89 readers. However, in computing the analysis of variance, the comparisons between the two experimental diets were based on eight subjects.
misleading
C. N. CHEN A. H. CRISP J. KOVAL B. MCGUINNESS
Academic Department of Psychiatry, St George’s Hospital Medical School,
London SW 17
PLEURAL EFFUSIONS AFTER PRACTOLOL
SiR,-Fleming and Hickling’ have described a case in which practolol may have caused pleural effusions. We have seen pleural involvement, with cutaneous and ocular reactions and L.E. syndrome, in a patient who had been taking practolol for three years. A 66-year-old retired coalminer with complicated pneumoconiosis was admitted to this unit in August, 1974, complaining of rapidly increasing breathlessness for 12 weeks, patchy scaling skin lesions, irritation of the eyes, and mistiness of vision. He had had ischxmic heart-disease since 1965. During 1971 practolol was prescribed, 200 mg daily increasing to 600 mg with dramatic relief of angina. His forced expiratory volume in 1(F.E.V.1), forced vital capacity, airways resistance did not change. In 1973, because of a recurrence of angina, the dose was increased to 800 mg daily with good effect, and he had remained well until the time of presentation. Examination revealed a pale man who was apyrexial and orthopnceic. There were scaling psoriasiform lesions over the extensor aspects of both elbows and knees and the skin of the palms was thickened. Discoid erythematous lesions were present on the forearms. The right eye had the appearance of a conjunctivitis. There were signs of a pleural effusion in the left chest. Practolol was discontinued. The chest radiograph showed a category B progressive massive fibrosis of coalworkers’ pneumoconiosis, unchanged since 1969. However, there was pleural thickening at the left lower zone and the right costophrenic angle with a left-sided pleural effusion, which had occurred since his previous radiograph in November, 1973. The principal abnormal laboratory findings were erythrocytesedimentation rate (Westergren) 36 mm/h (first); L.E. cells in peripheral blood and antinuclear factor positive; serum-alkaline-phosphatase 84 t.u./1 (normal 10-15), 5-nucleotidase 16.5 I.u/l (normal 4-11); bromsulphthalein retention 13% at 45 min but other liver-function tests normal. Pleural biopsy revealed collagenous thickening of pleura with lymphocytic infiltration of intercostal muscle. Skin biopsies showed moderate perivascular chronic inflammatory infiltrate in the upper dermis. The epidermis showed focal areas of atrophy with some focal parakeratosis and broadening of rete pegs. Liver biopsy revealed periponal small round-cell infiltration only. After withdrawal of practolol the skin lesions faded, although the eye symptoms persisted, as did the breathlessness which had reduced effort tolerance to 30 m on level ground. More detailed lung-function assessment revealed a reduced transfer factor 16-3ml min-’ mmHg-’ (normal 23-4) and total lung capacity 4560 ml (normal 5990),2 in addition to reduced ventilatory capacity. Although the skin lesions were disappearing the other abnormalities persisted, the E.S.R. increased to 60 mm, whilst the alkaline phosphatase increased to 110 Lv.!1 and the 5-nucleotidase rose to 19 t.u./1. In view of the persistence of these abnormalities we gave prednisone 40 mg daily reducing to a maintenance dose of 15 mg. Within 4 weeks he was no longer restricted by breathlessness whilst walking on level ground. Although pleural thickening persisted there was no recurrence of effusion; the skin lesions disappeared, but dryness of the eyes continued to prove 1. Fleming, H. A., Hickling, P. Lancet, 1975, ii, E. Lung Function. Oxford, 1975.
2. Cotes, J.
1202.
troublesome. L.E. cells were no longer present in the peripheral blood and the antinuclear factor became negative. The E.S.R. fell to 6 mm. All biochemical abnormalities returned to normal. The transfer factor and total lung capacity have returned to normal and the corticosteroid dose is down to 5 mg daily. Although some patients showing the oculomucocutaneous syndrome3 associated with practolol are reported to have had pleurisy, there have been no detailed descriptions of involvement of the pleura. A syndrome similar to L.E. may be induced by drugs such as hydrallazine4 and procainamide.’ Raftery and Oenman6 reported a similar syndrome in three patients treated with practolol. The normal serum complement and absence of renal involvement are characteristic of drug-induced S.L.E.’ Medical Research Council Pneumoconiosis Unit,
Llandough Hospital, Penarth,
Glamorgan CF6 1XW
A. D. MACKAY A. T. AXFORD
JOINT EFFUSIONS AND PRACTOLOL SIR,-Skin eruptions, keratoconjunctivitis sicca, and fibrosing peritonitis are well-recognised complications of prolonged therapy with practolol, and it would seem that pleural effusion and pleural thickening must now be added to this list (Dec. 13, p. 1202). We would like to report a case of yet another possible reaction to this drug. A 52-year-old man was admitted to hospital with an acute myocardial infarction in October, 1975. He had sustained a previous myocardial infarction in 1973, and for 6 years had had classical angina of effort. Apart from a 2-month period after his previous myocardial infarction he had taken practolol continuously for almost 3 years in a dose of between 200 and 400 mg daily; this had controlled his exertional chest pain. 6 weeks before this admission he developed pain and swelling of both knees which persisted for almost 2 weeks until he discontinued practolol. The swelling subsided over the next few days so he started treatment once more; however, after a further week the joint swelling returned, so he again stopped the drug and he has remained free of joint symptoms since that time. On admission to hospital he had a slight residual effusion in the right knee but otherwise no abnormality in this or other joints. He showed no evidence of skin or eye involvement. Investigations, including X-rays, rheumatoid factor, and
antinuclear factor, were negative, although his erythrocytesedimentation rate was rapid at 53mm in the first hour (possibly related to his myocardial infarction). It is now almost 3 months since practolol was discontinued, and joint symptoms have not recurred. It would seem reasonable, therefore, to implicate practolol as a cause of this patient’s reversible joint pain and effusions. Coronary Care Unit, Royal Infirmary, Edinburgh EH3 9YW.
DAVID M. FRASER NORMAN A. IRVINE
HOW DO DOCTORS LEARN ABOUT DRUGS?
StR,—May we suggest active cooperation between the clinical pharmacologist and drug-information pharmacist as a constructive approach to the problem of providing an effective information service. Workers in each of these disciplines have an important role to play in advising on the patient-drug-disease situation, and it ought to be stressed that pharmacy graduates do receive during their training a thorough grounding in those sciences relating to drug action and potency. Our experience 3. 4.
Wright, P. Br. med. J. 1975, i, 595. Alarcón-Segovia, D., Wakim, K. G., Worthington, J. W., Ward,
L. E. Medi-
cine, 1967, 46, 1. 5. Fakhro, A. M., Ritchie, R. F., Lown, B. Am. J. Cardiol. 1967, 20, 367. 6. Raftery, E. B., Denman, A. M. Br. med. J. 1973, ii, 452.
misleading
C. N. CHEN A. H. CRISP J. KOVAL B. MCGUINNESS
Academic Department of Psychiatry, St George’s Hospital Medical School,
London SW 17
PLEURAL EFFUSIONS AFTER PRACTOLOL
SiR,-Fleming and Hickling’ have described a case in which practolol may have caused pleural effusions. We have seen pleural involvement, with cutaneous and ocular reactions and L.E. syndrome, in a patient who had been taking practolol for three years. A 66-year-old retired coalminer with complicated pneumoconiosis was admitted to this unit in August, 1974, complaining of rapidly increasing breathlessness for 12 weeks, patchy scaling skin lesions, irritation of the eyes, and mistiness of vision. He had had ischxmic heart-disease since 1965. During 1971 practolol was prescribed, 200 mg daily increasing to 600 mg with dramatic relief of angina. His forced expiratory volume in 1(F.E.V.1), forced vital capacity, airways resistance did not change. In 1973, because of a recurrence of angina, the dose was increased to 800 mg daily with good effect, and he had remained well until the time of presentation. Examination revealed a pale man who was apyrexial and orthopnceic. There were scaling psoriasiform lesions over the extensor aspects of both elbows and knees and the skin of the palms was thickened. Discoid erythematous lesions were present on the forearms. The right eye had the appearance of a conjunctivitis. There were signs of a pleural effusion in the left chest. Practolol was discontinued. The chest radiograph showed a category B progressive massive fibrosis of coalworkers’ pneumoconiosis, unchanged since 1969. However, there was pleural thickening at the left lower zone and the right costophrenic angle with a left-sided pleural effusion, which had occurred since his previous radiograph in November, 1973. The principal abnormal laboratory findings were erythrocytesedimentation rate (Westergren) 36 mm/h (first); L.E. cells in peripheral blood and antinuclear factor positive; serum-alkaline-phosphatase 84 t.u./1 (normal 10-15), 5-nucleotidase 16.5 I.u/l (normal 4-11); bromsulphthalein retention 13% at 45 min but other liver-function tests normal. Pleural biopsy revealed collagenous thickening of pleura with lymphocytic infiltration of intercostal muscle. Skin biopsies showed moderate perivascular chronic inflammatory infiltrate in the upper dermis. The epidermis showed focal areas of atrophy with some focal parakeratosis and broadening of rete pegs. Liver biopsy revealed periponal small round-cell infiltration only. After withdrawal of practolol the skin lesions faded, although the eye symptoms persisted, as did the breathlessness which had reduced effort tolerance to 30 m on level ground. More detailed lung-function assessment revealed a reduced transfer factor 16-3ml min-’ mmHg-’ (normal 23-4) and total lung capacity 4560 ml (normal 5990),2 in addition to reduced ventilatory capacity. Although the skin lesions were disappearing the other abnormalities persisted, the E.S.R. increased to 60 mm, whilst the alkaline phosphatase increased to 110 Lv.!1 and the 5-nucleotidase rose to 19 t.u./1. In view of the persistence of these abnormalities we gave prednisone 40 mg daily reducing to a maintenance dose of 15 mg. Within 4 weeks he was no longer restricted by breathlessness whilst walking on level ground. Although pleural thickening persisted there was no recurrence of effusion; the skin lesions disappeared, but dryness of the eyes continued to prove 1. Fleming, H. A., Hickling, P. Lancet, 1975, ii, E. Lung Function. Oxford, 1975.
2. Cotes, J.
1202.
troublesome. L.E. cells were no longer present in the peripheral blood and the antinuclear factor became negative. The E.S.R. fell to 6 mm. All biochemical abnormalities returned to normal. The transfer factor and total lung capacity have returned to normal and the corticosteroid dose is down to 5 mg daily. Although some patients showing the oculomucocutaneous syndrome3 associated with practolol are reported to have had pleurisy, there have been no detailed descriptions of involvement of the pleura. A syndrome similar to L.E. may be induced by drugs such as hydrallazine4 and procainamide.’ Raftery and Oenman6 reported a similar syndrome in three patients treated with practolol. The normal serum complement and absence of renal involvement are characteristic of drug-induced S.L.E.’ Medical Research Council Pneumoconiosis Unit,
Llandough Hospital, Penarth,
Glamorgan CF6 1XW
A. D. MACKAY A. T. AXFORD
JOINT EFFUSIONS AND PRACTOLOL SIR,-Skin eruptions, keratoconjunctivitis sicca, and fibrosing peritonitis are well-recognised complications of prolonged therapy with practolol, and it would seem that pleural effusion and pleural thickening must now be added to this list (Dec. 13, p. 1202). We would like to report a case of yet another possible reaction to this drug. A 52-year-old man was admitted to hospital with an acute myocardial infarction in October, 1975. He had sustained a previous myocardial infarction in 1973, and for 6 years had had classical angina of effort. Apart from a 2-month period after his previous myocardial infarction he had taken practolol continuously for almost 3 years in a dose of between 200 and 400 mg daily; this had controlled his exertional chest pain. 6 weeks before this admission he developed pain and swelling of both knees which persisted for almost 2 weeks until he discontinued practolol. The swelling subsided over the next few days so he started treatment once more; however, after a further week the joint swelling returned, so he again stopped the drug and he has remained free of joint symptoms since that time. On admission to hospital he had a slight residual effusion in the right knee but otherwise no abnormality in this or other joints. He showed no evidence of skin or eye involvement. Investigations, including X-rays, rheumatoid factor, and
antinuclear factor, were negative, although his erythrocytesedimentation rate was rapid at 53mm in the first hour (possibly related to his myocardial infarction). It is now almost 3 months since practolol was discontinued, and joint symptoms have not recurred. It would seem reasonable, therefore, to implicate practolol as a cause of this patient’s reversible joint pain and effusions. Coronary Care Unit, Royal Infirmary, Edinburgh EH3 9YW.
DAVID M. FRASER NORMAN A. IRVINE
HOW DO DOCTORS LEARN ABOUT DRUGS?
StR,—May we suggest active cooperation between the clinical pharmacologist and drug-information pharmacist as a constructive approach to the problem of providing an effective information service. Workers in each of these disciplines have an important role to play in advising on the patient-drug-disease situation, and it ought to be stressed that pharmacy graduates do receive during their training a thorough grounding in those sciences relating to drug action and potency. Our experience 3. 4.
Wright, P. Br. med. J. 1975, i, 595. Alarcón-Segovia, D., Wakim, K. G., Worthington, J. W., Ward,
L. E. Medi-
cine, 1967, 46, 1. 5. Fakhro, A. M., Ritchie, R. F., Lown, B. Am. J. Cardiol. 1967, 20, 367. 6. Raftery, E. B., Denman, A. M. Br. med. J. 1973, ii, 452.
