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FEVER AND INSULIN RESISTANCE
505
of the disease.
Nor is there
In
rat rickettsiosis is extremely but typhus in epidemic form non-existent, lean years by the lice themselves. The life of an whereas in the neighbouring country true typhus is infected louse is usually less than a fortnight, always present but no rat typhus can be found. though one observer (MOSING) notes survival in This speaks strongly against such a transformation, full infectivity for 45 days at 32° C.-a period which at least as a happening common enough to account might well suffice to maintain a smouldering for the rebirth of human typhus year after year. One factor, to which both GIROUD and MOSING endemicity in poorly supervised communities. attach great importance, is the effect of fatigue, But there is no transmission from louse to louse and, though infection to a second generation famine, and other diseases in lowering the resisthrough the egg has been alleged, the general tance of the human subject and, more important, opinion now is that this does not take place. in raising the amount of virus circulating in the It is The discovery of the rat rickettsia infections and blood which facilitates louse infection. their occasional transmission to man, producing possible that the final extinction of typhus, as of mild forms of typhus fever (Brill’s disease, Mexican tuberculosis and leprosy, ,may come through the typhus, ship typhus), has suggested that the rat world-wide amelioration of the conditions of may be the original reservoir, and that in favour human life. It is certain that as long as human able circumstances, such as frequent transmission agglomerations can be found semi-starved and huddled together, as in some regions of Asia, to specially susceptible human subjects, the rat rickettsia may rise in virulence, become capable of Africa, and South America, so long will the threat infecting Pediculus humanus in natural conditions, of invasion with typhus fever hang over the rest and thus set up the cycle of the classical typhus. of humanity.
persistence
gation
or
reason
to think that the virus is harboured in its
Tunis, however,
common
ANNOTATIONS CHEMOTHERAPY IN CANCER OF MICE IN Science for Feb. 11th Dr. L. C. Strong of Yale describes an important development in his work on spontaneous mammary carcinoma in mice. The feeding of these animals on a diet containing a few drops of oleum gaultherise, harmless to normal mice, had previously been found to provoke a haemorrhage into the tumours followed by a connective tissue reaction and by a slowing of their rate of growth. This was not due to methyl salicylate, for the synthetic compound was without significant effect. Fractional distillation of the true oil revealed that the responsible
agent
was
in
a
fraction, containing heptyl aldehyde,
which distilled at a comparatively low temperature. This fraction caused a longer survival time in the mice and a definite slowing in the growth of the tumours, with softening, sometimes liquefaction, and in 4 out of 34 cases complete regression. The addition of heptyl aldehyde itself to an otherwise normal diet has given remarkable results. Of the tumours in the first 25 test animals, 6 showed complete regression, and liquefaction was so pronounced in the remainder that sterile fluid could be aspirated through a hypodermic needle. The fact that the drug is apparently harmless to normal animals points to a high degree of specificity in its action. Dr. Strong wisely makes no sensational forecasts, but his claim that the investigation opens up the possibility that " spontaneous tumours, in mice at least, may eventually be controlled by " chemotherapy is justified. We understand that no symptoms accompany the complete regression of the earlier tumours, but naturally the liquefaction of large tumours may lead to ill effects from haemorrhage or toxic absorption. FEVER AND INSULIN RESISTANCE
IT has been generally recognised since the early days of insulin that bacterial infection may substantially increase the insulin requirement of a diabetic patient. The reason for this decrease in sensitivity to the action of insulin has been a source
speculation and inquiry for many years, but no satisfactory explanation has been reached. The investigations of Houssayand others on the relationship of the anterior pituitary gland to carbohydrate metabolism have shown that this gland has an important role in the regulation of the sensitivity of the body to the hypoglycaemic action of insulin. In the absence of the anterior lobe this sensitivity increases ; while on the other hand injection of a suitable anterior pituitary extract will induce a of
the action of insulin administered to normal animals. It seems possible, therefore, that the anterior pituitary lobe is concerned in producing the insulin resistance that follows bacterial infection and Wien2 has pursued this suggestion. As the secretion of the pituitary gland has a profound influence on the thyroid gland and on the adrenals, the part that may be played by these glands was also examined. It was found that the pyrexia following subcutaneous administration to cats, rabbits, and rats, of a killed culture of Bacillus coli communis, did not cause a rise of blood-sugar, but almost abolished the hypoglycaemic response to the subcutaneous injection of 0-5 unit of insulin per kg. of body-weight. In hypophysectomised rats, and in thyroidectomised or adrenalectomised rats and cats, the bacterial pyrexia was somewhat diminished in intensity, and had little effect on the insulin sensitivity. In rabbits, on the other hand, the bacterial pyrexia was little altered by removal of the thyroid or adrenal glands, and still diminished the response to injected insulin in the absence of these
resistance to
intravenously
glands. It seems probable from these results that the diminished rise of temperature caused by B. coli in cats and rats which lacked thyroid or adrenal glands is related to the failure of these animals to develop the insulin resistance which usually followed B. coli administration. The evidence suggests that the hypophysis, and the thyroid and adrenal glands, may all be concerned in the
pyrexia
production of bacterial the hypoglycaemic
and the resistance to
B. A., New Engl. J. Med. 1936, 214, 971. Wien, R., Quart. J. Pharm. 1937, 10, 621.
1 Houssay, 2
506 action of insulin which normally accompanies it. How these glands influence both bacterial pyrexia and insulin sensitivity is still far from clear.
predominate among them. In its gross and microscopic features the disease resembles ulcerative colitis as ordinarily seen in the terminal segments of the there is diffuse ulceration of the mucosa, in the submucosa, and thickening and induration of all the coats of the bowel; in the late stage there may be polypoid hyperplasia. The disease behaves as though it were an infection, beginning with fever and prostration, and spreading proximally and distally. The bacteriology of the fseces or of tissue cultures taken from specimens removed at operation throws no light on its nature; the usual dysenteric organisms and protozoal parasites are absent. During the active stage there is diarrhoea, but this is rarely very severe, and there is not the urgency, nor the passage of blood-stained mucus with tenesmus that is so common when the rectum is seriously affected. Cramps, abdominal pain, fever, loss of weight, anaemia, and a tender palpable mass in the lower right abdominal quadrant are found ; and radiography after barium enema gives a diagnostic picture of colitis ; but there is not the "string sign " so typical of regional or terminal ileitis. American authors find primary ileocaecal tuberculosis of the hyperplastic type so unusual that it does not appear to be a stumbling-block in diagnosis. From the experience of Crohn and Berg this form of ulcerative colitis is not amenable to ordinary medical methods of treatment ; they have operated on 14 cases and propose to operate on 2 more of the 17 they report. The usual methods of caecostomy, ileostomy, and other procedures that make an artificial anus have been unsuccessful. The method preferred begins with anastomosis of the transected terminal ileum into the lower sigmoid ; the remainder of the bowel then has its proximal end closed and its distal end brought up to the surface temporarily, and at a later stage the excluded part of the colon is removed by two or more operations. Thus the continuity of the alimentary tract is maintained without a permanent stoma. Five patients thus treated have done well.
colon:
A HYPOTHETICAL CASE
A
has invited an opinion on a case for the purpose of abstract discussion, may be propounded as hypothetical. A women’s journal provides among other features a weekly service of advice on general health, the management of pregnancy, and birth control. Subscribers who fill in a coupon can enrol themselves as members of a Health Club. They are then entitled to put their questions to a registered medical practitioner who either answers them directly through the post or gives printed replies in the columns of the paper. The CORRESPONDENT
which,
registered medical practitioner has written a book explaining fully what are described as the various medically approved methods of birth control. In answers to correspondents the applicants are referred to this book and are informed of the price and the publisher’s name and address. The hypothetical point on which opinion is invited is whether a registered medical practitioner, writing regularly in a weekly or other newspaper under an assumed pen-name, is allowed to advertise his or her book in which he or she has a commercial interest. The practice, it is suggested on the one side, is one which might be dangerously extended to all sort of popular fads apart from the somewhat controversial topic of birth control. On the other side it might be said that many practitioners publish books in the course of an honourable professional career and are entitled to whatever advertisement or profit may result. In the hypothetical case propounded above, it may be said, the medical journalist is placed in touch with otherwise unknown and inaccessible patients through the medium of the newspaper. They may be drawn away from their own medical attendant. But notices in the hypothetical newspaper make it clear that the medical journalist does not pretend or desire to deal by correspondence with the treatment or diagnosis of disease ; on these subjects the applicant is advised to consult her own The hypothetical answers to medical attendant.
correspondents, too, usually begin by recommending the inquirer to go to a sympathetic doctor or to attend a clinic. Still the journalist is in effect using the system of the Health Club to advertise the already published book. Is this conduct to be described as unprofessional’1 If hypothetical cases can arouse any
interest, what do
our
readers think’1
REGIONAL COLITIS IN the absence of a strict aetiological classification of non-specific ulcerative colitis, it has been possible only to group cases of this kind according to the severity of the invasion and the resistance of the patient. A further division was offered by J. A. Bargen in 1932 when he drew attention to a rightsided localisation of the disease in some 10 per cent. of all cases of so-called non-specific ulcerative colitis. In nine cases out of ten the condition involves the rectum and lower sigmoid and tends to spread orally over the various segments until the whole mucosal surface of the large intestine may be involved. Bargen, however, reported 23 instances of right-sided regional colitis and Crohn and Berggive their findings in 17 others. It appears that nearly all the patients are between 20 and 30 years of age. and males 1 Crohn, B. B., 1938, p. 32
and Berg, A. A., Amer. med. Ass., Jan. 1st,
suppuration
SUPERNORMAL PERCEPTION
PSYCHOLOGY has much to do in the study of individual differences, a field so little cultivated that there is still only a thin line dividing some of the unfamiliar extremes of human capacity from the mysterious and the miraculous. Synaesthesia in its more striking forms is almost as extraordinary to most people as second sight, the mathematical intuitions of an Euler or a Ramanujan scarcely less supernatural than magic. In remoteness from normal understanding there is little to choose between a prodigy-Mozart composing sonatas in his nursery or Koltanowski playing 34 games of chess blindfoldand, at a less credible level, a medium who levitates tables and reads thoughts. Mediums are not so rare as prodigies (though rather more expensive) and their apparent powers are well worth psychological study.
Unfortunately a good deal of time has usually to be spent in demonstrating that they cannot work miracles. The University of London Council for Psychical Investigation has done much to bring paranormal " manifestations into line with the known abilities of man, and a report1 has just been published of an inquiry of this kind made under its auspices. In an excellently conducted and recorded series of experiments Mr. S. G. Soal has investigated "
1 Preliminary Studies of a Vaudeville Telepathist. By S. G. Soal, M.A., B.Sc. Bulletin III. London: University of London 1937. Pp. 96. 5s. Council for Psychical Investigation.
of the disease.
Nor is there
In
rat rickettsiosis is extremely but typhus in epidemic form non-existent, lean years by the lice themselves. The life of an whereas in the neighbouring country true typhus is infected louse is usually less than a fortnight, always present but no rat typhus can be found. though one observer (MOSING) notes survival in This speaks strongly against such a transformation, full infectivity for 45 days at 32° C.-a period which at least as a happening common enough to account might well suffice to maintain a smouldering for the rebirth of human typhus year after year. One factor, to which both GIROUD and MOSING endemicity in poorly supervised communities. attach great importance, is the effect of fatigue, But there is no transmission from louse to louse and, though infection to a second generation famine, and other diseases in lowering the resisthrough the egg has been alleged, the general tance of the human subject and, more important, opinion now is that this does not take place. in raising the amount of virus circulating in the It is The discovery of the rat rickettsia infections and blood which facilitates louse infection. their occasional transmission to man, producing possible that the final extinction of typhus, as of mild forms of typhus fever (Brill’s disease, Mexican tuberculosis and leprosy, ,may come through the typhus, ship typhus), has suggested that the rat world-wide amelioration of the conditions of may be the original reservoir, and that in favour human life. It is certain that as long as human able circumstances, such as frequent transmission agglomerations can be found semi-starved and huddled together, as in some regions of Asia, to specially susceptible human subjects, the rat rickettsia may rise in virulence, become capable of Africa, and South America, so long will the threat infecting Pediculus humanus in natural conditions, of invasion with typhus fever hang over the rest and thus set up the cycle of the classical typhus. of humanity.
persistence
gation
or
reason
to think that the virus is harboured in its
Tunis, however,
common
ANNOTATIONS CHEMOTHERAPY IN CANCER OF MICE IN Science for Feb. 11th Dr. L. C. Strong of Yale describes an important development in his work on spontaneous mammary carcinoma in mice. The feeding of these animals on a diet containing a few drops of oleum gaultherise, harmless to normal mice, had previously been found to provoke a haemorrhage into the tumours followed by a connective tissue reaction and by a slowing of their rate of growth. This was not due to methyl salicylate, for the synthetic compound was without significant effect. Fractional distillation of the true oil revealed that the responsible
agent
was
in
a
fraction, containing heptyl aldehyde,
which distilled at a comparatively low temperature. This fraction caused a longer survival time in the mice and a definite slowing in the growth of the tumours, with softening, sometimes liquefaction, and in 4 out of 34 cases complete regression. The addition of heptyl aldehyde itself to an otherwise normal diet has given remarkable results. Of the tumours in the first 25 test animals, 6 showed complete regression, and liquefaction was so pronounced in the remainder that sterile fluid could be aspirated through a hypodermic needle. The fact that the drug is apparently harmless to normal animals points to a high degree of specificity in its action. Dr. Strong wisely makes no sensational forecasts, but his claim that the investigation opens up the possibility that " spontaneous tumours, in mice at least, may eventually be controlled by " chemotherapy is justified. We understand that no symptoms accompany the complete regression of the earlier tumours, but naturally the liquefaction of large tumours may lead to ill effects from haemorrhage or toxic absorption. FEVER AND INSULIN RESISTANCE
IT has been generally recognised since the early days of insulin that bacterial infection may substantially increase the insulin requirement of a diabetic patient. The reason for this decrease in sensitivity to the action of insulin has been a source
speculation and inquiry for many years, but no satisfactory explanation has been reached. The investigations of Houssayand others on the relationship of the anterior pituitary gland to carbohydrate metabolism have shown that this gland has an important role in the regulation of the sensitivity of the body to the hypoglycaemic action of insulin. In the absence of the anterior lobe this sensitivity increases ; while on the other hand injection of a suitable anterior pituitary extract will induce a of
the action of insulin administered to normal animals. It seems possible, therefore, that the anterior pituitary lobe is concerned in producing the insulin resistance that follows bacterial infection and Wien2 has pursued this suggestion. As the secretion of the pituitary gland has a profound influence on the thyroid gland and on the adrenals, the part that may be played by these glands was also examined. It was found that the pyrexia following subcutaneous administration to cats, rabbits, and rats, of a killed culture of Bacillus coli communis, did not cause a rise of blood-sugar, but almost abolished the hypoglycaemic response to the subcutaneous injection of 0-5 unit of insulin per kg. of body-weight. In hypophysectomised rats, and in thyroidectomised or adrenalectomised rats and cats, the bacterial pyrexia was somewhat diminished in intensity, and had little effect on the insulin sensitivity. In rabbits, on the other hand, the bacterial pyrexia was little altered by removal of the thyroid or adrenal glands, and still diminished the response to injected insulin in the absence of these
resistance to
intravenously
glands. It seems probable from these results that the diminished rise of temperature caused by B. coli in cats and rats which lacked thyroid or adrenal glands is related to the failure of these animals to develop the insulin resistance which usually followed B. coli administration. The evidence suggests that the hypophysis, and the thyroid and adrenal glands, may all be concerned in the
pyrexia
production of bacterial the hypoglycaemic
and the resistance to
B. A., New Engl. J. Med. 1936, 214, 971. Wien, R., Quart. J. Pharm. 1937, 10, 621.
1 Houssay, 2
506 action of insulin which normally accompanies it. How these glands influence both bacterial pyrexia and insulin sensitivity is still far from clear.
predominate among them. In its gross and microscopic features the disease resembles ulcerative colitis as ordinarily seen in the terminal segments of the there is diffuse ulceration of the mucosa, in the submucosa, and thickening and induration of all the coats of the bowel; in the late stage there may be polypoid hyperplasia. The disease behaves as though it were an infection, beginning with fever and prostration, and spreading proximally and distally. The bacteriology of the fseces or of tissue cultures taken from specimens removed at operation throws no light on its nature; the usual dysenteric organisms and protozoal parasites are absent. During the active stage there is diarrhoea, but this is rarely very severe, and there is not the urgency, nor the passage of blood-stained mucus with tenesmus that is so common when the rectum is seriously affected. Cramps, abdominal pain, fever, loss of weight, anaemia, and a tender palpable mass in the lower right abdominal quadrant are found ; and radiography after barium enema gives a diagnostic picture of colitis ; but there is not the "string sign " so typical of regional or terminal ileitis. American authors find primary ileocaecal tuberculosis of the hyperplastic type so unusual that it does not appear to be a stumbling-block in diagnosis. From the experience of Crohn and Berg this form of ulcerative colitis is not amenable to ordinary medical methods of treatment ; they have operated on 14 cases and propose to operate on 2 more of the 17 they report. The usual methods of caecostomy, ileostomy, and other procedures that make an artificial anus have been unsuccessful. The method preferred begins with anastomosis of the transected terminal ileum into the lower sigmoid ; the remainder of the bowel then has its proximal end closed and its distal end brought up to the surface temporarily, and at a later stage the excluded part of the colon is removed by two or more operations. Thus the continuity of the alimentary tract is maintained without a permanent stoma. Five patients thus treated have done well.
colon:
A HYPOTHETICAL CASE
A
has invited an opinion on a case for the purpose of abstract discussion, may be propounded as hypothetical. A women’s journal provides among other features a weekly service of advice on general health, the management of pregnancy, and birth control. Subscribers who fill in a coupon can enrol themselves as members of a Health Club. They are then entitled to put their questions to a registered medical practitioner who either answers them directly through the post or gives printed replies in the columns of the paper. The CORRESPONDENT
which,
registered medical practitioner has written a book explaining fully what are described as the various medically approved methods of birth control. In answers to correspondents the applicants are referred to this book and are informed of the price and the publisher’s name and address. The hypothetical point on which opinion is invited is whether a registered medical practitioner, writing regularly in a weekly or other newspaper under an assumed pen-name, is allowed to advertise his or her book in which he or she has a commercial interest. The practice, it is suggested on the one side, is one which might be dangerously extended to all sort of popular fads apart from the somewhat controversial topic of birth control. On the other side it might be said that many practitioners publish books in the course of an honourable professional career and are entitled to whatever advertisement or profit may result. In the hypothetical case propounded above, it may be said, the medical journalist is placed in touch with otherwise unknown and inaccessible patients through the medium of the newspaper. They may be drawn away from their own medical attendant. But notices in the hypothetical newspaper make it clear that the medical journalist does not pretend or desire to deal by correspondence with the treatment or diagnosis of disease ; on these subjects the applicant is advised to consult her own The hypothetical answers to medical attendant.
correspondents, too, usually begin by recommending the inquirer to go to a sympathetic doctor or to attend a clinic. Still the journalist is in effect using the system of the Health Club to advertise the already published book. Is this conduct to be described as unprofessional’1 If hypothetical cases can arouse any
interest, what do
our
readers think’1
REGIONAL COLITIS IN the absence of a strict aetiological classification of non-specific ulcerative colitis, it has been possible only to group cases of this kind according to the severity of the invasion and the resistance of the patient. A further division was offered by J. A. Bargen in 1932 when he drew attention to a rightsided localisation of the disease in some 10 per cent. of all cases of so-called non-specific ulcerative colitis. In nine cases out of ten the condition involves the rectum and lower sigmoid and tends to spread orally over the various segments until the whole mucosal surface of the large intestine may be involved. Bargen, however, reported 23 instances of right-sided regional colitis and Crohn and Berggive their findings in 17 others. It appears that nearly all the patients are between 20 and 30 years of age. and males 1 Crohn, B. B., 1938, p. 32
and Berg, A. A., Amer. med. Ass., Jan. 1st,
suppuration
SUPERNORMAL PERCEPTION
PSYCHOLOGY has much to do in the study of individual differences, a field so little cultivated that there is still only a thin line dividing some of the unfamiliar extremes of human capacity from the mysterious and the miraculous. Synaesthesia in its more striking forms is almost as extraordinary to most people as second sight, the mathematical intuitions of an Euler or a Ramanujan scarcely less supernatural than magic. In remoteness from normal understanding there is little to choose between a prodigy-Mozart composing sonatas in his nursery or Koltanowski playing 34 games of chess blindfoldand, at a less credible level, a medium who levitates tables and reads thoughts. Mediums are not so rare as prodigies (though rather more expensive) and their apparent powers are well worth psychological study.
Unfortunately a good deal of time has usually to be spent in demonstrating that they cannot work miracles. The University of London Council for Psychical Investigation has done much to bring paranormal " manifestations into line with the known abilities of man, and a report1 has just been published of an inquiry of this kind made under its auspices. In an excellently conducted and recorded series of experiments Mr. S. G. Soal has investigated "
1 Preliminary Studies of a Vaudeville Telepathist. By S. G. Soal, M.A., B.Sc. Bulletin III. London: University of London 1937. Pp. 96. 5s. Council for Psychical Investigation.