816
THE LANCET, OCTOBER 25,1975
costeroid on the adrenal response to tetracosactrin showed no change in the mean responses in the two groups, but there were individual abnormal responses which were not satisfactorily explained. Using the criteria of Wood et aLI it has already been shown that there is no effect on adrenal function after the inhalation of 400 flg betamethasone valerate":" or when the drug is introduced into the nose in seasonal allergic rhinitis.' The lack of systemic side-effects or of adrenal suppression makes the newer inhaled corticosteroids a great advance in the treatment of asthma. It should, however, be pointed out that, in the trial described, the manufacturers of the beclomethasone dipropionate must have formulated a special aerosol for the trial, and this is not mentioned, because normally each puff of the commercially available preparation 'Becotide' is only 50 flg while that of the betamethasone valerate ('Sextasol') is 100 flg. This was not, therefore, a trial of 8 puffs of the commercially available pressurised steroid aerosol, but of the same amount of the two aerosols. St Mary's Hospital, Praed Street,
London W2 1NY.
No. tested
HBsAg positive
ami-HB s positive
67 11 (16'4%) 48 (716%) I t seems therefore that some commercial y-globulin preparations may contain HBsAg. Moreover, it is possible that some of the anti-Hfk-positive samples were obtained when the preparation contained immune complexes with excess antibody. IIIrd Department of Internal NICOLA DIOGUARDI Medicine, ROBERTO DE FRANCHIS. University of Milan, Italy.
HBAg IN SPINAL FLUID IN LEUKlEMIA A. W. FRANKLAND
FORMALIN ASTHMA IN HOSPITAL LABORATORY STAFF SIR,-The personal anecdote of Dr Porter (Sept. 27, p. 603) about his acute respiratory distress following formalin inhalation, and your leading article (Oct. 11, p. 691) on non-allergic provocation of asthma, prompted me to recall a patient I saw in 1962. A hospitallaboratory technican, aged 57, working at the time in the morbid-anatomy department, had had pulmonary tuberculosis, controlled by bilateral artificial pneumothorax. He was a moderate smoker,but not a chronic bronchitic. He had not previouslyhad bronchial asthma and he was not an atopic subject. In 1962 he began to have attacks of cough and severechest wheezing; and after investigation, there could be no doubt that they were asthmatic attacks related to exposure to formalin vapour during his work with pathological specimens and the preparation of histological sections. On several occasions, severebronchial asthma followed the slightest inhalation of formalin vapour. At weekends, or on holiday, he was free of attacks, but his symptomsrecurred immediately he returned to work. He was forcedto give up his post in the morbid-anatomy department. I regarded this as late-onset bronchial asthma of non-allergic type, caused by chemical irritation of the bronchi by formalin vapour. The possibility of formalin sensitivity must be borne in mind whenever hospital laboratory staff have asthma. Redhill General Hospital, Redhill, Surrey RH1 6LA.
ALEX SAKULA
HEPATITIS-B SURFACE ANTIGEN IN COMMERCIAL GAMMA-GLOBULIN Sm,-During the past few months, an anti-allergic drug containing y-globulin has been implicated in numerous cases of hepatitis B in Italy. We tested 67 commercial y-globulin samples for hepatitis-B surface antigen (HBsAg) and antibody (anti-Hls.) by radioimmunoassay C' Ausria II ' and ' Ausab " respectively) to determine whether they were contaminated by HBsAg. Preparations for intravenous as well as for intramuscular administration were tested. Each sample was tested in triplicate, the protein concentration being adjusted to 7·5-8%-i.e., the optimum protein concentration for these methods of HBsAg and anti-H'B, determination. 1. Wood, J. B., Frankland, A. W., Dames, V. H. T., Landon,
J. Lancet, 1965,
i,243. 2. Dash, C. H. Postgrad. med.J. 1974, SO, suppl. 4,p. 25. 3. Friedman, M., Frears, ]. ibid. p. 33.
4. Miyamoto, T" Makino, S., Osawa, N., Horiuchi, Y. ibid. 1975, suppl. 5, p. 5.
Samples which were positive for HBsAg or anti-Hll, were tested again to confirm the result. The ausria II confirmatory neutralisation test was also used in those samples in which the presence of HBsAg had been confirmed by re-testing. The results are given below:
25. Frankland, A. W. o Walker, S. R. Clin. Allergy, 1975, S, 295.
SIR,-Dankert et aJ.1 found HBAg in both blood and spinal fluid in 3 of 34 leukremic children. We studied 21 children with acute lymphoblastic leukremia in hsematologic remission. 2 had meningeal leukremia. HBAg tests were carried out by radioimmunoassay (Ausria II). HBAg was detected in the blood of 8 patients (39%). Only 2 of them had previously had clinical hepatitis. Spinal-fluid samples were taken without any traces of blood and tested for the presence of HBAg. HBAg was found in the spinal fluid of 2 of the 8 children. 1 of the 2 patients had previously had hepatitis and the other had meningealleukremia, which was active and untreated at the time of this investigation. The other patient with meningeal leukremia was negative for HBAg in both blood and spinal fluid. The frequency of HBAg in our leukremic patients is much higher than that reported in one survey," although another a reported a very low frequency of HBAg in leukremic patients. During induction therapy our patients received only two or three transfusions of whole blood from their parents or relatives. Since the frequency of HBAg in the normal Sicilian population is only 2%,' we cannot explain the high frequency in our group of patients. In contrast with the findings of Dankert et al.,' who detected HBAg in the spinal fluid of all carriers studied, we found HBAg in spinal fluid from only 2 of the 8 patients who had it in their blood. This suggests that the antigen does not usually cross the blood/brain barrier. The reasons for the presence of the HBAg in the spinal fluid are not clear. 1 of our patients with HBAg in the spinal fluid had had clinical hepatitis, but the other with recovered hepatitis and persistence of HBAg in the blood had no antigen in the spinal fluid. Furthermore, HBAg was absent in the spinal fluid of two non-leukremic children with HBAg-positive hepatitis. These findings are similar to those of Trepo et al.," who were unable to find HBAg in the spinal fluid of patients with hepatitis and other liver diseases. Our second patient with HBAg-positive spinal fluid presented active meningeal leukremia. 1 of the patients of Dankert et al. 1 also had meningealleukremia. The passage of HBAg in spinal fluid in these cases could be due to the same changes in permeability which produce increased protein levels during C.N.S. involvement. Our hypothesis for explaining the sporadic presence of HBAg in the spinal 1. Dankert, J., Postma, A., de Vries, J. A., Zijlstra, J. B. Lancet, 1975, i, 690. 2. Sutnick, A. I., London, W. T., Blumberg, B. S., Yankee, R. A., Gerstley, B. J. S., Millman, I.J. natn, Cancer Inst. 1970,44,1241. 3. Sutnick, A. I., Levine, P., London, W. T., Blumberg, B. S. Lancer, 1971, i, 1200. 4. Musumeci, S. Unpublished. 5. Trepo, C., Bolot, J. F., Robert, D., Serpetjian, M., Price, A. M. Lancet, 1974, ii, 1514.
THE LANCET, OCTOBER 25,1975
costeroid on the adrenal response to tetracosactrin showed no change in the mean responses in the two groups, but there were individual abnormal responses which were not satisfactorily explained. Using the criteria of Wood et aLI it has already been shown that there is no effect on adrenal function after the inhalation of 400 flg betamethasone valerate":" or when the drug is introduced into the nose in seasonal allergic rhinitis.' The lack of systemic side-effects or of adrenal suppression makes the newer inhaled corticosteroids a great advance in the treatment of asthma. It should, however, be pointed out that, in the trial described, the manufacturers of the beclomethasone dipropionate must have formulated a special aerosol for the trial, and this is not mentioned, because normally each puff of the commercially available preparation 'Becotide' is only 50 flg while that of the betamethasone valerate ('Sextasol') is 100 flg. This was not, therefore, a trial of 8 puffs of the commercially available pressurised steroid aerosol, but of the same amount of the two aerosols. St Mary's Hospital, Praed Street,
London W2 1NY.
No. tested
HBsAg positive
ami-HB s positive
67 11 (16'4%) 48 (716%) I t seems therefore that some commercial y-globulin preparations may contain HBsAg. Moreover, it is possible that some of the anti-Hfk-positive samples were obtained when the preparation contained immune complexes with excess antibody. IIIrd Department of Internal NICOLA DIOGUARDI Medicine, ROBERTO DE FRANCHIS. University of Milan, Italy.
HBAg IN SPINAL FLUID IN LEUKlEMIA A. W. FRANKLAND
FORMALIN ASTHMA IN HOSPITAL LABORATORY STAFF SIR,-The personal anecdote of Dr Porter (Sept. 27, p. 603) about his acute respiratory distress following formalin inhalation, and your leading article (Oct. 11, p. 691) on non-allergic provocation of asthma, prompted me to recall a patient I saw in 1962. A hospitallaboratory technican, aged 57, working at the time in the morbid-anatomy department, had had pulmonary tuberculosis, controlled by bilateral artificial pneumothorax. He was a moderate smoker,but not a chronic bronchitic. He had not previouslyhad bronchial asthma and he was not an atopic subject. In 1962 he began to have attacks of cough and severechest wheezing; and after investigation, there could be no doubt that they were asthmatic attacks related to exposure to formalin vapour during his work with pathological specimens and the preparation of histological sections. On several occasions, severebronchial asthma followed the slightest inhalation of formalin vapour. At weekends, or on holiday, he was free of attacks, but his symptomsrecurred immediately he returned to work. He was forcedto give up his post in the morbid-anatomy department. I regarded this as late-onset bronchial asthma of non-allergic type, caused by chemical irritation of the bronchi by formalin vapour. The possibility of formalin sensitivity must be borne in mind whenever hospital laboratory staff have asthma. Redhill General Hospital, Redhill, Surrey RH1 6LA.
ALEX SAKULA
HEPATITIS-B SURFACE ANTIGEN IN COMMERCIAL GAMMA-GLOBULIN Sm,-During the past few months, an anti-allergic drug containing y-globulin has been implicated in numerous cases of hepatitis B in Italy. We tested 67 commercial y-globulin samples for hepatitis-B surface antigen (HBsAg) and antibody (anti-Hls.) by radioimmunoassay C' Ausria II ' and ' Ausab " respectively) to determine whether they were contaminated by HBsAg. Preparations for intravenous as well as for intramuscular administration were tested. Each sample was tested in triplicate, the protein concentration being adjusted to 7·5-8%-i.e., the optimum protein concentration for these methods of HBsAg and anti-H'B, determination. 1. Wood, J. B., Frankland, A. W., Dames, V. H. T., Landon,
J. Lancet, 1965,
i,243. 2. Dash, C. H. Postgrad. med.J. 1974, SO, suppl. 4,p. 25. 3. Friedman, M., Frears, ]. ibid. p. 33.
4. Miyamoto, T" Makino, S., Osawa, N., Horiuchi, Y. ibid. 1975, suppl. 5, p. 5.
Samples which were positive for HBsAg or anti-Hll, were tested again to confirm the result. The ausria II confirmatory neutralisation test was also used in those samples in which the presence of HBsAg had been confirmed by re-testing. The results are given below:
25. Frankland, A. W. o Walker, S. R. Clin. Allergy, 1975, S, 295.
SIR,-Dankert et aJ.1 found HBAg in both blood and spinal fluid in 3 of 34 leukremic children. We studied 21 children with acute lymphoblastic leukremia in hsematologic remission. 2 had meningeal leukremia. HBAg tests were carried out by radioimmunoassay (Ausria II). HBAg was detected in the blood of 8 patients (39%). Only 2 of them had previously had clinical hepatitis. Spinal-fluid samples were taken without any traces of blood and tested for the presence of HBAg. HBAg was found in the spinal fluid of 2 of the 8 children. 1 of the 2 patients had previously had hepatitis and the other had meningealleukremia, which was active and untreated at the time of this investigation. The other patient with meningeal leukremia was negative for HBAg in both blood and spinal fluid. The frequency of HBAg in our leukremic patients is much higher than that reported in one survey," although another a reported a very low frequency of HBAg in leukremic patients. During induction therapy our patients received only two or three transfusions of whole blood from their parents or relatives. Since the frequency of HBAg in the normal Sicilian population is only 2%,' we cannot explain the high frequency in our group of patients. In contrast with the findings of Dankert et al.,' who detected HBAg in the spinal fluid of all carriers studied, we found HBAg in spinal fluid from only 2 of the 8 patients who had it in their blood. This suggests that the antigen does not usually cross the blood/brain barrier. The reasons for the presence of the HBAg in the spinal fluid are not clear. 1 of our patients with HBAg in the spinal fluid had had clinical hepatitis, but the other with recovered hepatitis and persistence of HBAg in the blood had no antigen in the spinal fluid. Furthermore, HBAg was absent in the spinal fluid of two non-leukremic children with HBAg-positive hepatitis. These findings are similar to those of Trepo et al.," who were unable to find HBAg in the spinal fluid of patients with hepatitis and other liver diseases. Our second patient with HBAg-positive spinal fluid presented active meningeal leukremia. 1 of the patients of Dankert et al. 1 also had meningealleukremia. The passage of HBAg in spinal fluid in these cases could be due to the same changes in permeability which produce increased protein levels during C.N.S. involvement. Our hypothesis for explaining the sporadic presence of HBAg in the spinal 1. Dankert, J., Postma, A., de Vries, J. A., Zijlstra, J. B. Lancet, 1975, i, 690. 2. Sutnick, A. I., London, W. T., Blumberg, B. S., Yankee, R. A., Gerstley, B. J. S., Millman, I.J. natn, Cancer Inst. 1970,44,1241. 3. Sutnick, A. I., Levine, P., London, W. T., Blumberg, B. S. Lancer, 1971, i, 1200. 4. Musumeci, S. Unpublished. 5. Trepo, C., Bolot, J. F., Robert, D., Serpetjian, M., Price, A. M. Lancet, 1974, ii, 1514.
