Complementary therapies for asthma.
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Adult↗
Biomedical subjects
M Williams
Publications and source records attributed to M Williams.
A nine year old who still wets the bed.
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Administration, Inhalation↗
Expression of N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptor genes in neuroblastoma, medulloblastoma, and other cells lines.
We evaluated expression of N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptor (GluR) genes by reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blotting in nine established cell lines: rat CG-4 (oligodendroglial lineage) and RINm5F insulinoma cells; human CHP134, SMS-KCNR, SKNSH, and Nb69 neuroblastoma cells; and human D384Med, D425Med, and D458Med medulloblastoma cells. CG-4 expressed mRNAs encoding GluR2-7, KA-1, and KA-2 non-NMDA GluR (Yoshioka et al.: J Neurochem 64:2442-2448, 1995) and NR1 (NMDAR1) and NR2D NMDA GluR. After differentiation to oligodendrocyte-like cells, CG-4 also expressed NR2B mRNA. Rat insulinoma cells expressed GluR5 and KA-2 non-NMDA and NR1 and NR2D NMDA GluR mRNAs. The four human neuroblastoma lines all expressed mRNAs encoding GluR2-4, 6, 7 and KA-1 non-NMDA and NR1 NMDA GluR, and the three human medulloblastoma cell lines all expressed mRNAs encoding GluR1, 6 and KA-1, but none of the NMDA GluRs. Whereas CG-4 is susceptible to kainate excitotoxicity, treatment of insulinoma, neuroblastoma, and medulloblastoma lines with L-glutamate, kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), or NMDA failed to cause cell damage or to augment 45Ca2+ influx. Thus, despite expressing a variety of non-NMDA and NMDA GluR genes, the human neuroblastoma and medulloblastoma and rat insulinoma lines failed to assemble Ca(2+)-permeable NMDA or non-NMDA GluR channels. This failure confers protection against excitotoxicity and may contribute to progression of tumors of these types.
Animals↗
Management of acute myocardial infarction in Auckland.
AIM: To analyse the utilisation of therapies in coronary care units for patients with acute myocardial infarction. METHODS: An evaluation form was completed prospectively by a designated nurse in each coronary care unit of the four Auckland hospitals in 1993. RESULTS: One thousand and eighty one patients who were admitted with definite or probable acute myocardial infarction had a coronary care unit stay of 63.4 (SD 49.3) hours, and hospital stay of 7.3 (5.1) days. The mortality for definite myocardial infarction was 13.7% (< 70 years 7.1%). Coronary angiography was performed on 10% of patients during their hospital admission, and 4.9% underwent revascularisation. Thrombolytic therapy was administered to 52% (495/948) of patients with definite infarction and 4% had contraindications. Patients aged > or = 70 years (47% vs 55% p = 0.02) or diabetics (46% vs 56%, p = 0.04) were less likely to receive thrombolysis. The utilisation of aspirin and oral beta-blockers was 86% and 40%, respectively, in patients with definite infarction and both were used less frequently in patients > or = 70 years. Intravenous beta-blockers were administered to < 1% of patients. Angiotensin converting enzyme (ACE) inhibitors were prescribed in 21%, intravenous or long acting nitrates in 41% and calcium antagonists in 14%; the latter two therapies were used more frequently in patients > or = 70 years. There was no evidence of gender or ethnic bias for either investigation or treatment. CONCLUSION: On the basis of results of recent clinical trials, there may be under utilisation of some treatments for acute myocardial infarction including aspirin, thrombolytic therapy, beta-blockers and ACE inhibitors, while calcium antagonists may be over used.
Adrenergic beta-Antagonists↗
Novel 3-Pyridyl ethers with subnanomolar affinity for central neuronal nicotinic acetylcholine receptors.
Recent evidence indicating the therapeutic potential of cholinergic channel modulators for the treatment of central nervous system (CNS) disorders as well as the diversity of brain neuronal nicotine acetylcholine receptors (nAChRs) have suggested an opportunity to develop subtype-selective nAChR ligands for the treatment of specific CNS disorders with reduced side effect liabilities. We report a novel series of 3-pyridyl ether compounds which possess subnanomolar affinity for brain nAChRs and differentially activate subtypes of neuronal nAChRs. The synthesis and structure-activity relationships for the leading members of the series are described, including A-85380 (4a), which possesses ca.50 pM affinity for rat brain [(3)H]-(-)-cytisine binding sites and 163% efficacy compared to nicotine to stimulate ion flux at human alpha4beta2 nAChR subtype, and A-84543 (2a), which exhibits 84-fold selectivity to stimulate ion flux at human alpha4beta2 nAchR subtype compared to human ganglionic type nAChRs. Computational studies indicate that a reasonable superposition of a low energy conformer of 4A with (S)-nicotine and (-)-epibatidine can be achieved.
Alkaloids↗
Deprivation and cause specific morbidity: evidence from the Somerset and Avon survey of health.
OBJECTIVE: To investigate the association between cause specific morbidity and deprivation in order to inform the debates on inequalities in health and health services resource allocation. DESIGN: Cross sectional postal questionnaire survey ascertaining self reported health status, with validation of a 20% sample through general practitioner and hospital records. SETTING: Inner city, urban, and rural areas of Avon and Somerset. SUBJECTS: Stratified random sample of 28,080 people aged 35 and over from 40 general practices. MAIN OUTCOME MEASURES: Age and sex standardised prevalence of various diseases; Townsend deprivation scores were assigned by linking postcodes to enumeration districts. Relative indices of inequality were calculated to estimate the magnitude of the association between socioeconomic position and morbidity. RESULTS: The response rate was 85.3%. The prevalence of most of the conditions rose with increasing material deprivation. The relative index of inequalilty, for both sexes combined, was greater than 1 for all conditions except diabetes. The conditions most strongly associated with deprivation were diabetic eye disease (relative index of inequality 3.21; 95% confidence interval 1.84 to 5.59), emphysema (2.72; 1.67 to 4.43) and bronchitis (2.27; 1.92 to 2.68). The relative index of inequality was significantly higher in women for asthma (P < 0.05) and in men for depression (P < 0.01). The mean reporting of prevalent conditions was 1.07 for the most deprived fifth of respondents and 0.77 in the most affluent fifth (P < 0.001). CONCLUSIONS: Material deprivation is strongly linked with many common diseases. NHS resource allocation should be modified to reflect such morbidity differentials.
Adult↗
The influence of merocyanine 540 and protoporphyrin on physicochemical properties of the erythrocyte membrane.
The interaction of the red cell membrane with merocyanine 540 or protoporphyrin led to four phenomena, most probably interrelated. (i) The morphology changed from the normal discoid to an echinocytic form. This morphological change persisted when followed over a period of 24 h. (ii) Simultaneously, cell deformability was decreased, as revealed by viscosity measurements and a cell-filtration technique. (iii) Both drugs caused swelling of the erythrocytes in isotonic medium, due to a very-short-term increased permeability of the membrane, also for larger molecules such as lactose. The pathway of this temporary leak seems to be unrelated to the Na+/K+ -ATPase, the K+/Cl- and the Na+/K+/Cl- cotransport systems, the Ca2+-activated Gardos pathway, the oxidation/deformation-activated leak pathway and the so-called residual transport route. Despite the morphological changes, K+-leakage induced by mechanical stress was not increased. (iv) During osmotic swelling, the critical hemolytic volume was found to be increased in the presence of either merocyanine 540 or protoporphyrin. The increase critical volume protected erythrocytes against osmotic hemolysis.
Antiviral Agents↗
Challenges in developing P2 purinoceptor-based therapeutics.
Advances in the molecular cloning, expression and functional characterization of the P2 purinoceptor superfamily have provided a wealth of data to support a diverse functional role for ATP and related nucleotides in the regulation of tissue function. As with other receptor superfamilies, it is likely that distinct subtypes of each receptor will subserve discrete functions depending on tissue distribution and disease pathophysiology. At the present time, ATP is being evaluated as an anticancer agent and as an anaesthesia adjunct whereas UTP is studied as a novel treatment for cystic fibrosis. ARL67085 is a potent and selective P2T receptor antagonist that has potential as a novel antithrombotic agent. The key to exploiting the P2 purinoceptor area to enhance understanding of disease aetiology and concurrent therapeutic potential will be to focus efforts on the identification of novel pharmacophores that have potent and selective interactions with the various receptor subtypes as potential new leads. To this end, the use of high-throughput screening in conjunction with combinatorial chemical, conventional chemical and natural product library compound sources will be critical.
Adenosine Triphosphate↗
Patient-controlled sputum removal during chest physiotherapy in cystic fibrosis: a system for use in closed-circuit assessment of energy expenditure.
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Adolescent↗
A-85380 [3-(2(S)-azetidinylmethoxy) pyridine]: in vitro pharmacological properties of a novel, high affinity alpha 4 beta 2 nicotinic acetylcholine receptor ligand.
The in vitro pharmacological properties of a novel cholinergic channel ligand, A-85380 [3-(2(S)-azetidinylmethoxy)pyridine], were examined using tissue preparations that express different putative nAChR subtypes. In radioligand binding studies, A-85380 is shown to be a potent and selective ligand for the human alpha 4 beta 2 nAChR subtype (Ki = 0.05 + 0.01 nM) relative to the human alpha 7 (Ki = 148 +/- 13 nM) and the muscle alpha 1 beta 1 dg subtype expressed in Torpedo electroplax (Ki = 314 +/- 12 nM). The R-enantiomer of A-85380, A-159470, displays little enantioselectivity towards the alpha 4 beta 2 and alpha 1 beta 1 delta gamma subtypes but does not display 12-fold enantioselectivity towards the alpha 7 subtype (Ki = 1275 +/- 199 nM). (+)- and(-)-Epibatidine display similar potencies at the human human alpha 4 beta 2 (Ki = 0.04 +/- 0.02 nM and 0.07 +/- 0.02 nM, respectively), human alpha 7 (Ki = 16 +/- 2 nM and 22 +/- 3 nM, respectively) and muscle alpha 1 beta 1 delta gamma g (Ki = 2.5 +/- 0.9 nM and 5.7 +/- 1.0 nM, respectively) nAChRs. Functionally, A-85380 is a potent activator of cation efflux through the human alpha 4 beta 2 (EC50 = 0.7 +/- 0.1 microM) and ganglionic (EC50 = 0.8 +/- 0.09 microM) subtypes, effects that are attenuated by pretreatment with mecamylamine (10 microM). Further, A-85380 can activate (EC50 = 8.9 +/- 1.9 microM) currents through channels formed by injection of the human alpha 7 subunit into Xenopus oocytes, effects that are attenuated by pretreatment with the alpha 7 nAChR antagonist, methyllycaconitine (10 nM). In all cases, A-85380 is more potent than (-)-nicotine but less potent than (+/-)-epibatidine. In neurotransmitter release studies, A-85380 stimulates the release of dopamine with an EC 50 value of 0.003 +/- 0.001 microM which is equipotent to (+/-)-epibatidine, and 20-fold more potent than (-)-nicotine (EC50 = 0.04 +/- 0.009 microM). Thus, A-85380 displays a profile of robust activation of a number of nAChR subtypes with substantially less affinity for [125I] alpha-BgT sites than [3H](-)-cytisine sites, suggesting that it may serve as a more selective pharmacologic probe for the alpha 4 beta 2 subtype relative to the alpha 7 and alpha 1 beta 1 delta g nAChRs than (+/-)-epibatidine.
Animals↗
Accelerated fetal lung maturity profiles and maternal cocaine exposure.
OBJECTIVE: To determine the effect of maternal cocaine exposure on fetal lung maturity as measured by surfactant-albumin ratios determined by the TDx-FLM test. METHODS: A case-control study design was used to compare fetal lung maturity as assessed by a surfactant-albumin ratio assay (TDx-FLM) in amniotic fluid (AF) obtained from women who were known to use cocaine and those who were not known to use cocaine during the study pregnancy. Multiple logistic regression procedures were used to control for gestational age and possible confounders, such as obstetric and nonobstetric complications, other substance abuse, race, infant sex, and payer status. RESULTS: Maternal cocaine use during pregnancy was associated with an accelerated fetal lung maturity profile (adjusted odds ratio [OR] 2.04, 95% confidence interval [CI] 1.04-4.00) as determined by the TDx-FLM test. Other variables found to be statistically significant predictors of a mature fetal lung profile were cigarette smoking during the current pregnancy (OR 1.61, 95% CI 1.02-2.56). Preterm labor, preterm rupture of membranes, nonobstetric illness during pregnancy, and exposure to other abused substances were not associated with accelerated fetal lung maturity. CONCLUSION: Maternal cocaine use during pregnancy is associated with a doubling of the probability of a mature fetal lung profile as determined by TDx-FLM analysis of AF. Tobacco use is also a predictor of accelerated fetal lung maturity profiles.
Adolescent↗
Biochemical analysis of the interaction of fibronectin with IgG and localization of the respective binding sites.
Fibronectin (Fn), a mosaic protein composed of multiple copies of three different module types (Fl, F2 and F3), has been found associated with circulating immune complexes (ICs) and immunoglobulin (Ig) aggregates in a variety of IC diseases and myeloproliferative disorders. We have previously shown that a proteolytic fragment of Mr = 25,900 Da, from the NH2-terminal domain of Fn, composed of five type 1 modules (1Fl -5Fl) binds to the major Ig classes under physiologic conditions, suggesting that the presence of Fn in ICs and cryoglobulins results from a physicochemical binding interaction between these two molecules. Using an ELISA, we now show that the interaction between Fn and IgG is: (1) not influenced by any other constituent of plasma; (2) unaffected by temperature; and (3) has an estimated Kd of 3.77 x 10(-9) M. In addition, we have further delineated the respective sites involved in the interaction between Fn and IgG. Recombinant type l module pairs (1Fl.2Fl and 4Fl.5Fl) from the NH2-terminus of Fn, expressed in yeast, were employed in an ELISA and affinity chromatography and compared with the 25.9 kDa (1Fl - 5Fl) fragment and intact Fn for binding to IgG. The 4Fl.5Fl and the 25.9 kDa fragment bound to immobilized IgG and inhibited Fn binding to IgG to nearly the same extent as the intact molecule (IC50: Fn = 6.77 x 1O(-9) M; 25.9 kDa fragment = 5 x 10(-9) M; 4Fl.5Fl = 7.6 x 10(-9) M). Thus, the binding site for IgG on the Fn molecule is localized to and completely conferred by the 4Fl.5Fl module pair (residues 151-244). Similar experiments using papain-generated Fab and Fc fragments of IgG localized the Fn binding site on IgG to the Fe region of the IgG molecule. Fn bound to the Fc fragment with a nearly identical Kd of 3.69 x 10(-9) M, as to intact IgG (3.77 x 10(-9) M). These studies support the hypothesis that the interaction between Fn and Ig may contribute to the pathophysiology of immune complex related disorders.
Binding Sites↗
Post-operative nerve damage and the removal of the mandibular third molar: a matter of common consent.
The aim of this study was to seek a consensus regarding written preoperative warning of possible nerve damage for patients having outpatient surgical removal of mandibular third molar teeth with local analgesia in Oral and Maxillofacial surgical units throughout the UK. The person first advising the patient is not always the one undertaking the operative procedure, and confusion concerning consent may arise in such circumstances. Questionnaires were sent to 140 consultants in Oral and Maxillofacial surgery units throughout the UK. Replies were received from 101 consultants. Of these, 29.7% routinely provided patients with a written warning of potential nerve damage. 66.3% routinely provided a verbal warning, and 4% did not routinely provide either a written or verbal warning.
Duty to Warn↗
Psychopathological syndromes in the functional psychoses: associations with course and outcome.
The aim of this study was to identify underlying dimensions of psychopathology in a cohort of patients with functional psychosis of recent onset, and to examine their prognostic value. Factor analysis of the psychopathological features of 166 consecutively admitted patients with functional psychosis of recent onset revealed seven psychopathological dimensions, which explained 63% of the variance. Five of these seven syndromes bore differential associations with subsequent treatment and illness course, independent of: (i) associations with DSM-III-R diagnosis; (ii) associations with other prognostic factors; and (iii) associations with the baseline values of outcome variables. The most striking associations were shown for an early and insidious onset syndrome with affective flattening, which predicted a more disabled course of illness on three of four outcome dimensions, and which was more common in males and unmarried individuals. A second syndrome, characterized by bizarre behaviour, inappropriate affect, catatonia, and poor rapport showed similar, slightly less striking, associations with illness course, as well as with poor pre-morbid social functioning. A third syndrome, characterized by positive psychotic symptoms was to a lesser degree associated with poorer outcome, whereas a fourth syndrome distinguished by manic symptomatology predicted a more benign illness course. A fifth syndrome identified by lack of insight predicted more time in hospital and admission under a section of the Mental Health Act during the follow-up period. A further finding was that dimensional representations of psychopathological features were considerably more useful than categorical representations (DSM-III-R and ICD-10) as predictors of illness course and treatment decisions.
Adolescent↗
Age and forgetfulness: confidence in ability and attribution for memory failures.
Perceivers read a script of a forgetful young, middle-aged, or older male or female target being interviewed for a volunteer position. Afterward perceivers rated their opinion of the target's memory, confidence in the target's capability of performing tasks, and attributions for the target's memory failures. Perceivers were more confident and attributed failures more to lack of effort and attention when targets experienced episodic than semantic memory failures. Perceivers' memory opinion was less negative for older than for young and middle-aged targets, but their confidence ratings were equivalent across target age groups. Perceivers used an age-based double standard in their attribution ratings. However, double-standard evidence was not as strong as in prior studies using less evaluative contexts.
Adolescent↗
The new era of hospital epidemiology: what you need to succeed.
Managed care and competition are creating pressures to control costs and prevent adverse outcomes in health care. These forces are also creating a new era in hospital epidemiology, one in which there are many opportunities for the infectious disease physician. The ability to create and administer a hospital epidemiology program is a valuable asset in this environment. Included in hospital epidemiology programs are activities such as infection control, quality management, employee health, risk management, and microbiology and clinical pharmacy consultations. The hospital epidemiologist must be prepared to take advantage of the opportunities created.
Epidemiology↗
Epstein-Barr virus-induced infectious mononucleosis complicated by acute renal failure: case report and review.
Infectious mononucleosis, most commonly caused by Epstein-Barr virus (EBV), is generally a benign, self-limited illness. Occasionally, however, more severe complications may arise such as acute renal insufficiency. While subclinical renal involvement appears to be relatively common in patients with infectious mononucleosis, patients with significant renal parenchymal dysfunction have rarely been described in the English-language literature. In this report, we review 27 previous cases ad present a case of oliguric renal failure complicating heterophil-positive infectious mononucleosis. The patient required hemodialysis but recovered promptly with treatment with the combination of corticosteroids plus acyclovir. Renal biopsy revealed interstitial nephritis, and immunoperoxidase studies demonstrated a predominance of suppressor/cytotoxic T cells, which has been described in only one previous case report. In situ hybridization done on renal biopsy tissue failed to reveal evidence of EBV-encoded RNA-1. Acute renal failure in infectious mononucleosis is rare, often self-limited, and usually caused by interstitial nephritis that is likely the result of immunopathologic injury precipitated by EBV infection.
Acute Kidney Injury↗
Sampling for qualitative research using quantitative methods. 1. Measuring GPs' attitudes towards discussing smoking with patients.
BACKGROUND: Interview studies which employ qualitative methodology are often concerned with classifying behaviours or attitudes and an ideal sample of research subjects displays variety in the attitudes or behaviours under scrutiny. OBJECTIVE: This paper describes the development of a questionnaire which measures GPs' attitudes towards discussing smoking with patients with the intention of using this instrument to select GPs with diverse views for a qualitative interview study. METHOD: Thirteen attitude statements with an accompanying Likert-type scale were completed by 327 GPs in one FHSA area. Factor analysis of responses produced two subscales: 'perceived efficacy' and 'enthusiasm'. Reliability and validity of these were examined. RESULTS: Each subscale had good internal reliability and preliminary exploration of construct validity supported the notion that the subscales were valid. CONCLUSION: The use of this type of instrument in sampling GPs for qualitative studies could be effective for selecting subjects with a diversity of views towards the research topic.
Attitude of Health Personnel↗