Descarga la aplicación para disfrutar aún más
Vista previa del material en texto
INGLÉS Alfabetización Académica y Científica Material de cátedra para las carreras de Farmacia y Bioquímica MÓDULO 2: Los géneros discursivos de las ciencias de la salud Clase 9: El estudio de caso Karina De Francesco – Laura Roseti Cátedra de INGLÉS Profesoras de cátedra: Lic. Laura Roseti – Lic. Karina De Francesco Jefes de Trabajos Prácticos: Lic. Sandra Lauría – Lic. Natalia Bron – Lic. Érika Barochiner Ayudantes de Cátedra: Trad. Marisa Tumbeiro – Lic. Leandro Carreño – Trad. Victoria Fernández – Prof. María Laura Castiglioni – Prof. Brenda Ertel – Lic. Constanza Barbariol PRE-READING SECTION 1. We have reached our ninth text. Read the title and the key points and zoom in on the familiar words and expressions to come up with the general topic of the text. What do you think it is about? 2. State a general reading hypothesis based on the information collected so far. 3. Let’s advance a bit further and focus on the rhetorical organisation of this new text. What distinctive features can you identify now? Does this text have any characteristics in common with the previous ones? Does it correspond to the genres we have analysed so far? Why? /Why not? Account for your answer. You might find it useful to refer to “Teóricos Nº 6 & Nº 7”. 4. Have you identified the different moves? Now, fill in the following table. Have a look at the example provided. If it is necessary, refer to the text again. General reading hypothesis: ………………………………………………………..........................……………………………………………………… …………………………………………………………………………………………………………………………………… …………………………………………………………………………………………………………………………………… TEXT 9: Probst, Mareike & Kühn, Jens-Peter & Modeß, Christiane & Scheuch, Eberhard & Seidlitz, Anne & Hosten, Norbert & Siegmund, Werner & Weitschies, Werner. (2017). Muscle Injury After Intramuscular Administration of Diclofenac: A Case Report Supported by Magnetic Resonance Imaging. Drug Safety - Case Reports. 4. 10.1007/s40800-017-0049-9. 1 Does this text include this information? Yes/No If so, where? How is it introduced? If not, why do you think so? Does it state an objective? Yes In the abstract (The aim of this study was to evaluate local toxicity in a patient using magnetic resonance imaging)1 Does it provide any information about the state of the arts or antecedents? Does it pose a problem? Does it put forward a hypothesis? Does it present any materials/ procedures/ methods? Does it mention and depict the participants involved? Does it compare/contrast other researchers’ conclusions/positions? Does the discussion analyse the results yielded in this work? Is the discussion based on the analysis of other trials? Does it come to any conclusions based on an experimental trial? 1 Where else is the objective stated? In which of the other moves? Remember that it is always stated twice. 2 5. Let’s make the most of our discipline-specific genre competence and select two moves that will provide you with a general overview of the text. Once you have chosen them, scan them to find central ideas. Did you finally identify the genre? It would be a good idea to discuss your selection with a peer. 6. It is now time to state a very specific reading hypothesis based on the information collected so far. 1. The prereading section has just finished. Now, read the text in full. 7. The pre-reading section has just finished. Now, read the text in full. WHILE-READING SECTION 8. Let’s concentrate on the problem now. Explain the scenario the authors have detected. How do they account for the niche that needs to be filled? ……………………………………………………………………………………………………………………………… ……………………………………………………………………………………………………………………………… ……………………………………………………………………………………………………………………………… ……………………………………………………………………………………………………………………………… 9. List the main procedures carried out in this study. How are these procedures expressed? What verbal forms are used to express them? ……………………………………………………………………………………………………………………………… ……………………………………………………………………………………………………………………………… ……………………………………………………………………………………………………………………………… ……………………………………………………………………………………………………………………………... Specific reading hypothesis: ………………………………………………………...........................................………………………………………. ………………………………………………………………………………………………………………………………… ………………………………………………………………………………………………………………………………… 3 10. Complete the table below with the main findings. INDICATORS MAIN FINDINGS Pain or other symptoms at the site of diclofenac administration Recovered volume at injection site Depot volume T2-weighed signal enhancement Plasma concentration Plasma creatine kinase activity Plasma concentrations of CRP, PCT and IL-6 11. Explain the paradox about the signs and clinical symptoms in this case. ……………………………………………………………………………………………………………………………… ……………………………………………………………………………………………………………………………… ……………………………………………………………………………………………………………………………… ……………………………………………………………………………………………………………………………… 4 12. Summarise the main conclusions and recommendations in your own words. Is the hypothesis confirmed or rejected? ……………………………………………………………………………………………………………………………… ……………………………………………………………………………………………………………………………… ……………………………………………………………………………………………………………………………… ……………………………………………………………………………………………………………………………… Focus on linguistic and discursive aspects Focus on causative verbs The authors have resorted to several to show cause and effects in this study. Let’s concentrate on the discussion move. “Initially, the tissue damage was most likely by local ion disequilibrium by infiltration of the highly hypertonic solution.” This rapid enhancement of the T2-weighted MR signal (…).” “Cell death is likely by activation of the caspase signalling cascade, proteolytic fragmentation of DNA and degradation of the cells (…).” 13. Now, find other examples of causative verbs, transcribe them below and explain the sense expressed by them. ……………………………………………………………………………………………………………………………… ……………………………………………………………………………………………………………………………… ……………………………………………………………………………………………………………………………… ……………………………………………………………………………………………………………………………… 5 Focus on impersonality is a recurrent feature in scientific discourse. is one of the resources to show in a given scenario because the and or doer of the action. Let’s have a look at the following examples taken from the methods and discussion moves: “Diclofenac organ injury indirectly by inhibition of cyclooxygenase or by metabolic activation of reactive metabolites (…).” Who knows what? Who induces organ injury? “This treatment .” Who tolerates what? Who is the doer of the action? “All measurements according to the instructions.” Is the doer of the action mentioned? What is the result of this action? 14. There are many other examples in the methods and results moves. Why do you think so? Transcribe the examples you find and provide a Spanish equivalent for each of them. ………………………………………………………………………………………………………………….…………… ………………………………………………………………………………………………………………..……………… …………………………………………………………………………………………………………..…………………… ……………………………………………………………………………………………………………………………….. 6 Focus on negative sense • Expressing is a central dimension in scientific discourse, especially when scientists aim to convey niches, problems and vacant aspects that science has not studied or solved yet. Thus, we will now focus on , which are . Let’s have a look at the following example extracted from the discussion move.“The contradiction between the impressive morphological and laboratory signs and of clinical symptoms might also result from long-lasting tissue deposition of diclofenac, which is known to exert local anaesthetic effects.” As we can see, this is a noun that is not negative in form, but in fact conveys absence (of clinical symptoms). If we refer to the abstract, we will find the same concept though expressed with a negative element in form (not) and a non-assertive item (any). “Interestingly, the patient did complain about clinical symptoms at the injection site.” There are other which are very frequent in scientific discourse, such as: , , , , , , , , , , , , , , , , , among others. Pay close attention to them because they can be tricky if you fail to interpret the involved. 7 Problems and scientific niches are also expressed by means of . Let’s have a look at these examples taken from the abstract and introduction moves: “Intramuscular injection of diclofenac is still frequently practiced, although there is ample evidence that the risk of local tissue intolerability is highly .” “Therefore, obligatory guidelines for safe intramuscular injection, including site, dose, and injection technique, are provided by the manufacturers of parenteral diclofenac dosage forms; however, the safety issue seems to be highly .” There are many other examples headed by which are very frequent in scientific discourse, such as: , , , , , (in this text), (in this text, too), , , , , , , , , , , , , among others. Pay close attention to these as they can also be problematic if you do not interpret the negative meaning involved. A bit more on subjectivity: presenting concluding remarks At the end of a case study, authors discuss the main findings and come to conclusions, in which they . In this final move, we are likely to find expressions showing , such as “injection of diclofenac ”. 8 15. Go over the text and find other expressions showing explicit subjectivity. Remember that they convey the subject’s position towards a scenario. ………………………………………………………………………………………………………………….…………… ………………………………………………………………………………………………………………..……………… …………………………………………………………………………………………………………..…………………… …………………………………………………………………………………………………………............................... 16. Select three linking adverbials which are used to express key concepts in the text. Analyse the relationship established and the concepts each of them links. Linking adverbial Relationship expressed Concept 1 Concept 2 17. Explain why you selected the linking adverbials above. ………………………………………………………………………………………………………………….…………… ………………………………………………………………………………………………………………..……………… …………………………………………………………………………………………………………..…………………… …………………………………………………………………………………………………………............................... 9 AFTER-READING SECTION 18. Write the main idea discussed in this text in ONE summative sentence. It must be coherent, conceptually correct, complete and specific. Remember your discourse must stage an epistemic ethos. Go back to “Teórico Nº 1” to reflect upon the interplay between epistemic ethos and scientific discourse. You may also refer to “Teórico Nº 3” for further information on main ideas. ……………………………………………………………………………………………………………………………… ……………………………………………………………………………………………………………………………… ……………………………………………………………………………………………………………………………… ……………………………………………………………………………………………………………………………… Bonus track on the ninth text: focus on discourse features of case study reports We have analysed a . This discourse genre refers to a study research paper which examines a person, place, event, phenomenon, or other type of subject of analysis in order to extrapolate key themes and results that help predict future trends, illuminate previously veiled issues that can be applied to practice, and/or provide a means for understanding an important research problem with greater clarity. A case study report usually examines a single subject of analysis but can also be designed as a comparative investigation that shows relationships between two or among more than two subjects. • The methods used to study a case can rest within a quantitative, qualitative, or mixed-method investigative paradigm. • It is highly descriptive. It refers to other voices of authority. It shows a high degree of modality expressions to refer to deduction, possibility and probability. It also shows signs of explicit subjectivity in the discussion and conclusion moves. 10 CASE REPORT Muscle Injury After Intramuscular Administration of Diclofenac: A Case Report Supported by Magnetic Resonance Imaging Mareike Probst1 • Jens-Peter Kühn2,3 • Christiane Modeß4 • Eberhard Scheuch4 • Anne Seidlitz1 • Norbert Hosten2 • Werner Siegmund4 • Werner Weitschies1 Published online: 25 March 2017 � The Author(s) 2017. This article is an open access publication Abstract Intramuscular injection of diclofenac is still frequently practiced, although there is ample evidence that the risk of local tissue intolerability is highly underesti- mated. The aim of this study was to evaluate local toxicity in a patient using magnetic resonance imaging. A patient who gave written informed consent received a medically indicated intramuscular administration of diclofenac 75 mg/2 mL. Simultaneously with magnetic resonance imaging of the depot, a clinical–chemical evaluation and quantification of diclofenac in plasma was performed. A manifold enhancement of the T2-weighted magnetic reso- nance signal was observed in a muscle area of approxi- mately 60 mL volume, with maximum signal intensity 30 min after injection, the time of maximum diclofenac plasma exposure. Plasma creatine kinase activity was ele- vated approximately sixfold within 8 h and normalized within 1 week, whereas the magnetic resonance enhance- ment disappeared within 5 weeks. Interestingly, the patient did not complain about any clinical symptoms at the injection site. Asymptomatic tissue injury after intramus- cular injection of diclofenac, caused by intramuscular dosing, can be reliably evaluated by magnetic resonance imaging and should be applied early during the develop- ment of parenteral dosage forms. Clinical Trials Registration Number: BB130/16 (Ethics Committee of the University Medicine Greifswald). Key Points Local tissue injury following intramuscularly administered diclofenac can be proven noninvasively by magnetic resonance imaging. Introduction The relief of acute pain syndromes by administration of intramuscular injections of diclofenac is still frequently practiced and seems to be a safe and well-tolerated treat- ment option. The incidence of local adverse events seems to be rather low—0.05% for abscesses and 0.02% for necrosis [1]. Common reasons for local complications are bacterial contamination [2], wrong injection technique, and wrong injection site [3]. Therefore, obligatory guidelines for safe intramuscular injection, including site, dose, and injection technique, are provided by the manufacturers of parenteral diclofenac dosage forms; however, the safety issue seems to be highly underestimated. In a survey con- ducted between 1978 and 2003, only 171 cases with local & Mareike Probst mareike.probst@uni-greifswald.de 1 Department of Biopharmaceutics and Pharmaceutical Technology, Center of Drug Absorption and Transport (C_DAT), Ernst Moritz Arndt University Greifswald, Felix- Hausdorff-Straße 3, 17487 Greifswald, Germany 2 Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Ferdinand-Sauerbruch- Straße, 17475 Greifswald, Germany 3 Institute of Radiology, University Medicine, Carl Gustav Carus UniversityDresden, Fetscherstraße 74, 01307 Dresden, Germany 4 Department of Clinical Pharmacology,Center of Drug Absorption and Transport (C_DAT), University Medicine Greifswald, Felix-Hausdorff-Straße 3, 17487 Greifswald, Germany Drug Saf - Case Rep (2017) 4:7 https://doi.org/10.1007/s40800-017-0049-9 http://orcid.org/0000-0001-5350-928X http://crossmark.crossref.org/dialog/?doi=10.1007/s40800-017-0049-9&domain=pdf http://crossmark.crossref.org/dialog/?doi=10.1007/s40800-017-0049-9&domain=pdf https://doi.org/10.1007/s40800-017-0049-9 injuries, including necrosis, abscess, necrotizing fasciitis and myositis, were related to the consumption of 100 million ampules of Voltarol�, and only nine patients complained of pain at the injection site [4]. Since local tissue injury after diclofenac is rarely asso- ciated with relevant subjective symptoms, it can be assumed that many cases are not recognized in clinical practice. The issue may be more severe than assumed to date. In a recent experimental study in rats to investigate the disposition of intramuscularly injected depots, we incidentally observed that all animals that received an aqueous solution or oily suspension of diclofenac respon- ded with local inflammatory intolerance [5]. This included long-lasting fluid accumulation at the site of intramuscular injection and infiltration of the muscle tissue with neu- trophil granulocytes, as well as the development of necrotic changes as confirmed by magnetic resonance (MR) imag- ing and histopathological evaluation. The severity of inflammation was dependent on dose and the pharmaceu- tical formulation of the drug. To support our hypothesis that intramuscular injection of diclofenac leads to muscle damage in humans, we provide the clinical case report of a patient who gave written consent to take extra blood specimens for laboratory evaluations and determination of diclofenac pharmacokinetics, as well as for MR imaging after a medicinally indicated intramuscular diclofenac injection. Methods A physician (aged 65 years, body weight 90 kg, body height 182 cm) who is familiar with the safety issue described above, prescribed himself an intragluteal injec- tion of diclofenac (Diclofenac-Ratiopharm� 75 mg/2 mL; Ratiopharm, Ulm, Germany) as a result of a painful enthesopathy of the right musculus gluteus minimus, and initiated additional clinical–chemical evaluations and MR imaging of the left gluteal region to evaluate a potential muscle injury at the injection site. The diagnosis was confirmed by MR imaging approximately 1 year prior to commencement of the study. The patient commonly swallowed ibuprofen lysine (684 mg) or diclofenac (50 mg) on demand, i.e. after the occurrence of pain fol- lowing stronger physical exercise. This treatment has been well tolerated. The additional diagnostic procedures have been approved by the local ethics committee under registry number BB130/16. The osmolality of the aqueous diclofenac solution was 2850 ± 121 mOsmol/kg (Vapour Pressure Osmometer; Knauer, Berlin, Germany) and the pH was 8.19 ± 0.03 (Five Easy; Mettler Toledo, Grei- fensee, Switzerland). MR imaging in the supine position was performed using a 3-Tesla scanner (Verio; Siemens Healthcare, Erlangen, Germany) before and 2, 12, 22, 32, 47, 62, 92, 122, 182, 242 min after, as well as 7.5 h and 1, 2, 7 and 14 days after intramuscular administration. A T2- weighted turbo spin echo sequence including fat saturation was applied with the following parameters: 6960 ms rep- etition time, 91 ms echo time, 60 slices of 2-mm thickness and 2-mm spacing in between, 150 � flip angle, 450 9 370 mm field of view, and 256 9 170 mm matrix. Volume and signal intensity of the depot was assessed using the OsiriX Imaging Software 3.9 32-Bit (Pixmeo Sarl, Bernex, Switzerland). Blood was sampled via an indwelling cannula placed in a forearm vein before and 10, 20, 30 and 45 min after, as well as 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8 and 24 and 48 h after administration to measure plasma concentrations of diclofenac and the biomarkers creatine kinase (CK), C-reactive protein (CRP), Procalci- tonin (PCT) and Interleukin-6 (IL-6). Quantitative analysis of diclofenac concentration in plasma was performed using a validated liquid chromatography-tandem mass spec- trometry (LC–MS/MS) method as previously described [5]. The biomarkers were quantified using commercially available kits for PCT (ADVIA Centaur; Siemens Health- care, Eschborn, Germany), IL-6 (Brahms, Hennigsdorf, Germany; and Cobas e411, Roche, Mannheim, Germany), CRP and CK (Dimension Vista; Siemens Healthcare, Eschborn, Germany). All measurements were carried out according to the instructions of the manufacturer, and complied with the national regulations on laboratory quality assurance [6]. Results The patient did not complain of pain and other symptoms at the site of diclofenac administration, neither immedi- ately nor some time after the injection, despite the expectant attitude of the informed subject. The contralat- eral tendinous gluteal pain was relieved for approximately 4 h but occurred again thereafter, however with tolerable intensity. Shortly after intragluteal administration of diclofenac 75 mg in 2 mL aqueous solution, the recovered volume at the injection site was approximately 6 mL, as measured using T2-weighted, MR-based volumetry. The depot vol- ume increased to 37 mL within 45 min, then decreased to 17 mL after approximately 4 h, before it increased again to reach a maximum of 60 mL 24 h after injection. The watery inhomogeneity was seen in the MR images over several weeks. The T2-weighted signal enhancement, quantified as contrast-to-noise ratio (CNR), reached its maximum just immediately after injection, and then declined rapidly within 2 h to a long-lasting plateau level that disappeared after several weeks (Figs. 1, 2). 7 Page 2 of 5 M. Probst et al. After intramuscular injection, diclofenac reached a maximum plasma concentration of approximately 1.4 lg/ mL after 30 min and was eliminated in a biphasic manner, with half-lives of 0.63 h (a-slope) and 1.36 h (b-slope). Plasma creatine kinase activity was elevated more than sixfold within 8 h after diclofenac injection, and returned to baseline levels after 1 week (Fig. 2). Plasma concen- trations of CRP, PCT and IL-6 were not changed from baseline after diclofenac administration. Fig. 1 T2-weighted transverse magnetic resonance images of the left gluteal region before and after a 2 mL injection of diclofenac watery solution. Arrows indicate the site of injection and volume of the enhanced muscle tissue MRI Study of Intramuscular Diclofenac Page 3 of 5 7 Discussion The single MR-guided intramuscular injection of diclofe- nac 75 mg in 2 mL solution unexpectedly damaged approximately 60 mL of gluteal muscle tissue of the patient, as confirmed by long-lasting, manifold enhance- ment of the T2-weighted MR signal in that area and ele- vation of the plasma CK activity for longer than 48 h. Initially, the tissue damage was most likely triggered by local ion disequilibrium caused by infiltration of the highly hypertonic solution (2850 mOsmol/kg). This resulted in rapid enhancement of the T2-weighted MR signal, with maximum signal intensity approximately 30 min after injection, which was also the time of maximum diclofenac plasma exposure. This means that diclofenac must have been almost fully absorbed from the injection depot at that time. Consequently, the highest volume of the injured muscle area being detected 24 h after the injection cannot be explained by the osmotic pressure of the injected solu- tion alone. Diclofenac is known to induce organ injury indirectly by inhibition of the cyclooxygenase (e.g. gastrointestinal erosions and bleedings, renal tubular damage) or by metabolic activation of reactive metabolites that exert cell stress, impair mitochondrial functions, or trigger specific immune reactions in genetically predisposed subjects (e.g. drug-induced liverinjury) [7]. However, tissue injury after intramuscular injection into the recommended gluteal region is most likely caused by direct cytotoxicity, as already observed in gastric mucosal cells [8], osteoblasts [9], and tumor cells [10]. Cell death is likely induced by activation of the caspase signaling cascade, leading to proteolytic fragmentation of DNA and degradation of the cells [11], even though the activation mechanisms of the proapoptotic signal pathways by diclofenac have not been fully understood to date. However, local toxicity of diclofenac can be influenced by the pH-dependent solu- bility of the drug [12]. Traces of diclofenac might precip- itate at the injection site even after a minor drop in the pH value, as caused by local tissue congestion, ion disequi- librium, or inflammatory changes, leading to longer lasting exposure of the affected area and perpetuation of the local toxicity. The plasma CK activity, a biomarker for the muscle tissue injury, was already elevated 1 h after injec- tion of the drug and reached its maximum, at the earliest, after 8 h (Fig. 2). The biphasic elimination profile, with half-lives of 0.63 and 1.4 h, supports the hypothesis that parts of the dose are absorbed from a depot with a slower input rate. Furthermore, the patient did not complain of any pain at the injection site, as expected by the extent of the putative muscle injury visualized by MR imaging. The contradiction between the impressive morphological and laboratory signs and lack of clinical symptoms might also result from long-lasting tissue deposition of diclofenac, which is known to exert local anesthetic effects [13, 14]. In that context, it should be reminded that every single rat in our previous experimental study showed a massive T2 enhancement at the injection site [5]. Conclusion Asymptomatic tissue injury after intramuscular adminis- tration of diclofenac seems to be a frequent or regular local finding, even though the injection technique is fully in adherence with the obligatory guidelines for intramuscular Fig. 2 CNR of the T2- enhanced muscle area (filled square), plasma concentrations of diclofenac (ng/mL, filled circle), and activity of creatine kinase (lkatal/L, filled triangle) after intramuscular injection of diclofenac 75 mg in a 2-mL solution. CNR contrast-to-noise ratio 7 Page 4 of 5 M. Probst et al. administration in humans. Therefore, intramuscular injec- tion of diclofenac should be carefully practiced, focusing on the individual benefit–risk balance. To our experience, local toxicity caused by intramuscular dosing of drugs can be reliably evaluated by non-invasive MR imaging, and should be applied in the very early stages of the evaluation of parenteral dosage forms. Acknowledgements The authors thank Gitta Schumacher, Sabine Bade, Danilo Wegner, Andrea Seidel, and Stefan Hadlich for excel- lent technical assistance. Compliance with Ethical Standards Funding This work was supported by the InnoProfile grant COM_- DAT [03IPT612X] of the German Federal Ministry of Education and Research (BMBF). Conflicts of interest Mareike Probst, Jens-Peter Kühn, Christiane Modeß, Eberhard Scheuch, Anne Seidlitz, Norbert Hosten, Werner Siegmund and Werner Weitschies declare that they have no conflicts of interest. Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent Informed consent was obtained from all individ- ual participants included in the study. Open Access This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which per- mits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. References 1. Serratrice G. Study of diclofenac injectable. Tribune Med. 1982;46:43–8. 2. Rygnestad T, Kvam AM. Streptococcal myositis and tissue necrosis with intramuscular administration of diclofenac (Volta- ren). Acta Anaesthesiol Scand. 1995;39:1128–30. 3. Hegan T. Non steroidals, needles and negligence. Medical Pro- tection Society casebook. Leeds: Medical Protection Society; 2002. p. 12–3. 4. O’Sullivan DP. Intramuscular diclofenac: 25 years worldwide safety perspective is vital to consider. Response to: Wright PJ, English PJ, Hungin APS, Marsden SNE. Managing acute renal colic across the primary-secondary care interface: a pathway of care based on evidence and consensus. BMJ. 2002;325:1408–12. 5. Probst M, Kühn J-P, Scheuch E, Seidlitz A, Hadlich S, Evert K, et al. Simultaneous magnetic resonance imaging and pharma- cokinetic analysis of intramuscular depots. J Control Release. 2016;227:1–12. 6. Revision of the. ‘‘Guideline of the German Medical Association on Quality Assurance in Medical Laboratory Examinations— Rili-BAEK’’ (unauthorized translation). J, Lab Med. 2015;39:26–69. 7. Aithal GP, Ramsay L, Daly AK, Sonchit N, Leathart JBS, Alexander G, et al. Hepatic adducts, circulating antibodies, and cytokine polymorphisms in patients with diclofenac hepatotoxi- city. Hepatology. 2004;39:1430–40. 8. Kusuhara H, Matsuyuki H, Matsuura M, Imayoshi T, Okumoto T, Matsui H. Induction of apoptotic DNA fragmentation by nons- teroidal anti-inflammatory drugs in cultured rat gastric mucosal cells. Eur J Pharmacol. 1998;360:273–80. 9. Chang J-K, Wang G-J, Tsai S-T, Ho M-L. Nonsteroidal anti- inflammatory drug effects on osteoblastic cell cycle, cytotoxicity, and cell death. Connect Tissue Res. 2005;46:200–10. 10. Kim T, Jin S, Kim W, Kang E, Choi K, Kim H, et al. Prolonged activation of mitogen-activated protein kinases during NSAID- induced apoptosis in HT-29 colon cancer cells. Int J Colorectal Dis. 2001;16:167–73. 11. Gómez-Lechón MJ, Ponsoda X, O’Connor E, Donato T, Jover R, Castell JV. Diclofenac induces apoptosis in hepatocytes. Toxicol In Vitro. 2003;17:675–80. 12. Ledwidge MT, Corrigan OI. Effects of surface active character- istics and solid state forms on the pH solubility profiles of drug– salt systems. Int J Pharm. 1998;174:187–200. 13. Cairns BE, Mann MK, Mok E, Dong X-D, Svensson P. Diclofenac exerts local anesthetic-like actions on rat masseter muscle afferent fibers. Brain Res. 2008;1194:56–64. 14. Nakamura M, Jang I-S. pH-dependent inhibition of tetrodotoxin- resistant Na? channels by diclofenac in rat nociceptive neurons. Prog Neuropsychopharmacol Biol Psychiatry. 2016;64:35–43. MRI Study of Intramuscular Diclofenac Page 5 of 5 7 Muscle Injury After Intramuscular Administration of Diclofenac: A Case Report Supported by Magnetic Resonance Imaging Abstract Introduction Methods Results Discussion Conclusion Acknowledgements References
Compartir