983
IMPLICATED AND NON-IMPLICATED DONORS POSITIVE IN ANTI-HCV (ELISA)
(1) Dystrophin constitutes only 0-002% of the total protein in skeletal muscle, at a ratio of one molecule for every fifteen muscle nuclei.’ It is difficult to envisage a satisfactory mechanical role for a molecule present in such low concentration. (2) Dystrophin is also expressed in nervous tissue. It has been localised immunohistochemically to synaptic regions such as neuromuscular junctions, comea, and the outer plexiform layer of the retina, taste buds, and neurons in the brain.5 The presence of dystrophin in the brain may account for the high frequency (about 30%) of mental retardation in DMD.6,7 A mechanical function of dystrophin in muscle cannot explain this association. (3) In DMD hypercontraction of muscle precedes breaks in the cell membrane.8 There is excessive hypercontraction of sarcomeres, especially in the early stages.9 A mechanical role for dystrophin cannot explain the hypercontraction (or tetanic state) of the sarcomeres.
*Absorbance/cut-off ratio WB =whole blood; FFP=fresh frozen plasma; PC platelet concentrate, RBC=red blood cell concentrate, ND= not done
counselling.1-3 We have now had the opportunity to use the Chiron recombinant immunoblot assay (RIBA) for detecting HCV antibody. This test is distributed by Ortho Diagnostic Systems (for research use only). This RIBA uses recombinant antigen c-100 expressed in yeast (as does the ELISA) plus a sub-sequence of c-100 (5-1-1) expressed in Escherichia coli. Both antigens have been coated in distinct bands on nitrocellulose strips. The result (reactive, borderline, or negative) is read by comparing the colour of an antigen band with positive controls. We have applied the ELISA and the RIBA to a frozen panel of donor and patient samples from a prospective study in 1987-89 in open heart surgery (unpublished). 685 patients, who received on average 12-3 units of blood products, were followed up for six months postoperatively. 11 patients (1-6%) acquired posttransfusion hepatitis, all being non-A, non-B. 7 had received a product from an anti-HCV (ELISA) positive donor. On the other hand, when 1029 of the donor samples not associated with a hepatitis case were tested 6 were found to be anti-HCV (ELISA) positive. The ELISA and RIBA results on these "implicated" and 6 "non-implicated" donors are shown in the table. All 6 donor samples that were reactive for antigen bands 5-1-1 and c-100 were associated with hepatitis in the recipient, this being accompanied by seroconversion in 5. No donor specimen that was not linked with hepatitis or seroconversion in the recipient showed reactivity for more than one band. The RIBA may offer help in differentiating infective from non-infective blood donors. Reactivity for both antigens, and 5-1-1 especially, is associated with infectivity. RIBA kits
were
kindly provided by Ortho.
Finnish Red Cross Blood Transfusion Service, SF-00310 Helsinki, Finland
FREJA EBELING
JUHANI LEIKOLA
antibody. Lancet 1989; ii: 505. Flegg PJ. Ethics of screening for hepatitis C virus. Lancet 1989; ii:
1221.
Dystrophin function: calcium-related
rather than mechanical SIR,-Dystrophin1,2 is thought to have a mechanical function,
helping
1. Love DR, Davies KE. Duchenne muscular Biol Med 1989; 6: 7-17
dystrophy: the gene and the protein. Mol
2.
Campbell KP, Kahl SD. Association of dystrophin and an integral membrane glycoprotein. Nature 1989; 338: 259-62 3. Beam KG. Duchenne muscular dystrophy: localizing the gene product. Nature 1988; 333: 798-99.
Koenig M, Hoffman EP, Bertelson CJ, Monaco AP, Feener C, Kunkel LM. Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD in normal and affected individuals. Cell 1987; 50: 509-17. 5. Miike T, Miyatake M, Zhao J, Yoshioka K, Uchino M. Immunohistochemical dystrophin reaction in synaptic regions. Brain Devel 1989; 11: 344-46. 6. Dubowitz V. Mental retardation in Duchenne muscular dystrophy. In: Rowland LP, ed. Pathogenesis of human muscular dystrophies. Amsterdam: Excerpta Medica, 4.
1977: 688-94.
Karagan N. Intellectual functioning in Duchenne muscular dystrophy a review. Psychol Bull 1979; 86: 250-59. 8. Mastaglia FL, Kakulas BA. The natural history of human muscle diseases studied by means of serial biopsy. Proc Aust Assoc Neurol 1968, 5: 537-43. 9. Kakulas BA. Observations on the pathogenesis of Duchenne muscular dystrophy in the light of recent progress m molecular genetics. Aust Pædiatr J 1988 (suppl): 4-8. 10. Emery AEH. Duchenne muscular dystrophy. Oxford. Oxford University Press, 1988; 7
55-57.
RUTH NAUKKARINEN
1. Contreras M, Barbara JAJ. Screening for hepatitis C virus antibody. Lancet 1989; ii: 505. 2. Cash JD, McClelland DBL, Urbaniak SJ, Brookes E. Screening for hepatitis C virus 3
We suggest that the function of dystrophin is calcium-related rather than mechanical. Dystrophin may be causally related to the hypercontractions seen in the early stages of the disease. Calciumpositive fibres are increased in preclinical cases.1o There could be a relation with the exposure of more myosin binding sites on actin or failure of the release mechanism or some mild defect in the calciumpump mechanism. (A major defect of the calcium pump would cause immediate necrosis due to massive activation of calciumsensitive proteases in the cytosol.9) It is unlikely to be related to the function of the sarcoplasmic reticulum or the triadic junction because of the cellular distribution of dystrophin.l A strong dystrophin reaction has been observed at the neuromuscular junction rather than on the surface membrane of extrafusal muscle fibres.s A calcium-related role for dystrophin could explain its function in nervous tissue. JOHN S. H. TAY P. S. Low Division of Human Genetics, W. L. LEE Department of Paediatrics, P. S. LAI National University of Singapore, G. C. GAN Singapore 0511
to resist stresses associated with muscle contraction.1,3 A lack of dystrophin in Duchenne muscular dystrophy (DMD) is postulated to predispose to the rupture of the cell membrane and early necrosis of the muscle cell. In our view, however, a mechanical function of dystrophin is not consistent with three important observations:
Use of ’Nebuhaler’ and face-mask in young asthmatic children SIR,-Inhaled therapy for the treatment of asthma is difficult in children aged under 3 years since their inhalation technique might be faulty and they may dislike closing their mouths over inhaler mouthpieces. To overcome these difficulties the firing of a metered-dose aerosol into a coffee cup, or equipping a large-volume spacer with an anaesthetic mask sealed around the nose and mouth have been proposed.l,2 I report a cheap, portable, and convenient method of administering inhaled drugs to very young patients. The system3 consists of a 750 ml pear-shaped spacer (’Nebuhaler’, Astra Pharmaceuticals) fitted with a nebuliser face-mask (’Intersurgical Life-line 1148’) with the angled connecting piece removed and the side-holes covered with adhesive tape. The mask can be used by the parent. In small children and infants the mask is used upside down. Because of the shape of the
984
face at this age a good fit can be achieved, although a seal is not enforced. When used in this way the nebuhaler should be held at an angle with the mouthpiece down to ensure that the valve stays open. In difficult patients, the nebuhaler can be "charged" and the system applied when the child is asleep. The system is suitable for the administration of the four principal types of asthma therapy-ie, budesonide (inhaled steroid: ’Pulmicort LS’), terbutaline (&bgr;2 agonist: ’Bricanyl’), sodium cromoglycate (mast cell stabiliser. ’Intal’), or ipratropium bromide (anti-cholinergic: ’Atrovent’). The nebuhaler was assessed in a total of 54 asthmatic patients aged up to 312 years. Asthma was diagnosed on the basis of a chronic
night-time cough and/or cough predictably precipitated by exercise, and repeated episodic wheezing not due to bronchiolitis; all patients had a family history of asthma and/or atopy. Drug treatment by this means was withdrawn if side-effects or lack of efficacy were noted, or if the patient progressed to self-administered inhalation. The age and sex distribution at the start of therapy was as follows:
Y)
Total
1 y
In 48 patients budesonide was given (50 (ig twice daily), with terbutaline added in 18 (250 µg twice to four times daily); in 4 sodium cromoglycate (5 mg twice daily) and in 2 ipratropium (20 Ilg thrice daily) were used. In some patients two drugs were given. 9 patients gave up the initial treatment: 2 after 11months because of sleep disturbance (&bgr;2 agonist); 3 after 5-7 months because of regression of symptoms (inhaled steroid); and 2 stopped using ipratropium. In addition, 2 went on to use other inhaler systems. The remaining 45 (83%) patients are well-controlled and their parents are satisfied with the treatment after between 1 and 37 months of use (9 for up to 6 months, 17 for 7-12 months, 3 for 12-18 months, and 16 for over 18 months). The results show that the use of a nebuhaler and an inexpensive mask provides a satisfactory means for home administration of inhaled anti-asthma drugs for infants, and that compliance was good. In young children, despite the lack of a seal between the mask and the child’s face, the dose of budesonide used (50 µg twice daily) is effective. In exacerbations of asthma, the same system and drugs can be used by a doctor,3 and this may reduce the parent’s anxiety associated with the use of nebulisers. A mask of my design without side holes, the angled connecting piece, and the elastic face strap is now available on request from Astra Pharmaceuticals, Kings Langley, UK.
period or metoestrus.1 Splenocyte natural killer cell activity, a potentially important metastatic defence, was substantially higher in mid-cycle in the female mouse.2 In the patients described by Powles et al, the higher proportion of patients in the "perimenstrual" category suggests that more non-cycling women may have been included, and it is not stated whether women taking oral contraceptives were excluded. Our data may not be relevant to non-cycling or irregularly cycling women and we excluded those taking oral contraceptives. The 55% survival of Powles’ 81 patients contrast with our 10-year-survival rate of about 87%, so the two populations differ in respect of risk of dying from breast cancer. To interpret these data we need to know about the stage of disease at diagnosis and about other risk factors. No mention is made of the comparability of risk determinants across the two menstrual groups, while our groups were strictly comparable. Finally, it is not clear whether Powles’ data were subjected to multivariate analysis. Goldhirsch and colleagues’ retrospective series represents the summation of a variety of therapeutic approaches tested in two major cooperative studies. His patients differed substantially from ours in several potentially important ways. Firstly, the much higher proportion of women in the perimenstrual group is very different from the equal distribution of our premenopausal patients. The menstrual
inclusion in this group of women whose last menstrual period was up to 326 days before the initial surgical procedure indicates that many women had been irregular or not cycling at all for some time. There were no such women in our series. Every woman in the Goldhirsch study had a total mastectomy and axillary clearance at the very least while two-thirds of our patients were treated with a simple lumpectomy and node sampling and more than half were node negative. Goldhirsch’s patients may have had more advanced breast cancer. This is suggested by the probability of survival. As with Powles’ series, it would be valuable to know how comparable the two menstrually referenced subgroups were with regard to sources of outcome variability. The accuracy of menstrual cycle data across several institutions and in two multi-armed studies must also be rigorously evaluated, especially since it is not clear whether or not these women were taking oral contraceptives. One-fifth of Goldhirsch’s patients underwent oophorectomy close in time, presumably, to the resection of the primary breast tumour. How more aggressive breast surgery and this surgical procedure might affect the balance between host and tumour is open to speculation. Our results suggest that the timing of surgery may be important in stage I patients. Series of early-stage, normally cycling patients, more precisely comparable to ours are needed to test our hypothesis, however. We do agree that the date of the first day of the last menstrual period should be recorded at the time of her primary breast cancer surgery. Were this simple step to be taken in adjuvant breast cancer trials reliable data would soon be available to support or refute our observation.
VA Medical Center,
Hardwicke House, Stour Street, Sudbury, Suffolk CO10 6AY, UK
Albany, NY 12208, USA
T. P. MCCARTHY 1.
1.
WILLIAM J. M. HRUSHESKY AVRUM Z. BLUMING SCOTT A. GRUBER
Warner JO, Gotz M, Landau LI, et al. Management of asthma: a consensus statement. Arch Dis Child 1989; 64: 1065-79.
2
O’Callaghan C, Milner AD, Swarbrick A. Spacer device with face mask attachment for giving bronchodilators to infants with asthma. Br Med J 1989; 298: 160-61. 3. McCarthy TP. Rapid response to budesonide (Pulmicort) inhaled via the Nebuhaler in asthmatic children. Br J Clin Pract (in press). 2.
Ratajczak HV, Sothern RB, Hrushesky WJM. Estrous stage influences surgical cure of a mouse breast cancer. J Exp Med 1988; 168: 88-96 Hrushesky WJM, Gruber SA, Sothern RB, et al. Natural killer cell activity, age, estrous-and circadian-stage dependence and inverse correlation with metastatic potential. J Natl Cancer Inst 1988; 80: 1232-37
CORRECTIONS Menstrual influence breast
on
surgical
cure
of
cancer
SIR,—There are important differences between our series (Oct 21, 949) and those reported by Dr Powles, Dr Goldhirsch, and their colleagues (Dec 2, pp 1344 and 1345). To explain some of the variability of breast cancer outcome after p
resection
studied the effect of the timing of surgery within the fertility cycle in female mice and in premenopausal women. If the operation was done at the mid-point of the cycle metastatic spread and death were less common than if resection was done nearer to the we
ACE inhibitors after myocardial infarction. In this letter by Dr F. X. Kleber (Feb 3, p 295) the closing paragraph should have read "My point is that both left ventricular dilatation and congestive heart failure development/ progression can be favourably influenced by ACE inhibition. This parallel influence on the two phenomena supports the hypothesis that left ventricular dilatation unfavourably influences progression of congestive heart failure and should be avoided".
Drug compliance in asthma In this letter by Dr S. J. Louw (March 17, 673), the last sentence of item (5) should have read "The solution lies in efforts to recognise such asthmatics as rapid metabolisers ...".
p
IMPLICATED AND NON-IMPLICATED DONORS POSITIVE IN ANTI-HCV (ELISA)
(1) Dystrophin constitutes only 0-002% of the total protein in skeletal muscle, at a ratio of one molecule for every fifteen muscle nuclei.’ It is difficult to envisage a satisfactory mechanical role for a molecule present in such low concentration. (2) Dystrophin is also expressed in nervous tissue. It has been localised immunohistochemically to synaptic regions such as neuromuscular junctions, comea, and the outer plexiform layer of the retina, taste buds, and neurons in the brain.5 The presence of dystrophin in the brain may account for the high frequency (about 30%) of mental retardation in DMD.6,7 A mechanical function of dystrophin in muscle cannot explain this association. (3) In DMD hypercontraction of muscle precedes breaks in the cell membrane.8 There is excessive hypercontraction of sarcomeres, especially in the early stages.9 A mechanical role for dystrophin cannot explain the hypercontraction (or tetanic state) of the sarcomeres.
*Absorbance/cut-off ratio WB =whole blood; FFP=fresh frozen plasma; PC platelet concentrate, RBC=red blood cell concentrate, ND= not done
counselling.1-3 We have now had the opportunity to use the Chiron recombinant immunoblot assay (RIBA) for detecting HCV antibody. This test is distributed by Ortho Diagnostic Systems (for research use only). This RIBA uses recombinant antigen c-100 expressed in yeast (as does the ELISA) plus a sub-sequence of c-100 (5-1-1) expressed in Escherichia coli. Both antigens have been coated in distinct bands on nitrocellulose strips. The result (reactive, borderline, or negative) is read by comparing the colour of an antigen band with positive controls. We have applied the ELISA and the RIBA to a frozen panel of donor and patient samples from a prospective study in 1987-89 in open heart surgery (unpublished). 685 patients, who received on average 12-3 units of blood products, were followed up for six months postoperatively. 11 patients (1-6%) acquired posttransfusion hepatitis, all being non-A, non-B. 7 had received a product from an anti-HCV (ELISA) positive donor. On the other hand, when 1029 of the donor samples not associated with a hepatitis case were tested 6 were found to be anti-HCV (ELISA) positive. The ELISA and RIBA results on these "implicated" and 6 "non-implicated" donors are shown in the table. All 6 donor samples that were reactive for antigen bands 5-1-1 and c-100 were associated with hepatitis in the recipient, this being accompanied by seroconversion in 5. No donor specimen that was not linked with hepatitis or seroconversion in the recipient showed reactivity for more than one band. The RIBA may offer help in differentiating infective from non-infective blood donors. Reactivity for both antigens, and 5-1-1 especially, is associated with infectivity. RIBA kits
were
kindly provided by Ortho.
Finnish Red Cross Blood Transfusion Service, SF-00310 Helsinki, Finland
FREJA EBELING
JUHANI LEIKOLA
antibody. Lancet 1989; ii: 505. Flegg PJ. Ethics of screening for hepatitis C virus. Lancet 1989; ii:
1221.
Dystrophin function: calcium-related
rather than mechanical SIR,-Dystrophin1,2 is thought to have a mechanical function,
helping
1. Love DR, Davies KE. Duchenne muscular Biol Med 1989; 6: 7-17
dystrophy: the gene and the protein. Mol
2.
Campbell KP, Kahl SD. Association of dystrophin and an integral membrane glycoprotein. Nature 1989; 338: 259-62 3. Beam KG. Duchenne muscular dystrophy: localizing the gene product. Nature 1988; 333: 798-99.
Koenig M, Hoffman EP, Bertelson CJ, Monaco AP, Feener C, Kunkel LM. Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD in normal and affected individuals. Cell 1987; 50: 509-17. 5. Miike T, Miyatake M, Zhao J, Yoshioka K, Uchino M. Immunohistochemical dystrophin reaction in synaptic regions. Brain Devel 1989; 11: 344-46. 6. Dubowitz V. Mental retardation in Duchenne muscular dystrophy. In: Rowland LP, ed. Pathogenesis of human muscular dystrophies. Amsterdam: Excerpta Medica, 4.
1977: 688-94.
Karagan N. Intellectual functioning in Duchenne muscular dystrophy a review. Psychol Bull 1979; 86: 250-59. 8. Mastaglia FL, Kakulas BA. The natural history of human muscle diseases studied by means of serial biopsy. Proc Aust Assoc Neurol 1968, 5: 537-43. 9. Kakulas BA. Observations on the pathogenesis of Duchenne muscular dystrophy in the light of recent progress m molecular genetics. Aust Pædiatr J 1988 (suppl): 4-8. 10. Emery AEH. Duchenne muscular dystrophy. Oxford. Oxford University Press, 1988; 7
55-57.
RUTH NAUKKARINEN
1. Contreras M, Barbara JAJ. Screening for hepatitis C virus antibody. Lancet 1989; ii: 505. 2. Cash JD, McClelland DBL, Urbaniak SJ, Brookes E. Screening for hepatitis C virus 3
We suggest that the function of dystrophin is calcium-related rather than mechanical. Dystrophin may be causally related to the hypercontractions seen in the early stages of the disease. Calciumpositive fibres are increased in preclinical cases.1o There could be a relation with the exposure of more myosin binding sites on actin or failure of the release mechanism or some mild defect in the calciumpump mechanism. (A major defect of the calcium pump would cause immediate necrosis due to massive activation of calciumsensitive proteases in the cytosol.9) It is unlikely to be related to the function of the sarcoplasmic reticulum or the triadic junction because of the cellular distribution of dystrophin.l A strong dystrophin reaction has been observed at the neuromuscular junction rather than on the surface membrane of extrafusal muscle fibres.s A calcium-related role for dystrophin could explain its function in nervous tissue. JOHN S. H. TAY P. S. Low Division of Human Genetics, W. L. LEE Department of Paediatrics, P. S. LAI National University of Singapore, G. C. GAN Singapore 0511
to resist stresses associated with muscle contraction.1,3 A lack of dystrophin in Duchenne muscular dystrophy (DMD) is postulated to predispose to the rupture of the cell membrane and early necrosis of the muscle cell. In our view, however, a mechanical function of dystrophin is not consistent with three important observations:
Use of ’Nebuhaler’ and face-mask in young asthmatic children SIR,-Inhaled therapy for the treatment of asthma is difficult in children aged under 3 years since their inhalation technique might be faulty and they may dislike closing their mouths over inhaler mouthpieces. To overcome these difficulties the firing of a metered-dose aerosol into a coffee cup, or equipping a large-volume spacer with an anaesthetic mask sealed around the nose and mouth have been proposed.l,2 I report a cheap, portable, and convenient method of administering inhaled drugs to very young patients. The system3 consists of a 750 ml pear-shaped spacer (’Nebuhaler’, Astra Pharmaceuticals) fitted with a nebuliser face-mask (’Intersurgical Life-line 1148’) with the angled connecting piece removed and the side-holes covered with adhesive tape. The mask can be used by the parent. In small children and infants the mask is used upside down. Because of the shape of the
984
face at this age a good fit can be achieved, although a seal is not enforced. When used in this way the nebuhaler should be held at an angle with the mouthpiece down to ensure that the valve stays open. In difficult patients, the nebuhaler can be "charged" and the system applied when the child is asleep. The system is suitable for the administration of the four principal types of asthma therapy-ie, budesonide (inhaled steroid: ’Pulmicort LS’), terbutaline (&bgr;2 agonist: ’Bricanyl’), sodium cromoglycate (mast cell stabiliser. ’Intal’), or ipratropium bromide (anti-cholinergic: ’Atrovent’). The nebuhaler was assessed in a total of 54 asthmatic patients aged up to 312 years. Asthma was diagnosed on the basis of a chronic
night-time cough and/or cough predictably precipitated by exercise, and repeated episodic wheezing not due to bronchiolitis; all patients had a family history of asthma and/or atopy. Drug treatment by this means was withdrawn if side-effects or lack of efficacy were noted, or if the patient progressed to self-administered inhalation. The age and sex distribution at the start of therapy was as follows:
Y)
Total
1 y
In 48 patients budesonide was given (50 (ig twice daily), with terbutaline added in 18 (250 µg twice to four times daily); in 4 sodium cromoglycate (5 mg twice daily) and in 2 ipratropium (20 Ilg thrice daily) were used. In some patients two drugs were given. 9 patients gave up the initial treatment: 2 after 11months because of sleep disturbance (&bgr;2 agonist); 3 after 5-7 months because of regression of symptoms (inhaled steroid); and 2 stopped using ipratropium. In addition, 2 went on to use other inhaler systems. The remaining 45 (83%) patients are well-controlled and their parents are satisfied with the treatment after between 1 and 37 months of use (9 for up to 6 months, 17 for 7-12 months, 3 for 12-18 months, and 16 for over 18 months). The results show that the use of a nebuhaler and an inexpensive mask provides a satisfactory means for home administration of inhaled anti-asthma drugs for infants, and that compliance was good. In young children, despite the lack of a seal between the mask and the child’s face, the dose of budesonide used (50 µg twice daily) is effective. In exacerbations of asthma, the same system and drugs can be used by a doctor,3 and this may reduce the parent’s anxiety associated with the use of nebulisers. A mask of my design without side holes, the angled connecting piece, and the elastic face strap is now available on request from Astra Pharmaceuticals, Kings Langley, UK.
period or metoestrus.1 Splenocyte natural killer cell activity, a potentially important metastatic defence, was substantially higher in mid-cycle in the female mouse.2 In the patients described by Powles et al, the higher proportion of patients in the "perimenstrual" category suggests that more non-cycling women may have been included, and it is not stated whether women taking oral contraceptives were excluded. Our data may not be relevant to non-cycling or irregularly cycling women and we excluded those taking oral contraceptives. The 55% survival of Powles’ 81 patients contrast with our 10-year-survival rate of about 87%, so the two populations differ in respect of risk of dying from breast cancer. To interpret these data we need to know about the stage of disease at diagnosis and about other risk factors. No mention is made of the comparability of risk determinants across the two menstrual groups, while our groups were strictly comparable. Finally, it is not clear whether Powles’ data were subjected to multivariate analysis. Goldhirsch and colleagues’ retrospective series represents the summation of a variety of therapeutic approaches tested in two major cooperative studies. His patients differed substantially from ours in several potentially important ways. Firstly, the much higher proportion of women in the perimenstrual group is very different from the equal distribution of our premenopausal patients. The menstrual
inclusion in this group of women whose last menstrual period was up to 326 days before the initial surgical procedure indicates that many women had been irregular or not cycling at all for some time. There were no such women in our series. Every woman in the Goldhirsch study had a total mastectomy and axillary clearance at the very least while two-thirds of our patients were treated with a simple lumpectomy and node sampling and more than half were node negative. Goldhirsch’s patients may have had more advanced breast cancer. This is suggested by the probability of survival. As with Powles’ series, it would be valuable to know how comparable the two menstrually referenced subgroups were with regard to sources of outcome variability. The accuracy of menstrual cycle data across several institutions and in two multi-armed studies must also be rigorously evaluated, especially since it is not clear whether or not these women were taking oral contraceptives. One-fifth of Goldhirsch’s patients underwent oophorectomy close in time, presumably, to the resection of the primary breast tumour. How more aggressive breast surgery and this surgical procedure might affect the balance between host and tumour is open to speculation. Our results suggest that the timing of surgery may be important in stage I patients. Series of early-stage, normally cycling patients, more precisely comparable to ours are needed to test our hypothesis, however. We do agree that the date of the first day of the last menstrual period should be recorded at the time of her primary breast cancer surgery. Were this simple step to be taken in adjuvant breast cancer trials reliable data would soon be available to support or refute our observation.
VA Medical Center,
Hardwicke House, Stour Street, Sudbury, Suffolk CO10 6AY, UK
Albany, NY 12208, USA
T. P. MCCARTHY 1.
1.
WILLIAM J. M. HRUSHESKY AVRUM Z. BLUMING SCOTT A. GRUBER
Warner JO, Gotz M, Landau LI, et al. Management of asthma: a consensus statement. Arch Dis Child 1989; 64: 1065-79.
2
O’Callaghan C, Milner AD, Swarbrick A. Spacer device with face mask attachment for giving bronchodilators to infants with asthma. Br Med J 1989; 298: 160-61. 3. McCarthy TP. Rapid response to budesonide (Pulmicort) inhaled via the Nebuhaler in asthmatic children. Br J Clin Pract (in press). 2.
Ratajczak HV, Sothern RB, Hrushesky WJM. Estrous stage influences surgical cure of a mouse breast cancer. J Exp Med 1988; 168: 88-96 Hrushesky WJM, Gruber SA, Sothern RB, et al. Natural killer cell activity, age, estrous-and circadian-stage dependence and inverse correlation with metastatic potential. J Natl Cancer Inst 1988; 80: 1232-37
CORRECTIONS Menstrual influence breast
on
surgical
cure
of
cancer
SIR,—There are important differences between our series (Oct 21, 949) and those reported by Dr Powles, Dr Goldhirsch, and their colleagues (Dec 2, pp 1344 and 1345). To explain some of the variability of breast cancer outcome after p
resection
studied the effect of the timing of surgery within the fertility cycle in female mice and in premenopausal women. If the operation was done at the mid-point of the cycle metastatic spread and death were less common than if resection was done nearer to the we
ACE inhibitors after myocardial infarction. In this letter by Dr F. X. Kleber (Feb 3, p 295) the closing paragraph should have read "My point is that both left ventricular dilatation and congestive heart failure development/ progression can be favourably influenced by ACE inhibition. This parallel influence on the two phenomena supports the hypothesis that left ventricular dilatation unfavourably influences progression of congestive heart failure and should be avoided".
Drug compliance in asthma In this letter by Dr S. J. Louw (March 17, 673), the last sentence of item (5) should have read "The solution lies in efforts to recognise such asthmatics as rapid metabolisers ...".
p
