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THE INFLUENCE OF TRHODOTHYROACETIC ACID ON THE CIRCULATING LIPIDS AND LIPOPROTEINS IN EUTHYROID MEN WITH CORONARY DISEASE
124 THE INFLUENCE OF TRHODOTHYROACETIC ACID ON THE CIRCULATING LIPIDS AND LIPOPROTEINS IN EUTHYROID MEN WITH CORONARY DISEASE
M. F. OLIVER M.B. Edin., M.R.C.P.E. RESEARCH
FELLOW, DEPARTMENT OF CARDIOLOGY, INFIRMARY, EDINBURGH
ROYAL
G. S. BOYD LECTURER,
DEPARTMENT
Ph.D. Edin. OF BIOCHEMISTRY,
UNIVERSITY
OF
EDINBURGH
IT has now been established beyond reasonable doubt that the circulating cholesterol, the cholesterol/phospholipid ratio, and the proportion of cholesterol which is attached to &bgr;-lipoprotein are all raised in coronary disease (Morrison et al. 1948, Gertler et al. 1950, Barr et al. 1951, Steiner et al. 1952, Nikkila 1953, Oliver and Boyd 1953, Rosenberg et al. 1954, Oliver and Boyd 1955). But it has not yet been established in man that correction of the abnormal pattern of circulating lipids and lipoproteins will retard the atherosclerotic process or decrease the tendency to thrombosis. Hence any compound which lowers the levels of cholesterol and &bgr;-lipoprotein cholesterol in the plasma requires
consideration. It has been known for many years that
thyroid
extract
lowers the plasma-cholesterol and plasma-phospholipid levels in hypothyroid and euthyroid subjects and at the same time increases their metabolic requirements (Levy and Levy 1931, Turner and Steiner 1939, Gildea et al. 1939). More recently it has been shown that thyroxine reduces the &bgr;-lipoprotein fraction (Malmros and Swahn 1953). Triiodothyroacetic acid (triac), an acetic acid analogue of triiodothyronine first synthesised by Pitt-Rivers (1953), also lowers the plasma-cholesterol, but in small doses it may not produce a concomitant rise in the basal metabolic rate (B.M.R.) (Lerman and Pitt-Rivers 1955). A similar lowering of the plasma-cholesterol without anv rise in the B.M.R. has been observed in euthyroid subjects after larger doses of triac (Trotter 1956) and after small doses of triiodothyronine (Oliver and Boyd 1956, Boyd and Oliver 1957). In general, thyroid derivatives are not suitable for administration to patients with coronary disease, because they may increase metabolic requirements enough to provoke angina and to reduce exercise-tolerance, but a derivative which decreases the plasma-cholesterol without apparently increasing metabolic requirements has obvious
From the start of the course the men attended weekly between 9 A.M. and 10 A.M. for withdrawal of blood and recording their
weight. Results
Small Dosage To six men triac was administered orally in divided and increasing doses from 0-5 mg. to 4.0 mg. daily for 95 days (fig. 1). There was no significant change in the levels of the circulating lipids and lipoproteins until .
30 mg. was given daily. At the end of the course, when 4.0 mg. had been given daily for 10 days, the mean plasma-cholesterol had fallen by 21%, but the mean cholesterol/phospho. lipid ratio was not significantly altered. The proportion of cholesterol attached to &bgr;-lipoprotein had fallen by 26% and the proportion attached to x-lipoprotein had risen by 45%. There was no loss of weight, and the mean B.M.R. of the six men was not significantly altered: the mean readings before the course were +1% and-5% and at the end of the course +1% and -3%. There was no significant change in the electrocardiograms during or after the course. In two of the six men the B.M.R. had risen by the end of the course. In one of them the B.M.R. rose by 20% and this rise was associated with a fall of 15% in the plasma-cholesterol and of 19% in the -lipoprotein cholesterol. In the other man the B.Ivf.R. rose by 13% and this rise was associated with a fall of 29% in the plasma-cholesterol and of 29% in the &bgr;-lipoprotein cholesterol. This man complained of decreased exercise. tolerance and of about three attacks of effort angina daily ; previously he had only had angina once or twice weekly on strenuous exertion. This increase in the incidence of angina necessitated recourse to glyceryl trinitrate, which he had not required for 3 years. In another man, who previously had excellent exercisetolerance and no angina, the B.M.R. fell during the course
potentialities. Methods
The subjects were twelve hypercholesterolæmic men between the ages of 33 and 49 (mean 42) who had experienced classical myocardial infarction, confirmed electrocardiographically, more than 9 months before the clinical trial of triiodothyroacetic acid. All the men had returned to their usual full-time occupations, and of them were off work 3 months preceding it.
none
during
the trial
or
in the
The plasma-cholesterol was estimated by the SperrySchoenheimer procedure modified by Sperry and Webb (1950) ; the plasma-phospholipids were estimated by the method of Allen (1940) ; and the distribution of cholesterol between the a and &bgr; lipoproteins was estimated by filterpaper zone electrophoresis with subsequent elution of The B.M.R. was determined on a cholesterol (Boyd 1954). standard Benedict-Roth apparatus by the linear formula of Aub and DuBois (1917). All the men were admitted to hospital for two nights for this purpose, the B.M.R. being determined on two consecutive mornings. Electrocardiography was done before the administration of triac, with every change in its dosage, and after the end of the course.
Fig. I—Effects of increasing dosages of triac (05-40 mg. daily) on the plasma levels of lipids and lipoproteins, the B.M.R., and the weight of six euthyroid men with coronary disease.
125 of triac, but he developed classical angina of effort twice or three times each day ; his plasma-cholesterol had fallen by 13% and his p-lipoprotein cholesterol
by 15%. When triac was withdrawn, both of these men experienced rapid regression of their symptoms, and they now have little
angina Large Dosage To six
men
or
triac
increasing doses 3 months (fig. 2). and
impairment
of exercise-tolerance.
There was no loss of weight, and the B.M.R. of these six men was not significantly altered ; the mean readings before the course were +7% and --2%, after 6 weeks on triac they were +7% and +2%, and at the end of the course they were +4% and z-2%. There was no significant change in the electrocardiograms In one of the six men or after the course. during exercise-tolerance was less as shown by more angina and breathlessness on exertion.
administered orally in divided from 3.0 mg. to 5.0 mg. daily for
was
After 3.0 mg. had been administered daily for 1 month, the mean plasma-cholesterol had fallen by 4% and the mean cholesterol/phospholipid ratio by 12%. After the administration of 4.0 mg. daily for a week the plasmacholesterol had fallen by a further 10% (making a total fall of 14%) and the cholesterol/phospholipid by a further 8% (making a total fall of 20%). After the administration of 4.0 mg. daily for 2 weeks the p-lipoprotein cholesterol had fallen by 12% and the a-lipoprotein cholesterol had risen by 15%. During the subsequent 2 weeks, when the men received 4.0 mg. daily, the plasma-cholesterol and the cholesterol/phospholipid ratio rose to control values or higher. When 5.0 mg. was administered daily for a month, there was a further slight fall in the plasma-cholesterol, but this was much less impressive than the original fall at the beginning of the course of triac with the 3.0 mg. dosage. At the end of the administration of 5.0 mg. of triac daily for a month, the proportions of cholesterol attached to x- and 3-lipoproteins had returned When triac was withdrawn, there to control values. were rebound rises in the plasma-cholesterol and in the cholesterol/phospholipid ratio.
Discussion
In
with coronary disease triiodoeuthyroid acid thyroacetic (triac) lowered the plasma-cholesterol, the cholesterol/phospholipid ratio, and the proportion of cholesterol attached to p-lipoprotein without raising the basal metabolic rate. The dosage of triac that will produce this dissociation varies from patient to patient, but the optimum is usually 3-4 mg. daily-i.e., six or eight times what is required by hypothyroid patients (Boyd and Oliver 1957). In three out of twelve men the normally good exercisetolerance was reduced, and angina developed or was greatly aggravated. In one of these three triac raised men
the B.M.R., and the reduction of exercise-tolerance is therefore not surprising. In the other two the B.M.R. did not change, yet their exercise-tolerance certainly diminished as was evident from our previous observation of the patients for several years. It has been shown that the administration of triac to euthyroid and to hypothyroid rats increases the oxygen uptake of heart tissue to a greater extent than that of liver, skeletal muscle, and kidney (Barker and Lewis 1956, Boyd and Oliver 1957). It has been suggested that triac may increase the oxygen requirements of the myocardium without causing any observable increase in the B.M.R. (Boyd and Oliver 1957). It is possible, therefore, that the dissociation of its action on the circulating lipids and lipoproteins from any effect on the B.M.R. is more apparent than real; it may depend partly on inadequacy of the B.M.R. to reflect a selective increase in the oxygen requirements of a comparatively small tissue. Fig. 2 shows that depression of the plasma-cholesterol could not be maintained over long periods even when the dosage of triac was increased. In this
graded study a comparatively large dosage (such as 5 mg. daily) was no more effective than a smaller one. Moreover such large dosage may be undesirable in some patients because it may induce angina more readily. Summary
and Conclusions
euthyroid hypercholesterolaemic men with coronary triiodothyroacetic acid (triac) lowered the plasmacholesterol, and cholesterol/phospholipid ratio, and the &bgr;-Jipoprotein-cholesterol without raising the basal In
disease
metabolic rate. After a course of triac two out of twelve men developed angina of effort, and their exercise-tolerance was decreased even though their basal metabolic rates were not raised. The fall in the plasma-cholesterol level could not be maintained for long even by increasing the dosage of triac. It is concluded that triac may not prove suitable for the long-term control of hypercholesterolaemia in patients with clinical coronary disease. We wish to thank Dr. Rae Gilchrist and Prof. G. F. Marrian, F.R.s., for their advice and encouragement ; Dr. H. M. Walker,
Fig. 2-Effects of increasing doses of triac (3 0-Smg. daily) on the plasma levels of lipids and lipoproteins, the B.M.R., and the weight of six euthyroid
men
with coronary disease.
of Glaxo Laboratories, for the triiodothyroacetic acid : and Mr. Fraser Syme and Mr. William Cooper for technical assistance. This research was supported by the Scottish Hospital Endowments Research Trust as part of their programme for the study of coronary disease.
References overleaf
’
126
ROVSING’S OPERATION FOR POLYCYSTIC KIDNEY
J. G. YATES-BELL UROLOGICAL
M.B. Lond., F.R.C.S. KING’S COLLEGE HOSPITAL,
SURGEON,
LONDON
SINCE Rovsing described his operation in 1911, little has been written about the results obtained. Most of the series have been published in the United States, but neither there nor in Britain is the value of the operation widely recognised. Apparently most surgeons try it once or twice and then abandon it because the mortalityrate is high. This is easy to explain. Uraemia is not relieved, and indeed may be fatally aggravated by, Rovsing’s operation. Hence the surgeons who try it as a last resort in patients deteriorating in spite of medical treatment, are likely to be disappointed. On the other hand, those who use it in earlier cases are often more
favourably impressed. Catrill and Fish (1941) operated on 23 of their 58 cases with They found that the results were poor when the
2 deaths.
kidneys
were
failing.
Rathbun (1942) claims that hsematuria. is particularly likely to benefit from Rovsing’s operation, and quotes an interesting misadventure leading to nephrectomy. Newman (1950) reviews the literature and observes that all authors claim good results from surgery in polycystic disease ; he reports 24 cases treated by operation and maintains that considerable benefit may be expected for pain and bleeding, but not for renal function. Goldstein (1951) treated 18 patients conservatively and 18 by his own operation. He claims to have doubled their expectation of life and to have improved their general health by reducing the severity of symptoms.
I have been tapping polycystic kidneys for twentyfive years, and have operated on nearly half the patients I have seen. I should now recommend surgery for a much higher proportion. Methods
Preoperative C’
-
—
-
—
usual curved lumbar approach can be used for the front of the kidney and no scar tissue will be present to make difficulties. The peritoneum, which extends very far posteriorly with the colon over these large kidneys, should be carefully freed towards the front. The posterior and postero-lateral cysts are punctured, or rather slit, with a small knife (diathermy is not favoured), and, as the kidney shrinks, more and more cysts come into view. To avoid shock, the operation should not be prolonged. The ilio-inguinal nerve should be protected : otherwise there may be postoperative pain. The wound is drained for about six days and rarely breaks down. Results
I have There
patients with polycystic kidneys. postoperative deaths. One patient suddenly a week after operation, with a
operated were
on
18
two
(case 5) died blood-urea of 230 mg. per 100 ml. In the other (case 14) a biopsy specimen of the polycystic liver was taken at a physician’s request. To control the bleeding took a long time ; she became shocked and soon died. Both were very advanced cases, but in the light of present knowledge they should not have died. In case 5 the operation should have been delayed and the man’s condition further improved ; in case 14 the liver-biopsy should have been avoided. This series does not include patients operated on during the war whose notes are lost and who have not been followed up. As there was no death after operation in those cases, the mortality-rate in my experience is less than 2 in 18. In most published series it appears to be just under 10% for advanced cases. Of the 16 surviving patients, symptoms were relieved or improved in 15 ; the other (case 7) had no symptoms but satisfactorily withstood a prostatectomy a month after operation. 6 patients were relieved of pain and 5 of bleeding; in 3 renal function improved temporarily. 2 with infection were improved. Hypertension is a symptom for which improvement is not usually claimed, yet 8 of these 16 cases had benefit. It was often dramatic with relief of headache and papilloedema, though most relapsed after three or four years. Such a relief is surely worth achieving. The results are summarised in tables i and 11. Illustrative Cases Case l.-The right kidney was tapped in 1933 and no further deterioration was observed on that side for over 11 years, but the left kidney continued to deteriorate and was tapped in 1944. The patient is alive and well 23 years after the first operation. Case 2.-A woman of 26 had her right kidney operated in 1937. The preoperative X-rays report reads : Grosg enlargement lower pole of right kidney. Pelvis and calyces displaced upwards and stretched over this swelling. Ureter displaced inwards. General excretion rate is good." Intravenous pyelography was repeated in 1956, and Dr. Blewett, who did not know the history, reported : " Both kidneys are secreting a good concentration but the pelves were not completely filled. Both are large and, so far as is shown, the outline of the left is consistent with a large cyst polycystic kidney. The right one, although the pelvis is large, shows no characteristic cystic impression but may be of a small cyst type." In other words, the radiologist could not be sure that the right kidney (on which we had operated) was cystic, whereas the untreated left kidney was enormous Clinically the right kidney (which was tapped) is only just palpable, whereas the left is very large and knobbly. This supports the suggestion that the tapped cysts do not re-form. "
on
Case 11.-A priest, aged 43, was in extreme hypertensive heart-failure in 1951. His blood-pressure was 205/120 nun Hg and his blood-urea 58 mg. per 100 ml. A bilateral Rovsing was performed as a life-saving measure. A month blood-pressure was 156/104 and the blood-urea 28 mg
operation later his
M. F. OLIVER M.B. Edin., M.R.C.P.E. RESEARCH
FELLOW, DEPARTMENT OF CARDIOLOGY, INFIRMARY, EDINBURGH
ROYAL
G. S. BOYD LECTURER,
DEPARTMENT
Ph.D. Edin. OF BIOCHEMISTRY,
UNIVERSITY
OF
EDINBURGH
IT has now been established beyond reasonable doubt that the circulating cholesterol, the cholesterol/phospholipid ratio, and the proportion of cholesterol which is attached to &bgr;-lipoprotein are all raised in coronary disease (Morrison et al. 1948, Gertler et al. 1950, Barr et al. 1951, Steiner et al. 1952, Nikkila 1953, Oliver and Boyd 1953, Rosenberg et al. 1954, Oliver and Boyd 1955). But it has not yet been established in man that correction of the abnormal pattern of circulating lipids and lipoproteins will retard the atherosclerotic process or decrease the tendency to thrombosis. Hence any compound which lowers the levels of cholesterol and &bgr;-lipoprotein cholesterol in the plasma requires
consideration. It has been known for many years that
thyroid
extract
lowers the plasma-cholesterol and plasma-phospholipid levels in hypothyroid and euthyroid subjects and at the same time increases their metabolic requirements (Levy and Levy 1931, Turner and Steiner 1939, Gildea et al. 1939). More recently it has been shown that thyroxine reduces the &bgr;-lipoprotein fraction (Malmros and Swahn 1953). Triiodothyroacetic acid (triac), an acetic acid analogue of triiodothyronine first synthesised by Pitt-Rivers (1953), also lowers the plasma-cholesterol, but in small doses it may not produce a concomitant rise in the basal metabolic rate (B.M.R.) (Lerman and Pitt-Rivers 1955). A similar lowering of the plasma-cholesterol without anv rise in the B.M.R. has been observed in euthyroid subjects after larger doses of triac (Trotter 1956) and after small doses of triiodothyronine (Oliver and Boyd 1956, Boyd and Oliver 1957). In general, thyroid derivatives are not suitable for administration to patients with coronary disease, because they may increase metabolic requirements enough to provoke angina and to reduce exercise-tolerance, but a derivative which decreases the plasma-cholesterol without apparently increasing metabolic requirements has obvious
From the start of the course the men attended weekly between 9 A.M. and 10 A.M. for withdrawal of blood and recording their
weight. Results
Small Dosage To six men triac was administered orally in divided and increasing doses from 0-5 mg. to 4.0 mg. daily for 95 days (fig. 1). There was no significant change in the levels of the circulating lipids and lipoproteins until .
30 mg. was given daily. At the end of the course, when 4.0 mg. had been given daily for 10 days, the mean plasma-cholesterol had fallen by 21%, but the mean cholesterol/phospho. lipid ratio was not significantly altered. The proportion of cholesterol attached to &bgr;-lipoprotein had fallen by 26% and the proportion attached to x-lipoprotein had risen by 45%. There was no loss of weight, and the mean B.M.R. of the six men was not significantly altered: the mean readings before the course were +1% and-5% and at the end of the course +1% and -3%. There was no significant change in the electrocardiograms during or after the course. In two of the six men the B.M.R. had risen by the end of the course. In one of them the B.M.R. rose by 20% and this rise was associated with a fall of 15% in the plasma-cholesterol and of 19% in the -lipoprotein cholesterol. In the other man the B.Ivf.R. rose by 13% and this rise was associated with a fall of 29% in the plasma-cholesterol and of 29% in the &bgr;-lipoprotein cholesterol. This man complained of decreased exercise. tolerance and of about three attacks of effort angina daily ; previously he had only had angina once or twice weekly on strenuous exertion. This increase in the incidence of angina necessitated recourse to glyceryl trinitrate, which he had not required for 3 years. In another man, who previously had excellent exercisetolerance and no angina, the B.M.R. fell during the course
potentialities. Methods
The subjects were twelve hypercholesterolæmic men between the ages of 33 and 49 (mean 42) who had experienced classical myocardial infarction, confirmed electrocardiographically, more than 9 months before the clinical trial of triiodothyroacetic acid. All the men had returned to their usual full-time occupations, and of them were off work 3 months preceding it.
none
during
the trial
or
in the
The plasma-cholesterol was estimated by the SperrySchoenheimer procedure modified by Sperry and Webb (1950) ; the plasma-phospholipids were estimated by the method of Allen (1940) ; and the distribution of cholesterol between the a and &bgr; lipoproteins was estimated by filterpaper zone electrophoresis with subsequent elution of The B.M.R. was determined on a cholesterol (Boyd 1954). standard Benedict-Roth apparatus by the linear formula of Aub and DuBois (1917). All the men were admitted to hospital for two nights for this purpose, the B.M.R. being determined on two consecutive mornings. Electrocardiography was done before the administration of triac, with every change in its dosage, and after the end of the course.
Fig. I—Effects of increasing dosages of triac (05-40 mg. daily) on the plasma levels of lipids and lipoproteins, the B.M.R., and the weight of six euthyroid men with coronary disease.
125 of triac, but he developed classical angina of effort twice or three times each day ; his plasma-cholesterol had fallen by 13% and his p-lipoprotein cholesterol
by 15%. When triac was withdrawn, both of these men experienced rapid regression of their symptoms, and they now have little
angina Large Dosage To six
men
or
triac
increasing doses 3 months (fig. 2). and
impairment
of exercise-tolerance.
There was no loss of weight, and the B.M.R. of these six men was not significantly altered ; the mean readings before the course were +7% and --2%, after 6 weeks on triac they were +7% and +2%, and at the end of the course they were +4% and z-2%. There was no significant change in the electrocardiograms In one of the six men or after the course. during exercise-tolerance was less as shown by more angina and breathlessness on exertion.
administered orally in divided from 3.0 mg. to 5.0 mg. daily for
was
After 3.0 mg. had been administered daily for 1 month, the mean plasma-cholesterol had fallen by 4% and the mean cholesterol/phospholipid ratio by 12%. After the administration of 4.0 mg. daily for a week the plasmacholesterol had fallen by a further 10% (making a total fall of 14%) and the cholesterol/phospholipid by a further 8% (making a total fall of 20%). After the administration of 4.0 mg. daily for 2 weeks the p-lipoprotein cholesterol had fallen by 12% and the a-lipoprotein cholesterol had risen by 15%. During the subsequent 2 weeks, when the men received 4.0 mg. daily, the plasma-cholesterol and the cholesterol/phospholipid ratio rose to control values or higher. When 5.0 mg. was administered daily for a month, there was a further slight fall in the plasma-cholesterol, but this was much less impressive than the original fall at the beginning of the course of triac with the 3.0 mg. dosage. At the end of the administration of 5.0 mg. of triac daily for a month, the proportions of cholesterol attached to x- and 3-lipoproteins had returned When triac was withdrawn, there to control values. were rebound rises in the plasma-cholesterol and in the cholesterol/phospholipid ratio.
Discussion
In
with coronary disease triiodoeuthyroid acid thyroacetic (triac) lowered the plasma-cholesterol, the cholesterol/phospholipid ratio, and the proportion of cholesterol attached to p-lipoprotein without raising the basal metabolic rate. The dosage of triac that will produce this dissociation varies from patient to patient, but the optimum is usually 3-4 mg. daily-i.e., six or eight times what is required by hypothyroid patients (Boyd and Oliver 1957). In three out of twelve men the normally good exercisetolerance was reduced, and angina developed or was greatly aggravated. In one of these three triac raised men
the B.M.R., and the reduction of exercise-tolerance is therefore not surprising. In the other two the B.M.R. did not change, yet their exercise-tolerance certainly diminished as was evident from our previous observation of the patients for several years. It has been shown that the administration of triac to euthyroid and to hypothyroid rats increases the oxygen uptake of heart tissue to a greater extent than that of liver, skeletal muscle, and kidney (Barker and Lewis 1956, Boyd and Oliver 1957). It has been suggested that triac may increase the oxygen requirements of the myocardium without causing any observable increase in the B.M.R. (Boyd and Oliver 1957). It is possible, therefore, that the dissociation of its action on the circulating lipids and lipoproteins from any effect on the B.M.R. is more apparent than real; it may depend partly on inadequacy of the B.M.R. to reflect a selective increase in the oxygen requirements of a comparatively small tissue. Fig. 2 shows that depression of the plasma-cholesterol could not be maintained over long periods even when the dosage of triac was increased. In this
graded study a comparatively large dosage (such as 5 mg. daily) was no more effective than a smaller one. Moreover such large dosage may be undesirable in some patients because it may induce angina more readily. Summary
and Conclusions
euthyroid hypercholesterolaemic men with coronary triiodothyroacetic acid (triac) lowered the plasmacholesterol, and cholesterol/phospholipid ratio, and the &bgr;-Jipoprotein-cholesterol without raising the basal In
disease
metabolic rate. After a course of triac two out of twelve men developed angina of effort, and their exercise-tolerance was decreased even though their basal metabolic rates were not raised. The fall in the plasma-cholesterol level could not be maintained for long even by increasing the dosage of triac. It is concluded that triac may not prove suitable for the long-term control of hypercholesterolaemia in patients with clinical coronary disease. We wish to thank Dr. Rae Gilchrist and Prof. G. F. Marrian, F.R.s., for their advice and encouragement ; Dr. H. M. Walker,
Fig. 2-Effects of increasing doses of triac (3 0-Smg. daily) on the plasma levels of lipids and lipoproteins, the B.M.R., and the weight of six euthyroid
men
with coronary disease.
of Glaxo Laboratories, for the triiodothyroacetic acid : and Mr. Fraser Syme and Mr. William Cooper for technical assistance. This research was supported by the Scottish Hospital Endowments Research Trust as part of their programme for the study of coronary disease.
References overleaf
’
126
ROVSING’S OPERATION FOR POLYCYSTIC KIDNEY
J. G. YATES-BELL UROLOGICAL
M.B. Lond., F.R.C.S. KING’S COLLEGE HOSPITAL,
SURGEON,
LONDON
SINCE Rovsing described his operation in 1911, little has been written about the results obtained. Most of the series have been published in the United States, but neither there nor in Britain is the value of the operation widely recognised. Apparently most surgeons try it once or twice and then abandon it because the mortalityrate is high. This is easy to explain. Uraemia is not relieved, and indeed may be fatally aggravated by, Rovsing’s operation. Hence the surgeons who try it as a last resort in patients deteriorating in spite of medical treatment, are likely to be disappointed. On the other hand, those who use it in earlier cases are often more
favourably impressed. Catrill and Fish (1941) operated on 23 of their 58 cases with They found that the results were poor when the
2 deaths.
kidneys
were
failing.
Rathbun (1942) claims that hsematuria. is particularly likely to benefit from Rovsing’s operation, and quotes an interesting misadventure leading to nephrectomy. Newman (1950) reviews the literature and observes that all authors claim good results from surgery in polycystic disease ; he reports 24 cases treated by operation and maintains that considerable benefit may be expected for pain and bleeding, but not for renal function. Goldstein (1951) treated 18 patients conservatively and 18 by his own operation. He claims to have doubled their expectation of life and to have improved their general health by reducing the severity of symptoms.
I have been tapping polycystic kidneys for twentyfive years, and have operated on nearly half the patients I have seen. I should now recommend surgery for a much higher proportion. Methods
Preoperative C’
-
—
-
—
usual curved lumbar approach can be used for the front of the kidney and no scar tissue will be present to make difficulties. The peritoneum, which extends very far posteriorly with the colon over these large kidneys, should be carefully freed towards the front. The posterior and postero-lateral cysts are punctured, or rather slit, with a small knife (diathermy is not favoured), and, as the kidney shrinks, more and more cysts come into view. To avoid shock, the operation should not be prolonged. The ilio-inguinal nerve should be protected : otherwise there may be postoperative pain. The wound is drained for about six days and rarely breaks down. Results
I have There
patients with polycystic kidneys. postoperative deaths. One patient suddenly a week after operation, with a
operated were
on
18
two
(case 5) died blood-urea of 230 mg. per 100 ml. In the other (case 14) a biopsy specimen of the polycystic liver was taken at a physician’s request. To control the bleeding took a long time ; she became shocked and soon died. Both were very advanced cases, but in the light of present knowledge they should not have died. In case 5 the operation should have been delayed and the man’s condition further improved ; in case 14 the liver-biopsy should have been avoided. This series does not include patients operated on during the war whose notes are lost and who have not been followed up. As there was no death after operation in those cases, the mortality-rate in my experience is less than 2 in 18. In most published series it appears to be just under 10% for advanced cases. Of the 16 surviving patients, symptoms were relieved or improved in 15 ; the other (case 7) had no symptoms but satisfactorily withstood a prostatectomy a month after operation. 6 patients were relieved of pain and 5 of bleeding; in 3 renal function improved temporarily. 2 with infection were improved. Hypertension is a symptom for which improvement is not usually claimed, yet 8 of these 16 cases had benefit. It was often dramatic with relief of headache and papilloedema, though most relapsed after three or four years. Such a relief is surely worth achieving. The results are summarised in tables i and 11. Illustrative Cases Case l.-The right kidney was tapped in 1933 and no further deterioration was observed on that side for over 11 years, but the left kidney continued to deteriorate and was tapped in 1944. The patient is alive and well 23 years after the first operation. Case 2.-A woman of 26 had her right kidney operated in 1937. The preoperative X-rays report reads : Grosg enlargement lower pole of right kidney. Pelvis and calyces displaced upwards and stretched over this swelling. Ureter displaced inwards. General excretion rate is good." Intravenous pyelography was repeated in 1956, and Dr. Blewett, who did not know the history, reported : " Both kidneys are secreting a good concentration but the pelves were not completely filled. Both are large and, so far as is shown, the outline of the left is consistent with a large cyst polycystic kidney. The right one, although the pelvis is large, shows no characteristic cystic impression but may be of a small cyst type." In other words, the radiologist could not be sure that the right kidney (on which we had operated) was cystic, whereas the untreated left kidney was enormous Clinically the right kidney (which was tapped) is only just palpable, whereas the left is very large and knobbly. This supports the suggestion that the tapped cysts do not re-form. "
on
Case 11.-A priest, aged 43, was in extreme hypertensive heart-failure in 1951. His blood-pressure was 205/120 nun Hg and his blood-urea 58 mg. per 100 ml. A bilateral Rovsing was performed as a life-saving measure. A month blood-pressure was 156/104 and the blood-urea 28 mg
operation later his