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CANCER CLUES
392 NASHsuggests that ephedrine may be effective because of its stimulating and sleep-diminishing effect, and not its local action on the bladder. Belladonna and ephedrine have a modern counterpart in methanthelinium bromide (’Banthine’). This very effective ganglion-blocking agent has been shown to abolish the uninhibited contractions that occur in the bladders of some enuretics. But like many effective remedies, methanthelinium will fall into disrepute if used indiscriminately; in enuresis it should be reserved for cases with uninhibited contractions. Whatever the primary cause or causes of enuresis, the immediate fault is the failure to wake when the bladder empties; and a direct attack may be made at this point. Parents often waken the child shortly before they think the wetting is due to take place ; or an alarm-clock may be used for this purpose. These methods are disappointing. But if the full bladder fails to ring a bell figuratively, the emptying bladder may be made to ring a bell actually and so establish a simple conditioned reflex. This
Conversely
7. Nash, D. F. E.
Lancet, 1950, ii, 485.
Annotations THE
THE PITUITARY AND PIGMENTATION pituitary glands of vertebrates secrete a hormone
variously called melanocyte-stimulating hormone (M.s.H.), melanophore-expanding hormone, and intermedin, whose target organs are the pigment cells-principally those of the skin. In amphibia these pigment cells can quickly darken the skin by expanding black tendrils under the direct influence of M.s.H. In mammals the pigment cells are stimulated by to synthesise more melanin, which darkens the skin more slowly than the mechanism in amphibia. Since the original report by Joresin 1933 several workers have demonstrated this activity in human blood; and in this week’s issue Dr. Hudson and Dr. Bentley show that man, like other animals, has melanocyte-stimulating hormone (they prefer to call it melanophore-expanding hormone) in his pituitary. Lerner and his group at Portland, Oregon,2 injected into volunteers large amounts of a preparation of M.s.H. containing very little corticotrophin or other pituitary hormone. They describe specific, if somewhat cumbersome, methods for urinary and blood assay of the hormone.3 This is important, since biological assay on depends changes in colour in isolated frog’s skin, and various substances, contained in blood and urine, which are not pituitary hormones affect the result. Lerner has defined the normal limits for M.s.H. in blood and urine, and has shown these to be the same for men and women and for albino, white, and coloured people. During pregnancy excretion of M.s.H. increases progressively from the eighth or ninth week until term, after which it reverts to normal in a few days. Excretion of M.S.H. was increased in some patients with Addison’s disease, and in others after bilateral adrenalectomy. Cortisone inhibited heavy excretion of M.s.H. Administration of M.s.H. led to darkening of the skin and formation of new pigmented moles-evidence that the hormone causes multiplication of melanocytes as well as increased melanin synthesis. Some deepening of skin colour was detectable as early as ten hours after high doses. It is now clear that skin darkening produced by commercial preparations of corticotrophin is due to contamination by M.s.H. For some time it was difficult to separate these hormones, and it seemed possible that 1. 2. 3.
Jores, A. Z. ges. exp. Med. 1933, 87, 266. Lerner, A. B., Shizumek, K., Bunding, I. 1954, 14, 1463. Shizume, K., Lerner, A. B. Ibid, p. 1471.
J. clin. Endocrin.
method is perfectly sound, provided that all known factors are also treated and organic disease is excluded. The patient lies on a pad containing an open electrical circuit which is closed immediately the pad is wetted by an electrolytic solution (urine), and this rings a bell. This method, introduced some years ago in the U .8.A., has been tested in this country by DAvIDSoN and DOUGLASS 9 ; and last year BOSTOCK 10 reported from Australia that it had proved successful in 8 out of 12 patients. The method has several disadvantages. The apparatus is expensive, complex, and delicate, and it can be used by only one patient at a time ; the method requires the intelligent cooperation of the child ; and establishing the conditioned reflex may take many weeks. Nevertheless, this method, based on such sound physiological principles, has much to commend it. We are not so well equipped to treat enuresis that we can ignore any promising
technique. 8. Mowrer, O. H. Amer. J. Psychiat. 1938, 51, 163. Mowrer, O. Mowrer, W. M. Amer. J. Orthopsychiat. 1938, 8, 436. 9. Davidson, J. R., Douglass, E. Brit. med. J. 1950, i, 1345. 10. Bostock, J. Med. J. Aust. 1954, ii, 141.
H.,
corticotrophin and M.S.H. were one and the same.4 But M.s.H., unlike corticotrophin, is stable to alkali.5 Complete separation of the activities is difficult, and the purest M.S.H. may possibly have a slight intrinsic corticotrophin-like effect.6 Are these two in fact separated in Nature ? In man, at any rate, they may not be.’ Many states associated with general increase in pigmentation are known to be associated also with increased production of corticotrophin, and adrenal cortical hormones inhibit both corticotrophin and M.S.H.2 There is still no good evidence that M.s.H. causes such pigmentary disturbances as melanomatosis, retinitis pigmentosa, or vitiligo. In man this hormone seems to be a kind of endocrine vestige, of little importance to metabolism and survival but of great interest to phys-
corticotrophin,
icians because it is the inseparable twin of and hence in certain conditions skin pigmentation is a guide to corticotrophin production. Much remains to be learnt. Is there in man a melanocyte-inhibiting hormone analogous to that described for fish by Enami,8 and foreshadowed by the earlier work of Hogben ?9 Does the placenta produce M.s.H., as might be expected if it indeed produces corticotrophin ? 10 At just what stage in melanin synthesis does M.s.H. actWith their methods of assay Dr. Lerner and his colleagues may be able to answer these and other questions. CANCER CLUES
Edgar Allan Poe once wrote of an object being successfully hidden almost literally under the searcher’s nose. Perhaps some vital clues in the cancer mystery may similarly lie under our noses, awaiting discovery an astute observer. There have lately been two reminders of such a possibility-one from Israel and the other from Arizona. Dr. Kalman J. Mann, director of the Hadassah Medical Organisation in Israel, has stated11 that not a single case of lung cancer has been reported among Yemenite Jews in Israel in the last fifteen years. Dr. Mann painted out that these people do not smoke cigarettes but do smoke a narghile-an oriental pipe in which tobacco smoke is drawn through water. An extensive investigation has
by
4. Lancet, 1952, i, 1150. 5. Morris, C. J. O. R. Ibid, p. 1210. 6. Benfey, B. G., Saffran, M., Schally, A. V. Nature, Lond. 1954, 174, 1106. 7. Sulman, F. G. Lancet, 1952, ii, 247. 8. Enami, M. Science, 1955, 121, 36. 9. Hogben, L., Slome, D. Proc. roy. Soc. B. 1931, 108, 10 ; Ibid, 1936, 120, 158. 10. Opsahl, J. C., Long, C. N. H. Yale J. Biol. Med. 1951, 24, 199. 11. New York Times, Feb. 1, 1955.
393 been started, with the purpose of establishing the cause of this remarkable- finding. From Arizona the publichealth commissioner, Dr. Clarence G. Salsbury, has reported 12 somewhat similar findings, with reference to cancer generally, among the Navaho Indians. Apparently In cancer is hardly ever found in the 75,000 Navahos. a study of the records of all hospitals serving these people, Salsbury and his associates discovered in 1953 that 60,000 admissions had included only 208 cases of cancer; and the 118 cases in females included no more than 3 instances of cancer of the breast. Salsbury believes that the Navaho diet may be the key to the comparative lack of cancer. Highly refined foods are absent from the typical diet, which " consists mainly of meat, corn, squash, some fruits and nuts, herbs, native tea andsquaw bread ’-a type of crisp panbread." PIONEERS IN PSYCHIATRY THREE years after the fall of the Bastille, Philippe Pinel struck the chains from the lunatics in the Paris Bicetre. To the student of medical history-as the discussion at a meeting on Jan. 8 of the section of psychiatry of the Royal Society of Medicine showedhis action is significant not only as a landmark in the development of psychotherapy but also as a reflection of the spirit of his age. Indeed, all his achievements bear witness to the influence of that " Age of Enlightenment." As Prof. Aubrey Lewis pointed out, Pinel realised early the importance of applying the mathematical methods of the exact sciences, then making their appearance in medicine. He was among the first to evaluate the effects of treatment statistically, and to appreciate the need for accurate case-records, regular progress-notes, and carefully controlled therapeutic trials. In the field of psychology Pinel was much indebted to British writers -particularly Locke-and by his humane treatment of the mentally ill he set an example which was followed
throughout Europe. One of Pinel’s most enthusiastic disciples was the versatile James Cowles Prichard, who combined an extensive knowledge of ethnology and philology with an understanding of insanity well in advance of his times. His best-known medical work, the Treatise on Insanity (1835), owed much to French influence, and in particular to Pinel’s brilliant pupil Esquirol. Dr. A. D. Leigh, speaking of Prichard’s contributions to British psychiatry, moral recalled that he was the first to distinguish forms of mental from other disorders-a coniusanity troversial concept that has since received little favour. Prichard showed the influence of his Quaker upbringing in his persistent attempts to secure more humane conditions in asylums, and in his ardent support of the antislavery movement. In 1816 he became physician to the Bristol Infirmary, where his learning, skill, and energy made him well known as a physician with enlightened views on psychiatry. Both Pinel and Prichard had advocated a humane policy in the treatment of the insane ;William Browne, the medical officer of Crichton Royal Hospital, Dumfries, carried this into effect and amplified it with outstanding success. Dr. James Harper, discussing Browne’s thesis, What Asylunts lI’ere, Atie, and What They Ought To Be, showed how closely Browne’s conception of a mental hospital resembled that of modern times. Browne proposed that mental hospitals should be well planned, spacious, and beautiful-"like the palace of a peer "with extensive gardens and fields in which patients could enjoy sunshine and fresh air, and the freedom to which they were entitled. He appreciated to the full the value of occupational therapy : his patients at the Crichton Royal were provided each day with a detailed programme of activities, including games, lectures, dancing, exercises in the open, and even the "
"
12.
Ibid, Dec. 28, 1954.
production of plays. He clinician, keeping copious
an excellent the progress and
was, moreover,
notes
on
treatment of each of his patients, making systematic records of their dreams, and including in each case" history a philosophical analysis of the patient’s mind." Browne held that the staff of mental hospitals should be the companions, friends, and teachers of their patients as well as their guardians ; and he continually recommended " moral treatment of the most extended and exquisite form." In his hands the methods championed by Pinel and Prichard at last found full and practical
expression. CHLORPROMAZINE FOR HICCUP IT is not surprising that chlorpromazine should be tried in the treatment of hiccup ; for the drug powerfully inhibits many central reflexes,l and hiccup may sometimes represent the motor component of a reflex pathway -although there is good evidence that this is not always so.2 Certainly the results now claimed by Friedgood and Ripstein3 are impressive. 50 patients with hiccup attributed to various causes ranging from coronary thrombosis to thoracic, abdominal, and urological operations were treated with chlorpromazine, and in 41 a single intravenous dose of 50 mg. stopped the hiccups. Some of these responses can best be described by the dramatic " ; for example, in a man favoured epithet, aged 57 who had had hiccups for nine days after an operation for cancer of the rectum, the hiccups stopped three minutes after the injection of chlorpromazine and did not return. Chlorpromazine will presumably now take its place in the list of remedies to be tried in the treatment of intractable hiccup. "
WATER ABSORPTION WHEN heavy water is placed in the stomach or small bowel, serial samples of arterial blood show the presence of deuterium within a few minutes. The level of deuterium in the arterial blood reaches a peak at about ten minutes after intestinal administration, but at thirty minutes after gastric administration. The disappearance of intravenously injected deuterium can be estimated, and used to correct the curves obtained after alimentary administration, so giving a measure of the rate of absorption. By such studies Scholer and Code4 estimate that moderate quantities of water placed in the stomach are absorbed at a rate of of the dose per minute ; absorption from the small bowel is much more rapid26-1% per minute. They point out that water in the stomach remains in a "puddle," demonstrable by suspended barium ; whereas water introduced into the intestine is rapidly dispersed over a large mucosal surface. Even allowing for this, the absorptive activity of the small intestine, which has been shown to be an active process,5 is probably greater than that of the stomach ; the demonstration that appreciable water absorption goes on in the stomach confirms in man the findings in isolated gastric pouches in the dog.6 The deuterium method of studying water absorption has been applied to the practical problem of whether to give water by mouth to patients with abdominal and other injuries. This work, reported by Howard,7may have set up a record in long-range collaboration ; for the deuterium was given in Korea and was estimated in Washington, D.C. The assessment of absorption in this study was based, not on the form of the early arterial curves, but on the time taken to reach equilibrium, judged by constancy of the deuterium level in venous
2-5%
1. See Lancet, Feb. 12, 1955, p. 337. 2. Ibid, 1954, i, 661. 3. Friedgood, C. E., Ripstein, C. B. J. Amer. med. Ass. 1955, 157, 309. 4. Scholer, J. F., Code, C. F. Gastroenterology, 1954, 27, 565. 5. Visscher, M. B., Fetcher, E. S., Carr, C. W., Gregor, H. P., Bushey, M. S., Barker, D. E. Amer. J. Physiol. 1944, 142, 550. 6. Cope, O., Blatt, M. H., Ball, M. R. J. clin. Invest. 1943, 22, 111. 7. Howard. J. M. Surg. Gynec. Obstet. 1955, 100, 69.
Conversely
7. Nash, D. F. E.
Lancet, 1950, ii, 485.
Annotations THE
THE PITUITARY AND PIGMENTATION pituitary glands of vertebrates secrete a hormone
variously called melanocyte-stimulating hormone (M.s.H.), melanophore-expanding hormone, and intermedin, whose target organs are the pigment cells-principally those of the skin. In amphibia these pigment cells can quickly darken the skin by expanding black tendrils under the direct influence of M.s.H. In mammals the pigment cells are stimulated by to synthesise more melanin, which darkens the skin more slowly than the mechanism in amphibia. Since the original report by Joresin 1933 several workers have demonstrated this activity in human blood; and in this week’s issue Dr. Hudson and Dr. Bentley show that man, like other animals, has melanocyte-stimulating hormone (they prefer to call it melanophore-expanding hormone) in his pituitary. Lerner and his group at Portland, Oregon,2 injected into volunteers large amounts of a preparation of M.s.H. containing very little corticotrophin or other pituitary hormone. They describe specific, if somewhat cumbersome, methods for urinary and blood assay of the hormone.3 This is important, since biological assay on depends changes in colour in isolated frog’s skin, and various substances, contained in blood and urine, which are not pituitary hormones affect the result. Lerner has defined the normal limits for M.s.H. in blood and urine, and has shown these to be the same for men and women and for albino, white, and coloured people. During pregnancy excretion of M.s.H. increases progressively from the eighth or ninth week until term, after which it reverts to normal in a few days. Excretion of M.S.H. was increased in some patients with Addison’s disease, and in others after bilateral adrenalectomy. Cortisone inhibited heavy excretion of M.s.H. Administration of M.s.H. led to darkening of the skin and formation of new pigmented moles-evidence that the hormone causes multiplication of melanocytes as well as increased melanin synthesis. Some deepening of skin colour was detectable as early as ten hours after high doses. It is now clear that skin darkening produced by commercial preparations of corticotrophin is due to contamination by M.s.H. For some time it was difficult to separate these hormones, and it seemed possible that 1. 2. 3.
Jores, A. Z. ges. exp. Med. 1933, 87, 266. Lerner, A. B., Shizumek, K., Bunding, I. 1954, 14, 1463. Shizume, K., Lerner, A. B. Ibid, p. 1471.
J. clin. Endocrin.
method is perfectly sound, provided that all known factors are also treated and organic disease is excluded. The patient lies on a pad containing an open electrical circuit which is closed immediately the pad is wetted by an electrolytic solution (urine), and this rings a bell. This method, introduced some years ago in the U .8.A., has been tested in this country by DAvIDSoN and DOUGLASS 9 ; and last year BOSTOCK 10 reported from Australia that it had proved successful in 8 out of 12 patients. The method has several disadvantages. The apparatus is expensive, complex, and delicate, and it can be used by only one patient at a time ; the method requires the intelligent cooperation of the child ; and establishing the conditioned reflex may take many weeks. Nevertheless, this method, based on such sound physiological principles, has much to commend it. We are not so well equipped to treat enuresis that we can ignore any promising
technique. 8. Mowrer, O. H. Amer. J. Psychiat. 1938, 51, 163. Mowrer, O. Mowrer, W. M. Amer. J. Orthopsychiat. 1938, 8, 436. 9. Davidson, J. R., Douglass, E. Brit. med. J. 1950, i, 1345. 10. Bostock, J. Med. J. Aust. 1954, ii, 141.
H.,
corticotrophin and M.S.H. were one and the same.4 But M.s.H., unlike corticotrophin, is stable to alkali.5 Complete separation of the activities is difficult, and the purest M.S.H. may possibly have a slight intrinsic corticotrophin-like effect.6 Are these two in fact separated in Nature ? In man, at any rate, they may not be.’ Many states associated with general increase in pigmentation are known to be associated also with increased production of corticotrophin, and adrenal cortical hormones inhibit both corticotrophin and M.S.H.2 There is still no good evidence that M.s.H. causes such pigmentary disturbances as melanomatosis, retinitis pigmentosa, or vitiligo. In man this hormone seems to be a kind of endocrine vestige, of little importance to metabolism and survival but of great interest to phys-
corticotrophin,
icians because it is the inseparable twin of and hence in certain conditions skin pigmentation is a guide to corticotrophin production. Much remains to be learnt. Is there in man a melanocyte-inhibiting hormone analogous to that described for fish by Enami,8 and foreshadowed by the earlier work of Hogben ?9 Does the placenta produce M.s.H., as might be expected if it indeed produces corticotrophin ? 10 At just what stage in melanin synthesis does M.s.H. actWith their methods of assay Dr. Lerner and his colleagues may be able to answer these and other questions. CANCER CLUES
Edgar Allan Poe once wrote of an object being successfully hidden almost literally under the searcher’s nose. Perhaps some vital clues in the cancer mystery may similarly lie under our noses, awaiting discovery an astute observer. There have lately been two reminders of such a possibility-one from Israel and the other from Arizona. Dr. Kalman J. Mann, director of the Hadassah Medical Organisation in Israel, has stated11 that not a single case of lung cancer has been reported among Yemenite Jews in Israel in the last fifteen years. Dr. Mann painted out that these people do not smoke cigarettes but do smoke a narghile-an oriental pipe in which tobacco smoke is drawn through water. An extensive investigation has
by
4. Lancet, 1952, i, 1150. 5. Morris, C. J. O. R. Ibid, p. 1210. 6. Benfey, B. G., Saffran, M., Schally, A. V. Nature, Lond. 1954, 174, 1106. 7. Sulman, F. G. Lancet, 1952, ii, 247. 8. Enami, M. Science, 1955, 121, 36. 9. Hogben, L., Slome, D. Proc. roy. Soc. B. 1931, 108, 10 ; Ibid, 1936, 120, 158. 10. Opsahl, J. C., Long, C. N. H. Yale J. Biol. Med. 1951, 24, 199. 11. New York Times, Feb. 1, 1955.
393 been started, with the purpose of establishing the cause of this remarkable- finding. From Arizona the publichealth commissioner, Dr. Clarence G. Salsbury, has reported 12 somewhat similar findings, with reference to cancer generally, among the Navaho Indians. Apparently In cancer is hardly ever found in the 75,000 Navahos. a study of the records of all hospitals serving these people, Salsbury and his associates discovered in 1953 that 60,000 admissions had included only 208 cases of cancer; and the 118 cases in females included no more than 3 instances of cancer of the breast. Salsbury believes that the Navaho diet may be the key to the comparative lack of cancer. Highly refined foods are absent from the typical diet, which " consists mainly of meat, corn, squash, some fruits and nuts, herbs, native tea andsquaw bread ’-a type of crisp panbread." PIONEERS IN PSYCHIATRY THREE years after the fall of the Bastille, Philippe Pinel struck the chains from the lunatics in the Paris Bicetre. To the student of medical history-as the discussion at a meeting on Jan. 8 of the section of psychiatry of the Royal Society of Medicine showedhis action is significant not only as a landmark in the development of psychotherapy but also as a reflection of the spirit of his age. Indeed, all his achievements bear witness to the influence of that " Age of Enlightenment." As Prof. Aubrey Lewis pointed out, Pinel realised early the importance of applying the mathematical methods of the exact sciences, then making their appearance in medicine. He was among the first to evaluate the effects of treatment statistically, and to appreciate the need for accurate case-records, regular progress-notes, and carefully controlled therapeutic trials. In the field of psychology Pinel was much indebted to British writers -particularly Locke-and by his humane treatment of the mentally ill he set an example which was followed
throughout Europe. One of Pinel’s most enthusiastic disciples was the versatile James Cowles Prichard, who combined an extensive knowledge of ethnology and philology with an understanding of insanity well in advance of his times. His best-known medical work, the Treatise on Insanity (1835), owed much to French influence, and in particular to Pinel’s brilliant pupil Esquirol. Dr. A. D. Leigh, speaking of Prichard’s contributions to British psychiatry, moral recalled that he was the first to distinguish forms of mental from other disorders-a coniusanity troversial concept that has since received little favour. Prichard showed the influence of his Quaker upbringing in his persistent attempts to secure more humane conditions in asylums, and in his ardent support of the antislavery movement. In 1816 he became physician to the Bristol Infirmary, where his learning, skill, and energy made him well known as a physician with enlightened views on psychiatry. Both Pinel and Prichard had advocated a humane policy in the treatment of the insane ;William Browne, the medical officer of Crichton Royal Hospital, Dumfries, carried this into effect and amplified it with outstanding success. Dr. James Harper, discussing Browne’s thesis, What Asylunts lI’ere, Atie, and What They Ought To Be, showed how closely Browne’s conception of a mental hospital resembled that of modern times. Browne proposed that mental hospitals should be well planned, spacious, and beautiful-"like the palace of a peer "with extensive gardens and fields in which patients could enjoy sunshine and fresh air, and the freedom to which they were entitled. He appreciated to the full the value of occupational therapy : his patients at the Crichton Royal were provided each day with a detailed programme of activities, including games, lectures, dancing, exercises in the open, and even the "
"
12.
Ibid, Dec. 28, 1954.
production of plays. He clinician, keeping copious
an excellent the progress and
was, moreover,
notes
on
treatment of each of his patients, making systematic records of their dreams, and including in each case" history a philosophical analysis of the patient’s mind." Browne held that the staff of mental hospitals should be the companions, friends, and teachers of their patients as well as their guardians ; and he continually recommended " moral treatment of the most extended and exquisite form." In his hands the methods championed by Pinel and Prichard at last found full and practical
expression. CHLORPROMAZINE FOR HICCUP IT is not surprising that chlorpromazine should be tried in the treatment of hiccup ; for the drug powerfully inhibits many central reflexes,l and hiccup may sometimes represent the motor component of a reflex pathway -although there is good evidence that this is not always so.2 Certainly the results now claimed by Friedgood and Ripstein3 are impressive. 50 patients with hiccup attributed to various causes ranging from coronary thrombosis to thoracic, abdominal, and urological operations were treated with chlorpromazine, and in 41 a single intravenous dose of 50 mg. stopped the hiccups. Some of these responses can best be described by the dramatic " ; for example, in a man favoured epithet, aged 57 who had had hiccups for nine days after an operation for cancer of the rectum, the hiccups stopped three minutes after the injection of chlorpromazine and did not return. Chlorpromazine will presumably now take its place in the list of remedies to be tried in the treatment of intractable hiccup. "
WATER ABSORPTION WHEN heavy water is placed in the stomach or small bowel, serial samples of arterial blood show the presence of deuterium within a few minutes. The level of deuterium in the arterial blood reaches a peak at about ten minutes after intestinal administration, but at thirty minutes after gastric administration. The disappearance of intravenously injected deuterium can be estimated, and used to correct the curves obtained after alimentary administration, so giving a measure of the rate of absorption. By such studies Scholer and Code4 estimate that moderate quantities of water placed in the stomach are absorbed at a rate of of the dose per minute ; absorption from the small bowel is much more rapid26-1% per minute. They point out that water in the stomach remains in a "puddle," demonstrable by suspended barium ; whereas water introduced into the intestine is rapidly dispersed over a large mucosal surface. Even allowing for this, the absorptive activity of the small intestine, which has been shown to be an active process,5 is probably greater than that of the stomach ; the demonstration that appreciable water absorption goes on in the stomach confirms in man the findings in isolated gastric pouches in the dog.6 The deuterium method of studying water absorption has been applied to the practical problem of whether to give water by mouth to patients with abdominal and other injuries. This work, reported by Howard,7may have set up a record in long-range collaboration ; for the deuterium was given in Korea and was estimated in Washington, D.C. The assessment of absorption in this study was based, not on the form of the early arterial curves, but on the time taken to reach equilibrium, judged by constancy of the deuterium level in venous
2-5%
1. See Lancet, Feb. 12, 1955, p. 337. 2. Ibid, 1954, i, 661. 3. Friedgood, C. E., Ripstein, C. B. J. Amer. med. Ass. 1955, 157, 309. 4. Scholer, J. F., Code, C. F. Gastroenterology, 1954, 27, 565. 5. Visscher, M. B., Fetcher, E. S., Carr, C. W., Gregor, H. P., Bushey, M. S., Barker, D. E. Amer. J. Physiol. 1944, 142, 550. 6. Cope, O., Blatt, M. H., Ball, M. R. J. clin. Invest. 1943, 22, 111. 7. Howard. J. M. Surg. Gynec. Obstet. 1955, 100, 69.