A granulomatous conundrum: Concurrent necrobiosis lipoidica,cutaneous sarcoidosis and erythema nodosum in a nondiabetic patient

Necrobiosis lipoidica (NL) and cutaneous sarcoidosis are granulomatous disorders with a largely unknown aetiopathogenesis. Evidence of co‐existing NL and sarcoidosis in the same patient may suggest a degree of overlap between these entities through shared granulomatous inflammatory pathways. Occasionally, one condition can mimic the other, making their distinction difficult. We report a novel case of a non‐diabetic woman who presented with concurrent NL, cutaneous sarcoidosis and erythema nodosum. We discuss some of the complexities distinguishing these entities and propose that they may represent different stages of the same granulomatous process linked through yet unknown pathomechanisms.     

Psychiatric Care in Epilepsy Surgery: Who Needs It?

At present there is considerable variability in the psychiatric evaluation and follow-up of patients in epilepsy surgery programs globally. There is a large body of research now demonstrating heightened risk for psychological disturbance in surgically remedial patients before and after surgery. This evidence provides a compelling case for the routine provision of psychiatric and psychological treatment to optimize the benefits of epilepsy surgery and patient outcomes. In a comprehensive model of care, presurgical psychiatric and psychosocial evaluation plays an integral role in shaping the team''s understanding of surgical candidacy and the patient''s capacity for informed consent. After surgery, efficacious treatment of psychiatric comorbidity increases the likelihood of seizure freedom as well as optimizes psychosocial functioning and quality of life. By contrast, failure to treat can allow psychiatric comorbidity to persist or psychological difficulties to develop as the patient adjusts to life after surgery.     

Making meaning: the creative component in qualitative research

Findings in qualitative research are often wondrous and exciting, expounding new knowledge and perceptions previously unknown. Qualitative research requires the researcher to ponder and reflect on the data collected so as to find the meaning within. Helping researchers learn how to perform this step is not well discussed in the qualitative literature, yet this is one of the more crucial components of this type of research. In this article, the incubation, the meaning-making phase of qualitative research, is discussed in relation to the experiences of five researchers who have used traditional processes, models, metaphors, plays, pastiche, poetry, and quilt making and design to help them make meaning.     

Common human UGT1A polymorphisms and the altered metabolism of irinotecan active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38)

7-Ethyl-10-hydroxycamptothecin (SN-38) is the pharmacologically active metabolite of irinotecan, in addition to being responsible for severe toxicity. Glucuronidation is the main metabolic pathway of SN-38 and has been shown to protect against irinotecan-induced gastrointestinal toxicity. The purpose of this study was to determine whether common polymorphic UDP-glucuronosyltransferase (UGT) affects SN-38 glucuronidation. First, kinetic characterization of SN-38-glucuronide (SN-38-G) formation was assessed for all known human UGT1A and UGT2B overexpressed in human embryonic kidney 293 cells. To assess the relative activity of UGT isoenzymes for SN-38, rates of formation of SN-38-G were monitored by liquid chromatography/mass spectrometry analysis and normalized by level of UGT cellular expression. Determination of intrinsic clearances predicts that hepatic UGT1A1 and UGT1A9 and the extrahepatic UGT1A7 are major components in SN-38-G formation, whereas a minor role is suggested for UGT1A6, UGT1A8, and UGT1A10. In support of the involvement of UGT1A9, a strong coefficient of correlation was observed in the glucuronidation of SN-38 and a substrate, mainly glucuronidate, by UGT1A9 (flavopiridol) by human liver microsomes (coefficient of correlation, 0.905; p = 0.002). In vitro functional experiments revealed a negative impact of the UGT1A1 allelic variants. Residual activities of 49, 7, 8, and 11% were observed for UGT1A1*6 (G(71)R), UGT1A1*27 (P(229)Q), UGT1A1*35 (L(233)R), and UGT1A1*7 (Y(486)D), respectively. Common variants of UGT1A7, UGT1A7*3 (N(129)K;R(131)K;W(208)R), and UGT1A7*4 (W(208)R), displayed residual activities of 41 and 28% compared with the UGT1A7*1 allele. Taken together, these data provide the evidence that molecular determinants of irinotecan response may include the UGT1A polymorphisms studied herein and common genetic variants of the hepatic UGT1A9 isoenzyme yet to be described.     

Collaboration among nurse executives in complex environments: fostering administrative best practice

In the past decade, many healthcare institutions have formed new partnerships, alliances, and networks. Collaboration among chief nursing officers and other leaders from affiliating institutions is essential to the success of these new organizational structures. The authors explore the nature of the collaboration among chief nursing officers and senior nurse leaders at 5 Harvard-affiliated teaching hospitals that provide cancer care. In particular, this article examines how collaborative relationships have been fostered and highlights the challenges, benefits, and outcomes of successful cross-institutional collaboration.