Increased IL-17 expression in degenerated human discs and increased production in cultured annulus cells exposed to IL-1ß and TNF-α.

IL-17 is expressed in a number of tissues including the intervertebral disc, where it exerts strong inflammatory properties. We evaluated IL-17 using immunolocalization in herniated and non-herniated human discs, IL-17 gene expression, and the production of IL-17 by annulus cells cultured in three dimensions in the presence of IL-1ß or TNF-α. There was no difference in the percentage of IL-17 positive cells in annulus or nucleus in herniated vs. non-herniated disc specimens. Molecular studies confirmed expression of IL-17 in disc tissue, with significantly increased expression in more degenerated discs; there was no difference in expression between herniated vs. non-herniated discs. Exposure to IL-1ß or TNF-α resulted in significantly greater production of IL-17. Our findings expand understanding of IL-17 production by disc cells and reveal the importance of non-canonical IL-17 production in the disc. Significantly greater expression of IL-17 in more degenerated discs adds to our understanding of the changes in disc cell function with advancing stages of disc degeneration.

Human adipose-derived mesenchymal stem cells: serial passaging, doubling time and cell senescence.

Adult adipose-derived mesenchymal stem cells (AD-MSC) are very interesting to our research group because they are easy to harvest, they are abundant in humans, and they have potential clinical applications in autologous cell therapy for disc degeneration. We examined these cells through sequential serial passages to assess osteogenic and chondrogenic capabilities, mean doubling time and cell senescence. Osteogenic and chondrogenic potencies were maintained through 13 passages. Mean passage doubling time increased significantly with increasing passage number. When donor age was evaluated, passages 1-4 from older donors had significantly longer doubling times compared to cells from younger donors. Passages 5-11 showed similar findings when analyzed by donor age. The mean percent senescence increased significantly with cell passaging, rising from 0% at passage 1 to 3.4% at passage 13. These novel data suggest that caution should be exercised when using AD-MSC with long passage times.

Comparison of coronary artery calcification scores and National Cholesterol Education program guidelines for coronary heart disease risk assessment and treatment paradigms in individuals with chronic traumatic spinal cord injury.

OBJECTIVE: To investigate the risk of coronary heart disease (CHD) in individuals with spinal cord injury (SCI) according to the National Cholesterol Educational Program (NCEP) guidelines and CT coronary artery calcium scores (CCS). RESEARCH: Cross-sectional study of consecutive sample of males with SCI presenting to a single site for CHD risk assessment. PARTICIPANTS/METHODS: Males age 45-70 with traumatic SCI (American Spinal Injury Association (ASIA) A, B, and C) injured for at least 10 years with no prior history of clinical CHD. Medical history, blood-pressure, and fasting lipid panel were used to calculate risk for CHD with the use of the Framingham risk score (FRS). Risk and treatment eligibility status was assessed based on NCEP/FRS recommendations and by presence and amount of CCS. Percent agreement (PA) and kappa were calculated between the two algorithms. Spearman correlations were calculated between CCS and FRS and individual risk factors. RESULTS: A total of 38 men were assessed; 18 (47.4%) had CCS > 0. The PA between NCEP/FRS assessment and CCS was 18% with a kappa of -0.03. 11 (28.9%) had CCS > 100 or >75th percentile for their age, sex, and race, which might qualify them for lipid-lowering treatment. Only 26 were placed into the same treatment category by NCEP/FRS and CCS, for a PA of 68% with a kappa of 0.35. In all, 20 (52.6%) were eligible for lipid-lowering treatment by either NCEP/FRS (n=9) or CCS (n = 11). Seven subjects were above the treatment threshold based on CCS, but not NCEP/FRS and five subjects were above the NCEP/FRS threshold, but not CCS. Just four subjects were eligible by both algorithms. CCS only correlated with FRS (r = 0.508, P = 0.001) and age (r = 0.679, P < 0.001).

Course of relapsing-remitting multiple sclerosis before, during and after natalizumab.

The consequences of interruption of natalizumab treatment are incompletely known. The objective was to assess the confirmed annualized relapse rates for patients preceding initiation, during and following suspension of natalizumab therapy. A chart review was conducted and data were analyzed using the Generalized Estimating Equations. During natalizumab therapy the confirmed annualized relapse rate was 0.08, compared to 0.52 (p = 0.0003) during the prior 12 months and to 0.35 (p = 0.0032) during the following 3 to 24 months. Similar results were found when confirmed and unconfirmed were analyzed. To conclude, following cessation of natalizumab therapy disease activity rapidly returned to pre-natalizumab levels.

Pushing the envelope in biomaterial research: initial results of prosthetic coating with stem cells in a rat model.

BACKGROUND: Coating prosthetic for hernia repair with a patient's own cells could improve biocompatibility by decreasing inflammation and adhesion formation and by increasing tissue ingrowth and resistance to infection. The objective of this study was to prove the feasibility of prosthetic coating with stem cells and to assess its resistance to adhesion formation when implanted in an animal model. METHODS: Adult Lewis rat bone marrow stem cells were harvested and cultured. Stem cells were then implanted on three different prosthetics. The prosthetic with the best stem cell adherence was implanted intraperitoneally into six adult rats. Untreated prosthetic was implanted in control animals (n = 12). After 2 weeks, intra-abdominal adhesions were graded using an adhesion scoring scale by two surgeons who were blinded to the animal group. Data were analyzed using the Wilcoxon rank-sum test. RESULTS: Stem cells demonstrated the best adherence and growth on polyglactin prosthetics. After implantation, the stem cell-coated polyglactin prosthetic had <25% of its surface area covered with adhesions in five (83%) samples, whereas the control polyglactin group had only one sample (8.3%) with <25% adhesions, and seven of its samples (58.3%) had >50% surface area adhesions (p < 0.05). CONCLUSIONS: The feasibility of hernia prosthetic coating with stem cells was demonstrated. Furthermore, stem-cell coated polyglactin prosthetic exhibited improved biocompatibility by decreasing adhesion formation in an animal model. Further study is needed to determine the factors that promote stem cell adherence to prosthetics and the in vivo prosthetic biomechanics after stem cell coating. This work is underway in our laboratory.

Reduction of dietary magnesium by only 50% in the rat disrupts bone and mineral metabolism.

INTRODUCTION: The objective of this study was to determine the effect of a moderate reduction of dietary magnesium [50% of nutrient requirement (50% NR)] on bone and mineral metabolism in the rat, and to explore possible mechanisms for the resultant reduced bone mass. METHODS: Female rats were 6 weeks of age at the start of study. Serum magnesium (Mg), calcium (Ca), parathyroid hormone (PTH), 1,25(OH)(2)-vitamin D, alkaline phosphatase, osteocalcin, and pyridinoline were measured during the study at 3- and 6-month time points in control (dietary Mg of 100% NR) and Mg-deficient animals (dietary Mg at 50% NR). Femurs and tibias were also collected for mineral content analyses, micro-computerized tomography, histomorphometry, and immunohistochemical localization of substance P, TNFalpha, and IL-1beta at 3 and 6 months. RESULTS: Although no significant change in serum Mg was observed, Mg deficiency developed, as assessed by the reduction in bone Mg content at the 3- and 6-month time points (0.69+/-0.05 and 0.62+/-0.04% ash, respectively, in the Mg depletion group compared to 0.74+/-0.04 and 0.67+/-0.04% ash, respectively, in the control group; p=0.0009). Hypercalcemia did not develop. Although serum Ca level remained in the normal range, it fell significantly with Mg depletion at 3 and 6 months (10.4+/-0.3 and 9.6+/-0.3 mg/dl, respectively, compared to 10.5+/-0.4 and 10.1+/-0.6 mg/dl, respectively, in the control group; p=0.0076). The fall in serum Ca in the Mg-depleted animals was associated with a fall in serum PTH concentration between 3 and 6 months (603+/-286 and 505+/-302 pg/ml, respectively, although it was still higher than the control). The serum 1,25(OH)(2)-vitamin D level was significantly lower in the Mg depletion group at 6 months (10.6+/-7.1 pg/ml) than in the control (23.5+/- 12.7 pg/ml) (p<0.01 by the t-test). In Mg-deficient animals, no difference was noted in markers of bone turnover. Trabecular bone mineral content gain was less over time in the distal femur with Mg deficiency at 3 and 6 months (0.028+/-0.005 and 0.038+/-0.007 g, respectively, compared to 0.027+/-0.004 and 0.048+/-0.006 g, respectively, in the control group; p<0.005). Histomorphometry at these time points demonstrated decreased trabecular bone volume (15.76+/-1.93 and 14.19+/-1.85%, respectively, compared to 19.24+/-3.10 and 17.30+/-2.59%, respectively, in the control group; p=0.001). Osteoclast number was also significantly increased with Mg depletion (9.07+/-1.21 and 13.84+/-2.06, respectively, compared to 7.02+/-1.89 and 10.47+/-1.33, respectively, in the control group; p=0.0003). Relative to the control, immunohistochemical staining intensity of the neurotransmitter substance P and of the cytokines TNFalpha and IL-1beta was increased in cells of the bone microenvironment in the Mg depletion group, suggesting that inflammatory cytokines may contribute to bone loss. CONCLUSION: These data demonstrate that Mg intake of 50% NR in the rat causes a reduced bone mineral content and reduced volume of the distal femur. These changes may be related to altered PTH and 1,25(OH)(2)-vitamin D formation or action as well as to an increase release of substance P and the inflammatory cytokines TNFalpha and IL-1beta.

Evaluation of adhesion formation, mesh fixation strength, and hydroxyproline content after intraabdominal placement of polytetrafluoroethylene mesh secured using titanium spiral tacks, nitinol anchors, and polypropylene suture or polyglactin 910 suture.

BACKGROUND: The purpose of this study is to evaluate fixation methods for polytetrafluoroethylene (ePTFE) mesh with an in vivo model of laparoscopic ventral hernia repair. METHODS: In 40 New Zealand white rabbits, a 4 x 4-cm ePTFE mesh (n = 80, two per animal) was attached to an intact peritoneum with polyglactin 910 (PG 910) (n = 20) or polypropylene (PP) (n = 20) suture, titanium spiral tacks (TS) (n = 20), or nitinol anchors (NA) (n = 20). Mesh was harvested at 8 and 16 weeks for fixation strength testing, adhesion assessment, and collagen (hydroxyproline) content. Fixation strength on day 0 was determined with mesh attached to harvested abdominal wall. Statistical significance was determined as p < 0.05. RESULTS: There was no difference in fixation strength between PP (39.1 N) and PG 910 (40.0 N) sutures at time zero. At week 8, PP (25.7 N) was significantly stronger (p < 0.05) than PG 910 (11.4 N) suture, but not at week 16. The fixation strength of TS and NA (day 0, 15.4 vs 7.4 N; week 8, 17.5 vs 15.3 N; week 16, 19.1 vs 13.8 N) was not significantly different. Fixation with PP suture was significantly (p < 0.05) stronger than that with TS and NA at day 0 (39.1, 15.4, and 7.4 N, respectively) but not at weeks 8 or 16. The fixation strength of suture decreased significantly (p < 0.05) from day 0 to week 16 (PP: day 0 = 39.1 N, week 8 = 25.7 N, week 16 = 21.4 N; PG 910: day 0 = 40.0 N, week 8 = 11.4 N, week 16 = 12.8 N). The fixation strength of NA and TS did not change significantly (NA: day 0 = 7.4 N, week 8 = 15.3 N, week 16 = 13.8 N; TS: week 0 = 15.4 N, week 8 = 17.5 N, week 16 = 19.1 N). There were no differences in adhesion area based on fixation device used; however, there were more (p < 0.05) mesh samples using NA with adhesions compared to TS and adhesion tenacity was greater (p < 0.05) compared to that of TS, PP, and PG. Hydroxyproline content at weeks 8 and 16 was similar for all fixation devices. CONCLUSIONS: The initial fixation strength for nonabsorbable suture is significantly greater than that of the metallic fixation devices, but after 8 weeks there is no difference. Laparoscopic ventral hernia repair without transabdominal suture fixation may be predisposed to acute failure. The metallic devices have similar fixation strength, although the incidence of adhesions and tenacity of adhesions appear to be greater with the nitinol anchors. Since these devices have similar fixation strengths and most likely provide adequate supplementation to transabdominal sutures for mesh fixation after laparoscopic ventral hernia repair, their use should be based on other factors, such as their propensity for adhesions, ease of application, and cost.

Randomized controlled trial of pilocarpine hydrochloride for the moderation of oral mucositis during autologous blood stem cell transplantation.

Pilocarpine hydrochloride has been reported to increase salivation and decrease oral mucositis in patients receiving head and neck radiotherapy, but there is only one report of its use in a cancer chemotherapy patient population. This prospective, double-blinded, randomized, placebo-controlled trial was undertaken to determine the efficacy of pilocarpine for the moderation of oral mucositis during autologous blood stem cell transplantation. Subjects were randomized to receive a 5 mg tablet of pilocarpine, or a placebo, during and following chemotherapy. Subjects were seen every other day and evaluated for gingival, oral, and oropharyngeal mucositis; nutrition; oral hygiene; eating; speaking; sleeping; pain at rest and/or with swallowing; and mouth dryness. We recorded the mean and highest scores and duration of problems, along with white blood cell counts and differentials, and the use of systemic narcotics for oral mucosal pain. We enrolled and randomized 36 subjects, and there were no statistically or clinically significant differences for the primary outcome of severity of mucositis and no clinically significant differences in any of the other outcome measures. Pilocarpine has no benefit for the moderation of the incidence, severity, or duration of mucositis in patients receiving autologous blood stem cell transplantation.

Effect of carbon dioxide pneumoperitoneum and wound closure technique on port site tumor implantation in a rat model.

BACKGROUND: The purpose of this study was to evaluate the effects of carbon dioxide (CO2) pneumoperitoneum and wound closure technique on port site tumor implantation. METHODS: A standard quantity of rat mammary adenocarcinoma (SMT2A)was allowed to grow in a flank incision in Wistar-Furth rats (n = 90) for 14 days. Thereafter, 1-cm incisions were made in each animal in three quadrants. There were six control animals. The experimental animals were divided into a 60-min CO2 pneumoperitoneum group (n = 42) and a no pneumoperitoneum (n = 42) group. The flank tumor was lacerated transabdominally in the experimental groups. The three wound sites were randomized to closure of (a) skin; (b) skin and fascia; and (c) skin, fascia, and peritoneum. The abdominal wounds were harvested en bloc on postoperative day 7. RESULTS: Histologic comparison of the port sites in the pneumoperitoneum and no-pneumoperitoneum groups did not demonstrate a statistically significant difference in tumor implantation for any of the closure methods. Evaluation of the closure techniques showed no statistical difference between the pneumoperitoneum group and the no-pneumoperitoneum group in the incidence of port site tumor implantation. Within the no-pneumoperitoneum group, there was a significant increase (p = 0.03) in tumor implantation with skin closure alone vs all three layers. Additionally, when we compared all groups by closure technique, the rate of tumor implantation was found to be significantly higher (p = 0.01) for skin closure alone vs closure of all three layers. CONCLUSIONS: This study suggests that closure technique may influence the rate of port site tumor implantation. The use of a CO2 pneumoperitoneum did not alter the incidence of port site tumor implantation at 7 days postoperatively.

Alterations in growth plate and articular cartilage morphology are associated with reduced SOX9 localization in the magnesium-deficient rat.

Insufficient dietary magnesium (Mg) intake has been associated with low bone mass in humans,and recent basic science studies have indicated that this bone loss may be secondary to increased release of substance P and TNFc Much less is known about the effects of low Mg intake on cartilage. We have evaluated growth plate and articular cartilage in rats following a 6 month dietary Mg restriction. Histomorphometry demonstrated significantly decreased distal femur articular cartilage chondrocyte density and decreased tibial growth plate width in experimental animals compared to controls. Growth plates of Mg-restricted animals showed reduced chondrocyte column formation. Extracellular matrix of both articular cartilage and growth plates in experimental animals contained reduced amounts of proteoglycans. Immunolocalization of Sox9 was decreased in both articular and growth plate cartilage in experimental animals compared to controls, suggesting that reduced Mg intake causes cartilage changes that may be secondary to reduced levels of the SOX9 transcription factor.

Cell shape and gene expression in human intervertebral disc cells: in vitro tissue engineering studies.

The objective of the present study was to examine the relation between gene expression and the shape of human intervertebral disc cells cultured in vitro in three-dimensional (3D) scaffolds. Disc cells from 19 subjects were seeded into either a collagen sponge or collagen gel and cultured for 10 days. In situ hybridization was performed on serial sections of paraffin embedded specimens and assessed for expression of selected genes important for extracellular matrix formation: Types I and II collagen, aggrecan and chondroitin-6 sulfotransferase. Rounded cells grown in collagen gel showed expression of Types I and II collagen, aggrecan and chondroitin-6 sulfotransferase; expression of these genes was absent in spindle shaped cells. Cells in the collagen sponge that lay on the sponge margin were frequently spindle shaped; these cells expressed type I collagen, but not type II collagen, aggrecan or chondroitin-6 sulfotransferase. Results presented here provide novel data concerning disc cell gene expression with collagen 3D constructs. This information is useful for future tissue engineering studies that have the challenging goal of selectively modulating gene expression.

Is Chlamydia pneumoniae found in spinal fluid samples from multiple sclerosis patients? Conflicting results.

Cerebrospinal fluid samples from controls and patients with multiple sclerosis (MS) were split and sent to laboratories with different experiences for the detection of Chlamydia pneumoniae by polymerase chain reaction. Vanderbilt investigators identified C. pneumoniae in the majority of patients with MS and uncommonly in controls. Laboratories at Johns Hopkins University, University of Umeå, and the Centers for Disease Control and Prevention did not identify C. pneumoniae in any of the samples. Conflicting reports of C. pneumoniae detection in the some samples from patents with MS highlight the need to exchange detection techniques among laboratories involved in this controversy.

Clinical and demographic prognostic indicators for human disc cell proliferation in vitro: pilot study.

STUDY DESIGN: Human anulus cells were cultured under control and experimental conditions to study associations between proliferation and clinical-demographic features of subjects from which cells were obtained. Statistical multiple regression analyses were applied to develop mathematic models relating proliferation to age, gender, Thompson score (denoting stage of disc degeneration), and status (control donor [postmortem]; surgical patient). OBJECTIVES: To identify the effect of donor characteristics on proliferative capacities of human disc cells. SUMMARY OF BACKGROUND DATA: As therapeutic options for disc degeneration increase, novel biologic options are important future considerations. Little is known about the influence of clinical-demographic features on cell proliferation. METHODS: Anulus cells were studied in two designs: 1) Cells from 12 individuals were grown in monolayer with 50 ng/mL interleukin growth factor-1 (IGF-I), 100 ng/mL insulin, or control conditions. 2) Cells from nine individuals were grown in three-dimensional culture with 10 ng/mL IGF-I or control conditions. Cell proliferation data and data on age, gender, Thompson score, and status were collected. Standard statistical analyses were used to develop correlation models. RESULTS: Data from monolayer experiments produced significant models fitting proliferation in the presence of low serum, 50 ng/mL IGF-I, or insulin, with age, gender, Thompson score, and status (respective R2: 0.827, 0.680, 0.850). Three-dimensional cultures exposed to 10 ng/mL IGF-I resulted in proliferation that correlated in a significant negative manner with Thompson score (r = -0.798). CONCLUSIONS: Clinical-demographic prognostic indicators may help predict levels of proliferation. Greater age, greater disc degeneration, female gender, and surgical derivation had deleterious effects on proliferation potential in this model.

Breast conservation: trends in a major southern metropolitan area compared with surrounding rural counties.

Despite randomized prospective studies and National Institutes of Health recommendations, surgeons especially in the southern United States have been slow to adopt breast conservation surgery (BCS). Data were analyzed regarding 3,349 cases of stage 0, I, and II breast cancer (1991-1998) from Charlotte-Mecklenburg County, NC; 1057 cases from six surrounding rural counties (1995-1997); and 90,398 cases (1995) from the National Cancer Data Base. During 1995 through 1997 Charlotte-Mecklenburg County had statistically significantly higher rates of BCS compared with six surrounding rural counties for stage I (59% and 42% respectively, P = 0.001) and stage II (37% and 19%, respectively, P = 0.001) breast cancer. The BCS rates in Charlotte-Mecklenburg County (1991-1998) showed the following: Stage 0 rate increased from 17 per cent in 1991 to 78 per cent in 1998 (P = 0.001), stage I rate increased from 31 per cent in 1991 to 65 per cent in 1998 (P = 0.001), and stage II rate increased from 18 per cent in 1991 to 42 per cent in 1998 (P = 0.001). BCS rates for early-stage breast cancer in Charlotte-Mecklenburg County have increased over the last 8 years and now equal national rates; however, patients in surrounding rural counties are not receiving BCS as frequently. There is a need for more widespread education of surgeons, other health care providers, and the general public to increase the use of BCS.

The influence of patient strength, aerobic capacity and body composition upon outcomes after coronary artery bypass grafting.

BACKGROUND: Physical activity, physical fitness and body habitus of patients may be important predictors of outcomes after cardiac surgery. This study sought to quantify physical fitness and determine whether components of fitness enhance the prediction of outcomes in a group of patients undergoing coronary artery bypass grafting. METHODS: A group of 200 patients were evaluated prior to coronary artery bypass surgery. A Veterans Specific Activity Questionnaire (VSAQ) measured aerobic capacity. A grip dynamometer assessed strength. Skin-fold thickness was used to calculate percent body fat and lean body mass index. Patients were divided into low risk (0-2.5%) and high risk (>2.5%) groups based on the STS National Cardiac Surgery Database prediction of operative mortality. RESULTS: Patients with both a high percent body fat and a low VSAQ were at higher risk for at least one serious complication (p<0.05) and a longer postoperative length of stay (p<0.05). CONCLUSION: This study suggests: 1) An index of physical fitness can be obtained preoperatively in cardiac surgical patients; 2) This information aids in the prediction of operative risk.

Effects of combined aerobic and resistance training versus aerobic training alone in cardiac rehabilitation.

PURPOSE: This study examined the effects of performing combined resistance and aerobic training, versus aerobic training alone, in patients with coronary artery disease. METHODS: Thirty-six patients with coronary artery disease were randomized to either an aerobic-only training group (AE) or a combined aerobic and resistance training group (AE + R). Both groups performed 30 minutes of aerobic exercise 3 days/week for 6 months. In addition, AE + R group performed two sets of resistance exercise on seven different Nautilus machines after completion of aerobic training each day. Twenty patients (AE: n = 10; AE + R: n = 10) completed the training protocol with > 70% attendance. RESULTS: Strength gains for AE + R group were greater than for AE group on six of seven resistance machines (P < 0.05). VO2peak increased after training for both AE and AE + R (P < 0.01) with no difference in improvement between the groups. Resting and submaximal exercise heart rates and rate-pressure product were lower after training in the AE + R group (P < 0.01), but not in the AE group. AE + R increased lean mass in arm, trunk, and total body regions (P < 0.01), while AE increased lean mass in trunk region only (P < 0.01). Percent body fat was reduced for AE + R after training (P < 0.05) with a between group trend toward reduced body fat (P = 0.09). Lean mass gain significantly correlated with strength increase in five of seven resistance exercises for AE + R. CONCLUSIONS: Resistance training adds to the effects of aerobic training in cardiac rehabilitation patients by improving muscular strength, increasing lean body mass, and reducing body fat.

Is surgical excision necessary for atypical ductal hyperplasia of the breast diagnosed by Mammotome?

BACKGROUND: Core biopsy findings of atypical ductal hyperplasia (ADH) underestimates the diagnosis of malignancy by 18% to 88%. Using the Mammotome biopsy technique, more accurate assessment of the lesion is possible, making selective excision of these lesions a consideration. METHODS: The records of 62 patients who were found to have ADH at Mammotome biopsy and subsequently underwent excision of the lesion were reviewed. Patient data were statistically analyzed for predictors of malignancy at the time of surgical excision. RESULTS: Of the 62 patients, 9 (15%) had malignancy at excision. Variables predicting for malignancy included markedly atypical hyperplasia and incomplete removal of calcifications at Mammotome biopsy, a previous contralateral breast cancer, and a family history of breast cancer, with a combined sensitivity of 100% and specificity of 80%. CONCLUSIONS: Mild ADH found on Mammotome, not associated with a personal or family history of breast cancer, may not need excision if all calcifications have been removed.

Use of injury severity variables in determining disability and community integration after traumatic brain injury.

BACKGROUND: Long-term outcome is important in managing traumatic brain injury (TBI), an epidemic in the United States. Many injury severity variables have been shown to predict major morbidity and mortality. Less is known about their relationship with specific long-term outcomes. METHODS: Glasgow Coma Scale, Revised Trauma Score, Injury Severity Score, and Trauma and Injury Severity Score, along with other demographic and premorbid values, were obtained for 378 consecutive patients hospitalized after TBI at a Level I trauma center between September 1997 and May 1998. Of this cohort, 120 patients were contacted for 1-year follow-up assessment with the Disability Rating Scale, Community Integration Questionnaire, and employment data. RESULTS: Univariate analyses showed these to be significant single predictors of 1-year outcome. Multivariate analyses revealed that the Revised Trauma Score and Glasgow Coma Scale had significant additive value in predicting injury variables Disability Rating Scale scores when combined with other demographic and premorbid variables studied. Predictive models of 1-year outcome were developed. CONCLUSION: Injury severity variables are significant single outcome predictors and, in combination with premorbid and demographic variables, help predict long-term disability and community integration for individuals hospitalized with TBI.

Anti-apoptotic effects of IGF-1 and PDGF on human intervertebral disc cells in vitro.

STUDY DESIGN: Human cells from the anulus were grown in tissue culture in an experimental design to study the anti-apoptotic effect of two selected cytokines. OBJECTIVES: To determine whether two selected cytokines, insulin-like growth factor-1 and platelet-derived growth factor, were effective in decreasing apoptosis in human cells from the anulus grown in culture for 10 days. SUMMARY OF THE BACKGROUND DATA: Previous studies have shown that there is a small cell population in the aging human intervertebral disc. Earlier work from the authors' laboratory suggested that apoptosis (programmed cell death) may be a major contributing factor to the decrease in cell number. A wide variety of inhibitors of apoptosis have now been identified; the present report presents findings on the actions of insulin-like growth factor-1 and platelet-derived growth factor in retarding or preventing apoptosis. METHODS: Using previously published culture methods, cells from the anulus of 25 subjects (mean age, 41.7 years) were grown in monolayer culture for 10 days and tested under the following conditions: 1) control growth in the presence of 20% fetal bovine serum; 2) positive control conditions promoting the development of apoptosis in the absence of serum; or 3) in dose-response regimes where insulin-like growth factor-1 or platelet-derived growth factor were added in the presence of only 1% fetal bovine serum (necessary for basal cell maintenance). Specimens were derived from 18 lumbar, 9 cervical, and 1 thoracic sites; the average Thompson score was III. Cells were grown on chambered slides and evaluated in situ using the TdT in situ apoptosis detection reaction to identify apoptotic cells. An average of 300 cells were counted in replicate cultures at each dose to determine the incidence of apoptosis; results were analyzed with standard statistical techniques. Cultured cells also were examined with transmission electron microscopy. RESULTS: Serum withdrawal to a 1% level was used as a positive apoptosis control in vitro and resulted in a significantly greater percentage of apoptosis compared with the 20% serum negative control (1.02% +/- 0.34 (28) versus 0.14% +/- 0. 04 (27; mean +/- SEM (n)), P < 0.0001). Exposure to 50 ng/mL insulin-like growth factor-1 significantly reduced the percentage of apoptosis (vs.- 1% serum) to 0.49% +/- 0.26 (P = 0.005); 500 ng/mL was also significantly effective (% apoptosis = 0.09% +/- 0.04 (P = 0.0001). Platelet-derived growth factor at a dose of 100 ng/mL also significantly reduced apoptosis (0.18 +/- 0.11, P = 0.0001). CONCLUSIONS: Data demonstrate a significant reduction in the percentage of apoptotic disc cells after exposure to 50-500 ng/mL insulin-like growth factor-1 or exposure to 100 ng/mL platelet-derived growth factor. These findings expand the understanding of the cell biology of the disc cell and show that selected cytokines can retard or prevent programmed cell death in vitro. The administration of these cytokines may have future therapeutic potential in the treatment of disc degeneration.

Value of point-of-care blood testing in emergent trauma management.

BACKGROUND: No prospective study demonstrates the value of point-of-care laboratory testing (POCT) in the management of major trauma. METHODS: In a prospective, noninterventional, study of 200 major trauma patients, we evaluated the influence of a blood POCT profile (hemoglobin, Na+, K+, Cl-, blood urea nitrogen, glucose, pH, PCO2, PO2, HCO3-, base deficit, and lactate) on emergent diagnostic and therapeutic interventions. Physicians responded to a standardized set of questions on their diagnostic and therapeutic plans before and after the availability of POCT results. Management plan changes were deemed emergently appropriate, if they were influenced by the POCT results and, within the ensuing 30 minutes, the change in management was likely to reduce morbidity or conserve resources. RESULTS: For emergently appropriate plan changes, Na+, Cl-, K+, and blood urea nitrogen were never influential, whereas in each of 6.0% of cases (95% confidence interval [CI], 3.5%-10.2%) at least one of the remaining POCT parameters was influential. An emergently appropriate change was based on hemoglobin in 3.5% of cases (95% CI, 1.0%-6.1%), blood gas parameters in 3.0% of cases (95% CI, 0.64%-5.7%), lactate in 2.5% of cases (95% CI, 1.1%-5.7%), and glucose in 0.5% of cases (95% CI, 0.1%-2.8%). All of these cases involved blunt injury. CONCLUSION: Na+, Cl-, K+, and blood urea nitrogen levels do not influence the initial management of major trauma patients. In patients with severe blunt injury, hemoglobin, glucose, blood gas, and lactate measurements occasionally result in morbidity-reducing or resource-conserving management changes.