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1.
Br J Dermatol ; 180(6): 1377-1389, 2019 06.
Article in English | MEDLINE | ID: mdl-30501016

ABSTRACT

BACKGROUND: Living with alopecia areata (AA) totalis and universalis (collectively referred to here as AA) involves unpredictable, sometimes rapid hair loss. There is currently no effective treatment and patients describe feelings of shock, loss, trauma and disrupted identity. Cultural meanings attached to hair and hair loss, including associations between hair and femininity, and hair loss and cancer may exacerbate distress. Consequently, wigs and make-up are frequently used as camouflage, but this can produce feelings of inauthenticity, shame and anxiety. OBJECTIVES: This article explores how meanings associated with hair and hair loss influence experiences of living with AA. We also aim to identify how this understanding might inform practice by healthcare professionals to best support patients to cope with the condition. METHODS: A total of 95 participants with AA completed an online qualitative survey about their experiences of living with the condition. Data were subjected to thematic analysis within a critical realist theoretical framework. RESULTS: The following four themes were identified: (i) It's (not) only hair; (ii) A restricted life; (iii) Abandon hope all ye who lose their hair and (iv) Seeking support in 'a highly personal journey'. CONCLUSIONS: Findings suggest that negative cultural meanings of hair and hair loss are pervasive and may drive social avoidance and camouflage behaviours in people with AA. Normalizing social interactions with healthcare practitioners, significant others and peers were cited as pivotal to positive adjustment. Support groups and online forums were highly valued particularly as few had been offered specialist psychological support. Future research should develop and evaluate psychological support in order to address the specific challenges of living with AA.


Subject(s)
Adaptation, Psychological/physiology , Alopecia Areata/psychology , Activities of Daily Living , Adolescent , Adult , Aged , Attitude to Health , Emotions , Female , Hope/physiology , Humans , Interpersonal Relations , Male , Middle Aged , Self Concept , Social Support , Young Adult
2.
Public Health ; 127(5): 467-72, 2013 May.
Article in English | MEDLINE | ID: mdl-23615297

ABSTRACT

OBJECTIVES: To estimate and identify characteristics of tobacco use, including use of roll-your-own (RYO) cigarettes and second-hand smoke (SHS) exposure, among a self-identified lesbian, gay, bisexual and transgender (LGBT) community in Ireland. STUDY DESIGN: Web-based self-administered questionnaire survey using a cross-sectional study design. METHODS: A convenience sample of 661 self-identified LGBT respondents was recruited through a well-advertised web-based survey tool method between March and May 2012. Prevalence rates were adjusted for age, sexual orientation, social class and nationality. Multivariable logistic regression was performed to characterize tobacco use profile and SHS exposure levels for estimating adjusted odds ratios (AOR) with 95% confidence intervals (CI). RESULTS: Of the 661 respondents, 45.3% (95% CI 44.9-45.7) reported current use of tobacco and 15.6% reported current use of RYO cigarettes (results were significantly higher for lesbians in both categories). In addition, 40.3% (95% CI 39.9-40.6) of respondents reported SHS exposure at home (significantly higher in gays), and 50.1% (95% CI 49.3-50.8) reported SHS exposure in cars (significantly higher in lesbians); these two groups were not mutually exclusive. The oldest individuals and non-Irish nationals were more than twice as likely to report SHS exposure in cars compared with the youngest individuals and Irish nationals, and the least-educated individuals were more than twice as likely to report current use of RYO cigarettes compared with the most-educated individuals (AOR 2.26; 95% CI 1.06-4.79). Non-tobacco users were less likely to report SHS exposure at home compared with current tobacco users (AOR 0.31; 95% CI 0.21-0.46). DISCUSSION: Despite inherent methodological limitations associated with identification of such a study sample, the adjusted rates indicate that tobacco use is very high among the LGBT community in Ireland compared with the general Irish population (smoking rate 29%). High levels of SHS exposure at home and in cars further underscore the significance of smoke-free private vehicle and 100% smoke-free home policies. A targeted tobacco control strategy should be explored for this vulnerable population.


Subject(s)
Bisexuality/psychology , Environmental Exposure/statistics & numerical data , Homosexuality, Female/psychology , Homosexuality, Male/psychology , Smoking/psychology , Tobacco Smoke Pollution/statistics & numerical data , Transgender Persons/psychology , Adolescent , Adult , Aged , Bisexuality/statistics & numerical data , Cross-Sectional Studies , Female , Homosexuality, Female/statistics & numerical data , Homosexuality, Male/statistics & numerical data , Humans , Ireland/epidemiology , Male , Middle Aged , Risk Factors , Smoking/epidemiology , Surveys and Questionnaires , Transgender Persons/statistics & numerical data , Young Adult
3.
Ir J Med Sci ; 179(3): 423-6, 2010 Sep.
Article in English | MEDLINE | ID: mdl-19618234

ABSTRACT

OBJECTIVE: We hypothesized that smoking rates among the Gay and Lesbian Community (GLC) in Ireland are not significantly different from the general Irish population. METHODS: A convenience sampling of self-identified GLC was recruited using electronic (n = 700) and print (n = 500) media procedures in response to survey call advertisements (December 2006-March 2007). In all, 1,113 had complete smoking data and were analyzed. Data on a random sample of 4,000 individuals, using the Irish Office of Tobacco Control monthly telephone survey, were analyzed for the same period. RESULTS: Adjusted smoking rates in GLC were 26 and 24.6% in the general Irish population (P = 0.99), while "heavy" (> or =20 cigarettes/day) smoking prevalence was 44.1 and 36.6%, respectively (P = 0.02). Upper SES GLCs are "heavy" smokers compared with general population of similar SES group (P = 0.01). CONCLUSION: When considering two different sampling methodologies, this study suggests that smoking rates among the GLC in Ireland are not significantly different from the general Irish population.


Subject(s)
Homosexuality, Female/statistics & numerical data , Homosexuality, Male/statistics & numerical data , Smoking/epidemiology , Adult , Female , Humans , Ireland/epidemiology , Male , Prevalence
4.
BJOG ; 116(13): 1782-7, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19832830

ABSTRACT

OBJECTIVE: It is well-established that maternal smoking has adverse birth outcomes (low birthweight, LBW, and preterm births). The comprehensive Irish workplace smoking ban was successfully introduced in March 2004. We examined LBW and preterm birth rates 1 year before and after the workplace smoking ban in Dublin. DESIGN: A cross-sectional observational study analysing routinely collected data using the Euroking K2 maternity system. SETTING: Coombe University Maternal Hospital. POPULATION: Only singleton live births were included for analyses (7593 and 7648, in 2003 and 2005, respectively). METHODS: Detailed gestational and clinical characteristics were collected and analysed using multivariable logistic regression analyses and subgroup analyses. MAIN OUTCOME MEASURES: Maternal smoking rates, mean birthweights, and adjusted odds ratios (ORs) of LBW and preterm births in 2005 versus 2003. RESULTS: There was a 25% decreased risk of preterm births (OR, 0.75; 95% CI, 0.59-0.96), a 43% increased risk of LBW (OR, 1.43; 95% CI, 1.10-1.85), and a 12% fall in maternal smoking rates (from 23.4 to 20.6%) in 2005 relative to 2003. Such patterns were significantly maintained when specific subgroups were also analysed. Mean birthweights decreased in 2005, but were not significant (P=0.99). There was a marginal increase in smoking cessation before pregnancy in 2005 (P=0.047). CONCLUSIONS: Significant declines in preterm births and in maternal smoking rates after the smoking ban are welcome signs. However, the increased LBW birth risks might reflect a secular trend, as observed in many industrialised nations, and merits further investigations.


Subject(s)
Infant, Low Birth Weight , Premature Birth/epidemiology , Smoking/epidemiology , Adolescent , Adult , Birth Weight , Cross-Sectional Studies , Female , Gestational Age , Humans , Infant, Newborn , Ireland/epidemiology , Maternal Age , Pregnancy , Premature Birth/etiology , Prenatal Exposure Delayed Effects , Smoking/adverse effects , Smoking/legislation & jurisprudence , Smoking Cessation/statistics & numerical data , Workplace/legislation & jurisprudence , Young Adult
5.
Neuropharmacology ; 47(3): 363-72, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15275825

ABSTRACT

Kainate receptors are implicated in a variety of physiological and pathological processes in the CNS. Previously we demonstrated that (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid (ATPA), a selective agonist for the GLU(K5) subtype of kainate receptor, depresses monosynaptically evoked inhibitory postsynaptic potentials (IPSPs) in the CA1 region of the rat hippocampus. In the current study, we provide a more detailed characterisation of this effect. Firstly, our data demonstrate a rank order of potency of domoate>kainate>ATPA>alpha-amino-3-(3-hydroxy-5-methyl-4-isoxalolyl)propionic acid Secondly, we confirm that the effects of ATPA are not mediated indirectly via the activation of gamma-aminobutyric acid receptors (i.e. either GABA(A) or GABA(B)). Thirdly, we show that the small increase in conductance induced by ATPA is insufficient to account for the depression of monosynaptic inhibition. Fourthly, we show that the effects of ATPA on IPSPs are antagonised by the GLU(K5)-selective antagonist (3S, 4aR, 6S, 8aR)-6-(4-carboxyphenyl)methyl-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid (LY382884). However, LY382884 is less potent as an antagonist of the effects of ATPA on IPSPs compared to its depressant effect on EPSPs.


Subject(s)
Hippocampus/drug effects , Isoxazoles/pharmacology , Kainic Acid/analogs & derivatives , Propionates/pharmacology , Receptors, Kainic Acid/agonists , Synaptic Transmission/drug effects , Valine/analogs & derivatives , gamma-Aminobutyric Acid/metabolism , Animals , Benzodiazepines/pharmacology , Dose-Response Relationship, Drug , Drug Interactions , Electric Impedance , Excitatory Amino Acid Agonists/pharmacology , Excitatory Amino Acid Antagonists/pharmacology , Excitatory Postsynaptic Potentials/drug effects , GABA Agents/pharmacology , Glutamic Acid/metabolism , Hippocampus/cytology , In Vitro Techniques , Kainic Acid/pharmacology , Membrane Potentials/drug effects , Neural Inhibition/drug effects , Pyramidal Cells/drug effects , Rats , Rats, Wistar , Receptors, Kainic Acid/antagonists & inhibitors , Valine/pharmacology
6.
Neuropharmacology ; 42(7): 889-902, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12069899

ABSTRACT

Kainate receptors are involved in a variety of synaptic functions in the CNS including the regulation of excitatory synaptic transmission. Previously we described the depressant action of the GLU(K5) selective agonist (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid (ATPA) on synaptic transmission in the Schaffer collateral-commissural pathway of rat hippocampal slices. In the present study we report several new features of the actions of ATPA at this synapse. Firstly, the effectiveness of ATPA is developmentally regulated. Secondly, the effects of ATPA decline during prolonged or repeated applications. Thirdly, the effects of ATPA are not mediated indirectly via activation of GABA(A), GABA(B), muscarinic or adenosine A(1) receptors. Fourthly, elevating extracellular Ca(2+) from 2 to 4 mM antagonises the effects of ATPA. Some differences between the actions of ATPA and kainate on synaptic transmission in the Schaffer collateral-commissural pathway are also noted.


Subject(s)
Excitatory Postsynaptic Potentials/physiology , Hippocampus/physiology , Isoxazoles/pharmacology , Propionates/pharmacology , Receptors, Kainic Acid/agonists , Receptors, Kainic Acid/physiology , Synaptic Transmission/physiology , Animals , Excitatory Postsynaptic Potentials/drug effects , Hippocampus/drug effects , In Vitro Techniques , Isoquinolines/pharmacology , Pyramidal Cells/drug effects , Pyramidal Cells/physiology , Rats , Rats, Wistar , Receptors, Kainic Acid/antagonists & inhibitors , Synaptic Transmission/drug effects
7.
Intern Med J ; 32(5-6): 215-23, 2002.
Article in English | MEDLINE | ID: mdl-12036219

ABSTRACT

BACKGROUND: Debate about testing for prostate cancer using prostate-specific antigen (PSA) and digital rectal examination (DRE) continues. The evidence of benefit from screening for prostate cancer using PSA tests is inconclusive, and it is unclear how PSA can be used most effectively in the detection of prostate cancer. Given the lack of consensus, it is important that consumers understand the issues in a way that will permit them to decide whether or not to have a test and, if symptomatic, how their condition is managed. AIMS: To compare prostate cancer knowledge, attitudes and testing experiences reported by male doctors and men in the community, despite the lack of evidence of a benefit. METHODS: The primary method for ascertaining the attitudes of male doctors (MD) was a telephone survey, with some doctors electing to complete a written survey. Each MD was selected, at random, from a register of male practitioners aged > or = 49 years of age. A total of 266 MD participated in the survey. The community sample (CS) was accessed using a telephone survey. Five hundred male Victorian residents aged > or = 49 years of age participated in the study. RESULTS: Knowledge - Overall, 55% of the CS indicated correctly that prostate disease is sometimes cancer, compared to 83% of MD. Attitudes - Fifty-five per cent of MD believed men should be tested for prostate disease at least every 2 years, compared to 68% of men in the CS. Testing experience - Forty-five per cent of MD had been tested for prostate cancer in the past, and 92% of those tests were reported as negative. In the CS, 56% had been tested for prostate cancer in the past, and 78% of the results were reported as negative. The significant independent predictors of having had a prostate test among MD were: (i) age (> or = 60 years; odds ratio (OR): 1.59; 95% confidence intervals (CI): 1.30-1.88) and (ii) positive attitudes towards regular testing for prostate cancer (OR: 2.27; 95% CI: 1.98-2.56). The significant independent predictors for the CS were: (i) age (> or = 60 years; OR: 1.65; 95% CI: 1.40-1.89), (ii) being married (OR: 1.30; 95% CI: 1.00-1.60), (iii) knowledge that prostate disease was sometimes cancer (OR: 1.46; 95% CI: 1.26-1.66) and (iv) positive attitudes towards regular testing for prostate cancer (OR: 2.12; 95% CI: 1.90-2.34). CONCLUSIONS: The results highlight that testing for prostate cancer is widespread in the community and in the medical profession. Further research should be undertaken to identify how to help men make fully informed decisions about prostate cancer testing.


Subject(s)
Health Knowledge, Attitudes, Practice , Prostatic Neoplasms/diagnosis , Aged , Data Collection , Humans , Interviews as Topic , Logistic Models , Male , Middle Aged , Palpation , Physicians , Prostate-Specific Antigen/analysis
8.
Neuropharmacology ; 41(8): 907-15, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11747895

ABSTRACT

The development of GluR5-selective kainate receptor ligands is helping to elucidate the functions of kainate receptors in the CNS. Here we have further characterised the actions of a GluR5 selective agonist, ATPA, and a GluR5 selective antagonist, LY382884, in the CA3 region of rat hippocampal slices. In addition, we have used LY382884 to study a novel synaptic mechanism. This antagonist substantially reduces frequency facilitation of mossy fibre synaptic transmission, monitored as either AMPA or NMDA receptor-mediated EPSCs. This suggests that GluR5-containing kainate receptors on mossy fibres function as autoreceptors to facilitate the synaptic release of L-glutamate, in a frequency-dependent manner.


Subject(s)
Mossy Fibers, Hippocampal/physiology , Receptors, AMPA/physiology , Receptors, Kainic Acid/physiology , Receptors, Presynaptic/physiology , Synapses/physiology , Synaptic Transmission/physiology , Animals , Excitatory Amino Acid Agonists/pharmacology , Excitatory Postsynaptic Potentials/drug effects , Excitatory Postsynaptic Potentials/physiology , In Vitro Techniques , Isoxazoles/pharmacology , Mossy Fibers, Hippocampal/drug effects , Propionates/pharmacology , Rats , Receptors, Kainic Acid/agonists , Receptors, Kainic Acid/antagonists & inhibitors , Receptors, Presynaptic/agonists , Receptors, Presynaptic/antagonists & inhibitors , Signal Transduction/drug effects , Signal Transduction/physiology , Synapses/drug effects , Synaptic Transmission/drug effects
9.
J Neurosci ; 21(22): 8734-45, 2001 Nov 15.
Article in English | MEDLINE | ID: mdl-11698585

ABSTRACT

To study the role of mGlu7 receptors (mGluR7), we used homologous recombination to generate mice lacking this metabotropic receptor subtype (mGluR7(-/-)). After the serendipitous discovery of a sensory stimulus-evoked epileptic phenotype, we tested two convulsant drugs, pentylenetetrazole (PTZ) and bicuculline. In animals aged 12 weeks and older, subthreshold doses of these drugs induced seizures in mGluR7(-/-), but not in mGluR7(+/-), mice. PTZ-induced seizures were inhibited by three standard anticonvulsant drugs, but not by the group III selective mGluR agonist (R,S)-4-phosphonophenylglycine (PPG). Consistent with the lack of signs of epileptic activity in the absence of specific stimuli, mGluR7(-/-) mice showed no major changes in synaptic properties in two slice preparations. However, slightly increased excitability was evident in hippocampal slices. In addition, there was slower recovery from frequency facilitation in cortical slices, suggesting a role for mGluR7 as a frequency-dependent regulator in presynaptic terminals. Our findings suggest that mGluR7 receptors have a unique role in regulating neuronal excitability and that these receptors may be a novel target for the development of anticonvulsant drugs.


Subject(s)
Genetic Predisposition to Disease , Glycine/analogs & derivatives , Receptors, Metabotropic Glutamate/deficiency , Seizures/genetics , Animals , Anticonvulsants/pharmacology , Bicuculline , Cerebral Cortex/drug effects , Cerebral Cortex/physiopathology , Convulsants , Drug Resistance/genetics , Electroencephalography , Excitatory Amino Acid Agonists/pharmacology , Gene Targeting , Glycine/pharmacology , Hippocampus/drug effects , Hippocampus/physiopathology , Homozygote , In Vitro Techniques , Mice , Mice, Knockout , Pentylenetetrazole , Phenotype , Physical Chromosome Mapping , Receptors, Metabotropic Glutamate/genetics , Seizures/chemically induced , Seizures/physiopathology , Seizures/prevention & control
10.
Health Educ Res ; 16(5): 533-40, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11675801

ABSTRACT

Optimistic bias is a commonly observed but poorly explained phenomenon. Our aim was to determine whether optimistic bias varied according to the nature of the event. Two event characteristics were explored: control and delay. A sample of 100 participants aged 18-30 years was randomly selected from the local residential telephone directory. Respondents were interviewed over the telephone. The highly structured interview schedule assessed respondents' perceptions of their own risk, and the risk of an average person of their age and sex for experiencing four negative life events: developing skin cancer, being involved in a serious car accident as the driver, being involved in a serious car accident as a passenger and having to wear a hearing aid. It also assessed respondents' perceptions of control and delay for each event. Data analysis using a repeated-measures MANOVA showed that optimistic bias occurred for all four events. Optimistic bias was significantly greater for the two events high in control (skin cancer and accident as the driver) than for those low in control (accident as a passenger and hearing aid). Delay was not related to the magnitude of optimistic bias. These findings have implications for health promotion campaigns and self-protective behaviors.


Subject(s)
Attitude to Health , Health Behavior , Risk Assessment , Self-Assessment , Accidents, Traffic , Adolescent , Adult , Australia , Confounding Factors, Epidemiologic , Hearing Aids , Humans , Interviews as Topic , Life Change Events , Skin Neoplasms
11.
Aust Health Rev ; 24(2): 40-4, 2001.
Article in English | MEDLINE | ID: mdl-11496470

ABSTRACT

The allocation of resources to providers and the way in which the resources are then prioritised to specific service areas and patients remain the critical ethical decisions which determine the type of health system a community receives. Health care providers will never be given enough resources to satisfy all the demands placed upon them by a community that is becoming increasingly informed and demanding. This paper discusses the matter of justice as it relates to the distribution of health resources. It translates the theoretical constructs of distribution into a practical situation that arose at The Geelong Hospital. It is important to emphasise that the aim of giving the example is not necessarily to provide the right answer but rather to assist in determining what ought to be the questions.


Subject(s)
Cardiology Service, Hospital , Ethics, Institutional , Health Care Rationing/standards , Hospital Planning/standards , Social Justice , Health Priorities , Health Services Needs and Demand/trends , Humans , Quality Assurance, Health Care , Victoria
12.
Issues Compr Pediatr Nurs ; 24(3): 153-63, 2001.
Article in English | MEDLINE | ID: mdl-12141834

ABSTRACT

During the first three years of life, many health problems are preventable, and health maintenance visits present an excellent opportunity to prevent disease and disability. Unfortunately, preventive child health care services are underutilized. Children who do not adequately use preventive health care services are often seen late in the course of an illness. Thus, they do not receive the continuing care that could eliminate the onset of preventable health problems. In our research, we sought to determine whether mothers' health beliefs influence their use of preventive child health care services and whether their use of preventive child health care services influence their perceptions of the child's health status. The sample was composed of low-income mothers living in an urban environment. No significant relationships were found between the variables. These results indicate the need to develop more sensitive tools to measure these variables in a similar sample.


Subject(s)
Attitude to Health , Health Status , Mother-Child Relations , Mothers/psychology , Preventive Health Services/statistics & numerical data , Adult , Child Welfare/psychology , Child, Preschool , Female , Humans , Male , New Jersey/epidemiology
13.
J Behav Med ; 23(4): 367-76, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10984865

ABSTRACT

Why do people fail to engage in positive behaviors which will promote their health and well-being? Researchers addressing this question adopt primarily one of two perspectives, drawing either on theories of health behavior, such as the Health Belief Model (HBM), or on theories of risk perception, such as unrealistic optimism. To overcome this compartmentalization, two studies of cancer screening behavior assessed the extent to which unrealistic optimism occurred in relation to each of the elements of the HBM: severity and curability of cancer and the benefits of, and barriers to, having a screening test. Data were collected using telephone interviews, dialing numbers randomly selected from the telephone directory. In the first study 164 women aged 50 to 70 years responded to questions about breast cancer and screening mammography, while in the second study 200 men aged 45 to 60 years responded to questions about prostate cancer and screening using the prostate specific antigen test. Women had an optimistic bias in relation to breast cancer risk and severity and barriers to having a screening mammogram but not in relation to the benefits of screening. For prostate cancer, there was an optimistic bias for all HBM variables: risk and severity of prostate cancer and barriers to and benefits of screening. It was concluded that unrealistic optimism is broader than perceived risk, being evident for all elements of the HBM.


Subject(s)
Defense Mechanisms , Health Behavior , Aged , Breast Neoplasms/prevention & control , Breast Neoplasms/psychology , Female , Health Knowledge, Attitudes, Practice , Humans , Male , Mass Screening/psychology , Middle Aged , Patient Acceptance of Health Care/psychology , Prostatic Neoplasms/prevention & control , Prostatic Neoplasms/psychology , Risk Assessment
15.
Nature ; 402(6759): 297-301, 1999 Nov 18.
Article in English | MEDLINE | ID: mdl-10580501

ABSTRACT

The ability of synapses to modify their synaptic strength in response to activity is a fundamental property of the nervous system and may be an essential component of learning and memory. There are three classes of ionotropic glutamate receptor, namely NMDA (N-methyl-D-aspartate), AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid) and kainate receptors; critical roles in synaptic plasticity have been identified for two of these. Thus, at many synapses in the brain, transient activation of NMDA receptors leads to a persistent modification in the strength of synaptic transmission mediated by AMPA receptors. Here, to determine whether kainate receptors are involved in synaptic plasticity, we have used a new antagonist, LY382884 ((3S, 4aR, 6S, 8aR)-6-((4-carboxyphenyl)methyl-1,2,3,4,4a,5,6,7,8,8a-decahydro isoquinoline-3-carboxylic acid), which antagonizes kainate receptors at concentrations that do not affect AMPA or NMDA receptors. We find that LY382884 is a selective antagonist at neuronal kainate receptors containing the GluR5 subunit. It has no effect on long-term potentiation (LTP) that is dependent on NMDA receptors but prevents the induction of mossy fibre LTP, which is independent of NMDA receptors. Thus, kainate receptors can act as the induction trigger for long-term changes in synaptic transmission.


Subject(s)
Long-Term Potentiation/physiology , Receptors, Kainic Acid/physiology , Synapses/physiology , Animals , Cell Line , Excitatory Amino Acid Antagonists/pharmacology , Excitatory Postsynaptic Potentials , Hippocampus/physiology , Humans , In Vitro Techniques , Isoquinolines/pharmacology , Kynurenic Acid/pharmacology , Long-Term Potentiation/drug effects , Mossy Fibers, Hippocampal/physiology , Rats , Rats, Sprague-Dawley , Receptors, AMPA/drug effects , Receptors, AMPA/metabolism , Receptors, Kainic Acid/antagonists & inhibitors , Receptors, N-Methyl-D-Aspartate/drug effects , Receptors, N-Methyl-D-Aspartate/metabolism , Synaptic Membranes/metabolism , Synaptic Transmission
16.
Nat Genet ; 23(3): 309-13, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10610179

ABSTRACT

The unicellular parasite Plasmodium falciparum is the cause of human malaria, resulting in 1.7-2.5 million deaths each year. To develop new means to treat or prevent malaria, the Malaria Genome Consortium was formed to sequence and annotate the entire 24.6-Mb genome. The plan, already underway, is to sequence libraries created from chromosomal DNA separated by pulsed-field gel electrophoresis (PFGE). The AT-rich genome of P. falciparum presents problems in terms of reliable library construction and the relative paucity of dense physical markers or extensive genetic resources. To deal with these problems, we reasoned that a high-resolution, ordered restriction map covering the entire genome could serve as a scaffold for the alignment and verification of sequence contigs developed by members of the consortium. Thus optical mapping was advanced to use simply extracted, unfractionated genomic DNA as its principal substrate. Ordered restriction maps (BamHI and NheI) derived from single molecules were assembled into 14 deep contigs corresponding to the molecular karyotype determined by PFGE (ref. 3).


Subject(s)
Genome, Protozoan , Physical Chromosome Mapping/methods , Plasmodium falciparum/genetics , Animals , Chromosomes/genetics , Chromosomes, Artificial, Yeast/genetics , Contig Mapping/methods , Electrophoresis, Gel, Pulsed-Field , Expressed Sequence Tags , Genomic Library , Image Processing, Computer-Assisted , Karyotyping/methods , Optics and Photonics , Reproducibility of Results , Restriction Mapping/methods , Sensitivity and Specificity
17.
Cancer Nurs ; 22(4): 320-6, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10452210

ABSTRACT

A review of the literature on breast self-examination training indicated that any training in breast self-examination improves compliance, confidence, and proficiency; the evidence is unclear about the relative effectiveness of group or individual training; practice on breast models and on the woman's own breasts should be included in breast self-examination training; additional training sessions improve compliance and proficiency; reminders increase compliance, but the effect ceases when the reminders cease; and it is particularly important for older women to search their breasts slowly and thoroughly. Several other new approaches to breast self-examination training are discussed.


Subject(s)
Breast Neoplasms/nursing , Breast Neoplasms/prevention & control , Breast Self-Examination , Oncology Nursing , Patient Education as Topic , Breast Self-Examination/nursing , Breast Self-Examination/standards , Female , Humans , Patient Education as Topic/methods
18.
Med Pediatr Oncol ; 32(5): 331-5, 1999 May.
Article in English | MEDLINE | ID: mdl-10219333

ABSTRACT

BACKGROUND: Intensification chemotherapy improves the prognosis for children with acute lymphoblastic leukemia (ALL), but results in considerable morbidity, primarily due to myelosuppression with resultant neutropenia. Recombinant granulocyte colony-stimulating factor (G-CSF) shortens neutropenia following intensive chemotherapy, but potential benefits in the therapy of ALL remain inadequately explored. Accordingly, a randomized, crossover study was undertaken to clarify this issue. PROCEDURE: Seventeen children with acute lymphoblastic leukemia or T-cell non-Hodgkin lymphoma and treated on standard protocols were randomized to receive G-CSF following either the first or second intensification blocks of chemotherapy. G-CSF was administered as a single daily subcutaneous injection of 5 mcg/kg from day 9 following the start of intensification therapy, and continued until the neutrophil count exceeded 0.5 x 10(9)/l for 3 days. Study endpoints were days of neutropenia (neutrophils < 1 x 10(9)/l) and severe neutropenia (neutrophils < 0.5 x 10(9)/l), days in hospital, days of fever, and days on antibiotics. RESULTS: There were significant reductions in the duration of neutropenia (95% confidence interval 3.8-8 days, P = 0.0001), severe neutropenia (95% confidence interval 1.8-7.4 days, P = 0.002), and days in hospital (95% confidence interval 0.9-6.3 days, P = 0.01) for children receiving G-CSF. Overall, the duration of neutropenia was longer following the second block (95% confidence interval 2.2-6.4 days, P = 0.0003), but this difference was abolished by G-CSF, and children, receiving G-CSF after the second intensification were more likely to restart maintenance chemotherapy on schedule (P = 0.05). CONCLUSIONS: G-CSF reduces the hematological toxicity of intensification chemotherapy and may allow improved compliance with treatment scheduling.


Subject(s)
Antineoplastic Agents/adverse effects , Granulocyte Colony-Stimulating Factor/therapeutic use , Lymphoma, Non-Hodgkin/drug therapy , Lymphoma, T-Cell/drug therapy , Neutropenia/therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Adolescent , Antineoplastic Agents/administration & dosage , Child , Child, Preschool , Female , Granulocyte Colony-Stimulating Factor/administration & dosage , Humans , Infant , Injections, Subcutaneous , Male , Neutropenia/chemically induced , Neutropenia/prevention & control , Patient Compliance
19.
Trends Pharmacol Sci ; 20(1): 26-35, 1999 Jan.
Article in English | MEDLINE | ID: mdl-10101959

ABSTRACT

Although it is well established that kainate receptors constitute an entirely separate group of proteins from AMPA receptors, their physiological functions remain unclear. The molecular cloning of subunits that form kainate receptors and the ability to study recombinant receptors is leading to an increased understanding of their functional properties. Furthermore, the development of kainate receptor-selective agonists and antagonists over the past few years is now allowing the physiological roles of these receptors and, in some cases, specific subunits to be investigated. As a consequence, the synaptic activation of postsynaptic kainate receptors and the presence of presynaptic kainate receptors that serve to regulate excitatory and inhibitory synaptic transmission have been described, and will be discussed in this article by Ramesh Chittajallu, Steven Braithwaite, Vernon Clarke and Jeremy Henley.


Subject(s)
Receptors, Kainic Acid/physiology , Synapses/metabolism , Animals , Cloning, Molecular , Humans , Receptors, Kainic Acid/genetics , Receptors, Kainic Acid/metabolism , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Synaptic Transmission/physiology
20.
Neuropharmacology ; 37(10-11): 1269-77, 1998.
Article in English | MEDLINE | ID: mdl-9849664

ABSTRACT

Activation of kainate receptors depresses excitatory synaptic transmission in the hippocampus. In the present study, we have utilised a GluR5 selective agonist, ATPA [(RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid], and a GluR5 selective antagonist, LY294486 [(3SR,4aRS,6SR,8aRS)-6-([[(1H-tetrazol-5-y l)methyl]oxy]methyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3 -carboxylic acid], to determine whether GluR5 subunits are involved in this effect. ATPA mimicked the presynaptic depressant effects of kainate in the CA1 region of the hippocampus. It depressed reversibly AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptor-mediated field excitatory postsynaptic potentials (field EPSPs) with an IC50 value of approximately 0.60 microM. The dual-component excitatory postsynaptic current (EPSC) and the pharmacologically isolated NMDA (N-methyl-D-aspartate) receptor-mediated EPSC were depressed to a similar extent by 2 microM ATPA (61 +/- 7% and 58 +/- 6%, respectively). Depressions were associated with an increase in the paired-pulse facilitation ratio suggesting a presynaptic locus of action. LY294486 (20 microM) blocked the effects of 2 microM ATPA on NMDA receptor-mediated EPSCs in a reversible manner. In area CA3, 1 microM ATPA depressed reversibly mossy fibre-evoked synaptic transmission (by 82 +/- 10%). The effects of ATPA were not accompanied by any changes in the passive properties of CA1 or CA3 neurones. However, in experiments where K+, rather than Cs+, containing electrodes were used, a small outward current was observed. These results show that GluR5 subunits comprise or contribute to a kainate receptor that regulates excitatory synaptic transmission in both the CA1 and CA3 regions of the hippocampus.


Subject(s)
Excitatory Amino Acid Agonists/pharmacology , Hippocampus/physiology , Isoxazoles/pharmacology , Propionates/pharmacology , Receptors, Kainic Acid/physiology , Synaptic Transmission/physiology , Animals , Hippocampus/drug effects , Patch-Clamp Techniques , Rats , Rats, Wistar , Receptors, Kainic Acid/drug effects , Synaptic Transmission/drug effects
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