Michael J. Buckley

Correlation of inflammatory cytokines with arthroscopic findings in patients with temporomandibular joint internal derangements

PURPOSE The goal of this study was to evaluate the presence of the inflammatory cytokines interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) within the superior temporomandibular joint (TMJ) space in patients with internal derangements and to compare these values with the pathologic findings seen arthroscopically. PATIENTS AND METHODS Thirty patients with symptomatic TMJ dysfunction and clinical and imaging evidence of internal derangements of the TMJ were evaluated. Before entering the superior joint space with the arthroscope, 2 mL sterile saline was injected and, after 30 seconds of equilibration, was aspirated for analysis. The surgeon then performed diagnostic arthroscopy. The degree of synovitis, degeneration, percent condylar roofing, and any pathologic changes, such as perforations, were recorded. The level of total protein in each sample was ascertained, as well as the levels of IL-1 beta, IL-6, and TNF-alpha. RESULTS Of 30 samples tested, three were discarded because of failure to gain access into the superior joint space. Of the 27 remaining samples, IL-6 showed the closest correlation with the level of acute synovitis demonstrated arthroscopically. Two of the higher IL-6 levels (167 and 324 pg/microg protein) were seen with patients with a significant disc perforation. In patients with a high degree of vascularity, IL-6 was found to be between 0 to 581 pg/microg protein with an average of 80 pg/microg protein and a median value of 43 pg/mg. These values significantly correlated with the degree of vascularity (P < or = .02). This is in comparison with the 10 remaining patients, who showed significantly fewer vascular changes arthroscopically. In these patients, the range of IL-6 was 0 to 35 pg/microg protein, with an average of 19 pg/microg protein and a median value of 14.5 pg/microg. These values significantly correlated with the smaller degree of vascularity (P < or = .02). In seven patients, the role of nonsteroidal antiinflammatory drug (NSAID) use resulted in decreased levels of IL-6, which has been noted in previous studies. In patients with higher rated redundancy of the synovial tissue, the average IL-6 level was 92 pg/microg protein, whereas the median value was 44 pg/microg protein. In patients with little or no redundant synovial tissue, an average IL-6 level of 22 pg/microg protein was present. The median value in these same joints was 15 pg/microg protein. These IL-6 values significantly correlated with the degree of redundancy (P < or = .03). The degree of degenerative change (chondromalacia, fibrillation), disc displacement (roofing), and the presence or absence of adhesions did not significantly affect the levels of IL-6 within the patients studied. The presence of IL-1 beta and TNF-alpha was not found to correlate with the arthroscopic findings in the superior joint space. CONCLUSIONS The presence of IL-6 correlated with the degree of acute synovitis. IL-1 beta and TNF-alpha were not found in significant levels within the superior joint space. These findings correlated with those reported by other investigators. The production of IL-6 by synovial cells and its role in TMJ disease warrants further investigation.

Cyclic Tensile Strain Acts as an Antagonist of IL-1β Actions in Chondrocytes

Inflammatory cytokines play a major role in cartilage destruction in diseases such as osteoarthritis and rheumatoid arthritis. Because physical therapies such as continuous passive motion yield beneficial effects on inflamed joints, we examined the intracellular mechanisms of mechanical strain-mediated actions in chondrocytes. By simulating the effects of continuous passive motion with cyclic tensile strain (CTS) on chondrocytes in vitro, we show that CTS is a potent antagonist of IL-1β actions and acts as both an anti-inflammatory and a reparative signal. Low magnitude CTS suppresses IL-1β-induced mRNA expression of multiple proteins involved in catabolic responses, such as inducible NO synthase, cyclo-oxygenase II, and collagenase. CTS also counteracts cartilage degradation by augmenting mRNA expression for tissue inhibitor of metalloproteases and collagen type II that are inhibited by IL-1β. Additionally, CTS augments the reparative process via hyperinduction of aggrecan mRNA expression and abrogation of IL-1β-induced suppression of proteoglycan synthesis. Nonetheless, the presence of an inflammatory signal is a prerequisite for the observed CTS actions, as exposure of chondrocytes to CTS alone has little effect on these parameters. Functional analysis suggests that CTS-mediated anti-inflammatory actions are not mediated by IL-1R down-regulation. Moreover, as an effective antagonist of IL-1β, the actions of CTS may involve disruption/regulation of signal transduction cascade of IL-1β upstream of mRNA transcription. These observations are the first to show that CTS directly acts as an anti-inflammatory signal on chondrocytes and provide a molecular basis for its actions.

Neurosensory recovery following the mandibular bilateral sagittal split osteotomy

PURPOSE This prospective study evaluated the neurosensory recovery pattern of the inferior alveolar nerve following the bilateral sagittal split osteotomy (BSSO). PATIENTS AND METHODS Forty-two consecutive patients undergoing BSSO were studied using five neurosensory tests: 1) static light touch, 2) moving touch discrimination, 3) two-point discrimination, 4) nociception, and 5) thermoreception. Intraoperative assessment of inferior alveolar nerve damage was made; other variables recorded included type of fixation, age, concomitant procedures, advancement vs setback, and magnitude of the movement. A subjective questionnaire was completed by the patient. RESULTS The variables that affected neurosensory function following BSSO were degree of nerve damage and the amount of time elapsed following surgery. Larger myelinated fibers (A-alpha) recovered slower and to a lesser degree at all time intervals up to 2 years when compared with small myelinated and unmyelinated nerve fibers. The magnitude of nerve damage directly correlated with early neurosensory deficit, but equalized over time. CONCLUSION The long term (6 months and greater) chance for neurosensory recovery is good despite intraoperative nerve manipulation. Patients seem to adapt and report normal neurosensory function even though objective testing indicates continued neurosensory deficit.

The effects of mechanical strain on osteoblasts in vitro

The effect of mechanical strain on bone is important to the field of oral and maxillofacial surgery. Oral and maxillofacial surgeons are involved on a daily basis with problems including alveolar ridge resorption, implant stability, craniofacial growth, and bone resorption related to trauma and pathology. To understand and control these effects on bone, it is important to examine the effects of mechanical strain on the osteoblasts. This series of experiments provides the changes in alkaline phosphatase, collagen synthesis, and protein synthesis in osteoblast-like cell subjected to mechanical strain.

Low Magnitude of Tensile Strain Inhibits IL-1β-dependent Induction of Pro-inflammatory Cytokines and Induces Synthesis of IL-10 in Human Periodontal Ligament Cells in vitro

Applied mechanical loading induces inflammation in the periodontal ligament (PDL). However, the mechanisms involved in bone deposition at tension sites in an inflammatory environment are not clear. Here, in an in vitro model system, we show that equibiaxial tensile strain of low magnitude (TENS) provokes potent anti-inflammatory signals in PDL cells. TENS inhibits IL-1β-induced synthesis of IL-1β, IL-6, and IL-8 by inhibiting their mRNA expression, and thus significantly suppresses the amplification of IL-1 (3-induced inflammatory responses in PDL cells. Additionally, as an anti-inflammatory signal, TENS induces IL-10 synthesis in the presence and absence of IL-1β. These observations are the first to demonstrate that TENS antagonizes IL-1β actions on PDL cells by (i) inhibiting IL-1β-induced transcriptional regulation of proinflammatory cytokines, and (ii) inducing synthesis of IL-10, which may post-transcriptionally suppress the synthesis of proinflammatory cytokines.

Cyclic Tensile Strain Suppresses Catabolic Effects of Interleukin-1β in Fibrochondrocytes From the Temporomandibular Joint

OBJECTIVE To discern the effects of continuous passive motion on inflamed temporomandibular joints (TMJ). METHODS The effects of continuous passive motion on TMJ were simulated by exposing primary cultures of rabbit TMJ fibrochondrocyte monolayers to cyclic tensile strain (CTS) in the presence of recombinant human interleukin-1beta (rHuIL-1beta) in vitro. The messenger RNA (mRNA) induction of rHuIL-1beta response elements was examined by semiquantitative reverse transcriptase-polymerase chain reaction. The synthesis of nitric oxide was examined by Griess reaction, and the synthesis of prostaglandin E2 (PGE2) was examined by radioimmunoassay. The synthesis of proteins was examined by Western blot analysis of the cell extracts, and synthesis of proteoglycans via incorporation of 35S-sodium sulfate in the culture medium. RESULTS Exposure of TMJ fibrochondrocytes to rHuIL-1beta resulted in the induction of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2), which were paralleled by NO and PGE2 production. Additionally, IL-1beta induced significant levels of collagenase (matrix metalloproteinase 1 [MMP-1]) within 4 hours, and this was sustained over a period of 48 hours. Concomitant application of CTS abrogated the catabolic effects of IL-1beta on TMJ chondrocytes by inhibiting iNOS, COX-2, and MMP-1 mRNA production and NO, PGE2, and MMP-1 synthesis. CTS also counteracted cartilage degradation by augmenting expression of mRNA for tissue inhibitor of metalloproteinases 2 that is inhibited by rHuIL-1beta. In parallel, CTS also counteracted rHuIL-1beta-induced suppression of proteoglycan synthesis. Nevertheless, the presence of an inflammatory signal was a prerequisite for the observed CTS actions, because fibrochondrocytes, when exposed to CTS alone, did not exhibit any of the effects described above. CONCLUSION CTS acts as an effective antagonist of rHuIL-1beta by potentially diminishing its catabolic actions on TMJ fibrochondrocytes. Furthermore, CTS actions appear to involve disruption/regulation of signal transduction cascade of rHuIL-1beta upstream of mRNA transcription.

The influence of craniofacial structure on obstructive sleep apnea in young adults

PURPOSE This study compares craniofacial measurements of lateral cephalometric radiographs of young obstructive sleep apnea patients with those of nonapneic snorers and controls. PATIENTS AND METHODS Forty-eight patients (BM=28.0+/-3.8) with obstructive sleep apnea, 25 patients (BMI=26.3+/-3.5) with nonapneic snoring, and 54 controls (BMI=24.8+/-2.7) were evaluated. All subjects were between 18 and 40 years of age. Nineteen lateral cephalometric measurements were performed by a single investigator blinded to the results of the polysomnograms. RESULTS Univariate logistic regression analysis of the 19 variables showed significantly increased midfacial height (ANS-N), narrowed middle airway space (MAS), steep mandibular plane angle (FMA), elongated pharynx (PNS-Eb), and inferiorly positioned hyoid bone (PNS-H, MP-H) in the obstructive sleep apnea group. The nonapneic snoring group showed only a tendency toward maxillary and mandibular retrognathia (SNA and SNB). No significant differences were found for cranial base angle (S-N-Ba), PAS, inferior airway space, maxillary unit length (ANS-PNS) mandibular unit length (Cd-Gn), tongue height (Tng-Ht), soft palate length (PNS-P), and palatal vault height (Ocl-Pal 6). The OSA group was also found to have multiple sites of abnormality of both the upper and lower pharynx, with 58% of the patients having two or more abnormal values (1 standard deviation from the mean) as opposed to 40% of the nonapneic snoring group. CONCLUSIONS Highly significant craniofacial abnormalities were found in the upper and lower pharynx in young obstructive sleep apnea patients. Most of these patients (58%) had abnormalities in both the upper and lower pharynx, suggesting that palatal surgery alone may be an inadequate treatment. This information may define future investigations needed to determine how to more effectively treat this subgroup of young obstructive sleep apnea patients.

Interaction of strain and interleukin-1 in articular cartilage: effects on proteoglycan synthesis in chondrocytes

In temporomandibular joint disorders, the release of proinflammatory cytokines such as interleukin-1 (IL-1) initiates an inflammatory process disrupting cartilage homeostasis, ultimately leading to cartilage destruction. Additionally, mechanical stimuli affect articular chondrocyte metabolism. While articular chondrocytes generate nitric oxide (NO) in the presence of IL-1 proteoglycan synthesis is consecutively suppressed. The purpose of this study was to assess the effects of proinflammatory cytokines and mechanical strain in the form of cyclic tensile stretch on proteoglycan synthesis in chondrocytes, as compared to the NO competitive inhibitor L-N-monomethyl arginine (LMA), and to assess whether this effect is secondarily related to the activity of growth factors such as transforming growth factor beta (TGF-beta). Lapine articular chondrocytes were exposed to one of four different treatment regimens: no cyclic tensile stretch, IL-1, cyclic tensile stretch, or IL-1 plus cyclic tensile stretch. NO production was determined as medium nitrite accumulation. TGF-beta-bioactivity in chondrocyte conditioned medium was measured with the mink-lung epithelial cell bioassay. Proteoglycan synthesis was measured as the incorporation of 35-[S]-sodium sulfate into macromolecules separated from unincorporated label by gel filtration on PD-10 columns. In resting chondrocyte cultures, only baseline levels of NO were measured and the application of stretch for 24 h did not affect NO production. Addition of IL-1 provoked a large increase in NO synthesis which was abrogated in the presence of LMA. Application of stretch decreased the IL-1 induced NO synthesis, but did not modify the effect of LMA (being a competitive inhibitor of the inducible NO synthase) inhibiting IL-1 induced NO production. Glucosaminoglycan production was noted as proteoglycan synthesis showing almost no effect of cyclic stretch alone in comparison to the control condition, which correlates with the missing NO production in control and stretch conditions. Addition of IL-1 strongly inhibited proteoglycan synthesis, which was partly restored in the presence of LMA. However, cyclic stretch acted as a stronger restorer of proteoglycan synthesis in IL-1 treated conditions in the absence, and even more in the presence, of LMA. It was concluded that motion in the form of cyclic tensile stretch is a remarkable anti-inflammatory stimulus reversing the IL-1 induced suppression of proteoglycan synthesis in chondrocytes. These findings have therapeutic implications for the treatment of temporomandibular joint disorders, supporting early onset of postoperative and post-traumatic continuous passive motion therapy.

Changes in facial movement after maxillary osteotomies

PURPOSE Determine changes in facial movement while smiling after maxillary Le Fort I osteotomies. MATERIALS AND METHODS Twenty patients (ages 15 to 38) treatment-planned for maxillary Le Fort I osteotomies were divided into two groups. Group A consisted of 10 patients who underwent superior and/or posterior positioning of the maxilla. Group B consisted of 10 patients who underwent anterior and/ or inferior repositioning of the maxilla. All patients underwent preoperative and postoperative (3 to 8 months) videographic analysis of a maximal closed mouth smile by the Johnson Maximal Static Response Assay, evaluating four landmarks around the mouth and nose (alar base--A, cheilion--C, labrale superioris--Ls, and intermediate between cheilion and labrale superioris--Im). RESULTS Group A was noted to have a statistically significant decrease in movement of the face at points C and Im. No significant change was seen for points Ls and A. Group B was noted to have a statistically significant increase in movement of the face at point A, C, and Im. Point Ls was also found to increase, however not significantly. CONCLUSION Surgical repositioning of the maxilla anteriorly and/or inferiorly lengthens the facial musculature resulting in an increase in facial movement while smiling. Likewise surgically repositioning the maxilla superiorly and/or posteriorly reduces the length of the facial musculature, resulting in a decrease in facial movement while smiling.

Comparison of propofol and methohexital continuous infusion techniques for conscious sedation.

PURPOSE Methohexital and propofol have been shown to be effective agents for continuous intravenous infusion to produce conscious sedation during oral surgical procedures. The current study was conducted to compare these techniques for intraoperative cardiopulmonary stability, patient cooperation, amnesia, comfort, recovery time, and postoperative nausea and vomiting. METHODS Seventy ASA Class I or Class II patients between the ages of 18 and 40 years, scheduled for surgical extraction of impacted third molars, were entered into the study. Thirty-five patients were assigned to group A (methohexital) and 35 were assigned to group B (propofol). Intravenous sedation was accomplished using premedication with 1.5 microg/kg of fentanyl and 0.05 mg/kg of midazolam followed by the continuous infusion of methohexital or propofol at a rate of 50 microg/kg/min. The infusion was then titrated to 100 microg/kg/min to accomplish a level of sedation in which the eyes were closed and the patients were responsive to verbal commands. Subjects were monitored for variability of heart rate, blood pressure, oxygen saturation, amnesia, comfort, cooperation, nausea and vomiting, and recovery time based on cognitive, perceptual, and psychomotor tests. RESULTS There was no statistical difference between the two medication groups except for heart rate, which was found to increase by 11 beats/min for group A and only three beats/min in group B. CONCLUSION A continuous infusion technique using either methohexital or propofol (50 to 100 microg/kg/min) was found to be safe and effective, with no clinically significant differences in cooperation, cardiopulmonary stability, recovery time, amnesia, comfort, and the incidence of nausea or vomiting. However, the cost-effectiveness of methohexital is superior to that of propofol.