- Email: [email protected]
Ozone depletion quickens
1132
in various sites.12,13 Concerns exist about an increased prevalence of leukaemia in GH-treated children.14 For normal elderly people, it is unknown whether GH supplementation with the existing regimen carries any risk. GH supplementation to prevent or delay some of the manifestations of ageing raises ethical issues. If, after extensive clinical trials, the beneficial actions of GH are shown to predominate, the prolongation of useful, active life seems a legitimate aim of medical care. There are financial implications-the annual cost of the thrice weekly protocol in the UK is about
tumours
L6700 ($USll 000). 1. Florini JR, Prinz PN, Vitiello
MV, Hintz RL. Somatomedin-C levels in
healthy young and old men: relationship to peak and 24-hour integrated levels of growth hormone. J Gerontol 1985; 40: 2-7. 2. Goodman HG, Grumbach MM, Kaplan SL. Growth and growth hormone. II. Comparison of isolated growth hormone deficiency and multiple pituitary hormone deficiencies in 35 patients with idiopathic hypopituitary dwarfism. N Engl J Med 1968; 278: 57-68. 3. Jørgensen JOL, Thuesen L, Ingemann-Hansen T, et al. Beneficial effects of growth hormone treatment in GH-deficient adults. Lancet 1989; i: 1221-25. 4. Salomon F, Cuneo RC, Hesp R, Sönksen PH. The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. N Engl J Med 1989; 321: 1797-803. 5. Cuneo RC, Salomon F, Wiles CM, Hesp R, Sonksen PH. Growth hormone treatment in growth hormone-deficient adults. II. Effects on exercise performance. J Appl Physiol 1991; 70: 695-700. 6. Cuneo RC, Salomon F, Wiles CM, Hesp R, Sönksen PH. Growth hormone treatment in growth hormone-deficient adults. I. Effects on muscle mass and strength. J Appl Physiol 1991; 70: 688-94. 7. Thoren M, Degerblad M, Sääf M, Ringertz H, Sjöberg HE. Growth hormone treatment improves bone mineral density in adults with hypopituitarism. In: Ring EFJ, ed. Current research in osteoporosis and bone mineral measurement. London: British Institute of Radiology, 1990: 92. 8. Whitehead HM, McIlrath E, Atkinson AB, Kennedy AL, Hadden DR. Growth hormone treatment of adults with growth hormone deficiency: effect on protein, fat and bone metabolism. Proceedings of 72nd annual meeting, The Endocrine Society, Atlanta, USA, 1990: 293 (abstr
1074).
R, Butterfield G, Holloway L, et al. Effects of short term administration of recombinant human growth hormone to elderly people. J Clin Endocrinol Metab 1990; 70: 519-27. 10. Rudman D, Feller AG, Nagraj HS, et al. Effects of human growth hormone in men over 60 years old. N Engl J Med 1990; 323: 1-5. 11. Rosen T, Bengtsson B-A. Premature mortality due to cardiovascular 9. Marcus
disease in hypopituitarism. Lancet 1990; 336: 285-88. 12. Alexander L, Appleton D, Hall R, Ross WM, Wilkinson R. Epidemiology of acromegaly in the Newcastle region. Clin Endocrinol 1980; 12: 71-79. 13. Bengtsson B-A, Edén S, Ernest I, Odén A, Sjögren B. Epidemiology and long-term survival in acromegaly. Acta Med Scand 1988; 223: 327-35. 14. Stahnke N, Zeisel HJ. Growth hormone therapy and leukaemia. Eur J Pediatr 1989; 148: 591-96.
Ozone depletion quickens Last month’sannouncement by the U S space agency, NASA,1 that ozone depletion is occurring globally and is progressing faster than previously realised has once again focused attention on this important threat to human health and planetary ecosystems.2,3 Much has happened since a 1989 Lancet editorial4 in which the role of chlorofluorocarbons (CFCs) in depleting stratospheric ozone was mentioned, and not all of it is bad. In June last year the main producers and consumers of ozone-depleting
chemicals met in London to agree phase 2 of the Montreal Protocol, which commits signatory nations to a phase-out of CFCs, halons, and carbon tetrachloride by the year 2000. Unfortunately, the phase-out date for methylchlorofonn has been put back to 2005, there is a 10-year derogation for non-industrialised nations, and other ozonedepleting chemicals are not included in the Protocol. The new data from NASA will undoubtedly reopen this debate-the US Environmental Protection Agency has already called for these clauses to be
renegotiated.5 The atmospheric residence times of CFCs are so long that action taken now will not be reflected in falling levels of atmospheric chlorine for decades.6 Under the Protocol, chlorine levels will rise by the year 2000 to almost 5 parts per billion (ppb), and will not fall back to their current
levels until the year 2050. Natural levels of chlorine are around 0-6 ppb, the ozone hole over Antarctica appeared at concentrations between 1 -5 and 2 ppb, and existing levels are just below 3 ppb. To allow chlorine to rise from 3 to 5 ppb is a dangerous enterprise that might have catastrophic consequences for the stability of the stratosphere and the integrity of global ecosystems. The chemical industry has been promoting the benefits of chemical substitutes such as hydrochlorofluorocarbons (HCFCs) and
hydrofluorocarbons.4 Although hydrofluorocarbons are ozone-friendly, HCFCs have some ozonedepleting potential. Moreover, both classes of considerable contribution to global warming.4,7-9 Germany has already announced its intention to phase out HCFC 22 by the year 2000, and the chemical company ICI is abandoning its plans to produce HCFC 123. Meanwhile, both Du Pont and ICI are proceeding with plans to produce hydrofluorocarbon 134A as a substitute for the fully halogenated CFCs in air-conditioning systems, despite the fact that this compound is not very efficient as a refrigerant and has a global warming potential 2800 times greater than an equivalent weight of carbon dioxide. 10 Ultimately all of these substitutes are doomed to extinction. If they are not caught by phase 3 of the Montreal Protocol, they will be laid to rest by any international convention on global warming. Meanwhile, the Protocol needs to be strengthened by bringing forward the phase-out date to 1995, by including methylchloroform, and by abandoning all but the essential uses of halons immediately. In the UK, attempts to monitor ultraviolet flux at ground level have been pitiful. Ideally one needs a network of high-resolution spectral measurements at sites adjacent to and remote from heavily populated
chemical could make
There is
a
such device--an Optronics 742 spectroradiometer-which monitors UV flux at 2 nm intervals throughout the UVB range (280-320 nm). This machine has been functioning at Reading in Berkshire for the past 2 years, but it is too early to areas.
one
1133
identify any chronological trends associated with falling levels of ozone. Local pollution in urban areas might well affect readings more than do changes in stratospheric ozone. These issues are being addressed at the European level and worldwide. The International Geosphere Biosphere Project will be meeting this month to coordinate UV monitoring globally, while the DG 12 directorate at the European Commission is funding a project under the auspices of Science and Technology for Environmental determine standards for a UV network. Let them produce their monitoring recommendations quickly. Politicians like nothing better than an excuse to delay remedial action-the trend in the levels of atmospheric ozone does not allow them that luxury.
Protection
to
1. National Aeronautics and
Space Agency. Ozone observations. Press prepared by Robert T. Watson, Process Studies Program Office, Earth Science and Application Division, NASA. April 1991. 2. Russell Jones R. The health effects of stratospheric ozone depletion. In: Russell Jones R, Wigley T, eds. Ozone depletion: health and environmental consequences. Chichester: Wiley, 1989: 207-27. 3. Worrest R. Effects of ultraviolet-B radiation on terrestrial plants and marine organisms. In: Russell Jones R, Wigley T, eds. Ozone depletion: health and environmental consequences. Chichester: Wiley, statement
1989: 197-206. 4. Editorial. Health in the greenhouse. Lancet 1989; i: 819-20. 5. Reilly W. Ozone depletion. Washington, DC: U.S. Environmental Protection Agency, April 4, 1991. 6. Russell Jones R. Ozone depletion and cancer risk. Lancet 1987; ii: 443-46. 7. Shine K. The greenhouse effect. Ozone depletion: health and environmental consequences. In: Russell Jones R, Wigley T, eds. Chichester: Wiley, 1989: 71-83. 8. Wigley T. Future CFC concentrations under the Montreal Protocol and their greenhouse-effect implications. Nature 1988; 335: 333. 9. Ramarathan V, Cicerone R, Singh H, Kiehl J. Trace gas trends and their potential role in climate change. J Geophys Res 1985; 90: 5547-66. 10. Trace gases and their relative contribution to the greenhouse effect. Atomic Energy Research Establishment AERE 13716. London: HM Stationery Office, 1990.
Nausea and
vasopressin
The remarkably potent influence of nausea on the release of vasopressin was a serendipidous observation in a group of healthy individuals who were taking part in experiments designed to lower plasma vasopressin concentrations.1 Volunteers who experienced nausea during an oral water-loading test had plasma concentrations of vasopressin several orders of magnitude greater than normal. Earlier reports had documented the association of antidiuresis with emesis, nausea, and motion-sickness.2-4 Using an optokinetic stimulus to produce the illusion of selfmotion, Koch and co-workers5 have now extended these observations; they report that vasopressin secretion is increased only in subjects who become nauseated and not in those who manifest merely
abnormal gastric myoelectrical activity. Little is known about the underlying mechanisms for nausea-induced vasopressin release. Emetic stimuli may act via the chemoreceptor trigger zone of the area postrema in the floor of the fourth ventricle, on
the
medullary vomiting
centre,
or
through vagal
stimulation. The observations by Koch et al militate against direct gastric mechanisms. Chemical substances known to produce nausea in man, and food aversion, which can be equated with nausea in animals, illustrate intriguing species differences in the vasopressin response to nausea. Thus in man and most animals, except rats, these agents lead to increases in plasma vasopressin concentration 5 to 500 fold greater than basal values, with very little change in plasma oxytocin concentration.6-9 Rats do not mount a significant vasopressin response to these stimuli whereas plasma oxytocin concentrations are increased greatly.1,10,11 Apomorphine, a Ddopamine agonist, is one such chemical stimulus. Its effect on vasopressin release depends on the degree of nausea induced and not on the dose administered.9 Cholecystokinin, which seems to cause dose-related gastrointestinal symptoms including nausea and vomiting, also tends to produce dose-dependent rises in plasma concentration. 12 contrast, By vasopressin a ipecacuanha, powerful emetic stimulus, does not stimulate vasopressin secretion in man.7 What then is the purpose of this neuroendocrine reflex? After emesis the antidiuretic effect of vasopressin to retain body water is an appropriate physiological response, but the plasma concentrations attained far exceed those required to achieve maximum antidiuresis. However, such high concentrations are required to induce the vasopressor actions of the hormone, and it is noteworthy that hypotension may develop in severely nauseated man,1,7 Could nausea-induced vasopressin secretion be a counter-regulatory mechanism to maintain blood pressure and volume? Or do these concentrations of vasopressin contribute to glucose homoeostasis via a glycogenolytic effect on the liver, even though such a response would be more appropriate after emesis than after nausea alone? Little is known about the action of vasopressin on the gut, but there is a suggestion that it may reduce
motility. 13
Despite the lack of an obvious explanation for nausea-induced vasopressin secretion, there is an important clinical consequence of nausea-induced antidiuresis. Any patient with nausea and/or emesis (perhaps as a result of abdominal surgery or the administration of drugs, especially chemotherapeutic agents) who is given inappropriate quantities of oral or intravenous fluids will get hyponatraemia. Plasma vasopressin concentrations can be extremely high after nausea/emesis and it may be many hours before physiological levels are attained. Clinicians should therefore assess the patient’s state of hydration, degree of nausea/emesis, and serum electrolytes to guide fluid replacement therapy and not base requirements on urine output alone. 1. Rowe JW, Shelton RL, Helderman JH, Vestal RE, Robertson GL. Influence of the emetic reflex on vasopressin release in man. Kidney Internat 1979; 16: 729-35. 2. Anderson B, Larsson S. Inhibitory effect of emesis on water diuresis in the dog. Acta Physiol Scand 1954; 32: 19-27.
in various sites.12,13 Concerns exist about an increased prevalence of leukaemia in GH-treated children.14 For normal elderly people, it is unknown whether GH supplementation with the existing regimen carries any risk. GH supplementation to prevent or delay some of the manifestations of ageing raises ethical issues. If, after extensive clinical trials, the beneficial actions of GH are shown to predominate, the prolongation of useful, active life seems a legitimate aim of medical care. There are financial implications-the annual cost of the thrice weekly protocol in the UK is about
tumours
L6700 ($USll 000). 1. Florini JR, Prinz PN, Vitiello
MV, Hintz RL. Somatomedin-C levels in
healthy young and old men: relationship to peak and 24-hour integrated levels of growth hormone. J Gerontol 1985; 40: 2-7. 2. Goodman HG, Grumbach MM, Kaplan SL. Growth and growth hormone. II. Comparison of isolated growth hormone deficiency and multiple pituitary hormone deficiencies in 35 patients with idiopathic hypopituitary dwarfism. N Engl J Med 1968; 278: 57-68. 3. Jørgensen JOL, Thuesen L, Ingemann-Hansen T, et al. Beneficial effects of growth hormone treatment in GH-deficient adults. Lancet 1989; i: 1221-25. 4. Salomon F, Cuneo RC, Hesp R, Sönksen PH. The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. N Engl J Med 1989; 321: 1797-803. 5. Cuneo RC, Salomon F, Wiles CM, Hesp R, Sonksen PH. Growth hormone treatment in growth hormone-deficient adults. II. Effects on exercise performance. J Appl Physiol 1991; 70: 695-700. 6. Cuneo RC, Salomon F, Wiles CM, Hesp R, Sönksen PH. Growth hormone treatment in growth hormone-deficient adults. I. Effects on muscle mass and strength. J Appl Physiol 1991; 70: 688-94. 7. Thoren M, Degerblad M, Sääf M, Ringertz H, Sjöberg HE. Growth hormone treatment improves bone mineral density in adults with hypopituitarism. In: Ring EFJ, ed. Current research in osteoporosis and bone mineral measurement. London: British Institute of Radiology, 1990: 92. 8. Whitehead HM, McIlrath E, Atkinson AB, Kennedy AL, Hadden DR. Growth hormone treatment of adults with growth hormone deficiency: effect on protein, fat and bone metabolism. Proceedings of 72nd annual meeting, The Endocrine Society, Atlanta, USA, 1990: 293 (abstr
1074).
R, Butterfield G, Holloway L, et al. Effects of short term administration of recombinant human growth hormone to elderly people. J Clin Endocrinol Metab 1990; 70: 519-27. 10. Rudman D, Feller AG, Nagraj HS, et al. Effects of human growth hormone in men over 60 years old. N Engl J Med 1990; 323: 1-5. 11. Rosen T, Bengtsson B-A. Premature mortality due to cardiovascular 9. Marcus
disease in hypopituitarism. Lancet 1990; 336: 285-88. 12. Alexander L, Appleton D, Hall R, Ross WM, Wilkinson R. Epidemiology of acromegaly in the Newcastle region. Clin Endocrinol 1980; 12: 71-79. 13. Bengtsson B-A, Edén S, Ernest I, Odén A, Sjögren B. Epidemiology and long-term survival in acromegaly. Acta Med Scand 1988; 223: 327-35. 14. Stahnke N, Zeisel HJ. Growth hormone therapy and leukaemia. Eur J Pediatr 1989; 148: 591-96.
Ozone depletion quickens Last month’sannouncement by the U S space agency, NASA,1 that ozone depletion is occurring globally and is progressing faster than previously realised has once again focused attention on this important threat to human health and planetary ecosystems.2,3 Much has happened since a 1989 Lancet editorial4 in which the role of chlorofluorocarbons (CFCs) in depleting stratospheric ozone was mentioned, and not all of it is bad. In June last year the main producers and consumers of ozone-depleting
chemicals met in London to agree phase 2 of the Montreal Protocol, which commits signatory nations to a phase-out of CFCs, halons, and carbon tetrachloride by the year 2000. Unfortunately, the phase-out date for methylchlorofonn has been put back to 2005, there is a 10-year derogation for non-industrialised nations, and other ozonedepleting chemicals are not included in the Protocol. The new data from NASA will undoubtedly reopen this debate-the US Environmental Protection Agency has already called for these clauses to be
renegotiated.5 The atmospheric residence times of CFCs are so long that action taken now will not be reflected in falling levels of atmospheric chlorine for decades.6 Under the Protocol, chlorine levels will rise by the year 2000 to almost 5 parts per billion (ppb), and will not fall back to their current
levels until the year 2050. Natural levels of chlorine are around 0-6 ppb, the ozone hole over Antarctica appeared at concentrations between 1 -5 and 2 ppb, and existing levels are just below 3 ppb. To allow chlorine to rise from 3 to 5 ppb is a dangerous enterprise that might have catastrophic consequences for the stability of the stratosphere and the integrity of global ecosystems. The chemical industry has been promoting the benefits of chemical substitutes such as hydrochlorofluorocarbons (HCFCs) and
hydrofluorocarbons.4 Although hydrofluorocarbons are ozone-friendly, HCFCs have some ozonedepleting potential. Moreover, both classes of considerable contribution to global warming.4,7-9 Germany has already announced its intention to phase out HCFC 22 by the year 2000, and the chemical company ICI is abandoning its plans to produce HCFC 123. Meanwhile, both Du Pont and ICI are proceeding with plans to produce hydrofluorocarbon 134A as a substitute for the fully halogenated CFCs in air-conditioning systems, despite the fact that this compound is not very efficient as a refrigerant and has a global warming potential 2800 times greater than an equivalent weight of carbon dioxide. 10 Ultimately all of these substitutes are doomed to extinction. If they are not caught by phase 3 of the Montreal Protocol, they will be laid to rest by any international convention on global warming. Meanwhile, the Protocol needs to be strengthened by bringing forward the phase-out date to 1995, by including methylchloroform, and by abandoning all but the essential uses of halons immediately. In the UK, attempts to monitor ultraviolet flux at ground level have been pitiful. Ideally one needs a network of high-resolution spectral measurements at sites adjacent to and remote from heavily populated
chemical could make
There is
a
such device--an Optronics 742 spectroradiometer-which monitors UV flux at 2 nm intervals throughout the UVB range (280-320 nm). This machine has been functioning at Reading in Berkshire for the past 2 years, but it is too early to areas.
one
1133
identify any chronological trends associated with falling levels of ozone. Local pollution in urban areas might well affect readings more than do changes in stratospheric ozone. These issues are being addressed at the European level and worldwide. The International Geosphere Biosphere Project will be meeting this month to coordinate UV monitoring globally, while the DG 12 directorate at the European Commission is funding a project under the auspices of Science and Technology for Environmental determine standards for a UV network. Let them produce their monitoring recommendations quickly. Politicians like nothing better than an excuse to delay remedial action-the trend in the levels of atmospheric ozone does not allow them that luxury.
Protection
to
1. National Aeronautics and
Space Agency. Ozone observations. Press prepared by Robert T. Watson, Process Studies Program Office, Earth Science and Application Division, NASA. April 1991. 2. Russell Jones R. The health effects of stratospheric ozone depletion. In: Russell Jones R, Wigley T, eds. Ozone depletion: health and environmental consequences. Chichester: Wiley, 1989: 207-27. 3. Worrest R. Effects of ultraviolet-B radiation on terrestrial plants and marine organisms. In: Russell Jones R, Wigley T, eds. Ozone depletion: health and environmental consequences. Chichester: Wiley, statement
1989: 197-206. 4. Editorial. Health in the greenhouse. Lancet 1989; i: 819-20. 5. Reilly W. Ozone depletion. Washington, DC: U.S. Environmental Protection Agency, April 4, 1991. 6. Russell Jones R. Ozone depletion and cancer risk. Lancet 1987; ii: 443-46. 7. Shine K. The greenhouse effect. Ozone depletion: health and environmental consequences. In: Russell Jones R, Wigley T, eds. Chichester: Wiley, 1989: 71-83. 8. Wigley T. Future CFC concentrations under the Montreal Protocol and their greenhouse-effect implications. Nature 1988; 335: 333. 9. Ramarathan V, Cicerone R, Singh H, Kiehl J. Trace gas trends and their potential role in climate change. J Geophys Res 1985; 90: 5547-66. 10. Trace gases and their relative contribution to the greenhouse effect. Atomic Energy Research Establishment AERE 13716. London: HM Stationery Office, 1990.
Nausea and
vasopressin
The remarkably potent influence of nausea on the release of vasopressin was a serendipidous observation in a group of healthy individuals who were taking part in experiments designed to lower plasma vasopressin concentrations.1 Volunteers who experienced nausea during an oral water-loading test had plasma concentrations of vasopressin several orders of magnitude greater than normal. Earlier reports had documented the association of antidiuresis with emesis, nausea, and motion-sickness.2-4 Using an optokinetic stimulus to produce the illusion of selfmotion, Koch and co-workers5 have now extended these observations; they report that vasopressin secretion is increased only in subjects who become nauseated and not in those who manifest merely
abnormal gastric myoelectrical activity. Little is known about the underlying mechanisms for nausea-induced vasopressin release. Emetic stimuli may act via the chemoreceptor trigger zone of the area postrema in the floor of the fourth ventricle, on
the
medullary vomiting
centre,
or
through vagal
stimulation. The observations by Koch et al militate against direct gastric mechanisms. Chemical substances known to produce nausea in man, and food aversion, which can be equated with nausea in animals, illustrate intriguing species differences in the vasopressin response to nausea. Thus in man and most animals, except rats, these agents lead to increases in plasma vasopressin concentration 5 to 500 fold greater than basal values, with very little change in plasma oxytocin concentration.6-9 Rats do not mount a significant vasopressin response to these stimuli whereas plasma oxytocin concentrations are increased greatly.1,10,11 Apomorphine, a Ddopamine agonist, is one such chemical stimulus. Its effect on vasopressin release depends on the degree of nausea induced and not on the dose administered.9 Cholecystokinin, which seems to cause dose-related gastrointestinal symptoms including nausea and vomiting, also tends to produce dose-dependent rises in plasma concentration. 12 contrast, By vasopressin a ipecacuanha, powerful emetic stimulus, does not stimulate vasopressin secretion in man.7 What then is the purpose of this neuroendocrine reflex? After emesis the antidiuretic effect of vasopressin to retain body water is an appropriate physiological response, but the plasma concentrations attained far exceed those required to achieve maximum antidiuresis. However, such high concentrations are required to induce the vasopressor actions of the hormone, and it is noteworthy that hypotension may develop in severely nauseated man,1,7 Could nausea-induced vasopressin secretion be a counter-regulatory mechanism to maintain blood pressure and volume? Or do these concentrations of vasopressin contribute to glucose homoeostasis via a glycogenolytic effect on the liver, even though such a response would be more appropriate after emesis than after nausea alone? Little is known about the action of vasopressin on the gut, but there is a suggestion that it may reduce
motility. 13
Despite the lack of an obvious explanation for nausea-induced vasopressin secretion, there is an important clinical consequence of nausea-induced antidiuresis. Any patient with nausea and/or emesis (perhaps as a result of abdominal surgery or the administration of drugs, especially chemotherapeutic agents) who is given inappropriate quantities of oral or intravenous fluids will get hyponatraemia. Plasma vasopressin concentrations can be extremely high after nausea/emesis and it may be many hours before physiological levels are attained. Clinicians should therefore assess the patient’s state of hydration, degree of nausea/emesis, and serum electrolytes to guide fluid replacement therapy and not base requirements on urine output alone. 1. Rowe JW, Shelton RL, Helderman JH, Vestal RE, Robertson GL. Influence of the emetic reflex on vasopressin release in man. Kidney Internat 1979; 16: 729-35. 2. Anderson B, Larsson S. Inhibitory effect of emesis on water diuresis in the dog. Acta Physiol Scand 1954; 32: 19-27.