of such contact lens solutions led to resolution of signs and symptoms, usually within a few weeks. Re-exposure of the eye to thiomersal elicits an acute inflammatory response as early as 12 hours after administration. Vaccines preserved with 0-01% thiomersal will contain much more thiomersal than that contained in our intradermal test, and vaccination can result in immunisation to thiomersal. A possible effect of including this preservative in a vaccine, for an individual who has CMI to thiomersal, will be to enhance the cell-mediated immune response to the vaccine antigen. CMI to thiomersal does not seem to be associated with an increased risk of local reactions to vaccines, possibly because they are usually given subcutaneously or intramuscularly.1 However, individual cases of severe hypersensitivity reactions to thiomersal, including that contained in hepatitis B vaccine, do occur. 1,6 Thiomersal has been reported as the probable cause of acute laryngeal obstruction after 36 hours’ use of a throat spray, preserved with 0-033% thiomersal, by a patient found to have CMI to this agent.7 Other antiseptic preservatives can also induce a CMI response: for chlorhexidine this happens in 0-1% or so of patients, and our series of 116 patients challenged with phenol is too small to exclude a 0-1% rate of CMI. Thiomersal is unstable and only weakly antibacterial, and it elicits an unacceptably high rate of CMI response via mucosal or dermal exposure and by injection. Eye and nose drops should be supplied in single-dose, non-preserved sterile units. Contact lens care solutions in multiple-dose containers become contaminated in the home environment whether or not they contain preservatives. The use of single-use, sterile, non-preserved solutions in disposable sachets, and of disposable contact lens storage cases, would be a better approach and would avoid thiomersal-associated keratoconjunctivitis occurring in contact lens use
4-hydroxybenzoic acid by pine, cedar, wattle, and C macrocarpa. trace of them was found in the allergenic pollens ryegrass and privet. We have not sustained the birch resultfinding benzoic acid only. The substances were produced in microgram quantities per gram of pollen. We suggest that these substances, alone or in combination, exacerbate protein-associated allergy or act in a way solely related to their individual pharmacological activities. Despite the useful properties of salicylates, 2-hydroxybenzoic acid and other salicylates adversely affect a small proportion of the population. In the United States, for example, this is estimated at 250 000 individuals.4 Salicylates also induce and provoke asthma in
up to 10% of asthmatics .5 In the UK, where some 3-6% of adults may be asthmatic,6 some 200 000 may be salicylate-sensitive. Benzoic acid and 4-hydroxybenzoic acid are used as preservatives yet a low proportion of the population exhibit drug intolerance symptoms toward them.7 The clinical significance of these findings is difficult to assess. In many western countries pollen is consumed as a health food, and in China Pinus pollen is ingested in gram quantities as a tonic. Airborne pollen offers an invisible and hitherto unrecognised entry vehicle, at uncontrolled rates, of these compounds. One of us (D. W. F.) exhibits drug intolerance to benzoic acid and salicylates, and exposure to Pinus and Acacia pollen produces urticaria and symptoms of respiratory stress. We suggest the possibility arising of occupational or domestic exposure similar to the more familiar
sensitivity of some asthmatics to other low-molecular-weight organic compounds such as plicatic acid, chlorogenic acid, and formaldehyde. Botany and Zoology Department, Massey University, Palmerston North, New Zealand Fruit and Trees Division,
DAVID SEAL* LINDA FICKER PETER WRIGHT VICTOR ANDREWS
Moorfields Eye Hospital, London EC1, UK *Present address: UK
Department of Bacteriology, Wolfson Centre, Glasgow G4 0NA,
1. Cox NH, Forsyth A. Thiomersal allergy and vaccination reactions. Contact Dermatitis 1988; 18: 229-33. 2. Ficker L, Ramakrishnan M, Seal D, Wnght P. Role of cell-mediated immunity to staphylococci in blepharitis. Am J Ophthalmol 1991; 111: 473-79. 3. Hansson H, Moller H. Patch test reactions to merthiolate in healthy young subjects. Br J Dermatol 1970; 83: 349-56. 4. Wilson LA, McNatt J, Reitschel R. Delayed hypersensitivity to thiomersal in soft contact lens wearers. Ophthalmology 1981; 88: 804-09. 5. Cox NH, Morley WN, Forsythe A. Vaccination reactions and thiomersal. Br Med J
1987; 294: 250. 6. Rietschel RL. Reactions to thiomersal in hepatitis B vaccines. Dermatol Clinics 1990; 8: 161-64. 7. Maibach H. Acute laryngeal obstruction presumed secondary to thiomersal (merthiolate) delayed hypersensitivity. Contact Dermatitis 1975; 1: 221-22.
Pollen and bin,—Although
released from airborne
grains and spores have an established role in the aetiology of respiratory conditions such as hayfever and allergic asthma, we are examining the possibility that low-molecular-weight chemical species may also affect respiratory health. Such a possibility has been raised before in relation to bracken spores and certain cancers,’ and in allergy induced by birch pollen ascribed to natural salicylates.2 We were also prompted by a survey in New Zealand3in which some respondents claimed hayfever symptoms, provoked by pollens from species for which there is little or no evidence of potency of protein allergens. Our findings show that for several pollens, compounds in the benzoic and hydroxybenzoic acid series are leached into aqueous solution. These substances possess
pharmacological activity. Ether-soluble substances were obtained by extraction of aqueous leachings and were analysed by gas-chromatography/massspectrometry. Benzoic acid was produced by pollen of birch (Betula pendula), pine (Pinus radiata), wattle (Acacia dealbata), cedar (Cedrus atlantica), and Cupressus macrocarpa; salicylic acid (2-hydroxybenzoic acid) by pollen of wattle and cedar; and
Department of Scientific and
D. W. FOUNTAIN C. A. CORNFORD G. J. SHAW J. M. ALLEN
1. Evans IA, Galpin OP. Bracken and leukaemia. Lancet 1990; 335: 231. 2. Shelley WB. Birch pollen and aspirin psoriasis, a study in salicylate hypersensitivity.
JAMA 1964; 189: 985-88. 3. Cornford CA, Fountain DW, Burr RG, O’Leary L. Hayfever in university students. NZ Med J 1988; 101: 520. 4. Abrishami MA, Thomas J. Aspirin intolerance: a review. Ann Allergy 1977; 39: 28-37. 5. MacDonald JR, Mathison DA, Stevenson DD. Aspirin intolerance in asthma, J Allergy Clin Immunol 1972; 50: 198. 6. Lane DJ, Storr A. Asthma. Oxford: OUP, 1979. 7. Zanussi C. Allergenic potential of food additives. In: Galli CL, Paoletti R, Vettorazzi G, eds. Chemical toxicology of food. Amsterdam: Elsevier/North Holland Publishers, 1978.
Portal vein thrombosis after extracorporeal shock wave lithotripsy MR,—A 51-year-old woman had a 1-year hustory 01 right upper to four small radioluscent gallstones. On admission liver function tests were normal and the patient denied alcohol consumption. She had a history of two pulmonary embolisms secondary to sural phlebitis in 1962 and pelvic surgery in 1987. Because she was obese, extracorporeal shock wave lithotripsy was done; premedication consisted of alfentanyl and midazolam. 7200 16-kV shocks were delivered in three sessions. After the first two sessions, one week apart, ultrasonography showed partial stone fragmentation and no portal vein anomalies. Two days after the third session six weeks later, the patient had right upper quadrant pain. Ultrasound and magnetic resonance imaging revealed occlusion of the left portal vein. The bileducts, gallbladder walls, and head of the pancreas were normal. Routine laboratory tests were normal apart from a slight rise in alanine aminotransferase and aspartate aminotransferase concentrations. Plasma concentrations of coagulation inhibitors (antithrombin III, protein C, total protein S, and heparin cofactor II) were normal, but the euglobulin clot lysis time was not shortened after 10 min of venous occlusion. Hypofibrinolysis was attributable to a deficient release of tissue plasminogen activator (tPA) by endothelial cells, as suggested by undetectable tPA activity and antigen in the plasma before and after
quadrant pain due
occlusion. The plasma activity of fast-acting plasminogen activator inhibitor (PAI-1) and plasminogen was normal. Intravenous heparin (250 mg/day) was given for six days then venous
replaced by oral anticoagulants. Five months later, the patient was well and ultrasonography showed partial regression of the occlusion. In a report of iliac vein thrombosis after lithotripsy for ureterolithiasis,1 a possible role for a mechanical factor (microtraumatisation of the vein wall) was proposed. Cavitation bubbles are common in the hepatic and portal venous system during lithotripsy, but portal vein thrombosis has not been recorded, even in large series.2 The disturbance of the fibrinolytic system would thus seem to have been a determining factor in the onset of thrombosis in our patient. When there is a history of thrombosis, in addition to basic coagulation tests (including coagulation inhibitors), we recommend that the euglobulin clot lysis time before and after venous occlusion should be determined before extracorporeal shock wave lithotripsy. J. P. ABECASSIS Service of Radiology A, Surgical Clinic, and Service of Haematology,
Hopital Cochin, 75014 Paris, France
B. DELAITRE M. P. MOREL P. TOULON D. PARIENTE A. BONNIN
since the onset of spasm by this route could happen after the procedure and reversal by intracoronary nitrates could not be done. However, spasm was triggered by the lowest (0005 mg) intravenous dose of methylergometrine, at blood concentrations equivalent to those obtained by oral route.3 Coronary spasm triggered by oral methylergometine is rare and its routine use in obstetrics is warranted, but we advise caution if chest pain arises during this treatment. Hôpital Cochin, 75014, Paris, France
CHRISTIAN SPAULDING SIMON WEBER FRANCOIS GUERIN
C. H. de Fontainbleau, Fontainbleau
ME, Lablanche JM, Tilmant PY, Thieuleux FA, Delforge MR, Carré AG. Frequency of provoked coronary artery spasm in 1089 consecutive patients undergoing coronary arteriography. Circulation 1982; 65: 1299-306. 2. Novak J. Gynecological therapy. New York: McGraw-Hill, 1960: 144-46. 3. Berde B, Sturmer E. Introduction to the pharmacology of ergot alkaloids and related compounds as a basis of their therapeutic application. In: Berde B, Schild HO, eds. Ergot alkaloids and related compounds. Handbuch de Experimentallen Pharmakologie, vol 49. Berlin: Springer-Verlag, 1978: 1-28. 1. Bertrand
W, Baert L, Vandeursen H, Vermylen J. Iliac vein thrombosis after extracorporeal shock wave lithotripsy. N Engl JMed 1989; 321: 907. 2. Sackmann M, Delius M, Sauerbruch T, et al. Shock wave lithotripsy of gallbladder stones: the first 175 patients. N Engl J Med 1988; 318: 393-97.
Coronary artery spasm triggered by oral administration of methylergometrine S!R,—Intravenous ergot derivatives are routinely used as a provocative test for coronary spasm during coronary arteriography.1 However, no case of variant angina shown by their oral administration has been reported. We describe a patient in whom variant angina occurred during oral treatment with methylergometrine. A 33-year-old woman was admitted for chest pain. Cigarette smoking was the only risk factor. She had had an abortion 6 weeks earlier, followed by oral administration of methylergometrine 12 mg thrice daily for four days. On the third and fourth day, two hours after breakfast, she had retrostemal pressure pain, at rest, associated with pain in the neck and both arms, lasting fifteen minutes. These symptoms then reappeared several times during the following week. Electrocardiography revealed subepicardial ischaemia in leads V4, V5, V6. Coronary arteriography and left ventriculography showed apical akinesia and normal coronary arteries. A spasm on the proximal left anterior descending artery was observed two minutes after intravenous injection of 0-05 mg of methylergometrine, immediately followed by transmural ischaemia and retrostemal pain. These symptoms disappeared after intracoronary injection of nitrates. An oral regimen of diltiazem and oral nitrates was started. After three days, a second provocative test was done in the coronary care unit, with close monitoring of the electrocardiogram. An intravenous injection of 0-05 mg of methylergometrine was followed by retrostemal chest pain and subendocardial ischaemia which disappeared after an intravenous bolus of 0-5 mg of nitroglycerine. Nifedipine 10 mg four times daily was then added to her regimen. A third provocative test was done three days later with electrocardiographic (ECG) monitoring and progressive doses of methylergometrine (0-05 to 0-4 mg), which failed to provoke chest pain or ECG changes. She was discharged and has noted no chest pain in two months of follow-up. Ergot derivatives are routinely used for the prevention and treatment of haemorrhage postpartum and after abortion and provocative tests with ergot derivatives are sensitive and useful for the diagnosis of coronary spasm. However, no case of variant angina revealed by their oral administration has been reported. In our patient chest pain experienced after two days of oral administration was reproduced by an intravenous provocative test with concomitant spasm on the left anterior descending coronary artery and important ECG changes. Oral methylergometrine might therefore have a role as a trigger for coronary spasm. We did not try a provocative test with oral methylergometrine at catheterisation
SIR,-Our laboratory receives 2000 samples a year for the investigation of toxoplasmosis associated with pregnancy. This figure represents 30% of the work undertaken by the reference unit. Most tests are prompted by worried but well mothers-to-be or by clinicians investigating symptoms and signs compatible with toxoplasmosis in a mother or her child. Most samples are forwarded after screening for specific IgG in local laboratories. We advise that these women be counselled before testing is undertaken. We test sera for IgG antibodies using the latex agglutination test and a modified version of the dye test and for specific IgM by ELISA and an immunosorbent agglutination assay (ISAGA).1 We assiduously follow up women who have evidence of recent infection. When indicated, infants are investigated at birth and then every 2 months to monitor the decline of passively acquired antibody of maternal origin. Thus, treatment can be initiated at the earliest opportunity for the otherwise clinically normal child whose findings indicate production of specific antibodies.2 The outcome for the child of an acutely infected mother can be categorised as: Congenitally infected-Confirmed by specific IgM or isolation of parasite or by persistence of specific IgG at age 1 year. Not congenitally infected-Confirmed by loss of all specific IgG within a year of birth. (Absence of IgM in the newborn does not exclude congenital infection; nor does an initial decline of IgG since this is to be expected in infected and uninfected infants as passively acquired antibody is removed from the circulation .3) Under investigation/decision never reached-Mother/child received but none of the above criteria satisfied. We have reviewed our records from Jan 1, 1989, to April 1,1991, and identified 12 cases of congenital infection (11 infants and 1 stillborn). None of the mothers had been screened prospectively. 8 infants had specific IgM; 3 were diagnosed on the basis of serological monitoring and specific symptoms; the parasite was identified in the stillborn baby. In the same period we were able to clear 25 infants of congenital infection; 23 mothers were followed prospectively. However, still under investigation were 57 infants under a year old, and 58 pregnant women were being monitored. No decision was ever reached for 62 women monitored prospectively from Jan 1,1989, from whom we received no neonatal or infant sera; and a final diagnosis has not been established for a further 42 children who were initially monitored. We ask for repeat sera until the infant can be categorised as definitely infected or uninfected. Some children from among those screened by our laboratory initially and those from whom sera was never received may have been investigated locally. This is not a practice we encourage. Only a reference laboratory can make full economic use of low volume samples and apply several tests, not always available in a local laboratory, in parallel with the investigation of previous samples. sera