1051 The availability to the industry of these clinical units calls in question the ethics of volunteer drug studies in laboratories that are sometimes a long way from the nearest hospital.
PRESCRIBING IN THE N.H.S.
tent.
SIR,-A letter from the Secretary of State for Social Services and the chairman of the B.M.A. Council (April 29, p. 946), which has been circulated to the profession exhorting them to restrict Health Service prescribing at this 30th anniversary of the N.H.S., is most logical and needed. One cannot feel, however, that it will have very much effect whilst the nation continues to be told that unlimited service is available to everyone on demand at no,cost. Most doctors endeavour to restrict their prescribing. They will find it hard to cut back further, and many will be irritated by the fact that hospital prescribers are exhorted not to order drugs which will increase their own hospital bill but to persuade general practitioners to order the drugs via local chemists at a higher price. This last point alone may cost more than can possibly be saved by the changes requested of the profession. In any case, wastage need not be sought in prescribing habits until some of the other waste and extravagances has been controlled.
Department of Clinical Pharmacology, St. Bartholomew’s Hospital Medical College,
SHIGELLOSIS AND HÆMOLYTIC URÆMIC SYNDROME
SIR,-You refer (Jan. 7,
p. 26) to a number of probable ofhaemolytic urxmic syndrome (H.u.s.), but fail to mention shigellosis as a proven cause of this condition. In Bangladesh we have seen many patients with H.u.s. accompanied by a leuksmoid reaction after dysentery, particularly that due to Shigella dysenteriae type 1, the Shiga bacillus. 1,2 Many published cases of H.u.s. have been in association with diarrhoea or have been preceded by an episode of causes
General
Hospital, Birmingham B4 6NH
diarrhoea. More detailed studies on patients having H.u.s. in association with shigella have shown an association between circulating endotoxin and this syndrome.3 The circulating endotoxin preceded the episode of H.u.s. rather than accompanying it. It serves as a predictor that H.u.s. may develop later in patients with dysentery. We feel that the association with shigella dysentery is important and may give significant clues towards the mechanism of this important syndrome of childhood.
GEORGE T. WATTS
VOLUNTEER STUDIES WITHIN THE PHARMACEUTICAL INDUSTRY
SiR,-Dr Butler’s paper (April 15, p. 816) on the ethics of volunteer studies conducted within the pharmaceutical industry resembled his contribution to a symposium on the subject about a year ago, at which contrary views were expressed by others. Butler states "The accuracy of the data may be greater in studies conducted by the clinical monitor in industry". With whom is he making the comparison? A monitor who does not have "to meet stringent scrutiny by his scientific colleagues" (of whom there are some examples within the pharmaceutical industry) ? Or does he mean that good laboratory practice can only be assured or assumed within the pharmaceutical industry and that those engaged in academic medical research pay less attention to detail? He acknowledges that there are "some limitations to what can be done within the pharmaceutical companies but danger arises only if the limitations are not recognised and the type of study undertaken is too ambitious". Surely it is precisely those limitations, which are recognised only in retrospect when damage may already have been done which make volunteer studies outside a clinical unit so undesirable. Human variation in response to drugs is such that unwanted effects in individuals are often unpredictable. His suggestion that "it should also be possible to do tolerance and activity studies on appropriately selected new compounds" fills me with dismay, for how can one predict the tolerability and safety of "new" compounds ? Perhaps he really means "me-too" products". Butler’s safeguards to ensure the ethical conduct of such studies-including volunteer selection, volunteer motivation, informed consent, insurance, and ethical review—omit the most important, the relationship of the volunteer to the investigator. This should be no less close than that between patient and doctor. In most, if not all, academic medical research departments involved in the investigation of drugs, volunteers receive the same consideration and have the same clinical resources for recognition and management of unexpected adverse effects as do patients. This cannot be said of the pharmaceutical industry. Even possession of a higher medical qualification by a medical adviser and the availability of modern resuscitation equipment will not ensure that volunteers within the industry receive treatment as good as that available in clinical departments.
dustry
Cholera Research
Laboratory, Dacca-12, Bangladesh
M. M. RAHAMAN W. B. GREENOUGH, III
INHIBITION OF PLATELET AGGREGATION BY ONION EXTRACTS
,
SIR,-Baghurst et al." reported the effect of onions on platelet aggregation in people who had consumed a high fat meal. We have, therefore, examined the effect of onion extracts on platelet aggregation in vitro. Platelet-rich plasma was obtained from volunteers (four men, one woman) aged 22-47 years. Platelet aggregation was measured at 37°C by turbidornetrys in an Upchurch B1037 346 aggregometer connected to a Vitatron pen recorder. Aqueous or ethanolic extracts were obtained by homogenising onion at 300 g in either 100 ml normal saline or 100 ml ethanol using a Polytron homogeniser and filtering. The pH of the saline extract was 5.5. The ethanolic extract was evaporated to dryness at 45 °C and the residue dissolved in 1 ml normal saline. Aggregation of platelets from all five volunteers in response to arachidonic acid (500 .g/ml) and adenosine diphosphate (A.D.P.) (}jLmol/l) was completely inhibited by 0-1ml of both saline and’reconstituted alcoholic extracts of onion. Platelet aggregation induced with collagen from rabbit tendon was also inhibited by both extracts (two subjects only tested) but thrombin-induced aggregation was not. Activity was reduced in the saline extract by boiling for 30 min at pH 5.5and destroyed by boiling for 10 min at pH 9-5. In an attempt to separate the active constituent, 700 g onion was homogenised in 100 ml ethanol, filtered, and evaporated to dryness. The residue was redissolved in 67% ethanol and partitioned with petroleum spirit (b.p. 60-80°C). The ethano1. Rahaman, M. M., Alam, A. K., Islam, M. R. Lancet, 1974, i, 1004. 2. Rahaman, M. M., Alam, A. K. M. S., Islam, M. R., Greenough III, W.
B.,
Lindenbaum, J.Johns Hopkins med.J. 1975, 136, 65.
In the U.K. there
cology
PAUL TURNER
London EC1A 7BE
many departments of clinical pharmacollaborate with the pharmaceutical inprepared in volunteer research, however modest its scientific conto
are
3. Presented in part in abstract form for the American Federation for Clinical Research. Clin. Res. 1977, 25, 379A. 4. Baghurst, K, I., Raj, M. J., Truswell, A. S. Lancet, 1977, i, 101. 5. Born, G. V. R.J. Physiol. Lond. 1962, 162, 67P.
.
PRESCRIBING IN THE N.H.S.
tent.
SIR,-A letter from the Secretary of State for Social Services and the chairman of the B.M.A. Council (April 29, p. 946), which has been circulated to the profession exhorting them to restrict Health Service prescribing at this 30th anniversary of the N.H.S., is most logical and needed. One cannot feel, however, that it will have very much effect whilst the nation continues to be told that unlimited service is available to everyone on demand at no,cost. Most doctors endeavour to restrict their prescribing. They will find it hard to cut back further, and many will be irritated by the fact that hospital prescribers are exhorted not to order drugs which will increase their own hospital bill but to persuade general practitioners to order the drugs via local chemists at a higher price. This last point alone may cost more than can possibly be saved by the changes requested of the profession. In any case, wastage need not be sought in prescribing habits until some of the other waste and extravagances has been controlled.
Department of Clinical Pharmacology, St. Bartholomew’s Hospital Medical College,
SHIGELLOSIS AND HÆMOLYTIC URÆMIC SYNDROME
SIR,-You refer (Jan. 7,
p. 26) to a number of probable ofhaemolytic urxmic syndrome (H.u.s.), but fail to mention shigellosis as a proven cause of this condition. In Bangladesh we have seen many patients with H.u.s. accompanied by a leuksmoid reaction after dysentery, particularly that due to Shigella dysenteriae type 1, the Shiga bacillus. 1,2 Many published cases of H.u.s. have been in association with diarrhoea or have been preceded by an episode of causes
General
Hospital, Birmingham B4 6NH
diarrhoea. More detailed studies on patients having H.u.s. in association with shigella have shown an association between circulating endotoxin and this syndrome.3 The circulating endotoxin preceded the episode of H.u.s. rather than accompanying it. It serves as a predictor that H.u.s. may develop later in patients with dysentery. We feel that the association with shigella dysentery is important and may give significant clues towards the mechanism of this important syndrome of childhood.
GEORGE T. WATTS
VOLUNTEER STUDIES WITHIN THE PHARMACEUTICAL INDUSTRY
SiR,-Dr Butler’s paper (April 15, p. 816) on the ethics of volunteer studies conducted within the pharmaceutical industry resembled his contribution to a symposium on the subject about a year ago, at which contrary views were expressed by others. Butler states "The accuracy of the data may be greater in studies conducted by the clinical monitor in industry". With whom is he making the comparison? A monitor who does not have "to meet stringent scrutiny by his scientific colleagues" (of whom there are some examples within the pharmaceutical industry) ? Or does he mean that good laboratory practice can only be assured or assumed within the pharmaceutical industry and that those engaged in academic medical research pay less attention to detail? He acknowledges that there are "some limitations to what can be done within the pharmaceutical companies but danger arises only if the limitations are not recognised and the type of study undertaken is too ambitious". Surely it is precisely those limitations, which are recognised only in retrospect when damage may already have been done which make volunteer studies outside a clinical unit so undesirable. Human variation in response to drugs is such that unwanted effects in individuals are often unpredictable. His suggestion that "it should also be possible to do tolerance and activity studies on appropriately selected new compounds" fills me with dismay, for how can one predict the tolerability and safety of "new" compounds ? Perhaps he really means "me-too" products". Butler’s safeguards to ensure the ethical conduct of such studies-including volunteer selection, volunteer motivation, informed consent, insurance, and ethical review—omit the most important, the relationship of the volunteer to the investigator. This should be no less close than that between patient and doctor. In most, if not all, academic medical research departments involved in the investigation of drugs, volunteers receive the same consideration and have the same clinical resources for recognition and management of unexpected adverse effects as do patients. This cannot be said of the pharmaceutical industry. Even possession of a higher medical qualification by a medical adviser and the availability of modern resuscitation equipment will not ensure that volunteers within the industry receive treatment as good as that available in clinical departments.
dustry
Cholera Research
Laboratory, Dacca-12, Bangladesh
M. M. RAHAMAN W. B. GREENOUGH, III
INHIBITION OF PLATELET AGGREGATION BY ONION EXTRACTS
,
SIR,-Baghurst et al." reported the effect of onions on platelet aggregation in people who had consumed a high fat meal. We have, therefore, examined the effect of onion extracts on platelet aggregation in vitro. Platelet-rich plasma was obtained from volunteers (four men, one woman) aged 22-47 years. Platelet aggregation was measured at 37°C by turbidornetrys in an Upchurch B1037 346 aggregometer connected to a Vitatron pen recorder. Aqueous or ethanolic extracts were obtained by homogenising onion at 300 g in either 100 ml normal saline or 100 ml ethanol using a Polytron homogeniser and filtering. The pH of the saline extract was 5.5. The ethanolic extract was evaporated to dryness at 45 °C and the residue dissolved in 1 ml normal saline. Aggregation of platelets from all five volunteers in response to arachidonic acid (500 .g/ml) and adenosine diphosphate (A.D.P.) (}jLmol/l) was completely inhibited by 0-1ml of both saline and’reconstituted alcoholic extracts of onion. Platelet aggregation induced with collagen from rabbit tendon was also inhibited by both extracts (two subjects only tested) but thrombin-induced aggregation was not. Activity was reduced in the saline extract by boiling for 30 min at pH 5.5and destroyed by boiling for 10 min at pH 9-5. In an attempt to separate the active constituent, 700 g onion was homogenised in 100 ml ethanol, filtered, and evaporated to dryness. The residue was redissolved in 67% ethanol and partitioned with petroleum spirit (b.p. 60-80°C). The ethano1. Rahaman, M. M., Alam, A. K., Islam, M. R. Lancet, 1974, i, 1004. 2. Rahaman, M. M., Alam, A. K. M. S., Islam, M. R., Greenough III, W.
B.,
Lindenbaum, J.Johns Hopkins med.J. 1975, 136, 65.
In the U.K. there
cology
PAUL TURNER
London EC1A 7BE
many departments of clinical pharmacollaborate with the pharmaceutical inprepared in volunteer research, however modest its scientific conto
are
3. Presented in part in abstract form for the American Federation for Clinical Research. Clin. Res. 1977, 25, 379A. 4. Baghurst, K, I., Raj, M. J., Truswell, A. S. Lancet, 1977, i, 101. 5. Born, G. V. R.J. Physiol. Lond. 1962, 162, 67P.
.
