* zyI.pflmifl Descriptiem: ZYLOPRIM presents a unique approach to the therapy of hyperuricaemia associated with gout and other conditions. ZYLOPRIM reduces both the serum and urinary uric acid levels by blocking the formation of uric acid. lmullcetlens: ZYLOPRIM is intended for the treatment of gout as well as secondary hyperuricaemia. The treatment aims at preventing the deposition of urates in the tissues and development of bone, joint and renal damage. By its unique action in reducing the formation of uric acid rather than merely increasing the excretion of urates, it presents definite advantages over uricosuric agents or simple anti-inflammatory drugs, especially in patients with gouty nephropathy. in those who form renal urate stones, and those with unusually severe disease. Therapy with ZYLOPRIM relieves chronic joint pain and increases joint mobility. In most patients with extensive tophaceous deposits, progressive formation of tophi has been halted and draining urate sinuses have healed. The size of the tophi has been reduced. ZYLOPRIM is particularly effective in preventing the occurrence and recurrence of uric acid stones and gravel. No further deterioration in kidney function attributable to urate precipitation was noted in the course of treatment with ZYLOPRIM in patients who had renal damage priorto therapy. ZYLOPRIM is useful in the therapy and prophylaxis of acute urate nephropathy in patients with neoplastic disease who are particularly susceptible to hyperuricaemia and uric acid stone formation, especially after radiation therapy or the use of antineoplastic drugs. Preca.tiems end Centre-Indlcetloas: Prophylactic administration of colchicine is advisable during early stages of therapy. ZYLOPRIM is not recommended for use during pregnancy or in women of child-bearing potential unless in the judgment of the physician, the potential benefits outweigh the possible risks to the fetus. In patients receiving PURINETHOL* Mercaptopurine or IMURAN* Azathioprine, the concomitant administration of 300-600mg of ZYLOPRIM/day will require a reduction in dose to approximately 1/3 to 1/4 of the usual dose of PURINETHOL or IMURAN. Subsequent adlustment of doses of PURINETHOL or IMURAN should be made on the basis of therapeutic response and any toxic effects. Side Effects: Diarrhoea and intermittent abdominal pain, skin rashes and mild fever have been reported occasionally. Symptoms suggestive of drug idiosyncrasy, characterized by fever, chills, leucopenia, skin rash, pruritus, nausea and vomiting have been reported in two cases. Hepatomegaly and jaundice have been noted in two patients, one of whom showed purpura and a skin rash; and transient abnormal liver enzyme levels have been detected in several cases. The changes reverted to normal after stopping all medication and their significance is not yet entirely clear. Dosage end Aiministretien: The average dose is 200to 300mg per day in single or divided doses for patients with mild gout and 400to 600mg per day for those with moderately severe tophaceous gout. For the prevention of uric acid nephropathy during the vigorous therapy of neoplastic disease, treatment with BOO to 800 mg daily for two or three days prior to chemotherapy or X-irradiation is advisable. In prolonged treatment, 300 to 400 mg of ZYLOPRIM daily is usually enough to control the serum uric acid level. The appropriate dosage may be administered in divided doses or as a single equivalent dose with the 300 mg tablet. It is essential that a daily urinary output of two litres or more be maintained during ZYLOPRIM therapy, and neutral or alkaline urine is desirable. How supplIed: ZYLOPRIM 100 mg scored white tablets, Bottles of 100 and 500 tablets; Code: Wellcome U4A. ZYLOPRIM 300mg scored peach coloured tablets, Bottles of 100 tablets; Code: Wellcome C9B. Product Memogreph evellehle em request.

.

MontrealPO.

T.ade

weight and both received a large portion of the total dose over a short period of time. W.G.L. CARR, MD Caledonian Medical-Surgical Clinic P0 Box 512 Nanaimo, BC

Insect-venom allergy To the editor: A course of desensitization injections for patients anaphylactically allergic to stings of insects of the order Hymenoptera has been accepted therapy for some years.1 Results of a retrospective study of over 2600 such cases reported by the American Academy of Allergy in 19652 supported ibe efficacy of the 3-year course usually prescribed: 90% of patients who underwent desensitization therapy reported less severe reactions when they were stung again, in contrast to only 9% of control patients who did not undergo such therapy. Several case reports have indicated that this therapy may confer some immunity after as little as a month of injections; however, this cannot be counted on, and every other reasonable precaution must be taken by the patient at all times.1 To date, the standard approach1 to immunotherapy has been as follows: Patients are selected for this treatment on the basis of results of an analysis of their response to one or more stings, considering their general health and lifestyle. Skin testing is of limited value in identifying the responsible insect3 but is considered helpful in determining the appropriate first dose of antigen. In most instances a mixture of commercial extracts of Hymenoptera insect bodies is used, on the basis of data on shared antigens.4 Maximum protection is thought to be afforded by serial injections up to the "maximum tolerated dose , after which injections are given every 2 to 4 weeks. The recent report of treatment failtires,1 although not unexpected, is disturbing and deserves our attention. Eight such cases have been documented over 11 years. All patients had received "significant" desensitization; four were still receiving injections. Three died despite administration of epinephrine and three died despite sublingual administration of isoproterenol hydrochloride. One died almost certainly from a bee sting after having tolerated a bee sting without much reaction only 3 weeks before. The reasons for the occasional failure of treatment are unknown and await a clearer understanding of the mechanisms of this type of allergic reaction and of desensitization.3 Until then, how should these patients be managed? Immunotherapy should be consid-

24 CMA JOURNAL/JANUARY 10, 1976/VOL. 114

ered for any person at risk for an anaphylactic reaction to an insect sting - for example, one who has had a constitutional reaction or progressively more severe local reactions. Patients with cardiovascular disease and those taking propranolol are especially vulnerable. Patients taking psychostimulants such as imipramine and monoamine oxidase inhibitors are at risk from immunotherapy, epinephrine administration and a subsequent sting, and should not be started on treatment without consultation. The program used to date, in which injections of a mixture of whole-body extracts are given for 3 years, has proved eminently satisfactory for the majority of patients. At present, however, we cannot be confident that either prolonged immunotherapy or apparent tolerance of a subsequent sting is associated with permanent loss of hypersensitivity in all cases.6 Some allergists, therefore, are recommending immunotherapy of indefinite duration at intervals of 1 to 4 months. However, there are no criteria for determining who needs injection treatment indefinitely, and the efficacy of giving injections at intervals of 3 to 4 months has yet to be convincingly demonstrated. The practical solution appears to be to treat the patient for 3 years, then reappraise his total situation. The use of pure venom extract has been suggested for certain patients7 and has recently been shown to be effective.8 However, such extracts are not widely available and are expensive. The patient should be counselled to take self-protective measures and should be instructed in how to administer epinephrine, the drug of choice after a sting. Aerosol inhalations of epinephrine are probably of limited value. Since death has been reported as long as 2 to 18 days after sting (without complicating infection),8 the absence of early symptoms should not be taken casually, and careful observation is indicated. Although corticosteroids do not protect against anaphylaxis, they do facilitate the action of sympathomimetics, and in most cases it is safer to use them early than to withhold them for possible later use. J.D. HORAN, MD, FRcP[c] M.A.J. MANDL, MB, M sc, FRcP[c]

1750 East 10th Ave. Vancouver, BC

References 1. SHELDON JM: A Manual ol Clinical Allergy,

second ed, Philadelphia, Saunders, 1967 2. KAILIN EW: Interim report of the Committee

on Insect Allergy. J Allergy Clin Immunol

36: 190, 1965 3. SoBoTKA AK, VALENTINE MD, BENTON AW, et al: Allergy to insect stings. I. Diagnosis of IgE-mediated Hymenoptera sensitivity by venom-induced histamine release. / Allergy

Cli,, Immunol 53: 170, 1974

continued on page 26

be. Marriage may not necessarily be, as a French saying goes, the tomb of love, but it is not usually the womb of poetry. (Coventry Patmore comes to mind as an exception.) And the poetry that stays in one's thoughts is the poetry that moved one in youth. There are poems about ageing, but death is a more "poetic" subject when it occurs young. There is a gentle and sad poem by Ruckert about becoming 40, beautifully set to music by Brahms, and a harsh and deeply bitter poem by Matthew Arnold: ... Ah, 'tis not what in youth we dreamed 't would be. 'Tis not to have our life Mellowed and softened as with sunset-glow, A golden day's decline... It is to spend long days And not once feel that we were ever young. For the most part we must face the later decades without the consolations of poetry, and what seems a decline in poetry may then be my own decline in response. I envy those whose minds are stocked with poetry. Archibald Wavell, general and viceroy, made a long anthology, mainly of narrative poems, and claimed to know nearly all by heart. Men in solitary confinement have saved their sanity by telling over their memories of verse. My small supply would be used up in half an hour. One does not read poetry at any hour of the day, as one might read a novel or a technical book. A sense of sacrilege prevents me from reading poetry in the toilet, though the brevity of the occasion would in some ways be suitable. My favourite time and place are my tree house on a summer's evening, my dog at my side. Winter does not seem to offer the same opportunities, and we sit in the dark, staring at the stars. The mood, however, is much the same. Yes, I have written some poetry myself, under the pressure of adolescent sexuality and at one or two crucial moments. Sometimes I was amusing, or others found it so, but only once the white heat of a personal emotion seems to me to have transmuted words into magic. And by the nature of that situation they remain locked in a suitcase in an attic. Perhaps many of us have one or two such poems. Not many of us would say with George I "I don't like poetry and I don't like painting"; even if true we would be ashamed to admit it. Yet someone who had not opened a book of poetry for 20 years would recognize the difference between the poetry and the prose of life. And there is little doubt which he would choose.E

CORRESPONDENCE continued from page 24 4. FOUBERT EL, STIER RA: Antigenic relationships between honey-bees, wasps, yellow hornets, ..nd yellow jackets. J Allergy Clin Immunol 29: 13, 1958 5. TORSNEY PJ: Treatment failure: insect desensitization. Case reports of fatalities. I Allergy Clin Immunol 52: 303, 1973 6. REISMAN RE: Stinging insect allergy - treatmcnt failures (E). Ibid, p 257 7. SHULMAN 5, L,a..Giois C, ARBESMAN CE: The allergic response to stinging insects. I. Preparation of extracts and their biochemical

characterization. J Allergy Clin immunol 35: 446, 1964 8. BARNARD JH: Severe hidden delayed reactions from insect stings. NY State I Med 66: 1206, 1966 9. LicHENsTEiN LM, VALENTINE MD, SOBOTRA AK: A case for venom treatment in anaphylactic sensitivity to hymenoptera sting. N Engi J Med 290: 1223, 1974

Electron microscopy in enteric virology To the editor: There has been much interest in the last 3 years in the etiology of acute nonbacterial gastroenteritis. Until recently, most investigators failed to incriminate either pathogenic bacteria or viruses as usual etiologic agents, although a few cases and outbreaks were attributed to picornaviruses, parvoviruses or adenoviruses. A far-reaching discovery was made in Melbourne in 1973 by Bishop and colleagues,1 who found by electron microscopy viruses resembling morphologically members of the Orbivirus group of reoviruses in biopsies of the duodenal mucosa of babies. The virus particles were present in epithelial cells. These observations were soon confirmed and similar reovirus-like particles demonstrated in fecal suspensions.2'3 In Toronto, Middleton and colleagues4 reported demonstrating similar orbiviruses in feces, duodenal aspirates and duodenal biopsies of 60 hospitalized infants and in necropsy material (upper jejunal mucosa) from seven infants who had died before admission. Virus activity was greatest in infants in the winter months. Although there is some difference of opinion, these viruses appear to resemble the Orbivirus group of reoviruses. In electron micrographs there are individual particles that resemble a wheel and appear as double shells. For the moment we prefer the term "reovirus-like", although others use the term orbivirus, duovirus or rotavirus.5'3'4 Subrahmanyan and Hamvas in Toronto identified reovirus-like particles in feces of several patients with acute gastroenteritis in the winter of 1974-75. Spence, also in Toronto, likewise identified this virus in fecal specimens. Their reports will shortly be published. Much has been written on this subject, and undoubtedly a major "breakthrough" has been made in the etiology of gastroenteritis of young children, a serious worldwide condition. Although these viruses were first de-

26 CMA JOURNAL/JANUARY 10, 1976/VOL. 114

scribed only 2 years ago, we have recently obtained evidence that they have been in circulation in this area for at least 7 years. In 1969, in a paper published in the Journal, we discussed the usefulness of direct examination of specimens for virus particles by the electron microscope.5 In presenting some of our own findings we included several micrographs of viruses from clinical specimens; one such specimen was an ultracentrifuged deposit of stool collected from a child taken sick in 1968. At that time we identified the viruses in this stool as classic reoviruses. Re-examination of the micrographs now reveals that these viruses were indeed the reovirus-like agent that has recently been associated with gastroenteritis (Fig 1)

FIG. 1-Left reovirus like particles from ultracentrifuged deposit of stool (xlOO 000). Right higher magnification of virus particles from same specimen, exhibiting typical wheel-like appearance and double shell of gastroenteritis agent (x292 000). It is expected that in due course the International Committee on Taxonomy of Viruses, of which one of us (A.J.R.) is a member, will decide how the above-described viruses should be classified; they will probably be considered members of the family Reoviridae.6 JJ. HAMYAS, P END

Electron microscopy unit Medical director Ontario Ministry of Health Laboratories Toronto, ON AJ. RHODES, MD, iRcP[CJ

F.W. DOANE, MA Electron microscopy unit Department of microbiology and parasitology University of Toronto Toronto, ON

References 1. BIsHOP RF, DAvIDSON GP, HOLMES IH, et ai: Virus particles in epitheliai cells of duodenal mucosa from children with acute nonbacterial gastroenteritis. Lancet 2: 1281, 1973 2. FLEWETr TH, BRYDEN AS, DAVIES H: Virus particles in gastroenteritis. Ibid, p 1497 3. BISHoP RF, DAVIDSON GP, HOLMES IH, et al: Detection of a new virus by electron microscopy of faecal extracts from children with acute gastroenteritis. Lancet 1: 149, 1974 4. MIDDLETON PJ, SZYMANSKI MT, ABBOI-F GD, et al: Orbivirus acute gastroenteritis of infancy. Ibid. p 1241 5. DOANE FW, ANDERSON N, ZB5TNEW A, et al: Application of electron microscopy to the diagnosis of virus infections. Can Med Assoc 1 100: 1043, 1969 6. FENNER F, PEREIRA HG, PORTERFIELD JS, et al: Family and generic names for viruses approved by the International Committee on Taxonomy of Viruses, June 1974. Intervirology 3: 193, 1974

Letter: Insect-venom allergy.

* zyI.pflmifl Descriptiem: ZYLOPRIM presents a unique approach to the therapy of hyperuricaemia associated with gout and other conditions. ZYLOPRIM re...
606KB Sizes 0 Downloads 0 Views