DEXTRAN OR HEPARIN?

899 PROLACTIN SECRETION IN XYY MALES

50)

report in-

creased plasma-prolactin levels in three 47, XYY

SIR,-Dr Price and colleagues (July 1,

men at a

p.

security hospital. In a similar French institution, we did a T.R.H. test on six dangerous, mentally ill patients of 47, XYY chromosome constitution.’ These patients, aged 19-33 years and 176-197 cm in height, had not been receiving neuroleptic treatment for 2 months. Four had normal basic prolactin levels (7-5-10 ng/ml) and two a raised level of plasma-protein by radioimmunoassay (’Prolactin RIA’, C.I.S.). After injection of 200 g of T.R.H., the prolactin response was positive in five cases and negative in one.’ Basal plasma-prolactin concentrations (ng/ml) were: 55.0, 475, 7.5, 70, 90, and 10-0. Thus in this small series of patients, no definite relationship could be established between prolactin secretion and 47, XYY constitution. maximum

Service de Sûreté, Centre Hospitalier Spécialisé, 33410 Cadilac-sur-Garonne, France

M. BENEZECH

Laboratoire de Cytogénétique, Centre de Transfusion Sanguine, 73011 Chambéry

B. NOËL

DEXTRAN OR HEPARIN?

of Mr Powley (July 29, p. 261) and Mr Davies (Sept. 30, p. 732) prompt me to respond to their criticism of low-dose heparin prophylaxis. I agree that to deny adult surgical patients some form of prophylaxis is irresponsible and that dextran 70 is much less widely used than subcutaneous heparin for prophylaxis. However, Davies’ statement that "the efficacy of 1 litre of dextran given intravenously after induction of anaesthesia was established in a large multicentre double-blind controlled clinical trial" is not accurate; the trial was not double-blind nor were its results statistically significant. A symposium sponsored by the International Committee on Thrombosis and Hasmostasis, held in Leuven on July 19, discussed the design of several clinical trials. The Cardiff trial was presented in detail by Davies. It became evident that the trial was not double-blind, since the anoesthetist could easily recognise the difference between the two solutions simply by inverting the bottle, and therefore easily choose to give or not to give dextran 70; this resulted in a substantial number of patients who did not receive a dextran infusion. This trial also failed to provide information regarding the comparability of the groups with respect to factors known to influence the occurrence of the thromboembolic complications. Prof. M. Vessey (Oxford) also pointed out that the difference in the frequency of fatal pulmonary embolism in the two groups (i.e., 7 patients in the saline group and 1 in the dextran group) is not statistically significant when a two-tail analysis is used. The details of these discussions will be published. During the past 4 years, thirty-one trials have assessed the value of low-dose heparin prophylaxis in patients undergoing a variety of surgical operations. This experience, based on several thousand patients, is different from the misleading information presented in Davies’ table outlining the advantages and disadvantages of dextran and heparin. These trials show

SIR,--The

comments

the full doses of heparin needed to treat patients with thromboembolic disease. (e) No evidence has ever been presented that thrombi formed in vivo in the presence of dextran are more easily lysed by the patient’s own fibrinolytic system. (f) Before the cost of these two methods of prevention can be compared, the efficacy of dextran prophylaxis in preventing deaths due to fatal pulmonary embolism must be demonstrated. It also remains to be determined whether a single dextran infusion or three or more infusions will be required to produce a protective effect. to receive

Powley claims that surgeons in busy peripheral hospitals are offering routine heparin prophylaxis. Data on heparin sales point to the contrary. In 1974, only three firms, compared with seven in 1978, were marketing heparin specifically prepared for prophylactic use. Furthermore, Department of Health data on heparin usage in England, Wales, and Northern Ireland for 1975/76, 1976/77, and 1977/78 indicate that heparin usage has increased by approximately 15% per year during this period. Certainly Powley’s solution is simple and does not require any nursing supervision. But, however attractive and appealing a device may be, it remains useless unless its efficacy, in preventing deaths due to fatal pulmonary embolism, has been not

demonstrated. I hope that these misleading letters will not hinder the wider adoption of low-dose heparin prophylaxis.

even

Thrombosis Research Unit,

King’s College Hospital Medical School, London SE5 8RX

V. V. KAKKAR

SIR,-Mr Davies (Sept. 30, p. 732) states "It is widely held that to deny adult surgical patients some form of prophylaxis is irresponsible". Although he does not specifically declare himself for this policy, his remarks will add support to the philosophy of such treatment. May I make a plea against this type of blanket principle in treatment, which, I think, will bring the use of prophylactic heparin or dextran into disrepute. Despite the improved diagnosis of both deep-vein thrombosis and pulmonary embolism, I think few surgeons would deny that fatal pulmonary embolism now is much less common on well-run units that it was a quarter of a century ago. This must surely be due to a much better control of infection by improved surgical technique and antibiotics and also to the disappearance of the old butcher type of surgeon who tore at tissues and left hasmatomas, often infected. Some of the trials for prophylactic heparin have been on very selective groups of patients such as the elderly who have undergone trauma, and it is not logical to translate experience in limited groups to all surgery. We should be seeking, not to encourage indiscriminate use of prophylactic anticoagulation, but to identify patients in whom it is less dangerous and to find those in whom it increases the postoperative morbity. I think we shall discover that infection and tissue damage, whether by the surgeon or trauma, are the most important factors in producing unwanted intravascular coagulation and its

sequelar. General

Hospital, Birmingham B4 6NH

GEORGE T. WATTS

that:

(a) Low-dose heparin does not require monitoring. (b) The frequency of bleeding in general surgical patients receiving low doses of subcutaneous heparin is 7.7 compared with the 5.6 in the control group and not as great as 27*? as suggested by Davies. (c) Anti-thrombm-III depletion has never been observed in patients on

low-dose

s.c.

heparin.

(d) The only contraindication to low-dose heparin prophylaxis is a history of haemorrhagic disorders or bleeding diathesis; the other contraindications listed in the table are applicable only to patients who are 1. Benezech, M., Croizet, M.,

Belabas, M., Mathieu, C., Mathieu, P., Noël, B., Ferret-Bouin, P. Ann. Endocr., 1978, 39, 89.

SIR,-In his letter comparing dextran with heparin, Mr Davies does not stress sufficiently the risk of severe anaphylactoid reaction to dextran. We have seen a fatal reaction to this agent. A healthy 41-year-old ex-nurse with a history of deepvenous thrombosis but no allergies was admitted for sterilisation. Before anaesthesia was induced a prophylactic infusion of dextran 70 was started. After approximately 50 ml had been given over 2 min the patient collapsed, became cyanosed and pulseless, and had a convulsion. The infusion was stopped and the seizure controlled with intravenous diazepam. Despite

900

vigorous treatment with cardiac massage, intermittent positive-pressure ventilation, intravenous hydrocortisone, and adrenaline, the patient could not be resuscitated. Necropsy findings were compatible with a severe anaphylactoid reaction. Dextran hypersensitivity reactions, ranging from mild urticaria to fatal anaphylaxis, have been reported previously, 1-6 and the estimated incidence is one reaction per 22 852 bottles.3 Our experience highlights the risk involved in using dextran even in a patient with no history of allergy. It is necessary, therefore, to consider carefully the value of dextran compared with other methods of preventing postoperative thrombosis. Department of Obstetrics and Gynæcology, University Hospital of South Manchester, Manchester M20 8LR

P. DONALD WILSON ALAN D. G. BROWN

ANTIFERTILITY EFFECT IN MICE OF MEDICINAL PLANT OF FAMILY ACANTHACEÆ

VASCULAR PERMEABILITY FACTOR AND NEPHROTIC SYNDROME

SIR The mechanisms which cause the abnormal permeaof the glomeruli in steroid-responsive nephrotic syndrome are not understood. Sensitisation of circulating lymphocytes to fetal kidney antigens and their cytotoxicity for renal tubular epithelial cells have been described, suggesting a role for cell-mediated immunity.I.2 However, lymphocytes cannot be identified histologically in the kidney during relapse, though T cells might produce lymphokines at a distal site that are responsible for the proteinuria. Lagrue and his colleagues3,4 reported increased in-vitro production of a factor which enhances guineapig skin capillary permeability by peripheralblood lymphocytes from patients with the nephrotic syndrome, including those with minimal histological changes. Injection of supernatants from stimulated cell culture containing such a

bility

factor into the renal artery of a rat caused immediate proteinuria. Couser et al. studied the effect on capillary and glo-

SIR,-We have examined the antifertility effect in mice of a

commonly

used

plant

in

Bangladesh belonging to the family

Acanthaceae, genus Andrographis Wall. The plant is about 2

VASCULAR PERMEABILITY FACTORS FROM LYMPHOCYTES IN NEPHROTIC SYNDROME

ft (60 cm) high having 2-3 in (5-7.5 cm) long leaves. It gives small red flowers, usually at the end of rainy season and continues to do so until the beginning of winter, ending with small fruits. This plant is widely used in India and Bangladesh for

snakebite, malaria, dysentery, diarrhoea, hepatic dysfunction, and in the prevention of fertility in man. All parts of this plant are

used and no unpleasant effects have been reported.

Young white mice, Swiss strain, aged 6 weeks or more and weighing approximately 23 g, from the animal colony of the Cholera Research Laboratory, Dacca, were used. Four male and eight female mice were caged separately before puberty. Each group of male and female mice received normal mouse chow supplemented with the powdered material of sun-dried stem of the plant in the proportion of 40 mg per mouse per day for 14 days. The control group (8 females and 4 males in separate cages) received normal mouse chow alone. All the groups received water ad libitum. After 14 days the males and females of the control group were kept in one cage and the males and females under experiment were kept in another cage for mating. The diet supplemented with the powdered plant which they were receiving before mating was continued for a further period of 3 weeks to the experimental group. After this period the males of each group were separated and the females were individually caged. Both males and females were put on normal mouse chow after separation. None of the females of the group that received normal chow supplemented with the powdered stem showed evidence of pregnancy after the first mating. However, all 8 females of the control group became pregnant and gave birth to offspring of usual litter size. The mating was repeated five times. On every occasion the experimental mouse fed only once with the powdered stem remained sterile whereas those of the control group became pregnant and gave birth to normal offspring. The experiment is continuing. No untoward effect was observed in any mouse of the group fed with the experimental diet. Further experiments are being conducted to find out the active ingredient of the plant and its mechanism of action as well as pharmacological, toxicological, and clinical properties on other laboratory animals with special reference to its con-

mouse

traceptive activity. Medical Research Council, Institute of Public Health, Mohakhali, Dacca 12, Bangladesh

Bangladesh

Drug Testing Laboratory, Institute of Public Health, Dacca

M. SHAMSUZZOHA M. SHAMSUR RAHMAN M. MOHIUDDIN AHMED A. K. M. AMINUL ISLAM

1. Bailey, G., and others J. Am. med. Ass. 1967, 200, 889. 2. Brisman, R., Park, L., Haller, J. A., Jr. ibid. 1968, 204, 824. 3. Fanous, L. H., Gray, A., Felmingham, J. Br. med. J. 1977, ii, 1189. 4. Fothergill, R., Heaney, G. A. ibid. 1976, ii, 1502. 5. Michelson, E. New Engl. J. Med. 1968, 278, 552. 6. Ring, J., Messmer, K. Lancet, 1977, i, 466.

merular permeability of factors released by the T cells of a patient with Hodgkin’s disease and minimal-change nephrotic syndrome and observed no difference in this system between the patients and controls, or patients with the nephrotic syndrome due to membranous nephropathy. We have studied the effect on skin capillary permeability of factors released by the lymphocytes of six children with steroid-responsive nephrotic syndrome during relapse and of six healthy controls. The proportion of T cells, enumerated by the E-rosette test, were the same in the patients and controls (patients 37%±9% S.D.; controls 63%±9%). Heparinised blood was passed through a glass-wool column to remove adherent cells, and the eluate was diluted with a 3% gelatin solution and allowed to sediment. The washed lymphocyte-rich supernatant was cultured at a concentration of 106 cells/ml with and without concanavalin A (5 µg/ml) for 24 h in serum-free medium. The cell-free supernatants were assessed for vascular permeability factor3 by injection of 0.1 ml intradermally into the freshly shaven abdominal skin of guineapigs immediately followed by intravenous injection, 0.5 ml/100 g body weight, of a 1°/ solution of Evans’ blue and measurement of the area of blueing. Male Hartley strain guineapigs weighing 350±50 g were used in all experiments and supernatants were tested in two different animals. A vascular permeability factor was demonstrable in the supernatants of both stimulated and unstimulated cell cultures, but we failed to demonstrate a significant difference between the patient and control groups (table), and thus cannot confirm Lagrue’s results. Institute of Child

Health, University of London, London WC1N 1EH

R. S. TROMPETER T. M. BARRATT L. LAYWARD

1. Mallick, N. P., Williams, R. J., McFarlane, H., Orr, W. M., Taylor, G., Williams, G. Lancet, 1972, i, 507. 2. Eyres, K., Mallick, N. P., Taylor, G. ibid. 1976, i, 1158. 3. Lagrue, G., Xheneumont, S., Branellec, A., Hirbec, G., Weil, B. Biomedi-

cine, 1975, 23, 57. Lagrue, G., Xheneumont, S., Branellec, A., Weil, B. Lancet, 1975, i, 271 5. Couser, W., Badger, A., Cooperbrand, S., Stilmant, M., Jemanovich, N.,

4.

Aurora, S., Doner, D., Schmitt, G. ibid. 1977, i, 912.