Bronchial allergen challenge: dose versus concentration

This study was designed to investigate if two equivalent doses of allergen administered by different dosing regimes--two breaths and 10 breaths of each concentration--would result in the same magnitude of the early and late asthmatic response. Fifteen patients with extrinsic allergic asthma were challenged twice with either two or 10 breaths of twofold increasing allergen concentrations. The challenge was continued until a 20% decrease in FEV1 had been achieved. A non-cumulative PC20FEV1 allergen was derived, and the cumulative dose of allergen given was similarly derived. In order to assess the reproducibility of the challenge, seven patients were challenged twice with two-breath regime. The mean value of allergen PC20 obtained by the two-breath regime was 4.1 fold (95% CI: 2.3-7.1 fold) greater than those obtained by the 10-breath regime (P less than 0.05), whereas the difference was 1.4 fold (95% CI: -3.3-0.5 fold) for the cumulative dose (P greater than 0.05). A statistically significant larger magnitude of the early asthmatic response, as determined by the maximum per cent fall in FEV1, and late asthmatic response determined by the maximum per cent fall in peak expiratory flow domiciliary recorded during the following 24 hr after challenge, was observed in favour of the 10-breath regime compared to the two-breath regime (mean difference 6%, 95% CI: 0.6-11%). The reproducibility of the provocation test was acceptable (+/- 1.8 two-fold concentration difference). These results confirm the 'equivalent dose hypothesis', and demonstrates that dosage rather than concentration appears to determine the early and late asthmatic response after bronchial allergen challenge.     

Reproducibility of responsiveness to a standardized bronchial allergen provocation—Rt compared to FEV1 as measurement of response to provocation

Standardized bronchial allergen provocation was performed twice in nineteen extrinsic, well defined, stable asthmatic patients, with an interval of median 15 days (range 14–19) to study the reproducibility of the bronchial response. Smoking and medications were withheld prior to the provocation after a rigid scheme. Ten-fold increasing concentrations of allergen solution 0.9 ml were inhaled by tidal volume breathing for 5 min with intervals of 10 min. The bronchial response to inhaled allergen was determined by forced expiratory volume in the first sec (FEV₁) and by total resistance to breathing (R_t) determined by an opening interrupter method. The provocation was continued until an allergen concentration causing at least 20% decrease of the postsaline FEV₁ or a 40% increase in R_t was reached. A PC₂₀-FEV₁ and a PC₄₀-R_t was calculated by interpolation on the log-dose-response curve. The reproducibility of PC₂₀-FEV₁ allergen was high with a 95% confidence interval (CI) for a single determination being the observed value ±0.83, ten-fold concentration difference, the intraclass correlation (IC) was 0.99 and the coefficient of variation 8.46%. Concerning PC₄₀-R_t a 95% CI for a single determination was calculated being the observed value ±0.58, ten-fold concentration difference, IC was 0.99 and the coefficient of variation was 5.79%. No significant correlation was found between differences in pre-challenge FEV₁ and R_t values and the corresponding PC₂₀-FEV₁ and PC₄₀-R_t values. Least square regression between PC₂₀-FEV₁ and PC₄₀-R₁ was performed for the first and the second provocation (P < 0.05). We conclude that bronchial allergen challenge performed in stable asthmatics is highly reproducible and as such a valuable test in the diagnosis of allergic asthma when connected with anamnesis, skin-prick test and the level of specific immunoglobulin E in peripheral blood.     

The prognostic value of maximal exercise testing soon after first myocardial infarction

The prognostic value of ST-segment depression during maximalexercise test performed in the third to fourth week after acutemyocardial infarction (AMI), was studied in 126 consecutivepatients with no evidence of previous myocardial infarction,unstable angina pectoris or severe heart failure. All patientson average increased their pressure-rate product by 2.6 andno complications occurred. Within the first year of follow-up,major cardiac events occurred in 9 patients (20%), and werefatal in 6 (13%), of the 46 patients who developed ST-segmentdepression during exercise. Only 3 major cardiac events (4%)occurred in the 80 patients without exercise induced ST-segmentdepression. Depression of the ST-segment on maximal exercisewas a significant predictor of subsequent cardiac events inthese survivors of first AMI.     

Lifetime costs of cerebral palsy

This study quantified the lifetime costs of cerebral palsy (CP) in a register-based setting. It was the first study outside the US to assess the lifetime costs of CP. The lifetime costs attributable to CP were divided into three categories: health care costs, productivity costs, and social costs. The population analysed was retrieved from the Danish Cerebral Palsy Register, which covers the eastern part of the country and has registered about half of the Danish population of individuals with CP since 1950. For this study we analysed 2367 individuals with CP, who were born in 1930 to 2000 and were alive in 2000. The prevalence of CP in eastern Denmark was approximately 1.7 per 1000. Information on productivity and the use of health care was retrieved from registers. The lifetime cost of CP was about €860 000 for men and about €800 000 for women. The largest component was social care costs, particularly during childhood. A sensitivity analysis found that alterations in social care costs had a small effect, whereas lowering the discount rate from 5 to 3 per cent markedly increased total lifetime costs. Discounting decreases the value of costs in the future compared with the present. The high social care costs and productivity costs associated with CP point to a potential gain from labour market interventions that benefit individuals with CP.     

A PATIENT WITH HEREDITARY GALACTOKINASE DEFICIENCY

A case of hereditary galactokinase deficiency is reported, occurring in a newborn boy and detected through routine screening of newborns for increased blood concentration of galactose. Symptoms were equivocal and consisted only of mild feeding difficulties and a slightly insufficient weight gain. The only abnormality found on clinical examination was lens opacities which were obvious when the boy was 5 weeks old. The biochemical abnormalities found were: excretion of large amounts of galactose and ga-lactitol in the urine, galactosemia, and essentially no galactokinase activity in the red blood cells. On a galactose-free diet, introduced when the boy was 3½ weeks old, he grew and developed normally, his cataracts had improved considerably after 4 months. The boy's both parents, one brother and possibly one sister were considered carriers of the autosomal recessive gene, as the enzyme activity found in their red blood cells was roughly half of the normal value. The clinical findings in patients with the various enzyme defects leading to galactosemia are described and related to the biochemical abnormalities caused by the defects. Possible screening methods are discussed.     

Electron Microscopy of the Red Cells in Erythropoietic Porphyria

With the aid of electron microscopy two different red cell lines have beenidentified in erythropoietic porphyria. A normal red cell series has been foundin association with hemoglobin containing normoblastic nuclei and ferritinladen reticulocytes. The abnormal line presumably represents the porphyrincontaining cells. A possible explanation to account for the abnormality inheme synthesis has been proposed.

Submitted on February 24, 1964 Accepted on April 17, 1964