Mast cell activation ameliorates pentylenetetrazole-induced seizures in rats: The potential role for serotonin.

Neuroinflammation plays a key role in the pathogenesis of epilepsy, but the underlying mechanisms are not well understood. Mast cells are multifunctional immune cells that are also activated by stress. The effects of activated mast cells on epileptogenesis are not yet known. This study investigated the effects and mechanisms of compound 48/80-stimulated mast cell activation on pentylenetetrazole-induced epileptic seizures in rats. Male Wistar rats were separated into seven groups (n = 12). Group-1(NS+PTZ) received intraperitoneal saline solution, while groups 2(C-48/80+PTZ-1), 3(C-48/80+PTZ-2), and 4(C-48/80+PTZ-3) received compound-48/80 at doses of 0.5, 1, and 2 mg/kg, respectively, 30 min before 45 mg/kg pentylenetetrazole administration. Similarly, Group-5(Cr+C-48/80+PTZ) received 10 mg/kg cromolyn plus 2 mg/kg compound-48/80 before pentylenetetrazole, and Group-6(MC Dep+C-48/80+PTZ) was exposed to a mast cell-depletion process, and then received 2 mg/kg compound-48/80. Group-7(5-HT+PTZ) received 10 mg/kg serotonin. Seizure stages were evaluated using Racine's scale. Compound-48/80 at 2 mg/kg induced anticonvulsive effects against pentylenetetrazole-induced seizures by extending onset-times of both myoclonic-jerk and generalized tonic-clonic seizures (p = 0.0001), and by shortening the duration of generalized tonic-clonic seizure (p = 0.008). These effects were reversed by cromolyn (p = 0.0001). These effects were not observed in mast cell-depleted rats. Similarly to compound 48/80, serotonin also exhibited anticonvulsive effects against seizures (p < 0.05). Compound 48/80 acts as an anticonvulsant by activating mast cells in a dose-dependent manner. The anticonvulsive effects of mast cell activation may be mediated by serotonin. Mast cell activation may therefore provide protective activity against seizures under appropriate circumstances.

The Derivatives of Cromolyn Ameliorate the Abnormal Misfolding of Amyloid Proteins and Neuroinflammation in the Neural Cells.

BACKGROUND: The representative symptom of Alzheimer's Disease (AD) has mainly been mentioned to be misfolding of amyloid proteins, such as amyloid-beta (Aß) and tau protein. In addition, the neurological pathology related to neuroinflammatory signaling has recently been raised as an important feature in AD. Currently, numerous drug candidates continue to be investigated to reduce symptoms of AD, including amyloid proteins misfolding and neuroinflammation. OBJECTIVE: Our research aimed to identify the anti-AD effects of two chemical derivatives modified from cromoglicic acid, CNU 010 and CNU 011. METHODS: CNU 010 and CNU 011 derived from cromoglicic acid were synthesized. The inhibitory effects of Aß and tau were identified by thioflavin T assay. Moreover, western blots were conducted with derivates CNU 010 and CNU 011 to confirm the effects on inflammation. RESULTS: CNU 010 and CNU 011 significantly inhibited the aggregation of Aß and tau proteins. Moreover, they reduced the expression levels of mitogen-activated protein (MAP) kinase and nuclear factor kappa-light-chain-enhancer of activated B cells (NF- κB) signaling proteins, which are representative early inflammatory signaling markers. Also, the inhibitory effects on the lipopolysaccharide (LPS)-induced cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) expression referring to late inflammation were confirmed. CONCLUSION: Our results showing multiple beneficial effects of cromolyn derivatives against abnormal aggregation of amyloid proteins and neuroinflammatory signaling provide evidence that CNU 010 and CNU 011 could be further developed as potential drug candidates for AD treatment.

The actual role of sodium cromoglycate in the treatment of asthma--a critical review.

INTRODUCTION: Despite international consensus and clearly written guidelines urging wider use of corticosteroids or combinations of inhaled short- and long-acting ß-agonists (SABA and LABA) and corticosteroids in persistent asthma, prescribing patterns and compliance rates fall far short of recommendations. OBJECTIVES: The failure to use steroids more aggressively is due, in part, to their side effects, even with inhaled forms of the drug. There is a role for expanded use of sodium cromolyn in asthma. Its potent anti-inflammatory effects, lack of side effects, and acceptable dosing and method of delivery, as well as its special role in exercise-induced asthma, make it a very suitable choice in the initial therapy for control of asthma. CONCLUSION: Compared to SABA and LABA, cromoglycates alone are unsuspicious of being used to enhance physical performance.

Cromoglycate, reproterol, or both--what's best for exercise-induced asthma?

OBJECTIVE: International guidelines recommend short- (SABA) or long-acting b-agonists for the prevention of bronchoconstriction after exercise (EIB) in patients with exercise-induced asthma (EIA). However, other drugs are still in discussion for the prevention of EIB. We investigated the efficacy of a combination of inhaled sodium cromoglycate and the ß-mimetic drug reproterol versus inhaled reproterol alone and both versus inhaled placebo in subjects with exercise-induced asthma (EIA). METHODS: The study aimed to prove the preventive effect of a combination of 1-mg reproterol and 2-mg disodium cromoglycate (DSCG) and its single components vs. placebo, measuring the decrease of FEV1 after a standardized treadmill test in 11 patients with recorded EIA. The study medication was twice as high as those of drugs which are commercially available (e.g., Allergospasmin®, Aarane®). RESULTS: The results revealed that the combination of reproterol and DSCG was significantly effective against a decrease of FEV1 after a standardized exercise challenge test (ECT) compared to placebo. The short-acting b-agonist reproterol alone had almost the same effectiveness as the combination of reproterol and DNCG. The difference between the combination with DNCG and reproterol alone was less than 10% and insignificant (p 0.48). DNCG alone did not show a difference in the effectiveness compared to placebo. CONCLUSION: Prevention of EIA with the combination of reproterol and DSCG or with reproterol only is effective. An exclusive recommendation in favor of the combination cannot be given due to the low difference in the effectiveness versus reproterol alone. Due to the limited number of subjects and some probands showing protection under DSCG, it cannot be completely excluded that there is some preventive power of DSCG in individual cases.

A double-masked study to compare the efficacy and safety of topical cromolyn for the treatment of allergic conjunctivitis.

BACKGROUND/PURPOSE: To compare the efficacy and safety of topical cromolyn between with and without preservative for the treatment of allergic conjunctivitis. METHODS: A double-masked study was performed in patients with allergic conjunctivitis. Each cromolyn sodium 2% ophthalmic solution with or without 0.01% benzalkonium chloride (BAK) was randomized to apply on either eye. The efficacy and safety were evaluated every other week by a questionnaire about ocular itching, redness and foreign body sensation, and objective scores of conjunctival redness, chemosis, cornea erosion and discharge using slit-lamp biomicroscopy. An overall response was also rated by physician's impression. RESULTS: A total of 37 subjects were enrolled in this study but only 33 completed the study. All of subjective questionnaire scores showed a significant improvement after treatment in both groups. Objective score of redness significantly decreased after treatment in either groups but not chemisos or discharge. After 4-week treatment, corneal erosion diminished significantly in the group without preservative but not in the group with 0.01% BAK. There was no significant difference between with and without 0.01% BAK groups in each subjective or objective score. No adverse effect related with medication was observed. CONCLUSION: Cromolyn 2 % ophthalmic solution was effective and safe to treat allergic conjunctivitis. A short-term use of cromolyn 2 % ophthalmic solution with 0.01% BAK would not cause any significant toxicity in patients with allergic conjunctivitis. Preservative-free cromolyn may be beneficial to the compromised eyes or eyes required of long-term medication.

Treatment of allergic rhinitis.

Allergic rhinitis is a common chronic respiratory illness that affects quality of life, productivity, and other comorbid conditions, including asthma. Treatment should be based on the patient's age and severity of symptoms. Patients should be advised to avoid known allergens and be educated about their condition. Intranasal corticosteroids are the most effective treatment and should be first-line therapy for mild to moderate disease. Moderate to severe disease not responsive to intranasal corticosteroids should be treated with second-line therapies, including antihistamines, decongestants, cromolyn, leukotriene receptor antagonists, and nonpharmacologic therapies (e.g., nasal irrigation). With the exception of cetirizine, second-generation antihistamines are less likely to cause sedation and impair performance. Immunotherapy should be considered in patients with a less than adequate response to usual treatments. Evidence does not support the use of mite-proof impermeable covers, air filtration systems, or delayed exposure to solid foods in infancy.

Seasonal allergic rhinitis: limited effectiveness of treatments.

(1) Seasonal allergic rhinitis, otherwise known as hayfever, is a harmless condition, although it can cause major discomfort and interfere with activities of daily living. We conducted a review of the literature, based on our in-house methodology, to determine the risk-benefits of treatments used in this setting. (2) Placebo-controlled trials show that sodium cromoglicate relieves symptoms, especially if it is used before symptoms appear. Adverse effects are rare with sodium cromoglicate nasal solutions and eye drops. (3) Nasal steroids have well-documented efficacy. Beclometasone is the best choice. Adverse effects include epistaxis, nasal irritation and, occasionally, systemic disorders. (4) Oral antihistamines are less effective than nasal steroids. They also provoke adverse effects, especially drowsiness. Nasal azelastine seems to have a similar efficacy as oral antihistamines. (5) The adverse effects of systemic steroids must not be overlooked, especially with long-term use. Oral administration is an alternative for severe symptoms that do not respond to other treatments, although this is rarely the case. Long-acting intramuscular steroids carry an increased risk of adverse effects. (6) Despite evaluation in several randomised controlled trials, there is no firm evidence that homeopathic preparations have any specific efficacy in allergic rhinitis. (7) Vasoconstrictors, ipratropium and montelukast, have negative risk-benefit balances in hay fever. (8) When a single allergen is responsible (grasses, ragweed, birch), clinical trials suggest that specific desensitisation can provide a modest improvement. However, this treatment carries a risk of local adverse effects, as well as a risk of rare but severe anaphylactic reactions, especially in patients who also have unstable severe asthma. (9) Sublingual desensitisation seems to be even less effective than subcutaneous desensitisation in adults. Follow-up is too short to know whether there is a risk of severe anaphylactic reactions. The results of paediatric studies are even less convincing. (10) In practice, when drug therapy is needed to relieve symptoms of seasonal allergic rhinitis, sodium cromoglicate is the first-line treatment. If a nasal steroid solution is chosen, it should be used for the shortest possible period.

Effects of nebulized sodium cromoglycate on adult patients with severe refractory asthma.

Many patients with severe refractory asthma, which is insufficiently controlled by additional high-dose of inhaled corticosteroids, require oral corticosteroids and/or immunosuppressant. Clinicians should seek for suitable medications, for its' chronic use may induce high risk of side effects. The purpose of this study was to evaluate the efficacy and safety of nebulized sodium cromoglycate (3-4 times/day) in adult severe asthmatic patients with poorly controlled asthmatic symptoms, despite treatments with high-dose inhaled corticosteroids. Adult patients with severe asthma (n=251) were enrolled in a randomized clinical trial at 30 medical centers in Japan. Isotonic saline was used as placebo. The study was conducted for 10 weeks; with initial 2 weeks of observation followed by 8 weeks of treatments. Efficacy was primarily evaluated based on improvements in morning peak expiratory flow after treatment. All patients who applied inhalation of nebulized sodium cromoglycate (SCG group) or saline (Controls) were treated with high-dose of inhaled corticosteroids (median of beclomethasone dipropionate equivalent dose: 1600 microg/days) and second-line control therapy including oral corticosteroids. There was no significant difference in morning peak expiratory flow between SCG group and controls. However, when patients were stratified into atopic and non-atopic groups, morning peak expiratory flow had significantly improved in the atopic SCG group compared to atopic Controls. Additional inhalation of nebulized sodium cromoglycate with inhaled corticosteroids is effective even in patients with severe atopic asthma. This finding shows that nebulized sodium cromoglycate is expected to be new second-line therapeutic option in severe asthma.

Liver disease and vasculitis in a patient taking cromolyn.

Hypersensitivity reactions to cromolyn sodium occur rarely. On several occasions they have been associated with peripheral eosinophilia and granulomatous inflammation. Liver disease has not been reported previously as a complication of inhaled cromolyn. We describe here a woman in whom marked peripheral eosinophilia, liver disease, and systemic vasculitis developed while taking cromolyn and resolved or improved on discontinuation of the drug and treatment with corticosteroids. The liver disease was similar to primary biliary cirrhosis except that marked eosinophilic infiltration and granulomas were present initially. Studies of the patient's serum for binding of carbon 14-labeled cromolyn, the skin for deposits of the drug, and the circulating lymphocytes for stimulation by cromolyn failed to demonstrate any abnormalities. However, the elevated IgG and IgM levels, the positive rheumatoid factor and antimitochondrial antibody, and the reduced serum complement, which returned to normal on discontinuation of the drug therapy, suggests that immunologic mechanisms may have played a role in the pathogenesis of this patient's illness.

Comparison of the therapeutic efficacy of cromolyn sodium with that of combined chlorpheniramine and cimetidine in systemic mastocytosis. Results of a double-blind clinical trial.

Both antihistamines and cromolyn sodium have been suggested for the treatment of systemic mastocytosis. To determine if one drug regimen was superior to the other, eight patients with systemic mastocytosis were admitted to a double-blind, double-crossover study in which the therapeutic efficacy of cromolyn sodium was compared with that of a combination of chlorpheniramine and cimetidine. Response to therapy was assessed by the patients using symptom scores and by the attending physicians during clinic examinations in addition to sequential plasma and urinary histamine determinations. In the six patients who completed the trial, the patient symptom scores and the physician evaluations indicated that there was no advantage of one drug regimen over the other. Plasma and urinary histamine levels, markedly elevated in most of the patients, were not consistently altered by administration of either cromolyn sodium or the combined antihistamines. Thus, cromolyn sodium and the combined antihistamines were indistinguishable when used for the symptomatic treatment of systemic mastocytosis, and neither regimen altered systemic histamine levels.

Cromolyn sodium in the treatment of children with severe, perennial asthma.

Cromolyn sodium is a recently introduced drug used in the prophylactic treatment of severe, perennial, bronchial asthma, particularly in the pediatric age group. In a multicenter trial, 276 chronic asthmatic patients of eight pediatric allergists entered a randomized, double-blind, placebo-controlled, crossover study lasting 12 weeks. Test compounds of cromolyn sodium or placebo were inhaled four times a day, and daily scores were kept of symptom severity as well as frequency of use of other medications. Patients had statistically significant lower average daily symptom scores when treated with cromolyn sodium as compared to treatment with placebo. A strong subjective preference for cromolyn sodium was expressed by 60% of those completing the trial, versus 9% for placebo. The patients' need for other symptomatic medications also dropped significantly during the cromolyn treatment period.

A double-blind study comparing the effectiveness of cromolyn sodium and sustained-release theophylline in childhood asthma.

The effectiveness of cromolyn sodium and theophylline on asthma in children was compared during a 3-month trial. Forty-six children (aged 5 to 15 years) with asthma were assigned at random to cromolyn or theophylline (Theo-Dur) treatment groups. Each subject received theophylline placebo or cromolyn placebo in addition to the active drugs. A methacholine challenge test was done at the start of the study to document asthma and was repeated during the third month. The theophylline dosage was regulated to obtain serum levels of 10 to 15 micrograms/mL by a physician not involved directly with patient care. Forty patients completed the study. Both theophylline and cromolyn treatment groups showed improvement from base-line status in terms of symptom scores, pulmonary function, and decreased use of inhaled albuterol. Patients treated with theophylline had more side effects and required more frequent office visits than those treated with cromolyn. Both groups had decreased sensitivity to methacholine, and for one statistical test patients treated with cromolyn improved significantly. These results indicate that cromolyn is as effective as theophylline in treating mild to moderate asthma in children; additional benefits were fewer side effects and a possible decrease in bronchial hyperactivity.

Methotrexate treatment of severe asthma in children.

Seven children from 3 to 14 years old with chronic steroid-dependent asthma were treated with methotrexate (MTX). Asthma in all of the patients had been poorly controlled for at least 2 years despite the use of oral theophylline and inhaled corticosteroids, cromolyn and albuterol. All presented with significant side effects as a result of chronic systemic steroid therapy. Five patients were atopic and had been unable to tolerate immunotherapy because of systemic reactions. Forced expiratory volume in 1 second and forced expiratory flow, mid-expiratory phase, improved in four patients after 4 to 6 months of treatment with doses of MTX ranging from 7.5 to 17.5 mg/wk. Three patients were able to discontinue their systemic corticosteroids. Laboratory values including complete blood cell count with differential and liver enzymes remained at baseline in all except one patient, who had transient elevation in alanine aminotransferase and aspartate aminotransferase. One patient experienced side effects sufficient to require discontinuation of MTX. It is concluded that MTX is effective for reducing the need for systemic corticosteroids and for improving pulmonary functions in some individuals. The benefits of MTX in this group of severe asthmatics appear to justify the potential risks involved in its use.

Ocular sodium cromoglycate. An overview of its therapeutic efficacy in allergic eye disease.

Sodium cromoglycate stabilizes mast cell membranes and prevents the release of histamine and other biochemical mediators. When topically applied to the eye before allergen exposure, ocular sodium cromoglycate prevents many of the signs and symptoms associated with type I allergic reactions (which includes hayfever, acute allergic and chronic allergic conjunctivitis, and vernal keratoconjunctivitis) and giant papillary conjunctivitis. Although difficulties exist in evaluating clinical trials in allergic eye disease, both open and controlled studies have shown ocular sodium cromoglycate to be very effective in relieving the subjective symptoms and clinical signs of the above ocular disorders. In addition, ocular sodium cromoglycate may decrease the need for supplementary oral antihistamines and, more importantly, the need for ocular corticosteroids, thus decreasing the incidence of steroid-induced ocular side effects. However, in severe cases and in instances of acute exacerbation of symptoms, the combined ocular application of sodium cromoglycate and corticosteroids may be very effective. No systemic or severe adverse reactions have been attributed to ocular sodium cromoglycate, which is not surprising since systemic drug absorption from the eye is minimal. However, transient local stinging and burning have been reported. Thus, although further studies in giant papillary conjunctivitis and comparative studies with corticosteroids in allergic conjunctivitis and vernal keratoconjunctivitis are needed to more clearly define the extent of benefits that may be obtained from ocular sodium cromoglycate, it is clear that the safety and efficacy of the drug in type I allergic eye diseases is such that it should be considered as a first-line agent when drug therapy of these disorders is indicated.

Nedocromil sodium is more effective than cromolyn sodium for the treatment of chronic reversible obstructive airway disease.

In a multicenter, double-blind, group comparative trial, the efficacy of nedocromil sodium (nedocromil, 4 mg, four times daily [qid]), cromolyn sodium (2 mg, qid), and placebo was compared in patients receiving inhaled beta 2-agonists and inhaled corticosteroids for the treatment of chronic reversible obstructive airway disease. After a 2-week baseline period, 132 patients (8 centers) between the ages of 20 and 75 years entered a 4-week run-in period in which the dose of inhaled corticosteroid was reduced by 50 percent. During the run-in phase, deterioration of symptoms (total symptom score) by ten points qualified patients to enter the 6-week drug trial period. Patients in the nedocromil treatment group showed the most robust and consistent improvements over placebo and cromolyn sodium for all daily dairy variables. Statistically significant improvements over placebo were noted for both active treatment groups for daytime, nighttime, and total symptom score. Symptom scores for nedocromil were statistically significantly improved over both cromolyn sodium and placebo for both daytime and nighttime asthma. Patients treated with nedocromil also demonstrated a significant reduction in the use of nighttime as needed (prn) beta 2-agonists as compared with either the placebo- or cromolyn sodium-treated groups. Only nedocromil-treated patients demonstrated a statistically significant improvement in morning peak expiratory flow rate (PEFR) as compared with placebo. Both nedocromil and cromolyn sodium groups demonstrated statistically significant improvements in afternoon and evening PEFRs. Collectively, the improvements in nighttime symptoms, decreased bronchodilator use, and improved morning PEFR show that patients treated with nedocromil had improved nocturnal symptoms. Pulmonary function tests (FEV1, FVC, PEFR) demonstrated no statistically significant differences between the two active treatments, although trends favored nedocromil for both FEV1 and PEFR. Although symptoms improved in patients treated with cromolyn sodium, the level of symptom control was less than that achieved by nedocromil. As compared with baseline control (regular dose of inhaled steroids), patients treated with nedocromil plus the 50 percent reduced dosage of inhaled corticosteroid consistently demonstrated comparable or better symptom control. Although both active drugs reduced symptoms, nedocromil proved to be more effective than cromolyn sodium for treatment of reversible obstructive airway disease in patients normally well maintained on regimens of low to moderate doses of inhaled corticosteroids.

A comparative study of the clinical efficacy of nedocromil sodium and placebo. How does cromolyn sodium compare as an active control treatment?

Nedocromil sodium and cromolyn sodium are the only two currently available nonsteroid anti-inflammatory agents for treatment of asthma. Clinical differences between the two agents remain under continuous investigation with reports differentiating the two on the basis of atopy of the patient and reversibility of bronchoconstriction. This study investigated the efficacy of nedocromil sodium (4 mg, qid) for treatment of mild-to-moderate asthma in comparison to placebo using cromolyn sodium (2 mg, qid) as an active control treatment. Patients were primarily allergic asthmatics (with at least 15% reversibility) previously maintained on a regimen of regular bronchodilator therapy. During a 2-week run-in period, the patient's slow-release theophylline therapy was removed, and the patients were randomized to treatment after deterioration of asthma control (asthma symptom summary score of 3 for 7 of the 14 days). After 8 weeks of treatment, patients were returned to as occasion requires bronchodilator therapy, as per the 2-week baseline period. The results demonstrate that patients treated with nedocromil sodium showed statistically significant improvements during the primary time period (mean weeks 3 through 8) over placebo-treated patients as evidenced by all indexes of asthma symptoms, pulmonary function measures, and decreased bronchodilator reliance (p<0.05). Patients treated with cromolyn sodium demonstrated similar improvements over placebo-treated patients. Comparisons between nedocromil sodium and cromolyn sodium showed the two agents to be comparable in this group of primarily allergic patients with reversible disease. Between-group differences were noted for 3 of the 13 variables (nighttime asthma, FEV1, and forced expiratory flow rate between 25 % and 75% of the FVC) in favor of cromolyn sodium when the data were pooled during the primary time period. The number of patients missing 1 or more days from work/school/regular activity due to asthma was significantly fewer compared with placebo, and favoring nedocromil sodium over cromolyn sodium. No differences were observed among the three treatments for adverse events. This study demonstrated that in primarily allergic patients with reversible airways disease, nedocromil sodium and cromolyn sodium are both significantly more effective than placebo for treatment of mild-to-moderate asthma.

Acute chemotic reaction to cromolyn.

Two cases of an acute chemotic reaction of the conjunctiva occurred after the topical administration of cromolyn sodium (cromoglycate disodium). The reaction was not serious for the health or life of the patient but it caused symptoms and signs that might have veen confused with the disease for which the patient was being treated.

A comparison of the efficacy and tolerability of olopatadine hydrochloride 0.1% ophthalmic solution and cromolyn sodium 2% ophthalmic solution in seasonal allergic conjunctivitis.

BACKGROUND: Treatments for allergic conjunctivitis have various mechanisms of action. Cromolyn sodium stabilizes conjunctival mast cells by preventing calcium influx across the cell membrane, whereas olopatadine hydrochloride is both an antihistamine and a mast cell stabilizer. OBJECTIVE: This study compared the efficacy and tolerability of olopatadine and cromolyn in controlling the ocular signs and symptoms of seasonal allergic conjunctivitis. METHODS: This was a multicenter, randomized, double-masked, parallel-group trial. One group instilled olopatadine 0.1% ophthalmic solution and placebo BID, and the other instilled cromolyn 2% ophthalmic solution QID, both for 6 weeks. The formulation of cromolyn used in this study is currently available only in Europe and Australia. RESULTS: The intent-to-treat efficacy and safety analyses included 185 patients, 91 in the olopatadine group and 94 in the cromolyn group. At 30 minutes after the first instillation, respective decreases of approximately 30% and approximately 20% were reported in self-rated ocular itching and redness with both treatments; by 4 hours, itching had decreased by approximately 38% in both groups. Differences between treatments were not statistically significant. At 4 hours, redness had decreased by approximately 38% and approximately 26% in the respective treatment groups. By day 42, both treatments had produced significant reductions from baseline in ocular signs and symptoms; however, the reductions in itching and redness were significantly greater with olopatadine compared with cromolyn (both variables, P < 0.05). The difference in physicians' impression of overall improvement on days 30 and 42 significantly favored olopatadine over cromolyn (both days, P < 0.05). Most patients (62.2%) had reacted positively to grass pollen at baseline. The regression slopes correlating itching and redness with pollen count were 5 times lower for olopatadine compared with cromolyn (P = 0.002 and P = 0.016, respectively), indicating that olopatadine's efficacy increased as the pollen count increased. CONCLUSIONS: Six weeks' instillation of olopatadine 0.19% ophthalmic solution BID had a significantly greater effect on the ocular signs and symptoms of allergic conjunctivitis compared with 6 weeks' instillation of cromolyn 2% ophthalmic solution QID. Both treatments were well tolerated by patients in all age groups; however, olopatadine appeared to have better local tolerability in children aged <11 years.

Multifocal neuropathy with vasculitis in hypereosinophilic syndrome. An entity or drug-induced effect?

A 56-year-old male with a 2-year history of bronchial asthma, together with pulmonary infiltration and marked eosinophilia, developed a subacute multifocal sensorimotor neuropathy. Electrodiagnostic studies demonstrated both multifocal and generalized nerve involvement. Sural nerve and muscle biopsies revealed axonal degeneration with almost complete loss of myelinated fibres, lymphomononuclear vasculitis of interstitial vasa nervorum without eosinophils, and neurogenic atrophy of muscle without angiitis. Although eosinophilia decreased drastically with corticosteroid treatment, neuropathy rapidly progressed to total disability. The patient died from pulmonary embolism 4 months after the onset of neurological signs. Autopsy disclosed vasculitis of epineurial vessels of peripheral nerves and severe axonal neuropathy, particularly of the lower limbs, without vasculitis or other inflammatory lesions in any other organ system, including the lungs. Retrospective analysis revealed that the onset of pulmonary infiltration and eosinophilia coincided with the administration of cromolyn sodium (Intal), which is known to produce PIE syndrome (pulmonary infiltration and eosinophilia), vasculitis and allergic granulomatosis, while multifocal neuropathy with vasculitis appears not to have been reported in connection with this substance.

Efficacy and safety of lodoxamide 0.1% vs cromolyn sodium 4% in patients with vernal keratoconjunctivitis.

A multicenter, double-masked, parallel-group clinical study compared the efficacy and safety of lodoxamide 0.1% ophthalmic solution and cromolyn sodium 4% ophthalmic solution in 120 patients with vernal keratoconjunctivitis. On various follow-up visits, the clinical efficacy of lodoxamide 0.1% was statistically superior to cromolyn sodium 4% in alleviating four of the primary symptoms (itching, tearing, foreign-body sensation, and discomfort) and five of the primary signs (Trantas' dots, palpebral conjunctival changes, bulbar conjunctival hyperemia, erythema/swelling of the eyelids and periorbital tissues, and epithelial disease). At no time during the study was cromolyn sodium 4% statistically superior to lodoxamide 0.1% in demonstrating improvements in clinical signs and symptoms of vernal keratoconjunctivitis. The physician's clinical judgment of patients' response to treatment showed lodoxamide 0.1% effected a greater and earlier improvement than cromolyn sodium 4%. Both drugs were safe for topical ophthalmic use when used four times daily for up to 28 days.