453 resulted from enhanced bioavailability of the drug, their plasma levels of labetalol 1 h after taking their first 100 mg tablet being 343 and 262 ng/ml, respectively, compared with 0-144 ng/ml in 9 other patients. In these 2 patients, the firstdose effect of labetalol was similar to that of prazosin2 but, in
swellings; in these patients the minimum effective dose was 600 mg daily (three) and 400 mg daily (one). In our opinion, the more severe the H.A.E. the shorter time the patients can remain off therapy. The figure shows the effect of continuous and intermittent
contrast, the patients remained sensitive to labetalol and needed only very small doses for satisfactory control of hyper-
tension. University of Clinical Pharmacology and Therapeutics Unit, University of Melbourne, Austin Hospital, Heidelberg, 3084 Victoria, Australia
WILLIAM J. LOUIS MICHAEL J. BRIGNELL JOHN J. MCNEIL NICHOLAS CHRISTOPHIDIS FRANK J. E. VAJDA
with danazol on serum concentrations of ClE.i. and the functional activity of C1E.!. When the treatment was stopped for 7 days the functional activity of ClE. i. fell while the concentration Of ClE.i. remained high. C4 and
3 Cattedra Patologia Medica Università, Ospedale L. Sacco, Milan, Italy
A. AGOSTONI B. MARASINI M. CICARDI G. C. MARTIGNONI
INTERMITTENT THERAPY WITH DANAZOL IN HEREDITARY ANGIŒDEMA
SERUM-GASTRIN INCREASING EFFECT OF SOMATOSTATIN INFUSION IN ACROMEGALY
SIR,—Following a report’ of its efficacy in hereditary angioedema (H.A.E.), danazol was given to ten H.A.E. patients (eight with A variant, two with B variant and Ph3 phenotype2) for 8 months. All were given 600 mg daily for the first month and attacks disappeared. Because adverse side-effects of long-term treatment are unknown, we tried to determine the minimum effective dose for each patient. As reported previously’ serumCl-esterase inhibitor (ClE.!.) levels returned to pretreatment
SiR,--Bloom et al.’ reported that in acromegalic patients the serum-gastrin always fell after intravenous (i.v.) infusion of somatostatin. Somatostatin (Ferring) was administered i.v. to nine acromegalic patients. The serum-gastrin rose in six (see figure) and fell in the other three. In all cases there was a striking decrease in the serum growth hormone and insulin concentrations, followed by the expected rebound.
Somatostatin infusion causing different patterns of serum-gastrin increase in six acromegalic patients. Three other similar acromegalics exhibited a moderate decrease in
serum-gastrin (not shown). Effects of danazol therapy Mean concentration of C1E.I.•—•, C4 •— — —&bul et;, and mean functional activity of C1E.I..-. - . -. in serum of three patients on and off danazol therapy (600 mg/day). Values expressed as percentage of normal mean.
values some days after danazol was stopped. Danazol was therefore given intermittently (600 mg daily for 7 days every other week). At every course the dosage was tapered if there was no attack. Six patients have been treated successfully, one on 600 mg per day, three on 400 mg per day, and two on 300 mg per day. The other four patients could not remain off the drug for longer than 5 days because of the high frequency of H.A.E. 1 2
Gelfand, J. A., Sherins, R. J., Alling, D. W., Frank, M. M. New Engl. J. Med. 1976, 295, 1444 Gadek, J. E., Hosea, S. W., Gelfand, J. A., Frank, M. M. Clin. Res. 1977, 25, 357A.
Serum-gastrin was assayed by a radioimmunosorbent technique.2 The gastrin antisera (no. 2604) were kindly donated by Dr J. Rehfeld, Copenhagen, and had been characterised with respect to cross-reactivity against the different components of gastrin and other gastrointestinal hormones.3 Human synthetic gastrin i (I.C.I.) was used for the preparation of 125I-gastrin and also as a standard in the assay.Serum-gastrin concentrations are expressed as picomole equivalents of synthetic human gastrin !/1. A methodological difference is that Bloom et al.1 infused mg/i.v. over a period of 75 min whereas we gave a single intravenous injection of 200 µg followed by the continuous infusion of 200 µg in 100 ml saline over a 60 min period. Perhaps our dose was too low to suppress the serum-gasBloom, S. R., Mortimer, C. H., Thorner, M. O., Besser, G. M., Hall, R., Gomez-Pan, A., Roy, V. M., Russel, R. C. G., Coy, D. H., Kastin, A J, Schally, A. V. Lancet, 1974, ii, 1106. 2. Lundquist, G., Wide, L. Clinica Chim. Acta, 1977, 79, 357. 3. Rehfeld, J. F., Stadie, F., Rubin, B. Scand. J. clin. Lab. Invest. 1972, 30, 1.