hyponatraemia (Na 126 mmol/1) and functional renal failure (urea 19 mmolll, creatinine 160 (imol/1). A stool smear was positive for leucocytes, and stool samples were negative for routine culture and for parasites. Flexible proctosigmoidoscopy showed a pseudomembranous mucosa. Histopathological examination confirmed the diagnosis of pseudomembranous colitis. The patient was treated with 500 mg vancomycin daily and she rapidly improved. Some serious lower gastrointestinal tract side-effects of NSAIDs have been described: non-specific colitis,l activation of quiescent idiopathic inflammatory bowel disease,2 collagenous colitis3 ulceration of the colon,4 and acute eosinophilic colitis.5 However, pseudomembranous colitis has never been reported in association with NSAIDs. A link with antibiotics is well known.6 Pseudomembranous colitis has also been reported during gold therapyNSAIDs are widely used, especially in the elderly, and we suggest that rectosigmoidoscopy should be done when diarrhoea develops after the start of NSAID therapy. Harvier Medical Clinic, Central University Hospital, 29609 Brest Cédex, France
A. GENTRIC Y. L. PENNEC
1 Ravi S, Keat AC, Keat ECB. Colitis caused by non-steroidal anti-inflammatory drugs.
Postgrad Med J 1986; 62: 773-76. 2. Kaufmann HJ, Taubin HL. Non-steroidal anti-inflammatory drug activates quiescent inflammatory bowel disease. Ann Intern Med 1987; 107: 513-16. 3 Giardiello FM, Hansen FC, Lazenby AJ, et al. Collagenous colitis in setting of non-steroidal anti-inflammatory drugs and antibiotics. Dig Dis Sci 1990; 35: 257-60. 4. Uribe A, Hohansson C, Slezak P, et al. Ulcerations of the colon associated with naproxen and acetylsalicylic acid treatment. Gastrointest Endosc 1986; 32: 242-43. 5 Bridges AJ, Marshall JB, Diaz-Arias AA. Acute eosinophilic colitis and hypersensitivity reaction associated with naproxen therapy. Am J Med 1990; 89: 526-27. 6. Price AB, Davies DR. Pseudomembranous colitis. J Clin Pathol 1977; 30: 1-12. 7. Reinhart WH, Kappeler M, Halter F. Severe pseudomembranous and ulcerative colitis during gold therapy. Endoscopy 1983; 15: 70-72.
Peripheral neuropathy associated with fluoroquinolones have been associated with adverse system (0-9-4-4% of patients), including headache, agitation, dizziness, sleep disturbance, and seizures in those with predisposing factors.1 We report a case of peripheral neuropathy associated with fluoroquinolones therapy. A 37-year-old man with chronic vertebral osteomyelitis, caused by a methicillin-susceptible Staphylococcus aureus, received oral pefloxacin 400 mg twice daily with excellent clinical and microbiological response. Many other oral regimens had failed previously, including flucloxacillin and clindamycin. After 5 months of pefloxacin, the patient had paraesthesia in his lower legs with a stocking-glove distribution, followed by progressive right foot weakness and difficulty in walking. Common peroneal nerve conduction velocity was 43 m/s. Electromyography (EMG) revealed fibrillations and polyphasic motor unit potentials in the tibialis anterior and peroneus longus muscles. Laboratory profile was normal and he denied alcohol misuse. Biopsy of rectal mucosa was negative for amyloidosis. No epidural abscess, transverse myelitis, or other causes could be found. The patient had been cured 15 years before from Hodgkin’s disease with radiochemotherapy, including vincristine for a total dose of 18 mg. Discontinuation of pefloxacin resulted in a dramatic improvement of peripheral neuropathy within 10 days. Osteomyelitis recurred 6 months later, and treatment with ofloxacin 200 mg twice a day resulted in relapse of peripheral neuropathy within 15 days, which remitted within 7 days of stopping ofloxacin. He was treated with flucloxacillin and fusidic acid for 2 months, which was stopped for a relapse of infection, which most probably resulted from poor compliance due to gastrointestinal tolerance. Because it was the only antibiotic that had demonstrated efficacy in this patient, pefloxacin, at the same dose, was resumed cautiously. Unfomtunately, peripheral neuropathy recurred within 15 days. Ciprofloxacin 250 mg twice daily orally was given instead and could be maintained for 2 months with minimum limb paraesthesia. Thereafter, these symptoms became unbearable, necessitating withdrawal of ciprofloxacin. The common peroneal nerve
effects in the central
was then 37 m/s with reduced amplitide of the digitorum brevis muscle (< 1 mV). EMG was typical of a subacute neuropathy with fibrillations and prolonged polyphasic motor unit potentials ( > 17 ms). Such alterations are indicative of a probably toxic axonal neuropathy. Patients receiving prolonged therapy with fluoroquinolones, and who had previously received neurotoxic drugs such as vinca alkaloids, should be evaluated carefully for peripheral neuropathy. Other neurotoxic agents or conditions may have the same capacity to potentiate fluoroquinolone-induced peripheral neuropathy.
conduction velocity extensor
Infectious Diseases Clinic and Microbiology Laboratory, Institut Jules Bordet, 1000 Bruxelles, Belgium
Institut Jules Bordet
M. AOUN C. JACQUY L. DEBUSSCHER D. BRON
Neurology Service, Hôpital de Tivoli
Neurology Service, Hôpital Saint-Pierre
Institut Jules Bordet
1. Wolfson JS, Hooper DC. Fluoroquinolone antimicrobial agents. Clin Microbiol Rev 1989; 2: 378-424. 2. Donofrio PD, Albers JW. Polyneuropathy: classification by nerve conduction studies and electromyography. Muscle Nerve 1990; 13: 889-903.
Cholesterol inhibition, cancer, and coronary heart disease SIR,-Professor Buchwald’s hypothesis (May 9, p 1154) that cholesterol inhibition can inhibit tumour growth exposes a fascinating paradox. Reductase inhibitors have been marketed for cholesterol lowering in the hope of decreasing coronary heart disease. Yet, there is evidence that they may actually increase coronary endpoints when used in the secondary prevention of coronary disease. Reductase inhibitors inhibit 3-hydroxy-3-methylglutarylcoenzyme A reductase, the rate limiting enzyme of the cholesterogenesis pathway, resulting in a decreased formation of mevalonate from its precursor 3-hydroxy-3-methylglutarylcoenzyme A. It is the inhibition of mevalonate and not cholesterol that is linked to inhibition of tumour cell replication.2 Other metabolites of mevalonate besides cholesterol that are decreased by reductase inhibitors include ubiquinone and isoprenoids. Isoprenoids are involved in the prenylation of proteins, and prenylated proteins are linked to DNA synthesis and ensuing cell division.3 Therein lies the connection with reductase inhibitors and tumour growth inhibition. Reductase inhibitors result in lower tissue levels of ubiquinone, a compound indispensable for the bioenergetics of cardiac muscle function. There is evidence that the reduction of ubiquinone results in a measurable decrease in cardiac function.4 This may be especially bothersome in those with
impaired coronary reserve. In the Expanded Clinical Evaluation of Lovastatin Study5,6 33 (0-5%) of 6582 patients in the drug treated group died compared with 3 (0-18%) of 1663 patients in the placebo group during 48 weeks. 31 of the 36 deaths were attributed to coronary disease and were predominantly individuals with known coronary disease at baseline.7 These findings suggest that reductase inhibitors could be deleterious in the secondary prevention of coronary disease, perhaps via the reduction of ubiquinone. Therefore, it is plausible that reductase inhibitors can lead to an increase in coronary endpoints in those with known coronary disease, mediated by decreases in ubiquinone, and equally plausible that they can lead to an inhibiton of the growth of tumours via decreases in isoprenoids. These possibilities raise several questions. Will reductase inhibitors prove beneficial in the primary prevention of coronary disease? Will they be efficacious in the secondary prevention of such disease in subsets of individuals with normal coronary reserve? Will reductase inhibitors help to prevent certain malignant diseases. Will lipophilic reductase inhibitors be more advantageous than hydrophilic reductase inhibitors in tumour inhibition? Will reductase inhibitors increase deaths due to one disease while decreasing deaths from