Citations

AbstractTissue kallikrein KLK1 and the kallikrein-related peptidases KLK2–15 are a subfamily of serine proteases that have defined or proposed roles in a range of central nervous system (CNS) and non-CNS pathologies. To further understand their potential activity in multiple sclerosis (MS), serum levels of KLK1, 6, 7, 8 and 10 were determined in 35 MS patients and 62 controls by quantitative fluorometric ELISA. Serum levels were then correlated with Expanded Disability Status Scale (EDSS) scores determined at the time of serological sampling or at last clinical follow-up. Serum levels of KLK1 and KLK6 were elevated in MS patients (p≤0.027), with highest levels associated with secondary progressive disease. Elevated KLK1 correlated with higher EDSS scores at the time of serum draw and KLK6 with future EDSS worsening in relapsing remitting patients (p≤0.007). Supporting the concept that KLK1 and KLK6 promote degenerative events associated with progressive MS, exposure of murine cortical neurons to either kallikrein promoted rapid neurite retraction and neuron loss. These novel findings suggest that KLK1 and KLK6 may serve as serological markers of progressive MS and contribute directly to the development of neurological disability by promoting axonal injury and neuron cell death.

Abstract Background: We investigated whether higher concentrations of N-terminal pro–B-type natriuretic peptide (NT-proBNP) predicts cardiovascular adverse events (CV-AEs) in patients with osteoarthritis treated with antiinflammatory drugs. Methods: NT-proBNP was measured in baseline samples from 433 patients enrolled in a prospective randomized study designed to test the therapeutic effect of a novel metalloproteinase inhibitor. We monitored CV-AEs and retrospectively investigated their relationship to the concomitant use of selective cyclooxygenase-2 inhibitors (coxibs), traditional nonsteroidal antiinflammatory drugs (tNSAIDs), and glucocorticoids. CV-AEs included myocardial infarction, stroke, new or worsening of preexisting arterial hypertension, congestive heart failure, and several less severe CV-AEs. Results: We observed 82 mild to serious CV-AEs during an observational period of 200 days. The risk of such events was 1.95-fold higher in patients who were taking tNSAIDs, glucocorticoids, or coxibs (i.e., any inhibitor) and who had NT-proBNP concentrations ≥100 ng/L than in patients taking any inhibitor who had NT-proBNP values <100 ng/L (P < 0.05). Patients taking coxibs (alone or in addition to tNSAIDs or glucocorticoids) with baseline NT-proBNP values ≥100 ng/L had a 7.41-fold higher risk for CV-AEs than those with baseline values <100 ng/L (P < 0.01). Patients who were taking 2 or more antiinflammatory drugs and had NT-proBNP values ≥100 ng/L had a 3.74-fold higher risk for CV-AEs than those with NT-proBNP values <100 ng/L (P < 0.05). An NT-proBNP value <100 ng/L was associated with negative predictive values of >85% across all treatment groups. Conclusions: NT-proBNP may be a useful marker for anticipating cardiovascular risk associated with the use of antiinflammatory drugs for osteoarthritis.

✓Reconstruction of extensive nerve defects is hampered by the amount of autogenous nerve tissue available for transplantation and by donor site morbidity. Nerve allografts, being of foreign origin and potentially unlimited in supply, provide a solution to these problems. Studies have shown that nerve allotransplants require immunosuppression only until end-organ connections are made and that immunosuppressant therapy may be subsequently discontinued with no negative effect on functional outcome. Also, recent experimental and clinical focus has been on shorter periods of immunosuppression in order to reduce risk, even stopping immunosuppression after regeneration has reached the distal suture line rather than before recovery of end-organ connections. In the pediatric population, the increased disease burden and increased potential for nerve regeneration as well as the frequent availability of a living related donor make allografts all the more attractive as solutions to nerve reconstructive problems. Nevertheless, the risks of immunosuppression must not be underemphasized, and they deserve more attention in the current nerve transplantation literature. The authors report on a child who, at the age of 1 year, received a nerve allograft from a living related donor who was positive for Epstein–Barr virus (EBV). The child quickly developed a symptomatic EBV infection concurrent with immunosuppressant drug therapy. The immunosuppression regimen was stopped prematurely, and the patient suffered only a short illness, but the EBV infection could have developed into a life-threatening posttransplant lymphoproliferative disorder (PTLD). The patient is consequently predisposed to develop PTLD and will have to be monitored for the rest of his life. This case highlights the importance of considering the potentially fatal risks associated with this elective procedure. Future studies are needed to quantify and minimize this complication. Nevertheless, it should be weighed against the potential functional benefit from using nerve allografts.

The objective of this study was to assess growth patterns of hyperlipidemic children enrolled in a preventive cardiovascular health clinic. A retrospective chart review of hyperlipidemic children enrolled in the Mayo Clinic Cardiovascular Health Clinic for the Young was performed. All participants were counseled to eat an American Heart Association Step-One Diet and exercise regularly. Weight and height were measured every 3 months. Growth was assessed using attained heights and weights and body-mass index Z scores compared to standard distributions for North American children. Sixty-three patients (33 males and 30 females) were enrolled in the study. Mean age at clinic entrance was 7.8 ± 3.5 years (range: 2 to 16 years). We conclude that participation in a preventive health clinic is generally safe for hyperlipidemic children. However, medical management of hyperlipidemic children must include meticulous surveillance to detect the infrequent occurrence of excessive weight loss or weight stabilization resulting from inappropriate response to dietary counseling.

To study the effect of severe undernutrition on linear growth during adolescence, a report was obtained on the ultimate adult height of 71 patients who had had anorexia nervosa at or before age 16 years. At time of diagnosis (ages 9-16 years) median height percentile was 49; at adult follow-up (ages 18-29 years) the median height percentile was 55. This change favoring growth was statistically significant (p < 0.01). Height percentile was maintained or increased in 45 patients and decreased in 26 patients. In only four patients did it change by more than 20 percentile points downward; in 12 patients height percentile increased by more than 20 points. We conclude that, despite weight loss of up to 45 percent at or before age 16 years, most patients with anorexia nervosa continue to grow in stature according to expected norms.