Comparison of once- and twice-daily dosing of fluticasone propionate 200 micrograms per day administered by diskus device in patients with asthma treated with or without inhaled corticosteroids.

BACKGROUND: There are limited published data regarding the efficacy of once- versus twice-daily administration of flutica-sone propionate. OBJECTIVE: Our purpose was to evaluate the effectiveness of fluticasone propionate powder 200 microg/d administered as a once- or twice-daily dosage regimen in patients who were currently being treated with bronchodilators only (BD patients) and in patients who required inhaled corticosteroids for maintenance treatment of asthma (ICS patients). METHODS: Five hundred seventy patients were randomly assigned to receive one of the following inhaled treatments through the Diskus device (Glaxo Wellcome, Research Triangle Park, NC) for 12 weeks: fluticasone propionate 100 microg twice daily (FP100BID) or 200 microg once daily (FP200QD) or placebo. RESULTS: BD patients treated with FP100BID, FP200QD, and placebo had mean increases in FEV(1) from baseline to end point of 0. 49 L, 0.37 L, and 0.21 L, respectively (P <.001, FP100BID vs placebo; P =.05, FP200QD vs placebo). ICS patients treated with FP100BID and FP200QD had mean increases in FEV(1) of 0.27 L and 0.11 L, respectively, compared with a decrease in FEV(1) of -0.08 L with placebo (P <.001, FP100BID vs placebo; P =.023, FP200QD vs placebo). BD patients treated with FP100BID and FP200QD had mean increases in morning peak expiratory flow from baseline to end point of 31 L/min and 27 L/min, respectively, compared with a 1 L/min increase in patients treated with placebo. ICS patients treated with FP100BID had a mean increase in morning peak expiratory flow (from baseline to end point) of 18 L/min compared with mean decreases of -3 L/min and -12 L/min in the FP200QD and placebo groups, respectively. More patients were withdrawn from placebo (26% and 48%, in BD and ICS patients, respectively) than from fluticasone propionate (7%-9% [BID-QD] and 18%-32% [BID-QD], in BD and ICS patients, respectively) because of failure to meet predetermined asthma stability criteria. CONCLUSION: The efficacies of FP100BID and FP200QD were comparable with regard to improvement in pulmonary function and asthma stability in BD patients. In ICS patients, asthma control was maintained with FP200QD, whereas FP100BID provided greater improvements in pulmonary function and asthma stability.

Once-daily mometasone furoate dry powder inhaler in the treatment of patients with persistent asthma.

BACKGROUND: Although inhaled glucocorticoids are recommended for all stages of persistent asthma, compliance with long-term therapy is often poor, leading to significant morbidity and mortality. A simplified, once-daily dosing regimen may foster improved compliance. OBJECTIVE: To compare the efficacy and safety of once-daily (AM) administration of mometasone furoate dry powder inhaler (MF DPI) 200 microg and 400 microg with placebo in patients with asthma previously maintained only on short-acting inhaled beta-adrenergic receptor agonists. METHODS: This was a 12-week, double-blind, placebo-controlled, parallel group study. The mean change from baseline to endpoint (last treatment visit) for FEV1 was the primary efficacy variable. RESULTS: At endpoint, both doses of MF DPI were significantly more effective than placebo (P < or = .05) in improving FEV1. Based on morning peak expiratory flow rate, once-daily MF DPI 400 microg was more effective than placebo (P < or = .001) at endpoint. Both active treatments also demonstrated improvement at endpoint in asthma symptom scores, physician-evaluated response to therapy and use of rescue medication. Although both MF DPI dosages were efficacious, MF DPI 400 microg provided additional improvement in some measures of pulmonary function (eg, morning PEFR) when these agents were administered once daily in the morning. Both doses of MF DPI were well tolerated and treatment-related adverse events occurred at a similar incidence among the three treatment groups. CONCLUSIONS: The results of this study indicate that once-daily (AM) MF DPI provides a convenient and effective treatment option for patients with mild or moderate persistent asthma.

Comparison of ipratropium bromide 0.03% with beclomethasone dipropionate in the treatment of perennial rhinitis in children.

OBJECTIVE: To compare the safety and efficacy of ipratropium bromide 0.03% (IB) with beclomethasone dipropionate 0.042% (BDP) in the treatment of perennial rhinitis in children. METHODS: Thirty-three children with nonallergic perennial rhinitis (NAPR) and 113 with allergic perennial rhinitis (APR) were randomly assigned to either IB or BDP for 6 months in a single-blind, multicenter protocol in which the physician was blinded to treatment. At each visit, patients and physicians rated symptom control of rhinorrhea, nasal congestion, and sneezing. Patients also completed quality of life questionnaires at baseline and after 6 months of therapy. RESULTS: Both treatments showed a significant improvement in control of rhinorrhea, congestion, and sneezing compared with baseline over the 6 months of treatment (P < .05). Only for the control of sneezing was BDP consistently better than IB (P < .05). Among the patients given IB, 61% to 73% assessed the control of rhinorrhea as good or excellent on different study visit days, 43% to 60% similarly rated the control of nasal congestion, and 39% to 43% the control of sneezing. The results for BDP were 68% to 78% for the control of rhinorrhea, 55% to 72% for the control of nasal congestion, and 54% to 68% for the control of sneezing. Quality of life assessment documented that both drugs significantly reduced interference with daily activities and disturbance of mood due to rhinorrhea compared with baseline (P < .05). Both treatments were well tolerated with IB causing less nasal bleeding and irritation than BDP. CONCLUSIONS: Ipratropium bromide was safe and effective in controlling rhinorrhea and diminishing the interference by rhinorrhea in school attendance, concentration on school work, and sleep. Ipratropium bromide was as effective as BDP in the control of rhinorrhea and showed a relatively good effect on congestion. Patient and physician assessment favored BDP in the control of sneezing.

Effectiveness of short-course therapy (5 days) with grepafloxacin in the treatment of acute bacterial exacerbations of chronic bronchitis.

Three hundred eighty-nine patients were enrolled in a double-masked, multicenter, randomized clinical trial comparing the clinical and bacteriologic efficacies and safety of a 5-day course (n = 195) versus a 10-day course (n = 194) of grepafloxacin 400 mg once daily in the treatment of acute bacterial exacerbations of chronic bronchitis (ABECB). Patients in the 5-day treatment group received placebo on days 6 through 10. Bacteriologic assessments were based on cultures of sputum specimens obtained before and, when possible, during and after treatment. Organisms were isolated from the pretreatment sputum specimens of 332 of 388 (86%) patients, the primary pathogens being Haemophilus parainfluenzae, Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Staphylococcus aureus (29%, 19%, 4%, 5%, and 5% of isolates, respectively). Among isolates tested for beta-lactamase production, results were positive in 25% of H influenzae isolates and 90% of M catarrhalis isolates. Forty-two percent of S pneumoniae isolates demonstrated reduced susceptibility (intermediate or high-level resistance) to penicillin. A satisfactory clinical outcome (cure or improvement) was achieved in 83% (128 of 155) and 81% (122 of 150) of clinically evaluable patients treated with grepafloxacin for 5 or 10 days, respectively. Pathogens were eradicated or presumed eradicated in 77% (106 of 138) and 80% (98 of 123) of bacteriologically evaluable patients treated with grepafloxacin for 5 or 10 days, respectively. The 2 treatment groups were equivalent with respect to both clinical and bacteriologic efficacy, and no statistically significant differences in the incidence of drug-related adverse events were seen between the 2 groups. Substantial symptom relief was evident with both treatment regimens by the first during-treatment measurement, which occurred between days 3 through 5. These results indicate that treatment with 400 mg grepafloxacin once daily for 5 days is as well tolerated and effective as treatment for 10 days in patients with ABECB. The lower cost compared with a 10-day regimen and the increased likelihood that patients will complete the entire shorter, once-daily regimen make the 5-day grepafloxacin regimen a useful therapeutic option in the treatment of ABECB.

A placebo-controlled, dose-ranging study of montelukast, a cysteinyl leukotriene-receptor antagonist. Montelukast Asthma Study Group.

BACKGROUND: The cysteinyl leukotrienes are important mediators of bronchial asthma. The clinical effect of montelukast, a potent cysteinyl leukotriene-receptor antagonist, was investigated in a randomized, placebo-controlled, multicenter, parallel-group, dose-ranging study. METHODS: After a 3-week, single-blind, placebo run-in period, 343 asthmatic patients (FEV1 40% to 80% of the predicted value with an improvement in FEV1 of at least 15% [absolute value] after receiving inhaled beta-agonists on at least two occasions) were randomly assigned to one of six treatment groups: placebo; 10, 100, or 200 mg once daily montelukast in the evening; or 10 or 50 mg twice daily montelukast for a 6-week, double-blind treatment period followed by a 1-week placebo washout period. All patients used inhaled, short-acting beta-agonists as needed. RESULTS: All montelukast doses caused similar and significant differences compared with placebo in asthma control endpoints. The least-square mean difference between pooled montelukast groups and placebo in the percentage change from baseline in morning FEV1 (10.30%; 95% CI: 5.56 to 15.04), as-needed beta-agonist use (-0.98 puffs; 95% CI: -1.53 to -0.44), morning peak expiratory flow rate (18.80 L/min; 95% CI: 8.62 to 28.98), physicians' and patients' global evaluations, and asthma-specific quality-of-life scores were all significant (p < or = 0.050). The incidence of adverse experiences was not dose related and was similar between placebo and montelukast treatment. CONCLUSION: Montelukast caused a significant improvement in chronic asthma at an oral, once daily evening dose as low as 10 mg.

Ipratropium nasal spray in children with perennial rhinitis.

OBJECTIVE: To compare the efficacy and safety of ipratropium nasal spray and placebo administered twice each day for 4 weeks in pediatric patients with perennial rhinitis who had rhinorrhea as a major complaint. METHODS: This was a multicenter, double-blind, parallel group study. Patients aged 6 to 18 years with symptoms of perennial nonallergic (PNAR) or perennial allergic rhinitis (PAR) were randomized to receive ipratropium (42 micrograms per nostril) or placebo nasal spray, double-blind, twice each day for 4 weeks. Efficacy was evaluated by nasal symptoms, especially anterior rhinorrhea, and quality of life. Previous caregivers for rhinitis and medications used in the past were also evaluated. RESULTS: A total of 202 patients were empanelled, 162 with PAR, 40 with PNAR; of these 151 with mild-severe rhinorrhea were evaluated for efficacy. Treatment with ipratropium reduced symptoms of rhinorrhea primarily in patients with PNAR. In patients with PAR this response was less pronounced, and was seen as a modest decrease in the severity of rhinorrhea noted in the first 2 weeks of treatment. Quality of life assessments confirmed that rhinorrhea was bothersome to these pediatric patients, and suggested that treatment with ipratropium nasal spray was associated with an improvement, especially in the patients with PNAR. There were few adverse events; these were similar in the two treatment groups. CONCLUSIONS: Ipratropium nasal spray 0.03% administered at a dose of 42 micrograms/nostril bid is a safe and effective new therapy for control of anterior rhinorrhea in pediatric patients with PNAR. Twice daily administration is adequate for patients with PNAR, but patients with PAR might benefit from more frequent administration (e.g., tid).

Preseasonal, once daily triamcinolone acetonide nasal aerosol for seasonal allergic rhinitis.

BACKGROUND: Seasonal allergic rhinitis is a common and distressing illness for which treatment is often inadequate. There is a clinical need for safe and effective therapeutic options, including preseasonal treatment, to manage many of these patients. OBJECTIVE: The goal of this study was to evaluate the clinical effects of preseasonal administration of triamcinolone acetonide nasal aerosol in the management of this illness. METHODS: This multicenter, double-blind, placebo-controlled, randomized, parallel group study involved otherwise healthy subjects with a 2-year consecutive history of ragweed-induced seasonal allergic rhinitis. Patients were asymptomatic when randomized to receive 220 micrograms triamcinolone acetonide or placebo nasal aerosol (n = 56 each) once daily for 6 weeks, beginning at least 1 week before significant ragweed pollen was airborne. RESULTS: Triamcinolone acetonide was significantly (P < .001) more effective than placebo in preventing nasal symptoms as determined by mean placebo-adjusted nasal index scores. Patients in the triamcinolone acetonide group had significantly (P < or = .0004) lower scores in the severity of individual nasal symptoms and the overall mean nasal index score. Severity of ocular symptoms was reduced more in the triamcinolone acetonide than in the placebo group (not significant). Physicians' and patients' global evaluations of efficacy favored triamcinolone acetonide, with statistically significant between-group differences in moderate or complete prevention of rhinitis symptoms. The incidence of adverse effects was similar in the two groups, with the most common being headache and increased rhinitis. CONCLUSIONS: This study demonstrates that preseasonal administration of triamcinolone acetonide nasal aerosol is safe and effective for managing seasonal allergic rhinitis.

Efficacy and safety of triamcinolone acetonide aqueous nasal spray in patients with seasonal allergic rhinitis.

BACKGROUND: In order to accommodate increasing patient preferences a new aqueous formulation of triamcinolone acetonide nasal spray was developed for the relief of symptoms associated with seasonal and perennial allergic rhinitis. OBJECTIVE: This multicenter, randomized, double-blind study was designed to compare the efficacy and safety of once-daily triamcinolone acetonide aqueous nasal spray (220 micrograms/day) with placebo in relieving the symptoms of seasonal allergic rhinitis due to ragweed. METHODS: One hundred forty patients received either a once daily 220-microgram dose of triamcinolone acetonide aqueous nasal spray or placebo for 2 weeks. Patients evaluated the severity of seasonal allergic rhinitis symptoms daily for 2 weeks according to a 4-point scale (0 = absent, 1 = mild, 2 = moderate, 3 = severe). Physician and patient global evaluations of overall treatment effectiveness were assessed at the end of the treatment period. RESULTS: Patients receiving triamcinolone acetonide aqueous nasal spray, 220 micrograms/day, had significantly (P < .05) greater improvements in all rhinitis symptoms at weeks 1 and 2 and overall for the 2-week treatment period compared with the placebo group. A significant (P = .006) improvement in the nasal index occurred as early as 12 hours after the first dose of triamcinolone acetonide aqueous nasal spray. Both patients and physicians reported a greater overall improvement in symptoms for the triamcinolone acetonide aqueous nasal spray group. There were no differences between the two treatment groups in the incidence of adverse events. CONCLUSIONS: This study confirmed that a 220-microgram dose of triamcinolone acetonide aqueous nasal spray, administered once daily for 2 weeks, is well tolerated and reduces effectively the severity of symptoms of seasonal allergic rhinitis due to ragweed.

Double-strength beclomethasone dipropionate (84 micrograms/spray) aqueous nasal spray in the treatment of seasonal allergic rhinitis.

BACKGROUND: The use of intranasally administered corticosteroid sprays is an established treatment option for seasonal allergic rhinitis. METHODS: In this double-blind, placebo-controlled, multicenter study, 438 patients with moderate to severe symptoms of seasonal allergic rhinitis were treated for 4 weeks with double-strength beclomethasone dipropionate (BDP) aqueous nasal spray (84 micrograms/spray: BDP-ds), once daily; regular-strength BDP (42 micrograms/spray: BDP-rs), twice daily; high-strength BDP (336 micrograms/spray: BDP-hs), once daily; or placebo. BDP-hs was included as a safety comparison group. All treatments were given as two sprays per nostril. RESULTS: Physician-rated nasal symptom scores were significantly improved in all three active treatment groups compared with those of the placebo group within the initial 3 days of treatment. Improvement was maintained throughout the 4-week treatment period. BDP-ds and BDP-rs were equivalent at all time points. The BDP-ds, BDP-rs, and BDP-hs groups had greater numbers of patients with a good or excellent therapeutic response at end point than the placebo group. All treatments were well-tolerated, and no unexpected adverse events were reported. No effects on laboratory evaluations or vital signs were evident for any treatment group. CONCLUSIONS: The results of this study show that BDP-ds given once a day and BDP-rs given twice a day in the same total daily dose are comparably safe and effective in the treatment of patients with seasonal allergic rhinitis.

A 12-week dose-ranging study of fluticasone propionate powder in the treatment of asthma.

Fluticasone propionate (FP) administered via metered-dose inhaler is a potent corticosteroid effective in the treatment of asthma. To evaluate the efficacy and safety of FP powder administered via a breath-activated inhaler (Diskhaler), a multicenter, double-blind, randomized, placebo-controlled, parallel-group study was conducted in adolescent and adult patients (n = 331) with mild-to-moderate asthma previously treated with beta 2-agonist therapy alone. Patients received FP powder 50, 100, or 250 micrograms or placebo twice daily for 12 weeks. FP-treated patients compared with placebo-treated patients had significantly (p < 0.001) greater improvements in morning predose forced expiratory volume in 1 sec (21-22% increase vs. 9%). Improvement in morning peak flow rate were also significantly (p < 0.001) greater with FP than with placebo (8-10% increase vs. 2% increase). There was also a significant overall treatment difference in the frequency of inhaled albuterol use (p < 0.001) and number of nighttime awakenings due to asthma (p = 0.005). There were no statistically significant difference among the FP treatment groups in any outcome measure. Physicians' global assessments also indicated significant (p < 0.001) differences in efficacy, with 67-74% of FP-treated patients rated as having "effective" or "very effective" treatment compared with 41% of placebo-treated patients. Significant beneficial effects of FP were observed in lung function and diary card parameters after just 1 week of treatment. Adverse events were similar across treatment groups and primarily related to local irritation. Effect on hypothalamic-pituitary-adrenal axis function was minimal. In summary, all three dosages of inhaled FP powder were well tolerated and improved various asthma-related variables. Improvements in pulmonary function, beyond those achieved with beta 2-agonist therapy alone, were maintained for the duration of the 12-week study.

[Evaluation of variability of duration of pregnancy in mares]. / Hodnocení proménlivosti délky gravidity klisen.

In a set of mares of English Thoroughbred horse of the Napajedla stock the gravidity length in the time period from 1880 to 1972 was evaluated. The variability of the gravidity length was evaluated in sets which were put together by combination of two age groups with a division of the studied time period into ten-year stages. Variance and sample means of the gravidity lengths in these sub-groups are significantly different in the period under study. In order to eliminate the action of non-genetic influences qualifying the variability of the gravidity length, and to increase the objectivity of their evaluation it is proposed not to calculate with absolute values of the gravidity length, but on the contrary with transformed values: (xi - x) divided by s which would be computed for corresponding year of the foaling period. Another methodical approach to exclude the variability of the gravidity length depending on seasonal influences was based on the use of correction factors which were determined for individual months of foaling, on the basis of the sinusoid form of the curve of the gravidity length in the course of the calendar year. When observing the influence of the age of sires on the gravidity length, the shortening of the gravidity length in dependence on their higher age has been suggested, however this relation was significant only sporadically. The submitted work is a part of a larger theme referring, to the reproduction of horses.

[An analysis of stallion fertility based on the number of matings per heat]. / Rozbor plodnosti hrebcu podle poctu pripustení klisen v jedné ríji.

The fertility problems were studied in the herd of the English Thoroughbred horse on the Napajedla stud farm. Breeding records for the period from 1880 to 1972 were used as the starting data. The survey comprised 32 stallions. The relationship between fertility and the number of matings was calculated by the chi 2 quantity. The calculated values are highly variable. However, it is generally seen in most of the stallions that the number of matings per heat (i. e. one or several matings) had no significant influence on the pregnancy of mares and on the fertility values of the stallions. A higher variability among the stallions was found both in fertility and in the number of abortions. The evaluation of pregnancy in mares for the period from 1880 to 1972 indicates that its level was significantly higher before World War I than in the post-war period. The results are interpreted in the discussion.

[The effect of the age of stallions and mares on their fertility]. / Vliv veku hrebcu a klisen na jejich plodnost.

The study was based on the documentation of the Napajedla Stud Farm of the English Thoroughbred horse for 1888-1972. Evaluating the effect of the age of stallions on their fertility (leaving aside the variability of the age of their mothers), such an effect was found to be significant only in four out of the 26 studs evaluated. In 65% of the selected stallions, the correlation coefficients were found to be negative, but without statistical significance. However, the objective of the study was to evaluate stallions and mares parallelly as to their age variability and fertility. The relationships of the effect of the age of the stallion and of the mare on fertility were evaluated by different modificatons of the value chi2. The prerequisite for the analyses of the effect of different stallion age at a constant age of mares was the calculation of the global chi2 used jointly for the evaluation of the variable age of stallions and mares. The result are varied and report on the individuality of the effect of stallions, giving no clear basis for generalizing any fertility-decreasing tendency with the higher age of the parents. The problem is analyzed from the physiological viewpoint.

[Estimation of the heritability coefficient of stud fertility]. / Odhad koeficientu dedivosti plodnosti hrebcu.

The breeding documentation of the English Thoroughbred horse breeding farm at Napajedla was analyzed to study some effects acting upon the fertility of studs and mares and the length of gravidity. The heritability of fertility is the subject of this report. The normality of the distribution of fertility was tested by processing 300 data on fertility at the given significance level sup / Fn(xi) - F(xi) / less than or equal to Dn(a). The value of the supreme D(300) = 0.108 is lower than the critical level for alpha 0.05. The estimation of fertility heritability coefficient indicates that h2 = 0.31; the heritability coefficient is at the boundary of low and medium heritability. The method of half-sib correlation was used for the calculation; 25% genetic similarity is involved in this case. The calculated value is an estimate characterizing the evaluated population. In view of the number of the observed studs, this value is regarded as informative. The problems under study are part of a wider range of problems concerning the evaluation of reproduction in the breeding of the English Thoroughbred Horse.

Goodpasture's syndrome--effects of plasmapheresis.

Two patients with Goodpasture's syndrome, who underwent plasmapheresis are presented. One patient received prednisone but the other patient received no concomitant cytotoxic therapy. Results indicate that plasmapheresis reduces morbidity in patients with Goodpasture's syndrome. The possible mode of action of plasmapheresis is discussed. The use of cytotoxic therapy as an adjunct to plasmapheresis may not be necessary since the anti-GBM production appears to be a self-limiting process.

Disseminated coccidioidomycosis: clinical, immunologic and therapeutic aspects.

A patient with disseminated coccidioidomycosis initially had pulmonary and skin manifestations and survived for 14 years before dying of meningitis due to Coccidioides immitis. In addition to several courses of amphotericin B therapy the patient received injections of transfer factor derived from appropriate donors and miconazole nitrate therapy. The immunologic defence mechanisms of the patient during the course of his disease were studied and the possibility of a cell-mediated immunologic defect, potentially reversible by transfer factor, was demonstrated.

Acute lindane poisoning with development of muscle necrosis.

A 35-year-old man ingested food contaminated with lindane, an insecticide containing almost pure gamma hexachlorocyclohexane. Grand mal seizures and severe acidemia developed rapidly. The seizures recurred for nearly 2 hours, then ceased. In addition, the patient had muscle weakness and pain, headaches, episodic hypertension, myoglobinuria, acute renal failure and anemia. Pancreatitis developed 13 days after the ingestion of lindane. A muscle biopsy on the 15th day of illness demonstrated widespread necrosis and regeneration of muscle fibres. The patient's condition improved and he was discharged 24 days after the onset of his illness. During the year following the poisoning the patient noted difficulty with recent memory, loss of libido and easy fatigability. One year after lindane ingestion the results of physical examination, including those for muscle power and bulk, were normal.

Pheochromocytoma presenting with pulmonary edema and hyperamylasemia.

A 28-year-old woman was admitted to hospital with acute pulmonary edema, mild abdominal discomfort and hyperamylasemia. From the 2nd hospital day hypertensive episodes occurred daily. The furosemide screening test for renovascular hypertension revealed elevated plasma renin activity (PRA) but an intravenous pyelogram revealed a right suprarenal mass and no evidence of renovascular compression. Elevated values of plasma and urinary catecholamines indicated a pheochromocytoma, and a single chromaffin tumour was resected. It is important to monitor left ventricular filling pressure during operative removal of a pheochromocytoma. Postoperatively the patient had normal blood pressure and PRA. Decreased urinary amylase clearance and abnormal pancreatic and salivary amylase isoenzymes were found.