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PubMed2003

Peak physiologic responses to arm and leg ergometry in male and female patients with airflow obstruction.

STUDY OBJECTIVE: To investigate differences in work capacity for the arms and legs in patients with moderate-to-severe COPD. DESIGN: Cross-sectional investigation. PATIENTS: One hundred twenty-four patients (90 men and 34 women) aged 45 to 81 years with moderate-to-very severe COPD. FEV(1) ranged from 0.70 to 2.79 L/min (FVC, 1.73 to 5.77 L; FEV(1)/FVC, 24 to 69%). All patients were in stable condition at the time of testing and receiving a stable drug regime. MEASUREMENTS: Each patient completed a demographic and medical history questionnaire, pulmonary function studies (spirometry, lung volumes, and diffusion capacity), peak exercise ergometry with gas exchange for the arms and legs; they also rated their subjective assessment of perceived dyspnea and extremity fatigue using Borg scores during exercise. RESULTS: Patients were of comparable age, with men taller and heavier than women. Smoking history was significantly less for women (47.9 pack-years vs 66.6 pack-years for men) even though each group presented with equivalent age (p > 0.05). Women were less obstructed than men, with FEV(1)/FVC (mean +/- SD) of 46.5 +/- 10.9% vs 40.2 +/- 9.3%, respectively. Ventilatory limitation during exercise was noted for all patients studied. Peak work capacity was greater for men, and leg peak responses were greater than arm values for each gender. As airway obstruction increased, work capacity became more limited. Peak arm work achieved was 38.9 +/- 19.6 W, oxygen uptake (VO(2)) was 903.9 +/- 263.5 mL/min, and minute ventilation (VE) was 33.7 +/- 9.5 L. Peak leg work value was 62.9 +/- 24.8 W, VO(2) was 1,091.4 +/- 321.5 mL/min, and VE was 39.3 +/- 12.0 L. Hence, arm values were 62%, 83%, and 85% of the measured leg values, respectively. Dyspnea and extremity effort scores were similar for men and women, and for arms and legs. Regression analysis was used to derive prediction equations for arm work from measured leg ergometry testing. For watts of work, a three-variable model emerged explaining 66% of the variance; VO(2) yielded a four-variable model with 80% of the variance explained; and VE yielded a three-variable model explaining 72% of the variance. CONCLUSION: Arm work is reduced by 38% that of the legs, while more modest reductions are noted for VO(2) and VE, suggesting greater mechanical efficiency for leg work as compared to arm work. These data also suggest greater metabolic demand for respiratory muscles and arm ergometry. Dyspnea and extremity Borg scores were equivalent for each modality and level of airway obstruction studied, suggesting that perception plays an important role in limiting exercise, and that a threshold for termination of exercise may exist. Further, peak leg ergometry results can be used with pulmonary function indexes to predict peak arm workload in watts, VO(2), and VE. These data may be used to assist the clinician in prescribing rehabilitation or estimating arm exercise ability when arm testing is unavailable.

Activities of Daily Living↗

PubMed2004

Improving the diagnosis related grouping model's ability to explain length of stay of elderly medical inpatients by incorporating function-linked variables.

INTRODUCTION: This study first aimed to determine the adequacy of the Diagnosis Related Grouping (DRG) model's ability to explain (1) the variance in the actual length of stay (LOS) of elderly medical inpatients and (2) the LOS difference in the same cohort between the departments of Geriatric Medicine (GRM) and General Medicine (GM). We then looked at how these explanatory abilities of the DRG changed when patients' function-linked variables (ignored by DRG) were incorporated into the model. MATERIALS AND METHODS: Basic demographic data of a consecutively hospitalised cohort of elderly medical inpatients from GRM and GM, as well as their actual LOS, discharge DRG codes [with their corresponding trimmed average length of stay (ALOS)] and selected function-linked variables (including premorbid functional status, change in functional profile during hospitalisation and number of therapists seen) were recorded. Beginning with ALOS, function-linked variables that were significantly associated with LOS were then added into two multiple liner regression models so as to quantify how the functional dimension improved the DRGs' abilities to explain LOS variances and interdepartmental LOS differences. Forward selection procedure was employed to determine the final models. For the interdepartmental analysis, the study sample was restricted to patients who shared common DRG codes. RESULTS: 114 GRM and 118 GM patients were studied. Trimmed ALOS alone explained 8% of the actual LOS variance. With the addition of function-linked variables, the adjusted R2 of the final model increased to 28%. Due to common code restrictions, the data of 79 GRM and 78 GM patients were available for the analysis of interdepartmental LOS differences. At the unadjusted stage, the median stay of GRM patients was 4.3 days longer than GM's and with adjustments made for the DRGs, this difference was reduced to 3.9 days. Additionally adjusting for the patients' functional features diminished the interdepartmental LOS discrepancy even further, to 2.1 days. CONCLUSION: This study demonstrates that for elderly medical inpatients, the incorporation of patients' functional status significantly improves the DRG model's ability to predict the patients' actual LOS as well as to explain interdepartmental LOS differences between GRM and GM.

Age Factors↗

PubMed2002

Evolution of functionally conserved enhancers can be accelerated in large populations: a population-genetic model.

The evolution of cis-regulatory elements (or enhancers) appears to proceed at dramatically different rates in different taxa. Vertebrate enhancers are often very highly conserved in their sequences, and relative positions, across distantly related taxa. In contrast, functionally equivalent enhancers in closely related Drosophila species can differ greatly in their sequences and spatial organization. We present a population-genetic model to explain this difference. The model examines the dynamics of fixation of pairs of individually deleterious, but compensating, mutations. As expected, small populations are predicted to have a high rate of evolution, and the rate decreases with increasing population size. In contrast to previous models, however, this model predicts that the rate of evolution by pairs of compensatory mutations increases dramatically for population sizes above several thousand individuals, to the point of greatly exceeding the neutral rate. Application of this model predicts that species with moderate population sizes will have relatively conserved enhancers, whereas species with larger populations will be expected to evolve their enhancers at much higher rates. We propose that the different degree of conservation seen in vertebrate and Drosophila enhancers may be explained solely by differences in their population sizes and generation times.

Animals↗

PubMed1991

A model for diagnosing and explaining multiple disorders.

The ability to diagnose multiple interacting disorders and explain them in a coherent causal framework has only partially been achieved in medical expert systems. This paper proposes a causal model for diagnosing and explaining multiple disorders whose key elements are: physician-directed hypotheses generation, object-oriented knowledge representation, and novel explanation heuristics. The heuristics modify and link the explanations to make the physician aware of diagnostic complexities. A computer program incorporating the model currently is in use for diagnosing peripheral nerve and muscle disorders. The program successfully diagnoses and explains interactions between diseases in terms of underlying pathophysiologic concepts. The model offers a new architecture for medical domains where reasoning from first principles is difficult but explanation of disease interactions is crucial for the system's operation.

Acid-Base Imbalance↗

PubMed1993

Comparison of alternative models for predicting the uptake of chlorinated hydrocarbons by oligochaetes.

The uptake of chlorinated hydrocarbons from contaminated sediments by oligochaetes was analyzed using three alternative models. Uptake appears to be best explained using a model that explicates the relationship of oligochaete body burden as a function of weight-dependent feeding rates, fractional absorption, and exposure times. The model explains observed variations in body burdens with oligochaete weights. Oligochaetes appear to absorb small fractions of ingested hydrocarbons. Fractional absorption of ingested contaminants appears to have a parabolic relationship with octanol-water partition coefficients and may decrease over time.

Animals↗

PubMed1993

Deformations in the cytoplasmic membrane of Escherichia coli direct the synthesis of peptidoglycan. The hernia model.

To explain the growth of the Gram-negative envelope and in particular how it could be strengthened where it is weakest, we propose in the hernia model that local weakening of the peptidoglycan sacculus allows turgor pressure to cause the envelope to bulge outwards in a hernia; the consequent local alteration in the radius of curvature of the cytoplasmic membrane causes local alterations in phospholipid structure and composition that determine both the synthesis and hydrolysis of peptidoglycan. This proposal is supported by evidence that phospholipid composition determines the activity of phospho-N-acetylmuramic acid pentapeptide translocase, UDP-N-acetylglucosamine:N-acetylmuramic acid-(pentapeptide)-P-P-bactoprenyl-N-acetylglucosamine transferase, bactoprenyl phosphate phosphokinase, and N-acetylmuramyl-L-alanine amidase. We also propose that the shape of Escherichia coli is maintained by contractile proteins acting at the hernia. Given the universal importance of membranes, these proposals have implications for the determination of shape in eukaryotic cells.

Bacterial Proteins↗

PubMed1999

Circular permutations in the molecular evolution of DNA methyltransferases.

Circular permutations of genes during molecular evolution often are regarded as elusive, although a simple model can explain these rearrangements. The model assumes that first a gene duplication of the precursor gene occurs in such a way that both genes become fused in frame, leading to a tandem protein. After generation of a new start codon within the 5' part of the tandem gene and a stop at an equivalent position in the 3' part of the gene, a protein is encoded that represents a perfect circular permutation of the precursor gene product. The model is illustrated here by the molecular evolution of adenine-N6 DNA methyltransferases. beta- and gamma-type enzymes of this family can be interconverted by a single circular permutation event. Interestingly, tandem proteins, proposed as evolutionary intermediates during circular permutation, can be directly observed in the case of adenine methyltransferases, because some enzymes belonging to type IIS, like the FokI methyltransferase, are built up by two fused enzymes, both of which are active independently of each other. The mechanism for circular permutation illustrated here is very easy and applicable to every protein. Thus, circular permutation can be regarded as a normal process in molecular evolution and a changed order of conserved amino acid motifs should not be interpreted to argue against divergent evolution.

DNA Modification Methylases↗

PubMed1988

Altered plasma membrane ultrastructure in multidrug-resistant cells.

Multidrug resistance is mediated by P-glycoprotein, an integral plasma membrane component which is thought to function as a drug export pump. This model can explain drug resistance, but fails to account for the broader pleiotropy of the multidrug resistance phenotype. We report here a freeze-fracture study revealing increases in the densities of protoplasmic face intramembrane particles in multidrug-resistant Chinese hamster ovary (CHO) and human leukemic cells. The intramembrane particle density in a CHO cell revertant which had lost the characteristics of the multidrug resistance phenotype was indistinguishable from that of the drug-sensitive parental cell line. This demonstration of a global multidrug resistance-linked change in plasma membrane architecture may have significant implications for understanding the variety of concurrent membrane-related changes which are not easily explained by the current model for multidrug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1992

Capillary net and injection modeling.

A former work proved that the physiological Krogh model is valid and can be used as a tool by physicians and biologists in order to simulate drug injections. Here, after a short critical review, a more complete model describing the capillary net is established. A numerical method which can be used to solve the associate mathematical model is explained. Then, the results are discussed and used to explain why the Krogh model is valid despite its simplifying hypotheses. Diffusion and permeability coefficients are also estimated.

Algorithms↗

PubMed1989

Superiority of perfusion over bolus administration in cancer chemotherapy: proposition of a compartmental model.

Recent studies indicate that, for cancer chemotherapy, prolongation of drug injection time yields lower toxicity and better efficacy. We propose a compartmental pharmacological model to explain these observations. The model has been simulated on an analog computer. The curves obtained give a credible explanation for the clinical data. The superiority of perfusion over bolus injection may be attributed to plasma peak suppression.

Antineoplastic Agents↗

PubMed2000

The myosin motor: muscle contraction and in vitro movement.

The molecular mechanism of in vitro movement is assumed, by most investigators, to be identical to that of muscle contraction. We discuss this view, which raises various problems. We believe there are mechanisms for muscle contraction (in this case considerable forces are developed, with small displacements) and other mechanisms for in vitro movement (giving large displacements, without necessarily generating substantial forces). Hybrid models may explain muscle contraction. The traditional swinging-crossbridge model may explain in vitro movement. For muscle contraction, movement may result partly from the swinging-crossbridge mechanism and partly from other factors. Comparisons of different fibres at different moments of the Mg-ATPase cycle suggest that both the value of the isometric force in muscle and in vitro and that of the Mg-ATPase activity used in vitro need to be reconsidered. The recently reported dependence of the isometric active tension of smooth skinned fibres on temperature appears to be weaker than predicted by the swinging-crossbridge theory alone. This recent observation is compatible with the existence of other forces (electrostatic repulsions) decreasing with temperature as has been known for some years. From recent experimental data, we think the biochemistry of myosin and actomyosin should be reassessed, to try to find new details of the mechanisms of muscle contraction and in vitro motility.

Animals↗

PubMed1998

Interactions among P450 enzymes when combined in reconstituted systems: formation of a 2B4-1A2 complex with a high affinity for NADPH-cytochrome P450 reductase.

The purpose of this study is to characterize the interactions among P450 1A2, P450 2B4, and P450 reductase in mixed reconstituted systems. Previously, our laboratory demonstrated that in the presence of certain substrates, 1A2 can influence the catalytic characteristics of 2B4 [Cawley et al. (1995) Biochemistry 34, 1244-1247]. The goal of the current study is to distinguish between two models to explain these interactions: one model where substrate increases the affinity of one P450 enzyme for the reductase, and another model where substrate increases the affinity of one P450 for the reductase through the formation of a 1A2-2B4 complex. According to this model, the 1A2 moiety of 1A2-2B4 forms a high-affinity complex with reductase. Reductase, 1A2, and 2B4 were reconstituted with dilauroylphosphatidylcholine, and the effect of reductase concentration on 7-pentoxyresorufin-O-dealkylation was examined with 2B4-reductase and 1A2-reductase binary systems, and in ternary systems containing different 2B4:1A2 ratios. At subsaturating [reductase], there was a dramatic inhibition of the 2B4-dependent activity in the ternary system as compared with the binary systems. These results are consistent with the formation of a ternary (reductase-1A2-2B4) complex where the reductase is bound specifically to 1A2. At higher reductase concentrations where the reductase-binding sites on 1A2 become saturated, the results are consistent with the formation of a quaternary complex in which reductase binds to both P450 enzymes (reductase-1A2-2B4-reductase). Analogous experiments using the 1A2-preferred substrate 7-ethoxyresorufin showed a stimulation of 7-ethoxyresorufin-O-deethylation in the mixed reconstituted system, demonstrating that the high-affinity 2B4-1A2-reductase complex was functionally active and not merely an inhibitory complex.

Animals↗

PubMed2001

Carryover bias in visual assessment.

Carryover of stimuli in sequential judgments was studied for a visual assessment task involving estimation of the percentage cover of black circles on a white image. Seven image types with different levels of cover density were arranged in a sequentially balanced design in which each image type was preceded the same number of times by all image types. In the absence of carryover, when images were preceded by images with the same cover density, the response scores were well fitted by a power function of percentage cover with a mean exponent of 0.73 over subjects. Carryover took the form of an assimilation, so that the cover estimate for a target image was generally higher when preceded by an image with higher cover, and lower when preceded by an image with lower cover. However, the magnitude of the carryover effect showed little evidence of increasing with difference in cover between successive images. Nonparametric and parametric methods for testing for carryover are presented. The need for development of psychological models to explain the proposed statistical models is discussed.

Adolescent↗

PubMed1985

The determinants of spatial distribution of hospital utilization in a region.

This article presents a series of models for explaining hospital utilization. The models belong to the multinomial logit class, which relate the probability of hospital selection to factors that include travel time between patients and hospitals, hospital attractiveness factors, physician characteristics, and patient characteristics. Separate models for different population groups (sex, age, socioeconomic classes) and medical services (general medicine, obstetrics, pediatrics, psychiatry, and general surgery) are estimated and compared with the general hospital model. The results, which are based on an extensive data base and new estimation procedures, are superior to those of past studies. A number of differences between utilization patterns for the various populations are also observed.

Adolescent↗

PubMedDate not supplied

Who develops acute stress disorder after accidental injuries?

BACKGROUND: Acute stress disorder (ASD) is still a much discussed diagnosis, and research on predictors of ASD is sparse. The aim of this study was to assess the prevalence of ASD in a random sample of accident victims and to investigate the associations between different independent variables and ASD symptomatology with the objective to find a regression model best explaining the variance in ASD symptom level. METHODS: We collected a randomized sample of hospitalized accident victims (n = 323). ASD was assessed using the Peritraumatic Dissociative Experiences Questionnaire and the Clinician-Administered Posttraumatic Stress Disorder Scale. Correlations and multiple regression analyses were computed with four groups of variables. This yielded the variables entered into a final multiple regression analysis. RESULTS: Thirteen patients (4.0%) met all criteria for a diagnosis of ASD. Thirty-two patients (9.9%) met the criteria for a diagnosis of subsyndromal ASD. Thirty-eight percent of the variance in ASD symptom level was explained with a regression model including stay at the intensive care unit, preexisting psychiatric disorder, sense of coherence, sense of death threat, appraisal of accident severity, preventability of the accident by others, pain and appraisal of coping ability regarding physical recovery. CONCLUSIONS: This study furthers the discussion about the requirements for the ASD diagnosis. It also points to the importance of not only assessing objective accident-related variables in the aftermath of an accident but also of giving more consideration to the subjective experience and appraisal of the accident in the prevention of ASD.

Acute Disease↗

PubMed1996

Epigenetic control of mammalian centromere protein binding: does DNA methylation have a role?

Chromosome 1 of the inbred mouse strain DBA/2 has a polymorphism associated with the minor satellite DNA at its centromere. The more terminal block of satellite DNA sequences on this chromosome acts as the centromere as shown by the binding of CREST ACA serum, anti-CENP-B and anti-CENP-E polyclonal sera. Demethylation of the minor satellite DNA sequences accomplished by growing cells in the presence of the drug 5-aza-2'-deoxycytidine results in a redistribution of the CENP-B protein. This protein now binds to an enlarged area on the more terminal block and in addition it now binds to the more internal block of minor satellite DNA sequences on chromosome 1. The binding of the CENP-E protein does not appear to be affected by demethylation of the minor satellite sequences. We present a model to explain these observations. This model may also indicate the mechanism by which the CENP-B protein recognises specific sites within the arrays of minor satellite DNA on mouse chromosomes.

Animals↗

PubMed1994

The role of presynaptic calcium in short-term enhancement at the hippocampal mossy fiber synapse.

The mossy fiber synapse between dentate granule cells and CA3 pyramidal cells in the guinea pig hippocampus shows a robust short-term synaptic enhancement. We have simultaneously measured presynaptic residual free calcium ([Ca2+]i) and postsynaptic field potentials at this synapse to examine the role of [Ca2+]i in this enhancement. Single action potentials produced an increase in [Ca2+]i of 10-50 nM that decayed to resting levels with a time constant of about 1 sec. Trains of action potentials produced larger [Ca2+]i increases that returned more slowly to resting levels. Following the onset of moderate frequency stimulus trains (0.1-5 Hz), synaptic transmission and [Ca2+]i both increased and eventually plateaued. During the steady-state phase a linear relationship between [Ca2+]i and synaptic enhancement was observed. During the initial buildup, however, [Ca2+]i rose more rapidly than synaptic enhancement. Similarly, during the decay phase immediately following termination of a stimulus train, [Ca2+]i returned to prestimulus levels faster than synaptic enhancement. High concentrations of the calcium buffer EGTA in the presynaptic terminal slowed the buildup and decay of both [Ca2+]i and synaptic enhancement produced by stimulus trains. Under these conditions, the time course of [Ca2+]i and synaptic enhancement were well matched. This suggests that, despite the differences in kinetic rates observed for normal buffering conditions, increases in [Ca2+]i play a causal role in short-term enhancement. An increase in [Ca2+]i of 10-30 nM produced a twofold enhancement. We propose a simple kinetic model to explain these results. The model assumes that synaptic enhancement is controlled by a Ca-dependent first-order reaction. According to this scheme, a change in [Ca2+]i alters neurotransmitter release, but the slow kinetics of the underlying reaction introduces a temporal filter, producing a delay in the change in synaptic enhancement.

Animals↗

PubMed1999

Animal group forces resulting from predator avoidance and competition minimization

A new model to explain animal spacing, based on a trade-off between foraging efficiency and predation risk, is derived from biological principles. The model is able to explain not only the general tendency for animal groups to form, but some of the attributes of real groups. These include the independence of mean animal spacing from group population, the observed variation of animal spacing with resource availability and also with the probability of predation, and the decline in group stability with group size. The appearance of "neutral zones" within which animals are not motivated to adjust their relative positions is also explained. The model assumes that animals try to minimize a cost potential combining the loss of intake rate due to foraging interference and the risk from exposure to predators. The cost potential describes a hypothetical field giving rise to apparent attractive and repulsive forces between animals. Biologically based functions are given for the decline in interference cost and increase in the cost of predation risk with increasing animal separation. Predation risk is calculated from the probabilities of predator attack and predator detection as they vary with distance. Using example functions for these probabilities and foraging interference, we calculate the minimum cost potential for regular lattice arrangements of animals before generalizing to finite-sized groups and random arrangements of animals, showing optimal geometries in each case and describing how potentials vary with animal spacing. Copyright 1999 Academic Press.

Journal Article↗