263 INTERACTION BETWEEN CEPHALOSPORINS AND ALCOHOL
’Antabuse’ effect with moxalactam and wonder if such a reaction is a risk with other 9-lactams. We have seen a similar response to cefamandole, another Mactam with a slightly different side-chain. A 68-year-old man with a bladder cancer had a right nephrectomy because of pyonephrosis complicated by severe renal failure. We gave him cefamandole 750 mg intravenously every 8 h together with amikacin 250 mg i.v. every 36 h for Staphylococcus epidermidis septicaemia and urinary tract infection due to Proteus mirabilis and Pseudomonas ceruginosa. On the sixth day of the treatment the patient asked for some wine, and 30 min after drinking it he had a severe peripheral flush with shock (blood pressure 40-50 mm Hg) that responded to plasma expansion with 2 litres of ’Plasmion’. The same thing happened 48 h later when he took a another drink of wine.
SIR,-Neu and Prince’ have described
Faculty of Medicine, University of Dijon, and C.H.U. de Dijon, 21034 Dijon, France
an
H. PORTIER J. M. CHALOPIN M. FREYSZ Y. TANTER
decreased from 6:1 below 60 years of age tients over 80 years.
to
about 1:1 in pa-
patients undergoing amputation appeared to have more arterially reconstructed; gangrene was reported in 80% versus 7% in the arterial reconstruction group. Further, diabetes was reported in 11% of the ampuThe
advanced disease than those
group versus 4% of those who had arterial reconstruction. Cardiac disease and malignant neoplasms, however, were reported equally frequently in the two groups-in 12% and in tated
2% respectively. The results indicate that the higher mortality after amputation than after arterial reconstruction is not just due to the higher mean age in the amputation group, but also to more advanced lower limb disease and, to a certain degree; to accumulation of specific risk factors such as diabetes. The mortality after operation for lower limb ischamuc disease can probably be reduced by operating at an earlier state of ischaemia before the patients become exhausted from rest pain and intoxicated by gangrene. On the other hand, as more and more elderly patients are offered arterial reconstruction for limb salvage, the mortality after arterial reconstruction is bound to increase appreciably from its present modest level. Ved Ermelunden 16,
DK-2820 Gentofte,
JENS
Denmark
REVASCULARISATION OF THE LOWER LIMB
SIR,-Your editorial (July 5, p. 23) compares the results of arterial reconstruction with the results of amputation in the treatment of severe lower limb ischaemia. Few would deny that arterial reconstruction is the treatment of choice: the quality of life and the capacity for work and for self-care is higher after successful revascularisation than after amputation. The frequently reported higher mortality after amputation than after arterial reconstruction may, however, not be due to the risks of the two types of operation per se. It could very well be the result of the differences in patient selection, resulting in MORTALITY AFTER AMPUTATION AND AFTER ARTERIAL
RECONSTRUCTION FOR LOWER LIMB ISCH1F.MIA: MEN AND
WOMEN, DANISH HOSPITALS, APRIL 1 TO DEC.
31, 1976.
H. EICKHOFF
NEUROLOGICAL DISEASE IN FORMER FAR-EAST PRISONERS OF WAR
SiR,—The report by Dr Gibberd and Dr Simmonds (July 19, p. 135) is of particular interest in that in some. of their pa-
neurological disease first developed many years after repatriation. May I suggest that these clinicians may have been observing the long-term sequeloc of virus infection, particularly tients
with one or more arboviruses? We have an experiment of Nature in that non-immune young adults were exposed, in an area bounded by China,. Thailand, Japan, and Indonesia and over several years, to infections with Japanese encephalitis (JE), dengue, and, probably, tick-borne encephalitis (TBE) viruses. Even in a favourable environment, travellers to endemic zones acquire antibodies to arboviruses,l and we may safely assume that almost all prisoners-of-war became infected, clinically or sub’
clinically.
accumulation of non-specific (high age) and specific (advanced lower limb disease, complicating diseases) risk factors in the amputation group. A study of amputations and arterial reconstructions done for arterial insufficiency of the lower limbs covering all Danish hospitals gave us an opportunity to study this possibility.2 During the period April 1, 1976, to Dec 31, 1976, 813 patients (862 admissions) were treated by amputation, 580 patients, (595 admissions) had arterial reconstructions, and 29 patients had both types of operation. The hospital mortality was the same in both sexes for both types of operation. The table shows that the mortality for all patients was more than three times higher in the amputation group than in the arterial reconstruction group. However, the ratio between the % mortality-rates 1. Neu HC, Prince AS. Interaction between moxalactam and alcohol. Lancet 1980; i:1422. 2. Eickhoff JH, Buchardt Hansen HJ, Lorentzen JE. The effect of arterial reconstruction on lower limb amputation rate: an epidemiological survey based on reports from Danish hospitals. Acta Chir Scand suppl 502: 181-87.
The relation of arboviruses to chronic neurological disease has been suspected since TBE virus infection was shown to be an antecedent of Kozhevnikov’s epilepsy.2 In a recent review,3 a variety of chronic and progressive neurological syndromes, including seizure disorders, paralysis, and dementia, have been demonstrated as late sequels to TBE. Of particular relevance to Gibberd and Simmonds’ paper are descriptions of the late development of such disease in Japanese patients who had had TBE as prisoners-of-war in Siberia from 8 to 13 years earlier. Previous JE virus infection may also be related to the subsequent development of chronic neurological disease.’ My suggestion is probably biased by an interest in the possible long-term neurological effects of virus infection.5 Nevertheless, it is capable of verification and some good might have B, Sutton RNP. Arbovirus infections in travellers J Infect 1979; 1: 257-61. 2. Brody JA. Chronic sequelæ of tick-borne encephalitis and Vilyuisk encephalitis. In: Gajdusek DC, Gibbs CJ, Alpers M, eds. Slow, latent and temperate virus infections (NINDB Monogr no 2). 3. Asher DM. Persistent tick-borne encephalitis infection in man and monkeys: Relation to chronic neurologic disease. In: Kurstah E. Arctic and tropical arboviruses. New York: Academic Press, 1979; 179-95. 4. Edelman R, Schneider RJ, Vejjajiva A, Pornpibul R, Voodhikul P. Persistence of virus-specific IgM and clinical recovery after Japanese encepha1. E1 Tahir
5.
litis. Am J Trop Med Hyg 1976; 25: 733-38. Sequeira LW, Jennings LC, Carrasco LH, Lord MA, Curry A, Sutton RNP. Detection of herpes simplex viral genome in brain tissue. Lancet 1979; ii: 609-12.
264 from the experiences of these be shed on the aetiology of idiopathic
come
if thereby light could parkinsonism or dementia. men
Department of Virology, Withington Hospital,
R. N. P. SUTTON
Manchester M20 8LR
SKIN CANCERS IN XERODERMA PIGMENTOSUM: RESPONSE TO INDOMETHACIN AND STEROIDS skin
linked to ultraviolet exposure are and rarely metastasise. This is true in basal cell carcinomas, squamous cell carcinomas of the face,I,2 and malignant melanomas arising in lentigo maligna.3 Even the most malignant-looking fibroxanthoma behaves as a benign tumour. Thus it is feasible that in these lesions systemic immunity prevents or delays metastasis while diminished local immunity allows tumours to invade surrounding structures. This argument may also hold for xeroderma pigmentosum (XP) where the evidence linking tumours with UV exposure is, unlike that for the other tumours mentioned, very strong and attributed to a genetically determined defect in DNA repair of damage inflicted by UV light. Our findings (unpublished) indicate that XP neoplasms can be highly pleomorphic, with morphological evidence of neoplastic progression, even within the tumour itself-yet they are usually slowgrowing and late to metastasise. Thus it is likely that immunological mechanisms do indeed operate in XP. Poorly repaired damaged DNA, or the tumour antigens, may encourage the generation of suppressor lymphocytes. These cells may produce prostaglandins in excessive amounts, as happens in Hodgkin’s disease.5 This overproduction may be neutralised by indomethacin, while steroids could eliminate the precursors of the suppressor cells.6 For these reasons we have experimented with these drugs in patients with XP tumours seen at this hos-
SIR,-In
man
cancers
generally slow-growing
pital. Nine patients were selected from a series of twenty-five referred during the past year who met standard criteria for the diagnosis of XP,2 including sensitivity to sunlight, excessive freckling, hyperpigmentation, and early onset of skin tumours (all histologically confirmed). Patients with inoperable tumours and those who refused surgery were treated medically. Inpatients and those living in Baghdad were 1. Lever
WF, Schaumburg-Lever G, eds. Histopathology of the skin. Philadelphia: J. B. Lppincott, 1975; 537.
2. Lund HZ. How often does squamous cell carcinoma of the skin metastasize? Arch Derm 1965; 92: 635-36. 3. Clark WH Jr, Mihn MC Jr. Lentigo-maligna and lentigo-maligna melanoma.
Am J Path 1969; 55: 39-67. DF, Helwig EB. Atypical
fibroxanthoma of the skin. Cancer 1973; 31: 1541-52. 5. Goodwin JS, Messner RP, Bankhurst AD, et al. Prostglandin-producing suppressor cells in Hodgkin’s disease: N Engl J Med 1977; 297: 963-68. 6. Schechter B, Felman M. Hydrocortisone affects on tumour growth by eliminating precursors of suppressor cells. J Immunol 1977; 119: 1563-68.
4. Rretzin
XP
Patient 2: SCC of forehead.
Left: before treatment. Right: 3 weeks after combination therapy.
given indomethacin 25-100 mg daily; if the response was unsatisfactory after 2 weeks prednisolone 0.25-0.5 mg/kg daily was added. Patients from out of town were given the combination from the start. Follow-up was done weekly by tumour measurement and laboratory and radiological investigations.
patients had a complete regression of their tumours (see table). Patient 1 had an extensive, inoperable squamous cell carcinoma of the lower lip metastatic to a submental lymph Three
node. The tumour regressed on indomethacin alone, but the patient wanted further therapy so prednisolone was added. Within 3 weeks the tumour of the lip had regressed completely and the submental node had shrunk from 2 -6 to 0.6cm in diameter and was easily removed surgically. He has now been free of recurrence for 9 months. Patient 3 had extensive squamous cell carcinoma of the forehead (see figure). On indomethacin and prednisolone the tumour regressed completely within 3 weeks. A second extensive primary of the nose, arising while the dose was being tapered off, regressed completely within 6 weeks with a higher dose. 6 months later he has had no recurrence. Patient 4 refused surgery; the tumour regressed completely within 3 weeks on combination therapy. A second primary developed 6 months later (an ulcerative lesion of the cheek); this regressed completely when the patient took indomethacin on his own. Patient 8 had many facial tumours which had been long neglected, with the eyeball bulging out presumably due to retrobulbar invasion. All exophytic tumours disappeared with 6 weeks on indomethacin 100 mg daily. Her eyeball returned almost to normal. Only one patient (no. 7) did not respond to treatment; she later agreed to extensive surgery.
PATIENTS, TUMOURS, TREATMENT,
SCC=Squamous cell carcinoma. I=indomethacin. P=Prednisolone.
AND RESPONSE