Airway hyperresponsiveness as a determinant of the early asthmatic response to inhaled allergen.
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Administration, Inhalation↗
Biomedical subjects
B E Davis
Publications and source records attributed to B E Davis.
The links between allergen skin test sensitivity, airway responsiveness and airway response to allergen.
BACKGROUND: The allergen-induced early asthmatic response [provocation concentration (PC)20, the concentration causing a 20% forced expiratory volume in 1 s (FEV)1 fall] depends on the level of IgE sensitivity and the degree of nonallergic airway hyperresponsiveness (AHR) and can be predicted from histamine PC20 and allergen skin test endpoint. OBJECTIVES: We examined the relationships between allergen PC20, methacholine PC20, and allergen skin test endpoint and assessed the accuracy of both the histamine PC20-based prediction of allergen PC20 (using methacholine) and a new methacholine PC20-based prediction equation. METHODS: From 158 allergen challenges, the allergen PC20, the methacholine PC20, and the skin test endpoint were recorded and relationships between these three were sought. We compared the measured allergen PC20 to that predicted from the previous histamine PC20-based and the new methacholine-based formulae. RESULTS: In single regressions, allergen PC20 correlated with both methacholine PC20 (r=0.25, P=0.0015) and skin test endpoint (r=0.52, P <0.00005). The relationship was improved by multiple regression of log-allergen PC20vs. log-methacholine PC20 and log-endpoint (r=0.61, P <0.00005). The histamine-based formula predicted allergen PC20 to within 2 doubling concentrations in 80% and within 3 in 92%. The new methacholine-based formula to within 2 and 3 concentrations in 81% and 94%, respectively; only nine of 158 subjects were outside the 3 concentrations. CONCLUSIONS: We have confirmed the dependence of the allergen-induced early asthmatic response upon the level of allergic sensitivity and the degree of AHR, the latter as assessed by methacholine challenge. The allergen PC20 can be predicted to within 3 doubling concentrations in 94% of cases.
Adult↗
Regular salbutamol use increases CXCL8 responses in asthma: relationship to the eosinophil response.
Regular salbutamol use can exacerbate allergen-induced airway eosinophilia in asthmatics, but its effect on airway eosinophil chemokine responses is unknown. Asthmatic subjects (n=14) were treated for 10 days with placebo or salbutamol in a double-blind, cross-over study, then given same-dose allergen challenges. Their sputa were then analysed 1 and 7 h later for a panel of eosinophil-related cytokines. Eosinophils from five test and three control subjects were tested for expression of CXCL8/interleukin (IL)-8, and its receptors and responsiveness to CCL11/eotaxin and CXCL8/IL-8. Sputum CXCL8/IL-8, but not IL-5, CCL5/regulated on activation, T-cell expressed and secreted, CCL7/monocyte chemotactic protein-3, CCL11/eotaxin, granulocyte-macrophage colony-stimulating factor or tumour necrosis factor levels, were increased (42%) by the salbutamol treatments. The CXCL8/IL-8 levels correlated with the proportions of sputum eosinophils and these cells, but not other sputum cells, stained strongly for CXCL8/IL-8. The circulating eosinophils of the tested subjects (n=5) expressed CXCL8/IL-8 receptors and secreted high levels of this chemokine. Neutralisation of sputum CXCL8/IL-8 reduced eosinophil chemotactic responses to these samples by 19 +/- 5%. These data suggest that regular use of salbutamol can augment airway CXCL8/interleukin-8 responses to allergen challenge and that this CXCL8/interleukin-8 could contribute to the airway inflammatory response.
Adult↗
Do clerkship experiences affect medical students' attitudes toward chronically ill patients?
PURPOSE: To measure changes in medical students' attitudes toward chronically ill patients, and to identify experiences, specifically during clerkships, that contributed to students' attitudes. METHOD: A cohort of students from five U.S. medical schools voluntarily participated in three surveys longitudinally administered before and after required clinical rotations. The first two questionnaires were identical and asked for demographic information and pre-matriculation experiences with chronically ill patients. The third was modified to include questions about clinical experiences with chronically ill patients. Responses from the first and third questionnaires were linked for analysis. RESULTS: A total of 502 of 695 students (69%) completed both the first and the third questionnaires. Many students (36%) had had pre-matriculation experiences with chronic illness. After clinical training, 25% of the respondents stated that they would seek another career specialty if the incidence of chronically ill patients increased in their chosen field, compared with the 9% who responded so before clinical training (p <.001). While 73% of the students had favorable perceptions toward chronically ill patients, and 91% felt involved in care, significantly fewer students (p <.01) had had positive patient care experiences when working with residents (57%) and attendings (59%). Gender, age, prior experiences, and school site were not associated with attitudinal changes. CONCLUSION: Students begin medical school with positive attitudes toward caring for chronically ill patients, but this perception depreciates with clinical experience, which may affect specialty decisions. Contributing factors may include adequate role modeling by residents and attendings and a perceived discrepancy in the quality of care patients receive.
Adult↗
Regular inhaled salbutamol : effect on airway responsiveness to methacholine and adenosine 5'-monophosphate and tolerance to bronchoprotection.
OBJECTIVE: Regular treatment with inhaled beta(2)-agonists increases airway responsiveness consistently to indirect bronchoconstrictors (allergen, exercise, hypertonic saline solution, etc) and inconsistently to direct bronchoconstrictors (histamine, methacholine). Studies demonstrating tolerance to beta(2)-agonist bronchoprotection against the indirect bronchoconstrictor adenosine 5'-monophosphate (AMP) have not examined changes in baseline AMP responsiveness. This study assessed the effect of regular salbutamol on AMP and methacholine responsiveness and on tolerance to bronchoprotection. DESIGN: Double-blind, randomized, crossover study. SETTING: University hospital bronchoprovocation laboratory. PATIENTS: Fourteen atopic asthmatic subjects with FEV(1) > 65% predicted, and methacholine provocative concentration causing a 20% fall in FEV(1) (PC(20)) < 8 mg/mL. INTERVENTIONS: Salbutamol, 100 microg, and placebo inhalers, two puffs qid, each for 10 days. MEASUREMENTS: Methacholine PC(20) and AMP PC(20) measured 12 h after blinded inhaler after each treatment period. Methacholine PC(20) and AMP PC(20) repeated 10 min after salbutamol, 200 microg (eight subjects). RESULTS: There was no difference between placebo and salbutamol treatment in geometric mean methacholine PC(20) (0.85 mg/mL vs 0.82 mg/mL, p = 0.86) or AMP PC(20) (22 mg/mL vs 17.4 mg/mL, p = 0.21; n = 14). The acute bronchoprotective effect of salbutamol was greater vs. AMP than vs methacholine (5.1 doubling concentrations vs. 3.5 doubling concentrations, p = 0.06) and loss of protective effect of salbutamol (mean +/- SD) was greater vs AMP than vs. methacholine (2.4 +/- 0.33 doubling concentration loss vs 0.8 +/- 0.21 doubling concentration loss, p = 0.008; n = 8). CONCLUSION: Regular salbutamol (mean +/- SD) treatment did not enhance airway responsiveness to either the indirect bronchoconstrictor AMP or the direct bronchoconstrictor methacholine. Compared to its effect on methacholine, salbutamol had a greater acute protective effect vs AMP and produced greater loss of protection vs AMP when used regularly.
Adenosine Monophosphate↗
Longevity of patients born with myelomeningocele.
There are limited data concerning the life expectancy for individuals born with myelomeningocele (MM), with and without hydrocephalus. To ascertain such data was our first purpose. We have selected all patients with MM in our computer database, The Patient Data Management System (PDMS/fx). Data were transferred to Excel for primary and SPSS/PC for final analysis by Kaplan-Meier life survival curves. Of the 1,054 patients with MM in the Birth Defects Clinic and the University of Washington Medical Center (UWMC) of Seattle, 505 are now over the age of 21 (391) or have died (114). Follow-up information was available since 1994 for 132, 62% of whom we have had contact within the past 2 years. The second purpose was to identify potential health factors associated with long-term outcome of patients with MM. Patient variables chosen as relevant to survival included hydrocephalus, treatment before or after 1975, and health maintenance determined by outcome for those receiving care within the last 5 years or those last seen before. Age at last appointment and reason for visit were determined in order to identify age-specific health care needs of the adult population. Survival and medical needs were obtained from the UWMC's computer database, Mindscape, and by telephone survey for adult patients not seen in the last 2 years. Death is more frequent earlier in life for those MM patients with hydrocephalus. Ordinary degenerative disorders affect MM patients earlier in life than normals. Our data extend life expectancy for patients with MM and hydrocephalus to age 40 years with some reliability for those treated from 1957 to 1974, but only 24 years for those treated with modern techniques after 1974. More data is needed to determine long-term survival.
Adolescent↗
Calculation of provocative concentration causing a 20% fall in FEV(1): comparison of lowest vs highest post-challenge FEV(1).
BACKGROUND: Considerable, unexamined controversy exists surrounding the use of the highest vs the lowest FEV(1) for calculating the provocative concentration causing a 20% fall in FEV(1) (PC(20)) during direct bronchoprovocation challenges. OBJECTIVE: To compare the PC(20) calculated using the lowest FEV(1) post-diluent and post-histamine/methacholine vs the PC(20) calculated using the highest FEV(1) post-diluent and post-histamine/methacholine. METHOD: Retrospective analysis of 225 challenges: 75 research methacholine challenges, 75 research histamine challenges, and 75 clinical methacholine challenges. For each test, the PC(20) was calculated twice, first using the lowest post-diluent FEV(1) to the lowest post-histamine/methacholine FEV(1), and then using the highest to the highest. RESULTS: The intraclass correlation coefficients for methacholine research, histamine research, and methacholine clinic challenges were 0.99, 0.98, and 0.95, respectively. The PC(20) calculated using the lowest to lowest FEV(1) was slightly and significantly lower in all three groups (paired t test p < 0.0001). CONCLUSIONS: The PC(20) values calculated using the highest FEV(1) are almost identical to the PC(20) values calculated using the lowest FEV(1). The difference, although clinically irrelevant, holds statistical significance.
Bronchial Hyperreactivity↗
Periurethral transurethral microwave thermotherapy for the treatment of benign prostatic hyperplasia: an interim 1-year safety and efficacy analysis using the thermatrx TMx-2000.
Transurethral microwave thermotherapy (TUMT) represents an accepted minimally invasive approach to the management of patients with benign prostatic hyperplasia (BPH). The TherMatrx TMx-2000 represents a further evolution in TUMT technique. This device uses periurethral transurethral microwave thermotherapy (P-TUMT) technology to directly target the BPH tissue adjacent to the prostatic urethra by using a catheter without a urethral-cooling surface. This article provides a technical review of the device and describes the results of a randomized, controlled multicenter study of P-TUMT for the treatment of symptomatic BPH. A discussion of the physiologic effects of P-TUMT is presented and compared to conventional TUMT. A comparison of P-TUMT to contemporary TUMT series in relation to efficacy and complications is also described. This study concludes that P-TUMT using the TherMatrx TMx-2000 device represents a minimally invasive, efficacious, and well-tolerated treatment for symptomatic BPH.
Aged↗
Prone infant sleeping despite the "Back to Sleep" campaign.
OBJECTIVES: To determine sleep position variation during the first 6 months of life and to identify risk factors for prone sleeping. DESIGN: Cohort study of healthy term newborns recruited from November 1995 to September 1996 and followed up to age 6 months. Pediatricians were surveyed about sleep position advice. At recruitment, all parents were instructed to avoid prone sleeping. Parents were telephoned at 1 week and then monthly to ensure that they recorded sleep position. Investigators were unaware of sleep position until the infant was 6 months of age, when sleep log data and reasons for sleep position choice were ascertained. SETTING: Practice-based study conducted by the Children's National Medical Center Pediatric Research Network, Washington, DC. PARTICIPANTS: A total of 402 consecutive healthy term newborns followed up by a Pediatric Research Network pediatrician were enrolled. Exclusion criteria were prematurity, a serious medical condition, and absence of a telephone. Of the 402 enrolled newborns, 348 (86.6%) completed the study. RESULTS: Only 34.0% of infants maintained a consistent sleep position. Prone sleeping increased from 12.2% at birth to 32.0% at 6 months. One third of pediatricians discussed sleep position beyond the newborn period. The following were associated (P<.05) with prone sleeping: male sex, lower maternal education level, single marital status, having siblings, and black race. Perceived infant comfort was the main reason for prone sleeping. CONCLUSIONS: Most newborns are placed by parents in nonprone sleep positions. Pediatricians need to consistently reinforce the "Back to Sleep" message when the infants are 2 to 4 months of age because this is the most likely time that they are switched to prone sleeping and the highest risk period of sudden infant death syndrome. Parents should not use prone sleeping as a means of comforting infants.
Cohort Studies↗
Severe early onset preeclampsia secondary to bilateral ureteral obstruction reversed by stenting.
BACKGROUND: Severe early onset preeclampsia might be reversed by correction of an underlying pathophysiologic condition. CASE: A 22-year-old nullipara with a history of antivesicoureteral reflux surgery in childhood presented at 23 weeks' gestation with severe headaches, hypertension, proteinuria, edema, and acute renal failure. Severe preeclampsia was diagnosed, and bilateral distal ureteral obstruction was documented by cystoscopy, fluoroscopy, and retrograde pyelography. Bilateral ureteral stent placement completely resolved the preeclampsia and prolonged pregnancy until term. CONCLUSION: Pregnant women with a history of antireflux surgery in childhood might be at risk for acute renal failure and severe preeclampsia caused by bilateral ureteral obstruction. Ureteral stent placement might reverse obstruction, renal failure, and preeclampsia.
Adult↗
Tolerance to the bronchoprotective effect of beta2-agonists: comparison of the enantiomers of salbutamol with racemic salbutamol and placebo.
BACKGROUND: Regular use of racemic salbutamol results in the partial loss of its bronchoprotective effect. The 2 enantiomers of salbutamol, the bronchodilator R-salbutamol and nonbronchodilator S-salbutamol, are now available. OBJECTIVE: We sought to compare the effect of regular use of S-salbutamol, R-salbutamol, racemic salbutamol, and placebo on the bronchoprotective effect of a single dose of racemic salbutamol against methacholine-induced bronchoconstriction. METHODS: Eleven of 13 well-controlled beta2 -agonist-free asthmatic subjects completed a double-blind, randomized study comparing racemic salbutamol 2.5 mg, S-salbutamol 1. 25 mg, R-salbutamol 1.25 mg, and diluent placebo nebulized and inhaled 3 times daily for 6 days (>/=6-day washout period). Ten to 12 hours after the last dose, the subjects performed measurement of FEV1, methacholine PC20, and a repeat methacholine PC20 done 1 hour after the first methacholine test and 10 minutes after 2 puffs (200 microgram) of racemic salbutamol administered from a metered-dose inhaler. The primary endpoint was the methacholine PC20 dose shift (Deltalog PC20/log 2) from before to after administration of 200 microgram of racemic salbutamol. RESULTS: The methacholine dose shift was 3.2 doubling doses (9-fold increase in methacholine PC20 after 200 microgram of racemic salbutamol) during the placebo treatment and was unaltered (3.2) after administration of S-salbutamol. The dose shift was significantly lower after both the R-salbutamol and racemic salbutamol treatments (2.2 and 2.6 doubling doses, respectively); there was no significant difference between R-salbutamol and racemic salbutamol. There was no treatment effect on baseline FEV1, baseline methacholine PC20, or bronchodilation. CONCLUSION: Regular treatment with racemic salbutamol or R-salbutamol, but not S-salbutamol, results in a partial loss of bronchoprotection, without loss of bronchodilation, compared with placebo.
Adrenergic beta-Agonists↗
Dose versus concentration of methacholine.
BACKGROUND: The methacholine challenge test is a common investigation used to identify airway hyperresponsiveness. There has been recent debate as to whether the airway effect is due to the concentration or the dose of methacholine. OBJECTIVE: To determine whether the airway response during a methacholine challenge test is due to the concentration or the dose of methacholine. METHODS: Ten subjects with stable, mild asthma were enrolled in this study. Two methacholine challenge tests, one with 30-second inhalations of methacholine and the other with two minute inhalations of methacholine, were performed on each subject in a random order on 2 days within a 1-week period at approximately the same time each day. RESULTS: The geometric mean 2-minute PC20 was 1.1 mg/mL and the geometric mean 30-second PC20 was 5.7 mg/mL, 5.2-fold greater than the mean 2-minute PC20. The paired t-test comparison of the 2-minute PC20 multiplied by 4 and the 30-second PC20 revealed no significant difference (P > .2). CONCLUSIONS: The dose of methacholine is primarily responsible for the degree of bronchial response rather than the concentration.
Asthma↗
Salmeterol, inhaled corticosteroids, and tolerance to allergen bronchoprotection.
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Administration, Inhalation↗
Clinical efficacy and safety of tolterodine compared to placebo in detrusor overactivity.
PURPOSE: We evaluated the efficacy, patient acceptability and side effect profile of tolterodine, a new antimuscarinic agent for treating bladder overactivity. MATERIALS AND METHODS: In our randomized, placebo controlled, parallel group study 123, 129 and 64 patients 18 years old or older with proved detrusor overactivity (idiopathic detrusor instability or detrusor hyperreflexia) were randomized to receive 1 or 2 mg. tolterodine, or placebo, respectively, twice daily for 12 weeks. Main outcome measures were number of voids per 24 hours, urine volume per void and episodes of urge incontinence per 24 hours on a frequency-volume chart with detailed recording of side effects. RESULTS: After 12 weeks of treatment mean number of voids per 24 hours plus or minus standard deviation decreased from 11.2 +/- 3.1 to 9.0 +/- 2.6 with the 2 mg. dosage (p = 0.0045 versus placebo). At this dose mean urine volume per void increased from 155 +/- 52 to 190 +/- 70 ml. (p <0.0001 versus placebo), while mean number of incontinence episodes per 24 hours decreased from 3.6 +/- 4.0 to 1.8 +/- 3.1 (p = 0.19 versus placebo). Similar efficacy was observed in patients receiving the 1 mg. dose. Severe dry mouth was reported by only 2, 1 and 2% of patients given the 1 and 2 mg. dose, and placebo, respectively. There was no clinical or electrocardiographic evidence of significant cardiac adverse events. CONCLUSIONS: Tolterodine administration resulted in a significant decrease in the frequency of voiding and improved voided volume but it was seldom associated with troublesome or severe side effects.
Adult↗
Effects of sleep position on infant motor development.
BACKGROUND: As a result of the American Academy of Pediatrics' recommendation that healthy infants be placed on their side or back for sleep, the percentage of infants sleeping prone has decreased dramatically. With the increase in supine sleeping, pediatricians have questioned if there are differences in the rate of acquisition of early motor milestones between prone and supine sleeping infants. METHODS: To examine this question, we performed a prospective, practice-based study of healthy term infants. Infants were recruited before the age of 2 months. Parents were asked to record infant sleep position and awake time spent prone until 6 months of age. A developmental log was used to track milestones from birth until the infant was walking. Age of acquisition of eight motor milestones was determined, and the mean ages of milestone attainment of prone and supine sleepers were compared. RESULTS: Three hundred fifty-one infants completed the study. Prone sleepers acquired motor milestones at an earlier age than supine sleepers. There was a significant difference in the age of attainment of rolling prone to supine, tripod sitting, creeping, crawling, and pulling to stand. There was no significant difference in age when infants walked. CONCLUSIONS: The pattern of early motor development is affected by sleep position. Prone sleepers attain several motor milestones earlier than supine sleepers. However, all infants achieved all milestones within the accepted normal age range. Pediatricians can use this information to reassure parents. This difference in milestone attainment is not a reason to abandon the American Academy of Pediatrics' sleep position recommendations.
Child Development↗
Selected topics in dermatology for the primary care physician.
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Diagnosis, Differential↗
Novel 2- and 5-azido-N-(diphenylcarbamoyl)proline methyl esters. Examples of a novel proline oxidation.
The crystal structures of two azido-substituted proline derivatives are reported. Racemic 2-azido-1-(diphenyl-carbamoyl)proline methyl ester, (I), C19H19N5O3, is resolved upon crystallization from methylene chloride-diethyl ether. The azido moieties are nonlinear with N--N--N angles of 173 (1) and 170.3 (2) degrees for (I) and (II) [cis-5-azido-N-(diphenylcarbamoyl)proline methyl ester, C19H19N5O3], respectively. Close intramolecular contacts between the carbonyl O atom of the amide and the central N atom of the azido group are found. The contact distances between N7 and O14 are 2.780 (14) and 2.815 (2) A for (I) and (II), respectively.
Crystallography, X-Ray↗
4,7-Dimethoxybenzo[c]furan.
The title compound, C10H10O3, is nearly planar with a maximum deviation from planarity of 0.140 (2) A for methoxy atom C11. The geometry of the benzo[c]furan moiety is indicative of a non-aromatic ring system. The bond lengths more closely resemble those of two non-interacting diene systems than those of an aromatic one. There are alternating long and short bond lengths around the ring skeleton with the long and short C-C bonds averaging 1.437 (2) and 1.354 (2) A, respectively. There are close C-H ... O intermolecular contacts which may help stabilize the molecule in the solid state.
Benzofurans↗