A resonance sonorheometry guided dose reduction of plasma transfusion in repetitive hip surgery in a patient with a severe factor XI deficiency: a case report.

Factor XI deficiency is a rare disorder with an unpredictable bleeding tendency. Here, we report the successful use of the sonic estimation of elasticity via resonance sonorheometry for guiding the management of haemostasis in a patient with a severe factor XI deficiency in repeated revision hip surgeries. Regardless of an administration of fresh frozen plasma, a significant haemorrhage occurred at the first of three hip surgeries. The repeat application of fresh frozen plasma normalised the prolonged activated partial thromboplastin time and the resonance sonorheometry clot time values; the factor XI activity increased to a sufficient level. No significant bleeding occurred in the second and third hip surgery. Using a resonance sonorheometry guided approach in haemostasis management has the potential to improve safety for patients with factor XI deficiency undergoing surgery by ensuring sufficient clotting and preventing side effects.

Assessment of the genotoxic and carcinogenic risks of p-nitrophenol when it is present as an impurity in a drug product.

According to the 2008 US FDA (draft) and 2006 EMEA guidance documents for genotoxic impurities, an impurity that is positive in an in vitro genotoxicity study, in the absence of in vivo genotoxicity or carcinogenicity data, should be treated as genotoxic and typically controlled to 1.5 microg/day for chronic use. For p-nitrophenol (PNP), existing study results (i.e., positive in vitro clastogenicity in mammalian cells, no information on its in vivo genotoxicity, and negative with respect to carcinogenicity in a dermal mouse study with no confirmation of systemic exposure) indicated that it should be considered genotoxic and exposure as a drug impurity limited. Therefore, to more completely characterize the genotoxic potential of PNP (consistent with the guidance documents), in vivo mouse micronucleus and dermal pharmacokinetic bridging studies were conducted. In the micronucleus study, PNP was negative, demonstrating that the reported in vitro clastogenicity is not present in vivo. In the pharmacokinetic study, PNP was well absorbed dermally, validating the negative dermal carcinogenicity assessment. These results indicate that PNP should be considered a non-genotoxic impurity and, as a drug impurity, a threshold limit of 4 mg/day would be set (per ICH Q3C). This threshold limit is higher than the EPA reference dose (listed in the 2006 Edition of the Drinking Water Standards and Health Advisories), so if present at such levels, the specification limits for PNP should be determined on a case-by-case basis, based on risk-benefit.

The General Electric-Association of University Radiologists Radiology Research Academic Fellowship (GERRAF). An industry-academic collaboration to improve clinical research in radiology.

The association of GE Medical Systems and the AUR represents a unique collaboration between academic radiology and industry that bears important potential for elevating the quality of clinical research in radiology and developing a cadre of high-quality radiologist researchers for the future. The establishment of the GERRAF is especially timely given the new imperatives of the rapidly changing health care environment, with its emphasis on expenditure reduction. The ultimate goals of GERRAF are to develop research leaders for radiology that will provide guidance for appropriate clinical practice, better train future researchers, and secure the role of radiologists in caring for patients.