Temporomandibular joint surgery: the past, present, and future.

Temporomandibular joint surgery for various pathological conditions and diseases affecting the integrity, mobility, and function of the joint has a long history. However, the greatest explosion of knowledge regarding the diagnosis and management of temporomandibular joint pain, pathology, and rehabilitation has occurred in the last 50 years. This review focuses on the incremental expansion of knowledge over time that led to the development of concepts that support our current surgical decisions and techniques, with the aim of identifying gaps in knowledge that require well-designed studies to move the field forward. Using this approach will allow an enhancement of our understanding of temporomandibular joint form and function, and enable focus to be placed on the evaluation, diagnosis, and non-surgical and surgical management strategies that are the most efficacious for our patients.

Challenges in diagnosis and management of neutropenia upon exposure to immune-checkpoint inhibitors: meta-analysis of a rare immune-related adverse side effect.

BACKGROUND: Cancer immunotherapy via immune-checkpoint inhibition (ICI) by antibodies against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and cell death protein 1 (PD-1) have significantly improved the outcome of metastasized melanoma and of a rapidly increasing number of other cancer types. The anti-tumor effect is often accompanied by immune-related adverse events (irAE). Hematological irAE, specifically neutropenia, are rarely observed. However, neutropenia is associated with high morbidity and mortality due to infection complications. Thus, early detection and treatment is crucial. METHODS: We present the clinical course of two patients with severe neutropenia after ICI therapy and demonstrate the difficulty of the diagnosis when a comedication of metamizole, a well-known analgesic drug used to treat cancer pain, is present. Further, we provide a comprehensive descriptive and statistical analysis of published data on diagnostics, treatment and infection complication in patients with at least grade 4 neutropenia by a systematic database search. RESULTS: Finally, 34 patients were analyzed, including the two case reports from our cohort. The median onset of neutropenia was 10.5 weeks after first ICI administration (interquartile range: 6 weeks). In 76% (N = 26), a normalization of the neutrophil count was achieved after a median duration of neutropenia of 13 days. In a subsample of 22 patients with detailed data, the infection rate was 13%, proven by positive blood culture in 3 cases, but 68% (N = 15) presented with fever > 38 °C. Treatment regime differed relevantly, but mainly included G-CSF and intravenous corticosteroids. Death was reported in 14 patients (41%), 3 of whom (9%) were associated with hematological irAE but only two directly associated with neutropenia. CONCLUSION: With an increasing number of cancer patients eligible to ICI therapy, the incidence of severe hematological toxicities may rise substantially over the next years. Clinicians working in the field of cancer immune therapies should be aware of neutropenia as irAE to provide immediate treatment.

Ambient and laboratory evaluation of a low-cost particulate matter sensor.

Low-cost, light-scattering-based particulate matter (PM) sensors are becoming more widely available and are being increasingly deployed in ambient and indoor environments because of their low cost and ability to provide high spatial and temporal resolution PM information. Researchers have begun to evaluate some of these sensors under laboratory and environmental conditions. In this study, a low-cost, particulate matter sensor (Plantower PMS 1003/3003) used by a community air-quality network is evaluated in a controlled wind-tunnel environment and in the ambient environment during several winter-time, cold-pool events that are associated with high ambient levels of PM. In the wind-tunnel, the PMS sensor performance is compared to two research-grade, light-scattering instruments, and in the ambient tests, the sensor performance is compared to two federal equivalent (one tapered element oscillating microbalance and one beta attenuation monitor) and gravimetric federal reference methods (FEMs/FRMs) as well as one research-grade instrument (GRIMM). The PMS sensor response correlates well with research-grade instruments in the wind-tunnel tests, and its response is linear over the concentration range tested (200-850 µg/m3). In the ambient tests, this PM sensor correlates better with gravimetric methods than previous studies with correlation coefficients of 0.88. However additional measurements under a variety of ambient conditions are needed. Although the PMS sensor correlated as well as the research-grade instrument to the FRM/FEMs in ambient conditions, its response varies with particle properties to a much greater degree than the research-grade instrument. In addition, the PMS sensors overestimate ambient PM concentrations and begin to exhibit a non-linear response when PM2.5 concentrations exceed 40 µg/m3. These results have important implications for communicating results from low-cost sensor networks, and they highlight the importance of using an appropriate correction factor for the target environmental conditions if the user wants to compare the results to FEM/FRMs.

Mouse preferential incising force orientation changes during jaw closing muscle hyperalgesia and is sex dependent.

INTRODUCTION: Mouse incising is controlled by a central pattern generator and this activity can change in the presence of pain. The incising frequency and maximum force generation decreases with pain. In this study, we used repetitive acidic injections in the left masseter muscle of male and female mice to determine differences between baseline and jaw muscle pain conditions and the effect of sex on preferential incising direction. METHODS: A within subject design was used to evaluate data previously acquired using multi-axis force data (X, Y and Z) from the 4th baseline recording day and day 7 post-injection (day of maximal pain response) for each mouse of each sex. A total of 34 female and male (age 3-9months) CD-1 mice were evaluated. After mathematically rotating the X and Y axes to align the Y axis to be parallel to the wire struts of the cage top, data were analyzed to determine incising direction preference during baseline (non-pain) and pain (day 7) conditions and between sex. Radar plots of X-Y, X-Z and Y-Z axes depicted the average direction of incising preference between baseline and pain conditions for each sex. Statistical differences among groups were tested using a mixed model ANOVA. RESULTS: Similar to previous findings, female mice had a more robust difference in incising direction preference when comparing male and female pain conditions and this was most evident in the X-Z axes. The incising frequencies most commonly affected were 5.3, 6.2 and 7.6Hz. Male mice varied little in their incising direction preference between the baseline and pain conditions. In addition, statistical comparison of ratios of the percent of time spent incising in the Z versus X axes for each incising frequency found that the incising preference was not different when comparing 5.3 and 7.6Hz frequencies. Finally, female mice used a novel approach to minimize pain while incising by rotating their head and body nearly 180 degrees while males did not use this strategy as frequently. CONCLUSIONS: The preferred incising direction changes in a jaw muscle pain condition and this information can be used to further characterize functional pain in the masticatory muscle system. The changes were dependent on the incising frequency generated by the central pattern generator for incising.

Assessment of incising ethology in the absence and presence of jaw muscle hyperalgesia in a mouse home cage environment.

INTRODUCTION: Assessment of oral motor behavior in a mouse is challenging due to the lack of currently available techniques that are non-invasive and allow long-term assessment in a home cage environment. The purpose of this study was to evaluate incising behavior using mouse chow attached to a three-dimensional force transducer that was mounted on the existing home cage. In addition, a persistent hyperalgesia condition was introduced to evaluate the sensitivity of the technique to identify incising behavioral changes. METHODS: Incising activity of CD-1 male and female mice (n=48) was evaluated over a 24 hour recording session during four baseline and six longitudinal hyperalgesia assessment sessions using custom written software. A pre-clinical persistent pain model was used to induce hyperalgesia in the masseter muscle by repetitive acidic saline injections. Sex and age differences were evaluated for multiple incising variables during both light and dark cycles during baseline and hyperalgesia conditions. RESULTS: Significant sex differences were found for multiple incising variables but not for age. Discrete incising frequencies were identified in the range of 4.6-10.4 Hz and were reproducibly found in both female and male mice. A significant shift to lower incising frequencies was observed after repetitive acidic saline injections compared to neutral saline injections. This shift to lower frequencies of incising returned to baseline levels after approximately four weeks but was statistically longer in female compared to male mice. Significant differences were also found for chow intake (reduced) and weight change during the hyperalgesia condition. No significant differences were found for total number of incisions or number of incising episodes per day or incising force. CONCLUSIONS: The findings from this study support the use of recording three dimensional incising forces as a sensitive measure of incising behavior. This novel technique allowed the identification of specific incising variables that were differentially affected in female and male mice during a persistent hyperalgesia. The data were collected in the home cage environment with minimal bias such as experimenter interaction. Similar to other dental pain studies, mice were able to maintain normal incising activity levels per day (total incisions, total number of incising episodes) even in the presence of hyperalgesia.

Total alloplastic temporomandibular joint reconstruction using Biomet stock prostheses: the University of Florida experience.

The purpose of this study was to report the subjective and objective outcomes of temporomandibular joint (TMJ) replacement with Biomet stock prostheses at a single institution in Florida. In this retrospective study, patients who underwent TMJ replacement using a Biomet stock prosthesis from 2005 to 2012 were analyzed. Subjective (pain, diet) and objective (maximal incisal opening) information was obtained. In addition, a quality of life measure was obtained pre- and postoperatively. Significance was set at <0.01. Thirty-six patients (26 bilateral, 6 left, and 4 right) who underwent TMJ replacement using a Biomet stock prosthesis were eligible for the study. Maximal incisal opening improved from 26.1mm preoperatively to a mean of 34.4mm postoperatively. The pain score decreased from 7.9 preoperatively to a mean of 3.8 postoperatively. Diet restriction decreased from 6.8 preoperatively to a mean of 3.5 postoperatively. Quality of life improved from a median of 4 preoperatively to a postoperative median of 2. Four implants were removed/replaced because of heterotopic bone formation, infection, and/or loose hardware. Follow-up ranged from 6 to 83 months. Overall, TMJ reconstruction using the Biomet stock joint is effective and safe in this patient population.

Antidote treatment for cyanide poisoning with hydroxocobalamin causes bright pink discolouration and chemical-analytical interferences.

Here we report the case of a 70-year-old woman who committed suicide by cyanide poisoning. During resuscitation cares, she underwent an antidote treatment by hydroxocobalamin. Postmortem investigations showed marked bright pink discolouration of organs and fluids, and a lethal cyanide blood concentration of 43 mg/L was detected by toxicological investigation. Discolouration of hypostasis and organs has widely been studied in forensic literature. In our case, we interpreted the unusual pink coloration as the result of the presence of hydroxocobalamin. This substance is a known antidote against cyanide poisoning, indicated because of its efficiency and poor adverse effects. However, its main drawback is to interfere with measurements of many routine biochemical parameters. We have tested the potential influence of this molecule in some routine postmortem investigations. The results are discussed.

Limb, respiratory, and masticatory muscle compartmentalization: developmental and hormonal considerations.

Neuromuscular compartments are subvolumes of muscle that have unique biomechanical actions and can be activated singly or in groups to perform the necessary task. Besides unique biomechanical actions, other evidence that supports the neuromuscular compartmentalization of muscles includes segmental reflexes that preferentially excite motoneurons from the same compartment, proportions of motor unit types that differ among compartments, and a central partitioning of motoneurons that innervate each compartment. The current knowledge regarding neuromuscular compartments in representative muscles involved in locomotion, respiration, and mastication is presented to compare and contrast these different motor systems. Developmental features of neuromuscular compartment formation in these three motor systems are reviewed to identify when these compartments are formed, their innervation patterns, and the process of refinement to achieve the adult phenotype. Finally, the role of androgen modulation of neuromuscular compartment maturation in representative muscles of these motor systems is reviewed and the impact of testosterone on specific myosin heavy chain fiber types is discussed based on recent data. In summary, neuromuscular compartments are pre-patterned output elements in muscle that undergo refinement of compartment boundaries and muscle fiber phenotype during maturation. Further studies are needed to understand how these output elements are selectively controlled during locomotion, respiration, and mastication.

Developmental and functional considerations of masseter muscle partitioning.

The masseter muscle participates in a wide variety of activities including mastication, swallowing and speech. The functional demands for accurate mandibular positioning and generation of forces during incising or a power stroke require a diverse set of forces that are determined by the innate muscle form. The complex internal tendon architecture subdivides the masseter into multiple partitions that can be further subdivided into neuromuscular compartments representing small motor unit territories. Individual masseter compartments have unique biomechanical properties that, when activated individually or in groups, can generate a wide range of sagittal and off-sagittal torques about the temporomandibular joint. The myosin heavy chain (MyHC) fibre-type distribution in the adult masseter is sexually dimorphic and is influenced by hormones such as testosterone. These testosterone-dependent changes cause a phenotype switch from slower to faster fibre-types in the male. The development of the complex organization of the masseter muscle, the MyHC fibre-type message and protein expression, and the formation of endplates appear to be pre-programmed and not under control of the muscle nerve. However, secondary myotube generation and endplate maturation are nerve dependent. The delayed development of the masseter muscle compared with the facial, tongue and jaw-opening muscles may be related to the delayed functional requirements for chewing. In summary, masseter muscle form is pre-programmed prior to birth while muscle fibre contractile characteristics are refined postnatally in response to functional requirements. The motor control mechanisms that are required to coordinate the activation of discrete functional elements of this muscle remain to be determined.

Differential activation of neuromuscular compartments in the rabbit masseter muscle during different oral behaviors.

The rabbit masseter muscle is composed of multiple anatomical partitions that produce different mechanical actions. The purpose of this study was to test the hypothesis that these compartments are differentially activated during the performance of different oral behaviors. Rhythmic activation of the masticatory muscles was elicited by stimulating the cortical masticatory area (CMA) while recording forces generated at the incisors in three dimensions with the mandible immobilized. Torques about the right temporomandibular joint (TMJ) were calculated using these forces recorded during isometric function. A set of 1-15 unique rhythmic behaviors was identified for each rabbit using torque phase plot patterns. Electromyographic recordings were made at nine different compartments in the right masseter, two compartments in the left masseter, two regions in the right digastric, and single locations in the left digastric and right and left medial pterygoid muscles. In activation cycles producing similar mechanical actions, activity patterns at the 16 recording sites were clustered into three to six groups using principal component analysis (PCA). To test for similarities in the activation of masseter compartments, pair-wise comparisons of the PCA assignment for the nine masseter compartments were conducted and frequencies of common assignment were compiled for each unique rhythmic behavior for each rabbit. Masseter muscle compartments were found to vary significantly in their PCA from the expected distribution of 100% common principal component (PC) assignment (i.e., similar activation pattern). This finding is consistent with the independent activation of masseter compartments.

Modeling rabbit temporomandibular joint torques during a power stroke.

Little information exists regarding the effects of changes in mandibular form as a result of orthognathic surgery on torques produced about the temporomandibular joint (TMJ). In this study, we have modeled torques produced about the working side TMJ by selected compartments of the rabbit masseter muscle based on published electromyographic activity. The masseter muscle is composed of multiple subregions or compartments that have unique mechanical actions. In a previous study, forces were elicited by electrical stimulation of each compartment and were recorded by a multiaxis force transducer attached to the anterior mandible. Torques were calculated using mandibular lever arms measured from the center of the TMJ. We have extended this modeling to include variations in mandibular width, length, or height to determine the torques that would be generated with variations in mandibular form. Three superficial masseter compartments on the working side and one posterior deep compartment from the balancing side masseter were examined using data collected from a companion study. It was found that the working and balancing side compartments were synergists for pitch torque components but were antagonists for roll and yaw. In modeling an increase of each mandibular dimension by 20%, nonuniform changes in compartment-generated torques were found. The largest increase was found for the posterior superficial masseter yaw torque component. The effects of changing mandibular form on torques produced about the TMJ may be greater than predicted by previous models that assumed a single line of force produced by each jaw muscle.

Spatial distribution of myosin heavy-chain isoforms in mouse masseter.

There is a paucity of information regarding the anatomy and muscle fiber phenotype of the masseter. The objective of this study was to characterize the distribution of each myosin heavy-chain (MyHC) isoform within different anatomical regions of male and female mouse masseters. Masseters from male and female CD-1 mice (2-4 months old) were examined for description of the anatomical partitioning of muscle fibers and endplate distribution. The spatial distribution of MyHC isoforms--embryonic, neonatal, slow, alpha-cardiac, IIa, and IIb--was determined within the defined masseter partitions by means of Western blot analysis and immunofluorescent localization. Types IIa, IIx, and IIb were the predominant MyHC isoforms observed. Distinct differences in the spatial distribution of these MyHC isoforms were found between muscle regions and varied between sexes. The regionalization of muscle fiber types in the mouse masseter is consistent with the functional compartmentalization of the masseter observed in other species.

Evidence for functional partitioning of the rabbit digastric muscle.

The rabbit digastric muscle has a single belly that opens and retracts the mandible. It does not contain connective tissue partitions, and all fibers arise from the same tendon and insert into a single broad site. Historically, it was assumed that the muscle functioned as a single unit. Since we had preliminary evidence that this might not be the case, we carried out five small studies in rabbits. First, we showed that electromyographic (EMG) activity varies between recording sites within the muscle during the masticatory cycle induced by repetitive stimulation of the sensorimotor cortex. We found that EMG activity in the caudal region sometimes began before the anterior EMG during mastication when the jaw swung to the side of the muscle, but the two regions became active at the same time during other patterns. We next showed that separate branches of the mylohyoid nerve enter the anterior, intermediate and caudal regions of the digastric. However, a separate study showed that the motor endplates were distributed across a continuous sheet, consistent with a single anatomical partition. We then stimulated single nerve branches to deplete glycogen. By comparing the optical density of fibers labeled by the periodic acid-Schiff method for glycogen, we were able to show that the three branches innervate separate regions of the muscle. Finally, we applied either FluoroGold or Fast Blue dyes to the central cut ends of the branches to label the cell bodies of the three pools of motoneurons. These were found within the middle and caudal thirds of the trigeminal motor nucleus, but there appeared to be no spatial separation of the three pools or double labeling of cells. We conclude that the digastric muscle contains two and possibly three functional subregions. The fact that the motoneurons are intermingled suggests that the distribution of motor commands to the three pools is not based on their location.

Role of charged residues at the OmpF porin channel constriction probed by mutagenesis and simulation.

The channel constriction of OmpF porin, a pore protein in the bacterial outer membrane, is highly charged due to the presence of three arginines (R42, R82, and R132) and two acidic residues (D113 and E117). The influence of these charges on ion conductance, ion selectivity, and voltage gating has been studied with mutants D113N/E117Q, R42A/R82A/R132A/D113N/E117Q, and V18K/G131K, which were designed to remove or add protein charge at the channel constriction. The crystal structures revealed no or only local changes compared to wild-type OmpF, thus allowing a comparative study. The single-channel conductance of the isosteric D113N/E117Q variant was found to be 2-fold reduced, and that of the pentuple mutant was 70% of the wild-type value, despite a considerably larger pore cross section. Ion selectivity was drastically altered by the mutations with cation/anion permeability ratios ranging from 1 to 12. Ion flow through these and eight other mutants, which have been characterized previously, was simulated by Brownian dynamics based on the detailed crystal structures. The calculated ion selectivity and relative channel conductance values agree well with the experimental data. This demonstrates that ion translocation through porin is mainly governed by pore geometry and charge, the two factors that are properly represented in the simulations.

[Measuring blood pressure at the upper arm and wrist: are there differences?]. / Blutdruckmessung am Oberarm und am Handgelenk: Gibt es Unterschiede?

Reliability and accuracy of a wrist and an upper arm sphygmomanometer were compared. Only in one of 27 persons were measurements at the wrist impossible. The 26 remaining volunteers showed good agreement between arm and wrist measurement (118/71 and 118/69 mmHg respectively). The variance was expectedly larger for systolic than diastolic values (10 vs 8 mmHg). As expected the correlation between the two methods was high (0.83 for systolic, 0.75 for diastolic values). Reproducibility of measurements was also equivalent for both methods. Devices for blood pressure measurements at the wrist are thus suitable. In order to identify individuals in which measurements at the wrist are impossible for technical reasons comparative measurements on the upper arm should precede the recommendation for a wrist device.

Lead isotope measurements on aerosol samples with ICP-MS.

Size fractionated aerosols were collected with low pressure Berner impactors on a radio/TV tower 110 m above ground on a hill 10 km east of Bern at a total elevation of 1060 m asl. Two different wind sectors were chosen with the goal of assessing any differences in lead concentration and the 3 radiogenic lead isotopes (206,207,208) for east and west wind, respectively. A leaching technique was used to extract the lead quantitatively from the surface of the impaction foils. This method has been proven to be better suited for airborne particles than complete microwave digestion because it is less time consuming and contamination risk is smaller. Blank considerations played a major role in choosing all the chemicals, tubes, beakers and selecting the analytical method. Lead concentrations were determined with GF-AAS and lead isotopes with two different ICP-MS systems, one being a multicollector system. Precision of the simultaneous multicollector system was found to be at least a factor of 3 better than that of the sequentially operating ICP-MS. The small variations in isotope ratios from the two wind sectors can be distinctly seen with this enhanced precision. The observed relative difference in isotope ratios between east- and westwind was approximately 0.6% for 207Pb/206Pb and approximately 0.5% for 208Pb/206Pb.

[Value of invasive preoperative imaging in kidney tumors of malignant or uncertain character]. / Stellenwert der invasiven präoperativen Bildgebung bei Nierentumoren maligner oder unklarer Dignität.

Preoperative staging of malignant renal tumors or undetermined dignity is mainly performed noninvasively using CT or MRI. In cases with vascular invasion or a solitary kidney extensive invasive evaluation of the tumor can influence preoperative planning. We report two cases of oncocytoma and renal cell carcinoma with extensive imaging using DSA or helical CT-cavography.

Development of trigeminal mesencephalic and motor nuclei in relation to masseter muscle innervation in mice.

This study evaluated temporospatial changes in the central organization of trigeminal mesencephalic (mesV) and motor (motV) nuclei during their development. Very little is known regarding the timing of formation of these trigeminal nuclei and the role that target tissue interactions may have on their spatial organization. Cells located in motV innervate muscles of mastication while the mesV nucleus contains populations of primary afferent cells that innervate muscle spindles in jaw closing muscles and periodontal mechanoreceptors around the roots of teeth. To label mesV afferents and motV efferents during their development, lipophilic dyes, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) or 4-(4-dihexadecylamino)styryl)-N-methylpyridinium iodide (DiA), were inserted into various jaw muscles, the dorsomedial mesencephalic region or tooth buds of maxillary or mandibular teeth of embryonic or postnatal mouse pups. Parasagittal sections were evaluated under epifluorescence to determine the temporospatial organization of trigeminal nuclei and the timing of outgrowth of their processes to target tissues. Early in development, motV motoneurons were organized in columns or clusters closely associated with groups of motoneuron axon fascicles that innervated a specific muscle. Double labelling of masseter and temporalis muscles showed that the columns containing motoneurons associated with these muscles were interdigitated early in development but later condensed into respective motoneuron pools. In contrast, no spatial organization of mesV afferent cell bodies was observed throughout the developmental sequence examined. The results of this study also demonstrated that motV processes enter into jaw muscle at least 1 day prior to proprioceptive afferents. MesV afferent appearance at the tooth was further delayed by 10 days suggesting different signaling mechanisms for these two targets.

The role of pharmacy in the management of patients with temporomandibular disorders and orofacial pain.

OBJECTIVE: To provide information regarding the current understanding of the etiology and treatment, both nonpharmacologic and pharmacologic, of orofacial pain conditions including temporomandibular disorders (TMDs). This review briefly discusses the etiology and pathophysiology underlying the development of TMDs, generally accepted nonpharmacologic methods of treatment, and the most common current pharmacologic management approaches. DATA SOURCES: Current medical literature and the authors' clinical experiences. DATA SYNTHESIS: TMDs encompass a number of diagnostic subgroups that involve the masticatory musculature, the temporomandibular joint(s), and associated structures. More than 10 million individuals in the United States are affected by TMDs. Most current pharmacologic management approaches in the treatment of orofacial pain conditions, including TMDs, involve the use of antidepressants, anticonvulsants, muscle relaxants, corticosteroids, and nonsteroidal anti-inflammatory drugs. CONCLUSION: Inclusion of pharmacists who are knowledgeable in the nonpharmacologic and pharmacologic treatment approaches on the TMD management team would improve therapeutic monitoring, follow-up, and outcomes in these patients.