183
of pump and materials, which remain the major .2 weaknesses of large cell ripple mattresses Manufacturers of pressure-relieving equipment should have a code of practice that would insist on laboratory evaluations of pressure profiles for a range of body weights and builds, clinical trial evidence of efficacy, and a description of the patients and conditions for which the product is most suitable.
reliability
Department of Health Care of the Elderly, St Luke’s Hospital, Bradford BD5 0NA, UK
JOHN YOUNG
Disabled Services Centre, Leeds
DUNCAN COTTER
1. Young JB. Aids to prevent pressure sores. Br Med J 1990; 300: 1002-04. 2. Stapleton M. Preventing pressure sores: an evaluation of three products. Geriatric Nursing 1986 (March/April): 23-25. 3. Bliss MR, McLaren R, Exton-Smith AN. Preventing pressure sores in hospital: controlled trial of a large celled ripple mattress. Br Med J 1967; i: 394-97. 4. Bliss M. The use of ripple beds. Age Ageing 1978; 7: 25-27.
Testicular cancer in Poland SIR,-Dr Boyle and colleagues (April 28, p 1033) conclude from an analysis based on two time points that mortality from testicular cancer continues to increase in Central and Eastern Europe. However, at least in Poland, a more detailed epidemiological analysis shows that the time trends of testicular cancer incidence and mortality are qualitatively similar to those observed in western countries (figure). Although incidence rates continue to climb, there has clearly been a decline in mortality, starting about 1981.1,2 Thus, the mortality pattern is similar to that in Western Europe, albeit with a lag of about 10 years.
dihydroxyphenylacetic acid and homovanillic acid, but it did increase 2-phenylethylamine concentrations to 160-350% of controls.6 The effect on 2-phenylethylamine was observed within 15 min of the injection. The lack of effect on dopamine metabolism is probably due to the absence of MAO-B in dopamine terminals .7 In electrophysiological studies deprenyl 2 mg/kg potentiated caudate neuron responses to dopamine agonists, an effect that is similar to the actions of small doses of 2-phenylethylamine.8 Deprenyl, therefore, can potentiate dopamine transmission without altering dopamine metabolism. We propose that deprenyl potentiates dopamine transmission indirectly by increasing 2phenylethylamine levels. 2-phenylethylamine has a high rate of synthesis and turnover and is present in high concentrations in the striatum.9 We have proposed that it acts as an autoregulator of dopaminergic transmission in the striatum.9 2-phenylethylamine is synthesised in dopaminergic neurons in the nigrostriatal projection by the decarboxylation of phenylalanine. It is not stored in granules and it diffuses down a concentration gradient to astrocytes where it is oxidised by MAO-B. The synthesis of 2-phenylethylamine is regulated by activity at dopamine receptors such that levels can increase in response to a failure of dopamine transmission and produce a compensatory potentiation of the efficacy of dopamine.9 The decrease in dopamine turnover observed after repeated deprenyl administration’" may also be due to changes in 2phenylethylamine concentrations. The action of deprenyl on 2-phenylethylamine levels may explain the drug’s efficacy in Parkinson’s disease. Such a mechanism introduces the possibility of new drug treatments such as 2phenylethylamine pro-drugs" or different centrally acting inhibitors of MAO-B. I. A. PATERSON A. V. JUORIO
Neuropsychiatric Research Unit, Department of Psychiatry, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 0N0, Canada
1.
A. A. BOULTON
Riederer P, Ambrozi L, Youdim MB. Implications of combined with ’Madopar’ and L-deprenyl m Parkinson’s disease: a long term study. Lancet 1977; i: 439-43. Tetrud JW, Langston JW. The effect of deprenyl (Selegiline) on the natural history of Parkinson’s disease. Science 1989; 245: 519-22 The Parkinson Study Group. Effect of deprenyl on the progression of diability in early Parkinson’s disease. N Engl J Med 1989; 321: 1364-71. Marsden CD. Parkinson’s disease. Lancet 1990; 335: 948-52. Yu PH. Monoamine oxidase. In: Boulton AA, Baker GB, Yu PH, eds. Neuromethods 5. neurotransmitter enzymes. Clifton, NJ: Humana Press, 1986: 235-72. Juorio AV, Paterson IA. (-)Deprenyl and dopamine transmission: lack of effect on striatal dopamine metabolism. Soc Neurosci Abstr (in press). Levitt P, Pintar JE, Breakfield XO. Immunocytochemical demonstration of monoamine oxidase B in brain astrocytes and serotonergic neurons. Proc Natl Acad Sci ( USA) 1982; 79: 6385-89. Paterson IA, Berry MD, Juono AV. (-)Deprenyl and dopamine transmission: electrophysiological recordings in the rat caudate nucleus. Soc Neurosci Abstr (in
Birkmayer W, treatment
2.
3. 4. 5. 6. 7.
Cancer of the testis, Poland, 1963-88.
The
recent
increase in
dialogue
with
certainly help oncologists in eastern Europe rapid scientific advances in the West. Department of Cancer Control and Epidemiology, Institute of Oncology, 00973 Warsaw, Poland
countries will benefit from the
western to
WITOLD ZATONSKI KRZYSZTOF JEZIORSKI JERZY TYCZYNSKI
W, et al, eds. Cancer in Poland m 1987. Warsaw: M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 1990. 2. Zatonski W, Becker N. Atlas of cancer mortality in Poland 1975-1979. Heidelberg: Springer-Verlag, 1988. 1. Zatonski
8.
press). 9. Paterson IA, Juono AV, Boulton AA. Is 2-phenylethylamine a modulator of catecholamine transmission in the mammalian central nervous system? J Neurochem (in press). 10. Riederer P, Youdim MBH. Monoamine oxidase activity and monoamine metabolism in brains of parkinsonian patients treated with L-deprenyl.J Neurochem 1986; 46: 1359-65. 11. Rao TS, Baker GB, Coutts RT. N,N-Diproargyl-2-phenylethylamine, a potent prodrug of 2-phenylethylamine. neurochemical and neuropharmacological studies in the rat. Brain Res Bull 1987; 19: 47-55.
Erythromelalgia Possible mechanism of action of deprenyl in
parkinsonism S!R,—(-)-deprenyl (’Selegiline’) is useful in the treatment of Parkinson’s disease’ and interest in this drug has been renewed by reports that deprenyl slows the progression of the disease and delays the need to start levodopa.2,3Deprenyl is a selective inhibitor of monoamine oxidase type B (MAO-B) but its mechanism of action in Parkinson’s disease is unclear. We wish to propose a mechanism for the acute effects of this drug on dopamine transmission. Despite the fact that dopamine is a substrate for both forms of MAO,5 intraperitoneal deprenyl 05-4 mg/kg in Wistar rats did not affect striatal levels of dopamine or its metabolites 3,4-
versus
erythermalgia
SiR,—The letters by Dr Slutsker (April 7, p 853) and Dr Lazareth and Dr Priollet (May 26, p 1286) on the coexistence of Raynaud’s syndrome and erythromelalgia are confusing, because the authors do not stick to well-defined descriptions of erythromelalgia, erythermalgia, and Raynaud’s syndrome. The burning distress and red congestion of "classic" erythromelalgia is restricted to the chronic myeloproliferative disorders, where platelet-mediated inflammation and microvascular thrombotic disease of the extremities occur because of thrombocythaemia.1-3 In what appears to be the antithesis of Raynaud’s disease, warmth intensifies discomfort and cold provides relief. A single dose of aspirin gives complete relief for several days, because it irreversibly inhibits platelet cyclo-oxygenase activity, and
of pump and materials, which remain the major .2 weaknesses of large cell ripple mattresses Manufacturers of pressure-relieving equipment should have a code of practice that would insist on laboratory evaluations of pressure profiles for a range of body weights and builds, clinical trial evidence of efficacy, and a description of the patients and conditions for which the product is most suitable.
reliability
Department of Health Care of the Elderly, St Luke’s Hospital, Bradford BD5 0NA, UK
JOHN YOUNG
Disabled Services Centre, Leeds
DUNCAN COTTER
1. Young JB. Aids to prevent pressure sores. Br Med J 1990; 300: 1002-04. 2. Stapleton M. Preventing pressure sores: an evaluation of three products. Geriatric Nursing 1986 (March/April): 23-25. 3. Bliss MR, McLaren R, Exton-Smith AN. Preventing pressure sores in hospital: controlled trial of a large celled ripple mattress. Br Med J 1967; i: 394-97. 4. Bliss M. The use of ripple beds. Age Ageing 1978; 7: 25-27.
Testicular cancer in Poland SIR,-Dr Boyle and colleagues (April 28, p 1033) conclude from an analysis based on two time points that mortality from testicular cancer continues to increase in Central and Eastern Europe. However, at least in Poland, a more detailed epidemiological analysis shows that the time trends of testicular cancer incidence and mortality are qualitatively similar to those observed in western countries (figure). Although incidence rates continue to climb, there has clearly been a decline in mortality, starting about 1981.1,2 Thus, the mortality pattern is similar to that in Western Europe, albeit with a lag of about 10 years.
dihydroxyphenylacetic acid and homovanillic acid, but it did increase 2-phenylethylamine concentrations to 160-350% of controls.6 The effect on 2-phenylethylamine was observed within 15 min of the injection. The lack of effect on dopamine metabolism is probably due to the absence of MAO-B in dopamine terminals .7 In electrophysiological studies deprenyl 2 mg/kg potentiated caudate neuron responses to dopamine agonists, an effect that is similar to the actions of small doses of 2-phenylethylamine.8 Deprenyl, therefore, can potentiate dopamine transmission without altering dopamine metabolism. We propose that deprenyl potentiates dopamine transmission indirectly by increasing 2phenylethylamine levels. 2-phenylethylamine has a high rate of synthesis and turnover and is present in high concentrations in the striatum.9 We have proposed that it acts as an autoregulator of dopaminergic transmission in the striatum.9 2-phenylethylamine is synthesised in dopaminergic neurons in the nigrostriatal projection by the decarboxylation of phenylalanine. It is not stored in granules and it diffuses down a concentration gradient to astrocytes where it is oxidised by MAO-B. The synthesis of 2-phenylethylamine is regulated by activity at dopamine receptors such that levels can increase in response to a failure of dopamine transmission and produce a compensatory potentiation of the efficacy of dopamine.9 The decrease in dopamine turnover observed after repeated deprenyl administration’" may also be due to changes in 2phenylethylamine concentrations. The action of deprenyl on 2-phenylethylamine levels may explain the drug’s efficacy in Parkinson’s disease. Such a mechanism introduces the possibility of new drug treatments such as 2phenylethylamine pro-drugs" or different centrally acting inhibitors of MAO-B. I. A. PATERSON A. V. JUORIO
Neuropsychiatric Research Unit, Department of Psychiatry, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 0N0, Canada
1.
A. A. BOULTON
Riederer P, Ambrozi L, Youdim MB. Implications of combined with ’Madopar’ and L-deprenyl m Parkinson’s disease: a long term study. Lancet 1977; i: 439-43. Tetrud JW, Langston JW. The effect of deprenyl (Selegiline) on the natural history of Parkinson’s disease. Science 1989; 245: 519-22 The Parkinson Study Group. Effect of deprenyl on the progression of diability in early Parkinson’s disease. N Engl J Med 1989; 321: 1364-71. Marsden CD. Parkinson’s disease. Lancet 1990; 335: 948-52. Yu PH. Monoamine oxidase. In: Boulton AA, Baker GB, Yu PH, eds. Neuromethods 5. neurotransmitter enzymes. Clifton, NJ: Humana Press, 1986: 235-72. Juorio AV, Paterson IA. (-)Deprenyl and dopamine transmission: lack of effect on striatal dopamine metabolism. Soc Neurosci Abstr (in press). Levitt P, Pintar JE, Breakfield XO. Immunocytochemical demonstration of monoamine oxidase B in brain astrocytes and serotonergic neurons. Proc Natl Acad Sci ( USA) 1982; 79: 6385-89. Paterson IA, Berry MD, Juono AV. (-)Deprenyl and dopamine transmission: electrophysiological recordings in the rat caudate nucleus. Soc Neurosci Abstr (in
Birkmayer W, treatment
2.
3. 4. 5. 6. 7.
Cancer of the testis, Poland, 1963-88.
The
recent
increase in
dialogue
with
certainly help oncologists in eastern Europe rapid scientific advances in the West. Department of Cancer Control and Epidemiology, Institute of Oncology, 00973 Warsaw, Poland
countries will benefit from the
western to
WITOLD ZATONSKI KRZYSZTOF JEZIORSKI JERZY TYCZYNSKI
W, et al, eds. Cancer in Poland m 1987. Warsaw: M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 1990. 2. Zatonski W, Becker N. Atlas of cancer mortality in Poland 1975-1979. Heidelberg: Springer-Verlag, 1988. 1. Zatonski
8.
press). 9. Paterson IA, Juono AV, Boulton AA. Is 2-phenylethylamine a modulator of catecholamine transmission in the mammalian central nervous system? J Neurochem (in press). 10. Riederer P, Youdim MBH. Monoamine oxidase activity and monoamine metabolism in brains of parkinsonian patients treated with L-deprenyl.J Neurochem 1986; 46: 1359-65. 11. Rao TS, Baker GB, Coutts RT. N,N-Diproargyl-2-phenylethylamine, a potent prodrug of 2-phenylethylamine. neurochemical and neuropharmacological studies in the rat. Brain Res Bull 1987; 19: 47-55.
Erythromelalgia Possible mechanism of action of deprenyl in
parkinsonism S!R,—(-)-deprenyl (’Selegiline’) is useful in the treatment of Parkinson’s disease’ and interest in this drug has been renewed by reports that deprenyl slows the progression of the disease and delays the need to start levodopa.2,3Deprenyl is a selective inhibitor of monoamine oxidase type B (MAO-B) but its mechanism of action in Parkinson’s disease is unclear. We wish to propose a mechanism for the acute effects of this drug on dopamine transmission. Despite the fact that dopamine is a substrate for both forms of MAO,5 intraperitoneal deprenyl 05-4 mg/kg in Wistar rats did not affect striatal levels of dopamine or its metabolites 3,4-
versus
erythermalgia
SiR,—The letters by Dr Slutsker (April 7, p 853) and Dr Lazareth and Dr Priollet (May 26, p 1286) on the coexistence of Raynaud’s syndrome and erythromelalgia are confusing, because the authors do not stick to well-defined descriptions of erythromelalgia, erythermalgia, and Raynaud’s syndrome. The burning distress and red congestion of "classic" erythromelalgia is restricted to the chronic myeloproliferative disorders, where platelet-mediated inflammation and microvascular thrombotic disease of the extremities occur because of thrombocythaemia.1-3 In what appears to be the antithesis of Raynaud’s disease, warmth intensifies discomfort and cold provides relief. A single dose of aspirin gives complete relief for several days, because it irreversibly inhibits platelet cyclo-oxygenase activity, and
