Diabetic Retinopathy-Scott et al. JOUM" haziness of the media in a large proportion of diabetics made it difficult to visualize the capillaries in this study. Although, in Fig. 6 B, an arterial injection of fluorescein has shown up zones of capillary closure alongside arteries and scattered small areas of capillary closure (Ashton, 1953), we have been able to discern this phenomenon in only three patients after intravenous Dollery, C. T., Hodge, J. V., and Engel, M. (1962). Brit. med. 7., 2, 1210Brit. med. 7., 2, . (1963. Med. biol. Ill., 13, 4. Friedenwald, J. S. (1950). Amer. 7. Ophthal., 33, 1187. Gartner, S. (1950. Ibid., 33, 727. Goodman, L. S., and Gilman, A. (1955 , 1964, 1, 814-817 This paper describes a study of a simple physical sign of diffuse airway obstruction undertaken to see how accurate it is in comparison with more refined methods. Diffuse airway obstruction is a feature of asthma and of the chronic nonspecific disease which in Great Britain is commonly labelled as chronic bronchitis and emphysema. Clinical examination as usually practised is not a very good method of detecting or

1 The plasma concentrations and urinary excretion of nedocromil sodium have been determined following single dose administration in six healthy volunteers dosed orally (1 mg kg-1) and intravenously (0.2 ,ug kg-1 for 30 min). Similar parameters were measured in six volunteers and twelve asthmatic patients dosed by inhalation (4 mg). Multiple dose kinetic measurements were also made. 2 The intravenous data demonstrated that nedocromil sodium is a high clearance drug (10.2 ± 1.3 ml min-' kg-'). The data were fitted by a two compartment model with very rapid elimination from the central compartment (klo = 0.088 ± 0.021 min-1; ,B = 0.013 + 0.002 min-'). 81% of the dose was excreted in the urine.3 Oral absorption was low (2-3% of the dose) and contributed negligibly to the plasma profile after inhalation. 4 After inhalation of single doses of 4 mg in volunteers and patients plasma concentration rose rapidly, plateaued and then fell monoexponentially with a half-life of approximately 2 h. The data fitted a 'ffip-flop' model with two absorption components. The extent of absorption was up to 6% of the dose with less in patients. 5 After multiple dosing with 4 mg four times daily for 7 days in volunteers negligible accumulation was observed. The pattern was similar in patients treated with 4 mg four times daily after 1, 6 and 12 months.

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ABSTRACr Nedocromil sodium (FPL 59002) is a pyranoquinoline dicarboxylic acid that has been developed for the management of bronchial asthma. We report the results of a double blind group comparative trial in which the disodium salt of nedocromil delivered by pressurised aerosol and a placebo were compared in the management of patients with a diagnosis of bronchial asthma who entered the double blind period on a minimum dose of beclomethasone dipropionate. In almost all the assessments of clinical activity nedocromil sodium was shown to be more effective than placebo. These include improvements in diary card symptom scores, reduction in concomitant use of a bronchodilator aerosol, and patients' and investigators' assessments of efficacy. Unwanted effects were few and mild. No patients were withdrawn from the trial.Nedocromil (FPL 59002) is a pyranoquinoline dicarboxylic acid (chemical name 9-ethyl-6, 9-dihydro-4,6-dioxo-10-propyl-4H-pyrano (3,2-g) quinoline-2,8-dicarboxylic acid) and its disodium salt (FPL 59002KP) was identified from a range of pharmacological and immunological tests as a compound worthy of clinical evaluation in asthmatic patients. In antigen challenge studies nedocromil sodium was shown to protect against the immediate reaction, and the results suggested that the compound may be useful in the treatment of bronchial asthma.We Nine patients were found to have minimal symptoms even when beclomethasone dipropionate was discontinued altogether. These patients were then managed with a 12 agonist only and did not take further part in the study. One group received nedocromil sodium at a dose of 4 mg (two inhalations of 2 mg from a pressurised aerosol) four times daily.The other group received two inhalations four times daily from an identical placebo pressurised aerosol containing the same propellants and surfactant but without the active drug. Both treatments were continued for 28 days. Before starting on the trial aerosols each patient completed a diary card for two weeks to establish baseline values. They rated symptoms of night time and daytime asthma, morning chest tightness, and cough on a 0-4 scale related to each symptom-for example, night asthma would be rated from 0 (undisturbed sleep) to 4 (being awake all night). Patients were supplied with a mini Wright peak flow meter and they recorded the best of three readings morning and evening on the diary card. They also recorded all medication taken, including the test medication.At each clinic visit the severity of the patient's 809 on 12 May 2018 by guest. Protected by copyright.

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