Abstract
This article emphasizes the role of nuclear medicine in the monitoring of function to prevent or limit injury in organs in which toxicity related to cancer therapy may have implications for the survival and/or the quality of life of the patient. After a brief discussion of the advantages of nuclear medicine techniques in detecting organ injury, the effect of radiation therapy and chemotherapy on normal tissue is discussed, underlining the need to characterize adverse effects of cancer therapy in long-term survivors. The use of radionuclides to document organ injury and effects from cancer therapy in heart, digestive tract, kidneys, lungs, major salivary glands, skeleton and brain is then reviewed. In a short section the potential applicability of positron emission tomography in documenting organ toxicity during cancer therapy is discussed. Thanks to the various available radiopharmaceuticals, the ability of the tracers to document specific functional aspects, the improved methods for visualization and quantitation of organ injury and the possibilities of physiological or pharmacological intervention, nuclear medicine gives the clinician potent tools for the monitoring of organ function at risk during cancer therapy. The trend to intensify cancer treatment by combining various treatment modalities and the increasing chances of prolonged survival in a large number of patients call for effective integration of nuclear medicine methods into the recommended guidelines for grading organ injury in clinical oncology.
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References
Haskell CM. Principles and modalities of cancer treatment. In: Haskell CM, ed. Cancer treatment. Philadelphia: Saunders, 1990:3–9.
Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer 1981; 47:207–214.
Skinner R, Pearson ADJ, Coulthard MC, Skillen AW, Hodson AW, Goldfinch ME, Gibb I, Craft AW. Assessment of chemotherapy-associated nephrotoxicity in children with cancer. Cancer Chemother Pharmacol 1991; 28:81–92.
Steinherz LJ, Graham T, Hurwitz R, Sondheimer EM, Sandor G, Benson L, Williams R. Guidelines for cardiac monitoring of children during and after anthracycline therapy: report of the Cardiology Committee of the Childrens Cancer Study Group. Pediatrics 1992; 89:942–949.
Rubin P, Constine LS, van Ess JD. Special lecture: scoring of late effects. Interaction of two modalities. NCI Monographs 1988; 6:9–18.
Morgan GW, Freeman AP, McLean RG, Jarvie BH, Giles RW. Late cardiac, thyroid, and pulmonary sequelae of mantle radiotherapy for Hodgkin's disease. Int J Radiat Oncol Biol Phys 1985; 11:1925–1931.
Lipshultz SE, Colan SD, Gelber RD, Perez-Atayde AR, Sallan SE, Sanders SP. Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood. N Engl J Med 1991; 324:808–815.
Hammond GD. Late adverse effects of treatment among patients cured of cancer during childhood. CA 1992; 42:261–262.
DeLaat CA, Lampkin BC. Long-term survivors of childhood cancer: evaluation and identification of sequelae of treatment. CA 1992; 42:263–282.
Kornblith AB, Anderson J, Cella DF, Tross S, Zuckerman E, Cherin E, Henderson ES, Weiss RB, Cooper MR, Silver RT, Leone L, Canellos GC, Gottlieb A, Holland JC. Quality of life assessment of Hodgkin's disease survivors: a model for cooperative clinical trials. Oncology 1990; 4:93–101.
Hancock SL, Hoppe RT, Horning SJ, Rosenberg SA. Intercurrent death after Hodgkin disease therapy in radiotherapy and adjuvant MOPP trials. Ann Intern Med 1988; 109:183–189.
Hancock SL, Cox RS, Rosenberg SA. Correction: deaths after treatment of Hodgkin's disease. Ann Intern Med 1991; 114:810.
D'Angio GJD. An overview and historical perspective of late effects of treatment for childhood cancer. In: D'Angio GJD, ed. Late effects of treatment for childhood cancer. New York: Wiley-Liss; 1992: 1–6.
Rubin P. The Franz Buschke lecture: late effects of chemotherapy and radiation therapy: a new hypothesis. Int J Radiat Oncol Biol Phys 1984; 10:5–34.
Rotman MZ. Chemoirradiation: a new initiative in cancer treatment. Radiology 1991; 184:319–327.
Muggia FM, Green MD. New anthracycline antitumor antibiotics. Crit Rev Oncol Hematol 1991; 11:43–64.
Chlebowski RT. Adriamycin (doxorubicin) cardiotoxicity: a review. West J Med 1979; 131:364–368.
Henderson I. Adriamycin cardiotoxicity. Am Heart J 1980; 99:671–674.
Von Hoff DD, Rozencweig M, Piccart M. The cardiotoxicity of anticancer agents. Semin Oncol 1982; 9:23–33.
Legha SS, Benjamin RS, Mackay B, Ewer M, Wallace S, Valdivieso M, Rasmussen SL, Blumenschein GR, Freireich EJ. Reduction of doxorubicin-induced congestive heart failure. Ann Intern Med 1982; 96:133–139.
Billingham ME, Mason JW, Bristow MR, Daniels JR. Anthracycline cardiomyopathy monitored by morphologic changes. Cancer Treat Rep 1978;62:865–872.
Benjamin RS, Chawla SP, Ewers MS, Carrasco CH, MacKay B, Haynie TP III, Yap HY, Blumenschein GR, Holmes F, Ali MK, Bodey GP. Evaluation of mitoxantrone cardiac toxicity by nuclear angiography and endomyocardial biopsy. ASCO abstracts 1984: C-156.
Torti FM, Bristow MM, Lum BL Carter SK, Howes AE, Aston DA, Brown BW, Hannigan JF, Meyers FJ, Mitchell EP, Billinghan ME. Cardiotoxicity of epirubicin and doxorubicin: assessment by endomyocardial biopsy. Cancer Res 1986; 46: 3722–3727.
Steinherz LJ, Steinherz PG, Tan CTC, Heller G, Murphy M. Cardiac toxicity 4 to 20 years after completing anthracycline therapy. JAMA 1991; 266:1672–1677.
Geidel S, Garn M, Grävinghoff L, Hausdorf G, Morf G, Bielack S, Knop J, Winkler K. Kardiomyopathie nach Osteosarkombehandlung: ein Beitrag zur Kardiotoxizität von Adriamycin. Klin Pädiatr 1991; 203:257–261.
Combs AB, Acosta D. Toxic mechanisms of the heart: a review. Toxicol Pathol 1990; 18: 583–596.
Milei J, Marantz A, Ale J, Vazquez A, Buceta JE. Prevention of adriamycin-induced cardiotoxicity by prenylamine: a pilot double blind study. Cancer Drug Delivery 1987; 4:129–136.
Lenzhofer R, Ganzinger U, Rameis H, Moser K. Acute cardiac toxicity in patients after doxorubicin treatment and the effect of combined tocopherol and nifedipine pretreatment. J Cancer Res Clin Oncol 1983; 106:143–147.
Nooter K, Oostrum R, Duerloo J. Effects of verapamil on the pharmacokinetics of daunomycin in the rat. Cancer Chemother Pharmacol 1987; 20:176–178.
Workman P. Infusional anthracyclines; is slower better? if so, why? Ann Oncol 1992; 3:591–594.
Doroshow JH. Doxorubicin-induced cardiac toxicity. N Engl J Med 1991; 324:843–845.
Speyer JL, Green MD, Kramer E, Rey M, Sanger J, Ward C, Dubin N, Ferrans V, Stecy P, Zeleniuch-Jacquote A, Wernz J, Feit F, Slater W, Blim R, Muggia F. Protective effect of the bispiperazinedione ICRF-187 against doxorubicin-induced cardiac toxicity in women with advanced breast cancer. N Engl J Med 1988; 319:745–752.
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.
Druck MN, Gulenchyn KY, Evans WK, Gotheb A, Srigley JR, Bar-Shlomo, Feiglin DH, McEwan P, Silver MD, Millband L, Winter K, Hilton JD, Jablonsky G, Morch JE, McLaughlin P. Radionuclide angiography and endomyocardial biopsy in the assessment of doxorubicin cardiotoxicity. Cancer 1984; 53:1667–1674.
Dardir MD, Ferrans VJ, Mikhael S, El-Guindy MS, El-Aasar AB, El-Zawahry HM, Alling DW, Banks SM, El-Mawla NG. Cardiac morphologic and functional changes induced by epirubicin chemotherapy. J Clin Oncol 1989; 7:947–958.
Torti FM, Bristow MR, Bowes AE, Aston D, Stockdale FE, Carter SK, Kohler M, Brown B, Billingham ME. Reduced cardiotoxicity of doxorubicin delivered on a week schedule. Ann Intern Med 1983; 99:745–749.
Isner JM, Ferrans VJ, Cohen SR. Clinical and morphological cardiac findings after anthracycline chemotherapy: analysis of 64 patients studied at necropsy. Am J Cardiol 1983; 51:1167–1174.
Alexander J, Dainiak N, Berger HJ, Goldman L, Johnstone D, Reduto L, Duffy T, Schwartz P, Gottschalk A, Zaret BL. Serial assessment of doxorubicin cardiotoxicity with quantitative radionuclide angiocardiograpby. N Engl J Med 1979; 300:278–283.
Schwartz RG, McKenzie WB, Alexander J, Sager P, D'Souza A, Manatunga A, Schwartz PE, Berger HJ, Setaro J, Surkin L, Wackers FJT, Zaret BL. Congestive heart failure and left ventricular dysfunction complicating doxorubicin therapy. Seven-year experience using serial radionuclide angiocardiography. Am J Med 1987; 82:1109–1118.
Alth G, Ogris E. Lungenszintigraphische Langzeitbeobachtungen bei postoperativer Bestrahlung der Mammaregion. Strahlentherapie 1975; 149: 41–48.
Jain D, Zaret BL. Antimyosin cardiac imaging: will it play a role in the detection of doxorubicin cardiotoxicity? J Nucl Med 1990; 31:1970–1974.
McKillop JH, Bristow MR, Goris ML, Billingham ME, Bockemuehl K. Sensitivity and specificity of radionuclide ejections fractions in doxorubicin cardiotoxicity. Am Heart J 1983; 106:1048–1056.
Palmeri ST, Bonow RO, Myers CE, Seipp C, Jenkins J, Green MV, Bacharach SL, Rosenberg SA. Prospective evaluation of doxorubicin cardiotoxicity by rest and exercise radionuclide angiography. Am J Cardiol 1986; 56:607–613.
Knesewitsch P, Göldel NH, Fritsch S, Moser E. Equilibrium radionuclide ventriculography in the evaluation of adriamycin cardiotoxicity. II. Results under exercise. Nuklearmedizin 1987; 26: 212–219.
Strashun A. Adriamycin, congestive cardiomyopathy, and metaiodobenzylguanidine. J Nucl Med 1992; 2:215–220.
Shekenberg TD, Von Hoff D. Mitoxantrone: a new anticancer drug with significant clinical activity. Ann Intern Med 1986; 105:67–81.
Cowan JD, Neidhart J, McClure S, Coltman CA, Gumbart C, Martino S, Hutchins LF, Stephens RL, Vaughan CL, Osborne CK. Randomized trial of doxorubicin, bisantrene, and mitoxantrone in advanced breast cancer: a Southwest Oncology Group study. J Natl Cancer Inst 1991; 83:1077–1084.
Hortobagyi GN, Frye D, Buzdar AU. Decreased cardiac toxicity of doxorubicin administered by continuous intravenous infusion in combination chemotherapy for metastatic breast carcinoma. Cancer 1989; 63:37–45.
Casper ES, Gaynor JJ, Hadju SL, Magill GB, Tan CT, Friedrich C, Brennan MF. A prospective randomized trial of adjuvant chemotherapy with bolus versus continuous infusion of doxorubicin in patients with high grade extremity soft tissue sarcoma and an analysis of prognostic factors. Cancer 1991; 68:1221–1229.
Ten Bokkel Huinink WW, Schreuder JE, Dubbelman R, Bierhorst F, van Tinteren H, Dalesio O, Valdes Olmos RA, McVie JG. ICRF-187 protects against doxorubicin-induced cardiomyopathy [abstract]. Ann Oncol 1992; 3 Suppl 1:114.
Alcan KE, Robison W, Graham MC, Palestro C, Oliver FH, Benua RS. Early detection of anthracycline-induced cardiotoxicity by stress radionuclide cineangiography in conjunction with Fourier amplitude and phase analysis. Clin Nucl Med 1985; 10:160–166.
Barendswaard EC, Prpic H, van der Wall EE, Camps JAJ, Keyzer HJ, Pauwels EKJ. Right ventricle wall motion abnormalities in patients treated with chemotherapy. Clin Nucl Med 1991; 16: 513–516.
Lee BH, Goodenday LS, Muswick GJ, Yasnoff WA, Leighton RF, Skeel RT. Alterations in left ventricular diastolic function with doxorubicin therapy. J Am Coll Cardiol 1987; 9:184–188.
Parmentier S, Melin JA, Piret L, Beckers C. Assessment of left ventricular diastolic function in patients receiving anthracycline therapy. Eur J Nucl Med 1988; 13:563–567.
Massing JL, Caillot D, Casasnovas RO, Cottin Y, Guy H, Wolf JE, Louis P, Brunotte F. Early detection of anthracycline cardiotoxicity: interest of radionuclide angiography analysis of left ventricular (LV) filling parameters [abstract]. Eur J Nucl Med 1992; 19:667.
Mortensen SA, Olsen HS, Baandrup U. Chronic anthracycline cardiotoxicity: haemodynamic and histopathological manifestations suggesting a restrictive endomyocardial disease. Br Heart J 1986; 55:274–282.
Dey HM, Kassamali H. Radionuclide evaluation of doxorubicin cardiotoxicity: the need for cautious interpretation. Clin Nucl Med 1988; 13:565–568.
Hains ADB, Al-Khawaja I, Hinge DA, Lahiri A, Raftery EB. Radionuclide left ventricular ejection fraction: a comparison of three methods. Br Heart J 1987; 57:242–246.
Pauwels EKJ, Horning SJ, Goris ML. Sequential equilibrium gated radionuclide angiocardiography for the detection of doxorubicin cardiotoxicity. Radiother Oncol 1983; 1:83–87.
Palacios I, Powers E, Powell WJ Jr. Effect of end-diastolic volume on the canine left ventricular ejection fraction. Am Heart J 1985; 109:1059.
Kiess MC, Dimsdale JE, Moore RH, Liu P, Newell J, BarlaiKovach M, Boucher CA, Strauss HW. The effect of stress on left ventricular ejection fraction. Eur J Nucl Med 1988; 14:12–16.
Estorch M, Carrió I, Berná L, Martínez-Duncker C, Alonso C, Germá JR, Ojeda B. Indium-111-antimyosin scintigraphy after doxorubicin therapy in patients with advanced breast cancer. J Nucl Med 1990; 31:1965–1969.
Carrió I, Estorch M, Berna L, Germa JR, Alonso C, Ojeda B, de Andrés L, Lopez-Pousa A, Martinez-Duncker C, Torres G. Assessment of anthracycline-induced myocardial damage by quantitative indium 111 myosin-specific monoclonal antibody studies. Eur J Nucl Med 1991; 18:806–812.
Carrió I, Estorch M, Berná L, Duncker D, Torres G. Early detection of patients at risk of congestive heart failure during adriamicin therapy by means of In-111 antimyosin studies [abstract]. J Nucl Med 1992; 33:895.
Jensen RA. Doxorubicin cardiotoxicity: contractile changes after long-term treatment in the rat. J Pharmacol Exp Ther 1986; 236:197–203.
Robison TW, Giri SN. Effects of chronic administration of doxorubicin on myocardial beta-adrenergic receptors. Life Sci 1986; 39:731–736.
Sisson JC, Shapiro B, Meyers L, Mallette S, Mangner TJ, Wieland DM, Glowniak JV, Sherman P, Beierwaltes WH. Metaiodobenzylguanidine to map scintigraphically the adrenergic nervous system in man. J Nucl Med 1987; 28:1625–1636.
Sisson JC, Wieland DM, Sherman P, Mangner TJ, Tores MC, Jacques S. Metaiodobenzylguanidine as an index of the adrenergic nervous system integrity and function. J Nucl Med 1987; 28:1620–1624.
Henderson EB, Kahn JK, Corbett JR, Jansen DE, Pippin JJ, Kulkarni P, Ugolini V, Akers MS, Hansen C, Buja LM, Parkey RW, Willerson JT. Abnormal I-123 metaiodobenzylguanidine myocardial washout and distribution may reflect adrenergic derangement in patients with congestive cardiomyopathy. Circulation 1988; 78:1192–1199.
Glowniak JV, Turner FE, Gray LL, Palac RT, Lagunas-Solar MC, Woodward WR. Iodine-123 metaiodobenzylguanidine imaging of the heart in idiopathic congestive cariomyopathy and cardiac transplants. J Nucl Med 1989; 30:1182–1191.
Yamakado K, Takeda K, Kitano T, Nakagawa, Futagami Y, Konishi T, Hamada M, Nakanao T, Ichihara T. Serial change of iodine-123 metaiodobenzylguanidine (MIBG) myocardial concentration in patients with dilated cardiomyopathy. Eur J Nucl Med 1992; 19:265–270.
Wakasugi S, Wada A, Hasegawa Y, Nakano N, Shibata N. Detection of abnormal cardiac adrenergic neuron activity in adriamycin-induced cardiomyopathy with iodine-125-metaiodobenzylguanidine. J Nucl Med 1992; 33:208–214.
Valdes Olmos RA, ten Bokkel Huinink WW, Greve JC, Hoefnagel CA. I-123 MIBG and serial radionuclide angiocardiography in doxorubicin related cardiotoxicity. Clin Nucl Med 1992; 17:163–167.
Wakasugi S, Babich J, Nakaki M, Strauss HW. Prediction of congestive heart failure due to adriamycin cardiomyopathy with I-125-metaiodobenzylguanidine [abstract]. J Nucl Med 1992; 33:935.
Merlet P, Valette H, Dubois-Randé JL, Moyse D, Duboc D, Dove P, Bourguignon MH, Benvenuti C, Duval AM, Agostini D, Loisance D, Castaigne A, Syrota A. Prognostic value of cardiac metaiodobenzylguanidine imaging in patients with heart failure. J Nucl Med 1992; 33:471–477.
Miyagawa M, Tanada S, Hamamoto K. Scintigraphic evaluation of myocardial uptake of thallium 201 and technetium 99m pyrophosphate utilizing a rat model of chronic doxorubicin cardiotoxicity. Eur J Nucl Med 1991; 18:332–338.
Gosálvez M, van Rossum GDV, Blanco MF. Inhibition of sodium-potassium activated adenosine 5′-triphosphatase and ion transport by Adriamycin. Cancer Res 1979; 39:257–261.
Lenzhofer R, Dudczak R. Indication of doxorubicin cardiotoxicity by impairment of 131I-pIPPA utilization. Eur J Nucl Med 1986; 12:S32-S33.
Piwnica-Worms D, Chiu ML, Kronauge JF. Detection of acute adriamycin cardiotoxicity in cultured chick heart cells with Tc-99m-SESTAMIBI [abstract]. J Nucl Med 1992; 33:864.
Saini J, Rich MW, Liss AP. Reversibility of severe left ventricular dysfunction due to doxorubicin cardiotoxicity: report of three cases. Ann Intern Med 1987; 106:814–816.
Piver MS, Marchetti DL, Parthasarathy KL, Bakshi S, Reese P. Doxorubicin hydrochloride (adriamycin) cardiotoxicity evaluated by sequential radionuclide angiocardiography. Cancer 1985; 56:76–80.
Awad HK. Late reacting tissues: radiation-induced heart disease. In: Awad HK, ed. Radiation oncology. Dordrecht: Kluwer Academic; 1991:449–456.
Stewart JR, Fajardo LF. Radiation-induced heart disease: an update. Prog Cardiovasc Dis 1984; 27:173–194.
Corn BW, Track BJ, Goodman RL. Irradiation-related ischemic disease. J Clin Oncol 1990; 8:741–750.
Burns RJ, Bar-Shlomo BZ, Druck MN, Herman JG, Gilbert BW, Perrault DJ, McLaughlin PR. Detection of radiation cardiomyopathy by gated radionuclide angiography. Am J Med 1983; 74:297–302.
Gottdiener JS, Katin MJ, Borer JS, Bacharach SL, Green MV. Late cardiac effects of therapeutic mediastinal irradiation. Assessment by echocardiography and radionuclide angiography. N Engl J Med 1983; 308: 569–572.
Applefeld MM, Wierink PH. Cardiac disease after radiation therapy for Hodgkin's disease: analysis of 48 patients. Am J Cardiol 1983; 51:1679–1681.
Savage DE, Constine LS, Scwartza RD, Rubin P. Radiation effects on left ventricular function and myocardial perfusion in long term survivors of Hodgkin's disease. Int J Radiat Oncol Biol Phys 1990; 19:721–727.
Gustavsson A, Eskilsson J, Landberg T, Svahn-Tapper G, White T, Wollmer P. Late cardiac effects after mantle radiotherapy in patients with Hodgkin's disease. Ann Oncol 1990; 1:355–363.
Maunory C, Pierga JY, Valette H, Tchernia G, Cosset JM, Desgrez A. Myocardial perfusion damage after mediastinal irradiation for Hodgkin's disease: a thallium-201 single photon emission tomography study. Eur J Nucl Med 1992; 19:871–873.
Lagrange JL, Darcourt J, Benoliel J, Bensadoun RJ, Migneco O. Acute cardiac effects of mediastinal irradiation: assessment by radionuclide angiography. Int J Radiat Oncol Biol Phys 1992; 22:897–903.
Ricart Y, Petriz L, Prat L, Garcia A, Sierra J, Segarra MI, Mora J, Martin-Comin J. 111In-antimyosin myocardial scintigraphy in patients undergoing mediastinum or whole body irradiation [abstract]. Eur J Nucl Med 1992; 19:672.
Allen-Mersh TG, Wilson EJ, Hope-Stone HF. Has incidence of radiation-induced bowel damage following treatment of uterine carcinoma changed in the last 20 years? J R Soc Med 1986; 79:387–390.
Fischer L, Kimose HH, Spjeldnaes N, Wara P. Late radiation injuries of the small intestine. Management and outcome. Acta Chir Scand 1989; 155:47–51.
Busch DB. Pathology of the radiation-damaged bowel. In: Galland RB, Spencer J, eds. Radiation enteritis. London: Edward Arnold; 1990:66–87.
Galland RB, Spencer J. The natural history of clinically established radiation enteritis. In: Galland RB, Spencer J, eds. Radiation enteritis. London: Edward Arnold; 1990: 136–146.
Merrick MV. Bile acid malabsorption. Clinical presentation and diagnosis. Dig Dis 1988; 6: 159–169.
Newman A, Katsaris J, Blendis LM, Charlesworth M, Walter LH. Small-intestinal injury in women who have had pelvic radiotherapy. Lancet 1973; 11:1471–1473.
Heaton KW. Disturbances of bile acid metabolism in intestinal disease. Clin Gastroenterol 1977; 6:69–89.
Ludgate SM, Merrick MV The pathogenesis of post-irradiation chronic diarrhoea: measurement of SeHCAT and B12 absorption for differential diagnosis determines treatment. Clin Radiol 1985; 36:275–278.
Miholic J, Vogelsang H, Schlappack O, Kletter K, Szepesi T, Moeschl P. Small bowel function after surgery for chronic radiation enteritis. Digestion 1989; 42:30–38.
Valdes Olmos RA, den Hartog Jager FCA, Hoefnagel CA. Taal BG. Imaging and retention measurements of selenium 75 homocholic acid conjugated with taurine, combined with carbon 14 glycochol breath test to document ileal dysfunction due to late radiation damage. Eur J Nucl Med 1991; 18:124–128.
Danielsson A, Nyhlin H, Persson H, Stendahl U, Stenling R, Suhr O. Chronic diarrhoea after radiotherapy for gynaecological cancer: occurrence and aetiology. Gut 1991; 32:1180–1187.
Valdés Olmos RA, den Hartog Jager FCA, Hoefnagel CA, Taal BG. Effect of loperamide and delay of bowel motility on bile acid malabsorption caused by late radiation damage and ileal resection. Eur J Nucl Med 1991; 18:346–350.
Valdes Olmos RA, Boersma LJ, den Hartog Jager FCA, Hoefnagel CA, Lebesque JV, Taal BG. Value of 75SeHCAT in the study of ileal bile acid absorption in patients treated with radiotherapy for pelvic malignancies [abstract]. Rev Esp Med Nucl 1992; 11 Suppl I:54.
Merrick MV, Eastwood MA, Ford MJ. Is bile acid malabsorption underdiagnosed? An evaluation of accuracy of diagnosis by measurement of SeHCAT retention. Br Med J 1985; 290:665–668.
Craft AW, Kay HEM, Lawson DN, McElwain TJ. Methotrexate-induced malabsorption in children with acute lymphoblastic leukaemia. Br Med J 1977; 2:1511–1512.
Levi S, Hodgson HJ. The medical management of radiation enteritis. In: Galland RB, Spencer J, eds. Radiation enteritis. London: Edward Arnold; 1990:176–198.
Mearns AJ, Hart GC, Cox JA. Dynamic radionuclide imaging with 99mTc-sucralfate in the detection of oesophageal ulceration. GUT 1989; 30:1256–1259.
Taal BG, Valdes Olmos RA, Stokkel M. Assessment of sucralfate coating by sequential radionuclide imaging in radiation induced esophageal lesions [abstract]. Neth J Med 1993 (in press).
Davis SS, Hardy JG, Newman SP, Wilding IR. Gamma scintigraphy in the evaluation of pharmaceutical dosage forms. Eur J Nucl Med 1992; 19:971–986.
Perry MC. Hepatoxicity of chemotherapeutic agents. Semin Oncol 1982; 9:65–74.
Daugaard G, Abildgaard U. Cisplatin nephrotoxicity. Cancer Chemother Pharmacol 1989; 25:1–9.
Pratt CB, Meyer WH, Jenkins JJ, Avery L; McKay CP, Wyatt RJ, Hancock ML. Ifosfamide, Fanconi's syndrome, and rickets. J Clin Oncol 1991; 9:1495–1499.
Van Luijk WHJ, Ensing GJ, Meijer S, Donker AJM, Piers DA. Is the relative 99-Tc-DMSA clearance a useful marker of proximal tubular dysfunction?. Eur J Nucl Med 1984; 9:439–442.
Taylor A. Quantitation of renal function with static imaging agents. Semin Nucl Med 1982; 12:330–344.
Van Luijk WHJ, Ensing GJ, Piers DA. Low renal uptake of 99mTc-DMSA in patients with proximal tubular dysfunction. Eur J Nucl Med 1983; 8:404–405.
De Lange MJ, Piers DA, Kosterink JG, Van Luijk WHJ, Meijer S, De Zeeuw D, Van der Hem GK. Renal handling of technetium-99m DMSA: evidence for glomerular filtration and peritubular uptake. J Nucl Med 1989; 30:1219–1223.
Anninga JK, De Kraker J, Hoefnagel CA, Voûte PA. Ifosfamide induced nephrotoxicity evaluated by 99mTc-DMSA renal scintigraphy [abstract]. Med Pediatr Oncol 1990: 18:406.
Potvin WJ, Gross ML, Windham JP, Gupta BK, Clarke HS, Riccobono XJ, Nally JV. Water loading improves specificity in renal imaging. J Nucl Med Technol 1991; 19:168–172.
Landuyt W, van der Kogel AJ, De Roo M, Hoogmartens M, Ang KK, van der Schucren E. Unilateral kidney irradiation and late retreatment with cis-dichlorodiammineplatinum (II): functional measurements with 99mtechnetium-dimercap-tosuccinic acid. Int J Radiat Oncol Biol Phys 1988; 14:95–101.
Williams MV. The cellular basis of renal injury by irradiation. Br J Cancer 1986; 53:257–264.
Palestro C, Fineman D, Goldsmith SJ. Acute radiation nephritis. Its evolution on sequential bone imaging. Clin Nucl Med 1988; 13:789–791.
Titelbaun DS, Fowble BF, Powe JE, Martinez FJ. Renal uptake of technetium-99m methylene diphosphonate following therapeutic radiation for vertebral metastases. J Nucl Med 1989; 30:1113–1114.
Anninga JK, Hoefnagel CA, Dewit L. The role of quantitative 99mTc-DTPA renography and 99mTc-DMSA scintigraphy in detection and follow up of radiation nephropathy. In: Schmidt HAE, Chambron J, eds. Nuclear medicine. Quantitative analysis in imaging and function. Stuttgart: Schattauer; 1990:417–419.
Dewit L, Anninga JK, Hoefnagel CA, Nooijen WJ. Radiation injury in the human kidney: a prospective analysis using specific scintigraphic and biochemical endpoints. Int J Radiat Oncol Biol Phys1990; 19:977–983.
Verheij M, Dewit LGH, Valdés Olmos RA, Hoefnagel CA, Arisz L. Captopril Tc-99m-DTPA renography in patients with radiation-induced renovascular hypertension. In: Schmidt HAE, Höfer R, eds. Nuclear medicine in research and practice. Stuttgart New York: Schattauer; 1992: 545–548.
Groshar D, Embon OM, Frenkel A, Front D. Renal function and technetium-99m-dimercaptosuccinic acid uptake in single kidneys: the value of in vivo SPECT quantitation. J Nucl Med 1991; 32:766–768.
Ginsberg SJ, Comis RL. The pulmonary toxicity of antineoplastic agents. Semin Oncol 1982; 9:34–51.
Comis RL. Bleomycin pulmonary toxicity: current status and future directions. Semin Oncol 1992; 19:64–70.
O'Driscoll BR, Hasleton PS, Taylor PM, Poulter LW, Rao Gattamaneni H, Woodcock AA. Active lung fibrosis up to 17 years after chemotherapy with carmustine (BCNU) in childhood. N Engl J Med 1990; 323:378–382.
Richman SD, Levenson SM, Bunn PA, Flinn GS, Johnston GS, DeVita VT. 67Ga accumulation in pulmonary lesions associated with bleomycin toxicity. Cancer 1975; 36:1966–1972.
Sostman HD, Putman CE, Gamsu G. Diagnosis of chemotherapy lung. Am J Roentgenol 1981, 136:33–40.
MacMahon H, Bekerman C. The diagnostic significance of gallium lung uptake in patients with normal chest radiographs. Radiology 1978; 127:189–193.
O'Doherty Mj, Van de Pette JE, Page CJ, Bateman NT, Singh AK, Croft DN. Pulmonary permeability in hematologic malignancies. Effects of the disease and cytotoxic agents. Cancer 1986; 58:1286–1288.
Ugur O, Caner B, Balbay MD, Ozen HA, Remzi D, Ulutuncel N, Bekdik C. Bleomycin lung toxicity detected by technetium-99m diethylene triamine penta-acetic acid aerosol scintigraphy. Eur J Nucl Med 1993; 20:114–118.
Van der Schoot JB, Green AS, Jong J. Gallium-67 scintigraphy in lung diseases. Thorax 1972; 27:543–546.
Kataoka M, Kawamura M, Itch H, Hamamoto K. Ga-67 citrate scintigraphy for the early detection of radiation pneumonitis. Clin Nucl Med 1992; 17:27–31.
Rubin P, Finkelstein J, Shapiro D. Molecular biology mechanisms in the radiation induction of pulmonary injury syndromes: interrelationship between the alveolar macrophage and the septal fibroblast. Int J Radiat Oncol Biol Phys 1992; 24:93–101.
Shinoara S, Arikawa K. Radioisotopic assessment on development of radiation pneumonitis and fibrosis. Autralas Radiol 1972; 16:363–366.
Alth G, Ogris E. Lungenszintigraphische Langzeitbeobachtungen bei postoperativer Bestrahlung der Mammaregion. Strahlentherapie 1975; 149:41–48.
Prato FS, Kurdyak R, Salbil EA, Rider WD, Aspin N. Physiological and radiographic assessment during the development of pulmonary radiation fibrosis. Radiology 1977; 122:389–397.
Groth S, Zaric A, Sorensen PB, Larsen J, Sorensen PG, Bossing N. Regional lung function impairment following post-operative radiotherapy for breast cancer using direct or tangential field techniques. Br J Radiol 1986; 59:445–451.
Suga K, Ariyoshi I, Nishigauchi, Yoshimizu T, Nakanishi T, Utsumi H, Yamada N. Altered regional clearance of 99m-TcDTPA in radiation pneumonitis. Nucl Med Commun 1992; 13:357–364.
Van Zandwijk N, Zwijnenburg A, Hoefnagel CA, Marcuse HR. N-isopropyl-p[123I]iodoamphetamine, a new agent for lung imaging studies. Thorax 1986; 41:801–803.
Zwijnenburg A, Lebesque J, Roos CM, Jansen HM, van der Schoot JB, Marcuse HR. Early detection of irradiation-induced lung damage using ventilation-perfusion single photon emission computed tomography. In: Zwijnenburg A, ed. Ventilation-perfusion studies using SPECT. Amsterdam: Thesis; 1989:43–53.
Boersma LJ, Damen EMF, de Boer, Hoefnagel CA, Valdés Olmos RA, van Zandwijk N, Lebesque JV. Three-dimensional superimposition of SPECT and CT data to quantify radiation induced ventilation and perfusion changes of the lung, as a function of the locally delivered dose. In: Schmidt HAE, Höfer R, eds. Nuclear medicine in research and practice. Stuttgart New York: Schattauer; 1992:44–47.
Balogh JM, Sutherland SE. Osteoradionecrosis of the mandible: a review. J Otolaryngol 1989; 18:245–250.
Korsten MA, Rosman AS, Fishbein S, Shlein RD, Goldberg HE, Biener A. Chronic xerostomia increases esophageal acid exposure and is associated with esophageal injury. Am J Med 1991; 90:701–706.
Chang VST, Downs J, Herbert D, Aramany M. The function of the parotid gland following radiation therapy for head and neck cancer. Int J Radiat Oncol Biol Phys 1981; 7:253–258.
Makkonen TA, Nordman E. Estimation of long term salivary gland damage induced by radiotherapy. Acta Oncol 1987; 26:307–312.
Awad HK. Early reacting tissues: the digestive tract. In: Awad HK, ed. Radiation oncology. Dordrecht: Kluwer Academic; 1991:291–322.
Awad HK. The influence of X irradiation on the iodide-trapping mechanism of the human parotid gland. Br J Radiol 1959; 32:259–262.
Tsujii H. Quantitative dose-response analysis of salivary function following radiotherapy using sequential RI-sialography. Int J Radiat Oncol Biol Phys 1985; 11:1603–1612.
Albrecht HH, Creutzig H. Functional scintigraphy of the salivary gland after high dose radio-iodine therapy. Fortschr Röntgenstr 1976; 125:546–551.
Reiners C, Eilles C, Eichner R, Spiegel W, Börner W. Speicheldrüsenfunktionsszintigraphie zur Verlaufskontrolle bei der Therapie des Schilddrüsen-Karzinoms mit Radiojod. Der Nuklearmediziner 1980; 3:281–286.
Delprat CC, Hoefnagel CA, Marcuse HR (1983) The influence of 131I therapy in thyroid cancer on the function of salivary glands. Acta Endocrinol 1983; Suppl 252:73–74.
Beckerman C, Hoffer PB. Salivary gland uptake of 67Ga-citrate following radiation therapy. J Nucl Med 1976; 17:685–687.
Kashima HK, McKusick KA, Malmud LS, Wagner HN Jr. Gallium-67 scanning in patients with head and neck cancer. Laryngoscope 1974; 84:1078–1089.
Lentle BC, Jackson FI, McGowan DG. Localization of gallium-67 citrate in salivary glands following radiation therapy. J Can Assoc Radiol 1976; 27:89–91.
Cox PH. Abnormalities in skeletal uptake of 99mTc polyphosphate complexes in areas of bone associated with tissues which have been subjected to radiation therapy. Br J Radiol 1974; 47:851–856.
Yankelevitz DF, Henschke CI, Knapp PH, Nisce L, Fi Y, Cahill P. Effect of radiation therapy on thoracic and lumbar bone marrow: evalution with MR imaging. Am J Roentgenol 1991; 157:87–92.
Reske SN, Karstens JH, Gloekner W, Steinsträsser A, Schwarz A, Ammon J, Buell U. Radioimmunoimaging for diagnosis of bone marrow involvement in breast cancer and malignant lymphoma. Lancet 1989; II:299–301.
Sacks EL, Goris ML, Glatstein E, Gilbert E, Kaplan HS. Bone marrow regeneration following large field radiation. Influence of volume, age, dose, and time. Cancer 1978; 42:1057–1065
Rubin P, Constine LS, Nelson DF. Late effects of cancer treatment: radiation and drug toxicity. In: Perez CA, Brady LW, eds. Principles andpractice of radiation oncology. Philadelphia: Lippincott; 1992:124–161.
Jacobson M, Albrektsson T, Turesson I. Dynamics of irradiation injury to bone tissue. Acta Radial Oncol 1985; 24:343–350.
King MA, Casarett GW, Weber DA. A study of irradiated bone: I. Histopathologic and physiologic changes. J Nucl Med 1979; 20:1142–1149.
Israel O, Gorenberg M, Frenkel A, Kuten A, Jerushalmi J, Kolodny GM, Front D. Local and systemic effects of radiation on bone metabolism measured by quantitative SPECT. J Nucl Med 1992; 33:1774–1782.
Charkes ND, Silverman C. Does radiotherapy affect regional bone formation? J Nucl Med 1992; 33:1780–1782.
Hubbard SM, Longo DL. Treatment-related morbidity in patients with lymphoma. Curr Opin Oncol 1991; 3:852–862.
Donaldson SS. Effects of irradiation on skeletal growth and development. In: D'Angio GJD, ed. Late effects of treatment for childhood cancer. New York: Wiley-Liss; 1992:63–70.
Silber JH, Littman PS, Meadows AT. Stature loss following skeletal irradiation for childhood cancer. J Clin Oncol 1990; 8:304–312.
Hortobagyi GN, Libshitz HI, Seabold JE. Osseous metastases of breast cancer. Clinical, biochemical, radiographic and scintigraphic evaluation of response to therapy. Cancer 1984; 55:577–582.
Rossleigh MA, Lovegrove FTA, Reynolds PM, Byrne MJ, Whitney BP. The assessment of response to therapy of bone metastases in breast cancer. Aust NZ J Med 1984; 14:19–22.
Sundkvist GMG, Ahlgren L, Lilja B, Mattson S, Abrahamsson PA, Wadström LB. Repeated quantitative bone scintigraphy in patients with prostatic carcinoma treated with orchiectomy. Eur J Nucl Med 1988; 14:203–206.
Coleman RE, Mashiter G, Whitaker KB, Moss DW, Rubens RD, Fogelman I. Bone scan flare predicts successful systemic therapy for bone metastases. J Nucl Med 1988; 29:1354–1359.
Stokkel MPM, Valdés Olmos RA, Hoefnagel CA, Richel DJ. Tumor and therapy associated abnormal changes in bone scintigraphy: old and new phenomena. Clin Nucl Med 1993 (in press).
Symann M. Hematopoietic growth factors as supportive therapy for cancer- and chemotherapy-induced conditions. Curr Opin Oncol 1991; 3:648–655.
Lieschke GJ, Burgess AW. Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. N Engl J Med 1992; 327:28–35.
Reske SN. Recent advances in bone marrow scanning. Eur J Nucl Med 1991; 18:203–221.
Ihde DC, DeVita VT. Osteonecrosis of the femoral head in patients with lymphoma treated with intermittent combination chemotherapy (including corticosteroids). Cancer 1975; 36:1585–1588.
Timothy AR, Tucker AK. Osteonecrosis in Hodgkin's disease. Br J Radiol 1978; 51:328–332.
Thorne JC, Evans WK, Alison RE, Fournasier V. Avascular necrosis of bone complicating treatment of malignant lymphoma. Am J Med 1981; 71:751–757.
Mould JJ, Adam NM. The problem of avascular necrosis of bone in patients treated for Hodgkin's disease. Clin Radiol 1983; 34:231–236.
Harper PG, Trask C, Souhami RL. Avascular necrosis of bone caused by combination chemotherapy without corticosteroids. Br Med J 1984; 288:267–268.
Mankin HJ. Nontraumatic necrosis of bone (osteonecrosis). N Engl J Med 1992; 326:1473–1478.
Sheline GE, Wara WM, Smith V. Therapeutic irradiation and brain injury. Int J Radiat Oncol Biol Phys 1980; 6:1215–1228.
Silber JH, Radcliffe J, Peckham V, Perilongo G, Kishnani P, Fridman M, Goldwein JW, Meadows AT. Whole-brain irradiation and decline in intelligence: the influence of dose and age on IQ score. J Clin Oncol 1992; 10:1390–1396.
Kaplan WD, Takvorian T, Morris JH, Rumbaugh CL, Connolly BT, Atkins HL. Thallium-201 brain tumor imaging: a comparative study with pathologic correlation. J Nucl Med 1987; 28:47–52.
Stafford-Schuk K, Mountz JM, McKeever P, Taren J, Beierwaltes WH. Thallium-201 imaging and estimation of residual high grade astrocytoma. J Nucl Med Tech 1987; 15:109–114.
Black KL, Hawkins RA, Kim KT. 201Tl (SPECT): a quantitative technique to distinguish low grade from malignant brain tumours. J Neurosurg 1989; 71:342–346.
Kim KT, Black KL, Marciano D, Mazziota JC, Guze BH, Grafton S, Hawkins RA, Becker DP. 210Tl SPECT imaging of brain tumors: methods and results. J Nucl Med 1990; 31:965–969.
O'Tuama LA, Janicek MJ, Barnes PD, Scott RM, Black PM, Sallan SE, Tarbell NJ, Kupsky WJ, Wagenaar D, Ulanski JS, Treves ST. 201Tl/99mTc-HMPAO SPECT imaging of treated childhood brain tumors. Pediatr Neural 1991; 7:249–257.
Schwartz RB, Carvahlo PA, Alexander E, Loeffler JS, Folkerth R, Holman BL. Radiation necrosis vs high-grade recurrent glioma: differentiation by using dual-isotope SPECt with 201Tl and 99mTc-HMPAO. AJNR 1991; 12:1187–1192.
Ell PJ. PET reflections. Eur J Nucl Med 1990; 17:1–2.
Hoh CK, Khanna S, Harris GC, Chen TT, Black KL, Becker DP, Maddahi J, Mazziota JC, Marciano DM, Hawkins RA. Evaluation of brain tumor recurrence with T1–201 SPECT studies: correlation with FDG PET and histological results. J Nucl Med 1992; 33:867.
Macapinlac H, Finlay J, Caluser C, Yeh S, Scott A, DeLaPaz R, Lindsley K, Finn W, Muraki A, Larson S, Abdel-Dayem H. Comparison of Tl-201 SPELT and F-18FDG imaging with MRI (Gd-DTPA) in the evaluation of recurrent supratentorial and infratentorial tumors [abstract]. J Nucl Med 1992; 33:867–868.
Biersack HJ, Coenen HH, Stöcklin G, Reichmann K, Bockisch A, Oehr P, Kashab M, Rollman O. Imaging of brain tumors with l-3-[123I]Iodo-alpha-methyl tyrosine and SPELT. J Nucl Med 1989; 30:110–112.
Guth-Tougelidis B, Müller SP, Mehdorn HM, Machulla HJ, Knust EJ, Reinders C. I-123-alpha-methyl-tyrosine in brain tumor recurrences [abstract]. J Nucl Med 1990; 31:766.
Macapinlac H, Scott A, Caluser C, Finlay J, DeLaPaz R, Lindsley K, Al-Mohannadi A, Macalintal S, Kalagian H, Yeh S, Larson S, Abdel-Dayem H. Comparison of T1–201 and Tc 99m-2-methoxy isobutyl isonitrile (MIBI) with MRI in the evaluation of recurrent brain tumors [abstract]. J Nucl Med 1992; 33:867.
Holman BL, Zimmerman RE, Johnson KA, Carvalho PA, Schwartz RB, Loeffler JS, Alexander E, Pelizzari CA, Chen GTY. Computer-assisted superimposition of magnetic resonance and high-resolution technetium-99m-HMPAO and thallium-201 SPELT images of the brain. J Nucl Med 1991; 32:1478–1484.
Powis GP, Hacker MP. Toxicity of biological response modifiers. In: Powis G, Hacker MP, eds. The toxicity of anticancer drugs. New York: Pergamon Press; 1991:198–215.
Podoloff DA, Kim EE, Haynie TP. SPELT in the evaluation of cancer patients: not quo vadis; rather, ibi fere summus. Radiology 1992; 183:305–317.
Di Chiro G, Oldfield E, Wright DC, DeMichele D, Katz DA, Patronas NJ, Doppman JL, Larson SM, Ito M, Kufta CV. Cerebral necrosis after radiotherapy and/or intracranial chemotherapy for brain tumors: PET and neuropathologic studies. Am J Roentgenol 1988; 150:189–197.
Valk PE, Budinger TF, Levin VA, Silver P, Gutin PH, Doyle WK. PET of malignant cerebral tumors after interstitial brachytherapy. Demonstration of metabolic activity and correlation with clinical outcome. J Neurosurg 1988; 69:830–838.
Glantz MJ, Hoffman JM, Coleman E, Friedman AH, Hanson MW, Burger PC, Herndon JE, Meisler WJ, Schold SC. Identification of early recurrence of primary central nervous system tumors by [18F]fluorodeoxyglucose positron emmission tomography. Ann Neurol 1991; 29:347–355.
Francavilla TL, Miletich RS, DeMichele D, Patronas NJ, Oldfield EH, Weintraub BD, DiChiro G. Positron emission tomography of pituitary macroadenomas: hormone production and effects of therapies. Neurosurgery 1991; 28:826–833.
Hoffman JM, Hanson MW, Friedman HS, Hockenberg BM, Oakes WJ, Halperin EC, Coleman RE. FDG-PET in pediatric posterior fossa brain tumors. J Comput Assist Tomogr 1992; 16:62–68.
Griebel M, Friedman HS, Halperin EC, Wiener MD, Marks L, Oakes WJ, Hoffman JM, DeLong R, Schold SC, Hockenberger B, Freeman CR, Kun L. Reversible neurotoxicity hyperfractionated radiation therapy of brain stem glioma. Med Pediatr Oncol 1991; 19:182–186.
Coleman RE, Hoffman JM, Hanson MW, Sostman HD, Schold SC. Clinical application of PET for the evaluation of brain tumors. J Nucl Med 1991; 32:616–622.
Kim EE, Chung S, Haynie TP, Podoloff DA, Tilbury RS, Yang DJ, Yung WKA, Moser RP, Ajani JA. Differentiation of residual or recurrent tumours from post-treatment changes with F-18 FDG PET. RadioGraphics 1992; 12:269–279.
Strauss LG, Conti PS. The applications of PET in clinical oncology. J Nucl Med 1991; 32:623–648.
Ito K, Kato T, Tadokoro M, Ishiguchi T, Oshima M, Ishigaki T, Sakuma S. Recurrent rectal cancer and scar: differentiation with PET and MR imaging. Radiology 1992; 182:549–552.
Beaney RP, Gibbs JSR, Brooks DJ, McKenzie CG, Joplin GF, Jones T. Absence of irradiation induced ischaemic temporal lobe damage in patients with pituitary tumours. J Neurooncol 1987; 5:129–137.
Valk PE, Dillon WP. Radiation injury of the brain. Am J Roentgenol 1991; 156:689–706.
Ott RJ, Brada M, Flower MA, Babich JW, Cherry SR, Deehan BJ. Measurements of blood-brain barrier permeability in patients undergoing radiotherapy and chemotherapy for primary cerebral lymphoma.Eur J Cancer 1991; 27:1356–1361.
Wagner HN. Positron emission tomography at the turn of the century: a perspective. Semin Nucl Med 1992; 22:285–288.
Mélon P, Schwaiger M. Imaging of metabolism and autonomic innervation of the heart by positron emission tomography. Eur J Nucl Med 1992; 19:453–464.
Miller RF, O'Doherty MI. Pulmonary nuclear medicine. Eur J Nucl Med 1992; 19:355–368.
Hawkins RA, Hoh C, Glapsy J, Choi Y, Dahlbom M, Rege S, Messa C, Nietszche E, Hoffman S, Seeger L, Maddahi J, Phelps ME. The role of positron emission tomography in on cology and other whole-body applications. Semin Nucl Med 1992; 22:268–284.
Powis GP.Toxicity of anticancer drugs to humans: a unique opportunity to study human toxicology. In: Powis M, Hacker MP, eds. The toxicity of anticancer drugs. New York: Pergamon Press; 1991:1–8.
Woodhouse CRJ. Urinary tract injuries. In: Galland RB, Specer J, eds. Radiation enteritis. London: Edward Arnold; 1990:155–175.
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Valdes Olmos, R.A., Hoefnagel, C.A. & van der Schoot, J.B. Nuclear medicine in the monitoring of organ function and the detection of injury related to cancer therapy. Eur J Nucl Med 20, 515–546 (1993). https://doi.org/10.1007/BF00175165
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DOI: https://doi.org/10.1007/BF00175165