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NEPHROTOXICITY OF PENTAVALENT ANTIMONIALS
584 NEPHROTOXICITY OF PENTAVALENT ANTIMONIALS
SIR,-In their letter from Brazil, Veiga et all drew attention to the possible nephrotoxic effect of the pentavalent antimonials used in leishmaniasis therapy. After initial observations of apparent renal tubular dysfunction in 5 patients with Leishmania braziliensis braziliensis infection treated with
high-dose pentavalent antimony
Veiga et al described a detailed study of 3 patients treated with meglumine antimonate (’Glucantime’) in a dose of 20 mg/kg Sbv daily for 30 days. These patients were able to attain a maximum urinary osmolarity of >800 mosmol/1 following 14 h water
deprivation before but not after therapy. Pre- and post-treatment plasma urea and creatinine clearance were normal. Veiga and his colleagues said that they would be trying to determine whether this tubular dysfunction was reversible and what was the best dose of antimony base for patients with L braziliensis braziliensis infection. PLASMA UREA, MAXIMUM URINARY OSMOLARITY, AND CREATININE CLEARANCE IN 16 SOLDIERS BEFORE AND AFTER 10 DAYS’
PENTOSTAM THERAPY
youngsters to abstain from smoking. The young are more influenced by the promotion of smoking as sexy and "macho" by tobacco manufacturers. Virag’s study lacks any description of a satisfactory control group, the distribution of risk factors in 440 impotent men being compared with that in controls recorded in an MD thesis. Only two states for each risk factor were considered (for instance "smoker" was defined 15 + cigarettes per day for 15 + years, fig 3), so no dose response could be demonstrated. What is needed is a comparison of the distribution of risk factors in the impotent with that in an agematched group of normal men and of penile blood pressure indices in patients (their figs 4 and 5) with those of normal men. Since impotence is not uncommon among middle-aged men, further research is needed. Sperm abnormalities amongst cigarette smokers have also been reported.4 We need to know whether impotence and sperm abnormalities can be reversed by giving up smoking and by an improved diet. Such knowledge could greatly aid
smoking prevention programmes. Department of Medical Computing and Statistics, University of Wales College of Medicine, Cardiff CF4 4XN
T. KHOSLA R.R.WEST
Surgeon General’s Advisory Committee on Smoking and Health 1964. Nostrand Company Royal College of Physicians. Smoking and health now. London, Pitman Medical,
1. The 2.
1971 3 Khosla T. Ineffectiveness of health warning
4.
These results indicate that sodium stibgluconate, given to otherwise healthy young men in a dose of 600 daily for 10 days, does not appear to adversely affect either glomerular or tubular renal function. Larger doses of pentavalent antimonial drugs given to sick, elderly, or malnourished patients may have more serious effects on renal function.
mg Sb
Since September, 1983, 16 British soldiers with a mean age of 24 years (range 18-33) with cutaneous leishmaniasis acquired in Belize have been treated in this department with sodium stibogluconate (’Pentostam’) given intravenously in a standard dose of 600mg Sbv daily for 10 days. Positive cultures were obtained from only 10 of these patients. Promastigotes of L mexicana mexicana were cultured from 3 soldiers and L braziliensis braziliensis from 7 others. Renal function was checked before and after therapy by measurement of plasma urea, electrolytes, creatinine clearance, 24 h urinary protein excretion, and urine and plasma osmolarity after 14 h water deprivation. Eight patients did not attain a post-treatment urinary osmolarity of 800 mosmol/l but 4 of these patients had not achieved this concentration before therapy. Pre- and post-treatment measurements of plasma urea, urinary osmolarity, and creatinine clearance are summarised in the table and show no significant differences. Department of Dermatology, Cambridge Military Hospital, Aldershot, Hants GU 11 1
2AN
DAVID
S. JOLLIFFE
PD. Renal tubular dysfunction in patients with mucocutaneous leishmaniasis treated with pentavalent antimonials. ii:
SiR,—Dr Virag’s article on impotence as an arterial disorder provides a valuable contribution to a topic that is sparsely covered in the British literature. We would like to comment on three aspects. The referral pattern to Virag’s clinic reflects his international practice in vasculogenic impotence. This, and the absence of selection criteria for the 222 males discussed in his article, means that his conclusion that 80% of impotent males have an organic cause is not aplicable to impotent populations as a whole. Secondly, subgroups with differing numbers of arterial risk factors (ARF) were not age matched (ARF=0, mean age 37; ARF = 3 + 4, mean age 56). The increase in vascular lesions and the decrease in penile brachial pulse index could therefore be an ARF or be age related. This is further supported by Virag’s finding that no individual ARF except diabetes was associated with a lowered penile brachial pulse index. Thirdly, controversy exists over the lower limit of normal for the penile brachial pusle index (World Congress on Vasculogenic Impotence, Paris, 1984). Its diagnostic use is still limited to a small group in whom the index is 0 - 6 or less. Virag’s presentation is an enlightening epidemiological study, but does not emphasise the current need for a reliable diagnostic index of vasculogenic impotence. Surgical Professorial Unit, St Bartholomew’s Hospital, London EC1A 7BE
Veiga JPR, Wolff ER, Sampaio RN, Marsden Lancet 1983,
in cigarette smoking related diseases. Hlth Edn J 1979; 38, 2: 58-60. Evans HJ, Fletcher J, Torrance M, Hargreave TB. Sperm abnormalities and cigarette smoking. Lancet 1981, i: 627-29.
569.
ARTERIAL RISK FACTORS AND IMPOTENCE
SIR,-The finding by Dr Virag and his colleagues (Jan 26, p 181) a link between arterial risk factors (diabetes, smoking, hyperlipidaemia, and hypertension) and impotence could be a
of
powerful encouragement in programmes to decrease the prevalence of smoking, since smoking habits are generally formed in teenage years. Many advisory committees on smoking and health describe the diseases associated with smoking 1,2 and mortality ratios or risk ratios have been summarised for fourteen diseases.3However, because most of these diseases (cancer, bronchitis, coronary heart disease, and general arteriosclerosis) occur in later life, they are perceived as too distant in time to act as effective deterrents for
P. F. BLACKLAY
J. S. P. LUMLEY
SiR,—Dr Virag and his colleagues draw attention to rare citations of arterial lesions being involved in the aetiology of impotence. One explanation of the apparent scarcity of information on this subject is that much of the published work has appeared in the British journal of Sexual Medicine, which is as yet not listed in Index Medicus or Current Contents. Seven years ago, this journal carried a comprehensive account of arterial disorder in impotence by Dr Vaclar Michal (1978; 5: 13-18), who also discussed revascularisation of the penile arterial tree using bypass procedures. The results were excellent but British surgeons have been disinclined to enter into what is generally seen as the esoteric area of sexual medicine, and so there has been little progress. This being so patients will continue to suffer with their organic impotence, although publicisation of the risk factors mentioned by Virag et al, which include smoking, might be helpful prophylactically. Journals Division, Medical News
Group,
Tower House, Southampton Street, London WC2E 7LS
ERIC TRIMMER
SIR,-In their letter from Brazil, Veiga et all drew attention to the possible nephrotoxic effect of the pentavalent antimonials used in leishmaniasis therapy. After initial observations of apparent renal tubular dysfunction in 5 patients with Leishmania braziliensis braziliensis infection treated with
high-dose pentavalent antimony
Veiga et al described a detailed study of 3 patients treated with meglumine antimonate (’Glucantime’) in a dose of 20 mg/kg Sbv daily for 30 days. These patients were able to attain a maximum urinary osmolarity of >800 mosmol/1 following 14 h water
deprivation before but not after therapy. Pre- and post-treatment plasma urea and creatinine clearance were normal. Veiga and his colleagues said that they would be trying to determine whether this tubular dysfunction was reversible and what was the best dose of antimony base for patients with L braziliensis braziliensis infection. PLASMA UREA, MAXIMUM URINARY OSMOLARITY, AND CREATININE CLEARANCE IN 16 SOLDIERS BEFORE AND AFTER 10 DAYS’
PENTOSTAM THERAPY
youngsters to abstain from smoking. The young are more influenced by the promotion of smoking as sexy and "macho" by tobacco manufacturers. Virag’s study lacks any description of a satisfactory control group, the distribution of risk factors in 440 impotent men being compared with that in controls recorded in an MD thesis. Only two states for each risk factor were considered (for instance "smoker" was defined 15 + cigarettes per day for 15 + years, fig 3), so no dose response could be demonstrated. What is needed is a comparison of the distribution of risk factors in the impotent with that in an agematched group of normal men and of penile blood pressure indices in patients (their figs 4 and 5) with those of normal men. Since impotence is not uncommon among middle-aged men, further research is needed. Sperm abnormalities amongst cigarette smokers have also been reported.4 We need to know whether impotence and sperm abnormalities can be reversed by giving up smoking and by an improved diet. Such knowledge could greatly aid
smoking prevention programmes. Department of Medical Computing and Statistics, University of Wales College of Medicine, Cardiff CF4 4XN
T. KHOSLA R.R.WEST
Surgeon General’s Advisory Committee on Smoking and Health 1964. Nostrand Company Royal College of Physicians. Smoking and health now. London, Pitman Medical,
1. The 2.
1971 3 Khosla T. Ineffectiveness of health warning
4.
These results indicate that sodium stibgluconate, given to otherwise healthy young men in a dose of 600 daily for 10 days, does not appear to adversely affect either glomerular or tubular renal function. Larger doses of pentavalent antimonial drugs given to sick, elderly, or malnourished patients may have more serious effects on renal function.
mg Sb
Since September, 1983, 16 British soldiers with a mean age of 24 years (range 18-33) with cutaneous leishmaniasis acquired in Belize have been treated in this department with sodium stibogluconate (’Pentostam’) given intravenously in a standard dose of 600mg Sbv daily for 10 days. Positive cultures were obtained from only 10 of these patients. Promastigotes of L mexicana mexicana were cultured from 3 soldiers and L braziliensis braziliensis from 7 others. Renal function was checked before and after therapy by measurement of plasma urea, electrolytes, creatinine clearance, 24 h urinary protein excretion, and urine and plasma osmolarity after 14 h water deprivation. Eight patients did not attain a post-treatment urinary osmolarity of 800 mosmol/l but 4 of these patients had not achieved this concentration before therapy. Pre- and post-treatment measurements of plasma urea, urinary osmolarity, and creatinine clearance are summarised in the table and show no significant differences. Department of Dermatology, Cambridge Military Hospital, Aldershot, Hants GU 11 1
2AN
DAVID
S. JOLLIFFE
PD. Renal tubular dysfunction in patients with mucocutaneous leishmaniasis treated with pentavalent antimonials. ii:
SiR,—Dr Virag’s article on impotence as an arterial disorder provides a valuable contribution to a topic that is sparsely covered in the British literature. We would like to comment on three aspects. The referral pattern to Virag’s clinic reflects his international practice in vasculogenic impotence. This, and the absence of selection criteria for the 222 males discussed in his article, means that his conclusion that 80% of impotent males have an organic cause is not aplicable to impotent populations as a whole. Secondly, subgroups with differing numbers of arterial risk factors (ARF) were not age matched (ARF=0, mean age 37; ARF = 3 + 4, mean age 56). The increase in vascular lesions and the decrease in penile brachial pulse index could therefore be an ARF or be age related. This is further supported by Virag’s finding that no individual ARF except diabetes was associated with a lowered penile brachial pulse index. Thirdly, controversy exists over the lower limit of normal for the penile brachial pusle index (World Congress on Vasculogenic Impotence, Paris, 1984). Its diagnostic use is still limited to a small group in whom the index is 0 - 6 or less. Virag’s presentation is an enlightening epidemiological study, but does not emphasise the current need for a reliable diagnostic index of vasculogenic impotence. Surgical Professorial Unit, St Bartholomew’s Hospital, London EC1A 7BE
Veiga JPR, Wolff ER, Sampaio RN, Marsden Lancet 1983,
in cigarette smoking related diseases. Hlth Edn J 1979; 38, 2: 58-60. Evans HJ, Fletcher J, Torrance M, Hargreave TB. Sperm abnormalities and cigarette smoking. Lancet 1981, i: 627-29.
569.
ARTERIAL RISK FACTORS AND IMPOTENCE
SIR,-The finding by Dr Virag and his colleagues (Jan 26, p 181) a link between arterial risk factors (diabetes, smoking, hyperlipidaemia, and hypertension) and impotence could be a
of
powerful encouragement in programmes to decrease the prevalence of smoking, since smoking habits are generally formed in teenage years. Many advisory committees on smoking and health describe the diseases associated with smoking 1,2 and mortality ratios or risk ratios have been summarised for fourteen diseases.3However, because most of these diseases (cancer, bronchitis, coronary heart disease, and general arteriosclerosis) occur in later life, they are perceived as too distant in time to act as effective deterrents for
P. F. BLACKLAY
J. S. P. LUMLEY
SiR,—Dr Virag and his colleagues draw attention to rare citations of arterial lesions being involved in the aetiology of impotence. One explanation of the apparent scarcity of information on this subject is that much of the published work has appeared in the British journal of Sexual Medicine, which is as yet not listed in Index Medicus or Current Contents. Seven years ago, this journal carried a comprehensive account of arterial disorder in impotence by Dr Vaclar Michal (1978; 5: 13-18), who also discussed revascularisation of the penile arterial tree using bypass procedures. The results were excellent but British surgeons have been disinclined to enter into what is generally seen as the esoteric area of sexual medicine, and so there has been little progress. This being so patients will continue to suffer with their organic impotence, although publicisation of the risk factors mentioned by Virag et al, which include smoking, might be helpful prophylactically. Journals Division, Medical News
Group,
Tower House, Southampton Street, London WC2E 7LS
ERIC TRIMMER