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.
1134
3.
Taylor NBG, Hunter J, Johnson WH. Antidiuresis as a measurement of laboratory induced motion sickness. Can J Biochem Physiol 1957; 35:
410-17. 4. Coutinho EM. Oxytocin and antidiuretic effect of nausea in women. Am J Obstet Gynecol 1969; 105: 127-31. 5. Koch KL, Summy-Long BJ, Bingaman S, Sperry N, Stem RM. Vasopressin and oxytocin responses to illusory self-motion and nausea in man. J Clin Endocrinol Metab 1990; 71: 1269-75. 6. Verbalis JG, Richardson DW, Sticker EM. Vasopressin release in response to nausea-producing agents and cholecystokinin in monkeys. Am J Physiol 1987; 252: R749-53. 7. Nursey SS, Hawthorn J, Page SR, Ang VTY, Jenkins JS. Responses of plasma oxytocin and arginine vasopressin to nausea induced by apomorphine and ipecacuanha. Clin Endocrinol 1988; 28: 297-304. 8. Hawthorn J, Andrews PLR, Ang VTY, Jenkins JS. Differential release of vasopressin and oxytocin in response to abdominal vagal afferent stimulation or apormorphine in the ferret. Brain Res 1988; 438: 193-98. 9. Feldman M, Samson WK, O’Dorisio TM. Apomorphine-induced nausea in humans: release of vasopressin and pancreatic polypeptide. Gastroenterology 1988; 95: 721-26. 10. Verbalis JG, McCann MC, McHale CM, Stricker EM. Oxytocin secretion in response to cholecystokinin and food; differentiation of nausea from satiety. Science 1986; 232: 1417-19. 11. Verbalis JG, McHale CM, Gardiner TW, Stricker EM. Oxytocin and vasopressin secretion in response to stimuli producing learned taste aversions in rats. Behav Neurosci 1986; 100: 466-75. 12. Miaskiewicz SL, Stricker EM, Verbalis JG. Neurohypophyseal secretion in response to cholecystokinin but not meal-induced gastric distension in humans. J Clin Endocrinol Metab 1989; 68: 837-43. 13. Mitchell A, Collin J. Vasopressin effects on the small intestine: a possible factor in paralytic ileus? Br J Surg 1972; 72: 462-65.
Abdominal wall tenderness test: could Carnett cut costs? A simple but largely neglected clinical test for obscure abdominal pain was described by Carnett in 1926.1 The patient is examined supine and the site of maximum tenderness is identified; then he folds his arms across the upper chest and sits half way up. If continued local palpation causes greater tenderness, the Carnett test is said to be positive. Carnett’s hypothesis was that the tensed abdominal wall protects the underlying viscera and therefore the pain is likely to originate in the abdominal wall itself. The weakness of this postulate lies in the parietal peritoneum. Visceral disease with involvement of the parietal peritoneum may produce inflammation of the overlying muscle, giving a false-positive result. The possible causes of a true-positive abdominal wall tenderness test are muscle strain, nerve entrapment, or myositis (possibly viral). The test is not suitable for children, or for adults with generalised pain, and cannot be used in elderly and infirm people who are unable to participate fully in the manoeuvres. Carnett admitted that most patients who benefited from his test were rather complex and often bore "the stigma of being called neurotic, just short of a faker or malingerer"; investigations were usually normal and surgery was generally unhelpful. In retrospect he overemphasised the concept of neuralgia in specific nerves and attributed exacerbations of pain to various unidentified "toxaemias". His test was resurrected in 1977 in a prospective study of 120 patients admitted as emergencies with abdominal pain; 24 had a positive abdominal wall tenderness test, only 1 of whom had a detectable
intra-abdominal lesion.This
solitary exception was
vitally important-a patient with a gangrenous appendix lying against the anterior abdominal wallbut the diagnosis was presumably suspected from other clinical features. Clearly this test will never be infallible and must be interpreted in conjunction with a good history and repeated physical examination. The same Carnett sign has now been evaluated in obscure chronic abdominal pain.372 patients with a positive test from the surgical clinics of one consultant over 8 years were followed up, mainly by postal questionnaire, after an average of almost 10 years. There was an 80% complete response and incomplete information was available for the remainder. Patients were typically young women with right-sided abdominal pain that had been present for several years before inclusion in the study. They had usually been seen by other specialists, mainly orthopaedic surgeons and gynaecologists, and had undergone numerous investigations, often with repeatedly normal results. Although incidental abnormalities were detected, none of the radiological findings, for example, was thought to account for the pain and caused the management to be changed. If such patients are followed for long enough, common conditions such as diverticular disease of the colon, peptic ulcer, and malignant tumours will gradually accrue, but there was no evidence that the abdominal wall tenderness was causally linked. The test complements history-taking and physical examination. It should enable doctors to place such "difficult" patients safely into a review and reassurance category rather than subject them to costly and extensive investigations on a diagnosis-byexclusion principle. In those with a conclusively positive test, injection of a local anaesthetic agent (with or without steroid) is worth trying;4,S although as a group these patients may be abnormally suggestible, a placebo-controlled study would be difficult to justify
ethically. Carnett’s test does not seem to be widely used in contemporary hospital practice, possibly because of the increasing availability of non-invasive imaging procedures such as ultrasound and computed tomographic scanning, especially in hospitals that deal with acute abdominal emergencies. It is reassuring that in an era of high technology a basic clinical manoeuvre can still prove its worth. The message for fiscally prudent doctors is that Carnett could cut costs.
1. Camett
JB. Intercostal neuralgia as a cause of abdominal pain and tenderness. Surg Gynecol Obstet 1926; 42: 625-32. 2. Thomson WHF, Francis DMA. Abdominal wall tenderness: a useful sign in the acute abdomen. Lancet 1977; ii: 1053-54. 3. Thomson WHF, Dawes RFH, Carter SSTC. Abdominal wall tenderness: a useful sign in chronic abdominal pain. Br J Surg 1991; 78: 223-25. 4. Hall PN, Lee APB. Rectus nerve entrapment causing abdominal pain. Br J Surg 1988; 75: 917. 5. Gallegos NC, Hobsley M. Recognition and treatment of abdominal wall pain. J R Soc Med 1989; 82: 343-44.
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.
1134
3.
Taylor NBG, Hunter J, Johnson WH. Antidiuresis as a measurement of laboratory induced motion sickness. Can J Biochem Physiol 1957; 35:
410-17. 4. Coutinho EM. Oxytocin and antidiuretic effect of nausea in women. Am J Obstet Gynecol 1969; 105: 127-31. 5. Koch KL, Summy-Long BJ, Bingaman S, Sperry N, Stem RM. Vasopressin and oxytocin responses to illusory self-motion and nausea in man. J Clin Endocrinol Metab 1990; 71: 1269-75. 6. Verbalis JG, Richardson DW, Sticker EM. Vasopressin release in response to nausea-producing agents and cholecystokinin in monkeys. Am J Physiol 1987; 252: R749-53. 7. Nursey SS, Hawthorn J, Page SR, Ang VTY, Jenkins JS. Responses of plasma oxytocin and arginine vasopressin to nausea induced by apomorphine and ipecacuanha. Clin Endocrinol 1988; 28: 297-304. 8. Hawthorn J, Andrews PLR, Ang VTY, Jenkins JS. Differential release of vasopressin and oxytocin in response to abdominal vagal afferent stimulation or apormorphine in the ferret. Brain Res 1988; 438: 193-98. 9. Feldman M, Samson WK, O’Dorisio TM. Apomorphine-induced nausea in humans: release of vasopressin and pancreatic polypeptide. Gastroenterology 1988; 95: 721-26. 10. Verbalis JG, McCann MC, McHale CM, Stricker EM. Oxytocin secretion in response to cholecystokinin and food; differentiation of nausea from satiety. Science 1986; 232: 1417-19. 11. Verbalis JG, McHale CM, Gardiner TW, Stricker EM. Oxytocin and vasopressin secretion in response to stimuli producing learned taste aversions in rats. Behav Neurosci 1986; 100: 466-75. 12. Miaskiewicz SL, Stricker EM, Verbalis JG. Neurohypophyseal secretion in response to cholecystokinin but not meal-induced gastric distension in humans. J Clin Endocrinol Metab 1989; 68: 837-43. 13. Mitchell A, Collin J. Vasopressin effects on the small intestine: a possible factor in paralytic ileus? Br J Surg 1972; 72: 462-65.
Abdominal wall tenderness test: could Carnett cut costs? A simple but largely neglected clinical test for obscure abdominal pain was described by Carnett in 1926.1 The patient is examined supine and the site of maximum tenderness is identified; then he folds his arms across the upper chest and sits half way up. If continued local palpation causes greater tenderness, the Carnett test is said to be positive. Carnett’s hypothesis was that the tensed abdominal wall protects the underlying viscera and therefore the pain is likely to originate in the abdominal wall itself. The weakness of this postulate lies in the parietal peritoneum. Visceral disease with involvement of the parietal peritoneum may produce inflammation of the overlying muscle, giving a false-positive result. The possible causes of a true-positive abdominal wall tenderness test are muscle strain, nerve entrapment, or myositis (possibly viral). The test is not suitable for children, or for adults with generalised pain, and cannot be used in elderly and infirm people who are unable to participate fully in the manoeuvres. Carnett admitted that most patients who benefited from his test were rather complex and often bore "the stigma of being called neurotic, just short of a faker or malingerer"; investigations were usually normal and surgery was generally unhelpful. In retrospect he overemphasised the concept of neuralgia in specific nerves and attributed exacerbations of pain to various unidentified "toxaemias". His test was resurrected in 1977 in a prospective study of 120 patients admitted as emergencies with abdominal pain; 24 had a positive abdominal wall tenderness test, only 1 of whom had a detectable
intra-abdominal lesion.This
solitary exception was
vitally important-a patient with a gangrenous appendix lying against the anterior abdominal wallbut the diagnosis was presumably suspected from other clinical features. Clearly this test will never be infallible and must be interpreted in conjunction with a good history and repeated physical examination. The same Carnett sign has now been evaluated in obscure chronic abdominal pain.372 patients with a positive test from the surgical clinics of one consultant over 8 years were followed up, mainly by postal questionnaire, after an average of almost 10 years. There was an 80% complete response and incomplete information was available for the remainder. Patients were typically young women with right-sided abdominal pain that had been present for several years before inclusion in the study. They had usually been seen by other specialists, mainly orthopaedic surgeons and gynaecologists, and had undergone numerous investigations, often with repeatedly normal results. Although incidental abnormalities were detected, none of the radiological findings, for example, was thought to account for the pain and caused the management to be changed. If such patients are followed for long enough, common conditions such as diverticular disease of the colon, peptic ulcer, and malignant tumours will gradually accrue, but there was no evidence that the abdominal wall tenderness was causally linked. The test complements history-taking and physical examination. It should enable doctors to place such "difficult" patients safely into a review and reassurance category rather than subject them to costly and extensive investigations on a diagnosis-byexclusion principle. In those with a conclusively positive test, injection of a local anaesthetic agent (with or without steroid) is worth trying;4,S although as a group these patients may be abnormally suggestible, a placebo-controlled study would be difficult to justify
ethically. Carnett’s test does not seem to be widely used in contemporary hospital practice, possibly because of the increasing availability of non-invasive imaging procedures such as ultrasound and computed tomographic scanning, especially in hospitals that deal with acute abdominal emergencies. It is reassuring that in an era of high technology a basic clinical manoeuvre can still prove its worth. The message for fiscally prudent doctors is that Carnett could cut costs.
1. Camett
JB. Intercostal neuralgia as a cause of abdominal pain and tenderness. Surg Gynecol Obstet 1926; 42: 625-32. 2. Thomson WHF, Francis DMA. Abdominal wall tenderness: a useful sign in the acute abdomen. Lancet 1977; ii: 1053-54. 3. Thomson WHF, Dawes RFH, Carter SSTC. Abdominal wall tenderness: a useful sign in chronic abdominal pain. Br J Surg 1991; 78: 223-25. 4. Hall PN, Lee APB. Rectus nerve entrapment causing abdominal pain. Br J Surg 1988; 75: 917. 5. Gallegos NC, Hobsley M. Recognition and treatment of abdominal wall pain. J R Soc Med 1989; 82: 343-44.
