788
resuscitation in these conditions has received careful consideration, with advice on prophylaxis.l,2 There are doubts about whether HIV infections can be transmitted in this way.’ It is generally recommended that mouth-to-mouth resuscitation be done with care and that barrier devices should be used when possible.3,4 It may be advisable to extend the use of barrier devices to cases where salmonella infection is suspected. A strong case’ can be made for including these devices in first-aid kits and for including a description of the technique in the Resuscitation Council’s handbook.’ Bishop Auckland General Hospital, Co Durham DL14 6AD, UK
F. AHMAD D. C. A. SENADHIRA
South West Durham Health Authority, Bishop Auckland
J. CHARTERS S. ACQUILLA
1. Benson AS. Control of communicable disease in man. 4th ed. Washington: American Public Health Association, 1985. 2. Department of Health and Social Security, Joint Committee on Vaccination and Immunisation. Immunisation against infectious disease. London: HM Stationery Office, 1988. 3. Saliteer SM, White GC, Cohen MS. HTLV-III exposure during cardio-pulmonary resuscitation. N Engl J Med 1985; 313: 1606-07. 4. Nickalls RWD, Thompson CW. Mouth-to-mask respiration. Br Med J 1986; 292: 1350. 5. Resuscitation Council (UK). Resuscitation for the citizen. London: Resuscitation Council (UK), 1984.
Loperamide poisoning
in children
SiR,—Dr Bhutta and Dr Tahir (Feb 10, p 363) express concern about the use of loperamide in very young children: there have been previous reports of ileus after therapeutic use in children.1,2 Whilst loperamide has been shown to be safe when used as an adjunct to oral rehydration in well-nourished children, this may not be true for malnourished populations in developing countries. We have commented on respiratory depression in a 15-month-old child after a single dose of loperamide 4 Toxicity was reversed by naloxone. This sensitivity to the drug may have been related to low serum protein concentrations or impaired hepatic function-factors which would be pertinent in the children reported from Pakistan. We also highlight the discrepancy in recommended dosage: while the lower age limit in many developing countries is 1 year, loperamide is not indicated below the age of 2 years in the USA5 and 4 years in the UK.s,6 Since all the children affected in Pakistan were aged 2 years or under, and all those who died were under 61 months, the lower age limit may need to be revised, and some way should be found of giving clearer instructions concerning use. There should be more control over community use ofloperamide in developing countries, especially since the use of antidiarrhoeal medications may distract from the urgent priority of oral rehydration. Poisons Unit,
Guy’s Hospital, London SE1 9RT,UK
NEIL A. MINTON JOHN A. HENRY
BK,Tripp JH, Milla PJ, Harries JT. Loperamide in severe protracted diarrhoea. Arch Dis Child 1983; 58: 39-43. von Muhlendahl KE, Bunjes R, Krienke EG. Loperamide-induced ileus. Lancet 1980; i: 209. Diarrhoeal Diseases Study Group (UK). Loperamide in acute diarrhoea in childhood: results of a double blind, placebo controlled multicentre clinical trial. Br Med J 1984; 289: 1263-67. Minton NA, Smith PGD. Loperamide toxicity in a child after a single dose. Br Med J 1987; 294: 1383. Reynolds JEF, ed. Martindale: the extra pharmacopoeia, 29th ed. London: Pharmaceutical Press, 1989: 1094. ABPI data sheet compendium 1989-90. London: Datapharm Publications, 1989 683-84.
1. Sandhu 2.
3.
4.
5. 6.
Ginkgo biloba extracts SIR,-The letter from the Dr Willmar Schwabe company (Feb 24, 475) on your Dec 23/30 Round the World report seems misleading. The fact that pharmacological or clinical studies exist is not itself proof of efficacy: it is the scientific quality of the evidence p
that matters, and none of the published data has appeared in medical journals of high reputation or high standards of peer review. Expert opinions, via biometric analysis or meta-analysis, are sometimes
commissioned by a drug company, and the outcome may be determined by the choice of whom to invite and by those who accept the invitation. Such studies cannot always be regarded as
independent. Our evaluation of data on Ginkgo biloba extract! has been criticised only by the company and by scientists who have done studies sponsored by that company. The criticisms consisted more of personal disparagement than of scientific comment and were not accepted for publication. All studies regarded by the company as proof of efficacy were included in our evaluation of ’Tebonin’ and ‘rokan’.1 The company tried to suppress negative information2 on its product by suing the author and the association of health insurance doctors, seeking a retraction of the statement and the payment damages. The Hamburg court judgment of Feb 5,1988, rejected the claims, and stated that the author had presented sufficient scientific evidence for his criticism. Having failed in court the company is continuing its strategy of suppressing negative scientific information by attempting to exclude critics from
meetings. There is little evidence that prescribing habits are indicators of proof of efficacy. The company seems to misinterpret successful marketing as indicating drug quality. It is not by chance that in Germany such conflicts arise more often with "natural" drug products. Such drugs can be licensed in Germany without proof of efficacy and the manufacturers feel that this entitles them to demand the same weak standards from scientists when evaluating such drugs. The preference for legal action may reflect manufacturer’s lack of skill and experience in scientific argument. Klinge Pharma GmbH, producer of a horsechestnut extract (’Venostasin’) licensed for chronic venous insufficiency, is attempting to sue authors of books or articles who have published negative verdicts on the drug. The freedom of science will be seriously restricted in Germany if such attempts succeed in court, but German medical scientists have not yet recognised the threat. Institute of Clinical Pharmacology, ZKH St-Jurgen-Strasse, D-2800 Bremen, West Germany
PETER S. SCHÖNHOFER
PS, Schulte-Sasse H, Manhold C, Werner B. Sind Extrakte aus den bei des Ginkgobaumes peripheren Durch-blutungs-und Himleistungsstorungen im Alter wirksam? Beurteilung von Tebonin und Rokan Intern Praxis 1989; 29: 585-601. Kassenarztliche Vereinigung Hamburg. KV Journal 1987 (Nov): 24-25.
1. Schonhofer
Blattern
2.
Zopiclone SiR,—Your March 3 editorial (p 507) is timely since, apart from the clinical study in insomnia by our group,l little has been published in the UK about the new non-benzodiazepine (BDZ) drug zopiclone. That such compounds (as opposed to tranquilliser analogues) are required is emphasised by the fact that the prescription of BDZ hypnotics continues unabated, whilst that for BDZ tranquillisers is dwindling rapidly. The implication is that, despite reluctance on the part of the doctor to prescribe and the patient to take these compounds, the need for them outweighs the potential harmful effects of dependence and withdrawal. Indeed, persistent insomnia can adversely affect daytime functioning and health (eg, in junior hospital doctors2). You express surprise that zopiclone, though not a BDZ, binds to BDZ receptors. But so do barbiturates and other drugs, such as the hypnotic agent zolpidem.3 These receptors are not specific for one class of drug (BDZ) but may be specific for hypnotic and anxiolytic compounds. Langer et a14 have proposed a classification into three receptor subtypesmega-1(? hypnotic), omega-2 (? anxiolytic), and omega-3 (peripheral)--which seems more logical. Just as the BDZs themselves may be phased out of clinical practice, so too should the term "BDZ receptor". Whether or not these new non-BDZ hypnotics and their tranquilliser cousins suriclone and alpidem5 will be clinically useful must depend on their being shown to be free of the problems associated with the BDZ compounds that they may replace. As your editorial stresses, the evidence that this is so remains equivocal.
resuscitation in these conditions has received careful consideration, with advice on prophylaxis.l,2 There are doubts about whether HIV infections can be transmitted in this way.’ It is generally recommended that mouth-to-mouth resuscitation be done with care and that barrier devices should be used when possible.3,4 It may be advisable to extend the use of barrier devices to cases where salmonella infection is suspected. A strong case’ can be made for including these devices in first-aid kits and for including a description of the technique in the Resuscitation Council’s handbook.’ Bishop Auckland General Hospital, Co Durham DL14 6AD, UK
F. AHMAD D. C. A. SENADHIRA
South West Durham Health Authority, Bishop Auckland
J. CHARTERS S. ACQUILLA
1. Benson AS. Control of communicable disease in man. 4th ed. Washington: American Public Health Association, 1985. 2. Department of Health and Social Security, Joint Committee on Vaccination and Immunisation. Immunisation against infectious disease. London: HM Stationery Office, 1988. 3. Saliteer SM, White GC, Cohen MS. HTLV-III exposure during cardio-pulmonary resuscitation. N Engl J Med 1985; 313: 1606-07. 4. Nickalls RWD, Thompson CW. Mouth-to-mask respiration. Br Med J 1986; 292: 1350. 5. Resuscitation Council (UK). Resuscitation for the citizen. London: Resuscitation Council (UK), 1984.
Loperamide poisoning
in children
SiR,—Dr Bhutta and Dr Tahir (Feb 10, p 363) express concern about the use of loperamide in very young children: there have been previous reports of ileus after therapeutic use in children.1,2 Whilst loperamide has been shown to be safe when used as an adjunct to oral rehydration in well-nourished children, this may not be true for malnourished populations in developing countries. We have commented on respiratory depression in a 15-month-old child after a single dose of loperamide 4 Toxicity was reversed by naloxone. This sensitivity to the drug may have been related to low serum protein concentrations or impaired hepatic function-factors which would be pertinent in the children reported from Pakistan. We also highlight the discrepancy in recommended dosage: while the lower age limit in many developing countries is 1 year, loperamide is not indicated below the age of 2 years in the USA5 and 4 years in the UK.s,6 Since all the children affected in Pakistan were aged 2 years or under, and all those who died were under 61 months, the lower age limit may need to be revised, and some way should be found of giving clearer instructions concerning use. There should be more control over community use ofloperamide in developing countries, especially since the use of antidiarrhoeal medications may distract from the urgent priority of oral rehydration. Poisons Unit,
Guy’s Hospital, London SE1 9RT,UK
NEIL A. MINTON JOHN A. HENRY
BK,Tripp JH, Milla PJ, Harries JT. Loperamide in severe protracted diarrhoea. Arch Dis Child 1983; 58: 39-43. von Muhlendahl KE, Bunjes R, Krienke EG. Loperamide-induced ileus. Lancet 1980; i: 209. Diarrhoeal Diseases Study Group (UK). Loperamide in acute diarrhoea in childhood: results of a double blind, placebo controlled multicentre clinical trial. Br Med J 1984; 289: 1263-67. Minton NA, Smith PGD. Loperamide toxicity in a child after a single dose. Br Med J 1987; 294: 1383. Reynolds JEF, ed. Martindale: the extra pharmacopoeia, 29th ed. London: Pharmaceutical Press, 1989: 1094. ABPI data sheet compendium 1989-90. London: Datapharm Publications, 1989 683-84.
1. Sandhu 2.
3.
4.
5. 6.
Ginkgo biloba extracts SIR,-The letter from the Dr Willmar Schwabe company (Feb 24, 475) on your Dec 23/30 Round the World report seems misleading. The fact that pharmacological or clinical studies exist is not itself proof of efficacy: it is the scientific quality of the evidence p
that matters, and none of the published data has appeared in medical journals of high reputation or high standards of peer review. Expert opinions, via biometric analysis or meta-analysis, are sometimes
commissioned by a drug company, and the outcome may be determined by the choice of whom to invite and by those who accept the invitation. Such studies cannot always be regarded as
independent. Our evaluation of data on Ginkgo biloba extract! has been criticised only by the company and by scientists who have done studies sponsored by that company. The criticisms consisted more of personal disparagement than of scientific comment and were not accepted for publication. All studies regarded by the company as proof of efficacy were included in our evaluation of ’Tebonin’ and ‘rokan’.1 The company tried to suppress negative information2 on its product by suing the author and the association of health insurance doctors, seeking a retraction of the statement and the payment damages. The Hamburg court judgment of Feb 5,1988, rejected the claims, and stated that the author had presented sufficient scientific evidence for his criticism. Having failed in court the company is continuing its strategy of suppressing negative scientific information by attempting to exclude critics from
meetings. There is little evidence that prescribing habits are indicators of proof of efficacy. The company seems to misinterpret successful marketing as indicating drug quality. It is not by chance that in Germany such conflicts arise more often with "natural" drug products. Such drugs can be licensed in Germany without proof of efficacy and the manufacturers feel that this entitles them to demand the same weak standards from scientists when evaluating such drugs. The preference for legal action may reflect manufacturer’s lack of skill and experience in scientific argument. Klinge Pharma GmbH, producer of a horsechestnut extract (’Venostasin’) licensed for chronic venous insufficiency, is attempting to sue authors of books or articles who have published negative verdicts on the drug. The freedom of science will be seriously restricted in Germany if such attempts succeed in court, but German medical scientists have not yet recognised the threat. Institute of Clinical Pharmacology, ZKH St-Jurgen-Strasse, D-2800 Bremen, West Germany
PETER S. SCHÖNHOFER
PS, Schulte-Sasse H, Manhold C, Werner B. Sind Extrakte aus den bei des Ginkgobaumes peripheren Durch-blutungs-und Himleistungsstorungen im Alter wirksam? Beurteilung von Tebonin und Rokan Intern Praxis 1989; 29: 585-601. Kassenarztliche Vereinigung Hamburg. KV Journal 1987 (Nov): 24-25.
1. Schonhofer
Blattern
2.
Zopiclone SiR,—Your March 3 editorial (p 507) is timely since, apart from the clinical study in insomnia by our group,l little has been published in the UK about the new non-benzodiazepine (BDZ) drug zopiclone. That such compounds (as opposed to tranquilliser analogues) are required is emphasised by the fact that the prescription of BDZ hypnotics continues unabated, whilst that for BDZ tranquillisers is dwindling rapidly. The implication is that, despite reluctance on the part of the doctor to prescribe and the patient to take these compounds, the need for them outweighs the potential harmful effects of dependence and withdrawal. Indeed, persistent insomnia can adversely affect daytime functioning and health (eg, in junior hospital doctors2). You express surprise that zopiclone, though not a BDZ, binds to BDZ receptors. But so do barbiturates and other drugs, such as the hypnotic agent zolpidem.3 These receptors are not specific for one class of drug (BDZ) but may be specific for hypnotic and anxiolytic compounds. Langer et a14 have proposed a classification into three receptor subtypesmega-1(? hypnotic), omega-2 (? anxiolytic), and omega-3 (peripheral)--which seems more logical. Just as the BDZs themselves may be phased out of clinical practice, so too should the term "BDZ receptor". Whether or not these new non-BDZ hypnotics and their tranquilliser cousins suriclone and alpidem5 will be clinically useful must depend on their being shown to be free of the problems associated with the BDZ compounds that they may replace. As your editorial stresses, the evidence that this is so remains equivocal.
