1389
whether the higher doses
epirubicin that greater antineoplastic of
be tolerated have a activity than conventional doses of doxorubicin can
or
daunorubicin. Finally, because of individual variation in susceptibility to toxicity, identification of patients who are at risk of cardiac damage is important and early detection of impairment is essentia1.21 There is a need for an easily available technique to detect cardiotoxicity at an early stage. Abnormalities of left ventricular diastolic function as assessed by pulsed wave doppler transmitral flow velocity measurements precede systolic abnormalities in other forms of heart disease. These abnormalities have been identified in both adults22 and children23 who have received the long-term implications of such abnormalities are unknown. The true incidence of clinically significant progressive cardiac impairment will only become clear as survivors of childhood cancer are followed into adulthood. Although cardiotoxicity limits the dose of anthracyclines, this hazard can be ignored when addition of anthracyclines to treatment protocols substantially increases the chance of cure.
19.
Speyer JL, Green MD, Kramer E, et al. Protective effect of the bispiperazinedione ICRF-187 against doxorubicin-induced cardiotoxicity in women with advanced breast cancer. N Engl J Med
1988; 319: 745-52. 20. Green MD, Alderton P, Gross J, Muggia FM, Speyer JL. Evidence of the selective alteration of anthracycline activity due to modulation by ICRF-187 (ADR-529). Pharmacol Ther 1990; 48: 61-69. 21. Yeung ST, Yoong C, Spink J, Galbraith A, Smith PJ. Functional myocardial impairment in children treated with anthracyclines for cancer. Lancet 1991; 337: 816-18. 22. Marchandise B, Schroeder E, Bosley A, et al. Early detection of doxorubicin cardiotoxicity: interest of doppler echocardiographic analysis of left ventricular filling dynamics. Am Heart J 1989; 118: 92-98. 23. Bu’Lock FA, Mott MG, Martin RP. Doppler echocardiographic detection of anthracycline induced changes in diastolic ventricular function in children. Br Heart J 1990; 64: 85 (abstr).
Dry eyes and visual acuity
anthracyclines, although
1. Weiss RB, Sarosy G, Clagett-Carr, et al. Anthracycline analogs: the past present and future. Cancer Chemother Pharmacol 1986; 18: 185-97. 2. Evans AE, Baehner RL, Chard RL, et al. Comparison of daunorubicin (NSC-83142) with Adriamycin (NSC-123127) in the treatment of late-stage childhood solid tumours. Cancer Chemother Rep 1974; 58: 671-76. 3. Blum RH, Carter SK. Adriamycin: a new anticancer drug with significant clinical activity. Ann Intern Med 1974; 80: 249-59. 4. Arico M, Pedroni E, Nespoli L, et al. Long term survival after heart transplantation for doxorubicin induced cardiomyopathy. Arch Dis Child 1991; 66: 985-86. 5. Jenney MEM, Morris-Jones PH. Long term survival after heart transplantation for doxorubicin induced cardiomyopathy. Arch Dis Child 1992; 67: 153. 6. Di Marco A, Cassinelli G, Arcamone F. The discovery of daunorubicin. Cancer Treat Rep 1981; 65 (suppl 4): 3-8. 7. Benjamin RS. A practical approach to adriamycin toxicology. Cancer Chemother Rep 1975; 6: 191-94. 8. Gotdieb JA, Lefrak EA, O’Bryan, Burgess MA. Fatal adriamycin cardiomyopathy (CMY): prevention by dose limitation. Proc Am Assoc Cancer Res 1973; 14: 88 (abstr). 9. Praga C, Beretta G, Vigo PL, et al. Adriamycin cardiotoxidty: a survey of 1273 patients. Cancer Treat Rep 1979; 63: 827-34. 10. Von Hoff DD, Rozencweig M, Layard M, Slavik M, Muggia FM. Daunomycin-induced cardiotoxicity in children and adults: a review of 110 cases. Am J Med 1977; 62: 200-08. 11. Pratt CB, Ransom JL, Evans WE. Age-related adriamycin cardiotoxicity in children. Cancer Treat Rep 1978; 62: 1381-85. 12. Steinherz LJ, Steinherz PG, Tan CTC, Heller G, Murphy L. Cardiac toxicity 4 to 20 years after completing anthracycline therapy. JAMA 1991; 266: 1672-77. 13. Lipshultz SE, Colan SD, Gelber RD, Perez-Atayde AR, Sallan SE, Sanders SP. Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukaemia in childhood. N Engl J Med 1991; 324: 808-15. 14. Shapira J, Goffried M, Lishner M, Ravid M. Reduced cardiotoxicity of doxorubicin by a 6-hour infusion regimen. Cancer 1990; 65: 870-73. 15. Legha SS, Benjamin RS, Makay B, et al. Reduction of doxorubicin cardiotoxicity by prolonged continuous intravenous infusion. Ann Intern Med 1982; 96: 133-39. 16. Bode U, Erps M, Kohler W. Doxorubicin-dauerinfusionen eine Pilotstudie bei jugendlichen Patienten. Klin Padiatr 1988; 200: 271-73. 17. Weiss AJ, Metter GE, Fletcher WS, et al. Studies on Adriamycin using a weekly regimen demonstrating its clinical effectiveness and lack of cardiac toxicity. Cancer Treat Rep 1976; 60: 813-22. 18. Lippens RJJ, van Lier HJJ, Zwagmakers JFC. Tolerance of 24-hour infusions of low and high-dose bolus injections of Adriamycin in children. Pediatr Hematol Oncol 1987; 4: 189-97.
Patients with dry eyes complain most of discomfort; far less importance has been attached to the functional significance of a poor tear film. Reigerl lately reported improvement in visual function in dry-eyed patients who had been given a tear-substitute drop. Sixty
patients recently diagnosed as having dry eyes were given a test of visual function which was repeated shortly after administration of a single drop of tear-substitute to the right eye only. Half the patients had visual acuity measured and the other half underwent computed central visual sensitivity testing. Reiger found a significant improvement in both visual acuity and central sensitivity in the treated right eye but not in the untreated left. Is this effect likely to be clinically important? A close look at the results reveals that mean improvement in acuity after tear drops was only +2-33 letters on the testing chart. This difference is unlikely to pass or fail someone for driving purposes, unless they are on the borderline of a test that is notoriously difficult to standardise accurately between patients. What about the effect on visual field testing? In practice, the programme specified for the study is likely to be used only in the very limited setting of screening for antimalarial drug toxicity, since the serial sensitivities are more helpful in a clinical setting than are the absolute values. The results of the study are unlikely to be relevant in dry-eyed patients whose visual fields are being screened for glaucoma, for example. Nevertheless, it may be wise for dry-eyed patients to use their drops when driving, especially at night when glare from a poor tear film is most obvious. Airline passengers or crew may find that their vision improves if they use tear substitutes to counteract the desiccating air-conditioning in the aircraft cabin. Dry-eyed photographers or those who use visual display units (whose rate of blinking is low) might appreciate the optical benefit of tear substitutes. The results do not necessarily mean that large numbers of dry-eyed drivers are putting themselves and others at risk by failing to use lubricating eye drops. 1.
Reiger G. The importance of precorneal tear film for the quality of optical imaging. Br J Ophthalmol 1992; 76: 157-58.
whether the higher doses
epirubicin that greater antineoplastic of
be tolerated have a activity than conventional doses of doxorubicin can
or
daunorubicin. Finally, because of individual variation in susceptibility to toxicity, identification of patients who are at risk of cardiac damage is important and early detection of impairment is essentia1.21 There is a need for an easily available technique to detect cardiotoxicity at an early stage. Abnormalities of left ventricular diastolic function as assessed by pulsed wave doppler transmitral flow velocity measurements precede systolic abnormalities in other forms of heart disease. These abnormalities have been identified in both adults22 and children23 who have received the long-term implications of such abnormalities are unknown. The true incidence of clinically significant progressive cardiac impairment will only become clear as survivors of childhood cancer are followed into adulthood. Although cardiotoxicity limits the dose of anthracyclines, this hazard can be ignored when addition of anthracyclines to treatment protocols substantially increases the chance of cure.
19.
Speyer JL, Green MD, Kramer E, et al. Protective effect of the bispiperazinedione ICRF-187 against doxorubicin-induced cardiotoxicity in women with advanced breast cancer. N Engl J Med
1988; 319: 745-52. 20. Green MD, Alderton P, Gross J, Muggia FM, Speyer JL. Evidence of the selective alteration of anthracycline activity due to modulation by ICRF-187 (ADR-529). Pharmacol Ther 1990; 48: 61-69. 21. Yeung ST, Yoong C, Spink J, Galbraith A, Smith PJ. Functional myocardial impairment in children treated with anthracyclines for cancer. Lancet 1991; 337: 816-18. 22. Marchandise B, Schroeder E, Bosley A, et al. Early detection of doxorubicin cardiotoxicity: interest of doppler echocardiographic analysis of left ventricular filling dynamics. Am Heart J 1989; 118: 92-98. 23. Bu’Lock FA, Mott MG, Martin RP. Doppler echocardiographic detection of anthracycline induced changes in diastolic ventricular function in children. Br Heart J 1990; 64: 85 (abstr).
Dry eyes and visual acuity
anthracyclines, although
1. Weiss RB, Sarosy G, Clagett-Carr, et al. Anthracycline analogs: the past present and future. Cancer Chemother Pharmacol 1986; 18: 185-97. 2. Evans AE, Baehner RL, Chard RL, et al. Comparison of daunorubicin (NSC-83142) with Adriamycin (NSC-123127) in the treatment of late-stage childhood solid tumours. Cancer Chemother Rep 1974; 58: 671-76. 3. Blum RH, Carter SK. Adriamycin: a new anticancer drug with significant clinical activity. Ann Intern Med 1974; 80: 249-59. 4. Arico M, Pedroni E, Nespoli L, et al. Long term survival after heart transplantation for doxorubicin induced cardiomyopathy. Arch Dis Child 1991; 66: 985-86. 5. Jenney MEM, Morris-Jones PH. Long term survival after heart transplantation for doxorubicin induced cardiomyopathy. Arch Dis Child 1992; 67: 153. 6. Di Marco A, Cassinelli G, Arcamone F. The discovery of daunorubicin. Cancer Treat Rep 1981; 65 (suppl 4): 3-8. 7. Benjamin RS. A practical approach to adriamycin toxicology. Cancer Chemother Rep 1975; 6: 191-94. 8. Gotdieb JA, Lefrak EA, O’Bryan, Burgess MA. Fatal adriamycin cardiomyopathy (CMY): prevention by dose limitation. Proc Am Assoc Cancer Res 1973; 14: 88 (abstr). 9. Praga C, Beretta G, Vigo PL, et al. Adriamycin cardiotoxidty: a survey of 1273 patients. Cancer Treat Rep 1979; 63: 827-34. 10. Von Hoff DD, Rozencweig M, Layard M, Slavik M, Muggia FM. Daunomycin-induced cardiotoxicity in children and adults: a review of 110 cases. Am J Med 1977; 62: 200-08. 11. Pratt CB, Ransom JL, Evans WE. Age-related adriamycin cardiotoxicity in children. Cancer Treat Rep 1978; 62: 1381-85. 12. Steinherz LJ, Steinherz PG, Tan CTC, Heller G, Murphy L. Cardiac toxicity 4 to 20 years after completing anthracycline therapy. JAMA 1991; 266: 1672-77. 13. Lipshultz SE, Colan SD, Gelber RD, Perez-Atayde AR, Sallan SE, Sanders SP. Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukaemia in childhood. N Engl J Med 1991; 324: 808-15. 14. Shapira J, Goffried M, Lishner M, Ravid M. Reduced cardiotoxicity of doxorubicin by a 6-hour infusion regimen. Cancer 1990; 65: 870-73. 15. Legha SS, Benjamin RS, Makay B, et al. Reduction of doxorubicin cardiotoxicity by prolonged continuous intravenous infusion. Ann Intern Med 1982; 96: 133-39. 16. Bode U, Erps M, Kohler W. Doxorubicin-dauerinfusionen eine Pilotstudie bei jugendlichen Patienten. Klin Padiatr 1988; 200: 271-73. 17. Weiss AJ, Metter GE, Fletcher WS, et al. Studies on Adriamycin using a weekly regimen demonstrating its clinical effectiveness and lack of cardiac toxicity. Cancer Treat Rep 1976; 60: 813-22. 18. Lippens RJJ, van Lier HJJ, Zwagmakers JFC. Tolerance of 24-hour infusions of low and high-dose bolus injections of Adriamycin in children. Pediatr Hematol Oncol 1987; 4: 189-97.
Patients with dry eyes complain most of discomfort; far less importance has been attached to the functional significance of a poor tear film. Reigerl lately reported improvement in visual function in dry-eyed patients who had been given a tear-substitute drop. Sixty
patients recently diagnosed as having dry eyes were given a test of visual function which was repeated shortly after administration of a single drop of tear-substitute to the right eye only. Half the patients had visual acuity measured and the other half underwent computed central visual sensitivity testing. Reiger found a significant improvement in both visual acuity and central sensitivity in the treated right eye but not in the untreated left. Is this effect likely to be clinically important? A close look at the results reveals that mean improvement in acuity after tear drops was only +2-33 letters on the testing chart. This difference is unlikely to pass or fail someone for driving purposes, unless they are on the borderline of a test that is notoriously difficult to standardise accurately between patients. What about the effect on visual field testing? In practice, the programme specified for the study is likely to be used only in the very limited setting of screening for antimalarial drug toxicity, since the serial sensitivities are more helpful in a clinical setting than are the absolute values. The results of the study are unlikely to be relevant in dry-eyed patients whose visual fields are being screened for glaucoma, for example. Nevertheless, it may be wise for dry-eyed patients to use their drops when driving, especially at night when glare from a poor tear film is most obvious. Airline passengers or crew may find that their vision improves if they use tear substitutes to counteract the desiccating air-conditioning in the aircraft cabin. Dry-eyed photographers or those who use visual display units (whose rate of blinking is low) might appreciate the optical benefit of tear substitutes. The results do not necessarily mean that large numbers of dry-eyed drivers are putting themselves and others at risk by failing to use lubricating eye drops. 1.
Reiger G. The importance of precorneal tear film for the quality of optical imaging. Br J Ophthalmol 1992; 76: 157-58.
