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Biomedical subjects

S Love

Publications and source records attributed to S Love.

At least 55 records · Page 3Linked to original sources

Antigen-specific IgG(T) responses in natural and experimental cyathostominae infection in horses.

Equine clinical larval cyathostominosis is caused by simultaneous mass emergence of previously inhibited larvae from the mucosa of the colon. Clinical signs include diarrhoea, colic, weight loss and malaise, and in up to 50% of cases, the disease results in death. Cyathostominae spend a large part of their life cycle as larval stages in the intestinal mucosa. Definitive diagnosis is difficult due to the lack of diagnostic methods for pre-patent infection. In the present study, the enzyme-linked immunosorbent assay (ELISA) was used to investigate isotype responses to larval cyathostominae somatic antigen. Measurement of anti-larval IgG(T) responses appeared to have the most immunodiagnostic potential. An increase in IgG(T) response was detected to crude larval antigen by 5 weeks post-infection (PI) in individual infected ponies. Subsequently, IgG(T) responses to larval and adult somatic extracts were examined by Western blotting using sera from experimentally-infected horses and helminth-naive animals (n=6). Two antigen complexes, designated A and B, in larval somatic antigen were recognised specifically by the infected animals by 7 weeks PI. Sera taken from 23 endemically-infected animals, whose cyathostominae burdens had been enumerated, were also used to identify putative diagnostic antigens. Eighteen horses had positive mucosal worm burdens (range 723-3,595,725) and all but two of these animals had serum IgG(T) antibody specific to either complex. Moreover, IgG(T) responses specific to antigen complexes A and B were absent in all five parasite negative horses that were tested. Serum IgG(T) responses to either of the two complexes were identified in five clinical cases tested. IgG(T) responses to adult antigen somatic extracts were more heterogeneous, with no clear pattern between experimentally-infected ponies and helminth-free controls. The results indicate that increases in serum IgG(T) to mucosal larvae occur in the pre-patent period and that two antigenic complexes within somatic preparations of these stages have immunodiagnostic potential.

Animals↗

Bone density in chronic low back pain: a pilot study.

BACKGROUND AND OBJECTIVE: Levels of physical activity in chronic low back pain patients are relatively low due to their fear of provoking pain. This may have a secondary impact on maintenance of bone mass. The objective of this study is to determine if patients with chronic low back pain are at a higher risk of bone demineralization. DESIGN: Bone mineral density (BMD) was measured in 25 chronic low back pain patients at the lumbar spine, hip and distal forearm. SETTING: A university hospital. SUBJECTS: Twenty-five chronic low back pain patients (mean age 45 years) enrolled on a residential back pain rehabilitation programme. RESULTS: Thirteen patients (52%) were osteopenic or osteoporotic in one or more sites. BMD at the lumbar spine was generally lower than the mean BMD of age-matched subjects (p = 0.04). There was no significant relationship between BMD and duration of pain, disability, sex or previous surgical intervention. CONCLUSIONS: Chronic low back pain patients have an increased incidence of osteopenia and osteoporosis. This finding reinforces the importance of motivating patients to incorporate exercise into daily life. Given the limited set of subjects used in the present study, further studies are required.

Adult↗

The effects of xylazine, detomidine, acepromazine and butorphanol on equine solid phase gastric emptying rate.

The aim of this study was to measure the effects of specific commonly used sedative protocols on equine solid phase gastric emptying rate, using the 13C-octanoic acid breath test (13C-OABT). The gastric emptying of a standard 13C-labelled test meal was measured once weekly in 8 mature horses over two 4 week treatment periods. Each horse acted as its own control. In treatment Period 1, saline (2 ml i.v.), xylazine (0.5 mg/kg i.v.), detomidine (0.01 mg/kg i.v.) or detomidine/butorphanol combination (0.01/0.02 mg/kg i.v.) was administered in randomised order after ingestion of the test meal. During treatment Period 2, test meal consumption was followed by saline, xylazine (1.0 mg/kg i.v.), or detomidine (0.03 mg/kg i.v.) administration, or preceded by acepromazine (0.05 mg/kg i.m.) in randomised order. The 13C:12C ratio of sequential expiratory breath samples was determined by isotope ratio mass spectrometry, and used to measure the gastric half-emptying time, t 1/2, and duration of the lag phase, t lag, for each of the 64 tests. In treatment Period 1, detomidine/butorphanol prolonged both t 1/2 and t lag with respect to xylazine 0.5 mg/kg and the saline control (P < 0.05). In Period 2, detomidine 0.03 mg/kg delayed each parameter with respect to saline, acepromazine and xylazine 1.0 mg/kg (P < 0.001). Xylazine 1.0 mg/kg also lengthened t lag relative to the saline control (P = 0.0004), but did not cause a significant change in t 1/2. Comparison of treatment periods showed that the inhibitory effect of detomidine on gastric emptying rate was dose related (P<0.05). These findings may have clinical significance for case selection when these agents are used for purposes of sedation and/or analgesia.

Acepromazine↗

Quantitative detection of atropine-delayed gastric emptying in the horse by the 13C-octanoic acid breath test.

The 13C-octanoic acid breath test has been correlated significantly to radioscintigraphy for measurement of gastric emptying indices in healthy horses. The objective of this study was to investigate the validity of the test for measurement of equine delayed gastric emptying, prior to its potential clinical application for this purpose. A model of atropine-induced gastroparesis was used. Gastric emptying rate was measured twice in 8 horses using concurrent radioscintigraphy and/or breath test after treatment i.v. with either atropine (0.035 mg/kg bwt) or saline in randomised order. Analysis of both data sets demonstrated that the atropine treatment had caused a significant delay in gastric emptying rate. Paired breath test data showed an atropine-induced delay in gastric half-emptying time (t 1/2), with no overlap in the 99% CI range (P < 0.001). Significant correlations were found between scintigraphy and 13C-octanoic acid breath test for calculation of both t 1/2 (P < 0.01) and lag phase duration (P < 0.05) in the atropine-delayed emptying results. The mean (s.d.) bias in breath test t 1/2 when compared with scintigraphy was 1.78 (0.58) h. The results demonstrated that the 13C-octanoic acid breath test was an effective diagnostic modality for the measurement of equine delayed gastric emptying. The technique offers advantages to existing methods for clinical investigation, as it is noninvasive, not radioactive, quantitative and requires minimal equipment or training to perform.

Animals↗

Sentinel practice-based survey of the management and health of horses in northern Britain.

Details of the management, feeding, level of activity and routine health care of horses in Scotland and the five northernmost counties in England were recorded through a stratified random sample of horse owners who had responded to a previous survey. Sixty-eight per cent of the horses were kept where their owners resided, and 32 per cent were kept away from the owner's home. More than 99 per cent were turned out to grazing for at least part of the year and 81 per cent were stabled for at least part of the time, most commonly bedded on straw (50 per cent) or shavings (34 per cent). Hay was fed to 87 per cent, sugar beet pulp to 64 per cent and commercially prepared concentrate mixes to 60 per cent of the horses. Hacking was the most popular activity (52 per cent of horses) followed by riding/pony club events (28 per cent) and showing (21 per cent). The majority of the horses were involved in more than one activity. There were an estimated 0.88 veterinary visits per horse per year and 29 per cent of the horses were reported to suffer from at least one permanent or recurrent health disorder. The median annual numbers of administrations of vaccines (influenza and tetanus) and anthelmintics were one and seven respectively per horse, and each horse was shod a median seven times. There were significant differences in the management of horses kept in different types of premises and in areas of different human population density.

Animal Feed↗

Damage to nuclear DNA in Lewy body disease.

To assess the significance of damaged nuclear DNA in autopsy brain tissue in Lewy body disease (LBD), we examined the patterns of expression of two DNA repair enzymes (PARP and DNA-PKCS), TUNEL and caspase-3 activation, in sections of midbrain and frontal cortex from nine patients with LBD who had not received L-DOPA, and from five neurologically normal controls. In LBD but not controls, many neurons and glia in the midbrain had translocated DNA-PKCS and PARP from the cytoplasm into the nucleus, particularly in the substantia nigra. LBD midbrains contained sparse TUNEL-positive neurons. Caspase-3 activity was largely restricted to microglia but was detected in an occasional nigral neuron. Nuclear DNA damage occurs in vivo in LBD but only rarely indicates neuronal apoptosis.

Aged↗

Jugular venous emboli of brain tissue induced in sheep by the use of captive bolt guns.

Emboli of central nervous tissue were detected in the jugular venous blood of two of 15 sheep stunned with a conventional cartridge-operated captive bolt gun and in two of 15 sheep stunned with a pneumatically activated gun. No emboli were detected in arterial blood from these sheep or in venous blood from sheep stunned electrically. Emboli from an animal with BSE could transmit the disease to people.

Abattoirs↗

Involvement of apolipoprotein E in herpes simplex encephalitis.

APOE polymorphism may influence risk for cold sores and, by interacting with latent HSV-1, risk for Alzheimer's disease (AD). APOE genotype also influences outcome after brain injury. We sought to determine whether APOE genotype influences risk for herpes simplex encephalitis (HSE), whether apoE is involved in the response to HSE and if APOE genotype influences outcome from HSE. There was increased immunoreactivity of neurons, neuropil and glia for apoE areas of brain damaged by HSE. APOE genotypes for cases of HSE (n = 57) were similar to those of controls (n = 41). APOE genotypes for survivors of HSE were similar to those of patients who died. We conclude that apoE is involved in the response to damage associated with HSE, as in other forms of brain injury. However, APOE genotype does not appear to influence either the risk of developing HSE or subsequent mortality.

Adolescent↗

Damage to intracranial optic pathways in fatal closed head injury in man.

Head injury is a leading cause of visual impairment. This is partly due to direct trauma to the eye and optic nerve but much of the damage involves the intracranial optic pathways. We have studied the frequency, distribution and nature of the intracranial lesions of the optic pathways at autopsy in 45 cases of severe closed head injury, and examined the correlation between these post-mortem lesions and the ante-mortem clinical findings. Twenty-four of the patients had been involved in road traffic accidents. The ages ranged from 9 to 88 years (mean 46.4), the Glasgow Coma Score (GCS) on admission ranged from 3 to 15 (mean 5), and the survival time after injury from 2.5 h to15 days (mean 3.3 days). Skull fractures were present in 75.6% of the cases. Histological assessment included the use of immunohistochemistry for beta-amyloid precursor protein (beta-APP) and the microglial marker CD68. Axonal injury of varying severity was demonstrable in all cases, and in 39 (87%) the optic chiasm, tracts or radiations were involved, usually in more than one region. The severity of axonal injury was mild in 11 (24%), moderate in 9 (20%) and severe in 19 (42%) cases. The optic radiation at the level of the trigone of the lateral ventricle was particularly frequently and severely affected. The least affected parts of the intracranial optic pathways were the optic chiasm and the posterior segment of the optic nerve. The severity of injury to the optic pathways did not always reflect severity of axonal injury elsewhere in the brain and correlated poorly with the type of trauma (high- or low-velocity), presence of skull fractures or evidence of raised intracranial pressure (ICP). Of the 39 patients who survived more than 6 h, histological evidence of ischaemic injury to the primary optic cortex was present in 26 (67%) and was severe in 12. We conclude that the visual pathways are affected in a high proportion of patients with fatal closed head injury, nerve fibres in the optic radiations being particularly vulnerable. The findings suggest that damage to the posterior parts of the optic pathways may be under-diagnosed among patients with head injury.

Adolescent↗

Delayed cerebral edema and fatal coma after minor head trauma: role of the CACNA1A calcium channel subunit gene and relationship with familial hemiplegic migraine.

Trivial head trauma may be complicated by severe, sometimes even fatal, cerebral edema and coma occurring after a lucid interval ("delayed cerebral edema"). Attacks of familial hemiplegic migraine (FHM) can be triggered by minor head trauma and are sometimes accompanied by coma. Mutations in the CACNA1A calcium channel subunit gene on chromosome 19 are associated with a wide spectrum of mutation-specific episodic and chronic neurological disorders, including FHM with or without coma. We investigated the role of the CACNA1A gene in three subjects with delayed cerebral edema. Two subjects originated from a family with extreme FHM, and one subject was the previously asymptomatic daughter of a sporadic patient with hemiplegic migraine attacks. In all three subjects with delayed severe edema, we found a C-to-T substitution resulting in the substitution of serine for lysine at codon 218 (S218L) in the CACNA1A gene. The mutation was absent in nonaffected family members and 152 control individuals. Haplotype analysis excluded a common founder for both families. Neuropathological examination in one subject showed Purkinje cell loss with relative preservation of granule cells and sparing of the dentate and inferior olivary nuclei. We conclude that the novel S218L mutation in the CACNA1A calcium channel subunit gene is involved in FHM and delayed fatal cerebral edema and coma after minor head trauma. This finding may have important implications for the understanding and treatment of this dramatic syndrome.

Adolescent↗

Inter-laboratory comparison of DNA preservation in archival paraffin-embedded human brain tissue from participating centres on four continents.

DNA extracted from formalin-fixed and paraffin-embedded brain tissue is known to contain as yet ill-characterized inhibitors of the PCR process. As part of a project that aims to clarify the role of mitochondrial DNA sequence variation in human neurodegenerative diseases using DNA from various ethnic backgrounds, we have investigated factors that influence the preservation of archival DNA and its suitability for PCR. In this study, neuropathological tissue samples were analysed that had been routinely processed in 18 international centres on four continents. Following DNA extraction, PCR amplification of mitochondrial and nuclear DNA sequences was performed with and without additional purification of the template DNA. In addition, the DNA used for PCR was analysed by HPLC. Phosphate-buffered formalin proved to be a superior fixative compared with unbuffered aldehyde: DNA extraction resulted in greater yields, the molecular weight of the isolated DNA was higher and PCR was more successful. PCR inhibitors were identified as (1) high concentrations of small (<300 bp) DNA fragments that competitively compete with template DNA and (2) contaminants of the DNA template solution including denatured protein that cannot be completely removed by phenolic extraction. HPLC analysis did not reveal significant qualitative differences between DNA isolated from fresh-frozen tissue samples and DNA recovered from formalin-fixed, paraffin-embedded brain tissue. The fact that DNA could be amplified from the majority of tissue specimens in this study suggests that rare diseases and diseases where ethnic background plays an important role can be sampled for genetic polymorphism analysis on a global scale using archival neuropathological collections.

Alzheimer Disease↗

Evaluation of the specificity of five oligoprobes for identification of cyathostomin species from horses.

Here, we report evaluation of five oligoprobes designed from intergenic spacer (IGS) region sequences for identification of cyathostomin species. Oligoprobes were designed for identification of Cylicocyclus ashworthi, Cylicocyclus nassatus, Cylicostephanus longibursatus, Cylicostephanus goldi and a fifth probe designed to identify all members of this tribe. PCR amplification of IGS DNA from 16 cyathostomin species allowed sequence comparison and identification of four putative species-specific probes. Southern blotting of amplified products from 16 species showed that all probes were species-specific. The fifth probe recognised all 16 cyathostomin species but did not bind to members of the genus Strongylus. Furthermore, these probes were used to identify individual infective L3, eggs and L4 indicating that they will be invaluable to furthering the study of the epidemiology and pathogenesis of these important equine nematodes.

Animals↗

Control of enzymatic browning in potato (Solanum tuberosum L.) by sense and antisense RNA from tomato polyphenol oxidase.

Polyphenol oxidase (PPO) activity of Russet Burbank potato was inhibited by sense and antisense PPO RNAs expressed from a tomato PPO cDNA under the control of the 35S promoter from the cauliflower mosaic virus. Transgenic Russet Burbank potato plants from 37 different lines were grown in the field. PPO activity and the level of enzymatic browning were measured in the tubers harvested from the field. Of the tubers from 28 transgenic lines that were sampled, tubers from 5 lines exhibited reduced browning. The level of PPO activity correlated with the reduction in enzymatic browning in these lines. These results indicate that expression of tomato PPO RNA in sense or antisense orientation inhibits PPO activity and enzymatic browning in the major commercial potato cultivar. Expression of tomato PPO RNA in sense orientation led to the greatest decrease in PPO activity and enzymatic browning, possibly due to cosuppression. These results suggest that expression of closely related heterologous genes can be used to prevent enzymatic browning in a wide variety of food crops without the application of various food additives.

Biotechnology↗

Trigeminal neuralgia due to multiple sclerosis: ultrastructural findings in trigeminal rhizotomy specimens.

Trigeminal neuralgia is a well-recognized complication of multiple sclerosis. In patients with neuralgia not responding to medical treatment or transcutaneous ablative procedures, the pain can often be treated successfully by partial rhizotomy of the trigeminal sensory root. We have examined partial trigeminal rhizotomy specimens from six multiple sclerosis patients, aged between 34 and 77 years, with intractable trigeminal neuralgia lasting between 18 months and 11 years. The rhizotomy specimens were placed in buffered glutaraldehyde immediately after resection, and subsequently processed for electron microscopy. In all cases, this revealed demyelination in the proximal (CNS) part of the nerve root, with associated gliosis and variable inflammation. A consistent feature was the presence of clusters of juxtaposed axons without intervening glial processes. Similar juxtaposition of axons was previously observed in trigeminal neuralgia due to vascular compression of the nerve root. Experimental studies indicate that this arrangement of demyelinated axons is conducive to both spontaneous impulse activity and ephaptic spread of excitation. The demyelination and associated juxtaposition of axons may therefore account for key aspects of the pathogenesis of trigeminal neuralgia.

Adult↗

Expression of P-selectin and intercellular adhesion molecule-1 in human brain after focal infarction or cardiac arrest.

Data from experimental studies indicate that acute inflammation contributes to ischaemic brain damage. Tethering of neutrophils to brain endothelium is mediated by selectins, and subsequent adhesion and migration by endothelial intercellular adhesion molecule-1 (ICAM-1) and neutrophil CD18. In experimental studies of ischaemia-reperfusion injury, brain damage has been ameliorated by administration of antibodies to these adhesion molecules. We studied the expression of P-selectin and ICAM-1 in sections of brain from patients who had experienced cardiac arrest or focal brain infarction, and who died 3.5 h to 9 days later. Endothelial immunopositivity for both adhesion molecules was maximal at about 2-3 days then declined. Between 1 day and 3 days, P-selectin was also detected on platelets in blood vessels within infarcted tissue. Within infarcts, but not sections of brain from cardiac arrest patients, P-selectin and ICAM-1 were again detectable at 1 week, when hyperplastic endothelial cells were labelled in capillaries in and immediately adjacent to the infarcted tissue. The finding that P-selectin and ICAM-1 are upregulated within focally infarcted brain tissue supports the concept that blocking neutrophil adhesion may be of benefit in treating atherothrombotic strokes in man.

Adult↗

The effect of botulinum toxin type A and a variable hip abduction orthosis on gross motor function: a randomized controlled trial.

Hip displacement is the second most common deformity after equinus in children with cerebral palsy (CP), and may result in dislocation, pain, fixed deformity and loss of function. We studied the combined effects of intramuscular injections of botulinum toxin type A (BTX-A) to the adductors and hamstrings and a variable hip abduction orthosis (SWASH), on gross motor function, hip displacement and progression to surgery, in a randomized clinical trial. Thirty-nine children, with bilateral spastic cerebral palsy, and mean age 3 years + 2 months (range 1 year+7 months--4 years +10 months) entered the trial. Gross Motor Function Classification System (GMFCS) levels were as follows: one child was level II, 11 were level III, 13 were level IV and 14 were level V. After concealed randomization, 20 were allocated to the control group and 19 to the intervention group. Thirty-five children completed the follow up at 1 year. The novel intervention group received up to 4.0 U BOTOX/kg/muscle, 16 U/kg/body weight every 6 months plus the use of a SWASH brace. The control group received clinical best practice comprising physiotherapy but no hip abduction bracing. Both groups showed improvements in total Gross Motor Function Measure (GMFM) score [mean 6.0% BTX-A group; 6.1% Control; 95% CI -- 6.7, 6.5 (NS)], however, there was no additional treatment effect for the study group. There were similar improvements on GMFM goal scores and GMFM-66 scores, but again no additional treatment effect was observed. Multiple regression of change in total GMFM by GMFCS classification for each group showed greater improvement in the total scores from baseline in the BTX-A/SWASH treated group than the control group. In the first year, nine children (two in the intervention group and seven in the control group) required soft tissue surgery because of progressive hip migration in excess of 40%. A longer-term follow up of a larger cohort may be required to determine the effect of the combined treatment on hip displacement.

Botulinum Toxins, Type A↗