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Biomedical subjects

P Green

Publications and source records attributed to P Green.

At least 19 recordsLinked to original sources

World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) guidelines for evaluating the efficacy of parasiticides for the treatment, prevention and control of flea and tick infestation on dogs and cats.

These guidelines are intended to assist the planning and conduct of laboratory and clinical studies to assess the efficacy of ectoparasiticides applied to dogs or cats for the purpose of treating, preventing and controlling flea and tick infestations. The term ectoparasiticide includes insecticidal and acaricidal compounds, as well as insect growth regulators. The range of biological activities accruing from animal treatment that are considered include: repellency and anti-feeding effects, knockdown, speed of kill, immediate and persistent lethal effects, and interference with egg fertility and subsequent development of off-host life cycle stages. Information is provided on the selection of animals, dose determination, dose confirmation and field studies, record keeping, interpretation of results and animal welfare. These guidelines are also intended to assist registration authorities involved in the approval and registration of new parasiticides, and to facilitate the worldwide adoption of harmonized procedures.

Animals↗

Scan of human genome reveals no new Loci under ancient balancing selection.

There has been much speculation as to what role balancing selection has played in evolution. In an attempt to identify regions, such as HLA, at which polymorphism has been maintained in the human population for millions of years, we scanned the human genome for regions of high SNP density. We found 16 regions that, outside of HLA and ABO, are the most highly polymorphic regions yet described; however, evidence for balancing selection at these sites is notably lacking--indeed, whole-genome simulations indicate that our findings are expected under neutrality. We propose that (i) because it is rarely stable, long-term balancing selection is an evolutionary oddity, and (ii) when a balanced polymorphism is ancient in origin, the requirements for detection by means of SNP data alone will rarely be met.

ABO Blood-Group System↗

Identifying the impact of diabetes research.

AIMS: Assessment of the impact of health research is a growing but problematic field. We examined how a combination of approaches might together inform assessment of the impact of a body of diabetes research published in 1981 and help identify factors behind success. METHODS: Three broad approaches were applied to the work of one team leader of acknowledged influence. Standard bibliographic analysis was complemented by a second approach which categorized the importance of the primary publications to the papers citing them, in four domains. In parallel, a third approach involved qualitative assessment using surveys, critical pathway analysis by, and interviews of, co-authors and external experts. Extending the approach incorporated key additional publications from other years. RESULTS: In 1981, the team leader published 29 papers. Citations to these 29 first generation papers varied from 1 to 76 and resulted in 799 second generation papers. Citations to these produced 12 891 third generation papers. Analysis of second generation papers suggested the cited first generation paper was thought to be of considerable or essential significance in only 9% of cases. While much research made little impact, qualitative analysis included a wealth of information, sometimes missed by standard bibliographic techniques, on where the identified research influenced important streams of clinical development. Analysis covered major research studies (such as the Diabetes Control and Complications Trial), insulin pump therapy, and career development of co-authors. CONCLUSIONS: Understanding the impact of research requires multiple approaches. With refinement, these techniques could be employed more widely and potentially could inform research policy.

Acarbose↗

S100A8 triggers oxidation-sensitive repulsion of neutrophils.

The inflammatory response to tissue injury is a multi-faceted process. During this process, neutrophils migrate in the extravascular spaces, directed to the site of injury by chemical gradients generated by chemotactic molecules. S100A8, a protein associated with a wide variety of inflammatory conditions, is heavily over-expressed in association with inflammation. We hypothesized that human S100A8 possesses neutrophil-repelling properties that result in an anti-inflammatory effect in vivo. The chemotactic activity of S100A8 on neutrophils was tested in Transwell chemotaxis assays. Analysis of the data indicates that S100A8 causes a repulsion of peripheral neutrophils, an activity that S100A8 loses upon its oxidation. Using a mutant of S100A8 resistant to oxidation and consistent with the in vitro findings, we demonstrated that S100A8 causes a strong anti-inflammatory effect in the rat air-pouch model of inflammation in vivo. These data highlight a naturally occurring novel anti-inflammatory pathway and provide potential molecular targets for the development of novel anti-inflammatory therapeutics. Abbrevations: ethylene diamine tetraacetic acid (EDTA); limulus amoebocyte lysate assay (LAL); pertussis toxin (PTX); forward scatter (FSC); Interleukin-8 (IL-8); formyl-Met-Leu-Phe (fMLP); monocyte chemotactic protein 1 (MCP1).

Alanine↗

World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) guidelines for evaluating the efficacy of acaricides against ticks (Ixodidae) on ruminants.

These guidelines have been prepared to assist in the planning, conduct and interpretation of studies for the assessment of the efficacy of acaricides (excluding vaccines and other bio-control agents) against single and multi-host ticks (Ixodidae) on ruminants. Information is provided on the selection of animals, dose determination, dose confirmation and field studies, record keeping and result interpretation. The use of pen facilities is advocated for dose determination and confirmation studies for defining therapeutic and persistent efficacy. A minimum of two studies per tick species for which claims are sought is recommended for each dose determination and dose confirmation investigation. If dose confirmation studies demonstrate greater than 95% efficacy the sponsor may proceed to field studies, where a minimum of two studies per geographical location is preferred to confirm the therapeutic and persistent efficacy under field conditions. If dose confirmation studies demonstrate less than 95% efficacy then longer-term field studies can be conducted over two tick seasons with a minimum of two studies per geographical location. These studies can incorporate other control methods such as tick vaccines, to demonstrate stable long-term tick management. Specific advice is also given on conducting studies with paralysis ticks. These guidelines are also intended to assist investigators on how to conduct specific experiments, to provide specific information for registration authorities involved in the decision-making process, to assist in the approval and registration of new acaricides, and to facilitate the worldwide adoption of standard procedures.

Animals↗

World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) guidelines for evaluating the efficacy of ectoparasiticides against biting and nuisance flies on ruminants.

These guidelines have been prepared to assist in the planning, conduct and interpretation of studies for the assessment of the efficacy of ectoparasiticides (excluding repellents) against the biting and nuisance dipteran flies of ruminants. Information is provided on the selection of animals, dose determination and dose confirmation studies, field studies, record keeping and result interpretation. These guidelines advocate the use of pen facilities for dose determination and dose confirmation studies. These guidelines also are intended to assist investigators on how to conduct specific studies, to provide specific information for registration authorities involved in the decision-making process, to assist in the approval and registration of new ectoparasiticides, and to facilitate the worldwide adoption of standard procedures.

Animals↗

World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) guidelines for evaluating the efficacy of ectoparasiticides against myiasis causing parasites on ruminants.

These guidelines have been prepared to assist in the planning, conduct and interpretation of studies for the assessment of efficacy of ectoparasiticides against the myiasis causing parasites of ruminants. These guidelines specifically focus on larvicidal efficacy against myiasis causing flies. Information is provided on the selection of animals, dose determination and dose confirmation studies, field studies, record keeping and result interpretation. These guidelines advocate the use of pen facilities for dose determination and dose confirmation studies for defining therapeutic and persistent efficacy. These guidelines are also intended to assist investigators on how to conduct specific experiments, to provide specific information for registration authorities involved in the decision-making process, to assist in the approval and registration of new ectoparasiticides, and to facilitate the world-wide adoption of standard procedures.

Animals↗

World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) guidelines for evaluating the efficacy of ectoparasiticides against biting lice, sucking lice and sheep keds on ruminants.

These guidelines have been prepared to assist in the design, implementation and interpretation of studies for the assessment of the efficacy of ectoparasiticides against biting and sucking lice and sheep keds on ruminants. Information is provided on the selection of animals, dose determination, dose confirmation and field studies, record keeping and result interpretation. These guidelines advocate the use of pen facilities for dose determination and dose confirmation studies for defining therapeutic and persistent efficacy. These guidelines are also intended to assist investigators on how to conduct specific experiments, to provide specific information for registration authorities involved in the decision making process, to assist in the approval and registration of new ectoparasiticides, and to facilitate the world-wide adoption of standard procedures.

Animals↗

Vagus nerve stimulation for epilepsy: randomized comparison of three stimulation paradigms.

Vagus nerve stimulation (VNS) is an effective adjunctive treatment for intractable epilepsy. However, the optimal range of device duty-cycles [on/(on + off times)] is poorly understood. The authors performed a multicenter, randomized trial of three unique modes of VNS, which varied primarily by duty-cycle. The results indicate that the three duty-cycles were equally effective. The data support the use of standard duty-cycles as initial therapy.

Cough↗

Measurement of the Michel parameter rho in muon decay.

The TWIST Collaboration has measured the Michel parameter rho in normal muon decay, mu(+)--> e(+)nu(e)nu (mu). In the standard model, rho = 3/4. Deviations from this value imply mixing of left- and right-handed muon and electron couplings. We find rho=0.750 80+/-0.000 32(stat) +/- 0.000 97(syst) +/- 0.000 23, where the last uncertainty represents the dependence of rho on the Michel parameter eta. This result sets new limits on the W(L)-W(R) mixing angle in left-right symmetric models.

Journal Article↗

Outcome of fetal pyelectasis diagnosed antenatally.

UNLABELLED: Renal pelvis dilatation is a common anomaly detected at the 20-week anomaly scan. The aim of this study was to evaluate the postnatal outcome of fetal pyelectasis in an unselected obstetric population. This was a retrospective study of fetal pyelectasis detected at midtrimester anomaly scan. Fetal pyelectasis was classified as mild if the anteroposterior renal pelvis diameter measured >5 mm-< or= 7 mm, moderate >7-< or = 10 mm and severe as >10 mm. Persistant fetal pyelectasis was defined as >7 mm in the third trimester. RESULTS: During the study period fetal pyelectasis was identified in 74 women. 6 were excluded, as case records were not available. Mild pyelectasis was identified in 38/67(56.7%), moderate pyelectasis in 20/67(29.8%) and severe pyelectasis in 9/67(13.4%). None of the infants in the mild pyelectasis subgroup required surgery. 3/29(10%) in the moderate and severe pyelectasis subgroup required postnatal surgery. Of the 38 with mild fetal pyelectasis 13.1% had a positive postnatal diagnosis out of which 7.9% had vesico-ureteric reflux, 2.6% renal dysplasia and 2.6% pelvi-ureteric junction (PUJ) stenoses. CONCLUSION: 74% of pregnancies in the mild pyelectasis subgroup demonstrated spontaneous resolution. However persistent mild pyelectasis may lead to postnatal morbidity and should be followed up.

Adult↗

An initial investigation of spinal mechanisms underlying pain enhancement induced by fractalkine, a neuronally released chemokine.

Fractalkine is a chemokine that is tethered to the extracellular surface of neurons. Fractalkine can be released, forming a diffusible signal. Spinal fractalkine (CX3CL1) is expressed by sensory afferents and intrinsic neurons, whereas its receptor (CX3CR1) is predominantly expressed by microglia. Pain enhancement occurs in response both to intrathecally administered fractalkine and to spinal fractalkine endogenously released by peripheral neuropathy. The present experiments examine whether fractalkine-induced pain enhancement is altered by a microglial inhibitor (minocycline) and/or by antagonists/inhibitors of three putative glial products implicated in pain enhancement: interleukin-1 (IL1), interleukin-6 (IL6) and nitric oxide (NO). In addition, it extends a prior study that demonstrated that intrathecal fractalkine-induced mechanical allodynia is blocked by a neutralizing antibody to the rat fractalkine receptor, CX3CR1. Here, intrathecal anti-CX3CR1 also blocked fractalkine-induced thermal hyperalgesia. Furthermore, blockade of microglial activation with minocycline prevented both fractalkine-induced mechanical allodynia (von Frey test) and thermal hyperalgesia (Hargreaves test). Microglial activation appears to lead to the release of IL1, given that pretreatment with IL1 receptor antagonist blocked both fractalkine-induced mechanical allodynia and thermal hyperalgesia. IL1 is not the only proinflammatory cytokine implicated, as a neutralizing antibody to rat IL6 also blocked fractalkine-induced pain facilitation. Lastly, NO appears to be importantly involved, as l-NAME, a broad-spectrum NO synthase inhibitor, also blocked fractalkine-induced effects. Taken together, these data support that neuronally released fractalkine enhances pain via activation of spinal cord glia. Thus, fractalkine may be a neuron-to-glia signal triggering pain facilitation.

Animals↗

Reducing call-to-needle times: the critical role of pre-hospital thrombolysis.

BACKGROUND: Current guidelines recommend that patients with acute myocardial infarction should receive thrombolysis within 60 min of seeking professional help. AIM: To compare current rates of pre-hospital thrombolysis in Grampian with historical data, and assess the effect of pre-hospital thrombolysis on the proportion of patients achieving 'call-to-needle' times within national guidelines. DESIGN: Prospective audit. METHODS: Data were collected on all patients (n=535) admitted to the coronary care unit and thrombolysed, either in hospital or in the community from July 2000 to June 2002, using standardized forms. RESULTS: One hundred and thirty-three patients (25%) received pre-hospital thrombolysis and 402 (75%) received in-hospital thrombolysis. This compares with a 19% (195/1046) pre-hospital thrombolysis rate in the mid-1990s (p=0.005). Median 'call-to-needle' times were 45 min for pre-hospital thrombolysis and 105 min for patients who received in-hospital thrombolysis (p < 0.001). Only 24% (96/396) of patients receiving in-hospital thrombolysis were treated within the recommended guideline, vs. 79% (88/111) of pre-hospital thrombolysis patients (p <0.001). DISCUSSION: Pre-hospital thrombolysis rates in Grampian are increasing. Administration of thrombolysis in the community greatly increases the proportion of patients achieving a 'call-to-needle' time of 60 min, with a median time saving of approximately 1 h.

Acute Disease↗

Evidence that exogenous and endogenous fractalkine can induce spinal nociceptive facilitation in rats.

Recent evidence suggests that spinal cord glia can contribute to enhanced nociceptive responses. However, the signals that cause glial activation are unknown. Fractalkine (CX3C ligand-1; CX3CL1) is a unique chemokine expressed on the extracellular surface of spinal neurons and spinal sensory afferents. In the dorsal spinal cord, fractalkine receptors are primarily expressed by microglia. As fractalkine can be released from neurons upon strong activation, it has previously been suggested to be a neuron-to-glial signal that induces glial activation. The present series of experiments provide an initial investigation of the spinal pain modulatory effects of fractalkine. Intrathecal fractalkine produced dose-dependent mechanical allodynia and thermal hyperalgesia. In addition, a single injection of fractalkine receptor antagonist (neutralizing antibody against rat CX3C receptor-1; CX3CR1) delayed the development of mechanical allodynia and/or thermal hyperalgesia in two neuropathic pain models: chronic constriction injury (CCI) and sciatic inflammatory neuropathy. Intriguingly, anti-CX3CR1 reduced nociceptive responses when administered 5-7 days after CCI, suggesting that prolonged release of fractalkine may contribute to the maintenance of neuropathic pain. Taken together, these initial investigations of spinal fractalkine effects suggest that exogenous and endogenous fractalkine are involved in spinal sensitization, including that induced by peripheral neuropathy.

Animals↗

Comparative analyses of multi-species sequences from targeted genomic regions.

The systematic comparison of genomic sequences from different organisms represents a central focus of contemporary genome analysis. Comparative analyses of vertebrate sequences can identify coding and conserved non-coding regions, including regulatory elements, and provide insight into the forces that have rendered modern-day genomes. As a complement to whole-genome sequencing efforts, we are sequencing and comparing targeted genomic regions in multiple, evolutionarily diverse vertebrates. Here we report the generation and analysis of over 12 megabases (Mb) of sequence from 12 species, all derived from the genomic region orthologous to a segment of about 1.8 Mb on human chromosome 7 containing ten genes, including the gene mutated in cystic fibrosis. These sequences show conservation reflecting both functional constraints and the neutral mutational events that shaped this genomic region. In particular, we identify substantial numbers of conserved non-coding segments beyond those previously identified experimentally, most of which are not detectable by pair-wise sequence comparisons alone. Analysis of transposable element insertions highlights the variation in genome dynamics among these species and confirms the placement of rodents as a sister group to the primates.

Animals↗

Possible benefit of intravenous immunoglobulin therapy in a lung transplant recipient with West Nile virus encephalitis.

During the summer of 2000, a countrywide epidemic of West Nile fever (WNF) occurred in Israel, with 417 confirmed cases and 35 deaths. Immunosuppressed patients had a 31% case-fatality rate, which was significantly higher compared to non-immunosuppressed patients (13%). We describe a 42-year-old male lung-transplant recipient with serologically confirmed West Nile virus (WNV) encephalitis and deteriorating level of consciousness. He was treated with 0.4 g/kg intravenous immunoglobulin preparation from Israeli donors that contained a high titer of anti-WNV antibodies (1 : 1600). The patient showed rapid improvement within 24 h and complete disappearance of signs and symptoms within 48 h. This is the second case of an immunosuppressed patient responding to the same preparation of intravenous immunoglobulins. Larger studies are required in order to establish the therapeutic role of immunoglobulins in patients with WNF.

Adult↗

Reactive carbonyl formation by oxidative and non-oxidative pathways.

The spectrophotometric protein carbonyl assay is used as an indicator of protein damage by free radical reactions in vitro and in a variety of pathologies. We investigated model proteins and a variety of oxidative and non-oxidative reactions, as well as what effects hemoglobin, myoglobin, and cytochrome c might have on levels of protein carbonyls. We show that oxidative as well as non-oxidative mechanisms introduce carbonyl groups into proteins, providing a moiety for quantification with 2,4-dinitrophenylhydrazine (DNPH). Bovine serum albumin exposed to oxidative scenarios, such as hypochlorous acid, peroxynitrite, and metal-catalyzed oxidation exhibited variable, but increased levels of carbonyls. Other non-oxidative modification systems, in which proteins are incubated with various aldehydes, such as malondialdehyde, acrolein, glycolaldehyde, and glyoxal also generated significant amounts of carbonyls. Furthermore, purified myoglobin, hemoglobin, and cytochrome c show high absorbance at the same wavelengths as DNPH. The high levels observed are due to the innate absorbance of hemoglobin, myoglobin, and cytochrome c near the assay spectra of DNPH. These studies show that carbonyl content could be due to oxidative as well as non-oxidative mechanisms and that heme-containing compounds may effect carbonyl quantification.

Aldehydes↗