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Biomedical subjects

M Kirk

Publications and source records attributed to M Kirk.

At least 37 records · Page 2Linked to original sources

Isoflavonoids and chronic disease: mechanisms of action.

Soy and its isoflavones are associated with a reduced risk of chronic disease. The mechanisms of action of isoflavones include their roles as weak estrogens, inhibitors of tyrosine kinase-dependent signal transduction processes and as cellular antioxidants. Although estrogen receptor beta binds genistein with an affinity close to that of 17beta-estradiol, it remains to be determined whether it is a mediator of genistein's activity in vivo. Genistein's inhibition of protein tyrosine kinases is not limited to direct effect on these kinases, but may result from alteration in kinase expression. Genistein is not a particularly good scavanger of cellular oxidants; however, it reacts vigorously with the prooxidant hypochlorous acid, produced by neutrophils as part of the inflammatory response. The chlorinated isoflavones may have altered biochemical and biological effects compared to their parent compounds and may provide increased protection against inflammatory disease.

Animals↗

Predicting PTSD symptoms in victims of violent crime: the role of shame, anger, and childhood abuse.

To examine the role of cognitive-affective appraisals and childhood abuse as predictors of crime-related posttraumatic stress disorder (PTSD) symptoms, 157 victims of violent crime were interviewed within 1 month post-crime and 6 months later. Measures within 1 month post-crime included previous physical and sexual abuse in childhood and responses to the current crime, including shame and anger with self and others. When all variables were considered together, shame and anger with others were the only independent predictors of PTSD symptoms at 1 month, and shame was the only independent predictor of PTSD symptoms at 6 months when 1-month symptoms were controlled. The results suggest that both shame and anger play an important role in the phenomenology of crime-related PTSD and that shame makes a contribution to the subsequent course of symptoms. The findings are also consistent with previous evidence for the role of shame as a mediator between childhood abuse and adult psychopathology.

Adolescent↗

Indigenous women's perceptions of breast cancer diagnosis and treatment in Queensland.

OBJECTIVE: To identify social, structural and personal factors among indigenous women in Queensland associated with the detection of breast cancer, and the treatment and post-treatment care and support of cancer. METHODS: Qualitative research including interviews, case studies and focus group discussions were conducted, among Aboriginal women and service providers in urban, rural and remote areas of Queensland over nine months in 1998/99. RESULTS: A range of factors were identified as influencing women's willingness to perform BSE, receive screening mammograms, and receive and complete treatment compared to the non-indigenous population. Personal history of health services, provision of information about mammography, the cost of treatment and care, and availability of personal support, all influenced women's willingness to access services and maintain treatment. Indigenous women in Queensland experience various barriers to effective and appropriate detection, treatment and care of breast cancer. CONCLUSION: Barriers to diagnosis, treatment and care can be addressed by increasing women's awareness of breast cancer and the benefits of preventative health behaviour, and improving the quality and appropriateness of health care and counselling services for Indigenous women and their families. IMPLICATIONS: Indigenous women's knowledge and practice relating to the early diagnosis and prevention of breast cancer may improve through outreach work with women, to encourage their confidence in preventative health. Women's commitment to preventive health will also be enhanced by improved quality and access to health care, and improved relationships between practitioners and patients.

Adult↗

How well does a telephone questionnaire measure drinking water intake?

BACKGROUND: Few studies have assessed the validity or reliability of drinking water intake estimations. In studies investigating potential waterborne disease, this is very important. METHODS: We carried out a validity and reliability study to evaluate water intake estimations. The validity part of the study compared a telephone questionnaire to a diary. The reliability part of the study compared two telephone questionnaires. RESULTS: 253 participants were recruited. The most commonly consumed water intake categories were plain and boiled tap water. For persons aged less than 12 years, the median volume of plain water consumption was 2.9 glasses/day according to the diary. For persons aged 12 years and over, the median volume of plain water consumption was 3.0 glasses/day and for boiled water 3.0 glasses/day according to the diary. There was negligible systematic over or under reporting by participants for the telephone questionnaire in comparison to the diary and for the comparison of both telephone questionnaires. Water intake estimates were converted to categorical variables and the per cent agreement and weighted kappa statistics were calculated. For both the validity and reliability parts of the study the per cent agreement was 57-78% and the weighted kappa was 0.57-0.81. CONCLUSION: Water intake estimates show only moderate levels of validity and reliability when using a telephone questionnaire in comparison to a diary. IMPLICATIONS: Investigators of potential waterborne disease or nutritional research should exercise some caution in drawing conclusions from minor differences in drinking water intake that are obtained from a telephone questionnaire.

Adolescent↗

Genetics, ethics and education: considering the issues for nurses and midwives.

The rapid advances and scope of the Human Genome Project bring into sharp focus the relevance of genetics and ethics for nursing and midwifery practice in the new millennium. This article offers a UK perspective on how education plays a crucial part in preparing practitioners to integrate clinical advances effectively and ethically, yet may be failing in this role. Provision for teaching genetics in the UK has been found to be largely inadequate and the ethical implications of this are reviewed. The context of genetics teaching is a further issue. Genetics is classified in the bioscience component of training courses in nearly 70% of UK nursing colleges; this may be of significance in its perceived relevance to practice. Finally, the ethical issues around the teaching of genetics will be discussed. Educators who are involved in delivering the genetics component of the curriculum are under an obligation to consider how learning is best achieved and how the delivery itself should be 'ethical'.

Curriculum↗

Chlorination and nitration of soy isoflavones.

Diets enriched in soy foods containing a high concentration of isoflavonoids are associated with a decrease in the incidence of several chronic inflammatory diseases. Studies with experimental models of diseases, such as atherosclerosis, suggest that these effects can be ascribed to the biological properties of the isoflavones. Since the isoflavones and tyrosine have structural similarities and modifications to tyrosine by inflammatory oxidants such as hypochlorous acid (HOCl) and peroxynitrite (ONOO(-)) have been recently recognized, we hypothesized that the isoflavones also react with HOCl and ONOO(-). Using an in vitro approach, we demonstrate in the present study that the isoflavones genistein, daidzein, and biochanin-A can be chlorinated and nitrated by these oxidants. These reactions were investigated using high-performance liquid chromatography, mass spectrometry, and nuclear magnetic resonance. In the reaction with HOCl, both mono- and dichlorinated derivatives of genistein and biochanin-A are formed, whereas with daidzein only a monochlorinated derivative was detected. The reaction between genistein or daidzein and ONOO(-) yielded a mononitrated product. However, no nitrated product was detected with biochanin-A. Furthermore, the reaction between genistein and sodium nitrite and HOCl yielded a chloronitrogenistein derivative, as well as a dichloronitrogenistein derivative. These results indicate that the ability of the isoflavones to react with these oxidant species depends on their structure and suggest that they could be formed under conditions where these reactive species are generated under pathological conditions.

Chromatography, High Pressure Liquid↗

[Complications in two children with acute lymphatic leukemia caused by vaccination against varicella zoster virus].

Complications in two varicella zoster virus (VZV) vaccinated children with leukemia in remission are reported. Case I presented with varicella on day 30 after vaccination, with a relapse on day 49 and development of zoster on day 70. VZV was detected in vesicles by PCR on days 49 and 70. Case II presented with varicella on day 32 after vaccination, and VZV was detected in vesicles and nasal secretion. The manifestations were mild and responded to treatment. PCR methods were directed toward the R5 and PS regions. The virus from the two children was unambiguously identified as the Oka vaccine strain. The majority of Danish field strains had only one copy of the 112 basepair repeat element in the R5 region, but two, four and presumably higher copy numbers were also seen. All Danish field strains had the Pst1 cleavage site in the PS region.

Chickenpox↗

Nitration of unsaturated fatty acids by nitric oxide-derived reactive species.

Reactions of linoleate (and presumably other unsaturated fatty acids) with reactive nitrogen species that form in biological systems from secondary reactions of .NO yield two main nitration product groups, LNO2 (formed by ONOO-, .NO2, or NO2+ reaction with linoleate), and LONO2 (formed by HONO reaction with 13(S)-HPODE, or .NO termination with LOO.). Comparison of HPLC retention times and m/z for lipid nitration products indicate that the mechanisms of nitrated product formation converge at several points: (i) The initial product of HONO attack on LOOH will be LOONO, which is identical to the initial termination product of LOO. reaction with .NO. (ii) Dissociation of LOONO to give LO. and .NO2 via caged radicals, which recombine to give LONO2 (m/z 340) will occur, regardless of how LOONO is formed (Fig. 7). (iii) In some experiments, the reaction of O2- (where oxidation is initiated by xanthine oxidase-derived O2- production and metal-dependent decomposition of H2O2) with .NO will result in generation of ONOO-. Nitration of unsaturated lipid by this species will yield a species demonstrated herein to be LNO2. Lipid oxidation leads to formation of bioactive products, including hydroxides, hydroperoxides, and isoprostanes. In vivo, nitrated lipids (LNO2, LONO2) may also possess bioactivity, for example through eicosanoid receptor binding activity, or by acting as antagonists/competitive inhibitors of eicosanoid receptor-ligand interactions. In addition, nitrated lipids could mediate signal transduction via direct .NO donation, transnitrosation, or following reductive metabolism. Similar bioactive products are formed following ONOO- reaction with glucose, glycerol, and other biomolecules.

Animals↗

Emergency department hazardous materials protocol for contaminated patients.

Emergency department handling and treatment of chemically contaminated patients can have potentially serious consequences. Medical staff can be exposed to hazardous chemicals through dermal contact or inhalation of volatile compounds or particulate matter. Exposure can result in symptomatic illness from either a direct chemical toxic effect or an odor-mediated psychologic response. Either situation can severely affect ED function and lead to facility evacuation. The Joint Commission on Accreditation of Healthcare Organizations standards and the Occupational Safety and Health Administration regulations for participation in community hazardous materials incident emergency response plans require hospital EDs to prepare for hazardous materials incidents. This study provides a template protocol for ED preparation for and treatment of patients exposed to hazardous materials.

Clinical Protocols↗

A randomized controlled trial of individual psychological debriefing for victims of violent crime.

BACKGROUND: It has been suggested that giving people the opportunity talk about a traumatic experience may prevent the development of later disorder. We tested the efficacy of two brief interventions, education and psychological debriefing, designed to prevent adverse psychological reactions to criminal victimization. METHODS: Individuals who had been the victims of a violent crime within the past month were written to and invited to take part in a study of their attitudes to crime and punishment: 2161 were contacted and 243 replied, of whom 157 were eligible and were randomly assigned either to an education condition, to a psychological debriefing plus education condition, or to an assessment only condition. Education involved providing information about normal post-traumatic reactions. Debriefing involved in-depth probing about events, thoughts and feelings experienced during the crime. Subjects were recruited from police and hospital sources and interviewed in their own homes: 138 were followed up at 6 months, and 92 at 11 months. RESULTS: Outcome was assessed using a DSM-III-R diagnosis of PTSD, the Post-traumatic Symptom Scale, the Impact of Event Scale and the Beck Depression Inventory. All groups improved over time but there were no between-group differences. CONCLUSIONS: No evidence was found to support the efficacy of brief one-session interventions for preventing post-traumatic symptoms in individual victims of violent crime.

Adolescent↗

Nitration of unsaturated fatty acids by nitric oxide-derived reactive nitrogen species peroxynitrite, nitrous acid, nitrogen dioxide, and nitronium ion.

Reactive nitrogen species derived from nitric oxide are potent oxidants formed during inflammation that can oxidize membrane and lipoprotein lipids in vivo. Herein, it is demonstrated that several of these species react with unsaturated fatty acid to yield nitrated oxidation products. Using HPLC coupled with both UV detection and electrospray ionization mass spectrometry, products of reaction of ONOO- with linoleic acid displayed mass/charge (m/z) characteristics of LNO2 (at least three products at m/z 324, negative ion mode). Further analysis by MS/MS gave a major fragment at m/z 46. Addition of a NO2 group was confirmed using [15N]ONOO- which gave a product at m/z 325, fragmenting to form a daughter ion at m/z 47. Formation of nitrated lipids was inhibited by bicarbonate, superoxide dismutase (SOD), and Fe3+-EDTA, while the yield of oxidation products was decreased by bicarbonate and SOD, but not by Fe3+-EDTA. Reaction of linoleic acid with both nitrogen dioxide (*NO2) or nitronium tetrafluoroborate (NO2BF4) also yielded nitrated lipid products (m/z 324), with HPLC retention times and MS/MS fragmentation patterns identical to the m/z 324 species formed by reaction of ONOO- with linoleic acid. Finally, reaction of HPODE, but not linoleate, with nitrous acid (HONO) or isobutyl nitrite (BuiONO) yielded a product at m/z 340, or 341 upon reacting with [15N]HONO. MS/MS analysis gave an NO2- fragment, and 15N NMR indicated that the product contained a nitro (RNO2) functional group, suggesting that the product was nitroepoxylinoleic acid [L(O)NO2]. This species could form via homolytic dissociation of LOONO to LO* and *NO2 and rearrangement of LO* to an epoxyallylic radical L(O)* followed by recombination of L(O)* with *NO2. Since unsaturated lipids of membranes and lipoproteins are critical targets of reactive oxygen and nitrogen species, these pathways lend insight into mechanisms for the formation of novel nitrogen-containing lipid products in vivo and provide synthetic strategies for further structural and functional studies.

Chromatography, High Pressure Liquid↗

Preparing for the future: the status of genetics education in diploma-level training courses for nurses in the UK.

This paper offers new information about genetics education provided by diploma level training programmes for nurses in the UK. Those responsible for the development and provision of curricula were asked to complete a questionnaire that attempted to assess the nature of genetics education and their attitudes towards it. The response rate was 84%. Whist genetics teaching is included on all but two training courses, variation in content, delivery and timetable allocation indicates disparity. Genetics is taught for 10 hours or less on most courses, utilizing a limited number of approaches. Most courses do not have compulsory assessment. The majority of respondents (81%) agreed that genetics will have a major impact on health care, and will become an increasingly important issue in education. A small majority (58%) agreed that genetics should have a higher profile in professional training yet many respondents (68%) felt that the teaching they were already offering was appropriate to meet patients' needs. In the absence of any clear national framework for delivery and assessment of genetics education, the author questions whether current training is sufficient to provide nurses with the basic genetic literacy needed to respond to developments in genetics as they impact on health care.

Clinical Competence↗

Acute stress disorder and posttraumatic stress disorder in victims of violent crime.

OBJECTIVE: In a group of crime victims recruited from the community, the authors investigated the ability of both a diagnosis of acute stress disorder and its component symptoms to predict posttraumatic stress disorder (PTSD) at 6 months. METHOD: A mixed-sex group of 157 victims of violent assaults were interviewed within 1 month of the crime. At 6-month follow-up 88% were reinterviewed by telephone and completed further assessments generating estimates of the prevalence of PTSD. RESULTS: The rate of acute stress disorder was 19%, and the rate of subsequent PTSD was 20%. Symptom clusters based on the DSM-IV criteria for acute stress disorder were moderately strongly interrelated. All symptom clusters predicted subsequent PTSD, but not as well as an overall diagnosis of acute stress disorder, which correctly classified 83% of the group. Similar predictive power could be achieved by classifying the group according to the presence or absence of at least three reexperiencing or arousal symptoms. Logistic regression indicated that both a diagnosis of acute stress disorder and high levels of reexperiencing or arousal symptoms made independent contributions to predicting PTSD. CONCLUSIONS: This exploratory study provides evidence for the internal coherence of the new acute stress disorder diagnosis and for the symptom thresholds proposed in DSM-IV. As predicted, acute stress disorder was a strong predictor of later PTSD, but similar predictive power may be possible by using simpler criteria.

Acute Disease↗

Nitrosation of uric acid by peroxynitrite. Formation of a vasoactive nitric oxide donor.

Peroxynitrite (ONOO-), formed by the reaction between nitric oxide (. NO) and superoxide, has been implicated in the etiology of numerous disease processes. Low molecular weight antioxidants, including uric acid, may minimize ONOO---mediated damage to tissues. The tissue-sparing effects of uric acid are typically attributed to oxidant scavenging; however, little attention has been paid to the biology of the reaction products. In this study, a previously unidentified uric acid derivative was detected in ONOO--treated human plasma. The product of the uric acid/ONOO- reaction resulted in endothelium-independent vasorelaxation of rat thoracic aorta, with an EC50 value in the range of 0.03-0.3 microM. Oxyhemoglobin, a .NO scavenger, completely attenuated detectable .NO release and vascular relaxation. Uric acid plus decomposed ONOO- neither released .NO nor altered vascular reactivity. Electrochemical quantification of .NO confirmed that the uric acid/ONOO- reaction resulted in spontaneous (thiol-independent) and protracted (t1/2 approximately 125 min) release of .NO. Mass spectroscopic analysis indicated that the product was a nitrated uric acid derivative. The uric acid nitration/nitrosation product may play a pivotal role in human pathophysiology by releasing .NO, which could decrease vascular tone, increase tissue blood flow, and thereby constitute a role for uric acid not previously described.

Animals↗

Chemical modification of isoflavones in soyfoods during cooking and processing.

The principal chemical forms of isoflavones in soybean are their 6''-O-malonyl-beta-glucoside (6OMalGlc) conjugates. Experiments were carried out to determine the best conditions for extraction of isoflavones from soyfoods and the effects of commercial processing procedures and of cooking on isoflavone concentrations and composition. Hot alcohol extraction of ground soybeans deesterified 6OMalGlc conjugates. Although room temperature extraction slowed the conversion, extraction at 4 degrees C for 2-4 h led to the highest yield of 6OMalGlc conjugates and the lowest proportion of beta-glucoside conjugates. Analysis of soyfood products by reversed-phase HPLC-mass spectrometry revealed that defatted soy flour that had not been heat treated consisted mostly of 6OMalGlc conjugates; in contrast, toasted soy flour contained large amounts of 6''-O-acetyl-beta-glucoside conjugates, formed by heat-induced decarboxylation of the malonate group to acetate. Soymilk and tofu consisted almost entirely of beta-glucoside conjugates; low-fat versions of these products were markedly depleted in isoflavones. Alcohol-washed soy-protein concentrates contained few isoflavones. Isolated soy protein and textured vegetable protein consisted of a mixture of all 3 types of isoflavone conjugates. Baking or frying of textured vegetable protein at 190 degrees C and baking of soy flour in cookies did not alter total isoflavone content, but there was a steady increase in beta-glucoside conjugates at the expense of 6OMalGlc conjugates. The chemical form of isoflavones in foods should be taken into consideration when evaluating their availability for absorption from the diet.

Chromatography, High Pressure Liquid↗