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We interviewed 34 patients admitted to Frederiksberg Hospital, Department of Internal Medicine, all of whom had been subject to erroneous handling, to determine how they experienced errors during hospitalization and how they perceived the staff-handled errors. 36% thought that the staff handled the errors badly. Communication mistakes were the most common. We found that the patients wanted the staff to recognize errors, to inform more about the treatment, to speak politely and to spend more time during discharge.

In a nonviral gene delivery system, localization of a plasmid DNA in the nucleus is a prerequisite for expression of a desired therapeutic protein encoded in the plasmid DNA. In this study, a reducible polymer-based gene delivery system for improved intracellular trafficking and nuclear translocation of plasmid DNA is introduced. The system is consisted of two components, a plasmid DNA having repeated binding sequence for a karyophilic protein, NFkappaB, and a reducible polymer. A reducible poly(amido ethylenimine), poly(TETA-CBA), was synthesized by a Michael-type addition polymerization between cystamine bisacrylamide and triethyl tetramine. The polymer forming tight complexes with plasmid DNA could be degraded in the reductive cytosol to release the plasmid DNA. The triggered release mechanism in the cytosol could facilitate the interaction between cytosolic NFkappaB and the plasmid DNA having repeated NFkappaB biding motif. Upon activation of NFkappaB by interleukin-1beta (IL-1beta), most of the plasmid distributed in the cytoplasm was localized within the nucleus, resulting in significantly higher gene transfection efficiency than controls with nondegradable PEI. The current study suggests an alternative way of improving transfection efficiency by taking advantage of endogenous transport machinery for intracellular trafficking and nuclear translocation of a plasmid DNA.

The application of plasmid DNA (pDNA)-based gene therapy is limited by its inefficient transgene expression. In this study, minicircle DNA was evaluated for efficient vascular endothelial growth factor (VEGF) expression in skeletal muscle cells. Production of minicircle DNA encoding VEGF was studied by a semi-quantitative electrophoresis method leading to optimized bacterial culture conditions and producing high purity (86.6%) minicircle DNA. The VEGF minicircle DNA under control of the SV40 promoter (pMini-SV-VEGF) showed an increased amount of VEGF mRNA and up to 8 times more VEGF expression than a conventional plasmid (pSV-VEGF) in two different skeletal muscle cell lines (C2C12 and L8). Minicircle DNA with different promoters, including the SV40, CMV and chicken beta-actin, was tested for VEGF expression in a C2C12 skeletal muscle cell line. The high VEGF expression generated by minicircle DNA stimulated efficient endothelial cell growth in vitro. Furthermore, minicircle DNA expressed higher VEGF compared to conventional plasmid in the tibialis anterior (TA) muscle of mice. Taken together, the results suggest that minicircle DNA is an efficacious gene vector for angiogenic VEGF expression in skeletal muscle and may be useful for treating peripheral arterial disease (PAD).

Background: The aim of this trial was to evaluate the induction and recovery characteristics of microemulsion propofol (Aquafol; Daewon Pharmaceutical Co., Ltd., Seoul, Korea). Pharmacokinetics, pharmacodynamics, and safety profile were investigated. Lipid emulsion propofol (Diprivan; AstraZeneca, London, United Kingdom) was used as a comparator., Methods: Thirty-one healthy volunteers aged 20-79 yr were given an intravenous bolus of propofol 2 mg/kg, followed by variable rate infusion for 60 min. Each volunteer was studied twice with different formulations at an interval of 1 week. Arterial concentrations of propofol were measured, and Bispectral Index was used as a surrogate measure of propofol effect. The induction and recovery characteristics including bioequivalence were evaluated by noncompartmental analysis. The pharmacokinetics and pharmacodynamics were investigated using a population approach with mixed effects modeling. The rate, severity, and causal relation of adverse events were analyzed., Results: Both formulations were bioequivalent. The observed time to peak effect after a bolus of both formulations was 1.5 min. Plasma concentration of propofol at loss of consciousness, time to loss of consciousness after a bolus, and time to recovery of consciousness after discontinuation of infusion did not show significant differences. The population pharmacokinetics and pharmacodynamics revealed a variety of differences between two formulations. Aquafol showed similar safety profile to Diprivan., Conclusions: The efficacy and safety of Aquafol were not different from those of Diprivan within the dose range in this study.

Naked plasmid DNA (pDNA)-based gene therapy has low delivery efficiency, and consequently, low therapeutic effect. We present a biodegradable nonionic triblock copolymer, PEG(13)-PLGA(10)-PEG(13), to enhance gene delivery efficiency in skeletal muscle. Effects of PEG(13)-PLGA(10)-PEG(13) on physicochemical properties of pDNA were evaluated by atomic force microscopy (AFM) imaging, gel electrophoresis and zeta-potential analysis. AFM imaging suggested a slightly compacted structure of pDNA when it was mixed with the polymer, while zeta-potential measurement indicated an increased surface potential of negatively charged pDNA. PEG(13)-PLGA(10)-PEG(13) showed a relatively lower toxicity compared to Pluronic P85 in a skeletal muscle cell line. The luciferase expression of pDNA delivered in 0.25% polymer solution was up to three orders of magnitude more than branched polyethylenimine (bPEI(25 k))/pDNA and three times more than that of naked pDNA five days after intramuscular administration. This in vivo gene delivery enhancement was also observed displaying a two-fold higher expression of human vascular endothelial growth factor (VEGF). Based on fluorescence labeled pDNA distribution, it is speculated that the greater diffusivity of PEG(13)-PLGA(10)-PEG(13)/pDNA compared to bPEI(25 k)/pDNA accounts for better transfection efficiency in vivo. To summarize, combining PEG(13)-PLGA(10)-PEG(13) with pDNA possesses the potential to improve gene delivery efficiency in skeletal muscle.

Delivery of the hypoxia-inducible vascular endothelial growth factor (RTP-VEGF) plasmid using a novel reducible disulfide poly(amido ethylenediamine) (SS-PAED) polymer carrier was studied in vitro and in vivo. In vitro transfection of primary rat cardiomyoblasts (H9C2) showed SS-PAED at a weighted ratio of 12:1 (polymer/DNA) mediates 16 fold higher expression of luciferase compared to an optimized bPEI control. FACS analysis revealed up to 57+/-2% GFP positive H9C2s. The efficiency of plasmid delivery to H9C2 using SS-PAED was found to depend upon glutathione (GSH) levels inside the cell. SS-PAED mediated delivery of RTP-VEGF plasmid produced significantly higher levels of VEGF expression (up to 76 fold) under hypoxic conditions compared to normoxic conditions in both H9C2 and rat aortic smooth muscle cells (A7R5). Using SS-PAED, delivery of RTP-VEGF was investigated in a rabbit myocardial infarct model using 100 mug RTP-VEGF. Results showed up to 4 fold increase in VEGF protein expression in the region of the infarct compared to injections of SS-PAED/RTP-Luc. In conclusion, SS-PAED mediated therapeutic delivery improves the efficacy of ischemia-inducible VEGF gene therapy both in vitro and in vivo and therefore, has potential for the promotion of neo-vascular formation and improvement of tissue function in ischemic myocardium.

Designing synthetic macromolecular vehicles with high transfection efficiency and low cytotoxicity has been a major interest in the development of non-viral gene carriers. A reducible poly(amido ethylenimine) (SS-PAEI) synthesized by addition copolymerization of triethylenetetramine and cystamine bis-acrylamide (poly(TETA/CBA)) was used as a carrier for small interference RNA (siRNA). Poly(TETA/CBA) could efficiently condense siRNA to form stable complexes under physiological conditions and perform complete release of siRNA in a reductive environment. When formulated with VEGF-directed siRNA, poly(TETA/CBA) demonstrated significantly higher suppression of VEGF than linear-polyethylenimine (PEI) (L-PEI, 25kDa) in human prostate cancer cells (PC-3). After 5h of transfection, substantial dissociation and intracellular distribution of siRNA was observed in the poly(TETA/CBA) formulation, but not in the L-PEI formulation. The triggered release of siRNA by reductive degradation of poly(TETA/CBA) in the cytoplasm may affect the RNAi activity by increasing cytoplasmic availability of siRNA. These results suggest that the rational design of non-viral carriers should involve considerations for intracellular dissociation and trafficking of a nucleic acid drug to maximize its effect, in conjunction with formation of stable complexes under physiological conditions.

Vascular endothelial growth factor (VEGF) is an endogenous mediator of tumor angiogenesis. Blocking associations of the VEGF with its corresponding receptors (Flt-1, KDR/flk-1) have become critical for anti-tumor angiogenesis therapy. Previously, we synthesized PEI-g-PEG-RGD conjugate and evaluated as an angiogenic endothelial polymeric gene carrier. In this study, PEI-g-PEG-RGD/pCMV-sFlt-1 complexes are evaluated in terms of tumor growth inhibition in vivo. Complexes were repeatedly injected systemically via tail vein into subcutaneous tumor-bearing mice. As a result, tumor growth was inhibited in the PEI-g-PEG-RGD/pCMV-sFlt-1 injected group. However, this effect was not identified in PEI-g-PEG/pCMV-sFlt-1 or PEI-g-PEG-RGD/pCMV-GFP control groups. Moreover, the survival rate increased in the PEI-g-PEG-RGD/pCMV-sFlt-1 group compared with the controls group. These results suggest that delivery of pCMV-sFlt-1 using PEG-g-PEG-RGD may be effective for anti-angiogenic gene therapy.

Vascular endothelial growth factor (VEGF) is a multifunctional angiogenic growth factor that is a primary stimulant of the development and maintenance of a vascular network in the vascularization of solid tumors. It has been reported that a blockade of VEGF-mediated angiogenesis is a powerful method for tumor regression. RNA interference represents a naturally occurring biological strategy for inhibition of gene expression. In mammalian systems, however, the in vivo application of small interfering RNA (siRNA) is severely limited by the instability and poor bioavailability of unmodified siRNA molecules. In this study, we tested the hypothesis that a hydrophobically modified protein transduction domain, cholesteryl oligo-d-arginine (Chol-R9), may stabilize and enhance tumor regression efficacy of the VEGF-targeting siRNA. The noncovalent complexation of a synthetic siRNA with Chol-R9 efficiently delivered siRNA into cells in vitro. Moreover, in a mouse model bearing a subcutaneous tumor, the local administration of complexed VEGF-targeting siRNA, but not of scrambled siRNA, led to the regression of the tumor. Hence, we propose a novel and simple system for the local in vivo application of siRNA through Chol-R9 for cancer therapy.

Poly(amido ethylenimine) polymers, a new type of peptidomimetic polymer, containing multiple disulfide bonds (SS-PAEIs) designed to degrade after delivery of plasmid DNA (pDNA) into the cell were synthesized and investigated as new carriers for triggered intracellular gene delivery. More specifically, three SS-PAEIs were synthesized from Michael addition reactions between cystamine bisacrylamide (CBA) and three different ethylene amine monomers, i.e., ethylenediamine (EDA), diethylenetriamine (DETA), or triethylenetetramine (TETA). Complete addition reactions were confirmed by (1)H NMR. The molecular weight, buffer capacity, and relative degree of branching for each SS-PAEI was determined by gel permeation chromatography (GPC), acid-base titration, and liquid chromatography-mass spectroscopy (LC-MS), respectively. Physicochemical characteristics of polymer/pDNA complexes (polyplexes) were analyzed by gel electrophoresis, particle size, and zeta-potential measurements. All three SS-PAEIs effectively complex pDNA to form nanoparticles with diameters less than 200 nm and positive surface charges of approximately 32 mV. The in vitro gene transfer properties of SS-PAEIs were evaluated using mouse embryonic fibroblast cell (NIH3T3), primary bovine aortic endothelial cell (BAEC), and rat aortic smooth muscle cell (A7R5) lines. Interestingly, polyplexes based on all three SS-PAEIs exhibited remarkably high levels of reporter gene expression with nearly 20x higher transfection efficiency than polyethylenimine 25k. The high transfection efficiency was maintained in the presence of 10% serum in the transfection medium. Furthermore, confocal microscopy experiments using labeled pDNA indicated that polyplexes of SS-PAEI displayed greater intracellular distribution of pDNA as compared to PEI, most likely due to environmentally triggered release. Therefore, SS-PAEIs are a new class of transfection agents that facilitate high gene expression while maintaining a low level of toxicity.

Novel ABA triblock copolymers consisting of low molecular weight linear polyethylenimine (PEI) as the A block and poly(ethylene glycol) (PEG) as the B block were prepared and evaluated as polymeric transfectant. The cationic polymerization of 2-methyl-2-oxazoline (MeOZO) using PEG-bis(tosylate) as a macroinitiator followed by acid hydrolysis afforded linear PEI-PEG-PEI triblock copolymers with controlled compositions. Two copolymers, PEI-PEG-PEI 2100-3400-2100 and 4000-3400-4000, were synthesized. Both copolymers were shown to interact with and condense plasmid DNA effectively to give polymer/DNA complexes (polyplexes) of small sizes (<100 nm) and moderate zeta-potentials (approximately +10 mV) at polymer/plasmid weight ratios > or =1.5/1. These polyplexes were able to efficiently transfect COS-7 cells and primary bovine endothelial cells (BAECs) in vitro. For example, PEI-PEG-PEI 4000-3400-4000 based polyplexes showed a transfection efficiency comparable to polyplexes of branched PEI 25000. The transfection activity of polyplexes of PEI-PEG-PEI 4000-3400-4000 in BAECs using luciferase as a reporter gene was 3-fold higher than that for linear PEI 25000/DNA formulations. Importantly, the presence of serum in the transfection medium had no inhibitive effect on the transfection activity of the PEI-PEG-PEI polyplexes. These PEI-PEG-PEI triblock copolymers displayed also an improved safety profile in comparison with high molecular weight PEIs, since the cytotoxicity of the polyplex formulations was very low under conditions where high transgene expression was found. Therefore, linear PEI-PEG-PEI triblock copolymers are an attractive novel class of nonviral gene delivery systems.

The purpose of this study was to evaluate the effect of a tricyclic antidepressant (amitriptyline) on nocturnal masseteric activity and duration of sleep in bruxists. Using a randomized, double blind, crossover design, ten females (mean age 39 yrs, +/- sd seven yrs) received active (amitriptyline 25 mg/night) and inactive (placebo 25 mg/night) medication, over a period of four weeks each. A portable EMG integrator recorded the nocturnal, unilateral, and cumulative myoelectrical activity (microV/min of sleep) of the masseter muscle during the fourth and eighth weeks of the study. The results showed that amitriptyline did not significantly decrease the mean EMG activity (df = 9, alpha = 0.05, paired-t = 0.892, p = 0.3964), nor did it significantly increase the duration of sleep (df = 9, alpha = 0.05, paired-t = 2.140, p = 0.061). The results of this study do not support the administration of 25 mg of amitriptyline per night over a period of four weeks for the management of sleep bruxism.

To study mandibular motions with respect to time (kinematics) and the forces causing and resulting from these motions (kinetics), four subjects generated rapid depression and elevation of the mandible (displacement of 0.224 m; peak velocity of 0.237 m s(-1) during depression and 0.269 m s(-1) during elevation). The motion of depression (duration of 0.195 s; kinetic energy of 2.072 x 10(-3) J) could be divided into a phase of acceleration (2.742 m s(-2); +/- 0.28 gn) and a phase of deceleration (2.264 m s(-2); - 0.23 gn), and the terminal excess kinetic energy of depression was absorbed and dissipated by, primarily, the temporomandibular joint. Similarly, the ensuing motion of elevation (duration of 0.182 s; kinetic energy of 2.948 x 10(-3) J) could be divided into a phase of acceleration (3.498 m s(-2); + 0.36 gn) and a phase of deceleration (2.931 m s(-2); -0.30 gn), and the terminal excess kinetic energy of elevation was absorbed and dissipated by, primarily, the dentitions and, secondarily, by the temporomandibular joint. Rapid depression of the mandible appeared to be under the central control of a preprogrammed motor command, and ensuing rapid elevation of the mandible appeared to be under the peripheral control of a segmental and/or transcortical reflex. During rapid depression and elevation of the mandible, the anterior suprahyoid, anterior temporalis, and sternocleidomastoid muscles were myoelectrically active 56%, 73%, and 71% of the time, respectively, and myomechanically active 42%, 59%, and 57% of the time, respectively. Over a follow-up period of 12 months, the studied mandibular motions did not cause injury to the dentitions and temporomandibular joint.

Following an introduction to the functional properties of a three-dimensional instantaneous helical axis pertaining to circular (rotatory) and linear (translatory) motions of the mandible, this feasibility study applied the concept of a mandibular average finite helical axis to the maneuver of cyclic opening and closing of the mouth in three healthy subjects. Through the accelerations and decelerations of a mandibular incisor point (instead of a mandibular condylar point) as well as the laws of physics, the kinetic reaction forces and reaction pressures in the upper and lower cavities of the temporomandibular joint (TMJ) were estimated over opening-closing distances of five and ten mm from centric occlusion. The translatory reaction pressures in the upper TMJ cavity (17-29 mm Hg) exceeded the rotatory reaction pressures in the lower TMJ cavity (5-12 mm Hg). The estimated reaction pressures were in close agreement with synovial fluid pressures measured in vivo in the TMJ of humans and pigs, and the biologic significance of frequent and/or prolonged increased TMJ hydrostatic pressures is discussed.

Albeit never substantiated through experimental and clinical evidence, the theoretical linchpin of the mechanics of a so-called whiplash injury of the temporomandibular joint (TMJ) is the postulate that a pre-existing depressor force (continual anchoring force), generated by the anterior suprahyoid (SH) muscles, will always act on the mandible and cause traumatic mouth opening (anterior acceleration of the TMJ condyles) when the neck is extended (posterior acceleration of the head). To test aspects of this postulate, six subjects assumed the positions of neutral (0 degrees ), medium (32 degrees ) and maximum (58 degrees ) neck extension while the mandible was in its postural positions of rest and light centric occlusion. By means of surface electromyography, it was shown that the relative contractile activities of the anterior SH muscles never exceeded 7.3% of the contractile activity required to anchor the mandible in a position of maximum depression. By means of electrognathography, it was shown that the maxillary and mandibular incisors were never separated by more than 2.6 mm during neutral, medium, and maximum extension of the neck. In other words, during neck extensions there was no evidence of a continual or induced voluntary or involuntary depressor force that would and could anchor the mandible in a position of traumatic mouth opening. Accordingly, and in agreement with other biophysical and biomedical evidence, it was concluded that there is no foundation for the pseudoscientific speculations and unsubstantiated opinions offered in support of a concept and diagnosis of a so-called TMJ whiplash injury. Additionally, this study found co-activation of cervical flexor muscles and mandibular elevator as well as depressor muscles.

Referring to the temporomandibular joint (TMJ) of the human mandibular locomotor system, it has been asserted that displacement of the TMJ disc and inflammation of TMJ tissues are the results of acute and indirect trauma to the TMJ; on occasion this is allegedly experienced in motor vehicle accidents and commonly known as a TMJ whiplash injury. It is postulated that the TMJ whiplash injury is released in the occupant or occupants of a target vehicle when its rear end is impacted by the front end of a bullet vehicle. On the basis of detailed analyses of TMJ trauma/pain histories and TMJ magnetic resonance images, presented as circumstantial evidence in favour of the postulated TMJ whiplash injury, and detailed analyses of the mathematical biophysics of the mandibular locomotor system as well as direct experimental evidence, it is concluded that the postulated TMJ whiplash injury does not exist as a single and independent disease entity caused by motor vehicle accidents. If TMJ disc displacement and inflammation are present, they are expressions of an insidious and progressive pre-existing (pre-accident) disease entity that is comprised of TMJ synovitis/osteoarthritis (phase of inflammation with presence of immune system cells), TMJ internal derangement (phase of disc displacement and deformation with presence of proteinases), and TMJ osteoarthrosis (phase of degeneration with absence of immune system cells). For the asserted TMJ whiplash manoeuvre and ensuing injury to occur as postulated, the laws of physics and biology would have to be suspended.

Using a double-blind and randomized experimental design, ten adult subjects with sleep bruxism were administered amitriptyline (25 mg/night) and placebo (25 mg/night), each compound over a period of one week. Neither the intensities and locations of pains nor the nocturnal masseteric electromyographic activities were significantly affected by the tricyclic antidepressant. In fact, intake of amitriptyline was unpredictably associated with either an increase or a decrease in masseteric electromyographic activity (microV.s/min of sleep). On the basis of this study, small doses of amitriptyline cannot be recommended for the control of sleep bruxism and associated discomforts.

Because a so-called mandibular whiplash injury requires the absence of short-latency jaw-closing reflexes in order to explain the postulated mechanism of injury (excessive jaw opening); the authors studied the presence and absence and more importantly, the kinematics (duration, displacement, velocity, acceleration) of monosynaptic and possibly, polysynaptic myotatic (stretch) reflexes in the jaw elevator muscles. In six healthy adults jaw jerk maneuvers were elicited through a brisk tap on the chin, and surface electromyography identified elevator reflexes while translational electrognathography identified the kinematics of the reflexes. The maneuvers were done while maintaining the rest position (3% MVC) and moderate clenching of the teeth (30% MVC). Electromyography was also used to identify phasic elevator excitations during a passive brisk neck extension maneuver. A sudden and unexpected elongation of the jaw elevators released autogenic reflex responses that, in conjunction with augmented tissue elasticity (stiffness), elevated the mandible into centric occlusion within approximately 150 milliseconds. In 86% of trials, the responses occurred regardless of the prevailing resting and clenching contractile activities. There was no evidence of a depressor force that consistently would and could anchor the mandible in a position of extreme or moderate depression, the theoretical linchpin of the mandibular whiplash injury. It was concluded that the mandibular locomotor system is very efficient in maintaining the rest and intercuspal positions of the mandible. This study found no evidence corroborating the mechanism claimed to release a so-called mandibular whiplash injury.

Using the mouth as an "in vivo articulator," the bilateral nonmasticatory ("empty") contact patterns of opposing cuspid and first molar teeth were determined in two healthy subjects with well-defined cuspid function and two healthy subjects with well-defined group function. The electronically recorded "empty" contact patterns pertained to the static intercuspal position and dynamic laterotrusion to the right and the left. On the basis of the "empty" tooth contact patterns and the number of electronically recorded masticatory cycles of one masticatory sequence, we postulated two simple models that attempted to predict the masticatory ("functional") tooth contacts of one sequence of unilateral mastication of apple and banana. Statistical comparisons between the predictions of the two models and the actual ("functional") contacts of in vivo mastication showed that the models predicted fairly well the observed tooth contacts on the nonchewing-side of the mouth, but not the observed tooth contacts on the chewing-side of the mouth. In consequence, "empty" (nonmasticatory) tooth contact patterns should not be equated with "functional" (masticatory) tooth contact patterns.

In 46 non-patients and 46 patients, the authors examined the presence (+) and absence (-) of canine tooth guidance (CG), i.e. dynamic dental articulation events in contrast to static dental occlusion events. During a right and a left laterotrusion of the mandible, the number of simple, mutually exclusive and exhaustive tooth guidance events (possibilities) was four. In addition, the authors examined the associations between temporomandibular joint (TMJ) sounds and canine guidance events. In non-patients, CG+ was relatively infrequent (30%), and CG- was relatively frequent (70%). In patients, CG+ was relatively infrequent (22%), and CG- was relatively frequent (78%). In both non-patients and patients, bilateral CG+ was rather infrequent (15%). In both non-patients and patients with the presence of TMJ sounds, CG+ was relatively infrequent (38%) while CG- was relatively frequent (61%). In non-patients as well as patients, no evidence was found that distal CG+ (putative lateral retrusive guidance) was associated with ipsilateral TMJ sounds (relative risk = 0%), nor that the association between mesial CG+ (putative lateral protrusive guidance) and ipsilateral TMJ sounds was beyond that of mere chance (relative risk = 50%).

As it specifically pertains to temporomandibular disorders (TMD), this article is an educational analysis and discussion of some recently proposed diagnostic criteria, diagnostic methods, and diagnostic decision processes. On the basis of a discussion of classic probability theory, classic measurement theory, and examples using nonparametric inferential statistical tests, it is suggested that certain TMD diagnostic criteria and methods, and their associated decision matrix, favor subjective clinical opinions (largely pseudoscientific observations) and arbitrary clinical indices rather than objective scientific facts.

In ten healthy subjects, bilateral contacts between opposing cuspid and first molar teeth were recorded during one sequence of unilateral chewing of apple, peanuts, and banana. Unknown magnitudes of mechanophysical (masticatory) forces were inferred to act directly on the chewing-side cuspid teeth in 71% of all masticatory cycles and on the nonchewing-side cuspid teeth in 68% of all masticatory cycles. In addition, unknown magnitudes of mechanophysical forces were inferred to act directly on the chewing-side first molar teeth in 74% of all masticatory cycles and on the nonchewing-side first molar teeth in 86% of all masticatory cycles. During the chewing of peanuts, the total number of chewing-side cuspid contacts exceeded significantly the total number of nonchewing-side cuspid contacts, suggesting more repetitive direct mechanophysical loading of the chewing-side cuspid teeth. During the chewing of apple, the total number of nonchewing-side first molar contacts exceeded significantly the total number of chewing-side first molar contacts, suggesting more repetitive direct mechanophysical loading of the nonchewing-side first molar teeth. The variable contact patterns were, to a large extent, explained by rotational movements of the entire mandible resulting in translational movements of the hemimandible.

In 46 non-patients and 46 patients, the authors examined the presence (+) and the absence (-) of laterotrusive (LG) and mediotrusive (MG) tooth guidance, i.e. dynamic dental articulation events in contrast to static dental occlusion events. During a right and left laterotrusion/mediotrusion of the mandible, the number of compound, mutually exclusive and exhaustive tooth guidance events (possibilities) was six. In addition, the presence and the absence of temporomandibular joint (TMJ) sounds, provoked TMJ pains, and the associations between TMJ sounds and tooth guidance events were examined. In non-patients, LG+ and MG+ was relatively infrequent (30%) while LG+ and MG- was relatively frequent (70%). In patients, LG+ and MG+ was relatively frequent (58%) while LG+ and MG- was relatively infrequent (42%). LG- and MG+ was absent in non-patients and rare in patients (3%). Either unilateral or bilateral MG+ was relatively infrequent in non-patients (30%) and relatively frequent in patients (59%). Bilateral MG+ was relatively infrequent in non-patients (20%) and relatively frequent in patients (52%). Either unilateral or bilateral TMJ sounds were relatively infrequent in non-patients (39%) and relatively frequent in patients (74%). Either unilateral or bilateral provoked TMJ pains were absent in non-patients and relatively frequent in patients (72%). The authors found no evidence that TMJ sounds were associated with the ipsilateral absence of so-called balancing contacts (MG-) in non-patients and patients. Finally, no evidence supporting the use of a so-called positive predictive value, and "extension concept' of probability theory was found.

Twelve healthy subjects performed 10 s, 15 s, 20 s, and 25 s of right-sided and, subsequently, left-sided gum chewing. The contractile activities of the ipsilateral (chewing side) and contralateral (non-chewing side) masseter muscles, mainly the concentric contractions of the phase of jaw closing and the isometric contractions of the phase of dental occlusion, were recorded through cumulative surface electromyography (EMG). A linear function (y = ax + b) described the association between an increase in the duration (x) of unilateral gum chewing and the cumulative EMG (y) of both the ipsilateral and the contralateral masseter muscle, and because of different slopes (a) of the two straight lines a geometric function (y = aqx) described the progressively larger differences between the paired and straight lines. When differential calculus was applied to the exponential functions, it became evident that the chewing forces generated by the ipsilateral masseter muscle continually exceeded those generated by the contralateral masseter muscle, and that the positive work (force x distance) produced by the concentric contractions of the ipsilateral masseter muscle continually exceeded that produced by the concentric contractions of the contralateral masseter muscle. It was inferred that mechano-physical work plays a major role if clinical muscle fatigue develops during prolonged unilateral gum chewing.

This article is an educational analysis and discussion of some recently proposed diagnostic criteria, diagnostic methods, and diagnostic decision processes, pertaining specifically to temporomandibular disorders (TMD). On the basis of a discussion of classic probability theory, classic measurement theory, and examples using nonparametric inferential statistical tests, it is suggested that certain TMD diagnostic criteria and methods, and their associated decision matrix, favor subjective clinical opinions (largely pseudoscientific observations) and arbitrary clinical indices rather than objective scientific facts.

To study possible associations between gum chewing and fatigue and pains in the jaw muscles, eight healthy adults performed prolonged idling, prolonged unilateral chewing of gum, and brief vigorous clenching of the teeth (MVC). Through surface electromyography (EMG), the authors monitored the cumulative (microV.s) as well as the average rates (microV.s-1) of contractile activities in the right and left masseter muscles. During 10 min of idling there was an absence of muscle fatigue and muscle pains when the EMG rates of the right and left masseter muscles were 2% and 3%, respectively, of those required to elicit isometric muscle pains through MVC. During 10 min of right-sided gum chewing at a rate of 1.2 Hz, the majority of subjects (75%) experienced weak jaw muscle fatigue-not jaw muscle pains-when the EMG rates of the right and left masseter muscles were 38% and 19%, respectively, of those required to elicit isometric pains through MVC. In comparison with 10 min of idling, the weak muscle fatigue of 10 min of unilateral gum chewing appeared when the total contractile activities of the right and left masseter muscles were increased by 1664% and 519%, respectively. It seemed as if prolonged unilateral gum chewing and previous pain-releasing MVC caused some sensitization of muscle nociceptors which, in turn, aggravated subsequent isometric jaw muscle pains elicited through MVC. Even though the right masseter muscle was the most frequent site of clinical fatigue and pains, the authors found no evidence supporting the theoretical foundation of the myofascial pain/dysfunction syndrome.

In seven (88%) of eight healthy subjects, weak to moderate pains were elicited in the masseter muscles through the isometric contractions of maximum voluntary teeth clenching. Integrated surface electromyograms of the right and left masseter muscles were used to quantify the absolute and relative contractile activities of the two muscles. The risk (relative probability) of inducing pain onset in the single masseter muscle generating the larger amount of isometric activity was 2.5 times the risk of eliciting pain onset in the single masseter muscle generating the lesser amount of isometric activity. However, as an aid in the diagnosis of pain onset, the method of masseteric surface electromyography had a false diagnostic ratio of 0.67.

Frontal plane mandibular rotations and corresponding hemimandibular translations were studied in vitro by using direct observations of a human cadaver mandible and in vivo by using the indirect observations of rotational electrognathography. A comparison between the two methods showed that rotational electrognathography erred in measuring the clinically relevant hemimandibular translations resulting from mandibular rotations having a unilateral molar point (simulated occlusal interference) as the pivot of frontal plane torque. In vitro frontal plane rotations about a unilateral mandibular molar tooth (simulated occlusal interference) suggested that the resulting hemimandibular upward translations of the lateral portion of the mandibular condyle, contralateral to the molar tooth, would cause considerable compressive loading of the temporomandibular joint disc.

In 12 subjects, a pliable, yet unbreakable, intercuspal interference (aluminum shim onlay splint; uniform height of 0.25 mm) was placed between either the right or left maxillary and mandibular second premolars and first molars. During brief and forceful biting (dynamic chewing stroke of about 20 kg force) the interference emulated a semisoft food bolus, and at the end of biting (subsequent static clenching stroke of about 20 kg force) it emulated a rigid metal interference. During dynamic/static biting, rotational electrognathography measured maximum frontal and horizontal plane torque of the right and left mandibular condyles. Eleven subjects (92%) showed frontal plane upward rotation (mean of 1.0 degree) of the condyle contralateral to the interference, and one subject (8%) showed frontal plane upward rotation (0.4 degree) of the condyle ipsilateral to the interference. Two subjects (17%) showed no horizontal plane rotation; seven subjects (58%) showed backward rotation (mean of 0.4 degree) of the condyle contralateral to the interference; and three subjects (25%) showed backward rotation (mean of 0.3 degree) of the condyle ipsilateral to the interference. It is suggested that, in the presence of an occlusal interference, mastication may have both short- and long-term detrimental effects.

A rigid intercuspal interference (minimum mean height of 0.24 mm) was placed on either the right or left mandibular second premolar and first molar of 12 subjects. During brisk and forceful biting on the interference, rotational electrognathography measured maximum torque of the right and left mandibular condyles in the frontal and horizontal planes of orientation. All subjects showed frontal plan upward rotation (mean of 0.7 degrees) of the mandibular condyle contralateral to the interference. In 33% of the subjects there was no horizontal plane backward rotation. In 58% of the subjects there was horizontal plane backward rotation (mean of 0.5 degrees) of the mandibular condyle ipsilateral to the interference, and in one subject (8%) there was backward horizontal plane rotation (0.1 degree) of the mandibular condyle contralateral to the interference. It was inferred that the masseter muscle, ipsilateral to the interference, generated negative work in order to decelerate frontal plane 'unseating' of the mandibular condyle ipsilateral to the interference. It was inferred that the masseter muscle, contralateral to the interference, produced positive work in order to accelerate frontal plane 'seating' of the mandibular condyle contralateral to the interference. Finally, it was speculated that the impact forces of frontal plane 'seating' of the mandibular condyle, contralateral to the interference, might lead to 'vacuum sticking' of the temporomandibular joint disc because of the formation of negative hydrostatic pressures.

This review shows that experimental occlusal interferences (prematurities) may cause changes in the myoelectric contraction patterns of the human jaw muscles, and changes in the translatory motion patterns of the human mandible. However, it has not been unequivocally established that the observed changes have specific long-term detrimental effects. On the other hand, it is apparent that experimental occlusal interferences are associated with short-term clinical symptoms and signs, such as jaw muscle fatigue and pains, headaches, pains and clickings in the temporomandibular joints. This review suggests that new paradigms involving experimental occlusal interferences should be introduced.

In 12 subjects, a rigid unilateral intercuspal interference (minimum mean height of 0.24 mm) was placed on either the right or left mandibular second premolar and first molar (sagittal physiological equilibrium point of the hemimandibular dental arch). During brisk and forceful clenching on the interference, bipolar surface electromyograms were obtained from the right and left masseter muscles. On the side opposite the interference, myoelectric clenching activity was significantly reduced. Correlation analyses showed that the interference elicited a non-linear (complex) co-ordination of the amplitude, but not the duration, of bilateral masseteric clenching activity, i.e. frequently there was significant motor facilitation on the side of the interference, and significant motor inhibition on the side opposite the interference. Theoretical considerations predicted that brief clenching on the interference would easily lead to frontal plane rotatory motions of the mandible which, indeed, occurred clinically.

In six healthy subjects, the integrated electromyographic (IEMG) activity of the right masseter muscle was recorded during 10 s of maximum voluntary teeth clenching, without and with manual movements (at a rate of 1.6 Hz, with a force of approximately 3N) of the bipolar surface electrodes affixed to the cheek. All IEMG recordings were undertaken at discrimination thresholds of 1 microV and 30 microV. Electrode movements were the likely source of some distortion (artefact) of the IEMG readings. An increase in the discrimination threshold (30 microV vs. 1 microV) seemed to decrease the artefactual effects of electrode movements, possibly because the movements exerted their major distorting effects on the smaller (low voltages) masseteric motor units.

Patients with temporomandibular joint disorders (TMD) report a myriad of problems including headaches, facial pain, limited mouth opening capacity, and clicking and/or grating sounds from the temporomandibular joints. Although conservative therapy with an occlusal splint can bring relief for many of these patients, a small number of subjects must be treated by means of surgical procedures. Direct injections of either air or fluids (saline, local anesthetic, corticosteroid, hyaluronate) into the superior and/or inferior temporomandibular joint (TMJ) cavities have gained popularity. The injection of a local anesthetic and hyaluronic acid can provide relief for patients with persistent, painful nontranslatory closed-lock conditions of the TMJs. As documented through objective electronic and computer-enhanced measurements, this case report describes the effect of sodium hyaluronate on a closed lock condition of the TMJ. This case report explains the methodology employed for a larger group of closed lock patients treated and monitored for over one year. The results of that larger group will be reported at a later time after long-term efficacy is confirmed.

In clinical dentistry, the solidborne vibrations (tissue pressure waves) produced by the temporomandibular joints (TMJ) may signify dysfunction or disease of the mandibular locomotor system. This article discusses aspects of the applied mathematics and electronic recording of solidborne vibrations of the TMJ (electrovibratography).

In clinical dentistry, the sounds (clicking) and noises (grating) produced by the temporomandibular joints (TMJ) usually signify dysfunction or disease of the mandibular locomotor system. In an attempt to provide guidance to the general practitioner, this article discusses some pertinent parameters defining the physics of airborne and solid-borne vibrations.

Through electrognathography and surface electromyography of the right and left masseter muscle (MM), this methodologic study examined the excentric (lengthening) and concentric (shortening) contractions of brief (2000 ms) voluntary teeth grinding performed through canine as well as group function of the opposing teeth. We inferred that the most anterior and superior portions of the right and left MM were lengthened and shortened by at least 4.23 mm (right MM) and 4.82 mm (left MM). For the negative work efforts (excentric contractions) of canine function, the tensions of the ipsilateral MM ranged from 10 to 20% MVC and those of the contralateral MM from 4 to 14% MVC. For the positive work efforts (concentric contractions) of canine function, the tensions of the ipsilateral MM ranged from 11 to 44% MVC and those of the contralateral MM from 20 to 41% MVC. A comparison between canine and group function showed that the negative as well as positive work efforts of group function exceeded those of canine function.

Surface electrovibratographic (EVG) recordings were obtained from the temporomandibular joints (TMJ) of clinically normal subjects (absence of TMJ sounds) and clinically abnormal subjects (presence of TMJ sounds). As examined through single factor analyses of variance and coefficients of intraclass correlation, the EVG recordings showed excellent reproducibility. The analyses showed also that, in comparison with clinically normal TMJs, the vibrations of clinically abnormal TMJs had higher median (+79%) and peak (+137%) frequencies, higher peak amplitudes (+740%), and higher intensities as expressed through the estimated total energy contents (+1843%) and the integrals (+1215%) of power spectrum density functions.

Surface electromyographic (EMG) recordings were obtained from the masseter muscles in healthy subjects performing brisk maximum voluntary teeth clenching (MVC) for about 1 s. During the onset (0-600 ms) of ballistic MVC activity, the peak amplitude of the EMG interference patterns showed a consistent and significant increase, on examination for 0-200 ms, 200-400 ms, and 400-600 ms of MVC activity. The peak (maximum) and median (centroid) frequencies of power spectrum density functions of the raw surface EMGs (interference patterns) showed an absence of consistent and significant changes during 0-600 ms of ballistic MVC activity. However, the estimated total energy contents (peak amplitude x peak frequency) of the surface interference patterns showed a consistent and significant increase from 0 to 600 ms of ballistic MVC activity, and this was interpreted as global recruitment/rate coding of masseteric motor units.

In a sample of 20 non-patients, 60% of the subjects had an absence of subjective temporomandibular joint (TMJ) complaints (noises/sounds) that agreed with objective joint vibration analyses (electrovibratography). Among the remaining 40% of subjects, only 50% of the examined joints showed agreement between subjective and objective findings. Subjects appeared to be unable to reliably detect "weak" (early) symptoms of TMJ dysfunction but were able to reliably detect "strong" (late) symptoms of TMJ dysfunction and possibly disease. As measured through active protrusion and laterotrusion of the mandible, the guidance angles of the anterior teeth could not explain the absence and presence of TMJ vibrations.

The temporomandibular joints of 20 human cadaver heads were examined by means of photography (gross anatomic images) and radiography (lateral oblique transcranial images), using the angle created by a line parallel to the Frankfurt horizontal and a line coinciding with the posterior slope of the most lateral (outermost) portion of the articular tubercle. This lateral eminence angle, made visible through an attached metal wire and a straight stick pin and pertaining to the outermost (zygomatic) portion of the eminentia, was about 45 degrees on both enlarged photographs and enlarged radiographs. There were no significant differences between the photographic and radiographic lateral eminence angles on the right and left sides. A more medially placed angle, yet pertaining to the lateral - and supposedly functional (protrusion) - portion of the glenoid fossa, was about 56 degrees on the right side and 51 degrees on the left side of the radiographic images. There were significant differences between the ipsilateral radiographic lateral and medial eminence angles. A separate decision-making analysis concluded that lateral oblique transcranial radiography is an effective, reliable, and inexpensive method for detection of bony changes in the lateral portions of the temporomandibular joints.

Using laser Doppler flowmetry (LDF), the blood microcirculation of the masseter muscle was studied in one healthy male subject performing clenching and grinding of the teeth. LDF suggested that blood flow was increased during clenching, and that it did not change appreciably during grinding. In one female patient (acute pain from myofibrostic lesion in masseter muscle), LDF suggested that flow within the lesion was increased during rest (postural position). In three healthy adults, subjected to simulated traumatic occlusion of the incisors, LDF suggested an absence of consistent changes in pulpal blood flow.

To determine the relative contribution of the masseter and anterior temporalis muscles to global isometric bite force, activity indices were constructed on the basis of the peak mean voltage (microV) and the integrated voltage (microV.s) of bipolar surface electromyograms obtained during brief maximum voluntary teeth clenching (MVC). The index that was based on integrated myoelectrical activity showed that the masseter muscle contributed the major part of the isometric MVC force. The index that was based on instantaneous peak myoelectrical activity also showed that activity in the masseter muscle predominated over that in the anterior temporalis muscle. In addition, the latter index showed a negative linear association with the initial (0-50% MVC) isometric contraction velocities of the masseter and anterior temporalis muscles. Both indices appear to be promising clinical diagnostic tools.

The maxillary and mandibular casts of 45 healthy and dentulous subjects, with conspicuous wear facets on canines and molars, were mounted on a semiadjustable articulator. The sagittal condylar guidance was determined by two methods: (1) using a protrusion wax interocclusal record and (2) by matching the wear facets of opposing canines and contralateral molars. There was a substantial bilateral symmetry of the right and left sagittal condylar guidance angles using both methods. There were, however, significant differences between the mean angles of the two methods, about 31 degrees (protrusion record) versus about 24 degrees (wear facets). This, in association with rather low coefficients of linear determination, suggested that the two methods of recording the sagittal condylar guidance angle were based on totally different phenomena.

Experimental subjects (n = 29) were patients who had undergone orthodontic treatment in combination with extraction of maxillary or mandibular premolar teeth, or both. Control subjects (n = 29) were healthy dental students with no orthodontic or extraction experience. Sagittal (corrected axis) tomograms of the TMJs were used to determine the narrowest linear distances between the anterior and posterior outlines of the TMJ condyle and the TMJ fossa, expressed as the joint space ratio. There were no significant (p greater than 0.05) differences between the control and experimental ratios. Bipolar surface electromyograms of the masseter and anterior temporalis muscles were used to determine the isometric contraction velocities of these muscles until 50% and 100% voluntary isometric contraction effort (teeth clenching) was achieved. There were no significant (p greater than 0.05) differences between the control and experimental subjects. Electromyograms were also used to determine the relative contribution of the masseter and anterior temporalis muscles to the bite force developed during brief maximum voluntary tooth clenching, expressed as the activity index. There were no significant (p greater than 0.05) differences between the control and experimental subjects.

As induced by an occlusal splint over a period of 1 week, this study monitored surface electromyographic changes in the postural contractile activities of jaw elevator and depressor muscles in six healthy adults. The immediate effect of the occlusal splint was to increase the postural contractile activities of the suprahyoid muscles. All postural muscle activities showed wide-ranging biological variation, but the activities induced by the splint tended to stabilize within 1 week, with decreased postural activities in the masseter and anterior temporalis muscles, and increased postural activities in the suprahyoid muscles.

Three-dimensional electrognathography of an incisor point was used to detect peripheral correlates of deprogramming of the jaw elevator muscles. Putative deprogramming was attempted through the clinically recommended use of a leaf gauge, placed for 10-15 min between the maxillary and mandibular anterior teeth and disoccluding the posterior teeth by about 2 mm. Studied mandibular displacements were those that occurred during voluntary elevation of the mandible from the postural to the intercuspal position. Use of the leaf gauge did not affect the displacement patterns. Within a freeway space of about 0.2 mm3, the incisor point moved about 2 mm vertically, about 1 mm sagittally, and about 0.2 mm laterally.

Without artificial feedback control, maximum voluntary isometric contractions were performed for about 1 s by six subjects. Randomly selected surface electromyograms of the anterior temporalis and masseter muscles suggested that, in some cases, the motor control of the entire isometric contraction might have been preprogrammed through the phenomenon of anticipation. In the majority of cases, the control of the initial contraction phase might have been preprogrammed, followed by a phase of servo-controlled motor activity. As a functional basis for the servo-control of isometric force generation, it was suggested that compartmentalized 'extrafusal and intrafusal motor units' were recruited and decruited in an orderly manner, and periods of alpha-motor inhibition were interpreted as signs of switching from one control scheme to another, possibly via a transcortical loop.