Necrotizing soft tissue infection following routine third molar extraction: report of two cases and review of the literature.

Necrotizing cellulitis, necrotizing fasciitis, and necrotizing myositis are a constellation of severe soft tissue infections characterized by rapid progression, dusky soft tissue changes, and edema and induration expanding beyond the clinical wound edges. The cases of two female patients with type II necrotizing soft tissue infections occurring after routine third molar extraction are reported here. The patients were treated for the infections at the University of North Carolina Hospitals in 2016. Both were previously healthy. Of particular interest, recent inoculation of group A Streptococcus appears to have contributed to the infection in both cases.

Are bioresorbable polylactate devices comparable to titanium devices for stabilizing Le Fort I advancement?

The purpose of this study was to evaluate whether skeletal and dental outcomes following Le Fort I surgery differed when stabilization was performed with polylactate bioresorbable devices or titanium devices. Fifty-seven patients with preoperative records and at least 1 year postoperative records were identified and grouped according to the stabilization method. All cephalometric X-rays were traced and digitized by a single operator. Analysis of covariance was used to compare the postsurgical change between the two stabilization methods. Twenty-seven patients received bioresorbable devices (group R), while 30 received titanium devices (group M). There were no statistically significant differences between the two groups with respect to gender, race/ethnicity, age, or dental and skeletal movements during surgery. Subtle postsurgical differences were noted, but were not statistically significant. Stabilization of Le Fort I advancement with polylactate bioresorbable and titanium devices produced similar clinical outcomes at 1 year following surgery.

Non-invasive therapy for altered facial sensation following orthognathic surgery: an exploratory randomized clinical trial of intranasal vitamin B12 spray.

AIM: The aim of the study was to obtain pilot data on the putative effects of intranasal spray Vitamin B12 in lessening the impairment from orthognathic surgery on large and small diameter nerve fiber functions. METHODS: Thirty-five subjects scheduled for a mandibular osteotomy were enrolled in an open-label two-group parallel stratified-block randomized clinical trial: Intranasal Vitamin B12 Spray (B12), with weekly doses self-administered two weeks before until 6 months after surgery, or no intranasal spray. All subjects received sensory retraining exercises. Large fiber tactile (contact detection) and small fiber thermal (warm, cool, heat discomfort, and cold discomfort) thresholds were obtained before and at 1, 3, and 6 months after surgery. For each, the mean maximum impairment was estimated for group and visit, controlling for age and type of surgery. RESULTS: The demographics and pre-surgery threshold values of the two groups did not differ (P>0.16). At and 6 months after surgery, serum B12 levels were substantially higher in the B12 group (P<0.01). At one month post, average impairment for every threshold measure was less for the B12 group. From 1 to 3 months, the differences between the two groups decreased for the tactile measures but stayed the same (cool and warm perception) or increased (cold and heat discomfort perception) for the thermal measures. At 6 months, the B12 group remained less impaired for the thermal measures. CONCLUSION: This pilot RCT indicates that the effects of intranasal Vitamin B12 spray, initiated prior to surgery, on sensory function are sufficiently promising to justify progression to a Phase III RCT.

Prediction of periodontal pathology around third molars using linear mixed effects modeling.

OBJECTIVE: To compare the random intercept multilevel model with other linear mixed effects models in an assessment of the effect of quadrant-, jaw-, and person level covariates on probing depth of asymptomatic third molars. BASIC RESEARCH DESIGN: Five different covariance models were considered: 1) the random intercept multilevel 2) multi-level with unequal jaw variance 3) multi-level with unequal tooth variance 4) multi-level with unequal jaw and side variance and 5) the general linear model for correlated data with unstructured covariance matrix. PARTICIPANTS: 235 subjects with all four third molars erupted were included. Fifty-one percent were female and 75% Caucasian. The average age was 29.1 years (sd = 7.0). RESULTS: The extended multi-level with unequal residual variance was the best fit to the data. Likelihood ratio tests in a stepdown selection approach resulted in a final model for mean probing depth that included one statistically significant three-way interaction (age x gingival inflammation x gender), two statistically significant two-way interactions (jaw x gingival inflammation and jaw x gender) and one significant main effect (ethnicity). CONCLUSIONS: Linear mixed effects modeling is a powerful tool for the analysis of correlated dental data. However, no one covariance structure is appropriate for all purposes.

Pharmacokinetic and pharmacodynamic assessment of a five-probe metabolic cocktail for CYPs 1A2, 3A4, 2C9, 2D6 and 2E1.

AIMS: The primary objectives of the present study were to establish whether there was a pharmacokinetic or pharmacodynamic interaction between the probe drugs caffeine (CYP1A2), tolbutamide (CYP2C9), debrisoquine (CYP2D6), chlorzoxazone (CYP2E1) and midazolam (CYP3A4), when administered in combination as a cocktail. Furthermore, the tolerability of these probe drugs, both alone and in combination as a cocktail was assessed. METHODS: Twelve healthy volunteer subjects (age range 22-48 years) were entered into an open, fixed sequence, 6-limb, single centre study. The randomization was such that all drugs were given individually followed by the full "cocktail" as the last treatment limb. The phenotypic index used to assess the intrinsic activity of the CYP isoforms included metabolite/parent ratios in plasma and urine (CYPs 1A2, 2E1 & 2C9), parent/metabolite ratios in urine (CYP2D6) and plasma AUClast (CYP3A4). Blood pressure and blood glucose measurements were used to assess pharmacodynamic interactions. Tolerability was assessed through reporting of adverse events RESULTS: Overall, there was little evidence that the probe drugs interacted metabolically when co-administered as the cocktail. The ratio of the geometric mean (and 90% confidence interval) of the phenotypic index, obtained after administration of the probe as part of the cocktail and when given alone were: caffeine, 0.86 (0.67-1.10), midazolam, 0.96 (0.74-1.24), tolbutamide, 0.86 (0.72-1.03), debrisoquine 1.04 (0.97-1.12) and chlorzoxazone, 0.95 (0.86-1.05). There was no difference in blood pressure and blood glucose concentrations following the cocktail and dosing of the individual probes. There was no effect on ECG recordings at any time-point. The adverse events reported for individual drug administrations were mild, transient and expected. Overall no more adverse events were reported on the cocktail study days than on the days when the drugs were administered alone. CONCLUSIONS: The five probe drugs when coadministered, in this dosing regimen, demonstrated no evidence of either a metabolic or pharmacodynamic interaction that might confound the conclusions drawn during a cocktail study. The present cocktail methodology has the potential to become a useful tool to aid the detection of clinically important drug-drug interactions during drug development.

Modulation of human vestibular-evoked postural responses by alterations in load.

The effects of body loading and unloading on human postural responses elicited by 1 mA bilateral, bipolar galvanic vestibular stimulation (GVS) were investigated. Subjects stood symmetrically, and in separate experiments were either loaded by 16, 33 and 50 % of their body weight with weights attached to the trunk, or unloaded by 10, 20 and 30 % using a whole-body harness that partially lifted the body but was free to translate horizontally. Randomised blocks of stimuli for each loading/unloading condition were compared to a non-loaded control condition. The rate of lateral reaction force development over the period 200-350 ms poststimulus increased in both legs with loading and decreased with unloading. The rate of force development was always larger from the leg on the side of cathodal stimulation. Vertical force responses were equal and opposite in the two legs, increasing on the side of the cathode and decreasing on the side of the anode. The rate of vertical force development over the period 200-350 ms after stimulus onset was increased with loading and decreased with unloading. In the frontal plane, the rate of head and trunk tilt in space was increased and decreased with loading and unloading, respectively. However, the relative rate of head tilt with respect to the trunk was not affected by loading conditions. These experiments provide further evidence that load-related afferent feedback influences the processing of vestibular information for the control of balance.

Safety, tolerability, and pharmacokinetics of remacemide in children.

Eleven patients (nine males, two females), 9-14 years of age, received adjunctive therapy with remacemide in an open ascending-dose study at two residential centers in the United Kingdom. Children taking enzyme-inducing drugs were given remacemide twice daily, starting at approximately 4 mg/kg per day and doubling the dose at two weekly intervals to a target dose of approximately 16 mg/kg per day. Children not taking enzyme-inducing drugs (n = 5) received half of these doses. After the dose-escalation phase, remacemide was slowly withdrawn over 2 weeks except in two children who, because of apparent benefit, entered a continuation phase. Remacemide generally was well tolerated in doses up to 13.5 mg/kg per day. Adverse events were similar to those reported in adults, with central nervous system and gastrointestinal events being the most common. One patient died after a suspected seizure, which was unlikely to have been related to remacemide treatment. No adverse effects on neuropsychologic functioning were observed; effects on vital signs and laboratory variables were not clinically significant. The pharmacokinetic profile for remacemide and its desglycinyl metabolite in children is similar to that seen in adult patients. Plasma concentrations of remacemide and the desglycinyl metabolite are reduced in the presence of concomitant antiepileptic drugs with hepatic enzyme-inducing activity.

Evaluation of a pharmacokinetic interaction between remacemide hydrochloride and phenobarbitone in healthy males.

AIMS: To determine whether there is a pharmacokinetic interaction between the antiepileptic drugs remacemide and phenobarbitone. METHODS: In a group of 12 healthy adult male volunteers, the single dose and steady-state kinetics of remacemide were each determined twice, once in the absence and once in the presence of phenobarbitone. The effect of 7 days remacemide intake on initial steady-state plasma phenobarbitone concentrations was also investigated. RESULTS: Apparent remacemide clearance (CL/F) and elimination half-life values were unchanged after 7 days intake of the drug in the absence of phenobarbitone (1.25 +/- 0.32 vs 1.18 +/- 0.22 l kg(-1) h(-1) and 3.29 +/- 0.68 vs 3.62 +/- 0.85 h, respectively). Concomitant administration of remacemide with phenobarbitone resulted in an increase in the estimated CL/F of remacemide (1.25 +/- 0.32 vs 2.09 +/-0.53 l kg-1 h-1), and a decreased remacemide half-life (3.29 +/- 0.68 vs 2.69 +/- 0.33 h). The elimination of the desglycinyl metabolite of remacemide also appeared to be increased after the phenobarbitone intake (half-life 14.72 +/- 2.82 vs 9.61 +/- 5.51 h, AUC 1532 +/- 258 vs 533 +/- 281 ng ml(-1) h). Mean plasma phenobarbitone concentrations rose after 7 days of continuing remacemide intake (12.67 +/- 1.31 vs 13.86 +/- 1.81 microgram ml(-1)). CONCLUSIONS: Phenobarbitone induced the metabolism of remacemide and that of its desglycinyl metabolite. Remacemide did not induce its own metabolism, but had a modest inhibitory effect on the clearance of phenobarbitone.

Who seeks surgical-orthodontic treatment: a current review.

Records for more than 2,000 individuals seen in the Dentofacial Clinic of the University of North Carolina were examined to evaluate trends in referral patterns for orthognathic surgery and acceptance of surgical treatment The vast majority of patients have been white and female from the beginning, and the female-male ratio remained constant at 2:1 throughout the 1990s. The proportion of nonwhite patients increased significantly after 1995, with the change resulting almost totally from more Hispanic and Asian patients. The proportion of African Americans, who represent 22% of the general population, remained almost constant at 10%. Class III and long-face individuals were more likely to seek evaluation than those with Class II problems, but of those who were offered orthognathic surgery, relatively more of the Class II group accepted it. This may reflect greater severity of a Class II problem before a patient seeks treatment. More than 1 of the Clinic population had some sort of facial asymmetry, but the presence of asymmetry did not seem to influence the decision to have surgical treatment. The dental and skeletal characteristics of those who had surgery were similar to those of patients who did not have surgery, suggesting that the decision to elect a surgical treatment plan was influenced by factors other than clinical characteristics.

Patients' perception of recovery after third molar surgery.

PURPOSE: This study evaluated patients' perceptions of recovery after third molar surgery. METHODS: Two hundred forty-nine patients (age 13 to 37 years) at 2 clinical centers were enrolled in a prospective study before the surgical removal of third molars. Each patient was given a 21-item Health-Related Quality of Life instrument (HRQOL) to be completed each postoperative day (POD) for 14 days. The instrument was designed to assess patients' perception of recovery: pain, oral function, general activity measures, and other symptoms. Pain dimensions were recorded with a 7-point Likert-type scale; all other conditions were measured on 5-point Likert-type scales. The impact of each predictor variable such as age, gender, and length of surgery on recovery was assessed with Cochran-Mantel-Haenszel statistics, controlling for clinical center. RESULTS: After the 14-day postoperative period, 201 of the original 249 patients returned the completed HRQOL instrument; the 48 patients who did not return their diary had third molar conditions and surgery similar to the 201 patients who responded. On POD 1, 63.5% of patients reported their worst pain as severe (score, 5 to 7/7) at some time during the day. By POD 7, only 15% of patients reported their worst pain as severe. Average pain levels were much less; 29% reported their average pain as severe (score, 5 to 7/7) on POD 1, decreasing to 5.5% by POD 7. Patients experienced substantial interference in oral function; chewing, 85%; mouth opening 78.5%, and speaking 37.5% on POD 1. By POD 6, oral function had improved; chewing, 19%, mouth opening, 15%; and speaking, 1.5%. General measures also were affected on POD 1; social activity, 61.5%; recreation, 70.5%; and daily routine, 60%. Patients assumed a more normal lifestyle by POD 5. Swelling seemed to be at its maximum on PODs 1 and 2 (day 1, 53%; day 2, 61%) and decreased markedly by POD 5 (10%). Food collection in the surgical sites posed the biggest problem for patients on POD 9 (20%). Age was not a predictor of prolonged recovery. However, surgery time 30 minutes or longer, or having all third molars below the occlusal plane, did prolong recovery. Females also reported a longer recovery period. CONCLUSIONS: This information is valuable to patients deciding on third molar surgery and to clinicians providing informed consent.

Development of an assay for the extraction and quantification of nine 5-n-alkyl-5-ethyl barbituric acids in various rat tissues.

Methods were developed to quantify a series of nine homologous 5-n-alkyl-5-ethyl barbituric acids in 15 rat tissues. Tissue homogenates were spiked with one of four multicomponent mixtures (methyl to n-propyl, n-propyl to n-pentyl, n-pentyl to n-heptyl and n-pentyl to n-nonyl). Liquid-liquid extraction was used to extract the homologues from the rat tissues. Reverse phase HPLC with UV detection at 214 nm was used to separate and quantify the individual barbiturates. The limit of detection for each respective homologue was 1 microg x g(-1) except skin and bone (2 microg x g(-1)). The methodology developed reduced a potential 135 individual assays to a more manageable 16.

Bilateral sagittal split osteotomies in an ambulatory care setting.

Orthognathic surgery has made many advances since its inception. This, combined with modern day health economics, has necessitated changes in orthognathic surgical practice. The bilateral sagittal split osteotomy is evaluated as an ambulatory surgical procedure. Studies have proven the sagittal split osteotomy can be performed as an ambulatory procedure. Patient costs, as well as other issues that impact on the patient and health care provider, are reviewed. The need for additional outcome data to determine whether patient care or perception of care is affected is discussed.

Quantitative structure-pharmacokinetics relationships: I. Development of a whole-body physiologically based model to characterize changes in pharmacokinetics across a homologous series of barbiturates in the rat.

As part of an overall program to develop a framework for evaluating the contribution of structural and physicochemical properties to pharmacokinetics, the distribution kinetics of nine 5-n-alkyl-5-ethyl barbituric acids in arterial blood and 14 tissues (lung, liver, kidney, stomach, pancreas, spleen, gut, muscle, adipose, skin, bone, heart, brain, testes) was examined after i.v. bolus administration in rats. The barbituric acids studied form a true homologous series; therefore any differences in pharmacokinetics, noted between congeners, can be directly linked to the increase in lipophilicity, resulting from the addition of a methylene group. A whole-body physiologically based pharmacokinetic model has been developed, assuming most of the tissues to be well-stirred compartments. Brain and testes, in which distribution for the lower homologues was permeability rate-limited, were represented by two compartments. For each homologue, the model parameters have been optimized, using the tissue concentration-time data. The initial distribution processes in the system were very rapid, making it quite stiff, and essentially over before the first samples were taken. A progressively increasing redistribution from lean tissues into adipose on ascending the homologous series was observed, characterized by a tendency for a progressive decrease in the magnitude of the concentration-time profiles for some of the lean and well-perfused tissues, an increase in the adipose concentration-time profile, and an increase in the time to reach the maximum adipose concentration. A shift from permeability rate limitation to perfusion rate limitation of the distribution processes for brain and testes, as well as an increase in the intrinsic hepatic clearance and decrease in the renal clearance with the increase of lipophilicity of the homologues, were quantified. An increase in the total unbound volume of distribution on ascending the homologous series was also observed. Muscle was found to be the major drug depot at steady state, accounting for approximately 50% of the total unbound volume of distribution, regardless of the lipophilicity of the homologue; the unbound volume of distribution of adipose increases more than 10-fold with the increase of lipophilicity.

Clinical/biological outcomes of treatment for pericoronitis.

PURPOSE: This prospective clinical study was designed to determine the clinical and biologic outcomes of treatment for minor signs and symptoms of pericoronitis. PATIENTS AND METHODS: Patients (n = 20) with all third molars, presenting consecutively to an academic clinical center for treatment of minor signs and symptoms of pericoronitis, were enrolled in the study. At the initial visit, gingival crevicular fluid (GCF) samples to assess levels of the cytokines interleukin- 1b (IL-1b) IL-1b and prostaglandin E2 (PGE2) as a measure of the host inflammatory response, and plaque samples to identify microorganisms, were collected from the distal of all second molars and the mesial of first molars. Standardized vertical bite wing radiographs were taken to assess alveolar bone height on the distal of the second molars and the inclination and the degree of eruption of the third molar. Full-mouth periodontal probing was conducted to determine probing depths and relative clinical attachment levels (CAL). Pain levels were assessed with Gracely verbal descriptor scales for sensory intensity and unpleasantness and 10-cm visual analog scales. Symptomatic third molar sites were treated with local debridement and irrigation after baseline data collection. One week after entry, data were collected again. Subsequently, the patients were scheduled for removal of all third molars. Data collection was repeated 3 months postsurgery. As controls, data were collected from 12 subjects who had asymptomatic third molars removed previously. RESULTS: At entry, symptomatic mandibular third molars (n = 21) were mostly vertical (n = 18) and at or above the occlusal plane (n = 19). No maxillary teeth had symptoms. Microbial counts were elevated for specific anaerobic microorganisms. GCF IL-1b levels were elevated at the distal of second molars adjacent to symptomatic third molars, as compared with asymptomatic third molars and second molars in control patients. Alveolar bone levels and CAL on the distal of second molars were normal. At 1 week, patients' pain symptoms and IL-1b levels were reduced, but microbial counts remained high. Three months after surgery, patients had no pain symptoms, and alveolar bone levels and CAL were similar to entry levels. IL-1b levels were elevated at both the distal of second molars and the mesial of first molars for all patients; microbial counts decreased, although not to levels of control patients. No increase in microbial counts for Porphyromonas gingivalis or Bacteroides forsythus, or GCF PGE2 levels, risk factors for progressive periodontal disease, was detected in samples taken from the study patients. CONCLUSION: Pericoronitis expressed by minor signs/symptoms in these patients was associated with considerable discomfort. Symptomatic mandibular third molars were vertical and at or near the occlusal plane. Additionally, this condition was characterized by microbial flora and GCF inflammatory mediator levels that are more consistent with gingivitis than periodontitis. Removal of third molars eliminated symptoms, but the microbial burden and an affected patient's inflammatory response, as measured by IL-1b levels, remained elevated as compared with controls. Further study is needed to determine which of these factors can be used to identify patients at risk for pericoronitis before symptoms arise.

Confocal and conventional immunofluorescence and ultrastructural localisation of intracellular strength-giving components of human amniochorion.

Key cytoskeletal polypeptides of human fetal membranes have been localised at subcellular level using confocal and conventional indirect immunofluorescence microscopy. Correlation with electron microscope data has allowed us to examine how cellular compartments of this multilaminar tissue maintain their mechanical integrity until the time of membrane rupture at parturition. Evidence is presented for myofibroblastic characteristics of cells in both the fibroblast and reticular layers which may therefore have tension-generating, position-adjustment and wound-healing roles in the amniochorion. Desmin and vimentin are coexpressed in these cells, but a small localised population of cells in the fibroblast layer contains vimentin alone. An interaction of cytokeratin filaments with nuclei and desmosomes of amniotic epithelium in vivo is demonstrated, indicating that nuclei of cells of ectodermal origin are integrated into a mechanical structure extending throughout the tissue as a whole. Cells of the basal 1 or 2 layers of trophoblast have been shown to have a more extensive and better integrated cytoskeletal organisation than those overlying and forming the boundary with decidua. Structures within the trophoblast, identified previously as degenerate villi, contain cells with intermediate filaments with similar immunofluorescence properties to those of the neighbouring reticular layer and thus may represent papillae that prevent shearing at this interface.

Lingual nerve injury associated with superior border wire fixation.

The sagittal ramus osteotomy of the mandible is the most frequently performed orthognathic surgical procedure. Stabilization of the osteotomy may be accomplished by rigid internal or wire fixation. This article illustrates lingual nerve injury following a bilateral sagittal ramus osteotomy of the mandible and fixation with a superior border wire. The etiology and surgical management of this injury are described.