- Email: [email protected]
NEW TREATMENT FOR PROSTATIC CANCER
916 them.
Perhaps the frequency of Coxsackie-B-virus-specific IgM responses in patients with IDDM exhibits geographical and temporal variation. Our data and results from routine clinical practice confirm that infants and younger children tend to exhibit homotypic responses. Results on sera collected from older people may be more difficult to interpret; one can only state that the patient has had a recent enterovirus infection. However, clinicians appreciate such reports, particularly in patients with pericarditis/myocarditis, since they provide evidence of current or recent infection by a group of viruses which conventional techniques have until now failed to provide. of Virology, St Thomas’ Hospital Medical School, London SE1 7EH and Institute of Zoology, Zoological Society of London, London NW1
Department
MARY L. KING D. BIDWELL A. VOLLER JENNIFER BRYANT J. E. BANATVALA
ARE BRASSICA VEGETABLES AGGRAVATING FACTORS IN TRIMETHYLAMINURIA (FISH ODOUR SYNDROME)?
SiR,-Fish odour syndrome is caused by an inherent metabolic involving the microsomal mixed-function oxidase which
tannins occur in many foods. Brussels sprouts, swede, and kohlrabi are especially rich sources of PG, and significant amounts are also found in cabbage and cauliflawer. Levels of PG in brussels sprouts in excess of 80 mg per 100 g fresh weight (about 25mg OZT/100 g) are not uncommon. A study funded by the Ministry of Agriculture, Fisheries and Food has produced a figure of 7 mg for the average daily intake of PG, although this varies with the seasonal production of many brassicas, with variations in what people choose or can afford to eat, and with the species itself and where it grows. The PG content of typical helpings of cooked brussels sprouts and cabbage range from 65 to 140 mg (20-40 mg OZT) and from 9 to 42 mg (3-12 mg OZT), respectively. We know of no report of the influence of green vegetables or tannins on TMA metabolism in patients with fish odour syndrome, but the similarities between this condition and egg taint merit examination of the value of low-brassica (or low-tannin) diets in the management of this socially undesirable disease. ARC Food Research Institute, Norwich, Norfolk NR4 7UA
G. R. FENWICK
Houghton Poultry Research Station, Huntingdon, Cambridgeshire
E. J. BUTLER
Metabolic Laboratory, Arkansas Children’s Little Rock, Arkansas, USA
Hospital,
M. A. BREWSTER
defect
trimethylamine (TMA) to its non-volatile N-oxide. Excessive TMA in the sweat, breath, and urine produces the offensive odour. There appear to be no other physical symptoms though severe psychosocial problems may develop. The condition seems to be more common than first supposed,23 and TMA metabolism may also be impaired in patients with chronic liver disease.4 TMA is released by the action of enteric bacteria on dietary choline and TMA oxide, and the fishy odour is usually diminished by a severe diet (no 3eggs, fish, or legumes).3 In some instances neomycin has helped.3 Our (G. R. F., E. J. B.) interest in this condition arose from work on fishy taint in eggs.5 This taint is also produced by TMA derived from dietary choline and TMA oxide and is caused partly by an inherited defect severely restricting the synthesis of TMA oxidase. However, studies with Brassica napus and B campestris (rapeseed) meals; which are fed as protein supplements to poultry, have identified potent inhibitors of TMA oxidase in vitro and in vivo-namely, a tannin (polyphenolic) fractionand a discrete converts
7
compound, 5-vinyloxazolidine-2-thione (OZT), a goitrogen formed in the gut by the enzymic breakdown of progoitrin (PG), a thioglucoside. A daily PG dose of 10 mg/kg body weight can depress TMA oxidation capacity in hens possessing the genetic defect by well over 90%, and much lower doses may still increase the egg’s TMA content above that necessary for taint (about 1 ppm). OZT inhibits TMA oxidase by competing with substrate, and this behaviour is attributable to the CSNH grouping9which is also a feature of certain antithyroid drugs. Mammalian mixed-function oxidase is also inhibited by thioamides in this way. Tannins appear to inhibit TMA oxidase by a different mechanism. The significance of our work in poultry for the fish odour syndrome of man lies in the fact that PG (and hence OZT) and Psychological problems as the major complication of an adolescent with trimethylaminuria. J Pediatr 1979; 94: 936-37. Brewster MA, Schedewie H. Trimethylaminuria. Ann Clin Lab Sci 1983; 13: 20-24. Danks DM, Hammond J, Schlesinger P, Faull K, Burke D, Halpern B. Trimethylaminuria: diet does not always control the fishy odor. N Engl J Med 1976;
NEW TREATMENT FOR PROSTATIC CANCER
SIR,-Your Aug 20 editorial (p 438) discusses two analogues of luteinising-hormone-releasing hormone (LHRH), ICI 118,630 and buserelin (HOE 766), and states that both seem equally potent in the treatment of prostatic cancer, but that buserelin given by intranasal spray has the potential drawback of irregular dosing. We disagree. Publicationsl-4 on buserelin treatment have reported long-term (2-14 months) maintenance of castration levels of testosterone and markedly decreased levels of LH and follicle-stimulating hormone (FSH). So far at least 77 buserelin-treated cases of advanced prostatic cancer have been recorded and 40 have been published. Most of these patients were given subcutaneous injections for one week, followed by intranasal spray. Peak levels of serum testosterone were reached after 3-6 days of treatment. After 2 weeks’
treatment
testosterone
serum
reductions of 60-90%
(comparable with results of parental therapy 5) were achieved, LH being reduced by 60-7507o and FSH by 40-85%. In 37 patients (92%) clinical response (relief of symptoms and/or regression of bone lesions or tumour mass) has been observed. Though not conclusive, these results do
not support the view that intranasal administration is likely to cause irregular dosing. Faure et al,6 on the contrary, have demonstrated the effect of intranasal administration. On practical grounds, after a short phase of parenteral treatment maintenance therapy with pernasal buserelin treatment may be the
answer.7
Clinical Research Department, Hoechst Holland NV, 1100 AZ Amsterdam, Netherlands
DEV R. CHADHA A. MATROOS
1. Todd WA. 2
3
295: 962. 4. Marks R, Dudley F, Wan A. Trimethylamine metabolism in liver disease. Lancet 1978; i 1106-07. 5. Butler EJ, Fenwick GR. Trimethylamine and fishy taint in eggs. Wld Poultry Sci J (in 6.
press). Fenwick GR, Pearson AW, Greenwood NM, Butler EJ. Rapeseed meal tannins and egg
taint. Anim Fd Sci Technol 1981; 6: 421-31. 7. Pearson AW, Greenwood NM, Butler EJ, Fenwick GR. The inhibition of trimethylamine oxidation in the domestic fowl (Gallus domesticus) by antithyroid compounds. Comp Biochem Physiol 1981, 69C: 307-12 8. Fenwick GR, Heaney RK, Mullin WJ. Glucosinolates and their breakdown products in food and food plants. CRC Crit Rev Fd Sci Nutr 1983; 18: 123-201. 9. Pearson AW, Greenwood NM, Butler EJ, Fenwick GR The effect ofthionamides and related compounds on trimethylamine oxidase activity in hepatic microsomes isolated from chickens (Gallus domesticus). Comp Biochem Physiol 1982; 73C: 389-93
1.
Borgmann V, et al. Sustained suppression oftestosterone production by the luteinisinghormone releasing-hormone agonist buserelin in patients with advanced prostate Lancet 1982; i: 1097-99. al. Tumor growth inhibition in patients with prostatic carcinoma treated with luteinising hormone-releasing hormone agonists. Proc Natl Acad Sci USA carcinoma.
2. Tolis
G,
et
1982, 79: 1658-62. JH, et al. Treatment with gonadotrophin releasing hormone analogue in advanced prostatic cancer. Br Med J 1983; 286: 1309-12. Wenderoth UK, et al. Endocrine studies with a gonadotropin-releasing hormone
3. Wasman 4.
analogue 5.
to
achieve withdrawal of testosterone in prostate
Urol 1982; 8: 243-47. Ahmed SR, et al. Treatment of advanced prostatic
carcioma
patients Eur
with LHRH analogue ICI 1983; ii: 415-19 6. Faure N, et al. Sensitivity of luteinising hormone and gonadal steroid responses to single intranasal administration of an LHRH agonist (HOE 766) in young normal adult men. J Endocrinol Invest 1982; 5: 355-60. 7. Jacobi GH, Wenderoth UK. Gonadotropin-releasing hormone analogues for prostate cancer: Untoward side effects of high-dose regimens acquire a therapeutical dimension Eur Urol 1982; 8: 129-34. cancer
118630. Clinical response and hormonal mechanisms. Lancet
Perhaps the frequency of Coxsackie-B-virus-specific IgM responses in patients with IDDM exhibits geographical and temporal variation. Our data and results from routine clinical practice confirm that infants and younger children tend to exhibit homotypic responses. Results on sera collected from older people may be more difficult to interpret; one can only state that the patient has had a recent enterovirus infection. However, clinicians appreciate such reports, particularly in patients with pericarditis/myocarditis, since they provide evidence of current or recent infection by a group of viruses which conventional techniques have until now failed to provide. of Virology, St Thomas’ Hospital Medical School, London SE1 7EH and Institute of Zoology, Zoological Society of London, London NW1
Department
MARY L. KING D. BIDWELL A. VOLLER JENNIFER BRYANT J. E. BANATVALA
ARE BRASSICA VEGETABLES AGGRAVATING FACTORS IN TRIMETHYLAMINURIA (FISH ODOUR SYNDROME)?
SiR,-Fish odour syndrome is caused by an inherent metabolic involving the microsomal mixed-function oxidase which
tannins occur in many foods. Brussels sprouts, swede, and kohlrabi are especially rich sources of PG, and significant amounts are also found in cabbage and cauliflawer. Levels of PG in brussels sprouts in excess of 80 mg per 100 g fresh weight (about 25mg OZT/100 g) are not uncommon. A study funded by the Ministry of Agriculture, Fisheries and Food has produced a figure of 7 mg for the average daily intake of PG, although this varies with the seasonal production of many brassicas, with variations in what people choose or can afford to eat, and with the species itself and where it grows. The PG content of typical helpings of cooked brussels sprouts and cabbage range from 65 to 140 mg (20-40 mg OZT) and from 9 to 42 mg (3-12 mg OZT), respectively. We know of no report of the influence of green vegetables or tannins on TMA metabolism in patients with fish odour syndrome, but the similarities between this condition and egg taint merit examination of the value of low-brassica (or low-tannin) diets in the management of this socially undesirable disease. ARC Food Research Institute, Norwich, Norfolk NR4 7UA
G. R. FENWICK
Houghton Poultry Research Station, Huntingdon, Cambridgeshire
E. J. BUTLER
Metabolic Laboratory, Arkansas Children’s Little Rock, Arkansas, USA
Hospital,
M. A. BREWSTER
defect
trimethylamine (TMA) to its non-volatile N-oxide. Excessive TMA in the sweat, breath, and urine produces the offensive odour. There appear to be no other physical symptoms though severe psychosocial problems may develop. The condition seems to be more common than first supposed,23 and TMA metabolism may also be impaired in patients with chronic liver disease.4 TMA is released by the action of enteric bacteria on dietary choline and TMA oxide, and the fishy odour is usually diminished by a severe diet (no 3eggs, fish, or legumes).3 In some instances neomycin has helped.3 Our (G. R. F., E. J. B.) interest in this condition arose from work on fishy taint in eggs.5 This taint is also produced by TMA derived from dietary choline and TMA oxide and is caused partly by an inherited defect severely restricting the synthesis of TMA oxidase. However, studies with Brassica napus and B campestris (rapeseed) meals; which are fed as protein supplements to poultry, have identified potent inhibitors of TMA oxidase in vitro and in vivo-namely, a tannin (polyphenolic) fractionand a discrete converts
7
compound, 5-vinyloxazolidine-2-thione (OZT), a goitrogen formed in the gut by the enzymic breakdown of progoitrin (PG), a thioglucoside. A daily PG dose of 10 mg/kg body weight can depress TMA oxidation capacity in hens possessing the genetic defect by well over 90%, and much lower doses may still increase the egg’s TMA content above that necessary for taint (about 1 ppm). OZT inhibits TMA oxidase by competing with substrate, and this behaviour is attributable to the CSNH grouping9which is also a feature of certain antithyroid drugs. Mammalian mixed-function oxidase is also inhibited by thioamides in this way. Tannins appear to inhibit TMA oxidase by a different mechanism. The significance of our work in poultry for the fish odour syndrome of man lies in the fact that PG (and hence OZT) and Psychological problems as the major complication of an adolescent with trimethylaminuria. J Pediatr 1979; 94: 936-37. Brewster MA, Schedewie H. Trimethylaminuria. Ann Clin Lab Sci 1983; 13: 20-24. Danks DM, Hammond J, Schlesinger P, Faull K, Burke D, Halpern B. Trimethylaminuria: diet does not always control the fishy odor. N Engl J Med 1976;
NEW TREATMENT FOR PROSTATIC CANCER
SIR,-Your Aug 20 editorial (p 438) discusses two analogues of luteinising-hormone-releasing hormone (LHRH), ICI 118,630 and buserelin (HOE 766), and states that both seem equally potent in the treatment of prostatic cancer, but that buserelin given by intranasal spray has the potential drawback of irregular dosing. We disagree. Publicationsl-4 on buserelin treatment have reported long-term (2-14 months) maintenance of castration levels of testosterone and markedly decreased levels of LH and follicle-stimulating hormone (FSH). So far at least 77 buserelin-treated cases of advanced prostatic cancer have been recorded and 40 have been published. Most of these patients were given subcutaneous injections for one week, followed by intranasal spray. Peak levels of serum testosterone were reached after 3-6 days of treatment. After 2 weeks’
treatment
testosterone
serum
reductions of 60-90%
(comparable with results of parental therapy 5) were achieved, LH being reduced by 60-7507o and FSH by 40-85%. In 37 patients (92%) clinical response (relief of symptoms and/or regression of bone lesions or tumour mass) has been observed. Though not conclusive, these results do
not support the view that intranasal administration is likely to cause irregular dosing. Faure et al,6 on the contrary, have demonstrated the effect of intranasal administration. On practical grounds, after a short phase of parenteral treatment maintenance therapy with pernasal buserelin treatment may be the
answer.7
Clinical Research Department, Hoechst Holland NV, 1100 AZ Amsterdam, Netherlands
DEV R. CHADHA A. MATROOS
1. Todd WA. 2
3
295: 962. 4. Marks R, Dudley F, Wan A. Trimethylamine metabolism in liver disease. Lancet 1978; i 1106-07. 5. Butler EJ, Fenwick GR. Trimethylamine and fishy taint in eggs. Wld Poultry Sci J (in 6.
press). Fenwick GR, Pearson AW, Greenwood NM, Butler EJ. Rapeseed meal tannins and egg
taint. Anim Fd Sci Technol 1981; 6: 421-31. 7. Pearson AW, Greenwood NM, Butler EJ, Fenwick GR. The inhibition of trimethylamine oxidation in the domestic fowl (Gallus domesticus) by antithyroid compounds. Comp Biochem Physiol 1981, 69C: 307-12 8. Fenwick GR, Heaney RK, Mullin WJ. Glucosinolates and their breakdown products in food and food plants. CRC Crit Rev Fd Sci Nutr 1983; 18: 123-201. 9. Pearson AW, Greenwood NM, Butler EJ, Fenwick GR The effect ofthionamides and related compounds on trimethylamine oxidase activity in hepatic microsomes isolated from chickens (Gallus domesticus). Comp Biochem Physiol 1982; 73C: 389-93
1.
Borgmann V, et al. Sustained suppression oftestosterone production by the luteinisinghormone releasing-hormone agonist buserelin in patients with advanced prostate Lancet 1982; i: 1097-99. al. Tumor growth inhibition in patients with prostatic carcinoma treated with luteinising hormone-releasing hormone agonists. Proc Natl Acad Sci USA carcinoma.
2. Tolis
G,
et
1982, 79: 1658-62. JH, et al. Treatment with gonadotrophin releasing hormone analogue in advanced prostatic cancer. Br Med J 1983; 286: 1309-12. Wenderoth UK, et al. Endocrine studies with a gonadotropin-releasing hormone
3. Wasman 4.
analogue 5.
to
achieve withdrawal of testosterone in prostate
Urol 1982; 8: 243-47. Ahmed SR, et al. Treatment of advanced prostatic
carcioma
patients Eur
with LHRH analogue ICI 1983; ii: 415-19 6. Faure N, et al. Sensitivity of luteinising hormone and gonadal steroid responses to single intranasal administration of an LHRH agonist (HOE 766) in young normal adult men. J Endocrinol Invest 1982; 5: 355-60. 7. Jacobi GH, Wenderoth UK. Gonadotropin-releasing hormone analogues for prostate cancer: Untoward side effects of high-dose regimens acquire a therapeutical dimension Eur Urol 1982; 8: 129-34. cancer
118630. Clinical response and hormonal mechanisms. Lancet