Headache characteristics in patients after migrainous stroke.
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Headache↗
Biomedical subjects
R White
Publications and source records attributed to R White.
Symptomatic asthma: attendance and prescribing in general practice.
Under-prescribing and low attendance continue to be cited as reasons for ongoing asthma symptoms in primary care despite marked increases in prescribing and structured care for asthma over the past 10 years. The objective of this study was to determine the relationship between continuing asthma morbidity and the attendance of and prescribing for symptomatic asthmatic patients in primary care. A random sample of 402 subjects from 801 who reported at least one of six symptoms in the previous month on most or every day were identified from responses to a validated morbidity questionnaire. An analysis of their care over a 2-year period (1 year before and 1 year after the questionnaire) was carried out from their general practice case-notes. Data on 308 patients was available for analysis. Ninety-four per cent of these symptomatic asthma patients attended over the 2-year period, with 77% attending for an asthma related consultation. Most patients were managed exclusively in primary care. Inhaled steroids were prescribed for 78% of patients and high dose inhaled steroids (> or = 800 mcg of beclomethasone or equivalent per day) were prescribed for 38%. Patients with most symptoms were more likely to be prescribed inhaled steroids. Rescue courses of oral steroids were prescribed for 29% of patients. Changes in asthma medications were recorded for 31% during the study period. Metered dose inhalers (MDI) were prescribed for 86% with more than half prescribed MDIs combined with some other delivery device. Elements of structured care were more frequently recorded in patients who reported most symptoms. In conclusion the asthma management of the majority of patients in this study was active with high levels of steroid prescribing. There appeared to be room to increase prescribing and to improve the structure of care. While patients who were 'symptomatic on steroids' should have had their medications, delivery devices and structured care reviewed regularly many were already on maximal treatment and were therefore likely to remain symptomatic. It is unclear how practitioners could improve morbidity in many of these patients as under-treatment and low attendance seem unlikely to be the principal causes of continuing symptoms.
Administration, Oral↗
Effects of propofol as an anaesthetic agent in adult lions (Panthera leo): a comparison with two established protocols.
The aims of this study were to evaluate the effects of a ketamine/propofol anaesthetic protocol in lions (Panthera leo), and to compare it to two commonly used anaesthetic protocols. Seventeen adult lions were anaesthetised using three different protocols. Group XK (n=6) was anaesthetised with intramuscular (i.m.) injections of xylazine and ketamine. Group KD (n=5) was anaesthetised with an i.m. injection of ketamine, followed by an intravenous (i.v.) injection of ketamine and diazepam. Group KP (n=6) was anaesthetised with an i.m. injection of ketamine followed by an i.v. injection of propofol. There was a significant difference in heart rate (P<0.0002), which was lowest in group XK and highest in KD. Jaw tone was significantly lower in Group XK (P<0.05). No undesirable effects were noted following injection of the propofol. Propofol was a suitable and safe drug for maintenance of anaesthesia in adult lions.
Anesthesia↗
Reaching homeless youths for Chlamydia trachomatis and Neisseria gonorrhoeae screening in Denver, Colorado.
BACKGROUND AND RATIONALE: The availability of urine based testing for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) provides a unique opportunity to screen for these pathogens outside traditional clinical settings. The researchers investigated the feasibility of street based CT/GC screening in the context of an outreach programme among street/homeless adolescents in Denver. OBJECTIVES: To describe the integration of urine based CT/GC screening into an existing outreach programme among street/homeless youths and the yield of CT/GC testing in this setting. METHODS: The Denver Department of Public Health (DPH) collaborated with outreach staff from Urban Peak (a community based organisation serving street/homeless youths in Denver) to offer urine based CT/GC testing to males and females in street settings. Tests were conducted on the street in areas where street/homeless youths congregate. RESULTS: Urban Peak outreach staff were trained by DPH staff to conduct CT testing, process urine specimens, and provide test results to participating youths. DPH remained responsible for treatment of people with CT or GC infection as well as CT/GC case reporting. CT testing started in January 2000; GC testing was added in July 2000. Throughout April 2002 a total of 414 CT and 302 GC tests were conducted, respectively 11.6% and 2.7% of which were positive. Among first testers, 13.0% were positive for CT and 3.7% for GC. CONCLUSIONS: CT/GC urine testing can be incorporated into existing outreach programmes without considerable extra effort. Overall CT rates were high and suggest the need for ongoing screening in this manner. LEARNING OBJECTIVE: To understand the role of CT/GC screening in the context of services provided to street/homeless youths in outreach settings.
Adolescent↗
Particulate air pollution standards and morbidity and mortality: case study.
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Air Pollutants↗
Two methods of community detoxification from opiates: an open-label comparison of lofexidine and buprenorphine.
There is currently no consensus on the best approach to the management of opiate detoxification. In the current open-label study, 69 opiate-dependent individuals requesting outpatient detoxification were allocated to two different medication regimes: lofexidine and buprenorphine. Allocation was dependent on the timing of their presentation. Lofexifidine is a structural analogue of clonidine, and used widely in the UK. Buprenorphine is a partial opiate agonist with unusual pharmacological properties. Outcomes were better for the buprenorphine-receiving group (n=38). Clients receiving buprenorphine had a less severe withdrawal syndrome, and were more likely to complete their detoxification. In addition, for the buprenorphine-receiving group it was found that the withdrawal syndrome was least in those prescribed an initial dose of 4 mg. The findings and their implications are discussed. The design of the study precludes definitive conclusions regarding relative efficacy.
Adult↗
Compelling reasons to screen brain in HHT.
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Central Nervous System Vascular Malformations↗
Differential expression of glutamate and GABA-A receptor subunit mRNA in cortical dysplasia.
OBJECTIVE: Focal cortical dysplasia is characterized by disorganized cortical lamination, dysplastic and heterotopic neurons, and an association with epilepsy. The contribution that dysplastic and heterotopic neurons make to epileptogenesis in focal cortical dysplasia is unknown and the phenotype of these cells may be distinct. The authors hypothesized that the expression of genes encoding glutamatergic (glutamate [GluR] and N-methyl-D-aspartate NMDA receptors [NR]) and gamma-aminobutyric acid A receptor (GABA(A)R) subunits is distinct in dysplastic and heterotopic neurons and that changes in receptor gene expression could be defined in a cell-specific pattern. METHODS: Single immunohistochemically labeled dysplastic and heterotopic neurons were microdissected from human focal cortical dysplasia specimens obtained during epilepsy surgery. Pyramidal neurons were microdissected from postmortem control cortex and from temporal cortex without dysplasia resected during temporal lobectomy. Poly (A) messenger RNA (mRNA) from single neurons was amplified, radiolabeled, and used to probe complementary DNA (cDNA) arrays containing GluR(1-6), NR(1A,1B), NR(2A-D), and GABA(A)Ralpha(1-6), and -Rbeta(1-3) subunit cDNAS: The relative hybridization intensities of each mRNA-cDNA hybrid were quantified by phosphorimaging. RESULTS: GluR, NR, and GABA(A)R subunit mRNA expression did not differ between control neurons and nondysplastic epilepsy specimens. Expression of GluR(4), NR(2B), and NR(2C) subunit mRNA was increased, and NR(2A) and GABA(A)Rbeta(1) subunit mRNA was decreased in dysplastic compared with pyramidal and heterotopic neurons. In contrast, GABA(A)Ralpha(1), -Ralpha(2), and -Rbeta(2) as well as GluR(1) mRNA levels were reduced in both dysplastic and heterotopic neurons. CONCLUSIONS: Differential expression of GluR, NR, and GABA(A)R mRNA in dysplastic and heterotopic neurons demonstrates cell specific gene transcription changes in focal cortical dysplasia. These results suggest that dysplastic and heterotopic neurons may be pharmacologically distinct and make differential contributions epileptogenesis in focal cortical dysplasia.
Adolescent↗
An abnormal dipyridamole thallium/sestamibi fails to predict long-term cardiac events in vascular surgery patients.
Recent data demonstrate that dipyridamole-thallium (DTHAL) and sestamibi (DMIBI) are not predictive of adverse perioperative cardiac events in moderate-risk patients (one or more Eagle risk factors) undergoing major elective vascular surgery. Less data are available regarding the ability of DTHAL/DMIBI to predict adverse cardiac events on long term follow-up. We sought to determine whether an abnormal DTHAL/DMIBI is predictive of adverse cardiac events on long-term follow-up in moderate-risk patients undergoing major elective vascular surgery. Patients were enrolled prospectively between June 1997 and June 1999 at West Los Angeles VA and Harbor-UCLA Medical Centers. Adverse cardiac events were defined as congestive heart failure (CHF), myocardial infarction (MI), unstable angina (USA), and ventricular arrhythmias. Follow-up was obtained via clinic visits, telephone calls, and chart review. We studied 75 patients (76% male, 24% female) with a mean age of 65 years. Operative procedures were primarily femorodistal (83%) and aortic (16%). DTHAL/DMIBI results were normal in 35 patients (47%), demonstrated reversible ischemia in 26 (35%), and showed a fixed defect alone in 14 (18%). From the follow-up results of this study we conclude that there is no association between a reversible ischemia or an abnormal (fixed or reversible) DTHAL/DMIBI and adverse cardiac events or mortality on long-term follow-up in moderate-risk patients who have undergone major vascular surgery.
Aged↗
Trends in cardiac morbidity and mortality after endoluminal abdominal aortic aneurysm repair; discussion 999-1000.
HYPOTHESIS: The adverse cardiac event rate following endoluminal abdominal aortic aneurysm (EAAA) repair has decreased as experience in performing the procedure has increased. Aneurysm complexity affects the rate of adverse cardiac events. DESIGN AND PATIENTS: Data from 173 consecutive patients undergoing EAAA repair from 2 successive periods were compared. There were 82 patients in the early group (group 1) and 91 patients in the later group (group 2). MAIN OUTCOME MEASURES: Myocardial infarction, congestive heart failure, unstable angina, major dysrhythmias, death. RESULTS: The cardiac event rate was 8.5% for group 1 vs 16.5% for group 2 (P =.16). Predictors of adverse cardiac events on multivariate analysis were the use of 4 or more graft extensions (P =.04), female sex (P =.01), and number of Eagle risk factors (P<.001). There were 2 postoperative deaths (2.4%) in group 1 and 4 (4.4%) in group 2 (P =.7). CONCLUSIONS: Following EAAA repair: (1) adverse cardiac events were found to correlate with use of 4 or more graft extensions, female sex, and the number of Eagle risk factors; (2) cardiac morbidity and mortality remain significant despite greater experience and improved technology; and (3) operative mortality remains acceptably low.
Aged↗
Selective alterations in glutamate and GABA receptor subunit mRNA expression in dysplastic neurons and giant cells of cortical tubers.
The molecular pharmacologic basis of epileptogenesis in cortical tubers in the tuberous sclerosis complex is unknown. Altered transcription of genes encoding glutamatergic and gamma-aminobutyric acid (GABA)-ergic receptors and uptake sites may contribute to seizure initiation and may occur selectively in dysplastic neurons and giant cells. Arrays containing GABA A (GABAAR), GluR, NMDA receptor (NR) subunits, GAD65, the vesicular GABA transporter (VGAT), and the neuronal glutamate transporter (EAAC1) cDNAs were probed with amplified poly (A) mRNA from tubers or normal neocortex to identify changes in gene expression. Increased levels of EAAC1, and NR2B and 2D subunit mRNAs and diminished levels of GAD65, VGAT, GluR1, and GABAAR alpha1 and alpha2 were observed in tubers. Ligand-binding experiments in frozen tuber homogenates demonstrated an increase in functional NR2B-containing receptors. Arrays were then probed with poly (A) mRNA from single, microdissected dysplastic neurons, giant cells, or normal neurons (n = 30 each). Enhanced expression of GluR 3, 4, and 6 and NR2B and 2C subunit mRNAs was noted in the dysplastic neurons, whereas only the NR2D mRNA was upregulated in giant cells. GABAAR alpha1 and alpha2 mRNA levels were reduced in both dysplastic neurons and giant cells compared to control neurons. Differential expression of GluR, NR, and GABAAR mRNAs in tubers reflects cell-specific changes in gene transcription that argue for a distinct molecular phenotype of dysplastic neurons and giant cells and suggests that dysplastic neurons and giant cells make differential contributions to epileptogenesis in the tuberous sclerosis complex.
Adolescent↗
Generation of species cross-reactive aptamers using "toggle" SELEX.
Species cross-reactivity facilitates the preclinical evaluation of potentially therapeutic molecules in animal models. Here we describe an in vitro selection strategy in which RNA ligands (aptamers) that bind both human and porcine thrombin were selected by "toggling" the protein target between human and porcine thrombin during alternating rounds of selection. The "toggle" selection process yielded a family of aptamers, all of which bound both human and porcine thrombin with high affinity. Toggle-25, a characteristic member, inhibited two of thrombin's most important functions: plasma clot formation and platelet activation. If appropriate targets are available, the toggle strategy is a simple measure that promotes cross-reactivity and may be generalizable to related proteins of the same species as well as to other combinatorial library screening strategies. This strategy should facilitate the isolation of ligands with needed properties for gene therapy and other therapeutic and diagnostic applications.
Animals↗
Impact of rural hospital closures in Saskatchewan, Canada.
Canada's health care system has undergone major changes since 1990. In Saskatchewan, 52 small rural hospitals funded for less than eight beds stopped receiving funding for acute care services in 1993. Most were subsequently converted to primary health care centers. Since then, concerns have been raised about the impact of the changes on rural residents' access to care, their health status, and the viability of rural communities. To assess the impact of hospital closures on the affected communities, we conducted a multi-faceted, province-wide study. We looked at hospital use patterns, health status, rural residents' perceptions of the impact of these hospital closures, and how communities responded to the changes. We found the hospital closures did not adversely affect rural residents' health status or their access to inpatient hospital services. Despite widespread fears that health status would decline, residents in these communities reported that hospital closures did not adversely affect their own health. Although some communities continue to struggle with changes to health care delivery, others appear to have adapted as a result of strong community leadership, the development of widely accepted alternative services, and local support for creating innovative solutions. Good rural health care does not depend on the presence of a very small hospital that cannot, in today's environment, provide genuinely acute care. It requires creative approaches to the provision of primary care, good emergency services, and good communication with the public on the intent and outcomes of change.
Attitude to Health↗
Mechanisms of anandamide-induced vasorelaxation in rat isolated coronary arteries.
1. The cannabinoid arachidonyl ethanolamide (anandamide) caused concentration-dependent relaxation of 5-HT-precontracted, myograph-mounted, segments of rat left anterior descending coronary artery. 2. This relaxation was endothelium-independent, unaffected by the fatty acid amide hydrolase inhibitor, arachidonyl trifluoromethyl ketone (10 microM), and mimicked by the non-hydrolysable anandamide derivative, methanandamide. 3. Relaxations to anandamide were attenuated by the cannabinoid receptor antagonist, SR 141716A (3 microM), but unaffected by AM 251 (1 microM) and AM 630 (1 microM), more selective antagonists of cannabinoid CB(1) and CB(2) receptors respectively. Palmitoylethanolamide, a selective CB(2) receptor agonist, did not relax precontracted coronary arteries. 4. Anandamide relaxations were not affected by inhibition of sensory nerve transmission with capsaicin (10 microM) or blockade of vanilloid VR1 receptors with capsazepine (5 microM). Nevertheless capsaicin relaxed coronary arteries in a concentration-dependent and capsazepine-sensitive manner, confirming functional sensory nerves were present. In contrast, capsazepine and capsaicin did inhibit anandamide relaxations in methoxamine-precontracted rat small mesenteric arteries. 5. Relaxations to anandamide were inhibited by TEA (1 mM) or iberiotoxin (50 nM), blockers of large conductance, Ca(2+)-activated K(+) channels (BK(Ca)). Gap junction inhibition with 18alpha-glycyrrhetinic acid (100 microM) did not affect anandamide relaxations. 6. This study shows anandamide relaxes the rat coronary artery by a novel mechanism. Anandamide-induced relaxations do not involve the endothelium, degradation into active metabolites, or activation of cannabinoid CB(1) or CB(2) receptors, but may involve activation of BK(Ca). Vanilloid receptor activation also has no role in the effects of anandamide in coronary arteries, even though functional sensory nerves are present.
Amides↗
Heroin use, ethnicity and the environment: the case of the London Bangladeshi community.
AIMS: To describe the emergence of heroin use in the London Bangladeshi community, to delineate its key features and generate hypotheses to account for these. DESIGN: Analysis of all reports of treatment-related episodes to a central data base. Detailed interviews with 21 Bangladeshi heroin users and a comparison group. SETTING: Treatment centres in three London boroughs with large Bangladeshi populations. FINDINGS: For young Bangladeshi men living in London, the prevalence of problematic heroin use has increased from negligible levels in the early 1990s to levels proportionally higher than in the white population of the same age and sex. The proportion of first episode reports has remained constant during this time. Bangladeshi heroin use has certain distinct features: users are nearly all male, and are apparently less disadvantaged than comparable white users. They also have much greater contact with their non-drug-using families. CONCLUSIONS: Because the population of Bangladeshis continues to grow, the epidemic may continue to grow in step with this. However, Bangladeshis may represent a group of heroin users with a good prognosis, and treatment services should, arguably, be aiming for better outcomes for them. Greater involvement of families may help to achieve this.
Adult↗
Long-term asthma control with oral montelukast and inhaled beclomethasone for adults and children 6 years and older.
BACKGROUND: Leukotriene receptor antagonists have demonstrated clinical benefits in chronic asthma studies of up to 3 months in duration. The effects of these agents over extended periods of time have not been reported. OBJECTIVE: To describe the long-term effect of oral montelukast, a potent and specific cysteinyl leukotriene receptor antagonist, compared with inhaled corticosteroids in both adult and paediatric patients with chronic asthma. METHODS: Male and female patients with chronic, stable asthma (adults aged 15-85 years, children aged 6-14 years), who had completed double-blind, placebo-controlled clinical studies, participated in three extension studies with oral montelukast taken once daily (10 mg tablet for adults, 5 mg chewable tablet for paediatric patients) or inhaled corticosteroids (beclomethasone 200 microg twice daily for adults, beclomethasone 100 microg or equivalent three times daily for children). A double-blind adult extension study was 37 weeks in duration; open-label adult extension studies were 156 (adults) and 112 (paediatric) weeks in duration. A total of 436, 374, and 245 patients entered these extension studies, respectively. RESULTS: Treatment with both montelukast and inhaled corticosteroids resulted in improvement in multiple parameters of asthma control. Improvements in daytime symptom scores were generally comparable among treatment groups. No tachyphylaxis to the effects of montelukast was evident. In the adult open-label study, however, the effect of beclomethasone on mean forced expiratory volume in 1 second (FEV1) gradually decreased from start of the study to the end of the follow-up treatment period. CONCLUSION: Both montelukast and inhaled corticosteroids were effective in controlling mild to moderate chronic asthma; the relative effectiveness of montelukast and beclomethasone were similar in open-label conditions. The hypothesis, that clinical practice conditions (e.g., adherence) may have a significant impact on the effectiveness of these therapies, should be tested in future clinical trials.
Acetates↗
Homocysteine and methylmalonic acid as indicators of folate and vitamin B12 deficiency in pregnancy.
Deficiency of folate during pregnancy is associated with megaloblastic anaemia. Lower levels of folate and vitamin B12 have been reported in mothers whose offspring had neural tube defects compared to unaffected controls. Increased methylmalonic acid levels are a sensitive indicator of mild vitamin B12 deficiency and elevated homocysteine levels denote vitamin B12 or folate deficiency. We have investigated the relationship between serum concentration of total homocysteine, methylmalonic acid, vitamin B12 and folate in pregnancy. A significant inverse correlation was found between homocysteine and red cell folate and, to a lesser extent, serum folate. In addition, a significant inverse correlation was found between methylmalonic acid and vitamin B12. No significant relationship was found between homocysteine and vitamin B12. The relationship between red cell folate and serum folate and homocysteine may be useful for detecting borderline folate deficiency in pregnancy and indicate pregnancies at risk of neural tube defect. These sensitive assays are useful tools for the further investigation of folate vitamin B12 and metabolism in normal and abnormal pregnancy.
Adult↗
A method for assembling a collaborative research team from multiple disciplines and academic centers to study the relationships between ECG estimation and MRI measurement of myocardial infarct size.
A method has been developed for establishing a "University Without Walls" for the purpose of studying the relationship between electrocardiographic estimation and magnetic resonance imaging measurements of myocardial infarct size. The research team includes faculty and students from 4 medical centers, with expertise extending from clinical to technical. Weekly interactive videoconferences provide the key research communication method. Study patients are recruited from 2 of the sites, and the correlations between their electrocardiographic and magnetic resonance imaging data are considered by the research team in conference. Outcomes of this program are both scientific publications in international peer-review journals and formal postdoctoral degree attainment by the research trainees.
Academic Medical Centers↗