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Biomedical subjects

M Gunn

Publications and source records attributed to M Gunn.

At least 19 recordsLinked to original sources

Self-harm, capacity, and refusal of treatment: implications for emergency medical practice. A prospective observational study.

OBJECTIVES: In the context of increasing attention to the rights of adults to make treatment decisions for themselves, this study investigated, among patients who have engaged in self-harm (i) the extent of valid decision making; (ii) the impact of mental disorders; and (iii) the effect of systematically providing relevant clinical information. DESIGN: A prospective observational study. SETTING: The emergency department of a large teaching hospital in southeast England. PARTICIPANTS: Seventy one adult men and women who had presented for treatment following self-harm. MAIN OUTCOME MEASURES: Semi-structured interviews were used to make clinical judgements about participants' capacity to consent before, and following, the presentation of simple written information about the proposed treatment(s). Demographic data, and data about mental disorder and alcohol misuse, were also collected. RESULTS: Based on accepted legal criteria, only 28/71 (39.4%) of the patients were judged to have capacity to consent to the proposed intervention(s) initially. However, the number of patients judged to have capacity improved significantly (p<0.001) after the presentation of written information, to 45/71 (63.4%). Those judged incapable were significantly more likely (p<0.01) to refuse treatment. Continuing incapacity was significantly associated only with cognitive impairment (p<0.001) and/or severe psychiatric disturbance (p<0.01). CONCLUSIONS: Consistent with current views, capacity is not static, even among patients who have engaged in self-harm, but can be improved through a simple intervention. The findings are consistent with recent guidance about supporting this vulnerable group of patients, many of whom are ambivalent about treatment.

Adult↗

Prion protein (PrP) gene polymorphisms associated with natural scrapie cases and their flock-mates in Ireland.

The PrP genotypes associated with natural scrapie in Ireland were determined and a comparison was made between genotypes found in scrapie-infected sheep and those found in healthy animals from scrapie-infected flocks. Seven PrP genotypes were identified in scrapie-infected animals: VV(136)RR(154)QQ(171),VA(136)RR(154)QQ(171),VA(136)RR(154)QR(171),VA(136)RR(154)QH(171),AA(136)RR(154)QQ(171),AA(136)RR(154)QH(171) and AA(136)RR(154)HH(171). Of 11 scrapie-infected flocks, 15 genotypes were identified in the healthy flock-mates. The genotypes identified in scrapie-affected animals were also all identified in healthy flock-mates. In 9 of the 11 flocks studied, the genotype frequencies among scrapie-infected animals were significantly different from those among healthy flock-mates. The results show that there is a significant risk of developing the clinical signs of scrapie associated with particular PrP genotypes in the Irish sheep population. The association between the V(136)R(154)Q(171) allele and scrapie was evident, as was the association between A(136)R(154)R(171) and resistance to developing the clinical signs of scrapie. The presence of the A(136)H(154)Q(171) allele in the flocks examined resulted in a decreased risk of developing scrapie compared to the presence of the A(136)R(154)Q(171).

Alleles↗

A mass in the liver.

We report a case of alveolar echinococcosis. To our knowledge this is the first report of human alveolar echinococcosis to be confirmed in the UK and if contracted in Afghanistan the first report for that country.

Afghanistan↗

A family of closely related bovine viral diarrhea virus recombinants identified in an animal suffering from mucosal disease: new insights into the development of a lethal disease in cattle.

Induction of lethal mucosal disease (MD) in cattle is linked to the generation of cytopathogenic (cp) bovine viral diarrhea virus (BVDV) in animals persistently infected with a noncytopathogenic BVDV. In most cases the cp variants are generated by recombination with cellular or viral sequences. BVDV was obtained from the serum of an MD animal and propagated in tissue culture without plaque purification. Analysis of cDNA clones established from RNA of these cells showed that apparently a variety of different viral RNAs were present. Seven of the cDNA clones contained a cellular sequence coding for light chain 3 (LC3) of microtubule-associated proteins 1A and 1B. This insertion had already been found in the cp virus JaCP obtained from the same animal and isolated by plaque purification. Analysis of further plaque-purified cp viruses showed that the diseased animal contained a family of closely related cp BVDV recombinants. A set of viruses with different duplications of viral sequences in their genomes and a variety of defective viral RNAs with deletions were found that all contained the LC3* insertion. For all the recombinants the 3' recombination sites and, in all but one case, also the 5' recombination sites between cellular and viral sequence were identical. Variation between the individual deduced genome structures resulted from different duplications or deletions of viral sequences located upstream of the cellular insertion. These results suggest that within the animal a primary recombinant with a genome containing the LC3* insertion was generated. In a trimming process a set of secondary virus recombinants was generated from this hypothetical primary recombined RNA. These secondary recombinants display genome structures that represent variations of the basic scheme already present in the primary recombinant. Apparently this trimming process that finally led to an outbreak of MD lasted a long time since recombined RNA with the basic genome structure of the cp viruses could be demonstrated in samples already taken a long time before outbreak of the disease.

Animals↗

A rapid and sensitive PCR-based diagnostic assay to detect bovine herpesvirus 1 in routine diagnostic submissions.

We describe a rapid, sensitive and specific polymerase chain reaction (PCR) assay for the detection of BHV1 DNA in a range of routine diagnostic submissions without the need for prior virus isolation. The assay, which is based on the selected amplification of a portion of the viral tk gene, detected both BHV1.1 and BHV1.2 subtypes in a panel of 15 characterised field isolates, and its sensitivity was estimated to be <0.125 TCID(50). BHV2, alcephaline herpesvirus, BHV4, equine herpesvirus 1 (EHV1), EHV4 and pseudorabies virus were not detected confirming the specificity of the assay. One hundred and five diagnostic submissions, including tissues, nasal secretions and nasal swabs were taken from cattle with respiratory disease and tested using the routine methods of virus isolation (VI) and the fluorescent antibody test (FAT), and the results were compared with those obtained by PCR. The PCR assay detected BHV1 DNA in all samples that were positive by VI. BHV1 DNA was also detectable by PCR in raw and extended semen samples at a sensitivity of 1 TCID(50) per 50microl. The assay also detected BHV5, permitting differentiation between it and BHV1 by virtue of the size of the amplified PCR product. The PCR assay is more sensitive and independent of sample quality than either virus isolation or FAT, and it is faster than virus isolation. The sample preparation method is simple with few steps involved. There are no extra post-amplification blotting/hybridisation steps and the assay is not based on a nested PCR strategy that might otherwise exacerbate the problem of oversensitivity/contamination in the routine use of such a test in a diagnostic laboratory. This assay would permit discrimination between those animals naturally infected with wild type BHV1 and those vaccinated with tk-BHV1 strains.

Animals↗

The capacity of people with a 'mental disability' to make a health care decision.

BACKGROUND: Based on the developing clinical and legal literature, and using the framework adopted in draft legislation, capacity to make a valid decision about a clinically required blood test was investigated in three groups of people with a 'mental disability' (i.e. mental illness (chronic schizophrenia), 'learning disability' ('mental retardation', or intellectual or developmental disability), or, dementia) and a fourth, comparison group. METHODS: The three 'mental disability' groups (N = 20 in the 'learning disability' group, N = 21 in each of the other two groups) were recruited through the relevant local clinical services; and through a phlebotomy clinic for the 'general population' comparison group (N = 20). The decision-making task was progressively simplified by presenting the relevant information as separate elements and modifying the assessment of capacity so that responding became gradually less dependent on expressive verbal ability. RESULTS: Compared with the 'general population' group, capacity to make the particular decision was significantly more impaired in the 'learning disability' and 'dementia' groups. Importantly, however, it was not more impaired among the 'mental illness' group. All the groups benefited as the decision-making task was simplified, but at different stages. In each of the 'mental disability' groups, one participant benefited only when responding did not require any expensive verbal ability. CONCLUSIONS: Consistent with current views, capacity reflected an interaction between the decision-maker and the demands of the decision-making task. The findings have implications for the way in which decisions about health care interventions are sought from people with a 'mental disability'. The methodology may be extended to assess capacity to make other legally-significant decisions.

Adolescent↗

Significant association of cagA positive Helicobacter pylori strains with risk of premature myocardial infarction.

OBJECTIVE: To investigate whether genetic diversity of Helicobacter pylori influences its association with coronary heart disease, and specifically whether the risk is confined to infection with the more virulent strains bearing the cytotoxin associated gene-A (cagA) antigen. DESIGN AND SETTING: Case-control study in hospital admitting unselected patients with myocardial infarction. METHODS AND SUBJECTS: Serological status for cagA and H pylori were determined in 342 cases of acute myocardial infarction and 214 population based control subjects free of clinical coronary heart disease. RESULTS: 38.0% of cases and 30.8% of controls were cagA seropositive (odds ratio 1.38, 95% confidence interval (CI) 0.94 to 2.01, p = 0.08). In subjects < 65 years old (153 cases, 153 controls), cagA seropositivity was associated with a 1.80-fold increase (95% CI 1.07 to 3.03, p = 0.02) in myocardial infarction risk, which increased further to 2.25-fold (95% CI 1.12 to 4.53, p = 0.01) in subjects < 55 years. There was no significant association of cagA status with classical coronary heart disease risk factors. H pylori seropositivity was present in 60.2% of cases and 53.7% of controls (odds ratio 1.12, 95% CI 0.83 to 1.51, p = 0.43). H pylori seropositivity was not increased in young cases and did not show any interaction with age. CONCLUSIONS: The association of chronic H pylori infection with risk of myocardial infarction appears to be restricted to cagA bearing strains. The association is age dependent and stronger in younger subjects. Genetic heterogeneity of H pylori may explain some of the discordant findings with regard to the association of H pylori with coronary heart disease.

Aged↗

Insertion of a sequence encoding light chain 3 of microtubule-associated proteins 1A and 1B in a pestivirus genome: connection with virus cytopathogenicity and induction of lethal disease in cattle.

Pestiviruses represent the first RNA viruses for which recombination with cellular protein-coding sequences has been reported. As a result of such recombinations cytopathogenic (cp) pestiviruses can develop from noncytopathogenic (noncp) viruses. In the case of bovine viral diarrhea virus (BVDV), the generation of cp mutants is linked to the induction of the lethal syndrome mucosal disease (MD) in cattle. The cp BVDV JaCP was isolated from an animal which had come down with MD. The genome of JaCP contains a novel kind of cellular insertion (LC3*) which is flanked by duplicated pestivirus sequences. Neither insertion nor duplication is present in the genome of the accompanying noncp virus JaNCP. As part of the viral polyprotein, the insertion in the JaCP genome is translated into a polypeptide almost identical to a fragment of light chain 3, a subunit of the microtubule-associated proteins 1A and 1B from the rat. Transient-expression studies revealed that the LC3* sequence is able to induce an additional cleavage of the viral polyprotein. The respective cleavage occurs directly downstream of the LC3*-encoded sequence and is not dependent on the NS3 serine protease. Insertion of LC3* into an infectious noncp pestivirus cDNA clone without duplicated viral sequences resulted in recovery of a defective cp virus able to replicate only in the presence of a noncp helper virus. In contrast, introduction of both insertion and duplication led to an autonomously replicating cp virus.

Amino Acid Sequence↗

Establishment of serial persistent infections with bovine viral diarrhoea virus in cattle and sheep and changes in epitope expression related to host species.

A pestivirus was transmitted by contact from a persistently infected (P.I.) bullock to pregnant sheep. This resulted in the birth of P.I. lambs, one of which in turn was able to transmit virus by contact to pregnant cattle. Two of these animals gave birth to P.I. calves, from one of which the virus was again transmitted by contact with pregnant sheep, leading to another generation of P.I. lambs. The expression of one or more epitopes on the E2 glycoprotein of the viruses isolated from this series of alternate cattle-sheep transmissions appeared to depend on the host species. Thus, several monoclonal antibodies which bound strongly to, and neutralised, viruses isolated from the bovine hosts, failed to bind or neutralise in the case of sheep isolates. The viral consensus sequences of the E2 gene as well as parts of the 5' untranslated region and of the Npro and capsid genes were compared between the different isolates. This revealed a high degree of genetic stability. However, a single codon change at amino acid position 9 of the E2 gene correlated with and was able to cause the loss of particular epitopes.

Animals↗

A fine edge.

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Continuity of Patient Care↗

A truncated form of fibroblast growth factor receptor 1 inhibits signal transduction by multiple types of fibroblast growth factor receptor.

A truncated form of the type 1 fibroblast growth factor receptor (FGFR1) lacking most of its cytoplasmic domain was tested for its ability to inhibit signal transduction by each of three different wild-type FGFRs (FGFR1, 2, and 3). When the truncated FGFR1 was expressed in Xenopus oocytes in excess of each wild-type FGFR, mobilization of intracellular calcium mediated by the wild-type FGFRs was completely blocked. The truncated FGFR did not inhibit signal transduction by the co-expressed platelet-derived growth factor beta-receptor. A form of truncated FGFR1 which lacked the first immunoglobulin-like domain also inhibited signal transduction by wild-type FGFRs. Truncated FGFR formed complexes with wild-type FGFR in the presence of basic FGF in intact cells. These observations were consistent with the hypothesis that the truncated FGFR interacted with wild-type FGFRs to form nonfunctional heterodimers, thus eliminating the signaling by the wild-type FGFRs. The observation that signaling by multiple types of FGFR can be blocked by a single type of truncated FGFR suggests that the different types of FGFR can interact with each other in ligand-mediated complexes. These findings provide a molecular basis for inhibiting the actions of FGFs in vivo.

Animals↗

Comparative analysis of monoclonal antibodies against pestiviruses: report of an international workshop.

Thirty-three pestivirus strains were grown in cell culture and characterized by immunostaining with 19 monoclonal antibodies (MAbs) raised against hog cholera virus (HCV), with 42 MAbs against bovine viral diarrhoea virus (BVDV) and with 13 MAbs against border disease virus (BDV). Seven MAbs reacted with all pestivirus strains tested, eight MAbs detected only the seven HCV strains, three detected only the 16 BVDV strains. No MAb was found that was specific for BDV. BVDV and BDV strains were broadly cross-reactive with the MAbs, indicating a close relationship between these two species, whereas HCV strains were characterized as distinct from BVDV and BDV.

Animals↗