Nanoplough-constrictions on thin YBCO films made with atomic force microscopy.

Utilizing atomic force microscope (AFM) with a diamond tip, we were able to successfully plough nano-constrictions on epitaxially grown YBa2Cu3O(7-x) thin films deposited on MgO substrates. The thickness, width, and length of the obtained constrictions were in the range of a few 100 nm. Furthermore, we managed to produce a new S-type constriction, of which the dimensions are easier to control than for conventional constrictions.

Use of biological markers of airway inflammation to detect the efficacy of nurse-delivered asthma education.

OBJECTIVE: The purpose of this study was to determine whether analysis of the constituents of induced sputum could be used to document the efficacy of a nurse-delivered patient education intervention and whether changes in the biological markers of inflammation in sputum would correlate with improvements in pulmonary function and symptoms. DESIGN: The study design was prospective, open trial with repeated measures. SETTING: The study took place at a West Coast academic medical center laboratory. SUBJECTS: Subjects included 12 nonsmoking persons with asthma, ages 23 to 51 years, on prescribed daily anti-inflammatory inhaled therapy who had not required oral prednisone in the previous 4 weeks of enrollment. METHOD: The effect of one 30-minute asthma education session on spirometry, peak flow, symptoms, and biological markers of inflammation in sputum was tested for 8 weeks to determine whether biological markers reflect the efficacy of educational interventions. RESULTS: Mean symptom scores decreased and lung function increased slightly over 8 weeks. Markers of eosinophil degranulation decreased by 50% and albumin by 25% from baseline to 8 weeks. Eosinophil percentages dropped 20% over time but did not change consistently at all time points. Clinical markers of asthma control correlated in the low-to-moderate range with biological markers of airway inflammation. CONCLUSION: The results of this study show the effects of a patient education intervention can be detected in both clinical and biological outcomes. Individual education may influence self-care of asthma including adherence to inhaled corticosteroid therapy and thereby suppress airway inflammation.

Identification of sites phosphorylated by the vaccinia virus B1R kinase in viral protein H5R.

BACKGROUND: Vaccinia virus gene B1R encodes a serine/threonine protein kinase. In vitro this protein kinase phosphorylates ribosomal proteins Sa and S2 and vaccinia virus protein H5R, proteins that become phosphorylated during infection. Nothing is known about the sites phosphorylated on these proteins or the general substrate specificity of the kinase. The work described is the first to address these questions. RESULTS: Vaccinia virus protein H5R was phosphorylated by the B1R protein kinase in vitro, digested with V8 protease, and phosphopeptides separated by HPLC. The N-terminal sequence of one radioactively labelled phosphopeptide was determined and found to correspond to residues 81-87 of the protein, with Thr-84 and Thr-85 being phosphorylated. A synthetic peptide based on this region of the protein was shown to be a substrate for the B1R protein kinase, and the extent of phosphorylation was substantially decreased if either Thr residue was replaced by an Ala. CONCLUSIONS: We have identified the first phosphorylation site for the vaccinia virus B1R protein kinase. This gives important information about the substrate-specificity of the enzyme, which differs from that of other known protein kinases. It remains to be seen whether the same site is phosphorylated in vivo.

Ethnic differences: word descriptors used by African-American and white asthma patients during induced bronchoconstriction.

STUDY OBJECTIVES: To determine if African-American and white patients with asthma (1) differ in the words they use to describe their breathlessness, and (2) differ in their perception of breathlessness. DESIGN: Descriptive cross-sectional design. SETTING AND PARTICIPANTS: The study setting was located in Northern California, an ethnically and economically diverse area. A total of 32 subjects, 16 per group, completed the study. MEASUREMENTS: All had a provocation concentration of methacholine chloride causing a 30% fall in FEV(1) (PC(30)) of

End-of-life care content in 50 textbooks from multiple specialties.

CONTEXT: Prior reviews of small numbers of medical textbooks suggest that end-of-life care is not well covered in textbooks. No broad study of end-of-life care content analysis has been performed on textbooks across a wide range of medical, pediatric, psychiatric, and surgical specialties. OBJECTIVE: To determine the quantity and rate the adequacy of information on end-of-life care in textbooks from multiple medical disciplines. DESIGN AND SOURCES: A 1998 review of 50 top-selling textbooks from multiple specialties (cardiology, emergency medicine, family and primary care medicine, geriatrics, infectious disease and acquired immunodeficiency syndrome [AIDS], internal medicine, neurology, oncology and hematology, pediatrics, psychiatry, pulmonary medicine, and surgery) for the presence and adequacy of content in 13 end-of-life care domains. MAIN OUTCOME MEASURES: Chapters on diseases commonly causing death and those devoted to end-of-life care were identified, read, rated, and compared by textbook specialty, chapter, and domain for the presence of helpful information in the 13 domains. Content for each domain was rated as absent, minimally present, or helpful. Textbook indexes were analyzed for the number of pages relevant to end-of-life care. RESULTS: Overall, helpful information was provided in 24.1% (range, 8.7%-44.2%) of the expected end-of-life content domains; in 19.1% (range, 6.2%-38.5%), expected content received minimal attention; and in 56.9% (range, 23.1 %-77.9%), expected content was absent. As a group, the textbooks with the highest percentages of absent content were in surgery (71.8%), infectious diseases and AIDS (70%), and oncology and hematology (61.9%). Textbooks with the highest percentage of helpful end-of-life care content were in family medicine (34.4%), geriatrics (34.4%), and psychiatry (29.6%). In internal medicine textbooks, the content domains with the greatest amount of helpful information were epidemiology and natural history. Content domains covered least well were social, spiritual, ethical, and family issues, as well as physician after-death responsibilities. On average, textbook indexes cited 2% of their total pages as pertinent to end-of-life care. CONCLUSION: Top-selling textbooks generally offered little helpful information on caring for patients at the end of life. Most disease-oriented chapters had no or minimal end-of-life care content. Specialty textbooks with information about particular diseases often did not contain helpful information on caring for patients dying from those diseases.

Addition of anticholinergic solution prolongs bronchodilator effect of beta 2 agonists in patients with chronic obstructive pulmonary disease.

A randomized, double-blind placebo-controlled clinical trial was designed to assess the safety, efficacy, and duration of the bronchodilation resulting from the addition of 500 micrograms of ipratropium bromide (Atrovent; Boehringer Ingelheim, CT) inhalation solution to standard small volume nebulizer treatments with 2.5 mg albuterol inhalation solution. A total of 195 patients (63% men, average age 64 years) with > 10 pack-year smoking histories and stable, moderate-to- severe chronic obstructive pulmonary disease (COPD; forced expiratory volume in 1 second [FEV1] 1.02 liter, 38.8% predicted) from eight university-affiliated chest clinics in seven U.S. cities were enrolled into the study. Asthma, rhinitis, and eosinophilia were exclusions, as was daily use of > 10 mg of prednisone (or 20 mg on alternate days). There was a 2-week stabilization period during which the patients were instructed in the use of the small volume nebulizers, which they used three times daily with albuterol alone. They were asked to keep daily logs of peak flow rates, pulmonary symptoms, and additional medication usage. On their test day 1 the subjects came to the pulmonary function laboratory having been off theophylline for 24 hours and beta 2-agonists for 12 hours and performed a baseline spirometry. They then received their morning small volume nebulizer treatment of albuterol to which was added either 500 micrograms if ipratropium bromide or a saline placebo. Spirometry was repeated at 15, 30, and 60 minutes, and then hourly for 8 hours. Subjects then took home a 2-week supply of albuterol and test drug for thrice daily use in their small volume nebulizer. They were evaluated for pulmonary symptoms and adverse effects every 14 days. The 8-hour spirometry was repeated on test day 43 and finally on test day 85. Primary data evaluated were the peak increase in FEV1 and the area between the FEV1 baseline value and the 8-hour FEV1 curve. Similar calculations were made for forced vital capacity (FVC) and 25-75% forced expiratory flow (FEF25-75%). On test day 1 the peak increase in FEV1 for the ipratropium bromide + albuterol subjects was 26% greater than those on placebo + albuterol (p < 0.003). The area under the 8-hour FEV1 curve was 64% greater in those given ipratropium bromide on test day 1 (p < 0.0002). Similar increases were seen in FVC and FEF25-75%. The peak improvements in FEV1 and FVC with the addition of ipratropium bromide to albuterol were maintained on test days 43 and 85. Considering the safety and efficacy profiles of this combination, the data would suggest that ipratropium bromide inhalation solution should be considered first-line therapy for those patients with COPD requiring small volume nebulizer treatments.

Abnormal serum protein levels in infants with hyaline membrane disease--evidence of an underlying immunological disorder.

Evidence is presented that newborn infants who develop hyaline membrane disease (HMD) have higher levels of serum alpha-fetoprotein (AFP) than comparable infants who do not show evidence of the disease. A hypothesis is put forward that HMD is the result of an immune reaction between mother and infant, which may commence as early as the 2nd trimester of pregnancy. It is postulated that HMD infants, who generally have raised levels of serum IgM, produce IgM antibodies to foreign maternal IgG and that this reaction between the infant's IgM and maternal IgG accounts for the signs of systemic disease at birth. The onset of breathing during the intrapartum period may lead to an exacerbation of the immune response in the lung. It is known that AFP suppresses T-cell-dependent antibody responses. The presence of raised AFP levels may be an attempt to prevent formation of fetal or infant IgG antibodies resulting in an uncontrolled immune response and a lethal outcome.

Determination of avidity of anti-viral antibodies at 50% binding of antibody.

Binding studies with tobacco mosaic virus and specific IgG and Fab' fragments were done under conditions of 50% binding of antibody. When the log of the concentration of antigen sites required to bind 50% of the available antibody was plotted against the log of bound sites, a line was obtained which had a slope varying between 0 and 1. Instead of using the slope of this line as an index of avidity of the antiserum, it is suggested that the calculation K0 values over a range of reactant concentrations provides a better criterion for comparing the avidity of antiviral antibodies. The results of conventional binding tests were analyzed by means of Scatchard plots and were found to agree very closely with the data obtained at 50% binding of antibody.