THROMBOTIC SIDE-EFFECTS OF LOWER-LIMB PHLEBOGRAPHY

723 The significance of the observation that the increases in serum-lipids during diuretic therapy occurred in those with a lower pretreatment serum-cholesterol is also uncertain. Possibly in this subgroup the contribution of diet to the serum concentration of cholesterol was small, so that the lipid-lowering diets, if prescribed, had little effect in offsetting the hyperlipidaemic action of chlorthalidone. The clinical importance of these increases in serum-lipids is unclear. If serum-lipids are involved in the pathogenesis of atherosclerosis, as epidemiological4and experimental6 studies suggest, then these changes may be important. Especially in hypertension, where life-long therapy may be required, a small increase in serum-lipid concentration, if sustained over a long period, may have a cumulative effect. Whether this is important in the pathogenesis of atherosclerosis or not, it is useful for the practitioner to be aware of this effect. When lipid-lowering diets are prescribed at the same time as chlorthalidone, there may be little or no lowering of serum-lipid concentrations. For investigators these observations may

suggest a new avenue for the study of factors influencing the serum

concentration and metabolism of lipids.

Requests for reprints should be addressed to R. P. A., Roosevelt Hospital, 428 West 59th Street, New York 10019, U.S.A. REFERENCES 1. Laragh, J. H. Ann. intern. Med. 1967, 67, 606. 2. Kessler, G., Lederer, H. in Automation in Analytical Chemistry (edited by L.T.Skeggs, Jr,); Technicon Symposium). vol. ii, p. 341. White Plains, New York, 1966. 3. Fletcher, M. J. Clinica chim. Acta, 1968, 22, 393. 4. Kannel, W. B., Castelli, W. P., Gordon, T., McNamara, P. Ann. intern.

to be examined was not was instructed to relax the leg the and patient bearing weight, muscles. 60-120 ml ofmeglumine metrizoate (’Isopaque’ cerebral, 280 mg iodine/ml) was injected in a dorsal vein of the foot. A tourniquet was applied around the ankle during the first part of the examination. The contrast medium was injected intermittently using fluoroscopic control with a television image amplifier. The 125I-Iabelled fibrinogen-uptake test (F.U.T.) was performed as described elsewhere 3with slight modifications.5 The criteria for an abnormal result were those described by Negus et aI.,6 with additions by Browse et al.’7

table, tilted 30-45 degrees. The leg

RESULTS AND DISCUSSION

From May, 1974, one of us (C.G.O.) made a pilot study of the F.U.T. and the 99t"Tc-labelled streptokinase uptake test5 in the diagnosis of established deep-vein thrombosis. 63 patients were examined. In 10 patients, normal findings on initial phlebography were followed by a positive isotopic test indicating thrombosis. In 2 of these patients non-fatal pulmonary embolism occurred. In November, 1975, we started a consecutive study

comparing thorough clinical examination, strain-gauge plethysmography,. F.U.T., and phlebography in the diagnosis of deep-venous thrombosis. Of the 66 patients already examined, 33 had a normal initial phlebogram. In 10 of these 33 patients, fibrinogen uptake was normal in two or three measurements taken before phlebography, but became abnormal after it. In several of the patients with abnormal F.U.T. after phlebography there was a fairly uniform clinical picture. Some five to ten hours after phlebography, the patient

Med. 1971, 74, 1. 5. Albrink, M. J. Archs intern. Med. 1962, 109, 345. 6. Walton, K. W. Am. J. Cardiol. 1975, 35, 542.

THROMBOTIC SIDE-EFFECTS OF LOWER-LIMB PHLEBOGRAPHY ULF ALBRBCHTSSON

CARL-GUSTAV OLSSON

Departments of Diagnostic Radiology, Clinical Physiology, and Internal Medicine, University Hospital, Lund, Sweden

patients with initially normal phlebograms, uptake of 125I-labelled fibrinogen subsequently increased. In 4 (7%) cases, independent examinations (pulmonary scintigram or a new phlebogram) demonstrated a thromboembolic or throm-

Summary

In 20 of 61

botic process. These results suggest that thrombosis and embolism may be caused by phlebography. INTRODUCTION

PHLEBOGRAPHY of the legs sometimes

causes

pain and

superficial thrombophlebitis of the injected vein. It has even been claimed, that phlebography might produce

deep-vein thrombosis. 1Objective evidence confirming these fears is lacking. In comparing different methods for the diagnosis of thrombosis, we found that normal findings on phlebography were often followed by increased uptake of 12-11-fibrinogen, indicating thrombosis. METHODS

Phlebography was performed with the patient on an X-ray

Thrombosis developing after phlebography.

First examination (left) showed normal veins in the calf. Reexamination (right) 17 days later showed occlusive thrombi in both posterior tibial veins (arrows).

724 felt progressive pain around the site of contrast injection in the foot. This often occurred at night, sleep being disturbed. During the next few days, the pain gradually ascended along the calf, in step with abnormal uptake of 1-labelled fibrinogen. A typical case was that of a forty-one-year-old woman who had been aware of some oedema in her right calf for two days. Plethysmography and F.U.T. were normal, as

treated. Perhaps in the future its should be restricted by some screening procedure.

complications

We thank the Swedish Association

use

against Lung and Heart Dis(grant 14X-2872), and

eases, the Swedish Medical Research Council

the Medical Faculty of Lund for support.

Requests for reprints should be addressed to C. G. 0., Department Physiology, University of Lund, Lasarettet, S-221 85 Lund,

of Clinical Sweden.

subsequent phlebography. After phlebography, patient had pain and increased swelling and the

was a

the

in the

right foot and calf became abnormal. A second phlebogram showed a fresh thrombus in her right foot and distal calf (see accompanying figure). The true frequency of thrombotic complications after phlebography is difficult to assess. An increased growthF.U.T.

of an established thrombus would be hard to demonstrate by any method. Therefore, we feel it appropriate to assess the complication frequency only in those 61 patients in whom initial phlebography was normal (the total number of patients was 129). The F.u.T. became abnormal in 20 patients, a surprisrate

ingly large proportion (33%). This finding may have several explanations. In some cases the F.U.T. might not have revealed the original thrombus until the third or the fourth day of measurement. Small muscle-vein thrombi are not always detected by phlebography, but may become larger a day or two later. This might wrongly lead to the conclusion that the thrombus was phlebographically induced. However, this explanation assumes that phlebography often gives a false-negative result, which is very unlikely. Also the F.U.T. is not specific. Tissue accumulation of fibrin also occurs in inflammatory tissue and in heematomas. However, it seems unlikely that such processes would ascend a long way up the calf if they were caused by phlebography. independent evidence of thrombosis after phlebography in 4 patients. 2 of them had definite signs of pulmonary embolism some days after a normal phlebogram. The high uptake of fibrinogen in these legs possibly reflected the actual thrombotic process in these patients. In 2 other patients the isotopic findings were verified with a second phlebogram. Despite the high fibrinogen uptake, the second phlebogram showed normal results in a third patient; in a fourth patient, the new phlebography was technically not conclusive. Some patients refused a second phlebogram because the first examination was too painful. Harris et al. found new thrombi in 4 patients after phlebography. In a study of canine jugular veins, Ritchie et al.9 found infiltration of leucocytes, endothelial damage, and There

was

thrombus formation after exposure to contrast medium. Other contributory factors were jugular stasis produced by pressure (giving a prolonged contact between contrast medium and vascular endothelium and tissue damage around the vein). Our findings strongly suggest that thrombosis and embolism may be caused by phlebography. If this is true the method of phlebography must be changed. Complications seem to depend on contact with contrast medium. New contrast media-non-ionising compounds with low osmolarity’"—which we are now studying, may prove to be less harmful. Phlebography is indispensable for the accurate diagnosis of thrombosis. Nevertheless, its hazards should be recognised and its

REFERENCES 1. 2.

Söderström, N., Norberg,

B. Personal communication.

Harris, W. H., Salzman, E. W., Athanasoulis, C., Waltman, A., Baum, S., De Sanctis, R. W., Potsaid, M., Sise, H. New Engl. J. Med. 1975, 292,

665. 3. Atkins, P., Hawkins, L. A. Lancet, 1965, ii, 1217. 4. Kakkar, V. V. Personal communication. 5. Darte, L., Olsson, C. G., Persson, R. B. R. Thirteenth International Annual Meeting of the Society of Nuclear Medicine, Copenhagen, 1975. 6. Negus, D., Pinto, D. J., Le Quesne, L. P., Brown, N., Chapman, M.Br.J.

Surg. 1968, 55, 835. Browse, N. L., Clapham, W. F., Croft, D. N., Jones, D. J., Thomas, M. L., Williams, J. O. Br. med.J. 1971, iv, 325. 8. Hallböök, T., Göthlin, J. Acta chir. scand. 1971, 137, 37. 9. Ritchie, W. G. M., Lynch, P. R., Stewart, G. J. Invest. Radiol. 1974, 9, 444. 10. Almén, T. Third Congress of the European Radiological Society, Edinburgh, 1975 (abstr.). 7.

Hypothesis DOPAMINE ACETYLCHOLINE IMBALANCE IN PARKINSON’S DISEASE Possible Regenerative Overgrowth of Cholinergic Axon Terminals RAINER SPEHLMANN

Neurology Service, Veterans Administration Lakeside Hospital, and Departments of Neurology and Pharmacology, Northwestern University Medical School, Chicago STEPHEN M. STAHL

Departments of Pharmacological Physiological Sciences and Psychiatry, University of Chicago Parkinson’s disease is characterised by an imbalance between acetylcholine and dopamine which probably results from the degeneration of a dopaminergic nigrostriatal pathway. A new hypothesis is proposed to explain the development of this imbalance. Applying the concept that degeneration of nervefibres in the central nervous system can lead to collateral sprouting of uninjured fibres, it is suggested that the death of dopaminergic nigrostriatal neurons results in sprouting of axons of cholinergic interneurons in the caudate nucleus. This overgrowth could result in the cholinergic innervation of neuronal membranes vacated by degenerated dopaminergic terminals. Thus, the apparent changes in the activity of dopaminergic and cholinergic systems can be accounted for by faulty regeneration in the central nervous system.

Summary

INTRODUCTION

IT is now commonly believed that the manifestations of Parkinson’s disease (P.D.) are due to an imbalance between the major synaptic neurotransmitter candidates in the corpus striatum. 12 In particular, the balance