- Email: [email protected]
CHILDPROOFING THE MEDICINES BOTTLE
1286
myotonia and two with myotonia congenita, have been investigated. Clinical and neurophysiological examination was performed before and 30 minutes after the administration of baclofen. The initial dosage of baclofen was 01 mg. per kg. body-weight, given intravenously. In the clinical examination, percussion myotonia, relaxation-time after voluntary grasping, and frequency of voluntary grasprelaxation per minute were determined. The following recordings were registered: myotonic discharges in conventional electromyogram (E.M.G.), H-reflex amplitude, effect of repetitive nerve stimulation on action-potential amplitude, and E.M.G. activity in continuous voluntary extension-flexion movements of the ankle. After baclofen, the myotonic phenomenon produced by percussion was reduced noticeably, relaxation-time after grasp became shorter, and frequency of grasp-relaxation per minute increased about twofold. Myotonic discharges in the E.M.G. were still present, and the H-reflex remained unchanged. Action-potential amplitude decreased during repetitive nerve stimulation equally before and after baclofen. After baclofen, E.M.G. activity of the tibialis anterior muscle decreased during active plantar flexion of the ankle, compared with the E.M.G. pattern in the same situation before baclofen. Denny-Brown and Nevin’s findings in myotonic muscles indicate that the difficulty in willed relaxation may be due to reflex (central) spasm of prime movers and synergists.’ Landau regarded the after-spasm as a physiological response to the nature of a lengthening reaction in muscles stretched by sustained myotonic contraction in antagonists.8 Our observations suggest that baclofen may act by inhibiting an exaggerated stretch-reflex mechanism. However, there are no clinical indications for increased fusimotor activity (spasticity or exaggerated tendon reflexes) in myotonia. Therefore another inhibitory mechanism acting on the a-motoneurons of the ankle flexors should be considered. The essence of the myotonic phenomenon remains obscure. Myotonia probably has several causes (central and peripheral) rather than one single mechanism. There seem to be good theoretical reasons for believing that baclofen favourably affects myotonia. Department of Neurology, University of Helsinki, Finland.
P. KARLI LEA BERGSTRÖM.
CHILDPROOFING THE MEDICINES BOTTLE
SIR,-With the very greatest of respect, (June 1, p. 1092) falls into the regrettably of considering the medicine bottle simply
your editorial common error
as a full conin such bottles must be fact, tainer, whereas, opened and closed each time a dose is withdrawn. I have shown 9 that " childproof " caps for medicine bottles wear out so rapidly as to be of little real value. After being opened and closed 50 times the caps were no longer capable of keeping children from the bottle contents, and further investigation showed that this condition could be produced by as little as 10 deliberately brutal opening and closing operations. As far as I am aware, these findings have never been rebutted, nor have the caps been redesigned, so the position remains as it " " was in 1971-a cap can be made which is childproof when first fitted but its protection diminishes very rapidly with use. It is a very open question as to whether these closures give any protection at all after the first few doses have been withdrawn, and it is in this context that the American experience should be considered. For economic reasons, it is likely that the number of doses per dispensed container is likely to be lower in the
7. 8. 9.
Denny-Brown, D., Nevin, S. ibid. 1941, 64, 1. Landau, W. M. Neurology, Minneap. 1952, 2, 369. Pharm. J. July 10,1971.
U.S.A. than in Britain and, coupled with the initial, but short-lived, effectiveness of these closures, this may be sufficient to explain the results in North America. If the design of the closures could be so improved that they would withstand wear, or if the number of doses called for by the average prescription was to fall drastically and permanently, then this pharmacist would need no further encouragement or coercion to use them. 4 Myrtle Street, R. GARTSIDE. Liverpool 7.
TRANSPLACENTAL TRANSMISSION OF CELL-MEDIATED IMMUNITY
SIR,-Passive antibody-mediated immunity is regularly transferred to the human fetus in the form of maternal IgG. Little information is available with regard to the transplacental transmission of cell-mediated immunity (c.M.l.). Leiken et aLl reported that nearly one-third of cord-blood lymphocytes responded in lymphoblastic transformation to ubiquitous antigens such as streptolysin 0. In another report,2 concordant responses were observed between maternal-child pairs in lymphocyte responses to a number of antigens including P.P.D., although in another study3 these responses to P.P.D. could not be demonstrated. In order to further elucidate the problem, cord-blood samples were collected at the time of delivery in 11 normal newborns whose mothers gave no history of exposure to rubella virus during pregnancy. Rubella antibody was measured by the haEmagglutination-inhibition (H.A.I.) technique. Cell-mediated immunity to rubella virus was determined by the 5’Cr release microassay procedure employing BHK-21 cell lines persistently infected with rubella virus as target cells and parent virus-free cell lines as controls by methods described previously. Specific immune release values of 4% or greater were regarded as significantly positive. 4-6 The accompanying table shows that all 11 cord-serum specimens exhibited rubella H.A.I. antibody responses ranging in titre from 1/8 to 1/512. Of 11 newborns, 3 were found to have positive c.M.1. responses to rubella virus. This incidence could well be an underestimation of the actual, since immature cord lymphocytes do not have the full expression of killer functionand pregnancy itself renders maternal lymphocytes less reactive to rubella virus.5 Moreover, the possibility of congenital rubella syndrome seems further remote since a depression of specific C.M.I. has been demonstrated in this condition.’6 The survival advantage to the human fetus of passively transferred C.M.I. is obvious, not only in terms of protective immunity to viral and fungal agents, but also in terms of tumour surveillance. These findings lend further credence to Lowry’s hypothesis that passively transferred immunity may be a basis for the lowered incidence of childhood
malignancy during infancy.8 The mechanism(s) involved in the transplacental transmission of C.M.I. is far from being understood. One possi-
bility is that transfer of subcellular informational units such transfer factor may play a role. Another possibility is
as
1.
Leiken, S., Whang-Peng, J., Oppenheim, J. J. Proceedings of the Fifth Leukocyte Culture Conference (edited by J. Harris). New
York, 1970. Field, E. J., Caspary, E. A. Lancet, 1971, ii, 337. Fireman, P., Kumate, J., Gitlin, D. International Congress of Allergology. Excerpta med. sect. VII, no. 211, 1970. 4. Steele, R. W., Hensen, S. A., Vincent, M. M., Fuccillo, D. A., Bellanti, J. A. J. Immun. 1973, 110, 1502. 5. Thong, Y. H., Steele, R. W., Vincent, M. M., Hensen, S. A., Bellanti, J. A. N. Engl. J. Med. 1973, 289, 604. 6. Fuccillo, D. A., Steele, R. W., Hensen, S. A., Vincent, M. M., Hardy, J. B., Bellanti, J. A. Infect. Immun. 1974, 9, 81. 7. Rachelefsky, G. S., McConnachie, P. R., Terasaki, P. I., Stiehm, E. R. Society for Pediatric Research Abstracts. Pediat. Res. 1973,7, 2. 3.
371. 8.
Lowry,
W. S.
Lancet, April 6, 1974, p. 602.
myotonia and two with myotonia congenita, have been investigated. Clinical and neurophysiological examination was performed before and 30 minutes after the administration of baclofen. The initial dosage of baclofen was 01 mg. per kg. body-weight, given intravenously. In the clinical examination, percussion myotonia, relaxation-time after voluntary grasping, and frequency of voluntary grasprelaxation per minute were determined. The following recordings were registered: myotonic discharges in conventional electromyogram (E.M.G.), H-reflex amplitude, effect of repetitive nerve stimulation on action-potential amplitude, and E.M.G. activity in continuous voluntary extension-flexion movements of the ankle. After baclofen, the myotonic phenomenon produced by percussion was reduced noticeably, relaxation-time after grasp became shorter, and frequency of grasp-relaxation per minute increased about twofold. Myotonic discharges in the E.M.G. were still present, and the H-reflex remained unchanged. Action-potential amplitude decreased during repetitive nerve stimulation equally before and after baclofen. After baclofen, E.M.G. activity of the tibialis anterior muscle decreased during active plantar flexion of the ankle, compared with the E.M.G. pattern in the same situation before baclofen. Denny-Brown and Nevin’s findings in myotonic muscles indicate that the difficulty in willed relaxation may be due to reflex (central) spasm of prime movers and synergists.’ Landau regarded the after-spasm as a physiological response to the nature of a lengthening reaction in muscles stretched by sustained myotonic contraction in antagonists.8 Our observations suggest that baclofen may act by inhibiting an exaggerated stretch-reflex mechanism. However, there are no clinical indications for increased fusimotor activity (spasticity or exaggerated tendon reflexes) in myotonia. Therefore another inhibitory mechanism acting on the a-motoneurons of the ankle flexors should be considered. The essence of the myotonic phenomenon remains obscure. Myotonia probably has several causes (central and peripheral) rather than one single mechanism. There seem to be good theoretical reasons for believing that baclofen favourably affects myotonia. Department of Neurology, University of Helsinki, Finland.
P. KARLI LEA BERGSTRÖM.
CHILDPROOFING THE MEDICINES BOTTLE
SIR,-With the very greatest of respect, (June 1, p. 1092) falls into the regrettably of considering the medicine bottle simply
your editorial common error
as a full conin such bottles must be fact, tainer, whereas, opened and closed each time a dose is withdrawn. I have shown 9 that " childproof " caps for medicine bottles wear out so rapidly as to be of little real value. After being opened and closed 50 times the caps were no longer capable of keeping children from the bottle contents, and further investigation showed that this condition could be produced by as little as 10 deliberately brutal opening and closing operations. As far as I am aware, these findings have never been rebutted, nor have the caps been redesigned, so the position remains as it " " was in 1971-a cap can be made which is childproof when first fitted but its protection diminishes very rapidly with use. It is a very open question as to whether these closures give any protection at all after the first few doses have been withdrawn, and it is in this context that the American experience should be considered. For economic reasons, it is likely that the number of doses per dispensed container is likely to be lower in the
7. 8. 9.
Denny-Brown, D., Nevin, S. ibid. 1941, 64, 1. Landau, W. M. Neurology, Minneap. 1952, 2, 369. Pharm. J. July 10,1971.
U.S.A. than in Britain and, coupled with the initial, but short-lived, effectiveness of these closures, this may be sufficient to explain the results in North America. If the design of the closures could be so improved that they would withstand wear, or if the number of doses called for by the average prescription was to fall drastically and permanently, then this pharmacist would need no further encouragement or coercion to use them. 4 Myrtle Street, R. GARTSIDE. Liverpool 7.
TRANSPLACENTAL TRANSMISSION OF CELL-MEDIATED IMMUNITY
SIR,-Passive antibody-mediated immunity is regularly transferred to the human fetus in the form of maternal IgG. Little information is available with regard to the transplacental transmission of cell-mediated immunity (c.M.l.). Leiken et aLl reported that nearly one-third of cord-blood lymphocytes responded in lymphoblastic transformation to ubiquitous antigens such as streptolysin 0. In another report,2 concordant responses were observed between maternal-child pairs in lymphocyte responses to a number of antigens including P.P.D., although in another study3 these responses to P.P.D. could not be demonstrated. In order to further elucidate the problem, cord-blood samples were collected at the time of delivery in 11 normal newborns whose mothers gave no history of exposure to rubella virus during pregnancy. Rubella antibody was measured by the haEmagglutination-inhibition (H.A.I.) technique. Cell-mediated immunity to rubella virus was determined by the 5’Cr release microassay procedure employing BHK-21 cell lines persistently infected with rubella virus as target cells and parent virus-free cell lines as controls by methods described previously. Specific immune release values of 4% or greater were regarded as significantly positive. 4-6 The accompanying table shows that all 11 cord-serum specimens exhibited rubella H.A.I. antibody responses ranging in titre from 1/8 to 1/512. Of 11 newborns, 3 were found to have positive c.M.1. responses to rubella virus. This incidence could well be an underestimation of the actual, since immature cord lymphocytes do not have the full expression of killer functionand pregnancy itself renders maternal lymphocytes less reactive to rubella virus.5 Moreover, the possibility of congenital rubella syndrome seems further remote since a depression of specific C.M.I. has been demonstrated in this condition.’6 The survival advantage to the human fetus of passively transferred C.M.I. is obvious, not only in terms of protective immunity to viral and fungal agents, but also in terms of tumour surveillance. These findings lend further credence to Lowry’s hypothesis that passively transferred immunity may be a basis for the lowered incidence of childhood
malignancy during infancy.8 The mechanism(s) involved in the transplacental transmission of C.M.I. is far from being understood. One possi-
bility is that transfer of subcellular informational units such transfer factor may play a role. Another possibility is
as
1.
Leiken, S., Whang-Peng, J., Oppenheim, J. J. Proceedings of the Fifth Leukocyte Culture Conference (edited by J. Harris). New
York, 1970. Field, E. J., Caspary, E. A. Lancet, 1971, ii, 337. Fireman, P., Kumate, J., Gitlin, D. International Congress of Allergology. Excerpta med. sect. VII, no. 211, 1970. 4. Steele, R. W., Hensen, S. A., Vincent, M. M., Fuccillo, D. A., Bellanti, J. A. J. Immun. 1973, 110, 1502. 5. Thong, Y. H., Steele, R. W., Vincent, M. M., Hensen, S. A., Bellanti, J. A. N. Engl. J. Med. 1973, 289, 604. 6. Fuccillo, D. A., Steele, R. W., Hensen, S. A., Vincent, M. M., Hardy, J. B., Bellanti, J. A. Infect. Immun. 1974, 9, 81. 7. Rachelefsky, G. S., McConnachie, P. R., Terasaki, P. I., Stiehm, E. R. Society for Pediatric Research Abstracts. Pediat. Res. 1973,7, 2. 3.
371. 8.
Lowry,
W. S.
Lancet, April 6, 1974, p. 602.