A comparison of the performance of two modern multidose dry powder asthma inhalers.

Little is known about the shot potency and dose consistency of many of the inhalers in common use, and until recently there has been little consensus over the best way to evaluate these parameters. Since marked effects can be achieved with the inhaled route, more information is needed about the dosing characteristics of all available inhalers. As there are now two multidose powder inhalers available in the U.K. capable of supplying 1 month or more of treatment, this study was designed to compare the delivery characteristics of these two dry powder inhalers delivering glucocorticosteroids. The method used was in vitro analysis of the emitted dose and fine particle fraction throughout the life of five of each type of device. The multidose powder inhaler delivered between 87 and 93% of the label claim dosage, whilst the reservoir device delivered 40-58%. There was no fall off of shot potency towards the end of either device's life. Fine particle fraction for the multidose and reservoir systems, was 21 and 18%, respectively, at 60 l min-1 flow, but fell to 16 and 6% at 28.3 l min-1. In conclusion, there were statistically significant differences (P < 0.0001) in the drug emission of both dose and fine particle fraction of these two powder inhalers.

Context effects on misreading and suppression at UAG codons in human cells.

The effect of the 3' codon context on the efficiency of nonsense suppression in mammalian tissue culture cells has been tested. Measurements were made following the transfection of cells with a pRSVgal reporter vector that contained the classical Escherichia coli lacZ UAG allele YA559. The position of this mutation was mapped by virtue of its fortuitous creation of a CTAG MaeI restriction enzyme site. Determination of the local DNA sequence revealed a C-->T mutation at codon 600 of the lacZ gene: CAG-->TAG. Site-directed mutagenesis was used to create a series of vectors in which the base 3' to the nonsense codon was either A, C, G, or U. Suppression of the amber-containing reporter was achieved by cotransfection with genes for human tRNA(Ser) or tRNA(Gln) UAG nonsense suppressors and by growth in the translational error-promoting aminoglycoside drug G418. Nonsense suppression was studied in the human cell lines 293 and MRC5V1 and the simian line COS-7. Overall, the rank order for the effect of changes to the base 3' to UAG was C < G = U < A. This study confirms and extends earlier findings that in mammalian cells 3' C supports efficient nonsense suppression while 3' A is unsympathetic for read-through at nonsense codons. The rules for the mammalian codon context effect on nonsense suppression are therefore demonstrably different from those in E. coli.

Adenocarcinoma of the stomach and Fanconi's anaemia.

A case of Fanconi's anaemia is described. The patient developed gastric ulcers at 14 years and died of adenocarcinoma of the stomach at the age of 21 years. The need fully to investigate gastric pathology by endoscopy and biopsy, as well as radiology, is stressed. So far as the authors are aware this is the first description of adenocarcinoma of the stomach occurring in Fanconi's anaemia, a condition known to predispose to malignancy.

Regression of left ventricular hypertrophy during treatment with antihypertensive agents.

1 Echocardiography showed 14 of 24 patients with essential hypertension to have hypertrophy of their left ventricular walls. In eight of these 14 patients the left ventricular configuration initially fulfilled the criteria for asymmetric septal hypertrophy (ASH) and six were symmetrically hypertrophied, the remaining ten being normal. 2 Following 12 weeks' treatment of hypertension with the object of reducing the supine BP to 150/90 mmHg or below, there was a reduction of wall thickness so that only two of the eight continued to show ASH. 3 The six patients with symmetrical left ventricular hypertrophy also showed a significant reduction in the thickness of the septum and the posterior wall. Those with normal echocardiograms did not change. 4 This reduction of wall thickness produced by antihypertensive therapy may represent regression of left ventricular hypertrophy.

Relationship between hypertension and angina pectoris.

1 Many factors are of importance in the relationship between angina pectoris and hypertensive heart disease. Vascular resistance modifies the oxygen supply, whereas the oxygen demand is influenced by the systolic and diastolic BPs, the diastolic filling time and wall tension, the duration of systole and transmural pressure and the sympathetic stimulation to the heart. 2 The treatment of angina pectoris in patients with hypertensive heart disease should aim to reduce myocardial ischaemia, and it is suggested that beta-adrenoceptor antagonists are most suitable, as they reduce BP, heart rate and myocardial contractility and thus oxygen demand.