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AMOXYCILLIN/CLAVULANATE RESISTANTESCHERICHIA COLI

SIR,-About 60% of clinical isolates of Escherichia coli in HongKong are resistant to ampicillin and amoxycillin. Some of theseisolates resemble those reported by your correspondents fromMadrid and London (Dec 19, p 1473; Feb 6, p 304) in being alsorelatively resistant to amoxycillin/clavulanic acid. These organismsusually have amoxycillin minimum inhibitory concentrations

(MIC) of more than 128 mg/l which are reduced in the presence ofclavulanic acid to 16-64 mg/1 (amoxycillin:clavulanic acid ratio of2:1). This finding does not seem to be an artifact, since similarresults were obtained in repeated agar dilution and broth dilutiontests, and the isolates have reduced inhibition zones in disc diffusiontests. These Hong Kong strains are unlikely to be members of asingle clone, since they inhibit different biotypes, plasmid profiles,and p-Iactamases. About 80% produce TEM-1, but we have notyet determined whether they are enzyme hyperproducers. Theremainder of the isolates produce p-lactamases with pI valuesdifferent from those of TEM-1, and these are being furtherinvestigated.

SUSCEPTIBILITIES OF 341 AMOXYCILLIN-RESISTANT ISOLATES OF

E COLI TO AMOXYCILLIN AND AMOXYCILLIN/CLAVULANIC ACID

Your correspondents ask how frequently such strains occur. Wehave examined amoxycillin-resistant E coli isolated from 341

patients between 1985 and 1987 (101 from blood, 40 from bile, and200 from urine), and their amoxycillin and amoxycillin/clavulanicacid MICs are shown in the accompanying table. 36% of theseamoxycillin-resistant isolates were resistant to 8 mg/1 amoxycillin inthe presence of clavulanic acid. By extrapolation, about 20% of allHong Kong clinical isolates of E coli would be expected to showsimilar in-vitro resistance, and in our hospital we would encounterabout 480 such isolates per year. We do not know if these organismsare resistant to amoxycillin/clavulanic acid in vivo.

We are doing further studies of the mechanism of this resistance,which seems to be not uncommon in Hong Kong. Meanwhile, thereis a need to establish acceptable resistance breakpoints for

amoxycillin/clavulanic acid and similar P-lactamase inhibitorcombinations.

Department of Microbiology,Chinese University of Hong Kong,Shatin, Hong Kong

GARY FRENCHTHOMAS LING

ONE-MINUTE ENDOSCOPY ROOM TEST FORCAMPYLOBACTER PYLORI

SIR,-A means of diagnosing Campylobacter pylori infectionwhile the patient is still in the endoscopy room would be helpful.Culture methods and histological diagnosis take,days, however, andeven a gram stain of biopsy material takes a few hours. Modifiedurease tests may yield false-negative results if reported on tooquickly.’ Our modification permits the diagnosis to be made beforethe endoscope is removed.Two antral biopsy specimens were taken from 40 patients, 13

men and 27 women (mean age 53-5 years, range 26-84), with uppergastrointestinal symptoms in whom C pylori was suspected. Onespecimen was transported to the microbiology laboratory where itwas examined by gram staining; by culture on Oxoid BAB no 2 withSkirrow’s formula incubation at 37°C under microaerophilic(’Carnpypak’ envelopes) with examination after 4 and 7 days; and bya standard urease test on Christensen’s urea broth.’ The other

biopsy specimen was placed immediately, in the endoscopy room,into a capped 15 ml Eppendorf tube containing 1 ml of freshlyprepared 10% w/v urea in deionised water at pH 6-8 including two

COMPARATIVE EFFICACY OF DIAGNOSTIC TESTS FOR C PYLORI

drops of 1 % phenol-red. In this "one-minute urease test" a positiveresult was recorded if the colour changed from yellow to pink withina minute.

Culture identified C pylori in 21 (52%) of specimens. In theone-minute test, 19 of these 21 were positive and there were no falsepositives (table). Gram stain detected 16 of the 21 positive biopsies,again without false positives. The conventional urease test was lessreliable: although there were 20 positive biopsies, 3 were falsepositives (almost certainly due to coagulase-negative staphylococciand gram-negative rods) and there were 4 false negatives.By minor changes to a well-established urease test for C pylori we

now have a diagnostic test that is positive in more than 90% ofinfected individuals within a minute of biopsy. The urea-in-watersolution, unlike Christensen’s urea broth, is unbuffered so any pHchange will be detected rapidly. There were no false positives,which is a further advantage since other bacteria produce ureasethat, on prolonged culture, may be sufficient to effect a colourchange. The one-minute test missed 2 out of 21 culture-positivecases so a back-up culture should be set up. However, if the test ispositive appropriate treatment can be initiated immediately, if

clinically indicated.

We thank Julie Dent and Dr Cliodna McNulty, Public Health Laboratory,Gloucestershire Royal Hospital, for technical advice. M. J. G. F. is a

Wellcome Trust senior lecturer.

Departments of Gastroenterologyand Medical Microbiology,

St Bartholomew’s Hospital,London EC1A 7BE

A. S. ARVINDR. S. COOKS. TABAQCHALIM. J. G. FARTHING

1. McNulty CAM, Wise R. Rapid diagnosis of campylobacter-associated gastritis.Lancet 1985; i: 1443-44.

2. Moms A, McIntyre D, Rose T, Nicholson G. Rapid diagnosis of Campylobacterpyloridis infection Lancet 1986; i: 149

CROHN’S DISEASE IN MARRIED COUPLES

SIR,-Dr Schulz (Dec 12, p 1391) and Dr Colemont (Feb 6, p294) revive interest in the role of mycobacteria in Crohn’s disease. Ifan infectious agent is involved in the aetiology of Crohn’s diease thespouses of patients might be at particular risk of the disease. Wedescribe a couple in whom Crohn’s disease developed after

marriage, bringing the total number of affected couples reported inEngland and Wales to six.l-4 The finding of Crohn’s disease in thisnumber of married couples is unlikely to have resulted by chance.The couple married in 1942. The husband came from South

Wales and the wife from West Yorkshire. The wife first presentedin January, 1979, with diarrhoea and pain in the left iliac fossa.Colonoscopy showed discontinuous inflammation throughout thecolon and biopsies revealed histological features of Crohn’s disease.A small-bowel barium study was normal. Since diagnosis she hashad three relapses and is currently maintained on azathioprine. Thehusband had lower abdominal pain and rectal bleeding in August,1984. Colonoscopy showed aphthous ulceration as far as the hepaticflexure. In September, 1984, he underwent a subtotal colectomyand ileorectal anastomosis. Macroscopic and microscopicappearances of the colon were typical of Crohn’s disease.

Subsequently he has had anastomotic recurrence. He is not

currently on treatment.

705

Using the figure of 35 per 100 000 for the prevalence of Crohn’sdisease in the UK, Rhodes et al3 calculated that the chance of findingfive or more married couples with the disease is 0019; the chance offinding six or more is 0-004. However, these probability values areinfluenced by small variations in the estimate of prevalence.The occurrence of Crohn’s disease in a greater number of

married couples than expected by chance lends support to the viewthat an environmental factor, infectious or otherwise, is involved inthe aetiology of Crohn’s disease.

Gastroenterology Unit,General Infirmary,Leeds LS1 3EX

A. J. LOBOP. N. FOSTERG. M. SOBALAA. T. R. AXON

1. Whorwell PJ, Eade OE, Hossenbocus A, Bamforth J. Crohn’s disease m a husbandand wife. Lancet 1978; ii: 186-87.

2. Whorwell PJ, Hodges JR, Bamforth J, Wright R. Crohn’s disease in a husband andwife. Lancet 1981; i: 334.

3. Rhodes JM, Marshall T, Hamer JD, Allan RN. Crohn’s disease in two marriedcouples. Gut 1985; 26: 1086-87.

4. Holmes GKT, Painter NS. Crohn’s disease in married couples. Gut 1986; 27: 350.

ANTIGLIADIN AND ANTIRETICULIN ANTIBODIESIN COELIAC DISEASE

SIR,-Volta et all were surprised that 3 of our 4 patients withcoeliac disease2 were negative for antigliadin antibodies (AGA) butpositive for Rl reticulin antibodies. A better description would havebeen that 3 of the 4 proved to have atypical anti-reticulin antibodies,namely patterns other than the Rl pattern (ie, R2—R5).3 Hence ourresults agree with those of Volta et al.

Joint Academic Department of Child Health,Queen Elizabeth Hospital for Children,London E2 8PS

D. J. UNSWORTHJ. DIASJ. A. WALKER-SMITH

1 Volta U, Bonazzi C, Pisi E, Salardi S, Cacciari E. Antigliadin and antireticulinantibodies in coeliac disease and at onset of diabetes in children. Lancet 1987; ii:1034-35.

2. Dias J, Unsworth DJ, Walker-Smith JA. Antigliadin and antireticulin antibodies inscreening for coeliac disease. Lancet 1987; ii: 157-58.

3. Rizzetto M, Domiach D. Types of reticulin antibody detected in human sera byimmunofluorescence. J Clin Pathol 1973; 26: 841-51.

GEMFIBROZIL-INDUCED HEADACHE

SiR,—Gemfibrozil is a lipid-lowering drug whose majorindications are severe hypertriglyceridaemia (type V phenotype)and hyperlipoproteinaemia (IIB and III),’ and it reduces theincidence of coronary heart disease in men with dyslipidaemia.2 Thedrug is usually well tolerated, side-effects being infrequent andmild. The most reported side-effects are gastrointestinaldisturbances such as diarrhoea, gastric intolerance, abdominal pain,and constipation.3-7 Other adverse reactions include anorexia, drymouth, drowsiness, dizziness, rash, anaemia, leucopenia, blurredvision, musculoskeletal pain, and transient elevations oftransaminase levels.3-8 We report a case of headache in a patienttaking gemfibrozil.An otherwise healthy 46-year-old woman was started on

gemfibrozil, 600 mg twice daily on Dec 5, 1987, for treatment of"hypercholesterolaemia". A week later she had a frontotemporalheadache 30-90 min after taking the drug, which was easily relievedby analgesics and accompanied by dry mouth. These episodesoccurred only after she took her medication. She denied diplopia,loss of vision, fever, photophobia, nausea, or vomiting. The patienthad no papilloedema, her neck was supple, and the rest of herphysical examination was normal. The headaches continued untilshe stopped taking gemfibrozil on Jan 7,1988. She did not have anymore episodes after stopping the drug. Because the headache wasmild, she agreed to a re-exposure test, and started to take the samedose of gemfibrozil on Jan 27. A few hours later, her mouth becamedry, and on Feb 2 she had headache, which had the samecharacteristics as before but was severe enough to make the patientstop taking gemfibrozil.We have not found any other description of headache although

the datasheet states that headache is "occasionally and possibly

attributable". Drugs can induce headache by:9 (1) vasodilatation-not an effect of gemfibrozil; (2) benign intracranial hypertension,usually accompanied, for instance, by diplopia, loss of vision, orfacial nerve palsies—our patient had none of these; and (3) asepticmeningitis-this seems unlikely because our patient did not havefever, neck stiffness, or photophobia and this situation is alwaysdescribed in patients with systemic lupus erythematosus. We haveno satisfactory explanation for gemfibrozil-induced headaches inour patient, although it was accompanied by a dry mouth. Bothreactions may have a common aetiology. The temporal relation tothe drug administration and the fact that the headache disappearedwhen the drug was discontinued makes a gemfibrozil-inducedreaction likely and the positive re-exposure test confirms this.

Department of Clinical Pharmacology,Hospital "Marques de Valdecilla",39008 Santander, Spain;

and Spanish Pharmacovigilance System,Centro Regional de Cantabria

FÉLIX ARELLANOMARÍA A. DE COSROMÁN VALIENTECOVADONGA QUIRÓS

1. Illingworth DR. Lipid-lowering drugs: an overview of indications and optimumtherapeutic use. Drugs 1987; 33: 259-79.

2. Frick MH and the Helsinki Heart Study Group. Helsinki heart study: Primaryprevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety oftreatment, changes in risk factors, and incidence of coronary heart disease. N Engl JMed 1987; 317: 1237-45.

3. Owen JA Jr. Focus on gemfibrozil. Hosp Formul 1981; 16: 1271-72.4. Anonymous. Gemfibrozil. Med Lett 1982; 24: 59-60.5. Manninen V, Malkonen M, Elsalo A, Virtamo J, Tuomilheto J, Kuusisto P.

Gemfibrozil in the treatment of dyslipicaemia: a 5-year follow-up study. Acta MedScand 1982; 668 (suppl): 82-87.

6. Kovanen PT, Koskinen P, Manninen V. A comparison of different formulations anddosage administrations of gemfibrozil. Am J Cardiol 1986; 57: 316-46.

7. Lewis JE. Long-use of gemfibrozil (Lopid R) in the treatment of dyslipidemia.Angiology 1982; 33: 603-12.

8. Samuel P. Effects of gemfibrozil on serum lipids. Am J Med 1983; 74 (suppl 5A):23-27.

9. Blain PG, Stewart-Wynne E. Neurological disorders. In: Davies DM, ed. Textbook ofadverse drug reactions. Oxford: Oxford University Press, 1985: 495-514.

ORAL REHYDRATION WITHOUT CHLORIDE

SIR,-Dr Booth and Dr Smith (March 5, p 540) express concernthat ’Dioralyte Effervescent Tablets’ do not contain chloride andare recommended for use in infants and children. The datasheet,prescribing information, and all promotional material for thisproduct (launched in October, 1987) have made it clear that thepreparation should be used in children over the age of two years.Dioralyte in sachet form is recommended for infants and childrenless than two years old. We believe that an effervescent oral

rehydration therapy is an attractive alternative for children over twoyears and for adults, and that dioralyte effervescent tablets areentirely suitable for treating such patients for the type of acutegastroenteritis seen in Britain.

Rorer Health Care Ltd,Eastbourne,Sussex BN21 3YG G. W. R. HILL

POST-CHERNOBYL RADIOCAESIUM EXPOSURE INTHE UK

SIR,- The regional medical physics department of the NorthernRegional Health Authority is coordinating a national survey ofwhole-body radioactivity in the general population in the UK.Medical physics departments are using their own whole-bodycounters or a mobile whole-body counterl to monitor volunteers.The Chernobyl accident introduced radioactive material into thefood chain. Caesium-137 and caesium-134 were released during theincident and the ratio of the two activities was about 2:1. Theamount of radiocaesium deposited on the ground was about 20times greater in areas of heavy rainfall during the primary passage ofthe radioactive plume over the UK than in areas, mainly in the southand east, with little rain at that time Measurements detected bothforms of radiocaesium and the naturally radioactive isotopepotassium-40 that is always present in the body. Detailed resultswill be published later, but preliminary results are available forcontrasting areas surveyed by the mobile counter. Between July andNovember, 1987, 599 volunteers were measured in areas heavily