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A 26-year-old woman with debilitating juvenile rheumatoid arthritis was treated at a Mexican arthritis clinic with two unknown medications. She subsequently developed agranulocytosis and cholestatic hepatitis as an adverse reaction to these drugs, later identified as oxyphenbutazone and diazepam. The etiology of these drug-induced problems is reviewed, and the dangers of this unorthodox form of medical therapy are discussed.

Some of the factors influencing the likelihood of the appearance of adverse drug reactions in patients are identified and discussed. Ways of quantifying some of the risks of adverse reactions in different patients are demonstrated. It is pointed out that adverse reaction data can give valuable guidance for both day-to-day patient management and for the initiation or guidance of research projects. In this latter connection, this study highlights the difference in time of onset between aplastic anaemia and agranulocytosis, suggesting different mechanisms of reaction. The majority of adverse reactions occur during the first three weeks of treatment and it is during this time that patients must be most carefully supervised. The old patients should be watched with particular care. It is concluded that age, sex, disease being treated, length of treatment and even the geographical location where the patient lives, can affect the time, type, frequency and outcome of an adverse drug reaction.

130 patients with edema as the sequel of a traumatic incident were selected for this study, 43 patients were treated with 300 mg N-(2,6-dichloro-m-tolyl)anthranilic acid, sodium salt (meclofenamate sodium, Meclomen) per day for one week, 44 patients received 600 mg oxyphenbutazone per day and 43 patients received placebo. Medication could be terminated if edema and pain disappeared or if deterioration or intolerance occurred. Extent of edema and degree of pain were assessed at entry into the study and on days 3, 5 and 8. Efficacy was assessed by the number of days elapsed before definite reduction and/or complete disappearance of edema and by the decrease and disappearance of pain. Meclofenamate sodium proved to be significantly superior to placebo in the treatment of patients with post-traumatic edema and post-traumatic pain. Reduction and disappearance of edema and cessation of pain occurred significantly more promptly in patients receiving meclofenamate sodium than in those receiving placebo. Although no statistically significant differences were observed between meclofenamate sodium and oxyphenbutazone, the results suggested that meclofenamate sodium might be clinically superior. Meclofenamate sodium was well tolerated.

A double-blind randomized trial was carried out in 31 patients suffering from acute, minor ligamentous injuries to compare the efficacy of diflunisal in the relief of pain with that of oxyphenbutazone. Patients received either 500 mg diflunisal twice daily or 200 mg oxyphenbutazone 3-times daily for 3 days. The results of subjective assessments showed tha by Day 3 spontaneous pain had either completely resolved or markedly improved in all patients, and that diflunisal was significantly better than oxyphenbutazone on Days 1 and 3 in relieving pain on movement of the joint.

The bioavailability and gastric ulcerogenic activity of oxyphenbutazone and glafenine (acidic and basic nonsteroidal anti-inflammatory drugs), coated with different cellulose derivatives were assessed in albino rats. The cellulose derivatives chosen have different functional groups, acidic (carboxymethyl cellulose), basic (chitosan) and neutral (hydroxypropylmethyl cellulose). The bioavailability was dependent on the drug and polymers. Generally, all the cellulose derivatives chosen decreased the gastric ulcerogenic activity of the drugs studied.

A 48-year-old woman treated with oxyphenbutazone developed fever, gastrointestinal disturbances, mucocutaneous reactions, leukopenia, eosinophilia and thrombocytopenia. Bone marrow biopsy showed granulomatous lesions. Following withdrawal of the drug, all signs and symptoms subsided and the blood changes and the bone marrow biopsy normalized. The granulomatous reaction in the bone marrow is considered to be a hypersensitivity manifestation of oxyphenbutazone.

The authors report 18 children with toxic epidermal necrolysis (T.E.N.). The clinical and laboratory signs, the development of complications and sequelae and the drugs presumed to be responsible are compared with those of T.E.N. in adults. The onset was generally marked by a influenza-like state with development of mucosal signs between the first and the seventh days. The lips and buccal cavity were involved in 16 cases and the eyelids and conjunctiva were involved in 15 cases. Epidermal loss occurred after a variable interval of between one and eight days after the appearance of the erythema. The severity of the epidermal loss, expressed as a percentage of the body surface area, was a poor prognostic factor. Hypoproteinaemia was the most frequently observed laboratory abnormality. The complications were infectious and the 2 deaths in this series were due to septicaemia. Ocular complications were also observed: keratitis, responsible for sequelae such as distichiasis, conjunctival adhesions, sicca syndrome. As in adults, these children were frequently taking multiple drugs. Among the drugs prescribed during the classical interval of imputability, two drugs were particularity noted: phenobarbital and oxyphenbutazone. Treatment should only be undertaken in a specialized unit and is based on the principles of intensive care of burns patients: control of hypovolemia and infection. Ocular sequelae should be prevented by local treatments several times a day.

We describe two patients who developed generalized pustular psoriasis after taking phenylbutazone and oxyphenbutazone respectively, and discuss the possible pharmacological mechanism of this effect.

An overall study, accompanied by some statistics, is presented of delayed bone marrow injuries caused by drugs, such as chloramphenicol, phenylbutazone, oxyphenbutazone, gold salts, sulphamides and diphenylhydantoin. Unanimous agreement as to the aetiological interpretation of isolated cases, the seriousness of marrow damage, and the results obtained by treatment can be observed in various countries. The available epidemiological data are incomplete, though they point to a parallel between the appearance of panmyelopathy after chloramphenicol and the consumption of this drug. First noted in the U.S., this relationship later became apparent in several European countries and eventually in West Germany. Frequencies range from 1 per 6,000 to 1 per 36,000 subjects treated in California, Hamburg and Sweden.

A case history is presented of the occurrence of a high binding capacity for native DNA in the serum of a patient on phenylbutazone. This reverted to normal on stopping the drug. The patient also had a reversible neutropenia and leucopenia, and it is suggested that the high anti-DNA binding capacity was a feature of a drug-induced lupus-like phenomenon.

A woman who had taken oxyphenbutazone for 4 years because of back pain presented with goitre and hypothyroidism. This was shown to be due to an organification defect, caused or aggravated by oxyphenbutazone.

A review of the literature on the gastrointestinal side effects of the analgesic drugs has disclosed a disparity between generally held views and the scientific evidence. This is largely due to the paucity of large long term controlled trials since the cost of these is very high. The problems in mounting a large observational study with population controls are discussed against a backgrwound of exploratory work in Australia and New Zealand and the conclusion is reached that a comprehensive survey is needed. The difficulties in mounting such a survey are discussed.

Cases of drug-induced aplastic anaemia, haemolytic anaemia, thrombocytopenia, and agranulocytosis reported to the Swedish Adverse Drug Reaction Committee during the five-year period 1966-70 have been analysed and compared with cases of the same cytopenias from "all" causes. Oral diuretics were a dominant cause of drug-induced thrombocytopenia, methyldopa of haemolytic anaemia, and oxyphenbutazone of aplastic anaemia. Computer systems should help such studies, particularly in showing a changing pattern of complications and causes.