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PubMed2005

Adenylate cyclase toxin (ACT) from Bordetella hinzii: characterization and differences from ACT of Bordetella pertussis.

Bordetella hinzii is a commensal respiratory microorganism in poultry but is increasingly being recognized as an opportunistic pathogen in immunocompromised humans. Although associated with a variety of disease states, practically nothing is known about the mechanisms employed by this bacterium. In this study, we show by DNA sequencing and reverse transcription-PCR that both commensal and clinical strains of B. hinzii possess and transcriptionally express cyaA, the gene encoding adenylate cyclase toxin (ACT) in other pathogenic Bordetella species. By Western blotting, we also found that B. hinzii produces full-length ACT protein in quantities that are comparable to those made by B. pertussis. In contrast to B. pertussis ACT, however, ACT from B. hinzii is less extractable from whole bacteria, nonhemolytic, has a 50-fold reduction in adenylate cyclase activity, and is unable to elevate cyclic AMP levels in host macrophages (nontoxic). The decrease in enzymatic activity is attributable, at least in part, to a decreased binding affinity of B. hinzii ACT for calmodulin, the eukaryotic activator of B. pertussis ACT. In addition, we demonstrate that the lack of intoxication by B. hinzii ACT may be due to the absence of expression of cyaC, the gene encoding the accessory protein required for the acylation of B. pertussis ACT. These results demonstrate the expression of ACT by B. hinzii and represent the first characterization of a potential virulence factor of this organism.

Adenylate Cyclase Toxin↗

PubMed1998

Comparing the use of short-acting and long-acting calcium channel blockers in an HMO.

One of the questions surrounding the controversy over the risks of MI among hypertensives taking calcium channel blockers (CCBs) is the dosage form, and whether the short-acting form may be more likely than the long-acting to increase the risk of MI. This preliminary study compared HMO members receiving the two dosage forms by sociodemographic and clinical characteristics, and by utilization (hospital, office visits, emergency room, outside of HMO services) prior to and during CCB use. The sampling frame was members with one or more dispensings for a CCB 1990 through 1994. Incident users were those who received one or more CCB dispensings and no cardiovascular disease-related drugs the year prior to their first dispensing of a CCB. CCB users were those who had at least 90 days of continuous CCB use. Short-acting outnumbered long-acting users by eight to one. Few incident users of long-acting CCBs were found. Among incident users, diagnoses and comorbidities were similar. In general, short-acting users appeared to have less risk of exposure to heart-related medications, but similar risks of exposure to non-heart-related drugs and to utilization of the various services during the year prior to first use. The odds of being exposed to heart-related medications and non-heart related medications and use of services during periods of use of CCBs were similar in general, but where differences were observed, the odds of being exposed were less among short-acting users. Users of the two dosage forms in this setting prior to reports questioning the safety of short-acting CCBs were different quantitatively and qualitatively making a retrospective comparative study difficult, perhaps not possible, due to substantial selection bias among users. Further patient selection bias has also undoubtedly occurred subsequent to the reports. The final answer to the relative safety and effectiveness of the different dosage forms of calcium channel blockers is likely to have come from randomized clinical trials.

Journal Article↗

PubMed2000

Inhaled short acting beta2-agonist use in asthma: regular vs as needed treatment.

BACKGROUND: Inhaled beta2-adrenergic agonists delivered by inhalation are very widely used in asthma. There has been much controversy of the use and possible consequences of the use of these agents for regular, as opposed as-needed use in asthma. OBJECTIVES: This review to assessed the clinical trial evidence to test whether using regular use of short-acting beta2-agonists reduced asthma control and pulmonary function; worsened symptoms, airway reactivity and quality of life; and increased the rate of exacerbations. SEARCH STRATEGY: A search was carried out of the Cochrane Airways Group "Asthma and Wheez* RCT" register using the terms: regular AND [beta agonist OR bronchodilator OR salbutamol OR albuterol Or terbutaline OR isoproterenol OR reproterol OR fenoterol]. Bibliographies of existing trials were searched and primary trial authors and pharmaceutical companies were approached for additional trials. SELECTION CRITERIA: Randomised controlled trials in which the short-acting beta2-agonist was given regularly in the experimental group, together with an inhaled bronchodilator for relief of symptoms ('rescue use'). The control group consisted of matching placebo inhaled regularly, with an inhaled bronchodilator for as-needed 'rescue use'. DATA COLLECTION AND ANALYSIS: Data were extracted and quality assessments were made by both reviewers. Parallel group and cross-over trials were analysed separately. Where possible data were pooled using a fixed effects model. MAIN RESULTS: Over 800 abstracts were identified, following a review, 60 papers were requested for full assessment by both reviewers. 34 trials from 30 papers met the entry criteria. Data from 31 outcomes were analyzable. There was little difference between the treatments for nearly all outcomes. In cross-over studies, evening peak flow was better with regular treatment, weighted mean difference (WMD) 13.1 l/min (95% confidence interval 24.3, 1.9). In contrast, the FEV1 was better with as-needed treatment (WMD 157 ml (95% CI: 123, 192). Bronchial hyper reactivity was slightly better in the as-needed group, standardised mean difference 0.23, 95% CI: 0.52, 1.12. REVIEWER'S CONCLUSIONS: These results support current guidelines. There is little advantage in using short-acting beta2-agonists regularly, and potentially some small clinical disadvantage.

Adrenergic beta-Agonists↗

PubMedDate not supplied

Sociodemographic and economic comparisons of children prescribed longer-acting versus short-acting stimulant medications for attention deficit hyperactivity disorder.

Little research has been conducted on sociodemographic and cost disparities regarding the use of longer-acting versus short-acting stimulants in the pediatric population. Demographic characteristics and healthcare expenditures of children taking short-acting stimulants versus longer-acting stimulants for attention deficit hyperactivity disorder (ADHD) were compared. Data from the 2000 and 2001 Medical Expenditure Panel Survey, a nationally representative household survey, were analyzed for 221 children exclusively taking short-acting stimulants and 153 children exclusively taking longer-acting stimulants. No disparities in receiving short-acting as opposed to longer-acting stimulants were found by age, gender, race/ethnicity, region of the country, or insurance status. However, children in the latter group were more likely to come from higher income backgrounds and had greater psychotropic medication costs and total healthcare expenditures. For the most part, sociodemographic disparities in medication treatment for ADHD do not appear to exist once a diagnosis has been made.

Adolescent↗

PubMed1992

Clinical distinctions between long-acting and short-acting benzodiazepines.

After their clinical introduction in the 1960s, the benzodiazepines rapidly became the most widely prescribed sedative/hypnotics because of their many advantages over barbiturates and other older agents. Along with this popularity came controversy, which has continued to this day. The most recent form this has taken has been the concern that the short-acting benzodiazepines may have a predisposition to induce certain forms of clinical complications. The author reviews the historical framework in which this controversy arose. In the late 1970s and early 1980s, it became increasingly clear that long-acting agents were associated with daytime sedation as well as cognitive and psychomotor impairment, particularly in the elderly. The short-acting benzodiazepines, which greatly reduced the frequency of these types of effects, rapidly became the most widely prescribed agents. A growing body of data indicates that the short-acting hypnotics are less likely to be associated with falls and hip fractures in the elderly and also have less respiratory depressant qualities, compared with the older long-acting agents. The short-acting compounds may also be more efficacious in inducing sleep during the first night of administration. In contrast, the long-acting agents may be more desirable in those cases in which daytime sedation is desired and may be associated with a delayed and milder withdrawal sleep disturbance. With the short-acting agents, however, sleep disturbance upon drug cessation is dose dependent and may be greatly reduced by tapering the dose.

Accidental Falls↗

PubMed1983

Time of conscious intention to act in relation to onset of cerebral activity (readiness-potential). The unconscious initiation of a freely voluntary act.

The recordable cerebral activity (readiness-potential, RP) that precedes a freely voluntary, fully endogenous motor act was directly compared with the reportable time (W) for appearance of the subjective experience of 'wanting' or intending to act. The onset of cerebral activity clearly preceded by at least several hundred milliseconds the reported time of conscious intention to act. This relationship held even for those series (with 'type II' RPs) in which subjects reported that all of the 40 self-initiated movements in the series appeared 'spontaneously' and capriciously. Data were obtained in at least 6 different experimental sessions with each of 5 subjects. In series with type II RPs, onset of the main negative shift in each RP preceded the corresponding mean W value by an average of about 350 ms, and by a minimum of about 150 ms. In series with type I RPs, in which an experience of preplanning occurred in some of the 40 self-initiated acts, onset of RP preceded W by an average of about 800 ms (or by 500 ms, taking onset of RP at 90 per cent of its area). Reports of W time depended upon the subject's recall of the spatial 'clock-position' of a revolving spot at the time of his initial awareness of wanting or intending to move. Two different modes of recall produced similar values. Subjects distinguished awareness of wanting to move (W) from awareness of actually moving (M). W times were consistently and substantially negative to, in advance of, mean times reported for M and also those for S, the sensation elicited by a task-related skin stimulus delivered at irregular times that were unknown to the subject. It is concluded that cerebral initiation of a spontaneous, freely voluntary act can begin unconsciously, that is, before there is any (at least recallable) subjective awareness that a 'decision' to act has already been initiated cerebrally. This introduces certain constraints on the potentiality for conscious initiation and control of voluntary acts.

Adult↗

PubMedDate not supplied

'Acting out' and 'acting in' behavioural stress responses: the relevance of anxiety and personality style.

OBJECTIVE: To look for links between 'acting out' and 'acting in' behavioural stress responses with anxiety and disordered personality function. METHOD: Depressed patients completed a self-report measure of behavioural responses to stress 1 year after baseline assessment of anxiety levels, personality functioning and other study variables. RESULTS: Patients were assigned to four factorial groups on the basis of variable 'acting out' and 'acting in' scale scores, and effects of individual scale scores also examined. 'Acting in' styles were indicative of high trait anxiety, disordered personality functioning and, in particular, a Cluster C personality disorder style. 'Acting out' was linked most clearly with a Cluster B personality disorder style. CONCLUSIONS: We demonstrate links between behavioural stress responses and anxiety levels and disordered personality functioning. Assessing behavioural stresses responses may shape the clinical expression of some depressive disorders and inform the clinician about the likely salience of anxiety and personality styles.

Acting Out↗

PubMed1983

Reduced solubility of short-acting soluble insulins when mixed with longer-acting insulins.

Using insulins from three manufacturers, we examined the recovery by radioimmunoassay of short-acting soluble insulin when mixed with long-acting insulin as a function of the ratio of the mixture and the time of pre-mixing. In ratios of 1:2, 1:3, and 1:5 (short- to long-acting insulin), all Novo, Nordisk, and Lilly short-acting insulins tested showed a significant loss of solubility when mixed with the respective company's long-acting insulin either for less than 75 s or for 20 min before centrifugation. In ratios of 1:1, Novo's Actrapid (regular) with Monotard (lente) and Lilly's regular with lente showed no significant loss of solubility when pre-mixed for less than 75 s, and the regular insulin also showed no significant loss when pre-mixed for 20 min. However, when Lilly's regular was mixed with either NPH or ultralente in a 1:1 ratio, a significant loss of solubility of the short-acting insulin occurred regardless of time [as was also found with Nordisk's Velosulin (regular) with insulatard (NPH)]. When Lilly regular was incubated with Lilly lente in ratios of 1:3 for less than 75 s, 20 min, 4 h, and 24 h before centrifugation, there was a progressive loss of solubility. In contrast, with the same ratios and times of pre-mixing, Lilly regular when mixed with Lilly NPH showed a rapid initial loss of solubility that plateaued by 20 min before centrifugation.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Combinations↗

PubMedDate not supplied