Olecranon physeal nonunion in the adolescent athlete: identification of two patterns.

BACKGROUND: This study aimed to present the outcomes of patients undergoing surgical management of persistent, symptomatic olecranon physes. METHODS: Consecutive patients undergoing surgical management for symptomatic persistent olecranon physeal abnormalities were reviewed. Preoperative data, intraoperative findings, and postoperative clinical outcomes including physical examination findings, radiographs, complications, and reoperations were analyzed. RESULTS: A total of 13 elbows in 12 patients (100% male; average age, 18 ± 4 years) were identified. All patients were pitchers at the high-school or college level. Two unique radiographic patterns were identified: distal persistent olecranon physis (n = 9), identified by an irregular sclerotic lucency at the site of the olecranon physis; and proximal persistent olecranon physis (n = 4), identified by a radiolucency exiting proximal to the triceps insertion at the site of an accessory ossification center that failed to unite. Surgical management included débridement, autograft bone grafting, and internal fixation. There were 3 reoperations (1 for infection, 2 for painful hardware). All patients achieved successful radiographic union (average, 8 ± 2 weeks). At an average follow-up of 4.4 ± 1.2 years, the average postoperative Disabilities of the Arm, Shoulder, and Hand score was 1.1 ± 1.6; the Mayo Elbow Performance Score was 98.5 ± 2.4; the American Shoulder and Elbow Surgeons score was 99.3 ± 0.4; and average Likert score for satisfaction was 9.95 ± 0.2. At final follow-up, there were no significant differences in strength, motion, or stability in comparing the operative with the nonoperative elbow (P > .05 for all). CONCLUSIONS: Two unique patterns of olecranon physeal abnormalities in young, overhead throwing athletes have been identified. Open reduction with internal fixation is clinically and radiographically successful in obtaining union and symptom resolution in these patients.

Total shoulder arthroplasty with an augmented component for anterior glenoid bone deficiency.

BACKGROUND: Glenoid bone loss is a challenging problem when performing total shoulder arthroplasty (TSA). Posterior glenoid bone deficiency is more common than anterior deficiency, and so the literature on methods to treat anterior glenoid deficiency in the setting of TSA is not common. The purpose of this case series was to describe preoperative factors, surgical technique, and clinical outcomes in select patients who underwent placement of an anteriorly augmented glenoid component during TSA. METHODS: This was a retrospective case series of 5 patients who underwent TSA with an anteriorly augmented component. The medical records were reviewed, including preoperative demographics, clinical examination, radiographs, Penn Shoulder Score and American Shoulder and Elbow Surgeons score. RESULTS: Preoperative diagnoses were anterior glenoid erosion in 2 patients, and 1 patient each with malunited glenoid fracture, nonunited glenoid fracture, and post-traumatic arthritis. The mean age at the time of surgery was 67.4 years (range, 53-75 years). No patient demonstrated radiographic or clinical signs of glenoid component loosening at final follow-up. Postoperative Penn Shoulder Scores averaged 84.4 points (range, 58-100 points), and postoperative American Shoulder and Elbow Surgeons scores averaged 88.0 points (range, 68-100 points). Average postoperative active forward elevation was 140° (range, 80°-170°), and active external rotation was 29° (range 10°-45°). There were no dislocations or revision surgeries at an average of 33.2 months (range, 21.9-43.2 months) after surgery. CONCLUSION: In the short term, glenohumeral arthrosis in the setting of anterior glenoid deficiency can be treated with an anteriorly augmented glenoid component. Further follow-up and a larger series of patients are necessary to determine the long-term outcomes and complications associated with this technique.

Treatment of massive and recurrent rotator cuff tears augmented with a poly-l-lactide graft, a preliminary study.

BACKGROUND: The incidence of failed rotator cuff repairs remains high, especially in the setting of massive tears or revision repairs. The purpose of this study was to evaluate patient outcomes and repair integrity after augmentation with the repair patch, a poly-l-lactide synthetic polymer. METHODS: Sixteen consecutive patients with massive or recurrent rotator cuff tears underwent open repair with synthetic poly-l-lactide patch augmentation. Two patients required the patch to bridge defects, and 1 patient retore after a motor vehicle accident and had revision surgery at another institution. The 13 remaining patients were retrospectively evaluated from 1.2 to 1.7 years (average, 1.5 years) after surgery by PENN, American Shoulder and Elbow Surgeons, and Single Assessment Numeric Evaluation scores. Magnetic resonance imaging was used to examine the integrity of the repair at a minimum of 1 year of follow-up. RESULTS: The mean age was 57.3 years (42-68 years). Five patients (38%) had an intact rotator cuff at the time of follow-up. The remaining patients (62%) had full-thickness tears. PENN scores significantly improved from a preoperative score of 50.9 to 77.6 (P < .005). American Shoulder and Elbow Surgeons scores significantly improved from 32.8 to 74.2 (P = .0001). Single Assessment Numeric Evaluation scores at latest follow-up were 76.2. CONCLUSION: Poly-l-lactide repair patch augmentation of massive and recurrent large to massive rotator cuff tears demonstrates significant improvement in shoulder outcome measures for this difficult population, despite a retear rate of 62%. Further investigation with larger, prospective long-term studies is needed to determine whether this technique provides a true benefit compared with traditional, nonaugmented repair.

Magnetic resonance imaging evaluation of normal glenoid length and width: an anatomic study.

PURPOSE: The purpose of this study was to evaluate the measured dimensions of the normal glenoid on sagittal magnetic resonance (MR) imaging to determine whether a fixed ratio of glenoid length and width can be determined. METHODS: MR images of 90 glenoids in 84 patients were analyzed. The mean age was 54.8 years, with 44 male and 40 female patients. Glenoid length and width at the widest dimension were measured and recorded by 3 independent examiners. The ratio of length to width and the ratio of the length of the superior pole at the widest point to the total length were calculated. Intraclass correlation coefficients, Spearman and Pearson correlations, regression analysis with cross validation, and coefficients of variation were calculated. RESULTS: The mean glenoid length was 37.5 ± 3.8 mm, whereas the mean width was 24.4 ± 2.9 mm. The mean ratio of length to width was 1.55 ± 0.1, whereas the mean ratio of the distance from the superior pole to the widest point to the total glenoid length was 0.64 ± 0.03. The calculated ratios were less variable than the absolute length and width. Cross validation of length for width showed a 95% prediction band width of 4.48 mm, with an average absolute error of prediction of 1.46 mm, and was equally specific when separated by gender. The width was equal to 0.65 times the length. CONCLUSIONS: Measurement of glenoid length and width using MR imaging results in a consistent ratio of length to width independent of patient age and gender, where the width was equal to 0.65 times the length at a point two-thirds along the inferosuperior axis. LEVEL OF EVIDENCE: Level IV, case series.

Suprascapular nerve entrapment isolated to the spinoglenoid notch: surgical technique and results of open decompression.

BACKGROUND: Entrapment of the suprascapular nerve (SSN) at the spinoglenoid notch (SGN) specifically affects the infraspinatus, and isolated external rotation (ER) weakness can result. We describe the technique of open SSN decompression at the SGN for infraspinatus involvement and report the results of a consecutive series. MATERIALS AND METHODS: Twenty-nine shoulders underwent SSN decompression at the SGN. The mean age was 44 years (range, 15-69 years), and the mean follow-up was 4.3 years (range, 1-7 years). On manual muscle testing, ER strength was abnormal in all patients: 2/5 in 3, 3/5 in 21, and 4/5 in 5. The mean preoperative American Shoulder and Elbow Surgeons (ASES) score was 48 (range, 23-83). Atrophy of the infraspinatus was visible or palpable in 72% of shoulders. Magnetic resonance imaging showed ganglion cysts at the SGN in only 20.7% of shoulders. RESULTS: Of the patients, 19 (66%) regained full ER strength, 9 (31%) improved to 4/5, and 1 (3%) had ER strength of 3/5. The mean ASES score improved to 75 (range, 60-100) (P < .05). Of 29 shoulders, 23 (79%) showed improved ER strength within 1 week of surgery. All ganglion cyst cases regained full ER strength within a mean of 6 weeks. In all cases, ER strength improved by at least 1 full strength grade. DISCUSSION: A ganglion cyst is not necessary to produce SSN compression at the SGN. SSN compression at the SGN can present as an isolated entity or can occur in conjunction with rotator cuff pathology or a ganglion cyst. An index of suspicion, physical examination, magnetic resonance imaging, and electromyography confirm the diagnosis. The described operative approach detaches no muscle and allows rapid recovery, and in all cases, ER strength improved to normal or by 1 full grade.

Function after injection of benign bone lesions with a bioceramic.

BACKGROUND: A novel calcium sulfate-calcium phosphate composite injectable bone graft substitute has been approved by the FDA for filling bone defects in a nonweightbearing application based on preclinical studies. Its utility has not been documented in the literature. QUESTIONS/PURPOSES: We therefore determined postoperative function and complications in patients with benign bone lesions treated with this bioceramic. METHODS: We retrospectively reviewed all 56 patients with benign bone lesions treated with the bioceramic from 2006 to 2008. There were 29 male and 27 female patients with an average age of 17.6 years (range, 4-63 years). They were treated for the following diagnoses: unicameral bone cyst (13), aneurysmal bone cyst (10), nonossifying fibroma (eight), fibrous dysplasia (five), enchondroma (four), chondroblastoma (four), and other (12). We obtained a Musculoskeletal Tumor Society (MSTS) functional evaluation on all patients. The minimum followup was 26 months (average, 42 months; range, 26-57 months). RESULTS: The average MSTS score was 29 (range, 20-30). Most patients returned to normal function. There were three local recurrences, all of which were treated with repeat injection or curettage. Two patients had postoperative fractures treated in a closed manner. Two patients had wound complications, neither of which required removal of the graft material. CONCLUSION: Patients treated with this material reported high MSTS functional scores more than 24 months after operative intervention and experienced low complication rates. We believe the novel bioceramic to be a reasonable treatment option for benign bone lesions.

Arthroscopic repair for posterior shoulder instability.

PURPOSE: The purpose of this study was to evaluate outcomes of a consistent arthroscopic stabilization technique for recurrent posterior instability. METHODS: Thirty-four consecutive shoulders with symptomatic recurrent posterior instability were treated with arthroscopic repair and evaluated at a mean follow-up of 36 months (range, 12 to 67 months). Two patients were excluded because of prior surgery, leaving 32 for further analysis. The mean age was 21.4 years (range, 15 to 33 years). There were 26 male and 6 female patients, and in 59% the dominant shoulder was affected. A known traumatic injury had occurred in 25 (78%), but only 2 (6%) had a documented dislocation. Arthroscopic repair was performed with the patient in the lateral decubitus position through an anterosuperior 12-o'clock viewing portal. Suture anchor repairs were performed in 30 cases and plication to the intact labrum in 4. A sling and derotation wedge were used for 4 weeks, followed by progressive active range of motion, with weight lifting at 3 months and return to contact sports at 6 months. Of the 34 cases, 22 met the inclusion and exclusion criteria and had complete preoperative and postoperative shoulder outcome scores. RESULTS: Significant improvement (P = .001) from preoperatively to final follow-up was seen for American Shoulder and Elbow Surgeons scores, from 68 to 93; Simple Shoulder Test scores, from 9.3 to 11.6; and visual analog scale scores, from 3.5 to 0.8. All patients returned to their previous level of athletic activity. Two patients reported postoperative instability; none required reoperation. There were no other postoperative complications. CONCLUSIONS: This study represents a consecutive series of patients with recurrent posterior instability who underwent arthroscopic posterior stabilization. In this population arthroscopic posterior labral repair and capsular plication provided significant clinical improvement and low rates of recurrent instability and revision surgery. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Long head of the biceps tendinopathy: diagnosis and management.

Tendinopathy of the long head of the biceps brachii encompasses a spectrum of pathology ranging from inflammatory tendinitis to degenerative tendinosis. Disorders of the long head of the biceps often occur in conjunction with other shoulder pathology. A thorough patient history, physical examination, and radiographic evaluation are necessary for diagnosis. Nonsurgical management, including rest, nonsteroidal anti-inflammatory drugs, physical therapy, and injections, is attempted first in patients with mild disease. Surgical management is indicated for refractory or severe disease. In addition to simple biceps tenotomy, a variety of tenodesis techniques has been described. Open biceps tenodesis has been used historically. However, promising results have recently been reported with arthroscopic tenodesis.

Low-energy femoral shaft fractures associated with alendronate use.

OBJECTIVE: Increasing evidence suggests long-term alendronate use may overly suppress bone metabolism, limiting repair of microdamage and creating risk for insufficiency fractures. The purpose of this study is to demonstrate an association between alendronate use and a specific pattern of low-energy femoral shaft fracture. DESIGN, SETTING, AND PATIENTS: A retrospective review was performed of patients with femoral shaft fractures admitted to a Level 1 trauma center between January 2002 and March 2007. Seventy low-energy fractures were identified. MAIN OUTCOME MEASURE: The medical records were reviewed, and the incidence and duration of alendronate use were recorded. The incidence of a specific femoral shaft fracture in those patients taking alendronate compared with those not being treated was determined. RESULTS: There were 59 females and 11 males. The average age was 74.7 years. Twenty-five (36%) were being treated with alendronate. None of the patients had used or were using other bisphosphonates. Nineteen (76%) of these 25 patients demonstrated a simple, transverse fracture with a unicortical beak in an area of cortical hypertrophy. This fracture pattern was seen in only 1 patient (2%) not being treated with alendronate. Alendronate use was a significant risk factor for the fracture pattern (odds ratio [OR]) 139.33, 95% CI [19.0-939.4], P < 0.0001). This pattern was 98% specific to alendronate users. The average duration of alendronate use in those with the pattern was significantly longer than those who did not exhibit the pattern but were taking alendronate, 6.9 years versus 2.5 years of use, respectively (P = 0.002). Only 1 patient with the fracture pattern had been taking alendronate for less than 4 years. CONCLUSIONS: Low-energy fractures of the femoral shaft with a simple, transverse pattern and hypertrophy of the diaphyseal cortex are associated with alendronate use. This may result from propagation of a stress fracture whose repair is retarded by diminished osteoclast activity and impaired microdamage repair resulting from its prolonged use.

Subscapularis tendon tears: Management and arthroscopic repair.

Tears of the subscapularis tendon have been under-recognised until recently. Therefore, a high index of suspicion is essential for diagnosis.A directed physical examination, including the lift-off, belly-press and increased passive external rotation can help identify tears of the subscapularis.All planes on MR imaging should be carefully evaluated to identify tears of the subscapularis, retraction, atrophy and biceps pathology.Due to the tendency of the tendon to retract medially, acute and traumatic full-thickness tears should be repaired. Chronic tears without significant degeneration should be considered for repair if no contraindication exists.Arthroscopic repair can be performed using a 30-degree arthroscope and a laterally-based single row repair; one anchor for full thickness tears ⩽ 50% of tendon length and two anchors for those ⩾ 50% of tendon length.Biceps pathology, which is invariably present, should be addressed by tenotomy or tenodesis.Timing of post-operative rehabilitation is dictated by the size of the repair and the security of the repair construct. The stages of rehabilitation typically involve a period of immobilisation followed by range of movement exercises, with a delay in active internal rotation (IR) and strengthening in IR. Cite this article: EFORT Open Rev 2017;2:484-495. DOI: 10.1302/2058-5241.2.170015.

Na-K-Cl cotransporter-mediated intracellular Na+ accumulation affects Ca2+ signaling in astrocytes in an in vitro ischemic model.

Na-K-Cl cotransporter isoform 1 (NKCC1) plays an important role in maintenance of intracellular Na+, K+, and Cl- levels in astrocytes. We propose that NKCC1 may contribute to perturbations of ionic homeostasis in astrocytes under ischemic conditions. After 3-8 hr of oxygen and glucose deprivation (OGD), NKCC1-mediated 86Rb influx was significantly increased in astrocytes from NKCC1 wild-type (NKCC1+/+) and heterozygous mutant (NKCC1+/-) mice. Phosphorylated NKCC1 protein was increased in NKCC1+/+ astrocytes at 2 hr of OGD. Two hours of OGD and 1 hr of reoxygenation (OGD/REOX) triggered an 3.6-fold increase in intracellular Na+ concentration ([Na+]i) in NKCC1+/+ astrocytes. Inhibition of NKCC1 activity by bumetanide or ablation of the NKCC1 gene significantly attenuated the rise in [Na+]i. Moreover, NKCC1+/+ astrocytes swelled by 10-30% during 20-60 min of OGD. Either genetic ablation of NKCC1 or inhibition of NKCC1 by bumetanide-attenuated OGD-mediated swelling. An NKCC1-mediated increase in [Na+]i may subsequently affect Ca2+ signaling through the Na+/Ca2+ exchanger (NCX). A rise in [Ca2+]i was detected after OGD/REOX in the presence of a sarcoplasmic-endoplasmic reticulum (ER) Ca2+-ATPase inhibitor thapsigargin. Moreover, OGD/REOX led to a significant increase in Ca2+ release from ER Ca2+ stores. Furthermore, KB-R7943 (2-[2-[4(4-nitrobenzyloxy)phenyl]ethyl]isothiourea mesylate), an inhibitor of reverse-mode operation of NCX, abolished the OGD/REOX-induced enhancement in filling of ER Ca2+ stores. OGD/REOX-mediated Ca2+ accumulation in ER Ca2+ stores was absent when NKCC1 activity was ablated or pharmacologically inhibited. These findings imply that stimulation of NKCC1 activity leads to Na+ accumulation after OGD/REOX and that subsequent reverse-mode operation of NCX contributes to increased Ca2+ accumulation by intracellular Ca2+ stores.

Na-K-Cl cotransporter contributes to glutamate-mediated excitotoxicity.

We hypothesized that cation-dependent Cl- transport protein Na-K-Cl cotransporter isoform 1 (NKCC1) plays a role in the disruption of ion homeostasis in cerebral ischemia. In the current study, a role for NKCC1 in neuronal death was elucidated in neurotoxicity induced by glutamate and oxygen and glucose deprivation (OGD). Incubation of cortical neurons cultured for 14-15 d in vitro (DIV) with 100 microm glutamate for 24 hr resulted in 50% cell death. Three hours of OGD followed by 21 hr of reoxygenation led to 70% cell death. Inhibition of NMDA receptors with dizocilpine hydrogen maleate (1 microm) prevented both OGD- and glutamate-mediated cell death. Moreover, blocking of NKCC1 activity with bumetanide (5-10 microm) abolished glutamate- or OGD-induced neurotoxicity. Bumetanide was ineffective if added after 10-120 min of glutamate incubation or 3-6 hr of OGD treatment. Accumulation of intracellular Na+ and 36Cl content after NMDA receptor activation was inhibited by bumetanide. Blockage of NKCC1 significantly attenuated cell swelling after OGD or NMDA receptor activation. This neuroprotection was age dependent. Inhibition of NKCC1 did not protect DIV 7-8 neurons against OGD-mediated cell death. In contrast, cell death in DIV 7-8 neurons was prevented by the protein-synthesis inhibitor, cycloheximide. Taken together, the results suggest that NKCC1 activity is involved in the acute excitotoxicity as a result of excessive Na+ and Cl- entry and disruption of ion homeostasis.

Cytotoxicity of local anesthetics and nonionic contrast agents on bovine intervertebral disc cells cultured in a three-dimensional culture system.

BACKGROUND CONTEXT: Carragee et al. reported an accelerated progression of lumbar intervertebral disc (IVD) degeneration after discography in a human trial. Local anesthetics and contrast agents have exhibited toxicity to cardiac, renal, and neuronal cells. We hypothesize that local anesthetics or contrast agents commonly injected into the disc space during discography may result in cytotoxicity in vitro. In this study, we compared the cytotoxicity of these agents, alone or in combination, using nucleus pulposus (NP) and annulus fibrosus (AF) cells in a three-dimensional (3D) culture system. PURPOSE: The purpose of this study was to examine the effects of local anesthetics and contrast agents on IVD cells to help guide their usage in future clinical practices. STUDY DESIGN: Ours was an in vitro study to assess the cytotoxicity of local anesthetics and contrast agents commonly used in discography, using bovine NP and AF cells cultured in a 3D system. METHODS: Bovine NP and AF cells were isolated and encapsulated in alginate beads and cultured in media completed with serum and ascorbic acid. Beads were transferred to a 24-well plate and treated with local anesthetics, nonionic contrast agents, or with saline as a control for 2, 6, and 16 hours. Three different concentrations of local anesthetics, lidocaine and bupivacaine, were tested: 0.25%, 0.125%, and 0.0625%. Two different dilutions (1:2 or 1:4) of nonionic contras agents, iohexol and iopamidol, were tested. In a parallel study, beads were incubated with a combination of local anesthetics at equipotent concentrations and contrast agents for 6 hours. Cells were then examined with the LIVE/DEAD cell assay. Live cells (fluorescing green) and dead cells (fluorescing red) were visualized using fluorescent microscopy. The percentage of live cells after treatment was determined. RESULTS: More cell death was observed when NP and AF cells were incubated with anesthetics than contrast agents at the concentrations tested. When tested at equipotent concentrations, 0.125% bupivacaine (N=8) resulted in significantly more cell death than 0.5% lidocaine (N=6) in NP cells (p<.05). In these studies, cell death caused by bupivacaine was both dose and time dependent. When tested at the same dilutions, iopamidol diluted 1:2 caused slightly more cell death than iohexol. When incubating the cells with a combination of contrast and anesthetic agent, the cytotoxic effects of the anesthetics and contrast agent were not synergistic. In this culture system, AF cells were more sensitive to some of the agents than NP cells. CONCLUSIONS: Cell death was observed when AF and NP cells were incubated in a dose- and time-dependent manner with local anesthetics and contrast agents commonly used for discography. Relative toxicity of these compounds was noted in the order of bupivacaine, lidocaine, iopamidol, and iohexol. Future studies of the effects of these agents in organ culture or animal models are indicated to predict what happens in vivo.

Histological features of endplates of the mammalian spine: from mice to men.

STUDY DESIGN: Histological features of the intervertebral disc (IVD)-endplate interface were analyzed. OBJECTIVE: To define cartilaginous and bony vertebral endplate in commonly used laboratory animals and compare with that of the humans. SUMMARY OF BACKGROUND DATA: Endplates are crucial for the IVD nutrient supply: the IVDs have limited blood supply; most nutrients diffuse through endplates to nourish the discs. Various animal models of IVD and endplate degeneration have been used to study the etiology and treatments of spinal disorders. However, because humans are biped, the spine mechanics differ significantly from other mammals. Translation of animal research findings requires a characterization and comparison of the vertebral endplate in the respective species. In this study, we compared the endplate structure of laboratory animal species at the age range commonly used for modeling spine degeneration with that of an adult human. METHODS: Mouse, rat, rabbit, goat, and human IVDs and the adjacent vertebral bodies were isolated from the lower lumbar spine. Tissues were stained with Alcian Blue, counterstained with hematoxylin and eosin. RESULTS: Structure of the vertebral endplate varied significantly between the adult animal species and that of the humans. Growth plates persisted in all adult animals studied, whereas the growth plate is absent in the adult humans. In the mice and rats, the cartilaginous endplates are in continuation with the growth plates, with only a small bony center. Rabbits and goats have a bony layer between cartilaginous endplate and the growth plate. The human endplate consist of a cartilaginous layer and the bony endplate. CONCLUSION: Significant differences exist in histological features of the endplate across animal species and that of the humans. Consideration should be given when animal models are used to study IVD degeneration and surgical treatments. LEVEL OF EVIDENCE: 5.

Histological features of the degenerating intervertebral disc in a goat disc-injury model.

STUDY DESIGN: An in vivo study to develop a goat large-animal model for intervertebral disc (IVD) degeneration. OBJECTIVE: To determine an optimal method for inducing goat IVD degeneration suitable for testing disc regeneration therapies. SUMMARY OF BACKGROUND DATA: Although rodent, rabbit, and other small animal studies are useful, the narrow dimensions of IVDs in these species limit studies requiring injection of a relevant volume of therapeutics or implantation of engineered tissue constructs. For this study, the goat was selected because the size and shape of their IVDs are comparable with those of adult humans. METHODS: A minimally invasive approach that did not cause significant morbidity or mortality to adult goats (n = 6) was used. Under fluoroscopic guidance, goat lumbar IVDs were injured with a 4.5-mm drill bit or #15 or #10 surgical blades. Two months postinjury, the goats were killed and their IVDs with adjacent end plates were isolated, decalcified, and stained. RESULTS.: A numerical histologic scale to categorize the degree of goat IVD degeneration was developed on the basis of the histologic features of rabbit IVDs previously described by Masuda et al, goat IVDs described by Hoogendoorn et al, and human IVDs described by Boos et al. The interrater agreement of our scoring system was assessed (weighted kappa value = 0.6646). Mann-Whitney U tests were used to compare the injured IVDs with uninjured control. A 4.5-mm drill bit inserted to a 15-mm depth resulted in a significantly higher histologic score than uninjured controls (P = 0.01). Injury with a #15 or #10 blade did not result in increased histologic scores compared with uninjured controls. CONCLUSION: A comparison of the various injuries inflicted showed that the use of a 4.5-mm drill bit resulted in the most significant histologic changes.

Fibrillins 1 and 2 perform partially overlapping functions during aortic development.

Fibrillin-rich microfibrils are extracellular assemblies that impart structural properties to the connective tissue. To elucidate the contribution of fibrillin-rich microfibrils to organogenesis, we have examined the vascular phenotype of a newly created strain of mice that completely lacks fibrillin-1 and the consequences of combined deficiency of fibrillins 1 and 2 on tissue formation. The results demonstrated that fibrillins 1 and 2 perform partially overlapping functions during aortic development. Fbn1-/- mice died soon after birth from ruptured aortic aneurysm, impaired pulmonary function, and/or diaphragmatic collapse. Analysis of the neonatal Fbn1-/- aorta documented a disorganized and poorly developed medial layer but normal levels of elastin cross-links. Transcriptional profiling revealed that aneurysm progression in Fbn1 null mice is accompanied by unproductive up-regulation of gene products normally involved in tissue repair and vascular integrity, such as plasminogen activator inhibitor-1, activin A, and cysteine-rich angiogenic protein 61. In contrast to Fbn1-/- mice, Fbn2 null mice had a well developed and morphologically normal aortic wall. However, virtually all Fbn1-/-;Fbn2-/- embryos and about half of the Fbn1+/-;Fbn2-/- embryos died in utero and displayed a significantly more severe vascular phenotype than Fbn1-/- mice. Consistent with a specialized function of fibrillin-2, electron microscopy visualized ultrastructurally different microfibrils in Fbn1 null compared with control cell cultures. Collectively, these data demonstrate that involvement of fibrillin-2 in the initial assembly of the aortic matrix overlaps in part with fibrillin-1 and that continued fibrillin-1 deposition is absolutely required for the maturation and function of the vessel during neonatal life.

Increased tolerance to oxygen and glucose deprivation in astrocytes from Na(+)/H(+) exchanger isoform 1 null mice.

The ubiquitously expressed Na(+)/H(+) exchanger isoform 1 (NHE1) functions as a major intracellular pH (pH(i)) regulatory mechanism in many cell types, and in some tissues its activity may contribute to ischemic injury. In the present study, cortical astrocyte cultures from wild-type (NHE1(+/+)) and NHE1-deficient (NHE1(-/-)) mice were used to investigate the role of NHE1 in pH(i) recovery and ischemic injury in astrocytes. In the absence of HCO(3)(-), the mean resting pH(i) levels were 6.86 +/- 0.03 in NHE1(+/+) astrocytes and 6.53 +/- 0.04 in NHE1(-/-) astrocytes. Removal of extracellular Na(+) or blocking of NHE1 activity by the potent NHE1 inhibitor HOE-642 significantly reduced the resting level of pH(i) in NHE1(+/+) astrocytes. NHE1(+/+) astrocytes exhibited a rapid pH(i) recovery (0.33 +/- 0.08 pH unit/min) after NH(4)Cl prepulse acid load. The pH(i) recovery in NHE1(+/+) astrocytes was reversibly inhibited by HOE-642 or removal of extracellular Na(+). In NHE1(-/-) astrocytes, the pH(i) recovery after acidification was impaired and not affected by either Na(+)-free conditions or HOE-642. Furthermore, 2 h of oxygen and glucose deprivation (OGD) led to an approximately 80% increase in pH(i) recovery rate in NHE1(+/+) astrocytes. OGD induced a 5-fold rise in intracellular [Na(+)] and 26% swelling in NHE1(+/+) astrocytes. HOE-642 or genetic ablation of NHE1 significantly reduced the Na(+) rise and swelling after OGD. These results suggest that NHE1 is the major pH(i) regulatory mechanism in cortical astrocytes and that ablation of NHE1 in astrocytes attenuates ischemia-induced disruption of ionic regulation and swelling.