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Biomedical subjects

C C Peck

Publications and source records attributed to C C Peck.

At least 19 recordsLinked to original sources
PubMed2005

Ipsilateral interferences and working-side condylar movements.

UNLABELLED: There is limited knowledge of the effects of the occlusion on temporomandibular joint function. AIM: The aim was to investigate the influence of a working-side occlusal alteration (OA, i.e. interference) on trajectories of working-side condylar points during standardized lateral jaw movements (laterotrusion) tracked by a jaw-tracking system. METHODS: Ten trials of right laterotrusion were repeated under: control 1 (before OA), OA (immediately after placement of a working-side interference) and control 2 (immediately after removal of OA) conditions. RESULTS: During right jaw movement, the paths of the working-side condylar points under OA were significantly more inferior and anterior to those under control at the same amount of mid-incisor-point displacement from the intercuspal position. The OA significantly reduced the rotation of the mandible about the antero-posterior and supero-inferior axes and significantly increased the opening angle. Controls 1 and 2 were not significantly different. CONCLUSIONS: A working-side interference has an immediate, significant effect on working-side condylar movement.

Adult↗
PubMed2002

Forces resisting jaw displacement in relaxed humans: a predominantly viscous phenomenon.

Forces opening the relaxed human jaw are resisted by intrinsic restraints, including passive tensions in the jaw-closing muscles. These muscle tensions have been modelled as viscoelastic elements, and static measurements suggest their elastic portions contribute approximately a total of 5 N resistance at wide gape. As the viscous damping properties of muscles which affect the jaw's dynamic behaviour are unknown, we measured the jaw opening force required to reach maximum gape during fast and slow opening in six relaxed subjects. These data were then incorporated in a dynamic mathematical jaw model to determine the damping properties of the masticatory system. During the 3 and 8 s opening trials, forces increased with gape (6.7 +/- 3.3 and 3.9 +/- 2.3 N, respectively, at 50% gape) and reached their maxima at wide gape (19.9 +/- 4.5 and 13.2 +/- 4.4 N, respectively). The muscle damping constant needed by the model to emulate these results was 150 Nsm(-1), approximately 25% lower than the calculated critical damping constant. This study suggests low forces are required to open the jaw in relaxed humans, and that jaw viscosity, not elasticity, provides the major resistance to motion.

Adult↗
PubMed2000

Dynamic simulation of muscle and articular properties during human wide jaw opening.

Human mandibular function is determined in part by masticatory muscle tensions and morphological restraints within the craniomandibular system. As only limited information about their interactions can be obtained in vivo, mathematical modeling is a useful alternative. It allows simulation of causal relations between structure and function and the demonstration of hypothetical events in functional or dysfunctional systems. Here, the external force required to reach maximum jaw gape was determined in five relaxed participants, and this information used, with other musculoskeletal data, to construct a dynamic, muscle-driven, three-dimensional mathematical model of the craniomandibular system. The model was programmed to express relations between muscle tensions and articular morphology during wide jaw opening. It was found that a downward force of 5 N could produce wide gape in vivo. When the model's passive jaw-closing muscle tensions were adjusted to permit this, the jaw's resting posture was lower than that normally observed in alert individuals, and low-level active tone was needed in the closer muscles to maintain a typical rest position. Plausible jaw opening to wide gape was possible when activity in the opener muscles increased incrementally over time. When the model was altered structurally by decreasing its angles of condylar guidance, jaw opening required less activity in these muscles. Plausible asymmetrical jaw opening occurred with deactivation of the ipsilateral lateral pterygoid actuator. The model's lateral deviation was limited by passive tensions in the ipsilateral medial pterygoid, which forced the jaw to return towards the midline as opening continued. For all motions, the temporomandibular joint (TMJ) components were maintained in continual apposition and displayed stable pathways despite the absence of constraining ligaments. Compressive TMJ forces were presented in all the cases and increased to maximum at wide gape. Dynamic mathematical modeling appears a useful way to study such events, which as yet are unrecordable in the human craniomandibular system.

Adult↗
PubMed2000

A pharmacodynamic Markov mixed-effects model for the effect of temazepam on sleep.

BACKGROUND: A hypnogram shows how sleep travels through its various stages in the course of a night. The sleep stage changes can be quantified to study sedative drug effects. METHODS: Hypnograms from 21 patients with primary insomnia were collected during a randomized, placebo-controlled crossover study of 20 mg temazepam. A separate daytime session was performed to determine the pharmacokinetics of 20 mg temazepam and its effect on saccadic eye movement and electroencephalogram. A first-order Markov model was developed to describe the probability of sleep stage changes as a function of time after drug intake and time after last sleep stage change. The influence of temazepam concentration on the probability to change sleep stage was incorporated into the model. RESULTS: Transitions between sleep stages were profoundly influenced by the time of the night and by the time since the last change of sleep stage. Temazepam reduced the time spent awake. This effect could be attributed to four mechanisms: (1) transition to "deeper" sleep was facilitated, (2) transition to "lighter" sleep was inhibited, (3) regardless of sleep stage, the transition to wake state was inhibited, and (4) return to sleep was facilitated. Daytime sensitivities to temazepam, measured with the surrogate markers saccadic peak velocity and electroencephalogram beta activity, each correlated with one of the transition probabilities influenced by temazepam. CONCLUSIONS: By the development of a Markov model for these non-ordered six categorical data, the effect of temazepam on the sleep-wake status could be interpreted in terms of known mechanisms for sleep generation and benzodiazepine pharmacology.

Adolescent↗
PubMed2000

Prediction of the outcome of a phase 3 clinical trial of an antischizophrenic agent (quetiapine fumarate) by simulation with a population pharmacokinetic and pharmacodynamic model.

A completed phase 3 trial result was simulated 100 times on the basis of a simulation model of quetiapine fumarate (Seroquel), an antischizophrenic agent. The simulation was executed by analysts who were completely blinded from results of the actual trial until after the simulations were submitted to the holder of the trial results. Data from two clinical investigations of quetiapine in patients with schizophrenia were analyzed by use of nonlinear mixed effects modeling to derive a population pharmacokinetic- and pharmacodynamic-based simulation model. The time course of quetiapine concentrations was described by use of a one-compartment open linear pharmacokinetic model with first-order absorption and elimination. The combination of an inhibitory maximum effect pharmacodynamic model for the active treatment effect and a linear function of time for the placebo effect characterized the observed time course of change in the Brief Psychiatric Rating Scale. Simulation results were compared with those in the actual trial to evaluate how well the simulations predicted the outcome. The actual trial results for all doses except the placebo group fell within the predicted Brief Psychiatric Rating Scale scores +/- 1 SE. Unlike the phase 2 trial, from which the pharmacokinetic/pharmacodynamic model was developed, the placebo group in the actual phase 3 trial showed deterioration of Brief Psychiatric Rating Scale scores with time. We conclude that variable placebo responses observed in short-term studies of schizophrenia provide an inadequate basis for the modeling and simulation of placebo subjects in clinical trials. Knowledge of the range of placebo response observed in other studies may have provided an improved basis for the placebo effect model. The model for active drug produced adequate predictions of the actual trial outcomes.

Algorithms↗
PubMed2000

Simulation of clinical trials.

Computer simulation of clinical trials has evolved over the past two decades from a simple instructive game to "full" simulation models yielding pharmacologically sound, realistic trial outcomes. The need to make drug development more efficient and informative and the awareness that many industries make extensive use of simulation in product development have advanced considerably the use of simulation of clinical trials in pharmaceutical product development over the past decade. The structural and stochastic components of trial simulation models are explained as a prelude to a listing of representative simulation projects, reflecting investigative applications of statistical methods, trial design comparisons, and full simulation of new drugs being developed. Lessons learned from these projects are reviewed in the context of their current impact and potential for influencing the future of drug development.

Clinical Trials as Topic↗
PubMed2000

Optimizing the science of drug development: opportunities for better candidate selection and accelerated evaluation in humans.

Two international meetings were convened in 1998 to review the current science of drug development and the potential opportunities to optimize the evaluation of new drugs in humans. This report represents a synopsis of these meetings, and focuses on the current state of knowledge pertaining to drug development, future scientific and technical needs, and the relative merits of various strategies intended to accelerate the clinical development of drugs.

Animals↗
PubMed1999

Trajectories of condylar points during nonworking side and protrusive movements of the mandible.

STATEMENT OF PROBLEM: During lateral excursive and protrusive jaw movements, condylar points are distant from any instantaneous rotational center. Therefore, it is likely that different condylar points would follow similar trajectories during these movements. PURPOSE: This study evaluated the effect of changes in condylar point location on trajectories of condylar points on the nonworking side and during a protrusive jaw movement and compared these changes with the effects described for open-close and working-side condylar movements in the same group of subjects. METHODS: The movements of 5 clinically determined condylar points were recorded in 44 subjects during a contralateral excursion and during protrusion (7 radiographically determined condylar points in 2 subjects). RESULTS: During any single jaw movement, the trajectory of each condylar point was similar in form and dimension to the other condylar points within that subject. CONCLUSION: Changes in condylar point location had little effect on the trajectories of condylar points on the nonworking side and during protrusive jaw movement.

Adult↗
PubMed1999

Trajectories of condylar points during working-side excursive movements of the mandible.

STATEMENT OF PROBLEM: Trajectories of different condylar points provide different interpretations of condylar movement during open-close jaw movements. Movement of the working-side condyle is often assessed clinically by recording the trajectory of a single arbitrary condylar point. PURPOSE: This study examined the effect of the differences in condylar point location on condylar point movement trajectories during a working-side movement. METHODS: Different points exhibited different trajectories during a single working-side movement in each of 44 subjects. RESULTS: Up to 40% of a point's displacement could be attributed simply to the location of the point. CONCLUSIONS: Interpretation of condylar movement on the working side within a subject depends on the point chosen.

Adult↗
PubMed1997

Pharmacodynamics of temazepam in primary insomnia: assessment of the value of quantitative electroencephalography and saccadic eye movements in predicting improvement of sleep.

BACKGROUND AND OBJECTIVE: Quantitative electroencephalographic parameters and saccadic eye movements are frequently used as pharmacodynamic measures of benzodiazepine effect. We investigated the relationship between these measures and the hypnotic effect. METHODS: The correlation between the pharmacodynamic measures and sleep quality was determined in 21 patients with primary insomnia. The pharmacokinetic-pharmacodynamic relationships were characterized after administration of 20 mg oral temazepam. The hypnotic effect was determined on the basis of polysomnographic sleep recordings and a subjective sleep evaluation questionnaire. Correlations between pharmacodynamic measures and the improvement of sleep were investigated. RESULTS: The pharmacokinetic-pharmacodynamic relationships for the parameters derived from electroencephalography and saccadic eye movements showed considerable interindividual variability. Administration of temazepam led to a significant improvement in the objective parameters sleep period efficiency, wake time after sleep onset, and sleep efficiency and in the subjective assessment of sleep quality. No significant correlations were observed between the pharmacokinetic-pharmacodynamic-derived parameters and the improvement in objective or subjective sleep parameters. CONCLUSION: In subjects with primary insomnia the administration of 20 mg oral temazepam results in changes in both the pharmacodynamic measures and in quality of sleep. No individual correlations between the pharmacodynamic measures and quality of sleep were observed. We concluded that the investigated pharmacodynamic measures are of value in the first assessment of clinical efficacy and for the selection of the dose(s) to be investigated in subsequent trials that aim at showing clinical efficacy. However, the conclusive quantification of clinical efficacy should be performed only on the basis of the clinical end point itself.

Adult↗
PubMed1997

The variability of condylar point pathways in open-close jaw movements.

STATEMENT OF PROBLEM: Clinical assessments of condylar movement often rely on the movement of a single clinically determined or average value condylar point. PURPOSE: The aim of this investigation was to study the effect of differences in condylar point location on recorded movement trajectories with an open-close jaw movement. METHODS: Recordings were made of the movements of various condylar points in 44 subjects. The points were identified clinically (average value points) and radiographically. RESULTS: The trajectory of each condylar point, whether average value or radiographically determined, was different in form and dimension from any other condylar point within a subject for the same open-close jaw movement. CONCLUSIONS: Depending on the point chosen in the vicinity of the condyle, quite different interpretations of condylar movement within a subject could be made. The data underscore the caution that must be exercised when interpreting condylar movement from the movement of a single condylar point.

Adult↗