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BEDSIDE THEOPHYLLINE ASSAY IN SEVERE ACUTE ASTHMA
1394 BEDSIDE THEOPHYLLINE ASSAY IN SEVERE ACUTE ASTHMA
SiR,—Dr Walker (Nov 8,
p
1103) illustrates the dilemma in
administering intravenous aminophylline to severely ill patients who are already taking oral theophylline. Such patients have a wide range of serum theophylline concentrations on admission and the use of loading doses of aminophylline in these circumstances is imprecise.1 Rapid assays like that described by Walker would be useful but the kits are expensive. We have studied how knowing the serum theophylline concentration affects our calculation of the intravenous aminophylline dose in patients already taking oral theophylline.2 Intravenous loading doses can be safely given without immediate knowledge of serum theophylline concentration if the initial dose is low (2-5 mg/kg) the dose is adjusted for factors known to affect theophylline clearance3 and the calculated loading dose is infused over 30 min. We also noted that ideal treatment with aminophylline was not always achieved even when the serum theophylline concentration on admission was rapidly known. This probably reflects wide variability in theophylline disposition,3and both the infusion rate and the theoretical loading dose described by Walker may need to be
Lipid profiles before, during, and after use of nicotine gum. Gum
use
cholesterol;
began at A and stopped at B. = total cholesterol; . = LDL triglycerides; Q HDL cholesterol.
*
=
=
LDL from the plasma compartment. Extended residence time of LDL in the circulation would increase the likelihood of deposition on the arterial wall.6 The lipid modifications observed may be related to a greater rate of mobilisation of non-esterified fatty acids (NEFA) after nicotine administration. Nicotine sulphate injected intravenously in dogs produced increased plasma levels of NEFA.’ This increase results from stimulation of sympathetic ganglia whose post-ganglionic fibres innervate adipose tissue and from adrenal medullary discharge.8 Smoking one or two cigarettes can also result in significant increases in plasma NEFA,especially if the cigarettes have a high nicotine content. Mobilisation of NEFA produced by smoking may also augment acetylcoenzyme A, a cholesterol precursor. This observation is clinically important because of the widespread use of smokeless tobacco products9 and the increased prescription of nicotine chewing gum. 10 The regular use of nicotine gums may carry an increased risk of cardiovascular disease. Furthermore, the observation confirms the involvement of the adrenergic nervous system in the development of hypercholesterolaemia. Biochemical and Toxicology Laboratories, Faculty of Pharmacy, 31000 Toulouse, France;
and INSERM U101,
Hôpital Purpan, Toulouse
J. C. DOUSSET J. B. GUTIERRÈS N. DOUSSET
WB, Revotskie N, Stokes J, Kagan A, Gordon T. Some factors associated with the development of coronary heart disease. Am J Publ Health 1959; 49: 1349-56. 2. Friedman GD, Dales LG, Ury HK. Mortality in nuddleaged smokers and nonsmokers. N Engl J Med 1979; 300: 213. 3. Booyse FM, Osikowicz G, Quarfoot AJ. Effects of chronic oral consumption of nicotine on the rabbit aortic endothelium. Am J Pathol 1981; 102: 229-38. 4. Augustin J, Beedgen B, Spohr U, Winkel F. The influence of smoking on plasma lipoproteins. Innere Med 1982; 9: 104-08. 5. Cluette-Brown J, Mulligan J, Doyle K, Hugan S, Osmolski T, Hojnacki J. Oral nicotine induces an atherogenic lipoprotein profile. Proc Soc Exp Biol Med 1986; 182: 409-13. 6. Hojnacki J, Mulligan J, Cluette-Brown J, Igoe F, Osmolski T Oral nicotine impairs clearance of plasma low density lipoproteins Proc Soc Exp Biol Med 1986; 182: 414-18 7. Kersbaum A, Bellet S, Dickstein ER, Feinberg LJ. Effect of cigarette smoking and nicotine on serum free fatty acids based on a study in the human subject and the experimental animal. Circ Res 1961; 9: 631-38. 8. Havel RJ. Catecholamines in lipid pharmacology. In: Paoletti R, ed. New York. Academic Press, 1964. 9. Maxwell JC Jr Maxwell report: smokeless grows; cigars decline. Tobacco Rep 1983; 110: 56-57. 10. Cole PV. Effect of nicotine chewing gum on smoking behaviour and as aid to cigarette withdrawal, Br Med J 1976, ii: 391-93. 1. Dawber TR, Kannel
adjusted accordingly. Theophylline is difficult to use effectively and safely. Assays with rapidly available results will identify patients whose compliance with their oral therapy is poor, or whose serum theophylline concentration is already above the therapeutic range and in whom loading doses of aminophylline may be hazardous. Brompton Hospital,
JOHN WIGGINS
London SW3 6HP
1. Arbab OA, Wiggins J, Ayres JG, Stableforth DE. The use of parenteral aminophylline in patients taking slow release theophylline preparations an observation of clinical practice. Br J Dis Chest 1985; 79: 161-71. 2. Wiggins J, Arbab OA, Stableforth DE, Ayres JG. Intravenous aminophylline in patients already taking oral theophylline: effect on calculated dose of knowledge of serum theophylline concentration on admission. Thorax 1986; 41: 759-65. 3. Powell JR, Vozeh S, Hopewell P, Costello J, Sheiner LB, Riegelman S Theophylline disposition in acutely ill hospitalised patients. Am Rev Respir Dis 1978; 118: 229-38.
ACCEPTABILITY OF PRENATAL DIAGNOSIS FOR RETINITIS PIGMENTOSA
SIR,-Using DNA methods Reeders polycystic kidney disease in a fetus and
aP detected adult this was followed by termination of pregnancy. We agree with Reeders et al that with the advent of new prenatal diagnostic techniques their role in medical practice needs to be defined. For this purpose, it may be useful to investigate the attitude of patients, especially in view of increasing patient autonomy,2 the coverage by the media of ethical aspects of medical decisionsand public concern over the ethical impact of prenatal diagnosis by DNA methods. Molecular methods for prenatal testing for retinitis pigmentosa can be expected now that data on linked polymorphic markers in some types are accumulating.3°’ Those affected by retinitis pigmentosa are, like patients with adult polycystic kidney disease, of normal intelligence, and the main symptoms, such as blindness, tend not to occur until adulthood. In a collaborative study 414 patients with retinitis pigmentosa and allied diseases completed a questionnaire designed to investigate the factors influencing the acceptability of prenatal diagnosis by DNA methods. Almost all the patients were members of the German Retinitis Pigmentosa Society. 55 3% were male and 44-7% female; 63-9% were married. 44-0% were Protestant and 35-8% Catholic. The respondents said that they had learned about gene technology via the retinitis pigmentosa patients’ organisation (70-9%), or the media (58-7%), or by attending lectures on the patients’ day at the 4th Congress of the International Retinitis Pigmentosa Association, held in Bad Nauheim, in May, 1986 (18-5%). 61-0% of the respondents felt that there could be dangers in the application of DNA methods in medicine. However, 89 4% also expected to see advantages for RP. 94-8% wanted DNA research to continue, for the following purposes: to improve treatment (90-6%), for more accurate (83-9%) or earlier (82 3°-o’) et
SiR,—Dr Walker (Nov 8,
p
1103) illustrates the dilemma in
administering intravenous aminophylline to severely ill patients who are already taking oral theophylline. Such patients have a wide range of serum theophylline concentrations on admission and the use of loading doses of aminophylline in these circumstances is imprecise.1 Rapid assays like that described by Walker would be useful but the kits are expensive. We have studied how knowing the serum theophylline concentration affects our calculation of the intravenous aminophylline dose in patients already taking oral theophylline.2 Intravenous loading doses can be safely given without immediate knowledge of serum theophylline concentration if the initial dose is low (2-5 mg/kg) the dose is adjusted for factors known to affect theophylline clearance3 and the calculated loading dose is infused over 30 min. We also noted that ideal treatment with aminophylline was not always achieved even when the serum theophylline concentration on admission was rapidly known. This probably reflects wide variability in theophylline disposition,3and both the infusion rate and the theoretical loading dose described by Walker may need to be
Lipid profiles before, during, and after use of nicotine gum. Gum
use
cholesterol;
began at A and stopped at B. = total cholesterol; . = LDL triglycerides; Q HDL cholesterol.
*
=
=
LDL from the plasma compartment. Extended residence time of LDL in the circulation would increase the likelihood of deposition on the arterial wall.6 The lipid modifications observed may be related to a greater rate of mobilisation of non-esterified fatty acids (NEFA) after nicotine administration. Nicotine sulphate injected intravenously in dogs produced increased plasma levels of NEFA.’ This increase results from stimulation of sympathetic ganglia whose post-ganglionic fibres innervate adipose tissue and from adrenal medullary discharge.8 Smoking one or two cigarettes can also result in significant increases in plasma NEFA,especially if the cigarettes have a high nicotine content. Mobilisation of NEFA produced by smoking may also augment acetylcoenzyme A, a cholesterol precursor. This observation is clinically important because of the widespread use of smokeless tobacco products9 and the increased prescription of nicotine chewing gum. 10 The regular use of nicotine gums may carry an increased risk of cardiovascular disease. Furthermore, the observation confirms the involvement of the adrenergic nervous system in the development of hypercholesterolaemia. Biochemical and Toxicology Laboratories, Faculty of Pharmacy, 31000 Toulouse, France;
and INSERM U101,
Hôpital Purpan, Toulouse
J. C. DOUSSET J. B. GUTIERRÈS N. DOUSSET
WB, Revotskie N, Stokes J, Kagan A, Gordon T. Some factors associated with the development of coronary heart disease. Am J Publ Health 1959; 49: 1349-56. 2. Friedman GD, Dales LG, Ury HK. Mortality in nuddleaged smokers and nonsmokers. N Engl J Med 1979; 300: 213. 3. Booyse FM, Osikowicz G, Quarfoot AJ. Effects of chronic oral consumption of nicotine on the rabbit aortic endothelium. Am J Pathol 1981; 102: 229-38. 4. Augustin J, Beedgen B, Spohr U, Winkel F. The influence of smoking on plasma lipoproteins. Innere Med 1982; 9: 104-08. 5. Cluette-Brown J, Mulligan J, Doyle K, Hugan S, Osmolski T, Hojnacki J. Oral nicotine induces an atherogenic lipoprotein profile. Proc Soc Exp Biol Med 1986; 182: 409-13. 6. Hojnacki J, Mulligan J, Cluette-Brown J, Igoe F, Osmolski T Oral nicotine impairs clearance of plasma low density lipoproteins Proc Soc Exp Biol Med 1986; 182: 414-18 7. Kersbaum A, Bellet S, Dickstein ER, Feinberg LJ. Effect of cigarette smoking and nicotine on serum free fatty acids based on a study in the human subject and the experimental animal. Circ Res 1961; 9: 631-38. 8. Havel RJ. Catecholamines in lipid pharmacology. In: Paoletti R, ed. New York. Academic Press, 1964. 9. Maxwell JC Jr Maxwell report: smokeless grows; cigars decline. Tobacco Rep 1983; 110: 56-57. 10. Cole PV. Effect of nicotine chewing gum on smoking behaviour and as aid to cigarette withdrawal, Br Med J 1976, ii: 391-93. 1. Dawber TR, Kannel
adjusted accordingly. Theophylline is difficult to use effectively and safely. Assays with rapidly available results will identify patients whose compliance with their oral therapy is poor, or whose serum theophylline concentration is already above the therapeutic range and in whom loading doses of aminophylline may be hazardous. Brompton Hospital,
JOHN WIGGINS
London SW3 6HP
1. Arbab OA, Wiggins J, Ayres JG, Stableforth DE. The use of parenteral aminophylline in patients taking slow release theophylline preparations an observation of clinical practice. Br J Dis Chest 1985; 79: 161-71. 2. Wiggins J, Arbab OA, Stableforth DE, Ayres JG. Intravenous aminophylline in patients already taking oral theophylline: effect on calculated dose of knowledge of serum theophylline concentration on admission. Thorax 1986; 41: 759-65. 3. Powell JR, Vozeh S, Hopewell P, Costello J, Sheiner LB, Riegelman S Theophylline disposition in acutely ill hospitalised patients. Am Rev Respir Dis 1978; 118: 229-38.
ACCEPTABILITY OF PRENATAL DIAGNOSIS FOR RETINITIS PIGMENTOSA
SIR,-Using DNA methods Reeders polycystic kidney disease in a fetus and
aP detected adult this was followed by termination of pregnancy. We agree with Reeders et al that with the advent of new prenatal diagnostic techniques their role in medical practice needs to be defined. For this purpose, it may be useful to investigate the attitude of patients, especially in view of increasing patient autonomy,2 the coverage by the media of ethical aspects of medical decisionsand public concern over the ethical impact of prenatal diagnosis by DNA methods. Molecular methods for prenatal testing for retinitis pigmentosa can be expected now that data on linked polymorphic markers in some types are accumulating.3°’ Those affected by retinitis pigmentosa are, like patients with adult polycystic kidney disease, of normal intelligence, and the main symptoms, such as blindness, tend not to occur until adulthood. In a collaborative study 414 patients with retinitis pigmentosa and allied diseases completed a questionnaire designed to investigate the factors influencing the acceptability of prenatal diagnosis by DNA methods. Almost all the patients were members of the German Retinitis Pigmentosa Society. 55 3% were male and 44-7% female; 63-9% were married. 44-0% were Protestant and 35-8% Catholic. The respondents said that they had learned about gene technology via the retinitis pigmentosa patients’ organisation (70-9%), or the media (58-7%), or by attending lectures on the patients’ day at the 4th Congress of the International Retinitis Pigmentosa Association, held in Bad Nauheim, in May, 1986 (18-5%). 61-0% of the respondents felt that there could be dangers in the application of DNA methods in medicine. However, 89 4% also expected to see advantages for RP. 94-8% wanted DNA research to continue, for the following purposes: to improve treatment (90-6%), for more accurate (83-9%) or earlier (82 3°-o’) et