- Email: [email protected]
HELMINTHS IN THE SOIL
27
non-therapeutic conjugates of tetracyclines may prove more useful than the parent drugs. Other antibiotics also have properties useful for functional studies. The streptomycin-neomycin group, though highly soluble, are poorly absorbed from the gut. The penicillins undergo protein binding and are readily recoverable from urine, bile, and other situations into which their penetration is a measure of the state of the organ concerned. Exploitation of these properties offers opportunities for research in clinical pharmacology in the course of ordinary therapeutic procedures. The Prague conference closed with the renaming of an important site in the city as " Alexander Fleming Square ". Fleming was fascinated by the academic properties of penicillin, and he would have derived peculiar satisfaction from these applications of his have discovery.
and the pulse disappeared; finally, regular heartbeats returned and the original resting pattern of complexes was restored. Blood-pressure was normal, blood-sugar was normal, and the urinary output of catecholamines and ketogenic steroids was within normal limits. Thus, although the attacks could be attributed to a cardiac arrhythmia, the underlying abnormality remained obscure. Treatment was therefore a matter of trial and error. Phenobarbitone, dexamphetamine, and calcium gluconate did nothing to reduce the number of attacks. Guanethidine, however, suppressed them for 5 months; and inhibition of the -receptors of the sympathetic system by pronethalol was better still, and enabled the child to take more exercise. She had only one attack in 6 months while taking pronethalol (100 mg. twice
supervened
daily).
The girl’s 17-month-old brother then began to similar attacks; and the same prolongation of the QT interval was apparent. This child seemed more severely
affected, and pronethalol could only reduce the attacks from three or more to one a day. Trial of a newer &bgr;-receptor inhibitor made the child irritable. His parents withheld the drug, and 18 hours later he had a fatal attack. Another brother, aged 6 years, was healthy and his E.c.G. normal, and so was the father’s; but there was some lengthening of the QT interval in the mother’s E.c.G. Moreover, the mother had had a sister who repeatedly lost consciousness and who died during one of these episodes at the age of 30. Ward concludes that the disorder in this family was genetically determined, whatever its precise physiological basis. A similar condition has been described in congenital deaf-mutes; but there was no evidence of impairment of hearing in these children or their relatives. The syndrome may be a distinct entity, and, as Ward suggests, the investigation of children with obscure " fainting " fits should include electrocardiography. The new syndrome could then be assigned its proper place-as rare indeed, or
just long unrecognised. ANTIBIOTICS AS RESEARCH TOOLS
DESPITE their
widespread use, antibiotics have been as pharmacological instruments. But at the Antibiotic Congress held in Prague on June 15-19, whole sessions were devoted to the non-therapeutic uses of various major and minor antibiotics. The reason for this may be that the Czechs, who organised the meeting, have a flair for precision and detail in all their enterprises, among which is an admirable new institute for experi-
almost neglected
mental medicine and surgery, whence several useful
originated. They have extended the work on the deposition tetracyclines in hard tissues.l These drugs are known
papers
of to
tumours, and attempts have been made to or demarcate diagnose malignancy by fluorescent tracing of this localisation. This technique has limitations, probably owing to the fact (revealed by work in Czechoslovakia and elsewhere) that tetracyclines concentrate preferentially in necrotic tissue. Their presence in tumours is therefore due mainly to localisation in associated areas of inflammation and necrosis. Czechoslovak workers are tending now to use tetracyclines to gauge the extent of necrosis in burns and in ischsemic lesions of the heart and kidney. Growth of teeth and bone can be measured by fluorescent labelling, for which novel
localise in
some
1.
See
Lancet, 1963, ii,
283.
HELMINTHS IN THE SOIL
OF all the worms parasitic in man, those which are acquired from soil contaminated by human faeces have the simplest life stories and are most widely dispersed. The soil may be eaten deliberately (e.g., in pica) or incidentally, or the embryo worms may pass through the unbroken skin. Nowadays these worms are rare enough in Great Britain to be objects of interest in the laboratory, and as statistical causes of disease they are negligible; but in some parts of Africa where motorcars and radios are a commonplace it is unusual to examine a specimen of faeces which does not contain the ova of roundworms, whipworms, strongyloides, and perhaps hookworms. Race has nothing to do with these differences and climate not very much. At the beginning of the century 100 % of the miners in some Cornish mines harboured whipworms and 25 % roundworms, while the infants of Lambeth attending St. Thomas’s Hospital showed figures of the same order.! " Cousin Jack " had many admirable qualities, but underground his habits were no more hygienic than those of any other miner. The picturesque Lambeth of pearly kings in their donkey carts was no credit to the sanitary authorities. Both communities took quite a lot of human faeces in their diet. The study of the larger parasites in both man and animals has been bedevilled by the assumption (often by those who should have known better) that the presence of a worm or its ova is sufficient " cause " for whatever symptoms the patient may display. Such attributions must be treated with reserve, whether the population at risk is malarious and underfed or wealthy and neurotic. It is often better that the patient be kept in ignorance of his intestinal lodger. No-one, however, doubts the of even though it is not always hookworms, pathogenicity to correlate the of infestation with the incidence easy of Each takes 0-1-0-3 ml. worm prevalence symptoms. blood from the intestinal mucosa every day, and they may be there in their hundreds. Whether this loss of iron and protein can be made up from the diet is probably the deciding factor between a fatal termination and a sorry state of chronic ill-health. In small numbers roundworms and whipworms cause more alarm than illness, but many doctors with long experience in the less hygienic parts of the world believe that when present in large numbers these worms may cause disease of various kinds-e.g., roundworms are found in 60% of Japanese appendices 1.
Boycott,
A. E. Home Office
Report, Cd.
2066.
London, 1904.
28
removed
at operation. Toxocara canis, a roundworm native to the dog, may sometimes stray into the human body with bizarre results.2 The prevention of these infestations is easy-like access to the Ritz Hotel. Excepting those parasites derived from animals, all human infestations will be a thing of the past when the excreta of everyone in every country are passed into a water-closet connected with a well-maintained sewage farm. The installation of underground privies in the Cornish mines, together with the liberal use of thymol as a vermifuge, abolished ankylostomiasis in a short time. In practice the problem is a forbidding one. An expert committee of the World Health Organisation has now produced a report3 on the subject which is difficult to criticise, except for the absence of references. Its suggestions cover such subjects as the disinfection of excreta by heat or chemicals: the mass treatment of a population after careful epidemiological inquiry: and the possibilities of active immunisation. The range of subjects which the committee think suitable for future research indicates how little we know about what must be one of the simpler problems of parasitology.
BIRTHWEIGHT AND INTELLIGENCE
SATISFACTION over the improving survival-rates of very small premature babies has been tempered by concern about the frequency and severity of neurological disabilities in the now surviving children. Cerebral palsy, deafness, and visual defects are all commoner in such infants, affecting perhaps 10% of those with birthweights less than 4 lb.-this may be fifty or a hundred times the rate for infants of normal birthweight. Potentially an even greater cause for concern are those degrees of
neurological injury
or
maldevelopment
not
immediately
evident to medical examination at an early age. They could affect so high a proportion of small infants that their total load of disability could outweigh that carried the grossly disabled 10%. A new study 4 by Alison McDonald tackles the problem of intelligence in infants of less than 4 lb. birthweight. A group of 1066 such infants were studied in an inquiry into the aetiology of cerebral palsy. The in the test was the used Termanmajority intelligence Merrill revision of the Stanford-Binet test (form L) applied at ages 6 to 9 years. Other tests, as thought appropriate, were used for disabled children. As judged from previous surveys, the expected mean score at the present time in this country is about 103. The mean score for children in the group tested was 96-8, or, if expected date of birth rather than actual date of birth was used for the calculation of age, the mean was 98-4. The score was fractionally higher than this for singletons and fractionally lower for twins and triplets. This result seems to have dealt at one blow with the main anxieties of the situation by demonstrating that there is no gross mental defect in the group as a whole. But the difference between the observed 98 and the expected 103 could perhaps represent something more significant in a small subgroup of the infants: so McDonald did not leave the matter here but proceeded to investigate this difficult problem in considerable detail.
by
2. See Lancet, 1962, i, 35; Brain, W. R., Allan, B. ibid. 1964, i, 1355. 3. Soil-Transmitted Helminths. Tech. Rep. Wld Hlth Org. 1964, no. 277. 5s. Obtainable from H.M. Stationery Office, P.O. Box 569, London, S.E.1. 4. McDonald, A. D. Brit. J. prev. soc. Med. 1964, 18, 59.
First, she showed that when children with cerebral palsy, blindness, deafness, and extremely low I.Q.S of less than 50 were excluded from the group, the mean I.Q. of the remaining children was 102.4 for singletons and 98-3 for twins. Evidently it is possible on clinical grounds to separate an abnormal group and to leave a majority whose mean i.Q. can be considered normal. The question whether there is a raised proportion of children with very low i.Q. is a difficult one to assess because of uncertainty whether such children were fully ascertained in the studies used to standardise the intelligence tests. 1-8% of those without cerebral palsy, blindness, or deafness, however, had an i.Q. less than 50 (altogether 3-1% less than 70), and these figures are certainly higher than those quoted for the population. These proportions were even higher in those infants weighing 3 lb. or less at birth, 3-6% having an I.Q. less than 50 and 5-7% less than 70. The infants weighing 3 lb. or less also differed from the heavier infants in the mean l.Q. among children whose I.Q. was over 50: for these small babies the mean I.Q. was 98-6 compared with 103.4 in those between 3 and 4 lb. The conclusion from this is that apart from the children with cerebral palsy, deafness, and visual defects, there is another readily recognised small group of severely defective infants, and they are found especially among those with birthweights of 3 lb. or less. On the other hand, when these seriously disabled children have been separated, the remainder, perhaps 85% of infants of 4 lb. or less, can be regarded as normally distributed in terms of subsequent i.Q. Among the other interesting results was a confirmation of the well-recognised l.Q. differential according to social class, and it was evident at all birthweights and at different gestational ages. Consequently, it is not a secondary result of the effect of social class upon these variables. Tabulations of the effects of gestational age were interesting. They showed an irregular effect among the heavier infants, but in children weighing less than 3 lb. at birth a gestational age less than 33 weeks was associated with a higher score than was a gestational age of 33 weeks or more. This was true in each social class. Apparently, it is better to have a low birthweight because the foetus is young than to have a low birthweight because it has failed to grow at the normal rate. This applies both to singletons and to twins, yet there was no difference in i.Q. scores between heavier and lighter twins. The conclusion is that there is " an aggregation among children weighing 3 lb. or less at birth of abnormalities which affect both foetal growth and intelligence ". This seems to confirm the findings of Baird,5 who, in a smaller group of infants, observed that for a given birthweight the l.Q. was lower in those who were born relatively near to term. He also concluded that there is " no clear indication that within wide limits premature expulsion from the uterus does the foetus any serious harm ". Provided that the 10-15% of seriously disabled children are not forgotten and that this statement is taken, by implication, to apply to the remainder, McDonald seems to
agree.
Prof. R. V. BRADLAW, dean of the Postgraduate Institute of Dental Surgery of the University of London, has succeeded Sir WILFRED FISH as president of the General Dental Council. 5.
Baird, D. J. Obstet. Gynœc. Brit. Emp. 1959, 66,
743.
non-therapeutic conjugates of tetracyclines may prove more useful than the parent drugs. Other antibiotics also have properties useful for functional studies. The streptomycin-neomycin group, though highly soluble, are poorly absorbed from the gut. The penicillins undergo protein binding and are readily recoverable from urine, bile, and other situations into which their penetration is a measure of the state of the organ concerned. Exploitation of these properties offers opportunities for research in clinical pharmacology in the course of ordinary therapeutic procedures. The Prague conference closed with the renaming of an important site in the city as " Alexander Fleming Square ". Fleming was fascinated by the academic properties of penicillin, and he would have derived peculiar satisfaction from these applications of his have discovery.
and the pulse disappeared; finally, regular heartbeats returned and the original resting pattern of complexes was restored. Blood-pressure was normal, blood-sugar was normal, and the urinary output of catecholamines and ketogenic steroids was within normal limits. Thus, although the attacks could be attributed to a cardiac arrhythmia, the underlying abnormality remained obscure. Treatment was therefore a matter of trial and error. Phenobarbitone, dexamphetamine, and calcium gluconate did nothing to reduce the number of attacks. Guanethidine, however, suppressed them for 5 months; and inhibition of the -receptors of the sympathetic system by pronethalol was better still, and enabled the child to take more exercise. She had only one attack in 6 months while taking pronethalol (100 mg. twice
supervened
daily).
The girl’s 17-month-old brother then began to similar attacks; and the same prolongation of the QT interval was apparent. This child seemed more severely
affected, and pronethalol could only reduce the attacks from three or more to one a day. Trial of a newer &bgr;-receptor inhibitor made the child irritable. His parents withheld the drug, and 18 hours later he had a fatal attack. Another brother, aged 6 years, was healthy and his E.c.G. normal, and so was the father’s; but there was some lengthening of the QT interval in the mother’s E.c.G. Moreover, the mother had had a sister who repeatedly lost consciousness and who died during one of these episodes at the age of 30. Ward concludes that the disorder in this family was genetically determined, whatever its precise physiological basis. A similar condition has been described in congenital deaf-mutes; but there was no evidence of impairment of hearing in these children or their relatives. The syndrome may be a distinct entity, and, as Ward suggests, the investigation of children with obscure " fainting " fits should include electrocardiography. The new syndrome could then be assigned its proper place-as rare indeed, or
just long unrecognised. ANTIBIOTICS AS RESEARCH TOOLS
DESPITE their
widespread use, antibiotics have been as pharmacological instruments. But at the Antibiotic Congress held in Prague on June 15-19, whole sessions were devoted to the non-therapeutic uses of various major and minor antibiotics. The reason for this may be that the Czechs, who organised the meeting, have a flair for precision and detail in all their enterprises, among which is an admirable new institute for experi-
almost neglected
mental medicine and surgery, whence several useful
originated. They have extended the work on the deposition tetracyclines in hard tissues.l These drugs are known
papers
of to
tumours, and attempts have been made to or demarcate diagnose malignancy by fluorescent tracing of this localisation. This technique has limitations, probably owing to the fact (revealed by work in Czechoslovakia and elsewhere) that tetracyclines concentrate preferentially in necrotic tissue. Their presence in tumours is therefore due mainly to localisation in associated areas of inflammation and necrosis. Czechoslovak workers are tending now to use tetracyclines to gauge the extent of necrosis in burns and in ischsemic lesions of the heart and kidney. Growth of teeth and bone can be measured by fluorescent labelling, for which novel
localise in
some
1.
See
Lancet, 1963, ii,
283.
HELMINTHS IN THE SOIL
OF all the worms parasitic in man, those which are acquired from soil contaminated by human faeces have the simplest life stories and are most widely dispersed. The soil may be eaten deliberately (e.g., in pica) or incidentally, or the embryo worms may pass through the unbroken skin. Nowadays these worms are rare enough in Great Britain to be objects of interest in the laboratory, and as statistical causes of disease they are negligible; but in some parts of Africa where motorcars and radios are a commonplace it is unusual to examine a specimen of faeces which does not contain the ova of roundworms, whipworms, strongyloides, and perhaps hookworms. Race has nothing to do with these differences and climate not very much. At the beginning of the century 100 % of the miners in some Cornish mines harboured whipworms and 25 % roundworms, while the infants of Lambeth attending St. Thomas’s Hospital showed figures of the same order.! " Cousin Jack " had many admirable qualities, but underground his habits were no more hygienic than those of any other miner. The picturesque Lambeth of pearly kings in their donkey carts was no credit to the sanitary authorities. Both communities took quite a lot of human faeces in their diet. The study of the larger parasites in both man and animals has been bedevilled by the assumption (often by those who should have known better) that the presence of a worm or its ova is sufficient " cause " for whatever symptoms the patient may display. Such attributions must be treated with reserve, whether the population at risk is malarious and underfed or wealthy and neurotic. It is often better that the patient be kept in ignorance of his intestinal lodger. No-one, however, doubts the of even though it is not always hookworms, pathogenicity to correlate the of infestation with the incidence easy of Each takes 0-1-0-3 ml. worm prevalence symptoms. blood from the intestinal mucosa every day, and they may be there in their hundreds. Whether this loss of iron and protein can be made up from the diet is probably the deciding factor between a fatal termination and a sorry state of chronic ill-health. In small numbers roundworms and whipworms cause more alarm than illness, but many doctors with long experience in the less hygienic parts of the world believe that when present in large numbers these worms may cause disease of various kinds-e.g., roundworms are found in 60% of Japanese appendices 1.
Boycott,
A. E. Home Office
Report, Cd.
2066.
London, 1904.
28
removed
at operation. Toxocara canis, a roundworm native to the dog, may sometimes stray into the human body with bizarre results.2 The prevention of these infestations is easy-like access to the Ritz Hotel. Excepting those parasites derived from animals, all human infestations will be a thing of the past when the excreta of everyone in every country are passed into a water-closet connected with a well-maintained sewage farm. The installation of underground privies in the Cornish mines, together with the liberal use of thymol as a vermifuge, abolished ankylostomiasis in a short time. In practice the problem is a forbidding one. An expert committee of the World Health Organisation has now produced a report3 on the subject which is difficult to criticise, except for the absence of references. Its suggestions cover such subjects as the disinfection of excreta by heat or chemicals: the mass treatment of a population after careful epidemiological inquiry: and the possibilities of active immunisation. The range of subjects which the committee think suitable for future research indicates how little we know about what must be one of the simpler problems of parasitology.
BIRTHWEIGHT AND INTELLIGENCE
SATISFACTION over the improving survival-rates of very small premature babies has been tempered by concern about the frequency and severity of neurological disabilities in the now surviving children. Cerebral palsy, deafness, and visual defects are all commoner in such infants, affecting perhaps 10% of those with birthweights less than 4 lb.-this may be fifty or a hundred times the rate for infants of normal birthweight. Potentially an even greater cause for concern are those degrees of
neurological injury
or
maldevelopment
not
immediately
evident to medical examination at an early age. They could affect so high a proportion of small infants that their total load of disability could outweigh that carried the grossly disabled 10%. A new study 4 by Alison McDonald tackles the problem of intelligence in infants of less than 4 lb. birthweight. A group of 1066 such infants were studied in an inquiry into the aetiology of cerebral palsy. The in the test was the used Termanmajority intelligence Merrill revision of the Stanford-Binet test (form L) applied at ages 6 to 9 years. Other tests, as thought appropriate, were used for disabled children. As judged from previous surveys, the expected mean score at the present time in this country is about 103. The mean score for children in the group tested was 96-8, or, if expected date of birth rather than actual date of birth was used for the calculation of age, the mean was 98-4. The score was fractionally higher than this for singletons and fractionally lower for twins and triplets. This result seems to have dealt at one blow with the main anxieties of the situation by demonstrating that there is no gross mental defect in the group as a whole. But the difference between the observed 98 and the expected 103 could perhaps represent something more significant in a small subgroup of the infants: so McDonald did not leave the matter here but proceeded to investigate this difficult problem in considerable detail.
by
2. See Lancet, 1962, i, 35; Brain, W. R., Allan, B. ibid. 1964, i, 1355. 3. Soil-Transmitted Helminths. Tech. Rep. Wld Hlth Org. 1964, no. 277. 5s. Obtainable from H.M. Stationery Office, P.O. Box 569, London, S.E.1. 4. McDonald, A. D. Brit. J. prev. soc. Med. 1964, 18, 59.
First, she showed that when children with cerebral palsy, blindness, deafness, and extremely low I.Q.S of less than 50 were excluded from the group, the mean I.Q. of the remaining children was 102.4 for singletons and 98-3 for twins. Evidently it is possible on clinical grounds to separate an abnormal group and to leave a majority whose mean i.Q. can be considered normal. The question whether there is a raised proportion of children with very low i.Q. is a difficult one to assess because of uncertainty whether such children were fully ascertained in the studies used to standardise the intelligence tests. 1-8% of those without cerebral palsy, blindness, or deafness, however, had an i.Q. less than 50 (altogether 3-1% less than 70), and these figures are certainly higher than those quoted for the population. These proportions were even higher in those infants weighing 3 lb. or less at birth, 3-6% having an I.Q. less than 50 and 5-7% less than 70. The infants weighing 3 lb. or less also differed from the heavier infants in the mean l.Q. among children whose I.Q. was over 50: for these small babies the mean I.Q. was 98-6 compared with 103.4 in those between 3 and 4 lb. The conclusion from this is that apart from the children with cerebral palsy, deafness, and visual defects, there is another readily recognised small group of severely defective infants, and they are found especially among those with birthweights of 3 lb. or less. On the other hand, when these seriously disabled children have been separated, the remainder, perhaps 85% of infants of 4 lb. or less, can be regarded as normally distributed in terms of subsequent i.Q. Among the other interesting results was a confirmation of the well-recognised l.Q. differential according to social class, and it was evident at all birthweights and at different gestational ages. Consequently, it is not a secondary result of the effect of social class upon these variables. Tabulations of the effects of gestational age were interesting. They showed an irregular effect among the heavier infants, but in children weighing less than 3 lb. at birth a gestational age less than 33 weeks was associated with a higher score than was a gestational age of 33 weeks or more. This was true in each social class. Apparently, it is better to have a low birthweight because the foetus is young than to have a low birthweight because it has failed to grow at the normal rate. This applies both to singletons and to twins, yet there was no difference in i.Q. scores between heavier and lighter twins. The conclusion is that there is " an aggregation among children weighing 3 lb. or less at birth of abnormalities which affect both foetal growth and intelligence ". This seems to confirm the findings of Baird,5 who, in a smaller group of infants, observed that for a given birthweight the l.Q. was lower in those who were born relatively near to term. He also concluded that there is " no clear indication that within wide limits premature expulsion from the uterus does the foetus any serious harm ". Provided that the 10-15% of seriously disabled children are not forgotten and that this statement is taken, by implication, to apply to the remainder, McDonald seems to
agree.
Prof. R. V. BRADLAW, dean of the Postgraduate Institute of Dental Surgery of the University of London, has succeeded Sir WILFRED FISH as president of the General Dental Council. 5.
Baird, D. J. Obstet. Gynœc. Brit. Emp. 1959, 66,
743.