- Email: [email protected]
ANABOLIC STEROIDS IN TREATMENT OF URÆMIA
886 based on the patient’s weight. The body-water figure is approximation, but any error will be constant for a particular patient and will not affect the results significantly. Each patient acted as his own control, the first four days being used for this purpose and the subsequent five days being used to assess the effect of nilevar. (In our experience the daily rise in blood-urea remains fairly constant in acute renal failure until renal function returns.) On the treatment days, nilevar 80 mg. daily by mouth in divided doses was given. 1 patient (case 2) received 100 mg. nilevar daily by intramuscular injection instead of 80 mg. by mouth. The healthy subjects had a period of equilibration on the low protein intake for five days before the control period started. 2 of the healthy subjects had control periods following and preceding the nilevar treatment period.
water an
RESULTS
The results are shown in the table. The figures given represent the urea production per day expressed as grammes of nitrogen, the mean figures for the control period being compared with the nilevar treatment period. There was distinct suppression of urea production in the obstetric group of patients when treated with nilevar, and relatively little effect in the non-obstetric patients or in healthy subjects on a very low protein diet. COMMENT
It is reasonable to conclude that nilevar dramatically reduces the rate of protein catabolism in obstetric patients with acute renal failure-a group which accounts for 40% of the patients with acute renal failure referred to this unit. Further study is required to find out the relative efficacy of similar steroids, and why there is a different response in the various groups of patients. The reduction of protein catabolism in the obstetric patients with acute renal failure in this study averaged 70%, and, if this can be maintained from the onset of renal failure by prompt administration of nilevar, it might largely eliminate the need for dialysis in the management of this group of patients. Nilevar has anabolic and progestational effects, but it is interesting that the 2 obstetric patients who had undergone hysterectomy responded in the same way as the others. We wish to thank Messrs. G. D. Searle & Co. for of ’Nilevar ’. B.SC., M.B.
University of Leeds
a
generous
B. H. MCCRACKEN Wales, M.D. Wisconsin,
supply
M.R.C.P.
Lecturer in Medicine
F. M. PARSONS B.SC., General Infirmary at Leeds
M.B.
Leeds
Assistant Director, Metabolic Disturbances in Surgery, Medical Research Council Unit
ANABOLIC STEROIDS IN TREATMENT OF
URÆMIA CLINICALLY useful anabolic substances have hitherto not been available for the treatment of urxmia. Testoand its derivatives have been found to be of limited value, and untoward endocrine reactions have restricted their application, at least over longer periods.1 Recently certain synthetic 19-nor-steroids-17-oc-aethyl19-nortestosterone (norethandrolone,Nilevar’) and sterone
19-nor-testosterone-17-p-phenyl-propionate (nondrolone, Durabolin ’) have been introduced as powerful anabolic
’
substances with minimal side reactions. The accompanying figure illustrates the effect of one of these substances (nilevar) on a patient with severe subacute renal failure. In the pretreatment period urxmia rapidly progressed despite minimal protein intake. In the treatment periods the levels of nitrogenous 1.
Freedman, P., Spencer,
A. G. Clin. Sci.
1957, 16, 11.
Observations during treatment of uraemia with anabolic steroid. The patient was a 50-year-old woman with severe renal failure; the 24-hour endogenous creatinine clearance remained below 5 ml. per minute. On the balance chart the intake of nitrogen per 24 hours is plotted upwards and the output downwards from the baseline; the daily external nitrogen balance is calculated as the difference between intake and output and indicated by hatched columns, upwards from baseline if positive and downwards if negative. The cumulative nitrogen balance is calculated from the external balance and corrected for changes in urea-nitrogen in the body-fluids. For experimental reasons nilevar was chosen in this study, since the short-lasting effect of this compound makes possible a sharp delineation between treatment and control periods.
products in the serum decreased, despite high protein intake, causing considerable retention of lean tissue and gain in body-weight. The compounds have been tested in 10 cases of severe chronic renal failure. In all, increased appetite, retention of lean tissue, gain in body-weight, and improvement of waste
the clinical condition were observed. In no case did the increased protein intake cause an increase in biochemical uraemia, and it was surprising that the most common immediate reaction to therapy was a decrease in blood urea-nitrogen and non-protein-nitrogen similar to that illustrated in the figure. Nilevar was given orally in doses of 50-100 mg. per 24 hr.; and durabolin was applied intramuscularly, generally in doses of 50 mg. per week. The effect of intramuscular durabolin was considerably longer than that of nilevar. With both drugs virilising side-effects were either not observed or minimal. In our hands nilevar had a definite progestative action, causing severe and long-continued withdrawal bleeding in 1 case.
887
From our preliminary observations we conclude that these 19-nor-steroids may break the vicious circle of progressive urasmic intoxication and approaching cachexia in patients with severe chronic renal failure. The ultimate prognosis naturally depends upon the possibilities for improving the underlying renal disorder. The clinical improvement brought about by the 19-nor-steroid treatment may, however, enhance the chances of adequate surgical or medical therapy of the renal disease. The 19-nor-steroids have also been tested in the treatof acute renal failure, in which condition they may retard the progression of biochemical ur2ernia.. We consider, however, that the use of 19-nor-steroids in acute renal failure should be restricted to centres where supplementary heamodialysis can be carried out whenever ment
necessary.
STEFFEN GJØRUP M.D. Copenhagen JØRN HESS THAYSEN M.D. Copenhagen
Hæmodialytic Unit, Department A, Rigshospitalet, University Hospital of Copenhagen
Medical
De Circulatione Two Anatomical
Sanguinis and Nine Letters
William
by Harvey. Essays KENNETH J. FRANKLIN, D.M., F.R.S., professor Translated by physiology, University
of of London. Oxford: Blackwell Scientific Publications. 1958. Pp. 184. 22s. 6d.
CANDIDATES for membership of the Royal College of of London were once required to show a certain competence in Greek or Latin by translating a short passage from one of these languages. That this did not tax all of them unduly is proved by the performance of one candidate (he was destined to become a regius professor of physic) who, doubtful of the examiner’s intentions, handsomely rendered into Greek the Latin excerpt, and vice versa. Since 1924 a knowledge of a classical language has not been an essential part of this particular qualification, and one consequence of the change may be that in years to come we shall be hard put to find a medical man sufficiently skilled to undertake such a work as Professor Franklin has now completed. The profession is already indebted to him for his masterly translation of De Motu Cordis, and that debt is now doubled. This translation comprises the original Latin text, and a new translation of William Harvey’s two essays addressed to Jean Riolan, together with nine letters to various
Physicians
colleagues. The Exercitationes of 1649
Reviews of Books Aubrey’s
Brief Lives
Editor: OLIVER Lnwsorr Dicx. 1958. Pp. 341. 35s.
London: Secker &
Warburg.
HISTORIANS and students of folk-lore have long been familiar with John Aubrey’s name. For them, his nine surviving books have always been a Mecca wherein to search for information not to be found elsewhere. A rather different group of readers are all the amateur antiquarians who have at some time toured Aubrey’s native county and, guide-book in hand, gazed at the enigmas of Stonehenge, Silbury Hill, and Avebury; for almost all the guide-books contain quotations from Aubrey’s Naturall Historie of Wiltshire, and he wrote the earliest known description of the Avebury Circles. But the vivid writings of this indefatigable author (he tells us that, while still a boy, he studied even " on horseback and in the house of office ") deserve to be more widely read. We hope Sir Geoffrey Keynes’ Harveian Oration, which appears at the beginning of this the popularity of this " charming and issue, will enhance " exasperating character. His most delightful work is probably the Memories of Lives, collection of biographical sketches, jotted down over some twenty years but never properly prepared for the press until more than a hundred years after his death. Several editions of Brief Lives, as the book came to be called, have since appeared. But their style and price have often restricted their popularity. For many of the original 426 lives in the full collection are of no interest or are incomplete. (All that Aubrey has to say of one John Holywood, for instance, is Dr. Pell is positive that his name was Holybushe "). The attractive edition prepared by Mr. Lawson Dick contains over 130 of the most important articles, well illustrated and prefaced by an admirable account of Aubrey’s own life.
were
written
to
refute Riolan’s
Enchiridion, a manual of anatomy which had appeared in the previous year, and in which the old Galenic fallacies about the circulation were repeated in an only slightly modified form. Till now these essays have seldom been read in the original text, and there has been a tendency to dismiss them as mere postscripts to the De Motu Cordis, published twenty years before. But, as Dr. Louis Chauvois has recently emphasised, they are important as showing how Harvey’s first conception of the circulation was ripened and perfected by meditation and experiment over that interval. Apart from adducing new evidence to support his contentions, in these essays he makes the all-important point (not to be found in the 1628 treatise) that the heart itself does not in any way recharge the blood with " heat " or vital spirits " More than an expert ability in physiology and in Latin is evident in this book. Harvey lived in the golden hey-day of English literature, and his lectures and his writings must have reflected this fact before they were rendered into the international language. We may never know how these essays and letters read in their original draft. But, so deft and graceful is Professor Franklin’s style, that it is easy to believe that they were not, in fact, dissimilar to the version he has now so handsomely provided. "
a
"
For the medical
reader, Aubrey’s
most
notable
William Harvey, whom he knew well in the
subject physician’s
was
last his Funerall, and helpt to carry him into the Vault But he also wrote of Willis, Hooke, and Descartes, to say nothing of a host of minor characters of medical interest who stray into his pages. (It is not difficult to diagnose the case of the licentious footman, whose Nostrils were stuffed and borne out with corks in which were quills to breathe through"). Though it may be difficult to persuade a hospital library committee to invest in this volume, the season of book tokens approaches, and, while the committee hesitate, a doctor with a token in his hand may confidently surrender it for the new years.
("I was
at
"
Aubrey.
Circulation
Proceedings of the Harvey Tercentenary Congress. Editor: JOHN
MCMICHAEL, F.R.C.P., professor of medicine, London. Oxford: F.R.S., Blackwell Scientific PublicaUniversity ofPp.M.D., tions. 1958.
503. 50s.
THOSE who were unable to attend the very successful international congress held in London in June last year-and indeed those who did-will be gratified by the publication of the collected papers in an elegant small volume. The list of contributors gives promise of a store of knowledge in matters of the circulation, from its outset with the changes which occur at birth to the latest developments in cardiovascular There is much to interest every kind of reader: surgery. no-one, for instance, could fail to be pleased by an account by Weidmann of the study by direct capillary electrode of the intimate electrochemistry of the heart-beat, or to be astonished by Kety’s revelation that cerebral blood-flow drops sharply at puberty, never to recover its earlier level. We might wonder whether after three hundred years this pure knowledge of function would interest William Harvey more than the miraculous achievements of heart and vessel surgery; or might he not perhaps, quite simply, being he, begin to look for the biggest unanswered question and start the great work anew.
water an
RESULTS
The results are shown in the table. The figures given represent the urea production per day expressed as grammes of nitrogen, the mean figures for the control period being compared with the nilevar treatment period. There was distinct suppression of urea production in the obstetric group of patients when treated with nilevar, and relatively little effect in the non-obstetric patients or in healthy subjects on a very low protein diet. COMMENT
It is reasonable to conclude that nilevar dramatically reduces the rate of protein catabolism in obstetric patients with acute renal failure-a group which accounts for 40% of the patients with acute renal failure referred to this unit. Further study is required to find out the relative efficacy of similar steroids, and why there is a different response in the various groups of patients. The reduction of protein catabolism in the obstetric patients with acute renal failure in this study averaged 70%, and, if this can be maintained from the onset of renal failure by prompt administration of nilevar, it might largely eliminate the need for dialysis in the management of this group of patients. Nilevar has anabolic and progestational effects, but it is interesting that the 2 obstetric patients who had undergone hysterectomy responded in the same way as the others. We wish to thank Messrs. G. D. Searle & Co. for of ’Nilevar ’. B.SC., M.B.
University of Leeds
a
generous
B. H. MCCRACKEN Wales, M.D. Wisconsin,
supply
M.R.C.P.
Lecturer in Medicine
F. M. PARSONS B.SC., General Infirmary at Leeds
M.B.
Leeds
Assistant Director, Metabolic Disturbances in Surgery, Medical Research Council Unit
ANABOLIC STEROIDS IN TREATMENT OF
URÆMIA CLINICALLY useful anabolic substances have hitherto not been available for the treatment of urxmia. Testoand its derivatives have been found to be of limited value, and untoward endocrine reactions have restricted their application, at least over longer periods.1 Recently certain synthetic 19-nor-steroids-17-oc-aethyl19-nortestosterone (norethandrolone,Nilevar’) and sterone
19-nor-testosterone-17-p-phenyl-propionate (nondrolone, Durabolin ’) have been introduced as powerful anabolic
’
substances with minimal side reactions. The accompanying figure illustrates the effect of one of these substances (nilevar) on a patient with severe subacute renal failure. In the pretreatment period urxmia rapidly progressed despite minimal protein intake. In the treatment periods the levels of nitrogenous 1.
Freedman, P., Spencer,
A. G. Clin. Sci.
1957, 16, 11.
Observations during treatment of uraemia with anabolic steroid. The patient was a 50-year-old woman with severe renal failure; the 24-hour endogenous creatinine clearance remained below 5 ml. per minute. On the balance chart the intake of nitrogen per 24 hours is plotted upwards and the output downwards from the baseline; the daily external nitrogen balance is calculated as the difference between intake and output and indicated by hatched columns, upwards from baseline if positive and downwards if negative. The cumulative nitrogen balance is calculated from the external balance and corrected for changes in urea-nitrogen in the body-fluids. For experimental reasons nilevar was chosen in this study, since the short-lasting effect of this compound makes possible a sharp delineation between treatment and control periods.
products in the serum decreased, despite high protein intake, causing considerable retention of lean tissue and gain in body-weight. The compounds have been tested in 10 cases of severe chronic renal failure. In all, increased appetite, retention of lean tissue, gain in body-weight, and improvement of waste
the clinical condition were observed. In no case did the increased protein intake cause an increase in biochemical uraemia, and it was surprising that the most common immediate reaction to therapy was a decrease in blood urea-nitrogen and non-protein-nitrogen similar to that illustrated in the figure. Nilevar was given orally in doses of 50-100 mg. per 24 hr.; and durabolin was applied intramuscularly, generally in doses of 50 mg. per week. The effect of intramuscular durabolin was considerably longer than that of nilevar. With both drugs virilising side-effects were either not observed or minimal. In our hands nilevar had a definite progestative action, causing severe and long-continued withdrawal bleeding in 1 case.
887
From our preliminary observations we conclude that these 19-nor-steroids may break the vicious circle of progressive urasmic intoxication and approaching cachexia in patients with severe chronic renal failure. The ultimate prognosis naturally depends upon the possibilities for improving the underlying renal disorder. The clinical improvement brought about by the 19-nor-steroid treatment may, however, enhance the chances of adequate surgical or medical therapy of the renal disease. The 19-nor-steroids have also been tested in the treatof acute renal failure, in which condition they may retard the progression of biochemical ur2ernia.. We consider, however, that the use of 19-nor-steroids in acute renal failure should be restricted to centres where supplementary heamodialysis can be carried out whenever ment
necessary.
STEFFEN GJØRUP M.D. Copenhagen JØRN HESS THAYSEN M.D. Copenhagen
Hæmodialytic Unit, Department A, Rigshospitalet, University Hospital of Copenhagen
Medical
De Circulatione Two Anatomical
Sanguinis and Nine Letters
William
by Harvey. Essays KENNETH J. FRANKLIN, D.M., F.R.S., professor Translated by physiology, University
of of London. Oxford: Blackwell Scientific Publications. 1958. Pp. 184. 22s. 6d.
CANDIDATES for membership of the Royal College of of London were once required to show a certain competence in Greek or Latin by translating a short passage from one of these languages. That this did not tax all of them unduly is proved by the performance of one candidate (he was destined to become a regius professor of physic) who, doubtful of the examiner’s intentions, handsomely rendered into Greek the Latin excerpt, and vice versa. Since 1924 a knowledge of a classical language has not been an essential part of this particular qualification, and one consequence of the change may be that in years to come we shall be hard put to find a medical man sufficiently skilled to undertake such a work as Professor Franklin has now completed. The profession is already indebted to him for his masterly translation of De Motu Cordis, and that debt is now doubled. This translation comprises the original Latin text, and a new translation of William Harvey’s two essays addressed to Jean Riolan, together with nine letters to various
Physicians
colleagues. The Exercitationes of 1649
Reviews of Books Aubrey’s
Brief Lives
Editor: OLIVER Lnwsorr Dicx. 1958. Pp. 341. 35s.
London: Secker &
Warburg.
HISTORIANS and students of folk-lore have long been familiar with John Aubrey’s name. For them, his nine surviving books have always been a Mecca wherein to search for information not to be found elsewhere. A rather different group of readers are all the amateur antiquarians who have at some time toured Aubrey’s native county and, guide-book in hand, gazed at the enigmas of Stonehenge, Silbury Hill, and Avebury; for almost all the guide-books contain quotations from Aubrey’s Naturall Historie of Wiltshire, and he wrote the earliest known description of the Avebury Circles. But the vivid writings of this indefatigable author (he tells us that, while still a boy, he studied even " on horseback and in the house of office ") deserve to be more widely read. We hope Sir Geoffrey Keynes’ Harveian Oration, which appears at the beginning of this the popularity of this " charming and issue, will enhance " exasperating character. His most delightful work is probably the Memories of Lives, collection of biographical sketches, jotted down over some twenty years but never properly prepared for the press until more than a hundred years after his death. Several editions of Brief Lives, as the book came to be called, have since appeared. But their style and price have often restricted their popularity. For many of the original 426 lives in the full collection are of no interest or are incomplete. (All that Aubrey has to say of one John Holywood, for instance, is Dr. Pell is positive that his name was Holybushe "). The attractive edition prepared by Mr. Lawson Dick contains over 130 of the most important articles, well illustrated and prefaced by an admirable account of Aubrey’s own life.
were
written
to
refute Riolan’s
Enchiridion, a manual of anatomy which had appeared in the previous year, and in which the old Galenic fallacies about the circulation were repeated in an only slightly modified form. Till now these essays have seldom been read in the original text, and there has been a tendency to dismiss them as mere postscripts to the De Motu Cordis, published twenty years before. But, as Dr. Louis Chauvois has recently emphasised, they are important as showing how Harvey’s first conception of the circulation was ripened and perfected by meditation and experiment over that interval. Apart from adducing new evidence to support his contentions, in these essays he makes the all-important point (not to be found in the 1628 treatise) that the heart itself does not in any way recharge the blood with " heat " or vital spirits " More than an expert ability in physiology and in Latin is evident in this book. Harvey lived in the golden hey-day of English literature, and his lectures and his writings must have reflected this fact before they were rendered into the international language. We may never know how these essays and letters read in their original draft. But, so deft and graceful is Professor Franklin’s style, that it is easy to believe that they were not, in fact, dissimilar to the version he has now so handsomely provided. "
a
"
For the medical
reader, Aubrey’s
most
notable
William Harvey, whom he knew well in the
subject physician’s
was
last his Funerall, and helpt to carry him into the Vault But he also wrote of Willis, Hooke, and Descartes, to say nothing of a host of minor characters of medical interest who stray into his pages. (It is not difficult to diagnose the case of the licentious footman, whose Nostrils were stuffed and borne out with corks in which were quills to breathe through"). Though it may be difficult to persuade a hospital library committee to invest in this volume, the season of book tokens approaches, and, while the committee hesitate, a doctor with a token in his hand may confidently surrender it for the new years.
("I was
at
"
Aubrey.
Circulation
Proceedings of the Harvey Tercentenary Congress. Editor: JOHN
MCMICHAEL, F.R.C.P., professor of medicine, London. Oxford: F.R.S., Blackwell Scientific PublicaUniversity ofPp.M.D., tions. 1958.
503. 50s.
THOSE who were unable to attend the very successful international congress held in London in June last year-and indeed those who did-will be gratified by the publication of the collected papers in an elegant small volume. The list of contributors gives promise of a store of knowledge in matters of the circulation, from its outset with the changes which occur at birth to the latest developments in cardiovascular There is much to interest every kind of reader: surgery. no-one, for instance, could fail to be pleased by an account by Weidmann of the study by direct capillary electrode of the intimate electrochemistry of the heart-beat, or to be astonished by Kety’s revelation that cerebral blood-flow drops sharply at puberty, never to recover its earlier level. We might wonder whether after three hundred years this pure knowledge of function would interest William Harvey more than the miraculous achievements of heart and vessel surgery; or might he not perhaps, quite simply, being he, begin to look for the biggest unanswered question and start the great work anew.