Albert S. Rohr

Immediate Hypersensitivity Reactions to Beta-Lactam Antibiotics

Allergic reactions to the beta-lactam antibiotics (penicillins, cephalosporins, carbapenems, and monobactams) are a major factor limiting their use. Immediate hypersensitivity reactions to penicillins depend on the presence of preformed allergic (IgE) antibodies to several penicillin determinants. These materials can be used in in-vivo skin testing to exclude those patients at risk for immediate or accelerated allergic reactions. The cephalosporins have not had their relevant determinants defined as related to allergic reactions. The results of in-vivo challenges of patients with IgE to penicillin suggest the incidence of reactivity of cephalosporins in patients allergic to penicillin is less than generally appreciated. The monocyclic beta-lactam antibiotic, aztreonam (a monobactam), failed to show cross-reactivity with penicillin antibodies, because immune reactivity toward the monobactam was directed against side chain rather than nuclear determinants. On the other hand, the new bicyclic carbapenem beta-lactam drugs, represented by imipenem, showed extensive in-vivo cross-reactivity with penicillins.

Compliance of patients with asthma with an experimental aerosolized medication: Implications for controlled clinical trials

A Nebulizer Chronolog, a portable device that houses a standard nebulizer canister, was used in a unique method to measure compliance with aerosolized medication. Each actuation is tabulated to within 4 minutes of the actual time of usage and can subsequently be displayed in a day-hour-minute format. Of the 19 patients studied for 12 weeks with a cromolyn-like agent, appropriate usage four times a day ranged from 4.3% to 94.8%. Underusage exceeded overusage and ranged from 5.2% to 95% of the study days. Younger subjects and male subjects were less likely to use the aerosol appropriately. Patients failed to write the truth in their diaries with overreporting of appropriate usage more than 50% of the times. Lack of compliance with aerosolized medication represents an important medical issue for the physicians caring for patients with asthma. The Nebulizer Chronolog elicits new insight into the disparity between reported and observed compliance.

The microbiology of chronic sinus disease in children with respiratory allergy

Chronic maxillary sinusitis is common in children with respiratory allergy and is associated with increased morbidity. The bacteriology of chronic sinus disease in these children has not been adequately evaluated. Between May 1987 and January 1988, 12 children (aged 3 to 9 years), all with documented respiratory allergy and chronic respiratory symptoms consistent with chronic sinusitis (greater than 30 days), were fully evaluated. History, physical examination, complete blood count, nasal smear, and Waters x-ray were done. All patients had opacification of one or both maxillary sinuses, failed to respond to multiple courses of antibiotics, and subsequently underwent maxillary sinus aspiration and irrigation. Specimens were cultured for aerobic and anaerobic organisms with standard technique, and sensitivities were obtained. Culture results revealed a single organism (Moraxella [Branhamella] catarrhalis) in five patients, one patient yielded M. catarrhalis plus Streptococcus species, three were negative, and three patients grew multiple organisms (two with multiple aerobic streptococcal species and one patient with aerobic streptococci and Peptostreptococcus). All children received appropriate culture-directed antimicrobial therapy. Sequential biweekly follow-up revealed progressive radiographic clearing and significant symptomatic improvement. M. catarrhalis is a common pathogen, whereas anaerobic organisms are unusual as a cause of chronic maxillary sinusitis in allergic children. Some children, despite negative cultures, may benefit from maxillary sinus irrigation.

Correlation between A-mode ultrasound and radiography in the diagnosis of maxillary sinusitis☆

A-mode ultrasound examination of the maxillary sinuses with the Echosine and Sinusvu 2500 units was compared with roentgenographic examination in the diagnosis of maxillary and frontal sinusitis. A-mode ultrasound was primarily useful in the detection of secretions within the sinus and not mucosal thickening. Both ultrasound devices had high specificities (92% for Echosine and 94% for Sinusvu 2500) in the diagnosis of maxillary sinusitis, but the Echosine had a greater overall sensitivity (61%) than the Sinusvu 2500 (29%). More significantly, as the opacification of the roentgenogram increased (a higher probability of secretion), the Echosine demonstrated better agreement with the x-ray film. Ultrasound appeared to be less helpful in diagnosing frontal sinusitis, but there were too few cases of frontal sinusitis for statistical analysis. The Echosine is a useful screening device because of the high specificity of a positive result. Although A-mode ultrasound provides limited value in diagnosing mucosal thickening, it is particularly useful in following the course of therapy once a positive diagnosis of sinusitis has been established without subjecting the patient to additional x-ray exposure.

Aspartame is no more likely than placebo to cause urticaria/angioedema: Results of a multicenter, randomized, double-blind, placebo-controlled, crossover study

BACKGROUND Anecdotes and single case reports have suggested that the high-intensity sweetener, aspartame, may be associated with allergic/hypersensitivity-type reactions. METHODS We conducted a multicenter, placebo-controlled clinical study to evaluate individuals who had experienced urticaria and/or angioedema allegedly associated with ingestion of an aspartame-containing product. Despite extensive recruiting efforts over 4 years, only 21 subjects could be enrolled. After admission to clinical research units, subjects were given aspartame and placebo in a randomized, double-blind, crossover fashion. Subjects received, on different days, increasing doses (50, 300, 600 mg) of aspartame and placebo at 8:00 AM, 10:00 AM, and noon. Subjects who weighed less than 40 kg received one half of these doses. Conversion products of aspartame, aspartyl-phenylalanine diketopiperazine and beta-aspartame, were also included in the aspartame arm of the study. Positive reactions were defined as urticaria (hives with wheals 4 mm or more in diameter with a collective diameter of at least 15 mm or one or more hives with a wheal of 4 mm or greater with a flare of 8 mm or greater) or as angioedema. RESULTS According to these criteria, four reactions were observed; two followed aspartame ingestion and two followed placebo ingestion (p = 1.00). The incidence of other adverse experiences was no different after aspartame versus placebo ingestion (p = 0.289). CONCLUSION These results indicate that aspartame and its conversion products are no more likely than placebo to cause urticaria and/or angioedema reactions in subjects with a history consistent with hypersensitivity to aspartame.

Pharmacodynamic evaluation of azelastine in subjects with asthma

A broad antiallergic compound called azelastine was studied pharmacodynamically in 34 subjects to correlate bronchodilator effect with blood levels of azelastine and desmethyl azelastine, its major metabolic product in man. Despite azelastine and desmethyl azelastine blood levels that were proportionate to the dosage range, the bronchodilator effect as measured by FEV1 and forced expiratory flow rate between 25% and 75% of FVC was proportionately greater with 4 mg of azelastine during the 8-hour study period than the anticipated bronchodilator response with the 8 and 16 mg doses. Azelastine, already proven effective in allergic rhinitis, has a bronchodilator effect at doses that do not produce intolerable side effects.

A comparison of imaging techniques in patients with chronic sinusitis (X-ray, MRI, A-mode ultrasound).

Thirty-five patients age 9 to 67 were evaluated for chronic sinusitis by history, physical and laboratory examination, and imaging techniques (X-ray, magnetic resonance imaging (MRI) and flexible rhinoscopy). MRI was the most predictive. To establish the diagnosis of sinusitis, it was more sensitive than plain X-ray for intrasinus disease. Findings of edema, erythema, and drainage on flexible rhinoscopy were consistent with chronic sinusitis and were confirmed by MRI and sinus X-rays in 41% of the cases. Nasal smears for polymorphonuclear cells and eosinophils were suggestive of a diagnosis of chronic sinusitis, but other laboratory tests (CBC, sedimentation rate, quantitative immunoglobulins, total IgEs) were of very limited value in the diagnosis of chronic sinusitis.