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TREATMENT OF ALLERGY TO COW'S MILK
337 of this apparent rise in the incidence of the disease in
Turkey. In North America, the number of reported cases in Canada increased about fourfold between 1967 and 1973, but the most recent published figures for the first five months of 1974 suggest that the incidence has now fallen 1; in the U.S.A. there has been no recent increase in meningococcal infections-indeed the number has been falling since 1969.õ The incidence of meningococcal meningitis has undoubtedly risen considerably in Brazil however,6.7 but from nowhere else in South America or in Oceania have I found any reported evidence that the disease is increasing in incidence at present. That the incidence of meningococcal meningitis has been rising in England and Wales since about 1967 there can be little doubt. This is shown both by the Registrar General’s notifications and by the laboratory-proven cases reported to the Public Health Laboratory Service; the estimated figures from the Hospital In-patient Inquiry, although at present only available up to 1972, lend support to this. Moreover, since the same sources show that the total number of cases of meningitis due to other bacteria has not been rising in parallel, it is likely that the reported increase in meningococcal meningitis in this country is real. Information from the Communicable Disease (Scotland) Unit in Glasgowsuggests not only that a similar increase in the incidence of the disease is occurring in Scotland but that the number of cases of meningococcal septicaemia has also risen. It is interesting to relate the present period of increased incidence with earlier periods. The figure shows the annual number of Registrar General’s notifications since 1929. Apart from the rise during the 1939-45 war, peaks of incidence have occurred in the early 1930s, perhaps in the early 1950s, and now in the 1970s. The numbers being notified at present have not yet proceeded much beyond the levels seen in the 1930s or 1940s. The ratio of deaths to notified cases, which has remained relatively static at between 20% and 30% for about 30 years, exaggerates the true death-rate because deaths are compulsorily certificated whereas notifications are incomplete. However, if it is assumed that the completeness of notifications has been about the same throughout this period, it is of some interest that the ratio has not altered very much since the introduction of chemotherapy in the late 1930s. I am grateful to Dr P. M. Lambert, senior medical statistician, Office of Population Censuses and Surveys, London, for his help and advice in the interpretation of some of the statistics. Central Public Health Laboratory, Colindale Avenue, London NW9 5HT.
N. D. NOAH.
DISINFECTANTS AND SMALLPOX SiR,-The Memorandum on the Control of Smallpox 8 recommends the use of a " white fluid " for terminal disinfection. Such fluids are not now commonly used in hospitals, having largely been replaced by clear soluble
phenolic fluids.
asked about be used instead of the white fluid
Questions
are
now
being
whether such fluids can recommended. The answer must be a regretful " no ". It would not be difficult to test the newer disinfectants against a suspension of a poxvirus, such as vaccinia, and it is probable that many would be found to be effective. However, an 5. U.S. Centre for Disease Control, Morbidity and Mortality. Annual Supplement 1973, 22, no. 53. 6. Wkly epidem. Rec. 1974, 49, 168, 381. 7. Communicable Diseases (Scotland) 1974, 74/44; and personal communication. 8. Ministry of Health and Scottish Home and Health Department. H.M. Stationery Office, 1964.
environment contaminated by a case of smallpox may contain crusts which are hard, dry, fragments of inspissated secretions containing the virus, and to be effective a With the steady disinfectant must penetrate these. reduction of smallpox throughout the world, crusts are exceedingly difficult to obtain, and no acceptable experimental model exists. The only well-defined disinfectant known to have been tested against such crusts is a white fluid to B.S. 2462: 1961 recommendation (Group WF or WG) at a concentration of 2-5%. Efforts are being made to obtain crusts from Asia and if these are successful it is hoped that tests will be made on them, in a laboratory competent to do so. Meanwhile, the recommendations for white fluids must stand. If difficulty’is experienced in obtaining them, the British Disinfectant Manufacturers’ Association, Alembic House, 93 Albert Embankment, London SE1, will advise. Public Health Laboratory Service Board, Colindale Hospital, Colindale Avenue, London NW9 5EQ.
J. C. KELSEY.
TREATMENT OF ALLERGY TO COW’S MILK SiR)—We were very interested in the paper (Jan. 18, p. 136) on cow’s milk allergy by Dr Shiner and her colleagues. Since we have been looking at the duodenal juice as a diagnostic test and have treated two babies with disodium cromoglycate, our experience may be of further interest. The second of twins, born on Feb. 5, 1974, weighed 3170 g. at birth. Symptoms started within a few days of birth: diarrhoea, vomiting, and poor weight gain. Investigation at the age of seven weeks excluded cystic fibrosis and various metabolic diseases. Jejunal biopsy showed broad villi and non-specific abnormalities. Enzyme studies were normal. Gel-precipitin test for milk antibodies were positive at 1/2 dilution. Duodenal juice was examined for precipitating antibodies to cow’s milk. A double diffusion (Ouchterlony) technique on commercial plain agar plates was used. The method comprised two separate diffusions on the same plate. (a) Neat cow’s milk was placed in the centre well of one set and doubling dilutions of duodenal juice (neat 1 : 16) placed in the outer wells. (b) Neat duodenal juice placed in the centre well of another set and doubling dilutions of cow’s milk (neat 1 : 16) placed in the outer wells. The plates were then incubated overnight at 4C and any precipitation arcs noted. Positive reactions were obtained to cow’s milk. Further tests were done on 8 duodenal juices and the following:Nutramigen’, ’ S.M.A.’, ’Ostermilk ’,Cow & Gate’, ’Velactin ’, and saline. The eight duodenal juices were negative to all, but the patient’s juice was negative only to saline and velactin. Further tests are in progress against &bgr;-Iactoglobulin and IgE antibodies against cow’s milk in the juice. The baby was started on cow’s-milk-free formula with complete cessation of symptoms within 48 hours and satisfactory progress. Reintroduction of cow’s milk at the age of six months resulted in diarrhoea and vomiting. At this stage disodium cromoglycate 50 mg. 4 times a day (in chloroform water) was given. Cow’s milk was reintroduced five days later. Since then the baby has been able to tolerate normal cow’s milk in adequate amounts.
A boy born on March 20 weighed 3120 g. He was discharged home after 48 hours. Diarrhoea and vomiting started from about that time. Various cow’s milk changes were made with poor general progress. At the age of six months he was wasted and not thriving satisfactorily. Jejunal biopsy showed minor, nonspecific abnormalities, and enzyme studies were normal in maltase, lactase, and sucrase activity. Duodenal-juice studies were positive to cow’s milk (see above). Withdrawal of cow’s milk resulted in cessation of symptoms. On challenge with cow’s milk, abdominal distension, vomiting, and diarrhoea occurred. For the first 3 months he was treated with cow’smilk-free formula and then was started on disodium cromoglycate 50 mg. 4 times daily. Cow’s milk was reintroduced five days later and since then he has been able to tolerate a perfectly normal diet. Tv’o months later disodium cromoglycate was reduced to
338 twice daily, but the symptoms returned. He remains well 4 doses daily and is able to tolerate cow’s milk.
on
We are grateful to Dr Clifford Clark, of Fison Laboratories, Loughborough, for the supply of disodium cromoglycate. J. A. KUZEMKO Peterborough District Hospital,
Peterborough PE3 6DA.
K. R. SIMPSON.
GASTRIC ACID AND DUODENOGASTRIC REFLUX Fischer 1 demonstrated that deterSIR,-Wesdorp and mination of basal acid output (B.A.o.) in relation to plasmagastrin (P.G.) does not distinguish between a major duodenal contribution to basal circulating gastrin and an autonomous release of gastrin, or alternatively that B.A.o. neither determines nor is determined by P.G. Lam and Sircus2 commented on the lack of a correlation between B.A.o. and P.G., pointing out the importance of eliminating the extraneous and variable influence of vagal stimulation, especially in studies during " basal conditions ". Duodenogastric reflux, which apparently influences B.A.o., is often overlooked. We determined the bile-acid content of the gastric fluid from several patients undergoing a pentagastrin test. The samples were originally sent to us for titration of acid and were obtained by continuous aspiration during the first hour after emptying of the overnight gastric contents. This portion is equivalent to2 that in which the B.A.O. was measured in other studies.l,2 The patients had a long history of gastritisor duodenal or gastric ulcer, verified by X-ray and/or gastroscopy. Bile acids were determined by using 3ac-hydroxy-steroid: N.A.D.oxidoreductase (’ Sterognost-3o:,’ Nyegaard). This method measures all bile acids containing a 3
2990 (Lmol and that for bile acids was 120 jjunol. (Samples with a bile-acid content of less than 10 jamol were excluded.) When the seven samples with acid contents above 5000 jjunol are excluded, the mean levels of acid and bile acid If the estimate were 1230 and 103 jamol, respectively. of the basic contents of duodenogastric reflux above is correct, about 200-350 (Lmol of gastric acid has been neutralised before titration. In most of our cases there was duodenogastric reflux under basal conditions. Admittedly, in some cases the contribution of endogenous
base is small in relation to the production of gastric acid, but in most cases the amount of base introduced by reflux is of the same order of magnitude as that of the titrated acid (see figure). A truncated mean, in which extremes of both components at both ends are excluded, indicates that the amounts of acid titrated should be increased by an average of 20-28% to compensate for endogenous neutralisation. Patients with gastric ulcer have an increased reflux of bile into the stomach. In view of this it is not surprising that Wesdorp and Fischer found a lower mean B.A.o. in patients with gastric ulcer as compared with those who had duodenal ulcer. Read and Grechfound that smoking initiated appreciable duodenogastric reflux. Unless corrections are made for duodenogastric reflux, it is doubtful whether conclusions based on acid output in the stomach, as determined by titration, are valid. Department of Clinical Chemistry, Karolinska Institutet
at
Serafimerlasarettet, Stockholm, Sweden.
ANDERS KALLNER.
Rhodes, J., Barrodo, D. E., Phillips, S. F., Rodelstad, R. A., Hofman, A. F. Gastroenterology, 1969, 57, 241. 7. Read, N. W., Grech, P. Br. med. J. 1973, iii, 313. 6.
Turkey. In North America, the number of reported cases in Canada increased about fourfold between 1967 and 1973, but the most recent published figures for the first five months of 1974 suggest that the incidence has now fallen 1; in the U.S.A. there has been no recent increase in meningococcal infections-indeed the number has been falling since 1969.õ The incidence of meningococcal meningitis has undoubtedly risen considerably in Brazil however,6.7 but from nowhere else in South America or in Oceania have I found any reported evidence that the disease is increasing in incidence at present. That the incidence of meningococcal meningitis has been rising in England and Wales since about 1967 there can be little doubt. This is shown both by the Registrar General’s notifications and by the laboratory-proven cases reported to the Public Health Laboratory Service; the estimated figures from the Hospital In-patient Inquiry, although at present only available up to 1972, lend support to this. Moreover, since the same sources show that the total number of cases of meningitis due to other bacteria has not been rising in parallel, it is likely that the reported increase in meningococcal meningitis in this country is real. Information from the Communicable Disease (Scotland) Unit in Glasgowsuggests not only that a similar increase in the incidence of the disease is occurring in Scotland but that the number of cases of meningococcal septicaemia has also risen. It is interesting to relate the present period of increased incidence with earlier periods. The figure shows the annual number of Registrar General’s notifications since 1929. Apart from the rise during the 1939-45 war, peaks of incidence have occurred in the early 1930s, perhaps in the early 1950s, and now in the 1970s. The numbers being notified at present have not yet proceeded much beyond the levels seen in the 1930s or 1940s. The ratio of deaths to notified cases, which has remained relatively static at between 20% and 30% for about 30 years, exaggerates the true death-rate because deaths are compulsorily certificated whereas notifications are incomplete. However, if it is assumed that the completeness of notifications has been about the same throughout this period, it is of some interest that the ratio has not altered very much since the introduction of chemotherapy in the late 1930s. I am grateful to Dr P. M. Lambert, senior medical statistician, Office of Population Censuses and Surveys, London, for his help and advice in the interpretation of some of the statistics. Central Public Health Laboratory, Colindale Avenue, London NW9 5HT.
N. D. NOAH.
DISINFECTANTS AND SMALLPOX SiR,-The Memorandum on the Control of Smallpox 8 recommends the use of a " white fluid " for terminal disinfection. Such fluids are not now commonly used in hospitals, having largely been replaced by clear soluble
phenolic fluids.
asked about be used instead of the white fluid
Questions
are
now
being
whether such fluids can recommended. The answer must be a regretful " no ". It would not be difficult to test the newer disinfectants against a suspension of a poxvirus, such as vaccinia, and it is probable that many would be found to be effective. However, an 5. U.S. Centre for Disease Control, Morbidity and Mortality. Annual Supplement 1973, 22, no. 53. 6. Wkly epidem. Rec. 1974, 49, 168, 381. 7. Communicable Diseases (Scotland) 1974, 74/44; and personal communication. 8. Ministry of Health and Scottish Home and Health Department. H.M. Stationery Office, 1964.
environment contaminated by a case of smallpox may contain crusts which are hard, dry, fragments of inspissated secretions containing the virus, and to be effective a With the steady disinfectant must penetrate these. reduction of smallpox throughout the world, crusts are exceedingly difficult to obtain, and no acceptable experimental model exists. The only well-defined disinfectant known to have been tested against such crusts is a white fluid to B.S. 2462: 1961 recommendation (Group WF or WG) at a concentration of 2-5%. Efforts are being made to obtain crusts from Asia and if these are successful it is hoped that tests will be made on them, in a laboratory competent to do so. Meanwhile, the recommendations for white fluids must stand. If difficulty’is experienced in obtaining them, the British Disinfectant Manufacturers’ Association, Alembic House, 93 Albert Embankment, London SE1, will advise. Public Health Laboratory Service Board, Colindale Hospital, Colindale Avenue, London NW9 5EQ.
J. C. KELSEY.
TREATMENT OF ALLERGY TO COW’S MILK SiR)—We were very interested in the paper (Jan. 18, p. 136) on cow’s milk allergy by Dr Shiner and her colleagues. Since we have been looking at the duodenal juice as a diagnostic test and have treated two babies with disodium cromoglycate, our experience may be of further interest. The second of twins, born on Feb. 5, 1974, weighed 3170 g. at birth. Symptoms started within a few days of birth: diarrhoea, vomiting, and poor weight gain. Investigation at the age of seven weeks excluded cystic fibrosis and various metabolic diseases. Jejunal biopsy showed broad villi and non-specific abnormalities. Enzyme studies were normal. Gel-precipitin test for milk antibodies were positive at 1/2 dilution. Duodenal juice was examined for precipitating antibodies to cow’s milk. A double diffusion (Ouchterlony) technique on commercial plain agar plates was used. The method comprised two separate diffusions on the same plate. (a) Neat cow’s milk was placed in the centre well of one set and doubling dilutions of duodenal juice (neat 1 : 16) placed in the outer wells. (b) Neat duodenal juice placed in the centre well of another set and doubling dilutions of cow’s milk (neat 1 : 16) placed in the outer wells. The plates were then incubated overnight at 4C and any precipitation arcs noted. Positive reactions were obtained to cow’s milk. Further tests were done on 8 duodenal juices and the following:Nutramigen’, ’ S.M.A.’, ’Ostermilk ’,Cow & Gate’, ’Velactin ’, and saline. The eight duodenal juices were negative to all, but the patient’s juice was negative only to saline and velactin. Further tests are in progress against &bgr;-Iactoglobulin and IgE antibodies against cow’s milk in the juice. The baby was started on cow’s-milk-free formula with complete cessation of symptoms within 48 hours and satisfactory progress. Reintroduction of cow’s milk at the age of six months resulted in diarrhoea and vomiting. At this stage disodium cromoglycate 50 mg. 4 times a day (in chloroform water) was given. Cow’s milk was reintroduced five days later. Since then the baby has been able to tolerate normal cow’s milk in adequate amounts.
A boy born on March 20 weighed 3120 g. He was discharged home after 48 hours. Diarrhoea and vomiting started from about that time. Various cow’s milk changes were made with poor general progress. At the age of six months he was wasted and not thriving satisfactorily. Jejunal biopsy showed minor, nonspecific abnormalities, and enzyme studies were normal in maltase, lactase, and sucrase activity. Duodenal-juice studies were positive to cow’s milk (see above). Withdrawal of cow’s milk resulted in cessation of symptoms. On challenge with cow’s milk, abdominal distension, vomiting, and diarrhoea occurred. For the first 3 months he was treated with cow’smilk-free formula and then was started on disodium cromoglycate 50 mg. 4 times daily. Cow’s milk was reintroduced five days later and since then he has been able to tolerate a perfectly normal diet. Tv’o months later disodium cromoglycate was reduced to
338 twice daily, but the symptoms returned. He remains well 4 doses daily and is able to tolerate cow’s milk.
on
We are grateful to Dr Clifford Clark, of Fison Laboratories, Loughborough, for the supply of disodium cromoglycate. J. A. KUZEMKO Peterborough District Hospital,
Peterborough PE3 6DA.
K. R. SIMPSON.
GASTRIC ACID AND DUODENOGASTRIC REFLUX Fischer 1 demonstrated that deterSIR,-Wesdorp and mination of basal acid output (B.A.o.) in relation to plasmagastrin (P.G.) does not distinguish between a major duodenal contribution to basal circulating gastrin and an autonomous release of gastrin, or alternatively that B.A.o. neither determines nor is determined by P.G. Lam and Sircus2 commented on the lack of a correlation between B.A.o. and P.G., pointing out the importance of eliminating the extraneous and variable influence of vagal stimulation, especially in studies during " basal conditions ". Duodenogastric reflux, which apparently influences B.A.o., is often overlooked. We determined the bile-acid content of the gastric fluid from several patients undergoing a pentagastrin test. The samples were originally sent to us for titration of acid and were obtained by continuous aspiration during the first hour after emptying of the overnight gastric contents. This portion is equivalent to2 that in which the B.A.O. was measured in other studies.l,2 The patients had a long history of gastritisor duodenal or gastric ulcer, verified by X-ray and/or gastroscopy. Bile acids were determined by using 3ac-hydroxy-steroid: N.A.D.oxidoreductase (’ Sterognost-3o:,’ Nyegaard). This method measures all bile acids containing a 3
2990 (Lmol and that for bile acids was 120 jjunol. (Samples with a bile-acid content of less than 10 jamol were excluded.) When the seven samples with acid contents above 5000 jjunol are excluded, the mean levels of acid and bile acid If the estimate were 1230 and 103 jamol, respectively. of the basic contents of duodenogastric reflux above is correct, about 200-350 (Lmol of gastric acid has been neutralised before titration. In most of our cases there was duodenogastric reflux under basal conditions. Admittedly, in some cases the contribution of endogenous
base is small in relation to the production of gastric acid, but in most cases the amount of base introduced by reflux is of the same order of magnitude as that of the titrated acid (see figure). A truncated mean, in which extremes of both components at both ends are excluded, indicates that the amounts of acid titrated should be increased by an average of 20-28% to compensate for endogenous neutralisation. Patients with gastric ulcer have an increased reflux of bile into the stomach. In view of this it is not surprising that Wesdorp and Fischer found a lower mean B.A.o. in patients with gastric ulcer as compared with those who had duodenal ulcer. Read and Grechfound that smoking initiated appreciable duodenogastric reflux. Unless corrections are made for duodenogastric reflux, it is doubtful whether conclusions based on acid output in the stomach, as determined by titration, are valid. Department of Clinical Chemistry, Karolinska Institutet
at
Serafimerlasarettet, Stockholm, Sweden.
ANDERS KALLNER.
Rhodes, J., Barrodo, D. E., Phillips, S. F., Rodelstad, R. A., Hofman, A. F. Gastroenterology, 1969, 57, 241. 7. Read, N. W., Grech, P. Br. med. J. 1973, iii, 313. 6.