natgillin/translations-raw huggingface dataset:
The increased potential to release gadolinium in the brain would be expected with the linear agents, which have a lower kinetic and thermodynamic stability and are thus more prone to release gadolinium in the tissue environment. 
Večja možnost sproščanja gadolinija v možgane bi se pričakovala pri linearnih sredstvih, ki imajo manjšo kinetično in termodinamično stabilnost ter so zato bolj nagnjena k sproščanju gadolinija v okolje tkiv.
A restriction by number of doses may not be possible in clinical practice, because previous exposures to GdCAs may not have been recorded sufficiently with regard to the type of GdCA used. 
Omejitev števila odmerkov v klinični praksi morda ne bi bila mogoča, ker predhodne izpostavljenosti sredstvom GdCA morda ne bi bile ustrezno evidentirane glede na vrsto uporabljenega sredstva GdCA.
All GdCAs have some degree of renal elimination, which varies from 50% for gadoxetic acid to 100% for most other members of the class. 
Vsa sredstva GdCA se v določeni meri izločajo skozi ledvice, gadoksetna kislina v 50 %, večina drugih članov tega razreda pa v 100 %.
Moreover, there is concern that gadolinium deposition could worsen existing inflammatory diseases, as accumulation in inflammatory lesions has been observed. 
Poleg tega obstaja pomislek, da bi odlaganje gadolinija lahko poslabšalo obstoječe vnetne bolezni, saj je bilo kopičenje ugotovljeno v vnetnih lezijah.
Gadolinium containing contrast agents (GdCAs) are complexes of paramagnetic gadolinium (III) with different types of organic chelators. 
Kontrastna sredstva, ki vsebujejo gadolinij (GdCA), so kompleksi paramagnetnega gadolinija (III) z različnimi vrstami organskih kelatorjev.
The design of any future clinical study to investigate the long-term safety of GdCAs in patients would require large numbers of patients to have sufficient power to detect small adverse effects on cognition (cognitive disorders) or physical abilities (fine motor skills). 
Vsaka prihodnja klinična študija za proučitev dolgoročne varnosti sredstev GdCA pri bolnikih bi morala biti zasnovana tako, da bi vključevala veliko bolnikov, da bi bilo mogoče ugotoviti majhne neželene učinke na kognitivne (kognitivne motnje) ali fizične sposobnosti (finomotorične sposobnosti).
In general, appropriate medications, equipment and staff experienced in the management of hypersensitivity reactions can be expected in any radiological practice. 
Na splošno je mogoče pričakovati, da imajo v vsaki radiološki ambulanti ustrezna zdravila, opremo in osebje, ki ima izkušnje z obvladovanjem preobčutljivostnih reakcij.
However linear agents are retained and persist for up to one year or longer. 
Vendar pa se linearna sredstva zadržijo in ohranijo do enega leta ali dlje.
Having reviewed the PRAC recommendation, the CHMP agrees with the PRAC overall conclusions and grounds for recommendation. 
Potem ko je odbor CHMP pregledal priporočilo odbora PRAC, se je strinjal s končnimi zaključki in razlogi za priporočilo.
There is also a concern that gadolinium deposits in some tissues, particularly bone, could be released at a later stage for example during loss of bone density in aging or pregnancy/breastfeeding, exposing patients to further systemic distribution of gadolinium. 
Obstaja tudi pomislek, da bi se lahko depoziti gadolinija v nekaterih tkivih, zlasti kostnih, sprostili pozneje, npr. med izgubo kostne gostote zaradi staranja ali med nosečnostjo/dojenjem, zaradi česar bi bili bolniki izpostavljeni nadaljnjemu sistemskemu razdeljevanju gadolinija.
In January 2016, in the framework of a PSUSA procedure, the PRAC reviewed all available literature and data related to the accumulation of gadolinium in the brain and recommended the removal of statements from the product information of all GdCAs that the products do not pass the intact blood brain barrier. 
Odbor PRAC je januarja 2016 v okviru postopka za redno posodobljeno poročilo o varnosti zdravila (PSUSA) pregledal vso razpoložljivo literaturo in podatke v zvezi s kopičenjem gadolinija v možganih ter priporočil, da se za vsa sredstva GdCA iz informacij o izdelku odstranijo navedbe, da izdelki ne prehajajo skozi nepoškodovano krvno-možgansko pregrado.
It was also mentioned that there is currently little, if any, concern amongst experts specifically about the use of macrocyclic agents in clinical practice, and the current safety concern laying over all GdCAs arises from the clinical use of linear GdCAs. 
Povedali so tudi, da je med strokovnjaki malo pomislekov, če sploh kaj, posebej glede uporabe makrocikličnih sredstev v klinični praksi, zdajšnji pomisleki v zvezi z varnostjo vseh sredstev GdCA pa izhajajo iz klinične uporabe linearnih sredstev GdCA.
Thus, rather weak binding of linear chelators to Gd becomes obvious in various experiments (including Port et al 2009, Sieber et al 2008), and this makes it unlikely that the complex is fully stable in vivo. 
Precej šibka vezava linearnih kelatorjev na gadolinij postane očitna pri različnih poskusih (vključno s Port idr., 2009, Sieber idr., 2008), zato ni verjetno, da bi bil kompleks in vivo povsem stabilen.
Notwithstanding this, and given the detailed grounds provided by the MAHs, the PRAC carried out a new assessment of the available data in the context of the reexamination. 
Kljub temu in glede na podrobno opisane razloge imetnikov dovoljenja za promet je v okviru ponovne proučitve znova ocenil razpoložljive podatke.
PRAC considered the detailed grounds as submitted by the MAHs within this re-examination procedure and the scientific data underlying these grounds. 
Odbor PRAC je proučil podrobno opisane razloge, ki sta jih predložila imetnika dovoljenja za promet z zdravilom v okviru tega postopka ponovne proučitve, in znanstvene podatke, na katerih temeljijo ti razlogi.
Also PRAC was not able to define a safe threshold level for exposure to gadolinium and retention of gadolinium in the brain, or to define a period of time during which a potential adverse effect would have time to manifest. 
Odbor PRAC prav tako ni mogel opredeliti varne mejne vrednosti za izpostavljenost gadoliniju in zadrževanje gadolinija v možganih ter časovnega obdobja, v katerem bi se morebitni neželeni učinek lahko pokazal.
The PRAC also noted that in contrast, for NSF a specific patient group (renal insufficiency and patients in the perioperative liver transplantation period) could be identified, and avoidance of use in these populations appears to have minimised the risk of NSF. 
Odbor PRAC je tudi poudaril, da je v nasprotju s tem za NSF mogoče opredeliti specifično skupino bolnikov (bolniki z ledvično insuficienco in bolniki v perioperativnem obdobju presaditve jeter), in zdi se, da se je zaradi izogibanja uporabi pri teh populacijah tveganje NSF zmanjšalo.
Gd presence in the brain following the last administration of other linear agents, gadopentetic acid and gadobenic acid also remained at the same level after the same period. 
Prisotnost gadolinija v možganih po prejemu zadnjega odmerka drugih linearnih sredstev, gadopentetske kisline in gadobenske kisline, je prav tako po enakem obdobju ostala na isti ravni.
The T1 signal enhancement was documented in several non-clinical as well as clinical studies, demonstrating that the data is consistent across mouse, rat and human, which confirms the robustness of the findings of signal intensity increases. 
Povečanje signala T1 je bilo dokumentirano v več nekliničnih in kliničnih študijah, kar dokazuje skladnost podatkov pri miših, podganah in ljudeh, kar potrjuje trdnost ugotovitev glede povečanja intenzivnosti signala.
The PRAC concluded that based on the available data Multihance can continue to be used in paediatric patients for delayed phase liver imaging. 
Odbor PRAC je zaključil, da se na podlagi razpoložljivih podatkov lahko sredstvo Multihance pri pediatričnih bolnikih za slikanje jeter v zapozneli fazi uporablja še naprej.
However, they did not favour the suspension of linear agents which could be preferred by some radiologists for their technical characteristics in some conditions (e.g., breast or brain imaging), especially in conditions that do not require frequent imaging procedures, or which could be used as “second line” agents. 
Niso pa podprli začasnega umika dovoljenja za promet z linearnimi sredstvi, ki jim nekateri radiologi morda dajejo prednost zaradi njihovih tehničnih značilnosti v nekaterih primerih (npr. pri slikanju dojk ali možganov), zlasti v primerih, kjer se postopek slikanja ne zahteva pogosto, ali ki bi se lahko uporabljali kot sredstva „druge izbire“.
• Gd retention was studied rather early (one week) after cessation of treatment so that detected Gd may not represent the long-term storage form. 
• zadrževanje gadolinija se je proučevalo precej zgodaj (en teden) po prekinitvi obravnave, tako da ugotovljeni gadolinij morda ne pomeni oblike dolgotrajnega shranjevanja.
Furthermore, recent publications have shown that gadolinium also accumulates in the brain. 
Poleg tega so nedavne publikacije dokazale, da se gadolinij kopiči tudi v možganih.
However, after the use of linear agents gadolinium is retained longer at measurable levels and persists for up to one year or more. 
Vendar pa se po uporabi linearnih sredstev gadolinij dlje zadrži na merljivih ravneh in se ohrani do enega leta ali dlje;
• To extend the posology to lower doses in specific applications and clinical settings where the advances in technology have shown that to be appropriate. 
• razširitev odmerjanja na manjše odmerke pri specifičnih uporabah in v kliničnem okolju, kjer je to ustrezno glede na tehnološki napredek.
These areas are involved in the regulation of voluntary and involuntary movement; adverse events could potentially include events such as ataxia, tremors and other movement disorders. 
Ta predela sta vključena v nadzorovanje hotnih in nehotnih gibov; neželeni dogodki bi lahko med drugim vključevali ataksijo, tremor in druge motnje gibanja.
Many of these are common but typically non-serious reactions, such as rash, urticaria, and flushing. 
Mnogi med njimi so pogosti, vendar pa navadno to niso hude reakcije, npr. izpuščaj, koprivnica in rdečica.
According to the current knowledge about gadolinium deposition in the brain, linear compounds have been detected in the brain at a higher magnitude than the macrocyclic compounds and they appear to be stored there in a form that does not allow an early washout. 
V skladu s sedanjimi podatki o odlaganju gadolinija v možganih so bile v možganih linearne spojine ugotovljene v večjem obsegu kot makrociklične spojine, pri čemer se zdi, da se tam shranjujejo v obliki, ki ne omogoča zgodnjega izpiranja.
It has shown clinical utility in imaging of the liver. 
Izkazala se je za klinično koristno pri slikanju jeter.
Toxicity has been seen in other tissues where it accumulates (including NSF, skin plaques) and in non-clinical data. 
Toksičnost je bila ugotovljena v drugih tkivih, kjer se ta kopiči (vključno z NSF, kožnimi plaki), in v nekliničnih podatkih.
Therefore, data shows that linear agents are deposited in the brain and are retained and persist for up to one year or longer. 
Podatki torej kažejo, da se linearna sredstva odlagajo v možganih in tam ohranijo do enega leta ali dlje.
• No specific patient group with less risk of accumulation in the brain can currently be identified. 
• trenutno ni mogoče opredeliti specifične skupine bolnikov z manjšim tveganjem kopičenja.
In summary, the PRAC considered that there are no new arguments which could convincingly challenge its previous views regarding the dechelation of Gd and hence the low stability of linear GdCA complexes playing a major role for its tissue disposition. 
Skratka, odbor PRAC je menil, da ni na voljo novih argumentov, s katerimi bi bilo mogoče prepričljivo izpodbijati njegovo predhodno stališče glede dekelacije gadolinija, zaradi česar ima nizka stabilnost linearnih kompleksov GdCA glavno vlogo pri njegovem odlaganju v tkivu.
In order to address the serious concerns of the potential neurological effects, PRAC considered the feasibility of clinical safety studies, both observational and interventional, and concluded that these would not be feasible within a reasonable period of time. 
Odbor PRAC je za obravnavanje resnih pomislekov glede morebitnih nevroloških učinkov proučil izvedljivost kliničnih opazovalnih in intervencijskih študij varnosti ter zaključil, da v razumnem času ne bi bile izvedljive.
Also the restriction of the number of doses administered during the lifetime of a patient raises practical difficulties and therefore would not be effective. 
Tudi pri omejitvi števila odmerkov, ki jih bolnik prejme v svojem življenju, bi se pojavile praktične težave, zato ta ne bi bila učinkovita.
Hence, the potential risk of brain accumulation and retention in the body tissues cannot be minimised by recommendations to contraindicate use in particular groups (e.g. children, pregnant women, those with renal impairment, other groups) or by avoiding use for particular scans or clinical settings, including repeated use or by restricting re-exposure to certain agents or product classes. 
Morebitnega tveganja kopičenja v možganih in zadrževanja v telesnih tkivih zato ni mogoče zmanjšati s priporočili o kontraindicirani uporabi pri določenih skupinah (npr. pri otrocih, nosečnicah, bolnikih z ledvično okvaro, drugih skupinah) ali s preprečevanjem uporabe za določeno slikanje ali klinično okolje, vključno z večkratno uporabo, ali z omejitvijo ponovne izpostavljenosti nekaterim sredstvom ali razredom izdelkov.
The CHMP, having considered the PRAC recommendation, is of the view that the following clarifications to the PRAC grounds and recommendation are necessary: 
Odbor CHMP, ki je proučil priporočilo odbora PRAC, meni, da so v zvezi s priporočilom in njegovimi razlogi potrebna naslednja pojasnila:
The evidence strongly suggests a correlation between the potential for release of gadolinium from the ligand and the extent of retention in these tissues and organs. 
Dokazi jasno kažejo povezavo med možnostjo sproščanja gadolinija iz liganda ter obsegom zadrževanja v teh tkivih in organih;
Therefore, a conclusion that there are significant and clinically relevant differences in diagnostic performance between two GdCAs needs to be supported by robust evidence from clinical studies including evidence on a better clinical outcome and patient management, which is currently lacking; the impact on diagnostic thinking and patient management was not proven. 
Zaključek, da so med obema sredstvoma GdCA znatne in klinično pomembne razlike glede diagnostične zmogljivosti, je treba podpreti s trdnimi dokazi iz kliničnih študij, vključno z dokazi za boljši klinični izid in obravnavanje bolnika, ki zdaj niso na voljo; učinek na diagnostično razmišljanje in obravnavanje bolnika ni bil dokazan.
Elimination of GdCAs is therefore reduced in patient with renal dysfunction. 
Izločanje sredstev GdCA je zato pri bolnikih s slabim delovanjem ledvic zmanjšano.
The experts also stated that it is plausible that adverse clinical consequences could be associated with gadolinium retention in the brain. 
Strokovnjaki so tudi povedali, da je verjetno, da so neželene klinične posledice povezane z zadrževanjem gadolinija v možganih.
Hypersensitivity or anaphylactoid reactions with GdCAs can manifest as a range of clinical signs and symptoms. 
Preobčutljivost ali anafilaktoidna reakcija na sredstva GdCA se lahko manifestira kot različni klinični znaki ali simptomi.
The available data in humans support a conclusion that while impaired renal function is not a necessary precondition for signal hyperintensity increases in the brain, impaired renal function does increase the extent of brain accumulation and signal hyperintensity. 
Razpoložljivi podatki o ljudeh podpirajo zaključek, da motnje v delovanju ledvic niso nujno predpogoj za povečanje hiperintenzivnosti signala v možganih, vendar pa povečajo kopičenje v možganih in hiperintenzivnost signala.
Further studies have tried to characterise and quantify the amount of deposition of gadolinium in the brain. 
Z nadaljnjimi študijami se je skušalo opredeliti in izmeriti količino odloženega gadolinija v možganih.
These observations leave the possibility that the method used for the Gd determination is unreliable under certain circumstances. 
Zaradi teh ugotovitev je še vedno mogoče, da metoda, uporabljena za določitev gadolinija, v nekaterih primerih ni zanesljiva.
Enhancement after gadobenate dimeglumine (Multihance) or gadopentetate dimeglumine (Magnevist) appeared more progressively compared with gadodiamide. 
Pokazalo se je, da je povečanje po gadobenat dimegluminu (Multihance) ali gadopentetat dimegluminu (Magnevist) v primerjavi z gadodiamidom progresivnejše.
Linear GdCAs are associated with a significant risk of NSF. 
Linearna sredstva GdCA so povezana z znatnim tveganjem NSF.
• Linear GdCAs are associated with a significant risk of NSF, although current risk minimisation measures appear to be effective based on spontaneous adverse drug reaction reporting. 
• linearna sredstva GdCA so povezana z znatnim tveganjem NSF, čeprav se na podlagi spontanega poročanja o neželenih učinkih zdravil zdajšnji ukrepi za zmanjšanje tveganja zdijo učinkoviti;
Therefore, the PRAC considered that the benefits of these products outweigh their risks. 
Odbor PRAC je zato menil, da koristi teh izdelkov prevladajo nad njihovimi tveganji.
• Clinical studies, both observational and interventional, to fully address the serious concerns of potential neurological effects are not considered feasible within a reasonable period of time. 
• opazovalne in intervencijske klinične študije za celovito obravnavanje resnih pomislekov glede morebitnih nevroloških učinkov v razumnem času ne bi bile izvedljive.
In addition, PRAC considered that it is not possible to restrict the use of intravenous linear GdCAs to certain indications or certain groups of patients as: 
Poleg tega je odbor PRAC menil, da uporabe intravenskih linearnih sredstev GdCA ni mogoče omejiti na nekatere indikacije ali skupine bolnikov, ker:
Lanthanide ions such as gadolinium can bind to Ca2+ binding enzymes and interfere with calcium channels, due to competition with Ca2+ in cellular and biochemical processes, which can lead to adverse biological effects (Sherry et al. 2009). 
Lantanoid, kot je gadolinij, se lahko veže na encime, ki vežejo Ca2+, in zaradi tekmovanja s Ca2+ v celičnih in biokemičnih procesih interferira s kalcijevimi kanalčki, kar lahko povzroči neželene biološke učinke (Sherry idr., 2009).
With regards to the use of Multihance in the paediatric population, it was noted that, while hepatocellular carcinoma as well as metastatic lesions are frequent in the adult population, liver diseases in children are rather diffuse than focal and tumours are rare. 
V zvezi z uporabo sredstva Multihance pri pediatrični populaciji je bilo poudarjeno, da so hepatocelični karcinomi in metastatične lezije pogoste pri odrasli populaciji, bolezni jeter pri otrocih pa prej razpršene kot zgoščene, tumorji pa redki.
• Gadolinium has been measured in the brain, both indirectly by studies showing signal intensity increases, and directly by studies measuring gadolinium concentrations with mass spectrometry, including methods that allow localisation in the brain (LA-ICP-MS) and separation of Gd species (GPC-MS). 
• opravljene so bile meritve gadolinija v možganih, neposredno s študijami, ki dokazujejo povečanje intenzivnosti signala, in posredno s študijami, ki koncentracije gadolinija merijo z masno spektrometrijo, vključno z metodami, ki omogočajo lokalizacijo v možganih (LA-ICP-MS) in razločevanje vrst gadolinija (GPC-MS);
• To update the SmPC to make the physician aware of the accumulation in the brain and to reduce exposure and communicate about such update; 
• posodobitev povzetka glavnih značilnosti zdravila za ozaveščanje zdravnikov o kopičenju v možganih in zmanjšanje izpostavljenosti ter obveščanje o tej posodobitvi;
• the study results from the Mayo Clinic Study of Ageing (MCSA) study (McDonald et al. 2017, manuscript in preparation), are limited by small sample sizes, relatively short follow-up with regard to potential long-term effects, lack of discussion of sensitivity of the envisaged endpoints regarding detection of potential adverse effects, lack of full detailed information on statistical methods and their robustness and that they are overall too limited to provide reassurance about the safety of usage of GdCAs. 
• rezultati iz študije klinike Mayo o staranju (MCSA) (McDonald idr., 2017, rokopis v pripravi) so omejeni zaradi majhnih vzorcev, sorazmerno kratkotrajnega nadaljnjega spremljanja morebitnih dolgotrajnih učinkov, odsotnosti razprave o občutljivosti predvidenih končnih točk pri ugotavljanju morebitnih neželenih učinkov, pomanjkanja popolnih in podrobnih informacij o statističnih metodah in njihovi zanesljivosti ter na splošno prevelike omejenosti, da bi lahko potrdili varnost uporabe sredstev GdCA.
The MAHs provided several proposals for risk minimization measures with regards the accumulation and retention of GdCA in the brain of patients exposed to these agents during diagnostic procedures: 
Imetniki dovoljenja za promet z zdravilom so predlagali več ukrepov za zmanjšanje tveganja v zvezi s kopičenjem in zadrževanjem sredstev GdCA v možganih bolnikov, ki so tem sredstvom izpostavljeni med diagnostičnimi postopki:
• the delayed phase that relies on selective uptake of a GdCA by functioning hepatocytes, which results in enhancement and visualisation of the normal hepatic parenchyma while improving the delineation and detection of lesions such as cysts and hepatocellular carcinomas. 
• zapoznele faze, ki je odvisna od selektivne absorbcije sredstva GdCA s strani funkcionalnih hepatocitov, s čimer se izboljšata kontrast in vizualizacija normalnega jetrnega parenhima, hkrati pa tudi prikaz in odkrivanje lezij, kot so ciste in hepatocelularni karcinomi.
• the dynamic phase, for which all the authorised GdCAs can provide enhancement of liver imaging, 
• dinamične faze, v kateri lahko vsa odobrena sredstva GdCA izboljšajo kontrast pri slikanju jeter;
The brain soluble fractions from animals receiving linear agents contained a proportion of macromolecules; gadolinium-bound macromolecules were not detected in the brain of animals that received macrocyclic agents. 
Topni deli možganov živali, ki so prejele linearna sredstva, so vsebovali delež makromolekul; v možganih živali, ki so prejele makrociklična sredstva, makromolekule, vezane na gadolinij, niso bile ugotovljene.
For all Gd contrast agents, the experts stated that the general “As Low As Reasonably Achievable” (ALARA) principles should be used and that the exposure to all GdCAs should be minimised, either by reducing the dose or using alternative diagnostic methods, if possible. 
Strokovnjaki so povedali, da bi bilo treba za vsa gadolinska kontrastna sredstva uporabljati splošna načela „tako nizko, kakor je to mogoče doseči z uporabo razumnih ukrepov“ in da bi bilo treba izpostavljenost vsem sredstvom GdCA zmanjšati z zmanjšanjem odmerka ali uporabo nadomestnih diagnostičnih metod, če je mogoče.
Perfusion imaging in MRI is typically performed both at rest and during pharmacological stress (for example, with adenosine or dipyridamole), and utilizes a dynamic imaging technique in which signal intensity in the myocardium is evaluated during the passage of the contrast bolus. 
Perfuzijsko slikanje pri MRI se po navadi opravi v mirovanju in med farmakološko obremenitvijo (npr. z adenozinom ali dipiridamolom) s tehniko dinamičnega slikanja, pri kateri se intenzivnost signala v miokardiju oceni med izločanjem kontrastnega sredstva iz bolusa.