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James H. Wible - One of the best experts on this subject based on the ideXlab platform.
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Cardiac magnetic resonance imaging safety following percutaneous coronary intervention
The International Journal of Cardiovascular Imaging, 2013Co-Authors: Jason W. Curtis, James H. Wible, Donna C. Lesniak, Pamela K. WoodardAbstract:In the first 8 weeks after percutaneous coronary intervention (PCI), possible negative interactions exist between the cardiac magnetic resonance (CMR) imaging environment and the weakly ferromagnetic material in coronary stents. There are circumstances when CMR would be indicated shortly following PCI, such as acute myocardial infarction (AMI). The purpose of this study is to demonstrate CMR safety shortly following stent PCI in AMI patients. We performed a retrospective analysis of safety data in AMI patients with recently placed coronary artery stents enrolled in a multi-center phase II trial for Gadoversetamide. Patients underwent 1.5T CMR within 16 days of PCI. Vital signs (blood pressure, heart rate, respiratory rate, and body temperature) and ECGs were taken pre-CMR, 1, 2, and 24 h post-CMR. Any major adverse cardiac event (MACE) or other serious adverse events in the first 24 h after MRI were recorded. There were 258 stents in 211 AMI patients. The mean delay to CMR following PCI was 6.5 ± 4 days, with 62 patients (29 %) receiving CMR within 3 days and 132 patients (63 %) within 1 week. Patients showed no significant vital sign changes following CMR. Ten patients (4.7 %) showed mild, transient ECG changes. Within the 24-h follow-up group, 4 patients (1.9 %) had moderate to severe events, including chest pain (1) and elevated cardiac enzymes (1), resolving in 24 h; heart failure (1) and ischemic stroke (1). There were no deaths. This study demonstrates fewer MACE in AMI patients undergoing 1.5T CMR within 16 days of stent placement in comparison to post-stent event rate reported in the literature. This study adds to the CMR after stent PCI safety profile suggested by previous studies and is the largest and first study that uses multicenter data to assess stent safety following CMR examination.
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Pharmacokinetics of Gadoversetamide injection, a gadolinium-based contrast agent, in pediatric patients.
Magnetic Resonance Imaging, 2009Co-Authors: James H. Wible, Prasad N.v. Tata, Alicia M. Napoli, Lisa H. Lowe, Gregory L. KearnsAbstract:Abstract Objective The pharmacokinetics of Gadoversetamide were examined in pediatric patients scheduled to undergo contrast-enhanced MRI of the central nervous system. Materials and Methods One hundred patients received an intravenous injection of Gadoversetamide at a dose of 0.1 mmol/kg for a contrast-enhanced MRI procedure. A subpopulation of 30 patients were enrolled to evaluate the pharmacokinetics of Gadoversetamide in patients 2–11 and 12–18 years of age. Serial blood and urine samples were collected before and after the administration of Gadoversetamide. Results The terminal half-life, initial concentration and area under the curve assessments for Gadoversetamide showed no significant ( P >.05) differences between the age groups or the sexes. Although no sex-related differences occurred in the volume of distribution or clearance, significant ( P Conclusions The pharmacokinetic behavior of Gadoversetamide was not significantly altered by differences in age or sex in pediatric patients from 2 to 18 years of age. Although significant differences in volumes of distribution, and clearance occurred between the age groups, these differences appeared to depend on body size rather than on age in pediatric patients between 2 and 18 years of age.
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performance of delayed enhancement magnetic resonance imaging with Gadoversetamide contrast for the detection and assessment of myocardial infarction an international multicenter double blinded randomized trial
Circulation, 2008Co-Authors: Timothy S E Albert, James H. Wible, Michele Parker, Michael D Elliott, John C Allen, Alicia Napoli, Robert M JuddAbstract:Background— The identification and assessment of myocardial infarction (MI) are important for therapeutic and prognostic purposes, yet current recommended diagnostic strategies have significant limitations. We prospectively tested the performance of delayed-enhancement magnetic resonance imaging (MRI) with gadolinium-based contrast for the detection of MI in an international, multicenter trial. Methods and Results— Patients with their first MI were enrolled in an acute (≤16 days after MI; n=282) or chronic (17 days to 6 months; n=284) arm and then randomized to 1 of 4 doses of Gadoversetamide: 0.05, 0.1, 0.2, or 0.3 mmol/kg. Standard delayed-enhancement MRI was performed before contrast (control) and 10 and 30 minutes after Gadoversetamide. For blinded analysis, precontrast and postcontrast MRIs were randomized and then scored for enhanced regions by 3 independent readers not associated with the study. The infarct-related artery perfusion territory was scored from x-ray angiograms separately. In total, 56...
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Safety of Gadoversetamide in patients with acute and chronic myocardial infarction.
Journal of Magnetic Resonance Imaging, 2008Co-Authors: Steffen Huber, James H. Wible, Raja Muthupillai, Benjamin Cheong, Dipan J. Shah, Pamela K. Woodard, Frank Grothues, Heiko Mahrholdt, Carlos E. Rochitte, O. MasoliAbstract:1,3–5Purpose: To assess the safety data from two large, multi-center, phase 2 trials on the use of Gadoversetamide (Op-tiMARK, Tyco Healthcare/Mallinckrodt, St. Louis, MO) as acontrast agent in delayed hyperenhancement magneticresonance imaging (DE-MRI) in patients with acute andchronic myocardial infarction (MI).Materials and Methods: The study population from bothtrials comprised 577 patients who were randomly assignedto one of four dose groups (0.05, 0.1, 0.2, or 0.3 mmol/kg)before undergoing DE-MRI. Safety evaluations includedphysical and electrocardiographic (ECG) examinations. Vi-tal signs, laboratory values, adverse events (AE), and seri-ous adverse events (SAE) were monitored before and aftercontrast administration.Results: Of the 577 patients who received gadoverset-amide, 124 (21.5%) reported a total of 164 AEs; most weremild (139 AEs; 84.8%) or moderate (25 AEs; 15.2%). ECG-related changes were the most frequent AE. Site investiga-tors judged only eight AEs as likely related to gadoverset-amide and only two of the eight as clinically relevant.Further evaluation suggested neither AE was related toGadoversetamide. Two SAEs were reported, but none wasjudged related to Gadoversetamide by the site investigators.Conclusion: Gadoversetamide is safe for use in patientswith acute or chronic MI up to a dose of 0.3 mmol/kg.Key Words: contrast agent; safety; Gadoversetamide; de-layed hyperenhancement magnetic resonance imaging;gadolinium chelatesJ. Magn. Reson. Imaging 2008;28:1368–1378.© 2008 Wiley-Liss, Inc.
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Measurement of serum calcium concentration after administration of four gadolinium-based contrast agents to human volunteers.
American Journal of Roentgenology, 2007Co-Authors: Jeffery J. Brown, Michael R. Hynes, James H. WibleAbstract:OBJECTIVE. The purpose of this study was to use three analytic methods to measure serum calcium concentration to assess the magnitude and time course of the effects of four gadolinium-based contrast agents.SUBJECTS AND METHODS. After providing informed consent, 12 healthy adult volunteers (mean age, 38.6 ± 13.6 [SD] years) received IV injections of Gadoversetamide, gadodiamide, gadopentetate dimeglumine, and gadoteridol at a dose of 0.1 mmol/kg. Blood samples were obtained before contrast administration and 5, 10, 15, 30, 60, 90, 120, 180, and 240 minutes after contrast injection. Serum calcium levels were measured with an orthocresolphthalein complexone method, an arsenazo III method, and inductively coupled plasma mass spectrometry (ICP-MS). Analyses of variance coupled with a Dunnett test were used to compare baseline serum calcium measurements with values at the different time points after injection.RESULTS. Administration of Gadoversetamide or gadodiamide caused no significant change in serum calcium...
Henrik S. Thomsen - One of the best experts on this subject based on the ideXlab platform.
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nephrogenic systemic fibrosis a serious adverse reaction to gadolinium 1997 2006 2016 part 2
Acta Radiologica, 2016Co-Authors: Henrik S. ThomsenAbstract:Most reports have been based on pathological or nephrological registers rather than the prospective examination of the skin of exposed patients. The prevalence of nephrogenic systemic fibrosis (NSF) after exposure to gadodiamide has been reported to be in the range of 3–7% in patients with reduced renal function (1). In patients with CKD 5 (GFR less than 15mL/min 1.73m) reviewed prospectively, it may be as much as 18% (2); all patients with suspicious lesions had a skin biopsy. The prevalence was higher after two or more injections (36%) than after a single injection (12%), indicating a cumulative effect (2). In Boston 30% of patients on dialysis had developed NSF based on a systematic examination of the patients in five dialysis centers, but skin biopsies were only taken in a few patients (3). In the peer-reviewed literature only one center has reported a large number (>10) of NSF cases after gadopentetate dimeglumine (3), but many centers have reported more than 10 cases after gadodiamide (1). This difference is not just a reflection of the market share of the two products, because gadopentetate dimeglumine has been administered to as many as 4–5 times the number of patients who have had gadodiamide. In the Four American University Study, the overall incidence was 0.039% after gadodiamide and 0.003% after gadopentetate dimeglumine (4). The benchmark incidence of NSF was one in 2913 patients who underwent gadodiamide-enhanced magnetic resonance imaging (MRI) and one in 44,224 patients who underwent gadopentetate dimeglumine-enhanced MRI (P< 0.001). The study was based on patient records from databases of dermatology, pathology, internal medicine, nephrology, transplant surgery, and radiology departments and not on a systematic examination of patients with reduced renal function exposed to a gadolinium-based contrast agent. By 1 February 2008, 190 cases (confirmed by biopsy and clinical examination) had been reported in the peerreviewed literature: 157 had had gadodiamide, eight gadopentetate, three Gadoversetamide, and in five no exposure could be verified. In 18, the agent could not be identified and four received several agents (5). Up to 2012, a total of 711 NSF cases were published (6), but it is likely that they are only a small percentage of all cases. The true number of patients who developed NSF is not known because only two studies included systematic inspection of the skin in patients with reduced renal failure or on dialysis, so patients may have died with or of undiagnosed NSF between 1996 and 2006. Simple review of patient records is not enough to determine the true prevalence.
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Nephrogenic systemic fibrosis: a serious adverse reaction to gadolinium – 1997–2006–2016. Part 2
Acta Radiologica, 2016Co-Authors: Henrik S. ThomsenAbstract:Most reports have been based on pathological or nephrological registers rather than the prospective examination of the skin of exposed patients. The prevalence of nephrogenic systemic fibrosis (NSF) after exposure to gadodiamide has been reported to be in the range of 3–7% in patients with reduced renal function (1). In patients with CKD 5 (GFR less than 15mL/min 1.73m) reviewed prospectively, it may be as much as 18% (2); all patients with suspicious lesions had a skin biopsy. The prevalence was higher after two or more injections (36%) than after a single injection (12%), indicating a cumulative effect (2). In Boston 30% of patients on dialysis had developed NSF based on a systematic examination of the patients in five dialysis centers, but skin biopsies were only taken in a few patients (3). In the peer-reviewed literature only one center has reported a large number (>10) of NSF cases after gadopentetate dimeglumine (3), but many centers have reported more than 10 cases after gadodiamide (1). This difference is not just a reflection of the market share of the two products, because gadopentetate dimeglumine has been administered to as many as 4–5 times the number of patients who have had gadodiamide. In the Four American University Study, the overall incidence was 0.039% after gadodiamide and 0.003% after gadopentetate dimeglumine (4). The benchmark incidence of NSF was one in 2913 patients who underwent gadodiamide-enhanced magnetic resonance imaging (MRI) and one in 44,224 patients who underwent gadopentetate dimeglumine-enhanced MRI (P< 0.001). The study was based on patient records from databases of dermatology, pathology, internal medicine, nephrology, transplant surgery, and radiology departments and not on a systematic examination of patients with reduced renal function exposed to a gadolinium-based contrast agent. By 1 February 2008, 190 cases (confirmed by biopsy and clinical examination) had been reported in the peerreviewed literature: 157 had had gadodiamide, eight gadopentetate, three Gadoversetamide, and in five no exposure could be verified. In 18, the agent could not be identified and four received several agents (5). Up to 2012, a total of 711 NSF cases were published (6), but it is likely that they are only a small percentage of all cases. The true number of patients who developed NSF is not known because only two studies included systematic inspection of the skin in patients with reduced renal failure or on dialysis, so patients may have died with or of undiagnosed NSF between 1996 and 2006. Simple review of patient records is not enough to determine the true prevalence.
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T1 hyperintensity in the brain after multiple intravenous injections of gadolinium-based contrast agents.
Acta Radiologica, 2016Co-Authors: Henrik S. ThomsenAbstract:Before 2006 gadolinium-based contrast media were considered to be safe and this led to very liberal use of these agents. They were even used for conventional X-ray and computed tomography (CT) in patients considered to be at increased risk of contrast-medium–induced nephropathy after administration of iodine-based contrast media. The link between gadolinium and the development of nephrogenic systemic fibrosis (NSF) shocked the radiological community. However, within 2 years of the first reports fromAustria andDenmark (1,2) it was clear thatNSFwas only seen after intravenous administration of the less stable agents and only in patients with severely reduced renal function or on renal replacement therapy. Not all patients who got the least stable agents developed NSF, and some patients had only received a small amount of the contrast agent while others had had large amounts (3). Also, the majority of patients who had reduced renal function and received a gadoliniumbased contrast medium did not develop NSF. Fortunately, stopping the use of the less stable agents in patients with reduced renal function in large part stopped patients developing NSF. However, there are still patients who develop NSFmany years after they had an injection of one of the less stable linear agents (gadodiamide [Omniscan ], gadopentetate dimeglumine [Magnevist ], Gadoversetamide [OptiMARK ]) (3). Just as we thought we were putting the problem of NSF behind us, a new adverse effect after gadoliniumbased contrast media was reported: a slow increase over time in the signal intensity of the dentate nucleus and the globus pallidus on unenhanced T1-weighted (T1W) images. The clinical significance of the increase in intensity is still not known. Unlike NSF, the overwhelming majority of reported cases had normal renal function at the time of administration. Almost 20 years ago, high signal intensity in the basal ganglia was documented in patients with high levels of manganese in the blood (4). The patients developed Parkinsonism-like symptoms. Manganese-based contrast agents were not marketed then, so the high manganese levels came from other sources, such as parenteral nutrition, or high levels of manganese in the air at steel plants. Hyperintensity on unenhanced T1-weighted images
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Gadolinium contrast media during pregnancy and lactation
Acta Radiologica, 2013Co-Authors: Judith A. W. Webb, Henrik S. ThomsenAbstract:Regulatory approval of new drugs, including subsequent new indications, requires that they have undergone preclinical and clinical testing which focuses on safety and efficacy. For contrast media these tests have never included pregnant and lactating women to investigate possible effects on the fetus and neonate. The summary of product characteristics or the package insert includes a statement about this lack of knowledge. Current practice is not based on formal testing, but on small series and case reports of pregnant and lactating women from the peer-reviewed literature, and on our understanding of the pharmacokinetics of contrast media in pregnant and lactating subjects based on animal data. Although no contrast media have been approved for use in pregnant and lactating women, this does not mean that they are contraindicated, but use of contrast media in these subjects will always be off-label. Before 2006 most radiologists believed that gadoliniumbased contrast media were safe and that they could be used when indicated in pregnant and lactating women. The documentation of a link between nephrogenic systemic fibrosis (NSF) and exposure to some gadolinium-based contrast media changed the situation. Now the most unstable agents (those most likely to release gadolinium) are absolutely contraindicated in pregnant women and in lactating women the milk produced within 24 h of administration must be discarded. The other more stable agents may be used in pregnant women if enhanced magnetic resonance imaging (MRI) is clinically indicated, and lactating women can continue breast feeding after enhanced MRI if they wish. Gadolinium-based contrast media have not shown mutagenic or teratogenic effects in animal experimental studies (1). They can cross the placenta in both directions and although they are water soluble, their molecular weight (500–850 Da) means that relatively small amounts cross the single layer of chorionic epithelium which separates the maternal blood from fetal tissue. Pharmacokinetic studies have used mice and rats because murine and human placentas are structurally similar. The maximum fetal concentration was 0.07% of the injected dose when pregnant mice were given high doses of gadoterate meglumine (0.5 mmol per kg) (2), and the maximum fetal gadolinium concentration was only 0.01% of the injected dose when pregnant rats were given 0.3 mmol per kg of gadodiamide (3). Gadolinium contrast agents in the fetal blood are excreted by the fetal kidneys into the bladder which empties into the amniotic fluid. Reabsorption of amniotic fluid occurs both by fetal swallowing and across membranes into the fetal circulation, from which it can cross the chorionic epithelium back into the mother. The whole amniotic fluid volume turns over every 24 h (4). The half-lives of gadodiamide in mouse fetal tissues and the amniotic fluid were 4 h and 5 h, respectively, after a dose of 0.5 mmol per kg to the pregnant mother, with only tiny amounts of gadolinium detectable in the fetus and none detectable in the amniotic fluid at 48 h (2). Similarly, only traces of gadodiamide were detected in fetal tissue at 24 h when pregnant rats were given gadodiamide 0.3 mmol per kg (3). A total of 57 infants whose mothers were given gadopentetate dimeglumine (0.1–0.2 mmol per kg) showed no adverse effects (5–10). Excretion of gadolinium contrast media into milk is limited because the molecules are water soluble and show minimal protein binding. When 20 lactating women were given 0.1–0.2 mmol per kg of gadopentetate, ,0.04% of the dose given was excreted in the milk over 24 h (11). It was estimated that ,1% of the recommended intravenous dose for an infant reaches the gut after a lactating mother is given gadolinium contrast agents intravenously (11). Doses of 0.1 to 0.2 mmol/kg of gadopentetate and gadodiamide are tolerated intravenously by neonates (12, 13). When gadolinium contrast agents are given orally, only tiny amounts are absorbed – ,1% in a study of gadopentetate (14). Thus only a very small amount of gadolinium contrast media should reach the fetal blood when a lactating woman is given gadolinium contrast agents. In gadolinium contrast media, the gadolinium is bound with a chelating agent to prevent exposure of the body to free gadolinium, which is toxic. The molecules of the nonionic linear gadolinium agents gadodiamide and Gadoversetamide are the least stable, so gadolinium is more likely to be released from them. Again, according to laboratory studies, ionic linear chelate molecules (gadopentetate dimeglumine, gadobenate dimeglumine and gadofosveset) have intermediate stability and the macrocyclic agents gadobutrol, gadoteridol, and gadoterate meglumine are the most stable. The stability of gadolinium contrast agents affects the amounts of gadolinium which are retained in the tissues after administration. Tweedle et al. (15) described retention of gadolinium in the liver and bone of mice and rats 14 days after administration of gadolinium agents, with greater amounts retained with linear than macrocyclic agents. Sieber et al. (16) gave high doses of gadolinium agents to rats and found the highest gadolinium concentrations in skin, bone, and liver with gadodiamide. There was 10 times less gadolinium retention in the skin with gadopentetate and 30 times less with gadoterate and gadobutrol. In patients who had received gadolinium agents, four times more gadolinium was retained in the bone after gadodiamide than after gadoteridol (17). The amounts of gadolinium retained in the skin increased over time in patients with NSF (18), raising the suggestion that gadolinium stored in bone might be released over time.
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response to the fda s may 23 2007 nephrogenic systemic fibrosis update
Radiology, 2008Co-Authors: Emanuel Kanal, Dale R Broome, Henrik S. Thomsen, Diego R MartinAbstract:Emanuel Kanal, MD Dale R. Broome, MD Diego R. Martin, MD, PhD Henrik S. Thomsen, MD On May 23, 2007, the Food and Drug Administration (FDA) requested that a “black box” warning (one of the more extreme mechanisms that the FDA may invoke for calling attention to observed serious adverse reactions) regarding the potential risk of nephrogenic systemic fibrosis (NSF) in patients with renal failure be added to the product descriptions of all five FDAapproved gadolinium-based magnetic resonance (MR) contrast agents marketed in the United States: Magnevist (gadopentetate dimeglumine; Bayer Healthcare, Wayne, NJ), MultiHance (gadobenate dimeglumine; Bracco Diagnostics,Princeton,NJ),Omniscan(gadodiamide; GE Healthcare, Oslo, Norway), OptiMARK (Gadoversetamide; Tyco-Mallinckrodt, St Louis, Mo), and ProHance (gadoteridol; Bracco Diagnostics). All five agents were treated equally, in this regard, despite data suggesting that certain agents possessed a seemingly greater risk for precipitating NSF than did others. The authors of this commentary believe this implied equality among the five gadolinium-based agents available in the United States to be imprudent in light of present information. We are concerned as to how the implicationof equivalent risk amonggadolinium-based contrast agents may impact agent selection for renally impaired patients. As such, we provide the following points of information so that all health care providers may make a more fully informed decision regarding the selection of contrast agents for use in patients with renal impairment. 1. Dr Shawn Cowper, who first described NSF in 2000, maintains the Yale NSF Registry, which contains nearly 250 patients. A retrospective review of this database has shown that among patients in whom an exposure could be verified within 2–3 months of NSF onset, approximately 85% of these patients had been administered Omniscan prior to receiving a diagnosis of NSF; the rest had been administered Magnevist (unpublished data, July 16, 2007). Similarly, Thomsen reported, “More than 150 patients have developed NSF after exposure to a Gd-based contrast medium. The overwhelming majority ( 90%) had had gadodiamide with certainty” (1). 2. As of March 12, 2007, a review of the peer-reviewed literature (2) revealed a total of 74 cases of NSF, 72 of which were associated with prior Omniscan administration; one, with prior Magnevist administration; and one, with no gadolinium-based agent identified. There is also one case reported in the peer-reviewed literature (3) of NSF developing in a patient who had received MultiHance and who subsequently received Omniscan before developing NSF. 3. Although the FDA MedWatch database is an unmonitored and largely unverified reporting system, as of April 17, 2007, there were 160 Omniscan-associated cases of NSF, 73 Magnevist-associated cases, and three OptiMARK-associated cases. There were also several known confounded cases reported in which more than one gadolinium-based agent had been administered. There were no reports of NSF after isolated MultiHance or ProHance administration. 4. The UK Commission on Human Medicines in conjunction with the European Pharmacovigilance Party (4) published that, as of June 26, 2007, 180 cases of NSF worldwide had been reported with Omniscan and 78, with Magnevist (with one case in a patient who had received MultiHance and Omniscan.) Several cases have also been reported with OptiMARK in the United States. 5. The June 26, 2007, public assessment report issued by the Commission Published online before print 10.1148/radiol.2461071267
Antonio Alberto Zuppa - One of the best experts on this subject based on the ideXlab platform.
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Radiological contrast media in the breastfeeding woman: a position paper of the Italian Society of Radiology (SIRM), the Italian Society of Paediatrics (SIP), the Italian Society of Neonatology (SIN) and the Task Force on Breastfeeding, Ministry of H
European Radiology, 2014Co-Authors: Maria Assunta Cova, Fulvio Stacul, Roberto Quaranta, Pierpaolo Guastalla, Guglielmo Salvatori, Giuseppe Banderali, Claudio Fonda, Vincenzo David, Massimo Gregori, Antonio Alberto ZuppaAbstract:Objectives Breastfeeding is a well-recognised investment in the health of the mother-infant dyad. Nevertheless, many professionals still advise breastfeeding mothers to temporarily discontinue breastfeeding after contrast media imaging. Therefore, we performed this review to provide health professionals with basic knowledge and skills for appropriate use of contrast media. Methods A joint working group of the Italian Society of Radiology (SIRM), Italian Society of Paediatrics (SIP), Italian Society of Neonatology (SIN) and Task Force on Breastfeeding, Ministry of Health, Italy prepared a review of the relevant medical literature on the safety profile of contrast media for the nursing infant/child. Results Breastfeeding is safe for the nursing infant of any post-conceptional age after administration of the majority of radiological contrast media to the mother; only gadolinium-based agents considered at high risk of nephrogenic systemic fibrosis (gadopentetate dimeglumine, gadodiamide, Gadoversetamide) should be avoided in the breastfeeding woman as a precaution; there is no need to temporarily discontinue breastfeeding or to express and discard breast milk following the administration of contrast media assessed as compatible with breastfeeding. Conclusions Breastfeeding women should receive unambiguous professional advice and clear encouragement to continue breastfeeding after imaging with the compatible contrast media. Key Points: • Breastfeeding is a well-known investment in the health of the mother-infant dyad. • Breastfeeding is safe after administration of contrast media to the mother. • There is no need to temporarily discontinue breastfeeding following administration of contrast media.
Michael R. Hynes - One of the best experts on this subject based on the ideXlab platform.
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Measurement of serum calcium concentration after administration of four gadolinium-based contrast agents to human volunteers.
American Journal of Roentgenology, 2007Co-Authors: Jeffery J. Brown, Michael R. Hynes, James H. WibleAbstract:OBJECTIVE. The purpose of this study was to use three analytic methods to measure serum calcium concentration to assess the magnitude and time course of the effects of four gadolinium-based contrast agents.SUBJECTS AND METHODS. After providing informed consent, 12 healthy adult volunteers (mean age, 38.6 ± 13.6 [SD] years) received IV injections of Gadoversetamide, gadodiamide, gadopentetate dimeglumine, and gadoteridol at a dose of 0.1 mmol/kg. Blood samples were obtained before contrast administration and 5, 10, 15, 30, 60, 90, 120, 180, and 240 minutes after contrast injection. Serum calcium levels were measured with an orthocresolphthalein complexone method, an arsenazo III method, and inductively coupled plasma mass spectrometry (ICP-MS). Analyses of variance coupled with a Dunnett test were used to compare baseline serum calcium measurements with values at the different time points after injection.RESULTS. Administration of Gadoversetamide or gadodiamide caused no significant change in serum calcium...
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Measurement of serum calcium concentration after administration of Gadoversetamide in dogs.
Radiology, 2004Co-Authors: James H. Wible, Michael R. HynesAbstract:PURPOSE: To measure serum calcium concentration with three different analytic methods after administration of Gadoversetamide and three other gadolinium chelates in dogs. MATERIALS AND METHODS: Six dogs were injected with 0.1-, 0.3-, 1.0-, and 3.0-mmol/kg doses of Gadoversetamide; 1.0-mmol/kg doses of gadodiamide, gadopentetate, and gadoteridol; and a 6-mL/kg dose of saline. Baseline blood samples were collected before injection; 5, 15, 30, and 60 minutes after each treatment; and 2, 4, 6, 12, and 24 hours after each treatment. Serum calcium levels were measured with inductively coupled plasma mass spectrometry, an arzenazo III dye assay, and an orthocresolphalthalin (OCP) complexone system. Analysis of variance coupled with the Dunnett procedure was used to compare serum calcium concentrations at different time points after injection with baseline values. RESULTS: Administration of Gadoversetamide caused no decrease in serum calcium levels, as measured with inductively coupled plasma mass spectrometry or...
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Safety assessment of Gadoversetamide (OptiMARK) administered by power injector.
Journal of Magnetic Resonance Imaging, 2003Co-Authors: Nancy Abdou, Alicia M. Napoli, Michael R. Hynes, John Carson Allen, James H. WibleAbstract:Purpose To evaluate the safety of OptiMARK® (Gadoversetamide injection) administered via power injector. Materials and Methods The study population included 144 healthy volunteers aged 18 years or older randomly assigned to one of seven treatment groups (N = 20/group). The safety assessment was based on changes in physical examination, vital signs, electrocardiograms (ECGs), standard clinical laboratory tests, and adverse events (AEs) through a 24-hour postinjection period. Results OptiMARK caused no serious AEs or unexpected changes in physical examinations or laboratory parameters. The changes observed in vital signs and ECG intervals did not vary with changes in injection rate and were not significantly (P < 0.05) different from those elicited by saline administration at the same rates. Conclusion This study demonstrated the safety of OptiMARK when administered via a power injector at rates of 2, 4, and 6 mL/second. J. Magn. Reson. Imaging 2004;19:133–140. © 2003 Wiley-Liss, Inc.
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Toxicological assessment of Gadoversetamide injection (OptiMARK), a new contrast-enhancement agent for use in magnetic resonance imaging.
Investigative Radiology, 2001Co-Authors: James H. Wible, Catherine Troup, Michael R. Hynes, Karen P. Galen, Janice Macdonald, Steven J. Barco, Jolette K. Wojdyla, Muthunadar P. Periasamy, Max D. AdamsAbstract:RATIONALE AND OBJECTIVES A series of preclinical tests were undertaken during the developmental process to determine the safety profile of Gadoversetamide injection (OptiMARK). METHODS Acute intravenous, acute intracisternal, and repeated-dose toxicities; cardiovascular effects; and genetic and reproductive toxicology characteristics were assessed in several animal species. RESULTS Gadoversetamide injection demonstrated an acute intravenous median lethal dose of 25 to 28 mmol/kg and a maximum nonlethal dose of 14 mmol/kg in mice. In the dog, acute administration of Gadoversetamide injection showed a no observable effect level at 3 mmol/kg. Dosed daily for 4 weeks, Gadoversetamide injection (0.1 mmol x kg(-1) x d(-1)) caused no serious irreversible changes in any organs in rats and dogs. At a dose of 0.1 mmol/kg, Gadoversetamide injection caused no significant (P < 0.05) changes in cardiovascular function in anesthetized dogs. Gadoversetamide injection showed no mutagenic activity. Fertility, reproductive performance, and postnatal fetal development were not affected at doses up to 0.5 mmol x kg(-1) x d(-1) in the rat. No teratogenicity was observed at doses up to 4.2 mmol x kg(-1) x d(-1) in the rat and up to 1.6 mmol x kg(-1) x d(-1) in the rabbit. CONCLUSIONS Data from our toxicological assessment demonstrate the safety of Gadoversetamide injection in a number of animal species at doses exceeding the intended human clinical dose.
Maria Assunta Cova - One of the best experts on this subject based on the ideXlab platform.
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Radiological contrast media in the breastfeeding woman: a position paper of the Italian Society of Radiology (SIRM), the Italian Society of Paediatrics (SIP), the Italian Society of Neonatology (SIN) and the Task Force on Breastfeeding, Ministry of H
European Radiology, 2014Co-Authors: Maria Assunta Cova, Fulvio Stacul, Roberto Quaranta, Pierpaolo Guastalla, Guglielmo Salvatori, Giuseppe Banderali, Claudio Fonda, Vincenzo David, Massimo Gregori, Antonio Alberto ZuppaAbstract:Objectives Breastfeeding is a well-recognised investment in the health of the mother-infant dyad. Nevertheless, many professionals still advise breastfeeding mothers to temporarily discontinue breastfeeding after contrast media imaging. Therefore, we performed this review to provide health professionals with basic knowledge and skills for appropriate use of contrast media. Methods A joint working group of the Italian Society of Radiology (SIRM), Italian Society of Paediatrics (SIP), Italian Society of Neonatology (SIN) and Task Force on Breastfeeding, Ministry of Health, Italy prepared a review of the relevant medical literature on the safety profile of contrast media for the nursing infant/child. Results Breastfeeding is safe for the nursing infant of any post-conceptional age after administration of the majority of radiological contrast media to the mother; only gadolinium-based agents considered at high risk of nephrogenic systemic fibrosis (gadopentetate dimeglumine, gadodiamide, Gadoversetamide) should be avoided in the breastfeeding woman as a precaution; there is no need to temporarily discontinue breastfeeding or to express and discard breast milk following the administration of contrast media assessed as compatible with breastfeeding. Conclusions Breastfeeding women should receive unambiguous professional advice and clear encouragement to continue breastfeeding after imaging with the compatible contrast media. Key Points: • Breastfeeding is a well-known investment in the health of the mother-infant dyad. • Breastfeeding is safe after administration of contrast media to the mother. • There is no need to temporarily discontinue breastfeeding following administration of contrast media.
