- Email: [email protected]
DARK PIGMENTATION OF EAR CERUMEN IN ALKAPTONURIA
577 obtain a urine sample. Although general screening for alkaptonuria is probably not justified at present, it might become so if treatment is developed which can prevent the serious arthritic complications of adult life.
were
Section of Medical Genetics,
Department of Respiratory Diseases,
Department of Medicine, Welsh National School of Medicine, Cardiff CF4 4XW
P. S. HARPER D. M. BRADLEY
careful not to make exaggerated claims for our results and were purely concerned with answering the question set out above. It is unfortunate that others have attempted to read into our work aspects which it did not contain. Lodge Moor Hospital, Sheffield S10 4LH.
P. B. ANDERSON
R. A. CLARK
Dr Hartley (Aug. 26, p. 481) point the need to examine the effect of the order of treatments in a study of combined therapy with salbutamol and beclomethasone aerosols. Just such a study is being conducted by the Research Committee of the British Thoracic Association.
SIR,-Dr Handslip and
out
DARK PIGMENTATION OF EAR CERUMEN IN
ALKAPTONURIA
SIR,-A comprehensive research project on alkaptonuria in Slovakia which has been running at this centre for over 10 years has focused on the diagnosis of the disease in childhood. .125 alkaptonurics registered with a confirmed diagnosis have been registered in this laboratory, including 39 in whom the disease was diagnosed in childhood. The urine is not darkcoloured in every case. Other signs are pigment changes (greenbluish, brownish to yellowish) in the axillary regions, which may appear in patients aged 8-10 years, and bluish and/or brownish staining of underwear near the axillary regions. However, an important additional sign is the ochronotic pigmentation of the ear cerumen. In alkaptonuric patients the cerumen is regularly stained dark brown to black even in the earliest childhood, especially in the subjects with poorly cleaned ears. This pigmentary change is found in newborns, and can be so conspicuous as to be a reason for complaint by mothers. I wish to draw attention to this type of cerumen pigmentation which may reveal alkaptonuria in a child who does not have classical signs of ochronosis and, rarely, may not have typical dark-coloured urine. Research
Laboratory for Clinical Genetics, Komensky University, 037 53 Martin, Czechoslovakia
Š. SRSEŇ
SALBUTAMOL AND BECLOMETHASONE IN CHRONIC ASTHMA
fully aware of the problems raised by Dr Handslip Hartley (Aug. 26, p. 481) regarding the limitations in our study (July 8, p. 70). That is why we make no mention of the mechanism in the discussion. We purely set out to show, and we believe we have, that by using a combination of salbutamol and beclomethasone dipropionate (B.D.P.) we SIR,-We
are
and Dr
obtain better control than with B.D.P. alone. It was a held opinion that the combination was more effective, but this had never been substantiated. Before investigating the possible mechanisms of a response, it would seem logical to ascertain that the response occurred. The next step in our investigation would have been along the lines laid out in their letter, were not the British Thoracic Association (B.T.A.) already undertaking such a study. However, the proposals as laid out are not without their limitations and, to be complete, the study would require periods in which placebo inhalers were introduced into the various combinations. Such a study becomes unwieldy and the B.T.A. have similarly had to restrict their objectives. We feel that our work is a necessary precursor and a valuable adjunct to the present B.T.A. study. On the matters raised at the end of the second paragraph of Handslip and Hartley’s letter we would point out that some of the patients during their placebo period received a similar dose of salbutamol in rescue use to that consumed during the period of salbutamol and B.D.P. and yet their control was not so good. This would make it unlikely that the improvement was due to the effect of salbutamol alone. However, the numbers were small and did not permit separate analysis. We agree that, in addition to our main objectives, we have confirmed the efficacy of salbutamol as a bronchodilator. We can
widely
Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO9 4XY.
A. D. MACKAY
BECLOMETHASONE DIPROPIONATE POWDER IN CHILDHOOD ASTHMA
SlR,—Ihave been trying out, in children,
a lactose-absorbed of beclomethasone preparation dipropionate (B.M.D.P.) (GlaxoAllenbury’s Research). It is inhaled in powder form from a capsule (cartridge) by means of a ’Rotahaler’ as used for salbutamol powder. One capsule contained 100 jjLg of the active
drug, equivalent to two puffs of the aerosol preparation. Seven girls and eight boys have received the drug. Seven children (ages 5, 6, 7, 8, 10, 12, and 15) were disodium cromoglycate failures already on long-term B.M.D.P. aerosol. A specific 8-week period of this treatment was continued, and then followed by an 8-week period of B.M.D.P. powder, using the same dose and frequency in both periods. Symptoms were recorded on diary cards and the frequency of bronchodilator consumption was recorded. Five of these children were able to inhale the powder satisfactorily, and a comparison of the aerosol and powder periods showed no significant difference in control of symptoms. Two of the five who completed the study expressed a preference for the aerosol. The other two (aged 5 and 12) disliked the powder and reverted to the aerosol before the study period was over. Three other children (ages 6, 7, and 10) were switched straight from B.M.D.P. aerosol to powder without attempting specific comparison. Their progress on the aerosol was so unsatisfactory that persistence with it could not be justified. All three showed prompt improvement on the powder, and over the subsequent 4 months had unquestionably better control, and they are now dependent upon it. Four children (ages 3, 3, 4, and 6) had been poorly controlled on cromoglycate and were switched straight to B.M.D.P. powder because it was felt that they would not cope with aerosols. As expected they inhaled the B.M.D.P. just as efficiently as the D.s.c.G. The 4 and 6 year olds did not show any alteration in their symptoms, and continued to have unsatisfactory control. The two 3-year-olds managed the powder well and for the 2 months they have been taking it seem to be reasonably well controlled, although it is too early to form a reliable impression. One B.M.D.P. B.M.D.P.
child, aged 4, proved unwilling
or
unable
to
take
powder, having previously failed on cromoglycate and aerosol. The control is thus unsatisfactory on all
medications. No child had thrush. Two had scanty growths of Candida in their throat swabs, which probably reflects an expected rate of the carrier state. None of the children complained of hoarseness.
My impression is that B.M.D.P. powder inhalations will prove very useful addition to the prophylactic drugs available for childhood asthma. Aerosols are generally difficult in children under 6 years of age whereas powder inhalations are often a
were
Section of Medical Genetics,
Department of Respiratory Diseases,
Department of Medicine, Welsh National School of Medicine, Cardiff CF4 4XW
P. S. HARPER D. M. BRADLEY
careful not to make exaggerated claims for our results and were purely concerned with answering the question set out above. It is unfortunate that others have attempted to read into our work aspects which it did not contain. Lodge Moor Hospital, Sheffield S10 4LH.
P. B. ANDERSON
R. A. CLARK
Dr Hartley (Aug. 26, p. 481) point the need to examine the effect of the order of treatments in a study of combined therapy with salbutamol and beclomethasone aerosols. Just such a study is being conducted by the Research Committee of the British Thoracic Association.
SIR,-Dr Handslip and
out
DARK PIGMENTATION OF EAR CERUMEN IN
ALKAPTONURIA
SIR,-A comprehensive research project on alkaptonuria in Slovakia which has been running at this centre for over 10 years has focused on the diagnosis of the disease in childhood. .125 alkaptonurics registered with a confirmed diagnosis have been registered in this laboratory, including 39 in whom the disease was diagnosed in childhood. The urine is not darkcoloured in every case. Other signs are pigment changes (greenbluish, brownish to yellowish) in the axillary regions, which may appear in patients aged 8-10 years, and bluish and/or brownish staining of underwear near the axillary regions. However, an important additional sign is the ochronotic pigmentation of the ear cerumen. In alkaptonuric patients the cerumen is regularly stained dark brown to black even in the earliest childhood, especially in the subjects with poorly cleaned ears. This pigmentary change is found in newborns, and can be so conspicuous as to be a reason for complaint by mothers. I wish to draw attention to this type of cerumen pigmentation which may reveal alkaptonuria in a child who does not have classical signs of ochronosis and, rarely, may not have typical dark-coloured urine. Research
Laboratory for Clinical Genetics, Komensky University, 037 53 Martin, Czechoslovakia
Š. SRSEŇ
SALBUTAMOL AND BECLOMETHASONE IN CHRONIC ASTHMA
fully aware of the problems raised by Dr Handslip Hartley (Aug. 26, p. 481) regarding the limitations in our study (July 8, p. 70). That is why we make no mention of the mechanism in the discussion. We purely set out to show, and we believe we have, that by using a combination of salbutamol and beclomethasone dipropionate (B.D.P.) we SIR,-We
are
and Dr
obtain better control than with B.D.P. alone. It was a held opinion that the combination was more effective, but this had never been substantiated. Before investigating the possible mechanisms of a response, it would seem logical to ascertain that the response occurred. The next step in our investigation would have been along the lines laid out in their letter, were not the British Thoracic Association (B.T.A.) already undertaking such a study. However, the proposals as laid out are not without their limitations and, to be complete, the study would require periods in which placebo inhalers were introduced into the various combinations. Such a study becomes unwieldy and the B.T.A. have similarly had to restrict their objectives. We feel that our work is a necessary precursor and a valuable adjunct to the present B.T.A. study. On the matters raised at the end of the second paragraph of Handslip and Hartley’s letter we would point out that some of the patients during their placebo period received a similar dose of salbutamol in rescue use to that consumed during the period of salbutamol and B.D.P. and yet their control was not so good. This would make it unlikely that the improvement was due to the effect of salbutamol alone. However, the numbers were small and did not permit separate analysis. We agree that, in addition to our main objectives, we have confirmed the efficacy of salbutamol as a bronchodilator. We can
widely
Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO9 4XY.
A. D. MACKAY
BECLOMETHASONE DIPROPIONATE POWDER IN CHILDHOOD ASTHMA
SlR,—Ihave been trying out, in children,
a lactose-absorbed of beclomethasone preparation dipropionate (B.M.D.P.) (GlaxoAllenbury’s Research). It is inhaled in powder form from a capsule (cartridge) by means of a ’Rotahaler’ as used for salbutamol powder. One capsule contained 100 jjLg of the active
drug, equivalent to two puffs of the aerosol preparation. Seven girls and eight boys have received the drug. Seven children (ages 5, 6, 7, 8, 10, 12, and 15) were disodium cromoglycate failures already on long-term B.M.D.P. aerosol. A specific 8-week period of this treatment was continued, and then followed by an 8-week period of B.M.D.P. powder, using the same dose and frequency in both periods. Symptoms were recorded on diary cards and the frequency of bronchodilator consumption was recorded. Five of these children were able to inhale the powder satisfactorily, and a comparison of the aerosol and powder periods showed no significant difference in control of symptoms. Two of the five who completed the study expressed a preference for the aerosol. The other two (aged 5 and 12) disliked the powder and reverted to the aerosol before the study period was over. Three other children (ages 6, 7, and 10) were switched straight from B.M.D.P. aerosol to powder without attempting specific comparison. Their progress on the aerosol was so unsatisfactory that persistence with it could not be justified. All three showed prompt improvement on the powder, and over the subsequent 4 months had unquestionably better control, and they are now dependent upon it. Four children (ages 3, 3, 4, and 6) had been poorly controlled on cromoglycate and were switched straight to B.M.D.P. powder because it was felt that they would not cope with aerosols. As expected they inhaled the B.M.D.P. just as efficiently as the D.s.c.G. The 4 and 6 year olds did not show any alteration in their symptoms, and continued to have unsatisfactory control. The two 3-year-olds managed the powder well and for the 2 months they have been taking it seem to be reasonably well controlled, although it is too early to form a reliable impression. One B.M.D.P. B.M.D.P.
child, aged 4, proved unwilling
or
unable
to
take
powder, having previously failed on cromoglycate and aerosol. The control is thus unsatisfactory on all
medications. No child had thrush. Two had scanty growths of Candida in their throat swabs, which probably reflects an expected rate of the carrier state. None of the children complained of hoarseness.
My impression is that B.M.D.P. powder inhalations will prove very useful addition to the prophylactic drugs available for childhood asthma. Aerosols are generally difficult in children under 6 years of age whereas powder inhalations are often a