LOW-DOSE HEPARIN

229 RAISED COMPLEMENT IN NEPHRITIS SIR,-Dr. Gabriel and his co-workers (July 8, p. 55) suggest that a raised serum-hxmolytic-complement level implies a poor prognosis. That serum-complement levels both above and below the normal range can be found in a rheumatoid arthsingle disease syndrome is recognised, ritis 1-3 and glomerulonephritis 3-5 being two good examples. Further, in some complement-mediated diseases complement metabolism may vary from the anabolic to the catabolic state.6However, actual measurement of complement metabolism is difficult and time-consuming. Another approach is to measure the breakdown products of complement as an index of complement utilisation. This can be done much more readily than measuring complement turnover.7 We have been using this technique to study complement conversion in rheumatoid arthritis, and find that complement-activation products (C3i and C4i) are nearly always found if repeatedly tested for, but are detectable in only 75% of cases on random single-sample testing. There is poor correlation between the variation of serum-complement levels (C3 or C4) from normal and the amount of activation products produced. Thus C3 or C4 levels by themselves are not a reliable index of complement involvement in the disease process in a patient. More interesting is the demonstration that in rheumatoid diseases there is a continuing striking fluctuation in all these values-C3, C3i, C4, and C4i. Thus random values will not give a true picture of the complement status in a patient, and it is impossible to say what complement level is representative .of a particular patient. It would therefore be interesting to know whether any of the 15 patients who initially had normal hasmolytic-complement (c.H.) values but who subsequently died, continued to have normal levels, in view of the final finding that none of the 52 surviving patients in whom c.H. was measured had raised levels. One further point: it does seem from our work that many factors, such as infections and non-specific inflammation,

cyclophosphamide therapy.

8

were

steroid-resistant

The steroid non-responders and 6 were fresh cases. had received a single dose of dexamethasone 2 mg. per kg. ideal body-weight on alternate days for at least 8 weeks. Cyclophosphamide 3-5 mg. per kg. ideal body-weight daily was also given orally to patients with proliferative glomerulonephritis (all types-14 cases), and membranous nephropathy (2 cases), who showed resistance to steroid therapy. The dose was continued for a minimum of 4 weeks and was then reduced to half when the urine became protein-free; it was continued for a further 3 months till biochemical remission was achieved. Where the patient still had proteinuria, the full dose was continued for 3 months. All patients were followed-up regularly for 3-22 months. 11 with minimal-change disease attained complete biochemical remission (78-57%) and 3 partial remission (21-43%). Out of 14 patients with proliferative change, 6 attained complete remission (exudative 1, mesangial 2, with crescents 1, membranoproliferative 2), 5 had partial response (exudative 1, mesangial 1, membranoproliferative 3), and 5 did not show any response (exudative 1, mesangial 1, and membranoproliferative 3). 1 patient with membranous nephropathy attained complete remission and the other showed partial remission. Cyclophosphamide was thus found to be effective not only in minimal-change nephrotic syndrome but also in other types. No serious side-effects were observed except hasmorrhagic cystitis in 1 patient and alopecia and leucopenia in 6; these improved with adjustment of the dosage. Further follow-up will tell us how long the effect of this immunosuppressive agent really lasts. This work was initially started by Dr. P. D. Gulati, who holds a Commonwealth Fellowship. Renal Unit, of Medicine, Maulana Azad Medical College, New Delhi, India.

Department

be accompanied by complement activation; thus, complement levels may not reflect only the disease-process

now

S. N. A. RIZVI H. VAISHNAVA.

can

REDUCED HEPARIN DOSAGE FOR HÆMODIALYSIS

under consideration. Department of Chemical Pathology, Westminster Hospital Medical School, London S.W.1. Department of Medicine, Royal Postgraduate Medical School, London W.12.

J. M. B. VERSEY J. R. HOBBS. P. J. L. HOLT.

CYCLOPHOSPHAMIDE IN MINIMAL-CHANGE NEPHROTIC SYNDROME SIR,-Like Dr. Uldall and his co-workers (June 10, p. 1250) we have had encouraging results with cyclophosphamide in adults with minimal-change nephrotic syndrome. Between 1962 and 1971, we collected 388 cases of nephrotic syndrome of varied astiology. 146 patients turned out to have primary renal disease, of whom 39 showed minimal change (26-71%) and 91 proliferative changes (all types 62’33%); the remaining 16 (10-96%) had membranous nephropathy. Like Uldall et al. we were disappointed with steroid therapy because of frequent relapses, and we treated the steroid-resistant as well as some new adult cases with cyclophosphamide. 14 adults with biopsy-proven minimal-change nephrotic syndrome, aged 18-40 years, entered an open trial of Townes, A. S. Johns Hopkins med. J. 1967, 120, 337. Schubert, A. F., Ewald, R. W., Schroeder, W. C., Rothschild, D. N., Bhatavadekar, D. N., Pullen, P. K. Ann. rheum. Dis. 1965, 24, 439. 3. Versey, J. M. B., Hobbs, J. R., Holt, P. J. L. Unpublished. 4. Franco, A. E., Schur, P. H. Arthritis Rheum. 1971, 14, 231. 5. Cameron, J. S., Glasgow, E. F., Ogg, C. S., White, R. H. R. Br. med. J. 1970, iv, 7. 6. Sliwinski, A. J., Zvaifler, N. J. Clin. exp. Immun. 1972, 11, 21. 7. Versey, J. M. B. Prot. biol. Fluids, 1971, 19, 565. 1. 2.

SIR,—Dr. Drukker (July 8, p. 91) points out the dangers bleeding in surgical and injured patients requiring heamodialysis, and of the difficulties of regional heparinisation. We have found that, by giving just sufficient heparin to keep the clotting-time of the blood entering the extracorporeal circuit between 10 and 15 minutes, that the dialyser does not clot, nor does the patient bleed, and dialysis can be continued for as long as necessary. Postdialysis administration of protamine sulphate is also of

unnecessary. Renal Unit, Whipton Hospital, Exeter.

P. G. BISSON M. J. BISSON.

LOW-DOSE HEPARIN SIR,-Influenced by reports from the King’s College Hospital team on the value of small subcutaneous doses of heparin in the prophylaxis of postoperative venous thrombosis, I have been using this method routinely in a small series of total hip replacements. Perhaps the fact that it is a small series underlines the occurrence of three major clinical thromboses almost consecutively and a number of wound hsematomata. Previously I would not have expected to see many more thromboses in a year, and hsematomata in the past have been uncommon. This underlines the remark of Kakkar and others (July 15, p. 101) that " another group of potential failures may be represented by patients subjected to total hip replacement ". My experience is also consistent with that of Mr. Charnley, reported in the

230 I would particularly support his of trials directed towards clinical the value emphasis thrombosis rather than towards that mythical creature for the practising surgeon, the silent clot only demonstrable same

issue

(p. 134), and

TABLE II—PLASMA-PROTEIN LEVELS IN

by

some

25 CASES OF NUTRITIONAL

ANEMIA

on

sophisticated technique.

I have

now

abandoned this method

as

useless and

dangerous in so far as the management of major elective hip surgery is concerned. Brook General Hospital, London S.E.18.

DAVID LE VAY.

HYPERPYREXIA AFTER ANÆSTHESIA

SiR,-Dr. Sonnenklar and Dr. Rendell-Baker (July 1, p. 43) suggest that electric-shock therapy may protect against malignant hyperpyrexia induced by suxamethonium. I have noticed that there is an extremely low incidence of muscle

pains following the use of suxamethonium for E.C.T., despite the fact that these patients are ambulant. It is generally thought that the presence of muscle pains is closely related of muscle fasciculations. However, suxamethonium before E.C.T. show the usual muscle fasciculations and yet do not develop " after pains ". The mechanism of this protective influence of electricshock therapy remains to be elucidated.

to

the

occurrence

patients given

Department of Anæsthetics, Withington Hospital,

V. M. HEY.

Manchester M20 8LR.

NUTRITIONAL STATE OF ELDERLY ASIAN AND ENGLISH SUBJECTS IN COVENTRY

SIR,-In their interesting paper (June 3, p. 1224), Dr. Elwood and his colleagues cited our study ’1 of a group of 25 hospital patients as possible evidence of suboptimal nutrition in the elderly in Britain. However, only 1 of these cases was " elderly " (a male of 65 years), and in fact he had pernicious anaemia. Nevertheless, we have no doubt from further investigations that an unsatisfactory nutritional state is found in elderly Asians in this part of the country. Table I gives some of the details of 6 Asians with nutritional megaloblastic anxmia. In the Coventry survey there were 24 males and 9 female Asians with serum-vitarnin-B12 levels less than 150 pg. per ml. All the males apparently " ate meat two or three times a week ". This being so, one is bound to wonder if there were not some cases of incipient pernicious anaemia among their subjects. Is any follow-up of these Asiansparticularly those who were anmmic-to be carried out, such as marrow examination or study of vitamin-B12 absorption ? There was no indication of the incidence of megaloblastic anaemia in the Coventry immigrant population as a whole. We have found a surprisingly high incidence in the London area. We would agree with Dr. Powell (June 24, p. 1389) that it would have been interesting to have included an 1.

Britt, R. P., Harper, C. M., Spray, G.

H.

Q. Jl Med. 1971, 40, 499.

TABLE I-DETAILS OF

6 ASIAN PATIENTS

S.H.B.D. = sertim-hvdzoxvbutyric dehydrogenase.

index of iron deficiency such as the estimation of serumiron. We have no experience of serum-transferrin estimation, but we have found only 2 Asian subjects out of 56 with subnormal total iron-binding capacity (unpublished

observations). We have measured plasma-protein levels in 25 cases of nutritional anxmia (table 11). All but 2 had total proteins in the normal range. However, the majority showed subnormal or borderline albumin levels (20 out of 25) and there was no correlation between albumin and haemoglobin. The globulin levels were normal in all but 4, and our findings are somewhat at variance with the Coventry survey, in which high globulin levels were found. The two groups are not, of course, exactly comparable. We are carrying out further work on this. Department of Clinical Pathology, Hillingdon Hospital, Uxbridge, Middlesex.

R. P. BRITT CHRISTINE M. HARPER.

HOSPITAL OPERATIONAL POLICIES

SIR,-The reference to the fire risks in hospitals (July 15, p. 141) emphasises the need for clearly and widely understood operational policies and procedures in long-stay hospitals. Unlike the general hospital, where emergencies and new problems are arising every day, the long-stay hospital has a stereotyped regular routine which sometimes by its very monotony tends to lower the morale of the staff and leads to their taking short-cuts, adopting slovenly ways, and paying less attention to detail than in the acute hospital, where such deviation might make all the difference between life and death. In the past the local-authority colonies for the mentally defective had their book of strict rules which the staff were compelled to read and sign that they were understood. Some psychiatric hospitals have continued to publish rules of this type which concentrate on what the staff should not do rather than on what they should do. Up-to-date statements of operational policies should be more positive and indicate the procedure to be followed in In psychiatric hospitals the risk of fire, any situation. patients going absent without permission, disturbed behaviour, and accidents are frequent daily situations where a clearly understood code of practice is needed. Military precision will seem an anathema -to most hospital staff, but the dire consequences of a laissez-faire attitude must WITH NUTRITIONAL MEGALOBLASTIC ANEMIA

N.A.

=

not

yet available.

N.D. = not

done.