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Biomedical subjects

R P Harper

Publications and source records attributed to R P Harper.

At least 19 recordsLinked to original sources

Modulation of the inflammatory response in the rat TMJ with increasing doses of complete Freund's adjuvant.

OBJECTIVES: Acute inflammation stresses the physiological system, which must respond in order to reestablish homeostasis. The purpose of this study was to determine whether bilateral temporomandibular joint (TMJ) injections of different doses of Complete Freund's Adjuvant (CFA) produced dose-dependent changes in biologic markers of acute inflammation. The ability to establish an animal model with varying degrees of joint inflammation would allow evaluation of agents or conditions that could modulate the severity of the disease. DESIGN: The TMJs of three groups of male Sprague-Dawley rats were injected with CFA containing varying doses of Mycobacterium tuberculosis (MT). A group of non-injected and a group of saline injected rats were used as controls. Food intake, body weights, swelling and chromodacryorrhea were recorded daily. Interleukin-1 beta (IL-1 beta) and corticosterone levels were assayed and condylar cartilage thickness was measured 48 h after injections. RESULTS: Twenty-four hours post-injection, bilateral TMJ swelling and chromodacryorrhea were significantly (P< 0.05) increased following 10 microg of MT and further increased with elevated MT dose. In the CFA groups food intake was attenuated (P< 0.01) 24 and 48 h post-injection and negatively correlated with dose at 24 h. Body weight was also negatively correlated with dose. TMJ retrodiscal tissues IL-1 beta was increased (P< 0.05) in a dose-dependent manner. CFA increased corticosterone (P< 0.05), but this elevation was not dose dependent. Condylar cartilage thickness was decreased in a dose-dependent manner. CONCLUSIONS: These data suggest that an intermediate dose of CFA can be used to effect submaximal levels of TMJ inflammation that will allow experimental modulation in future studies.

Acute-Phase Reaction↗

Calcitonin gene-related peptide and substance P immunoreactivity in rat trigeminal ganglia and brainstem following adjuvant-induced inflammation of the temporomandibular joint.

The immunoreactivity of two inflammatory mediators, calcitonin gene-related peptide (CGRP) and substance P, was measured in the trigeminal ganglia and brainstem to characterize an adjuvant-induced inflammation within the rat temporomandibular joint at various acute (6, 24 and 48 h) and intermediate (10 day) time intervals. Concentrations of adjuvant-related neuropeptides were compared to those in both contralateral vehicle-related tissues and non-injected controls. By 6 h, CGRP immunoreactivity in the trigeminal ganglia was significantly above that in contralateral vehicle-injected tissue. The CGRP had decreased at each of the following time-points, but remained significantly elevated at 10 days. Substance P in the ganglion on the injected side was significantly increased for all four time periods. In brainstem subnucleus caudalis, CGRP was significantly increased for all four time periods. Substance P immunoreactivity in the subnucleus caudalis was significantly increased for the initial three time periods, but by day 10 had been reduced to that of the control. These data show that the pattern of changes in neuropeptides following the induction of inflammation is different between substance P and CGRP. Moreover, the pattern of change varies between the brainstem and the trigeminal ganglion. This suggests that the two neuropeptides may have different roles in the inflammatory process, and that this process may be modulated by different mechanisms at the brainstem and ganglion.

Afferent Pathways↗

Force level and strain patterns during bilateral mandibular osteodistraction.

PURPOSE: Recent reports have demonstrated that device orientation is important during mandibular distraction osteogenesis. The purpose of this study was to evaluate the force level and strain patterns on the mandible during bilateral osteodistraction with devices oriented either parallel to the body of the mandible or parallel to the sagittal axis of distraction. MATERIALS AND METHODS: Five unembalmed human cadaver mandibles were placed in a specially designed apparatus for stabilization of the proximal segments during distraction. A force transducer was attached to the lateral aspect of the inferior ramus, and strain gauges were attached to the mandibular bone segments proximal and distal to the distraction device. Lateral force and bone strains were then measured at 5 and 10 mm of distraction. Osteodistraction proceeded first with the devices placed parallel to the mandibular body, then parallel to the axis of distraction. RESULTS: Significantly greater lateral forces were seen when the devices were oriented parallel to the mandibular body. With this device orientation, increased tensile strains were seen at the labial symphysis and medial ramus, and increased compressive strains were found at the lingual symphysis and lateral ramus. However, when the devices were oriented parallel to the axis of distraction, the forces and strains were not detected. CONCLUSIONS: The results suggest that device orientation has important biomechanical effects on lateral forces and strain patterns during mandibular osteodistraction.

Adult↗

TGF-beta 1 alone and in combination with calcium hydroxide is synergistic to TGF-beta 1 production by osteoblasts in vitro.

AIM: To examine the effects of calcium hydroxide (Ca(OH)2), transforming growth factor-beta (TGF-beta 1), and Ca(OH)2/TGF-beta 1 coadministration on TGF-beta 1 and interleukin-6 (IL-6) synthesis by early (subculture 1) and late (subculture 5) osteoblast cultures. METHODOLOGY: Early and late cultures were established using bone cells harvested from 21-day-old fetal rat calvaria. Cell cultures of both early and late osteoblasts were divided into four groups: group 1, control; group 2, cells challenged with Ca(OH)2; group 3, cells challenged with TGF-beta 1; and group 4, cells challenged with Ca(OH)2 and TGF-beta 1 in combination. TGF-beta 1 and IL-6 levels for all groups were determined using ELISA methodology. RESULTS: ANOVA and Tukey HS analyses revealed that osteoblasts of groups 3 and 4 significantly increased (P < 0.001) TGF-beta 1 synthesis in both early and late cultures of osteoblasts. IL-6 was not detected in any of the groups considered in this study. CONCLUSIONS: Exogenous TGF-beta 1 has an autocrine effect on cell cultures of osteoblasts. Administration of TGF-beta 1 alone or in combination with Ca(OH)2 increases the synthesis of TGF-beta 1 in osteoblast cultures. Ca(OH)2 and TGF-beta 1 are compatible when placed in a culture of osteoblasts. Ca(OH)2 provides a favourable environment for the anabolic effects of TGF-beta 1.

Analysis of Variance↗

Effects of calcium hydroxide and transforming [correction of tumor] growth factor-beta on collagen synthesis in subcultures I and V of osteoblasts.

Collagen protein synthesis by osteoblasts is influenced by transforming growth factor-beta (TGF-beta 1) and is essential to bone formation. The effectiveness of TGF-beta 1 depends on efficient delivery of the growth factor to target cells, adequate binding to cell surface receptors, and an optimum environment for promotion of collagen synthesis. The effects of calcium hydroxide (Ca(OH)2), TGF-beta 1, and Ca(OH)2/TGF-beta 1 co-administration on total protein, collagen protein, and noncollagen protein synthesis by early (subculture I) and late (subculture V) osteoblast cultures were tested. TGF-beta 1 significantly increased all protein synthesis in subculture I osteoblasts (p = 0.001; p < 0.001; p = 0.019). Ca(OH)2/TGF-beta 1 co-administration significantly increased total protein and collagen protein levels in subculture I osteoblasts as well (p = 0.048; p = 0.012). TGF-beta 1 increased total protein and collagen protein synthesis significantly in subculture V cells (p = 0.025; p = 0.01). These data indicate that co-administration of Ca(OH)2 and TGF-beta 1 enhances collagen synthesis by osteoblasts and may have implications for the clinical setting.

Analysis of Variance↗

Meal pattern analysis in response to temporomandibular joint inflammation in the rat.

Inflammation of the temporomandibular joint (TMJ) can alter behavioral responses such as food intake and mobilize stress hormones. The hypothesis of this study was that food intake and diurnal corticosterone analysis can be used as indicators of adjuvant-induced TMJ inflammation. Groups of rats received adjuvant or no injections at the beginning of the resting (AM) or activity (PM) phase. Forty-eight hours (early) or 6 weeks (late) after adjuvant injection, plasma corticosterone was assayed and food intake was recorded. Food intake was suppressed up to 4 days post-injection. As expected, the non-injected group showed low AM and high PM corticosterone. AM corticosterone was elevated, but PM corticosterone was attenuated in both early- and late-stage-injected rats. A computerized pair-fed experiment showed that adjuvant-induced hypophagia did not alter corticosterone levels. Meal pattern analysis revealed decreased food intake due to a decrease in the number of meals taken. Notably, meal size remained the same but meal duration increased. This model demonstrated that food intake and stress hormone analysis could be used as indicators for sequelae of adjuvant-induced TMJ inflammation.

Analysis of Variance↗

Effects of estrogen on the condylar cartilage of the rat mandible in organ culture.

PURPOSE: The effects of estrogen on bone have been well documented. However, very little is known about the regulatory role of estrogen on cartilage and, in particular, the secondary cartilage of the mandibular condyle. The aims of this study were to determine whether estrogen receptors are present in the condylar cartilage of the rat mandible and to assess the effect of varying 17beta-estradiol (E2) concentrations on the proteoglycan content of this tissue. MATERIALS AND METHODS: Mandibular condyles of 16 female Sprague-Dawley rats were resected. Eighteen of these condyles were divided into three groups and the condylar cartilage was removed and placed in organ culture for 4 days with media containing different concentrations of estrogen: 10(-11) mol/L, 10(-8) mol/L, and 10(-6) mol/L. The cartilage then was analyzed for proteoglycan content along with six specimens not passed through the organ culture. Six intact mandibular condyles also were resected and placed in organ culture with the same varying E2 concentrations, and the condylar cartilage was analyzed for estrogen receptors along with two condyles not passed through the culture system. RESULTS: Estrogen receptors were evenly distributed within the chondroblastic and hypertrophic zones in the control group and the group with 10(-11) mol/L E2. With E2 concentrations of 10(-8) mol/L and 10(-6) mol/L, there was a qualitative decrease in hypertrophic chondroblasts, thickness of the condylar cartilage, and a significant decrease in proteoglycan content. CONCLUSIONS: This study shows the presence of estrogen receptors in the secondary cartilage of the rat mandibular condyle. Estrogen has the potential to cause a decrease in extracellular matrix and thickness of this cartilage.

Analysis of Variance↗

Experimental tooth movement through regenerate alveolar bone: A pilot study.

The purpose of this pilot study was to experimentally evaluate tooth movement through regenerate bone at an early time point during the consolidation phase after bilateral mandibular osteodistraction. Two beagle dogs underwent 10 mm of bilateral mandibular lengthening via intraoral distraction osteogenesis between the fourth premolars and first molars. After 1 week of consolidation, retraction of the fourth premolars was initiated. Immediately after completing premolar retraction, the dogs were sacrificed and the mandibles were analyzed radiographically, histologically, and by dental cast measurements. Initially, all 4 fourth premolars moved distally, with 2 of the 4 touching the first molars at the time of sacrifice. Based on the current data, it is possible to move teeth through regenerate bone, and it appears that tooth movement can begin within weeks of starting the consolidation period.

Animals↗

Evaluation of inferior alveolar nerve function during distraction osteogenesis in the dog.

PURPOSE: A series of electrophysiologic studies were performed in a canine model to evaluate inferior alveolar nerve (IAN) function during distraction osteogenesis of the mandible. MATERIALS AND METHODS: Fourteen dogs, including two controls, were used in the study. Twelve dogs underwent a 10-mm bilateral mandibular lengthening with an intraoral bone-borne appliance and midbody osteotomy. By using sensory nerve action potentials, IAN function was assessed before and immediately after surgery, before and at the completion of distraction, and before necropsy after 4, 6, or 8 weeks of fixation. RESULTS: Twelve of the 24 nerves showed a complete loss of evoked potential after surgery without recovery at any point throughout the study. Acute nerve injury caused by either the osteotomy or screw encroachment was identified at necropsy. The other 12 nerves showed reproducible responses after surgery. Eight of these nerves had significant amplitude attenuation of the evoked potentials, which was identified at necropsy as a result of acute injury. The remaining four nerves did not show significant evoked potential abnormalities and appeared to be grossly normal at necropsy. During distraction, the amplitude of evoked potentials in all 12 nerves remained at the postoperative level, whereas latency showed a significant delay. In 7 of these 12 nerves, various degrees of evoked potential recovery were identified at the completion of the study. CONCLUSIONS: The high incidence of acute IAN injury in the current study was primarily related to device construction and osteotomy technique. If acute nerve injury is avoided at surgery, distraction osteogenesis with 10 mm mandibular lengthening appears to produce minimal deleterious effect on IAN function.

Action Potentials↗

Biomechanical considerations of mandibular lengthening and widening by gradual distraction using a computer model.

PURPOSE: Experience using distraction osteogenesis for limb lengthening has shown the importance of appliance orientation. Although successful results of mandibular lengthening using osteodistraction have been reported, optimal orientation of the distractors relative to the mandible has not been determined. The purpose of this study was to evaluate the biomechanical effects of linear distractors placed parallel to the body of the mandible or parallel to the axis of distraction. MATERIALS AND METHODS: A two-dimensional model of the human mandible was generated for computer simulation of mandibular osteodistraction. Linear distractors were then analyzed based on their orientation, either parallel to the body of the mandible or parallel to the axis of distraction. In addition, two types of distraction osteogenesis procedures for mandibular reconstruction were analyzed: 1) bilateral mandibular lengthening, and 2) bilateral mandibular lengthening in combination with midline mandibular widening. RESULTS: Distractors oriented parallel to the body of the mandible caused a lateral displacement of the posterior components of the distraction devices and a reduction of the midline distraction gap during mandibular lengthening. These effects were eliminated when the device was oriented parallel to the axis of distraction. Midline symphyseal widening created axial rotation of the mandibular condyles regardless of the orientation of the distractors. CONCLUSIONS: Distraction appliances must be oriented parallel to the axis of distraction to prevent adverse biomechanical effects during bilateral mandibular lengthening. Additional ramus osteotomies, using hinged devices for angular correction, may be necessary to compensate for rotational movements of the mandibular condyles secondary to midline osteodistraction.

Biomechanical Phenomena↗

Distraction osteogenesis to widen the mandible.

The purpose of this investigation was to elucidate the biology of distraction osteogenesis during mandibular widening. Midsymphyseal vertical interdental osteotomies were performed in nine Macaca mulatta monkeys. After a latency period a tooth-borne appliance was activated at a rate of 0.5 mm twice a day for 7-10 days. The appliance was then stabilized for a period of 4 or 8 weeks. The distraction gap at the inferior portion of the symphysis was bridged completely by new bony trabeculae. Bone formation in the interdental area was apparently related to the surgical technique. Newly formed bony trabeculae were oriented parallel to the direction of distraction. The location of the osteotomy site with an adequate margin of alveolar bone contiguous with the adjacent teeth was necessary for the induction of the distraction osteogenesis. Disproportional movement between superior and inferior portions of the distracted segments was noted.

Alveolar Process↗

Reactive changes in the temporomandibular joint after mandibular midline osteodistraction.

The purpose of this study was to evaluate the histologic changes within the condyle in response to mandibular widening using osteodistraction. Mandibular midline osteotomies were made in nine Macaca mulatta monkeys and tooth-borne distraction devices were bonded to the mandibular dentition. Distraction was continued until a 3-5 mm widening was achieved. The appliances were then stabilized for a period of 4 weeks. Non-decalcified sagittal sections of the lateral, middle and medial thirds of the condyles were analyzed. Although three of the seven animals showed no unusual morphology, four others exhibited morphologic differences within the fibrous layer, cartilage layer or bone/cartilage interface. Histologic changes were seen to occur in the fibrous layer, cartilaginous layer and cartilage/bone interface. The severity of these changes were correlated with the likely rotational forces directed at the condyle on the postero-lateral and antero-medial surfaces.

Analysis of Variance↗

Muscle activity during mandibular movements in normal and mandibular retrognathic subjects.

PURPOSE: The masticatory muscles function as a unit during precise mandibular positioning movements that occur during such activities as speech, singing, or playing musical instruments. This investigation was designed to assess jaw muscle recruitment patterns during controlled mandibular movement in normal subjects and in patients with mandibular retrognathism. PATIENTS AND METHODS: A computer-integrated electromyography (EMG) and movement monitoring (Selspot) system was used to collect data over 7 seconds of a sagittal border movement (Posselt envelope) of the mandible and 4 seconds each of rest position, light tooth contact, and maximum clench. Fine wire bipolar electrodes were placed into the inferior belly of the lateral pterygoid muscles bilaterally and surface electrodes were placed bilaterally over the anterior belly of the temporalis muscles and the masseter muscles. Ten subjects with Class I occlusion, normal cephalometric values, and an absence of temporomandibular joint (TMJ) dysfunction were compared with 12 patients with mandibular retrognathism, Class II malocclusion, and an absence of clinical signs of TMJ internal derangement before and after a bilateral sagittal split and advancement of the mandible. RESULTS: There was a wide variation in standard deviations of EMG activity for the lateral pterygoid muscles in the retrognathic patients compared with normal controls before surgery (P < .05). In light tooth contact, temporalis muscle activity increased after surgery with respect to both control and the presurgical levels (P < .05, P < .005, respectively). In maximum clench, activity in all muscle groups in the retrognathic patients, both before and after surgery, were below that of control subjects (P < .005). The lateral pterygoid muscles showed late recruitment, with low EMG activity levels during the forward movement phase of the envelope, before surgery compared with controls (P < .001). After surgery, the lateral pterygoid muscle showed early recruitment in the forward movement similar to control levels. CONCLUSION: The masticatory muscles function as a unit during mandibular positioning movements. Patients with mandibular retrognathism have different muscle recruitment patterns from those of normal subjects with the mandible at rest and during mandibular movement. After orthognathic surgery, adaptation occurs in the phasic timing of jaw muscle activity.

Adaptation, Physiological↗

Condylar movement and centric relation in patients with internal derangement of the temporomandibular joint.

This study was designed to compare the reproducibility of the condylar translation pathway and the centric relation position in patients with and without internal derangement of the temporomandibular joint. Reproducibility of condylar movement and variability of the axis point of condylar rotation in centric relation was studied in 15 patients with internal derangement of the temporomandibular joint and 15 patients with no history or clinical signs of mandibular dysfunction. Condylar movement and axis point location were recorded with a sagittal recording device at three separate recording sessions. Lead markers were placed on the skin over the axis and orbital points, and lateral cephalometric radiographs were taken at each session. Analysis of cephalometric and axiographic recordings included both linear and angular measurements. Analysis of the condylar movement pathway revealed greater within-subject reproducibility in the control group for both the right and left condyles (p < 0.0005 and p < 0.0003, respectively). The axis point of condylar rotation in centric relation, as shown by cephalometric analysis, had significantly more within-subject variability in the horizontal plane for the control group (p < 0.003). There was no significant difference between groups for within-subject variability of condylar position in the vertical direction. These findings are consistent with the contemporary concept of centric relation that a vertically stable condyle with a disk interposed against the anterior eminence is capable of functional adaptation in the horizontal plane. The results have implications with regard to treatment and rehabilitation of patients with temporomandibular joint internal derangement.

Adaptation, Physiological↗

Analysis of temporomandibular joint function after orthognathic surgery using condylar path tracings.

Condylar path tracings provide quantitative and qualitative data regarding the functional status of the temporomandibular joint. This study was designed to identify the functional status of the TMJ by means of condylar path tracings before treatment and to monitor the response of the TMJ to orthognathic surgery. Baseline data for condylar tracings using a sagittal recording device were established in relation to normal limits for opening, protrusive, and medial excursions of the mandible. In 54 patients 108 joints were studied before and up to 1 year after orthognathic surgery. Internal derangements were identified with condylar tracings before treatment in 72% of all joints studied. Also, condylar tracings identified internal derangements that were not found on clinical examination in 11 of 39 patients. Functional adaptation of the TMJ was found to be more favorable for mandibular reduction and maxillary impaction than for mandibular advancement or combined upper and lower jaw procedures. Condylar path tracings were shown to represent a noninvasive technique to identify and monitor the functional status of the TMJ in response to surgical orthodontics.

Adolescent↗

Lateral pterygoid muscle activity in mandibular retrognathism and response to mandibular advancement surgery.

Electromyographic patterns of muscle activity were recorded in 11 patients with mandibular retrognathism and compared with ten normal subjects. Categorization of facial morphology was based on standard cephalometric data. Seven patients in the retrognathic group have been studied 1 year after mandibular-lengthening surgery. A computer-based data acquisition and analysis system with a Selspot movement monitoring system was used to record and quantify simultaneously both mandibular movement patterns and associated electromyographic data. Of particular interest was the pattern of activity for the lateral pterygoid muscles of all patients in the retrognathic group compared with controls. Both the ipsilateral and contralateral lateral pterygoids contracted during either right or left lateral excursions for eight of the 11 patients in the retrognathic group compared to aphasic activity during this movement as expected in the control group. However, all seven of the patients tested 1 year after mandibular lengthening demonstrated normal aphasic firing patterns of the lateral pterygoid muscles (inferior belly) during right and left lateral excursions. The retrognathic group of patients also demonstrated abnormal recruitment patterns of the lateral pterygoid muscles during border movements of the mandible in the preoperative stage. Recruitment patterns approached normal levels after mandibular advancement surgery. The number of patients studied did not permit accurate statistical analysis. However, a trend is apparent that demonstrates previously unreported abnormal activity patterns of the lateral pterygoid muscles and an adaptive response of these muscles to orthognathic surgery.

Adult↗

Masticatory function in patients with juvenile rheumatoid arthritis.

PURPOSE: Children with Juvenile Rheumatoid Arthritis (JRA) rarely report temporomandibular joint (TMJ) pain, which may be due to pain avoidance mechanisms resulting in compromised masticatory function. This study examined the relationship between self-report measures of pain and dysfunction and measures of chewing performance in 44 JRA children and 34 normal controls. METHODS: The children were divided into three groups: Group 1, JRA children with temporomandibular joint disorder (TMD); Group 2, JRA children without TMD; Group 3, normal control children without TMD. Both visual and analog scales of jaw pain, ability to chew, and quality of life were administered before and after chewing tasks. Children chewed standardized portions of an artificial food for 20 cycles and expectorated the particles into a cup. This process was repeated five times. Median particle size and a broadness of particle distribution index were measured. Also, the number of chewing cycles prior to the child's first swallow for a cube of carrot was recorded. RESULTS: The broadness of particle distribution index was greater for Group 1 (P < 0.001) and Group 2 (P < 0.03) than for Group 3 with no difference in number of chews for carrot mastication among groups. Group 1 reported more pain and dysfunction before the chewing tasks than Groups 2 or 3 (P < 0.05). Interestingly, only Group 3 reported increased pain and decreased ability to chew after chewing tasks (P < 0.02). CONCLUSION: Children with JRA compromise their masticatory function as a pain avoidance mechanism. Such findings may have profound implications with regard to the nutritional status for these children.

Adolescent↗