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EAR-DROPS
896
when two encouraging results from fetal-liver have been reported: a boy given 8.5-weeks-gestation liver cells when he was 3 months old thrived for a year before he developed glomerulonephritis and died with nephrotic syndrome;13 and a Swiss child was thriving more than 18 months after her graft. 14 In both cases A.D.A.-positive lymphocytes appeared in the blood after the graft, and in the first case the cells which responded to in-vitro tests were of donor origin, so there was nothing to suggest that the recipient’s lymphocytes could make use of A.D.A. derived from the graft. Polmar et al.11 found increased in-vitro responsiveness in lymphocytes from an A.D.A.-deficient patient when exogenous A.D.A. was added to the culture medium, and the exciting outcome was their treatment of the same patient by transfusions of washed irradiated red cells, as a source of A.D.A. There was evidence of at least temporary benefit (increased lymphocyte-count and a thymus shadow appearing on chest X-ray), though the frequency with which further transfusions will be required is not yet known. Treatment by red cells is probably safer and easier than grafting, provided that suitable precautions are taken to remove or inactivate the lymphocytes, though what proportion of patients will respond remains to be seen.
lately, grafts
EAR-DROPS ANTISEPTICS’ and antibiotics, applied to the middle ear of laboratory animals in concentrations comparable = those used in clinical medicine, can produce severe and irreversible inner-ear deafness. In 1963, Patterson and Gullick’6 showed that topical application of a single, relatively low, dose of chloramphenicol to the round-window membranes of guineapigs and cats caused severe deafness-an observation confirmed by others.17—21 Spoendlin2z found extensive damage to the sensory hair-cells of the cochlea of the guineapig after intratympanic injection of very dilute solutions of streptomycin sulphate. Stupp et al. 23 enlarged the investigation to include polymyxin G, neomycin, tetracycline, erythromycin, and gentamicin, all of which, when instilled daily in equimolar amounts into the intact middle ear of guineapigs, produced extensive damage after three days. Only penicillin was free of ototoxic effects. Polymyxin G-which is an active principle of a popular brand of ear-drops-did a surprising amount of damage, to half the total population of hair-cells in every turn of the cochlea. Antiseptics such as chlorhexidine, and local-anaesthetic agents such as lignocaine, can damage the middle ear in a similar way, and the ototoxic effect is not due to the pH of the solution or to the vehicle in which it is dissolved. In every case ototoxic agents seem to reach the inner ear by diffusion through the round-window membrane or the 13.
Keightley,
R. G., I.awton, A.
R., Cooper,
M. D.,
Yunis, E. J. Lancet, 1975,
ii, 850. 14. Ackeret, C., Pluss, H. J., Hitzig, W. H. Pediat Res. 1976, 10, 67. 15. Polmar, S. H., Wetzler, E. M , Stern, R. C., Hirschhorn, R. Lancet, 1975,
ii, 743. 16. 17. 18.
Patterson, W. C., Gullick, W L. Ann. Otol 1963, 72, 50. Koide, Y., Hata, A., Hando, R. Acta otolar. 1966, 61, 332. D’Angelo, E. P., Patterson, W. C , Morrow, R. C. Archs Otolar 1967, 85,
19. 20. 21. 22. 23.
Proud, G. O., Mittleman, H., Seiden, G. D. ibid. 1968, 87, 580 Kohonen, A. Tarkkanen, J. Acta otolar. 1969, 68, 90. Morizono, T , Johnstone, B. M. Med. J. Aust. 1975, ii, 634. Spoendlin, H. Practica oto-rhino-lar. 1966, 28, 305. Stupp, H., Küpper, K., Lagler, F., Sous, H., Quante, M. Audiology, 1973, 12, 350.
682.
annular ligament of the footplate of the stapes, and the of the damage caused is directly related to the concentration in the perilymph rather than to any organ
extent
specificity.24 Are ear-drops
hazardous in man? McKelvie et a1.2j have been unable to detect significant differences in the hearing of two groups of patients, one treated with a commercial gentamicin preparation and the other with a placebo consisting of the vehicle used in this preparation. However, the trial only lasted 21 months and it was difficult to match the ears treated, some of which had chronic otitis media and the others mastoid cavities. McKelvie et al. admit that they cannot exclude the possibility of insidious hearing-loss after use of the drops, Sudded disastrous deafness must be rare indeed, butif animal results are applicable to man there must be a possibility of otoxicity: there has been litigation in at least one case. It is doubtful whether solutions in drop form are ever the most effective means of treating ear diseases. Wax can usually be removed by gentle extraction with a blunt hook or by syringing. Otitis externa is best treated by
thorough cleansing (with dry mopping, syringing, or suction), and, if topical applications are indicated, these should be contained in a ribbon-gauze dressing. Acute otitis media is not an indication for treatment with drops. Chronic otitis media usually requires thorough debridation of granulation tissue and collection of keratin using the operating microscope and a sucker, and acute exacerbations of infection in previously dry ears with large central perforations should be treated with cleansing of the ear and parenteral antibiotics, In mastoid and fenestration cavities ear-drops are probably useless; in addition there is the risk of skin sensitisation, and solutions containing antibiotics encourage the growth of monilia and other fungal forms. If drop! are to be used they should be used liberally: the affected tissues should be flooded with the solution and kept in contact with it for as long as possible (by getting the pa. tient to lie down with the effected ear uppermost). Ajod. hia and DiX26 condemn antibiotic ear-drops altogethei and suggest instead preparations containing antiseptic’ such as iodochlorhydroxyquinoline and halquinol which are non-toxic. Few otologists would go as far a! this. Nevertheless, in view of the possibility of toxicit) and the doubts about efficacy, ear-drops should seldom be prescribed, especially in the presence of large perforations, where there is a history of ear surgery, or foi
preoperative prophylaxis. HEADACHE AND BLOOD-PRESSURE THE association between headache and raised arterial
blood-pressure has long been debated. Bright" described the characteristics of headaches associated with threatened apoplexy, and Pickering2a regards an occipital headache on waking, which disappears as the day wears on, as almost pathognomonic of gross hypertension. Others have been less convinced about the characteristics of the 24. Morizono, T , Johnstone, B. M., Hadjar, E J. otolaryngol Soc. Aus 1973, 3, 550. 25. McKelvie, P., Johnston, I., Jamieson, I., Brooks, C. Br. J Audiol 1975, 9, 45. 26. 27.
28.
Adjodhia, J. M., Dix, M. R. Estr. Minerva otolar. 1975, 25, 117. Bright, R. Guy’s Hosp. Reps, 1836, 1, 9. Pickering, G. High Blood Pressure. London, 1968.
when two encouraging results from fetal-liver have been reported: a boy given 8.5-weeks-gestation liver cells when he was 3 months old thrived for a year before he developed glomerulonephritis and died with nephrotic syndrome;13 and a Swiss child was thriving more than 18 months after her graft. 14 In both cases A.D.A.-positive lymphocytes appeared in the blood after the graft, and in the first case the cells which responded to in-vitro tests were of donor origin, so there was nothing to suggest that the recipient’s lymphocytes could make use of A.D.A. derived from the graft. Polmar et al.11 found increased in-vitro responsiveness in lymphocytes from an A.D.A.-deficient patient when exogenous A.D.A. was added to the culture medium, and the exciting outcome was their treatment of the same patient by transfusions of washed irradiated red cells, as a source of A.D.A. There was evidence of at least temporary benefit (increased lymphocyte-count and a thymus shadow appearing on chest X-ray), though the frequency with which further transfusions will be required is not yet known. Treatment by red cells is probably safer and easier than grafting, provided that suitable precautions are taken to remove or inactivate the lymphocytes, though what proportion of patients will respond remains to be seen.
lately, grafts
EAR-DROPS ANTISEPTICS’ and antibiotics, applied to the middle ear of laboratory animals in concentrations comparable = those used in clinical medicine, can produce severe and irreversible inner-ear deafness. In 1963, Patterson and Gullick’6 showed that topical application of a single, relatively low, dose of chloramphenicol to the round-window membranes of guineapigs and cats caused severe deafness-an observation confirmed by others.17—21 Spoendlin2z found extensive damage to the sensory hair-cells of the cochlea of the guineapig after intratympanic injection of very dilute solutions of streptomycin sulphate. Stupp et al. 23 enlarged the investigation to include polymyxin G, neomycin, tetracycline, erythromycin, and gentamicin, all of which, when instilled daily in equimolar amounts into the intact middle ear of guineapigs, produced extensive damage after three days. Only penicillin was free of ototoxic effects. Polymyxin G-which is an active principle of a popular brand of ear-drops-did a surprising amount of damage, to half the total population of hair-cells in every turn of the cochlea. Antiseptics such as chlorhexidine, and local-anaesthetic agents such as lignocaine, can damage the middle ear in a similar way, and the ototoxic effect is not due to the pH of the solution or to the vehicle in which it is dissolved. In every case ototoxic agents seem to reach the inner ear by diffusion through the round-window membrane or the 13.
Keightley,
R. G., I.awton, A.
R., Cooper,
M. D.,
Yunis, E. J. Lancet, 1975,
ii, 850. 14. Ackeret, C., Pluss, H. J., Hitzig, W. H. Pediat Res. 1976, 10, 67. 15. Polmar, S. H., Wetzler, E. M , Stern, R. C., Hirschhorn, R. Lancet, 1975,
ii, 743. 16. 17. 18.
Patterson, W. C., Gullick, W L. Ann. Otol 1963, 72, 50. Koide, Y., Hata, A., Hando, R. Acta otolar. 1966, 61, 332. D’Angelo, E. P., Patterson, W. C , Morrow, R. C. Archs Otolar 1967, 85,
19. 20. 21. 22. 23.
Proud, G. O., Mittleman, H., Seiden, G. D. ibid. 1968, 87, 580 Kohonen, A. Tarkkanen, J. Acta otolar. 1969, 68, 90. Morizono, T , Johnstone, B. M. Med. J. Aust. 1975, ii, 634. Spoendlin, H. Practica oto-rhino-lar. 1966, 28, 305. Stupp, H., Küpper, K., Lagler, F., Sous, H., Quante, M. Audiology, 1973, 12, 350.
682.
annular ligament of the footplate of the stapes, and the of the damage caused is directly related to the concentration in the perilymph rather than to any organ
extent
specificity.24 Are ear-drops
hazardous in man? McKelvie et a1.2j have been unable to detect significant differences in the hearing of two groups of patients, one treated with a commercial gentamicin preparation and the other with a placebo consisting of the vehicle used in this preparation. However, the trial only lasted 21 months and it was difficult to match the ears treated, some of which had chronic otitis media and the others mastoid cavities. McKelvie et al. admit that they cannot exclude the possibility of insidious hearing-loss after use of the drops, Sudded disastrous deafness must be rare indeed, butif animal results are applicable to man there must be a possibility of otoxicity: there has been litigation in at least one case. It is doubtful whether solutions in drop form are ever the most effective means of treating ear diseases. Wax can usually be removed by gentle extraction with a blunt hook or by syringing. Otitis externa is best treated by
thorough cleansing (with dry mopping, syringing, or suction), and, if topical applications are indicated, these should be contained in a ribbon-gauze dressing. Acute otitis media is not an indication for treatment with drops. Chronic otitis media usually requires thorough debridation of granulation tissue and collection of keratin using the operating microscope and a sucker, and acute exacerbations of infection in previously dry ears with large central perforations should be treated with cleansing of the ear and parenteral antibiotics, In mastoid and fenestration cavities ear-drops are probably useless; in addition there is the risk of skin sensitisation, and solutions containing antibiotics encourage the growth of monilia and other fungal forms. If drop! are to be used they should be used liberally: the affected tissues should be flooded with the solution and kept in contact with it for as long as possible (by getting the pa. tient to lie down with the effected ear uppermost). Ajod. hia and DiX26 condemn antibiotic ear-drops altogethei and suggest instead preparations containing antiseptic’ such as iodochlorhydroxyquinoline and halquinol which are non-toxic. Few otologists would go as far a! this. Nevertheless, in view of the possibility of toxicit) and the doubts about efficacy, ear-drops should seldom be prescribed, especially in the presence of large perforations, where there is a history of ear surgery, or foi
preoperative prophylaxis. HEADACHE AND BLOOD-PRESSURE THE association between headache and raised arterial
blood-pressure has long been debated. Bright" described the characteristics of headaches associated with threatened apoplexy, and Pickering2a regards an occipital headache on waking, which disappears as the day wears on, as almost pathognomonic of gross hypertension. Others have been less convinced about the characteristics of the 24. Morizono, T , Johnstone, B. M., Hadjar, E J. otolaryngol Soc. Aus 1973, 3, 550. 25. McKelvie, P., Johnston, I., Jamieson, I., Brooks, C. Br. J Audiol 1975, 9, 45. 26. 27.
28.
Adjodhia, J. M., Dix, M. R. Estr. Minerva otolar. 1975, 25, 117. Bright, R. Guy’s Hosp. Reps, 1836, 1, 9. Pickering, G. High Blood Pressure. London, 1968.