633 was discontinued. She has remained well and her liver-function tests on June 13, 1978, were normal. The fourth patient, now aged 48, started treatment in August, 1973. She is working as an assistant nurse and feels well, but tests of liver function remain abnormal. A liver biopsy on June 8, 1976, showed no abnormality. Treatment with cyclophosphamide 25 mg daily and prednisolone 10 mg daily is being continued, and when seen on July 18, 1978 her liverfunction tests showed: bilirubin 9 p.mol/1, alkaline phosphatase 194 i.u./l, thymol turbidity 1 unit, A.S.T. 55 LU./l, A.L.T. 87 t.u./1, albumin 32 g/1, globulin 29 g/l. Electrophoresis: slight reduction in albumin only. We believe that the combination of cyclophosphamide with adrenocorticosteroids is a valuable method of treatment for active chronic hepatitis and should still be considered as an alternative to therapy with azathioprine and adrenocorticosteroids. None of our patients showed any of the toxic effects of cyclophosphamide found by Gilmore et al. who used larger doses over a short trial period. C. D. R. PENGELLY St Anne’s Hospital,
tests, and treatment
Bowdon, Altrincham, Chesire WA 14 2AQ
R. C. JENNINGS
RESPECT FOR CLASSICS
SIR,-In your issue of July 15you speak of eicosapentaenoic and eicosatetraenoic acids. This spelling has the approval of the Merck Index, but to anyone with a classical background these are "congenital malformations". Twenty in Greek is eikosi ; the final "i" may change to "a" in front of a vowel. But twenty-four and twenty-five are eikositetra and eikosipenta, re-
spectively. The British approved name sulphasomidine (instead of sulphisomidine, as in U.S., German, French, Spanish, and other versions) is also wrong. There is no connection between this drug and soma (Greek for "body"). Sulphisomidine is the isomer of sulphadimidine. A useful analogy is sulphisoxazole which nobody would have dreamt calling sulphasoxazole. The word loci has entered English scientific and medical terminology via genetics and allergology. Locus means "place". In classical Latin its plural, however, is loca and not loci. The latter means "places in books" (e.g., references); sunt plerumque /oc!
scripitis but loca sunt regiones was drummed into the heads of our forebears. Even so, I am familiar with at least one classical quotation (Horace) where places in books, too, are referred to as loca ("loca iam recitata revolvere", "to repeat passages already declaimed"). Thus by using loca scientists may err on the safe side. By wrongly using loci they expose themselves to ridicule, at least in those countries where the classics are still "in" among the educated. When the Merck Index, the British Pharmacopoeia Commision, and medical authors display ignorance of the classical languages should not The Lancet stop them? :M
the lociinscriptis but locasuntregioneswas drummed into
Aachenstrasse 38,
S190 Stolberg, West
H. E. SCHABLIN
Germany
This letter has been shown to the secretary of the Nomenclature Committee, British Pharmacopoeia Commission, whose
reply follows.-ED.L. SIR,-In showing commendable concern for the apparent misappropriation of classical Greek grammar in scientific nomenclature, Mr Schablin has regrettably lost sight of the technical content of the examples he cites. The chemical names eicosatetraenoic and eicosapentaenoic acids have nothing whatever to do with the concept of "twenty-four" and "twenty-five". Both names derive from eicosane, 5.
Gilmore, I. T., Cowan, 1977, 18, A952.
R.
E., Axon, A. T. R., Thompson, R. P. H. Gut,
the International Union of Pure and the parent hydrocarbon substance conApplied Chemistry taining twenty, straight-chain carbon atoms, CH3(CH2)lSCH3. When unsaturated chemical bonds are introduced, the stem of the systematic name changes to -ene, and their number, if more than one, is indicated by the appropriate multiplier, for example tetraene, pentaene. Acids are named by changing -ane or -ene to -anoic or -enoic and adding the word acid. Putting these rules together, the name eicostetraenoic acid emerges and tells the chemist that the substance in question is a C-20 acid containing four double bonds. A vowel is then interposed between thesand t for added euphony and to preserve the identity of each syllable, and perhaps a was deliberately chosen rather thani to avoid the very misinterpretation your correspondent has made. The approved name sulphasomidine makes use of the officially recommended generic stem sulpha- which tells the prescribing physician that the substance in question is an antimicrobial agent of the sulphonamide group and that appropriate precautions should be exercised. No such warning signals are borne by the terms sulphi- or sulpho-, both of which are used in non-proprietary names for substances quite unrelated to the sulphonamides. The synonym sulphisomidine is therefore by way of an exception to the rule and is recognisable as a sulphonamide only by virtue of its overall similarity to the name
the
name
assigned by to
sulphadimidine. Nomenclature Committee, British Pharmacopœia Commission, London W1M 5FT
R. B. TRIGG
DRUG-INDUCED GASTROINTESTINAL BLEEDING
SiR,—The unwary reader might extrapolate Dr Jick and Jane Porter’s calculations of the risk of gastrointestinal bleed-
ing due to drugs (which they claim to be "reasonably accurate and useful") to ordinary individuals (July 8, p. 87). I think this would be a mistake. If, as Jick and Porter suggest, aspirin given alone induces bleeding in 0-3% of hospital medical patients without known predisposing illness, then some rough calculations can be made to determine the expected frequency of such events in ordinary people, if their figures did apply to them. Annual aspirin product rates in the U.K. have been thought to be of the order of 1500 tons per year, enough for nearly 100 tablets per year for everyone in England and Wales. 100 tablets at two tablets four times a day, the usual dosage, is roughly equivalent to a fortnight’s course per head. Jick and Porter do not tell us about the length of treatment on average before bleeding, but let us suppose a fortnight is enough. Assuming most patients with a major bleed are admitted to hospital, then we would expect 0.3% of 50 million annually (for the population of England and Wales) or 150 000. Hospital Activity Analysis data show that 5000 to 7000 people are admitted annually with acute upper gastrointestinal bleeding of uncertain cause. Even if all these events were aspirin induced, which is very unlikely, the figure is still a twentieth to a thirtieth of those derived from their calculations. National aspirin consumption figures (falling) and admissions for bleeding (rising) emphasise that aspirin intake is very1 unlikely to be a prime cause of bleeding of undetermined cause. I prefer to believe, on current evidence, that aspirin can cause major bleeding (but rarely) and look for support in this view, amongst other data, to that of Levy derived from an earlier Boston collaborative drug study on outpatients.2 Levy found that light aspirin use did not appear to predispose to acute bleeding whilst heavy regular use (four or more days per week) did so, but only slightly, the calculated rate attributable being 15 per 100 000 per year. The risk may be very much higher in hospital inpatients and 1. 2.
Langman, M. J. S. Aust. N.Z. Jl Med. 1976, 6, suppl. 1, p. 22. Levy, M. New Engl.J.Med. 1976, 290, 1158.
634 if so, this would be interesting in itself; whether figures derived in hospital inpatients contain any lessons for the ordinary aspirin taker is another matter. Department of Therapeutics, City Hospital, Nottingham NG5 1PB
M. J. S. LANGMAN
nal fever (or some associated factor) in early pregnancy can inthe probability of a developmental disorder, particularly microphthalmia, in the unborn baby. Prospective studies will be required to assess the degree and nature of the risk. crease
Departments of Pediatrics and Biology, McGill University, Montreal, Quebec, Canada H3A 1BI
POSSIBLE TERATOGENICITY OF MATERNAL FEVER
SIR,-Evidence that maternal fever
teratogenic in man 12prompted us to review our family history records, collected over the past 25 years at the Montreal Children’s Hospital, for evidence of such an effect. From a random sample (every fifth in an alphabetical surname file), 479 cases were selected in which the proband had one or more of a variety of congenital malformations and/or cerebral palsy, mental retarmay be
dation or convulsive disorder, and there was a statement recorded as to whether there had been a febrile episode (55) or not (250). In 36 cases it was specified that the fever occurred in the first five months of gestation. These categories of disorder were chosen simply because they were indicators of ANOMALIES IN CHILDREN WITH A HISTORY OF MATERNAL FEVER DURING PREGNANCY
F. C. FRASER
J. SKELTON
BOTULISM IMMUNE PLASMA
(HUMAN)
interest in the therapy and prophylaxis of botulism. During the past 5 months we collected by plasmapheresis a large quantity of plasma from ten human donors hyperimmunised to five types of botulinal neurotoxins (types A, B, C, D, and E). Plasma from each of the donors has been shown in vivo to contain high levels of im-
SIR,-We share with others
an
munological specificity for all five types of neurotoxin. Collection and banking of this Botulism Immune Plasma (Human) is continuing, and the plasma will be fractionated and bottled as Botulism Immune Globulin (Human). Specific treatment of botulism in adults and children is at present directed towards neutralisation of circulating botulinal neurotoxin by polyvalent botulinum antitoxin, plus supportive care, such as maintenance of respiratory function. We are aware of only four commercial botulism antitoxin preparations available for human use: Serum Mod Botulismus, Type A, B, C, D, E, and F, Hesteserum, Statens Seruminstitut, Copenhagen ; Botulism Antitoxin Trivalent (Equine) Types A, B, and E (Connaught Medical Research Laboratories, Toronto); Botulism Antitoxin, Type E (Equine) (Connaught); and Bivalent Botulism Antitoxin (Equine Origin) Types A and B (Lederle Laboratories Division, American Cyanamid Co., Pearl River, N.Y.). However, these antitoxins prepared in horses often cause hypersensitivity reactions (anaphylaxis and serum sickness) in man. The Center for Disease Control, Atlanta, Georgia, has reported a 21% rate of adverse reactions to antitoxin of equine origin.’ The role of antitoxin in infant botulism is undetermined; administration of polyvalent antitoxin (equine) has been reported in only one patient with infant botulism.2 We read with interest the articles and editorial in your issue of June 17 concerning infant botulism and its relation to sudden-infant-death syndrome. As noted by Arnon et al.,3 confirmed cases of infant botulism have been recognised only in whose illness began sufficiently gradually to permit admission to hospital. If specific antitoxin of human origin were available, as it is for protection against tetanus, pertussis, rabies, herpes zoster, and vaccinia, there would have been an opportunity to augment supportive care with specific therapy. Indeed, a significant number of deaths from infant botulism may be preventable if antitoxin of human origin becomes available. We are unaware of any instances of hypersensitivity, as occurs with heterologous products, resulting from immune plasma or gamma-globulin of human origin. Botulism Immune Plasma (Human), and soon perhaps Botulism Immune Globulin (Human), would have the additional advantage of an extended effective half-life by remaining in the serum much longer than heterologous (horse) gamma-globulin. Turner et al. reported that stools from an infant with botulism were still positive for toxin 5 weeks after the onset of symptoms. This would imply that toxin could be entering the blood continuously over long periods in infant botulism rather
patients
possible prenatal developmental disturbance and without reference to the previous reports.’2 We recognised that the febrile episodes would be underreported, since the information was collected routinely, but if maternal fever predisposed the embryos to one or more specific disorders these should appear more frequently in the cases with a history of fever than in those without such a history. The table shows that microphthalmia shows a highly significant (P
tests, and treatment
Bowdon, Altrincham, Chesire WA 14 2AQ
R. C. JENNINGS
RESPECT FOR CLASSICS
SIR,-In your issue of July 15you speak of eicosapentaenoic and eicosatetraenoic acids. This spelling has the approval of the Merck Index, but to anyone with a classical background these are "congenital malformations". Twenty in Greek is eikosi ; the final "i" may change to "a" in front of a vowel. But twenty-four and twenty-five are eikositetra and eikosipenta, re-
spectively. The British approved name sulphasomidine (instead of sulphisomidine, as in U.S., German, French, Spanish, and other versions) is also wrong. There is no connection between this drug and soma (Greek for "body"). Sulphisomidine is the isomer of sulphadimidine. A useful analogy is sulphisoxazole which nobody would have dreamt calling sulphasoxazole. The word loci has entered English scientific and medical terminology via genetics and allergology. Locus means "place". In classical Latin its plural, however, is loca and not loci. The latter means "places in books" (e.g., references); sunt plerumque /oc!
scripitis but loca sunt regiones was drummed into the heads of our forebears. Even so, I am familiar with at least one classical quotation (Horace) where places in books, too, are referred to as loca ("loca iam recitata revolvere", "to repeat passages already declaimed"). Thus by using loca scientists may err on the safe side. By wrongly using loci they expose themselves to ridicule, at least in those countries where the classics are still "in" among the educated. When the Merck Index, the British Pharmacopoeia Commision, and medical authors display ignorance of the classical languages should not The Lancet stop them? :M
the lociinscriptis but locasuntregioneswas drummed into
Aachenstrasse 38,
S190 Stolberg, West
H. E. SCHABLIN
Germany
This letter has been shown to the secretary of the Nomenclature Committee, British Pharmacopoeia Commission, whose
reply follows.-ED.L. SIR,-In showing commendable concern for the apparent misappropriation of classical Greek grammar in scientific nomenclature, Mr Schablin has regrettably lost sight of the technical content of the examples he cites. The chemical names eicosatetraenoic and eicosapentaenoic acids have nothing whatever to do with the concept of "twenty-four" and "twenty-five". Both names derive from eicosane, 5.
Gilmore, I. T., Cowan, 1977, 18, A952.
R.
E., Axon, A. T. R., Thompson, R. P. H. Gut,
the International Union of Pure and the parent hydrocarbon substance conApplied Chemistry taining twenty, straight-chain carbon atoms, CH3(CH2)lSCH3. When unsaturated chemical bonds are introduced, the stem of the systematic name changes to -ene, and their number, if more than one, is indicated by the appropriate multiplier, for example tetraene, pentaene. Acids are named by changing -ane or -ene to -anoic or -enoic and adding the word acid. Putting these rules together, the name eicostetraenoic acid emerges and tells the chemist that the substance in question is a C-20 acid containing four double bonds. A vowel is then interposed between thesand t for added euphony and to preserve the identity of each syllable, and perhaps a was deliberately chosen rather thani to avoid the very misinterpretation your correspondent has made. The approved name sulphasomidine makes use of the officially recommended generic stem sulpha- which tells the prescribing physician that the substance in question is an antimicrobial agent of the sulphonamide group and that appropriate precautions should be exercised. No such warning signals are borne by the terms sulphi- or sulpho-, both of which are used in non-proprietary names for substances quite unrelated to the sulphonamides. The synonym sulphisomidine is therefore by way of an exception to the rule and is recognisable as a sulphonamide only by virtue of its overall similarity to the name
the
name
assigned by to
sulphadimidine. Nomenclature Committee, British Pharmacopœia Commission, London W1M 5FT
R. B. TRIGG
DRUG-INDUCED GASTROINTESTINAL BLEEDING
SiR,—The unwary reader might extrapolate Dr Jick and Jane Porter’s calculations of the risk of gastrointestinal bleed-
ing due to drugs (which they claim to be "reasonably accurate and useful") to ordinary individuals (July 8, p. 87). I think this would be a mistake. If, as Jick and Porter suggest, aspirin given alone induces bleeding in 0-3% of hospital medical patients without known predisposing illness, then some rough calculations can be made to determine the expected frequency of such events in ordinary people, if their figures did apply to them. Annual aspirin product rates in the U.K. have been thought to be of the order of 1500 tons per year, enough for nearly 100 tablets per year for everyone in England and Wales. 100 tablets at two tablets four times a day, the usual dosage, is roughly equivalent to a fortnight’s course per head. Jick and Porter do not tell us about the length of treatment on average before bleeding, but let us suppose a fortnight is enough. Assuming most patients with a major bleed are admitted to hospital, then we would expect 0.3% of 50 million annually (for the population of England and Wales) or 150 000. Hospital Activity Analysis data show that 5000 to 7000 people are admitted annually with acute upper gastrointestinal bleeding of uncertain cause. Even if all these events were aspirin induced, which is very unlikely, the figure is still a twentieth to a thirtieth of those derived from their calculations. National aspirin consumption figures (falling) and admissions for bleeding (rising) emphasise that aspirin intake is very1 unlikely to be a prime cause of bleeding of undetermined cause. I prefer to believe, on current evidence, that aspirin can cause major bleeding (but rarely) and look for support in this view, amongst other data, to that of Levy derived from an earlier Boston collaborative drug study on outpatients.2 Levy found that light aspirin use did not appear to predispose to acute bleeding whilst heavy regular use (four or more days per week) did so, but only slightly, the calculated rate attributable being 15 per 100 000 per year. The risk may be very much higher in hospital inpatients and 1. 2.
Langman, M. J. S. Aust. N.Z. Jl Med. 1976, 6, suppl. 1, p. 22. Levy, M. New Engl.J.Med. 1976, 290, 1158.
634 if so, this would be interesting in itself; whether figures derived in hospital inpatients contain any lessons for the ordinary aspirin taker is another matter. Department of Therapeutics, City Hospital, Nottingham NG5 1PB
M. J. S. LANGMAN
nal fever (or some associated factor) in early pregnancy can inthe probability of a developmental disorder, particularly microphthalmia, in the unborn baby. Prospective studies will be required to assess the degree and nature of the risk. crease
Departments of Pediatrics and Biology, McGill University, Montreal, Quebec, Canada H3A 1BI
POSSIBLE TERATOGENICITY OF MATERNAL FEVER
SIR,-Evidence that maternal fever
teratogenic in man 12prompted us to review our family history records, collected over the past 25 years at the Montreal Children’s Hospital, for evidence of such an effect. From a random sample (every fifth in an alphabetical surname file), 479 cases were selected in which the proband had one or more of a variety of congenital malformations and/or cerebral palsy, mental retarmay be
dation or convulsive disorder, and there was a statement recorded as to whether there had been a febrile episode (55) or not (250). In 36 cases it was specified that the fever occurred in the first five months of gestation. These categories of disorder were chosen simply because they were indicators of ANOMALIES IN CHILDREN WITH A HISTORY OF MATERNAL FEVER DURING PREGNANCY
F. C. FRASER
J. SKELTON
BOTULISM IMMUNE PLASMA
(HUMAN)
interest in the therapy and prophylaxis of botulism. During the past 5 months we collected by plasmapheresis a large quantity of plasma from ten human donors hyperimmunised to five types of botulinal neurotoxins (types A, B, C, D, and E). Plasma from each of the donors has been shown in vivo to contain high levels of im-
SIR,-We share with others
an
munological specificity for all five types of neurotoxin. Collection and banking of this Botulism Immune Plasma (Human) is continuing, and the plasma will be fractionated and bottled as Botulism Immune Globulin (Human). Specific treatment of botulism in adults and children is at present directed towards neutralisation of circulating botulinal neurotoxin by polyvalent botulinum antitoxin, plus supportive care, such as maintenance of respiratory function. We are aware of only four commercial botulism antitoxin preparations available for human use: Serum Mod Botulismus, Type A, B, C, D, E, and F, Hesteserum, Statens Seruminstitut, Copenhagen ; Botulism Antitoxin Trivalent (Equine) Types A, B, and E (Connaught Medical Research Laboratories, Toronto); Botulism Antitoxin, Type E (Equine) (Connaught); and Bivalent Botulism Antitoxin (Equine Origin) Types A and B (Lederle Laboratories Division, American Cyanamid Co., Pearl River, N.Y.). However, these antitoxins prepared in horses often cause hypersensitivity reactions (anaphylaxis and serum sickness) in man. The Center for Disease Control, Atlanta, Georgia, has reported a 21% rate of adverse reactions to antitoxin of equine origin.’ The role of antitoxin in infant botulism is undetermined; administration of polyvalent antitoxin (equine) has been reported in only one patient with infant botulism.2 We read with interest the articles and editorial in your issue of June 17 concerning infant botulism and its relation to sudden-infant-death syndrome. As noted by Arnon et al.,3 confirmed cases of infant botulism have been recognised only in whose illness began sufficiently gradually to permit admission to hospital. If specific antitoxin of human origin were available, as it is for protection against tetanus, pertussis, rabies, herpes zoster, and vaccinia, there would have been an opportunity to augment supportive care with specific therapy. Indeed, a significant number of deaths from infant botulism may be preventable if antitoxin of human origin becomes available. We are unaware of any instances of hypersensitivity, as occurs with heterologous products, resulting from immune plasma or gamma-globulin of human origin. Botulism Immune Plasma (Human), and soon perhaps Botulism Immune Globulin (Human), would have the additional advantage of an extended effective half-life by remaining in the serum much longer than heterologous (horse) gamma-globulin. Turner et al. reported that stools from an infant with botulism were still positive for toxin 5 weeks after the onset of symptoms. This would imply that toxin could be entering the blood continuously over long periods in infant botulism rather
patients
possible prenatal developmental disturbance and without reference to the previous reports.’2 We recognised that the febrile episodes would be underreported, since the information was collected routinely, but if maternal fever predisposed the embryos to one or more specific disorders these should appear more frequently in the cases with a history of fever than in those without such a history. The table shows that microphthalmia shows a highly significant (P
