INDOMETHACIN IN COMBINATION

830 which might be handled at the time the blood cultures were collected. A possible source was the sodium citrate solution in the bottles for haematological investigations, which were almost always filled at the same time as blood was collected for culture. Ten bottles containing sodium citrate were sampled by sterile pipette delivering 002 ml drops to the surface of each of two CLED plates, one of which was incubated at 30°C and the other at 37°C. All ten samples yielded a growth oaf 104-105 organisms/ml identical in cultural and biochemical characteristics with the isolates from the five blood cultures. Questioning of the medical staff revealed that the correct procedure of inoculating blood culture bottles before other containers were filled was not being followed. Sometimes, the bottle containing sodium citrate solution was filled first and the needle on the syringe was not changed before blood culture bottleswere inoculated. Even when the needle was changed, the neck of the sodium citrate bottle was such that contamination of the nozzle of the syringe, and hence contamination of the new needle, would have been unavoidable. A note of a similar occurrence was included in Communicable Disease Report 81/14, and when our report appeared in our local epidemiology newsletter, investigation of a further outbreak at Withington Hospital, Manchester, which had lasted for many months, was successfully concluded. Contaminated sodium citrate bottles may well be widespread, since the manufacturers do not specify that the contents are sterile.

BLEEDING AND DIVERTICULAR DISEASE

SIR.—Dr Masden and colleagues (Feb 5, p 298), while rightly emphasising that bleeding in patients with diverticular disease frequently arises from other conditions, fail to discuss the role of colonoscopy. Two large reviews have also shown that lower gastrointestinal bleeding in patients with diverticular disease occurs from diverticular disease in only 5-15% of cases. 1,2 The incidence of diverticular disease increases with age, and an association with carcinoma, adenomatous polyps, and inflammatory disease, which are also common with advancing years, must often be due to chance. In our series of barium enemas on 260 patients with diverticular disease there were 41 (16%) with evidence of blood loss as shown by a positive ’Haemocult’ test. Of these 41, 9 had additional lesions 2 5 polyps, 1 Crohn’s disease, and one angiodysplasia.3 In diverticular disease, severe distortion of the sigmoid colon with local spasm may prevent barium studies from adequately displaying the diseased segment.2 Even with technically satisfactory X-rays, the number of missed cancers and polyps may be as high as 1007o and 16%, respectively.2 As Masden and colleagues point out, vascular ectasias are

diagnosed by colonoscopy, including

increasingly being recognised

as

a

carcinomas,

source

of

gastrointestinal

haemorrhage. Barium enemas may demonstrate diverticular disease but cannot recognise vascular abnormalities, making colonoscopy or arteriography essential for adequate diagnosis. Colonoscopy is less invasive than angiography and, when done as a diagnostic procedure, has the advantage of allowing coagulation biopsyor snare polypectomy2 as a therapeutic manoeuvre. While Wolff and colleagues have claimed that endoscopy has made "radiologic guessing games passe"5we would urge that colonoscopy be mandatory for patients with evidence of rectal bleeding in whom only diverticular disease is seen on barium enema. Department of Medicine, University,

McMaster

Hamilton, Ontario L8N 3Z5, Canada

T. GLEDHILL RICHARD H. HUNT

PSEUDOBACTERAEMIA: A BEDSIDE FAULT

SIR,—A report of Serratia pseudobacteraemiaand previously identified episodes 7,8 prompt this description of another "outbreak" of pseudobacteraemia, this time involving Pseudomonas maltophilia, to draw attention to what appears to be a widespread

problem. An outbreak of bacteraemia occurred over a 10 day period and involved five patients from three infectious-disease wards in the same hospital. Between Sept 24 and Oct 2, 1982, gram-negative bacilli showing identical characteristics, and subsequently identified as P maltophilia, were isolated from the aerobic bottle of a pair of blood cultures after overnight incubation or on the second day, from five patients. The patients had been admitted with different diagnoses, and in only one of them could the isolation of the organism have seemed plausible. The blood cultures had been collected by different members of the junior medical staff, who at the same time collected blood for other investigations. The laboratory’s first task was to rule out contamination as a result of faulty preparation of the bottles or of faulty handling at the time of subculture. Exhaustive examination of the broth, uninoculated bottles, and laboratory technique failed to reveal the source. The distribution of the cases in the three wards suggested a source common to all the wards. The cultural characteristics of the organism and its preference for growth at 30 °C suggested an environmental origin, so we decided to examine other products Rigg BM, Ewing MR. Current attitudes on diverticulitis with particular reference to colonic bleeding. Arch Surg 1966; 92: 321-22. 2. Hunt RH. Rectal bleeding, Clin Gastroenterol 1978; 7: 719-40. 3. Leicester RJ, Lightfoot A, Miller J, Colin-Jones DG, Hunt RH. An evaluation of the accuracy and value of the Haemocult test in symptomatic patients. Br Med J (in press). 4. Howard OM, Buchanan JD, Hunt RH. Angiodysplasia of the colon: Experience of 26 cases Lancet 1982; ii: 16-19. 5. Wolff WI, Shmya H, Geffen A, Ozoktay S, DeBeer R Comparison of colonoscopy and the contrast enema m five hundred patients with colorectal disease. Am J Surg 1975, 1.

129: 181-86. 6. Cookson BD, Mehtar S, Sadler G. Serratia pseudobacteraemia. Lancet 1982; ii 1276. 7 Ives KN, Evans NAP, Thom BT, Harper EA Serratia marcescens pseudobacteraemia in a special care baby unit. Lancet 1982; ii: 994. 8 Willson PA, Petts DN, Baker SL. An outbreak of pseudobacteraemia. Br Med J 1981; 283: 866.

However, pseudobacteraemia will occur only if standard procedures are not adhered to and there is faulty technique at the bedside, as in all the episodes cited. A reminder to the junior medical staff at our hospital has resulted, possibly only temporarily, in the disappearof

tiresome problem which could have had serious for the patients and involved the laboratory in unnecessary and time-consuming investigations. Reports of Serratia marcescens bacteraemias and other bacteraemias apparently due to low grade, environmental pathogens seem to be on the increase; perhaps some of them are ance

a

implications

spurious. Department of Pathology, University of Manchester School of Medicine, North Manchester General Manchester M8 6RB

Hospital,

K. WHALE

DROWSINESS DUE TO HALOPERIDOL/ INDOMETHACIN IN COMBINATION have analgesic effects in their own and can also be used as analgesic-sparing agents in the treatment of chronic severe pain.3 Since neuroleptics form an essential part of drug therapy in chronic pain clinicsand since an earlier study5 also suggested efficacy of neuroleptic agents in the treatment of rheumatic pain, we decided to see if haloperidol might have a synergistic action with indomethacin in relieving the pain of osteoarthrosis.

SIR,—Neuroleptic drugs

right1,2

A placebo-controlled, double-blind, crossover study in 40 patients with osteoarthrosis of the knee, hip, or both on radiological grounds was planned. 14 days before admission to the study patients were stabilised on a constant dosage regimen of indomethacin 25 mg three times daily. After initial assessment patients were then allocated randomly in equal numbers to one of two treatment schedules-indomethacin 25 mg three times daily plus either 50 mg haloperidol or a placebo daily at night for 28 days, followed by a second treatment period of 28 days during which they received the other treatment. Assessments included duration of morning 1. Bloomfield S, Simard-Savoie S, Bernier

J, Tetrault L. Comparative analgesic activity of and morphine in patients with chronic pain. Can Med Assoc J 1964; 90: 1156-59 Lendle L Pharmakologische Seite der Schmerzbekampfung. Med Welt 1966, 21: 1188-89. Kocher R. The use of psychotropic drugs in the treatment of chronic, severe pains Eur Neurol 1976; 14: 458-64. Budd K. Psychotropic drugs in the treatment of chronic pain. Anaesthesia 1978, 33: 531-34 Hobkirk D, Rhodes M, Haslock I. Night medication in rheumatoid arthritis II Combined therapy with indomethacin and diazepam. Rheum Rehab 1977; 16: 125-27

levomepromazine

2. 3. 4. 5.

831

stiffness, range of knee flexion and/or intermalleolar distance, visual

stiffness, and at the end of the pain and investigator’s relative assessment of study, patient’s preference the treatments. A standard checklist of twelve side-effects and any other symptoms noted by the patient were recorded as none, mild, moderate, or severe. Changes in concurrent medication, although discouraged, were also recorded. The study was discontinued on ethical grounds after the recruitment of 20 patients. The age range was 41-75 years and the median duration of osteoarthrosis was 10 years (range 1-33). 13 of the 20 patients (11 on haloperidol and 2 on placebo) failed to complete the trial. 6 patients on haloperidol were withdrawn because of profound drowsiness or tiredness, a recognised sideeffect of this drug; another 4 were withdrawn for a variety of complaints thought to be due to haloperidol; and 1 withdrew because of deterioration in the osteoarthrosis. The 2 withdrawals from the placebo group were both for reasons unrelated to treatment (I failed to attend appointments and 1 required urgent

analogue rating scales for

and

antibodies were positive. The patient responded to steroids and was quite well from 1979 until muscle weakness was first noted in September, 1981. In November, 1981, she began to tire very easily and had generalised weakness, localised to the limbs at first and then to the eye muscles. Dyspnoea and dysphagia subsequently developed, and electromyography confirmed the clinical diagnosis. Mediastinal tomography revealed no thymic enlargement. Sera were available from 18 months before the development of weakness and were tested for anti-AChR and other autoantibodies. Anti-AChR was absent until about the time that weakness presented, increased over a period of 4-6 months, and then remained constant (figure). Over this period anti-ds-DNA was

genitourinary surgery). Because of withdrawals there was inadequate information to permit any conclusion about the merits of haloperidol! indomethacin. However, an inescapable conclusion was that 5.0 mg haloperidol per day added to 75 mg indomethacin per day in patients of this age group produced drowsiness and confusion so severe that in some cases the patient’s independent existence was in jeopardy; this side-effect was far more intense than anything that might have been expected for haloperidol alone. There was only one withdrawal because of worsening osteoarthrosis and further studies of the potential synergistic effect of neuropleptic and anti-inflammatory analgesic drugs seem warranted. We have started one such investigation-using sleep EEG recording to provide a more objective assessment of improvement-in a comparison of a nonsteroidal anti-inflammatory agent (diclofenac) and a hypnotic (temazepam). However, we would caution investigators against the addition of a neuroleptic agent to an anti-inflammatory drug that may itself cause central nervous system side-effects and also advise initial treatment with low doses in middle-aged and elderly patients. Clinical Pharmacology Unit

H. A. BIRD P. LE GALLEZ V. WRIGHT

(Rheumatism Research), Royal Bath Hospital, Harrogate HG1 2PS

APPEARANCE OF ANTI-ACETYLCHOLINE RECEPTOR ANTIBODIES COINCIDENT WITH ONSET OF MYASTHENIC WEAKNESS IN PATIENT WITH SYSTEMIC LUPUS ERYTHEMATOSUS of

myasthenia gravis in association with systemic lupus erythematosus (SLE) is well recognised. Usually the SLE presents after the appearance of myasthenia, sometimes after thymectomy, but it is rare to find both diseases active simultaneously.’More than 85% of patients with myasthenia gravis possess anti-acetylcholine receptor (anti-AChR) antibodies.2 However, though these antibodies are probably responsible for the loss of endplate acetylcholine receptors which underlies the myasthenia3 there has been little opportunity to relate their SIR, -The

occurrence

appearance to the onset of symptoms. We have studied a case of myasthenia gravis developing in a 30-year-old woman who had had SLE diagnosed 3 years previously on the basis of purpuric effusions, gingival bleeding, arthralgia, xerostomia, and keratoconjunctivitis sicca. There were no signs of renal involvement. Antinuclear (ANA) and the anti-ds-DNA4 1 Chan

MKL, Britton M. Comparative clinical features in patients with myasthenia gravis with systemic lupus erythematosus J Rheumatol 1980; 7: 838-40. 2 Lindstrom J An assay for antibodies to human acetylcholine receptor and serum from patients with myasthenia gravis. Clin Immunol Immunopathol 1977; 7: 36-43. 3 Vincent A Immunology of acetylcholine receptor in relation to myasthenia gravis. Physiol Rev 1980; 60: 757-824. 4 Valesini G, Masala C. The Trypaosoma lewisi immunofluorescence tests: a new simple technique for simultaneous determination of total antinuclear antibodies and the detection of antibodies to double-stranded DNA. J Immunol Methods 1982; 49: 257-65.

Correlation between onset of myasthenic symptoms and appearance of ACh-R antibodies in patient with SLE. SLE improved (1980-81), as indicated by absence of antibodies to ds-DNA and diminished ANA titres. Muscle weakness was first noted in September, 19sl, and the muscle receptor antibodies became detectable at the same time. ACh-R antibody titres are expressed in 10-10 mol.

and the ANA titre declined. Antibodies to striated and muscle, extractable nuclear antigen, salivary duct, mitochondria, thyroid, gastric parietal cells, and islet cells were

negative smooth

negative throughout. In this case, as in two others,l myasthenia gravis presented at a stage when SLE was quiescent after steroid treatment. Cytoplasmic organ-specific autoantibodies appear years before the onset of clinical symptoms in endocrine autoimmune disorders.5 What is still uncertain is whether anti-receptor antibodies behave in the same way. The appearance of serum anti-AChR close in time to the onset of clinical weakness in this case does point to a direct role for these autoantibodies in the pathogenesis of myasthenia gravis. GUIDO VALESINI ROSELLA PASTORE PIER GUISEPPE DE BERARDINIS UMBERTO SERAFINI

Medical Clinic I, University of Rome, 00161 Rome, Italy

Department of Neurological Science, Royal Free Hospital,

ANGELA VINCENT

London NW3

Department of Immunology, Middlesex Hospital,

GIAN FRANCO BOTTAZZO

London WIP 9PG

5 Doniach

D, Cudworth AG, Khoury EL, Bottazzo GF. Autoimmunity and the HLA-

system

in

endocrine diseases. In

endocrinology and metabolism:

O’Riordan

vol II.

JLH, ed. Recent advances in Edinburgh: Churchill Livingstone, 1982:

99-132

D, Whelan J, eds. London Pitman, 1982.

6 Evered

Receptors, antibodies and disease: Ciba Found Symp

90.