Search PubMed⌕ Search

Biomedical subjects

S Love

Publications and source records attributed to S Love.

At least 37 records · Page 2Linked to original sources
PubMed2004

Validation of a method for collection and assay of pentane in the exhaled breath of the horse.

Oxidative stress refers to an imbalance between the production of oxidising free radicals and the antioxidant defenses of the cell, and is associated with many pathogenic processes. Oxidative damage to cellular lipids results in the evolution of pentane and ethane gas, and detection of these hydrocarbons in the exhaled breath can be used to monitor in vivo oxidative stress. The aim of this study was to validate a gas chromatography (GC) method for measurement of breath pentane in the horse. The GC-system developed showed good specificity for discrimination of pentane from other breath hydrocarbons, and was sensitive to 0.5 ppb pentane. Pentane was detected in the exhaled breath of five horses investigated on two occasions. The results of this preliminary study demonstrate that breath pentane can be measured in the horse, and further work is now justified to investigate the feasibility of applying this method for monitoring in vivo oxidative stress in the horse.

Animals↗
PubMed2004

Frequency of brain tissue embolism associated with captive bolt gun stunning of sheep.

In accordance with controls instituted to protect the consumer from meat potentially infected with bovine spongiform encephalopathy (BSE), brain tissue emboli caused by the use of captive bolt gun (CBG) stunning have been identified as a potential public health risk that requires further investigation. As the natural occurrence of BSE in sheep remains uncertain we have investigated the frequency of brain tissue embolism associated with stunning by two types of CBG that are in commercial use in the United Kingdom. Blood samples collected from sheep following stunning were analysed by ELISA as well as by a combination of microscopy and immunocytochemistry. The combined positive results from each method of sample analysis were used to determine the frequency of brain tissue embolism in the sample population. The frequency of brain tissue embolism was found to be 23% in sheep stunned with a cartridge-activated CBG (95% confidence interval of 15.8-32.2%) and 14% in those stunned with a pneumatically activated CBG (95% confidence interval of 8.5-22%). The frequency of brain tissue embolism associated with the use of CBG stunning may represent a significant source of carcass contamination with brain tissue.

Abattoirs↗
PubMed2004

Post mortem sampling of the brain and other tissues in neurodegenerative disease.

The importance of the autopsy in neurodegenerative disease is often not appreciated. Yet clinical diagnosis of neurodegenerative disease is relatively inaccurate, many neurodegenerative diseases are inherited or are associated with specific genetic risk factors, and several non-transmissible neurodegenerative diseases may be confused clinically with prion diseases. In all these cases, the autopsy is the only practical way in which brain tissue can be obtained for diagnosis. The pathologist should ensure that consent by the next-of-kin to post mortem examination is based on clear information as to the nature, scope and limitations of the autopsy, and that any constraints on retaining brain and other tissues are documented. The autopsy should be preceded by a careful review of the clinical notes and ante mortem studies, and consideration of the possible and likely pathological processes. This may suggest the need to retain fixed or frozen samples of cerebrospinal fluid, skeletal muscle, peripheral nerve and other tissues in addition to brain and spinal cord. Ideally, the brain should be fixed intact for 2-3 weeks before it is sliced and blocks are taken. If the period of fixation is limited to a few days only, it is best to slice the brain whilst it is fresh and to allow the diagnostically relevant slices to fix flat; after about 3 days the fixed slices can be sliced further, examined macroscopically and sampled. Even if consent is limited to the retention of only a few tissue samples for histology, a reasonably confident diagnosis can still usually be made, provided that the sampling is careful and systematic. The selection of blocks or brain and spinal cord for histology should be based on internationally accepted guidelines for the pathological diagnosis of different types of neurodegenerative disease, where such guidelines are available. Illustrations are provided to indicate which regions of the brain are critical to establishing a diagnosis in the main categories of neurodegenerative disease. When difficulties arise in the pathological diagnosis of neurodegenerative disease, inadequate post mortem sampling or rapid processing of poorly fixed brain tissue is usually to blame.

Autopsy↗
PubMed2004

Histological indicators of prognosis in glioblastomas: retinoblastoma protein expression and oligodendroglial differentiation indicate improved survival.

AIM: To assess the potential prognostic significance of a range of molecular and morphological parameters in glioblastomas that can be applied in the setting of a routine diagnostic neuropathology laboratory. METHODS AND RESULTS: A consecutive series of 107 adult glioblastomas were studied. Retinoblastoma and deleted-in-colon cancer (DCC) protein expression were assessed using immunocytochemistry and chromosome 10 loss by in-situ hybridization. Loss of retinoblastoma expression was associated with a worse outcome, which appeared to be independent of age. There was no significant association between chromosome 10 loss or DCC protein expression and survival. Survival was significantly increased in the 5% of patients whose tumours had focal morphological features suggesting oligodendroglial differentiation. CONCLUSIONS: Glioblastomas containing areas of oligodendroglial differentiation or showing widespread immunocytochemical expression of retinoblastoma protein have a better prognosis than those without these features.

Adult↗
PubMed2004

Transforming growth factor-betas in a rat model of neonatal posthaemorrhagic hydrocephalus.

Posthaemorrhagic ventricular dilatation (PHVD) is a common complication of intraventricular haemorrhage in premature infants. The aim of this study was to investigate the role of transforming growth factor-betas (TGF-betas), a family of polypeptides with potent desmoplastic properties, in the aetiology of PHVD in a newly developed neonatal rat model of this disorder. Pups were injected with citrated rat blood or artificial cerebrospinal fluid (ACSF) into alternate lateral ventricles on postnatal days 7 and 8. The brains were perfusion-fixed 14 days later and immunohistochemistry was performed for TGF-beta1, -beta2 and -beta3, p44/42 mitogen-activated protein (MAP) kinases, and the extracellular matrix proteins laminin, vitronectin and fibronectin. Ventricular dilatation occurred in 58.3% of animals injected with blood and 36.7% of those injected with ACSF. Periventricular immunoreactivity for TGF-beta1 and -beta2 increased in injected animals irrespective of the presence or absence of ventricular dilatation, although the levels of both isoforms tended to be higher in animals with hydrocephalus. TGF-beta3 immunoreactivity was elevated in hydrocephalic rats only. The immunolabelling for phosphorylated p44/42 MAP kinases rose in a pattern similar to that for TGF-beta1 and -beta2. Expression of TGF-betas was accompanied by deposition of the extracellular matrix proteins fibronectin, laminin and vitronectin. The changes caused by injection of ACSF were the same as those caused by injection of blood. Our results raise the possibility that expression of TGF-betas, together with extracellular matrix protein deposition, may be involved in the development and/or maintenance of hydrocephalus after ventricular distension due to haemorrhage in the neonate.

Animals↗
PubMed2004

Dissemination of brain emboli following captive bolt stunning of sheep: capacity for entry into the systemic arterial circulation.

The epidemic of bovine spongiform encephalopathy in the United Kingdom and the recognition of a variant of Creutzfeldt-Jakob disease prompted revision of the guidelines for slaughter of cattle and sheep to prevent contamination of the edible parts of the carcass with central nervous system tissue. We previously showed that captive bolt gun stunning, which is routinely used for the slaughter of cattle and sheep, causes entry of fragments of central nervous system tissue into the jugular vein. To determine whether such tissue can traverse pulmonary capillaries to enter the systemic circulation, we introduced small volumes of brain tissue that had been disrupted by stunning with a captive bolt gun into the jugular vein of sheep sent for slaughter. We examined aortic blood samples by immunocytochemistry for neurofilament and S100 proteins and by enzyme-linked immunosorbent assay for glial fibrillary acidic protein and found fragments of neurofilament- and S100-immunopositive central nervous system tissue in samples from 2 of 11 sheep and elevated glial fibrillary acidic protein in 6 sheep. Our findings suggest that central nervous system tissue that is dislodged during routine captive bolt gun stunning and slaughter of sheep can enter the systemic arterial circulation and that, in some cases, this method of slaughter of an animal infected with bovine spongiform encephalopathy would be likely to contaminate edible parts of the carcass with infective material.

Abattoirs↗
PubMed2003

Association between interleukin-1A polymorphism and cerebral amyloid angiopathy-related hemorrhage.

BACKGROUND AND PURPOSE: It has been suggested that the interleukin-1A (IL-1A) allele 2 is a risk factor for Alzheimer's disease (AD). Because cerebral amyloid angiopathy-related hemorrhage (CAAH) often coexists with AD, we examined the IL-1A polymorphism in CAAH. METHODS: In a case-control study, patients with pathologically verified CAAH, AD patients without intracerebral hemorrhage, and neuropathologically normal control subjects were studied. DNA was extracted from brain tissue, and IL-1A was genotyped. Logistic regression was used to examine the IL-1A polymorphism in CAAH patients with and without AD compared with AD and non-AD control subjects. RESULTS: There were 42 patients with CAAH, 232 AD patients, and 167 non-AD control subjects. In age-adjusted analyses, there was no association between possession of IL-1A allele 2 and risk of CAAH compared with AD control subjects (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.45 to 1.97; P=0.87) or non-AD control subjects (OR, 0.94; 95% CI, 0.47 to 1.87; P=0.86). Stratifying for the presence of apolipoprotein E epsilon2 or epsilon4 demonstrated the known increased risk of CAAH from these lipoprotein E alleles. Subgroup analyses demonstrated a nonsignificant excess of the IL-1A 2,2 genotype in patients with CAAH and AD compared with those CAAH patients who did not have histological evidence indicating AD (OR, 2.17; 95% CI, 0.15 to 122.3; P=0.64). Comparisons between CAAH patients with AD and AD control subjects and between CAAH patients without AD and non-AD control subjects did not demonstrate an association between CAAH and possession of either the IL-1A allele 2 or the 2,2 genotype. CONCLUSIONS: The IL-1A allele 2 or 2,2 genotype does not appear to be a major risk factor for CAAH.

Aged↗
PubMed2003

Intravenous immunoglobulin for the treatment of Kawasaki disease in children.

BACKGROUND: Kawasaki disease is the most common cause of acquired heart disease in children in developed countries. The coronary arteries supplying the heart can be damaged in Kawasaki disease. The principal advantage of timely diagnosis is the potential to prevent this complication with early treatment. Intravenous immunoglobulin (IVIG) is widely used for this purpose. OBJECTIVES: The objective of this review was to evaluate the effectiveness of IVIG in treating, and preventing cardiac consequences, of Kawasaki disease in children. SEARCH STRATEGY: Electronic searches of the Cochrane Peripheral Vascular Disease Group Specialised Register, CENTRAL, MEDLINE, EMBASE, and CINAHL were performed (last searched April 2003). We also searched references from relevant articles and contacted authors where necessary. In addition we contacted experts in the field for unpublished works. SELECTION CRITERIA: Randomised controlled trials of intravenous immunoglobulin to treat Kawasaki disease were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Fifty-nine trials were identified in the initial search. On careful inspection only sixteen of these met all the inclusion criteria. Trials were data extracted and assessed for quality by at least two reviewers. Data were combined for meta-analysis using relative risk ratios for dichotomous data or weighted mean difference for continuous data. A random effects statistical model was used. MAIN RESULTS: The meta-analysis of IVIG versus placebo, including all children, showed a significant decrease in new coronary artery abnormalities (CAAs) in favour of IVIG, at thirty days RR (95% CI) = 0.74 (0.61 to 0.90). No statistically significant difference was found thereafter. A subgroup analysis excluding children with CAAs at enrollment also found a significant reduction of new CAAs in children receiving IVIG RR (95%) = 0.67 (0.46 to 1.00). There was a trend towards benefit from IVIG at sixty days (p=0.06). Results of dose comparisons showed a decrease in the number of new CAAs with increased dose. The meta-analysis of 400 mg/kg/day for five days versus 2 gm/kg in a single dose showed statistically significant reduction in CAAs at thirty days RR (95%) = 4.47 (1.55 to 12.86). This comparison also showed a significant reduction in duration of fever with the higher dose. There was no statistically significant difference noted between different preparations of IVIG. There was no statistically significant difference of adverse effects in any group. REVIEWER'S CONCLUSIONS: Children fulfilling the diagnostic criteria for Kawasaki disease should be treated with IVIG (2 gm/kg single dose) within 10 days of onset of symptoms.

Child↗
PubMed2003

A prospective study of discordance in diagnosis of osteoporosis using spine and proximal femur bone densitometry.

The T-score definition of osteoporosis, originally intended for epidemiologic research in this condition, is frequently used in making treatment decisions for individual patients. Discordance in classification depending on the site and type of measurement has been reported in retrospective and cross-sectional studies, but the impact of such discordance on clinical practice is unknown. This is potentially important in view of a recent proposal to confine osteoporosis diagnosis to densitometry at the hip. Having excluded those with degenerative changes in the lumbar spine, we compared the T-score classification of a prospective cohort of patients referred for their first dual-energy X-ray absorptiometry (DXA) scan, analyzing data for men and women in 10-year age groups. Total hip and neck of femur DXA identified significantly fewer osteoporotic patients than spine DXA, and this reduced sensitivity could not be improved by adjusting the T-score threshold without an unacceptable increase in non-osteoporotic cases. The majority of patients undetected by proximal femur DXA were at significantly increased risk of vertebral fracture. DXA at the lumbar spine had only moderate sensitivity and specificity for osteoporosis redefined by total hip densitometry, indicating differential rates of bone loss at the proximal femur and spine. We conclude that, as the most usual indication for bone densitometry is to aid the determination of an individual's fracture risk, both proximal femur and lumbar spine should continue to be assessed.

Absorptiometry, Photon↗
PubMed2003

A PCR-ELISA for the identification of cyathostomin fourth-stage larvae from clinical cases of larval cyathostominosis.

We report the use of six oligoprobes designed from intergenic spacer region sequences to identify fourth-stage larvae (L4) of the tribe Cyathostominae. Oligoprobes were designed for identification of the following species: Cylicocyclus ashworthi, Cylicocyclus nassatus, Cylicocyclus insigne, Cyathostomum catinatum, Cylicostephanus goldi, and Cylicostephanus longibursatus. A seventh probe was designed as a positive control to identify all these members of the Cyathostominae. The intergenic spacer region was amplified by PCR using conserved primers. Initially, three oligoprobes were used in Southern blot analysis. To facilitate high-throughput identification, these and a further four oligoprobes were developed for use in a PCR-ELISA. All probes were validated for their ability to detect cyathostomin PCR products in the PCR-ELISA, using DNA from morphologically identified adult parasites. Initially, 712 L4 were isolated from the diarrhoeic faeces from horses (n=17) with clinical larval cyathostominosis. PCR products from 522 of these L4 were subjected to analysis, with 413 L4 being identified as one of the aforementioned species. With reference to individual species analysis, 28.5% of the 522 L4 were identified as C. longibursatus, 25.7% as C. nassatus, 15.9% as C. ashworthi, 7.3% as C. goldi and 1.7% as C. catinatum. No L4 were identified as being C. insigne species. When L4 within faeces from individual horses were compared, no sample was found to comprise parasites of one species. The least number of species identified in a single sample was two. This study suggests that clinical larval cyathostominosis is predominantly caused by mixed-species infections.

Animals↗
PubMed2003

Purification and analyses of the specificity of two putative diagnostic antigens for larval cyathostomin infection in horses.

Cyathostomins are important equine gastrointestinal parasites. Mass emergence of mucosal stage larvae causes a potentially fatal colitis. Mucosal stages are undetectable non-invasively. An assay that would estimate mucosal larval stage infection would greatly assist in treatment, control and prognosis. Previously, we identified two putative diagnostic antigens (20 and 25 kDa) in somatic larval preparations. Here, we describe their purification and antigen-specific IgG(T) responses to them. Western blots confirmed the purity of the antigens and showed that epitopes in the 20 kDa complex were specific to larval cyathostomins. No cross-reactive antigens appeared to be present in Parascaris equorum or Strongyloides westeri species. Low levels of cross-reactivity were observed in Strongylus edentatus and Strongylus vulgaris species. Use of purified antigens greatly reduced background binding in equine sera. These results indicate that both antigen complexes may be of use in a diagnostic assay.

Animals↗
PubMed2003

Sequence variants of bovine papillomavirus E5 detected in equine sarcoids.

The equine sarcoid, one of the most common dermatological lesions in equids, is a benign, locally invasive dermal fibroblastic lesion. Previous studies have suggested an association with two bovine papilloma virus (BPV) types, BPV-1 and BPV-2. In the present study, we examined sarcoids from horses from two geographical areas, Switzerland and the UK, for the major transforming gene of BPV, E5. We detected BPV DNA for the E5 open reading frame and viral E5 RNA transcripts in most sarcoids. Sequence analysis of the E5 open reading frame of sarcoid-associated BPV detected several unique DNA sequence variants, three of which resulted in sarcoid specific amino acid sequence variations. It is unclear if these sequence variants contribute to the unique clinical presentation of the sarcoid. However, our work provides further evidence of the association between BPV and sarcoid development and the direct involvement of the virus in the pathogenesis of sarcoids.

Animals↗
PubMed2003

APOE epsilon 4 influences the pathological phenotype of Alzheimer's disease by favouring cerebrovascular over parenchymal accumulation of A beta protein.

The relative amounts of amyloid beta-protein (A beta) in cerebral blood vessels and parenchyma vary considerably amongst patients with Alzheimer's disease (AD). Although several mechanisms have been proposed to explain this variability, the underlying genetic and environmental determinants are still unclear, as are the functional consequences. Polymorphisms in APOE, the gene for apolipoprotein E (ApoE), influence the risk of developing AD and of deposition of A beta within the brain. We examined the relationship between the APOE genotype and the relative extent of accumulation of A beta as plaques within the cerebral parenchyma and in cortical blood vessels in the form of cerebral amyloid angiopathy (CAA), in autopsy brain tissue from 125 AD cases and from 53 elderly, neurologically normal controls of which 19 had CAA without other neuropathological features of AD. In the AD cases, we also assessed whether the severity of CAA was related to the age of onset and duration of dementia, risk factors for atherosclerotic vascular disease, and histologically demonstrable cerebral infarcts or foci of haemorrhage. The APOE genotype was determined by a standard polymerase chain reaction-based method. Paraffin sections of frontal, temporal and parietal lobes were immunolabelled for A beta and the parenchymal A beta load (total A beta minus vessel-associated A beta) was quantified by computer-assisted image analysis. CAA severity was scored for cortical and leptomeningeal vessels. The relevant clinical data were obtained from the database of the South West Brain Bank. In AD, we found the severity of CAA to be strongly associated with the number of epsilon 4 alleles (P < 0.0001) but the parenchymal A beta load to be independent of APOE genotype. Cases with severe CAA had a lower parenchymal A beta load than had those with moderate CAA (P = 0.003). Neither the severity of CAA nor the parenchymal A beta load correlated with age of onset, duration of disease or age at death, and the severity of CAA also did not correlate with the presence of cerebral infarcts or foci of haemorrhage. These findings indicate that possession of the APOE epsilon 4 allele favours vascular over parenchymal accumulation of A beta in AD. This may influence the pathogenesis of neurodegeneration in epsilon 4-associated AD.

Age of Onset↗
PubMed2003

Association of bovine papillomavirus with the equine sarcoid.

The equine sarcoid, a locally aggressive, fibroblastic skin tumour, is the most common dermatological neoplasm reported in horses; there is no consistently effective therapy. It is widely accepted that bovine papillomavirus (BPV) types 1 and 2 are associated with the pathogenesis of sarcoid disease. Most sarcoids appear to contain detectable viral DNA and RNA and are also known to express the BPV types 1 and 2 major transforming protein, E5, but appear not to produce infectious virions. While the mode of transmission of infection has not been elucidated, viral gene expression, in particular of E5, may contribute to virus persistence and disease pathogenesis by downregulating MHC class I expression. Here, the pathology and epidemiology of the sarcoid and its association with BPV is reviewed; the transforming functions of the BPV oncoproteins and their possible role in sarcoid pathogenesis are discussed; and the practical implications of BPV infection for diagnostic and therapeutic purposes are considered.

Animals↗
PubMed2003

Validation of the 13C-octanoic acid breath test for measurement of equine gastric emptying rate of solids using radioscintigraphy.

REASONS FOR PERFORMING STUDY: Disordered gastric motility may be a significant factor in the pathogenesis of many equine conditions. Although tests for liquid phase emptying rate have been validated in the horse, there are no effective tests for solid phase emptying measurement that can be performed routinely in the field. OBJECTIVES: The objective of this study was the assessment of a novel stable isotope technique, the 13C-octane acid breath test (13C-OABT), for the measurement of gastric emptying of solid ingesta, by direct comparison with the optimum method of gastric scintigraphy. METHODS: To facilitate dual measurement of gastric emptying, a test meal was used containing baked egg yolk labelled with both 13C-octanoic acid and 99mtechnetium sulphur colloid. Simultaneous, serial lateral gastric scintigraphs and expiratory breath samples were obtained in 12 healthy horses after voluntary ingestion of the test meal. Analysis of breath 13CO2:12CO2 ratio was performed by continuous flow isotope ratio mass spectrometry. Power regression was used to determine the gastric emptying coefficient, the gastric half-emptying time (t 1/2) and duration of the lag phase (tlag). RESULTS: Significant correlations (P < 0.001) were found between the 2 techniques for measurement of both t 1/2 and tlag. In addition, scintigraphic left t 1/2 was correlated significantly to breath test gastric emptying coefficient (P < 0.001). CONCLUSIONS: It was concluded that the 13C-octanoic acid breath test is a reliable diagnostic procedure to measure gastric emptying rate of solids in the horse. POTENTIAL RELEVANCE: Being safe, noninvasive and easy to perform, this test has potential value as both sensitive diagnostic modality and humane research tool for motility studies.

Animals↗