Search PubMed⌕ Search

Biomedical subjects

J J Collins

Publications and source records attributed to J J Collins.

At least 55 records · Page 3Linked to original sources
PubMed2000

Mortality surveillance and occupational hazards: the Solutia mortality experience 1980-94.

OBJECTIVES: Several investigators argue that company wide mortalities for recent workers allow early identification of potential workplace hazards. Mortalities for recent workers were compared with published studies of workers with specific exposures in the same company to find whether mortality surveillance results could be used to identify previously unknown health effects from workplace hazards. METHODS: Relative risks for causes of death in published substance specific studies at the plants were compared with the relative risks in the mortality surveillance of workers 20 or more years after first being employed. RESULTS: As reported by other companies, low mortalities were found among workers in the mortality surveillance. The mortality surveillance reports often found no increased risk of disease at plants in which substance specific studies had found no effects. However, disease specific relative risks were not found by the mortality surveillance predictions of relative risks in the substance specific studies with increased risk. CONCLUSION: Mortality surveillance is of limited use for identifying health effects from past workplace exposures to specific materials. The healthy worker and survivor effects, the failure to identify subsets of workers exposed to potentially toxic substances, the typically long induction period between exposure and disease, and the inability of recent mortality levels to reflect historical conditions all may make it difficult to use mortality surveillance to identify workplace hazards. Combining mortality surveillance with studies of workers with potentially toxic exposures helps identify occupational hazards.

Cause of Death↗
PubMed1999

Symmetry in locomotor central pattern generators and animal gaits.

Animal locomotion is controlled, in part, by a central pattern generator (CPG), which is an intraspinal network of neurons capable of generating a rhythmic output. The spatio-temporal symmetries of the quadrupedal gaits walk, trot and pace lead to plausible assumptions about the symmetries of locomotor CPGs. These assumptions imply that the CPG of a quadruped should consist of eight nominally identical subcircuits, arranged in an essentially unique matter. Here we apply analogous arguments to myriapod CPGs. Analyses based on symmetry applied to these networks lead to testable predictions, including a distinction between primary and secondary gaits, the existence of a new primary gait called 'jump', and the occurrence of half-integer wave numbers in myriapod gaits. For bipeds, our analysis also predicts two gaits with the out-of-phase symmetry of the walk and two gaits with the in-phase symmetry of the hop. We present data that support each of these predictions. This work suggests that symmetry can be used to infer a plausible class of CPG network architectures from observed patterns of animal gaits.

Animals↗
PubMed1999

Noise shaping in populations of coupled model neurons.

Biological information-processing systems, such as populations of sensory and motor neurons, may use correlations between the firings of individual elements to obtain lower noise levels and a systemwide performance improvement in the dynamic range or the signal-to-noise ratio. Here, we implement such correlations in networks of coupled integrate-and-fire neurons using inhibitory coupling and demonstrate that this can improve the system dynamic range and the signal-to-noise ratio in a population rate code. The improvement can surpass that expected for simple averaging of uncorrelated elements. A theory that predicts the resulting power spectrum is developed in terms of a stochastic point-process model in which the instantaneous population firing rate is modulated by the coupling between elements.

Mathematics↗
PubMed1999

The autonomous transactivation domain in helix H3 of the vitamin D receptor is required for transactivation and coactivator interaction.

A ligand-inducible transactivation function (AF-2) exists in the extreme carboxyl terminus of the vitamin D receptor (VDR) that is essential for 1alpha,25-dihydroxyvitamin D3 (1,25-(OH)2D3)-activated transcription and p160 coactivator interaction. Crystallographic data of related nuclear receptors suggest that binding of 1, 25-(OH)2D3 by VDR induces conformational changes in the ligand-binding domain (LBD), the most striking of which is a packing of the AF-2 helix onto the LBD adjacent to helices H3 and H4. In this study, a panel of VDR helix H3 mutants was generated, and residues in helix H3 that are important for ligand-activated transcription by the full-length VDR were identified. In particular, one mutant (VDR (Y236A)) exhibited normal ligand binding and heterodimerization with the retinoid X receptor (RXR) but was transcriptionally inactive. Yeast two-hybrid studies and in vitro protein interaction assays demonstrated that VDR (Y236A) was selectively impaired in interaction with AF-2-interacting coactivator proteins such as SRC-1 and GRIP-1. These data indicate an importance of helix H3 in the mechanism of VDR-mediated transcription, and they support the concept that helix H3 functions in concert with the AF-2 domain to form a transactivation surface for binding the p160 class of nuclear receptor coactivators.

Animals↗
PubMed1999

Assessing muscle stiffness from quiet stance in Parkinson's disease.

In previous studies, we developed a postural stiffness measure that is extracted from foot center-of-pressure (COP) trajectories from quietly standing individuals and is based on an analytical mechanical model of posture control. Here we apply this measure to patients with Parkinson's disease (PD). We correlated the postural stiffness measure with different clinical rating scales, obtained from patients. Kendall's rank correlation was highly significant between the stiffness measure and rigidity, bradykinesia, posture impairment, gait, and leg agility, respectively, as rated by the Unified Parkinson's Disease Rating Scale. These results provide further evidence that a higher intrinsic muscle stiffness may contribute to the aforementioned clinically defined symptoms. From a clinical standpoint, this work indicates that the proposed postural stiffness measure may be useful as an assessment tool for the evaluation of PD patients subsequent to pharmacological and surgical treatment.

Disability Evaluation↗
PubMed1999

The effects of stochastic galvanic vestibular stimulation on human postural sway.

Galvanic vestibular stimulation serves to modulate the continuous firing level of the peripheral vestibular afferents. It has been shown that the application of sinusoidally varying, bipolar galvanic currents to the vestibular system can lead to sinusoidally varying postural sway. Our objective was to test the hypothesis that stochastic galvanic vestibular stimulation can lead to coherent stochastic postural sway. Bipolar binaural stochastic galvanic vestibular stimulation was applied to nine healthy young subjects. Three different stochastic vestibular stimulation signals, each with a different frequency content (0-1 Hz, 1-2 Hz, and 0-2 Hz), were used. The stimulation level (range 0.4-1.5 mA, peak to peak) was determined on an individual basis. Twenty 60-s trials were conducted on each subject - 15 stimulation trials (5 trials with each stimulation signal) and 5 control (no stimulation) trials. During the trials, subjects stood in a relaxed, upright position with their head facing forward. Postural sway was evaluated by using a force platform to measure the displacements of the center of pressure (COP) under each subject's feet. Cross-spectral measures were used to quantify the relationship between the applied stimulus and the resulting COP time series. We found significant coherency between the stochastic vestibular stimulation signal and the resulting mediolateral COP time series in the majority of trials in 8 of the 9 subjects tested. The coherency results for each stimulation signal were reproducible from trial to trial, and the highest degree of coherency was found for the 1- to 2-Hz stochastic vestibular stimulation signal. In general, for the nine subjects tested, we did not find consistent significant coherency between the stochastic vestibular stimulation signals and the anteroposterior COP time series. This work demonstrates that, in subjects who are facing forward, bipolar binaural stochastic galvanic stimulation of the vestibular system leads to coherent stochastic mediolateral postural sway, but it does not lead to coherent stochastic anteroposterior postural sway. Our finding that the coherency was highest for the 1- to 2-Hz stochastic vestibular stimulation signal may be due to the intrinsic dynamics of the quasi-static postural control system. In particular, it may result from the effects of the vestibular stimulus simply being superimposed upon the quiet-standing COP displacements. By utilizing stochastic stimulation signals, we ensured that the subjects could not predict a change in the vestibular stimulus. Thus, our findings indicate that subjects can act as "responders" to galvanic vestibular stimulation.

Adolescent↗
PubMed1999

Vagal afferents from the uterus and cervix provide direct connections to the brainstem.

Previous anatomical studies demonstrated vagal innervation to the ovary and distal colon and suggested the vagus nerve has uterine inputs. Recent behavioral and physiological evidence indicated that the vagus nerves conduct sensory information from the uterus to the brainstem. The present study was undertaken to identify vagal sensory connections to the uterus. Retrograde tracers, Fluorogold and pseudorabies virus were injected into the uterus and cervix. DiI, an anterograde tracer, was injected into the nodose ganglia. Neurectomies involving the pelvic, hypogastric, ovarian and abdominal vagus nerves were performed, and then uterine whole-mounts examined for sensory nerves containing calcitonin gene-related peptide. Nodose ganglia and caudal brainstem sections were examined for the presence of estrogen receptor-containing neurons in "vagal locales." Labeling of uterine-related neurons in the nodose ganglia (Fluorogold and pseudorabies virus) and in the brainstem nuclei (pseudorabies virus) was obtained. DiI-labeled nerve fibers occurred near uterine horn and uterine cervical blood vessels, in the myometrium, and in paracervical ganglia. Rats with vagal, pelvic, hypogastric and ovarian neurectomies exhibited a marked decrease in calcitonin gene-related peptide-immunoreactive nerves in the uterus relative to rats with pelvic, hypogastric, and ovarian neurectomies with intact vagus nerves. Neurons in the nodose ganglia and nucleus tractus solitarius were immunoreactive for estrogen receptors. These results demonstrated: (1) the vagus nerves serve as connections between the uterus and CNS, (2) the nodose ganglia contain uterine-related vagal afferent neuron cell bodies, and (3) neurons in vagal locales contain estrogen receptors.

Animals↗
PubMed1999

Transdermal fentanyl in children with cancer pain: feasibility, tolerability, and pharmacokinetic correlates.

OBJECTIVES: (1) To assess the feasibility and tolerability of the therapeutic transdermal fentanyl system (TTS-fentanyl) by using a clinical protocol developed for children with cancer pain. (2) To estimate the pediatric pharmacokinetic parameters of TTS-fentanyl. METHODS: The drug was administered in open-label fashion; and measures of analgesia, side effects, and skin changes were obtained for a minimum of 2 doses (6 treatment days). Blood specimens were analyzed for plasma fentanyl concentrations. The pharmacokinetics of TTS-fentanyl were estimated by using a mixed effect modeling approach. RESULTS: Treatment was well tolerated. Ten of the 11 patients who completed the 2 doses continued treatment with TTS-fentanyl. The duration of treatment ranged from 6 to 275 days. The time to reach peak plasma concentration ranged from 18 hours to >66 hours in patients receiving the 25 microg/h patch. Compared with published pharmacokinetic data from adults, the mean clearance and volume of distribution of transdermal fentanyl were the same, but the variability was less. CONCLUSIONS: Treatment of children with TTS-fentanyl is feasible and well tolerated and yields fentanyl pharmacokinetic parameter estimates similar to those for adults. A larger study is required to confirm these findings and further test the clinical protocol.

Administration, Cutaneous↗
PubMed1999

Impact of body mass index and albumin on morbidity and mortality after cardiac surgery.

OBJECTIVE: Extremely thin and overly obese patients may not tolerate cardiac surgery as well as other patients. A retrospective study was conducted to determine whether the extremes of body mass index (weight/height(2) [kg/m(2)]) and/or cachexia increased the morbidity and mortality associated with cardiac operations. METHODS: Body mass index was used to objectively measure "thinness" (body mass index < 20) and "heaviness" (body mass index > 30); preoperative serum albumin was used to quantify nutritional status and underlying disease. Data were gathered between 1993 and 1997 from 5168 consecutive patients undergoing coronary artery bypass or valve operations, or both. RESULTS: No significant correlations were observed between body mass index and preoperative albumin levels. Low body mass index (<20) and low albumin level (<2.5 g/dL) were each independently associated with increased mortality after cardiopulmonary bypass (P </=.0005). Operative mortality was highest among those with both low body mass index and low albumin level. Multivariable logistic regression, adjusting for potentially confounding variables, demonstrated that an albumin level of less than 2.5 g/dL was independently associated with increased risk of reoperation for bleeding, postoperative renal failure, and prolonged ventilatory support, intensive care unit stay, and total length of stay. A body mass index of more than 30 was associated with increased sternal wound infection and saphenous vein harvest site infection. CONCLUSIONS: Hypoalbuminemia and low body mass index each independently predict increased morbidity and mortality after cardiac operations. Preoperative risk stratification with the use of body mass index and serum albumin may help to identify subgroups of patients at high risk for adverse outcomes after cardiac operations.

Aged↗
PubMed1999

Effectiveness of short-course therapy (5 days) with grepafloxacin in the treatment of acute bacterial exacerbations of chronic bronchitis.

Three hundred eighty-nine patients were enrolled in a double-masked, multicenter, randomized clinical trial comparing the clinical and bacteriologic efficacies and safety of a 5-day course (n = 195) versus a 10-day course (n = 194) of grepafloxacin 400 mg once daily in the treatment of acute bacterial exacerbations of chronic bronchitis (ABECB). Patients in the 5-day treatment group received placebo on days 6 through 10. Bacteriologic assessments were based on cultures of sputum specimens obtained before and, when possible, during and after treatment. Organisms were isolated from the pretreatment sputum specimens of 332 of 388 (86%) patients, the primary pathogens being Haemophilus parainfluenzae, Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Staphylococcus aureus (29%, 19%, 4%, 5%, and 5% of isolates, respectively). Among isolates tested for beta-lactamase production, results were positive in 25% of H influenzae isolates and 90% of M catarrhalis isolates. Forty-two percent of S pneumoniae isolates demonstrated reduced susceptibility (intermediate or high-level resistance) to penicillin. A satisfactory clinical outcome (cure or improvement) was achieved in 83% (128 of 155) and 81% (122 of 150) of clinically evaluable patients treated with grepafloxacin for 5 or 10 days, respectively. Pathogens were eradicated or presumed eradicated in 77% (106 of 138) and 80% (98 of 123) of bacteriologically evaluable patients treated with grepafloxacin for 5 or 10 days, respectively. The 2 treatment groups were equivalent with respect to both clinical and bacteriologic efficacy, and no statistically significant differences in the incidence of drug-related adverse events were seen between the 2 groups. Substantial symptom relief was evident with both treatment regimens by the first during-treatment measurement, which occurred between days 3 through 5. These results indicate that treatment with 400 mg grepafloxacin once daily for 5 days is as well tolerated and effective as treatment for 10 days in patients with ABECB. The lower cost compared with a 10-day regimen and the increased likelihood that patients will complete the entire shorter, once-daily regimen make the 5-day grepafloxacin regimen a useful therapeutic option in the treatment of ABECB.

Acute Disease↗
PubMed1999

Quantifying uncertainty in a risk assessment using human data.

A call for risk assessment approaches that better characterize and quantify uncertainty has been made by the scientific and regulatory community. This paper responds to that call by demonstrating a distributional approach that draws upon human data to derive potency estimates and to identify and quantify important sources of uncertainty. The approach is rooted in the science of decision analysis and employs an influence diagram, a decision tree, probabilistic weights, and a distribution of point estimates of carcinogenic potency. Its results estimate the likelihood of different carcinogenic risks (potencies) for a chemical under a specific scenario. For this exercise, human data on formaldehyde were employed to demonstrate the approach. Sensitivity analyses were performed to determine the relative impact of specific levels and alternatives on the potency distribution. The resulting potency estimates are compared with the results of an exercise using animal data on formaldehyde. The paper demonstrates that distributional risk assessment is readily adapted to situations in which epidemiologic data serve as the basis for potency estimates. Strengths and weaknesses of the distributional approach are discussed. Areas for further application and research are recommended.

Carcinogens↗
PubMed1999

CNS tumors and exposure to acrylonitrile: inconsistency between experimental and epidemiology studies.

Acrylonitrile is a potent CNS tumorigen in rats leading to concern that it may be a tumorigen in humans. There have been 12 epidemiology studies of 37,352 workers exposed to acrylonitrile which evaluate CNS cancers. We summarize and evaluate these epidemiology studies for CNS cancers using the methods of meta-analysis. Our analyses indicate that workers with acrylonitrile exposure have null findings for CNS cancer (relative risk = 1.1, 95% confidence interval 0.8-1.5), which are in stark contrast to the projected risk to humans using the rat findings (relative risk = 3.5, 95% confidence interval 3.0-4.0). We discuss several explanations for the inconsistency between animal and human findings, including the possibility that the acrylonitrile-induced rat CNS tumors may not be relevant to humans. Given the rarity of CNS tumors in humans and a lack of understanding of the causal mechanisms of these tumors in rats, however, a more definitive conclusion will have to await additional experimental and observational data. Nevertheless, the epidemiology evidence indicates that acrylonitrile is not a potent CNS tumorigen.

Acrylonitrile↗
PubMed1999

Synchronization of noisy systems by stochastic signals.

We study, in terms of synchronization, the nonlinear response of noisy bistable systems to a stochastic external signal, represented by Markovian dichotomic noise. We propose a general kinetic model which allows us to conduct a full analytical study of the nonlinear response, including the calculation of cross-correlation measures, the mean switching frequency, and synchronization regions. Theoretical results are compared with numerical simulations of a noisy overdamped bistable oscillator. We show that dichotomic noise can instantaneously synchronize the switching process of the system. We also show that synchronization is most pronounced at an optimal noise level-this effect connects this phenomenon with aperiodic stochastic resonance. Similar synchronization effects are observed for a stochastic neuron model stimulated by a stochastic spike train.

Journal Article↗
PubMed1999

Mechanism of stochastic resonance enhancement in neuronal models driven by 1/f noise.

Noise can assist neurons in the detection of weak signals via a mechanism known as stochastic resonance (SR). In a previous study [Phys. Lett. A 243, 281 (1998)], we showed that when colored noise with 1/f(beta) spectrum is added to the FitzHugh-Nagumo (FHN) neuronal model, the optimal noise variance for SR could be minimized with beta approximately 1. In this study, we investigate analytically how the noise color (beta) affects the SR profile in a linearized version of the FHN model. We demonstrate that the aforementioned effect of 1/f noise is related to the dynamical characteristics of the model neuron, i.e., the refractory period, the low-pass filtering effect of the membrane capacitance, and the high-pass filtering effect of the recovery variable.

Animals↗
PubMed1999

Using weak impulses to suppress traveling waves in excitable media.

Here we propose mechanisms for suppressing non-steady-state motions--propagating pulses, spiral waves, spiral-wave chaos--in excitable media. Our approach is based on two points: (1) excitable media are multistable; and (2) traveling waves in excitable media can be separated into fast and slow motions, which can be considered independently. We show that weak impulses can be used to change the values of the slow variable at the front and back of a traveling wave, which leads to wave front and wave back velocities that are different from each other. This effect can destabilize the traveling wave, resulting in a transition to the rest state.

Journal Article↗
PubMed1999

Coherence resonance in excitable and oscillatory systems: the essential role of slow and fast dynamics.

Stochastic noise of an appropriate amplitude can maximize the coherence of the dynamics of certain types of excitable systems via a phenomenon known as coherence resonance (CR). In this paper we demonstrate, using a simple excitable system, the mechanism underlying the generation of CR. Using analytical expressions for the spectral density of the system's dynamics, we show that CR relies on the coexistence of fast and slow motions. We also show that the same mechanism of CR holds in the oscillatory regime, and we examine how CR depends on both the excitability of the system and the nonuniformity of the motion.

Journal Article↗