- Email: [email protected]
DENTAL EROSION
1352 tion needed for differentiation must be carried in the cytoplasm. The morphogenetic substance has been identified as messenger R.N.A., which, after leaving the nucleus, migrates to the apex of the stalk. This has been shown by cutting the alga into small pieces: only the apical fragment of stalk can produce a cap, although the nucleus-containing rhizoid can, of course, regenerate and accumulate more messenger R.N.A. at a new apex. The various steps concerned in the control of morphogenesis have been investigated with specific chemical inhibitors. Thus, ribonuclease permanently blocks regeneration of the enucleate half of a divided cell, and it delays regeneration of the nucleate segment: all the existing messenger R.N.A. is destroyed, and replacement takes place only in the nucleate half, after removal of the enzyme. Actinomycin, which prevents synthesis of messenger R.N.A. by combining with its D.N.A. template, prevents regeneration of the nucleate half; but it has no effect on messenger R.N.A. already made, so that the tip of the stalk can continue to form caps. Finally, puromycin, like ribonuclease, prevents regeneration-permanently in enucleate fragments and temporarily in nucleate pieces-but it does so by blocking the assembly of aminoacids into proteins, showing that protein synthesis is required for the development of caps. Continuation of cap formation for three or more weeks in enucleate stalks therefore proves that protein synthesis can be maintained even in the absence of a nucleus. The eggs of sea-urchins and amphibia, because they are easy to handle, have long been the embryologists’ favourite experimental material; and this makes them especially attractive to those interested in the biochemical aspects of cell differentiation, since the fates of cells in the early embryo and the time at which they normally become capable of independent differentiation are very precisely known. In both sea-urchin and amphibian eggs protein synthesis can continue in enucleate half-cells which have been artificially activated, and such cells can develop to the blastula stage. Unfertilised whole eggs treated with actinomycin (which means, in effect, chemical enucleation, because all D.N.A.-dependent synthesis is eliminated) can also reach this stage, whereas puromycin stops development immediately. Thus, in these animals, as in Acetabularia, morphogenesis depends on protein synthesis, which in turn depends on the presence of messenger R.N.A. One curious problem of embryogenesis, which has been studied in detail in the sea-urchin egg, is why the mature unfertilised egg cannot manufacture proteins, whereas activation by an artificial stimulus (which rules out any specific contribution from the sperm) is immediately followed by rapid protein synthesis. The unfertilised egg contains messenger R.N.A., and at least some of it appears to be already attached to the ribosomes. Its synthesising potential can be released by treatment with trypsin-perhaps by removal of a protein coat. Something similar may happen in normal activation, for fertilisation is rapidly followed by production of proteolytic enzymes; but how this mechanism is stimulated is not clear. In the amphibian egg R.N.A. synthesis begins soon after fertilisation, and polysomes (ribosomes plus attached messenger R.N.A.) soon become distributed along the primary polarity gradient already present in the unfertilised egg. At gastrulation a new, more dynamic, gradient spreads from the dorsal to the ventral side; and interaction of the two R.N.A. gradients, together with synthesis of fresh R.N.A., results in a dorsoventral and a cephalocaudal gradient in the late gastrula or early neurula. The high
gradients coincide at the dorsal lip-the centre of greatest morphogenetic activity and protein synthesis-and disorganisation of the gradients by chemical or physical means always produces developmental points of the
two
abnormalities. These examples of progress in biochemical embryology are encouraging, though we are still a long way from solving the real problem of morphogenesis-how the activity of messenger R.N.A., controlled by localised gene action, leads to the differentiation of organs and tissues, But that will have to wait until the advent of molecular
embryology.
DENTAL EROSION
EROSION of the dental enamel, which usually affects the labial surfaces of the upper incisors, is the result of continued exposure to acids, either directly or as a consequence of air pollution. In people who drink fresh lemon juice daily as part of a slimming diet or for other reasonsI and in children who are too keen on fruit squashes and acid ice-lolliesthe acid comes into direct contact with the enamel. In workers employed in industries that use acid processes, such as the manufacture of munitions and health-salts, and galvanising,3the enamel is attacked indirectly. In both groups there is gradual loss of enamel and then of dentine from the surface, leaving the tooth smooth and often prone to discoloration. The teeth become shorter from the incisal edge, leaving a space between them and the lower incisors. Biting becomes difficult, and the cosmetic result is poor. The reportof the industrial diseases subcommittee of the Industrial Injuries Advisory Council disappointingly recommends that tooth erosion caused by industrial acid should not be designated as an industrial disease, on the ground that the erosion is trivial because it affects only the front teeth and causes no loss of function. The cosmetic disability, the report argues, is small; yet in some cases the loss of tooth substance needs complete crown restoration or extraction. Much of the report was based on a survey by Mr. H. J. ten Bruggen Cate, of Manchester, which disclosed a high prevalence of erosion of the labial surfaces of the upper incisors of men engaged in the manufacture of batteries, munitions, and in industrial pickling. Almost half had some evidence of erosion and in 9% it was severe. The defect seemed to cause the workers little concern; but the general dental state was poor. All the workers examined were men; and if some women in occupations known to cause erosion (such as the manufacture of health-salts) had been asked, they might have been less indifferent. The erosion can be remedied by means of porcelain inlays or porcelain jacket crowns; by removal of the nerve and the provision of a post-crown; or by extraction and provision of a bridge or a denture. The report goes on to say that these "are theoretically available under the National Health Service". This is true, but, in fact, the fitting of bridges is a specialised form of conservation not readily obtainable everywhere; and many dentists allege that the Estimates Board seldom gives approval for the 1. 2.
Allan, D. N. Unpublished data. Holloway, P. J., Mellanby, M., Stewart,
R.
J. C. Br. dent. J. 1958. 104,
305. 3.
4.
Boyes, J., Hartles, R. L., Slack, G. L., Stones, H. H., Steel, J. ibid. 1959, 106, 239. Report of the Industrial Injuries Advisory Council. Cmnd 3314. H.M. Stationery Office, 1966. 1s. 9d.
1353 work. As
to crowns,
the fee allowed is
not
regarded
as an
economic one by most dentists, and they say that they cannot afford to undertake this type of work. The likely the end is extraction of the damaged teeth and the fitting of a denture. One of the arguments advanced in the report against the designation of dental erosion as an industrial disease is the difficulty of disposing of doubtful claims for dental services. But if the disability were assessed on the life expectancy of the dentition as a whole, the finding of a neglected mouth would rule out conservation. Such a patient would have to have full dentures early, regardless of the erosion. The subcommittee was not unanimous in its opinion, so we hope that the subject may be outcome in
reconsidered.
ALCOHOL AND THE PANCREAS
THERE is a definite association between alcoholism and chronic pancreatitis, but the mechanism of this link is obscure. Certainly, one or two whiskies are unlikely to impair pancreatic secretion; in fact, intravenous alcohol in dogs stimulates secretion.’I Alcohol encourages the production of hydrochloric acid by the stomach, and that in turn releases secretin from the duodenum, followed by increased pancreatic secretion, and after total gastrectomy, alcohol given by mouth or intravenously has no effect on the volume of pancreatic juice.2 One suggestion was that pressure in the pancreatic duct may rise high enough to produce pancreatitis if there is coincidental obstruction by oedema of the papilla or spasm of the sphincter of Oddi, such as may accompany the gastroduodenitis often produced by alcohol.3 Davis et al .4 have now shown that alcohol given intravenously to healthy people greatly reduced the volume of duodenal aspirate evoked by secretin under strictly controlled conditions; but amylase and bicarbonate concentrations in the aspirate were normal or raised. The effects of intraduodenal alcohol were less striking, but the blood-alcohol levels reached under these conditions The were much less than after an intravenous dose. association of reduced volume with normal or raised enzyme and bicarbonate levels suggests obstruction of the pancreatic duct.5 Oral or intraduodenal alcohol might cause duodenitis and duct obstruction," but intravenous administration would be unlikely to do so. Davis et al. also stimulated pancreatic secretion by a constant infusion of secretin, and they found that intravenous alcohol caused a fall in the volume of duodenal aspirate from 9 ml. to 2 ml. in 5 minutes. Sublingual glyceryl trinitrate then raised the volume to 6 ml. in 5 minutes, suggesting that a readily reversible spasm of the outflow tract may have been responsible. These results suggest that the effects of acute administration of alcohol are due to obstruction of the pancreatic duct, and that this action is more closely related to blood-alcohol level than to the route of administration. 1. Walton, B. E., Schapiro, H., Woodward, E. R. Am. Surg. 1962, 28, 443. 2. Preston, F. W., Kukral, J. C. Surg. Clin. N. Am. 1962, 42, 203. 3. Cecil and Loeb’s Textbook of Medicine (edited by P. B. and W. McDermott). Philadelphia, 1963. 4. Davis, A. E., Pirola, R. C., Blagonravoff, L. Med. J Aust. 1966, ii, 757. 5 Dreiling, D. A., Janowitz, H. D Ciba Foundation Symposium on the Exocrine Pancreas (edited by A. V. S. de Reuck and M. P. Cameron). London, 1962 6. Dreiling, D. A., Richman, A., Fradkin, N. T. Gastroenterology, 1952, 20, 636.
The relevance of these findings to chronic pancreatitis is unknown. One difficulty is that chronic alcoholism is often associated with chronic gastritis and achlorhydria, which would abolish the acid-secretin secretory reflex in the pancreas. Moreover, though a long-continued increase in pancreatic-duct pressure sounds a likely cause of chronic pancreatitis, many workers disagree about this. While it can be shown that continued pancreatic secretion against an obstructed duct leads to a rise in serum-amylase levelsthis does not necessarily imply acinar necrosis, for the blood levels of amylase are determined by the sum of the processes of production and elimination; and if the elimination is restricted, the blood level rises. McCutcheon, summarising the evidence against the obstruction hypothesis, pointed to the fact that obstruction of the major pancreatic duct in cats, dogs, and rabbits causes atrophy of acini with preservation of the islets of Langerhans, but not pancreatitis 8; and, according to Thal et al.,9 experiments in which maximum secretory activity was provoked in the presence of complete duct obstruction failed to produce pancreatic necrosis. Nevertheless, these observations have been concerned largely with the production of acute pancreatitis, and their relevance to the chronic state is questionable. Chemical as well as mechanical factors may operate. For example, an excess of ethyl radicals may compete with methyl groups in a metabolic pathway analogous to that followed when the administration of ethionine to experimental animals is associated with severe pancreatic necrosis.3 10
OBESITY IN CHILDHOOD
COMMENTING 11 on the treatmemt of obesity in childhood, we remarked that most obese children grow into even more obese adults. But some do not, and in a survey Grant 12 has tried to distinguish between obesity in children which was likely to be temporary and that which would persist into adult life. Growth records of about 1000 English children showed that somatic types were remarkably constant over the whole period from below 8 to over 14 years of age. There was an average gain of 10% in weight with every 2 inches gained in height, and this was observed in children varying from l5O/., underweight to 15’% overweight. Progressive obesity resulted when a gain in weight of more than 10%, was maintained for eight or more years. A few children had transient obesity which was different from progressive obesity in its abrupt onset, high initial rate of gain, and rapid slowing down with a gradual return to the previous physique. The constancy of the individual growth-rates over long periods suggests that internal constitutional factors rather than environment play the biggest part in their production. It also suggests that short-term treatment with drugs or psychotherapy is unlikely to be of permanent value. The best chance of prophylactic success in preventing progressive obesity may be found in detecting growth-rates in excess of 10%, at the earliest opportunity, and regulating dietary intake from this stage to maintain them at or below this critical level. 7. 8. 9. 10. 11. 12.
McCutcheon, A. D. Lancet, 1962, i, 710. Wang, C., Strauss, L., Adlersberg, D. Gastroenterology, 1958, 35, Thai, A., Perry, J. F., Egner, W. Surgery Gynec. Obstet. 1957, 105, Meister, A. Biochemistry of the Ammo-acids. New York, 1965. Lancet, Aug. 6, 1966, p 327. Grant, M W. Med. Offr 1966, 115, 331
465. 191.
gradients coincide at the dorsal lip-the centre of greatest morphogenetic activity and protein synthesis-and disorganisation of the gradients by chemical or physical means always produces developmental points of the
two
abnormalities. These examples of progress in biochemical embryology are encouraging, though we are still a long way from solving the real problem of morphogenesis-how the activity of messenger R.N.A., controlled by localised gene action, leads to the differentiation of organs and tissues, But that will have to wait until the advent of molecular
embryology.
DENTAL EROSION
EROSION of the dental enamel, which usually affects the labial surfaces of the upper incisors, is the result of continued exposure to acids, either directly or as a consequence of air pollution. In people who drink fresh lemon juice daily as part of a slimming diet or for other reasonsI and in children who are too keen on fruit squashes and acid ice-lolliesthe acid comes into direct contact with the enamel. In workers employed in industries that use acid processes, such as the manufacture of munitions and health-salts, and galvanising,3the enamel is attacked indirectly. In both groups there is gradual loss of enamel and then of dentine from the surface, leaving the tooth smooth and often prone to discoloration. The teeth become shorter from the incisal edge, leaving a space between them and the lower incisors. Biting becomes difficult, and the cosmetic result is poor. The reportof the industrial diseases subcommittee of the Industrial Injuries Advisory Council disappointingly recommends that tooth erosion caused by industrial acid should not be designated as an industrial disease, on the ground that the erosion is trivial because it affects only the front teeth and causes no loss of function. The cosmetic disability, the report argues, is small; yet in some cases the loss of tooth substance needs complete crown restoration or extraction. Much of the report was based on a survey by Mr. H. J. ten Bruggen Cate, of Manchester, which disclosed a high prevalence of erosion of the labial surfaces of the upper incisors of men engaged in the manufacture of batteries, munitions, and in industrial pickling. Almost half had some evidence of erosion and in 9% it was severe. The defect seemed to cause the workers little concern; but the general dental state was poor. All the workers examined were men; and if some women in occupations known to cause erosion (such as the manufacture of health-salts) had been asked, they might have been less indifferent. The erosion can be remedied by means of porcelain inlays or porcelain jacket crowns; by removal of the nerve and the provision of a post-crown; or by extraction and provision of a bridge or a denture. The report goes on to say that these "are theoretically available under the National Health Service". This is true, but, in fact, the fitting of bridges is a specialised form of conservation not readily obtainable everywhere; and many dentists allege that the Estimates Board seldom gives approval for the 1. 2.
Allan, D. N. Unpublished data. Holloway, P. J., Mellanby, M., Stewart,
R.
J. C. Br. dent. J. 1958. 104,
305. 3.
4.
Boyes, J., Hartles, R. L., Slack, G. L., Stones, H. H., Steel, J. ibid. 1959, 106, 239. Report of the Industrial Injuries Advisory Council. Cmnd 3314. H.M. Stationery Office, 1966. 1s. 9d.
1353 work. As
to crowns,
the fee allowed is
not
regarded
as an
economic one by most dentists, and they say that they cannot afford to undertake this type of work. The likely the end is extraction of the damaged teeth and the fitting of a denture. One of the arguments advanced in the report against the designation of dental erosion as an industrial disease is the difficulty of disposing of doubtful claims for dental services. But if the disability were assessed on the life expectancy of the dentition as a whole, the finding of a neglected mouth would rule out conservation. Such a patient would have to have full dentures early, regardless of the erosion. The subcommittee was not unanimous in its opinion, so we hope that the subject may be outcome in
reconsidered.
ALCOHOL AND THE PANCREAS
THERE is a definite association between alcoholism and chronic pancreatitis, but the mechanism of this link is obscure. Certainly, one or two whiskies are unlikely to impair pancreatic secretion; in fact, intravenous alcohol in dogs stimulates secretion.’I Alcohol encourages the production of hydrochloric acid by the stomach, and that in turn releases secretin from the duodenum, followed by increased pancreatic secretion, and after total gastrectomy, alcohol given by mouth or intravenously has no effect on the volume of pancreatic juice.2 One suggestion was that pressure in the pancreatic duct may rise high enough to produce pancreatitis if there is coincidental obstruction by oedema of the papilla or spasm of the sphincter of Oddi, such as may accompany the gastroduodenitis often produced by alcohol.3 Davis et al .4 have now shown that alcohol given intravenously to healthy people greatly reduced the volume of duodenal aspirate evoked by secretin under strictly controlled conditions; but amylase and bicarbonate concentrations in the aspirate were normal or raised. The effects of intraduodenal alcohol were less striking, but the blood-alcohol levels reached under these conditions The were much less than after an intravenous dose. association of reduced volume with normal or raised enzyme and bicarbonate levels suggests obstruction of the pancreatic duct.5 Oral or intraduodenal alcohol might cause duodenitis and duct obstruction," but intravenous administration would be unlikely to do so. Davis et al. also stimulated pancreatic secretion by a constant infusion of secretin, and they found that intravenous alcohol caused a fall in the volume of duodenal aspirate from 9 ml. to 2 ml. in 5 minutes. Sublingual glyceryl trinitrate then raised the volume to 6 ml. in 5 minutes, suggesting that a readily reversible spasm of the outflow tract may have been responsible. These results suggest that the effects of acute administration of alcohol are due to obstruction of the pancreatic duct, and that this action is more closely related to blood-alcohol level than to the route of administration. 1. Walton, B. E., Schapiro, H., Woodward, E. R. Am. Surg. 1962, 28, 443. 2. Preston, F. W., Kukral, J. C. Surg. Clin. N. Am. 1962, 42, 203. 3. Cecil and Loeb’s Textbook of Medicine (edited by P. B. and W. McDermott). Philadelphia, 1963. 4. Davis, A. E., Pirola, R. C., Blagonravoff, L. Med. J Aust. 1966, ii, 757. 5 Dreiling, D. A., Janowitz, H. D Ciba Foundation Symposium on the Exocrine Pancreas (edited by A. V. S. de Reuck and M. P. Cameron). London, 1962 6. Dreiling, D. A., Richman, A., Fradkin, N. T. Gastroenterology, 1952, 20, 636.
The relevance of these findings to chronic pancreatitis is unknown. One difficulty is that chronic alcoholism is often associated with chronic gastritis and achlorhydria, which would abolish the acid-secretin secretory reflex in the pancreas. Moreover, though a long-continued increase in pancreatic-duct pressure sounds a likely cause of chronic pancreatitis, many workers disagree about this. While it can be shown that continued pancreatic secretion against an obstructed duct leads to a rise in serum-amylase levelsthis does not necessarily imply acinar necrosis, for the blood levels of amylase are determined by the sum of the processes of production and elimination; and if the elimination is restricted, the blood level rises. McCutcheon, summarising the evidence against the obstruction hypothesis, pointed to the fact that obstruction of the major pancreatic duct in cats, dogs, and rabbits causes atrophy of acini with preservation of the islets of Langerhans, but not pancreatitis 8; and, according to Thal et al.,9 experiments in which maximum secretory activity was provoked in the presence of complete duct obstruction failed to produce pancreatic necrosis. Nevertheless, these observations have been concerned largely with the production of acute pancreatitis, and their relevance to the chronic state is questionable. Chemical as well as mechanical factors may operate. For example, an excess of ethyl radicals may compete with methyl groups in a metabolic pathway analogous to that followed when the administration of ethionine to experimental animals is associated with severe pancreatic necrosis.3 10
OBESITY IN CHILDHOOD
COMMENTING 11 on the treatmemt of obesity in childhood, we remarked that most obese children grow into even more obese adults. But some do not, and in a survey Grant 12 has tried to distinguish between obesity in children which was likely to be temporary and that which would persist into adult life. Growth records of about 1000 English children showed that somatic types were remarkably constant over the whole period from below 8 to over 14 years of age. There was an average gain of 10% in weight with every 2 inches gained in height, and this was observed in children varying from l5O/., underweight to 15’% overweight. Progressive obesity resulted when a gain in weight of more than 10%, was maintained for eight or more years. A few children had transient obesity which was different from progressive obesity in its abrupt onset, high initial rate of gain, and rapid slowing down with a gradual return to the previous physique. The constancy of the individual growth-rates over long periods suggests that internal constitutional factors rather than environment play the biggest part in their production. It also suggests that short-term treatment with drugs or psychotherapy is unlikely to be of permanent value. The best chance of prophylactic success in preventing progressive obesity may be found in detecting growth-rates in excess of 10%, at the earliest opportunity, and regulating dietary intake from this stage to maintain them at or below this critical level. 7. 8. 9. 10. 11. 12.
McCutcheon, A. D. Lancet, 1962, i, 710. Wang, C., Strauss, L., Adlersberg, D. Gastroenterology, 1958, 35, Thai, A., Perry, J. F., Egner, W. Surgery Gynec. Obstet. 1957, 105, Meister, A. Biochemistry of the Ammo-acids. New York, 1965. Lancet, Aug. 6, 1966, p 327. Grant, M W. Med. Offr 1966, 115, 331
465. 191.