Involvement of ADAM10 in axonal outgrowth and myelination of the peripheral nerve

The disintegrin and metalloproteinase 10 (ADAM10) is a membrane‐anchored metalloproteinase with both proteolytic and disintegrin characteristics. Here, we investigate the expression, regulation, and functional role of ADAM10 in axonal outgrowth and myelination of the peripheral nerve. Expression pattern analysis of 11 ADAM family members in co‐cultures of rat dorsal root ganglia (DRG) neurons and Schwann cells (SCs) demonstrated the most pronounced mRNA expression for ADAM10. In further studies, ADAM10 was found to be consistently upregulated in DRG‐SC co‐cultures before the induction of myelination. Neurons as well as SCs widely expressed ADAM10 at the protein level. In neurons, the expression of ADAM10 was exclusively limited to the axons before the induction of myelination. Inhibition of ADAM10 activity by the hydroxamate‐based inhibitors GI254023X and GW280264X resulted in a significant decrease in the mean axonal length. These data suggest that ADAM10 represents a prerequisite for myelination, although its activity is not required during the process of myelination itself as demonstrated by expression analysis of myelin protein zero (P0) and Sudan black staining. Hence, during the process of myelin formation, ADAM10 is highly upregulated and appears to be critically involved in axonal outgrowth that is a requirement for myelination in the peripheral nerve. © 2009 Wiley‐Liss, Inc.     

Effects of cognitive behavioral therapy on work outcomes in vocational rehabilitation for participants with schizophrenia spectrum disorders

Designed to help persons with schizophrenia to persist and perform better at job placements, the Indianapolis Vocational Intervention Program (IVIP) is a program of cognitive-behavioral group and individual interventions. While its feasibility has been previously demonstrated, it is unknown whether IVIP assists persons to achieve greater levels of participation in vocational rehabilitation and higher levels of job performance. In this study, 100 participants with schizophrenia or schizoaffective disorder were offered a six month job placement and randomized to receive IVIP (n = 50) or support services (n = 50) matched for treatment intensity. Number of hours worked was recorded weekly and job performance was assessed biweekly using the Work Behavior Inventory with raters blind to condition. t-tests revealed that participants in the IVIP group worked a significantly greater number of weeks than those in the support condition. Also, repeated measures ANOVA revealed the IVIP group worked more hours across that 26 week period as well. And with regards to work performance, repeated measures of the 56 participants who worked for at least two-thirds of the intervention revealed that participants in the IVIP group had generally better work performance than those in the support condition. Results suggest a connection between cognitive-behavioral interventions and higher levels of work performance in people with schizophrenia.     

Comparison of effects and plasma concentrations of opioids between elderly and middle-aged patients after cardiac surgery

Background: In elderly patients, opioids may cause prominent postoperative sedation and respiratory depression. We evaluated the influence of age on the effects of opioids and plasma concentrations of fentanyl and oxycodone in cardiac surgery patients.
Methods: Thirty (≥75 years, gender M9/F21) and 20 (≤60 years, gender M20/F0) patients scheduled to undergo cardiac surgery. A standard anesthesia with fentanyl as an opioid was used. Fentanyl plasma concentrations were measured at the end of surgery and 2 h later. After tracheal extubation, when the pain intensity was at least moderate, blood samples for fentanyl and oxycodone plasma concentration measurements were taken. Thereafter, oxycodone hydrochloride 0.05 mg/kg i.v. was administered. After 15 and 45 min, pain intensity, sedation and oxycodone plasma concentration were determined. This test protocol was repeated twice.
Results: The elderly had a higher plasma concentration of fentanyl at the end of surgery than younger patients (5.7±2.2 vs. 3.8±1.2 ng/ml, P =0.001). The plasma concentrations of oxycodone were comparable between the groups. The interval between the second and the third oxycodone dose was longer in the elderly patients ( P =0.036). Pain intensity on the verbal rating scale was lower at the 45-min assessment point after all three oxycodone test doses ( P =0.008) and sedation scores were significantly higher after the third dose in the elderly patients ( P =0.035).
Conclusions: In elderly patients, the plasma concentration of fentanyl was higher but plasma levels of oxycodone were at a similar level compared with middle-aged patients. However, the elderly patients had less pain and were more sedated after doses of oxycodone.     

Results of non-operative treatment following hip fracture compared to surgical intervention

We followed all consecutive hip fracture patients admitted between 2004 and 2006, identified cases in which the intention was to treat non-operative and compared their functional outcome and mortality with a similar cohort treated surgically over the same period. We recorded length of hospital stay, place of discharge, pre and post-fracture mobility and residence, 30 days and 1 year mortality, re-admission due to same fracture and delayed surgery. The group treated surgically was recruited and matched for age, gender, pre and post-fracture mobility, mental confusion and independence. 25 patients were treated non-operative. 22 patients treated surgically over the same time period matched the patient characteristics of the non-operative arm. The mean hospital stay was 13 days in both groups. There were 4 extra-capsular fractures (3 displaced) and 21 intra-capsular fractures (5 displaced) in the non-operative arm and 11 extra-capsular fractures and 9 intra-capsular fractures in the surgically treated arm. 4 patients from the non-operative treatment group underwent late surgery because of persisting hip pain 20 days-2 months after the index event (2 cannulated screws, 1 hemiarthroplasty, 1 total hip arthroplasty). 11 patients in the surgical treatment arm underwent dynamic screw fixation, 1 had cannulated screw, 1 had total hip replacement and 7 had hemiarthroplasty. 14 of the non-operative treated patients were mobile independently or with aid before fracture but only 9 patients retained their pre-fracture mobility following treatment, compared to 16 patients pre-fracture and 11 patients post-fracture after surgery. 16 patients treated non-operative were living independently prior to injury but only 7 went back to their own residence. Of the operatively treated patients 14 patients were living independently and 10 patients went back to their previous residence. 1 month and 1 year mortality in the non-operative treated group was 4/21 and 7/21 respectively compared to 1/20 and 5/20 in the operative fixation group. There was no statistically significant difference in mobility, residence or mortality between the two groups (Fisher exact test, p > 0.05). Non-operative management after hip fracture is suitable for medically unfit patients and does not result in statistically significant difference in functional outcome or mortality compared to patients treated surgically.