Integrated plasma cortisol concentration in children with asthma receiving long-term inhaled corticosteroids.

We assessed the effect of long-term therapy with inhaled beclomethasone dipropionate (BDP) on the pituitary-adrenal axis, by measuring the integrated concentration (IC) of plasma cortisol in eight children with asthma (age, 6-16 years) who regularly used inhaled BDP in doses ranging from 8 to 26.5 micrograms/kg (200-450 micrograms/day) for 6 months to 4 years. The control group included six children (age, 6-16 years) who had the IC of plasma cortisol measured as part of an endocrinological evaluation and were found to be healthy. Cortisol concentration was measured in blood samples collected continuously over a 24-hr period. Mean IC of plasma cortisol in the study group was significantly lower than in the healthy controls (mean +/- SD, 4.9 +/- 3.3 vs 9.1 +/- 1.9 micrograms/mL; P less than 0.02). Cortisol response to 0.25 mg ACTH (iv) was abnormal in one of the eight BDP-treated patients. No correlation was found between IC of plasma cortisol and the BDP dose, severity of asthma, height percentile, or the Tanner stage. We conclude that long-term therapy, even with relatively conventional doses of inhaled BDP may cause reduction in the normal physiological secretion of cortisol. The clinical relevance of low IC of plasma cortisol is not clear, but it may reflect partial suppression of the pituitary-adrenal axis.     

Bipolar affective disorder. II. EEG, neuropsychological, and clinical correlates of CT abnormality

Since the clinical significance of CT abnormalities found in bipolar patients remains obscure, we studied 26 DSM-III bipolar patients who had specific CT abnormalities (third ventricle enlargement, and hyperdensity of the caudate, thalamus, anterior frontal white matter, and right temporal lobe) on numerous parameters such as EEG, the Halstead-Reitan Neuropsychological Battery, premorbid personality adjustment, family history of affective disorder, positive and negative symptoms, employment history, and response to lithium carbonate treatment. None of these measures could differentiate between the CT abnormal and CT normal subgroups. The implications of these findings are discussed.     

Kathon® CG reactivity in 1396 consecutively patch tested patients in the Copenhagen area

In 1396 consecutively patch tested patients 18 (1.3%) reacted to Kathon CG. Relevance was established in 4 of the 18 patients. The frequency of positive reactions to Kathon CG in eczema patients seems to have been stable in Denmark during the period 1983 to 1988.     

Short utterance recognition using a network with minimum training

A feedforward network is used to recognize short, digitized, isolated utterances. A high, multispeaker recognition rate is achieved with a small vocabulary with a single training utterance. This approach makes use of the pattern recognition property of the network architecture to classify different temporal patterns in the multidimensional feature space. The network recognizes the utterances without the need of segmentation, phoneme identification, or time alignment. We train the network with four words spoken by one single speaker. The network is then able to recognize 20 tokens spoken by 5 other speakers. We repeat the above training and testing procedure using a different speaker's utterances for training each time. The overall accuracy is 97.5%. We compare this approach to the traditional dynamic programming (DP) approach, and find that DP with slope constraints of 0 and 1 achieve 98.5% and 85% accuracies respectively. Finally we validate out statistics by training and testing the network of a four-word subset of the Texas Instruments (Tl) isolated word database. The accuracy with this vocabulary exceeds 96%. By doubling the size of the training set, the accuracy is raised to 98%. Using a suitable threshold, we are able to raise the accuracy of one network from 87% to 98.5%. Thresholding applied to all networks would then raise the overall accuracy to well over 99%.

This technique is especially promising because of the low overhead and computational requirements, which make it suitable for a low cost, portable, command recognition type of application.     

Comparison of the EUCAST-AFST broth dilution method with the CLSI reference broth dilution method (M38-A) for susceptibility testing of posaconazole and voriconazole against Aspergillus spp.

The susceptibilities of 40 clinical isolates of Aspergillus spp. (Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Aspergillus terreus) were determined for posaconazole and voriconazole by the CLSI M38-A and EUCAST-AFST broth dilution methods. Where a discrepancy was observed between the methods, the EUCAST method tended to give higher MIC values. Overall, the level of agreement was 92.5% and the intra-class correlation coefficient was > 0.90.     

Evaluation of hypothesis testing for comparing two populations using NONMEM analysis

In a simulation study of inference on population pharmacokinetic parameters, two methods of performing tests of hypotheses comparing two populations using NONMEM were evaluated. These two methods are the test based upon 95% confidence intervals and the likelihood ratio test. Data were simulated according to a monoexponential model and, in that context, power curves for each test were generated for (i)the ratio of mean clearance and (ii)the ratio of the population standard deviations of clearance. To generate the power curves, a range of these parameters was employed; other pharmacokinetic parameters were selected to reflect the variability typically present in a Phase II clinical trial. For tests comparing the means, the confidence interval tests had approximately the same power as the likelihood ratio tests and were consistently more faithful to the nominal level of significance. For comparison of the standard deviations, and when the volume of information available was relatively small, however, the likelihood ratio test was more able to detect differences between the two groups. These results were then compared to results on parameter estimation in order to gain insight into the question of power. As an example, the nonnormality of estimates of the ratio of standard deviations plays an important role in explaining the low power for the confidence interval tests. We conclude that, except for the situation of modeling standard deviations with only sparse information, NONMEM produces tests of significance that are effective at detecting clinically significant differences between two populations.Partial support from the Upjohn Company, NIH-BRSG SO RR 07066, and the Burroughs Wellcome Foundation.     

Patch testing with a mixture of 2 phenol-formaldehyde resins

1310 patients were routinely patch tested with a paratertiary-butylphenol-formaldehyde resin (PTBP-F-R), a resol resin based on phenol and formaldehyde (P-F-R-2), and a mixture of these 2 resins. Approximately 2.5 times more patients with contact allergy to phenol-formaldehyde resins were diagnosed when routinely patch tested with P-F-R-2 in addition to PTBP-F-R. Although patch testing with a mixture of both resins was not as good as patch testing with the 2 resins separately, it was better than testing only with PTBP-F-R, since 1.6 times more patients with contact allergy to phenol-formaldehyde resins were still diagnosed. P-F-R-2 is therefore recommended for routine patch testing, preferably as a separate patch test but otherwise as a mixture with PTBP-F-R.     

KCNJ2 mutations in arrhythmia patients referred for LQT testing: A mutation T305A with novel effect on rectification properties

BACKGROUND: Loss-of-function mutations in the KCNJ2 cause approximately 50% of Andersen-Tawil Syndrome (ATS) characterized by a classic triad of periodic paralysis, ventricular arrhythmia, and dysmorphic features. Do KCNJ2 mutations occur in patients lacking this triad and lacking a family history of ATS? OBJECTIVES: The purpose of this study was to identify and characterize mutations in the KCNJ2-encoded inward rectifier potassium channel Kir2.1 from patients referred for genetic arrhythmia testing. METHODS: Mutational analysis of KCNJ2 was performed for 541 unrelated patients. The mutations were made in wild type (WT) and expressed in COS-1 cells and voltage clamped for ion currents. RESULTS: Three novel missense mutations (R67Q, R85W, and T305A) and one known mutation (T75M) were identified in 4/249 (1.6%) patients genotype-negative for other known arrhythmia genes with overall incidence 4/541 (0.74%). They had prominent U-waves, marked ventricular ectopy, and polymorphic ventricular tachycardia but no facial/skeletal abnormalities. Periodic paralysis was present in only one case. Outward current was decreased to less than 5% of WT for all mutants expressed alone. Co-expression with WT (simulating heterozygosity) caused a marked dominant negative effect for T75M and R82W, no dominant negative effect for R67Q, and a novel selective enhancement of inward rectification for T305A. CONCLUSIONS: KCNJ2 loss of function mutations were found in approximately 1% of patients referred for genetic arrhythmia testing that lacked criteria for ATS. Characterization of three new mutations identified a novel dominant negative effect selectively reducing outward current for T305A. These results extend the range of clinical phenotype and molecular phenotype associated with KCNJ2 mutations.     

单宁酸处理带瓣牛颈静脉的生物学评价

目的从生物学角度评价单宁酸处理的带瓣牛颈静脉是否符合国家医用材料的要求。方法带瓣牛颈静脉经单宁酸处理后按国家医用材料的要求进行浸提液的制备、细胞毒性试验、过敏试验、皮内刺激试验、原发性皮肤刺激试验、溶血试验、急性全身毒性试验及热原试验等生物学评价试验。试验方法均参照《医用有机硅材料生物学评价试验方法》GB／T16175-1996。结果培养的L-929小鼠成纤维细胞经含浸提液的培养基培养后形态良好，增值旺盛，材料细胞毒性评级为0～1。无皮肤刺激反应和过敏反应，皮内刺激试验PⅡ（原发性刺激指数）为0．4，和阴性对照组差异无统计学意义。全身毒性实验受试动物未出现毒性症状。溶血试验溶血率0．7％，符合国家标准（〈5％）。热原试验经中国药品生物制品检定所检定，单宁酸处理后带瓣牛颈静脉无热原（样品批号：060802017）。结论单宁酸处理的带瓣牛颈静脉符合国家医用材料的要求，可以植入人体。