Citations

We have prospectively studied the outcome of infections associated with implants which were retained and treated using a standardised antimicrobial protocol. Over a period of four years, we studied 24 consecutive patients who had symptoms of infection for less than one year, a stable implant, no sinus tract and a known pathogen which was susceptible to recommended antimicrobial agents. The infections involved hip prostheses (14), knee prostheses (5), an internal fixation device (4), and an ankle prosthesis (1). Twenty patients had a successful outcome at a median follow-up of 3.7 years (1.8 to 4.7); four had failure of the implant after a median follow-up of 1.2 years (0.3 to 2.5). The probability of survival without failure of treatment was 96% at one year (95% confidence interval (CI) 88 to 100), 92% at two years (95% CI 80 to 100) and 86% at three years (95% CI 72 to 100). Patients with a short-term infection but with a stable implant, no sinus tract and a known pathogen may be successfully treated by retention of the implant and the use of a standardised regimen of antimicrobial treatment.

Abstract Mantle-cell lymphoma (MCL) is a unique subtype of B-cell non-Hodgkin lymphoma (NHL) that behaves aggressively and remains incurable. In order to understand the pathogenesis of MCL and design new therapies, it is important to accurately analyze molecular changes in pathways dysregulated in MCL. We used antibody microarrays to compare patterns of protein expression between CD19+ purified B lymphocytes from normal tonsil and 7 cases of histologically confirmed MCL. Protein overexpression was defined as a higher than 1.3-fold or 2-fold increase in at least 67% of tumor samples compared with normal B-cell control. Of the polypeptides, 77 were overexpressed using the higher than 1.3-fold cutoff, and 13 were overexpressed using the 2-fold cutoff. These included cell cycle regulators (regulator of chromosome condensation 1 [RCC1], murine double minute 2 [MDM2]), a kinase (citron Rho-interacting kinase [CRIK]), chaperone proteins (heat shock 90-kDa protein [Hsp90], Hsp10), and phosphatase regulators (A-kinase anchor protein 1 [AKAP149], protein phosphatase 5 [PP5], and inhibitor 2). The elevated expression of some of these polypeptides was confirmed by immunoblotting and immunohistochemistry, whereas elevated expression of others could not be confirmed, illustrating the importance of confirmatory studies. This study describes a novel technique that identifies proteins dysregulated in MCL.

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.