ЕФЕКТИ ЕНТЕРОСОРБЦІЇ ТА ФІЛГРАСТИМУ ПРИ СУБХРОНІЧНІЙ ДОКСОРУБІЦИНОВІЙ ТОКСИЧНОСТІ
DOI:
https://doi.org/10.11603/1811-2471.2019.v.i3.10510Ключові слова:
ентеросорбція, доксорубіцин, філграстим, щуриАнотація
РЕЗЮМЕ. Побічні реакції при проведенні протипухлинної хіміотерапії часто стають причиною переривання лікування.
Мета роботи – дослідити вплив ентеросорбента С2 та препарату гранулоцитарного колонієстимулювального фактора (Г-КСФ) на гематологічні параметри та біохімічні показники функціонування серця, нирок та печінки у щурів на моделі субхронічної доксорубіцинової токсичності.
Матеріал і методи. Субхронічну токсичність моделювали внутрішньочеревним введенням доксорубіцину (DOX) 1 раз на тиждень у дозі 5 мг/кг маси чотирикратно. Для корекції використовували вуглецевий гранульований ентеросорбент С2 та філграстим. На 29 добу після першої ін’єкції DOX вивчали основні гематологічні параметри, активність ферментів КФК-МВ, АлАТ, АсАТ, лужної фосфатази, рівні загального білка, церулоплазміну, креатиніну та сечовини, концентрацію МСМ1 та МСМ2.
Результати. На тлі субхронічної доксорубіцинової токсичності погіршуються гематологічні параметри досліджуваних щурів, порушуються білково-синтетична функція печінки та показники функціонування нирок, про що свідчить зростання рівнів сечовини та креатиніну на 26,2 % та 19,2 %. Усі ці процеси супроводжуються вираженим зростанням маркерів ендогенної інтоксикації: МСМ1 в 2 рази, МСМ2 – в 1,75 раза. На кардіотоксичність DOX вказує достовірне зростання активності АсАТ та КФК-МВ – маркерів пошкодження серцевого м’яза (на 75,1 та 64,2 % відповідно).
Застосування ентеросорбції зменшує побічні ефекти доксорубіцину, що проявляється покращенням гематологічних параметрів, функції нирок, зниженням показників ендогенної інтоксикації. Однак, саме комбінація ентеросорбента С2 з препаратом Г-КСФ демонструє більш суттєве покращення досліджуваних показників, особливо маркерів пошкодження міокарда: знижувалася активність ферментів АсАТ на 26,3 %, КФК-МВ – на 17,0 %; АлАТ – на 20,4 %.
Висновки. Отримані нами результати слугують основою для подальшого глибшого дослідження можливостей застосування ентеросорбції та Г-КСФ для зменшення побічних реакцій антрациклінових антибіотиків та їх імплементації в клінічну практику.
Посилання
Bondarenko, I.M., Zavizion, V.F., Artemenko, M.V., & Zavizion, M.B. (2012). Mozhlyvosti udoskonalennia terapii suprovodu pry tsytostatychnomu likuvanni pukhlyn [Possibilities of improving the therapy of support in the cytostatic treatment of tumors]. Medychni Perspektyvy – Medical Perspectives, (4), 48-53 [in Ukrainian].
Bruslov, K.M. (2013). Zastosuvannia preparatu tevahrastym u ditei z hostrymy leikemiiamy [Use of the drug tevagrastim in children with acute leukemia]. Onkolohiia – Oncology, 15 (1), 51-54 [in Ukrainian].
Baranova, O.Yu., & Volkova, M.A. (2001). Vozmozhnosti sovremennoy terapii ostrykh nelimfoblastnykh leykozov vzroslykh [Possibilities of modern therapy for acute non-lymphoblastic leukemia in adults]. Russkiy meditsinskiy zhurnal. Onkologiya – Russian Medical Journal. Oncology, 9 (22), 999-1003 [in Russian].
Lyman, G.H., Abella, E., & Pettengell, R. (2014). Risk factors for febrile neutropenia among patients with cancer receiving chemotherapy: A systematic review. Critical Reviews in Oncology/Hematology, 90 (3), 190-199. Retrieved from: https://doi.org/10.1016/j.critrevonc.2013.12.006
Liu, W., Zhang, C.-C., & Li, K. (2013, June). Prognostic value of chemotherapy-induced leukopenia in small-cell lung cancer. Cancer Biology & Medicine. Chinese Anti-Cancer Association. Retrieved from: https://doi.org/10.7497/j.issn.2095-3941.2013.02.005
Parkhill, A.L. (2013). Oral mucositis and stomatitis associated with conventional and targeted anticancer therapy. Journal of Pharmacovigilance, 01 (03). Retrieved from: https://doi.org/10.4172/2329-6887.1000112
Al-Ansari, S., Zecha, J.A.E.M., Barasch, A., de Lange, J., Rozema, F.R., & Raber-Durlacher, J.E. (2015). Oral mucositis induced by anticancer therapies. Current Oral Health Reports, 2 (4), 202-211. Retrieved from: https://doi.org/10.1007/s40496-015-0069-4
Stensvold, E., Magelssen, H., & Oskam, I.C. (2011). Fertility-preserving measures for girls and young women with cancer. Tidsskrift for Den Norske Lægeforening: Tidsskrift for Praktisk Medicin, Ny Række, 131 (15), 1429-1432. Retrieved from: https://doi.org/10.4045/tidsskr.11.0126
Diamond, O.M., Turgeman, O., & Blumenfeld, Z. (2015). Minimizing the doxorubicin- Induced gonadotoxicity by sphingosine-1- phosphate analogue FTY720. Am. J. Clin. Exp. Obstet. Gynecol., 2 (1), 24-33.
Keros, V., Hultenby, K., Borgstrom, B., Fridstrom, M., Jahnukainen, K., & Hovatta, O. (2007). Methods of cryopreservation of testicular tissue with viable spermatogonia in pre-pubertal boys undergoing gonadotoxic cancer treatment. Human Reproduction, 22 (5), 1384-1395. Retrieved from: https://doi.org/10.1093/humrep/del508
Kostakou, P.M., Kouris, N.T., Kostopoulos, V.S., Damaskos, D.S., & Olympios, C.D. (2018). Cardio-oncology: a new and developing sector of research and therapy in the field of cardiology. Heart Failure Reviews, 1-10. Retrieved from: https://doi.org/10.1007/s10741-018-9731-y
Denduluri, N., Patt, D.A., Wang, Y., Bhor, M., Li, X., Favret, A.M., … Lyman, G.H. (2015). Dose delays, dose reductions, and relative dose intensity in patients with cancer who received adjuvant or neoadjuvant chemotherapy in community oncology practices. JNCCN Journal of the National Comprehensive Cancer Network, 13 (11), 1383-1393. Retrieved from: https://doi.org/10.6004/jnccn.2015.0166
Minotti, Giorgio, Menna, P., Salvatorelli, E., Cairo, G., & Gianni, L. (2004). Anthracyclines: Molecular Advances and Pharmacologic Developments in Antitumor Activity and Cardiotoxicity. Pharmacological Reviews, 56 (2), 185-229. Retrieved from: https://doi.org/10.1124/pr.56.2.6
van Dalen, E.C., Raphaël, M.F., Caron, H.N., & Kremer, L.C. (2014). Treatment including anthracyclines versus treatment not including anthracyclines for childhood cancer. Cochrane Database of Systematic Reviews, (9), CD006647. Retrieved from: https://doi.org/10.1002/ 14651858.CD006647.pub4
Weiss, R.B. (1992). The anthracyclines: will we ever find a better doxorubicin? Seminars in Oncology, 19 (6), 670-686. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/1462166
Geisberg, C., & Sawyer, D.B. (2010). Mechanisms of anthracycline aardiotoxicity and strategies to decrease cardiac damage. Current Hypertension Reports, 12 (6), 404. Retrieved from: https://doi.org/10.1007/S11906-010-0146-Y
Mitry, M.A., & Edwards, J.G. (2016). Doxorubicin induced heart failure: Phenotype and molecular mechanisms. International Journal of Cardiology. Heart & Vasculature, 10, 17-24. Retrieved from: https://doi.org/10.1016/j.ijcha.2015.11.004
Licata, S., Saponiero, A., Mordente, A., & Minotti, G. (2000). Doxorubicin metabolism and toxicity in human myocardium: Role of cytoplasmic deglycosidation and carbonyl reduction. Chemical Research in Toxicology, 13 (5), 414-420. Retrieved from: https://doi.org/10.1021/tx000013q
Volkova, M., & Russell, R. (2011). Anthracycline cardiotoxicity: prevalence, pathogenesis and treatment. Current Cardiology Reviews, 7 (4), 214-220. Retrieved from: https://doi.org/10.2174/157340311799960645
Thorn, C.F., Oshiro, C., Marsh, S., Hernandez-Boussard, T., McLeod, H., Klein, T.E., & Altman, R.B. (2011). Doxorubicin pathways: pharmacodynamics and adverse effects. Pharmacogenetics and Genomics, 21 (7), 440-446. Retrieved from: https://doi.org/10.1097/FPC.0b013e32833ffb56
Chatterjee, K., Zhang, J., Honbo, N., & Karliner, J.S. (2010). Doxorubicin cardiomyopathy. Cardiology, 115 (2), 155-162. Retrieved from: https://doi.org/10.1159/000265166
Hrdina, R., Gersl, V., Klimtová, I., Simůnek, T., Machácková, J., & Adamcová, M. (2000). Anthracycline-induced cardiotoxicity. Acta Medica (Hradec Kralove), 43 (3), 75-82. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/11089274
Wallace, K.B., Hausner, E., Herman, E., Holt, G.D., Macgregor, J.T., Metz, A. L., … York, M.J. (2004). Serum troponins as biomarkers of drug-induced cardiac toxicity. Toxicologic Pathology, 32 (1), 106-121. Retrieved from: https://doi.org/10.1080/01926230490261302
Ky, B., & Carver, J.R. (2011). Biomarker approach to the detection and cardioprotective strategies during anthracycline chemotherapy. Heart Failure Clinics, 7 (3), 323-331. Retrieved from: https://doi.org/10.1016/j.hfc.2011.03.002
Tian, S., Hirshfield, K.M., Jabbour, S.K., Toppmeyer, D., Haffty, B.G., Khan, A.J., & Goyal, S. (2014). Serum biomarkers for the detection of cardiac toxicity after chemotherapy and radiation therapy in breast cancer patients. Frontiers in Oncology, 4, 277. Retrieved from: https://doi.org/10.3389/fonc.2014.00277
Minotti, G, Cairo, G., & Monti, E. (1999). Role of iron in anthracycline cardiotoxicity: new tunes for an old song? The FASEB Journal, 13 (2), 199-212. Retrieved from: https://doi.org/10.1096/fasebj.13.2.199
Matyash, M.G., Kravchuk, T.L., Vysotskaya, V.V., Chernov, V.I., & Goldberg, V.E. (2008). Indutsirovannaya antratsiklinami kardiotoksichnost: mekhanizmy razvitiya i klinicheskiye proyavleniya [Cardiotoxicity induced by anthracyclines: developmental mechanisms and clinical manifestations]. Sibirskiy onkologicheskiy zhurnal – Siberian Oncological Journal, 30 (6), 66-75. Retrieved from: https://elibrary.ru/item.asp?id=12515758 [in Russian].
Krischke, M., Hempel, G., Völler, S., André, N., D’Incalci, M., Bisogno, G., … Boos, J. (2016). Pharmacokinetic and pharmacodynamic study of doxorubicin in children with cancer: results of a “European Pediatric Oncology off-patents Medicines Consortium” trial. Cancer Chemotherapy and Pharmacology, 78 (6), 1175-1184. Retrieved from: https://doi.org/10.1007/s00280-016-3174-8
Creutzig, U., Diekamp, S., Zimmermann, M., & Reinhardt, D. (2007). Longitudinal evaluation of early and late anthracycline cardiotoxicity in children with AML. Pediatric Blood & Cancer, 48 (7), 651-662. Retrieved from: https://doi.org/10.1002/pbc.21105
Zambetti, M., Moliterni, A., Materazzo, C., Stefanelli, M., Cipriani, S., Valagussa, P., … Gianni, L. (2001). Long-term cardiac sequelae in operable breast cancer patients given adjuvant chemotherapy with or without doxorubicin and breast irradiation. Journal of Clinical Oncology, 19 (1), 37-43. Retrieved from: https://doi.org/10.1200/JCO.2001.19.1.37
Jain, D., Russell, R.R., Schwartz, R.G., Panjrath, G.S., & Aronow, W. (2017). Cardiac complications of cancer therapy: Pathophysiology, identification, prevention, treatment, and future directions. Current Cardiology Reports, 19 (5), 36. Retrieved from: https://doi.org/10.1007/s11886-017-0846-x
Oleshchuk, A.M., Nikolaeva, V.V., Klishch, I.N., Shevchuk, O.O., Maslenny, V.N. & Yastremskaya, S.O. (2009). Izucheniye effektivnosti ispolzovaniya enterosgelya v lekarstvennoy forme pasty dlya peroralnogo primeneniya pri yatrogennoy intoksikatsii protivotuberkuleznymi sredstvami [The study of the effectiveness of the use of enterosgel in the dosage form of an oral paste for iatrogenic intoxication with anti-TB drugs]. Ukrainskyi zhurnal klinichnoi ta laboratornoi Medytsyny – Ukrainian Journal of Clinical and Laboratory Medicine, 4 (4), 95-99 [in Russian].
Posokhova, K.A., Shevchuk, O.O., Prysliak, A.M., & Mosiechuk, I.L. (2010). Efektyvnist hlutarhinu ta enteros heliu pry urazhenni pechinky, vyklykanomu protytuberkuloznymy preparatamy [Efficacy of glutargin and enterosgel in liver damage caused by anti-tuberculosis drugs]. Medychna khimiia – Medical Chemistry, 12 (3), 61-65 [in Ukrainian].
Posokhova, K.A., Nikolaev, V.G., Shevchuk, O.O., Oleshchuk, O.M., Klishch, I.M., & Nikolaiev V.V. (2010). Vyvchennia mozhlyvostei korektsii hepatotoksychnoi dii antyretrovirusnykh zasobiv za dopomohoiu enterosorbentu enteros hel – pasta dlia peroralnoho zastosuvannia [Study of possibilities of correction of hepatotoxic action of antiretroviral agents by means of enterosorbent enterosgel – paste for oral administration]. Aktualni problemy suchasnoi medytsyny. Visnyk ukrainskoi medychnoi stomatolohichnoi akademii – Topical Problems of Modern Medicine. Bulletin of the Ukrainian Medical Dental Academy, 10 (4), 121-125 [in Ukrainian].
Posokhova, K.A., Nikolaev, V.H., Shevchuk, O.O., Oleshchuk, O.M., Klishch, I.M., Datsko, T.V., & Nikolaiev, V.V. (2010). Vplyv enteros·heliu na stan pechinky pry zastosuvanni antyretrovirusnykh preparativ [Effect of enterosgel on liver condition when using antiretroviral drugs]. Visnyk Morfolohii – Bulletin of Morphology, 16 (3), 548-551 [in Ukrainian].
Posokhova, K.A., & Shevchuk, O.O. (2010). Korektsiia hepatotoksychnoi dii antyretrovirusnykh zasobiv za dopomohoiu hlutarhinu ta enteros heliu [Correction of hepatotoxic action of antiretroviral agents with glutargin and enterosgel]. Ukrainskyi zhurnal klinichnoi ta laboratornoi medytsyny – Ukrainian Journal of Clinical and Laboratory Medicine, 5 (4), 130-133 [in Ukrainian].
Nikolaiev, V.H., Klishch, I.M., Zhulkevych, I.V., Oleshchuk, O.M., Nikolaiev, V.V., & Shevchuk, O.O. (2009). Zastosuvannia preparatu enteros hel dlia profilaktyky oksydatyvnoho stresu pry hostrii krovovtrati [The use of the drug enterosgel for the prevention of oxidative stress in acute blood loss]. Visnyk Naukovykh Doslidzhen – Bulletin of Scientific Research, (1), 72-74 [in Ukrainian].
Greek, O.R., Mishenina, S.V., & Pupyshev, A.B. (2002). Protektivnoye deystviye enterosgelya na lizosomy pecheni krys pri vvedenii kompleksa tsitostaticheskikh preparatov [The protective effect of enterosgel on rat liver lysosomes with the introduction of a complex of cytostatic drugs]. Byulleten eksperimentalnoy biologii i meditsiny – Bulletin of Experimental Biology and Medicine, 134 (10), 413-417 [in Russian].
Borodin, Yu.I., Lyubarskyy, M.S., Narov, Yu.E., Morozov, V.V., & Fursov, S.A. (2004). Korrektsiya endotoksikoza pri nekotorykh onkologicheskikh zabolevaniyakh [Correction of endotoxemia in some oncological diseases]. Byulleten SO RAMN – Bulletin SB RAMS, 112 (2), 7-12 [in Russian].
Bonatskaya, L.V., Plotnikov, V.M., & Nikolaev, V.G. (1989). Snizheniye gematotoksichnosti protivoopukholevykh preparatov pri enterosorbtsii [Decreased hematotoxicity of antitumor drugs during enterosorption]. Eksperimentalnaya Onkologiya – Experimental Oncology, 23 (11), 71-73 [in Russian].
Bonatskaya, L.V., & Zinevich, A.K. (1982). Enterosorbtsiya kak metod profilaktiki i lecheniya nekotorykh oslozhneniy konservativnoy terapii opukholevoy bolezni [Enterosorption as a method of prevention and treatment of some complications of conservative therapy of tumor disease]. Insorbtsionnyye metody detoksikatsii i immunokorrektsii v meditsine – Insorption Methods of Detoxification and Immunocorrection in Medicine [in Russian].
Ponomariova, O.V., Pivniuk, V.M., Nosko, M.M., Sakhno, L.O., Dekhtiar, T.V., Nikolaiev, V.H., & Chekhun, V.F. (2008). Profilaktyka za dopomohoiu vuhletsevoho enterosorbentu hostroi ta vidstrochenoi emetohennoi toksychnosti khimioterapevtychnoho likuvannia onkolohichnykh khvorykh [Prevention with the help of carbon enterosorbent acute and delayed emetogenic toxicity of chemotherapeutic treatment of cancer patients]. Onkolohiia – Oncology, 10 (3), 370–373. Retrieved from: http://dspace.nbuv.gov.ua/handle/123456789/11944 [in Ukrainian].
Nikolaev, V.G., Andreychin, M.A., Bardakhivskaya, K.I., Sakhno, L.A., Kopcha, V.S., Yushko, L.A., … Shevchuk, O.O. (2013). Practical recommendations on the use of granulated carbon enterosorbents “Carboline.” Nikolaev, V.G., & Andreychin, M.A. Eds.). Kyiv: DIA.
Datsun, A.I. (2006). Rol sorbtsiino-detoksykatsiinoi ta synhletno-kysnevoi terapii v optymizatsii likuvannia khvorykh na rezektabelnyi rak priamoi kyshky [The role of sorption-detoxification and singlet-oxygen therapy in optimizing the treatment of patients with resectable rectal cancer]. Onkolohiia – Oncology, 8 (4), 355-358. Retrieved from: http://dspace.nbuv.gov.ua/bitstream/handle/ 123456789/2254/11-Dacyn.pdf?sequence=1 [in Ukrainian].
Doesch, A.O., Konstandin, M., Celik, S., Kristen, A., Frankenstein, L., Hardt, S., … Dengler, T.J. (2009). Effects of protein A immunoadsorption in patients with advanced chronic dilated cardiomyopathy. Journal of Clinical Apheresis, 24 (4), NA-NA. Retrieved from: https://doi.org/10.1002/jca.20204
Reznikova, E.A., Kosenok, V.K., Nechaev, G.I., Merkulov, V.N., & Reznikov, A.S. (2004). Vliyaniye preparata Reamberin na kardiotoksicheskoye deystviye antratsiklinov v lechenii mestnorasprostranennogo raka molochnoy zhelezy [The effect of Reamberin on the cardiotoxic effect of anthracyclines in the treatment of locally advanced breast cancer]. Vestnik Sankt-Peterburgskoy Gosudarstvennoy Meditsinskoy Akademii im. I. I. Mechnikova – Bulletin of Saint Petersburg State Medical Academy by I.I. Mechnikov, (12), 123-126. Retrieved from: http://as-ma.com.ua/Library/Rmb/RmbVlianie/Rmb.pdf [in Russian].
Samura, B.B. (2008). Povrezhdeniya miokarda, indutsirovannyye antratsiklinami. Diagnostika i lecheniye [Myocardial damage induced by anthracyclines. Diagnosis and treatment]. Terapiia. Ukrainskyi medychnyi visnyk – Therapy. Ukrainian Medical Bulletin, (12), 46–52 [in Russian].
Loar, R.W., Noel, C., Tunuguntla, H., Colquitt, J.L., & Pignatelli, R.H. (2018). State of the art review: Chemotherapy induced cardiotoxicity in children. Congenital Heart Disease, 13 (1), 5-15. Retrieved from: https://doi.org/10.1111/chd.12564
Stefanov, O.V. (Ed.). (2001). Doklinichni doslidzhennia likarskykh zasobiv: metodychni rekomendatsii [Preclinical drug research: guidelines]. Kyiv: Avitsenna. Retrieved from: https://www.twirpx.com/file/537410/ [in Ukrainian].
Oskina, V.V., Chekalina, K.I., & Gabrielyan, N.I. (1987). Srednemolekulyarnyye peptidy spinnomozgovoy zhidkosti pri gnoynykh meningitakh [Medium molecular peptides of cerebrospinal fluid in purulent meningitis]. Lab. Delo – Lab. Case, (2), 23-25 [in Russian].
Gabrielyan, N.I., Dmitriev, A.A., & Kulakov, G.P. (1981). Diagnosticheskaya tsennost opredeleniya srednikh molekul v plazme krovi pri nefrologicheskikh zabolevaniyakh [The diagnostic value of determining the average molecules in the blood plasma with nephrological diseases]. Klin. Med. – Clinical Medicine, (10), 38-42 [in Russian].
Bonadonna, G., Moliterni, A., Zambetti, M., Daidone, M. G., Pilotti, S., Gianni, L., & Valagussa, P. (2005). 30 years’ follow up of randomised studies of adjuvant CMF in operable breast cancer: cohort study. BMJ (Clinical Research Ed.), 330 (7485), 217. Retrieved from: https://doi.org/10.1136/bmj.38314.622095.8F
Golubtsov, O.Yu., Tyrenko, V.V., Lyutov, V.V., Maslyakov, V.V., & Makiev, R.G. (2017). Kardiovaskulyarnyye oslozhneniya protivoopukholevoy terapii. [Cardiovascular complications of antitumor therapy]. Sovremennyye problemy nauki i obrazovaniya – Modern Problems of Science and Education, (2). Retrieved from https://www.science-education.ru/pdf/2017/2/26380.pdf [in Russian].
Szwajcer, D., Czaykowski, P., & Turner, D. (2011). Assessment and management of febrile neutropenia in emergency departments within a regional health authority-a benchmark analysis. Current Oncology (Toronto, Ont.), 18 (6), 280-284. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/22184489.
Dohle, G.R. (2010). Male infertility in cancer patients: Review of the literature. International Journal of Urology, 17 (4), 327-331. Retrieved from: https://doi.org/10.1111/j.1442-2042.2010.02484.x
Xie, J., Cao, J., Wang, J., Zhang, B., Zeng, X., Zheng, H., … Hu, X. (2018). Advantages with prophylactic PEG-rhG-CSF versus rhG-CSF in breast cancer patients receiving multiple cycles of myelosuppressive chemotherapy: an open-label, randomized, multicenter phase III study. Breast Cancer Research and Treatment, 168 (2), 389-399. Retrieved from: https://doi.org/10.1007/s10549-017-4609-6
Shevchuk, O.O., Posokhova, E.A., Sakhno, L.A., & Nikolaev, V.G. (2012). Theoretical ground for adsorptive therapy of anthracyclines cardiotoxicity. Experimental Oncology, 34 (4), 314-322.
Nikolaev, V.G. (2017). Sorption therapy with the use of activated carbons: Effects on regeneration of organs and tissues. In hemoperfusion, plasmaperfusion and other clinical uses of general, biospecific, immuno and leucocyte adsorbents. Retrieved from: https://doi.org/10.1142/ 9789814749084_0007
Muravskaya, G.V., Nikolaev, V.G., Sergeev, V.P., Krutilina, N.I., Bonatskaya, L.V., Klevtsov, V. N., … Sinajko, V.V. (1991). Enterosorption in oncotherapy. artificial cells. Blood Substitutes, and Biotechnology, 19 (1), 167-174. Retrieved from: https://doi.org/10.3109/10731199109117823
