Long-term Study of Disodium Cromoglycate in Treatment of Severe Extrinsic or Intrinsic Bronchial Asthma in Adults

The results are reported here of a long-term double-blind controlled clinical trial of disodium cromoglycate (D.S.C.G.) and isoprenaline, D.S.C.G. alone, isoprenaline alone, and a placebo given as a powder for inhalation in the treatment of severe bronchial asthma.At the end of one year 16 out of 20 patients on D.S.C.G.-isoprenaline remained on the allocated capsules, compared with 10 out of 15 on D.S.C.G., 5 out of 20 on isoprenaline, and 3 out of 19 taking the placebo. The differences between each of the D.S.C.G.-isoprenaline and D.S.C.G. regimens compared with the isoprenaline and placebo regimens were statistically significant. After eight weeks on four capsules a day the patients in each group were allocated at random so that half continued on full dosage and half on a reducing regimen. At the end of the year there was no significant difference in the failure rate between patients allocated the full dosage and the patients on the reducing dosage. The capsules were well tolerated and toxicity to D.S.C.G. was not observed.     

Trial of Disodium Cromoglycate in Bronchial Asthma

In a double-blind cross-over trial of disodium cromoglycate on 11 patients nine were symptomatically improved, and in all of these daily measurements of peak expiratory flow increased. The forced expiratory volume in the first second and specific airway conductance did not increase in all patients. In most cases the average values for residual volume and functional residual capacity fell; exercise capacity and ventilation did not change, but the pulse rate on exercise was lower. It is suggested that the changes produced by disodium cromoglycate are worth while.     

A double-blind trial of disodium cromoglycate (Intal) in the treatment of bronchial asthma

The result of a double-blind crossover trial with disodium cromoglycate (Intal) in 22 patients, nine with extrinsic asthma and 13 with intrinsic asthma, is reported. While eight extrinsic asthmatics showed considerable symptomatic improvement, only five of the intrinsic group improved while on disodium cromoglycate. Twelve out of 13 patients with symptomatic improvement had associated decrease in airway obstruction as measured by the FEV₁.It is concluded that disodium cromoglycate is useful in the treatment of asthma, particularly of the extrinsic type.     

运动后补充肉碱可提升骨骼肌糖原合成代谢

本研究旨在探讨单次口服肉碱是否有利于促进人体运动后骨骼肌糖原恢复。本研究为交叉实验设计,选取20名受试者,随机分为肉碱试验(实验组)和安慰剂试验(安慰剂组),两次实验间隔至少7 d。所有受试者接受单次60 min 70%VO_2max功率车测试,运动后立即给予高碳水化合物饮食补充和肉碱胶囊或安慰剂淀粉胶囊口服补充,同时观察运动后3 h恢复期内的生理反应。功率车运动后第0、第3小时从股外侧肌采集肌肉样本,同期间隔每30 min收集血液样本,每60 min收集10 min气体样本。研究发现,实验组肌糖原含量增加率显著增加,在血液生化值方面,两组的血糖浓度在各时间点均无显著差异,但实验组的胰岛素反应显著低于安慰剂组。同时在运动恢复期间,实验组呼吸交换率明显低于安慰剂组,这代表运动恢复期口服肉碱后,身体以脂肪为主要能量来源。研究表明,运动后立即补充肉碱能显著提升人体运动后肌糖原恢复,具备临床进一步推广应用的价值。     

Exercise Asthma and Disodium Cromoglycate

Exercise-induced asthma (defined as a fall in PEF of at least 25% of the pre-exercise value) was studied in adult patients with uncomplicated asthma. This was found to occur in 22 out of 52 patients. Pre-exercise inhalation of disodium cromoglycate reduced the mean fall in PEF after maximal exercise from 50% of the pre-exercise value to 23% (open assessment in 11 cases). After submaximal exercise for eight minutes the reduction was from 18% to 10% (double-blind crossover study in 28 cases). It is concluded that disodium cromoglycate partly inhibits the increase of airways resistance after exercise in asthmatic patients.     

Response to disodium cromoglycate in children with chronic asthma

Twenty-three children with chronic severe perennial asthma received randomly-allocated disodium cromoglycate or placebo four times a day for 12 weeks, and the alternative regimen for the subsequent 12 weeks. More than half the patients improved while on DSCG according to clinical assessment. There was a significant increase in the mean FEV_{0·75 second} during the drug period, largely owing to dramatic improvement in nine patients. No reduction in the mean decrease of FEV after exercise was demonstrated. Response, when it occurred, was evident within four weeks. The effect of the medication was consistent in individual patients throughout the 12-week period. No evidence of toxicity was discovered during the period of study.     

Changes in blood gas tensions and functional residual capacity in chronic asthmatics treated with disodium cromoglycate

Twenty chronic asthmatic subjects were treated with disodium cromoglycate in open trial. Although in the group as a whole spirometric findings improved, some patients showed a significant increase in arterial oxygen tension or a significant fall in functional residual capacity without any appreciable changes in spirometry. These changes may partly explain the clinical efficacy of this drug.     

Effect of Disodium Cromoglycate on Exacerbations of Asthma Produced by Hyperventilation

The prophylactic inhalation of disodium cromoglycate lessens the exacerbations which occur in some asthmatic patients after voluntary hyperventilation. Reasons are given for considering this to be a possible mechanism for certain types of emotional exacerbation of the disease and for disodium cromoglycate giving sypmtomatic relief of asthma disproportionate to the improvement in routine measurements of ventilatory capacity. It is suggested that one clinical indication for giving disodium cromoglycate is to observe whether a fall in FEV₁ occurs after two minutes hyperventilation.     

Multicentre,Short-term Therapeutic Trial of Disodium Cromoglycate,With and Without Prednisone,in Adults with Asthma

A total of 117 asthmatic patients were studied in a double-blind, cross-over trial with half-periods of three weeks in which disodium cromoglycate (D.S.C.G.) was compared with an inactive preparation. D.S.C.G. improved spirometric measurements, at a very high level of statistical significance, more than did placebo. The mean advantage of D.S.C.G. was less than 10% after three weeks. Symptomatic improvement by D.S.C.G. was small though significant; it was not correlated with spirometric improvement. A history of chronic cough was the only clinical characteristic associated with a better-than-average spirometric response to D.S.C.G.     

Sodium cromoglycate in chronic asthma.

A long-term double-blind trial of sodium cromoglycate (SCG) with and without isoprenaline, with a placebo control, was undertaken in Edinburgh to a similar design as a previously reported trial in London. The results from the two centres were compared and combined. In Edinburgh 41 patients were studied for 36 weeks and 40 for 52 weeks and in the combined series 121 were studied for 36 weeks and 114 for 52 weeks. In the second year 14 patients were followed-up in Edinburgh and 27 in London. The two SCG regimens were superior overall to placebo both in the Edinburgh and London patients. SCG was effective in similar proportions of patients with extrinsic and intrinsic asthma. In the second year the effectiveness of SCG was further tested by randomly allocating half the patients to a placebo. Some patients derived a continuing benefit from SCG, but its continued use did not appear to be necessary for others, whose progress on placebo was satisfactory.     

Bronchodilator effect of sodium cromoglycate and its clinical implications.

The bronchodilator effect of sodium cromoglycate (SCG) solution was investigated. Twenty asthmatic children aged 6-15 years (mean 11.3) were examined and the action of SCG compared with that of salbutamol and placebo (water). SCG produced a significantly raised peak expiratory flow rate (PEFR) before exercise, which reached a maximum immediately after exercise. The bronchodilatation was sustained for up to four hours, when the PEFR was still significantly above the resting value. This effect was comparable in degree and duration with that of salbutamol. In contrast, placebo produced insignificant bronchodilatation before exercise but significant albeit short-lived bronchodilatation after exercise, which is the characteristic response of the asthmatic to a short period of exercise. This powerful bronchodilator action of SCG and its equally potent inhibitory action on exercise-induced bronchoconstriction was achieved by administering the solution via an efficient nebuliser. In order to achieve maximum clinical effect the SCG must, therefore, be given in this form.     

Controlled Comparison of the Bronchodilator Effects of Three β-Adrenergic Stimulant Drugs Administered by Inhalation to Patients with Asthma

In a double-blind trial of the effect of inhaling three different β-adrenergic stimulants (isoprenaline sulphate 1,000 μg., orciprenaline sulphate 1,500 μg., and salbutamol 200 μg.) and a placebo on ventilatory function in 24 patients with chronic asthma salbutamol was found to have a much longer action than isoprenaline, and it produced a slightly more intense and prolonged effect than orciprenaline. In a double-blind subjective assessment 13 of the 24 patients selected salbutamol as the most effective preparation, while only five preferred isoprenaline and three orciprenaline. Hence salbutamol, given by inhalation, may prove to be the most effective drug at present available for the short-term relief of asthmatic symptoms.     

Clinical efficacy of Crataegus extract WS 1442 in congestive heart failure NYHA class II

In a randomised, placebo-controlled, double-blind clinical study the clinical efficacy and safety of Crataegus extract WS 1442, standardised to 18.75% oligomeric procyanidines, were investigated in 40 female and male outpatients suffering from congestive heart failure NYHA class II. Following a wash-out period of up to seven days, the patients were randomised to be treated for 12 weeks with either WS 1442 (3 x 1 capsule) or placebo. The primary outcome variable was exercise tolerance determined with bicycle exercise testing; as a secondary outcome variable the difference of the double product was calculated. On average, the exercise tolerance increased by 66.3 W x min (10.8%) in the WS 1442 group while in the placebo group a reduction of 105.3 W x min (16.9%) was measured. This difference between the groups was borderline statistically significant (p = 0.06). During the three month therapy the difference of the double product (heart rate x systolic blood pressure x 10(-2)) decreased by 14.4 mmHg s(-1) (26.8%) in the WS 1442 group and by 1.3 mmHg s(-1) (2.7%) in the placebo group, respectively. Recording of laboratory parameters and adverse events showed that WS 1442 was safe and well tolerated. The data show that Crataegus extract WS 1442 is clinically effective in patients with congestive heart failure corresponding to NYHA class II.     

Treatment of atopic eczema in children: clinical trial of 10% sodium cromoglycate ointment.

In a double-blind randomised group-comparative trial 21 children with chronic atopic eczema were treated twice daily for up to 12 weeks with an ointment containing 10% sodium cromoglycate (SCG) in white soft paraffin. A similar group of 21 children was treated for up to 12 weeks with a placebo ointment consisting of the white soft-paraffin base only. The number of patients who withdrew from the trial because treatment was ineffective was significantly greater in the placebo group (16) than in the SCG group (four). Comparison between the two groups also showed significant improvement in inflammation, lichenification, and cracking and the symptoms of itching and sleep disturbance among those on SCG treatment. At the end of treatment significantly more patients in the SCG group (16) had benefited from treatment compared with only two patients in the placebo group. No patients experienced side effects. I conclude that SCG ointment may be a safe alternative to topical steroids in the treatment of atopic eczema in children.     

Muscle sympathetic nerve responses to physiological changes in prostaglandin production in humans.

Previous studies suggest that prostaglandins may contribute to exercise-induced increases in muscle sympathetic nerve activity (MSNA). To test this hypothesis, MSNA was measured at rest and during exercise before and after oral administration of ketoprofen, a cyclooxygenase inhibitor, or placebo. Twenty-one subjects completed two bouts of graded dynamic and isometric handgrip to fatigue. Each exercise bout was followed by 2 min of postexercise muscle ischemia. The second exercise bouts were performed after 60 min of rest in which 11 subjects were given ketoprofen (300 mg) and 10 subjects received a placebo. Ketoprofen significantly lowered plasma thromboxane B(2) in the drug group (from 36 +/- 6 to 22 +/- 3 pg/ml, P < 0.04), whereas thromboxane B(2) in the placebo group increased from 40 +/- 5 to 61 +/- 9 pg/ml from trial 1 to trial 2 (P < 0.008). Ketoprofen and placebo did not change sympathetic and cardiovascular responses to dynamic handgrip, isometric handgrip, and postexercise muscle ischemia. There was no relationship between thromboxane B(2) concentrations and MSNA or arterial pressure responses during both exercise modes. The data indicate that physiological increases or decreases in prostaglandins do not alter exercise-induced increases in MSNA and arterial pressure in humans. These findings suggest that contraction-induced metabolites other than prostaglandins mediate MSNA responses to exercise in humans.     

A randomised double blind placebo controlled clinical trial of a standardised extract of fresh Crataegus berries (Crataegisan) in the treatment of patients with congestive heart failure NYHA II.

A placebo controlled, randomised, parallel group, multicentre trial conducted in accordance with the guidelines of Good Clinical Practice (GCP) shows the efficacy and safety of a standardised extract of fresh berries of Crataegus oxyacantha L. and monogyna Jacq. (Crataegisan) in patients with cardiac failure NYHA class II. A total of 143 patients (72 men, 71 women, mean age of 64.8 (8.0 years) were recruited and treated with 3 times 30 drops of the extract (n = 69) or placebo (n = 74) for 8 weeks. The primary variable for the evaluation of efficacy was the change in exercise tolerance determined with bicycle exercise testing, secondary variables included the blood pressure-heart rate product (BHP). Subjective cardiac symptoms at rest and at higher levels of exertion were assessed by the patient on a categorical rating scale. An overall assessment of efficacy at the final visit was provided by the patient and the investigator. In the ITT population there was a significant increase in exercise tolerance in both groups between visit 1 and visit 3. The difference between the treatment groups was 8.3 watts in favour of the standardised extract of fresh Crataegus berries (p = 0.045). The result is confirmed in the PP population (p = 0.047). Changes in BHP at 50 watts and at comparable maximum load were in favour of Crataegus extract but the results are not statistically significant. The subjective assessment of cardiac symptoms at rest and at higher levels of exertion did not change significantly and the patient and investigator overall assessment of efficacy were similar for the two groups. The medication was well tolerated and had a high level of patient acceptability. The significant improvement, due to the fact that dyspnoea and fatigue do not occur until a significantly higher wattage has been reached in the bicycle exercise testing allows the conclusion that the recruited NYHA II patients may expect an improvement in their heart failure condition under long term therapy with the standardised extract of fresh Crataegus berries.     

A double blind, placebo-controlled study of Andrographis paniculata fixed combination Kan Jang in the treatment of acute upper respiratory tract infections including sinusitis.

A double blind, placebo-controlled, parallel-group clinical study was carried out to evaluate the effect of an Andrographis paniculata (N.) extract SHA-10 fixed combination, Kan Jang, in the treatment of acute upper respiratory tract infections, including sinusitis. Ninety-five individuals in the treatment group and 90 individuals in the placebo group completed the study according to the protocol. The medication was taken for 5 days. Temperature, headache, muscle aches, throat symptoms, cough, nasal symptoms, general malaise and eye symptoms were taken as outcome measures with given scores. The total score analysis showed a highly significant improvement in the verum group versus the placebo. This result applied to the group as a whole and to the sinusitis subgroups. The individual symptoms of headache and nasal and throat symptoms together with general malaise showed the most significant improvement while cough and eye symptoms did not differ significantly between the groups. Temperature was moderately reduced in the verum group. It can be concluded that Kan Jang has a positive effect in the treatment of acute upper respiratory tract infections and also relieves the inflammatory symptoms of sinusitis. The study drug was well tolerated.     

Disodium Cromoglycate in the Prevention of Induced Asthma

In 13 patients with allergic asthma disodium cromoglycate protected fully only two from an allergen-induced asthmatic attack.Inhalation of disodium cromoglycate did not improve lung function in five patients with long-standing chronic asthma.Previous clinical trials do not show convincing evidence that this drug improves bronchial asthma in a high percentage of cases, but it seems to help a small minority of patients.     

Different Effects of Adrenergic Beta-receptor Blockade on Heart Rate Response to Mental Stress,Catecholamines, and Exercise

The magnitude and duration of effect of a single 40-mg oral tablet of oxprenolol on the tachycardias associated with motor-car driving, isoprenaline infusion, and walking were compared against placebo in six normal people by a double-blind study. The tachycardias due to driving and isoprenaline were both conspicuousy reduced for over eight hours; the magnitude and duration of the reduction in exercise tachycardia was substantially less. Thus relatively small doses of beta-receptor antagonists will suppress the increase in heart rate induced by mental stress or catecholamines with relatively little effect on the response to everyday exercise. Possibly smaller doses of these drugs would relieve emotionally-induced anginal pain and tachycardia.     

Beclomethasone Dipropionate Steroid Aerosol in Treatment of Perennial Allergic Asthma in Children

Thirty-one chronic perennial asthmatics aged from 2½ to 16 years were treated with beclomethasone dipropionate pressurized aerosols for up to 20 months. Of these, 16 patients dependent on oral corticosteroid or corticotrophin for up to 11 years were successfully transferred to this treatment, with one exception. Steroid withdrawal symptoms were slight. Loss of weight, disappearance of Cushingoid features, and resumption of growth indicated lack of systemic side effects. Fifteen others inadequately controlled on bronchodilators or disodium cromoglycate, were also effectively treated, and no clinical evidence of adrenal suppression was noted.