Aggrecan-like biomimetic proteoglycans (BPGs) composed of natural chondroitin sulfate bristles grafted onto a poly(acrylic acid) core for molecular engineering of the extracellular matrix.

Biomimetic proteoglycans (BPGs) were designed to mimic the three-dimensional (3D) bottlebrush architecture of natural extracellular matrix (ECM) proteoglycans, such as aggrecan. BPGs were synthesized by grafting native chondroitin sulfate bristles onto a synthetic poly(acrylic acid) core to form BPGs at a molecular weight of approximately ∼1.6 MDa. The aggrecan mimics were characterized chemically, physically, and structurally, confirming the 3D bottlebrush architecture as well as a level of water uptake, which is greater than that of the natural proteoglycan, aggrecan. Aggrecan mimics were cytocompatible at physiological concentrations. Fluorescently labeled BPGs were injected into the nucleus pulposus of the intervertebral disc ex vivo and were retained in tissue before and after static loading and equilibrium conditioning. BPGs infiltrated the tissue, distributed and integrated with the ECM on a molecular scale, in the absence of a bolus, thus demonstrating a new molecular approach to tissue repair: molecular matrix engineering. Molecular matrix engineering may compliment or offer an acellular alternative to current regenerative medicine strategies. STATEMENT OF SIGNIFICANCE: Aggrecan is a natural biomolecule that is essential for connective tissue hydration and mechanics. Aggrecan is composed of negatively charged chondroitin sulfate bristles attached to a protein core in a bottlebrush configuration. With age and degeneration, enzymatic degradation of aggrecan outpaces cellular synthesis resulting in a loss of this important molecule. We demonstrate a novel biomimetic molecule composed of natural chondroitin sulfate bristles grafted onto an enzymatically-resistant synthetic core. Our molecule mimics a 3D architecture and charge density of the natural aggrecan, can be delivered via a simple injection and is retained in tissue after equilibrium conditioning and loading. This novel material can serve as a platform for molecular repair, drug delivery and tissue engineering in regenerative medicine approaches.

A large animal model that recapitulates the spectrum of human intervertebral disc degeneration.

OBJECTIVE: The objective of this study was to establish a large animal model that recapitulates the spectrum of intervertebral disc degeneration that occurs in humans and which is suitable for pre-clinical evaluation of a wide range of experimental therapeutics. DESIGN: Degeneration was induced in the lumbar intervertebral discs of large frame goats by either intradiscal injection of chondroitinase ABC (ChABC) over a range of dosages (0.1U, 1U or 5U) or subtotal nucleotomy. Radiographs were used to assess disc height changes over 12 weeks. Degenerative changes to the discs and endplates were assessed via magnetic resonance imaging (MRI), semi-quantitative histological grading, microcomputed tomography (µCT), and measurement of disc biomechanical properties. RESULTS: Degenerative changes were observed for all interventions that ranged from mild (0.1U ChABC) to moderate (1U ChABC and nucleotomy) to severe (5U ChABC). All groups showed progressive reductions in disc height over 12 weeks. Histological scores were significantly increased in the 1U and 5U ChABC groups. Reductions in T2 and T1ρ, and increased Pfirrmann grade were observed on MRI. Resorption and remodeling of the cortical boney endplate adjacent to ChABC-injected discs also occurred. Spine segment range of motion (ROM) was greater and compressive modulus was lower in 1U ChABC and nucleotomy discs compared to intact. CONCLUSIONS: A large animal model of disc degeneration was established that recapitulates the spectrum of structural, compositional and biomechanical features of human disc degeneration. This model may serve as a robust platform for evaluating the efficacy of therapeutics targeted towards varying degrees of disc degeneration.

Terminal-end functionalization of chondroitin sulfate for the synthesis of biomimetic proteoglycans.

Chondroitin sulfate (CS) based bottle brush proteoglycan mimetics may be employed to restore tissue functionality. Synthesis of CS bottle brush structures requires immobilization of CS at its terminal end. In this study, we investigated commercially available natural CS for use in CS bottle brush synthesis. A terminal primary amine on CS was identified and utilized to conjugate amine-reactive vinyl monomers (i.e. acrylic acid and allyl glycidyl ether). Conjugation of vinyl monomers to the CS terminal amine was confirmed using a fluorescamine assay, (1)H NMR, and ATR-FTIR. CS was also immobilized onto epoxy functionalized surfaces via the CS terminal primary amine as confirmed by contact angle measurements of surface wettability. Attachment of polymeriziable end groups to CS and attachment of CS to functionalized substrates demonstrated here are the first steps towards synthesis of CS bottle brush PG mimics.

Fluoroscopically guided therapeutic sacroiliac joint injections for sacroiliac joint syndrome.

OBJECTIVE: To investigate the outcomes resulting from the use of fluoroscopically guided therapeutic sacroiliac joint injections in patients with sacroiliac joint syndrome. DESIGN: A retrospective study design with independent clinical review was utilized. Thirty-one patients were included; each patient met specific physical examination criteria and failed to improve clinically after at least 4 wk of physical therapy. Each patient demonstrated a positive response to a fluoroscopically guided diagnostic sacroiliac joint injection. Therapeutic sacroiliac joint injections were administered in conjunction with physical therapy. Outcome measures included Oswestry scores, Visual Analog Scale pain scores, work status, and medication usage. RESULTS: Patients' symptom duration before diagnostic injection averaged 20.6 mo. An average of 2.1 therapeutic injections was administered. Follow-up data collection was obtained at an average of 94.4 wk. A significant reduction (P = 0.0014) in Oswestry disability score was observed at the time of follow-up. Visual Analog Scale pain scores were reduced (P < 0.0001) at the time of discharge and at follow-up. Work status was also significantly improved at the time of discharge (P = 0.0313) and at follow-up (P = 0.0010). A trend (P = 0.0645) toward less drug usage was observed. CONCLUSIONS: These initial findings suggest that fluoroscopically guided therapeutic sacroiliac joint injections are a clinically effective intervention in the treatment of patients with sacroiliac joint syndrome. Controlled, prospective studies are necessary to further clarify the role of therapeutic injections in this patient population.

Side of symptomatic annular tear and site of low back pain: is there a correlation?

STUDY DESIGN: A retrospective chart review. OBJECTIVES: To report the correlation between the side of a concordantly painful, post-discography computer tomography (CT) visualized, annular tear, and the side of a patients' low back pain. SUMMARY OF BACKGROUND DATA: An annular fissure extending from the nucleus to the outer one-third of the annulus is thought to be the nociceptive source stimulated during provocative lumbar discography. To our knowledge, there are no studies that have attempted to delineate whether the side of the annular tear correlates with the side of the patient pain. METHODS: One hundred and one post-discography CT scans, performed on patients with single level, concordantly painful, and fissured discs identified during lumbar discography, were randomly obtained from the archived and current files of the Penn Spine Center's film library. These were reviewed by both the lead author and a spine radiologist, both of who were blinded to the side of the patients pain, to determine which scans demonstrated clearly definable tears extending to the outer one-third of the annulus. Statistical analysis via the exact method was used to determine the correlation between the side of the patients tear and the side of the patients pain. RESULTS: Forty post-discography CT scans met the inclusion criteria. There was a random correlation between the side of the patients concordantly painful annular tear and the side of the patients pain. CONCLUSIONS: The results of this study raise several questions regarding the embryologic development of the intervertebral disc and its somite, neurologic transmission of discogenic pain, distribution of chemical inflammagens, validity of discography, technique of ESI, and technique and validity of IDET.

Osseous stress reaction in a rower diagnosed with positron emission tomography (PET): a case report.

Back injury is one of the most frequently encountered injuries in the collegiate rower. The differential diagnosis of back pain in the competitive rower includes muscle strain, ligament/tendon injury, stress reaction, stress fracture, and a tear in the annulus fibrosis. Endurance sports, such as rowing, have an increased frequency of stress injury The diagnosis of stress reaction cannot be made with plain radiographs. Many studies have firmly established the efficacy of single photon emission computed tomography (SPECT) bone scans and magnetic resonance imaging in establishing the diagnosis of a stress reaction We present a case of a collegiate rower with mid back pain secondary to a stress reaction of the endplates of the costotransverse articulation at the T8 level diagnosed by a positive positron emission tomogram study in the setting of a negative SPECT scan.

Outcomes of therapeutic selective nerve root blocks for whiplash induced cervical radicular pain.

This study was designed to investigate the clinical efficacy of fluoroscopically guided therapeutic cervical selective nerve root blocks (SNRBs) in patients with whiplash induced cervical radicular pain. Study design was restrospective with independent clinical review. Twenty two patients were included. Each patient met specific physical examination criteria and failed to improve clinically after at least four weeks of physical therapy and the use of oral analgesics. Each patient demonstrated a positive response to a fluoroscopically guided diagnostic cervical SNRB. Patients were excluded for radiographic evidence of a focal disc protrusion or foraminal stenosis at the symptomatic level. Therapeutic cervical SNRBs were administered in conjunction with physical therapy. Data collection and analysis were performed by an independent clinical reviewer. Outcome measures included VAS pain scores, work status, medication usage, and Oswestry disability scores. Results showed the patients' symptom duration prior to diagnostic injection averaged 6 months. An average of 2.1 therapeutic injections was administered. Follow up data collection transpired at an average of 33.3 weeks following the final therapeutic injection. Good or excellent results were observed in 14% of patients. In higher functioning individuals a significantly greater (F=.0427) improvement in pain of 48.9% was observed. In these initial findings suggest that fluoroscopically guided therapeutic SNRBs, except possibly for higher functioning individuals, are not effective in the treatment of whiplash induced cervical radicular pain.

Thoracic spine spasms secondary to hemorrhagic intestinal ulcer.

A case of thoracic spine spasms secondary to a bleeding duodenal ulcer is presented. A 41-year-old male with 14-week history of thoracic spine spasm was treated with bed rest, spinal manipulation, physical therapy, medication, and a thoracolumbar brace. Subsequently, a provocative thoracic discogram performed at T9-T10 created periscapular pain and also reproduced the presenting thoracic spasms. Intradiscal electrothermal annuloplasty (IDET) was performed at the T9-T10 level, but without sustained relief. The patient presented to a spine center for evaluation. The diagnosis of thoracic discogenic disease was suspected. A second provocative thoracic discogram was performed and failed to reproduce his thoracic spasms. Three weeks after being referred to a chronic pain management physician, the patient presented to a local emergency room with hema-temesis. An endoscopic evaluation revealed a bleeding duodenal ulcer. Following medical treatment of the duodenal ulcer with a proton pump inhibitor the patient had complete resolution of his thoracic spasms. This represents the first reported case of thoracic spine spasms as an initial presenting symptom of a bleeding peptic ulcer.

Nonsurgical treatment for radicular of pain of zygoapophyseal joint cyst origin: therapeutic selective nerve root block.

We report the first case of zygoapophyseal joint cyst-induced radicular pain successfully treated with therapeutic selective nerve root block. A 56-year-old dentist presented with pain involving the lateral thigh, lateral calf, and foot dorsum that worsened with standing and walking. Magnetic resonance imaging of the lumbar spine showed a cyst emanating from the right L4-L5 zygoapophyseal joint, resulting in central canal and lateral recess stenosis. The patient was treated with two fluorscopically guided therapeutic L5 selective nerve root blocks. The patient remained pain free at 18-month follow-up.

Bioactive glass serves as a substrate for maintenance of phenotype of nucleus pulposus cells of the intervertebral disc.

The objective of the study was to investigate the capability of bioactive glass 45S5 to serve as a substrate for nucleus pulposus cells in vitro. Nucleus pulposus cells were isolated from adult rabbit discs and seeded onto bioactive glass. At selected time intervals, the cells and glass were evaluated. We found that the cells rapidly attached to the substrate, colonizing it within 12 h. By 21 days, they had formed a lawn of cells over the glass substrate. DNA measurements showed a progressive increase in cell number with time. The phenotype was maintained; the cells expressed aggrecan, and collagen type II and I, but were negative for collagen type X. CD44, a cell-surface glycoprotein that binds hyaluronate, was also expressed by these cells. Electron dispersive X-ray analysis and Fourier transform infrared spectroscopy revealed calcium phosphate-rich layer formation on the substrate surface. The results of this study suggest that nucleus pulposus cell proliferation may be an anchorage dependent event, and that the cells use the calcium phosphate-rich layer to facilitate cell adhesion, and subsequent proliferation. These findings point to the importance of the conditioned bioactive glass as a substrate for nucleus pulposus cells.

Therapeutic selective nerve root block in the nonsurgical treatment of atraumatic cervical spondylotic radicular pain: a retrospective analysis with independent clinical review.

OBJECTIVE: To investigate the outcomes resulting from the use of fluoroscopically guided therapeutic selective nerve root block (SNRB) in the nonsurgical treatment of atraumatic cervical spondylotic radicular pain. STUDY DESIGN: Retrospective study with independent clinical review. PARTICIPANTS: Twenty subjects (10 men, 10 women) with mean age 56.6 years. METHODS: Each patient met specific physical examination, radiographic, and electrodiagnostic criteria to confirm a level of cervical involvement. Those patients whose root level remained indeterminate were required to demonstrate a positive response to a fluoroscopically guided diagnostic SNRB prior to the initiation of treatment. Therapeutic injections were administered in conjunction with physical therapy. Data collection and analysis were performed by an independent clinical reviewer. MAIN OUTCOME MEASURES: Pain score, work status, medication usage, and patient satisfaction. RESULTS: Twenty patients with an average symptom duration of 5.8 months were included. An average of 2.2 therapeutic injections was administered. Follow-up data collection transpired at an average of 21.2 months following discharge from treatment. A significant reduction (p = .001) in pain score was observed at the time of follow-up. Medication usage was also significantly improved (p = .005) at the time of follow-up. An overall good or excellent result was observed in 60%. Thirty percent of patients required surgery. Younger patients were more likely (p = .0047) to report the highest patient satisfaction rating following treatment. CONCLUSIONS: This study suggests that fluoroscopically guided therapeutic SNRB is a clinically effective intervention in the treatment of atraumatic cervical spondylotic radicular pain.

Sacroiliac joint pain referral zones.

OBJECTIVE: To determine the patterns of pain referral from the sacroiliac joint. STUDY DESIGN: Retrospective. PARTICIPANTS/METHODS: Fifty consecutive patients who satisfied clinical criteria and demonstrated a positive diagnostic response to a fluoroscopically guided sacroiliac joint injection were included. Each patient's preinjection pain description was used to determine areas of pain referral, and 18 potential pain-referral zones were established. OUTCOME MEASURES: Observed areas of pain referral. RESULTS: Eighteen men (36.0%) and 32 women (64.0%) were included with a mean age of 42.5 years (range, 20 to 75 yrs) and a mean symptom duration of 18.2 months (range, 1 to 72 mo). Forty-seven patients (94.0%) described buttock pain, and 36 patients (72.0%) described lower lumbar pain. Groin pain was described in 7 patients (14.0%). Twenty-five patients (50.0%) described associated lower-extremity pain. Fourteen patients (28.0%) described leg pain distal to the knee, and 6 patients (14.0%) reported foot pain. Eighteen patterns of pain referral were observed. A statistically significant relationship was identified between pain location and age, with younger patients more likely to describe pain distal to the knee. CONCLUSIONS: Pain referral from the sacroiliac joint does not appear to be limited to the lumbar region and buttock. The variable patterns of pain referral observed may arise for several reasons, including the joint's complex innervation, sclerotomal pain referral, irritation of adjacent structures, and varying locations of injury with the sacroiliac joint.

Deep venous thrombosis and pulmonary embolism as a complication of bed rest for low back pain.

A case of bilateral lower extremity deep venous thrombosis and pulmonary embolism as a complication of bed rest prescribed for an acute low back pain episode is presented. A 29-year-old woman with low back pain was prescribed more than 2 weeks of bed rest, during which she developed progressive bilateral lower extremity complaints that were ascribed to nerve root irritation. Her symptoms were initially treated with physical therapy and epidural steroid injections. A Doppler examination and ventilation-perfusion scan revealed extensive deep venous thromboses and mismatches consistent with pulmonary embolism. This case illustrates an unusual extraspinal source of lower extremity symptoms associated with low back pain and further supports the role of early mobilization in the treatment of back pain.

Computed tomographic scanning of cervical spine fractures: does it influence treatment?

OBJECTIVE: To determine whether the superior sensitivity of computed tomography (CT) results in changes in treatment plans for cervical spine fractures that have been diagnosed on plain films alone. DESIGN: Retrospective review of radiographic studies for cervical spine trauma. SETTING/PARTICIPANTS: An orthopaedic spine surgeon (SS), an orthopaedic traumatologist (OT), an orthopaedic spine fellow (SF), and an orthopaedic chief resident (CR) were independently presented thirty-nine cases of cervical spine trauma imaged with adequate plain radiographs and with CT. MAIN OUTCOME MEASURES: Agreement was measured by calculation of kappa coefficients. RESULTS: The detection rate of total fractures on plain radiographs alone ranged from 47 percent to 71 percent, and the diagnosis changed an average 53 percent of cases. Change in treatment plans ranged from 10 percent (SS) to 46 percent (CR) of cases. Of these changes, undertreatment occurred as follows: SS =3 percent, OT =8 percent, SF =36 percent, and CR = 46 percent. The mean kappa coefficient for intraobserver agreement of treatment plans was 0.69. The experienced observers demonstrated "excellent" agreement with an average kappa coefficient of 0.85, whereas the mean coefficient for inexperienced observers was 0.54 or "moderate" agreement. Complete diagnostic agreement occurred between the experienced observers after review of both the plain films and CT scans. The interobserver agreement of treatment plans for the experienced observers increased from 0.79 to 0.88. CONCLUSIONS: CT scanning afforded additional information for all observers. Experienced observers can reliably determine treatment plans for cervical spine trauma diagnosed on plain films alone, whereas inexperienced observers are less reliable. For the experienced observers, interobserver agreement on treatment plans increased after the addition of CT.

Drain entrapment and titanium to ceramic head deposition: two unique complications following closed reduction of a dislocated total hip arthroplasty.

Postoperative dislocation remains one of the most frequent complications following total hip replacement. In this report, a case is presented that illustrates two potential concerns with postoperative dislocation and subsequent closed reduction. The first complication presented in this report is entrapment of a closed drainage system tube in the joint space following closed reduction. The second complication, transfer of metallic debris to a ceramic femoral head from contact with an acetabular shell during closed reduction, was documented by analysis of a femoral head using scanning electron microscopy and energy dispersive x-ray spectrometry. This report emphasizes the need for the surgeon to express caution when relocating a dislocated hip, particularly when a closed drainage system is used postoperatively.

The predictive value of provocative sacroiliac joint stress maneuvers in the diagnosis of sacroiliac joint syndrome.

OBJECTIVE: To determine the clinical validity of provocative sacroiliac joint (SIJ) maneuvers in making the diagnosis of sacroiliac joint syndrome (SIJS). DESIGN: Prospective constructive cohort study using sacroiliac joint block (SIJB) as the diagnostic gold standard. SETTING: Tertiary care center. PATIENTS: Consecutive patients describing low back pain including the region of the sacral sulcus. Physical examination revealed a positive response to three provocative SIJ maneuvers, two of which had to be Patrick's test and pain with palpation over the ipsilateral sacral sulcus. INTERVENTIONS: All subjects underwent fluoroscopically guided SIJB. MAIN OUTCOME MEASURES: Response to SIJB was assessed with visual analog scale (VAS) ratings before and after the block. A reduction of the VAS rating by at least 80% was considered a positive response to SIJB. RESULTS: Fifty consecutive patients met our criteria and underwent SIJB. Thirty patients had positive response to SIJB, making up the positive SIJS group. Twenty patients had less than 80% pain reduction with SIJB and thus comprised the negative SIJS group. The positive predictive value of provocative SIJ maneuvers in determining the presence of SIJS is therefore 60%. CONCLUSIONS: Our results do not support the use of provocative SIJ maneuvers to confirm a diagnosis of SIJS. Rather, these physical examination techniques can, at best, enter SIJS into the differential diagnosis.

Supracondylar femur fracture above a mature knee fusion treated with a long locked intramedullary rod.

Fracture around a mature knee fusion has been reported in the orthopedic literature, but little has been written regarding treatment options. Closed long anterograde rodding with interlocking screws offers distinct advantages over other methods of reduction and fixation. The closed nature of the procedure avoids excessive soft-tissue stripping. In comparison with a short unlocked rod or plate, the long locked rod imparts more stability and prevents shortening and rotation. We present a case of a supracondylar femur fracture above a mature knee fusion treated in this manner. The literature on this injury is also reviewed.

The value of radionuclide imaging in the diagnosis of sacroiliac joint syndrome.

STUDY DESIGN: A prospective study was done to assess the diagnostic value of radionuclide imaging (bone scan) in the evaluation of sacroiliac joint syndrome OBJECTIVES: To determine the sensitivity and specificity of radionuclide imaging in establishing a diagnosis of sacroiliac joint syndrome in patients with low back pain. SUMMARY OF BACKGROUND DATA: There is no pathognomonic symptom or sign to establish the diagnosis of sacroiliac joint syndrome. It has been accepted that confirmation of sacroiliac joint syndrome requires relief of pain, a positive response to a sacroiliac joint block. Bone scanning has been proposed as a useful imaging technique to evaluate for sacroiliac joint syndrome. The authors explored the use of nuclear imaging as a cost-effective and noninvasive technique in the diagnostic algorithm of sacroiliac joint syndrome. METHODS: Patients presenting to the author's Spine Center with complaints of low back pain including the region of the sacral sulcus were screened for inclusion into this study. Positive response to three provocative Sacroiliac joint maneuvers was requisite, two of which had to be Patrick's test and pain with palpation over the sacral sulcus. Patients who met these criteria were entered into a physical therapy program comprised of lumbar spine stabilization techniques and excluded any interventions considered specific for sacroiliac joint syndrome. Those whose symptoms failed to improve with this program underwent bone scan and fluoroscopically guided sacroiliac joint block. Response to sacroiliac joint block was assessed with pre- and post-block visual analog scale scores completed by the patient. A reduction of the VAS rating by at least 80% was considered a positive response to sacroiliac joint block. RESULTS: Fifty consecutive patients met the author's criteria and underwent bone scan and sacroiliac joint block. Thirty-one patients who had positive responses to sacroiliac joint block comprised the positive sacroiliac joint block group. Nineteen patients had less than 80% pain reduction with sacroiliac joint block and were labeled the negative sacroiliac-joint block group. Four patients had positive bone scans, all of whom were in the positive sacroiliac joint group. CONCLUSIONS: The results demonstrated very low sensitivity and high specificity of nuclear imaging in the evaluation of sacroiliac joint syndrome. The authors do not recommend bone scan in the diagnostic algorithm for sacroiliac joint syndrome.

Incidence of thigh pain after uncemented total hip arthroplasty as a function of femoral stem size.

Two hundred seventy-one patients (297 primary total hip arthroplasties) were evaluated for thigh pain 2 years after surgery. All femoral components were identical in wedge-shaped geometry but differed in size. All components were radiographically stable. Regression analysis revealed the presence of thigh pain to be directly correlated to increasing stem size (P = .014, r = .857). An even more significant positive correlation to thigh pain was present for proximal and distal component moments of inertia for bending in the mediolateral plane. Femoral stem size has a significant effect on the incidence of thigh pain.

Comparative risk of early postoperative pulmonary embolism after cemented total knee versus total hip arthroplasty with low-dose warfarin prophylaxis.

Four hundred thirteen cemented total hip arthroplasties and 852 cemented total knee arthroplasties were evaluated prospectively for postoperative pulmonary embolism. Inclusion criteria were a diagnosis of osteoarthritis, age 50 to 75 years old, cemented primary arthroplasty, and prophylaxis with low-dose warfarin (Coumadin, DuPont Pharma, Wilmington, Delaware). All patients underwent a preoperative perfusion scan and postoperative ventilation perfusion scan with all moderate probability scans evaluated with arteriogram. The overall incidence of pulmonary embolism was 3.8% after cemented total hip arthroplasty and 5.6% after cemented total knee arthroplasty. Because of a weight bias, patient age, weight, and gender-matched comparison was performed. Two hundred eighty-two patients from each group were matched with identical age, weight, and gender. The incidence of postoperative pulmonary embolism was 4.3% for total hip arthroplasty and 4.6% for total knee arthroplasty. These results do not support the contention that pulmonary embolism is higher after total hip arthroplasty than after total knee arthroplasty.