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David Bevan

Publications and source records attributed to David Bevan.

14 recordsLinked to original sources

A protective contribution of the Q allele of the R353Q polymorphism of the Factor VII gene in individuals with chronic stable angina?

BACKGROUND: Factor VII polymorphisms have been suggested in some studies to show an association with some aspects of coronary disease, and there is a known association between FVII levels and polymorphic variants in the gene. The aim of the study was to assess whether Factor VII polymorphism R353Q is associated with the extent of coronary artery disease in patients with chronic stable angina. METHODS AND RESULTS: There is evidence that Factor VII polymorphisms are markers of susceptibility to coronary artery disease (CAD), but two studies have suggested that there is no association between the degree of vessel disease and these polymorphisms. One of these studies did not exclude patients with unstable angina or MI. We therefore set up a prospective cohort study to determine Factor VIIa, VIIc and VIIAg levels, genotype for R353Q, lipid status, smoking history and the degree of vessel disease, in patients attending the hospital for routine day case angiography over a 20 month period. From 519 cases, 400 had no previous MI or revascularisation, including 153 with zero vessel disease, and were successfully genotyped: 9 (2%) QQ, 78 (20%) RQ and 313 (78%) RR. Compared with RR subjects, heterozygotes were 2.7 years older (95% CI: 0.3, 5.0; p=0.027), but were not significantly different regarding gender, cholesterol, extent of vessel disease or smoking history. If those with vessel disease were considered, then the heterozygotes were 3.5 years older than the RR homozygotes (95% CI: 0.6-6.4, p=0.016). There was a significant association between all measures of Factor VII and the R353Q polymorphism, with the Q allele associating with lower levels. There was no significant association between the degree of vessel disease and genotype. CONCLUSIONS: The degree of vessel disease as seen at day case angiography is independent of polymorphism status, but there appears nonetheless to be a moderate protective effect of the Q allele against stable angina, in that angiographic investigation occurs a few years later for RQ heterozygotes than RR homozygotes. The effect may be mediated by reduced levels of Factor VII.

Alleles↗

Functional genomic analysis of Arabidopsis thaliana glycoside hydrolase family 1.

In plants, Glycoside Hydrolase (GH) Family 1 beta -glycosidases are believed to play important roles in many diverse processes including chemical defense against herbivory, lignification, hydrolysis of cell wall-derived oligosaccharides during germination, and control of active phytohormone levels. Completion of the Arabidopsis thaliana genome sequencing project has enabled us, for the first time, to determine the total number of Family 1 members in a higher plant. Reiterative database searches revealed a multigene family of 48 members that includes eight probable pseudogenes. Manual reannotation and analysis of the entire family were undertaken to rectify existing misannotations and identify phylogenetic relationships among family members. Forty-seven members (designated BGLU1 through BGLU47 ) share a common evolutionary origin and were subdivided into approximately 10 subfamilies based on phylogenetic analysis and consideration of intron-exon organizations. The forty-eighth member of this family ( At3g06510; sfr2 ) is a beta -glucosidase-like gene that belongs to a distinct lineage. Information pertaining to expression patterns and potential functions of Arabidopsis GH Family 1 members is presented. To determine the biological function of all family members, we intend to investigate the substrate specificity of each mature hydrolase after its heterologous expression in the Pichia pastoris expression system. To test the validity of this approach, the BGLU44 -encoded hydrolase was expressed in P. pastoris and purified to homogeneity. When tested against a wide range of natural and synthetic substrates, this enzyme showed a preference for beta -mannosides including 1,4- beta -D-mannooligosaccharides, suggesting that it may be involved in A. thaliana in degradation of mannans, galactomannans, or glucogalactomannans. Supporting this notion, BGLU44 shared high sequence identity and similar gene organization with tomato endosperm beta -mannosidase and barley seed beta -glucosidase/ beta -mannosidase BGQ60.

Arabidopsis↗

Understanding the causes of problematic pain management in sickle cell disease: evidence that pseudoaddiction plays a more important role than genuine analgesic dependence.

Treatment of painful episodes in sickle cell disease (SCD) is sometimes complicated by disputes between patients and staff and patient behaviors that raise concerns about analgesic misuse. Those concern-raising behaviors could indicate either drug seeking caused by analgesic dependence or pseudoaddiction caused by undertreatment of pain. To make a systematic assessment of concern-raising behaviors and examine their associations with other factors, including DSM-IV symptoms of substance dependence, individual, in-depth interviews with SCD patients were conducted to apply pre-established criteria for concern-raising behaviors. These included disputes with staff tampering with analgesic delivery systems, passing prescribed analgesics from one person to another, being suspected or accused of analgesic misuse, self-discharging from hospital, obtaining analgesic prescriptions from multiple sources, using illicit drugs, and injecting analgesics. Assessments were also made of pain-related symptoms of substance dependence (where behaviors resemble substance dependence but reflect attempts to manage pain, increasing the risk of pseudoaddiction), non-pain-related symptoms of substance dependence (where substance dependence reflects analgesic use beyond pain management), and pain coping strategies (using the Pain Coping Strategies Questionnaire). Inter-rater reliability for the assessment of concern-raising behaviors was high, with Kappa coefficients of 0.63 to 1.0. The most frequent concern-raising behaviors were disputes with staff about pain or analgesics. The least frequent were tampering with analgesic delivery systems and passing analgesics between patients in hospital. The odds of concern-raising behaviors in hospital were raised eightfold by less use of ignoring pain as a coping strategy, and more than doubled by each additional pain-related symptom of substance dependence. Non-pain-related symptoms of substance dependence had no independent effect on concern-raising behaviors. Concern-raising behaviors were more closely associated with pain behaviors that make patients vulnerable to misperceptions of substance dependence than they were with genuine substance dependence. The results show how pseudoaddiction can adversely influence hospital pain management, and suggest that more emphasis should be placed on patients' pain and analgesic needs when responding to concern-raising behaviors in hospital.

Analgesics↗

Athenian echoes.

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Clinical Medicine↗

Infection control and anesthesia: lessons learned from the Toronto SARS outbreak.

PURPOSE: To describe the outbreak of severe acute respiratory syndrome (SARS) in Toronto, its impact on anesthesia practice and the infection control guidelines adopted to manage patients in the operating room (OR) and to provide emergency intubation outside the OR. CLINICAL FEATURES: The SARS outbreak in Toronto was the result of a single index patient. The causative virus, SARS-CoV, is moderately contagious, and is spread by droplets and contact. The virus gains access to host through the mucosa of the respiratory tract and the eyes. It can affect both healthy and compromised patients. The use of several precautionary measures such as goggles, gloves, gowns and facemasks and the application of various infection control strategies designed to minimize the spread of the virus are discussed. CONCLUSION: In containing the spread of SARS, vigilance and strict infection control are important. This results in the rediscovery of standards of infection control measures in daily anesthesia practice.

Aged↗

Pain management and symptoms of substance dependence among patients with sickle cell disease.

Concerns about dependence on prescribed analgesia may compromise pain management, but there was previously little reliable evidence about substance dependence among patients with sickle cell disease (SCD). We conducted in-depth, semi-structured interviews with SCD patients in London, UK, to assess DSM-IV symptoms of substance dependence and abuse. Criteria were applied to differentiate between pain-related symptoms, which corresponded to the DSM-IV symptoms but involved analgesics used to control pain, and non-pain-related symptoms, which involved analgesic use beyond pain management. Pain-related symptoms are informative about how the pattern of recurrent acute pain in SCD may make patients vulnerable to perceptions of drug dependence. Non-pain-related symptoms are informative about more stringently defined dependence on analgesia in SCD. Inter-rater reliability was high, with mean Kappa coefficients of 0.67-0.88. The criteria could be used to assess analgesic dependence in other painful conditions. Pain-related symptoms were more frequent, accounting for 88% of all symptoms reported. When pain-related symptoms were included in the assessment, 31% of the sample met the DSM-IV criteria for substance dependence, compared with only 2% when the assessment was restricted to non-pain-related symptoms. Qualitative analysis of participants' descriptions of analgesic use showed that active coping attempts (attempts to anticipate pain and avoid hospital admissions) and awareness of dependence were themes in descriptions of both pain-related and non-pain-related symptoms. Seeking a more normal lifestyle and impaired activities were themes associated with pain-related symptoms. Psychological disturbance was a theme associated with non-pain-related symptoms. The implications are for more responsive treatment of pain in SCD and greater awareness of how patients' pain coping may be perceived as analgesic dependence. Further research could examine ways that pain-related and non-pain-related symptoms of dependence may be associated with other pain coping strategies and with the outcomes of treatment for painful episodes in hospital.

Adult↗

Analgesic addiction and pseudoaddiction in painful chronic illness.

OBJECTIVES: Research is needed to enable more effective assessment and treatment of analgesic addiction among patients with painful chronic illnesses and to improve our understanding of the staff-patient interactions that give rise to pseudoaddiction. This study tested predictions that certain drug-use behaviors and pain-coping strategies were associated with analgesic addiction, and that certain were associated with risk of pseudoaddiction. METHODS: Analgesic addiction and risk of pseudoaddiction among patients with sickle cell disease were measured by symptom counts, using an interview method for classifying symptoms as pain-related (pseudoaddiction) or non-pain-related (analgesic addiction). Concern-raising drug-use behaviors and treatment requirements for pain were also assessed, and participants completed the pain-coping strategies questionnaire. Qualitative case descriptions of patients meeting criteria for analgesic addiction and pseudoaddiction were examined to identify common and distinctive features of the two groups. RESULTS: Consistent with predictions, multiple regression analyses showed that disputes about analgesics were independently associated with risk of pseudoaddiction. Physiological dependence and illicit drug use were both associated with analgesic addiction, independently of other factors. The qualitative data showed that analgesic addiction was not an obvious, clear-cut phenomenon: addiction and pseudoaddiction were superficially similar, and even symptoms of genuine addiction originated in patients' experiences of pain and illness. CONCLUSIONS: These tentative findings were broadly consistent with what is known about analgesic addiction and pseudoaddiction in other painful conditions. They also suggested that current recommendations about addiction in pain patients could understate the potential importance of physiological dependence. The findings could inform staff training programs to improve pain management and reduce the incidence of pseudoaddiction. The classification of pain-related and non-pain-related symptoms could be used in further research on the development of analgesic addiction and the factors that influence staff attributions about addiction in patients with pain.

Adult↗