- Email: [email protected]
WARTS AGAIN
933 the second generation would, if true. be an the inheritance of acquired characters, though example of of a special kind siuue t1 characters have been acquired 11,B the use of genetic material. The findings sus’gest that the chromosomes, instead of forming exaet replicas of themselves as they grow to dividing before cell division, are ready to assimilate foreign and slightly different forms of nucleic acid. Apar1 from their theoretical interest, the findings suggest important longterm prospects of treating and even curing genetically determined abnormalities. It should be noted, however, that Professor Benoit and his (’leagues stressed that these were preliminary reports, and judgment must be suspended until more experiments have been made and the results confirmed in other laboratories. One obvious precaution is that the strain of Peking ducks used in the experiments should be inbred without treatment. to make sure that they do not contain rec"sive genes ; for these might have some of the effects attributed to D.N.A. The effects of f.N.A. from blood-cells only should be studied, as testicular material might perhaps contain hormones affecting body shape and feather colour. The reverse experiment should be tried of injecting khaki-Campbell ducklings with D.N.A. from the Peking strain. In addition. it is important to trace what happens to D.N.A. injected intraperitoneally. The effects
on
THE FLUORIDATION
DEBATE IN NEW ZEALAND
ANOTHER thick volume has been added to the already considerable literature on fluoridation of water-supplies in the prophylaxis of dental caries. The latest contribution is the reportof a commission appointed by the New Zealand Government to consider whether fluoridation would be likely to help in combating dental decay, whether fluoridation would involve any danger to the general health of the public, whether the local authorities were the most suitable bodies to decide whether or not to initiate such schemes in each locality, and whether such schemes could be validly considered to infringe human rights or the liberty of the citizen. The commission, composed of a judge, a biochemist, and a non-scientific layman, reviewed all the available evidence on the first two questions, and drew the well-nigh inevitable conclusion that bringing the concentration of fluoride in public water-supplies artificially to one part in a million would almost certainly reduce dental decay in the population enough to justify the cost of the measure, and that such a low concentration would be very unlikely to result in fluoride poisoning of anyone drinking the water.
In addition to examining the results of all surveys and schemes of fluoridation in the United States and Canada, the commission held several public inquiries, at which objectors to fluoridation as a public-health Similar measure were able to state their case fully. objections were raised to those that were voiced here when it was proposed to initiate ten-year fluoridation experiments in various parts of this country. Apart from a supposed inherent danger to general health, probably the most important objection was that to tamper with the public water-supply would be tantamount to an infringement of the right of each citizen to pure water. The commission did not accept this view, on the ground that, though the right to unadulterated water was undeniable, puhlic water was seldom piped in its natural condition but was treated in one way or another beforehand. As to consume water long as no individual was containing any substance to which he objected, the treatment of supplies could not be held to infringe his right" in any way. Apparently this judgment was based on the view that few citizens of New Zealand would be without access to alternative sources of water from
experimental
compelled
1. Report of the Commission of
Inquiry on the Fluoridation of Government printer, Wellington, New 1957. Pp. 240. 8s.
Public Water Supplies. Zealand,
springs
or
wells if
they objected
to
drinking public
water. that The commission recommended fluoridation schemes should be started with as little delay as possible, and it concluded that the local authorities should carry these out. WARTS AGAIN "
vile excrescences," continue to exasWARTS, these perate the busy doctor and to intrigue him into speculation in moments of detachment. Their transmissibility is beyond question, and a virus is probably the culprit. Further definition is thwarted by the germ’s obstinate preference for human skin and its stout refusal of all substitutes. Clinical studies 12 point to the existence of two breeds of wart virus, and it is claimed that there are genuine the warts produced histological differences between 3 Pullar and them. Cochrane by support this view, having studied independently the clinical aspect and histological character of 400 warts in 164 patients. In 20% of cases, eosinophilic intranuclear inclusions are found in the wart cells. These occur almost exclusively in what Pullar and Cochrane call " inclusion warts " which are either solitary or few, painful, and deep, with a domed surface and a hyperkeratotic collar. They are often palmar (plantar warts were excluded from this study) and are commoner in adults than children. They may seem to be septic, but no pus is found on curettage. In the commoner type of warts, which they call " hypertrophic," such inclusions are rarely found. Such warts are more superficial and vegetating, often multiple and painless, and arise mostly in children. Inclusion bodies in warts have been described by many authors over the past half-century ; but there is no common agreement on what is significant. Blank,4for example, ignores all but the basophilic obliteration of the finer structure of the epidermal nuclei, but this is present in only a proportion of warts of all kinds. Lyell and Miles2 favour the eosinophilic body as the significant structure, while earlier observers were impressed by the intracytoplasmic structures which are so striking in many warts. The last word clearly remains to be said on the nature and specificity of these different structures, the correlation, if any, between them, and their relation to general histological pattern, clinical aspect, and site. There is also room for further inoculation experiments in in volunteers, order to decide whether the described differences in clinical appearance and histological character are constant and (presumably) a specific effect of the different viruses and not determined by age or site. This has been tried, but only on a small scale and with equivocal results. Pullar and Cochrane 3 also record their results in experiments using the chorioallantoic membrane of the developing hen’s egg. This was separately inoculated with cell-free filtrates of warts and extracts of normal skin. In a third series, pieces of normal skin were grafted on to the egg-membrane and then inoculated with wartfiltrates. Although interesting changes were observed, no differences were seen between preparations using filtrates from the two types of wart, and no inclusion bodies were found in any ; from which it may be inferred that neither type of wart was transmitted. Epidermal cells cornify as they ascend the epidermis. Even if cornification is abnormal in wart-infested cells, the virus must be able to survive in dead epithelial squames---that is, in some sort of keratin. Is it not possible that the virus can not only survive in keratin but also "
"
Bunting, H., Melnick, J. L. J. invest. Derm. 1950, 15, 433. 2. Lyell, A., Miles, J. A. R. Brit. med. J. 1951, i, 912. 3. Pullar, P., Cochrane, T. Scot. med. J. 1957, 2, 189. 4. Blank, H., Buerk, M., Weidman, F. J. invest. Derm, 1951, 16, 19. 1. Strauss, M. J.,
934 grow in itThis
thought is suggested by the occurrence of multiple warts at a distance from one another and their frequent occurrence on the pressure-bearing part of the sole. Though the sole is a likely area to be injured in daily life, it is also the most heavily protected against trauma by a massive horny layer. It seems improbable that every plantar wart arising in heavily cornified skin is the result of inoculation by a piercing injury of sufficient depth to reach the succulent layers of the epidermis. Does keratin offer a medium for growth of wart virus that might be exploited in the laboratory- .’ Would modification of the keratin render it unpalatable to the virus ??, Could such modification be the ultimate physical explanation of the successful psychotherapy or charming " of warts that have cheerfully survived onslaughts with fire and sword ? "
GASTRIC ACIDITY
gastric function, apart from radiological are used less commonly than they were, for. although they can answer certain definite questions, the information they yield does not, often influence diagnosis, prognosis, or treatment. The simplest way to exclude gastric anacidity is to examine the gastric contents after an appetising meal. Even in patients refractory to small doses of histamine this simple test often reveals the stomach’s power to TESTS
of
examination,
secrete acid.1 If no acid is found in this way, the maximal histamine test2 is the most reliable way of establishing
gastric anacidity. Originally the histamine test of gastric performed with small subcutaneous doses
secretion was of histamine. In the past decade the amount of histamine given has been increased,3 the route changed from subcutaneous to intravenous,34 and the side-effects made more tolerable by the prior intramuscular2 or simultaneous intravenous5 administration of anti-histamines. There is now evidence that the response to large doses of histamine can be used to assess the maximal power of the stomach to secrete acid and that this is usually proportional to the number of parietal cells.6 Although the information obtained by the histamine test is valuable in research, since it can be given a tentative quantitative interpretation, until recently it did not appear to have any special value in diagnosis except in addisonian anaemia.7 There is now a report of its use in the diagnosis of cancer of the stomach.5 The distinction between benign and malignant lesions of the stomach is based on well-known principles. some of which were put on a quantitative basis two decades ago.8 It was suggested that when the lesion was found radiologically to be larger than 4-5 cm. in diameter it should usually be regarded as malignant. When the lesion was smaller the acidity of the gastric contents one hour after taking a test-meal could in principle be of value in diagnosis. If the acidity lay between 0 and 20 mEq. per litre the possibilities of the lesion being malignant or simple were about eclual ; if the acidity lay between 20 and 40 the chances were 5 to 1 in favour of a simple lesion, and the odds rose to 14 to 1 if the acidity lay between 40 and 60 ineq. per litre. Furthermore, in an American centre the five-year survival of patients diagnosed a8 having cancer of the stomach was found to be greater the higher the gastric acidity. But these facts on acidity are rarely 1. Watkinson, G., James, A. H. Clin. Sci. 1951, 10, 255. Brit. med. J. 1953, ii, 77. 2. Kay, A. W. Amer. J. Physiol. 3. Hanson, M. D., Grossman, M. I.. Ivy. A. C. 1948, 153, 242. 4. Adam, H. M., Caid, W. I., Reddell, M. J., Roberts, M., Strong, J. A., Woolf, B. Brit. J. Pharmacol. 1954. 9, 329. 5. Hirschowitz. B. I., London, J. A., Wiggins, H. S. J. Lab. clin. Med. 1957,50, 417. 6. Card. W. I., Marks, I. N. Cited by W. I. Card and W. Sircus. Modern Trends in Gastroenterology : second series, London, 1957. 7. Card, W. I., Marks, I. N., Sircus, W. J. Physiol. 1955, 130, 18P. Amer. J. Surg. 1937. 35, 515. 8. Comfort, M. W., Butsch. W. L.
useful because most of the acidities for patients with ulcer or gastric cancer fall in the lower ran-’ewhich are common to both groups : and most clinicians in this country would not now endorse the statement that ulcers in the bodv of the stomach more than 4’.’) cm.
gastric
across are
always
malignant.
Hirschowitz et al.5 haveapplied the intravenous hi,tamine test. with an intravenous anti-histamine. to 15 patients with gastric carcinoma and 16 patients with gastric ulcer.5 In patients with gastric ulcer the concentrations of acid and chloride were always higher than HO and 135 mEq. per litre respectively ; but in patients with carcinoma of the stomach the values for acid and chloride were less than 80 and 135 mEq. per litre respectively. Thus in these small groups the results of the test gave an absolute discrimination between those patients with simple and those with malignant ulcers. Hirschowitz et al. themselves point out the smallne"t: of their two groups and also remark that the patients with cancer had advanced disease. There is thus no evidence in their paper that the The underlying abnormality test does aid diagnosis. low for the concentrations of acid and chloride responsible in the patients with gastric cancer is likely to be of more interest to the clinical physiologist than to those looking after the patient. Clinicians in this country have for some years been using the maximum histamine test with intramuscular injections of anti-histamine.27 Card et al. found not a single instance of anacidity in 500 tests, except in patients with addisonian a.na’mia -and 1 patient with hypopituita,rism.9 The mean amount of acid secreted per hour by patients with gastric cancer was less than half the usual amount. Card believes that a value which is clearly higher than the mean for normal subjects-i.e.. above 20 mEq. per hour-can be taken almost to exclude carcinoma.9 "
"
"
NOBEL PRIZE FOR CHEMISTRY
Sir Alexander Todd. who receives the Xobel prize tor chemistry, has worked especially on the structure and synthesis of substances of biological significance. In the early 1930s he and Robinson accomplished the syuthesis of the anthocyanin pigments of plants, and later, ill Barger’s laboratory, Todd made valuable observations on the structure of vitamin B , and particularly of the thiochrome that can be obtained from it by oxidation. He then turned his attention to the substances having vitamin-E activity (tocopherols). and from the Lister Institute published researches on the structure of these
vitamins. More recently he has concerned himself with the structure of nucleic acids and related substances. and his synthetic flair has led to the development of methods resulting in the synthesis of adenosine triphoswhich are of great phate and adenosine in reactions. His work on the importance biological structures of nucleotides, nucleosides. and other substances related to the nucleic acids brings the synthesis of nucleic acids themselves within the bounds of }108’
diphosphate,
sibility. During the past few years Todd and his colleagues Cambridge have been investigating also the structure
at 01
vitamin B12, and. thanks to their close association BBith Dr. Dorothy Crowfoot Hodgkin’s crystallographic studies at Oxford, structures for substances with this important vitamin activity have been provided. We maBhope that. at 50. Sir Alexander has manyfruitful years betore him in synthetic organic chemistry. .
Sir SIMON MARKS, a member of the court of patrons and a benefactor of the Hoyal College of Surgeons of Emland. has made a further contribution to the emllege funds so that work on the new buildings may be resumed. Details cc-ill be found
on
a
956
9. Card. W. I., Sircus, W.
Unpublished.
on
THE FLUORIDATION
DEBATE IN NEW ZEALAND
ANOTHER thick volume has been added to the already considerable literature on fluoridation of water-supplies in the prophylaxis of dental caries. The latest contribution is the reportof a commission appointed by the New Zealand Government to consider whether fluoridation would be likely to help in combating dental decay, whether fluoridation would involve any danger to the general health of the public, whether the local authorities were the most suitable bodies to decide whether or not to initiate such schemes in each locality, and whether such schemes could be validly considered to infringe human rights or the liberty of the citizen. The commission, composed of a judge, a biochemist, and a non-scientific layman, reviewed all the available evidence on the first two questions, and drew the well-nigh inevitable conclusion that bringing the concentration of fluoride in public water-supplies artificially to one part in a million would almost certainly reduce dental decay in the population enough to justify the cost of the measure, and that such a low concentration would be very unlikely to result in fluoride poisoning of anyone drinking the water.
In addition to examining the results of all surveys and schemes of fluoridation in the United States and Canada, the commission held several public inquiries, at which objectors to fluoridation as a public-health Similar measure were able to state their case fully. objections were raised to those that were voiced here when it was proposed to initiate ten-year fluoridation experiments in various parts of this country. Apart from a supposed inherent danger to general health, probably the most important objection was that to tamper with the public water-supply would be tantamount to an infringement of the right of each citizen to pure water. The commission did not accept this view, on the ground that, though the right to unadulterated water was undeniable, puhlic water was seldom piped in its natural condition but was treated in one way or another beforehand. As to consume water long as no individual was containing any substance to which he objected, the treatment of supplies could not be held to infringe his right" in any way. Apparently this judgment was based on the view that few citizens of New Zealand would be without access to alternative sources of water from
experimental
compelled
1. Report of the Commission of
Inquiry on the Fluoridation of Government printer, Wellington, New 1957. Pp. 240. 8s.
Public Water Supplies. Zealand,
springs
or
wells if
they objected
to
drinking public
water. that The commission recommended fluoridation schemes should be started with as little delay as possible, and it concluded that the local authorities should carry these out. WARTS AGAIN "
vile excrescences," continue to exasWARTS, these perate the busy doctor and to intrigue him into speculation in moments of detachment. Their transmissibility is beyond question, and a virus is probably the culprit. Further definition is thwarted by the germ’s obstinate preference for human skin and its stout refusal of all substitutes. Clinical studies 12 point to the existence of two breeds of wart virus, and it is claimed that there are genuine the warts produced histological differences between 3 Pullar and them. Cochrane by support this view, having studied independently the clinical aspect and histological character of 400 warts in 164 patients. In 20% of cases, eosinophilic intranuclear inclusions are found in the wart cells. These occur almost exclusively in what Pullar and Cochrane call " inclusion warts " which are either solitary or few, painful, and deep, with a domed surface and a hyperkeratotic collar. They are often palmar (plantar warts were excluded from this study) and are commoner in adults than children. They may seem to be septic, but no pus is found on curettage. In the commoner type of warts, which they call " hypertrophic," such inclusions are rarely found. Such warts are more superficial and vegetating, often multiple and painless, and arise mostly in children. Inclusion bodies in warts have been described by many authors over the past half-century ; but there is no common agreement on what is significant. Blank,4for example, ignores all but the basophilic obliteration of the finer structure of the epidermal nuclei, but this is present in only a proportion of warts of all kinds. Lyell and Miles2 favour the eosinophilic body as the significant structure, while earlier observers were impressed by the intracytoplasmic structures which are so striking in many warts. The last word clearly remains to be said on the nature and specificity of these different structures, the correlation, if any, between them, and their relation to general histological pattern, clinical aspect, and site. There is also room for further inoculation experiments in in volunteers, order to decide whether the described differences in clinical appearance and histological character are constant and (presumably) a specific effect of the different viruses and not determined by age or site. This has been tried, but only on a small scale and with equivocal results. Pullar and Cochrane 3 also record their results in experiments using the chorioallantoic membrane of the developing hen’s egg. This was separately inoculated with cell-free filtrates of warts and extracts of normal skin. In a third series, pieces of normal skin were grafted on to the egg-membrane and then inoculated with wartfiltrates. Although interesting changes were observed, no differences were seen between preparations using filtrates from the two types of wart, and no inclusion bodies were found in any ; from which it may be inferred that neither type of wart was transmitted. Epidermal cells cornify as they ascend the epidermis. Even if cornification is abnormal in wart-infested cells, the virus must be able to survive in dead epithelial squames---that is, in some sort of keratin. Is it not possible that the virus can not only survive in keratin but also "
"
Bunting, H., Melnick, J. L. J. invest. Derm. 1950, 15, 433. 2. Lyell, A., Miles, J. A. R. Brit. med. J. 1951, i, 912. 3. Pullar, P., Cochrane, T. Scot. med. J. 1957, 2, 189. 4. Blank, H., Buerk, M., Weidman, F. J. invest. Derm, 1951, 16, 19. 1. Strauss, M. J.,
934 grow in itThis
thought is suggested by the occurrence of multiple warts at a distance from one another and their frequent occurrence on the pressure-bearing part of the sole. Though the sole is a likely area to be injured in daily life, it is also the most heavily protected against trauma by a massive horny layer. It seems improbable that every plantar wart arising in heavily cornified skin is the result of inoculation by a piercing injury of sufficient depth to reach the succulent layers of the epidermis. Does keratin offer a medium for growth of wart virus that might be exploited in the laboratory- .’ Would modification of the keratin render it unpalatable to the virus ??, Could such modification be the ultimate physical explanation of the successful psychotherapy or charming " of warts that have cheerfully survived onslaughts with fire and sword ? "
GASTRIC ACIDITY
gastric function, apart from radiological are used less commonly than they were, for. although they can answer certain definite questions, the information they yield does not, often influence diagnosis, prognosis, or treatment. The simplest way to exclude gastric anacidity is to examine the gastric contents after an appetising meal. Even in patients refractory to small doses of histamine this simple test often reveals the stomach’s power to TESTS
of
examination,
secrete acid.1 If no acid is found in this way, the maximal histamine test2 is the most reliable way of establishing
gastric anacidity. Originally the histamine test of gastric performed with small subcutaneous doses
secretion was of histamine. In the past decade the amount of histamine given has been increased,3 the route changed from subcutaneous to intravenous,34 and the side-effects made more tolerable by the prior intramuscular2 or simultaneous intravenous5 administration of anti-histamines. There is now evidence that the response to large doses of histamine can be used to assess the maximal power of the stomach to secrete acid and that this is usually proportional to the number of parietal cells.6 Although the information obtained by the histamine test is valuable in research, since it can be given a tentative quantitative interpretation, until recently it did not appear to have any special value in diagnosis except in addisonian anaemia.7 There is now a report of its use in the diagnosis of cancer of the stomach.5 The distinction between benign and malignant lesions of the stomach is based on well-known principles. some of which were put on a quantitative basis two decades ago.8 It was suggested that when the lesion was found radiologically to be larger than 4-5 cm. in diameter it should usually be regarded as malignant. When the lesion was smaller the acidity of the gastric contents one hour after taking a test-meal could in principle be of value in diagnosis. If the acidity lay between 0 and 20 mEq. per litre the possibilities of the lesion being malignant or simple were about eclual ; if the acidity lay between 20 and 40 the chances were 5 to 1 in favour of a simple lesion, and the odds rose to 14 to 1 if the acidity lay between 40 and 60 ineq. per litre. Furthermore, in an American centre the five-year survival of patients diagnosed a8 having cancer of the stomach was found to be greater the higher the gastric acidity. But these facts on acidity are rarely 1. Watkinson, G., James, A. H. Clin. Sci. 1951, 10, 255. Brit. med. J. 1953, ii, 77. 2. Kay, A. W. Amer. J. Physiol. 3. Hanson, M. D., Grossman, M. I.. Ivy. A. C. 1948, 153, 242. 4. Adam, H. M., Caid, W. I., Reddell, M. J., Roberts, M., Strong, J. A., Woolf, B. Brit. J. Pharmacol. 1954. 9, 329. 5. Hirschowitz. B. I., London, J. A., Wiggins, H. S. J. Lab. clin. Med. 1957,50, 417. 6. Card. W. I., Marks, I. N. Cited by W. I. Card and W. Sircus. Modern Trends in Gastroenterology : second series, London, 1957. 7. Card, W. I., Marks, I. N., Sircus, W. J. Physiol. 1955, 130, 18P. Amer. J. Surg. 1937. 35, 515. 8. Comfort, M. W., Butsch. W. L.
useful because most of the acidities for patients with ulcer or gastric cancer fall in the lower ran-’ewhich are common to both groups : and most clinicians in this country would not now endorse the statement that ulcers in the bodv of the stomach more than 4’.’) cm.
gastric
across are
always
malignant.
Hirschowitz et al.5 haveapplied the intravenous hi,tamine test. with an intravenous anti-histamine. to 15 patients with gastric carcinoma and 16 patients with gastric ulcer.5 In patients with gastric ulcer the concentrations of acid and chloride were always higher than HO and 135 mEq. per litre respectively ; but in patients with carcinoma of the stomach the values for acid and chloride were less than 80 and 135 mEq. per litre respectively. Thus in these small groups the results of the test gave an absolute discrimination between those patients with simple and those with malignant ulcers. Hirschowitz et al. themselves point out the smallne"t: of their two groups and also remark that the patients with cancer had advanced disease. There is thus no evidence in their paper that the The underlying abnormality test does aid diagnosis. low for the concentrations of acid and chloride responsible in the patients with gastric cancer is likely to be of more interest to the clinical physiologist than to those looking after the patient. Clinicians in this country have for some years been using the maximum histamine test with intramuscular injections of anti-histamine.27 Card et al. found not a single instance of anacidity in 500 tests, except in patients with addisonian a.na’mia -and 1 patient with hypopituita,rism.9 The mean amount of acid secreted per hour by patients with gastric cancer was less than half the usual amount. Card believes that a value which is clearly higher than the mean for normal subjects-i.e.. above 20 mEq. per hour-can be taken almost to exclude carcinoma.9 "
"
"
NOBEL PRIZE FOR CHEMISTRY
Sir Alexander Todd. who receives the Xobel prize tor chemistry, has worked especially on the structure and synthesis of substances of biological significance. In the early 1930s he and Robinson accomplished the syuthesis of the anthocyanin pigments of plants, and later, ill Barger’s laboratory, Todd made valuable observations on the structure of vitamin B , and particularly of the thiochrome that can be obtained from it by oxidation. He then turned his attention to the substances having vitamin-E activity (tocopherols). and from the Lister Institute published researches on the structure of these
vitamins. More recently he has concerned himself with the structure of nucleic acids and related substances. and his synthetic flair has led to the development of methods resulting in the synthesis of adenosine triphoswhich are of great phate and adenosine in reactions. His work on the importance biological structures of nucleotides, nucleosides. and other substances related to the nucleic acids brings the synthesis of nucleic acids themselves within the bounds of }108’
diphosphate,
sibility. During the past few years Todd and his colleagues Cambridge have been investigating also the structure
at 01
vitamin B12, and. thanks to their close association BBith Dr. Dorothy Crowfoot Hodgkin’s crystallographic studies at Oxford, structures for substances with this important vitamin activity have been provided. We maBhope that. at 50. Sir Alexander has manyfruitful years betore him in synthetic organic chemistry. .
Sir SIMON MARKS, a member of the court of patrons and a benefactor of the Hoyal College of Surgeons of Emland. has made a further contribution to the emllege funds so that work on the new buildings may be resumed. Details cc-ill be found
on
a
956
9. Card. W. I., Sircus, W.
Unpublished.