Do signs of an effusion of the temporomandibular joint on magnetic resonance imaging correlate with signs and symptoms of temporomandibular joint disease?

Effusions are common among patients with disorders of the temporomandibular joint (TMJ), but publications are limited and results inconsistent about the correlation between them and important clinical variables, in particular severity of pain and degenerative disease. We organised a retrospective study of patients who presented for the evaluation and management of arthralgia of the TMJ and myofascial pain at the University of Michigan between 2011 and 2014. Inclusion criteria were: patients who had pain that was primarily arthrogenous, and coexisting myogenous pain, who had had initial non-surgical treatment, and arthroscopy of the TMJ with or without intramuscular injection of onabotulinumtoxinA (Botox,® Allegan, Weston, Fl, USA). The primary outcome variables were pain at rest as measured by visual analogue score (VAS) and the presence of degenerative disease of the joint. The secondary outcome variables included the position of the disc and whether it was perforated, signs of synovitis, maximal interincisal opening (MIO), and duration of symptoms. We studied 47 patients (94 TMJ) who met the inclusion criteria. We found no significant differences in pain at rest before or after arthroscopy, between patients with and without effusions, or in maximal MIO or duration of symptoms between the two groups. There was, however, a significant relation between effusions and degenerative joint disease. Effusions were also associated with a lower probability of the disc being in a normal position and a higher probability of anterior disc displacement without reduction.

Conditioned pain modulation dampens the thermal grill illusion.

BACKGROUND: The thermal grill illusion (TGI) refers to the perception of burning heat and often pain that arises from simultaneous cutaneous application of innocuous warm and cool stimuli. This study utilized conditioned pain modulation (CPM) to help elucidate the TGI's underlying neural mechanisms, including the debated role of ascending nociceptive signals in generating the illusion. METHODS: To trigger CPM, subjects placed the left hand in noxious cold (6 °C) water before placing the right volar forearm onto a thermal grill. Lower pain and unpleasantness ratings of the grill in this CPM run compared to those in a control run (i.e. 33 °C water) were taken as evidence of CPM. To determine whether CPM reduces noxious heat pain and illusory heat pain equally, an experimental group of subjects rated pain and unpleasantness of a grill consisting of innocuous alternating warm (42 °C) and cool (18 °C) bars, while a control group rated a grill with all bars controlled to a noxious temperature (45 °C). RESULTS: CPM produced significant and comparable reductions in pain, unpleasantness and perceived heat of both noxious heat and the TGI. CONCLUSIONS: This result suggests that the TGI results from signals in nociceptive dorsal horn convergent neurons, since CPM involves descending inhibition with high selectivity for this neuronal population. More broadly, CPM's ability to produce a shift in perceived thermal sensation of both noxious heat and the TGI from 'hot' to 'warm' implies that nociceptive signals generated by a cutaneous stimulus can contribute to its perceived thermal intensity. SIGNIFICANCE: Conditioned pain modulation reduces the perceived painfulness, unpleasantness and heat of the thermal grill illusion and noxious heat similarly. The results have important theoretical implications for both types of pain.

Pain Mechanisms and Centralized Pain in Temporomandibular Disorders.

Until recently, most clinicians and scientists believed that the experience of pain is perceptually proportional to the amount of incoming peripheral nociceptive drive due to injury or inflammation in the area perceived to be painful. However, many cases of chronic pain have defied this logic, leaving clinicians perplexed as to how patients are experiencing pain with no obvious signs of injury in the periphery. Conversely, there are patients who have a peripheral injury and/or inflammation but little or no pain. What makes some individuals experience intense pain with minimal peripheral nociceptive stimulation and others experience minimal pain with serious injury? It is increasingly well accepted in the scientific community that pain can be generated and maintained or, through other mechanisms, suppressed by changes in the central nervous system, creating a complete mismatch between peripheral nociceptive drive and perceived pain. In fact, there is no known chronic pain condition where the observed extent of peripheral damage reproducibly engenders the same level of pain across individuals. Temporomandibular disorders (TMDs) are no exception. This review focuses on the idea that TMD patients range on a continuum-from those whose pain is generated peripherally to those whose pain is centralized (i.e., generated, exacerbated, and/or maintained by central nervous system mechanisms). This article uses other centralized chronic pain conditions as a guide, and it suggests that the mechanistic variability in TMD pain etiology has prevented us from adequately treating many individuals who are diagnosed with the condition. As the field moves forward, it will be imperative to understand each person's pain from its own mechanistic standpoint, which will enable clinicians to deliver personalized medicine to TMD patients and eventually provide relief in even the most recalcitrant cases.

Prospective assessment of triage in an urban emergency department.

BACKGROUND: This study examined the effectiveness of a triage system based on patient complaints, medical history, vital signs, and triage nurse impression. Measurements included recognizing patients needing admission, in correlating with disposition, and its effectiveness in all age groups. METHODS: Data were collected prospectively on all patients coming to a general emergency department (ED) of an urban teaching hospital from October 1, 1992, through November 30, 1992. Data included assigned triage acuity, disposition waiting time to physician examination, and disposition, as well as return to the ED within 2 weeks. The patients were divided into age groups: 0 to 16 years, 17 years to 25 years, 25 years to 50 years, 50 years to 65 years, and >65 years of age. RESULTS: There were five patients (n = 4,993, 0.4%) who were triaged nonemergently and subsequently admitted. The sensitivity and specificity of an assigned triage 3 acuity assignment in correlating with lack of admission were 99% and 56%, respectively. Mean waiting time to physician examination was 61 +/- 14 minutes for triage 1, 129 +/- 19 for triage 2, and 182 +/- 22 for triage 3. Mean time to admission from sign-in was 246 +/- 10 minutes for triage 1 and 372 +/- 16 minutes for triage 2. CONCLUSIONS: This triage system accurately correlated with disposition and determined waiting time to examination.

Evolution of paired domains: isolation and sequencing of jellyfish and hydra Pax genes related to Pax-5 and Pax-6.

Pax proteins are a family of transcription factors with a highly conserved paired domain; many members also contain a paired-type homeodomain and/or an octapeptide. Nine mammalian Pax genes are known and classified into four subgroups: Pax-1/9, Pax-2/5/8, Pax-3/7, and Pax-4/6. Most of these genes are involved in nervous system development. In particular, Pax-6 is a key regulator that controls eye development in vertebrates and Drosophila. Although the Pax-4/6 subgroup seems to be more closely related to Pax-2/5/8 than to Pax-3/7 or Pax-1/9, its evolutionary origin is unknown. We therefore searched for a Pax-6 homolog and related genes in Cnidaria, which is the lowest phylum of animals that possess a nervous system and eyes. A sea nettle (a jellyfish) genomic library was constructed and two pax genes (Pax-A and -B) were isolated and partially sequenced. Surprisingly, unlike most known Pax genes, the paired box in these two genes contains no intron. In addition, the complete cDNA sequences of hydra Pax-A and -B were obtained. Hydra Pax-B contains both the homeodomain and the octapeptide, whereas hydra Pax-A contains neither. DNA binding assays showed that sea nettle Pax-A and -B and hydra Pax-A paired domains bound to a Pax-5/6 site and a Pax-5 site, although hydra Pax-B paired domain bound neither. An alignment of all available paired domain sequences revealed two highly conserved regions, which cover the DNA binding contact positions. Phylogenetic analysis showed that Pax-A and especially Pax-B were more closely related to Pax-2/5/8 and Pax-4/6 than to Pax-1/9 or Pax-3/7 and that the Pax genes can be classified into two supergroups: Pax-A/Pax-B/Pax-2/5/8/4/6 and Pax-1/9/3/7. From this analysis and the gene structure, we propose that modern Pax-4/6 and Pax-2/5/8 genes evolved from an ancestral gene similar to cnidarian Pax-B, having both the homeodomain and the octapeptide.

The increasing burden of pediatric firearm injuries on the emergency department.

INTRODUCTION: Surveillance of injuries is necessary in order to develop preventive strategies. The purpose of this study was to examine pediatric gunshot wounds over a seven-year period for changes in frequency, site of injury, and demographic variables. METHODS: The medical charts of all pediatric patients (age < 19 years) who presented to the two urban emergency departments (EDs) in Baton Rouge, Louisiana between January 1, 1987, and December 31, 1993, were retrospectively reviewed. Data included age, date and time of presentation, site(s) of injury, disposition, operative procedure, and hospital stay. Results were stratified into age < 1 year, 1-4 years, 5-9 years, 10-14 years, and 15-19 years. RESULTS: During the study period there were 465 pediatric firearm injuries seen in the two urban EDs. Of all patients, 302 (65%) were male, and the proportion remained unchanged during the study period. The incidence of firearm injury rose from 3.0/1000 pediatric ED patients in 1987 and 5.9 in 1993 (P < 0.05). Mean age rose from 12.2 +/- 2.1 years to 15.1 +/- 1.6 years (P < 0.05), and admission percentage rose from 7 to 46% (P < 0.05) between 1987 and 1993. The proportion of firearm injuries in the age group 15 to 19 years rose from 52% in 1987 and 82% in 1993 (P < 0.05). Operative procedures were required by 56 (12%) and intensive care admission by nine (2%); this did not change significantly over the study period. Thirty-three (7%) of all victims died. The most common sites of injury in decreasing order of frequency were extremity (60%), head/neck (14%), chest/back (13%), abdomen/flank (7%), and pelvis/buttocks (6%); they did not vary by age group. A significantly greater proportion of pediatric firearm injuries presented between 5 PM and 5 AM (65%), on Friday (24%) or Sunday (20%), and during the three summer months (29%) or December (11%). CONCLUSIONS: The frequency of pediatric gunshot wounds presenting to urban EDs has increased significantly since 1987. These findings confirm previous studies concerning site of injury as well as time, date, and month of presentation and suggest targeting preventative measures at the 15- to 19-year age group.

Infant diabetic ketoacidosis in the emergency department.

We present the case of an infant brought to the emergency department with complaints commonly associated with a typical childhood illness. Surprisingly, he was found to have diabetes mellitus with ketoacidosis. The usual symptoms of polyuria, polydipsia, and weight loss attributed to diabetes mellitus were not observed. A fruity smell on his breath led to appropriate laboratory tests and ultimately to the correct diagnosis. We review appropriate management of infantile diabetic ketoacidosis, emphasizing the importance of considering diabetes mellitus and ketoacidosis in infants admitted to the emergency department with common complaints such as vomiting and irritability. As in our case, the clinical finding of a fruity breath smell can be an important factor in diagnosis.

U-77,863: a novel cinnanamide isolated from Streptomyces griseoluteus that inhibits cancer invasion and metastasis.

Several cinnamoyl compounds have been shown to have antitumor activities, but not specifically anti-invasive or antimetastatic effects. U-77,863 (o-methyl cinnanamide) was originally isolated from a fermentation beer of Streptomyces griseoluteus and recently synthesized (Harper, DE and Welch DR. Journal of Antibiotics, in press). Based upon some differential activities of cinnanamides, in general, and U-77,863, specifically, we tested the hypothesis that U-77,863 could inhibit invasion and metastasis of human malignant melanoma cell lines C8161 and A375M. Pretreatment of melanoma cells in vitro with nontoxic doses of U-77,863 caused a dose-, and time-dependent, reversible reduction (IC50 = 12.5 micrograms/ml) of invasion through Matrigel-coated polycarbonate filters in the Membrane Invasion Culture System (MICS). Likewise, lung colonization was significantly (P < 0.05) inhibited when tumor cells were pretreated in vitro with U-77,863 prior to intravenous injection. Structure-activity analysis revealed that the acrylamide side-chain alone and cinnanamide were only slightly less potent than U-77,863, whereas cinnamic acid analogs did not inhibit tumor cell invasion at doses < or = 100 micrograms/ml. U-77,863 inhibits invasion and metastasis without decreasing growth rates or clonogenic potential. Adhesion to endothelial monolayers or extracellular matrices (Matrigel) is not affected by exposure to U-77,863. U-77,863 presumably inhibits metastasis by inhibiting tumor cell extravasation (invasion). U-77,863 is a lead compound for developing a novel class of anti-invasive/anti-metastatic drugs.

Isolation, purification, synthesis, and antiinvasive/antimetastatic activity of U-77863 and U-77864 from Streptomyces griseoluteus, strain WS6724.

In screening of actinomycetes for structures with differential solid tumor activity, Streptomyces griseoluteus, strain WS6724 was found to produce U-77863 and U-77864. U-77863 exhibited antiinvasive activity in vitro in the membrane invasion culture system (MICS) and a dose-dependent antimetastatic activity in vivo versus K1735-M2 and B16-F10 murine melanomas. The isolation, purification, and synthesis of both structures and biological activity is reported.

Reversibility of the covalent reaction of CC-1065 and analogues with DNA.

Covalent DNA adducts of the antitumor antibiotic CC-1065 and its analogues undergo a retrohomologous Michael reaction in aqueous/organic solvent mixtures to regenerate the initial cyclopropylpyrroloindole (CPI) structure and, presumably, intact DNA. This reaction, which at higher temperatures competes with depurination of the N3-alkylated adenine, also occurs to a significant extent at 37 degrees C in neutral aqueous solution. Tritium-labeled adozelesin, covalently bonded to a 3-kilobase DNA restriction fragment which was exhaustively extracted to remove unbonded drug, was efficiently transferred to a 1-kilobase fragment upon coincubation for 20 h at 37 degrees C in aqueous buffer. Covalent adducts of adozelesin, but not CC-1065, on calf thymus DNA were cytotoxic to L1210 cells after incubation for 3 days at 37 degrees C, indicating that reversal of DNA alkylation can mediate potent cellular effects for simplified CC-1065 analogues.

Chemical modification of steffimycin B.

Fifteen 3-substituted analogues of steffimycin B (1) have been synthesized and their activity against P388 murine leukemia has been determined. Three of these were substantially more active than the parent compound.