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Biomedical subjects

J J Collins

Publications and source records attributed to J J Collins.

At least 109 records · Page 6Linked to original sources

The effects of spaceflight on open-loop and closed-loop postural control mechanisms: human neurovestibular studies on SLS-2.

Stabilogram-diffusion analysis was used to examine how prolonged periods in microgravity affect the open-loop and closed-loop postural control mechanisms. It was hypothesized that following spaceflight: (1) the effective stochastic activity of the open-loop postural control schemes in astronauts is increased; (2) the effective stochastic activity and uncorrelated behavior, respectively, of the closed-loop postural control mechanisms in astronauts are increased; and (3) astronauts utilized open-loop postural controls schemes for shorter time intervals and smaller displacements. Four crew members and two alternates from the 14-day Spacelab Life Sciences 2 Mission were included in the study. Each subject was tested under eyes-open, quiet-standing conditions on multiple preflight and postflight days. The subjects' center-of-pressure trajectories were measured with a force platform and analyzed according to stabilogram-diffusion analysis. It was found that the effective stochastic activity of the open-loop postural control schemes in three of the four crew members was increased following spaceflight. This result is interpreted as an indication that there may be in-flight adaptations to higher-level descending postural control pathways, e.g., a postflight increase in the tonic activation of postural muscles. This change may also be the consequence of a compensatory (e.g., "stiffening") postural control strategy that is adopted by astronauts to account for general feeling of postflight unsteadiness. The crew members, as a group, did not exhibit any consistent preflight/postflight differences in the steady-state behavior of their closed-loop postural control mechanisms or in the functional interaction of their open-loop and closed-loop postural control mechanisms. These results are interpreted as indications that although there may be in-flight adaptations to the vestibular system and/or proprioceptive system, input from the visual system can compensate for such changes during undisturbed stance.

Humans↗

Age-related changes in open-loop and closed-loop postural control mechanisms.

In an earlier posturographic investigation (Collins and De Luca 1993) it was proposed that open-loop and closed-loop control mechanisms are involved in the regulation of undisturbed, upright stance. In this study, stabilogram-diffusion analysis was used to examine how the natural aging process affects the operational characteristics of these control mechanisms. Stabilogram-diffusion analysis leads to the extraction of repeatable center-of-pressure (COP) parameters that can be directly related to the steady-state behavior and functional interaction of the neuromuscular mechanisms underlying the maintenance of erect posture. Twenty-five healthy young males (aged 19-30 years) and twenty-five elderly males (aged 71-80 years) who were free of major gait and postural disorders were included in the study. An instrumented force platform was used to measure the time-varying displacements of the COP under each subject's feet during quiet standing. The COP trajectories were analyzed as one-dimensional and two-dimensional random walks, according to stabilogram-diffusion analysis. Using this technique, it was demonstrated cross-sectionally that healthy aging is associated with significant changes in the 'quasi-static' dynamics of the postural control system. (It was also shown that more traditional posturographic analyses, i.e., summary statistics, were not sensitive enough to detect these age-related differences.) It was found that the steady-state behavior of the open-loop postural control mechanisms in the elderly is more positively correlated and therefore perhaps more unstable, i.e., the output of the overall system has a greater tendency to move or drift away from a relative equilibrium point over the short term. In contrast with this result, it was also found that the steady-state behavior of the closed-loop postural control mechanisms in the elderly is more negatively correlated and therefore perhaps more stable, i.e., over the longer term, there is an increased probability that movements away from a relative equilibrium point will be offset by corrective adjustments back towards the equilibrium position. In addition, it was demonstrated that the elderly utilize open-loop control schemes for longer time intervals and correspondingly larger COP displacements during periods of undisturbed stance. This result suggests that in the elderly there is a greater delay, on average, before closed-loop feedback mechanisms are called into play. Finally, it was shown that there is an increased heterogeneity of postural control abilities in healthy older adults.

Adult↗

The effects of visual input on open-loop and closed-loop postural control mechanisms.

In an earlier posturographic investigation (Collins and De Luca 1993) it was proposed that open-loop and closed-loop control mechanisms are involved in the regulation of undisturbed, upright stance. In this study, stabilogram-diffusion analysis was used to examine how visual input affects the operational characteristics of these control mechanisms. Stabilogram-diffusion analysis leads to the extraction of repeatable center-of-pressure (COP) parameters that can be directly related to the resultant steady-state behavior and functional interaction of the neuromuscular mechanisms underlying the maintenance of erect posture. Twenty-five healthy male subjects (aged 19-30 years) were included in the study. An instrumented force platform was used to measure the time-varying displacements of the COP under each subject's feet during quiet standing. The subjects were tested under eyes-open and eyes-closed conditions. The COP trajectories were analyzed as one-dimensional and two-dimensional random walks, according to stabilogram-diffusion analysis. Using this technique, it was found that visual input affects the performance of the postural control system in one of two different ways--either it significantly modifies the steady-state behavior of the open-loop postural control mechanisms, or it significantly alters the characteristics of the other closed-loop feedback mechanisms that are involved in balance control. This result is interpreted as an indication that the visual system is integrated into the postural control system in one of two different ways. The experimental population was roughly evenly divided between these two schemes. For the first group (13 of 25 subjects), visual input principally caused a decrease in the "effective" stochastic activity of the open-loop control mechanisms in both the mediolateral and anteroposterior directions. For the second group (12 of 25 subjects), visual input caused an increase in the effective stochastic activity and uncorrelated behavior of the closed-loop control mechanisms in the anteroposterior direction only. On the basis of these results, it is hypothesized that visual input, in both schemes, serves to decrease the stiffness of the musculoskeletal system. In the former case, this may be accomplished by decreasing the level of muscular activity across the joints of the lower limb, whereas, in the latter case, reduced stiffness may be achieved by reducing the gain(s) of the other postural feedback mechanisms, i.e., the proprioceptive and/or vestibular systems. Using stabilogram-diffusion analysis, it was also found that the two groups of subjects behaved similarly under eyes-closed conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

The redundant nature of locomotor optimization laws.

A sagittal-plane model of the lower limb, which considered the possibility of antagonistic and synergistic muscle action and took account of the load-bearing roles of the cruciate ligaments, was applied to a dynamic analysis of level walking. It was hypothesized that: (1) the simple, one-sided constraints that intra-articular contact forces must be compressive and muscle and ligament forces tensile substantially reduce the redundancy of the load-transmitting structures of the lower limb, (2) many previously proposed optimization laws for muscle selection yield equivalent results, when they are applied to a finite set of admissible limiting solutions, and (3) the aforementioned optimization laws, when applied to a finite set of admissible limiting solutions, do not adequately predict the co-contraction of antagonistic muscles during gait. The problem of indeterminacy was resolved by considering all possible limiting solutions of the system unknowns on the dynamic equations. Although 498 limiting solutions of nine unknowns could arise at each sampled point on the gait cycle, the aforementioned one-sided constraints ruled out the large majority of them. It was shown that of the 498 possible, the minimum number of simultaneous admissible solutions for any subject was as few as three and the maximum number was only 18. The Principles of minimal total muscle force, squared muscle force, muscle stress, intra-articular contact force and instantaneous muscle power predicted remarkably similar patterns of muscle activity over the gait cycle. Of the six tested performance criteria, the Principle of minimal total ligament force was the least successful in terms of selecting solutions that closely matched the EMG patterns. This result implied that the muscles do not always act to protect the knee ligaments during gait. Finally, each of the above minimum principles failed to predict any antagonistic quadriceps-hamstrings action at the knee and hip around the event of heelstrike, although such activity was indicated by electromyography.

Adult↗

Intravenous amitriptyline in pediatrics.

Oral amitriptyline has been used as an analgesic in a wide range of pain settings. Despite long-term availability of a parenteral form, the few reports about this formulation have been limited to pharmacokinetic studies in normal volunteers, trials in depressed patients, and analyses of electroencephalogram (EEG) activation. We retrospectively reviewed our experience using intravenous (IV) amitriptyline at Children's Hospital, Boston and at Children's Hospital at Stanford. Eight children (aged 5-16.6 years), who were unable to tolerate medications by the oral route, received IV amitriptyline for a variety of indications, including neuropathic pain, depression, sleep disturbance, and as an adjuvant agent for opioid analgesia. One patient experienced an extrapyramidal reaction temporally related to the administration of IV amitriptyline, which was successfully managed with diphenhydramine. Further prospective, controlled studies are needed to further assess the safety, efficacy and tolerability of this novel use of amitriptyline.

Adolescent↗

Control of severe pain in children with terminal malignancy.

OBJECTIVE: To identify the characteristics of the subset of children with malignancy in whom massive opioid infusions are needed during the terminal phase. DESIGN: Retrospective review of the records of the 199 patients who died of malignancy after treatment at Children's Hospital, Boston, from March 1989 to July 1993, identifying characteristics of patients who required massive opioid infusions (operationally defined as infusion of > 3 mg/kg per hour of morphine dose equivalent) during the terminal phase. RESULTS: Twelve patients (6%) required massive opioid infusions, and eight of these patients required extraordinary measures (epidural or subarachnoid infusion and/or sedation) to achieve adequate analgesia. The duration of epidural or subarachnoid infusions in three patients ranged from 3 to 9 days, and minimal complications occurred. The duration of sedation ranged from 1 to 15 days. Maximal intravenous opioid dosing ranged from 3.8 to 518 mg/kg per hour of morphine equivalent. The maximal infusion rate (exceeding all previous published reports) occurred in an infant with an isolated metastasis in the periaqueductal gray matter, a brain-stem site linked to mediating analgesia and defense reactions. The need for massive opioid dosing in 11 of 12 patients was associated with tumor spread to the spinal nerve roots, nerve plexus, large peripheral nerve, or spinal cord compression. CONCLUSIONS: Standard dosing of opioids adequately treats most cancer pain in children; however, a significant group requires more extensive management. These problems occur more commonly among patients with solid tumors metastatic to spine and major nerves.

Adolescent↗

The effect of pathophysiology on the surgical treatment of ischemic mitral regurgitation: operative and late risks of repair versus replacement.

Operative correction of ischemic mitral regurgitation (IMR) is associated with high risk approach. The objective of this retrospective study was to examine the interaction between the various underlying pathophysiologic mechanisms, the operative procedure, and their influence on short- and long-term outcomes. Over a 10-year period starting January 1984, mitral valve repair or replacement was performed on 150 patients with IMR. The age range was 42-86, mean 67, years; 71 (47%) were females; 139 (93%) were in NYHA functional class III or IV; 23 (15%) were reoperations; and 30 (20%) were in atrial fibrillation. Functional IMR due to annular dilatation or restrictive leaflet motion was present in 106 (71%), and structural IMR due to ruptured chordae or papillary muscle in 44 (29%). Mitral valve repair was performed in 94 (63%) with an annuloplasty ring employed in 80 (85%) patients. Mitral valve replacement was performed in 56 (37%), with 40 (71%) receiving a bioprosthesis (32 Hancock and 8 Carpentier-Edwards valves) and 16 (29%) a St. Jude valve. Coronary artery bypass graft surgery was performed in 139 (93%) patients. The overall operative mortality (OM) was 14/150 (9.3%). The OM for repair was 9.5% compared to 8.9% for replacement (P = NS). There was higher OM in the elderly, particularly in the repair group (P = 0.053), and a trend towards reduced OM in the recent years of the study (P = NS). No predictors of OM were identified by multivariate logistic regression analysis. Long-term follow-up was 98% complete and ranged from 2-120, mean 31.2, months for a total of 935 patient-years. The overall 5-year survival rate was 71 +/- 6%, with 91 +/- 5% for the replacement group compared to 56% +/- 10% for the repair group (P = 0.01). The functional subset of IMR who had a repair had the worse long-term survival (43 +/- 13%) compared to the structural/repair (76 +/- 13%) and structural/replacement groups (89 +/- 8%), and 92 +/- 7% for the functional/replacement group ((P = 0.0049). Multivariate logistic regression analysis identified the functional/repair group (hazards ratio 4.4; +/- 95%, confidence interval 1.6, 11, (P = 0.0031); and earlier years of surgery (hazards ratio 4.7; +/- 95% confidence interval 1.021; (P = 0.046) to be predictors of worse long-term survival. These results suggest that, in IMR, the underlying responsible pathophysiologic mechanisms appear to be the major determinants of survival, rather than the choice of the operative procedure.

Adult↗

Effectiveness of short-course therapy (5 days) with cefuroxime axetil in treatment of secondary bacterial infections of acute bronchitis.

Five hundred thirty-seven patients were enrolled in two independent, investigator-blinded, multicenter, randomized clinical trials comparing the clinical and bacteriologic efficacies and the safety of 5- or 10-day treatment with cefuroxime axetil with those of 10-day treatment with amoxicillin-clavulanate in the treatment of secondary bacterial infections of acute bronchitis. Patients received either 5 or 10 days of treatment (n = 177 in each group) with cefuroxime axetil at 250 mg twice daily or 10 days of treatment (n = 183) with amoxicillin-clavulanate at 500 mg three times daily. Patients in the cefuroxime axetil (5 days) group received placebo on days 6 to 10. Bacteriologic assessments were based on sputum specimen cultures obtained preceding and, when possible, following treatment. Organisms were isolated from the pretreatment sputum specimens of 242 of 537 (45%) patients, with the primary pathogens being Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and Staphylococcus aureus (28, 25, 13, 9, and 8% of isolates, respectively). Pathogens were eradicated or presumed to be eradicated in 87% (52 of 60), 91% (53 of 58), and 86% (60 of 70) of bacteriologically evaluable patients treated with cefuroxime axetil (5 days), cefuroxime axetil (10 days), and amoxicillin-clavulanate, respectively. A satisfactory clinical outcome (cure or improvement) was achieved in 82% (107 of 130), 86% (117 of 136), and 83% (130 of 157) of the clinically evaluable patients treated with cefuroxime axetil (5 days), cefuroxime axetil (10 days), and amoxicillin-clavulanate, respectively. Treatment with amoxicillin-clavulanate was associated with a significantly higher incidence of drug-related adverse events than was treatment with cefuroxime axetil for either 5 or 10 days (P = 0.001), primarily reflecting a higher incidence of drug-related gastrointestinal adverse events (37 versus 19 and 15%, respectively; P < 0.001), particularly diarrhea and nausea. These results indicate that treatment with cefuroxime axetil at 250 mg twice daily for 5 days is as effective as treatment for 10 days with either the same dose of cefuroxime axetil or amoxicillin-clavulanate at 500 mg three times daily in patients with acute bronchitis. In addition, treatment with cefuroxime axetil for either 5 or 10 days is associated with significantly fewer gastrointestinal adverse events, particularly diarrhea and nausea, than is 10-day treatment with amoxicillin-clavulanate.

Acute Disease↗

Comparison of cefuroxime axetil and doxycycline in treatment of patients with early Lyme disease associated with erythema migrans.

A randomized, multicenter, investigator-blinded clinical trial was undertaken in order to compare the efficacies of cefuroxime axetil and doxycycline in the treatment of patients with Lyme disease associated with erythema migrans. A total of 232 patients with physician-documented erythema migrans were treated orally for 20 days with either cefuroxime axetil, 500 mg twice daily (119 patients), or doxycycline, 100 mg three times daily (113 patients), and clinical evaluations were conducted during treatment (8 to 12 days) and at 1 to 5 days and 1, 3, 6, 9, and 12 months posttreatment. Patients were assessed as to the resolution of erythema migrans and of the signs and symptoms related to early Lyme disease as well as to the prevention of late Lyme disease. A satisfactory clinical outcome (success or improvement) was achieved in 90 of 100 (90%) evaluable patients treated with cefuroxime axetil and in 89 of 94 (95%) patients treated with doxycycline (difference, -5%; 95% confidence interval, -12 to 3%). Patients with paresthesia, arthralgia, or irritability at enrollment were at higher risk for an unsatisfactory clinical outcome at 1 month posttreatment. Of the patients with satisfactory outcomes at 1 month posttreatment who were evaluable at 1 year posttreatment, a satisfactory outcome was achieved in 62 of 65 (95%) and in 53 of 53 (100%) patients treated with cefuroxime axetil and doxycycline, respectively (difference, -5%; 95% confidence interval, -10 to 4%). Twenty-eight percent of patients treated with doxycycline and 17% of those treated with cefuroxime axetil had one or more drug-related adverse events (P = 0.041). Doxycycline was associated with more photosensitivity reactions (6% compared with 0% for patients treated with cefuroxime axetil; P=0.006), and cefuroxime axetil was associated with more cases of diarrhea (5% compared with 0% for patients treated with doxycycline; P=0.030). Jarisch-Herxheimer reactions occurred in 12% of the patients in each treatment group. In summary, cefuroxime axetil is well tolerated and appears to be equally as effective as doxycycline in the treatment of early Lyme disease and in preventing the subsequent development of late Lyme disease.

Adult↗

Cefuroxime axetil in the treatment of sinusitis. A review.

Cefuroxime axetil is a beta-lactamase-stable, second-generation, oral cephalosporin that penetrates sinus tissue in concentrations exceeding the MIC90 values (the minimum concentration of drug needed to inhibit the growth of 90% of an isolate of a particular microorganism) for pathogens most commonly associated with acute sinusitis, including Streptococcus pneumoniae and Haemophilus influenzae. A review of all clinical data published to date demonstrates that cefuroxime axetil has been evaluated in the treatment of acute sinusitis and acute exacerbations of chronic sinusitis ("acute-on-chronic sinusitis") in 18 clinical trials involving 1516 assessable patients. In 12 randomized, comparative trials, the rates of satisfactory clinical outcomes (cure or improvement, 79% to 100%) and bacteriologic eradication (84% to 100%) reported with the use of 250 mg of cefuroxime axetil twice daily were similar to those observed with the use of amoxicillin, amoxicillin/clavulanate potassium, cefaclor, cefadroxil, cefixime, clarithromycin, and doxycycline. In these comparisons, no antibiotic demonstrated any therapeutic advantages over cefuroxime axetil regarding time to symptom abatement. Cefuroxime axetil was at least as well tolerated as the other antibiotics. Overall, the role of cefuroxime axetil in the treatment of sinusitis appears to be as one of the broad-spectrum antibiotics that can be used for infections due to the most commonly implicated sinus pathogens, especially those due to the increasing number of relatively penicillin-resistant strains of S pneumoniae and beta-lactamase-producing strains of H influenzae and Moraxella catarrhalis.

Acute Disease↗

A group-theoretic approach to rings of coupled biological oscillators.

In this paper, a general approach for studying rings of coupled biological oscillators is presented. This approach, which is group-theoretic in nature, is based on the finding that symmetric ring networks of coupled non-linear oscillators possess generic patterns of phase-locked oscillations. The associated analysis is independent of the mathematical details of the oscillators' intrinsic dynamics and the nature of the coupling between them. The present approach thus provides a framework for distinguishing universal dynamic behaviour from that which depends upon further structure. In this study, the typical oscillation patterns for the general case of a symmetric ring of n coupled non-linear oscillators and the specific cases of three- and five-membered rings are considered. Transitions between different patterns of activity are modelled as symmetry-breaking bifurcations. The effects of one-way coupling in a ring network and the differences between discrete and continuous systems are discussed. The theoretical predictions for symmetric ring networks are compared with physiological observations and numerical simulations. This comparison is limited to two examples: neuronal networks and mammalian intestinal activity. The implications of the present approach for the development of physiologically meaningful oscillator models are discussed.

Animals↗

Antagonistic-synergistic muscle action at the knee during competitive weightlifting.

A sagittal-plane model of the knee, which takes account of the movements of the flexion axis relative to the femur and tibia and considers the possibility of antagonistic and synergistic muscle action, is used to determine the values of the forces transmitted by the muscles, cruciate ligaments and intra-articular surfaces during the clean phase of the clean-and-jerk weightlift. The theoretical analyses demonstrate that it is geometrically and mechanically possible for the knee musculature to unload and thereby protect the cruciate ligaments throughout a substantial portion of the lift. The price to be paid for this protection, in the case of the co-contraction of antagonistic muscles, is larger muscle and tibio-fermoral contact forces. The application of synergistic muscle action, however, results in smaller individual muscle and intra-articular contact forces.

Biomechanical Phenomena↗

An analytic solution for energy deposition in model spherical tumours undergoing ultrasound-hyperthermia treatments.

In this paper, we develop a method to predict the energy deposition in tumours undergoing ultrasound-hyperthermia treatments. Energy depositions are calculated using an exact, analytic solution to the problem of ultrasound scattering from a spherical tumour. The biological tissues are modelled as solid, lossy elastic media so that (i) transverse-wave modes, in addition to longitudinal-wave modes, are considered, and (ii) mode coupling is fully accounted for during the scattering. The model tumour is of arbitrary size and no restrictions are placed on its material parameters relative to the surrounding tissue. Simpler analytic results are given for tumours that differ in densities and rigidities only slightly from the surrounding tissue. We briefly discuss how the above analysis could be extended to more complex systems, i.e., irregularly shaped tumours.

Humans↗

The Tc5 family of transposable elements in Caenorhabditis elegans.

We have identified Tc5, a new family of transposable genetic elements in the nematode Caenorhabditis elegans. All wild-type varieties of C. elegans that we examined contain 4-6 copies of Tc5 per haploid genome, but we did not observe transposition or excision of Tc5 in these strains. Tc5 is active, however, in the mut-2 mutant strain TR679. Of 60 spontaneous unc-22 mutations isolated from strain TR679, three were caused by insertion of Tc5. All three Tc5-induced mutations are unstable; revertants results from precise or nearly precise excision of Tc5. Individual Tc5 elements are similar to each other in size and structure. The 3.2-kb element is bounded by inverted terminal repeats of nearly 500 bp. Eight of the ten terminal nucleotides of Tc5 are identical to the corresponding nucleotides of Tc4. Further, both elements recognize the same target site for insertion (CTNAG) and both cause duplication of the central TNA trinucleotide upon insertion. Other than these similarities to Tc4, Tc5 is unrelated to the three other transposon families (Tc1, Tc3 and Tc4) that transpose and excise at high frequency in mut-2 mutant strains. Mechanisms are discussed by which four apparently unrelated transposon families are all affected by the same mut-2 mutation.

Animals↗

An approach for conducting epidemiological surveillance in industry.

There are three unresolved issues in epidemiological surveillance: 1) should surveillance be hypothesis generating, 2) how much effort should be put into the design and data collection of a surveillance project, and 3) can useful surveillance be done with questionable data? It is concluded that epidemiological surveillance should be approached as an epidemiology study that examines the potential association between specific exposure and disease. This would include 1) a feasibility study to determine if surveillance on a particular subject is possible, 2) a detailed protocol, and 3) plans for data reduction, interpretation of findings, and worker communication. Epidemiological surveillance must be well planned and resourced to be used as a screening mechanism for occupational illness or injury excess, monitoring the health of workers exposed to specific substances, or setting priorities for future special studies.

Adult↗