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TOLBUTAMIDE CONTROL OF DIABETES MELLITUS
670
Letters THE
to
obesity is expected
the Editor
COCKETT/ELGAN JONES (ST. THOMAS’S) OPERATION
SIR,-The CockettElgan Jones operation referred to by Dr. Rivlin (Oct. 3) as the St. Thomas’s operation emerged from the sweat, toil, and inspiration of these It gave us the anatomy, relations, and physiomen. pathology of the ankle perforating veins, and showed us how they became incompetent and caused eczema and ulceration. For fifty years surgeons had ligated large veins at the ankle (I started doing it in 1941), but we didn’t know where, how many veins there were, and how they came to be incompetent. I consider that this procedure is as notable a milestone in the treatment of the venous disorders of the lower limb as was the Brodie-Trendelenburg ligature of the long saphenous vein. The diagnosis in my series is 30% varicose, 30% ankle perforating veins, and 30% both (the remainder are
rarities).
of it can be detected in the blood. The standard dose of tolbutaminde, 0.5 g. four times a day, seems rather high. We have found the maximal doses for estimating reponsiveness to be, for tolbutamide, 500 mg. thrice daily, for chlorpropamide, 500 mg. once daily, and for metahexamide 300 mg. Increase beyond these doses has rarely if ever improved control, while large doses are probably responsible for many of the reports of toxicity, and therefore not advisable. Did the authors in fact find any benefit when they gave 4 g. daily ? While welcoming the advice to determine whether or not the patient requires either insulin or tolbutamide, I consider there is some danger in dealing with outpatients by their method of transferring from one to the other. Patients had insulin stopped for 48 hours; 2 became ketotic and required insulin immediately. I have seen a similar case lapse within this space of time into precoma and require intravenous therapy. The procedure which we recommend is to reduce the insulin, and then give tablets (we prefer chlorpropamide which necessitates only a single daily dose). If urine tests show excellent control, insulin is further reduced and, if oral therapy is to prove effective, withdrawn. After a period on tablets alone these too are withdrawn, and only if glycosuria and hyperglycasmia recur is it decided that continuing oral therapy is desirable. It is at this stage perhaps that inert tablets might be used-now truly a placebo " to obviate the fear of relapse which some patients exhibit when it is suggested that they discontinue the tablets in which they have come to place much faith. The Victoria Infirmary, IAN MURRAY. Glasgow.
trace
_
upwards of 500 ligations of ankle communicating veins, and have found it a first-class procedure I have done
for all ages.
The oldest done was 80, and she is still 86. An encouraging follow-up was publishedin this journal in December, 1957. I think it is an operation to be done only after a diagnosis has been made, based on symptoms and physical signs. It is not a procedure for the occasional surgeon. As with all radical surgery, points of management ensure its success. It has restored all my patients to circulation appropriate to their age-group. Recurrent ulceration occasionally after occurs, mainly trauma, but the benefits and activity by far exceed the results from bandaging only. The only physiotherapy those under my care have received (I see 60 to 75 per week) is that of following their daily occupation. They wear protection appropriate to their healed limbs. The scar, after 20 to 30 years of ulceration, cannot safely be left unbuffered. I have found the ligation of ankle perforating veins a major contribution to the cure of much recalcitrant ulceration in all social classes. HAROLD DODD. London, W.l.
circulating
in itself so essential, and since this alone may be to effect satisfactory diabetic control, it is at least debatable whether in such cases the administration of hypoglycxmic drugs is justifiable. It would be interesting to know how the other patients of this type responded in this trial-both as regards weight and diabetic control. During the period of observation after transfer from tolbutamide to the placebo the authors estimate the state of diabetic control during the second week. This is essential since complete remission may persist for several days after stopping tolbutamide-and for much longer if the drug used has been carbutamide or chlorpropamide-and long after any
at
"
THE ÆTIOLOGY OF LEUKÆMIAS
SIR,-In our time we all play many parts. I had cast Dr. Schoyer for the part of the villain who advocates the TOLBUTAMIDE CONTROL OF DIABETES doctrine of " special evil " of the cancer cell, but I now MELLITUS find from Professor Smithers’ letter of Oct. 10 that I am SIR,-Some aspects of the interesting paper by taking that part. I have for a long time believed that the process of Dr. Joplin, Professor Fraser, and Dr. Vallance-Owen (Oct. 17) merit greater emphasis. It is noteworthy that carcinogenesis is an aberration of the maintenance of the normal processes of growth and differentiation in in 11 of 38 patients receiving insulin but considered the tissues, as I have stated in print.l My work on suitable for trial with tolbutamide it was found that insulin was unnecessary. This illustrates the undoubted the relationship of carcinogenesis and regeneration in the liver (in the press), and on the surface properties of cells fact that many diabetics are taking insulin needlessly, all that in tissues undergoing carcinogenesis, and in tumours, is control is But adequate dietary being required. there is evidence that many patients now receiving sulbased on such an assumption. It now appears from the continue this It last paragraph of Dr. Schoyer’s letter that we are at least therapy quite unnecessarily. phonylureas is perhaps due to the careful selection of patients by the at one in believing in the importance of the properties of the cell surface, in " the cancer cell " if I may use this authors that this was found to be true in only 1 of their cases who responded satisfactorily to tolbutamide. latter term. It seems that Professor Smithers attributes Nevertheless even this patient might have been continued much evil to its use. on the had trial an inert not It is probable that the behaviour of all cells depends to with tablet indefinitely drug a considerable extent on their environment. No-one who been a regular feature of this investigation. It is noted that this particular patient lost a stone in weight. Is it to be has worked on the liver cell in the " normalstate, in regeneration, during carcinogenesis, and in tissue assumed that this was one of the cases referred to as having previously " proved hopeless " in the attempts to achieve culture would seriously doubt this. Yet it is convenient " necessary weight reduction " ? Since correction of to refer to certain general properties of the " liver cell ". 1.
Dodd, H., Calo,
A.
R., Mistry, M., Rushford,
A.
Lancet, 1957,[ii, 1249.
1
Laws, J. O. Med. Pr. 1958, 240, 943.
Letters THE
to
obesity is expected
the Editor
COCKETT/ELGAN JONES (ST. THOMAS’S) OPERATION
SIR,-The CockettElgan Jones operation referred to by Dr. Rivlin (Oct. 3) as the St. Thomas’s operation emerged from the sweat, toil, and inspiration of these It gave us the anatomy, relations, and physiomen. pathology of the ankle perforating veins, and showed us how they became incompetent and caused eczema and ulceration. For fifty years surgeons had ligated large veins at the ankle (I started doing it in 1941), but we didn’t know where, how many veins there were, and how they came to be incompetent. I consider that this procedure is as notable a milestone in the treatment of the venous disorders of the lower limb as was the Brodie-Trendelenburg ligature of the long saphenous vein. The diagnosis in my series is 30% varicose, 30% ankle perforating veins, and 30% both (the remainder are
rarities).
of it can be detected in the blood. The standard dose of tolbutaminde, 0.5 g. four times a day, seems rather high. We have found the maximal doses for estimating reponsiveness to be, for tolbutamide, 500 mg. thrice daily, for chlorpropamide, 500 mg. once daily, and for metahexamide 300 mg. Increase beyond these doses has rarely if ever improved control, while large doses are probably responsible for many of the reports of toxicity, and therefore not advisable. Did the authors in fact find any benefit when they gave 4 g. daily ? While welcoming the advice to determine whether or not the patient requires either insulin or tolbutamide, I consider there is some danger in dealing with outpatients by their method of transferring from one to the other. Patients had insulin stopped for 48 hours; 2 became ketotic and required insulin immediately. I have seen a similar case lapse within this space of time into precoma and require intravenous therapy. The procedure which we recommend is to reduce the insulin, and then give tablets (we prefer chlorpropamide which necessitates only a single daily dose). If urine tests show excellent control, insulin is further reduced and, if oral therapy is to prove effective, withdrawn. After a period on tablets alone these too are withdrawn, and only if glycosuria and hyperglycasmia recur is it decided that continuing oral therapy is desirable. It is at this stage perhaps that inert tablets might be used-now truly a placebo " to obviate the fear of relapse which some patients exhibit when it is suggested that they discontinue the tablets in which they have come to place much faith. The Victoria Infirmary, IAN MURRAY. Glasgow.
trace
_
upwards of 500 ligations of ankle communicating veins, and have found it a first-class procedure I have done
for all ages.
The oldest done was 80, and she is still 86. An encouraging follow-up was publishedin this journal in December, 1957. I think it is an operation to be done only after a diagnosis has been made, based on symptoms and physical signs. It is not a procedure for the occasional surgeon. As with all radical surgery, points of management ensure its success. It has restored all my patients to circulation appropriate to their age-group. Recurrent ulceration occasionally after occurs, mainly trauma, but the benefits and activity by far exceed the results from bandaging only. The only physiotherapy those under my care have received (I see 60 to 75 per week) is that of following their daily occupation. They wear protection appropriate to their healed limbs. The scar, after 20 to 30 years of ulceration, cannot safely be left unbuffered. I have found the ligation of ankle perforating veins a major contribution to the cure of much recalcitrant ulceration in all social classes. HAROLD DODD. London, W.l.
circulating
in itself so essential, and since this alone may be to effect satisfactory diabetic control, it is at least debatable whether in such cases the administration of hypoglycxmic drugs is justifiable. It would be interesting to know how the other patients of this type responded in this trial-both as regards weight and diabetic control. During the period of observation after transfer from tolbutamide to the placebo the authors estimate the state of diabetic control during the second week. This is essential since complete remission may persist for several days after stopping tolbutamide-and for much longer if the drug used has been carbutamide or chlorpropamide-and long after any
at
"
THE ÆTIOLOGY OF LEUKÆMIAS
SIR,-In our time we all play many parts. I had cast Dr. Schoyer for the part of the villain who advocates the TOLBUTAMIDE CONTROL OF DIABETES doctrine of " special evil " of the cancer cell, but I now MELLITUS find from Professor Smithers’ letter of Oct. 10 that I am SIR,-Some aspects of the interesting paper by taking that part. I have for a long time believed that the process of Dr. Joplin, Professor Fraser, and Dr. Vallance-Owen (Oct. 17) merit greater emphasis. It is noteworthy that carcinogenesis is an aberration of the maintenance of the normal processes of growth and differentiation in in 11 of 38 patients receiving insulin but considered the tissues, as I have stated in print.l My work on suitable for trial with tolbutamide it was found that insulin was unnecessary. This illustrates the undoubted the relationship of carcinogenesis and regeneration in the liver (in the press), and on the surface properties of cells fact that many diabetics are taking insulin needlessly, all that in tissues undergoing carcinogenesis, and in tumours, is control is But adequate dietary being required. there is evidence that many patients now receiving sulbased on such an assumption. It now appears from the continue this It last paragraph of Dr. Schoyer’s letter that we are at least therapy quite unnecessarily. phonylureas is perhaps due to the careful selection of patients by the at one in believing in the importance of the properties of the cell surface, in " the cancer cell " if I may use this authors that this was found to be true in only 1 of their cases who responded satisfactorily to tolbutamide. latter term. It seems that Professor Smithers attributes Nevertheless even this patient might have been continued much evil to its use. on the had trial an inert not It is probable that the behaviour of all cells depends to with tablet indefinitely drug a considerable extent on their environment. No-one who been a regular feature of this investigation. It is noted that this particular patient lost a stone in weight. Is it to be has worked on the liver cell in the " normalstate, in regeneration, during carcinogenesis, and in tissue assumed that this was one of the cases referred to as having previously " proved hopeless " in the attempts to achieve culture would seriously doubt this. Yet it is convenient " necessary weight reduction " ? Since correction of to refer to certain general properties of the " liver cell ". 1.
Dodd, H., Calo,
A.
R., Mistry, M., Rushford,
A.
Lancet, 1957,[ii, 1249.
1
Laws, J. O. Med. Pr. 1958, 240, 943.