Austin V. Stone

Pro-inflammatory stimulation of meniscus cells increases production of matrix metalloproteinases and additional catabolic factors involved in osteoarthritis pathogenesis

OBJECTIVE Meniscus injury increases the risk of osteoarthritis; however, the biologic mechanism remains unknown. We hypothesized that pro-inflammatory stimulation of meniscus would increase production of matrix-degrading enzymes, cytokines and chemokines which cause joint tissue destruction and could contribute to osteoarthritis development. DESIGN Meniscus and cartilage tissue from healthy tissue donors and total knee arthroplasties (TKAs) was cultured. Primary cell cultures were stimulated with pro-inflammatory factors [IL-1β, IL-6, or fibronectin fragments (FnF)] and cellular responses were analyzed by real-time PCR, protein arrays and immunoblots. To determine if NF-κB was required for MMP production, meniscus cultures were treated with inflammatory factors with and without the NF-κB inhibitor, hypoestoxide. RESULTS Normal and osteoarthritic meniscus cells increased their MMP secretion in response to stimulation, but specific patterns emerged that were unique to each stimulus with the greatest number of MMPs expressed in response to FnF. Meniscus collagen and connective tissue growth factor (CTGF) gene expression was reduced. Expression of cytokines (IL-1α, IL-1β, IL-6), chemokines (IL-8, CXCL1, CXCL2, CSF1) and components of the NF-κB and tumor necrosis factor (TNF) family were significantly increased. Cytokine and chemokine protein production was also increased by stimulation. When primary cell cultures were treated with hypoestoxide in conjunction with pro-inflammatory stimulation, p65 activation was reduced as were MMP-1 and MMP-3 production. CONCLUSIONS Pro-inflammatory stimulation of meniscus cells increased matrix metalloproteinase production and catabolic gene expression. The meniscus could have an active biologic role in osteoarthritis development following joint injury through increased production of cytokines, chemokines, and matrix-degrading enzymes.

The Effect of Botulinum Neurotoxin-A on Blood Flow in Rats: A Potential Mechanism for Treatment of Raynaud Phenomenon

PURPOSE Botulinum neurotoxin-A (BoNTA) is used to treat several disorders, including Raynaud phenomenon. Recent investigations cite toxin-induced increases in blood flow, but no mechanism for BoNTAs actions is proposed. This study hypothesized that local application of BoNTA causes arteriolar vasodilation through sympathetic blockade and results in increased blood flow. METHODS Microvascular effects of BoNTA were assessed using a rat cremaster preparation. Cremaster microvascular diameters were measured in the muscle before and after treatment with the muscle paralytic agent gallamine triethiodide. Preparations were then treated with one of the following: BoNTA (4, 6, or 10 units), BoNTA dilution vehicle, or denatured BoNTA. Arteriolar diameters were measured repeatedly over the observation period. Additional preparations were treated with either tetrodotoxin or prazosin and rauwolscine before BoNTA to confirm that the observed vasodilatory responses were the result of sympathetic neural inhibition. RESULTS The BoNTA application resulted in a significant dose-dependent vasodilation (13% to 15%) of observed cremaster arterioles. Control treatments did not cause vasodilation. Both tetrodotoxin and prazosin/rauwolscine treatments elicited similar vasodilatory effects, with no additional vasodilation elicited by BoNTA. Addition of sodium nitroprusside following BoNTA elicited further vasodilation. In addition, systemic arterial pressure was unaffected by the local administration of BoNTA. CONCLUSIONS Local application of BoNTA results in arteriolar dilation that yields an approximate 69% increase in blood flow, without changing systemic arterial pressure. A BoNTA-mediated vasodilation through sympathetic blockade is a likely mechanism to explain the increase in blood flow reported after treatment with the toxin. CLINICAL RELEVANCE The ability of BoNTA to inhibit sympathetic nervous input reduces vasoconstriction, which is the most likely mechanism for improvement seen in Raynaud phenomenon patients following BoNTA injection.

Dose‐ and volume dependent‐response to intramuscular injection of botulinum neurotoxin‐A optimizes muscle force decrement in mice

Botulinum neurotoxin‐A (BoNTA) is a potent neurotoxin used to alter muscle tone to manage spasticity and to provide tendon bioprotection; however, the appropriate dose and injection volume to administer is not defined. Male mice (n = 120) received BoNTA injections into one gastrocnemius with either a constant volume (10 µl) with a variable dose (1, 3, 6 U/kg) or a constant dose (3 U/kg) in a variable volume (2.5, 5, 10, 20, 30 µl). Electromyographic (EMG) examination, muscle force generation (MFG), and wet muscle mass were measured in the ipsilateral and contralateral limbs at 1, 2, 4, or 12 weeks post‐injection. MFG and EMG responses decreased to approximately 40% of contralateral after a 1 U/kg injection and 0% of contralateral by 3 and 6 U/kg injection at 1 week after injection. Neuromuscular blockade was greatest with a 10 µl injection volume. MFG, EMG examination, and wet muscle mass reached contralateral values 12 weeks after injection for all injection doses and volumes tested. Effective injection doses and volumes were identified for producing full and partial neuromuscular blockade in the mouse gastrocnemius. These findings have important clinical implications in the intramuscular administration of BoNTA to manage muscle tone.

Basic Hip Arthroscopy: Supine Patient Positioning and Dynamic Fluoroscopic Evaluation.

Hip arthroscopy serves as both a diagnostic and therapeutic tool for the management of various conditions that afflict the hip. This article reviews the basics of hip arthroscopy by demonstrating supine patient positioning, fluoroscopic evaluation of the hip under anesthesia, and sterile preparation and draping. Careful attention to detail during the operating theater setup ensures adequate access to the various compartments of the hip to facilitate the diagnosis of disease and treatment with minimally invasive arthroscopy. Furthermore, having a routine method for patient positioning and operative setup improves patient safety, as well as operative efficiency, as the operative team becomes familiar with the surgeons standard approach to hip arthroscopy cases.

Osteoarthritic changes in vervet monkey knees correlate with meniscus degradation and increased matrix metalloproteinase and cytokine secretion

OBJECTIVE Meniscus injury increases osteoarthritis risk but its pathobiology in osteoarthritis is unclear. We hypothesized that older adult vervet monkeys would exhibit knee osteoarthritic changes and the degenerative menisci from these animals would secrete matrix metalloproteinases (MMPs) and pro-inflammatory cytokines that contribute to the development of osteoarthritis. DESIGN In a cross sectional analysis of healthy young adult (9-12 years) and old (19-26 years) adult female vervet monkeys, knees were evaluated in vivo with computed tomography (CT) imaging, and joint tissues were morphologically graded at necropsy. Meniscus explants were subsequently cultured to evaluate meniscal MMP and cytokine secretion. RESULTS CT images revealed significant bony osteoarthritic changes in 80% of older monkeys which included increases in osteophyte number and meniscal calcification. Meniscus and cartilage degradation scores were greater in the older monkeys and were positively correlated (r > 0.7). Menisci from older animals exhibiting osteoarthritic changes secreted significantly more MMP-1, MMP-3, and MMP-8 than healthy menisci from younger monkeys. Older menisci without significant osteoarthritic changes secreted more IL-7 than healthy young menisci while older osteoarthritic menisci secreted more IL-7 and granulocyte-macrophage colony-stimulating factor than healthy older menisci. CONCLUSIONS Aged vervets develop naturally occurring knee osteoarthritis that includes involvement of the meniscus. Degenerative menisci secreted markedly increased amounts of matrix-degrading enzymes and inflammatory cytokines. These factors would be expected to act on the meniscus tissue and local joint tissues and may ultimately promote osteoarthritis development. These finding also suggest vervet monkeys are a useful animal model for studying the progression of osteoarthritis.

Basic Hip Arthroscopy: Anatomic Establishment of Arthroscopic Portals Without Fluoroscopic Guidance.

Hip arthroscopy has gained popularity in recent years for diagnostic and therapeutic hip preservation management. This article details the establishment of arthroscopic portals of the hip, specifically the anterolateral and modified anterior portals without fluoroscopic guidance. The anterolateral portal is established anatomically, and the modified anterior portal is then established under arthroscopic guidance. A through understanding of the hip anatomy allows for these portals to be made both safely and reliably for hip arthroscopies in the modified supine positioned patient. The reduced use of fluoroscopy with this technique lowers the risk of ionizing radiation exposure to the patient and surgeon.

A Critical Review: Management and Surgical Options for Articular Defects in the Hip

Patients with articular cartilage lesions of the hip may present with pain and symptoms that may be vague in nature and onset. Therefore, a thorough history and physical examination should be performed for every patient presenting with hip pain and/or disability. The management may be operative or nonoperative. Nonoperative management includes a trial of rest and/or activity modification, along with anti-inflammatory medications, physical therapy, and biologic injections. Operative treatment in the form of arthroscopic techniques continues to decrease morbidity and offer innovative solutions and new applications for microfracture, ACT, and AMIC.

Acute changes in glenohumeral range-of-motion following in-season minor league pitching starts

Abstract Background. Asymmetric glenohumeral range-of-motion (ROM) between the throwing and non-throwing arms of overhead athletes has been well described in the literature. Thresholds of internal rotation (IR) loss have been associated with throwing arm injury in baseball players. Acute changes in shoulder ROM following an individual pitching appearance remain poorly understood. Objectives: To determine the acute change of external rotation (ER), IR, and total arc-of-motion (TAM) in minor league starting pitchers immediately following an in-season starting pitching appearance. Methods. Nine minor league starting pitchers participated in the study with data collected for 22 individual starts. IR, ER and TAM were measured in the throwing shoulder and non-throwing shoulder at three time points for each appearance: before, immediately following, and at 24 hours following the pitching appearance. Results. In the throwing arm, IR significantly decreased (49.4 vs 46.0, p = 0.037) immediately after pitching, and ER significantly increased immediately following an appearance (150.7 vs 153.6, p = 0.030) and at 24 hours (150.7 vs 154.0, p = 0.028). No difference was detected in throwing arm TAM and IR at 24 hours, or TAM immediately following an appearance. Conclusions. Minor league pitchers demonstrate the dynamic glenohumeral ROM changes after starting appearances of increased ER and diminished IR with maintenance of TAM. At 24 hours, the observed loss of IR had resolved, whereas the gains in ER remained present. Our study supports the need to further assess the acute changes of glenohumeral ROM in pitchers, and the association of acute glenohumeral ROM change with the development of pathologic ROM profiles and injury.

Position and Distraction Options

Successful hip arthroscopy relies on safe and effective access. Regardless of a supine or lateral approach to the hip, one relies on traction to access the central compartment of the hip and a stable positioning system to facilitate exposure to the peripheral compartment. This chapter outlines the importance of an operative approach to hip arthroscopy that includes operative theater preparation, patient positioning, hip distraction systems, and methods to avoid the pitfalls and complications of hip arthroscopy access. Upon completion of the chapter, the reader will have an improved understanding of the importance of hip distraction in hip arthroscopy, an appreciation of the variety of commercial hip distractors available for hip arthroscopy, and a watch list of complications related to over- or underdistraction to avoid during a hip arthroscopy procedure.

Defining the long-toss: A professional baseball epidemiological study

Background: Despite widespread use of long-toss throwing in baseball as a component of arm conditioning, interval throwing programs, and rehabilitation, long-toss distance and throwing mechanics remain controversial. Purpose: To ascertain the perceived definition of long-toss throwing through a survey of professional pitchers, pitching coaches (PCs), and certified athletic trainers (ATCs) associated with Major League Baseball. Study Design: Descriptive epidemiology study. Methods: Pitchers, PCs, and ATCs associated with 5 Major League Baseball organizations completed an anonymous survey that collected demographic data, personal use of long-toss throwing, and their perception of the distance and throwing mechanics that comprised long-toss. Results: A total of 321 surveys were completed by 271 pitchers, 19 PCs, and 31 ATCs. For all respondents, the mean distance considered as long-toss was 175 ft (95% CI, 170-181 ft). Respondents categorized the throwing mechanics of long-toss, with 36% reporting throwing “on a line” and 70% reporting long-toss as “not on a line.” Of those throwing “on a line,” 28% reported using crow-hop footwork while 60% used crow-hop footwork when throwing “not on a line.” Interpretation of long-toss distance significantly varied by position: pitchers, 177 ft (95% CI, 171-183 ft); PCs, 177 ft (95% CI, 155-200 ft); and ATCs, 157 ft (95% CI, 144-169 ft) (P = .048). When asked when long-toss throwing is used, pitchers reported using it more frequently in preseason (P = .007), during the season (P = .015), and in the off-season (P = .002) compared with that by ATCs. Functional goals for long-toss throwing demonstrated that pitchers and PCs use long-toss for shoulder stretching more frequently than ATCs (P < .001 and P = .026, respectively). ATCs used long-toss more than pitchers for interval throwing programs (P < .001). Conclusion: The definition varies for long-toss throwing distance and throwing mechanics. Pitchers and PCs believe that long-toss comprised longer distances than ATCs and employed long-toss differently for strength conditioning, training, stretching, and rehabilitation. This discrepancy highlights a potential lost opportunity for protecting the shoulder. While long-toss is an important tool, a more scientific definition is warranted to better elucidate its role in enhancing throwing performance and rehabilitation.