231 treated with various anticonvulsants including hydantoins. However, the percentage of circulating lymphocytes positive for surface immunoglobulin were diminished in some patients. Some workers have suggested that T-cell-triggered immune reactions might also be affected by hydantoin medication, as evidenced by negative delayed-type skin tests to various common antigens, 1 2 11 diminished lymphocyte stimulation by phytohaemagglutinin,1 10 concanavalin A, or pokeweed mitogen,l1 and by a decrease of circulating T cells as measured by spontaneous rosette formation. 10 IgA deficiency and/or signs of defective T-cell functions were2 found in 40-50% of all hydantoin-treated patients.1 However, none of these workers have shown whether only epileptics treated with hydantoins or also non-epileptics treated with such drugs have T-cell deficiencies. Our present data give no further clue and further studies are now in progress. Hydantoin medication is known to be associated with serological and rarely with clinical manifestations of autoimmunity. Antinuclear antibodies were only detected in 2 of 112 tested patients treated with hydantoins. Also lymphocytotoxicity, known to be frequently detectable in systemic lupus erythematosus and various viral disorders was never found. This is in contrast to the incidence of antinuclear antibodies (10-55%) earlier reported by US2 and others. 12 113 These differences might be explained by the fact that patients in the present study only received low doses of hydantoins. A dose and time dependent relationship of hydantoin medication to the incidence of autoantibodies has been postulated by others. 14 A similar argument might explain why lymphadenopathies, frequently observed in earlier reports, were not encountered in the patients studied, and that the complement levels were normal in the present series in contrast to earlier data.22 Besides the question of which hydantoins might be responsible for lowering IgA levels the most interesting point is the postulated predisposition to low IgA, which is eventually linked to a more general immune defect. Further investigation in this direction may give an indication of the aetiology of epilepsy or its pathogenesis. Patients with selective IgA deficiency of unknown (primary) origin may suffer from recurrent infections. atopic disorders, certain gastrointestinal diseases, &c.1 However, when groups of patients with these disorder, are studied, IgA deficiency is rarely found. This is no the case in patients with ataxia teleangiectasia,16 0: whom up to 80% have been found to have low 19A, or as the present results suggest, in epileptics. It is possible that IgA might not only play an important role at thl body surfaces, but also in the defence system of thl brain at the serum/liquor barrier. I
We thank Dr P. Ruf of the Swiss Clinic for Epileptics for collecting the sera; Mrs H. Spichiger and Mrs C. Nillo for determing the drug plasma levels; Mrs R. Kellerhals for her assistance in measuring immunoglobulins ; and Mrs M. Schaich for secretarial help.
Requests for reprints should be addressed to P. J. G. REFERENCES 1. Sorrell, T.
C., Forbes, I. J., Burness, F. R., Rischbieth, R. H. C. Lancet, 1971, ii, 1233. 2 Grob, P J., Herold, G. E. Br. med J. 1972, ii, 561. 3. Seager, J., Jamison, D. L., Wilson, J., Hayward, A. R., Soothill, J. F. Lancet.
4
1975, ii, 632.
Rubenstein, K. E., Schneider, R. S., Ullman, E. F. Biochem. biophys. Res. Comm 1972, 47, 846.
VENTRICULAR ARRHYTHMIAS AND HYPOKALÆMIA PAUL CURRY WILLIAM STUBBS*
DAVID FITCHETT DENNIS KRIKLER
Cardiovascular Division, Royal Postgraduate Medical School Hammersmith Hospital, London W12 0HS
of life-threatening ventricular arrhythmia (torsade de pointes) due to chronic mild hypokalæmia, caused by hyperaldosteronism and familial periodic paralysis are described. Correction of the hypokalæmia, supplemented by mexiletine, controlled the arrhythmias.
Summary
Two
cases
Introduction HYPOKALAEMIA is known to cause cardiac arrhythmias and to impair atrioventricular (A.v.) conduction especially in patients receiving digoxin or suffering from heart-disease.1-3 Life-threatening ventricular arrhythmias may complicate profound and sudden hypokal aemia4 and can be controlled by potassium repletion.S We report two cases of torsade de pointesS presenting with Adams-Stokes attacks, resulting from chronic mildhypokalaemia due respectively to hyperaldosteronism and to periodic muscular paralysis; both cases responded to correction of the hypokalaemia and the administration of mexiletine.
Case-reports Case 1 A 28-year-old woman had had palpitations for 10 years after which they became more severe and were complicated by syncope. Her E.c.G. showed multiple ventricular extrasystoles closely related to the preceding T waves, u-wave accentuation, QT and Qu prolongation (QTC 0-66 s), and the Wolff-ParkinsonWhite syndrome type A (fig. 1). Her plasma-potassium ranged between 2.8 and 3-5 mmol/1. She deteriorated on disopyramide (100 mg 6-hourly) and was admitted to Hammersmith Hospital. Her blood-pressure was 160/100 mmHg. Electrophysiological studies confirmed prolonged ventricular repolarisation and increased ventricular vulnerability to premature depolarisation during the relative refractory period as well as a left-sided anomalous A.v. pathway; sinoatrial (s.A.) and A.v. nodal function were normal. Chest X-ray, echocardiogram, plasma-cortisol, and audiometry were normal. Urinary potassium excretion was high (131 mmol/24 h) but tests of renal tubular function including urinary acidification were normal. Plasma-renin activity was 1-50 pmol/h/ml recumbent (normal range 112-65) and *Present address:
Southampton
General
Hospital
5. Bastiani, R. J., Phillips, R. C., Schneider, R. S., Ullman, E. F. Am. J. med. Technol. 1973, 39, 211 6. Grob, P. J., Jemelka, H. Schweiz. med. Wschr. 1971, 101, 223. 7. Laurell, C. B. Ann. Biochem. 1966, 15, 45. 8. Terasaki, P. J., Clelland, J. D. Nature, 1964, 204, 998. 9. Slavin, B. N., Fenton, G. M., Laundy, M., Reynolds, E. H. J. neurol. Sci. 1974, 23, 353. 10. Massimo, L., Pasino, M., Rosanda-Vadala, C., Tonini, G P., De Negri, M., Saccomani, L. Lancet, 1976, i, 860. 11. Masi, M., Paolucci, P., Perocco, P., Franceschi, C. Lancet, 1976, i, 860. 12. Alarcon-Segovia, D., Fischbein, E., Reyes, P A., Dies, M., Schwadsky, S. Clin. exp. Immun. 1972, 12, 39. 13. Beernink, D. A., Miller, J. J. J. Pediat. 1973, 82, 113. 14. Alarcon-Segovia, D. Clins. rheum. Dis. 1975, 1, 573 15. Buckley, R. H. Birth Defects orig. Art. Ser. 1975, 11, 134. 16. Boder, E. ibid. p. 255.
232
Fig.
1-Case 1: E.C.G. leads
Increased ventricular
Fig. 2-Case
II, VI, and
V6..
ectopic activity,
torsade de
pointes, QT prolongation, and Wolff-Parkinson-White syndrome type A
are
shown.
2: E.C.G. leads II.
(a) Bidirectional ventricular tachycardia with Wenckebach block; there is a single ventricular hypokalaemia and on mexiletine.
S.A. depression; (b) suppression of the tachyarrhythmia by intravenous ajmaline, showing S.A. extrasystole; (c) sinus rhythm with normal S.A. and A.v. conduction following correction of the
2.58 pmoVh/ml erect (normal range 2.82-4-03); aldosterone excretion was 78-1 mnoV24 h (range 14-70 nmoV24 h) and was not suppressed after sodium loading (56-2 nmol/24 h; normally up to 19.5 nmol/24 h). Diurnal plasma-aldosterone concentrations after sodium loading were 0.45 nmol/1 (8-00 A.M.) and 1.56 nmol/1 (11-30 A.M.). Adrenal venograms showed enlargement of both adrenal glands, with no adenomata. Selective adrenal venous sampling showed plasma aldosterone/cortisol ratios of 3/1 (right) and 6/1 (left) (both high) compared with 0. 3/1 in the inferior vena cava. Quinidine aggravated the condition, producing torsade de pointes (fig. 1) culminating in ventricular fibrillation which required D.C. countershock. With potassium supplements (64 mmol in 24 h), spironolactone (25 mg 8-hourly), and mexiletine (100 mg 6-hourly), it was possible to suppress the arrhythmia (plasma-potassium 4-6 mmol/1 ; QTC 0-53 s). Case 2 A 32-year-old woman had developed arrhythmias at the age of 11 years and epileptiform fits sometimes preceded by syncope and attacks of muscular paralysis 16 years later. She also
had fluctuating muscle weakness, stiffness, and aching, especially after exertion. Neurological investigations had been normal. During the next few years she had three major myopathic crises consisting of stiffness, myalgia, rapid wasting, hypotonia, and variable paralysis, each resolving spontaneously in about 3 weeks. Examination revealed generalised muscular weakness and mild, mainly proximal, wasting. Her pulse was rapid and irregular and her blood-pressure 90/50 mm Hg. E.C.G. showed repetitive predominantly bidirectional ventricular tachycardia (fig. 2a), sinus arrhythmia, and varying second-degree A.v.
block. Intravenous ajmaline (25 mg) suppressed the ventricular arrhythmia but S.A. block was now seen (fig. 2b). The plasma-potassium was 3.22 mmol/1; chest X-ray and echocardiogram were normal. On the third day she had syncope due to ventricular fibrillation; D.c. shock’(100 J) and intravenous lignocaine (3 mg/min) converted the rhythm to bidirectional ventricular tachycardia followed by junctional rhythm and S.A. block with ventriculoatrial dissociation. Electrophysiological studies confirmed the ventricular tachycardia and showed lllcreased ventricular vulnerability, S.A. block, and depressed A.v. nodal conduction; His-Purkinje conduction was normal. Despite treatment with disopyramide (200 mg 6-hourly) and temporary ventricular pacing she had-further periods of ventricular fibrillation preceded by torsade de pointes. Her plasma-potassium was now 2.8 mmol/1, and she was given in-
potassium (20 mmol/4-hourly) followed by oral supplements (64 mmol/24 h), together with amiloride 5 mg (6-hourly) and mexiletine (200 mg 6-hourly). She had no further syncopal attacks. In view of the need for anti-arrhythmic agents in high dosage and evidence of partial S.A. and A.v. block, a permanent-demand pacemaker was implanted using an epicardial electrode. The ventricular wall was pale and thin and myocardial biopsy was deemed unsafe; peripheral muscle biopsy (by Prof. R. Edwards and Prof. V. Dubowitz) showed a myopathic process with typc-u fibre atrophy, mitochondrial abnormalities, vascular changes, and a marked increase in intra and peri fibre acid-phosphatase activity. On amiloride (5 mg 8-hourly), potassium supplements (32 mmol daily), and mexiletine (200 mg 6-hourly) she has now remained well for 18 months with good muscle function despite some irreversible atrophy. The E.c.G. is normal (fig. 2c! with occasional unifocal ventricular extrasystoles. travenous
233 Discussion
Preliminary Communication
Potassium depletion may have profound effects on impulse formation and conduction,6 spontaneous ectopic activity in pacemaker cells in particular being enhanced. Conduction velocity, especially in the A.v. node, is depressed in proportion to the hypokalaemia.7 The rate at which the serum level falls accounts for some of the differences between the experimental and the clinical effects of hypokalsemia. Clinically, there is a high incidence of arrhythmia when the plasma-potassium falls below 3.2 mmo1/l8 but there are very few reports of lifethreatening ventricular arrhythmias. Hypokalaemia is frequently due to prolonged or unbalanced use of powerful diuretics9 but may also result from intestinal disorders,10 renal dialysis," and corticosteroid therapy,t2 in which arrhythmias have been described.
COMPUTERISED AXIAL TOMOGRAPHY FOR DIAGNOSIS OF PANCREATIC CANCER G. WIGGANS
P. S. SCHEIN
D. SCHELLINGER J. S. MACDONALD J. HARBERT Divisions of Medical Oncology and Nuclear Medicine, Vincent T. Lombardi Cancer Research
Center, and Georgetown University Hospital, Washington, D.C. 20007, U.S.A.
Computerised axial tomography demonstrated the presence of a mass lesion in the pancreas in 9 (64%) of 14 patients with histologically confirmed pancreatic cancer. Since this was a retrospective analysis, the percentage of false positive and negative results using this technique is not as yet known. The technique appears accurate in detecting abnormal pancreatic masses of 10 cm in diameter or more, however, for masses less than 10 cm in diameter the yield at present is only 33%. With further technical refinement to increase resolution, the automatic computerised transverse axial scan should prove to be an invaluable procedure for the detection of pancreatic carcinoma, in designing radiation therapy ports, and in providing objective information regarding response of therapy and progression of disease.
Summary
In the first patient, hypokalaemia was due to primary hyperaldosteronism (Conn’s syndrome), probably bilateral adrenal hyperplasia. Only rarely has the hypokalaemia in this disorder caused serious cardiac arrhythmias,
described as recurrent ventricular flutter and fibrillation 13 14 but clearly torsade de pointes.5 QT/u prolongation could have been due to the combination of hypokalaemia, quinidine-like therapy, and abnormalities of repolarisation caused by pre-excitation; we cannot incriminate a congenital QT-prolongation syndrome.5 In the second patient the hypokalaemia was associated with periodic skeletal muscle dysfunction complicated by persistent myopathy. In this disorder acute alterations in the balance between the levels of intracellular and extracellular potassium are almost certainly part of a chronic abnormality of potassium exchange, Irreversible skeletal myopathyl5 may be partly due to the hypokalaemia itself,16 and this may have caused permanent myocardial damage in our second patient. Cardiac arrhythmias, usually ventricular extrasystoles, have been reported in familial periodic paralysis with or without hypokalwmia.6 15 17 In our case the hypokalaemia was associated not only with ventricular tachycardia, torsade de pointes, and ventricular fibrillation, but also with second-degree s.A. and A.v. nodal block. Special care is needed when correcting hypokalaemia in the presence of sinus-node dysfunction; if this is too rapid there may be further temporary sinus-node suppression; 18 our second patient was protected by a demand ventricular pacemaker. Other factors likely to cause torsade de pointes in our cases included bradycardia (case 2 between periods of ventricular arrhythmia), a long QT-interval" (case 1), and treatment with quinidine-like drugs (both
DR
CURRY AND OTHERS: REFERENCES
THE incidence of adenocarcinoma of the pancreashas increased over the past forty years and this disease now ranks as the fourth most common cause of cancer deaths in the U.S.A. exceeded only by cancers of the lung, large bowel, and breast.’ Early diagnosis is difficult. The disease is often insidious in onset and produces only vague and non-specific symptoms during its early stages. Current non-invasive techniques for the diagnosis of pancreatic cancer that might be used for screening, such as upper-gastrointestinal-tract X-ray examination, 75 Seselenomethione scans, and ultrasound, are either not
I
cases). Potassium repletion controlled the arrhythmias, but because of the possibility of permanent myocardial damage we have continued with mexiletine as an additional measure to prevent relapse. We are grateful to Dr B. Hollings and to Prof. P. Sleight for referring the patients, and to Dr J. D. H. Slater and Dr R. Wiggins for the endocrine and metabolic studies in case 1. This work was supported by a grant from the British Heart Foundation.
Requests for reprints should be addressed to D. K., Royal graduate Medical School, Du Cane Road, London W12 OHS.
Post-
1. Levine, H. D. Mod. Concepts cardiovasc. Dis. 1954, 23, 246. 2. Mason, D. T., Zebris, R., Lee, G., Hughes, J. L., Spann, J. F., Amsterdam, E. A. Am. J. Cardiol. 1971, 27, 546. 3. Surawicz, B., Lepeschkin, E. Circulation, 1953, 8, 801. 4. Kunin, A. S., Surawicz, B., Sims, A. New Engl. J. Med 1962, 266, 228. 5. Krikler, D. M., Curry, P. V. L. Br. Heart J. 1976, 38, 117. 6. Scherf, D., Schott, A. Extrasystoles and Allied Arrhythmias, p. 763. London, 1973. 7. Paes de Carvalho, A in Electrolytes and Cardiovascular Diseases (edited by E. Bajusz) p. 55. Basle, 1965. 8. Weaver, W. F., Burchell, H. B Circulation, 1960, 21, 505. 9. Redleaf, P. D., Lerner, I. J. J. Am. med. Ass. 1968, 206, 1302. 10. Scherf, D.. Cohen, I., Shafiha, H. Cardiologia, 1967, 50, 129. 11. Rubin, A. L.,Lubash, G. D., Cohen, B. D., Brailovsky, D., Braveman, W. W. S., Luckey, E. H. Circulation, 1958, 18, 227. 12. Lown, B., Weller, J. M., Wyatt, N., Hoigne, R , Merrill, J. P. J. clin. Invest. 1952, 31, 648. 13. Morton, P., Bekheit, S Irish J. med. Sci. 1970, 3, 357. 14. Sekso, M., Baric, L., Birtic, K. Wien. med Wschr. 1972, 122, 753. 15. Klein, R., Ganelin, R, Marks, J. F, Usher, P., Richards, C. J. Pediatrics, 1963, 62, 371. 16. Nayler, W. Personal communication. 17. Gass, H., Cherkassy, M., Savitzky, N. Medicine, 1948, 27, 105. 18. Zipes, D. P. in Cardiac Arrhythmias edited by L. S. Dreifus and W. Likoff). p. 55. New York, 1973.
We thank Dr P. Ruf of the Swiss Clinic for Epileptics for collecting the sera; Mrs H. Spichiger and Mrs C. Nillo for determing the drug plasma levels; Mrs R. Kellerhals for her assistance in measuring immunoglobulins ; and Mrs M. Schaich for secretarial help.
Requests for reprints should be addressed to P. J. G. REFERENCES 1. Sorrell, T.
C., Forbes, I. J., Burness, F. R., Rischbieth, R. H. C. Lancet, 1971, ii, 1233. 2 Grob, P J., Herold, G. E. Br. med J. 1972, ii, 561. 3. Seager, J., Jamison, D. L., Wilson, J., Hayward, A. R., Soothill, J. F. Lancet.
4
1975, ii, 632.
Rubenstein, K. E., Schneider, R. S., Ullman, E. F. Biochem. biophys. Res. Comm 1972, 47, 846.
VENTRICULAR ARRHYTHMIAS AND HYPOKALÆMIA PAUL CURRY WILLIAM STUBBS*
DAVID FITCHETT DENNIS KRIKLER
Cardiovascular Division, Royal Postgraduate Medical School Hammersmith Hospital, London W12 0HS
of life-threatening ventricular arrhythmia (torsade de pointes) due to chronic mild hypokalæmia, caused by hyperaldosteronism and familial periodic paralysis are described. Correction of the hypokalæmia, supplemented by mexiletine, controlled the arrhythmias.
Summary
Two
cases
Introduction HYPOKALAEMIA is known to cause cardiac arrhythmias and to impair atrioventricular (A.v.) conduction especially in patients receiving digoxin or suffering from heart-disease.1-3 Life-threatening ventricular arrhythmias may complicate profound and sudden hypokal aemia4 and can be controlled by potassium repletion.S We report two cases of torsade de pointesS presenting with Adams-Stokes attacks, resulting from chronic mildhypokalaemia due respectively to hyperaldosteronism and to periodic muscular paralysis; both cases responded to correction of the hypokalaemia and the administration of mexiletine.
Case-reports Case 1 A 28-year-old woman had had palpitations for 10 years after which they became more severe and were complicated by syncope. Her E.c.G. showed multiple ventricular extrasystoles closely related to the preceding T waves, u-wave accentuation, QT and Qu prolongation (QTC 0-66 s), and the Wolff-ParkinsonWhite syndrome type A (fig. 1). Her plasma-potassium ranged between 2.8 and 3-5 mmol/1. She deteriorated on disopyramide (100 mg 6-hourly) and was admitted to Hammersmith Hospital. Her blood-pressure was 160/100 mmHg. Electrophysiological studies confirmed prolonged ventricular repolarisation and increased ventricular vulnerability to premature depolarisation during the relative refractory period as well as a left-sided anomalous A.v. pathway; sinoatrial (s.A.) and A.v. nodal function were normal. Chest X-ray, echocardiogram, plasma-cortisol, and audiometry were normal. Urinary potassium excretion was high (131 mmol/24 h) but tests of renal tubular function including urinary acidification were normal. Plasma-renin activity was 1-50 pmol/h/ml recumbent (normal range 112-65) and *Present address:
Southampton
General
Hospital
5. Bastiani, R. J., Phillips, R. C., Schneider, R. S., Ullman, E. F. Am. J. med. Technol. 1973, 39, 211 6. Grob, P. J., Jemelka, H. Schweiz. med. Wschr. 1971, 101, 223. 7. Laurell, C. B. Ann. Biochem. 1966, 15, 45. 8. Terasaki, P. J., Clelland, J. D. Nature, 1964, 204, 998. 9. Slavin, B. N., Fenton, G. M., Laundy, M., Reynolds, E. H. J. neurol. Sci. 1974, 23, 353. 10. Massimo, L., Pasino, M., Rosanda-Vadala, C., Tonini, G P., De Negri, M., Saccomani, L. Lancet, 1976, i, 860. 11. Masi, M., Paolucci, P., Perocco, P., Franceschi, C. Lancet, 1976, i, 860. 12. Alarcon-Segovia, D., Fischbein, E., Reyes, P A., Dies, M., Schwadsky, S. Clin. exp. Immun. 1972, 12, 39. 13. Beernink, D. A., Miller, J. J. J. Pediat. 1973, 82, 113. 14. Alarcon-Segovia, D. Clins. rheum. Dis. 1975, 1, 573 15. Buckley, R. H. Birth Defects orig. Art. Ser. 1975, 11, 134. 16. Boder, E. ibid. p. 255.
232
Fig.
1-Case 1: E.C.G. leads
Increased ventricular
Fig. 2-Case
II, VI, and
V6..
ectopic activity,
torsade de
pointes, QT prolongation, and Wolff-Parkinson-White syndrome type A
are
shown.
2: E.C.G. leads II.
(a) Bidirectional ventricular tachycardia with Wenckebach block; there is a single ventricular hypokalaemia and on mexiletine.
S.A. depression; (b) suppression of the tachyarrhythmia by intravenous ajmaline, showing S.A. extrasystole; (c) sinus rhythm with normal S.A. and A.v. conduction following correction of the
2.58 pmoVh/ml erect (normal range 2.82-4-03); aldosterone excretion was 78-1 mnoV24 h (range 14-70 nmoV24 h) and was not suppressed after sodium loading (56-2 nmol/24 h; normally up to 19.5 nmol/24 h). Diurnal plasma-aldosterone concentrations after sodium loading were 0.45 nmol/1 (8-00 A.M.) and 1.56 nmol/1 (11-30 A.M.). Adrenal venograms showed enlargement of both adrenal glands, with no adenomata. Selective adrenal venous sampling showed plasma aldosterone/cortisol ratios of 3/1 (right) and 6/1 (left) (both high) compared with 0. 3/1 in the inferior vena cava. Quinidine aggravated the condition, producing torsade de pointes (fig. 1) culminating in ventricular fibrillation which required D.C. countershock. With potassium supplements (64 mmol in 24 h), spironolactone (25 mg 8-hourly), and mexiletine (100 mg 6-hourly), it was possible to suppress the arrhythmia (plasma-potassium 4-6 mmol/1 ; QTC 0-53 s). Case 2 A 32-year-old woman had developed arrhythmias at the age of 11 years and epileptiform fits sometimes preceded by syncope and attacks of muscular paralysis 16 years later. She also
had fluctuating muscle weakness, stiffness, and aching, especially after exertion. Neurological investigations had been normal. During the next few years she had three major myopathic crises consisting of stiffness, myalgia, rapid wasting, hypotonia, and variable paralysis, each resolving spontaneously in about 3 weeks. Examination revealed generalised muscular weakness and mild, mainly proximal, wasting. Her pulse was rapid and irregular and her blood-pressure 90/50 mm Hg. E.C.G. showed repetitive predominantly bidirectional ventricular tachycardia (fig. 2a), sinus arrhythmia, and varying second-degree A.v.
block. Intravenous ajmaline (25 mg) suppressed the ventricular arrhythmia but S.A. block was now seen (fig. 2b). The plasma-potassium was 3.22 mmol/1; chest X-ray and echocardiogram were normal. On the third day she had syncope due to ventricular fibrillation; D.c. shock’(100 J) and intravenous lignocaine (3 mg/min) converted the rhythm to bidirectional ventricular tachycardia followed by junctional rhythm and S.A. block with ventriculoatrial dissociation. Electrophysiological studies confirmed the ventricular tachycardia and showed lllcreased ventricular vulnerability, S.A. block, and depressed A.v. nodal conduction; His-Purkinje conduction was normal. Despite treatment with disopyramide (200 mg 6-hourly) and temporary ventricular pacing she had-further periods of ventricular fibrillation preceded by torsade de pointes. Her plasma-potassium was now 2.8 mmol/1, and she was given in-
potassium (20 mmol/4-hourly) followed by oral supplements (64 mmol/24 h), together with amiloride 5 mg (6-hourly) and mexiletine (200 mg 6-hourly). She had no further syncopal attacks. In view of the need for anti-arrhythmic agents in high dosage and evidence of partial S.A. and A.v. block, a permanent-demand pacemaker was implanted using an epicardial electrode. The ventricular wall was pale and thin and myocardial biopsy was deemed unsafe; peripheral muscle biopsy (by Prof. R. Edwards and Prof. V. Dubowitz) showed a myopathic process with typc-u fibre atrophy, mitochondrial abnormalities, vascular changes, and a marked increase in intra and peri fibre acid-phosphatase activity. On amiloride (5 mg 8-hourly), potassium supplements (32 mmol daily), and mexiletine (200 mg 6-hourly) she has now remained well for 18 months with good muscle function despite some irreversible atrophy. The E.c.G. is normal (fig. 2c! with occasional unifocal ventricular extrasystoles. travenous
233 Discussion
Preliminary Communication
Potassium depletion may have profound effects on impulse formation and conduction,6 spontaneous ectopic activity in pacemaker cells in particular being enhanced. Conduction velocity, especially in the A.v. node, is depressed in proportion to the hypokalaemia.7 The rate at which the serum level falls accounts for some of the differences between the experimental and the clinical effects of hypokalsemia. Clinically, there is a high incidence of arrhythmia when the plasma-potassium falls below 3.2 mmo1/l8 but there are very few reports of lifethreatening ventricular arrhythmias. Hypokalaemia is frequently due to prolonged or unbalanced use of powerful diuretics9 but may also result from intestinal disorders,10 renal dialysis," and corticosteroid therapy,t2 in which arrhythmias have been described.
COMPUTERISED AXIAL TOMOGRAPHY FOR DIAGNOSIS OF PANCREATIC CANCER G. WIGGANS
P. S. SCHEIN
D. SCHELLINGER J. S. MACDONALD J. HARBERT Divisions of Medical Oncology and Nuclear Medicine, Vincent T. Lombardi Cancer Research
Center, and Georgetown University Hospital, Washington, D.C. 20007, U.S.A.
Computerised axial tomography demonstrated the presence of a mass lesion in the pancreas in 9 (64%) of 14 patients with histologically confirmed pancreatic cancer. Since this was a retrospective analysis, the percentage of false positive and negative results using this technique is not as yet known. The technique appears accurate in detecting abnormal pancreatic masses of 10 cm in diameter or more, however, for masses less than 10 cm in diameter the yield at present is only 33%. With further technical refinement to increase resolution, the automatic computerised transverse axial scan should prove to be an invaluable procedure for the detection of pancreatic carcinoma, in designing radiation therapy ports, and in providing objective information regarding response of therapy and progression of disease.
Summary
In the first patient, hypokalaemia was due to primary hyperaldosteronism (Conn’s syndrome), probably bilateral adrenal hyperplasia. Only rarely has the hypokalaemia in this disorder caused serious cardiac arrhythmias,
described as recurrent ventricular flutter and fibrillation 13 14 but clearly torsade de pointes.5 QT/u prolongation could have been due to the combination of hypokalaemia, quinidine-like therapy, and abnormalities of repolarisation caused by pre-excitation; we cannot incriminate a congenital QT-prolongation syndrome.5 In the second patient the hypokalaemia was associated with periodic skeletal muscle dysfunction complicated by persistent myopathy. In this disorder acute alterations in the balance between the levels of intracellular and extracellular potassium are almost certainly part of a chronic abnormality of potassium exchange, Irreversible skeletal myopathyl5 may be partly due to the hypokalaemia itself,16 and this may have caused permanent myocardial damage in our second patient. Cardiac arrhythmias, usually ventricular extrasystoles, have been reported in familial periodic paralysis with or without hypokalwmia.6 15 17 In our case the hypokalaemia was associated not only with ventricular tachycardia, torsade de pointes, and ventricular fibrillation, but also with second-degree s.A. and A.v. nodal block. Special care is needed when correcting hypokalaemia in the presence of sinus-node dysfunction; if this is too rapid there may be further temporary sinus-node suppression; 18 our second patient was protected by a demand ventricular pacemaker. Other factors likely to cause torsade de pointes in our cases included bradycardia (case 2 between periods of ventricular arrhythmia), a long QT-interval" (case 1), and treatment with quinidine-like drugs (both
DR
CURRY AND OTHERS: REFERENCES
THE incidence of adenocarcinoma of the pancreashas increased over the past forty years and this disease now ranks as the fourth most common cause of cancer deaths in the U.S.A. exceeded only by cancers of the lung, large bowel, and breast.’ Early diagnosis is difficult. The disease is often insidious in onset and produces only vague and non-specific symptoms during its early stages. Current non-invasive techniques for the diagnosis of pancreatic cancer that might be used for screening, such as upper-gastrointestinal-tract X-ray examination, 75 Seselenomethione scans, and ultrasound, are either not
I
cases). Potassium repletion controlled the arrhythmias, but because of the possibility of permanent myocardial damage we have continued with mexiletine as an additional measure to prevent relapse. We are grateful to Dr B. Hollings and to Prof. P. Sleight for referring the patients, and to Dr J. D. H. Slater and Dr R. Wiggins for the endocrine and metabolic studies in case 1. This work was supported by a grant from the British Heart Foundation.
Requests for reprints should be addressed to D. K., Royal graduate Medical School, Du Cane Road, London W12 OHS.
Post-
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