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PubMed2000

Influence of central set on anticipatory and triggered grip-force adjustments.

The effects of predictability of load magnitude on anticipatory and triggered grip-force adjustments were studied as nine normal subjects used a precision grip to lift, hold, and replace an instrumented test object. Experience with a predictable stimulus has been shown to enhance magnitude scaling of triggered postural responses to different amplitudes of perturbations. However, this phenomenon, known as a central-set effect, has not been tested systematically for grip-force responses in the hand. In our study, predictability was manipulated by applying load perturbations of different magnitudes to the test object under conditions in which the upcoming load magnitude was presented repeatedly or under conditions in which the load magnitudes were presented randomly, each with two different pre-load grip conditions (unconstrained and constrained). In constrained conditions, initial grip forces were maintained near the minimum level necessary to prevent pre-loaded object slippage, while in unconstrained conditions, no initial grip force restrictions were imposed. The effect of predictable (blocked) and unpredictable (random) load presentations on scaling of anticipatory and triggered grip responses was tested by comparing the slopes of linear regressions between the imposed load and grip response magnitude. Anticipatory and triggered grip force responses were scaled to load magnitude in all conditions. However, regardless of pre-load grip force constraint, the gains (slopes) of grip responses relative to load magnitudes were greater when the magnitude of the upcoming load was predictable than when the load increase was unpredictable. In addition, a central-set effect was evidenced by the fewer number of drop trials in the predictable relative to unpredictable load conditions. Pre-load grip forces showed the greatest set effects. However, grip responses showed larger set effects, based on prediction, when pre-load grip force was constrained to lower levels. These results suggest that anticipatory processes pertaining to load magnitude permit the response gain of both voluntary and triggered rapid grip force adjustments to be set, at least partially, prior to perturbation onset. Comparison of anticipatory set effects for reactive torque and lower extremity EMG postural responses triggered by surface translation perturbations suggests a more general rule governing anticipatory processes.

Adult↗
PubMed2000

Dynamics of airborne fungal populations in a large office building.

The increasing concern with bioaerosols in large office buildings prompted this prospective study of airborne fungal concentrations in a newly constructed building on the Gulf coast. We collected volumetric culture plate air samples on 14 occasions over the 18-month period immediately following building occupancy. On each sampling occasion, we collected duplicate samples from three sites on three floors of this six-story building, and an outdoor sample. Fungal concentrations indoors were consistently below those outdoors, and no sample clearly indicated fungal contamination in the building, although visible growth appeared in the ventilation system during the course of the study. We conclude that modern mechanically ventilated buildings prevent the intrusion of most of the outdoor fungal aerosol, and that even relatively extensive air sampling protocols may not sufficiently document the microbial status of buildings.

Air Conditioning↗
PubMed2000

Vascular mechanics of the coronary artery.

UNLABELLED: This paper describes our research into the vascular mechanics of the coronary artery and plaque. The three sections describe the determination of arterial mechanical properties using intravascular ultrasound (IVUS), a constitutive relation for the arterial wall, and finite element method (FEM) models of the arterial wall and atheroma. METHODS: Inflation testing of porcine left anterior descending coronary arteries was conducted. The changes in the vessel geometry were monitored using IVUS, and intracoronary pressure was recorded using a pressure transducer. The creep and quasistatic stress/strain responses were determined. A Standard Linear Solid (SLS) was modified to reproduce the non-linear elastic behavior of the arterial wall. This Standard Non-linear Solid (SNS) was implemented into an axisymetric thick-walled cylinder numerical model. Finite element analysis models were created for five age groups and four levels of stenosis using the Pathobiological Determinants of Atherosclerosis Youth (PDAY) database. RESULTS: The arteries exhibited non-linear elastic behavior. The total tissue creep strain was epsilon creep = 0.082 +/- 0.018 mm/mm. The numerical model could reproduce both the non-linearity of the porcine data and time dependent behavior of the arterial wall found in the literature with a correlation coefficient of 0.985. Increasing age had a strong positive correlation with the shoulder stress level, (r = 0.95). The 30% stenosis had the highest shoulder stress due to the combination of a fully formed lipid pool and a thin cap. CONCLUSIONS: Studying the solid mechanics of the arterial wall and the atheroma provide important insights into the mechanisms involved in plaque rupture.

Animals↗
PubMed2000

Postural control model interpretation of stabilogram diffusion analysis.

Collins and De Luca [Collins JJ. De Luca CJ (1993) Exp Brain Res 95: 308-318] introduced a new method known as stabilogram diffusion analysis that provides a quantitative statistical measure of the apparently random variations of center-of-pressure (COP) trajectories recorded during quiet upright stance in humans. This analysis generates a stabilogram diffusion function (SDF) that summarizes the mean square COP displacement as a function of the time interval between COP comparisons. SDFs have a characteristic two-part form that suggests the presence of two different control regimes: a short-term open-loop control behavior and a longer-term closed-loop behavior. This paper demonstrates that a very simple closed-loop control model of upright stance can generate realistic SDFs. The model consists of an inverted pendulum body with torque applied at the ankle joint. This torque includes a random disturbance torque and a control torque. The control torque is a function of the deviation (error signal) between the desired upright body position and the actual body position, and is generated in proportion to the error signal, the derivative of the error signal, and the integral of the error signal [i.e. a proportional, integral and derivative (PID) neural controller]. The control torque is applied with a time delay representing conduction, processing, and muscle activation delays. Variations in the PID parameters and the time delay generate variations in SDFs that mimic real experimental SDFs. This model analysis allows one to interpret experimentally observed changes in SDFs in terms of variations in neural controller and time delay parameters rather than in terms of open-loop versus closed-loop behavior.

Computer Simulation↗
PubMed1999

Initial clinical experience of real-time three-dimensional echocardiography in patients with ischemic and idiopathic dilated cardiomyopathy.

The geometry of the left ventricle in patients with cardiomyopathy is often sub-optimal for 2-dimensional ultrasound when assessing left ventricular (LV) function and localized abnormalities such as a ventricular aneurysm. The aim of this study was to report the initial experience of real-time 3-D echocardiography for evaluating patients with cardiomyopathy. A total of 34 patients were evaluated with the real-time 3D method in the operating room (n = 15) and in the echocardiographic laboratory (n = 19). Thirteen of 28 patients with cardiomyopathy and 6 other subjects with normal LV function were evaluated by both real-time 3-D echocardiography and magnetic resonance imaging (MRI) for obtaining LV volumes and ejection fractions for comparison. There were close relations and agreements for LV volumes (r = 0.98, p <0.0001, mean difference = -15 +/- 81 ml) and ejection fractions (r = 0.97, p <0.0001, mean difference = 0.001 +/- 0.04) between the real-time 3D method and MRI when 3 cardiomyopathy cases with marked LV dilatation (LV end-diastolic volume >450 ml by MRI) were excluded. In these 3 patients, 3D echocardiography significantly underestimated the LV volumes due to difficulties with imaging the entire LV in a 60 degrees x 60 degrees pyramidal volume. The new real-time 3D echocardiography is feasible in patients with cardiomyopathy and may provide a faster and lower cost alternative to MRI for evaluating cardiac function in patients.

Cardiac Volume↗
PubMed1999

Do plasma melatonin concentrations decline with age?

PURPOSE: Numerous reports that secretion of the putative sleep-promoting hormone melatonin declines with age have led to suggestions that melatonin replacement therapy be used to treat sleep problems in older patients. We sought to reassess whether the endogenous circadian rhythm of plasma melatonin concentration changes with age in healthy drug-free adults. METHODS: We analyzed the amplitude of plasma melatonin profiles during a constant routine in 34 healthy drug-free older subjects (20 women and 14 men, aged 65 to 81 years) and compared them with 98 healthy drug-free young men (aged 18 to 30 years). RESULTS: We could detect no significant difference between a healthy and drug-free group of older men and women as compared to one of young men in the endogenous circadian amplitude of the plasma melatonin rhythm, as described by mean 24-hour average melatonin concentration (70 pmol/liter vs 73 pmol/liter, P = 0.97), or the duration (9.3 hours vs 9.1 hours, P = 0.43), mean (162 pmol/liter vs 161 pmol/liter, P = 0.63), or integrated area (85,800 pmol x min/liter vs 86,700 pmol x min/liter, P = 0.66) of the nocturnal peak of plasma melatonin. CONCLUSION: These results do not support the hypothesis that reduction of plasma melatonin concentration is a general characteristic of healthy aging. Should melatonin replacement therapy or melatonin supplementation prove to be clinically useful, we recommend that an assessment of endogenous melatonin be carried out before such treatment is used in older patients.

Adult↗
PubMed2000

Acute effects of bright light and caffeine on nighttime melatonin and temperature levels in women taking and not taking oral contraceptives.

Caffeine and bright light effects on nighttime melatonin and temperature levels in women were tested during the luteal phase of the menstrual cycle (n=30) or the pseudo luteal phase for oral contraceptive users (n=32). Participants were randomly assigned to receive either bright (5000 lux) or dim room light (<88 lux) between 20:00 and 08:00 h under a modified constant routine protocol. Half the subjects in each lighting condition were administered either caffeine (100 mg) or placebo in a double-blind manner at 20:00, 23:00, 02:00 and 05:00 h. Results showed that the combination of bright light and caffeine enhanced nighttime temperature levels to a greater extent than did either caffeine or bright light alone. Both of the latter groups had higher temperature levels relative to the dim light placebo condition and the two groups did not differ. Temperature levels in the bright light caffeine condition were maintained at near peak circadian levels the entire night in the luteal and pseudo luteal phase. Melatonin levels were reduced throughout the duration of bright light exposure for all women. Caffeine reduced the onset of melatonin levels for women in the luteal phase, but it had little effect on melatonin levels for oral contraceptive users. The results for women in the luteal phase of the menstrual cycle are consistent with our previous findings in men. The results also suggest that oral contraceptives may alter the effects of caffeine on nighttime melatonin levels.

Adolescent↗
PubMed2000

Rac-1 and Raf-1 kinases, components of distinct signaling pathways, activate myotonic dystrophy protein kinase.

Myotonic dystrophy protein kinase (DMPK) is a serine-threonine protein kinase encoded by the myotonic dystrophy (DM) locus on human chromosome 19q13.3. It is a close relative of other kinases that interact with members of the Rho family of small GTPases. We show here that the actin cytoskeleton-linked GTPase Rac-1 binds to DMPK, and coexpression of Rac-1 and DMPK activates its transphosphorylation activity in a GTP-sensitive manner. DMPK can also bind Raf-1 kinase, the Ras-activated molecule of the MAP kinase pathway. Purified Raf-1 kinase phosphorylates and activates DMPK. The interaction of DMPK with these distinct signals suggests that it may play a role as a nexus for cross-talk between their respective pathways and may partially explain the remarkable pleiotropy of DM.

Animals↗
PubMed1999

Combined effects of space flight factors and radiation on humans.

The probability that a dose of ionizing radiation kills a cell is about 10,000 times the probability that the cell will be transformed to malignancy. On the other hand, the number of cells killed required to significantly impact health is about 10,000 times the number that must be transformed to cause a late malignancy. If these two risks, cell killing and malignant transformation, are about equal, then the risk that occurs during a mission is more significant than the risk that occurs after a mission. The latent period for acute irradiation effects (cell killing) is about 2-4 weeks; the latent period for malignancy is 10-20 years. If these statements are approximately true, then the impact of cell killing on health in the low-gravity environment of space flight should be examined to establish an estimate of risk. The objective of this study is to synthesize data and conclusions from three areas of space biology and environmental health to arrive at rational risk assessment for radiations received by spacecraft crews: (1) the increased physiological demands of the space flight environment; (2) the effects of the space flight environment on physiological systems; and (3) the effects of radiation on physiological systems. One physiological system has been chosen: the immune response and its components, consisting of myeloid and lymphoid proliferative cell compartments. Best-case and worst-case scenarios are considered. In the worst case, a doubling of immune-function demand, accompanied by a halving of immune capacity, would reduce the endangering dose to a crew member to around 1 Gy.

Animals↗
PubMed1999

Predicting cancer rates in astronauts from animal carcinogenesis studies and cellular markers.

The radiation space environment includes particles such as protons and multiple species of heavy ions, with much of the exposure to these radiations occurring at extremely low average dose-rates. Limitations in databases needed to predict cancer hazards in human beings from such radiations are significant and currently do not provide confidence that such predictions are acceptably precise or accurate. In this article, we outline the need for animal carcinogenesis data based on a more sophisticated understanding of the dose-response relationship for induction of cancer and correlative cellular endpoints by representative space radiations. We stress the need for a model that can interrelate human and animal carcinogenesis data with cellular mechanisms. Using a broad model for dose-response patterns which we term the "subalpha-alpha-omega (SAO) model", we explore examples in the literature for radiation-induced cancer and for radiation-induced cellular events to illustrate the need for data that define the dose-response patterns more precisely over specific dose ranges, with special attention to low dose, low dose-rate exposure. We present data for multiple endpoints in cells, which vary in their radiosensitivity, that also support the proposed model. We have measured induction of complex chromosome aberrations in multiple cell types by two space radiations, Fe-ions and protons, and compared these to photons delivered at high dose-rate or low dose-rate. Our data demonstrate that at least three factors modulate the relative efficacy of Fe-ions compared to photons: (i) intrinsic radiosensitivity of irradiated cells; (ii) dose-rate; and (iii) another unspecified effect perhaps related to reparability of DNA lesions. These factors can produce respectively up to at least 7-, 6- and 3-fold variability. These data demonstrate the need to understand better the role of intrinsic radiosensitivity and dose-rate effects in mammalian cell response to ionizing radiation. Such understanding is critical in extrapolating databases between cellular response, animal carcinogenesis and human carcinogenesis, and we suggest that the SAO model is a useful tool for such extrapolation.

Animals↗
PubMed1999

Evidence of SV40 infections in hospitalized children.

Simian virus 40 (SV40) is known to have contaminated poliovirus vaccines used between 1955 and 1963. Accumulating reports have described the presence of SV40 DNA in human tumors and normal tissues, although the significance of human infections by SV40 is unknown. We investigated whether unselected hospitalized children had evidence of SV40 infections and whether any clinical correlations were apparent. Serum samples were examined for SV40 neutralizing antibody using a specific plaque reduction test; of 337 samples tested, 20 (5.9%) had antibody to SV40. Seropositivity increased with age and was significantly associated with kidney transplants (6 of 15 [40%] positive, P < .001). Many of the antibody-positive patients had impaired immune systems. Molecular assays (polymerase chain reaction and DNA sequence analysis) on archival tissue specimens confirmed the presence of SV40 DNA in 4 of the antibody-positive patients. This study, using 2 independent assays, shows the presence of SV40 infections in children born after 1980. We conclude that SV40 causes natural infections in humans.

Adolescent↗
PubMed2000

Medial prefrontal cortex acetylcholine injection-induced hypotension: the role of hindlimb vasodilation.

The injection of acetylcholine (ACh) into the cingulate region of the medial prefrontal cortex (MPFC) causes a marked fall in arterial blood pressure which is not accompanied by changes in heart rate. The purpose of the present study was to investigate the hemodynamic basis for this stimulus-induced hypotension in Sprague-Dawley rats. The study was designed to determine whether a change in the vascular resistance of hindlimb, renal or mesenteric vascular beds contributes to the fall in arterial pressure in response to ACh injection into the cingulate cortex. Miniature pulsed-Doppler flow probes were used to measure changes in regional blood flow and vascular resistance. The results indicated that the hypotensive response was largely due to a consistent and marked vasodilation in the hindlimb vascular bed. On this basis, an additional experiment was then undertaken to determine the mechanisms that contribute to hindlimb vasodilation. The effect of interrupting the autonomic innervation of one leg on the hindlimb vasodilator response was tested. Unilateral transection of the lumbar sympathetic chain attenuated the cingulate ACh-induced vasodilation in the ipsilateral, but not in the contralateral hindlimb. These results suggest that the hypotensive response to cingulate cortex-ACh injection is caused by skeletal muscle vasodilation mediated by a sympathetic chain-related vasodilator system.

Acetylcholine↗
PubMed2000

Ten-fold augmentation of endothelial uptake of vascular endothelial growth factor with ultrasound after systemic administration.

OBJECTIVES: In this study, the feasibility of delivering and enhancing the uptake of vascular endothelial growth factor (VEGF) into the intact endothelium by using ultrasound (US) facilitation was determined. BACKGROUND: A limitation of tissue-targeted drug delivery is the need for direct arterial cannulation. We postulate a mechanism by which agents injected intravenously may be targeted to a tissue using US and ultrasonic contrast agents. METHODS: We used a rat model to test the ability of US and an ultrasonic contrast agent perflurocarbon exposed sonicated dextrose albumin (PESDA) to increase uptake of VEGF in the myocardium. Continuous wave Doppler US (0.6 W/cm2 at 1 MHz for 15 min) was applied to the chest wall overlying the myocardium during intravenous injection with either VEGF (100 microg/kg) alone or a combination of VEGF and PESDA (0.1%). Control rats had VEGF infused without US or PESDA. The VEGF uptake was measured quantitatively in the heart, lung, liver and kidneys by enzyme-linked immunosorbent assay (ng/g of tissue) and morphologically by fluorescence microscopy. RESULTS: There was an eight-fold increase in VEGF uptake in the heart by US alone (16.86 +/- 1.56 vs. 2.11 +/- 0.953 ng/g of tissue, p < 0.0001) and a 13-fold increase with US + PESDA (26.78 +/- 2.88 vs. 2.11 +/- 0.953 ng/g of tissue, p < 0.0001) compared with control rats. Fluorescence microscopy revealed deposition of VEGF in the endothelium of small intramyocardial arterioles. CONCLUSIONS: These results show a marked increase in endothelial VEGF uptake with US and US + PESDA. Thus, US may be used to augment endothelial VEGF uptake 10-fold to 13-fold.

Animals↗
PubMed2000

Color M-mode Doppler flow propagation velocity is a preload insensitive index of left ventricular relaxation: animal and human validation.

OBJECTIVES: To determine the effect of preload in color M-mode Doppler flow propagation velocity (v(p)). BACKGROUND: The interpretation of Doppler filling patterns is limited by confounding effects of left ventricular (LV) relaxation and preload. Color M-mode v(p) has been proposed as a new index of LV relaxation. METHODS: We studied four dogs before and during inferior caval (IVC) occlusion at five different inotropic stages and 14 patients before and during partial cardiopulmonary bypass. Left ventricular (LV) end-diastolic volumes (LV-EDV), the time constant of isovolumic relaxation (tau), left atrial (LA) pre-A and LV end-diastolic pressures (LV-EDP) were measured. Peak velocity during early filling (E) and v(p) were extracted by digital analysis of color M-mode Doppler images. RESULTS: In both animals and humans, LV-EDV and LV-EDP decreased significantly from baseline to IVC occlusion (both p < 0.001). Peak early filling (E) velocity decreased in animals from 56 +/- 21 to 42 +/- 17 cm/s (p < 0.001) without change in v(p) (from 35 +/- 15 to 35 +/- 16, p = 0.99). Results were similar in humans (from 69 +/- 15 to 53 +/- 22 cm/s, p < 0.001, and 37 +/- 12 to 34 +/- 16, p = 0.30). In both species, there was a strong correlation between LV relaxation (tau) and v(p) (r = 0.78, p < 0.001, r = 0.86, p < 0.001). CONCLUSIONS: Our results indicate that color M-mode Doppler v(p) is not affected by preload alterations and confirms that LV relaxation is its main physiologic determinant in both animals during varying lusitropic conditions and in humans with heart disease.

Aged↗
PubMed2000

Subendocardial motion in hypertrophic cardiomyopathy: assessment from long- and short-axis views by pulsed tissue Doppler imaging.

BACKGROUND: Tissue Doppler imaging (TDI) is a recently developed technique that allows the instantaneous measurement of intrinsic regional myocardial motion velocity. Pulsed TDI is capable of separately assessing left ventricular (LV) regional motion velocity caused by circumferential and longitudinal fiber contraction. This particular feature of function is still controversial in patients with hypertrophic cardiomyopathy (HC). METHODS: To better characterize intrinsic circumferential and longitudinal LV systolic myocardial function in HC, we used pulsed TDI to measure short- and long-axis LV motion velocities, respectively. The subendocardial motion velocity patterns at the middle of the LV posterior wall (PW) and ventricular septum (IVS) in LV parasternal and apical long-axis views were recorded by pulsed TDI in 19 patients with nonobstructive HC and in 21 normal controls (NC). RESULTS: Peak short- and long-axis systolic subendocardial velocities in both the LV PW and IVS were significantly smaller in the HC group than in the NC group, and the time to peak velocity was significantly delayed. Furthermore, peak PW systolic velocity was significantly greater along the long axis than along the short axis in the NC group (8.8 +/- 1.5 cm/s vs 8.2 +/- 1.4 cm/s, P <.05), whereas the opposite was observed in the HC group (6.1 +/- 1.2 cm/s vs 7.5 +/- 1.0 cm/s, P <.0001). No significant differences were found in either group between the long- and short-axis IVS velocities (HC: 5.9 +/- 1.4 cm/s vs 5.5 +/- 1.3 cm/s; NC: 7.8 +/- 1.3 cm/s vs 7.9 +/- 1.6 cm/s). CONCLUSIONS: By using the capability of pulsed TDI for the evaluation of intrinsic myocardial velocity instantaneously in a specific region and direction, we found impairment of LV myocardial systolic function in patients with HC not only in the hypertrophied IVS but also in the nonhypertrophied LV PW. We also found a greater decrease in LV PW velocities along the long axis than the short axis, suggesting greater impairment of long-axis contraction in patients with HC. Because our HC patients did not appear to have excessive intracavitary pressure, these results suggest that the relatively normal-appearing PW is directly affected by the HC pathologic process.

Adult↗