825 intestinal illness; the penetration of the neuraminidase of intestinal flora into the bloodstream and uncovering of T antigen are secondary effects. We have not yet been able to identify these fluorescing particles. On the other hand, positive agglutination reaction of patient’s red cells with peanut agglutinin did not absolutely indicate the presence of bacterial neuraminidase. Department of Clinical Immunopathology, University Children’s Hospital, D-2000 Hamburg 20, West Germany

A. POSCHMANN K. FISCHER

MAINTENANCE DIGOXIN was most interested to read the article by Dr Johnand Professor McDevitt (March 17, p. 567). Many physicians would now accept that maintenance digoxin is not necessary for patients in sinus rhythm, but it is less commonly appreciated that many patients with atrial fibrillation do not require maintenance digoxin therapy. In my series’ a quarter of the 117 patients with atrial fibrillation studied prospectively for three years remained well without ever taking digoxin. In a recent study of 106 subjects aged 75 and over in the community, investigated by ambulatory 24 h E.C.G. monitoring,2 we found that 8 had established and 3 paroxysmal atrial fibrillation, and of those with established atrial fibrillation only 2 were receiving digoxin for control of heart-rate and in both the heart-rate fell intermittently below 40/min. Of the remaining 6 cases with established atrial fibrillation, 5 had controlled ventricular rates throughout the day of recording and none were receiving negative dromotropic drugs. In only 1 case without treatment was rapid atrial fibrillation seen with an averaged heart-rate exceeding 150/min. Of the 3 with paroxysmal atrial fibrillation, all had intermittently rapid ventricular

SIR,-I

ston

Immunofluorescent demonstration of T receptor on patient’s red cells. Purified peanut agglutinin (anti-T lectin) and fluorescein-labelled anti-peanut globulin serum of rabbits. (a) Pneumonia due to D. pneumonice: uniformly strong fluorescence of all patient’s red cells. (b) N.E.C.: heterogeneous "speckled" fluorescence. (Reduced to 2/3 of x 100.)

plasma proteins5 and damage the capillary endothelium.1-8 Exchange transfusion with heparinised fresh blood is important’3^ for the following reasons: Altered red cells and plasma proteins as well as bacterial toxins removed from patient’s blood. (2) In addition to fresh red cells with their good toxin-binding capacities fresh plasma proteins, leucocytes, and thrombocytes are given. (3) Components of non-specific and specific defence mechanisms are given under ideal conditions (immunoglobulins, complement, antitoxins, macrophages, and so on). (4) Heparinisation is started using fresh heparinised blood. We believe that heparinisation is indicated in all patients with T activation. Prophylactic heparinisation may prevent initiation of disseminated intravascular coagulation.

(1)

are

In 1970 we started to investigate all children with severe infections for T activation, using the simple and rapid screening test with peanut agglutinin.9 Since 1977 we tested all neonates with signs of N.E.C. for T activation. We have detected 4 infants with N.E.C. and T activation. In 2 cases C. perfringens was isolated. Several clostridia produce neuraminidase and clostridia are now thought to be an important pathogen in N.E.C.1O Therefore, we expected uniformly strong fluorescence of T-activated patient’s red cells in N.E.c. as seen in other infections with neuraminidase-producing bacteria (mostly Diplococcus pneumonice, but sometimes C. perfringens) (see figure a). However, in 2 out of 4 infants with N.E.C. we observed heterogeneous "speckled" fluorescence similar to that seen in infections due to influenza virus using snail agglutinin of Helix pomatia as test reagent.ll,12 This heterogeneous speckled fluorescence pattern of patient’s red cells in N.E.c. is still detectable up to 2 months after surgery and without signs of hxmolytic anxmia (see figure b). We believe, by analogy with influenza virus infection, that "virus-like particles" with T antigen (i.e., ,3-galactose in terminal position) react directly with the anti-T lectin. This agent may be the primary toxic pathogen for the 5 Müller, H. E. Dt. med. Wschr. 1970, 95, 513. 6 Poschmann, A., Fischer, K. Med. Klin. 1974, 69, 1821. 7. Poschmann, A., Fischer, K. Behring Inst. Mitt. 1974, 55, 129. 8 Klein, P. J., Bulla, M., Newman, R. A., Müller, P., Uhlenbruck, G., Schaefer, H. E., Krüger, G., Fisher, R. Lancet, 1977, ii, 1024. 9 Fischer, K., Poschmann, A., Oster, H. Mschr. Kinderheilk. 1971, 119, 2. 10. Koloske, A. M., Ulrich, J. A., Hoffman, H. Lancet, 1978, ii, 1014. 11 Poschmann, A., Fischer, K., Grundmann, A., Vongjirad, A. Mschr. Kinder-

heilk. 1976, 124, 15. 12

Graninger, W., Poschmann, A., Fischer, K., Schedl-Giovannoni, I., andner, H., Klaushofer, K.

Vox Sang.

1977, 32, 201.

Hör-

responses. It is likely that

most patients with atrial fibrillation can be well maintained without digoxin treatment for much of the time, and digoxin may only be necessary during periods of intercurrent illness and heart-failure.

Department of Geriatric Medicine, Crawley Hospital, Crawley, Sussex RH11 7DH

ANTHONY MARTIN

SiR,—The article by Dr Johnston and Professor McDevitt should draw attention to the misuse of digoxin. As these workers point out, the therapeutic dose range is narrow, and this means that some patients will receive ineffective doses while others will be at risk of digoxin toxicity. In 1972 you carried an editorial on the bioavailability of digoxin3 and in the same year an editorial in the Scottish Medical Journal4 was entitled "Digoxin-Self-Poisoning". These opinions together with numerous papers since 1970, all draw attention to the dangers of digoxin misuse. Most general physicians today care for many elderly patients with congestive cardiac failure, and such patients are often given oral diuretics plus digoxin. Many will also be receiving potassium supplements, but such supplementation is often insufficient. Dall and Gardiner5 found hypokalsemia in a significant number of geriatric admissions, due mainly to a below-normal intake of dietary potassium. Such patients would be at risk if offered digoxin. Dall6 considered that digoxin was unnecessary in 70% of his cases, and could be withdrawn safely. For more than fifteen years I have been "preaching" to my junior staff that digoxin must be prescribed selectively, 1. Martin, A. M.D. thesis, University of London, 1974. 2. Camm, A. J., and others. Unpublished. 3. Lancet, 1972, ii, 311. 4. Scottish Medical Journal, 1972, 17, 263. 5. Dall, J. L. C., Gardiner, H. S. Geront. Clin. 1971, 13, 119. 6. Dall, J. L. C. Br. med. J. 1970, iii, 705.

826

thoughtfully, and always with a caveat about toxicity. For far too long physicians have had the conditioned reflex that therapy for congestive cardiac failure must include digoxin. Gateside Hospital, Greenock, Inverclyde

ROBERT LAMB

SIR,-We read with great interest the paper by Mr Clarke and his colleagues entitled Severe Hypertension in Primary Aldosteronism and Good Response to Surgery (March 3, p. 452). Our experience with 51 patients with primary aldosteronism’ in many ways accords with that of Clarke et al. However, we would like to make some points about their paper. Although spontaneous hypokalaemia is the most practical screening method for detecting patients with primary aldosteronism, some patients will escape detection if this method alone is relied on. By evaluating the renin-angiotensin-aldosterone system in a selected but large population of hypertensive patients,2 we found that about 20% of patients with primary aldosteronism had serum-potassium at or above the lower limit of normal.I Our second point is related to the usefulness of the paradoxical fall in plasma-aldosterone when concentrations at 8 A.M. after overnight recumbency are compared with those obtained at noon after 4 h of ambulation. The anomalous response to upright posture is thought to be due to the predominant modulating effect of A.C.T.H. on aldosterone production in patients with aldosteronoma. 1.4 A.C.T.H. secretion is thought to reach a peak between 6 A.M. and 8 A.M. Thus, by sampling blood at 9 A.M. and noon Clarke et al. may have missed the peak aldosterone response and narrowed the difference between the plasmaaldosterone concentrations of the two samples during evaluation of postural response. Furthermore A.C.T.H. release is episodic and can be stimulated by venepuncture or other stresses. Hence, a single observation of the postural response of plasmaaldosterone has to be interpreted cautiously and in the light of the corresponding plasma-cortisol concentrations. Finally, at room temperature there is significant flux of aldosterone from the plasma to the red blood-cells,5 so the consistency of the handling and processing of the paired bloodsamples may be important. Only 1 of Clarke’s 4 adenoma patients had a discernible increase in plasma-aldosterone with ambulation. Thus, in all 3 of the patients demonstrating a failure of increase in plasma-aldosterone on standing, an adenoma was found. This is comparable with our experience (adenomas in 24/26 patients with the anomalous response)and with previous reports. 1,4,6.17 While we agree with Clarke et al. that no single diagnostic technique can be relied upon exclusively to separate adenoma from hyperplasia, our experience suggests that the anomalous plasma-aldosterone response, when observed, is a reliable indicator of the presence of adenoma. A.C.T.H.-stimulated adrenal venous sampling, in contrast to isotopic adrenal scanning, has been the more reliable localising technique in our hands.’ It is M. H., Grim, C E., Hollifield, J. W , Kem, D. C., Ganguly, A., Kramer, N J., Yune, H. Y., Wellman, H., Donohue, J. P. Ann. intern

1

Weinberger,

2.

Grim, C. E., Weinberger, M. H., Higgins, J. T., Kramer, N J. J. Am. med.

1979, 90, 386.

Ass 237,1331. Ganguly, A., Melada, G. A., Luetscher, J. A , Dowdy, A. J. J clin. Endocr. Metab 1973, 37, 765 4 Schambelan, M., Brust, N L., Chang, B. C. F., Slater, K. L., Biglieri,

3

E. G ibid 1976, 43, 155. 5 Chavarri, M., Luetscher, J. A , Dowdy, A J., Ganguly, A. ibid. 1977, 44, 752. 6 Biglieri, E G , Schambelan, M., Brust, N., Chang, B., Hogan, M. Circulation Res. 1974, 34/35, suppl 1, p 183. 7 Mantero, F , Gion, M , Aramanini, D., Opocher, G. Clin Sci. mol. Med.

1976, 51, 329s

cess.

cessful.8,9

PREOPERATIVE DISTINCTION OF ADENOMA FROM HYPERPLASIA IN PRIMARY ALDOSTERONISM

Med

difficult technique and demands considerable skill for sucThe prediction of probability of adenoma or hyperplasia by use of a multiple logistic function has also been highly suca

Clarke’s observation of severe hypertension in primary aldosteronism accords with our experience’ in which 33/51 such patients had diastolic blood-pressure >120 mm Hg. The response to surgery in our patients was also similar to that observed by Clarke et al. and other groups. Our preliminary experience of localisation of adenomas in 4 of 6 patients by computerised tomography’O suggests that this is a potentially useful, non-invasive technique. Center of Research in Hypertension, Indiana University Medical Center, Indianapolis, Indiana 46223, U.S.A.

Specialised

ARUNABHA GANGULY MYRON H. WEINBERGER

IS "IDIOPATHIC ŒDEMA" IDIOPATHIC?

SIR,-Dr MacGregor and his colleagues (Feb. 24, p. 397) have studied ten women with the so-called "idiopathic oedema" at a time when diuretics had been suddenly stopped. Nine patients gained several kilograms and oedema reappeared. MacGregor et al. stress the point that, on a normal sodium diet and without diuretics, seven patients progressively lost their oedema over a 20-day period. They concluded that these women had had diuretic-induced oedema and had become dependent on the drug. The reasons why these patients had started taking diuretics are unclear. The Charing Cross Hospital workers are right when they emphasise that, in the face of oedema of unknown origin, clinicians should look for diuretic abuse. However, in our opinion, iatrogenic oedema apart, multifactorial oedema does exist, and our reasons for thinking this are: (1) Our first published case (1955) was in a patient with oedema and weight gain which developed every time she ate a high-salt meal. At that time diuretics were not on the market. 1.2 (2) Patients with oedema not related to the consumption of diuretics, such as those described by J. A. Luetscher, D. H. P. Streeten, and their colleagues, do not tolerate an overload of salt without discomfort (severe headache, nausea, troubles of the vision, andsometimes papillary oedema). In these patients, urinary sodium excretion stays at a very low level and urinary aldosterone values do not return to normal. (3) Some cases seem to be due to psychological stresses. One of G. W. Thorn’s patients first had oedema a week after her husband’s death. Thorn called such cases "psychic" oedema. (4) Fig. 1 in the paper by MacGregor et al. shows that three of their ten patients maintained their weight gain after diuretics were withdrawn despite the fact that their aldosterone levels returned to normal. (5) Of six patients with idiopathic oedema now under investigation by us and on a low-salt diet (3-5 g a day) three have natriuretic-factor levels which accord with their salt intake, but the remaining three have high values of natriuretic factor in their urines equal to those observed in normal subjects on 9x-fludrocortisone the day before they escaped from the saltretaining effect of steroids. However, in contrast to these subjects who do escape from the salt-retaining effect of the steroid, natriuresis did not increase in the patients with oedema. Thus J B., Brown, J. J., Fraser, R., Kay, A. W., Neville, A. M., O’MuirI. G., Robertson, J. I. S., Symington, T., Lever, A F Lancet, 1970, ii, 995 9. Luetscher, J. A., Ganguly, A., Melada, G. A., Dowdy, A. J. Circulation Res 1974, 34/35, suppl 1, p. 34 10. Ganguly, A., Pratt, J H., Yune, H. Y., Grim, C. E., Wemberger. M H 8 Ferris,

cheartaigh,

Archs intern Med 1.

(in the press).

Mach, R. S , Fabre, J., Muller, A. F , Neher, R. Schweiz.

med. Wschr 1955,

85, 1229. 2 3.

Mach, R. S. Schweiz. med Wschr. 1976, 106, 161. Bourgoignie, J. J , Klahr, S., Bricker, N. S. J. clin. Invest, 1971, 50, 303

Maintenance digoxin.

825 intestinal illness; the penetration of the neuraminidase of intestinal flora into the bloodstream and uncovering of T antigen are secondary effect...
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