1128
THE LANCET, MAY
The provision of a central intravenous-additions service: at Burnley is to be welcomed and we hope that more deta!led results of this experience will be published, including the costs. In particular we should like to see evidence that the necessity for additions at ward level has been reduced to insignificance: the paper cited l does not include such evidence and the stated figure of only 6·5 pharmacy-prepared additions per day for a 700-bedded hospital seems low by comparison with other hospitals. Members of the working-pany were of the opinion that the provision of a dispensing serVice from the hospital pharmacy is an imponant objective, but that this could not in the short term provide a satisfactory answer to the problem without increased staffing resources and extended hours of service in hospital pharmacies. The rePon therefore placed a responsibility on health authorities "to ensure that staffing resources are adequate" (6·1) to implement and maintain safe practices, but, as long as a significant amount of dispensing at ward level is necessary, the main priorities to safeguard patients should be to reduce the need for additions and to ensure that staff undertaking these at ward level are competent to carry out the procedure involved. We were, above all, seeking a practical solu. tion to the problem and did not see the provision of a 24-hour pharmacy service in hospitals as a short-term reality. : Depanm
AUSDAIR M. BRECKENRIDGE
JOHN A. BAKER
DO TRlCYCUC ANTIDEPRESSANTS WORK? SIR,-Dr Hare (May 8, p. 1018) makes the inge~ious suggestion that depressed patients complain of drowsmess because their anxiety and tension produces fatigue; he also postuiates that antidepressant drugs, acting as sedatives, may, paradoxically, produce a lessening of drowsiness because of their anxiolytic propenies. We examined our (April 24, p. 914) baseline Hamilton rating scales (H.R.S.) and side-dfects check list (both completed before patients,had staned active medication). We studied the relationship between the anxiety items on the H.R.S. (items 10 and 11) and complaints of drowsiness on the side-effects check list (a four-point scale). The results are: H.R.S. t;lnrielY score (items 10 and 11) O,I,and2 3 and 4 ~5
Check list drorcsiness score
No. 6 11 10
Mean (and S.E.M.) 1·00 (0·37) 1·00 (0·33) 0·89 (0·26)
There is obviously no association between anxiety and drow~ siness before staning treatment. We also examined the same' items at 2 weeks and could find no correlation between reduction in anxiety and complaints of drowsiness. We maintain our conclusion that, since corrected side-efTects at 2 weeks (including drowsiness) are significantly negatively correlated with clinical improvement at 6 weeks, it is highly unlikely that tricyclic antidepressants are acting as non-specific sedatives. The interpretation of the results and, in general, the relation between depression and its alleviation and' sideeffects is obviously a complex one which would repay careful study. Medical Research Council Neuropsychiatry Laboratory, . West Park Hospital, . Epsom, Surrey
ALEC COPPEN KARABI GHOSE
1. Birch, P., Gee, N., Tallett, E. R.]. hosp. Pharm. May, 1974, p. 94.
22,1976
PITUITARY FUNCTION AND INTERMITTENT CYTOTOXIC AND CORTICOSTEROID THERAPY SIR -We wish to comment upon the observations by Dr 715). It is n~w ~e1! established that accurate assessment of hypothalamic/pituItary/adrenocortical (H.P.A.) function requires the use of dynamic tests, especially the plasma-corticosteroid responses to exogenous adrenoconicotrophin (A.C.T.H.) and,. more. important from the clinical standpoint, the ability of the aXIs to respond to stress, usually during insulin-induced hypoglyaemia. 1 At the end of treatment courses in patients receiving intermittent high-dose prednisolone and cytotoxic drugs, frequent impairment of A.C.T.H. output has been observed during insulininduced hypoglyaemia but the plasma-conicosteroid responses during this test and after administration of exogenous A.C.T.H. are less commonly abnormal. 2 While acceptinglhat the observed progressive diminution in diurnal variation of plasma-conicosteroids may reflect impairment of pan or whole of the H.P.A. axis when prednisolone therapy is stopped, its statistical significance only ?ec0m~ imponant when either clinical features of adrenal IOsuf!iclency develop or the specific dynamic tests of H.P.A. function are abnormal.. In our experience we have not found satisfactory agreement between suppression of plasma-thyroid-stimulatinghormone (T.S.H.) release in response to exogenous T.s.H.-releasing hormone (T.It.H.) and suppression of A.C:T.H. release during simultaneous insulin-induced hypoglyaeJrlla performed 36 h after the last dose of prednisolone, making it impossible to predict from the T.It.H. test alone which patients may be susceptible to anterior pituitary insufficiency. In addition, even in patients with depression of A.C.T.H. output, the plasmacorticosteroid responses are frequently normal. . Our results of plasma A.C.T.H. and conicosteroid responses in standard insulin-induced hypoglyca:mia tests, plasma-T.s.H. responses 20 min after the intravenous injection of T.R.H. 200 I'g, and plasma-<:onicosteroid responses 30 min ~ter th~ intr~ venous injection of tetracosactrin 250 I'g followmg the msuhn test at the conclusion of chemotherapy courses in thrc;e patients (2, 3, 6) with myeloma and three patients (1, 4, 5) with lymphoma are summarised below. .
Nays~ith and her colleagues (April 3, p.
ENDOCRINE TEST RESULTS
Peak pluma concentratioDt during insulin test
Patient (ngll)
Conicosteroid. (nmol/l)
25 26 27 -40 .80 86
635 655 500 325 7-45 6-45
A.C.T.H.
1 2 3 4 5 6
30 min conicosteroids after tetracosactrin
20 min .T.S.H.
(mU"'))
(nmol/l» 640 765 560 405 790 . 780
15·5 3·3 3·4 7·2 2·0 7·0
Much impaired A.C.T.H. responses may be associated with normal (patients 1 and 4) or subnormal (patients 2 and 3) T.S.H. responses. Although the 30 min tetracosactrin-stimulation test assesses only adrenoconical function, the results correlate well with the plasma-conicosteroid results obtained during insulin-induced hypoglyaemia, confirming previous comparative studies in conicosteroid-treated patients] an~ patients with hypothalamic-pituitary malfunction. 4 If the msulin-induced hypoglyaemia test is contraindicated we feel that the shon tetracosactrin test provides more valuable infonna1. Lancet. 1975, ii, 537. . . . 2. \'\'ilson, K. 5., Gray, Christina, E., Cameron, E. H. D., Seth, J., Parker, A. C. ibid. 1976, i, 610. 3. Kehlet, H., Binder, C.Br. mod.]. 1973, ii, 147. . '. . '. 4. Kohlet, II., Blichert-Toft, M., Lindholm, J., Rasmussen, P. ,bId. 1976, I, 249.
THE LANCET, MAY
22,1976
1129
tion than the T .R.H. test in patients whose corticosteroid therapy has been discontinued. KENNETH S. WILSON Royal Infirmary, Edinburgh EH3 9YW Regional Hormone Laboratory, Edinburgh
J. SETH A. C. E.
PARKER
H. D. CAMERON
EFFECT OF GASTRIC INlllBITORY POLVPEPTIDE ON JEJUNAL WATER AND ELECTROLYTE TRANSPORT IN MAN SIR,-Pharmacological doses of gastric inhibitory polypeptide (G.I.P.) stimulate small-bowel secretion in the dog. 1 We have studied the effect of G.I.P. on net jejunal water and electrolyte transport in five healthy volunteers using a modified triple-lumen tube perfusion system. Net flux of water and electrolytes was measured before, during, and after G.I.P. infusion. The dose of G;I.P. used (1 fls'inin for 30 min) is in the physiological range, giving serum-G.I.p. concentrations comparable with those obtained in normal subjects after ingestion of a meaJ.l . During G.t.P. infusion; net water absorption was. significantly reduced and chloride flux was switched from absorption to secretion when compared with the pre-G.I.p. and post-G.I.P. control periods. We conclude that G.t.P. induces secretion from the small bowel and that it may playa role in the normal regu·Iation of gut secretory processes in man. Gastrointestinal Clinic, Groote Schuur Hospital; Observatory 7925, Cape, South Afric.
C. G.
A.
HELMAN
O. BARBEZAT
PARACRINE SIR,-I was wrong in my interpretation (April 3, p. 744) of the meaning that Feyrter gave to the word paracrine and I thank Professor Pearse for setting the record straight (April 24, p. 915). It is now clear to me that Feyrter used the word paracrine in the same sense that it is being used today-i.e., to designate cells whose products act on neighbouring cells. Veterans Administration Wadsworth Hospital Center, Los Angeles, California 90073, U.S.A.
MORTON I. GROSSMAN
The third patient, a 12-year-old boy admitted to hospital a few weeks after the acute onset of ulcerative colitis, was given disodium cromoglycate only (250 mg three times a day, for 10 days a month). At present, 3 months after the beginning of treatment, he shows clinical improvement (weight gain, almost normal bowel movements, no obvious blood in the slOols). The remissions we obtained seem not to be merely fortuitous, even· bearing in mind the possibility of a spontaneous improvement of the disease. We believe that disodium cromogly. cate should be continued over a long time to prevent relapse. We cannot explain the effect of intermittent treatment by assuming that the drug acts merely by preventing a type-I, IgE-mediated hypersensitivity reaction in the colonic mucosa. 3 Divisione h1edicina Pa-diatrica, Istituto "G. Gaslini", Genova-Quarto,
Italy
GIULIANA DELLA CELLA LUIGI R. GARIBALDI PAOLO DURAND
DIETARY FIBRE REDEFINED SIR,-Dr Trowell and his colleagues (May 1, p. 967) have redefined dietary fibre as the "plant polysaccharides and lignin which are resistant to hydrolysis by the digestive enzymes of man". The stated purpose of their redefinition was to facilitate retrieval of information on the diverse actions of the various polysaccharide polymers. Since a comprehensive "terminological umbrella" is of importance to the subject itself, as well as for information retrieval, the limitations imposed by the use of the words dietary and plant would seem unnecessarily to restrict the usefulness of the definition. While, as redefined, the term "plant pol ysaccharides" includes storage as well as structural polysaccharides, substances which are in no sense "dietary" are precluded as, for example, ispaghula husk· fibre; neither does the redefinition include polysaccharide derivatives such as methylcellulose or the biosynthetic polysaccharides which are now being developed. Also, the restriction imposed by the word plant denies the action of the animal aminopolysaccharides-as witness the traditional diet of the Eskimo. The following modified definition appears to avoid these limitations-"Edible fibre: polysaccharides, related polymers, and lignin, which are resistant to hydrolysis by the digestive enzymes of man." l-"airtands, Totland, Jsl. of Wight P039 OEB
EDMUND
W. GODDING
ULCERATIVE COUTIS AND DISODIUM CROMOGLYCATE . SIR,-We read with interest the article by Dr Mani and his colleagues (Feb. 28, p. 439)/We have treated three patients with ulcerative colitis with oral disodium cr~moglycate, the drug being administered alone in two of them. The first patient, a 15-year-old boy, showing evidence of chronic active colitis with very short periods of remission on steroids and sulphasalazine, was given oral disodium cromoglycate (250 mg three times a day for 5 days a month, for 10 months); the previous therapy was stopped. A few months later there was a remission, which lasted 15 months after the end of the treatment. The second patient was a 16-year-old girl, admitted to hospital for a very severe, acute-onset ulcerative colitis. After 11 months, during which no substantial remission was obtained with steroids and sulphasalazine, disodium cromoglycate was added to the previous therapy at the same dose and for the same period as in the first case. A remission was achieved after a few months; this lasted for 8 months after the drug had been discontinued. 1. Barbezat, G. 0., Grossman, M.1. Science, 1971,174,422. 2. Brown, J. C., Dryburgb, J. R., Ross, S. A., Dupre, J. Rec. Progr. lIormone Res. 1975,31,487.
COLONIC INVOLVEMENT IN SALMONELLOSIS SIR,-Dr MandaI and Dr Mani (April 24, p. 887) describe inflammation of the colon as a consistent finding in their series of patients admitted to hospital in Manchester with acute salmonellosis. They found inflammatory histological abnormalities in 18 of 20 patients so examined, and cited the observation by Boyd' of acute colitis in a necropsy study of human Salmonella typhimurium infection and of colitis in monkeys experimentally infected with the same organism. 2 We find this of great interest because in a study of salmonellosis in general practice] we observed S. typhimurium to be . nearly twice as frequently associated with the presence of blood and pus cells in the freces as was the group of "other salmonellas". Such cells were seen in 154 of 315 (49%) of S. typhimurium, and 42 of 147 (29%) of "other salmonella" infections. Moreover, cells were still present in stools examined I. Boyd, J. F. Lancer, 1969, ii, 901. 2. Rout, \\'. R., Formal, S. 8., Dammin, G. j., GianelIa;R. A. Gaslroentcro/ogy, 19H,67,59. 3. Thomas, M., Mogford, H. E.J.II)"g. Camb. 1970,68,663.