Stability of extemporaneously prepared preservative-free methylphenidate 5 mg/mL intravenous solution.

PURPOSE: To advance the implementation of consciousness-promoting therapies in patients with acute disorders of consciousness, the availability of potential therapeutic agents in formulations suitable for administration in hospitalized patients in the presence of complex comorbid conditions is paramount. The purpose of this study is to evaluate the long-term stability of extemporaneously prepared preservative-free methylphenidate hydrochloride (HCl) 5 mg/mL intravenous solution for experimental use. METHODS: A methylphenidate 5 mg/mL solution was prepared under proper aseptic techniques with Methylphenidate Hydrochloride, USP, powder mixed in sterile water for solution. Methylphenidate HCl 5 mg/mL solution was sterilized by filtration technique under USP <797>-compliant conditions. Samples were stored refrigerated (2-8°C) and analyzed at approximately days 1, 30, 60, 90, 180, and 365. At each time point, chemical and physical stability were evaluated by visual inspection, pH measurement, membrane filtration procedure, turbidometric or photometric technique, and high-performance liquid chromatography analysis. RESULTS: Over the 1-year study period, the samples retained 96.76% to 102.04% of the initial methylphenidate concentration. There was no significant change in the visual appearance, pH level, or particulate matter during the study period. The sterility of samples was maintained and endotoxin levels were undetectable throughout the 1-year stability period. CONCLUSION: Extemporaneously prepared preservative-free methylphenidate 5 mg/mL intravenous solution was physically and chemically stable at 32, 61, 95, 186, and 365 days when stored in amber glass vials at refrigerated temperatures (2-8°C).

Specific neural substrate linking respiration to locomotion.

When animals move, respiration increases to adapt for increased energy demands; the underlying mechanisms are still not understood. We investigated the neural substrates underlying the respiratory changes in relation to movement in lampreys. We showed that respiration increases following stimulation of the mesencephalic locomotor region (MLR) in an in vitro isolated preparation, an effect that persists in the absence of the spinal cord and caudal brainstem. By using electrophysiological and anatomical techniques, including whole-cell patch recordings, we identified a subset of neurons located in the dorsal MLR that send direct inputs to neurons in the respiratory generator. In semi-intact preparations, blockade of this region with 6-cyano-7-nitroquinoxaline-2,3-dione and (2R)-amino-5-phosphonovaleric acid greatly reduced the respiratory increases without affecting the locomotor movements. These results show that neurons in the respiratory generator receive direct glutamatergic connections from the MLR and that a subpopulation of MLR neurons plays a key role in the respiratory changes linked to movement.

Chapter 15--chew before you swallow.

The main text of this chapter, written by James P. Lund, summarizes most of the work related to the neural control of mastication that he conducted with his collaborators throughout the years. From his early PhD work showing that mastication is centrally patterned to his latest work related to the interaction between pain and movement, Lund will have addressed many essential questions regarding the organization and functioning of the masticatory central pattern generator (CPG). His earliest studies examined how the CPG modulates reflexes and the excitability of primary afferents, interneurons, and motoneurons forming their circuitry. He then tackled the question of how the CPG itself was modulated by different types of sensory and cortical inputs. Another series of studies focused on the organization of the subpopulations of neurons forming the CPG, their intrinsic and network properties. Shortly before his untimely passing, he had turned his attention to the potential contribution of muscle spindle afferents to the patterning of mastication as well as to the development of chronic muscle pain.

Efficient resource use in simplified complete denture fabrication.

PURPOSE: Conventional dentures will remain the only treatment available to most edentulous people for the foreseeable future. In this study, we compared the efficiency of two methods of making complete conventional dentures-the traditional academic standard (T) and a simplified technique (S) used in private practice. We have previously shown that they produce similar levels of patient satisfaction and denture quality. MATERIALS AND METHODS: Data were gathered during a randomized controlled clinical trial of 122 subjects from initial examination until 6-month follow-up. For this report, the direct costs of providing one set of conventional complete dentures by T or S techniques were estimated. All materials used were recorded and their cost was calculated in Canadian dollars (CAN$). The costs of fabrication in an outside laboratory were added. Clinician's labor time was recorded for every procedure. Between-group comparisons for each clinical procedure were carried out with independent t-tests. The number of patients in each group who needed postdelivery treatment was compared with Chi-square tests. The effect of group assignment and of treatment difficulty on outcomes was analyzed with multiple regression analysis. RESULTS: The mean total cost of the T method was significantly greater than S (CAN$166.3; p < 0.001), and clinicians spent 90 minutes longer (p < 0.001) on clinical care. The difficulty of the case had no significant influence on outcomes. CONCLUSIONS: The results indicate that the S method is the more cost-efficient method and that there are no negative consequences that detract from the cost savings.

Assessment of the potential role of muscle spindle mechanoreceptor afferents in chronic muscle pain in the rat masseter muscle.

BACKGROUND: The phenotype of large diameter sensory afferent neurons changes in several models of neuropathic pain. We asked if similar changes also occur in "functional" pain syndromes. METHODOLOGY/PRINCIPAL FINDINGS: Acidic saline (AS, pH 4.0) injections into the masseter muscle were used to induce persistent myalgia. Controls received saline at pH 7.2. Nocifensive responses of Experimental rats to applications of Von Frey Filaments to the masseters were above control levels 1-38 days post-injection. This effect was bilateral. Expression of c-Fos in the Trigeminal Mesencephalic Nucleus (NVmes), which contains the somata of masseter muscle spindle afferents (MSA), was above baseline levels 1 and 4 days after AS. The resting membrane potentials of neurons exposed to AS (n = 167) were hyperpolarized when compared to their control counterparts (n = 141), as were their thresholds for firing, high frequency membrane oscillations (HFMO), bursting, inward and outward rectification. The amplitude of HFMO was increased and spontaneous ectopic firing occurred in 10% of acid-exposed neurons, but never in Controls. These changes appeared within the same time frame as the observed nocifensive behaviour. Ectopic action potentials can travel centrally, but also antidromically to the peripheral terminals of MSA where they could cause neurotransmitter release and activation of adjacent fibre terminals. Using immunohistochemistry, we confirmed that annulospiral endings of masseter MSA express the glutamate vesicular transporter VGLUT1, indicating that they can release glutamate. Many capsules also contained fine fibers that were labelled by markers associated with nociceptors (calcitonin gene-related peptide, Substance P, P2X3 receptors and TRPV1 receptors) and that expressed the metabotropic glutamate receptor, mGluR5. Antagonists of glutamatergic receptors given together with the 2(nd) injection of AS prevented the hypersensitivity observed bilaterally but were ineffective if given contralaterally. CONCLUSIONS/SIGNIFICANCE: Low pH leads to changes in several electrical properties of MSA, including initiation of ectopic action potentials which could propagate centrally but could also invade the peripheral endings causing glutamate release and activation of nearby nociceptors within the spindle capsule. This peripheral drive could contribute both to the transition to, and maintenance of, persistent muscle pain as seen in some "functional" pain syndromes.

Researching the impact of oral health on diet and nutritional status: methodological issues.

OBJECTIVES: Assessment of the impact of dental function on diet and nutritional status requires robust methodologies and a standardised approach to increase accuracy of results and to facilitate cross study comparisons. The objectives of this paper are: to report the outcomes of a consensus workshop that critically reviewed publications reporting on dietary methodologies in relation to the impact of oral health on nutrition; to highlight future directions for research and; to make recommendations for appropriate use of methodologies for future research. DATA: Data relevant to nutrition and dental status published from 1980 to 2005 in English were presented at the consensus workshop for discussion and appraisal. SOURCES: Relevant papers were retrieved through PubMed. Relevant texts were obtained from the library at Newcastle University, UK. STUDY SELECTION: A purposive sample of original articles that illustrated the application of a range of nutritional methodologies to the study of oral health impacts was identified. Original flagship texts on nutritional methodologies were reviewed. CONCLUSIONS: Numerous studies have shown an association between loss of teeth and inferior diet. Further research is required to elucidate the impact of novel approaches to prosthetic rehabilitation and the impact of contemporaneous dietary and dental intervention on diet, nutritional status, disease progression and quality of life. The recommendation of the consensus workshop was that future studies should adopt a comprehensive approach to the assessment of nutrition that encompasses measurement of diet, body composition, biochemical indices of intake and levels of nutrients, and functional biomarkers of disease.

Implant overdentures for edentulous elders: study of patient preference.

BACKGROUND: Studies show that elders wearing implant overdentures have improved nutrition and quality of life. However, upfront costs of this therapy are high, and the income of elderly edentulous populations is low. OBJECTIVES: This study was designed (i) to measure the preferences of edentulous patients for mandibular two-implant overdentures using Willingness-To-Pay (WTP) and Willingness-To-Accept (WTA), (ii) to assess the effect of long-term financing on WTP and (iii) to assess the desired role of health care plans in financing dental prostheses. METHODS: Edentulous elders (68-79 years; n = 36) wearing maxillary dentures and either a mandibular conventional denture (CD, n = 13) or a two-implant overdenture with ball attachments (IOD, n = 23) participated in this study. All had received their prostheses 2 years previously, as part of a randomised clinical trial. A three-part questionnaire was completed during a 20-min interview with a trained researcher. RESULTS: Forty-six per cent (6/13) of the CD wearers and 70% (16/23) of the IOD wearers were willing to pay three times more than the current cost of conventional dentures for implant prostheses. These percentages were increased to 77% (CD) and 96% (IOD) if participants could pay for implant overdentures in monthly instalments. Eighty-six per cent (31/36) of all participants in both groups (21/23 IOD; 10/13 CD) thought that the government should cover at least some of the cost of implant overdentures. CONCLUSIONS: This study shows that, the majority of elderly edentate individuals who have not experienced mandibular two-implant overdenture therapy are willing to pay the cost, particularly when payment can be made in monthly instalments.

Do mandibular implant overdentures and conventional complete dentures meet the expectations of edentulous patients?

OBJECTIVES: To measure expectations of satisfaction with implant and conventional denture treatment in 2 groups of edentulous people and compare them with their resultant ratings of satisfaction to determine if either treatment meets the pretreatment expectation. METHOD AND MATERIALS: One hundred sixty-two edentulous middle-aged (MA, n = 102) and senior (S, n = 60) patients were enrolled in 2 trials and, after randomization, received either a mandibular 2-implant overdenture (IOD) or a new conventional denture (CD). Before randomization, each subject rated their satisfaction with their current denture and expectations of satisfaction with both IOD and CD treatment on 100-mm visual analog scales (VAS). Six months posttreatment, all rated their satisfaction with their new prostheses on similar VAS. Expectations and satisfaction with treatment were compared. RESULTS: Posttreatment satisfaction with CD treatment was significantly lower than pretreatment expected satisfaction in both study populations (MA, P < .0001; S, P = .036). There was no (or only borderline) significant difference between pretreatment expectation and posttreatment satisfaction for patients receiving IODs in both study populations (MA, P = .078; S, P = .057). CONCLUSION: Posttreatment CD satisfaction failed to meet patients' pretreatment expectations of satisfaction; this was not the case for IODs, for which expectations were largely met.

Electrical properties of interneurons found within the trigeminal motor nucleus.

The trigeminal motor nucleus contains the somata of motoneurons innervating the jaw muscles, but also those of interneurons that we have characterized morphologically and immunohistochemically previously. Here we compare their basic physiological characteristics and synaptic inputs from the peri-trigeminal area (PeriV) to those of motoneurons using whole-cell recordings made with pipettes containing biocytin in brainstem slices of rats that had a tracer injected into their masseters. Values for input resistance, spike duration and overall duration of afterhyperpolarization (AHP) were greater for interneurons than for motoneurons. Some interneurons (44%) and motoneurons (33%) had an outward rectification during depolarization. Hyperpolarization-induced inward rectification was seen predominantly in interneurons (85% vs. 31% for motoneurons). Few interneurons (15%) showed depolarization and time-dependent firing frequency accommodation, while half (52%) of the motoneurons did. Rebound excitation at the offset of hyperpolarization was more common in interneurons than in motoneurons (62% vs. 34%). Both populations received synaptic inputs from PeriV. These inputs were predominantly excitatory and were mediated by non-N-methyl-d-aspartate glutamatergic receptors. Response latencies and rise times of the evoked potentials were longer in interneurons than in motoneurons, suggesting that some of the inputs to interneurons could be polysynaptic and/or occurring at distal dendritic locations. Miniature synaptic events could be seen in about half of the neurons in both populations. These results suggest that interneurons can be clearly distinguished from motoneurons on the basis of some electrophysiological properties like the input resistance and spike and AHP durations, and the kinetics of their synaptic inputs from adjacent areas.

Initial Investigation of the relation between extended computer use and temporomandibular joint disorders.

AIM: To determine if temporomandibular joint disorders (TMDs) are associated with extended computer use. MATERIALS AND METHODS: People with chronic pain and extensive computer use were recruited by means of a newspaper advertisement. Those who responded to the ad were asked to complete an online survey, which included questions on computer use, medical history, pain symptoms, lifestyle and mood. RESULTS: Ninety-two people completed the online survey, but none of them responded to all questions in the survey. Of the 88 respondents who reported their sex, 49 (56%) were female. Most of the respondents had used computers for more than 5 hours per day for more than 5 years, and most believed that their pain was linked to computer use. The great majority had pain in the neck (73/89 [82%]) or shoulder (67/89 [75%]), but many (40/91 [44%]) also had symptoms of TMD. About half of the participants reported poor sleep and fatigue, and many linked their pain to negative effects on lifestyle and poor quality of life. Two multiple regressions, with duration of pain as the dependent variable, were carried out, one using the entire sample of respondents who had completed the necessary sections of the survey (n = 91) and the other using the subset of people with symptoms suggestive of TMD (n = 40). Duration of computer use was associated with duration of pain in both analyses, but 6 other independent variables (injury or arthritis, hours of daily computer use, stress, position of computer screen relative to the eyes, sex, and age) were without effect. In these regression analyses, the intercept was close to 0 years, which suggests that the pain began at about the same time as computer use. DISCUSSION: This web-based survey provides the first evidence that chronic pain in jaw muscles and other symptoms of TMD are associated with long-term, heavy use of computers. However, the great majority of people with these symptoms probably also suffer from pain in the shoulder and neck.

A review of burst generation by trigeminal main sensory neurons.

In this paper, we present evidence that neurons in the dorsal part of the trigeminal main sensory nucleus participate in the patterning of mastication. These neurons have special membrane properties that allow them to generate rhythmical bursts of action potentials in the frequency range of natural mastication even when cut off from synaptic inputs. These properties mature during the third postnatal week in rats at the same time as mastication begins. Finally, we present evidence that a reduction on extracellular calcium concentration is an important step in the initiation of mastication.

Generation of the central masticatory pattern and its modification by sensory feedback.

Mammalian mastication results from the interaction of an intrinsic rhythmical neural pattern and sensory feedback generated by the interaction of the effecter system (muscles, bones, joints, teeth, soft tissues) with food. The main variables that explain variation in the pattern of human mastication are the subjects themselves, their age, the type of food being eaten, and time during a sequence of movements. The intrinsic pattern of mastication is generated by a central pattern generator (CPG) located in the pons and medulla. The output of the CPG is modified by inputs that descend from higher centers of the brain and by feedback from sensory receptors. Intraoral touch receptors, muscle spindles in the jaw-closing muscles, and specialized mechanoreceptors in the periodontal ligament have especially powerful effects on movement parameters.

Brainstem circuits that control mastication: do they have anything to say during speech?

UNLABELLED: Mastication results from the interaction of an intrinsic rhythmical neural pattern and sensory feedback from the mouth, muscles and joints. The pattern is matched to the physical characteristics of food, but also varies with age. There are large differences in masticatory movements among subjects. The intrinsic rhythmical pattern is generated by an assembly of neurons called a central pattern generator (CPG) located in the pons and medulla. The CPG receives inputs from higher centers of the brain, especially from the inferio-lateral region of the sensorimotor cortex and from sensory receptors. Mechanoreceptors in the lips and oral mucosa, in muscles, and in the periodontal ligaments around the roots of the teeth have particularly powerful effects on movement parameters. The central pattern generator includes a core group of neurons with intrinsic bursting properties, as well as a variety of other neurons that receive inputs from oral and muscle spindle afferents. Reorganization of subpopulations of neurons within the CPG underlies changes in movement pattern. In addition to controlling motoneurons supplying the jaw, tongue, and facial muscles, the CPG also modulates reflex circuits. It is proposed that these brainstem circuits also participate in the control of human speech. LEARNING OUTCOMES: Readers will be able to: (1) describe the general location and function of the central pattern generator for mastication, (2) identify the primary nuclei involved in the central pattern generator for mastication, (3) describe the general interactions among the central pattern generators of speech, mastication, respiration, and locomotion, and (4) compare/relate the brainstem systems controlling mastication and speech.

Emergence of intrinsic bursting in trigeminal sensory neurons parallels the acquisition of mastication in weanling rats.

There is increasing evidence that a subpopulation of neurons in the dorsal principal sensory trigeminal nucleus are not simple sensory relays to the thalamus but may form the core of the central pattern generating circuits responsible for mastication. In this paper, we used whole cell patch recordings in brain stem slices of young rats to show that these neurons have intrinsic bursting abilities that persist in absence of extracellular Ca(2+). Application of different K(+) channel blockers affected duration and firing rate of bursts, but left bursting ability intact. Bursting was voltage dependent and was abolished by low concentrations of Na(+) channel blockers. The proportion of bursting neurons increased dramatically in the second postnatal week, in parallel with profound changes in several electrophysiological properties. This is the period in which masticatory movements appear and mature. Bursting was associated with the development of an afterdepolarization that depend on maturation of a persistent sodium conductance (I(NaP)). An interesting finding was that the occurrence of bursting and the magnitude of I(NaP) were both modulated by the extracellular concentration of Ca(2+). Lowering extracellular [Ca(2+)] increased both I(NaP) and probability of bursting. We suggest that these mechanisms underlie burst generation in mastication and that similar processes may be found in other motor pattern generators.

Can general dentists produce successful implant overdentures with minimal training?

OBJECTIVES: This study was carried out to determine whether inexperienced dentists can provide two-implant overdentures that are as satisfactory and of the same cost as those provided by experienced prosthodontists. METHODS: Edentulous elders were enrolled in a randomized controlled clinical trial to compare the effects of mandibular conventional and two-implant overdentures on nutrition. They were randomly assigned to groups that were treated by either an experienced prosthodontist or by a newly-graduated dentist with minimal training in implant treatment. Data for this study were obtained during the treatment of the first 140 subjects enrolled. The change in patient ratings of satisfaction after treatment, laboratory costs and the number of unscheduled visits up to 6 months following prosthesis delivery were compared. RESULTS: Satisfaction was significantly higher with implant overdentures than with conventional dentures, but there were no differences in scores for either prosthesis between the groups treated by experienced specialists or new dentists. Furthermore, six of the seven inexperienced dentists reported that they found the mandibular two-implant overdenture easier to provide than the conventional denture. CONCLUSIONS: The results of this study suggest that general dentists can provide successful mandibular two-implant overdentures with minimal training.

The impact of conventional and implant supported prostheses on social and sexual activities in edentulous adults Results from a randomized trial 2 months after treatment.

OBJECTIVES: To determine the impact of mandibular two-implant overdentures or conventional complete dentures on leisure and sexual activities. METHODS: One hundred and two subjects, aged 35-65 years, received either mandibular overdentures retained by two implants (IOD; n=54) or new mandibular conventional complete dentures (CD; n=48) in a randomized controlled clinical trial. A Social Impact Questionnaire was used to assess the impact on social and sexual activity including avoiding conversation, refusing invitations, avoiding sport and feeling uneasy when kissing and in sexual relationships, and the looseness of the prostheses during such activities. Ratings were recorded on categorical scales at baseline and 2 months after treatment. Oral health related quality of life was measured with the Oral Health Impact Profile (OHIP). Between and within group comparisons were carried out using regression models. The correlation between post-treatment OHIP scores and the leisure and sexual impact items was assessed. RESULTS: Two months after delivery of the prosthesis there was significant improvements in the IOD group for looseness when eating, speaking, kissing and yawning. The IOD group reported significantly less post treatment looseness than the CD group for all parameters investigated (p<0.0001). IOD subjects felt less uneasy kissing and less uneasy during sexual activity than CD subjects. Correlations between the two sexual activity items (uneasiness when kissing and during sexual relations) and the OHIP scales were weak. CONCLUSIONS: Edentulism has a negative impact on social and sexual life. Mandibular overdentures provide greater improvement in of unease in intimate activities than new conventional mandibular dentures.

Do traditional techniques produce better conventional complete dentures than simplified techniques?

OBJECTIVES: To compare the quality of conventional complete dentures fabricated with two different techniques. A randomized controlled clinical trial was conducted to compare traditional (T) and simplified (S) methods of making complete conventional dentures on patients' ratings of satisfaction, comfort and function at 3 and 6 months following delivery. The quality of the prostheses was rated by prosthodontists at 6 months. MATERIALS AND METHODS: One hundred twenty-two male and female edentulous individuals, aged 45-75 years, were randomly allocated into groups that received dentures made with either T or S methods. Following delivery, patients' ratings of several denture-related factors were measured using 100mm visual analogue scales, and denture quality was assessed by blinded prosthodontists using ratings on a validated quantitative scale. RESULTS: There were no significant differences between the two groups in patient ratings for overall satisfaction (3 months: mean T = 83 mm, mean S = 83 mm, P = 0.97; 6 months: mean T = 79 mm, mean S = 79 mm, P = 0.96) or in prosthodontists' ratings of denture quality (T = 66, S = 63; P = 0.38). CONCLUSION: These results show that the quality of complete dentures does not suffer when manufacturing techniques are simplified to save time and materials. Dental educators should consider these findings when re-designing prosthodontic training programs.

Persistence of respiratory-swallowing coordination after laryngectomy.

The present study was designed to provide additional insights into the neural mechanisms underlying respiratory-swallowing coupling by studying potential alterations in movement coordination when upper airway protection is no longer necessary. Twelve laryngectomized participants, all at least 3 years postsurgery, were compared to age- and sex-matched controls. Respiration and swallowing were monitored before, during, and after mastication. No significant differences were found between the laryngectomized and normal control participants in the distribution of the respiratory phase in which swallowing occurs, our primary measure of respiratory-swallowing stability. Data suggest that the coupling between the swallowing and respiratory pattern generators is highly stable. Pronounced masticatory-related apnea was observed in 3 of the laryngectomized participants but in none of the controls, suggesting that masticatory/respiratory interactions may become abnormal in these patients.