Elevation of activated protein C in synovial joints in rheumatoid arthritis and its correlation with matrix metalloproteinase 2

OBJECTIVE: To investigate the involvement of the anticoagulant serine protease activated protein C (APC) in tissue remodeling in rheumatoid arthritis (RA). METHODS: PC/APC, matrix metalloproteinase 2 (MMP-2), and MMP-9 were detected in synovial fluid by Western blotting, and their antigen levels were quantified by enzyme-linked immunosorbent assay in patients with osteoarthritis (OA) or RA. Enzymatic activity of MMP-2 was assayed using a specific fluorogenic substrate. We developed an improved assay to measure APC activity in synovial fluid utilizing a chromogenic substrate following immunoprecipitation with a specific PC/APC antibody. PC/APC and MMP-2 were localized by immunohistochemistry in RA, OA, and normal synovial tissues. RESULTS: Synovial fluid analysis demonstrated that APC is present in both RA and OA synovial fluid, with APC activity being markedly higher in RA (mean +/- SEM 462 +/- 112 ng/ml versus 136 +/- 42 ng/ml; P < 0.02). A correlation (r(2) = 0.61) was found between APC and MMP-2 activity levels in RA patients, but not in OA patients. Immunohistochemical studies of synovial sections showed colocalization of APC and MMP-2 in endothelial and synovial lining cells. Additionally, APC and MMP-2 coimmunoprecipitated with an anti-PC/APC antibody. CONCLUSION: Our results show, for the first time, that APC and MMP-2 are coordinately up-regulated and tightly bound in RA synovial fluid and colocalized in synovia. Their association suggests that APC may modulate MMP-2 activity in RA.     

Comparison of Fentanyl Versus Meperidine for Analgesia in Pediatric Gastrointestinal Endoscopy

This study compared the safety and efficacy of fentanyl and meperidine for analgesia in pediatric gastrointestinal endoscopy. In a double-blind, randomized trial, 24 patients (11 males) received either fentanyl (1 microg/kg) or meperidine (1 mg/kg). These analgesics were administered in unmarked syringes by an investigator who did not participate in the procedure or in the evaluation of the patient's sedation. There were 17 Caucasians and 7 African-Americans whose mean age was 10.4 +/- 4.4 years. Thirteen patients received meperidine and 11 received fentanyl. Midazolam was given to all patients as needed to provide sufficient sedation for the procedure. Study subjects underwent EGD (n = 17) or colonoscopy (n = 7). There were no differences as assessed by patient, endoscopist, or assistant for tolerance, discomfort, procedure ease, recovery time, complications, heart rate, blood pressure, or oxygen saturation. We conclude that meperidine and fentanyl are equally effective in providing analgesia for pediatric gastrointestinal endoscopy.     

Non-invasive prenatal testing for single gene disorders: exploring the ethics

Non-invasive prenatal testing for single gene disorders is now clearly on the horizon. This new technology offers obvious clinical benefits such as safe testing early in pregnancy. Before widespread implementation, it is important to consider the possible ethical implications. Four hypothetical scenarios are presented that highlight how ethical ideals of respect for autonomy, privacy and fairness may come into play when offering non-invasive prenatal testing for single gene disorders. The first scenario illustrates the moral case for using these tests for ‘information only'', identifying a potential conflict between larger numbers of women seeking the benefits of the test and the wider social impact of funding tests that do not offer immediate clinical benefit. The second scenario shows how the simplicity and safety of non-invasive prenatal testing could lead to more autonomous decision-making and, conversely, how this could also lead to increased pressure on women to take up testing. In the third scenario we show how, unless strong safeguards are put in place, offering non-invasive prenatal testing could be subject to routinisation with informed consent undermined and that woman who are newly diagnosed as carriers may be particularly vulnerable. The final scenario introduces the possibility of a conflict of the moral rights of a woman and her partner through testing for single gene disorders. This analysis informs our understanding of the potential impacts of non-invasive prenatal testing for single gene disorders on clinical practice and has implications for future policy and guidelines for prenatal care.     

The Neurocognitive Performance of Female Veterans With Posttraumatic Stress Disorder

Neurocognitive problems are common with posttraumatic stress disorder (PTSD) and are important to understand because of their association with the success of PTSD treatment and its potential neural correlates. To our knowledge, this is the first neurocognitive study in an all‐female U.S. veteran sample, some of whom had PTSD. We examined neurocognitive performance and assessed whether learning deficits, common in PTSD, were associated with executive functioning. Veterans with PTSD (n = 56) and without (n = 53) were evaluated for psychiatric and neurocognitive status. The PTSD group had a lower estimated IQ (d = 0.53) and performed more poorly on all neurocognitive domains (d range = 0.57–0.88), except verbal retention (d = 0.04). A subset of the 2 groups that were matched on IQ and demographics similarly demonstrated poorer performance for the PTSD group on all neurocognitive domains (d range = 0.52–0.79), except verbal retention (d = 0.15). Within the PTSD group, executive functioning accounted for significant variance in verbal learning over and above IQ and processing speed (ΔR² = .06), as well as depression (ΔR² = .07) and PTSD severity (ΔR² = .06). This study demonstrated that female veterans with PTSD performed more poorly than females without PTSD on several neurocognitive domains, including verbal learning, processing speed, and executive functioning. Replication of these results using a control group of veterans with more similar trauma exposure, history of mild traumatic brain injury, and psychiatric comorbidities would solidify these findings.