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VITAMIN D AND THE PARATHYROIDS
1079 For the non-specialist, television has an important future in public-health education and programmes of= general medical interest. In America medical cases are!
presented in at least one regular weekly programme, and in France endoscopies have been demonstrated on the national television service. .
hypercalcaemia which may be induced by very large doses of vitamin D (never adequately explained by the action of vitamin D on absorption of calcium), and it may account for the secondary hyperparathyroidism often seen in rickets and osteomalacia. If vitamin D normally contributes to the maintenance of the serum-calcium
level, its deficiency would tend to lower the calcium
WHEEZING content and stimulate the parathyroid glands, leading to the parathyroid hyperplasia seen in rickets,8 and to the WHEEZING is the most obvious sign of an acute radiographic9 and histological 10 manifestations of paraasthmatic attack. Like many other familiar phenomena, thyroid overactivity reported in osteomalacia. In fact, it has had comparatively little serious thought, and until such parathyroid overactivity is very probably responhas that it suggested quite recently hardly anyone for the high phosphate-clearance observed in sible from the arise not (as generally supposed) passage may osteomalacia,l1 and so for the low serum-phosphate in The paper we of air through constricted bronchioles. this condition which cannot be attributed to malabsorppublish this week by Dr. Dekker and Dr. Groen should tion of phosphorus. But lack of vitamin D does not for a review of the least as a basis at serve prevalent always set in train this course of events. Hypocalcæmic ideas. Briefly, they maintain that the wheezing sound tetany is another familiar manifestation of this deficiency ; is generated in the larger bronchi and trachea by the but its precise relationship to rickets has never been of and turbulent flow respiratory gases through rapid fully understood. If rickets is regarded as a manifestation them when they are constricted by pressure from of secondary hyperparathyroidism, hypocalcaemia may without : the pressure is applied within the thorax be regarded as an indication of parathyroid the force of contraction legitimately against expiratory muscular by insufficiency, particularly when-as is often the casethe high resistance to gas flow offered by the constricted the content of inorganic phosphate in the serum is high. In their scheme of events bronchiolar bronchioles. The reason for this parathyroid insufficiency is unknown. constriction does not itself cause wheezing at all. Nutritional deficiency of vitamin D has become a rare This explanation is not so unlikely as it may seem cause of rickets and tetany, but both these conditions at first. One point in its favour is that the actual volume may arise in steatorrhoea. They are then indistinguishable of gas flowing through a bronchiole during expiration from the corresponding conditions produced by nutrimust be very small indeed, and probably flow is streamtional deficiency (except in the dosage of oral calciferol line in character : these are not the conditions in which which they need), and are commonly attributed to one would expect audible sounds, which require that flow should be turbulent and be of enough volume to malabsorption of fat-soluble vitamin D,12 though Dent 13 has sound of waves suitable and suggested that there may be some additional generate power frequency. metabolic disorder present. In a letter on p. 1086, Dr. A clinical observation which adds support is the wellJackson suggests that steatorrhoea and hypoparathyroidknown " pursed lip breathing often seen in emphysemaism are significantly associated, and he draws attention tous patients. this mode of By adopting expiration, He cites to cases presenting both disorders. is built tree reported within bronchial which the up pressure the attractive of and Salvesen Boe 14, that suggestions helps to prevent collapse of the larger branches. with steatorrhoea either osteoThe investigations on normal people are of interest patients may develop malacia or tetany according to the response of their in relation to so-called psychogenic asthma. It is easy to see how patients with anxiety states might acquire parathyroids to hypocalcæmia, and he suggests that some the same trick of wheezing expiration-and also why particular significance should be attached to the apparently high prevalence of parathyroid insufficiency in their asthma might be completely cured by psychotherapy. steatorrhœa.15 There may, of course, be evidence of endocrine insufficiency in steatorrhoea,16 and possibly VITAMIN D AND THE PARATHYROIDS parathyroid insufficiency should be regarded as a parWHEN Albright and Reifenstein1 drew attention to ticular manifestation of this general disorder ; in fact, the similarities between the metabolic effects of vitamin D amenorrhoea and absent body hair were prominent and of parathyroid hormone, they were not convinced features in Dr. Jackson’s own case.17 If, on the other action on bone ; that either exerted a direct calcsemic hand, these patients are in fact suffering from a deficiency but since then both substances have been found to of vitamin D, it seems more reasonable to seek a single possess this property. Thus experimentally it has been explanation for the tetany of steatorrhoea and that of shown beyond doubt that parathyroid extract raises the nutritional avitaminosis D. serum-calcium even after nephrectomy2 and that vitThe hypothesis that the parathyroids either respond to amin D raises the serum-calcium of rachitic rats in hypocalcæmia and cause osteomalacia, or fail to respond conditions which make it impossible to ascribe this effect and cause tetany, seems to be an oversimplification. to increased absorption of calcium from the intestine.3 Thus it fails to take into account or to explain the vital The close similarity between the effects of vitamin D fact that tetany and rickets may be found in the same and of parathyroid hormone on bone is underlined by patient. This is true not only of nutritional vitamin-D Barnicot’s observation 45 that local implants of calciferol deficiency, in which tetany is almost invariably associated and parathyroid-gland tissue evoke the same osteoclastic with rickets, though rickets is only occasionally accomreaction. panied by tetany,18 but also of the malabsorption The inference that vitamin D and parathyroid hormone syndrome.19 In both types of vitamin-D deficiency, are both concerned in regulating the equilibrium which is believed to exist between the calcium and phosphate 8. Pappenheimer, A. M., Minor, J. J. med. Res. 1921, 42, 391. Brit. med. J. 1956, 9. Davies, D. R., Dent, C. E., Wilicox, A. ions in the extracellular fluid and the crystals of a ii, 1133. 6 F. J. Beitr. 10. Anat. 142. Lang, path. 1931, 87, calcium-phosphate compound in the skeleton may 11. Nordin, B. E. C., Fraser, R. In Proceedings of Ciba Foundation shed some light on related problems. It explains the Symposium on Bone Structure and Metabolism. London, 1956. 12. Bodansky, M., Bodansky, O. The Biochemistry of Disease. 1. Albright, F., Reifenstein, E. C. New York, 1952. The Parathyroid Glands and Metabolic Bone Disease. Baltimore, 1948. 13. Dent, C. E. Brit. med J. 1956, ii, 1546. 2. Ingalls, T. H., Donaldson, G. A., Albright, F. 14. Salvesen, H. A., Böe, J. J. clin. Invest. Acta med. scand. 1953, 146, 290. 1943, 22, 603. 15. Salvesen, H. A., Böe, J. Acta endocr., Copenhagen, 1953, 14, 214. 3. Carlsson, A., Lindquist, B. Acta phys. scand. 1955, 35, 53. 16. Wintrobe, M. M. Clinical Hæmatology. London, 1956. 4. Barnicot, N. A. J. Anat., Lond. 1948, 82, 233. 17. Jackson, W. P. U., Hoffenburg, R., Linder, G. C., Irwin, L. "
"
5.
Barnicot, N. A. Ibid, 1951, 85, 120. 6. See Lancet, 1955, ii, 183. 7. Copp, D. H. Amer. J. Med. 1957, 22, 275.
"
J. clin. Endocrin. 1956, 16, 1043. 18. Hess, A. F. Rickets. Osteomalacia and Tetany. 19. Bloom, A. Proc. R. Soc. Med. 1955, 48, 321.
London, 1930.
1080
however, it
that whereas rickets may precede if ever develops into rickets.l8 These observations can be reconciled if it is accepted that the parathyroid glands may become " exhausted." On this hypothesis, an indeterminate period of parathyroid overactivity may lead to rickets or osteomalacia, but may culminate in parathyroid failure and tetany. The two possible parathyroid responses postulated by Salvesen and Boe can be regarded as the two extreme examples, but between them there can exist every degree of parathyroid activity represented by different combinations of serum contents of calcium and phosphate. A’ normal serum-calcium with a low serum-phosphate suggests complete parathyroid compensation : a low serum-calcium with a high serum-phosphate, complete parathyroid failure. Between these two extremes, the development of rickets will depend on the product of Ca x P in the extracellular fluid, and the development of tetany on the absolute content of calcium ions. The possibility remains that the hypoparathyroid state is more common in steatorrhoea than in nutritional vitamin-D deficiency, or that it differs in some other way in the two conditions. If Dr. Jackson can show this to be the case, his suggestion will be greatly strengthened. seems
tetany, tetany rarely
THE ENZYME DEFECT IN GALACTOSÆMIA Two years ago1 we discussed the genetically determined inborn error of metabolism known as galactossemia. Some of the questions raised then remain unanswered - for example, whether children with this metabolic error would be entirely protected from harm if they were kept on a lactose-free diet from birth. But another problem - the exact nature of the enzyme deficiency-has been solved. In 1955 Schwarz et al.2 had taken the first step by showing that the red cells of galactosæmic children who had just had a milk feed contained an accumulation of galactose-1-phosphate, but not of glucose-1-phosphate. Therefore galactose was being metabolised to galactose1-phosphate, but a stage in the conversion of galactose1-phosphate to glucose-1-phosphate was imperfect. This transformation involves three stages. First, combines with uridine diphosphogalactose-1-phosphate glucose to give glucose-1-phosphate and uridine diphosSecond, uridine diphosphogalactose is phogalactose. transformed to uridine diphosphoglucose. Third, uridine diphosphoglucose reacts with inorganic pyrophosphate to give uridine triphosphate and glucose-1-phosphate. Kalckar et al. have shown in haemolysates3 and in liver homogenates4 from patients with the disease that it is the enzyme for the first stage, galactose-1-phosphate uridyl transferase, that is missing. It is useful to know that the enzyme defect may be shown in cord-blood cells immediately after birth, so that in families at risk affected infants may be identified and put on a lactose-free diet from birth. Holzel and Komrower,5 in 1955, produced evidence that some of the parents, who are themselves heterozygous for the gene responsible for galactossemia, had an abnormal galactosetolerance curve. Unfortunately Kalckar and his associates have not been able to detect any abnormality in the amount of galactose-1-phosphate uridyl transferase in parents. It is a striking example of the uniformity of many biological processes in the animal kingdom that four mutant forms of the bacillus Escherichia coli are known with the same enzyme defect.s6 Three other galactoseLancet, 1955, ii, 77. 2. Schwarz, V., Solberg, L., Komrower, G. M., Holzel, A. Biochem. J. 1955, 59, xxii. 3. Kalckar, H. M., Anderson, E. P., Isselbacher, K. J. Biochem. biophys. acta, 1956, 20, 262. 4. Anderson, E. P., Kalckar, H. M., Isselbacher, K. J. Science, 1957, 125, 113. Arch. Dis. Childh. 1955, 30, 155. 5. Holzel, A., Komrower, G. M. 6. Kurahashi, K. Science, 1957, 125, 114. 1.
negative mutants of the bacillus lack instead the enzyme galactokinase concerned in the first step of all-the conversion of galactose to galactose-1-phosphate—but these have
as
yet
no
human counterparts.
ATYPICAL ACID-FAST BACILLI
MANY investigators have isolated from patients strains of mycobacteria which, for want of a better name, are called " atypical acid-fast bacilli." These bacilli are not new,l2 but in recent years they seem to have been recognised much more commonly. In man they are associated with pulmonary lesions, often serious and progressive, which in every way resemble typical pulmonary tuberculosis 3 ; but unhappily their response to most antituberculous drugs is poor. It is not yet certain whether these organisms comprise a homogeneous group or several different types. They differ from typical tubercle bacilli not only in their drug-sensitivity pattern but also in being chromogenic, and in showing greater catalase activity, poor cord formation, a negative neutral-red reaction, and avirulence for guineapigs. Usually they can be distinguished from typical acid-fast saprophytes by a rather slower growth. rate, especially at room-temperature (though they grow faster than typical tubercle bacilli) and by the type of lesions in certain laboratory animals. Wolinsky et al.3 found that in each of three cases of infection by these organisms in man, the strains produced orange or yellow pigment ; but in two they did so only in light. Crow et awl. describe 69 such cases, in which the organisms seemed to fall into three main groups judged by growth on Löwenstein-Jensen medium. In 64 cases the strains smooth, produced slow-growing buff colonies which became orange as the cultures aged ; in 3 the strains were more chromogenic but otherwise similar; and in 2 the strains gave rough colonies similar to those of Mycobacterium tuberculosis except that they grew much more rapidly-though not so rapidly as recognised acidfast saprophytes. Pathologically, according to Crow et al., these organ. isms give rise to lesions differing in no way from those due to typical tubercle bacilli; but the disease is less readily communicated : in none of their 69 cases was more than one member of a household known to be infected. On the other hand, the response to antituberculous treatment is disappointing: of 56 cases reviewed by Crow et al. only a third showed sputum conversion on chemotherapy. These studies and others 5-7 make it clear that atypical acid-fast bacilli present a fairly serious problem. It can hardly be doubted that infections with these organisms have become more prevalent since chemotherapy has been widely used ; and conceivably they represent mutants induced or selected by chemotherapy - a hypothesis that seems to be supported by the partial resistance of most strains to antituberculous drugs. Thus, incomplete treatment of tuberculosis due to drugsensitive typical bacilli may carry the danger of fostering these drug-resistant atypical forms, though so far this has by no means been proved. Meanwhile infections with these atypical organisms should, it seems, be treated as are infections with typical bacilli; and. despite their seemingly lesser infectivity, public-health measures should be applied no less rigorously than is usual in tuberculosis. Branch, A. Tubercle, Lond. 1933, 14, 337. Pinner, M. Amer. Rev. Tuberc. 1935, 32, 424, 440. Wolinsky, E., Smith, M. M., Mitchell, R. S., Steenken, W. jun. Ibid, 1957, 75, 180. 4. Crow, H. E., King, C. T., Smith, C. E., Corpe, R. F., Stergus, I. Ibid, p. 199. 5. Timpe, A., Runyon, E. H. J. Lab. clin. Med. 1954, 44, 202; see Lancet, 1955, ii, 758. 6. Wilson, G. C., Morton, D. E. Amer. Rev. Tuberc. 1956, 73, 351. 7. Tarshis, M. S., Frisch, A. W. Ibid, 1952, 65, 278, 289, 302. 1. 2. 3.
presented in at least one regular weekly programme, and in France endoscopies have been demonstrated on the national television service. .
hypercalcaemia which may be induced by very large doses of vitamin D (never adequately explained by the action of vitamin D on absorption of calcium), and it may account for the secondary hyperparathyroidism often seen in rickets and osteomalacia. If vitamin D normally contributes to the maintenance of the serum-calcium
level, its deficiency would tend to lower the calcium
WHEEZING content and stimulate the parathyroid glands, leading to the parathyroid hyperplasia seen in rickets,8 and to the WHEEZING is the most obvious sign of an acute radiographic9 and histological 10 manifestations of paraasthmatic attack. Like many other familiar phenomena, thyroid overactivity reported in osteomalacia. In fact, it has had comparatively little serious thought, and until such parathyroid overactivity is very probably responhas that it suggested quite recently hardly anyone for the high phosphate-clearance observed in sible from the arise not (as generally supposed) passage may osteomalacia,l1 and so for the low serum-phosphate in The paper we of air through constricted bronchioles. this condition which cannot be attributed to malabsorppublish this week by Dr. Dekker and Dr. Groen should tion of phosphorus. But lack of vitamin D does not for a review of the least as a basis at serve prevalent always set in train this course of events. Hypocalcæmic ideas. Briefly, they maintain that the wheezing sound tetany is another familiar manifestation of this deficiency ; is generated in the larger bronchi and trachea by the but its precise relationship to rickets has never been of and turbulent flow respiratory gases through rapid fully understood. If rickets is regarded as a manifestation them when they are constricted by pressure from of secondary hyperparathyroidism, hypocalcaemia may without : the pressure is applied within the thorax be regarded as an indication of parathyroid the force of contraction legitimately against expiratory muscular by insufficiency, particularly when-as is often the casethe high resistance to gas flow offered by the constricted the content of inorganic phosphate in the serum is high. In their scheme of events bronchiolar bronchioles. The reason for this parathyroid insufficiency is unknown. constriction does not itself cause wheezing at all. Nutritional deficiency of vitamin D has become a rare This explanation is not so unlikely as it may seem cause of rickets and tetany, but both these conditions at first. One point in its favour is that the actual volume may arise in steatorrhoea. They are then indistinguishable of gas flowing through a bronchiole during expiration from the corresponding conditions produced by nutrimust be very small indeed, and probably flow is streamtional deficiency (except in the dosage of oral calciferol line in character : these are not the conditions in which which they need), and are commonly attributed to one would expect audible sounds, which require that flow should be turbulent and be of enough volume to malabsorption of fat-soluble vitamin D,12 though Dent 13 has sound of waves suitable and suggested that there may be some additional generate power frequency. metabolic disorder present. In a letter on p. 1086, Dr. A clinical observation which adds support is the wellJackson suggests that steatorrhoea and hypoparathyroidknown " pursed lip breathing often seen in emphysemaism are significantly associated, and he draws attention tous patients. this mode of By adopting expiration, He cites to cases presenting both disorders. is built tree reported within bronchial which the up pressure the attractive of and Salvesen Boe 14, that suggestions helps to prevent collapse of the larger branches. with steatorrhoea either osteoThe investigations on normal people are of interest patients may develop malacia or tetany according to the response of their in relation to so-called psychogenic asthma. It is easy to see how patients with anxiety states might acquire parathyroids to hypocalcæmia, and he suggests that some the same trick of wheezing expiration-and also why particular significance should be attached to the apparently high prevalence of parathyroid insufficiency in their asthma might be completely cured by psychotherapy. steatorrhœa.15 There may, of course, be evidence of endocrine insufficiency in steatorrhoea,16 and possibly VITAMIN D AND THE PARATHYROIDS parathyroid insufficiency should be regarded as a parWHEN Albright and Reifenstein1 drew attention to ticular manifestation of this general disorder ; in fact, the similarities between the metabolic effects of vitamin D amenorrhoea and absent body hair were prominent and of parathyroid hormone, they were not convinced features in Dr. Jackson’s own case.17 If, on the other action on bone ; that either exerted a direct calcsemic hand, these patients are in fact suffering from a deficiency but since then both substances have been found to of vitamin D, it seems more reasonable to seek a single possess this property. Thus experimentally it has been explanation for the tetany of steatorrhoea and that of shown beyond doubt that parathyroid extract raises the nutritional avitaminosis D. serum-calcium even after nephrectomy2 and that vitThe hypothesis that the parathyroids either respond to amin D raises the serum-calcium of rachitic rats in hypocalcæmia and cause osteomalacia, or fail to respond conditions which make it impossible to ascribe this effect and cause tetany, seems to be an oversimplification. to increased absorption of calcium from the intestine.3 Thus it fails to take into account or to explain the vital The close similarity between the effects of vitamin D fact that tetany and rickets may be found in the same and of parathyroid hormone on bone is underlined by patient. This is true not only of nutritional vitamin-D Barnicot’s observation 45 that local implants of calciferol deficiency, in which tetany is almost invariably associated and parathyroid-gland tissue evoke the same osteoclastic with rickets, though rickets is only occasionally accomreaction. panied by tetany,18 but also of the malabsorption The inference that vitamin D and parathyroid hormone syndrome.19 In both types of vitamin-D deficiency, are both concerned in regulating the equilibrium which is believed to exist between the calcium and phosphate 8. Pappenheimer, A. M., Minor, J. J. med. Res. 1921, 42, 391. Brit. med. J. 1956, 9. Davies, D. R., Dent, C. E., Wilicox, A. ions in the extracellular fluid and the crystals of a ii, 1133. 6 F. J. Beitr. 10. Anat. 142. Lang, path. 1931, 87, calcium-phosphate compound in the skeleton may 11. Nordin, B. E. C., Fraser, R. In Proceedings of Ciba Foundation shed some light on related problems. It explains the Symposium on Bone Structure and Metabolism. London, 1956. 12. Bodansky, M., Bodansky, O. The Biochemistry of Disease. 1. Albright, F., Reifenstein, E. C. New York, 1952. The Parathyroid Glands and Metabolic Bone Disease. Baltimore, 1948. 13. Dent, C. E. Brit. med J. 1956, ii, 1546. 2. Ingalls, T. H., Donaldson, G. A., Albright, F. 14. Salvesen, H. A., Böe, J. J. clin. Invest. Acta med. scand. 1953, 146, 290. 1943, 22, 603. 15. Salvesen, H. A., Böe, J. Acta endocr., Copenhagen, 1953, 14, 214. 3. Carlsson, A., Lindquist, B. Acta phys. scand. 1955, 35, 53. 16. Wintrobe, M. M. Clinical Hæmatology. London, 1956. 4. Barnicot, N. A. J. Anat., Lond. 1948, 82, 233. 17. Jackson, W. P. U., Hoffenburg, R., Linder, G. C., Irwin, L. "
"
5.
Barnicot, N. A. Ibid, 1951, 85, 120. 6. See Lancet, 1955, ii, 183. 7. Copp, D. H. Amer. J. Med. 1957, 22, 275.
"
J. clin. Endocrin. 1956, 16, 1043. 18. Hess, A. F. Rickets. Osteomalacia and Tetany. 19. Bloom, A. Proc. R. Soc. Med. 1955, 48, 321.
London, 1930.
1080
however, it
that whereas rickets may precede if ever develops into rickets.l8 These observations can be reconciled if it is accepted that the parathyroid glands may become " exhausted." On this hypothesis, an indeterminate period of parathyroid overactivity may lead to rickets or osteomalacia, but may culminate in parathyroid failure and tetany. The two possible parathyroid responses postulated by Salvesen and Boe can be regarded as the two extreme examples, but between them there can exist every degree of parathyroid activity represented by different combinations of serum contents of calcium and phosphate. A’ normal serum-calcium with a low serum-phosphate suggests complete parathyroid compensation : a low serum-calcium with a high serum-phosphate, complete parathyroid failure. Between these two extremes, the development of rickets will depend on the product of Ca x P in the extracellular fluid, and the development of tetany on the absolute content of calcium ions. The possibility remains that the hypoparathyroid state is more common in steatorrhoea than in nutritional vitamin-D deficiency, or that it differs in some other way in the two conditions. If Dr. Jackson can show this to be the case, his suggestion will be greatly strengthened. seems
tetany, tetany rarely
THE ENZYME DEFECT IN GALACTOSÆMIA Two years ago1 we discussed the genetically determined inborn error of metabolism known as galactossemia. Some of the questions raised then remain unanswered - for example, whether children with this metabolic error would be entirely protected from harm if they were kept on a lactose-free diet from birth. But another problem - the exact nature of the enzyme deficiency-has been solved. In 1955 Schwarz et al.2 had taken the first step by showing that the red cells of galactosæmic children who had just had a milk feed contained an accumulation of galactose-1-phosphate, but not of glucose-1-phosphate. Therefore galactose was being metabolised to galactose1-phosphate, but a stage in the conversion of galactose1-phosphate to glucose-1-phosphate was imperfect. This transformation involves three stages. First, combines with uridine diphosphogalactose-1-phosphate glucose to give glucose-1-phosphate and uridine diphosSecond, uridine diphosphogalactose is phogalactose. transformed to uridine diphosphoglucose. Third, uridine diphosphoglucose reacts with inorganic pyrophosphate to give uridine triphosphate and glucose-1-phosphate. Kalckar et al. have shown in haemolysates3 and in liver homogenates4 from patients with the disease that it is the enzyme for the first stage, galactose-1-phosphate uridyl transferase, that is missing. It is useful to know that the enzyme defect may be shown in cord-blood cells immediately after birth, so that in families at risk affected infants may be identified and put on a lactose-free diet from birth. Holzel and Komrower,5 in 1955, produced evidence that some of the parents, who are themselves heterozygous for the gene responsible for galactossemia, had an abnormal galactosetolerance curve. Unfortunately Kalckar and his associates have not been able to detect any abnormality in the amount of galactose-1-phosphate uridyl transferase in parents. It is a striking example of the uniformity of many biological processes in the animal kingdom that four mutant forms of the bacillus Escherichia coli are known with the same enzyme defect.s6 Three other galactoseLancet, 1955, ii, 77. 2. Schwarz, V., Solberg, L., Komrower, G. M., Holzel, A. Biochem. J. 1955, 59, xxii. 3. Kalckar, H. M., Anderson, E. P., Isselbacher, K. J. Biochem. biophys. acta, 1956, 20, 262. 4. Anderson, E. P., Kalckar, H. M., Isselbacher, K. J. Science, 1957, 125, 113. Arch. Dis. Childh. 1955, 30, 155. 5. Holzel, A., Komrower, G. M. 6. Kurahashi, K. Science, 1957, 125, 114. 1.
negative mutants of the bacillus lack instead the enzyme galactokinase concerned in the first step of all-the conversion of galactose to galactose-1-phosphate—but these have
as
yet
no
human counterparts.
ATYPICAL ACID-FAST BACILLI
MANY investigators have isolated from patients strains of mycobacteria which, for want of a better name, are called " atypical acid-fast bacilli." These bacilli are not new,l2 but in recent years they seem to have been recognised much more commonly. In man they are associated with pulmonary lesions, often serious and progressive, which in every way resemble typical pulmonary tuberculosis 3 ; but unhappily their response to most antituberculous drugs is poor. It is not yet certain whether these organisms comprise a homogeneous group or several different types. They differ from typical tubercle bacilli not only in their drug-sensitivity pattern but also in being chromogenic, and in showing greater catalase activity, poor cord formation, a negative neutral-red reaction, and avirulence for guineapigs. Usually they can be distinguished from typical acid-fast saprophytes by a rather slower growth. rate, especially at room-temperature (though they grow faster than typical tubercle bacilli) and by the type of lesions in certain laboratory animals. Wolinsky et al.3 found that in each of three cases of infection by these organisms in man, the strains produced orange or yellow pigment ; but in two they did so only in light. Crow et awl. describe 69 such cases, in which the organisms seemed to fall into three main groups judged by growth on Löwenstein-Jensen medium. In 64 cases the strains smooth, produced slow-growing buff colonies which became orange as the cultures aged ; in 3 the strains were more chromogenic but otherwise similar; and in 2 the strains gave rough colonies similar to those of Mycobacterium tuberculosis except that they grew much more rapidly-though not so rapidly as recognised acidfast saprophytes. Pathologically, according to Crow et al., these organ. isms give rise to lesions differing in no way from those due to typical tubercle bacilli; but the disease is less readily communicated : in none of their 69 cases was more than one member of a household known to be infected. On the other hand, the response to antituberculous treatment is disappointing: of 56 cases reviewed by Crow et al. only a third showed sputum conversion on chemotherapy. These studies and others 5-7 make it clear that atypical acid-fast bacilli present a fairly serious problem. It can hardly be doubted that infections with these organisms have become more prevalent since chemotherapy has been widely used ; and conceivably they represent mutants induced or selected by chemotherapy - a hypothesis that seems to be supported by the partial resistance of most strains to antituberculous drugs. Thus, incomplete treatment of tuberculosis due to drugsensitive typical bacilli may carry the danger of fostering these drug-resistant atypical forms, though so far this has by no means been proved. Meanwhile infections with these atypical organisms should, it seems, be treated as are infections with typical bacilli; and. despite their seemingly lesser infectivity, public-health measures should be applied no less rigorously than is usual in tuberculosis. Branch, A. Tubercle, Lond. 1933, 14, 337. Pinner, M. Amer. Rev. Tuberc. 1935, 32, 424, 440. Wolinsky, E., Smith, M. M., Mitchell, R. S., Steenken, W. jun. Ibid, 1957, 75, 180. 4. Crow, H. E., King, C. T., Smith, C. E., Corpe, R. F., Stergus, I. Ibid, p. 199. 5. Timpe, A., Runyon, E. H. J. Lab. clin. Med. 1954, 44, 202; see Lancet, 1955, ii, 758. 6. Wilson, G. C., Morton, D. E. Amer. Rev. Tuberc. 1956, 73, 351. 7. Tarshis, M. S., Frisch, A. W. Ibid, 1952, 65, 278, 289, 302. 1. 2. 3.