Neutron reflectivity of supported membranes incorporating terminally anchored polymers: Protrusions vs. blisters.

The effect of terminally anchored chains on the structure of lipid bilayers adsorbed at the solid/water interface was characterized by neutron reflectivity. In the studied system, the inner leaflet, closer to the substrate, consisted of head-deuterated 1,2-distearoyl-sn-glycero-3-phosphorylcholine (DSPC) and the outer leaflet comprised a mixture of DSPC and polyethylene glycol (PEG) functionalized 1,2-distearoyl-sn-glycero-3-phosphoethanolamine. The DSPC headgroups were deuterated to enhance sensitivity and demarcate the bilayer/water interface. The effect on the inner and outer headgroup layers was characterized by w(1/2), the width at half-height of the scattering length density profile. The inner headgroup layer was essentially unperturbed while w(1/2) of the outer layer increased significantly. This suggests that the anchored PEG chains give rise to headgroup protrusions rather than to blister-like membrane deformations.

Atomic force microscopy of polymer brushes: colloidal versus sharp tips.

Force versus distance profiles acquired by atomic force microscopy probe the structure and interactions of polymer brushes. An interpretation utilizing the Derjaguin approximation and assuming local compression of the brush is justified when colloidal probes are utilized. The assumptions underlying this approach are not satisfied for sharp tips, and deviations from this model were reported for experiments and simulations. The sharp-tip force law proposed assumes that the free energy penalty of insertion into the brush is due to the osmotic pressure of the unperturbed brush. This static force law is in semiquantitative agreement with the simulation results of Murat and Grest (Murat, M.; Grest, G. S. Macromolecules 1996, 29, 8282).

A multivariate model for the prediction of relapse after outpatient treatment of decompensated chronic obstructive pulmonary disease.

PURPOSE: To develop and validate a multivariate model for predicting relapses after treatment of decompensated chronic obstructive pulmonary disease in an emergency department. METHODS: A 5-year survey was conducted, including training and validation periods. Stepwise logistic regression was used to develop a multivariate predictive model using clinical data obtained at the time of each visit. A relapse was defined as an unscheduled return to the emergency department within 48 hours. SITE: The study was conducted in the emergency department of the Albuquerque (New Mexico) Veterans Affairs Medical Center. SUBJECTS: The subjects were 289 patients with documented chronic obstructive pulmonary disease. MEASUREMENTS AND MAIN RESULTS: During the first 3 years, there were 705 visits in which the patient was treated and released from the emergency department. Relapse occurred 82 times (11.6%). Logistic regression showed that the following variables had an effect on the risk of relapse: the relapse rate for previous visits, a previous visit within 7 days, long-term home oxygen therapy, the number of doses of nebulized bronchodilators, the administration of aminophylline, and the use of antibiotics and prednisone at the time of discharge from the emergency department. During the next 2 years, the 48-hour relapse rate was 9.9% (47 of 476 discharges). When the model was fitted to these data, all of the original variables contributed to the prediction of relapse except antibiotic use and long-term home oxygen therapy. The logistic model was used to categorize each visit during the validation phase. The relapse rate for "high-risk" visits was significantly higher than that for "low-risk" visits (18.4% vs 6.1%). The method identified 57.4% of visits that ended in relapse at 48 hours. CONCLUSIONS: A multivariate model can be used to identify patients with a poor prognosis after the outpatient treatment of decompensated chronic obstructive pulmonary disease.

A multivariate model for predicting hospital admissions for patients with decompensated chronic obstructive pulmonary disease.

PURPOSE: To develop a method for predicting hospital admissions for patients with decompensated chronic obstructive pulmonary disease treated in an emergency department. METHODS: A 4-year survey including training and validation periods was conducted. Stepwise logistic regression was used to develop a multivariate model using information from the patient's previous visits and results of baseline pulmonary function tests. MEASUREMENTS AND MAIN RESULTS: During the first 2 years, there were 693 visits to the emergency department for decompensated chronic obstructive pulmonary disease. The patient was admitted to the hospital on 210 occasions (30.3%). Logistic regression showed that the probability of admission was related to the following: the admission and relapse rates for previous visits, the proportion of previous discharges from the emergency department in which "conservative therapy" was given, the highest baseline post-bronchodilator forced expiratory volume in 1 second within 3 years of entry, and the highest baseline pre-bronchodilator forced expiratory volume in 1 second-vital capacity ratio. A relapse was defined as an unscheduled return to the emergency department within 48 hours. "Conservative therapy" was any treatment regimen that did not include parenteral medications. During the next 2 years, the model was validated with patients not previously treated at this medical center. Seventy-six (28.3%) of 269 episodes resulted in hospital admission. The logistic model was used to categorize each visit during the validation phase. "High-risk" visits had calculated probabilities of admission greater than .208, while "low-risk" visits had values that were less. The admission rate for 98 low-risk visits (8.2%) was much lower than the rate for 171 high-risk visits (39.8%). CONCLUSIONS: A multivariate model can be used to identify patients with decompensated chronic obstructive pulmonary disease who are unlikely to need hospitalization. This model could be used to select episodes of decompensated chronic obstructive pulmonary disease for treatment at home.

Verapamil and propranolol in essential hypertension.

Twenty-four subjects with mild to moderate essential hypertension completed this 9-wk parallel, randomized, double-blind study of the antihypertensive effects of verapamil (V) (240 to 480 mg%) and propranolol (P) (120 to 360 mg%). V lowered systolic and diastolic blood pressures in all postural positions, with an average reduction of 20/16 mm Hg. With the exception of standing systolic blood pressure, P also lowered systolic and diastolic blood pressures in all postural positions, with an average reduction of 9/11 mm Hg. Differences between V and P were significant only for sitting systolic blood pressure. Heart rate was decreased by P but was not affected by V. The PR interval was prolonged by V. Plasma levels of V and P were directly related to dose. Plasma levels of V were linearly related to those of its major metabolite, norverapamil (r = 0.81). There was no correlation between clinical response and the dose or plasma level of V or P, but all subjects who received 480 mg% V had an average blood pressure reduction of 20/16 mm Hg and plasma levels of the parent drug above 200 ng/ml. V is an effective antihypertensive for mild to moderate essential hypertension. Constipation, pedal edema, and a maculopapular rash were reported as side effects of V.

The effect of a hospitalist service with nurse discharge planner on patient care in an academic teaching hospital.

PURPOSE: To evaluate the impact of implementing a hospitalist service with a nurse discharge planner in an academic teaching hospital. SUBJECTS AND METHODS: Inpatient medicine service was provided by hospitalists, general internists, and specialists. Service personnel were identical except that the hospitalist service also had a nurse discharge planner. Hospitalists attended 4 months per year (compared with the 1 month by most other attending physicians) and had no outpatient responsibilities during the ward months. Patients were admitted alternately based on resident call schedule. Major outcomes included average costs of hospitalization, length of stay, and resource utilization. Quality measures included inpatient mortality, 30-day readmission rates, and satisfaction of patients, residents and students. RESULTS: Hospitalist-attended services had lower mean (+/- SD) inpatient costs per patient ($4289 +/- $6512) compared with specialist-staffed services ($6066 +/- $7550, P < 0.0001), with a trend toward lower costs when compared with generalist-attended services ($4850 +/- $7027, P = 0.11). Hospitalist services had shorter mean lengths of stay (4.4 +/- 4.0 days), compared with generalists (5.2 +/- 5.2 days) and specialists (6.0 +/- 5.5 days, P < 0.0001 for hospitalists vs. both groups). Readmission rates were similar in all groups. Mortality rates were higher in the specialist group [5.0% (44 of 874)] compared with hospitalists [2.2% (18 of 829)] and generalists [2.6% (20 of 761), P = 0.002 for specialists vs. both groups, P = 0.09 for generalists vs hospitalists]. Satisfaction results were uniformly high in all groups, with no significant differences. CONCLUSION: Hospitalist services with a nurse discharge planner were associated with lower average cost and shorter average length of hospital stay, without any apparent compromise in clinical outcomes or patient satisfaction.

Antihypertensive effectiveness of the nifedipine gastrointestinal therapeutic system.

The results of a multicenter trial conducted in order to determine the therapeutic efficacy of the gastrointestinal therapeutic system (GITS) formulation of nifedipine in comparison with hydrochlorothiazide and placebo in the management of mild to moderate essential hypertension are presented. During a one-week wash-out phase, antihypertensive therapy was discontinued in all patients. After a three-week single-blind placebo period, eligible patients were randomly assigned in a double-blind fashion to one of three treatment groups for a one-week titration period and a nine-week efficacy period. Patients received either nifedipine GITS, 30 or 60 mg daily; hydrochlorothiazide, 25 or 50 mg daily; or placebo. Sitting and standing blood pressures decreased by an average 11.6/10.4 and 10.8/10.8 mm Hg, respectively, with nifedipine GITS therapy, and 14.8/10.8 and 14.3/8.2 mm Hg, respectively, with hydrochlorothiazide therapy. Compared with placebo, these changes were highly significant for both sitting (p less than or equal to 0.005) and standing (p less than or equal to 0.02) measurements. Heart rate remained essentially unchanged in all three groups. It was therefore concluded that monotherapy with nifedipine GITS, at doses of 30 or 60 mg given once daily, effectively reduces blood pressure in patients with hypertension to a degree comparable with that seen in hydrochlorothiazide therapy.

Intravenous and oral corticosteroids for the prevention of relapse after treatment of decompensated COPD. Effect on patients with a history of multiple relapses.

To determine if a regimen of intravenous and oral corticosteroids reduces the relapse rate after treatment of decompensated COPD in the ED, 30 patients were studied. Forty-five visits in which intravenous and oral corticosteroids were given (T visits) were compared with an equal number of matched visits in which they were withheld (N visits). No differences were noted between T and N visits with respect to clinical findings, laboratory results and other forms of therapy. Treatment with corticosteroids reduced the relapse rate within 24 h of discharge. At 48 h, the cumulative relapse rate for T visits (8.9 percent) was significantly lower than for N visits (33.3 percent; p = 0.005). For patients with a history of multiple relapses, a regimen consisting of intravenous and oral corticosteroids reduces the risk of relapse after ED treatment of decompensated COPD.

Aminophylline in the outpatient management of decompensated chronic obstructive pulmonary disease.

The objective of this study was to determine if IV aminophylline reduces the risk of relapse after treatment of decompensated COPD in an ED. Forty-six visits in which IV aminophylline was given (T visits) were compared with an equal number of visits in which it was withheld (N visits) with respect to pretreatment serum theophylline level, number of treatments with nebulized bronchodilators and use of parenteral beta-adrenergic drugs, IV corticosteroids and prednisone. The difference in 48-h relapse rates for T and N visits was examined by McNemar's test. No differences were found between T and N visits with respect to vital signs, pretreatment FEV1, arterial blood gas values, hematocrit level or blood leukocyte count. The 48-h relapse rate for T visits (22.2 percent) was significantly higher than for N visits (6.7 percent; p = 0.035). Aminophylline does not appear to be beneficial for outpatients with decompensated COPD and may be harmful.

The effect of nifedipine on cardiopulmonary responses during exercise in normal subjects.

We investigated the effects of a single dose of nifedipine (10 mg orally) on exercise performance during progressive incremental cycle ergometry in nine sedentary normal subjects in a double-blind, placebo-controlled crossover study. Maximum work load after nifedipine (213 +/- 42 watts; mean +/- SD) was less than after placebo (222 +/- 41 watts; p less than 0.05). Maximum oxygen consumption was unchanged. In addition, the drug decreased lactate threshold from 19.7 +/- 4.9 ml O2/min/kg to 15.5 +/- 5.5 ml O2/min/kg (p less than 0.02); gas exchange anaerobic threshold was unaffected. There were higher plasma lactate concentrations at low and intermediate exercise intensities after nifedipine compared with placebo (p less than 0.05). Systolic blood pressure was lower at high work loads (p less than 0.05) and heart rate was higher at low work loads (p less than 0.05) after nifedipine. We conclude that the short-term administration of nifedipine limits peak performance and increases plasma concentration of lactic acid in normal subjects. One or more of the following mechanisms may account for these observations: nifedipine decreases blood flow to skeletal muscle by diverting blood to nonexercising tissues; nifedipine increases catecholamine levels, thereby augmenting lactic acid production; and nifedipine decreases skeletal muscular contractility by selectively impairing fatigue-resistant fibers.

Extension of rod-coil multiblock copolymers and the effect of the helix-coil transition

The extension elasticity of rod-coil mutliblock copolymers is analyzed for two experimentally accessible situations. In the quenched case, when the architecture is fixed by the synthesis, the force law is distinguished by a sharp change in the slope. In the annealed case, where interconversion between rod and coil states is possible, the resulting force law is sigmoid with a pronounced plateau. This last case is realized, for example, when homopolypeptides capable of undergoing a helix-coil transition are extended from a coil state.

A comparison of the effects of nifedipine and verapamil on exercise performance in patients with mild to moderate hypertension.

Twenty-four patients completed a double-blind, randomized clinical trial comparing the effects of nifedipine GITS (N) and verapamil SR (V) on blood pressure (BP) control and exercise performance. After a 2-week placebo phase, all subjects had measurements of VO2max, maximal workload, and endurance time. They were then randomized to either N (30 to 90 mg/day) or V (240 to 480 mg/day) and retested when BPs had stabilized. At rest, N lowered systolic (S) BP by 12 mm Hg (P = .02 compared to baseline) and diastolic (D) BP by 11 mm Hg (P = .001). V lowered SBP by 8 mm Hg (P = .013) and DBP by 11 mm Hg (P = .002). Neither drug affected resting heart rate. V significantly decreased resting epinephrine (P = .05) and there was a tendency for V to reduce norepinephrine (P = .07) and dopamine (P = .08). N tended to increase plasma renin activity (P = .07). During graded cycle ergometry N, compared with placebo, significantly lowered DBP at all exercise levels (P = .011), but had no significant effect on heart rate (HR), SBP, or heart rate pressure product (HRPP). Pulse pressure (PP) was significantly increased (P = .045), which was most noticeable at high exercise levels. Compared with placebo, V caused a marked reduction of exercise HR (P < .001), which was more pronounced at high levels, SBP (P = .004), DBP (P = .004), mean arterial pressure (MAP) (P = .001), and HRPP (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of doxazosin monotherapy on blood pressure and plasma lipids in patients with essential hypertension.

The efficacy and safety of doxazosin (DOX) for the treatment of hypertension was investigated. A multicenter, double-blind, placebo-controlled, parallel design was employed. A 4-week placebo runin period was followed by a 9-week double-blind period during which patients were randomly assigned to placebo or 2, 4, or 8 mg doxazosin. Blood pressures (BP) and heart rates (HR) were measured 24 hours postdose. The mean changes in standing BP (mmHg) were -6.2/-6.9 (2-mg regimen), -5.7/-5.8 (4-mg regimen), -8.5/-7.7 (8-mg regimen) for DOX patients and 0.7/-2.9 for placebo patients. The mean changes in supine BP (mmHg) were -3.2/-4.7 (2-mg regimen), -4.0/-5.1 (4-mg regimen), -4.6/-5.6 (8-mg regimen) for DOX patients and -0.5/-3.3 for placebo patients. There was no evidence of a dose-response relationship for DOX; however, DOX serum levels were linearly related to the dose. Responder rate for the combined DOX patients was 38% (32/84) and for the placebo patients 27% (8/30). HR (24 hours postdose) was not modified by DOX. Patients in the 8-mg regimen had a significantly higher gain in mean body weight (+ 1.3 +/- 0.3 kg; P less than 0.05) compared to the 2-mg regimen, 4-mg regimen, and placebo groups. Plasma norepinephrine was not significantly modified by DOX. DOX had a favorable effect on plasma lipids. DOX lowered LDL cholesterol (P less than 0.05), total cholesterol, and apoprotein B and increased HDL/(LDL + VLDL) ratio (0.05 less than or equal to P less than 0.1) compared to placebo. Dropout rate and treatment-related side effects were equally distributed among the DOX and placebo groups. No patients had the dose of medication reduced because of side effects. Three DOX patients were withdrawn because of postural dizziness.

Linear IgA bullous dermatosis v dermatitis herpetiformis. Quantitative measurements of dermoepidermal alterations.

Linear IgA bullous dermatosis (LAD), also known as "atypical dermatitis herpetiformis," is a disorder that is distinct from classic dermatitis herpetiformis (DH). In eight patients with DH and six with LAD, quantitative assessment of a variety of histopathologic variables was made. The number of rete tips with neutrophils in basal vacuoles and the length of the epidermal basement membrane zone (BMZ) associated with these findings were greater in LAD than DH. The number of microabscesses of neutrophils in the dermal papillae and the length of epidermal BMZ associated with them were greater in DH than in LAD. By using the number of microabscesses and the number of rete tips with neutrophils in basal vacuoles in a probability model, we found by retrospective analysis that a correct diagnosis could be made for LAD in 75% of biopsy specimens with a probability of 97% and in all cases of DH with a probability of 92%. Using this model, we made no misdiagnoses. This is the first diagnostic probability model in dermatopathology that expresses a confidence level in diagnosis.

Educating residents for managed care: report on a multidisciplinary conference.

A growing number of residency programs are preparing their graduates for the realities of managed care practice. In 1996, The Cleveland Clinic Foundation, a private, nonprofit academic medical center, hosted a two-day conference on managed care education to develop innovative instructional and evaluative approaches that, where appropriate, would build on existing expertise. The conference was attended by invited national experts who had a stake in residents' education: clinical faculty, residents, medical educators, executives of managed care organizations, and representatives of other interested organizations. Participants spent much of their time in four small break out groups, each focusing on one of the following topics that were judged particularly relevant to managed care: preventive and population-based medicine, appropriate utilization of resources, clinician-patient communication, and interdisciplinary team practice. Participants shared existing materials, discussed teaching goals and objectives, and generated ideas for teaching methods, teaching materials, and evaluative methods for their respective topics. The authors summarize the recommendations from the four groups, with an overview of the issues that emerged during the conference concerning curriculum development, integration of managed care topics into existing curricula, staging of the curriculum, experiential teaching methods, negative attitudes and resistance, evaluation of trainees and profiling, program assessment, faculty development, and cooperation between academic medical centers and managed care organizations.

The effect of antihypertensive medications on exercise performance: a review.

This review describes the effects of antihypertensive drugs on the performance of aerobic exercise. All available antihypertensive drugs lower blood pressure both at rest and decrease the rate of increase during exercise. However, they differ in their effects on exercise performance. The ideal antihypertensive agent should not have significant depressant effects on the myocardium, should not promote arrhythmias, should preserve the distribution of blood flow to exercising muscle, and should not interfere with substrate utilization. Diuretics, one of the most commonly prescribed class of antihypertensives, have few deleterious effects on exercise performance but have adverse metabolic effects; beta blockers have many adverse effects on exercise performance. Agents which have the least potential for adverse effects on exercise performance and metabolic effects are the converting enzyme inhibitors, calcium channel blockers, and alpha blockers, and central alpha agonists. The literature concerning each of these drugs is reviewed and recommendations are made for prescribing for the hypertensive who wishes to engage in vigorous exercise.

Multidisciplinary evidence-based medicine journal clubs: curriculum design and participants' reactions.

BACKGROUND: Evidence-based medicine (EBM) is becoming an accepted educational paradigm in medical education at a variety of levels. It focuses on identifying the best evidence for medical decision making and applying that evidence to patient care. METHODS: Three EBM journal clubs were developed at the West Virginia University School of Medicine. One was for senior medical students, another for residents, and the third for primary care faculty members. In each, the sessions stressed answering clinical questions arising from actual patient-care issues. The curricular structure and development of the journal clubs are described. Participants anonymously evaluated aspects of the journal clubs regarding their educational value with Likert scale questions. RESULTS: Faculty members and residents generally gave high evaluations to all aspects of the EBM journal clubs. Student evaluations were more mixed. For each of the evaluation questions, the student means were lower than those of faculty and residents. However the differences reached statistical significance only in the responses to the usefulness of the sessions in understanding the medical literature (P < 0.01). Residents and faculty rated the EBM sessions more favorably than grand rounds or the resident lecture series. CONCLUSIONS: The establishment of evidence-based medicine journal clubs is feasible, and learners seem to value the sessions. More developed learners may gain more from the experience than those earlier in their medical education.

Effects of stacking on the configurations and elasticity of single-stranded nucleic acids.

Stacking interactions in single-stranded nucleic acids give rise to configurations of an annealed rod-coil multiblock copolymer. Theoretical analysis identifies the following resulting signatures for long homopolynucleotides: a nonmonotonic dependence of size on temperature, the corresponding effects on cyclization and a plateau in the extension force law. Explicit numerical results for polydeoxyadenylate [poly(dA)] and polyriboadenylate [poly(rU)] are presented.

Evaluating cardiac risk in noncardiac surgery patients.

The cornerstones of the evaluation of cardiac risk in patients undergoing noncardiac surgery remain a thorough history and physical examination, and a resting electrocardiogram. However, new techniques to assess cardiac function allow more complete evaluation of high-risk patients.

Fabrication of a maxillary complete denture utilizing the neuromuscular or centric occlusion position.

The patient was unable to wear a maxillary complete denture that had been made from a verifiable record in the centric jaw relation position or terminal hinge position. When she brought her teeth together, only a few touched. Clinical examination showed that this patient had a discrepancy of approximately 3 mm anteroposteriorly and a discrepancy of 1 mm mediolaterally between the terminal hinge position and the centric occlusion or neuromuscular position. A new denture was made for the patient. The neuromuscular position was used as the starting position and as the position of maximum intercuspation (centric occlusion), and the terminal hinge position was used as a mounted border position of reference for occlusal adjustment and equilibration.