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Biomedical subjects

T Self

Publications and source records attributed to T Self.

At least 19 recordsLinked to original sources
PubMed2000

Salmeterol administration by metered-dose inhaler alone vs metered-dose inhaler plus valved holding chamber.

STUDY OBJECTIVE: To determine whether a spacer device designed as a valved holding chamber with a flow signal increases the efficacy of the long-acting beta(2)-agonist, salmeterol, in patients who use incorrect technique with metered-dose inhaler (MDI) alone. DESIGN: Double-blind, randomized, placebo-controlled study. SETTING: University hospital outpatient rooms. PATIENTS: Twenty adult outpatients with stable persistent asthma, receiving a daily anti-inflammatory drug. INTERVENTIONS: Patients were randomized to either salmeterol MDI (incorrect use: 1 s after actuating MDI, inhale rapidly) and placebo plus spacer (correct use: inhale slowly as MDI is actuated, continue to inhale slowly and deeply) or placebo MDI (incorrect use) and salmeterol plus spacer (correct use). The following week, patients received the opposite treatment. The dose was two puffs from each device on each treatment day; each puff was separated by 1 min. MEASUREMENTS AND RESULTS: After baseline peak expiratory flow (PEF), salmeterol was administered and serial PEF determined (0.5, 1, 2, 3, 4, 6, 8, 10, and 12 h). Administration of salmeterol MDI plus spacer resulted in significantly greater increases in PEF from baseline vs MDI at 4 h (44 L/min vs 10 L/min; p < 0.01) and 6 h (49 L/min vs 24 L/min; p < 0.05). Both methods of administration were equally well tolerated. CONCLUSION: We conclude that patients who have poor timing and rapid inhalation with salmeterol MDI alone will have greater increases in PEF at 4 h and 6 h and no additional side effects if the dose is administered with a valved holding chamber that is used correctly. Further study is needed regarding other errors in MDI technique with salmeterol.

Adult↗
PubMed1999

Role of myosin VI in the differentiation of cochlear hair cells.

The mouse mutant Snell's waltzer (sv) has an intragenic deletion of the Myo6 gene, which encodes the unconventional myosin molecule myosin VI (K. B. Avraham et al., 1995, Nat. Genet. 11, 369-375). Snell's waltzer mutants exhibit behavioural abnormalities suggestive of an inner ear defect, including lack of responsiveness to sound, hyperactivity, head tossing, and circling. We have investigated the effects of a lack of myosin VI on the development of the sensory hair cells of the cochlea in these mutants. In normal mice, the hair cells sprout microvilli on their upper surface, and some of these grow to form a crescent or V-shaped array of modified microvilli, the stereocilia. In the mutants, early stages of stereocilia development appear to proceed normally because at birth many stereocilia bundles have a normal appearance, but in places there are signs of disorganisation of the bundles. Over the next few days, the stereocilia become progressively more disorganised and fuse together. Practically all hair cells show fused stereocilia by 3 days after birth, and there is extensive stereocilia fusion by 7 days. By 20 days, giant stereocilia are observed on top of the hair cells. At 1 and 3 days after birth, hair cells of mutants and controls take up the membrane dye FM1-43, suggesting that endocytosis occurs in mutant hair cells. One possible model for the fusion is that myosin VI may be involved in anchoring the apical hair cell membrane to the underlying actin-rich cuticular plate, and in the absence of normal myosin VI this apical membrane will tend to pull up between stereocilia, leading to fusion.

Age Factors↗
PubMed1999

Beta-blockers after myocardial infarction: do benefits ever outweigh risks in asthma?

beta-Blockers are well documented to prolong life in patients after myocardial infarction (MI), yet patients who also have asthma are frequently and understandably denied this therapy. We reviewed the literature (via MEDLINE) for the past 35 years for beta-blocker-induced asthma, and reexamined potential beta-blocker use in the context of NIH guidelines for asthma classification and management. Because beta-blockers can cause fatal or life-threatening asthma, their use should be avoided in moderate to severe persistent asthmatics. Benefits of low-dose beta(1)-blockers (e.g. atenolol 50 mg daily) may outweigh risks in some patients with mild intermittent or well-controlled mild persistent asthma. Further study is needed to verify that low doses of beta(1)-blockers are effective in prolonging life after MI, and that use specifically in mild intermittent or mild persistent asthma per NIH classification is safe.

Adrenergic beta-1 Receptor Antagonists↗
PubMed1999

Can we justify ipratropium therapy as initial management of acute exacerbations of COPD?

Although inhaled ipratropium is commonly accepted as the drug of choice for long-term management of chronic bronchitis and emphysema, little evidence is available to promote its administration in conjunction with a beta2-agonist as part of initial management of exacerbations of chronic obstructive pulmonary disease (COPD) in the acute care setting. Reasons for its widespread acceptance for acutely ill patients may include its status as a first-line agent for long-term therapy, its relative safety, and attempts to provide optimal patient care. Since inhaled ipratropium is beneficial as immediate therapy for asthma in the emergency department, some practitioners attempted to extrapolate these findings to treatment of COPD. Review of available studies reveals wide variability in methodologies and results. Although some studies reported improvement in pulmonary function tests, no clinically significant differences in patient outcomes, including shorter hospitalization, were evident. In patients who fail traditional therapies, inhaled ipratropium is reasonable. Double-blind, randomized, placebo-controlled trials in patients receiving emergency department care and in hospitalized patients that reveal shorter length of stay or other improved outcomes, are necessary to establish routine addition of inhaled ipratropium to beta2-agonists in the initial management of acute COPD.

Adrenergic beta-Agonists↗
PubMed1999

Peak expiratory flow associated with change in positioning of the instrument: comparison of five peak flow meters.

To determine if peak expiratory flow (PEF) is altered by incorrect positioning of five peak flow meters (PFMs), 16 adults with clinically stable persistent asthma were evaluated. After inhaling two puffs of albuterol via AeroChamber, patients were instructed over the next 15 min in correct PFM technique and two incorrect techniques (PFM angled 20 degrees left in mouth and PFM pointed 20 degrees downward as patient leaned forward with maximal exhalation). Order of use of five peak flow meters and correct vs. incorrect techniques were random. Although mean values generally indicated no clinically meaningful effect of positioning of the PFM, inaccurate PEFs were recorded for several subjects with both incorrect methods and all PFMs.

Adult↗
PubMed1998

Shaker-1 mutations reveal roles for myosin VIIA in both development and function of cochlear hair cells.

The mouse shaker-1 locus, Myo7a, encodes myosin VIIA and mutations in the orthologous gene in humans cause Usher syndrome type 1B or non-syndromic deafness. Myo7a is expressed very early in sensory hair cell development in the inner ear. We describe the effects of three mutations on cochlear hair cell development and function. In the Myo7a816SB and Myo7a6J mutants, stereocilia grow and form rows of graded heights as normal, but the bundles become progressively more disorganised. Most of these mutants show no gross electrophysiological responses, but some did show evidence of hair cell depolarisation despite the disorganisation of their bundles. In contrast, the original shaker-1 mutants, Myo7ash1, had normal early development of stereocilia bundles, but still showed abnormal cochlear responses. These findings suggest that myosin VIIA is required for normal stereocilia bundle organisation and has a role in the function of cochlear hair cells.

Animals↗
PubMed1998

Elevation of peak expiratory flow by a "spitting" maneuver: measured with five peak flowmeters.

STUDY OBJECTIVE: To determine if peak expiratory flow (PEF) is higher using incorrect technique versus correct technique with five marketed peak flowmeters. DESIGN: Randomized, nonblinded study. SETTING: University pulmonary medicine clinic. PATIENTS: Twenty adults with clinically stable asthma. INTERVENTIONS: After inhaling 2 puffs of albuterol via a valved aerosol holding chamber (Aerochamber), patients were instructed over the next 15 min in correct and incorrect (a "spitting" action) technique when using peak flowmeters. Order of use of five peak flowmeters and correct vs incorrect technique was random. MEASUREMENTS AND RESULTS: PEF (percentage of personal best) was recorded for best of three attempts with correct and incorrect technique. Each peak flowmeter had a statistically significant elevation in PEF with incorrect technique. The range for elevation in PEF using incorrect technique was 12.4 to 68.2% above the PEF with the subject using correct technique. CONCLUSION: Each of the five marketed peak flowmeters had a significant elevation in PEF when a "spitting action" was used. Clinicians need to instruct patients carefully regarding correct technique when using peak flowmeters.

Adult↗
PubMed1997

Decreased hypoprothrombinemic effect of warfarin associated with furosemide.

The authors describe a case of furosemide possibly inhibiting the hypoprothrombinemic effect of warfarin. The initiation of furosemide dosing in a patient receiving a stable dose of warfarin was associated with an 28% decrease in the international normalized ration (INR). Using normal volunteers, two previous controlled studies of an interaction between warfarin and chlorthalidone, and between warfarin and spironolactone, assert that volume depletion produced by forced diuresis results in the inhibition of warfarin's hypoprothrombinemia. Consistent with this hypothesis, the authors found that their patient's hematocrit (believed to reflect hydration status) correlated with the INR: r2 = 0.78, p < 0.05. This case provides further evidence suggesting that acute diuresis can decrease the hypoprothrombinemic effect of warfarin.

Anticoagulants↗
PubMed1997

Long-term management of asthma: how to improve outcomes.

Improved clinical outcomes in asthma patients have been demonstrated in several clinical trials that applied the National Institutes of Health (NIH) guidelines for the long-term management of asthma. Environmental control, objective monitoring, drug therapy, and partnership in patient education are the major components of optimal management. Inhaled antiinflammatory agents are of major importance for long-term control in patients with persistent asthma. Adequate patient education is absolutely essential for excellent, cost-effective care of patients with asthma. Improved outcomes in adults with asthma have been demonstrated at clinics initiated and managed by pharmacists. Further trials are needed with large numbers of patients in managed care organizations.

Adult↗
PubMed1997

Unravelling the genetics of deafness.

Hearing-impaired mouse mutants not only are good models for human hereditary deafness, but also are extremely useful for understanding the molecular basis of the cochlear defect. We describe here how we identified the gene responsible for the deafness and vestibular defects in the shaker-1 mouse mutant as a myosin VII gene. Three different mutations, all causing the same phenotype in different lines of mouse, were found, providing good evidence that we had, indeed, found the correct gene. The same gene was subsequently found to be involved in Usher's syndrome type 1B, which features deafness, vestibular dysfunction, and progressive retinitis pigmentosa. The myosin VII gene is expressed in sensory hair cells, but not in supporting cells or neurons. We are investigating the role of myosin VII in hair cell development and function. Analysis of the different mutant stocks suggests it has at least two functions. First it is involved in the development and maintenance of the stereocilia bundle. Second, it has a role in inner hair cell function. No evidence of retinal degeneration like that in Usher's syndrome has been found in the shaker-1 mutants so far studied. The benefits of understanding the function of the gene for families with Usher's type 1B are discussed. This gene is the first to be identified as causing the most common type of disorder in human hearing impairment, neuroepithelial abnormalities, and suggests a new class of candidate genes for involvement in such defects.

Animals↗
PubMed1996

Case report: interaction of rifampin and nortriptyline.

Rifampin is well documented to cause numerous clinically significant drug interactions because of its induction of the hepatic cytochrome P450 system. The metabolism of nortriptyline and other tricyclic antidepressants is induced and inhibited by this enzyme system. To the authors' knowledge, this is only the second case report in the literature regarding a possible interaction between rifampin and a tricyclic antidepressant. Nortriptyline serum concentrations were not detectable while rifampin was given concurrently. Two weeks after discontinuation of rifampin, nortriptyline concentrations increased dramatically. Further study of this possible interaction is warranted.

Adult↗
PubMed1996

Quinolones: a practical review of clinical uses, dosing considerations, and drug interactions.

A review of the literature on quinolones reveals numerous clinically relevant points regarding indications, dosing considerations, and drug interactions. Quinolones are useful in the treatment of several infectious diseases. Unfortunately, indiscriminate use of these valuable antimicrobials has resulted in increased patterns of resistance. It is important to consider carefully the site of infection and the potential pathogens in each patient before dosing. Quinolones have excellent oral absorption, with peak serum concentrations approaching those achieved with intravenous administration. When prescribing quinolones, the dose should be based on estimated creatinine clearance. Quinolones are associated with several clinically significant drug interactions. Some of these agents are well-documented inhibitors of hepatic metabolism of theophylline, caffeine, and warfarin. It has been well documented that divalent and trivalent cations in antacids, sucralfate, and some other products significantly reduce the absorption of quinolones. Avoidance or proper management of these interactions is required to ensure optimal safety and efficacy.

Anti-Infective Agents↗
PubMed1994

Theophylline.

Explore the source record for details and available documents.

Asthma↗
PubMed1992

Lysosomes as key organelles in the pathogenesis of prion encephalopathies.

The causation, structural origin, and mechanism of formation of spongiform lesions in transmissible encephalopathies are unknown. We have used immunogold electron microscopy to locate ubiquitin conjugates, hsp 70, and beta-glucuronidase (markers of the lysosomal compartment) and prion protein (PrP) in both control and scrapie-infected mouse brain. In scrapie-infected brain, lysosomes and lysosome-related structures (multivesicular and tubulovesicular dense bodies) are present in abnormally high numbers in neuronal cell processes. These structures contain PrP, together with the lysosomal markers ubiquitin conjugates, hsp 70, and beta-glucuronidase, which could also be identified spilling from tubulovesicular dense bodies into areas of early rarefaction in neuronal processes; we suggest that these areas of rarefaction are the precursor lesions of spongiform change. We advance the hypothesis that spongiform change is brought about by cytoskeletal disruption in neuronal processes caused by liberation of hydrolytic enzymes from lysosomes overloaded with the abnormal isoform of PrP (PrPsc). We suggest that the lysosomal system is probably acting as the bioreactor for processing of normal PrP to the abnormal isoform. The continuous production of increasing quantities of abnormal PrPsc in lysosome-related bodies will eventually cause disruption of the lysosomal membrane with destruction of the neuronal cytoskeleton and the initiation of vacuolation. Later, death of the cell will be associated with release of the PrPsc isoform into the extracellular environment. Repeated rounds of phagocytosis, lysosomal biogenesis of PrPsc, lysosomal membrane rupture, hydrolytic enzyme release, and neuronal lysis will lead to an exponential increase in cell damage and cell death.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Emergency department asthma treatment protocol.

OBJECTIVE: The purpose of this study was to determine if a brief educational intervention (INT) on the treatment of acute asthma improved prescribing patterns of internal medicine residents in an emergency department (ED). Additional objectives were to determine if optimal therapy reduced length of stay (LOS) in the ED and to determine if discharge prescribing patterns could be improved. DESIGN: Nonrandomized, single-blind INT study. SETTING: A large, urban, county-owned, university-affiliated ED. PATIENTS AND OTHER PARTICIPANTS: Eight internal medicine residents in each of three study periods; numbers of adult asthmatics for each period were: control group, 129 (Nov-Dec 1989); INT group A, 82 (Jan-Feb 1990); and INT group B, 139 (Nov-Dec 1990). INTERVENTIONS: INT consisted of a ten-minute verbal presentation, a three-page summary of the literature, and a posted protocol in the ED. Control data were collected prior to any INT. Prescribing patterns were covertly evaluated in each of the three study periods. Because discharge prescribing of long-term antiinflammatory therapy with inhaled corticosteroids was not improved in group A, emphasis on this point was added for group B. MAIN OUTCOME MEASURES: Percentage of patients who received desired acute and discharge therapies and LOS for each study period. RESULTS: Increased prescribing of desired acute therapy in the ED was seen in both INT groups. For discharge prescribing, the INT was partially successful. Reduced LOS was not found for the INT groups. CONCLUSIONS: A brief INT effectively improves prescribing of optimal acute therapy of asthma in the ED, yet does not appear to reduce LOS. Further strategies are needed to impact on therapy prescribed at discharge from the ED.

Adult↗