NORTHWICK PARK ECT TRIAL

500

al.1 that cephalosporins were the only suitable antibiotics for use in one outbreak of Staph. epidermidissepticaemia. However, we were to find that gentamicin, minocycline, and vancomycin tested, all are active against Staph. epidermidis in vitro.2 The

surprised were not

cephalosporin tested and used for treatment was not identified. This could be crucial: there may be

as

much

as an

80-fold difference in

activity against Staph. epidermidis between the most active and the least active ones (cephalexin, cephalosporin (cephaloridine) 2 mean

cephradine, and cefoxitin).2

Of greater inportance, however, is the fact that your editorial omits to mention two antibiotics which are highly active against Staph. epidermidis. Fusidic acid is effective in vitro and clinically against Staph. aureus3 and it is also highly active against most coagulase-negative staphylococci.4Rifampicin was the most active of sixty-five antibiotics tested by Sabath et al .,2 having a mean minimum inhibitory concentration (MIC) of 0-002 /-lg/mI. In another series5rifampicin was tested against strains isolated from infected prostheses: the MIC was 0-03 jLtg/ml, and the minimum bactericidal concentration was 0 -06 g/ml. There now appears to be a trend6 towards the wider clinical use of rifampicin in combination against staphylococci, and Archer et al. have reported its successful use in two cases of Staph. epidermidis prosthetic endocarditis. Sande8 has recomended the wider use of rifampicin for such indications: he reports favourable results, especially in combination with a (3-lactam antibiotic or vancomycin. Thus, both rifampicin and fusidic acid should be included in the group of antibiotics routinely tested against Staph. epidermidis, and serious consideration should be given to the use of one or the other (preferably in combination with another suitable antibiotic) in the treatment of infections caused by this species. Rifampicin and fusidic acid may not be suitable for combination with each other since this combination fails to prevent the emergence of resistant

strains.99

Department of Medical Microbiology, Royal Free Hospital, London NW3 2QG

W. BRUMFITT J. M. T. HAMILTON-MILLER

NON-INVASIVE STUDY OF THE CAROTID ARTERY

SIR,-Dr de Bono and Dr Warlow’s findings (Feb. 13,

p. 343) highlight the need for non-invasive studies of the carotid arteries in the search for cerebral emboli in patients with transient ischaemic attacks and amaurosis fugax in that 27 (43%) of their 63 carotid arteriograms were normal and a further 54 patients had no carotid studies at all. Ultrasonic techniques can accurately identify lesions of the carotid arteries. In Bristol, Lusby et al.10,11 have shown that the ’MAVIS’ Doppler imaging (G.E.C.) and ’ATL Duplex’ systems will safely and non-invasively detect occlusive atheroma at the

carotid bifurcation. In our hands use of these systems has reduced the proportion of negative carotid arteriograms from 46% to 21%. Further, surgically correctable carotid stenoses were found in patients with non-specific cerebral symptoms which were insufficiently typical to justify arteriography on clinical grounds alone. Ultrasonic imaging systems are making an increasing contribution towards stroke prevention by screening patients with worrying premonitory symptoms. Those in whom important lesions are shown can then proceed to arteriography with a view to carotid

endarterectomy. Departments of Surgery and Medical Physics, Bristol Royal Infirmary,

R. N. BAIRD

Bristol BS2 8HW

J. P. WOODCOCK NORTHWICK PARK ECT TRIAL

SIR,-Since your publication of the trial from Northwick Park (Dec. 20/27, p. 1317), a further double-blind trial has been reported by West. Not only did his simulated group fail to show any appreciable improvement but he also used alphadolone as an anaesthetic agent, whereas Dr Johnstone and her colleagues used methohexitone 155 mg/kg. Ayd2found that methohexitone shortened convulsions, and Witztum et al.showed a significant shortening of convulsions between 066 and 099 mg/kg. Lambourn and Gill4 used only 1 mg/kg methohexitone sodium. We believe that this high dose of a barbiturate anaesthetic with known anticonvulsant properties significantly shortened the therapeutic convulsions, leading to undertreatment of the real ECT group. In support of this we have re-plotted the results of Johnstone and colleagues (see figure) using the percent improvement as opposed to the absolute Hamilton rating scale scores, since the real group started at a higher score than the simulated group. Our figures are 1. West ED. Electric convulsion therapy m depression:

a

double-blind controlled trial. Br

Med J 1981; 282: 355-57. 2. Ayd FJ. Methohexital (Brevital): a new anesthetic for electroconvulsive therapy. Dis Nerv Syst 1961; 22: 388-90. 3. Witztum J, Baker M, Woodruff RA, Pitts FN. Electrotherapy: The effects of methohexital on EKG. Dis Nerv Syst 1970; 31: 193-95. 4. Lambourn J, Gill D. A controlled comparison of simulated and real ECT. Br J Psychiat 1978; 133: 514-19.

RA, Dixon C, Bernard K, et al. Staphylococcus epidermidis: an important pathogen. Sugery 1979; 86: 507-14. Sabath LD, Garner C, Wilcox C, Finland M. Susceptibility of Staphylococcus aureus and Staphylococcus epidermidis to 65 antibiotics. Antimicr Ag Chemother 1976; 9:

1. Forse 2.

962-69. 3. Kucers A, Bennett NMcK. The use of antibiotics. 3rd ed. London: Heinemann, 1979: 466. 4. Richardson JF, Marples RR. Differences in antibiotic susceptibility between Staphylococcus epidermidis and Staphylococcus saprophyticus. J Antimicr Chemother 1980; 6: 499-510. 5. Archer GL. Antimicrobial susceptibility and selection of resistance among Staphylococcus epidermidis isolates recovered from patients with infections of indwelling foreign devices. Antimcr Ag Chemother 1978; 14: 353-59. 6. Nessi R, Fowst G Clinical use of rifampicin in combination for non-mycobacterial infections: a survey of published evidence J Int Med Res 1979; 7: 179-86. 7. Archer GL, Tenenbaum MJ, Heywood HB. Rifampin therapy of Staphylococcus epidermidis. JAMA 1979; 240: 751-53. 8. Sande MA. Future trends in the prevention and theapy of endocarditis. Chemiot Antimicr 1980; suppl to no 2: 87-88. 9. Grüneberg RN, Emmerson AM. Failure to prevent emergence of bacterial resistance by combination of two antibiotics: Fusidic acid and rifampicin. J Antimicr Chemother 1980; 6: 562-64. 10.

11.

Lusby RJ, Woodcock JP, Skidmore R, Jeans WD, Clifford PC, Baird RN. Carotid artery disease: a prospective evaluation of ultrasonic imaging in the detection of low and high grade stenosis. Br J Surg 1980; 67: 823. Lusby RJ, Machleder HI, Jeans WD, Skidmore R, Woodcock JP, Clifford PC, Baird RN. Vessel wall and blood flow dynamics in arterial disease. Proc Roy Soc (in press).

Percent improvement of Hamilton Rating Scale versus time. The raw data are shown below:

501

necessarily approximate as the original paper showed only a graph, not a table. The real scores approximate very well to the exponential and the simulated group rather less well decay curve graph shows not only that the real toy=63(I-e’° ). This redrawn simulated the than faster group (50% improvement group improved at 1 - 7 weeks v. 3 weeks) but also they tended towards a better quality of remission (74-5% improvement v. 63%). The 1 month and 6 month improvement of the simulated group is not only below the previous trend line but has also broken through the asymptote at

SERUM LEVELS OF iPTH IN PATIENTS WITH RENAL FAILURE MEASURED BEFORE AND AFTER 15 DAYS’ TREATMENT WITH

CIMETIDINE

y=I-e-o’65X)

63%, and we believe that this

was

due

to

the effect of the anti-

depressants and ECT eventually prescribed for the majority. Similarly, the late results for the real group show a slight relapse which we believe was due to undertreatment. Lacking a rational guide, many clinicians continue ECT until the patient shows no further improvement, whereas in this trial at week 4 the real ECT group was still improving. An excellent recent article on the visual presentation of data has been written by Altman,5astatistician at the Clinical Research Centre. Department of Psychological Medicine, Welsh National School of Medicine, Whitchurch Hospital, Cardiff CF47XB

GARETH JONES KAY CALLENDER

5. Altman DG. Statistics and ethics in medical research VI: Presentation of results. Br Med J1980; 281: 1542-44.

EFFECTS OF CIMETIDINE ON PARATHYROID HORMONE METABOLISM

SIR,-Some observations indicate that cimetidine might inhibit the secretion of parathyroid hormone in normal subjects and in patients with primary and secondary hyperparathyroidism, since its administration is associated with a decrease in the circulating levels of immunoreactive parathyroid hormone (iPTH).1-7 These studies suggest that cimetidine might have a place in the management of disorders of PTH secretion, and this would be of importance in chronic renal failure where manoeuvres to raise the plasma calcium, including treatment with vitamin-D-like compounds, do not always succeed in controlling secondary hyperparathyroidism. With one notable exception,7 however, decreases in total serum calcium have not been found after treatment with cimetidine, whereas a decrease might have been expected if suppression of serum iPTH reflected a decrease in the biologically active fragment(s) of PTH. These observations prompted us to study the effects of cimetidine in renal failure using two different antisera-one raised in rabbits and reacting with the carboxy (C) terminal fragments of the PTH molecule,8 and the other, a chicken-antiserum which reacts predominantly, though not exclusively, with aminoterminal (N) fragments of PTH.9 Eight patients with end-stage chronic renal failure (endogenous creatinine clearance < 2 ml/min) were treated with cimetidine 600 mg daily by mouth for 15 days. Serum iPTH was measured before and on the 15th day of treatment. As expected, serum levels of iPTH using the C-terminal assay greatly exceeded both normal values and those measured by the N-terminal assay (table;) (p<001). Like others, we observed a fall in plasma iPTH 1 Sherwood JK, Ackroyd FW, Garcia M Effect of Cimetidine on circulating parathyroid hormone in primary hyperparathyroidism. Lancet 1980; i: 616-19. 2. Jacob AI, Lanier D, Canterbury J, Bourgoignie JJ. Reduction by Cimetidine of serum parathyroid hormone levels in uremic patients N Engl J Med 1980; 302: 671-74. 3 Fiore CE, Lunetta M, Costa M, Malatino LS, Infantone E, Tamburino C, Heynen G. Cimetidine and calciotropic hormone in normal subjects and in chronic renal failure. Mineral Metab Res Italy 1980; 1: 101-06 4 Heath H III. Cimetidine in hyperparathyroidism. Lancet 1980; i: 980. 5 Robinson MF, Hayles AB, Heath H. Failure of cimetidine to affect calcium homeostasis in familial primary hyperparathyroidism (multiple endocrine neoplasia, type 1). J Clin Endocrmol Metab 1980; 51: 912-14. 6 Palmer FJ, Sawyers TM, Wierzbinski SJ. Cimetidine and hyperparathyroidism N Engl J Med 1980; 302: 692. 7 Lamer D, Favre H, Jacob AI, Bourgoignie JJ. Cimetidine therapy for severe hypercalcaemia in two chronic hemodialysis patients. Ann Intern Med 1980; 93: 573-74 8 Fiore CE, Heynen G, Franchimont P. L’ormone paratiroideo nella condizione normale e patologica. Rec progr Med 1979; 66: 486-519. 9 Lindall AW. Radioimmunoassay of human parathyroid hormone. In. Il paratormone: Progressi metodoligici e clinici. Genoa: Ospedali Galliera 1978; 13-31

(C) (p<0 02, Wilcoxon’s test for paired differences) after treatment with cimetidine, but no fall in total serum calcium (2’37±EM 0 - 08 vs 2 38:t010). In contrast serum levels of iPTH(1 did not fall: indeed, a small but significant (p<0’002) increase occurred, which presumably reflects more accurately the changes in the biologically active fragment of PTH, The actions of cimetidine appear, therefore, more complex than merely the inhibition of PTH secretion, and our observations suggest that this drug may act predominantly, though perhaps not exclusively, on the peripheral metabolism of parathyroid hormone. The failure of cimetidine to suppress plasma levels of calcium and iPTH(N) throw doubts on the potential of this agent in managing disorders of parathyroid secretion, particularly in chronic renal failure. Institute of Medical

Pathology II, University of Catania, Garibaldi Hospital, 95100 Catania, Italy

C. E. FIORE L. S. MALATINO

Department of Human Metabolism and Clinical Biochemistry, University of Sheffield,

J. A. KANIS

Sheffield S10 2RX

"SPACE INVADER"EPILEPSY

SIR,-The flashing display on at least one type of arcade electronic space wars game (’Astro Fighter’) is of a size, brightness, and

frequency that can cause seizures in sensitive individuals. A 17-year-old youth attended, having had one grand mal seizure, preceded by an aura of temporal lobe type, with dija vu and intense memory recall. He had also had two similar auras on separate occasions without seizure. The attacks and auras had occurred after he had played the game in question for 20-30 minutes. He was unusually fatigued on the day of the seizure.’ When I accompanied the patient to the amusement arcade, I found that for about 2 seconds at the end of the game, the screen (subtending about 25 degrees of the visual field) was filled with a multicoloured stroboscopic effect, flashing at about 15 Hz. The patient confirmed that it was this part of the game, and not the movement or destruction of the astro fighters that provoked the

attack. There was no family history of epilepsy, but the patient did have a history of a single febrile convulsion as an infant in Romania. Examination was normal and an EEG showed only a normal following response on conventional photic stimulation. Since avoiding space war arcades, the patient has had no further auras or attacks. Department of Neurology, King’s College Hospital, London SE5 9RS

D. N. RUSHTON

CO-TRIMOXAZOLE FOR KALA-AZAR

SIR,-I read with interest the letter from Dr Murphy and Dr Bong (Feb. 7, p. 323) reporting successful therapy with co-trimoxazole in a case of systemic leishmaniasis (kala-azar). They suggest cotrimoxazole as a potential alternative to antimonials. I think that their case should be interpreted with care. The diagnosis of kalaazar seems doubtful since the organism was not seen in or cultured from the bone marrow, as it is in 95% of patients with this disease; serological diagnosis is unreliable.