364
BRITISH MEDICAL JOURNAL
Two of the references' 2 do, however, present data concerning the use of short-acting cardiac glycosides given before doxorubicin and it is true to say that the evidence of the protective effects of these in animal models is conflicting. However, as we stated in our paper, it seems illogical to us to use short-acting cardiac glycosides such as ouabain in this situation when they have a much shorter half life than either doxorubicin or its metabolites. We are not aware of any work in either animals or man in which digoxin has been used in the manner we described in the paper, but would welcome any information on this point from your readers. The next point on which we are taken to task is our alleged failure fully to report known risk factors. We did, in fact, precis this information in the paper in that all three groups of patients were comparable as regards these risk factors. We did not mention previous radiation to the heart or concomitant cyclophosphamide, as none of the patients had either of these. As regards the patient who developed electrocardiographic changes of doxorubicin toxicity after stopping her digoxin, a more accurate impression of the length of time she had been off the digoxin could perhaps have been conveyed by the use of the term "some months" rather than "some weeks," and hence we feel it unlikely that she was developing doxorubicin cardiotoxicity before stopping the
myopathy by the concomitant administration of digoxin in patients treated for gynaecological cancers. Supposedly digoxin acts as a competitive inhibitor for doxorubicin and its metabolites on receptor sites. If so, the action may hold good for the tumour tissue as well as cardiac and skeletal muscle. How far the efficacy of the drug is reduced by the digoxin blockade has to be studied. The findings are of clinical value only when it is proved that digitalisation does not reduce the chemotherapeutic efficacy of doxorubicin. T M MATHEW St Mary's Hospital, Rochester, New York
Labetalol and urinary catecholamines SIR,-In a recent letter (24 December, p 1673) Drs P M Harris and D A Richards describe interference by labetalol in the estimation of free catecholamines. They suggest that this might be by a metabolic mechanism, thus making it difficult to screen for phaeochromocytoma in patients being treated with labetalol. Several tests are available for this purpose. In our laboratory, on a 24-h urine collection, we normally estimate the normetadrenaline and metadrenaline by the method of Pisanol adapted by Crout et a12 and, in suspected abnormal patients, we estimate 4-hydroxy-3methoxy mandelic acid (HMMA) by the method of Pisano et al.3 We do not estimate free catecholamines. We found that labetalol affects the normetadrenaline and metadrenaline test such that quite high results are obtained when large doses of labetalol are taken. HMMA was estimated in these specimens and normal results were obtained. Cessation of labetalol treatment produced a large decrease in the normetadrenaline and metadrenaline levels after about a week while the HMMA values remained unaltered. We suggest that if a patient being treated with labetalol is to be screened for phaeochromocytoma this may be done by estimating the HMMA output in urine. Further work is being undertaken to clarify the interference by labetalol in the normetadrenaline and metadrenaline test, but our tests so far suggest that this is chemical rather than metabolic.
digoxin. The criticism of lack of data concerning the rate of administration of doxorubicin is quite justifiable and a lamentable omission on our part. In practice all patients had 50 mg/m2 doxorubicin given as a bolus injection lasting approximately one minute into the tubing of a fast-flowing saline drip. Such treatment was repeated every three or four weeks depending upon the patient's white cell count. It is unfortunate that Dr Williams should infer that we believe that oxytetracycline can improve necrosis of myofibrils in doxorubicin cardiotoxicity. We do not believe this, and, furthermore, only recorded the use of oxytetracycline so that all details concerning the management of these patients should be available. As we stated in the paper, "whether in fact it [oxytetracycline] played any part in the recovery of the patients remains a matter for conjecture." B P CHAPMAN We do not claim that digoxin will prevent ANGELA G VEITCH doxorubicin cardiotoxicity, a point which we BRIAN SHEPHERD felt was reflected in the title of the paper, but Hospital, it appears that it may allow clinicians to treat Raigmore Inverness patients with total doses higher than the present recommended upper limit. Our aim Pisano, J J, Clinica Chimica Acta, 1960, 5, 406. J R, Pisano, J J, and Sjoerdsma, A, Aierican in publishing these findings was to stimulate 2 Crout, Heart JIournal, 1961, 61, 375. interest and to hope that others may be able to Pisano, J J, Crout, J R, and Abraham, D, Clitica Chimica Acta, 1962, 7, 285. investigate further and hopefully redefine the safe upper limit of this most useful cytotoxic agent. D GUTHRIE Incontinence A L GIBSON Newcastle General Hospital, Newcastle upon Tyne Arena, G, et al, in International Symposium on Adriamycin, ed S Carter et al, pp 96-116. New York, Springer, 1972. 2 Philips, F, et al, Cancer Chemotherapy Reports, 1975, 6, 177. 3 Lefrak, E A, et al, Cancer, 1973, 32, 302.
SIR,-May I comment briefly on the article by Drs D Guthrie and A L Gibson (3 December, p 1447) ? It was interesting to see the significant reduction of doxorubicin-induced cardio-
SIR,-Your leading article on this subject (14 January, p 61) is timely and its orientation towards the elderly (omitted in the title) is welcomed. Amplification of the title is needed as, for example, the commonest cause of urinary retention with overflow in the general population is likely to be neuropathic, followed by prostatic hypertrophy. Incontinence in the elderly differs from that in other age groups in aetiology, investigation, and treatment. Detrusor instability is more common here and is believed to be due to cerebrovascular atherosclerosis leading to
11 FEBRUARY 1978
diminished cortical control of micturition. Its features are nocturia, urgency, urge incontinence, intermittent dribbling, and stress incontinence. The effect of these symptoms may be aggravated by the patient's relative immobility and by being unable to get out of bed at night (due to a high bed, presence of cot side, and excess night sedation). If hospital nursing and medical staff fail to appreciate the difficulties confronting the newly admitted older patient and do not recognise confusional states (which can easily occur) the problem will be further compounded. Investigations in the elderly should be minimal and selective. Conservative measures to control incontinence should be tried first. These include collection of a midstream specimen of urine for culture and sensitivity testing and a urinary diary to note the times when incontinence occurs: the latter will enable a simple regimen of 2-3-hourly toileting to be tried. If this fails two-channel cystometry (using bladder and rectal pressurerecording catheters to measure the detrusor pressure) can be used to detect detrusor instability. If present the treatment is medical, using flavoxate hydrochloride 200-300 mg four times a day, emepronium bromide, or imipramine hydrochloride 25-50 mg twice daily. When there is an uncomplicated history of stress incontinence in a patient who is mentally alert and physically fit and has a normal cystometrogram incontinence surgery should be offered. With modern anaesthesia and intensive postoperative care surgery in the elderly need not be restricted to life-saving measures and patients should not be excluded for reasons of age alone. Surgical management must include control of respiratory disease, avoidance of scopolamine as a premedication, early mobilisation following surgery, awareness on the part of the patient, relatives, and nurses of the expected rate of postoperative progress, and avoidance of night sedation (especially barbiturates and nitrazepam). The nursing staff should anticipate the needs and problems of the elderly and be aware of the ease with which confusional states may develop. If medical treatment fails and surgery is contraindicated or refused a vast array of incontinence garments, pads, and appliances is now available. The variety of measures and the large numbers of patients who can benefit necessitate the training of a nurse who is familiar with the problems of incontinence and of their methods of treatment and who can equip individual patients with the correct garment and appliances-something which the average surgical supplies officer has neither the training nor the time to do. The precedent for this type of nurse has already been set in the form of the "stoma care nurse," and her equivalent in the area of urinary incontinence is badly needed. STUART L STANTON LINDA CARDOZO PETER MILLARD HOPE TRENCHARD St George's Hospital Medical School, SW17
London
SIR,-Your leading article on incontinence (14 January, p 61) reveals only too well what a difficult subject this is to comprehend. It is obviously impossible in such a short space to cover such a vast subject comprehensively. There is, however, one error of fact which requires correction. The trigone of the bladder is not related developmentally to the vagina.
BRITISH MEDICAL JOURNAL
Two of the references' 2 do, however, present data concerning the use of short-acting cardiac glycosides given before doxorubicin and it is true to say that the evidence of the protective effects of these in animal models is conflicting. However, as we stated in our paper, it seems illogical to us to use short-acting cardiac glycosides such as ouabain in this situation when they have a much shorter half life than either doxorubicin or its metabolites. We are not aware of any work in either animals or man in which digoxin has been used in the manner we described in the paper, but would welcome any information on this point from your readers. The next point on which we are taken to task is our alleged failure fully to report known risk factors. We did, in fact, precis this information in the paper in that all three groups of patients were comparable as regards these risk factors. We did not mention previous radiation to the heart or concomitant cyclophosphamide, as none of the patients had either of these. As regards the patient who developed electrocardiographic changes of doxorubicin toxicity after stopping her digoxin, a more accurate impression of the length of time she had been off the digoxin could perhaps have been conveyed by the use of the term "some months" rather than "some weeks," and hence we feel it unlikely that she was developing doxorubicin cardiotoxicity before stopping the
myopathy by the concomitant administration of digoxin in patients treated for gynaecological cancers. Supposedly digoxin acts as a competitive inhibitor for doxorubicin and its metabolites on receptor sites. If so, the action may hold good for the tumour tissue as well as cardiac and skeletal muscle. How far the efficacy of the drug is reduced by the digoxin blockade has to be studied. The findings are of clinical value only when it is proved that digitalisation does not reduce the chemotherapeutic efficacy of doxorubicin. T M MATHEW St Mary's Hospital, Rochester, New York
Labetalol and urinary catecholamines SIR,-In a recent letter (24 December, p 1673) Drs P M Harris and D A Richards describe interference by labetalol in the estimation of free catecholamines. They suggest that this might be by a metabolic mechanism, thus making it difficult to screen for phaeochromocytoma in patients being treated with labetalol. Several tests are available for this purpose. In our laboratory, on a 24-h urine collection, we normally estimate the normetadrenaline and metadrenaline by the method of Pisanol adapted by Crout et a12 and, in suspected abnormal patients, we estimate 4-hydroxy-3methoxy mandelic acid (HMMA) by the method of Pisano et al.3 We do not estimate free catecholamines. We found that labetalol affects the normetadrenaline and metadrenaline test such that quite high results are obtained when large doses of labetalol are taken. HMMA was estimated in these specimens and normal results were obtained. Cessation of labetalol treatment produced a large decrease in the normetadrenaline and metadrenaline levels after about a week while the HMMA values remained unaltered. We suggest that if a patient being treated with labetalol is to be screened for phaeochromocytoma this may be done by estimating the HMMA output in urine. Further work is being undertaken to clarify the interference by labetalol in the normetadrenaline and metadrenaline test, but our tests so far suggest that this is chemical rather than metabolic.
digoxin. The criticism of lack of data concerning the rate of administration of doxorubicin is quite justifiable and a lamentable omission on our part. In practice all patients had 50 mg/m2 doxorubicin given as a bolus injection lasting approximately one minute into the tubing of a fast-flowing saline drip. Such treatment was repeated every three or four weeks depending upon the patient's white cell count. It is unfortunate that Dr Williams should infer that we believe that oxytetracycline can improve necrosis of myofibrils in doxorubicin cardiotoxicity. We do not believe this, and, furthermore, only recorded the use of oxytetracycline so that all details concerning the management of these patients should be available. As we stated in the paper, "whether in fact it [oxytetracycline] played any part in the recovery of the patients remains a matter for conjecture." B P CHAPMAN We do not claim that digoxin will prevent ANGELA G VEITCH doxorubicin cardiotoxicity, a point which we BRIAN SHEPHERD felt was reflected in the title of the paper, but Hospital, it appears that it may allow clinicians to treat Raigmore Inverness patients with total doses higher than the present recommended upper limit. Our aim Pisano, J J, Clinica Chimica Acta, 1960, 5, 406. J R, Pisano, J J, and Sjoerdsma, A, Aierican in publishing these findings was to stimulate 2 Crout, Heart JIournal, 1961, 61, 375. interest and to hope that others may be able to Pisano, J J, Crout, J R, and Abraham, D, Clitica Chimica Acta, 1962, 7, 285. investigate further and hopefully redefine the safe upper limit of this most useful cytotoxic agent. D GUTHRIE Incontinence A L GIBSON Newcastle General Hospital, Newcastle upon Tyne Arena, G, et al, in International Symposium on Adriamycin, ed S Carter et al, pp 96-116. New York, Springer, 1972. 2 Philips, F, et al, Cancer Chemotherapy Reports, 1975, 6, 177. 3 Lefrak, E A, et al, Cancer, 1973, 32, 302.
SIR,-May I comment briefly on the article by Drs D Guthrie and A L Gibson (3 December, p 1447) ? It was interesting to see the significant reduction of doxorubicin-induced cardio-
SIR,-Your leading article on this subject (14 January, p 61) is timely and its orientation towards the elderly (omitted in the title) is welcomed. Amplification of the title is needed as, for example, the commonest cause of urinary retention with overflow in the general population is likely to be neuropathic, followed by prostatic hypertrophy. Incontinence in the elderly differs from that in other age groups in aetiology, investigation, and treatment. Detrusor instability is more common here and is believed to be due to cerebrovascular atherosclerosis leading to
11 FEBRUARY 1978
diminished cortical control of micturition. Its features are nocturia, urgency, urge incontinence, intermittent dribbling, and stress incontinence. The effect of these symptoms may be aggravated by the patient's relative immobility and by being unable to get out of bed at night (due to a high bed, presence of cot side, and excess night sedation). If hospital nursing and medical staff fail to appreciate the difficulties confronting the newly admitted older patient and do not recognise confusional states (which can easily occur) the problem will be further compounded. Investigations in the elderly should be minimal and selective. Conservative measures to control incontinence should be tried first. These include collection of a midstream specimen of urine for culture and sensitivity testing and a urinary diary to note the times when incontinence occurs: the latter will enable a simple regimen of 2-3-hourly toileting to be tried. If this fails two-channel cystometry (using bladder and rectal pressurerecording catheters to measure the detrusor pressure) can be used to detect detrusor instability. If present the treatment is medical, using flavoxate hydrochloride 200-300 mg four times a day, emepronium bromide, or imipramine hydrochloride 25-50 mg twice daily. When there is an uncomplicated history of stress incontinence in a patient who is mentally alert and physically fit and has a normal cystometrogram incontinence surgery should be offered. With modern anaesthesia and intensive postoperative care surgery in the elderly need not be restricted to life-saving measures and patients should not be excluded for reasons of age alone. Surgical management must include control of respiratory disease, avoidance of scopolamine as a premedication, early mobilisation following surgery, awareness on the part of the patient, relatives, and nurses of the expected rate of postoperative progress, and avoidance of night sedation (especially barbiturates and nitrazepam). The nursing staff should anticipate the needs and problems of the elderly and be aware of the ease with which confusional states may develop. If medical treatment fails and surgery is contraindicated or refused a vast array of incontinence garments, pads, and appliances is now available. The variety of measures and the large numbers of patients who can benefit necessitate the training of a nurse who is familiar with the problems of incontinence and of their methods of treatment and who can equip individual patients with the correct garment and appliances-something which the average surgical supplies officer has neither the training nor the time to do. The precedent for this type of nurse has already been set in the form of the "stoma care nurse," and her equivalent in the area of urinary incontinence is badly needed. STUART L STANTON LINDA CARDOZO PETER MILLARD HOPE TRENCHARD St George's Hospital Medical School, SW17
London
SIR,-Your leading article on incontinence (14 January, p 61) reveals only too well what a difficult subject this is to comprehend. It is obviously impossible in such a short space to cover such a vast subject comprehensively. There is, however, one error of fact which requires correction. The trigone of the bladder is not related developmentally to the vagina.
