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At least 19 recordsLinked to original sources
PubMed2000

Short-acting beta 2 agonists for stable chronic obstructive pulmonary disease.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a chronic condition characterised by progressive airflow limitation that is at most partially reversible. Despite the lack of reversibility patients often report symptomatic improvement with short-acting beta 2 bronchodilator medications. They are used on either an "as required" or a "regular plus as required basis" and they may be used in conjunction with other bronchodilator medicines such as ipratropium and methylxanthines. These medicines are used in the management of both stable and acute exacerbations of COPD. This review examined the effect of short-acting beta 2 bronchodilators given by inhalation in stable COPD. OBJECTIVES: To determine the clinical effect and assess the adverse effects of inhaled short-acting beta 2 agonist bronchodilators compared with placebo in stable COPD. SEARCH STRATEGY: Only randomised controlled trials (RCTs) were considered. RCTs were identified using the Cochrane Airways Group database (CENTRAL). In addition, the reference lists of review articles and RCTs retrieved in full were searched for other potentially relevant citations. SELECTION CRITERIA: Only trials with adult patients with stable COPD, as defined by internationally accepted guidelines (ATS, ERS or BTS) were included in this review. All trials had a minimum duration of 7 days of regular treatment with short-acting beta 2 bronchodilators given by inhalation and compared with placebo. Data from trials where beta 2 agonists were used alone or in combination with other medicines (e.g. ipratropium bromide) were used only if there was a direct comparison between beta 2 bronchodilator alone and placebo. DATA COLLECTION AND ANALYSIS: Outcomes were analysed as continuous or dichotomous outcomes, using standard statistical techniques. For continuous outcomes, the weighted mean difference (WMD) and 95% confidence intervals were calculated and for dichotomous outcomes, the odds ratio was calculated with 95% confidence intervals by Peto's methods. Funnel plots were used to test for publication bias. MAIN RESULTS: Thirteen studies were included in this review. Most had small sample sizes and some of the sutides used very short-acting outdated compounds. All the studies used a cross-over design and were of high quality. Spirometry done at the end of study period was measured after administration of treatment (post-bronchodilator) which showed both FEV1 (0.150 L/min, 95%CI: 0. 02-0.28) and FVC (0.310 L, 95%CI: 0.00-0.62) to improve significanly but slightly when compared to placebo. A few studies measured FRC, airway resistance or conductance at the end of the study period. In all cases these measurements were done several hours after treatment, and no significant differences (p>0.05 in all cases) were found between the bronchodilator and placebo groups. Walking test Large increases in 6MW distance was observed in two studies, however one study did not show any positive improvements. There was a large increase in the 12MW distance as shown by one study. Due to the small number of studies reporting this outcome no significant differences were found in the walking distance between the bronchodilator and placebo groups. Peak Flow Rate Both morning (36. 04 L/min; 95%CI: 0.80-71.27) and evening (36.68 L/min; 95%CI: 2. 47-70.89) PEFR were significantly higher during active treatment than during placebo. Symptoms Breatlessness was measured on various scales therefore data that were presented in a suitable form were combined using standardized means for inclusion in the analysis. A significant improvement (-0.33; 95%CI: -0.58 to -0.07 with p=0.01) in the breathlessness score was observed during treatment with beta-2 agonist when compared to placebo. Cough was reported to improve significantly (data not usable) during treatment with beta2 agonist in one study but not in two others. A non-significant decrease in sputum production was reported by Wilson 1980, however four other studies reported no

Administration, Inhalation↗
PubMed2000

Diuretics acting on the distal renal tubule for preterm infants with (or developing) chronic lung disease.

OBJECTIVES: The aim of this review is to assess the risks and benefits of diuretics acting on distal segments of the renal tubule (distal diuretics) in preterm infants with or developing chronic lung disease (CLD). Primary objectives are to assess changes in need for oxygen or ventilatory support and effects on long-term outcome, and secondary objectives are to assess changes in pulmonary mechanics and potential complications of therapy. SEARCH STRATEGY: We used the standard method of the Cochrane Neonatal Review Group. We used the following keywords: ¿ or ¿ and , limited to and limited to or . We searched Medline (1966-1998), Embase (1974-1998) and the Cochrane Controlled Trials Register (CCTR) from the Cochrane Library (1999, issue 2). In addition, we hand searched several abstract books of national and international American and European Societies. SELECTION CRITERIA: We included in this analysis trials in which preterm infants with or developing CLD and at least five days of age were all randomly allocated to receive a distal diuretic (i.e., a diuretic acting on the distal renal tubule). Eligible studies needed to assess at least one of the outcome variables defined a priori for this systematic review. Primary outcome variables included changes in need for respiratory support and oxygen supplementation, mortality, bronchopulmonary dysplasia (BPD), death or BPD, chronic lung disease at 36 weeks of postconceptional age (gestational age + postnatal age), length of stay, and number of rehospitalizations during the first year of life. Secondary outcome variables included pulmonary mechanics and potential complications of therapy. DATA COLLECTION AND ANALYSIS: We used the standard method for the Cochrane Collaboration which is described in the Cochrane Collaboration Handbook. Two investigators extracted, assessed and coded separately all data for each study, using a form that was designed specifically for this review. Any disagreement was resolved by discussion. We combined parallel and cross-over trials and, whenever possible, transformed baseline and final outcome data measured on a continuous scale into change scores using Follmann's formula. MAIN RESULTS: Of six studies fulfilling entry criteria, most focused on pathophysiological parameters and did not assess effects on important clinical outcomes defined in this review, or the potential complications of diuretic therapy. In preterm infants > 3 weeks of age with CLD, a four-week treatment with thiazide and spironolactone improved lung compliance and reduced the need for furosemide. Thiazide and spironolactone decreased the risk of death and tended to decrease the risk for lack of extubation after 8 weeks in intubated infants. There is no evidence to support the hypothesis that adding spironolactone to thiazide or that adding metolazone to furosemide improves the outcome of preterm infants with CLD. REVIEWER'S CONCLUSIONS: In preterm infants > 3 weeks of age with CLD, acute and chronic administration of distal diuretics improve pulmonary mechanics. Chronic administration of diuretics (thiazide with spironolactone) reduces mortality in intubated patients. Large studies are needed to assess (1) whether chronic diuretic administration improves mortality, duration of oxygen dependency, ventilator dependency, length of hospital stay and long-term outcome in patients without long-term toxicity and (2) whether adding spironolactone to thiazides or adding metolazone to furosemide has any beneficial effect.

Chronic Disease↗
PubMed2004

A case of human insulin allergy induced by short-acting and intermediate-acting insulin but not by long-acting insulin.

A 66-year-old woman suffering from pollinosis developed generalized urticaria after injection of intermediate-acting insulin for diabetes mellitus. She had human insulin-specific IgE, and in skin tests was positive for human recombinant insulin and negative for additives. Uniquely, she reacted to fast-acting and slow-acting insulin but not to long-acting insulin. We further confirmed that human insulin preparations could stimulate her peripheral basophils to release a significant amount of histamine. Genetically generated human insulin analogs, aspart and lispro, induced positive skin tests and histamine release from basophils. She was recommended to use a long-acting insulin preparation and was free from symptoms thereafter.

Aged↗
PubMed1997

Revision of Department of Justice Freedom of Information Act and Privacy Act Regulations and Implementation of Electronic Freedom of Information Act Amendments of 1996--DoJ. Proposed Rule.

This document sets forth proposed revision of the Department's regulations under both the Freedom of Information Act (FOIA) and the Privacy Act of 1974. The FOIA and Privacy Act regulations have been streamlined and condensed, in accordance with the principles of the National Performance Reviews. With more "user-friendly" language wherever possible. These revisions also reflect the principles established by President Clinton and Attorney General Reno in their FOIA Policy Memoranda of October 4, 1993. The new statement of discretionary disclosure policy will supercede the existing regulation regarding discretionary access to records of historical interest. Additionally, the regulations have been updated to reflect developments in the case law and to include updated cost figures to be used in calculating and charging fees. These proposed revisions also contain new provisions implementing the Electronic Freedom of Information Act Amendments of 1996.

Government Agencies↗
PubMed1999

Effects of long-acting versus short-acting calcium channel blockers among older survivors of acute myocardial infarction.

OBJECTIVE: Recent studies have highlighted the potentially harmful effects of short-acting calcium channel blockers, especially of the dihydropyridine type, in patients with coronary heart disease. Some have argued that long-acting calcium channel blockers are safer, but few outcome data exist. The objective of the study was to compare the occurrence of adverse outcomes among recipients of long-acting versus short-acting calcium channel blockers, with dihydropyridines and non-dihydropyridines compared separately. SETTING: The New Jersey Medicare population. DESIGN: A retrospective cohort study using linked Medicare and drug claims data. PARTICIPANTS: Older survivors of acute myocardial infarction (MI) occurring in 1989 and 1990. Eligible subjects had survived at least 30 days after the MI, participated in Medicare and a drug benefits program, and were prescribed a single type of either a long-acting or a short-acting calcium channel blocker within 90 days after the MI. MEASUREMENTS: The two outcome measures were rates of all-cause mortality and cardiac rehospitalization. Using separate Cox regression models for dihydropyridines (nifedipine, nicardipine) and non-dihydropyridines (diltiazem, verapamil), we examined these outcomes for recipients of long-acting compared with short-acting calcium channel blockers. RESULTS: Of the 833 patients eligible for the study, 160 were prescribed long-acting and 673 short-acting calcium channel blockers. Clinical characteristics of long-acting and short-acting users were comparable. During 2 years of follow-up, 221 deaths and 300 rehospitalizations occurred. Controlling for age, sex, race, and indicators of disease severity and comorbidity, the relative risk of dying for recipients of long-acting, compared with short-acting, dihydropyridines was .42 (95% confidence interval (CI), 0.21-0.86). For cardiac rehospitalization, the relative risk was 0.57 (95% CI, 0.34-0.94). For the long-acting versus short-acting nondihydropyridines, the adjusted relative risk of dying was 1.43 (95% CI, 0.88-2.32), and for cardiac rehospitalization, .65 (95% CI, 0.40-1.05). CONCLUSION: Use of long-acting dihydropyridine calcium channel blockers after acute MI was associated with substantially lower rates of cardiac rehospitalization and death compared with use of their short-acting counterparts. More data are needed to address the possibility that long-acting, compared with short-acting, non-dihydropyridines could decrease rehospitalization rates but increase mortality.

Aged↗
PubMed2004

Measurement of activated clotting time in children--comparison of the Celite i-STAT ACT with the Medtronic ACT II.

BACKGROUND: To evaluate a recently introduced blood-saving method for the measurement of activated clotting time (ACT), the Celite i-STAT ACT, by comparing the values obtained with those from the widely used Medtronic ACT II device. METHODS: In a prospective clinical study, we compared ACT values from the i-STAT device with the Medtronic ACT II device in 60 paediatric, interventional, cardiac catheterization procedures necessitating prophylactic heparinization. Blood samples were pair-analyzed using two i-STAT analyzers and one Medtronic ACT II device with double-tube-cartridges before and after heparinization. Data were compared using Bland-Altman bias analysis, Student's t-test and simple regression analysis. RESULTS: Bias and precision between the Medtronic ACT II and the i-STAT ACT values was -5.4 +/- 26.3. The i-STAT and Medtronic ACT II values were similar before heparinization (P = 0.22), but i-STAT ACT values became significantly longer than Medtronic ACT II values after heparinization (P = 0.021). The increase of ACT after heparinization was greater (median 86.3; range 40-187 s) in the i-STAT analyzer than in the Medtronic ACT II analyzer (median 73.0; range 19-235.5 s). Increase in ACT values was inversely affected by intraoperative haemoglobin concentration in the Medtronic ACT II analyzer (P = 0.001) but not in the i-STAT analyzer. CONCLUSION: Activated clotting times obtained from the Celite i-STAT ACT and the Medtronic ACT II demonstrated poor agreement. The technical principles are quite different and the two methods showed diverse susceptibility to intraoperative haemoglobin concentration. Users have to be aware of technique-specific ACT target ranges and their confounders, which need to be provided by the manufacturers.

Adolescent↗
PubMed1984

Privacy Act of 1974: amendment of existing system of records--HHS. Notice of intent to amend a Privacy Act system of record for purposes of the Debt Collection Act of 1982.

The Department of Health and Human Services is amending system of records 09-90-0024 to add new routine uses for the purpose of collecting debts owed the Federal Government, and to add a disclosure to consumer reporting agencies as authorized by 5 U.S.C. 552a(b) (12) as added by the Debt Collection Act of 1982 (Pub. L. 97-365). A number of other amendments have been made to reflect changes of organization and titles. We invite public comment on these routine uses.

Civil Rights↗
PubMed2002

Is the increase in bronchial responsiveness or FEV1 shortly after cessation of beta2-agonists reflecting a real deterioration of the disease in allergic asthmatic patients? A comparison between short-acting and long-acting beta2-agonists.

Regular use of beta2-agonists might result in increased bronchial hyper-responsiveness (BHR) and decreased forced expiratory volume in 1 sec (FEV1). It has been suggested that these possible detrimental effects are not a real deterioration of the disease, but that it might be only a transient (rebound) effect shortly after discontinuing this regular use. Moreover, these effects are thought to occur especially during short-acting and not during long-acting beta2-agonists use. The aim of this study was to invest gate whether a rebound effect (a pharmacological deterioration effect diminishing after several hours) in FEV1 and PC20 (concentration of histamine causing a 20% fall in FEV1 with regard to baseline) occurred after cessation of regular use of beta2-agonists, and whether this occurred both after short-acting and long-acting beta2-agonists. Allergic asthmatic patients (n = 134) were randomly allocated to the use of a short-acting (salbutamol), a long-acting beta2-agonist (formoterol) or placebo for 12 weeks (double-blind, double-dummy). No other asthma medication was allowed, including inhaled corticosteroids. At the start and every 4 weeks later FEV and PC20 were measured, each time at least 12 h after the last doses of study medication, which is in the possible rebound period. To investigate whether a (transient) rebound effect occurred, parameters were additionally measured at least 72 h later after discontinuation of the study medication. After 12 weeks of short-acting beta2-agonist use, a drop was seen in FEV1 from 85.6 (+/- 2.21)% predicted to 78.8 (+/- 2.9)% predicted, measured 15 h (median) after the last doses of medication. This was significantly different compared to placebo. When measured 168 h (median) later FEV1 recovered to 85.5 (+/- 2.4)% predicted, comparable to baseline. PC20 decreased with -1.17 (+/- 0.44) doubling dose after 12 weeks of short-acting beta2-agonist use, measured 15 h after the last doses of medication, which was significantly different compared to placebo. However, 168 h later PC20 recovered slightly with +0.55 (+/- 0.34) doubling dose, but this value was still lower compared to placebo. In contrast, during long-acting beta2-agonist and placebo use no significant changes were seen. In conclusion, the use of short-acting beta2-agonists resulted in a transient (rebound) effect in FEV while the effects on PC20 may point to a real deterioration of the disease. Long-acting beta2-agonist and placebo use showed no changes. We conclude that a mono-therapy of short-acting and not of long-acting beta2-agonists might have deleterious effects in asthma.

Adrenergic beta-Agonists↗
PubMed1999

Molecular studies define the primary structure of alpha1-antichymotrypsin (ACT) protease inhibitor in Alzheimer's disease brains. Comparison of act in hippocampus and liver.

An alpha1-antichymotrypsin-like serpin has been implicated in Alzheimer's disease (AD) based on immunochemical detection of alpha1-antichymotrypsin (ACT) in amyloid plaques from the hippocampus of AD brains. The presence of neuroendocrine isoforms of ACTs and reported variations in human liver ACT cDNA sequences raise the question of the molecular identity of ACT in brain. In this study, direct reverse transcription-polymerase chain reaction and cDNA sequencing indicate that the hippocampus ACT possesses the reactive site loop that is characteristic of serpins, with Leu as the predicted P1 residue interacting with putative chymotrypsin-like target proteases. The deduced primary sequence of the human hippocampus ACT possesses more than 90% homology with reported primary sequences for the human liver ACT. Moreover, identical ACT primary sequences deduced from the cDNAs were demonstrated in the hippocampus of control and AD brains. Northern blots showed that ACT mRNA expression in hippocampus was 900 times lower than that in liver. Also, hippocampus and liver ACT proteins demonstrated differential sensitivities to deglycosylation. Overall, reverse transcription-polymerase chain reaction combined with cDNA and primary sequence analyses have defined the molecular identity of human hippocampus ACT in control and AD brains. The determined reactive site loop domain of hippocampus ACT will allow prediction of potential target proteases inhibited by ACT in AD.

Alzheimer Disease↗
PubMed2002

Regular treatment with long acting beta agonists versus daily regular treatment with short acting beta agonists in adults and children with stable asthma.

BACKGROUND: Selective beta-adrenergic agonists for use in asthma are: short acting (2-6 hours) and long acting (>12 hours). There has been little controversy about using short acting beta-agonists intermittently, but long acting beta-agonists are used regularly, and their regular use has been controversial. OBJECTIVES: To determine the benefit or detriment of treatment with regular short- or long acting inhaled beta-agonists in chronic asthma. SEARCH STRATEGY: A search was carried out using the Cochrane Airways Group register. Bibliographies of identified RCTs were searched for additional relevant RCTs. Authors of identified RCTs were contacted for other published and unpublished studies. SELECTION CRITERIA: All randomised studies of at least two weeks duration, comparing a long acting inhaled beta-agonist given twice daily with any short acting inhaled beta-agonist of equivalent bronchodilator effectiveness given regularly in chronic asthma. DATA COLLECTION AND ANALYSIS: Two reviewers performed data extraction and study quality assessment independently. Authors of studies were contacted for missing data. MAIN RESULTS: 31 studies met the inclusion criteria, 24 of parallel group and 7 cross over design. Salmeterol xinafoate was used as long acting agent in 22 studies and formoterol fumarate in 9. Salbutamol was the short acting agent used in 27 studies and terbutaline in 5. The treatment period was over 2 weeks in 29 studies, and at least 12 weeks in 20. 25 studies permitted a variety of co-intervention treatments, usually inhaled corticosteroid or cromones. One study did not permit inhaled corticosteroid. Long acting beta-agonists were significantly better than short acting for a variety of lung function measurements including morning PEF (Weighted Mean Difference (WMD) 33 l/min 95% CI 25, 42) or evening PEF (WMD 26 l/min 95% CI 18, 33); and had significantly lower scores for day and night time asthma symptom scores and percentage of days and nights without symptoms. They were also associated with a significantly lower use of rescue medication both during the day and night. Risk of exacerbations was not different between the two types of agent, but most studies were of short duration which limits the power to test for such differences. REVIEWER'S CONCLUSIONS: Long acting inhaled beta-agonists have advantages across a wide range of physiological and clinical outcomes for regular treatment.

Adrenergic beta-Agonists↗
PubMed2000

Long-acting beta2-agonists for chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitation which is only partially reversible. Long acting beta2-agonists, effective in the management of asthma,are also recommended for COPD management so it is important to establish whether these drugs are effective in reducing COPD symptoms in view of the potential side effect and cost burden. OBJECTIVES: To determine the effectiveness of long acting beta2-adrenoceptor agonists in improving lung function and quality of life and reducing dyspnoea in patients with COPD. SEARCH STRATEGY: A search was carried out using the Cochrane Airways Group register. Bibliographies of identified RCTs were searched for additional relevant RCTs. Authors of identified RCTs were contacted for other published and unpublished studies. In addition, unpublished studies were also obtained from the pharmaceutical companies that manufacture long acting beta2- adrenoceptor agonists. SELECTION CRITERIA: All randomised controlled trials over four weeks in duration comparing treatment with long-acting beta2-adrenoceptor agonists (salmeterol and formoterol) with placebo in patients with stable non-reversible COPD. Outcome measures included forced expiratory volume in one second (FEV1), peak expiratory flow rate (PEFR), symptom scores, six minute walk distance, quality of life scores, Borg scores for dyspnoea and rescue bronchodilator use. DATA COLLECTION AND ANALYSIS: Data extraction and study quality assessment was performed independently by two reviewers. Where further or missing data were required, authors of studies were contacted. MAIN RESULTS: Thirty three abstracts were identified as potentially relevant. Of these, four randomised controlled trials (RCTs) were included in this review. Two were parallel group studies of 16 week duration and two were cross-over studies with four week treatment arms. All four RCTs assessed the efficacy of salmeterol in COPD. In a 16 week study of salmeterol 50 mcg and 100 mcg twice daily treatment, a significant increase in FEV1 was seen in both treatment groups. The weighted mean difference (WMD) for the increase in FEV1 for the 50 mcg group was 0.10 litre (95% CI: 0.05;0. 15) and in the 100 mcg group the WMD was 0.12 litre (95% CI: 0.06; 0. 17 ). In the two cross-over studies of four weeks treatment, salmeterol 50 mcg twice daily treatment did not show significant increases in FEV1 (WMD = 0.04 litre, 95% CI: -0.06; 0.15). Similarly, morning and night time PEFR was not significantly improved with salmeterol treatment. In a 16 week study, disease-specific quality of life, measured using the St. George's Respiratory Questionnaire (SGRQ), showed a significant improvement after 50 mcg twice daily, but not after 100 mcg twice daily. This improvement exceeded the threshold for a clinically significant change with this questionnaire. General health status, as measured by the Medical Outcomes Short Form 36, did not improve in any of the eight components with either salmeterol dose. No significant difference was demonstrated in the mean change from baseline in the six minute walk distance (WMD = 1.9 metres, 95% CI: -15.4;19.3). Breathlessness was reduced in one study in patients receiving salmeterol 50 mcg twice daily group. Significantly more patients in this group had Borg scores for breathlessness less than three (a score of three indicating moderate dyspnoea) compared to the placebo treated group (Peto Odds Ratio = 0.60, 95% CI: 0.40; 0.88). Neither dose of salmeterol influenced the incidence of COPD exacerbations, (50 mcg: Peto Odds Ratio = 0.74, 95% CI: 0.47, 1.15) and (100 mcg: Peto Odds Ratio = 0.98, 95% CI: 0.64, 1.52). REVIEWER'S CONCLUSIONS: Treatment of patients with COPD with long acting beta2-agonists produces only small increases in FEV1. In one study, a dose of salmeterol 50 mcg twice daily produced a reduction in breathlessness and a clinically significant improvement in quality of life. (ABSTRACT TRUNCATED)

Adrenergic beta-Agonists↗
PubMed2000

Long acting beta-agonists versus theophylline for maintenance treatment of asthma.

BACKGROUND: Theophylline and long acting beta2-agonists are bronchodilators used for the management of persistent asthma symptoms, especially nocturnal asthma. They represent different classes of drug with differing side-effect profiles. OBJECTIVES: To assess the comparative efficacy, safety and side-effects of long-acting beta-agonists and theophylline in the maintenance treatment of asthma. SEARCH STRATEGY: Randomised, controlled trials (RCTs) were identified using the Cochrane Airways Group register. The register was searched using the following terms: asthma and theophylline and long acting beta-agonist or formoterol or foradile or eformoterol or salmeterol or bambuterol or bitolterol. Titles and abstracts were then screened to identify potentially relevant studies. The bibliography of each RCT was searched for additional RCTs. Authors of identified RCTs were contacted for other relevant published and unpublished studies. SELECTION CRITERIA: All included studies were RCTs involving adults and children with clinical evidence of asthma. These studies must have compared oral sustained release and/or dose adjusted theophylline with an inhaled long-acting beta-agonist. DATA COLLECTION AND ANALYSIS: Potentially relevant trials, identified by screening titles and/or abstracts, were obtained. Two reviewers independently assessed full text versions of these trials to decided whether the trial should be included in the review, and assessed its methodological quality. Where there was disagreement between reviewers, this was resolved by consensus, or reference to a third party. Data were extracted by two independent reviewers. Inter-rater reliability was assessed by simple agreement. Study authors were contacted to clarify randomisation methods, provide missing data, verify the data extracted and identify unpublished studies. Relevant pharmaceutical manufacturers were also contacted. MAIN RESULTS: Six trials met the inclusion criteria. Five used salmeterol and one, biltoterol. They were of varying quality. There was a trend for salmeterol to improve FEV1 more than theophylline in three studies and salmeterol use was associated with more symptom free nights. Bitolterol, used in only one study, was reported to be less effective than theophylline. Subjects taking salmeterol experienced fewer adverse events than those using theophylline (Relative Risk 0.38; 95%Confidence Intervals 0.25, 0.57). Significant reductions were reported for central nervous system adverse events (Relative Risk 0.51; 95%Confidence Intervals 0.30, 0.88) and gastrointestinal adverse events (Relative Risk 0.32; 95%Confidence Intervals 0.17, 0.59). REVIEWER'S CONCLUSIONS: Salmeterol may be more effective than theophylline in reducing asthma symptoms including night waking and improving lung function. More adverse events occurred in subjects using theophylline when compared to salmeterol.

Adrenergic beta-Agonists↗
PubMed1994

A multifunctional expression vector for an anti-HIV-1 ribozyme that produces a 5'- and 3'-trimmed trans-acting ribozyme, targeted against HIV-1 RNA, and cis-acting ribozymes that are designed to bind to and thereby sequester trans-activator proteins such as Tat and Rev.

We previously constructed a multiribozyme expression vector by combining cis- and trans-acting ribozymes and we showed that several ribozymes, each directed against a different target in the HIV genome and acting independently in a 'shotgun' manner, markedly increased the efficiency of cleavage of HIV RNA in vitro [Ohkawa et al., Proc. Natl Acad. Sci. USA 90, 11302 (1993)]. However, the cis-acting ribozymes that had trimmed the 5' and 3' ends of each trans-acting ribozyme were designed merely to await for degradation by RNases when they were used in vivo. Since several trans-activator proteins are essential for viral replication of HIV-1, we wondered whether a decoy function could be coupled with the cleavage activity of ribozymes. We therefore introduced the TAR or the RRE sequence into the stem II region of each cis-acting ribozyme. When the activity of each resulting cis-acting ribozyme that had been endowed with the decoy function was examined in vitro, it was found to retain almost full trimming activity. Moreover, cis-acting ribozymes with either the TAR or the RRE sequence were shown to be able to trap Tat or Rev protein successfully. It is, therefore, possible to endow the stem II region with a specific protein-binding function without the loss of ribozyme function. Thus, cis-acting ribozymes, endowed with the decoy function, can first trim the 5' and 3' ends of each trans-acting ribozyme and are then still available for trapping trans-activator proteins possibly prior to their degradation by RNases when they are to be used in vivo. Furthermore, it is also expected that the reduction in production of HIV RNA that is achieved by sequestering the trans-activator proteins might provide the trans-acting ribozymes, targeted to HIV RNA, with a better chance of eliminating the remaining HIV RNA.

Base Sequence↗
PubMed1994

Effect of dry-cow therapy on subclinical mastitis--an evaluation of long-acting and short-acting intramammaria.

This field study was conducted to evaluate the effect of selective dry-cow therapy with long-acting and short-acting antibiotics, respectively, and also in comparison to control groups without antibiotic treatment. A total of 684 cows from 288 different herds in three Norwegian regions fulfilled the criteria of the study design. There were 104 cows in control group A (sampling only), 115 cows in control group B (placebo), 221 cows treated with long-acting intramammaria Benestermycin vet. 'Leo' for 1 day at drying off in group C, and 244 cows treated with four short-acting intramammaria Leocillin with Dihydrostreptomycin vet. 'Leo' every second day before drying off in group D. The overall effect, measured as the cow being healthy after therapy, was 14.2% in control groups and 33.7% in therapy groups 30 +/- 17 days into the next lactation. Of quarters infected with S. aureus both in late lactation (45 +/- 32 days before drying off) and at drying off, 38.4% in the control group were bacteriologically negative 30 +/- 17 days into the next lactation, compared with 49.5% in the long-acting group and 68.6% in the short-acting group. Of quarters infected with Str. dysgalactiae both in late lactation (45 +/- 32 days before drying off) and at drying off, 10 out of 27 were still infected with Str. dysgalactiae in the control group 30 +/- 17 days into next lactation, compared with 0 out of 31 in the therapy groups. Dry-cow therapy in coagulase-negative Staphylococcus spp. (CNS)-infected quarters led to a 5.2 odds ratio of being healthy quarters 30 +/- 17 days into the next lactation, compared with control groups. Despite this, the overall frequency of CNS in the material was unchanged after therapy compared with controls. Short-acting compared to long-acting preparations had a significantly better effect in preventing new infection with S. aureus or Str. dysgalactiae in untreated healthy quarters in cows with fewer than three infected quarters. This difference in preventive effect was greater in cows with one infected quarter during previous lactation (the new infection rates being 0.078 for short-acting and 0.149 for long-acting) than in those with two infected quarters (the new infection rates being 0.042 and 0.063, respectively).

Animals↗
PubMed2003

Three immunoassays based on monoclonal antibodies specific for prostate specific antigen (PSA), alpha-1-antichymotrypsin (ACT), and the PSA-ACT complex.

BACKGROUND: Prostate specific antigen (PSA) has been widely used as a biomarker for the screening and diagnosis of prostate cancer. PSA in serum predominantly exists as a complex with alpha-1-antichymotrypsin (ACT), and measurement of free PSA and the PSA-ACT complex may improve the utility of the serum PSA assay for differential diagnosis of prostate cancer and non-malignant prostate diseases, such as benign prostatic hyperplasia (BPH). METHODS: Monoclonal antibodies (MAbs) against PSA, ACT, and the PSA-ACT complex were produced by immunizing mice with an incubated mixture of PSA and ACT, and characterized by Western blot analyses and several enzyme-linked immunosorbant assay (ELISA) methods. RESULTS: The MAbs produced in this study are capable of distinguishing the PSA-ACT complex from free PSA and ACT. Four MAbs have been selected and utilized to construct three ELISA systems for the separate measurements of free PSA, the PSA-ACT complex, and total PSA. CONCLUSIONS: The three PSA assay systems developed in this study can specifically measure free PSA, total PSA, and the PSA-ACT complex with equal molar sensitivity. It is expected that these PSA assay systems could be useful in the diagnosis of prostate cancer.

Animals↗
PubMed1997

Effect of long-acting and short-acting calcium antagonists on cardiovascular outcomes in hypertensive patients.

BACKGROUND: Short-acting calcium antagonists may increase coronary artery morbidity, mortality, and non-cardiovascular complications in hypertensive patients. We assessed whether this association was also true for long-acting calcium antagonists. METHODS: We did a case-control study, which was nested within a systematic hypertension control programme for a prospective cohort of 4350 people (first seen 1981-94). Cases (n = 189) were hypertensive patients who had had a first cardiovascular event, including all cardiovascular deaths and hospitalisations, between 1989 and 1995. Controls (n = 189) were individually matched to cases for sex, ethnic origin, age, type of previous antihypertensive treatment, year of entry into the study, and length of follow-up. We collected data on any prescribed drug regimen that was being taken on the event data for cases and on the same date for matched controls. Calcium antagonists were classified by duration of action. FINDINGS: Compared with those on beta-blocker monotherapy, patients on long-acting calcium antagonists (n = 136) had no increased risk of a cardiovascular event (adjusted odds ratio 0.76 [95% CI 0.41-1.43]), whereas patients on short-acting calcium antagonists (n = 27) were at significantly greater risk (adjusted odds ratio 3.88 [1.15-13.11], p = 0.029). Among 38 matched pairs who were both on calcium antagonists, the adjusted risk ratio for short-acting versus long-acting was 8.56 (1.88-38.97), p < 0.01. INTERPRETATION: Long-acting and short-acting calcium antagonists differ in cardiovascular outcomes. Consistent with earlier findings, the use of short-acting calcium antagonists was associated with increased risk of a cardiovascular event. This finding highlights the need to complete on-going clinical trials so that the relative cardiovascular impact of various antihypertensive agents can be assessed.

Antihypertensive Agents↗
PubMed1999

Higher incidence of severe hypoglycaemia leading to hospital admission in Type 2 diabetic patients treated with long-acting versus short-acting sulphonylureas.

AIMS: A comparison of the frequency of severe hypoglycaemia leading to hospital admission in people with Type 2 diabetes mellitus (DM) treated with long vs. short-acting sulphonylureas. METHODS: A community based study over a 12-year period in the population of the city of Basle, Switzerland. The number of diabetic patients treated with oral hypoglycaemic agents was established on the basis of tablet consumption and a defined daily dose, e.g. 7.5 mg for glibenclamide, and 50 mg for glibornuride. RESULTS: Twenty-eight Type 2 diabetic patients were admitted for severe hypoglycaemia, with a median age of 73 years. There were no deaths. Sixteen of these admissions were patients treated with long-acting sulphonylureas and 12 were patients treated with short-acting forms. Only 23.5% of the population with Type 2 DM in Basle were treated with long-acting sulphonylureas. With 30345 person-years of observation, the incidence of severe hypoglycaemia was 2.24 per 1000 person-years for long-acting sulphonylureas vs. 0.75 per 1000 person-year for short-acting forms, odds ratio 3.01 (95% confidence interval 1.35-6.77). Decreased food intake (nine patients) was a major contributing factor. CONCLUSIONS: Severe hypoglycaemia leading to hospital admission is more common in elderly Type 2 diabetic patients treated with long-acting compared to short-acting sulphonylureas. Such long-acting sulphonylureas should be avoided.

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