- Email: [email protected]
PACKAGING INTRAVENOUS DEVICES
95
Regional selectivity therefore does not explain the pharmacological profile of drugs such as clozapine or thioridazine. Extrapyramidal effects are correlated with drug potencies in both the striatum and tuberculum olfactorium. Antipsychotic effects can be predicted by the dose-response curves in either region. With this model we have been able to predict the clinical potency of thiethylperazine, a drug previously considered to be devoid of antipsychotic activity but recently shown in the clinic to be active at about three times the potency of chlorpromazine.7 Several butyrophenone analogues devoid of antipsychotic activity were inactive in our system.8 We have also found a reported non-antipsychotic drug, perlapine, with a dose-response profile in the striatum and tuberculum olfactorium virtually identical to chlorpromazine. The marked sedative properties of this agent may have complicated the clinical trials. We have predicted that reevaluation of this drug in the clinic will reveal its antipsychotic efficacy. Department of Pharmacology, Mount Sinai School
of Medicine,
SHERWIN WILK MICHAEL STANLEY
Of City University of New York, New York, N.Y. 10029, U.S.A.
MORPHINE AS ANTIPSYCHOTIC DRUG
SIR,-An interesting point is raised by Crow et al. 10 While morphine is not antipsychotic in the ordinary sense, many who are interested in the epidemiology of heroin addiction have formed the impression that addicts now include, though they are not confined to, people who would have become clinically psychotic if not addicted. It seems very probable that there is a group of people who do rely on morphinoid drugs as primary suppressants of intolerable prepsychotic sensations, and that these are the addicts who fail to display enough motivation to undertake the physical distress of withdrawal. This might suggest an alternative approach to addiction-there may even be psychotics for whom morphinoids are the only effective antipsychotic, despite the other risks which such drugs carry. Older experience with stabilised and supervised addicts seems to
bear this
out.
At the very least, however, the neurochemical
should be avoided. The drugs appear individually or as broad groups, and headings such as tricyclics, sympathomimetics (direct or indirect acting), benzodiazepines, and sulphonylureas are used. Some broad headings are listed under one drug of that type. Thus sulphonylureas such as glibenclamide are found under chlorpropamide, metformin appears under phenformin (biguanides), and perphenazine is found under
chlorpromazine (phenothiazines). The user must thus know how the ingredients of a medicine are classined, but the British National Formulary, MIMS, or the Data Sheet Compendium, do not give him this information for all drugs. Medisc contains 173 separate interactions, of which 28 are classified as potentially serious (and 14 of these relate to alcohol). The interactions were compiled from secondary reference sources which are themselves two or three years old, and while the accompanying leaflet states that the interaction disc is not comprehensive, this is not stated on the device itself. There are also some discrepancies between statements made about some interactions and current opinion. For example, it is suggested that thiazide diuretics will interact with cephaloridine with potentially serious results, yet no published evidence of such an interaction exists.’Hansten suggests that because of the severity of an interaction between frusemide and cephaloridine concomitant use should be avoided,’ but it is not possible to locate such an interaction on the disc. It is also suggested that indomethacin potentiates the effects of oral anticoagulants while evidence to the contrary is common.’ Although, in view of possible indomethacin-induced gastrointestinal bleeding, it may be necessary to use indomethacin with caution in such patients. To be of value, the disc should be brought up to date regularly, and the device should state that the interaction list is not comprehensive. The disc should be used in conjunction with the data sheet for the product and not as a replacement for it. Perhaps all data sheets could state exactly what type of drug is in the preparation. South-Western Regional Drug Information Service, Bristol Royal Infirmary
H. MCNULTY
Pharmacy Drug Information Centre, Hospital,
Southmead Bristol
R. A. MOORHOUSE
findings are suggestive. 683 Oak Grove Drive, Santa Barbara, California 93108, U.S.A.
GUIDE TO DRUG INTERACTIONS
SIR The pocket "Medisc", widely distributed by the Health Departments and now available for purchase, will increase awareness of drug interactions but it has limitations in its design, classification system, and information content. The outer part of the disc lists 61 drugs which may be matched with 16 drugs or groups of drugs (8 on each side of two separate inner rotating discs). The small number of drugs on the inner disc means that some well-documented interactions cannot be matched (e.g., between tetracyclines and antacids ; allopurinol and mercaptopurine; and levodopa and pyri-
doxine). The medisc
uses
the
following
terms:
potentially
serious in-
teraction, effect enhanced, effect diminished, and uncertain clinical significance. The disc indicates which drug effects are enhanced or diminished. However, the classification system does not differentiate between pharmacological and toxic effects and this may reduce the clinical value of the disc, as it does not indicate whether alteration of dosage will correct the effect of the interaction or whether concurrent use of the drugs 7. 8
Rotrosen, J., and others. Unpublished. Stanley, M., Wilk, S. in Proceedings of the Society of Neurosciences (Toronto, 1976), abstr. 1276. 9 Wilk, S., Stanley, M. Eur. J. Pharmac. (in the press). 10. Crow, T. J., Deakin, J. F. W., Johnstone, E. C., Longden, A. Lancet, 1976, ii, 1027.
WASTAGE OF PHARMACEUTICALS
ALEX COMFORT
SIR,-Hart and Marshall2 seem to recommend the re-issue of some drugs returned to the pharmacy for destruction. With a few exceptions, this practice is not to be recommended, because it cannot be known if such a drug is still satisfactory for use. Pharmacists always have to be confident of the quality of the drugs they dispense. Such quality assurance depends on the total control of manufacture, analytical testing, and storage. When drugs prescribed by general practititioners are returned to the pharmacy, it is not normally possible to know if they have been stored correctly and if they still meet the appropriate specification. I suggest that the wastage of pharmaceuticals be reduced by other methods (e.g., reduction in apparent overprescribing, patient education to improve compliance with instructions, and development of ward pharmacy services) and not by the re-issue of "second-hand" drugs. Regional Drug Information Centre, Southampton General Hospital, Southampton SO9 4XY
Wessex
D. E. HANDS
PACKAGING INTRAVENOUS DEVICES
SIR,-Pilsworth raises an important point.3 The safe use of intravenous devices depends on their sterility and thus on the integrity of the packaging. Many modern foodstuffs are very 1. Hansten, P. D. Drug Interactions. Philadelphia, 1976. 2. Hart, R. J., Marshall, F. S. V. Lancet, 1976, ii, 1239. 3 Pilsworth, R. Lancet, 1976, ii, 1256.
96
hygienically packaged, and their safety is frequently demonstrated by the use of vacuum packs. Would this not be an even better indication of sterility, in that damage to the packing would be even more immediately noticed? Department of Anaesthetics, Serafimerlasarettet, 112 83 Stockholm, Sweden
D. P. CARTWRIGHT
lished cases, and the investigator could establish a contact and may even launch a collaborative study with other investiga-
tor(s). Use of the chart and the catalogue and repositories, should avoid unnecessary and time-consuming literature searches. Division of Medical Genetics,
Department of Medicine, Johns Hopkins University School of Medicine, MICHAEL ABSATZ DIGAMBER S. BORGAONKAR Baltimore, Maryland 21205, U.S.A.
CHROMOSOME ARM INVOLVEMENT IN INTERCHANGES
PREVALENCE OF CHILDHOOD ASTHMA IN AFRICA
SIR,-Every chromosome is involved in chromosomal interchanges in man.’ Now that more data are available the chromosome arms involved (i.e., p and q arms of all the 24 chromosomes) can be tabulated. The figure shows that all 48 chromosome arms are involved in chromosomal rearrangements. In the future, the chart will probably be expanded to show the involvement of specific chromosomal segments such as regions and bands in interchanges.
Chart showing chromosome number and lished interchange. Filled-in squares indicate
an
arm
involved in
pub-
interchange. (Source: Borgaonkar’s
catalogue.2) Two computerised data banks facilitate the compilation of such data. However, data from only one of them, a catalogue,2 which lists selected references describing significant reports of all major kinds of chromosomal variants and anomalies, are used in the figure. The other, the repository,3 is a record of unpublished data of contributing laboratories. Through the use of banks, the data can be continuously updated and specific translocation points can be examined. A recent report. states that: "To our knowledge, no translocation between the short arm of a number 3 and the long arm of a number 19 have been reported ..." The information contained in this chart will help in establishing claims of priority for a translocation, and the investigator can locate the specific reports concerning the translocation from the catalogue. Likewise, the data, from the repository (or a similar chart constructed from data in the repository) would point to unpub1. 2.
3.
Borgaonkar, D. S., Boiling, D. R. J. reprod. Med. 1976, 17, 69. Borgaonkar, D. S. Chromosomal Variation in Man: A Catalog of Chromosomal Variants and Anomalies. Baltimore, 1975. Borgaonkar, D. S., Bolling, D. R. Repository of Chromosomal Variants and
Anomalies in Man, Baltimore, 1976. 4. Neu, R. L., Gardner, L. I. Pediat. Res. 1976,
10, 369.
SIR,-DR Carswell and his colleagues’ found asthma in 3.3% of a group of schoolchildren in an ascaris-endemic area of Tanzania and state that this figure is comparable with that found in developed countries. Their findings contradict the hypothesis that helminthic infestations give rise to total serumIgE levels which protect against asthma. We feel that no real conclusion can be drawn from their findings and that the prevalence of asthma in Black children they provide, which does not correspond with other figures for asthma in Black children,2-’ is too high. They base their conclusions on a highly selected group of children. They did not indicate the method of selection or the age ranges of the children studied. Their criterion for asthma-a fall in peak expiratory flow-rate (P.E.F.R.) of more than 9%-is also open to question. Many workers believe that a fall in the P.E.F.R. of 15% or more is necessary for the diagnosis of exercise-induced asthma.6-10 Anderson et al." state that the percentage fall in P.E.F.R. found in asthmatic children is usually between 25% and 50%. Only 2 of the Tanzanian children had a fall in P.E.F.R. of more than 15%. No information is given about serum-IgE levels for the children studied. An interesting observation from their study is the ages of the 8 children with asthma: the mean age is 11-75 years, the youngest being 10. Asthma is common in adults in different parts of Africa. The pattern, however, differs from that seen in countries with a temperate climate, where asthma occurs in the younger child who tends to outgrow it. In Blacks the age at onset tends to be in early adulthood; associated atopic diseases are uncommon; positive prick tests to house dust and house dust mites (Dermatophagoides farince and D. pteronyssinus) are common; and childhood asthma is rare.33 412-15 Smith attributes these differences to a lesser "allergic bombardment" to which persons from the tropics are exposed." We support the view that asthma is rare in Black children; especially in rural areas. At the Red Cross War Memorial Children’s Hospital 228 802 outpatients of three ethnic groups were seen during 1975; of these children 20 495 (9.0%) were White, 169965 (74.3%) were Coloured (mixed race), and 38-342 (16.7%) were Blacks. Children are seen at the hospital up to the age of 13 years only. The allergy clinic has 3515 asthmatic children of whom only 13 are Blacks (036%) According to the 1970 census, there were 107 877 Blacks living in Cape Town.’6 Most of the Black children attending this Carswell, F., Meakins, R. N., Harland, P. S. E. G. Lancet, 1976, ii, 706. Wesley, A. G., Clyde, J. H., Wallace, H. L. S. Afr. med. J. 1969, 87. Warrel, D. A., Fawcett, J. W., Harrison, B. D. W., Agamah, A. J., Ibu, J. O., Pope, H. M., Maberly, D. J. Q. Jl. Med. 1975, 174, 325. 4. Wasunna, A. E. O. E. Afr. med. J. 1968, 45, 70. 5. Johannson, S. G. O., Mellbin, T., Vahlquist, B. Lancet, 1968, i, 1118. 6. Cropp, G. J. A., Schmultzler, B. S. Pediatrics, 1975, 56, 689. 7. Fitch, K. D. ibid. p. 869. 8. Silverman, M., Andrea, T. Archs Dis. Childh. 1972, 47, 419. 9. Jones, R. S., Buston, M. H., Wharton, M. J. Br. J. Dis. Chest, 1962, 56,
1. 2. 3.
78. 10. Bierman, C. W., Pierson, W. E. Pediatrics, 1975, 56, suppl. p. 950. 11. Anderson, S. D., Silverman, M., König, P., Godfrey, S. Br. J. Dis. Chest, 1975, 69, 1. 12. Rees, P. H., Gitoho, F., Mitchell, H. S., Rees, C. E. Afr. med. J. 1974, 51, 729. 13. Sofowora, E. O. E. Afr. med. J. 1970, 47, 434. 14. Buchanan, D. J., Jones, I. G. Br. med. J. 1972, iii, 764. 15. Smith, J. M. Clin. Allergy, 1973, 3, 269. 16. van der Spuy, D. C. in South Africa 1974: Official Yearbook of the Republic of South Africa; p. 76. Preskor, Johannesburg, 1974.
Regional selectivity therefore does not explain the pharmacological profile of drugs such as clozapine or thioridazine. Extrapyramidal effects are correlated with drug potencies in both the striatum and tuberculum olfactorium. Antipsychotic effects can be predicted by the dose-response curves in either region. With this model we have been able to predict the clinical potency of thiethylperazine, a drug previously considered to be devoid of antipsychotic activity but recently shown in the clinic to be active at about three times the potency of chlorpromazine.7 Several butyrophenone analogues devoid of antipsychotic activity were inactive in our system.8 We have also found a reported non-antipsychotic drug, perlapine, with a dose-response profile in the striatum and tuberculum olfactorium virtually identical to chlorpromazine. The marked sedative properties of this agent may have complicated the clinical trials. We have predicted that reevaluation of this drug in the clinic will reveal its antipsychotic efficacy. Department of Pharmacology, Mount Sinai School
of Medicine,
SHERWIN WILK MICHAEL STANLEY
Of City University of New York, New York, N.Y. 10029, U.S.A.
MORPHINE AS ANTIPSYCHOTIC DRUG
SIR,-An interesting point is raised by Crow et al. 10 While morphine is not antipsychotic in the ordinary sense, many who are interested in the epidemiology of heroin addiction have formed the impression that addicts now include, though they are not confined to, people who would have become clinically psychotic if not addicted. It seems very probable that there is a group of people who do rely on morphinoid drugs as primary suppressants of intolerable prepsychotic sensations, and that these are the addicts who fail to display enough motivation to undertake the physical distress of withdrawal. This might suggest an alternative approach to addiction-there may even be psychotics for whom morphinoids are the only effective antipsychotic, despite the other risks which such drugs carry. Older experience with stabilised and supervised addicts seems to
bear this
out.
At the very least, however, the neurochemical
should be avoided. The drugs appear individually or as broad groups, and headings such as tricyclics, sympathomimetics (direct or indirect acting), benzodiazepines, and sulphonylureas are used. Some broad headings are listed under one drug of that type. Thus sulphonylureas such as glibenclamide are found under chlorpropamide, metformin appears under phenformin (biguanides), and perphenazine is found under
chlorpromazine (phenothiazines). The user must thus know how the ingredients of a medicine are classined, but the British National Formulary, MIMS, or the Data Sheet Compendium, do not give him this information for all drugs. Medisc contains 173 separate interactions, of which 28 are classified as potentially serious (and 14 of these relate to alcohol). The interactions were compiled from secondary reference sources which are themselves two or three years old, and while the accompanying leaflet states that the interaction disc is not comprehensive, this is not stated on the device itself. There are also some discrepancies between statements made about some interactions and current opinion. For example, it is suggested that thiazide diuretics will interact with cephaloridine with potentially serious results, yet no published evidence of such an interaction exists.’Hansten suggests that because of the severity of an interaction between frusemide and cephaloridine concomitant use should be avoided,’ but it is not possible to locate such an interaction on the disc. It is also suggested that indomethacin potentiates the effects of oral anticoagulants while evidence to the contrary is common.’ Although, in view of possible indomethacin-induced gastrointestinal bleeding, it may be necessary to use indomethacin with caution in such patients. To be of value, the disc should be brought up to date regularly, and the device should state that the interaction list is not comprehensive. The disc should be used in conjunction with the data sheet for the product and not as a replacement for it. Perhaps all data sheets could state exactly what type of drug is in the preparation. South-Western Regional Drug Information Service, Bristol Royal Infirmary
H. MCNULTY
Pharmacy Drug Information Centre, Hospital,
Southmead Bristol
R. A. MOORHOUSE
findings are suggestive. 683 Oak Grove Drive, Santa Barbara, California 93108, U.S.A.
GUIDE TO DRUG INTERACTIONS
SIR The pocket "Medisc", widely distributed by the Health Departments and now available for purchase, will increase awareness of drug interactions but it has limitations in its design, classification system, and information content. The outer part of the disc lists 61 drugs which may be matched with 16 drugs or groups of drugs (8 on each side of two separate inner rotating discs). The small number of drugs on the inner disc means that some well-documented interactions cannot be matched (e.g., between tetracyclines and antacids ; allopurinol and mercaptopurine; and levodopa and pyri-
doxine). The medisc
uses
the
following
terms:
potentially
serious in-
teraction, effect enhanced, effect diminished, and uncertain clinical significance. The disc indicates which drug effects are enhanced or diminished. However, the classification system does not differentiate between pharmacological and toxic effects and this may reduce the clinical value of the disc, as it does not indicate whether alteration of dosage will correct the effect of the interaction or whether concurrent use of the drugs 7. 8
Rotrosen, J., and others. Unpublished. Stanley, M., Wilk, S. in Proceedings of the Society of Neurosciences (Toronto, 1976), abstr. 1276. 9 Wilk, S., Stanley, M. Eur. J. Pharmac. (in the press). 10. Crow, T. J., Deakin, J. F. W., Johnstone, E. C., Longden, A. Lancet, 1976, ii, 1027.
WASTAGE OF PHARMACEUTICALS
ALEX COMFORT
SIR,-Hart and Marshall2 seem to recommend the re-issue of some drugs returned to the pharmacy for destruction. With a few exceptions, this practice is not to be recommended, because it cannot be known if such a drug is still satisfactory for use. Pharmacists always have to be confident of the quality of the drugs they dispense. Such quality assurance depends on the total control of manufacture, analytical testing, and storage. When drugs prescribed by general practititioners are returned to the pharmacy, it is not normally possible to know if they have been stored correctly and if they still meet the appropriate specification. I suggest that the wastage of pharmaceuticals be reduced by other methods (e.g., reduction in apparent overprescribing, patient education to improve compliance with instructions, and development of ward pharmacy services) and not by the re-issue of "second-hand" drugs. Regional Drug Information Centre, Southampton General Hospital, Southampton SO9 4XY
Wessex
D. E. HANDS
PACKAGING INTRAVENOUS DEVICES
SIR,-Pilsworth raises an important point.3 The safe use of intravenous devices depends on their sterility and thus on the integrity of the packaging. Many modern foodstuffs are very 1. Hansten, P. D. Drug Interactions. Philadelphia, 1976. 2. Hart, R. J., Marshall, F. S. V. Lancet, 1976, ii, 1239. 3 Pilsworth, R. Lancet, 1976, ii, 1256.
96
hygienically packaged, and their safety is frequently demonstrated by the use of vacuum packs. Would this not be an even better indication of sterility, in that damage to the packing would be even more immediately noticed? Department of Anaesthetics, Serafimerlasarettet, 112 83 Stockholm, Sweden
D. P. CARTWRIGHT
lished cases, and the investigator could establish a contact and may even launch a collaborative study with other investiga-
tor(s). Use of the chart and the catalogue and repositories, should avoid unnecessary and time-consuming literature searches. Division of Medical Genetics,
Department of Medicine, Johns Hopkins University School of Medicine, MICHAEL ABSATZ DIGAMBER S. BORGAONKAR Baltimore, Maryland 21205, U.S.A.
CHROMOSOME ARM INVOLVEMENT IN INTERCHANGES
PREVALENCE OF CHILDHOOD ASTHMA IN AFRICA
SIR,-Every chromosome is involved in chromosomal interchanges in man.’ Now that more data are available the chromosome arms involved (i.e., p and q arms of all the 24 chromosomes) can be tabulated. The figure shows that all 48 chromosome arms are involved in chromosomal rearrangements. In the future, the chart will probably be expanded to show the involvement of specific chromosomal segments such as regions and bands in interchanges.
Chart showing chromosome number and lished interchange. Filled-in squares indicate
an
arm
involved in
pub-
interchange. (Source: Borgaonkar’s
catalogue.2) Two computerised data banks facilitate the compilation of such data. However, data from only one of them, a catalogue,2 which lists selected references describing significant reports of all major kinds of chromosomal variants and anomalies, are used in the figure. The other, the repository,3 is a record of unpublished data of contributing laboratories. Through the use of banks, the data can be continuously updated and specific translocation points can be examined. A recent report. states that: "To our knowledge, no translocation between the short arm of a number 3 and the long arm of a number 19 have been reported ..." The information contained in this chart will help in establishing claims of priority for a translocation, and the investigator can locate the specific reports concerning the translocation from the catalogue. Likewise, the data, from the repository (or a similar chart constructed from data in the repository) would point to unpub1. 2.
3.
Borgaonkar, D. S., Boiling, D. R. J. reprod. Med. 1976, 17, 69. Borgaonkar, D. S. Chromosomal Variation in Man: A Catalog of Chromosomal Variants and Anomalies. Baltimore, 1975. Borgaonkar, D. S., Bolling, D. R. Repository of Chromosomal Variants and
Anomalies in Man, Baltimore, 1976. 4. Neu, R. L., Gardner, L. I. Pediat. Res. 1976,
10, 369.
SIR,-DR Carswell and his colleagues’ found asthma in 3.3% of a group of schoolchildren in an ascaris-endemic area of Tanzania and state that this figure is comparable with that found in developed countries. Their findings contradict the hypothesis that helminthic infestations give rise to total serumIgE levels which protect against asthma. We feel that no real conclusion can be drawn from their findings and that the prevalence of asthma in Black children they provide, which does not correspond with other figures for asthma in Black children,2-’ is too high. They base their conclusions on a highly selected group of children. They did not indicate the method of selection or the age ranges of the children studied. Their criterion for asthma-a fall in peak expiratory flow-rate (P.E.F.R.) of more than 9%-is also open to question. Many workers believe that a fall in the P.E.F.R. of 15% or more is necessary for the diagnosis of exercise-induced asthma.6-10 Anderson et al." state that the percentage fall in P.E.F.R. found in asthmatic children is usually between 25% and 50%. Only 2 of the Tanzanian children had a fall in P.E.F.R. of more than 15%. No information is given about serum-IgE levels for the children studied. An interesting observation from their study is the ages of the 8 children with asthma: the mean age is 11-75 years, the youngest being 10. Asthma is common in adults in different parts of Africa. The pattern, however, differs from that seen in countries with a temperate climate, where asthma occurs in the younger child who tends to outgrow it. In Blacks the age at onset tends to be in early adulthood; associated atopic diseases are uncommon; positive prick tests to house dust and house dust mites (Dermatophagoides farince and D. pteronyssinus) are common; and childhood asthma is rare.33 412-15 Smith attributes these differences to a lesser "allergic bombardment" to which persons from the tropics are exposed." We support the view that asthma is rare in Black children; especially in rural areas. At the Red Cross War Memorial Children’s Hospital 228 802 outpatients of three ethnic groups were seen during 1975; of these children 20 495 (9.0%) were White, 169965 (74.3%) were Coloured (mixed race), and 38-342 (16.7%) were Blacks. Children are seen at the hospital up to the age of 13 years only. The allergy clinic has 3515 asthmatic children of whom only 13 are Blacks (036%) According to the 1970 census, there were 107 877 Blacks living in Cape Town.’6 Most of the Black children attending this Carswell, F., Meakins, R. N., Harland, P. S. E. G. Lancet, 1976, ii, 706. Wesley, A. G., Clyde, J. H., Wallace, H. L. S. Afr. med. J. 1969, 87. Warrel, D. A., Fawcett, J. W., Harrison, B. D. W., Agamah, A. J., Ibu, J. O., Pope, H. M., Maberly, D. J. Q. Jl. Med. 1975, 174, 325. 4. Wasunna, A. E. O. E. Afr. med. J. 1968, 45, 70. 5. Johannson, S. G. O., Mellbin, T., Vahlquist, B. Lancet, 1968, i, 1118. 6. Cropp, G. J. A., Schmultzler, B. S. Pediatrics, 1975, 56, 689. 7. Fitch, K. D. ibid. p. 869. 8. Silverman, M., Andrea, T. Archs Dis. Childh. 1972, 47, 419. 9. Jones, R. S., Buston, M. H., Wharton, M. J. Br. J. Dis. Chest, 1962, 56,
1. 2. 3.
78. 10. Bierman, C. W., Pierson, W. E. Pediatrics, 1975, 56, suppl. p. 950. 11. Anderson, S. D., Silverman, M., König, P., Godfrey, S. Br. J. Dis. Chest, 1975, 69, 1. 12. Rees, P. H., Gitoho, F., Mitchell, H. S., Rees, C. E. Afr. med. J. 1974, 51, 729. 13. Sofowora, E. O. E. Afr. med. J. 1970, 47, 434. 14. Buchanan, D. J., Jones, I. G. Br. med. J. 1972, iii, 764. 15. Smith, J. M. Clin. Allergy, 1973, 3, 269. 16. van der Spuy, D. C. in South Africa 1974: Official Yearbook of the Republic of South Africa; p. 76. Preskor, Johannesburg, 1974.