- Email: [email protected]
α-AMYLASE INHIBITORS
1228 WAS IT SMON?
CHLOROQUINE-RESISTANT PLASMODIUM FALCIPARUM IN ZANZIBAR
SlR,—Dr Schwartz and colleagues (May 7, p 1003) report that in Zanzibar, Tanzania, "a full therapeutic regimen of chloroquine 25 mg base/kg can no longer be presumed curative". From August, 1979, to December, 1981, I worked on the island of Pemba (Zanzibar) at Chake Hospital as a member of the team of Italian doctors working on a cooperation programme with the Zanzibar government. The study by Schwartz et al confirms what we noted in Pemba from the beginning of 1980. We collected 30 cases (aged 10-22, 18 males and 12 females) in which parasitaeniia was not cleared within 7 days of treatment with the normal regimen of 25 mg base/kg given in three days. We concluded that at least an RII resistance could be presumed on both islands, thanks to the continuous migration of people from one to the other, especially during clove season, and that this implied changes in health policies. We wrote to the Zanzibar Ministry of Health and Social Welfare summarising our experience and adding that this resistance was also due to the use and misuse of chloroquine alone as antimalarial drug. We concluded that in-vitro studies were needed, that antimalarials apart from chloroquine were needed on the two islands (especially quinine), and that the concept of malaria control by antilarval methods and mass chemoprophylaxis with chloroquine was absurd.
SIR,-Professor Guy-Grand and his colleagues make a valiant attempt to defend their diagnosis of subacute myelo-optic neuropathy (SMON) (April 30, p 993). As this has happened twice before in your correspondence columns, 1,2 they are in good company. I would also refer them to other reports on SMON outside Japan.3-5 If you take 5839 patients anywhere in the world, not just in Japan, a percentage are bound to have "obvious nervousness and anxiety"; to suggest that these features are typical of SMON is clinical nonsense. This objection applies to the other less common findings they mention. They also missed my point about recovery-in Japan, within "six months after withdrawal"; in their case almost immediately. Further, their use of the term "optic neuritis" is not generally acceptable.6,7Having worked at the Salpetriere and as a titre d’etranger of the Societé Prançaise de Neurologie, I know that clinical neurology in France is second to none. Why did Guy-Grand et al not take advantage of this? The shades of Baron Dupuytren, whose statue stands in the grounds of their beautiful old hospital, must be stirring. Department of Neurology, Charing Cross Hospital, Fulham Palace Road, London W6 8RF
F. CLIFFORD ROSE
&agr;-AMYLASE INHIBITORS
L. Spallanzeni Hospital for Infectious Diseases,
LORENZO SAVIOLI
Rome, Italy
SIR,-The report by Professor Meyer and his colleagues (April 23, 934) on the effects of the a-amylase inhibitor HOE 467 on the blood glucose response to a standard starch meal, raises several important points. Their results show a significant dose-related reduction in the maximal blood glucose response caused by the p
PROGUANIL FOR MALARIA PROPHYLAXIS
SIR,-We agree with Dr Rombo and his colleagues (April 30, p 997) that in the present confusion about drugs to be used for prophylaxis in areas where Plasmodium falciparum shows multiple resistance proguanil should be reconsidered. However, their results may give a false sense of optimism. Of 50 parasitaemic children treated daily with 100 mg proguanil 39 had "negative blood smears" at the end of a week. Presumably thick blood smears were examined, although this is not specified. In semi-immune children parasitaemia often disappears spontaneously without treatmentespecially if it is asymptomatic, as in Rombo’s series. An untreated comparison group would have clarified this point. If thick blood find it difficult to believe that after this parasitaemias were recorded of less than 1 per 200 leucocytes, a low criterion of cure. Although these findings on the sensitivity of P falciparum to proguanil were made in semi-immunes given large doses, we would nevertheless reiterate that there seems to be a case for doing some properly controlled trials of proguanil, both alone and in combination with chloroquine, for prophylaxis. smears were
used,
we
treatment no
Ross Institute of Tropical Hygiene, London School of Hygiene and Tropical Medicine, London WC1E 7HT
M. J. COLBOURNE C. C. DRAPER
CLASSICAL CHOLERA
SIR,-The letter from Dr Cook and colleagues (April 879) contains data from this centre which contradict our findings. Cook el al state that between 1973 and September, 1982, over 5000 Vibrio cholerae 0 group 1 were examined in Dacca and only 5 classical strains were cultured, from 5 cases on one day in October, 1979. In fact, for 22 702 isolates of V cholerae 01from patients and environmental samples during the above period, there were besides those 5 classical isolates in 1979, 1 other isolation in 1979,3 in 1980, and 2 in 1981.
16, p
Disease Transmission Programme and Microbiology Branch, International Centre for Diarrhoeal Disease Research, Dacca 2, Bangladesh
1. Samadi
AZIZ R. SAMADI M. I. HUQ
AR, Huq MI, Shahid N, Khan MU, Eusof A, Rahman ASMM, Yunus M,
Faruque Lancet
ASG. Classical Vibrio cholerae
1983; i: 805-07.
biotype displaces
El Tor in
Bangladesh.
They comment that "inhibition of starch absorption incomplete" and refer to unpublished evidence that doses ... "higher totally inhibit starch absorption". Unfortunately Meyer et al fail to make the fundamental distinction between inhibition of amylase activity in the intestinal lumen and malabsorption of carbohydrate. Both result in flattening of the postprandial blood glucose curve and of the insulin response. Partial inhibition of amylase activity reduces the rate of digestion, and thus absorption, of ingested starch. In the healthy gut most absorption of carbohydrate occurs in the proximal 70 cm ofjejunum and pancreatic (and salivary) amylase are present in excess, so there is considerable absorptive and catalytic reserve. Only a small rise in blood glucose with a proportionally reduced insulin release occurs with slow uptake of glucose from starch hydrolysis, even though all the starch is eventually absorbed in the small intestine. When starch absorption is incomplete with blood glucose response is also reduced The malabsorbed carbohydrate is lost to bacterial fermentation in the colon resulting in flatulence, distension, and diarrhoea. On the evidence of flatulence reported by only a few of Meyer’s subjects, there was no appreciable malabsorption of starch at any of the inhibitor dosages used in these studies, despite the reduced blood glucose rises. Although Meyer et al, state that their findings do not support the view of Dr Garrow and colleagues (Jan 1/8, p 60) and a Lancet editorial (March 12, p 569), which suggested that absorption of starch calories in the presence of inhibitors is slowed but complete, their study presents enzyme inhibitor. was
evidence to the contrary. There is convincing evidence for the mechanism of modification of starch absorption from studies of acarbose, a no
1. Rose FC. Non-SMON. Lancet 1971; i: 37. 2. Rose FC. SMON in Singapore? Lancet 1973; ii: 40. 3. Rose FC. On the diagnosis of subacute myelo-optic neuropathy (SMON) outside Japan In: Epidemiological issues in reported drug-induced illnesses: SMON and other examples. Gent M, Shigematsu I, eds. Hamilton, Ontario; McMaster University Library Press, 1978: 271-82. 4. Baumgartner G, Gawel MJ, Kaeser HE, et al. Neurotoxicity of halogenated hydroxyquinolines: Clinical analysis of cases reported outside Japan. Neurol Neurosurg Psychiatry 1979; 42: 1073-83. 5. Thomas PK, Baumgartner G, Gawel MJ, et al. Neurotoxicity of halogenated hydroxyquinolines: an analysis of non-Japanese cases 12th World Congress of Neurology (Kyoto, Japan). Amsterdam: Excerpta Medica, 1981. 6. Rose FC Aetiology of optic neuritis. Br Med J 1975; ii: 703. 7. Perkins GD, Rose FC. Optic neuritis and its differential diagnosis. Oxford: Oxford University Press, 1974.
1229 which is a potent reversible, competitive inhibitor both of a-amylase and of a-glycoside hydrolases. Acarbose 200 mg taken immediately before a test meal of 50 g starch flattened the glycaemic response by 80-t7% and delayed its peak rise.1 Serial measurements of breath hydrogen, as an index of malabsorption, showed no change and the subjects reported no symptoms suggestive of malabsorption. There was a significant reduction in insulin and gastric inhibitory peptide responses2and a significant rise in the enteroglucagon response2,3 after acarbose compared with placebo given with a test breakfast. Motilin release is4 also significantly increased by acarbose, independent of the dose.4 This evidence indicates, firstly, that this amylase inhibitor can reduce the blood glucose response markedly without causing malabsorption of carbohydrate. Secondly, from the gut hormone responses it is clear that the slowed digestive and absorptive activity following a meal with an amylase inhibitor occurs further down the small intestine. Thus absorption is spread both in time and space but is complete, though the rise in blood glucose may be very small. Meyer et al, raise the important point that the timing and presentation of the inhibitor may be critical. In Garrow’s study the inhibitors were given 10 min before the starch meal and their results showed no difference in carbohydrate oxidation rate (n 5) or blood glucose and insulin responses (n = 2). Bo-Linn et al, gave two thirds of their inhibitors at the start of the meal and the remaining third halfway through the meal and showed no difference in excretion of faecal calories.5 Most of these inhibitors are polypeptides which may well be inactivated by gastric acid and pepsin. Equally, if given before the meal, they may pass into the small intestine ahead of the amylase released by the test meal and so not inhibit the amylase involved in digestion of the meal. By mixing their inhibitor with fat, Meyer et al, have obviously protected it from inactivation and delivered it effectively to its site of action intimately mixed with ’the
pseudotetrasaccharide
=
carbohydrate. These inhibitors of intestinal enzymes are of considerable scientific interest but their therapeutic role remains to be evaluated fully. The attenuated blood glucose response which they produce may have some value in management of diabetes but the accumulated evidence suggests that they have no place in the treatment of obesity. Indeed a state of iatrogenically induced malabsorption, which is the only way caloric uptake can be reduced, could have hazardous long term consequences. Department of Gastroenterology and Nutrition, Central Middlesex Hospital, London NW10 7NS
RODNEY H. TAYLOR HELEN M. BARKER
ANTIGENIC CHANGES IN MOUSE-ADAPTED INFLUENZA VIRUS STRAINS
SIR,-Many antigenic variants of influenza virus circulate in human and other animal populations. A factor contributing to this variation in viral surface antigens is the selective pressure from the immune human population. The introduction of human virus strain into an animal population leads to a prolonged conservation of the antigenic specificity of the viral haemagglutinin.b However, we do not know whether adaptation to a new host may be in itself a factor affecting the immunological properties of haemagglutinin. To study the problem experimentally we have adapted two human influenza strains of HI subtype (A/USSR/90/77 and A/USSR/50/79) to mice by consecutive passages with the use of intranasal inoculation: the strains acquired an ability to kill mice at 1. Jenkins DJA, Taylor RH, Goff, et al. Scope and specificity of acarbose in slowing carbohydrate absorption in man. Diabetes 1981; 30: 951-54. 2. Taylor RH, Jenkins DJA, Goff DV, et al. Gut hormone response to carbohydrate with acarbose and guar. In: Creutzfeldt W, ed. Proceedings of 1st International Symposium on Acarbose. Amsterdam; Excerpta Medica, 1982: 206-09. 3. Taylor RH, Jenkins DJA, Goff DV, Nineham R, Bloom SR, Sarson D. Enteroglucagon release stimulated by carbohydrate malabsorption. Gut 1980; 21: A449. 4 Uttenthal LO, Ukponmwan OO, Ghatei MA, Bloom SR. Acute and short term effects of intestinal alpha-glucosidase inhibition on gut hormone responses in man. Gut 1983; 24: A461-62. 5. Bo-Linn GW, Santa Ana CA, Morawski SG, Fordtran JS. Starch blockers: Their effect on calorie absorption from a high starch meal. N Engl J Med 1982, 307: 1413-36. 6. Kilbourne ED, ed. Influenza viruses and influenza. New York: Academic Press, 1975: 483.
REACTIVITY OF MONOCLONAL ANTIBODIES WITH MOUSE-ADAPTED INFLUENZA VIRUS STRAINS
the l lth and 8th passage, respectively. The original strains, after isolation from man, underwent three passages in chick embryos. The original strains and the mouse-adapted variants were tested by haemagglutination-inhibition (HAI) against a panel of seven antiHIA monoclonal antibodies raised against a closely related strain (A/Brazil/11/78). The antibodies were kindly donated by Dr J. J. Skehel and Dr A. Douglas (National Institute for Medical
Research, London). The results
(table) reveal a characteristic change in the reactivity
pattern in the course of the adaptation, virtually identical for both virus strains. The change is not a result of host-induced since both original and mouse-adapted variants were in chick embryos and the virus-containing allantoic fluid was used as antigen in the HAI test. The uniformity of the change in both strains suggests that it is not a result of a chance variation. Rather, ’it reflects the change in the receptor zone of the haemagglutinin associated with the adaptation to a new host
modification,
propagated
species.
Host-species-related antigenic groups within subtypes have been reported for avian influenza by H. Fukushi and colleagues (Arch Virol 1982; 72: 217). However, our data are the first, to our knowledge, to register a change in the immunological specificity of influenza haemagglutinin during the crossing of an interspecies barrier.
DI Ivanovsky Institute of Virology, USSR Academy of Medical Sciences, Moscow 123098, USSR
A. K. GITELMAN N. V. KAVERIN I. G. KHARITONENKOV I. A. RUDNEVA V. M. ZHDANOV
CARBAMAZEPINE-INDUCED NON-HEREDITARY ACUTE PORPHYRIA
SiR,—I found Dr Yeung Laiwah and colleagues’ report (April 9, p 790) of a case of non-hereditary acute porphyria induced by combined treatment with carbamazepine and several other antiepileptic drugs interesting but unconvincing. The clinical and biochemical evidence provided does suggest an acute attack of porphyria, but the conclusion that this was a chemically induced syndrome in the absence of genetic predisposition is not well founded. These workers
rest their case on two observations-erythrocyte uroporphyrinogen i synthetase activity rose to normal after withdrawal of carbamazepine therapy, and there was no family history. However, there is a significant overlap in the range of erythrocyte uroporphyrinogen I synthetase between patients with acute intermittent porphyria (AIP) and normal subjects, so a
normal result obtained after withdrawal of carbamazepine does not rule out AIP. How thorough was the family history? The father and mother had normal erythrocyte uroporphyrinogen i synthetase activity, but what about other relatives? If the family study was not exhaustive it cannot be regarded as conclusive. 1. Sassa S, Granick S, Bickers DR, Bradlow HL, Kappas A. A microassay for uroporphyrinogen I synthase, one of three abnormal enzyme activities in acute intermittent prophyria, and its application to the study of the genetics of this disease. Proc Natl Acad Sci USA 1974; 71: 732-36.
CHLOROQUINE-RESISTANT PLASMODIUM FALCIPARUM IN ZANZIBAR
SlR,—Dr Schwartz and colleagues (May 7, p 1003) report that in Zanzibar, Tanzania, "a full therapeutic regimen of chloroquine 25 mg base/kg can no longer be presumed curative". From August, 1979, to December, 1981, I worked on the island of Pemba (Zanzibar) at Chake Hospital as a member of the team of Italian doctors working on a cooperation programme with the Zanzibar government. The study by Schwartz et al confirms what we noted in Pemba from the beginning of 1980. We collected 30 cases (aged 10-22, 18 males and 12 females) in which parasitaeniia was not cleared within 7 days of treatment with the normal regimen of 25 mg base/kg given in three days. We concluded that at least an RII resistance could be presumed on both islands, thanks to the continuous migration of people from one to the other, especially during clove season, and that this implied changes in health policies. We wrote to the Zanzibar Ministry of Health and Social Welfare summarising our experience and adding that this resistance was also due to the use and misuse of chloroquine alone as antimalarial drug. We concluded that in-vitro studies were needed, that antimalarials apart from chloroquine were needed on the two islands (especially quinine), and that the concept of malaria control by antilarval methods and mass chemoprophylaxis with chloroquine was absurd.
SIR,-Professor Guy-Grand and his colleagues make a valiant attempt to defend their diagnosis of subacute myelo-optic neuropathy (SMON) (April 30, p 993). As this has happened twice before in your correspondence columns, 1,2 they are in good company. I would also refer them to other reports on SMON outside Japan.3-5 If you take 5839 patients anywhere in the world, not just in Japan, a percentage are bound to have "obvious nervousness and anxiety"; to suggest that these features are typical of SMON is clinical nonsense. This objection applies to the other less common findings they mention. They also missed my point about recovery-in Japan, within "six months after withdrawal"; in their case almost immediately. Further, their use of the term "optic neuritis" is not generally acceptable.6,7Having worked at the Salpetriere and as a titre d’etranger of the Societé Prançaise de Neurologie, I know that clinical neurology in France is second to none. Why did Guy-Grand et al not take advantage of this? The shades of Baron Dupuytren, whose statue stands in the grounds of their beautiful old hospital, must be stirring. Department of Neurology, Charing Cross Hospital, Fulham Palace Road, London W6 8RF
F. CLIFFORD ROSE
&agr;-AMYLASE INHIBITORS
L. Spallanzeni Hospital for Infectious Diseases,
LORENZO SAVIOLI
Rome, Italy
SIR,-The report by Professor Meyer and his colleagues (April 23, 934) on the effects of the a-amylase inhibitor HOE 467 on the blood glucose response to a standard starch meal, raises several important points. Their results show a significant dose-related reduction in the maximal blood glucose response caused by the p
PROGUANIL FOR MALARIA PROPHYLAXIS
SIR,-We agree with Dr Rombo and his colleagues (April 30, p 997) that in the present confusion about drugs to be used for prophylaxis in areas where Plasmodium falciparum shows multiple resistance proguanil should be reconsidered. However, their results may give a false sense of optimism. Of 50 parasitaemic children treated daily with 100 mg proguanil 39 had "negative blood smears" at the end of a week. Presumably thick blood smears were examined, although this is not specified. In semi-immune children parasitaemia often disappears spontaneously without treatmentespecially if it is asymptomatic, as in Rombo’s series. An untreated comparison group would have clarified this point. If thick blood find it difficult to believe that after this parasitaemias were recorded of less than 1 per 200 leucocytes, a low criterion of cure. Although these findings on the sensitivity of P falciparum to proguanil were made in semi-immunes given large doses, we would nevertheless reiterate that there seems to be a case for doing some properly controlled trials of proguanil, both alone and in combination with chloroquine, for prophylaxis. smears were
used,
we
treatment no
Ross Institute of Tropical Hygiene, London School of Hygiene and Tropical Medicine, London WC1E 7HT
M. J. COLBOURNE C. C. DRAPER
CLASSICAL CHOLERA
SIR,-The letter from Dr Cook and colleagues (April 879) contains data from this centre which contradict our findings. Cook el al state that between 1973 and September, 1982, over 5000 Vibrio cholerae 0 group 1 were examined in Dacca and only 5 classical strains were cultured, from 5 cases on one day in October, 1979. In fact, for 22 702 isolates of V cholerae 01from patients and environmental samples during the above period, there were besides those 5 classical isolates in 1979, 1 other isolation in 1979,3 in 1980, and 2 in 1981.
16, p
Disease Transmission Programme and Microbiology Branch, International Centre for Diarrhoeal Disease Research, Dacca 2, Bangladesh
1. Samadi
AZIZ R. SAMADI M. I. HUQ
AR, Huq MI, Shahid N, Khan MU, Eusof A, Rahman ASMM, Yunus M,
Faruque Lancet
ASG. Classical Vibrio cholerae
1983; i: 805-07.
biotype displaces
El Tor in
Bangladesh.
They comment that "inhibition of starch absorption incomplete" and refer to unpublished evidence that doses ... "higher totally inhibit starch absorption". Unfortunately Meyer et al fail to make the fundamental distinction between inhibition of amylase activity in the intestinal lumen and malabsorption of carbohydrate. Both result in flattening of the postprandial blood glucose curve and of the insulin response. Partial inhibition of amylase activity reduces the rate of digestion, and thus absorption, of ingested starch. In the healthy gut most absorption of carbohydrate occurs in the proximal 70 cm ofjejunum and pancreatic (and salivary) amylase are present in excess, so there is considerable absorptive and catalytic reserve. Only a small rise in blood glucose with a proportionally reduced insulin release occurs with slow uptake of glucose from starch hydrolysis, even though all the starch is eventually absorbed in the small intestine. When starch absorption is incomplete with blood glucose response is also reduced The malabsorbed carbohydrate is lost to bacterial fermentation in the colon resulting in flatulence, distension, and diarrhoea. On the evidence of flatulence reported by only a few of Meyer’s subjects, there was no appreciable malabsorption of starch at any of the inhibitor dosages used in these studies, despite the reduced blood glucose rises. Although Meyer et al, state that their findings do not support the view of Dr Garrow and colleagues (Jan 1/8, p 60) and a Lancet editorial (March 12, p 569), which suggested that absorption of starch calories in the presence of inhibitors is slowed but complete, their study presents enzyme inhibitor. was
evidence to the contrary. There is convincing evidence for the mechanism of modification of starch absorption from studies of acarbose, a no
1. Rose FC. Non-SMON. Lancet 1971; i: 37. 2. Rose FC. SMON in Singapore? Lancet 1973; ii: 40. 3. Rose FC. On the diagnosis of subacute myelo-optic neuropathy (SMON) outside Japan In: Epidemiological issues in reported drug-induced illnesses: SMON and other examples. Gent M, Shigematsu I, eds. Hamilton, Ontario; McMaster University Library Press, 1978: 271-82. 4. Baumgartner G, Gawel MJ, Kaeser HE, et al. Neurotoxicity of halogenated hydroxyquinolines: Clinical analysis of cases reported outside Japan. Neurol Neurosurg Psychiatry 1979; 42: 1073-83. 5. Thomas PK, Baumgartner G, Gawel MJ, et al. Neurotoxicity of halogenated hydroxyquinolines: an analysis of non-Japanese cases 12th World Congress of Neurology (Kyoto, Japan). Amsterdam: Excerpta Medica, 1981. 6. Rose FC Aetiology of optic neuritis. Br Med J 1975; ii: 703. 7. Perkins GD, Rose FC. Optic neuritis and its differential diagnosis. Oxford: Oxford University Press, 1974.
1229 which is a potent reversible, competitive inhibitor both of a-amylase and of a-glycoside hydrolases. Acarbose 200 mg taken immediately before a test meal of 50 g starch flattened the glycaemic response by 80-t7% and delayed its peak rise.1 Serial measurements of breath hydrogen, as an index of malabsorption, showed no change and the subjects reported no symptoms suggestive of malabsorption. There was a significant reduction in insulin and gastric inhibitory peptide responses2and a significant rise in the enteroglucagon response2,3 after acarbose compared with placebo given with a test breakfast. Motilin release is4 also significantly increased by acarbose, independent of the dose.4 This evidence indicates, firstly, that this amylase inhibitor can reduce the blood glucose response markedly without causing malabsorption of carbohydrate. Secondly, from the gut hormone responses it is clear that the slowed digestive and absorptive activity following a meal with an amylase inhibitor occurs further down the small intestine. Thus absorption is spread both in time and space but is complete, though the rise in blood glucose may be very small. Meyer et al, raise the important point that the timing and presentation of the inhibitor may be critical. In Garrow’s study the inhibitors were given 10 min before the starch meal and their results showed no difference in carbohydrate oxidation rate (n 5) or blood glucose and insulin responses (n = 2). Bo-Linn et al, gave two thirds of their inhibitors at the start of the meal and the remaining third halfway through the meal and showed no difference in excretion of faecal calories.5 Most of these inhibitors are polypeptides which may well be inactivated by gastric acid and pepsin. Equally, if given before the meal, they may pass into the small intestine ahead of the amylase released by the test meal and so not inhibit the amylase involved in digestion of the meal. By mixing their inhibitor with fat, Meyer et al, have obviously protected it from inactivation and delivered it effectively to its site of action intimately mixed with ’the
pseudotetrasaccharide
=
carbohydrate. These inhibitors of intestinal enzymes are of considerable scientific interest but their therapeutic role remains to be evaluated fully. The attenuated blood glucose response which they produce may have some value in management of diabetes but the accumulated evidence suggests that they have no place in the treatment of obesity. Indeed a state of iatrogenically induced malabsorption, which is the only way caloric uptake can be reduced, could have hazardous long term consequences. Department of Gastroenterology and Nutrition, Central Middlesex Hospital, London NW10 7NS
RODNEY H. TAYLOR HELEN M. BARKER
ANTIGENIC CHANGES IN MOUSE-ADAPTED INFLUENZA VIRUS STRAINS
SIR,-Many antigenic variants of influenza virus circulate in human and other animal populations. A factor contributing to this variation in viral surface antigens is the selective pressure from the immune human population. The introduction of human virus strain into an animal population leads to a prolonged conservation of the antigenic specificity of the viral haemagglutinin.b However, we do not know whether adaptation to a new host may be in itself a factor affecting the immunological properties of haemagglutinin. To study the problem experimentally we have adapted two human influenza strains of HI subtype (A/USSR/90/77 and A/USSR/50/79) to mice by consecutive passages with the use of intranasal inoculation: the strains acquired an ability to kill mice at 1. Jenkins DJA, Taylor RH, Goff, et al. Scope and specificity of acarbose in slowing carbohydrate absorption in man. Diabetes 1981; 30: 951-54. 2. Taylor RH, Jenkins DJA, Goff DV, et al. Gut hormone response to carbohydrate with acarbose and guar. In: Creutzfeldt W, ed. Proceedings of 1st International Symposium on Acarbose. Amsterdam; Excerpta Medica, 1982: 206-09. 3. Taylor RH, Jenkins DJA, Goff DV, Nineham R, Bloom SR, Sarson D. Enteroglucagon release stimulated by carbohydrate malabsorption. Gut 1980; 21: A449. 4 Uttenthal LO, Ukponmwan OO, Ghatei MA, Bloom SR. Acute and short term effects of intestinal alpha-glucosidase inhibition on gut hormone responses in man. Gut 1983; 24: A461-62. 5. Bo-Linn GW, Santa Ana CA, Morawski SG, Fordtran JS. Starch blockers: Their effect on calorie absorption from a high starch meal. N Engl J Med 1982, 307: 1413-36. 6. Kilbourne ED, ed. Influenza viruses and influenza. New York: Academic Press, 1975: 483.
REACTIVITY OF MONOCLONAL ANTIBODIES WITH MOUSE-ADAPTED INFLUENZA VIRUS STRAINS
the l lth and 8th passage, respectively. The original strains, after isolation from man, underwent three passages in chick embryos. The original strains and the mouse-adapted variants were tested by haemagglutination-inhibition (HAI) against a panel of seven antiHIA monoclonal antibodies raised against a closely related strain (A/Brazil/11/78). The antibodies were kindly donated by Dr J. J. Skehel and Dr A. Douglas (National Institute for Medical
Research, London). The results
(table) reveal a characteristic change in the reactivity
pattern in the course of the adaptation, virtually identical for both virus strains. The change is not a result of host-induced since both original and mouse-adapted variants were in chick embryos and the virus-containing allantoic fluid was used as antigen in the HAI test. The uniformity of the change in both strains suggests that it is not a result of a chance variation. Rather, ’it reflects the change in the receptor zone of the haemagglutinin associated with the adaptation to a new host
modification,
propagated
species.
Host-species-related antigenic groups within subtypes have been reported for avian influenza by H. Fukushi and colleagues (Arch Virol 1982; 72: 217). However, our data are the first, to our knowledge, to register a change in the immunological specificity of influenza haemagglutinin during the crossing of an interspecies barrier.
DI Ivanovsky Institute of Virology, USSR Academy of Medical Sciences, Moscow 123098, USSR
A. K. GITELMAN N. V. KAVERIN I. G. KHARITONENKOV I. A. RUDNEVA V. M. ZHDANOV
CARBAMAZEPINE-INDUCED NON-HEREDITARY ACUTE PORPHYRIA
SiR,—I found Dr Yeung Laiwah and colleagues’ report (April 9, p 790) of a case of non-hereditary acute porphyria induced by combined treatment with carbamazepine and several other antiepileptic drugs interesting but unconvincing. The clinical and biochemical evidence provided does suggest an acute attack of porphyria, but the conclusion that this was a chemically induced syndrome in the absence of genetic predisposition is not well founded. These workers
rest their case on two observations-erythrocyte uroporphyrinogen i synthetase activity rose to normal after withdrawal of carbamazepine therapy, and there was no family history. However, there is a significant overlap in the range of erythrocyte uroporphyrinogen I synthetase between patients with acute intermittent porphyria (AIP) and normal subjects, so a
normal result obtained after withdrawal of carbamazepine does not rule out AIP. How thorough was the family history? The father and mother had normal erythrocyte uroporphyrinogen i synthetase activity, but what about other relatives? If the family study was not exhaustive it cannot be regarded as conclusive. 1. Sassa S, Granick S, Bickers DR, Bradlow HL, Kappas A. A microassay for uroporphyrinogen I synthase, one of three abnormal enzyme activities in acute intermittent prophyria, and its application to the study of the genetics of this disease. Proc Natl Acad Sci USA 1974; 71: 732-36.