complementary studies, mutations of FKBP12 to the three critical amino acids of FKBP12.6, conferred selective binding to RyR2. Each of the FKBP12.6 and FKBP12 mutants retained binding to the skeletal muscle RyR1. We conclude that three amino acid residues (Gln31, Asn32, and Phe59) of human FKBP12.6 account for the selective binding to cardiac RyR2.

Amino Acid Sequence↗

An important role for major histocompatibility complex class I-restricted T cells, and a limited role for gamma interferon, in protection of mice against lethal herpes simplex virus infection.

Herpes simplex virus (HSV) inhibits major histocompatibility complex (MHC) class I expression in infected cells and does so much more efficiently in human cells than in murine cells. Given this difference, if MHC class I-restricted T cells do not play an important role in protection of mice from HSV, an important role for these cells in humans would be unlikely. However, the contribution of MHC class I-restricted T cells to the control of HSV infection in mice remains unclear. Further, the mechanisms by which these cells may act to control infection, particularly in the nervous system, are not well understood, though a role for gamma interferon (IFN-gamma) has been proposed. To address the roles of MHC class I and of IFN-gamma, C57BL/6 mice deficient in MHC class I expression (beta2 microglobulin knockout [beta2KO] mice), in IFN-gamma expression (IFN-gammaKO mice), or in both (IFN-gammaKO/beta2KO mice) were infected with HSV by footpad inoculation. beta2KO mice were markedly compromised in their ability to control infection, as indicated by increased lethality and higher concentrations of virus in the feet and spinal ganglia. In contrast, IFN-gamma appeared to play at most a limited role in viral clearance. The results suggest that MHC class I-restricted T cells play an important role in protection of mice against neuroinvasive HSV infection and do so largely by mechanisms other than the production of IFN-gamma.

Animals↗