39 too convincing to be negated by these This evidence is : (1) net negative nitrogen studies. elegant as balances range high as 20 g. per day, largely appearing as urinary urea; in the face of zero intake these losses are approximately three times those of starvation, and can be interpreted only as net catabolic loss of protein; (2) after major injury there is a net increase in urinary creatinine and creatine both of which suggest muscle breakdown; (3) there is a visible shrinkage of skeletal muscle during severe

injury is

such loss. The harmful effects of nitrogen loss over short periods may be minor. If the loss is large and continuing, it is crippling, and is felt most keenly by the patient with respiratory impairment or disease. Clinical significance is not at issue here, but rather the question of whether or not net transport of protein breakdown products occurs from muscle after injury. As the matter now stands it appears clear that, whatever the genesis, and whatever the clinical result, severe injury is followed by net loss of protein from muscle. Peter Bent Brigham Hospital, 721 Huntington Avenue, Boston, Massachusetts 02115, U.S.A.

MURRAY F. BRENNAN DAVID TWEEDLE FRANCIS D. MOORE.

PROSTAGLANDINS AND ASTHMA

SiR,—The report by Dr Green and colleagues (Dec. 14, p. 1419) indicating an increase in the prostaglandin metabolite 15-keto-13,14-dihydro-P.G.Fjin during antigen challenge induced asthma is of great interest. Their results, coupled with reports of the greatly increased sensitivity of asthmatic patients1 to p.G.F2u might lead some to conclude that P.G.F2a is an important mediator in bronchospasm in asthma. We have investigated the effects of indomethacin in asthmatic patients and find that doses reported to suppress over 90% of endogenous prostaglandin synthesis in man2 have no effect on either antigen challenge or exercise-induced asthma. Nine atopic asthmatics were challenged by inhalation of a house-dust mite extract before a trial of hyposensitisation and then took 25 mg. indomethacin four times daily and a 100 mg. suppository at night. A week later the challenge test was repeated. The results indicate that there was no inhibition of the antigen-challenge response: Antigen Patient

dose (w/v)

1 2 3 4 5 6 7 8 9

10-s 10-0 10-6 10-0 10-3 10-= 10-6 10-0 10-5

Mean (S.E.M.)

..

fall in F.E. V.l..* After Before 28-6 6 22-2 17-1 29-4 26 66-7 25 34-6 25 30-5 (4-8)t

30 13-7 9-5 19-6 51-5 33-3 33-3 26-9 23-1 26-5 (4-3)t

Forced expiratory volume in 1 second. t p > 0 (Wilcoxon’s test).

The

same

challenge

dose of indomethacin had in six patients:

no

effect

on

exercise

Mean (S.E.M.) change inF.E. V.1. (l.): After 5 min. exercise 1 min. 10 min. exercise 5 min.

Before

Before indomethacin After indomethacin *

3-0(0-3) 3-2(03) 2-1(0-4) 2-7(04) 2-8(0-4) 2-2(0-4)* r > 0-1 (Student’s t test).

2-2(0-3) 2-1 (0’5)*

p.G.F2