SUPPLIES OF FOLIC ACID FOR INJECTION

1445 In such

a

manner

immunological surveillance

may be

population

depressed. Hadassah University Hospital, Jerusalem, Israel.

D. NELKEN.

FEEDBACK CONTROL OF CELLULAR PRODUCTION

SiR,-Autostimulatory control of cellular production has attracted attention in recent months.1-7 Dr Riley’s letter7 mentions possible ambiguities in our formulation of an autostimulatory model.6 We will attempt to clarify our meaning. The kinetics of cell population number involves a balance of cellular production and cellular loss, either, both, or neither of which may be subject to active control by transmitted signals. For autonomous control (autoregulation) the production term and the loss term may each be considered a function of cell

number, N. Then, don

f1(N) — f.eN) steady-state is that f1CN) < f.CN) for small N. The usual assumptions made in particularising this general model are that fl(N) is a decreasing function of N while f2(N) is an increasing function of N. These assumptions have been used by Riley 8,9 and ourselves,lO among many others. The purpose of the autostimulatory model,6 whose biological realism we need not defend, was to illustrate that these usual assumptions are logically unnecessary. In particular, f1CN) can be an increasing function of N provided that f.eN) is also increasing with N and dominates for large N. Now, Riley has argued7 that the form of fl(N) which we chose to illustrate this point, viz.

fl(N) _ .N with x < 1, x > 0, implies the existence of negative feedback coexisting with autostimulation. This is, in fact, a valid interpretation of the equation, but it is by no means the only one. For example, depletion of stem cells with high levels of stimulation would constrain population growth in the same way, but without any element of negative feedback being involved. Dr Riley’s criticism is warranted in that the model admits of several different interpretations. Our point is perhaps better made by the more general argument. We cannot agree, however, that, with reference to the regulation of cellular proliferation, " ... the same principle, that of or indirect, must underlie negative feedback, whether direct it ",7 unless the meaning of " regulation " is more closely

specified. Negative feedback control was emphasised by Wiener as providing a deterministic mechanism for certain " goalseeking " processes in biology, especially neurobiology. Phenomena such as the recovery of cell population number following a transient perturbation are of a simpler character. Many natural processes (e.g., fluid flow) are such that transient disturbances have only transient effects. No element of " feedback control " need be involved in this property. Of course, where " regulation " means something more 1. 2. 3. 4. 5. 6. 7. 8. 9.

or the mechanism of restoration of the cell number is known to involve signal transmission, feedback control may well be indicated. Even here, the feedback could be positive rather than negative, provided the system is stabilised in some other way. Each case must therefore be analysed on its merits. The importance of (negative) feedback control in biology is not in question. The existence of stable dynamic systems in which it plays no part should not, however, be overlooked.

than this,

Robinson, W. A., Mangalik, A. Lancet, 1972, ii, 742. Wheldon, T. E., Kirk, J. ibid. p. 924. Barrett, A. J. ibid. Kurnik, J. E. ibid. Golde, D. ibid. p. 1397. Wheldon, T. E., Kirk, J. ibid. 1973, i, 838. Riley, P. A. ibid. p. 1184. Riley, P. A. Nature, 1969, 223, 1382. Riley, P. A. in Cell Differentiation (edited by R. Harris, P. Allin, and D. Viza); p. 288. Copenhagen, 1972. 10. Wheldon, T. E., Kirk, J., Gray, W. M. J. theor. Biol. 1973, 38, 627. 11. Wiener, N. Cybernetics. New York, 1948.

Department of Clinical Physics and Bio-Engineering, Western Regional Hospital Board, 11 West Graham Street, Glasgow G4 9LF.

T. E. WHELDON J. KIRK.

SUPPLIES OF FOLIC ACID FOR

INJECTION years ago you were kind enough to draw the fact that it was proposed to withdraw supplies ofAvertin ’ (bromethol) from the market and, following publication, it was found possible to obtain supplies. May I now draw attention to the difficulty we are experiencing in obtaining supplies of folic acid for injection ? Originally, supplies were produced by Lederle Laboratories, and when this firm stopped production supplies were obtained from Halewood Chemicals Ltd. We have now been advised that this firm can no longer supply parenteral folic acid and are unable to suggest an alternative source of supply. Perhaps an alternative supplier might be found if it was known that many clinicians still find a use for this preparation.

SIR,-Some

attention

to

Vale of Leven Hospital,

Alexandria, Dunbartonshire G83 OUA.

A. D. THURSZ.

THROMBOTIC THROMBOCYTOPENIC PURPURA AND GYNÆCOLOGICAL MANIFESTATIONS SIR,-Dr Mitch and his colleagues (April 21, p. 849) point out that vaginal bleeding may be a primary manifestation of thrombotic thrombocytopenic purpura (T.T.P.).

Surgical gynaecological procedures were performed on of these patients before the correct diagnosis of T.T.P.

two was

established.

septic abortion-somewhat commoner than T.T.P.-may masquerade as a T.T.p.-like picture.1 A case recently reported emphasises the importance of distinguishing septic abortion with disseminated intravascular coagulation from T.T.P. because of therapeutic implications. Septic abortion with disseminated intravascular coagulation (D.I.C.) can produce vaginal bleeding, Contrariwise,

thrombocytopenia, central-nervous-system haemorrhage, renal failure, and hsemolytic ansemia. Hence, it can simulate the picture of T.T.P. Since both entities may produce D.i.c., both heparin and dialytic therapy may be needed. However, if septic abortion is the cause of the D.I.C., then control of infection with antibiotics of broad spectrum and adequate dosage intravenously, as well as removal of the products of conception, are necessary. These products should be removed as soon as possible, for they provide a nidus for perpetuation of infection and release of thromboplastic material. Abington Memorial Hospital, Abington, Pennsylvania 19001, U.S.A. 1.

MELVIN YUDIS.

Yudis, M., Reid, J., Burd, R., Millerick, J. Am. J. Obstet. Gynec. 1971, 111, 350.