Citations

ABSTRACT The efficiency of viruses in cancer therapy is enhanced by proteins that mediate the fusion of infected cells with their neighbors. It was reported that replication-competent adenovirus particles can spread between nuclei within fusion-generated syncytia. To assess this conjecture, we generated fusogenic adenoviruses that express a balanced ratio of the F and H glycoproteins of measles virus. The viruses displayed enhanced cytotoxicity but largely unchanged replication efficiencies compared to a nonfusogenic virus. Most notably, the virus genomes did not spread through fusion-generated multinuclear cells. Hence, adenovirus replication in syncytia remains largely restricted to initially transduced nuclei.

AbstractA conference of genetic counseling and clinical nurse specialist graduate program directors was hosted by the National Society of Genetic Counselors and funded by the Ethical, Legal, and Social Implications Program of the National Center for Human Genome Research in June 1992. One aspect of the conference addressed implications of the Human Genome Initiative for graduate education in genetic counseling. Within this paper, the topics of human variation and diversity, genetic discrimination, issues in non‐directiveness, and genetic screening and policy development are reviewed and recommendations made for graduate curricula development and enhancement. In addition, suggestions are included for practicing genetic counselors.

OBJECTIVE: To review dexamethasone interaction with corticotropin stimulation testing, particularly as it applies to treating septic shock. DATA SOURCES: Pertinent literature was identified through MEDLINE (1966–February 2004) using combinations of the key words dexamethasone, adrenocorticotropic hormone stimulation, and pretreat. Only articles written in the English language and evaluating human subjects were considered. Reference lists of identified articles were reviewed for additional citations. DATA SYNTHESIS: Accurate interpretation of the corticotropin stimulation test is important to identify patients with septic shock who may benefit from corticosteroid supplementation. In healthy volunteers, short-term dexamethasone administration prior to the corticotropin stimulation test may depress the baseline cortisol level, but does not inhibit the response to the corticotropin challenge. This may result in a slight increase in the difference between baseline and post-stimulation values. CONCLUSIONS: In 2 small trials in healthy adults, short-term, low-dose dexamethasone pretreatment decreased baseline cortisol levels, but values following corticotropin stimulation were unaffected. Accordingly, caution in interpreting corticotropin stimulation test results is warranted. However, the application of the findings from these studies to patients with septic shock is difficult, given the important differences in physiology between normal and septic patients. As of December 29, 2004, a dexamethasone dose >2 mg or prolonged dexamethasone therapy (>2 days, totaling 4 mg) preceding corticotropin stimulation has not been studied in any population.

OBJECTIVE: To report a case of pulmonary hypersensitivity associated with furazolidone use and review the literature on this topic. CASE SUMMARY: A 43-year-old white female presented with fever and dyspnea. She had recently completed a course of furazolidone 125 mg 4 times daily for 10 days for enteritis. Investigations revealed bibasilar interstitial infiltrates on chest X-ray, hypoxia, and 21% eosinophilia. Her fever, hypoxia, and dyspnea rapidly abated following discontinuation of furazolidone and administration of corticoteroids. DISCUSSION: Furazolidone is a bactericidal agent used to treat infectious enteropathies. It is chemically similar to nitrofurantoin, which is well known to cause pulmonary hypersensitivity reactions. Application of the Naranjo probability scale suggests that a furazolidone adverse reaction in this patient was probable. A MEDLINE search from 1966 to October 2004 revealed 2 previously reported cases suggestive of furazolidone pulmonary hypersensitivity. All published reports closely resemble each other and descriptions of nitrofurantoin-associated pulmonary hypersensitivity reactions. CONCLUSIONS: Furazolidone may induce pulmonary hypersensitivity reactions; clinicians should be aware of this potentially serious adverse effect.

Abstract The physiology of early-diastolic filling comprises ventricular performance and fluid dynamical principles. Elastic recoil and myocardial relaxation rate determine left ventricular early diastolic performance. The integrity of left ventricular synchrony and geometry is essential to maintain the effect of their timely action on early diastolic left ventricular filling. These factors not only are prime determinants of left ventricular pressure decay during isovolumic relaxation and immediately after mitral valve opening; they also instigate the generation of a sufficient intra-ventricular pressure gradient, which enhances efficient early diastolic left ventricular filling. Accurate assessment of diastolic (dys)function by non-invasive techniques has important therapeutic and prognostic implications but remains a challenge to the cardiologist. The evaluation of left ventricular relaxation by the standard Doppler echocardiographic parameters is hindered by their preload dependency. The colour M-mode velocity propagation of early diastolic inflow (Vp) correlates with intra-ventricular pressure gradients and is a largely preload independent index of ventricular diastolic performance. In this article, the physiologic background, utility and limitations of this promising new tool for the study of early diastolic filling are reviewed.

Abstract The PAX8/PPARγ (PPFP) fusion-oncogene is moderately specific for follicular thyroid carcinomas (FTC). It remains unknown whether this can be translated into improved diagnosis, classification, or outcome prediction. We studied a cohort of well-characterized follicular adenomas (FA), FTC, and Hürthle cell carcinomas (HCC) from patients with complete clinical follow-up, to determine whether PPARγ immunohistochemistry (as a surrogate of PAX8/PPARγ expression) helps to distinguish FA from FTC and to assess its diagnostic accuracy as an adjunct to frozen section. We also correlated PPARγ staining with clinical outcomes to assess its role as a prognostic marker. PPARγ staining was more common in FTC (31 of 54; 57%) than in HCC (one of 23; 4%) or FA (four of 31; 13%) (P < 0.000001). Adjunctive use of PPARγ immunohistochemistry improved diagnostic sensitivity of intraoperative frozen section from 84% to 96% (P < 0.05) but reduced specificity from 100% to 90% (P < 0.05). PPARγ staining was associated with favorable prognostic indicators (female gender, better tumor differentiation, and lesser risk of metastases). PPARγ staining may be helpful in the differential diagnosis of FA, FTC, and HCC, particularly when diagnostic sensitivity of histomorphology is reduced (e.g. during intraoperative frozen section). PPARγ staining also shows an association with favorable prognosis and may have a role in risk stratification.