1202
medically qualified personnel with a special interest in drugs; in particular, we are able to provide advice on the practical management of individual
patients, as well as information on pharmacology, pharmacokinetics, therapeutic problems, and chnical toxicology. In the first six months since its inception in May, 1975, we inquiries. Of these, 67% have come from hospital doctors, 30% from general practitioners, and the remainder from drug firms, coroners, &c. 60% of our calls orginate from area health authorities in the Northern Region outhave received 249
side the Newcastle A.H.A.(teaching), 7% have originated outside the region (although we have made no attempt to publiclse our service beyond the boundaries of the R.H.A.), and 2% have come from overseas. Our initial experience in providing a clinical drug information service encourages us to believe that there is a considerable demand for this type of facility, and the staff who provide it feel that they are making a useful and interesting contribution to medical care. Department of Pharmacological Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne NE 1 7RU.
MICHAEL D. RAWLINS
Shotley Bridge General Hospital,
D. M. DAVIES
Consett, Co. Durham.
SKIN ERUPTION DUE TO CLOFIBRATE man was found to have Fredrickson and was prescribed clofibrate, 1 g twice type-iv hyperlipidxmia a day, on July 24, 1975. On Aug. 1, he had anorexia and nausea which gradually got worse. On Aug. 6, he began to vomit and fainted twice. He noticed a rash on the forearms on Aug. 7, but did not observe its further development. He stopped taking clofibrate on Aug. 9, on his own initiative. He was admitted to the Western Hospital on Aug. 12, as a suspected case of measles. On admission, he looked ill, he had a temperature of 39°C, and his blood-pressure was 110/80mm Hg. He had a rash affecting the whole body. His face was swollen and red and his eyes puffy. The rash on his limbs and trunk consisted of macules and papules which had for the most part become confluent, producing a blotchy appearance. On the distal parts of his limbs, some lesions had become purpuric. Over the next six days, the whole rash became purpuric and then gradually disappeared. On Aug. 21, at 11 A.M., a test dose of 1 g clofibrate was given with the patient’s consent. He became unwell at 1.30 P.M. with epigastric discomfort. An hour later he vomited and his temperature rose to 37.6°C. At 8 P.M., he developed a generalised itchy erythema. At 10 P.M. his temperature was 39°C. Then his eyes became puffy and his face swollen. By midnight, he had become shocked and his bloodpressure had dropped to 70/40mm Hg. He was given adrenaline subcutaneously and hydrocortisone intravenously, and the symptoms disappeared. His general condition rapidly improved. The erythema disappeared after 12 hours and it was followed by extensive desquamation which continued for several days. After recovery, he was given two clofibrate capsules containing corn oil in place of clofibrate. No reaction occurred. There have been few reports of skin eruptions due to clofibrate. Hollander’ studied 11 patients taking 500mg three times daily and 1 acquired a maculopapular rash. A papular rash appeared in 1 of the 17 patients treated with clofibrate by Dujovne, Weiss, and Bianchine.2 24 out of the 518 patients treated by Krasno and Kidera3 were taken off clofibrate because of dermatitis, headache, fatigue, or loss of libido. The Data Sheet Compendium 1975 does not mention skin eruption as a side-effect of clofibrate. Our patient developed a severe
SIR,-A 54-year-old
1. 2.
general reaction in addition to the skin eruption. We excluded the capsules themselves, as a cause, by giving ones containing corn oil. The reaction must, therefore, have been due to clofibrate itself. Infectious Diseases Unit, Western Hospital,
Seagrave Road, London SW6
PLEURAL EFFUSIONS AFTER PRACTOLOL
SIR,-Patients have had reactions to practolol as long as 18 months after stopping the drug.’ We wish to report a case in which practolol may have caused pleural effusions. The patient is now aged 54. In 1959 he had erythema nodosum and bilateral hilar adenopathy. Sarcoidosis was diagnosed and subsided without specific treatment. In 1971 he had symptoms of left heart failure with frequent multifocal ventricular ectopic beats. Kveim reaction was positive and the presumptive diagnosis was myocardial sarcoid.2 In May he was started on digoxin, cyclopenthiazide, and practolol up to 200 mg twice daily. From July he had prednisone (10 mg twice daily) for three months. In October practolol was increased to 300 mg twice daily because of a slight increase in ectopics. In February, 1972, an irritable psoriaform rash appeared on the limbs. It was relieved by betamethasone cream. A drug reaction seemed unlikely, but his diuretic was changed to chlorthalidone, without benefit. In March he was admitted with myocardial infarction and received short-term anticoagulants. By April the rash covered the whole body. Practolol was continued in a dose of 200 mg twice daily. The skin condition responded to triamcinolone (24 mg daily), but on a lower dose it deteriorated. In July azathioprine was added to the regimen, without much improvement. The next event was in July, 1974, when he complained of dry eyes, and bilateral keratoconjunctivitis sicca was diagnosed. An association with practolol was suspected, the drug was stopped, and his very severe skin condition improved miraculously. Triamcinolone and azathioprine were stopped and by September the skin was nearly normal. In December, 1974, he was short of breath and was found to have bilateral pleural effusions. These responded somewhat to increased diuretics and digitalis. In June, 1975, the effusions occupied about half the pleural cavity. On several chest aspirations the fluid was uniformly and heavily blood-stained. The pleura felt fibrotic and hard to puncture. There were no neoplastic or other abnormal cells in the fluid. Pleural biopsy showed fibrin on the surface of fibrotically thickened pleura with a few non-specific chronic inflammatory cells. Abdominal X-ray, barium meal, and bronchoscopy were negative, as were antinuclear factor and lupus-erythematosus cells. Lung-scan eliminated pulmonary embolism. At present, on digitalis and diuretics, his condition seems fairly stable. The eye dryness continues. We have been unable to find any reasonable explanation for the bilateral blood-stained pleural effusions and pleural thickening, other than the practolol. Addenbrooke’s Hospital,
Cambridge.
a cross-channel ferry to France, I responded to a call for a doctor, and was taken to see a young loudspeaker Black girl from Mozambique who was in considerable distress, complaining of a sensation in the throat which caused her tongue to protrude and which almost prevented her swallowing.
SIR,-On
1.
117.
J.J. Am
med. Ass.
1972, 219, 845
HUGH A. FLEMING PATRICIA HICKLING
POSSIBLE REACTION TO PROSTAGLANDINS
Hollander, W. Cardiovascular Drug Therapy; p. 339, New York, 1965. Dujovne, C. A., Weiss, P., Bianchine, J. R. Clin. Pharmac Ther. 1971, 12,
3. Krasno, L. R., Kidera, G.
M. A. ARIF J. VAHRMAN
Wright, P. Br. med.J. 1975, i, 595.
2. Fleming, H. A. Br. Heart J. 1974, 36, 54.
1203
accompanying medical report told of a therapeutic aborprevious day, involving an intrauterine prostaglandin administration, which was ineffective until followed by an intravenous prostaglandin drip. She was one of a coachload of similar patients, the rest of whom seemed perfectly well and were cheerfully singing in the bar. Faute de mieux, I prescribed four tablets of aspirin on the assumption that the symptoms were either hysterical, or an unusual side-effect of prostaglandins. In 30—40 min the symptoms had disappeared and the patient was eating a hearty An
tion the
meal. Since prostaglandins are supposed to disappear rapidly from the circulation, and since in any case aspirin is said to be an inhibitor of prostaglandin biosynthesis I am puzzled by the patient’s response to my treatment. Hertfordshire Area Health Authority, Hamilton House, 111 Marlowes, Hemel Hempstead, Herts, HP1 1EN
MICHAEL BALL
PROTHROMBIN-COMPLEX CONCENTRATE IN TREATMENT OF CLASSICAL HÆMOPHILIA WITH FACTOR-VIII ANTIBODY
SIR,-Successful use of activated and non-activated prothrombin-complex concentrates in the management of classical hemophiliacs with anti-factor-vm antibodies has been reported by several investigators.’-4 Failures have also been reported by Dr Bloom (Aug. 23, p. 369). However, the effect of such treat-
necessary to restrict its use to severe bleeding episodes, and (2) manufacturers should be encouraged to prepare prothrombincomplex concentrates free of factor vm for treatment of patients with antibody to factor viu. Centre pour Enfants Hémophiles, Croix Rouge Française, 78940-La Queue lez Yvelines, France.
SIR,-Dr Giraud and colleagues (Nov. 29,
p. 1088) report of babies born to mothers with severe hepatitis-B viral hepatitis. They observed the outcome and drew three conclusions, the second of which was that maternofetal contamination was likely to have been transplacental because the babies had been born by caesarean section and immediately separated from their mother. Although transplacental infection may occur, these cases did not confirm it. It is wrong to suggest that cxsarean section is an "immaculate" delivery in which the baby is not contaminated by the mother’s blood.- Infection could have occurred during delivery.
two cases
St Thomas’ Hospital, London SE1 7EH.
the inhibitor titre has not been stated in these reports. We have treated 2 patients with classical haemophilia, who also have antibody to factor-vm, with the French prothrombinCase 1.-This 11-year-old boy had a very painful haemarthrosis of the right knee. Aspiration was performed under the cover of two injections of 44 units/kg of factor ix given at 4-hourly intervals. Complete clinical and functional resolution was obtained within 3 days. Case 2.-This 6-year-old boy had a post-traumatic haematoma of the left costal cardiac region. His hasmatocrit was 25%, and he received two injections of 28.5units/kg of factor IX at 4-hourly intervals. Bleeding stopped immediately. Within 5 days his haematocrit had risen to 31 %.
In both cases treatment was monitored by standard tests of haemostasis. Antibody titres were determined at intervals by a modification of the method of Biggs and Bidwell6 and expressed in units as previously described.7 Both patients showed a striking decrease in the kaolin-activated partial thromboplastin-time and the prothromin-time, still present 4 hours after the second injection. No evidence of disseminated intravascular coagulation was observed, since the platelet-count and fibrin(ogen)-degradation products were stable. Before treatment, neither patient had clinical or laboratory signs of liver disease. This treatment was followed by an anamnestic resoonse in both cases. Patient 1 had a pretreatment titre of 1.8units, which rose to 85 units 15 days after treatment. Patient 2 had a titre of 0.2 units before treatment, and after 15 days the antibody level was 0.8 units. Although no factor-vm antigen could be detected by rocket immunoelectrophoresis, the anamnestic response may have been due to the presence of small amounts of factor vm in the concentrate. These two observations confirm that non-activated factor-tx concentrate may be effective in controlling bleeding in patients with classical haemophilia complicated by antibody (inhibitor) and was used without thrombotic complication or disseminated intravascular coagulation. Although clinically active, this material can trigger an anamnestic response. Thus, (1) it is 1. Kurczynski, E. M., Penner, J. A. New Engl. J. Med. 1974, 291, 164. 2. Sultan, Y., Brouet, J. C. ibid. p.1087. 3. Abildgaard, C. F., Britton, M., Roberts, R. Blood, 1974, 44, 933. 4. Bloom, A. L., Hutton, R. D. Lancet, 1975, ii, 370. 5. Soulier, J. P., Steinbuch, M. in Handbook of Haemophilia (edited by K. M. Bnnkhous and H. C. Hemker); p. 531. Amsterdam, 1975. 6. Biggs, R., Bidwell, E. Br. J. Hœmat. 1959, 5, 379. 7. Allain, J. P., Frommel, D. Blood, 1973, 43, 437.
P. ALLAIN
HEPATITIS-B VIRUS INFECTION OF CHILDREN BORN TO MOTHERS WITH SEVERE HEPATITIS
J. W. SCOPES
DIAGNOSIS OF ALPHA1-ANTITRYPSIN DEFICIENCY
ment on
complex concentrate P.P.S.B.’
J.
I G. R. KRIEGER
SIR,—Dr Millward-Sadler and his colleagues (Nov. 22,
p.
1050) refer to the frequent association between serum-ot-antitrypsin deficiency and retention of the antitrypsin as diastaseresistant periodic-acid/Schiff (P.A.S.) positive globular inclusions within the cytoplasm of liver cells.’2 They report, however, two patients in whom liver-cell inclusions, morphologically identical to those seen in «,-antitrypsin deficiency, were associated with normal serum--a,-antitrypsin levels and phenotype. Immunochemical staining of the inclusions in these two cases was negative for «,-antitrypsin. Intracytoplasmic globular inclusions in liver cells have been reported under a variety of experimental conditions3-’ although the staining characteristics of the inclusions is not always recorded. In man, P.A.s.-positive intracytoplasmic globules are often found in hepatomas;6unfortunately a,-antitrypsin concentrations have not been recorded in such cases. Mallory illustrates a paper on alcoholic cirrhosis with a figure (his fig. 4) which depicts intracytoplasmic globular inclusions in liver cells, interpreted as decolorised bile.8 Globular inclusions ultrastructurally quite different from those of &agr;1-antitrypsin deficiency, but of similar morphology on light microscopy, have been described in a patient without evidence of K,-antitrypsin deficiency9 (serum electrophoresis normal, no relevant family history, but serum-cxcantitrypsin not determined during life). It seems, therefore, that the presence of diastase-resistant P.A.s.-positive globules in the cytoplasm of liver cells is not exclusively diagnostic of a,-antitrypsin deficiency. This appearance, on light microscopy, simply reflects the retention of a cell product with the appropriate staining characteristics as globular cytoplasmic inclusions similar to the Russell bodies that are most often found in plasma cells. DeLellis, R. A., Balogh, K., Merk, F. B., Chirife, A. M. Archs Path. 1972, 94, 308. 2. Ward, A. M., Underwood, J. C. E.J. clin. Path. 1974, 27, 467. 3. Rosin, A., Doljanski, L. Br. J. exp. Path. 1944, 25, 111. 4. Weld, J. T., Von Glahn, W. C., Mitchell, L. D. Proc. Soc. exp. Biol. Med. 1941, 48, 229. 5. Fisher, E. R., Fisher, B. Am. J. Path. 1954, 30, 987. 6. Ishak, K. G., Glunz, P. R. Cancer, 1967, 20, 396. 7. Norkin, S. A., Campagna-Pinto, D. Archs Path. 1968, 86, 25. 8. Mallory, F. B. Am. J. Path. 1933, 9, 557. 9. Underwood, J. C. E.J. clin. Path. 1972, 25, 821. 1.
medically qualified personnel with a special interest in drugs; in particular, we are able to provide advice on the practical management of individual
patients, as well as information on pharmacology, pharmacokinetics, therapeutic problems, and chnical toxicology. In the first six months since its inception in May, 1975, we inquiries. Of these, 67% have come from hospital doctors, 30% from general practitioners, and the remainder from drug firms, coroners, &c. 60% of our calls orginate from area health authorities in the Northern Region outhave received 249
side the Newcastle A.H.A.(teaching), 7% have originated outside the region (although we have made no attempt to publiclse our service beyond the boundaries of the R.H.A.), and 2% have come from overseas. Our initial experience in providing a clinical drug information service encourages us to believe that there is a considerable demand for this type of facility, and the staff who provide it feel that they are making a useful and interesting contribution to medical care. Department of Pharmacological Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne NE 1 7RU.
MICHAEL D. RAWLINS
Shotley Bridge General Hospital,
D. M. DAVIES
Consett, Co. Durham.
SKIN ERUPTION DUE TO CLOFIBRATE man was found to have Fredrickson and was prescribed clofibrate, 1 g twice type-iv hyperlipidxmia a day, on July 24, 1975. On Aug. 1, he had anorexia and nausea which gradually got worse. On Aug. 6, he began to vomit and fainted twice. He noticed a rash on the forearms on Aug. 7, but did not observe its further development. He stopped taking clofibrate on Aug. 9, on his own initiative. He was admitted to the Western Hospital on Aug. 12, as a suspected case of measles. On admission, he looked ill, he had a temperature of 39°C, and his blood-pressure was 110/80mm Hg. He had a rash affecting the whole body. His face was swollen and red and his eyes puffy. The rash on his limbs and trunk consisted of macules and papules which had for the most part become confluent, producing a blotchy appearance. On the distal parts of his limbs, some lesions had become purpuric. Over the next six days, the whole rash became purpuric and then gradually disappeared. On Aug. 21, at 11 A.M., a test dose of 1 g clofibrate was given with the patient’s consent. He became unwell at 1.30 P.M. with epigastric discomfort. An hour later he vomited and his temperature rose to 37.6°C. At 8 P.M., he developed a generalised itchy erythema. At 10 P.M. his temperature was 39°C. Then his eyes became puffy and his face swollen. By midnight, he had become shocked and his bloodpressure had dropped to 70/40mm Hg. He was given adrenaline subcutaneously and hydrocortisone intravenously, and the symptoms disappeared. His general condition rapidly improved. The erythema disappeared after 12 hours and it was followed by extensive desquamation which continued for several days. After recovery, he was given two clofibrate capsules containing corn oil in place of clofibrate. No reaction occurred. There have been few reports of skin eruptions due to clofibrate. Hollander’ studied 11 patients taking 500mg three times daily and 1 acquired a maculopapular rash. A papular rash appeared in 1 of the 17 patients treated with clofibrate by Dujovne, Weiss, and Bianchine.2 24 out of the 518 patients treated by Krasno and Kidera3 were taken off clofibrate because of dermatitis, headache, fatigue, or loss of libido. The Data Sheet Compendium 1975 does not mention skin eruption as a side-effect of clofibrate. Our patient developed a severe
SIR,-A 54-year-old
1. 2.
general reaction in addition to the skin eruption. We excluded the capsules themselves, as a cause, by giving ones containing corn oil. The reaction must, therefore, have been due to clofibrate itself. Infectious Diseases Unit, Western Hospital,
Seagrave Road, London SW6
PLEURAL EFFUSIONS AFTER PRACTOLOL
SIR,-Patients have had reactions to practolol as long as 18 months after stopping the drug.’ We wish to report a case in which practolol may have caused pleural effusions. The patient is now aged 54. In 1959 he had erythema nodosum and bilateral hilar adenopathy. Sarcoidosis was diagnosed and subsided without specific treatment. In 1971 he had symptoms of left heart failure with frequent multifocal ventricular ectopic beats. Kveim reaction was positive and the presumptive diagnosis was myocardial sarcoid.2 In May he was started on digoxin, cyclopenthiazide, and practolol up to 200 mg twice daily. From July he had prednisone (10 mg twice daily) for three months. In October practolol was increased to 300 mg twice daily because of a slight increase in ectopics. In February, 1972, an irritable psoriaform rash appeared on the limbs. It was relieved by betamethasone cream. A drug reaction seemed unlikely, but his diuretic was changed to chlorthalidone, without benefit. In March he was admitted with myocardial infarction and received short-term anticoagulants. By April the rash covered the whole body. Practolol was continued in a dose of 200 mg twice daily. The skin condition responded to triamcinolone (24 mg daily), but on a lower dose it deteriorated. In July azathioprine was added to the regimen, without much improvement. The next event was in July, 1974, when he complained of dry eyes, and bilateral keratoconjunctivitis sicca was diagnosed. An association with practolol was suspected, the drug was stopped, and his very severe skin condition improved miraculously. Triamcinolone and azathioprine were stopped and by September the skin was nearly normal. In December, 1974, he was short of breath and was found to have bilateral pleural effusions. These responded somewhat to increased diuretics and digitalis. In June, 1975, the effusions occupied about half the pleural cavity. On several chest aspirations the fluid was uniformly and heavily blood-stained. The pleura felt fibrotic and hard to puncture. There were no neoplastic or other abnormal cells in the fluid. Pleural biopsy showed fibrin on the surface of fibrotically thickened pleura with a few non-specific chronic inflammatory cells. Abdominal X-ray, barium meal, and bronchoscopy were negative, as were antinuclear factor and lupus-erythematosus cells. Lung-scan eliminated pulmonary embolism. At present, on digitalis and diuretics, his condition seems fairly stable. The eye dryness continues. We have been unable to find any reasonable explanation for the bilateral blood-stained pleural effusions and pleural thickening, other than the practolol. Addenbrooke’s Hospital,
Cambridge.
a cross-channel ferry to France, I responded to a call for a doctor, and was taken to see a young loudspeaker Black girl from Mozambique who was in considerable distress, complaining of a sensation in the throat which caused her tongue to protrude and which almost prevented her swallowing.
SIR,-On
1.
117.
J.J. Am
med. Ass.
1972, 219, 845
HUGH A. FLEMING PATRICIA HICKLING
POSSIBLE REACTION TO PROSTAGLANDINS
Hollander, W. Cardiovascular Drug Therapy; p. 339, New York, 1965. Dujovne, C. A., Weiss, P., Bianchine, J. R. Clin. Pharmac Ther. 1971, 12,
3. Krasno, L. R., Kidera, G.
M. A. ARIF J. VAHRMAN
Wright, P. Br. med.J. 1975, i, 595.
2. Fleming, H. A. Br. Heart J. 1974, 36, 54.
1203
accompanying medical report told of a therapeutic aborprevious day, involving an intrauterine prostaglandin administration, which was ineffective until followed by an intravenous prostaglandin drip. She was one of a coachload of similar patients, the rest of whom seemed perfectly well and were cheerfully singing in the bar. Faute de mieux, I prescribed four tablets of aspirin on the assumption that the symptoms were either hysterical, or an unusual side-effect of prostaglandins. In 30—40 min the symptoms had disappeared and the patient was eating a hearty An
tion the
meal. Since prostaglandins are supposed to disappear rapidly from the circulation, and since in any case aspirin is said to be an inhibitor of prostaglandin biosynthesis I am puzzled by the patient’s response to my treatment. Hertfordshire Area Health Authority, Hamilton House, 111 Marlowes, Hemel Hempstead, Herts, HP1 1EN
MICHAEL BALL
PROTHROMBIN-COMPLEX CONCENTRATE IN TREATMENT OF CLASSICAL HÆMOPHILIA WITH FACTOR-VIII ANTIBODY
SIR,-Successful use of activated and non-activated prothrombin-complex concentrates in the management of classical hemophiliacs with anti-factor-vm antibodies has been reported by several investigators.’-4 Failures have also been reported by Dr Bloom (Aug. 23, p. 369). However, the effect of such treat-
necessary to restrict its use to severe bleeding episodes, and (2) manufacturers should be encouraged to prepare prothrombincomplex concentrates free of factor vm for treatment of patients with antibody to factor viu. Centre pour Enfants Hémophiles, Croix Rouge Française, 78940-La Queue lez Yvelines, France.
SIR,-Dr Giraud and colleagues (Nov. 29,
p. 1088) report of babies born to mothers with severe hepatitis-B viral hepatitis. They observed the outcome and drew three conclusions, the second of which was that maternofetal contamination was likely to have been transplacental because the babies had been born by caesarean section and immediately separated from their mother. Although transplacental infection may occur, these cases did not confirm it. It is wrong to suggest that cxsarean section is an "immaculate" delivery in which the baby is not contaminated by the mother’s blood.- Infection could have occurred during delivery.
two cases
St Thomas’ Hospital, London SE1 7EH.
the inhibitor titre has not been stated in these reports. We have treated 2 patients with classical haemophilia, who also have antibody to factor-vm, with the French prothrombinCase 1.-This 11-year-old boy had a very painful haemarthrosis of the right knee. Aspiration was performed under the cover of two injections of 44 units/kg of factor ix given at 4-hourly intervals. Complete clinical and functional resolution was obtained within 3 days. Case 2.-This 6-year-old boy had a post-traumatic haematoma of the left costal cardiac region. His hasmatocrit was 25%, and he received two injections of 28.5units/kg of factor IX at 4-hourly intervals. Bleeding stopped immediately. Within 5 days his haematocrit had risen to 31 %.
In both cases treatment was monitored by standard tests of haemostasis. Antibody titres were determined at intervals by a modification of the method of Biggs and Bidwell6 and expressed in units as previously described.7 Both patients showed a striking decrease in the kaolin-activated partial thromboplastin-time and the prothromin-time, still present 4 hours after the second injection. No evidence of disseminated intravascular coagulation was observed, since the platelet-count and fibrin(ogen)-degradation products were stable. Before treatment, neither patient had clinical or laboratory signs of liver disease. This treatment was followed by an anamnestic resoonse in both cases. Patient 1 had a pretreatment titre of 1.8units, which rose to 85 units 15 days after treatment. Patient 2 had a titre of 0.2 units before treatment, and after 15 days the antibody level was 0.8 units. Although no factor-vm antigen could be detected by rocket immunoelectrophoresis, the anamnestic response may have been due to the presence of small amounts of factor vm in the concentrate. These two observations confirm that non-activated factor-tx concentrate may be effective in controlling bleeding in patients with classical haemophilia complicated by antibody (inhibitor) and was used without thrombotic complication or disseminated intravascular coagulation. Although clinically active, this material can trigger an anamnestic response. Thus, (1) it is 1. Kurczynski, E. M., Penner, J. A. New Engl. J. Med. 1974, 291, 164. 2. Sultan, Y., Brouet, J. C. ibid. p.1087. 3. Abildgaard, C. F., Britton, M., Roberts, R. Blood, 1974, 44, 933. 4. Bloom, A. L., Hutton, R. D. Lancet, 1975, ii, 370. 5. Soulier, J. P., Steinbuch, M. in Handbook of Haemophilia (edited by K. M. Bnnkhous and H. C. Hemker); p. 531. Amsterdam, 1975. 6. Biggs, R., Bidwell, E. Br. J. Hœmat. 1959, 5, 379. 7. Allain, J. P., Frommel, D. Blood, 1973, 43, 437.
P. ALLAIN
HEPATITIS-B VIRUS INFECTION OF CHILDREN BORN TO MOTHERS WITH SEVERE HEPATITIS
J. W. SCOPES
DIAGNOSIS OF ALPHA1-ANTITRYPSIN DEFICIENCY
ment on
complex concentrate P.P.S.B.’
J.
I G. R. KRIEGER
SIR,—Dr Millward-Sadler and his colleagues (Nov. 22,
p.
1050) refer to the frequent association between serum-ot-antitrypsin deficiency and retention of the antitrypsin as diastaseresistant periodic-acid/Schiff (P.A.S.) positive globular inclusions within the cytoplasm of liver cells.’2 They report, however, two patients in whom liver-cell inclusions, morphologically identical to those seen in «,-antitrypsin deficiency, were associated with normal serum--a,-antitrypsin levels and phenotype. Immunochemical staining of the inclusions in these two cases was negative for «,-antitrypsin. Intracytoplasmic globular inclusions in liver cells have been reported under a variety of experimental conditions3-’ although the staining characteristics of the inclusions is not always recorded. In man, P.A.s.-positive intracytoplasmic globules are often found in hepatomas;6unfortunately a,-antitrypsin concentrations have not been recorded in such cases. Mallory illustrates a paper on alcoholic cirrhosis with a figure (his fig. 4) which depicts intracytoplasmic globular inclusions in liver cells, interpreted as decolorised bile.8 Globular inclusions ultrastructurally quite different from those of &agr;1-antitrypsin deficiency, but of similar morphology on light microscopy, have been described in a patient without evidence of K,-antitrypsin deficiency9 (serum electrophoresis normal, no relevant family history, but serum-cxcantitrypsin not determined during life). It seems, therefore, that the presence of diastase-resistant P.A.s.-positive globules in the cytoplasm of liver cells is not exclusively diagnostic of a,-antitrypsin deficiency. This appearance, on light microscopy, simply reflects the retention of a cell product with the appropriate staining characteristics as globular cytoplasmic inclusions similar to the Russell bodies that are most often found in plasma cells. DeLellis, R. A., Balogh, K., Merk, F. B., Chirife, A. M. Archs Path. 1972, 94, 308. 2. Ward, A. M., Underwood, J. C. E.J. clin. Path. 1974, 27, 467. 3. Rosin, A., Doljanski, L. Br. J. exp. Path. 1944, 25, 111. 4. Weld, J. T., Von Glahn, W. C., Mitchell, L. D. Proc. Soc. exp. Biol. Med. 1941, 48, 229. 5. Fisher, E. R., Fisher, B. Am. J. Path. 1954, 30, 987. 6. Ishak, K. G., Glunz, P. R. Cancer, 1967, 20, 396. 7. Norkin, S. A., Campagna-Pinto, D. Archs Path. 1968, 86, 25. 8. Mallory, F. B. Am. J. Path. 1933, 9, 557. 9. Underwood, J. C. E.J. clin. Path. 1972, 25, 821. 1.
