ABSTRACT
The emergence of an association between gadolinium-based contrast agents (GBCA) and the rare condition nephrogenic systemic fibrosis (NSF) led to a warning in 2006 from the Food and Drug Administration (FDA) restricting the use of the GBCAs to patients with an estimated glomerular filtration rate of >30 mL/min/1.73m(2) . We discuss our experience with a post-FDA restriction presentation of NSF and subsequent patient death in which the prolonged lead-time of â¼5.5 years led to challenges in ensuring a secure diagnosis of NSF and establishing risk exposures. Accurate contemporary records of contrast administration and clinical factors alongside clinical and pathological expertise ensured that we were able to confidently diagnose NSF, despite the length of lead time and confounding factors.
Subject(s)
Drug Approval , Gadolinium DTPA/adverse effects , Magnetic Resonance Imaging/adverse effects , Magnetic Resonance Imaging/standards , Nephrogenic Fibrosing Dermopathy/diagnosis , Practice Guidelines as Topic , Aged , Contrast Media/adverse effects , Diagnosis, Differential , Gadolinium/adverse effects , Humans , Male , United StatesABSTRACT
DNA damage in human spermatozoa has been associated with a range of adverse clinical outcomes, including infertility, abortion, and disease in the offspring. We have advanced a two-step hypothesis to explain this damage involving impaired chromatin remodeling during spermiogenesis followed by a free radical attack to induce DNA strand breakage. The objective of the present study was to test this hypothesis by determining whether impaired chromatin protamination is correlated with oxidative base damage and DNA fragmentation in human spermatozoa. DNA fragmentation, chromatin protamination, mitochondrial membrane potential, and formation of the oxidative base adduct, 8-hydroxy-2'-deoxyguanosine (8OHdG), were monitored by flow cytometry/fluorescence microscopy. Impairment of DNA protamination during late spermatogenesis was highly correlated (P < 0.001) with DNA damage in human spermatozoa. The disruption of chromatin remodeling also was associated with a significant elevation in the levels of 8OHdG (P < 0.001), and the latter was itself highly correlated with DNA fragmentation (P < 0.001). The significance of oxidative stress in 8OHdG formation was demonstrated experimentally using H2O2/Fe2+ and by the correlation observed between this base adduct and superoxide generation (P < 0.001). That 8OHdG formation was inversely associated with mitochondrial membrane potential (P < 0.001) suggested a possible role for these organelles in the creation of oxidative stress. These results clearly highlight the importance of oxidative stress in the induction of sperm DNA damage and carry significant implications for the clinical management of this condition.
Subject(s)
Chromatin Assembly and Disassembly/physiology , DNA Damage/physiology , Deoxyguanosine/analogs & derivatives , Oxidative Stress , Spermatozoa/metabolism , 8-Hydroxy-2'-Deoxyguanosine , Adult , Biomarkers/metabolism , Chromatin/metabolism , DNA Damage/genetics , Deoxyguanosine/metabolism , Efficiency , Humans , Infertility, Male/metabolism , Infertility, Male/pathology , Male , Membrane Potential, Mitochondrial/physiology , Oxidative Stress/genetics , Oxidative Stress/physiology , Protamines/metabolism , Spermatozoa/pathology , Spermatozoa/physiology , Superoxides/metabolism , Young AdultABSTRACT
The authors report a case of portal vein thrombosis, with no underlying malignant cause identified, which was initially detected by fludeoxyglucose positron emission tomography/CT (FDG PET/CT) and subsequently confirmed by both contrast enhanced CT and MRI. The multimodality imaging findings are outlined, the potential clinical implications discussed and note made of the possible FDG PET/CT mimics of this disorder.