Pathophysiology of nerve injury

The response to nerve injury is a complex and often poorly understood mechanism. An in-depth and current command of the relevant neuroanatomy, classifications systems, and responses to injury and regeneration are critical to current clinical success. Continued progress must be made in our current understanding of these varied physiologic mechanisms of neuro-regeneration if any significant progress in clinical treatments or outcome is to be expected in the future. Reconstructive surgeons have in many ways maximized the technical aspects of peripheral nerve repair. However, advances in functional recovery may be seen with improvements in sensory and motor rehabilitation after peripheral nerve surgery and with a combined understanding of the neurobiology and neurophysiology of nerve injury and regeneration.     

Effects of delaying FK506 administration on neuroregeneration in a rodent model

FK506 is an immunosuppressant drug that has been shown experimentally to stimulate nerve growth and speed functional recovery, when administered immediately after peripheral nerve injury. However, the clinical scenario of a peripheral nerve injury is often associated with either a delayed diagnosis or reconstruction. The purpose of this study was to determine the efficacy of FK506 on neuroregeneration with delayed administration. Thirty-two Lewis rats underwent tibial nerve transection with immediate repair. Animals were left untreated, or were treated with daily injections of FK506 (2 mg/kg), started on the day of surgery, postoperative day 3, or postoperative day 5. Animals underwent walking track analysis to assess functional nerve recovery. Nerves were harvested for histomorphometric analysis on postoperative days 21, 28, and 42. Histomorphometry demonstrated that all treatment groups, regardless of the time of drug initiation, demonstrated evidence of enhanced neuroregeneration, compared to the untreated group. Histomorphometric data from groups harvested on day 21 demonstrated a statistically significant improvement in neuroregeneration in the immediate and 3-day delay groups. Therefore, the beneficial effects of FK506 on neuroregeneration are not restricted to immediate administration, but these effects significantly diminish when FK506 is administered 3 days after nerve injury.     

Acute exercise and T-lymphocyte expression of the early activation marker CD69

PURPOSE: This study aimed to determine the effect of acute exercise on the proliferation and expression of activation markers on T-lymphocytes. METHODS: Seventeen well-trained male endurance runners completed 60 min of treadmill running at 95% of ventilatory threshold and a resting, no exercise, control session at the same time of day. Five blood samples were collected at each session: before exercise, mid-exercise, immediately after exercise, and 30 min and 60 min after exercise. Isolated peripheral blood mononuclear cells (PBMC) were stimulated with the mitogen PHA. Activation was measured using the expression of CD69 (assessed by three-color flow-cytometry), and cellular proliferation was assessed using 3-(4,5-dimethlthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye uptake. RESULTS: At all sampling points, there was a significant difference (P < 0.05) in the percentage of CD4 and CD8 cells that became activated (CD69+) after mitogen stimulation (68% of CD4 compared with 45% of CD8 cells). Exercise had no effect on the percentage of cells that became activated in response to mitogen. There was a significant exercise-induced decrease in lymphocyte proliferation of PBMC, but when expressed per-T-cell (CD3+), there was no difference between the exercise and control condition. CONCLUSION: This study indicated that on an individual cell basis 1 h of exercise at 95% of ventilatory threshold did not alter the ability of T-lymphocytes (CD3+) or T-lymphocyte subsets (CD3+CD4+ and CD3+CD8+) to become activated and did not alter the ability of T-lymphocytes to proliferate.     

The combination of cognitive testing and an informant questionnaire in screening for dementia

Aim: A cognitive test and an informant report questionnaire were used together to investigate whether their combined use could improve the accuracy of detecting dementia in a memory clinic, compared with either test used alone. METHOD: The subjects were 323 patients assessed at a memory clinic. The Mini-Mental State Examination and the short form of the Informant Questionnaire on Cognitive Decline in the Elderly were used. A method of combining the test scores developed by Mackinnon and Mulligan [Am J Psychiatry 1998; 155: 1529-35] was used. Dementia was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised criteria. RESULTS: Logistic regression analysis showed that the combination of the Mini-Mental State Examination and the Informant Questionnaire on Cognitive Decline in the Elderly produced a slightly more accurate prediction of dementia caseness than either test used alone. Using receiver operating characteristic analysis the performance of the combination of the tests according to a weighted sum rule was compared with the performance of either test used alone. This way of combining the tests resulted in a more accurate screening for dementia than when the Informant Questionnaire on Cognitive Decline in the Elderly was used alone. The area under the receiver operating characteristic curve for the Mini-Mental State Examination combined with the Informant Questionnaire on Cognitive Decline in the Elderly was 0.89 compared with 0.82 for the Informant Questionnaire on Cognitive Decline in the Elderly alone (chi-square = 10.63; P = 0.0011). However, there was no improvement in screening performance when the combination of Mini-Mental State Examination and Informant Questionnaire on Cognitive Decline in the Elderly was compared with the Mini-Mental State Examination used alone (area under the receiver operating characteristic curve = 0.89 versus 0.86; chi-square = 3.54; P = 0.060). CONCLUSION: The combination of cognitive testing and an informant report according to a weighted sum rule in this population did not result in any advantage over the use of the Mini-Mental State Examination alone. The mixed results of this study contrast with those of Mackinnon and Mulligan.     

Serum profiles of insulin-like growth factors and their binding proteins in adults with growth hormone receptor deficiency treated with insulin like growth factor I

Six adult patients with growth hormone receptor deficiency (GHRD) (2 men, 4 women) with an identical defect in the growth hormone receptor (GHR) gene, were treated with recombinant human insulin-like growth factor I (IGF-I), 40 μgikg S.C. twice daily, for 7 days. Serum concentrations of IGF peptide and IGF binding protein-3 (IGFBP-3) were measured by specific radioimmunoassays; serum IGFBPs were also measured by Western ligand blotting. The size distribution of both IGF-I and IGF-II was measured in serum following size-exclusion fast-performance liquid chromatography. IGF-I treatment resulted in a normalization of serum IGF-I levels on days 1–7 of treatment and a decrease in serum IGF-II levels. The fall in IGF-II levels and the simultaneous rise in IGF-I levels, however, resulted in an unchanged total serum IGF level. The low IGFBP-3 values did not significantly change during treatment, whereas there was a slight increase in IGFBP-2 levels. Preliminary analysis of size-fractionated sera suggested an increase in IGF-I levels in the 40 and 150 kDa regions at the expense of IGF-II levels. The results suggest that despite the failure of IGF-I treatment to increase IGFBPs significantly, serum IGFBP concentrations were sufficient to maintain normal levels of IGF-I. 0 Laron syndrome, growth hormone receptor deficiency, insulin-like growth factors, insulin-like growth factor binding protein