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1.
In a double-blind trial patients with atopic eczema received either oral evening primrose oil (EPO) (n= 14) or placebo (n= 11) for 12 weeks. In the EPO group a statistically significant improvement was observed in the overall severity and grade of inflammation and in the percentage of the body surface involved by eczema as well as in dryness and itch. Patients in the placebo group showed a significant reduction in inflammation. The patients receiving EPO showed a significantly greater reduction in inflammation than those receiving placebo. Evening primrose oil caused a significant rise in the amount of dihomogammatinolenic acid in the plasma phospholipid fatty acids. Plasma levels of TXB2, 6-keto-PGF1, and PGE1, and the amount of TXB2 released into serum during clotting were not altered by evening primrose oil.  相似文献   

2.

Background

Previous clinical trials with evening primrose oil in atopic dermatitis (AD) treatment have shown different results. In addition, the optimal dose and duration of treatment with evening primrose oil have not yet been determined.

Objective

The aim of this study is to investigate the dose-response treatment effects of evening primrose oil on clinical symptoms of AD and serum concentrations of polyunsaturated fatty acids.

Methods

Forty AD patients were enrolled for the study and randomly divided into 2 groups: those who received evening primrose oil 160 mg daily for 8 weeks and those who received 320 mg of evening primrose oil twice daily for 8 weeks. We evaluated the Eczema Area Severity Index (EASI) scores of all AD patients at weeks 0, 2, 4 and 8. In addition, we measured the levels of serum fatty acids, including C16 : 0 (palmitic), C18 : 2n (linoleic), C18 : 3n (linolenic) and C20 : 4 (arachidonic acid) using gas chromatography.

Results

The serum fatty acid levels C18 : 3n and C20 : 4 were higher in the 320 mg group than in the 160 mg group, with statistical significance. After evening primrose oil treatment, EASI scores were reduced in the 2 groups. The improvement in EASI scores was greater in the 320 mg group than in the 160 mg group. There were no side effects seen in either group during the study in the 2 groups.

Conclusion

The results of this study suggest that the 320 mg and 160 mg groups may be equally effective in treating AD patients and show dose-dependent effects on serum fatty acid levels and EASI scores.  相似文献   

3.
Although gamma-linolenic acid (GLA) has been shown to correct deficiencies in skin lipids associated with reduced delta-6-desaturase activity which should result in improvement of dysregulation of inflammation and immunity in atopic eczema, clinical studies with evening primrose oil containing 10% GLA have yielded contradictory results. We have therefore examined the effect of a higher percentage (at least 23%) GLA-containing borage oil in adults with stable atopic eczema of moderate severity in a double-blind, multicentre study. One hundred and sixty patients were randomized to take daily either 500 mg of borage oil-containing capsules or the bland lipid miglyol as a placebo over a 24-week period. Use of topical diflucortolone-21-valerate cream was allowed as rescue medication, with the amount used until response being defined as primary, and clinical improvement as secondary efficacy criteria. Although several clinical symptoms improved compared with placebo, the overall response to borage oil did not reach statistical significance. Significant differences in favour of borage oil were, however, observed in a subgroup excluding patients who failed to show increased erythrocyte dihomo-gamma-linolenic acid levels and in whom adherence to inclusion criteria and the study protocol were questionable. GLA metabolites increased in borage oil-treated patients only, and serum IgE showed a trend to decrease on overall and subgroup analysis. No substance-related adverse effects were observed. This study shows no overall efficacy of GLA-containing borage oil in atopic eczema, with steroid use being the primary response parameter, although it suggests that a subgroup of patients may benefit from this well-tolerated treatment.  相似文献   

4.
This study was designed to look at the effect of evening primrose oil (linoleic and gamma-linolenic acids) as an oral supplement for patients with atopic eczema. We used a double-blind, blocked crossover design with random assignment of patients to treatment groups. We used Wilcoxon's signed-ranks method of comparing changes during the trial. We observed no significant effect on erythema, scale, excoriation, lichenification, or overall severity in 123 patients with atopic eczema of average severity while they took oral doses of evening primrose oil (2 or 4 gm in children, 6 or 8 gm in adults).  相似文献   

5.
The effect of dietary supplementation with a combination of n-3 (marine oil) and n-6 (evening primrose oil) essential fatty acids in the treatment of chronic stable plaque psoriasis was observed. Thirty-seven patients in a double-blind parallel trial were studied. There was on significant improvement in clinical severity of psoriasis of change in transepidermal water loss.  相似文献   

6.
BACKGROUND: Previous uncontrolled trials have suggested that oral terbinafine, an antimycotic allylamine compound, could be useful in the treatment of seborrhoeic dermatitis. OBJECTIVES: To investigate in a placebo-controlled trial the clinical efficacy of oral terbinafine (Daskil(R), Mipharm, Milan, Italy) in patients with moderate to severe seborrhoeic dermatitis. METHODS: Sixty outpatients (mean +/- SD age 37 +/- 11 years; 32 men and 28 women) with moderate to severe seborrhoeic dermatitis were enrolled in a multicentre, randomized, placebo-controlled, investigator-blinded, parallel-group, 12-week study. After a 2-week wash-out period, enrolled patients were randomized to treatment with oral terbinafine 250 mg daily (n = 30) or placebo (moisturizing ointment) (n = 30) applied twice daily for 4 weeks (weeks 0-4). Patients were followed up for an additional 8 weeks after completion of treatment and were clinically evaluated at weeks 0, 2, 4 and 12 by an investigator unaware of the patient's type of treatment. The primary end-point of the study was clinical evaluation of erythema, scaling and itching, each scored on a 0-3 scale. A global clinical score, representing the sum of each evaluated symptom, was also calculated. RESULTS: Demographic and clinical data were equally balanced between the placebo and terbinafine groups. All enrolled patients concluded the study. At baseline, the mean +/- SD global clinical score was 7.4 +/- 1.3 in the placebo group and 7.7 +/- 1.0 in the terbinafine-treated group. At weeks 4 and 12 the mean +/- SD global clinical score in the placebo group was 5.9 +/- 1.7 and 6.3 +/- 1.2, respectively, which was not significantly different from baseline. As compared with baseline values and the placebo group, terbinafine treatment significantly (P < 0.0001, Tukey-Kramer test) reduced the mean +/- SD global clinical score (to 1.0 +/- 1.1 at week 4, and 1.2 +/- 1.4 at week 12), as well as the individual erythema, scaling and itching scores. No serious adverse events were recorded during the study in either group. CONCLUSIONS: This is the first controlled trial that has shown oral terbinafine to be effective in the treatment of moderate to severe seborrhoeic dermatitis. Clinical improvement following 4 weeks treatment with terbinafine was maintained 8 weeks after completing treatment.  相似文献   

7.
Background Reports on controlled trials on the efficacy and tolerability of sulfonated shale oils in atopic eczema are not available so far. The aim of this study was to investigate whether topically applied, specially prepared pale sulfonated shale oil (PSSO) cream is capable of improving symptoms/signs of mild to moderate atopic eczema in children more efficaciously than a corresponding vehicle cream. Patients and methods A total of 99 children suffering from mild to moderate atopic eczema were enrolled in this multicentre, randomized, vehicle‐controlled study. Verum or vehicle cream was applied to the affected skin area three times a day over 4 weeks. As the primary outcome parameter served the reduction of the total score after 4 weeks of treatment, compared with the initial examination. Secondary outcome parameters were addressed as well. Tolerability was judged by investigators and patients/parents, and adverse events were documented. Results After 4 weeks of treatment, the total score declined from 13.4 ± 3.7 to 4.5 ± 7.4 score points in the verum group and from 13.0 ± 3.1 to 11.7 ± 8.6 score points in the vehicle group (P < 0.0001). The superiority of verum regarding total score was already apparent after a treatment period of 1 week (reduction by 5.6 ± 4.3 vs. 1.3 ± 5.9 score points; P < 0.0001). Tolerability was found superior at the end of the treatment in the verum when compared with the control group – both by investigators (P < 0.0001) and patients/parents (P = 0.0051). Conclusion Pale sulfonated shale oil cream 4% is capable to treat mild to moderate atopic eczema in children more efficaciously than vehicle and is well tolerated. PSSO thus represents a valuable addition to our therapeutic armamentarium. PSSO should be considered in particular when valid alternatives for topical glucocorticoids are sought for.  相似文献   

8.
We have measured all the essential fatty acids (EFA) in plasma phospholipids in forty-one adults with atopic eczema and fifty normal controls. The major dietary n-6 EFA, linoleic acid, was significantly elevated, but all its metabolites, 18:3n-6, 20:3n-6, 20:4n-6, 22:4n-6, and 22:5n-6 were significantly reduced. The major dietary n-3 EFA, alpha-linolenic acid, was also elevated, though not significantly, while all its metabolites were also significantly reduced. These observations suggest that atopic eczema is associated not with any defect of EFA intake, but with abnormal metabolism, possibly involving the enzyme delta-6-desaturase. Treatment with oral evening primrose oil produced partial correction of the n-6 EFA abnormality, but had no effect on the n-3 EFAs.  相似文献   

9.
This review summarizes clinically important findings from 19 systematic reviews published between January 2006 and August 2007 on the topic of atopic eczema (AE). The evidence suggests that avoidance of allergenic foods during pregnancy or the use of hydrolyzed or soy formula milks does not prevent eczema. Delayed introduction of solids may decrease eczema risk. Asthma typically develops in around a third of children with eczema, and wheezing in early infancy is a predictor of risk. Established topical corticosteroids such as betamethasone should be used just once daily. Topical tacrolimus and pimecrolimus can be used for people who become dependent on topical corticosteroids, especially on sensitive sites such as the face. Wet wraps are useful in secondary care for inducing remission in a child, but they are not a treatment for mild eczema and they should not be used long term. Oral ciclosporin can be used for inducing a remission in severe eczema, and azathioprine can be considered for maintenance treatment. Narrowband ultraviolet (UV)B phototherapy can be used for chronic AE, and UVA1 may be useful for acute eczema. There is little convincing evidence of a clinical benefit with evening primrose oil for eczema, but there is some good new evidence that educational support to eczema families is beneficial. Future trials need to be larger, and include active comparators, patient-reported outcomes and longer-term aspects of disease control. They should be better reported, and registered on a public clinical trials register.  相似文献   

10.
目的评价中药利湿散冲剂治疗湿热型湿疹患者的临床疗效和安全性。方法101例湿热型湿疹患者随机分为三组,接受为期3周的随机、双盲、安慰剂对照试验,观察患者皮损分值(SDASS)、瘙痒分值以及舌象等相关症状分值变化。结果治疗后,各组患者皮损分值(SDASS)均较治疗前显著改善(P<0.01),尤以中西医结合治疗组明显。与治疗前相比,单纯利湿散治疗对瘙痒改善并不理想(P>0.05),而中西医结合治疗组和赛庚啶治疗组差异有显著性(P<0.01)。单纯利湿散和中西医结合治疗组患者舌象分值治疗后均显著性降低(P<0.01),单纯赛庚啶治疗组无显著性变化(P>0.05)。单纯利湿散治疗组(12.5%)不良反应发生率显著低于单纯赛庚啶治疗组(68.97%,P<0.001)和中西医结合治疗组(47.62%,P<0.01),中西医结合治疗没有出现不良反应叠加效应。复查部分患者的血常规及血清谷草转氨酶、谷丙转氨酶和肌酐等生化学指标无显著异常。结论利湿散冲剂可有效改善患者皮损表现,不良反应轻微。中西医结合治疗疗效更显,没有出现不良反应叠加效应。利湿散治疗对湿热型湿疹患者舌象的改善可能暗示了利湿散冲剂"清热利湿"的中医组方治则。  相似文献   

11.
The effect of topical n-6 essential tatty acids in the form of evening primrose oil on the epidermal atrophy caused by a potent topical steroid was studied in 24 normal volunteers by measuring epidermal thickness and cross-sectional area and by histological examination. Epidermal thickness and cross-sectional area were significantly lower in normal forearm skin treated with 0·1% betamethasone valerate twice daily without occlusion for 3 weeks when compared with placebo-treated skin. The addition of evening primrose oil to the topical steroid did not prevent steroid-induced epidermal atrophy suggesting that steroid-induced epidermal atrophy is not mediated by the inhibition of essential fatty acid release from cell membranes  相似文献   

12.
BACKGROUND: The Six Area, Six Sign Atopic Dermatitis (SASSAD) severity score is an objective atopic eczema severity index designed principally to assess response to treatment in therapeutic trials. Validity has been demonstrated in single and multicentre clinical trials, although data on the reliability of the index have not previously been published. OBJECTIVES: To assess inter- and intraobserver variability of the SASSAD index. METHODS: Six observers with experience in the assessment of atopic eczema were each asked to score disease severity in six patients with moderate to severe atopic eczema using the SASSAD index. Repeat observations were carried out on randomly selected patients by each observer to estimate intraobserver variation. RESULTS: The interobserver variation in total SASSAD scores for each patient ranged from 7 to 30 (median 15.5) out of a maximum possible score of 108. The intraclass correlation coefficient ri for the total scores among all six observers was quite high at 0.70, although interobserver agreement for individual components of the index was poor to moderate. The maximum recorded intraobserver variation in total SASSAD score in any of the examined patients was 8 units. CONCLUSIONS: As with many other tested atopic eczema scoring indices, the SASSAD index is subject to significant interobserver variation, reflecting the difficulties in reliably assessing eczema severity objectively.  相似文献   

13.
A multicentre, randomized, double-blind, controlled crossover clinical trial was conducted on 33 patients with severe refractory atopic dermatitis, to determine the effects of cyciosporin (5 mg/kg/day) on their health-related quality of life. Treatments were administered for 8-week periods. One group (n=16) received placebo followed by cyclosporin, and the other (n=17) received cyclosporin and then placebo. Health-related quality of life was assessed at o, 8 and 16 weeks using a general measure, the United Kingdom Sickness Impact Profile (UKSIP), an eczema-specibic measure, the Eczema Disability Index (EDI), and a global 5-point rating scale of overall health (very good to very poor). In addition, clinical assessments (i.e. extent and activity of disease) were made by the investigators. UKSIP and EDI scores indicated significant improvement in quality of life (P<0.05–P<0.01) of patients with atopic dermatitis after treatment with cyclosporin. Although no patient required withdrawal from the study. 20 patients receiving cyclosporin reported adverse events, compared with eight taking placebo. There was a close correlation (P<0.05–P<0.01) between the UKSIP and HDI scores. In contrast, there was either no correlation, or only a very poor correlation, between the quality of life parameters and clinical measures of extent and activity of eczema. When cyclosporin was stopped, relapse was rapid, but the mean scores for disease activity and extent of disease were less than their baseline values (i.e. an improvement of greater than 25% was maintained in 11 patients at week 4). However, there was no relapse in the overall quality of life scores 8 weeks after cyclosporin was withdrawn, contrary to what was seen when only the skin signs were assessed. Short-term treatment with cyclosporin has beneficial effects on the quality of life of patients with severe, refractory atopic dermatitis, and may be a valuable alternative to short courses of systemic steroids, giving patients a much needed period of remission that provides prolonged quality of life benefit in some patients. Quality of life can be successfully assessed in patients with atopic eczema using the UKSIP and the EDI.  相似文献   

14.
目的探讨复方多粘菌素B软膏联合地奈德乳膏治疗亚急性/慢性湿疹的临床疗效和安全性。方法采用多中心、随机、双盲、平行对照临床研究,入选亚急性湿疹患者144例(试验组72例,对照组72例),慢性湿疹患者144例(试验组72例,对照组72例)。试验组与对照组分别外用复方多粘菌素B软膏和复方多粘菌素B软膏基质,隔3h后两组均使用地奈德乳膏,每日交替使用各2次。记录患者的症状/体征(包括瘙痒程度、炎症程度、糜烂/渗出程度、浸润/肥厚程度及靶皮损面积)和时间指标(瘙痒减轻起效时间、瘙痒减轻缓解时间)。分析两组的疗效,评估安全性。结果试验组和对照组的症状/体征总分在用药7d(亚急性湿疹:试验组6.09±2.78,对照组8.26±3.17;慢性湿疹:试验组6.56±2.68,对照组8.84±2.90)和14 d(亚急性湿疹:试验组3.68±3.18,对照组5.28±4.05;慢性湿疹:试验组4.38±3.27,对照组6.25±3.78)均较基线水平(亚急性湿疹:试验组13.44±1.66,对照组13.60±1.75;慢性湿疹:试验组12.96±1.16,对照组12.64±1.18)有不同程度的下降。试验组亚急性、慢性湿疹患者在用药7、14 d后的症状/体征均较相应的对照组低,差异有统计学意义(均P<0.05)。亚急性湿疹患者中,试验组瘙痒和浸润肥厚评分的下降幅度均显著高于对照组(均P<0.01);慢性湿疹患者中,试验组瘙痒、浸润肥厚和靶皮损面积评分的下降幅度均显著高于对照组(均P<0.05)。亚急性湿疹患者试验组瘙痒减轻起效时间短于对照组,但瘙痒减轻缓解时间长于对照组(均P<0.05);慢性湿疹患者试验组瘙痒减轻起效时间短于对照组(P<0.0001),但瘙痒减轻缓解时间与对照组差异无统计学意义。试验组医生和患者对治疗效果的满意度均高于对照组(均P<0.05)。结论外用复方多粘菌素B软膏可增强外用地奈德乳膏治疗亚急性和慢性湿疹的疗效,且对亚急性湿疹的效果更为显著。复方多粘菌素B软膏还能较好地控制湿疹患者的瘙痒症状和浸润肥厚。  相似文献   

15.
BACKGROUND: In clinical practice or trials on hand eczema the severity of this disease can be 'measured' in different ways: by means of a physician-rated clinical severity score, a patient-rated clinical severity score or by an indicator of the burden of disease. We assume that the patient-rated severity score corresponds more with the (change in) burden of disease than with the physician-rated severity score. OBJECTIVES: To demonstrate how physicians and patients differ in their assessment of the severity of hand eczema as seen in a physician-rated severity score, patient-rated severity score and a burden of disease questionnaire. METHODS: We used data from an open-label randomized controlled trial which was set up in two university hospital dermatology departments in the Netherlands, specializing in hand eczema. One hundred and fifty-eight patients with moderate to severe chronic hand eczema were included. The main outcome measures were the physician-rated severity score, based on five visible aspects of hand eczema (desquamation, erythema, vesicles, infiltration, fissures), the patient-rated severity score (a self-rating scale), a burden of disease questionnaire (the Dermatology Life Quality Index, DLQI) and the correlations between these parameters, both at inclusion and over time. RESULTS: Only desquamation and infiltration were significantly correlated with patient-rated severity score. Patient-rated severity score correlated with seven of 10 DLQI items, but it did not correlate with the items regarding influence on clothes worn, impairment of sporting activities, and problems associated with treatment of the skin. The majority of patients showed improvement in all parameters after treatment. However, the improvement in patient-rated severity score was not clearly correlated with changes in physician-rated severity score. Except for DLQI item 1 (itch, soreness, pain, stinging), none of the changes in burden of disease was correlated with changes in patient-rated severity score. For each DLQI item, change over time correlated weakly with decreases in several, but not all, components of the physician-rated severity score. CONCLUSIONS: Disease severity can be expressed by different scores; these scores are not clearly correlated, and measure different aspects. Patient satisfaction is not guaranteed when treatment is focused solely on the visible aspects of hand eczema. Instead, burden of disease has a greater impact.  相似文献   

16.
BACKGROUND: Patients with dermatitis are known to have impaired quality of life. Whether this varies according to body site has not been evaluated. Patch tests have previously been shown to influence quality of life, although no previous studies have shown if this is dependent on the results of the patch tests. OBJECTIVES: To evaluate the impact of patch testing on quality of life according to the outcome of the investigations and to determine how quality of life varies according to eczema body site. METHODS: One hundred and sixty consecutive adult patients with active eczema were selected from a patch test clinic for inclusion into the study. Quality of life was determined using the Dermatology Life Quality Index (DLQI) and the SF-36, prior to patch testing and 2 months later. Perceived eczema severity at each time point was also noted, along with the outcome of patch testing. Baseline comparison of quality of life was performed between four body site groups (face, hand, generalized, other). RESULTS: Patients confirmed as having relevant positive contact allergens were shown to have a significant improvement in both perceived eczema severity (P = 0.0004) and DLQI score (P = 0.0015) at 2 months after patch testing. No significant changes were noted in the SF-36 score, other than a borderline improvement in the pain score (P = 0.048). The improvement in quality of life and eczema severity was not noted in patients with negative patch tests. Eighty-nine per cent of patients diagnosed as having contact allergy were able to comply with avoidance advice. No significant variation was noted in quality of life according to body site affected by eczema. There was a positive correlation between DLQI score and perceived eczema severity (P < 0.0001). CONCLUSIONS: Patients confirmed as having contact allergy show a subsequent improvement in eczema severity and an improvement in quality of life.  相似文献   

17.
This review provides a summary of key findings from 22 systematic reviews on atopic eczema (AE) published over the 2‐year period from January 2012 to 31 December 2013, focusing on prevention and treatment of AE. For an update of systematic reviews on the epidemiology, mechanisms of disease and methodological issues, see Part 1 of this update. Based on current systematic review evidence, the most promising intervention for the prevention of AE is the use of probiotics (and possibly prebiotics) during the late stages of pregnancy and early life. Exposure to household pets, especially dogs, may also be protective, but exclusive breastfeeding for up to 7 months does not confer benefit. The role of vitamin D in preventing AE is currently unclear. Very few of the systematic reviews provided additional evidence for the use of specific treatments for AE. Further research is required to establish the role of desensitization, Chinese herbal medicines, homeopathy and specialist clothing. Nevertheless, there is now clear evidence that evening primrose oil and borage oil are not effective for the treatment of AE. There have been no randomized controlled trials on the use of H1 anti‐histamines as monotherapy for the treatment of AE.  相似文献   

18.
Aim  The intent of our study was to determine the efficacy of oral naltrexone, an opiod antagonist, in the treatment of pruritus in patients with chronic eczema.
Methods  This double-blind, placebo-controlled study recruited 38 patients with eczema complaining from pruritus. Pruritus scores were evaluated. Patients were given placebo ( n  = 20) or naltrexone 50 mg ( n  = 18) for 2 weeks period. During the study, pruritus scores based on visual analogue scale system (VAS) were assessed three times: at the start of study, after 1 week, and after 2 weeks.
Results  In both groups, decreased VAS scores were observed, but naltrexone showed to be significantly more effective than placebo in decreasing VAS score after 1 week ( P <  0.005) and 2 weeks ( P <  0.001).
Conclusion  Naltrexone is more effective than placebo in the treatment of pruritus in patient with eczema. Naltrexone might be considered as an adjunct treatment in the treatment of pruritus. However, further studies in this aspect are highly fostered.

Conflicts of interest


This study and the authors were not supported by any company with a vested interest in the product being studied and the project was funded by Skin Research Center.  相似文献   

19.
Lais? allergoid tablets contain allergens that are modified by carbamylation. Due to their modified chemical structure, they are suitable for sublingual immunotherapy (SLIT) (13, 16, 17, 24). Based on their small molecule size of 12 to 40 kDa, they can be easily absorbed via the oral mucosa (1). In this review, we studied the efficacy of SLIT with carbamylated monomeric allergoid tablets in the treatment of grass pollen- and dust mite-induced allergic rhinoconjunctivitis on the basis of symptom and medication score improvements. Following a selective internet and databank search, six trials-some placebo-controlled-regarding the treatment of grass pollen- (n = 266) and dust mite-induced (n = 241) allergic rhinoconjunctivitis were used to draw conclusions regarding the clinical efficacy of allergoid tablets. The primary endpoints in these trials were decreases in the need for allergy medications and/or reductions in the occurrence of rhinoconjunctivitis symptoms. Data was recorded from patient diaries regarding their symptoms and medications used and conclusions were then drawn about the effectiveness and tolerabieity of Lais? tablets. The average improvement in symptom score in three trials of grass pollen allergy treatment was 34% in comparison to the placebo group. The treatment of dust mite-induced rhinoconjunctivitis produced an average symptom score improvement of 22% compared to the placebo or control groups. The intake of symptomatic rescue medication during allergoid tablet therapy declined. Treatment of grass pollen allergies and dust mite-induced rhinoconjunctivitis showed an average medication score improvement of 49% and 24%, respectively. Few side effects were documented in the trials and predominantly local effects were observed. Severe systemic side effects did not occur. On the basis of the trial results summarized in this review, we suggest that SLIT using Lais? sublingual tablets is an effective and well-tolerated form of treatment.  相似文献   

20.
10 adult patients with symptomatic urticaria pigmentosa were treated with ketotifen versus placebo in a double-blind cross-over study. A highly significant reduction of the daily symptom scores for pruritus and whealing was found with 2 mg ketotifen daily per os, and, compared to oral disodium cromoglycate, ketotifen was much more effective. Tiredness was the only side effect noted in 40% of the patients, and a transient worsening of symptoms was noted after discontinuation of the drug.  相似文献   

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