316
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
wearers.
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
No
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
the
allergy promotion
allergens
released from airborne
pollen
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
Industrial Research,
Palmerston North
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