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Biomedical subjects

B H Jennings

Publications and source records attributed to B H Jennings.

15 recordsLinked to original sources
PubMed1997

Albuterol via Turbuhaler versus albuterol via pressurized metered-dose inhaler in asthma.

BACKGROUND: Inhaled albuterol is most commonly self-administered by patients using a pressurized metered-dose inhaler (pMDI) but patients often have difficulty using the device. Dry powder devices such as the multi-dose, inspiratory flow driven inhaler (Turbuhaler) are often better handled by patients. OBJECTIVE: We sought to compare the efficacy and tolerability of 100 micrograms of albuterol delivered by a multi-dose, inspiratory flow driven inhaler (Turbuhaler) to a standard dose (200 micrograms) delivered by a pMDI (Ventolin) in chronic reversible obstructive airways disease. METHOD: In 6 centers, we studied 37 adults [19 men and 18 women, mean age 39 +/- 12 years; mean baseline forced expiratory volume in one second (FEV1) 72 +/- 13% (% predicted)] with stable but symptomatic reversible obstructive airways disease as demonstrated by 15% or greater increase in FEV1 following two puffs (200 micrograms) albuterol by pMDI. The crossover design comprised a 1-week run-in and two 2-week treatment periods separated by a 1-week washout. At the start and end of each treatment period, FEV1 was measured at the clinic. Patients self-administered albuterol 100 micrograms (2 x 50 micrograms) via Turbuhaler or 200 micrograms (2 x 100 micrograms) via pMDI in a double-blind fashion four times daily. Morning and evening peak expiratory flow (PEF) was noted daily. All non-study bronchodilators were withheld while open-label albuterol pMDI was offered for rescue. RESULTS: Of the 37 patients, 30 used inhaled steroids in constant doses throughout the study, one used inhaled cromoglycate and six used no anti-inflammatory therapy. There was no difference between treatment periods in morning PEF, diurnal fluctuation in PEF, increase in PEF following study drug, baseline FEV1 and FEV1 increase following study drug. Although there was no difference in symptom scores between treatments, the use of rescue beta 2-agonist was slightly but significantly higher during the Turbuhaler treatment period (1.34 versus 1.08 inhalations/ day, P = .04). Compliance with study drug was slightly but significantly lower during the Turbuhaler treatment period (87 versus 95%) such that the total number of beta 2-agonist puffs inhaled (scheduled plus rescue) was similar between treatments. With regard to adverse events, both treatments were well tolerated. CONCLUSIONS: These results suggest that the efficacy and tolerability of albuterol 100 micrograms qid inhaled via Turbuhaler is similar to albuterol 200 micrograms qid, inhaled via pMDI in stable reversible obstructive airways disease.

Adult↗
PubMed1991

The assessment of the systemic effects of inhaled glucocorticosteroids. The effects of inhaled budesonide vs oral prednisolone on calcium metabolism.

In a randomized, double-blind crossover study, the effects of 0.8, 1.6 and 3.2 mg/day inhaled budesonide and 5, 10 and 20 mg/day oral prednisolone on mineral metabolism were compared. Twelve healthy subjects (4 m, 8 f) were treated for 1 week at each dosage level, the graduated dosages being given in ascending order. Budesonide and prednisolone were given twice daily and once daily, respectively, which reflects the schedules common in clinical practice. Serum calcium and the regulatory hormones of calcium metabolism (parathyroid hormone, vitamin D metabolites and calcitonin) were not changed either by prednisolone or budesonide. Prednisolone significantly increased 24 h and 08.00 h fasting urinary calcium excretion and decreased renal calcium reabsorption, while budesonide had little or no effect on urinary calcium loss and increased renal reabsorption at the highest dose level. Both drugs significantly increased renal phosphate reabsorption and serum phosphate levels, but prednisolone caused greater increases than budesonide. In conclusion, during short-term treatment with the dosages used, inhaled budesonide had less effect on calcium and phosphate metabolism than oral prednisolone, and so it may have a lesser action on the skeleton of the type contributing to osteoporosis during long-term treatment.

Administration, Inhalation↗
PubMed1991

Assessment of systemic effects of inhaled glucocorticosteroids: comparison of the effects of inhaled budesonide and oral prednisolone on adrenal function and markers of bone turnover.

The effects of inhaled budesonide (BUD) and oral prednisolone (PRED) on markers of bone turnover and adrenal function were compared in a randomized, double-blind, double-dummy, crossover study. Twelve healthy subjects were treated for one week with 0.8, 1.6 and 3.2 mg/day BUD and 5, 10 and 20 mg/day PRED, the three doses being given in ascending order. Plasma cortisol and adrenal cortical androgens showed a significantly decreasing trend with the increasing doses of both drugs, although PRED caused a significantly greater decrease than BUD. Osteoblast function, reflected by serum osteocalcin and alkaline phosphatase was significantly reduced by PRED, but BUD had a significantly different effect as it affected only osteocalcin. Urinary hydroxyproline/creatinine, a marker of bone resorption, was not changed by either drug. The average potency ratio for equivalent systemic effects was PRED:BUD 3.9:1. During short-term treatment at equivalent anti-asthmatic doses, BUD has significantly less effect on adrenal function and bone turnover than PRED, and it may carry less risk of bone complications during long-term treatment.

Administration, Inhalation↗
PubMed1990

Assessment of the systemic effects of inhaled glucocorticosteroids: the influence of blood sampling technique and frequency on plasma cortisol and leucocytes.

Twelve healthy males (mean age 27.6 y, range 23-35 y) took part in a randomized, double-blind, cross-over study of the effect of blood sampling technique (separate isolated venepunctures vs use of an IV cannula) and frequency (overnight vs morning) on plasma cortisol and white blood cell count after inhalation of a single dose of budesonide 3.2 mg or placebo, in order to establish the more sensitive method for future use. Sampling technique and frequency affected neither leucocytes nor plasma or urinary cortisol. Budesonide suppressed both plasma and urine free cortisol and delayed the nocturnal rise due to the circadian rhythm, thus reducing the AUC of plasma cortisol vs time. Lymphocytes, eosinophils and monocytes were decreased and neutrophils and total white blood cells were increased by the high dose of budesonide used. Lymphocytes and neutrophils showed significant changes earlier than eosinophils and cortisol and may be the variables of choice under certain conditions. Frequent sampling gave more complete information about the systemic effect of the drug than single morning samples.

Administration, Inhalation↗
PubMed1990

A study of the mechanism of the antiasthmatic action of inhaled budesonide.

Inhaled antiasthmatic steroids have been assumed and yet never proved to exert their antiasthmatic effect by topical action in the airways. We tested the hypothesis that the efficacy of inhaled budesonide (BUD) might be due instead to its systemic activity after absorption. We compared inhaled and oral BUD with doses selected to ensure higher peak plasma levels and a greater area under the plasma concentration curve with the oral treatment. After pretreatment with beclomethasone to maximize asthma control, 47 adults with asthma were randomized to receive 0.4 mg of inhaled BUD per day (n = 16) or 1.4 mg of oral BUD per day (n = 15), or placebo (n = 16) in double-blind fashion and then followed weekly until asthma relapsed or for 8 weeks if no relapse occurred. "Relapse" was defined as a drop in the mean peak expiratory flow rate greater than 2 SEM below the mean during the baseline week before switching to the test drugs. The time to relapse was the primary outcome variable. Time to relapse was longer with inhaled than with oral BUD (medians, 22 versus 7.9 days; p = 0.003) or placebo (medians, 22 versus 9 days; p = 0.004). Oral BUD and placebo did not differ (p = 0.41). The morning serum cortisol levels remained normal during all three treatments. Thus, at conventional dosage the antiasthmatic effect of inhaled BUD may be fully explained by a local intrapulmonary action.

Administration, Inhalation↗
PubMed1989

Four-times-a-day dosing frequency is better than a twice-a-day regimen in subjects requiring a high-dose inhaled steroid, budesonide, to control moderate to severe asthma.

Fifty-three adult asthmatic subjects requiring 800 micrograms or more of inhaled beclomethasone dipropionate were enrolled in a double-blind parallel group study of 6-month duration to compare the efficacy and side effects of inhaled budesonide in doses of 800, 1,200, and 1,600 micrograms given two or four times a day (BID or QID). After a two-week observation period to establish baseline, subjects were given the same dose of budesonide as they would be for beclomethasone dipropionate; however, the frequency regimen (BID or QID) was randomly allocated. Subjects were asked to fill in diary cards describing their asthmatic symptoms, need for medication, and throat symptoms. They were assessed by a physician every 4 wk, at which time spirometry was performed. Throat swabs were done at every other monthly visit. Cortisol and response to cortisol after synthetic ACTH injection were assessed at the beginning and end of the trial. Thirty-six subjects, half in each group, completed the study. Those on the BID regimen had almost twice as many days with nocturnal asthma and cough and almost three times as many days with disability due to asthma. There were also twice as many relapses in the BID regimen as judged by the clinician. These relapses mainly occurred toward the end of the study. The maximal daily swings in peak expiratory flow rates were slightly greater in the BID group, although this difference was not physiologically significant. Spirometry, cortisol secretion, and the response after synthetic ACTH injection were not significantly different in either group from the beginning to the end of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1982

The crystal and molecular structure of 3 beta-acetoxy-5, 6 beta-dichloromethylene-5 beta-androstan-17-one.

The compound 3 beta-acetoxy-5, 6 beta-dichloromethylene-5 beta-androstan-17-one crystallizes in the orthorhombic space group, P212121, with four molecules per unit cell, having the following dimensions: a = 7.936(2) A, b = 11.593(2) A, and c = 22.955(4) A. X-ray analysis of single crystal data (1764 observed reflections), collected on a Syntex P1 autodiffractometer, led to complete structural assignment. Solution by direct methods and refinement by least-squares calculations resulted in a final R of 0.037. The conformation of ring A represents one of the few examples of a distorted boat and ring B approximates a distorted chair, both conformations attributable to the strain of the cyclopropyl ring. The spatial relationship between the endo chlorine atom, and the angular methyl group, C(19) is 3.095(5) A. Ring C is a normal chair and ring D adopts a 13 beta-envelope conformation. The steroid molecules pack perpendicular to the c axis with screw axes intersecting the A-B ring junction.

Androstanols↗
PubMed1981

The oxidation of a steroidal bromohydrin revisited.

A comparative study was made of the reactions of 5-bromo-3 beta, 6 beta-dihydroxy-5 alpha-androstan-17-one 3-acetate (1) with lead tetraacetate alone and in the presence of iodine in both high intensity visible light and in total darkness using a variety of solvents. Markedly different product profiles were obtained under the different reaction conditions, making our results of both practical importance and theoretical interest.

Androstanols↗
PubMed1980

Effect of corticosteroid on lymphocyte responsiveness in pigeon breeder's lung.

Four patients with pigeon breeder's lung and positive lymphocyte transformation tests to pigeon antigen were given 250 mg hydrocortisone intravenously, after which the test was repeated at 6, 24, and 30 hr. A significant reduction in lymphocyte responsiveness to pigeon antigen was evident 6 hr after the steroid dose, which reversed within 24 hr after the treatment. This was associated with transient 'false negative' lymphocyte transformation tests in two of the four patients, so this effect of steroid treatment may influence the reliability of this test, if used in the diagnosis of patients with allergic alveolitis. Phytohaemagglutinin responsiveness was not affected by the hydrocortisone treatment. This may indicate difference between the cell populations that respond, after steroid treatment, to antigen and to mitogenic stimulation.

Adrenal Cortex Hormones↗
PubMed1978

Reactions of 4beta,5-epoxy-5beta-androstan-3-ones with hydrogen fluoride in pyridine.

4beta,5-Epoxy-5beta-androstane-3,17-dione (1a), 17beta-hydroxy-4beta,5-epoxy-5beta-androstan-3-one (1b) and 17beta-acetoxy-4beta,5-epoxy-5beta-androstan-3-one (1c) were treated with anhydrous hydrogen fluoride in pyridine (70% solution) at 55 detrees and yielded the corresponding 4-en-4-ols, e.g. 4-hydroxy-4-androstene-3,17-dione (2a). As the reaction temperature was lowered each epoxide formed a second product which, at -75 degrees, was the major component of the reaction mixture and was identified as the 5alpha-fluoro-4alpha-ol derivative of the parent enone, e.g. 4alpha-hydroxy-5-fluoro-5alpha-androstane-3,17-dione (3a). These fluorohydrins are thermally unstable, losing hydrogen fluoride. The acetates of -he fluorohydrins were also prepared, characterized, and shown to be more stable than the parent alcohols.

Androstanes↗