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Biomedical subjects

M E Nelson

Publications and source records attributed to M E Nelson.

At least 55 records · Page 3Linked to original sources

Analysis of body-composition techniques and models for detecting change in soft tissue with strength training.

The purpose of this study was to compare the ability of various body-composition assessment techniques to detect changes in soft tissue in older, weight-stable women (50-70 y of age) completing a 1-y randomized, controlled trial of progressive resistance training. The intervention group (n = 20) performed high-intensity strength-training 2 d/wk with five different exercises; the control group (n = 19) was untreated. Hydrostatic weighing, 24-h urinary creatinine, computed tomography of thigh sections, total body potassium, and tritium dilution techniques were used to measure increases in total fat-free mass (FFM) and the muscle and water components of FFM. A decrease in fat mass (by hydrostatic weighing) was seen in the strength-trained women compared with the control subjects (P - 0.01-0.0001). Anthropometry, bioelectric impedance, dual-energy X-ray absorptiometry, and total body nitrogen and carbon did not measure any significant change in soft tissue. The choice of a body-composition technique is important when designing a study expected to affect soft tissue, because not all techniques available are precise enough to detect small changes.

Absorptiometry, Photon↗

Total-body skeletal muscle mass: evaluation of 24-h urinary creatinine excretion by computerized axial tomography.

A classic body-composition method is estimation of total-body skeletal muscle mass (SM, in kg) from 24-h urinary creatinine excretion (in g). Two approaches of unknown validity have been used to calculate SM from creatinine: one assumes a constant ratio of SM to creatinine, the so-called creatinine equivalence (k), and that SM = k x creatinine; the other suggests a highly variable ratio of SM to creatinine and is based on regression equations of the form SM = b + a x creatinine. We explored these two extreme possibilities by measuring SM with whole-body computerized axial tomography and collecting urinary creatinine during meat-free dietary conditions in 12 healthy adult men. Prediction equations were developed in the men that fit these two models: SM = 21.8 x creatinine (SD and CV of the ratio of SM to creatinine: 1.3 kg and 6.0%, respectively) and SM = 18.9 x creatinine + 4.1 (r = 0.92, P = 2.55 x 10(-5), SEE = 1.89 kg). The validity of each model is reviewed in the context of theoretical aspects of creatine-creatinine metabolism. This first investigation of the method of measuring urinary creatinine excretion to determine SM by using modern techniques raises important practical and basic questions related to SM prediction.

Adipose Tissue↗

Calibration of the delayed-gamma neutron activation facility.

The delayed-gamma neutron activation facility at Brookhaven National Laboratory was originally calibrated using an anthropomorphic hollow phantom filled with solutions containing predetermined amounts of Ca. However, 99% of the total Ca in the human body is not homogeneously distributed but contained within the skeleton. Recently, an artificial skeleton was designed, constructed, and placed in a bottle phantom to better represent the Ca distribution in the human body. Neutron activation measurements of an anthropomorphic and a bottle (with no skeleton) phantom demonstrate that the difference in size and shape between the two phantoms changes the total body calcium results by less than 1%. To test the artificial skeleton, two small polyethylene jerry-can phantoms were made, one with a femur from a cadaver and one with an artificial bone in exactly the same geometry. The femur was ashed following the neutron activation measurements for chemical analysis of Ca. Results indicate that the artificial bone closely simulates the real bone in neutron activation analysis and provides accurate calibration for Ca measurements. Therefore, the calibration of the delayed-gamma neutron activation system is now based on the new bottle phantom containing an artificial skeleton. This change has improved the accuracy of measurement for total body calcium. Also, the simple geometry of this phantom and the artificial skeleton allows us to simulate the neutron activation process using a Monte Carlo code, which enables us to calibrate the system for human subjects larger and smaller than the phantoms used as standards.

Body Composition↗

Logarithmic time course of sensory adaptation in electrosensory afferent nerve fibers in a weakly electric fish.

1. We recorded single unit activity from individual primary electrosensory afferent axons in the posterior branch of the anterior lateral line nerve of gymnotid weakly electric fish, Apteronotus leptorhynchus. We analyzed the responses of P-type (probability-coding) afferent fibers to externally applied amplitude step changes in the quasi-sinusoidal transdermal potential established by the fish's own electric organ discharge (EOD). 2. In response to AM step increases in transdermal potential, the firing rate of P-type afferents exhibited an abrupt increase followed by an initially rapid and subsequently more gradual decay back toward the baseline level. Afferent responses continued to adapt slowly throughout the duration of prolonged step stimuli lasting > 100 s. The time course of sensory adaptation was similar for all units tested. 3. We introduce a new functional form for describing the time course of sensory adaptation in which the change in firing rate delta r decays logarithmically with time: delta r(t) = A/[B In (t) + 1]. This logarithmic form accurately describes the adaptation time course of P-type afferents over five decades in time, from milliseconds to hundreds of seconds, with only two free parameters. Using a nonlinear least-squares fitting technique, we obtained a mean value of the parameter B, which characterizes the adaptation time course, of 0.149 +/- 0.028 (mean +/- SD, n = 49). 4. We compare logarithmic fits with traditional multiexponential and power law forms and demonstrate that the logarithmic form yields a better characterization of P-type afferent responses. This analysis helps explain the variability in previously reported adaptation time constants, which have ranged from 0.2 to 3.4 s, in gymnotid P-type afferents. 5. We tested the linearity of P-type afferent responses using positive and negative AM steps of varying amplitudes. Aside from nonlinearities associated with rectification (firing rates cannot be negative) and saturation (firing rates cannot exceed the EOD frequency), we found that P-type afferent responses scaled linearly with stimulus amplitude. 6. Based on the observed linearity, we predict the frequency domain response characteristics of P-type afferents and find that the predicted gain and phase are in good agreement with experimental measurements using sinusoidal AM stimuli over a range of AM frequencies from 1 to 100 Hz. Thus the logarithmic parameterization of the step appears to accurately capture the response dynamics of P-type afferents over a wide range of behaviorally relevant AM frequencies. 7. We conclude that the temporal filtering properties of pyramidal cells in the medullary electrosensory nucleus, the electrosensory lateral line lobe (ELL), need to be reevaluated in light of the logarithmic adaptation time course in the periphery, and we discuss implications for the role of P-type afferents in driving a feedback gain control mechanism that regulated ELL pyramidal cell responsiveness.

Action Potentials↗

Regional variation in iron and iron-binding proteins within the lungs of smokers.

The lungs of cigarette smokers are known to contain increased concentrations of extracellular ferritin-bound iron. Reductants present in cigarette smoke may mobilize alveolar ferritin-bound iron, which could then promote oxidative injury to lung cells. Because iron-mediated oxidative injury may be relevant to the pathogenesis of emphysema and lung cancer, which have a predilection for upper lobes, we sought to determine whether concentrations of extracellular iron, ferritin, and transferrin differed in upper and lower lobes of cigarette smokers. Bronchoalveolar lavage (BAL) was performed in the upper and lower lobes of 15 asymptomatic smokers and six healthy nonsmokers. BAL fluid recovered from upper lobes of smokers contained higher concentrations of iron (p < 0.01) and ferritin (p < 0.006) and lower concentrations of transferrin (p < 0.003) compared with the lower lobes. In contrast, BAL fluid recovered from upper and lower lobes of nonsmokers contained much lower concentrations of iron and ferritin, and concentrations were similar in both sites. These findings indicate that, compared with the lower lobes, upper lobes of the lungs of smokers contain higher extracellular concentrations of ferritin-bound iron and decreased concentrations of transferrin. This distribution of lung iron and iron-binding proteins may promote oxidative injury in the upper lobes of smokers.

Adult↗

The microvasculature in myeloproliferative disease. A study using retinal fluorescein angiography.

Microvascular occlusion is known to be a feature of myeloproliferative diseases. Acute manifestations are well documented in individuals causing a variety of symptoms. However, it is not known whether ongoing microvascular changes are present in asymptomatic individuals. We investigated this further by using retinal intravenous fluorescein angiography to image the microvasculature in patients with myeloproliferative disease. In our group of patients fluorescein angiography did not show any ongoing microvascular damage. There appears to be no intrinsic retinal vasculopathy in patients with myeloproliferative disease, suggesting that acute symptomatic events are caused by microemboli in an otherwise normal vascular tree.

Adult↗

Neural simulations of adaptive reafference suppression in the elasmobranch electrosensory system.

The electrosensory system of elasmobranchs is extremely sensitive to weak electric fields, with behavioral thresholds having been reported at voltage gradients as low as 5 nV/cm. To achieve this amazing sensitivity, the electrosensory system must extract weak extrinsic signals from a relatively large reafferent background signal associated with the animal's own movements. Ventilatory movements, in particular, strongly modulate the firing rates of primary electrosensory afferent nerve fibers, but this modulation is greatly suppressed in the medullary electrosensory processing nucleus, the dorsal octavolateral nucleus. Experimental evidence suggests that the neural basis of reafference suppression involves a common-mode rejection mechanism supplemented by an adaptive filter that fine tunes the cancellation. We present a neural model and computer simulation results that support the hypothesis that the adaptive component may involve an anti-Hebbian form of synaptic plasticity at molecular layer synapses onto ascending efferent neurons, the principal output neurons of the nucleus. Parallel fibers in the molecular layer carry a wealth of proprioceptive, efference copy, and sensory signals related to the animal's own movements. The proposed adaptive mechanism acts by canceling out components of the electrosensory input signal that are consistently correlated with these internal reference signals.

Adaptation, Physiological↗

Investigation of alternate droplet material bubble dosimeters.

Past theoretical research involving superheated liquid droplet (bubble) neutron dosimeters has shown the possibility of using alternate droplet materials in order to give the dosimeter improved temperature stability. Based on that research testing was conducted on HFC-134a, propylene, propane, and hexafluoropropylene to determine (1) the compatibility of the novel superheated liquid material with the detector gel matrix material; (2) the gamma sensitivity of the detector droplets; (3) the response of the dosimeters as a function of neutron energy; and (4) the response of the dosimeters as a function of temperature. These tests were conducted at the Armed Forces Radiobiology Research Institute using a 60Co source, the Naval Surface Warfare Center using a tandem neutron accelerator, and the United States Naval Academy using an unmoderated 252Cf source. The response of the alternate droplet material dosimeters was compared to the response of the original Freon 12 droplet material dosimeter. The data indicated that the propane and propylene materials were chemically incompatible with the gel material and that the hexafluoropropylene dosimeters were sensitive to gamma radiation, thus making these types of dosimeters unsuitable. However, the HFC-134a superheated liquid droplets were stable in the gel material, responded uniformly over varying neutron energies, and had a predictable temperature response.

Biophysical Phenomena↗

Hyperoxia amplifies TNF-alpha production in LPS-stimulated human alveolar macrophages.

Human alveolar macrophages (AM) produce a number of inflammatory mediators including tumor necrosis factor (TNF). TNF-alpha has been implicated in several forms of lung injury including that associated with oxygen toxicity. To investigate whether oxygen could induce or augment the release of TNF from AM, we acquired AM from nonsmoking volunteers and determined TNF release after in vitro hyperoxia. Although TNF release was not induced by oxygen exposure alone, if lipopolysaccharide (LPS) stimulation occurred simultaneously, there was significant augmentation by 60 and 95% oxygen over LPS-stimulated AM exposed to 21% oxygen. This increase was paralleled by a significant increase of interleukin (IL)-1 beta. Dimethylthiourea (DMTU), a hydroxyl radical scavenger, inhibited this release. The increase in TNF extracellular concentrations induced by hyperoxia was not associated with significant increases in intracellular concentration or detectable mRNA over LPS-stimulated AM exposed to 21% oxygen. We hypothesize that hyperoxia exposure may alter the LPS-stimulated AM cytoplasmic milieu, thus further enhancing TNF-alpha production by a post-transcriptional mechanism.

Bronchoalveolar Lavage Fluid↗

Transferrin concentrations in serum and lower respiratory tract fluid of mechanically ventilated patients with COPD or ARDS.

Transferrin serves as the primary iron transport protein in serum, but it also is present in the lower respiratory tract where it has antioxidant and antibacterial properties. Prior studies indicate that patients with respiratory failure (RF) due to ARDS have increased concentrations of transferrin in the lower respiratory tract, which is attributed to increased lung vascular permeability. It is unclear whether mechanical ventilation contributes to increased lung transferrin content in patients with ARDS, although mechanical ventilation may increase lung microvascular permeability. To assess whether mechanical ventilation in patients with RF due to causes other than ARDS is also associated with increased respiratory tract concentrations of transferrin, we compared transferrin concentrations in serum and lung lavage fluid obtained from 12 mechanically ventilated patients with RF attributable to COPD, 6 patients with ARDS, and 15 healthy volunteers. Serum transferrin concentrations in patients with RF due to COPD were variable, but mean concentrations were similar to those in control subjects (336 +/- 58 vs 307 +/- 9 [SE] mg/dL), whereas serum transferrin concentrations were decreased in patients with ARDS (182 +/- 68 mg/dL; p < 0.05). Compared with control subjects, lavage fluid recovered from patients with RF due to COPD contained significantly decreased concentrations of transferrin (1.56 +/- 0.24 vs 4.27 +/- 0.44 micrograms/mL; p < 0.001), whereas transferrin concentrations in lavage fluid recovered from patients with ARDS were increased (15.72 +/- 2.01 micrograms/mL; p < 0.001). Transferrin concentrations of lavage fluid also were decreased in COPD patients when normalized for lavage fluid protein content (4.35 +/- 0.72 vs 19.96 +/- 3.13 micrograms/mg in control subjects, p < 0.001). These data indicate that mechanical ventilation of patients with COPD is associated with decreased lung transferrin concentrations, in contrast to an increased transferrin concentration found in patients with ARDS. Decreased transferrin concentrations in the lower respiratory tract may decrease defenses against oxidant injury and bacterial infection in patients with RF due to COPD.

Adult↗

Strength improvements with 1 yr of progressive resistance training in older women.

Thirty-nine healthy women (59.5 +/- 0.9 yr) were randomized to either a control group (CON) or a progressive resistance training group (PRT) that trained twice weekly for 12 months. PRT trained at 80% or more (average of 84%) of their most recent one repetition maximum (1RM) on the lateral pull-down (LPD), knee extensor (KE), and double leg press (DLP) apparatus. One RM was measured for each exercise once monthly in PRT and at baseline, midstudy, and end of study in CON. One RM significantly increased in PRT for all muscle groups trained compared to CON (P < 0.0001). Increases of 73.7 +/- 12%, 35.1 +/- 3%, and 77.0 +/- 5%, respectively, for KE, DLP, and LPD in PRT and 12.7% +/- 8%, 3.7% +/- 3%, and 18.4% +/- 4%, respectively, in CON were observed. Approximately 50% of the gains in KE and LPD and 40% in the DLP were seen in the first 3 months of the study. In all three exercises, strength gains in PRT continued over the entire 12-month period. These data indicate that high-intensity strength training results in substantial, continual increases in strength in postmenopausal women for at least 12 months, with the greatest gains seen in the first 3 months of training.

Exercise↗

Synergism of intratracheally administered tumor necrosis factor with interleukin-1 in the induction of lung edema in rats.

Intratracheal (IT) instillation of human recombinant interleukin 1 (IL-1) in rats induces an influx of neutrophils into alveolar structures and a dose-dependent increase in lung vascular permeability. We sought to determine whether increased alveolar concentrations of tumor necrosis factor (TNF) enhanced lung injury induced by intrapulmonary administration of low-dose IL-1. Rats were divided into five groups and treated with IT instillation of saline (0.1 ml) containing (1) no additional compound (controls), (2) human recombinant IL-1 (10 ng), (3) human recombinant TNF (2 micrograms), (4) IL-1 + TNF (10 ng + 2 micrograms), or (5) lipopolysaccharide (LPS, 10 micrograms). At 3, 6, 24, and 48 hours after treatment, we counted neutrophils recovered by bronchoalveolar lavage (BAL), assessed TNF activity in BAL fluid, and measured lung wet:dry weight ratio. At 3 and 6 hours after treatment, we measured levels of the lipid peroxide derivative malondialdehyde (MDA) in lung homogenates. IT instillation of LPS, IL-1, or IL-1 + TNF rapidly increased BAL neutrophil recovery, whereas recovery was not increased by TNF alone. TNF activity in BAL fluid was markedly increased by LPS, TNF, and IL-1 + TNF, with a smaller increase induced by IL-1. Instillation of TNF or IL-1 alone at these doses did not increase the lung wet:dry ratio. IT administration of LPS increased the wet:dry ratio at 6 hours only (p < 0.05), whereas IL-1 + TNF increased this ratio beginning 3 hours (p < 0.01) after treatment with persistent increases through 48 hours (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of high-intensity strength training on multiple risk factors for osteoporotic fractures. A randomized controlled trial.

OBJECTIVE: To determine how multiple risk factors for osteoporotic fractures could be modified by high-intensity strength training exercises in postmenopausal women. DESIGN: Randomized controlled trial of 1-year duration. SETTING: Exercise laboratory at Tufts University, Boston, Mass. POPULATION: Forty postmenopausal white women, 50 to 70 years of age, participated in the study; 39 women completed the study. The subjects were sedentary and estrogen-deplete. INTERVENTIONS: High-intensity strength training exercises 2 days per week using five different exercises (n = 20) vs untreated controls (n = 19). MAIN OUTCOME MEASURES: Dual energy x-ray absorptiometry for bone status, one repetition maximum for muscle strength, 24-hour urinary creatinine for muscle mass, and backward tandem walk for dynamic balance. RESULTS: Femoral neck bone mineral density and lumbar spine bone mineral density increased by 0.005 +/- 0.039 g/cm2 (0.9% +/- 4.5%) (mean +/- SD) and 0.009 +/- 0.033 g/cm2 (1.0% +/- 3.6%), respectively, in the strength-trained women and decreased by -0.022 +/- 0.035 g/cm2 (-2.5% +/- 3.8%) and -0.019 +/- 0.035 g/cm2 (-1.8% +/- 3.5%), respectively, in the controls (P = .02 and .04). Total body bone mineral content was preserved in the strength-trained women (+2.0 +/- 68 g; 0.0% +/- 3.0%) and tended to decrease in the controls (-33+77 g; -1.2% +/- 3.4%, P = .12). Muscle mass, muscle strength, and dynamic balance increased in the strength-trained women and decreased in the controls (P = .03 to < .001). CONCLUSIONS: High-intensity strength training exercises are an effective and feasible means to preserve bone density while improving muscle mass, strength, and balance in postmenopausal women.

Aged↗

Exercise training and nutritional supplementation for physical frailty in very elderly people.

BACKGROUND: Although disuse of skeletal muscle and undernutrition are often cited as potentially reversible causes of frailty in elderly people, the efficacy of interventions targeted specifically at these deficits has not been carefully studied. METHODS: We conducted a randomized, placebo-controlled trial comparing progressive resistance exercise training, multinutrient supplementation, both interventions, and neither in 100 frail nursing home residents over a 10-week period. RESULTS: The mean (+/- SE) age of the 63 women and 37 men enrolled in the study was 87.1 +/- 0.6 years (range, 72 to 98); 94 percent of the subjects completed the study. Muscle strength increased by 113 +/- 8 percent in the subjects who underwent exercise training, as compared with 3 +/- 9 percent in the nonexercising subjects (P < 0.001). Gait velocity increased by 11.8 +/- 3.8 percent in the exercisers but declined by 1.0 +/- 3.8 percent in the nonexercisers (P = 0.02). Stair-climbing power also improved in the exercisers as compared with the nonexercisers (by 28.4 +/- 6.6 percent vs. 3.6 +/- 6.7 percent, P = 0.01), as did the level of spontaneous physical activity. Cross-sectional thigh-muscle area increased by 2.7 +/- 1.8 percent in the exercisers but declined by 1.8 +/- 2.0 percent in the nonexercisers (P = 0.11). The nutritional supplement had no effect on any primary outcome measure. Total energy intake was significantly increased only in the exercising subjects who also received nutritional supplementation. CONCLUSIONS: High-intensity resistance exercise training is a feasible and effective means of counteracting muscle weakness and physical frailty in very elderly people. In contrast, multi-nutrient supplementation without concomitant exercise does not reduce muscle weakness or physical frailty.

Aged↗

Comparison of topical and oral acyclovir in early herpes zoster ophthalmicus.

Poor systemic absorption has limited the efficacy of early oral acyclovir in herpes zoster ophthalmicus (HZO). Aqueous humour levels are substantially higher if the drug is administered topically to the eye. A multicentre open randomised study was performed to compare the ocular prophylactic effects of topical and oral acyclovir. Fifty-seven patients with HZO within 72 hours of the onset of rash received either topical acyclovir ointment or 800 mg oral acyclovir, both 5 times daily for 7 days, and were followed for 12 months. Patients receiving ointment were significantly more likely to have ocular complications (p < 0.02) and anterior uveitis was significantly more frequent (p < 0.01) and severe (p < 0.01). Corneal hypoaesthesia was significantly more frequently (p < 0.05) and severe (p < 0.02) at 1 month. From 2 weeks patients receiving ointment were more likely to have pain and at all times their pain was more severe, but these differences were not statistically significant. In spite of its apparently better penetration topical acyclovir appears to have no prophylactic value in the management of early HZO.

Acyclovir↗

Increased release of ferritin and iron by iron-loaded alveolar macrophages in cigarette smokers.

The lower respiratory tract of cigarette smokers contains an increased amount of iron that is predominantly sequestered within alveolar macrophages (AM), but is also present in alveolar epithelial fluid. Extracellular ferritin-bound iron could potentially be released by reductants present in cigarette smoke and catalyze generation of highly reactive hydroxyl radicals capable of causing oxidant injury. To determine whether AM are a source of alveolar extracellular ferritin and iron, we assessed in vitro release of iron, ferritin, and transferrin by AM recovered by bronchoalveolar lavage (BAL) of 27 healthy subjects including nine nonsmokers (NS), nine light smokers (LS), and nine heavy smokers (HS). Release of iron in vitro over 20 h was increased in AM recovered from LS (2.24 +/- 0.21 nmol/10(6) AM/20 h, p < 0.001) and HS (3.11 +/- 0.32 nmol/10(6) AM, p < 0.001) compared with NS (1.28 +/- 0.08 nmol/10(6) AM). Release of ferritin in vitro over 20 h was also increased in AM recovered from LS (71 +/- 24 ng/10(6) AM, p < 0.05) and HS (176 +/- 35 ng/10(6), p < 0.001) compared with NS (18 +/- 3 ng/10(6) AM). AM recovered from 12 smokers (8 HS, 4 LS) contained greater than 10 nmol of iron per 10(6) cells. These iron-loaded AM released a greater percentage of cell ferritin stores in vitro over 4 h (8.4% +/- 1.1, p < 0.01) than did AM from NS (3.2% +/- 0.6). Release of lactate dehydrogenase (LDH) over 4 h was substantially less (2.9% +/- 0.3, p < 0.001) than ferritin release.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

9-Aminoacridines act at a site different from that for Mg2+ in blockade of the N-methyl-D-aspartate receptor channel.

The effects of alkylene bis-9,9'-aminoacridines and 1,2,3,4-tetrahydro-9-aminoacridine (THA) were studied on single-channel currents activated by N-methyl-D-aspartate (NMDA) in outside-out patches from cultured rat hippocampal neurons. These compounds reduced the channel open times with concentration and voltage dependence, which was consistent with an open-channel blockade mechanism of action. In nominally Mg(2+)-free solutions, the forward blocking rate constants for 1,2-propane-bis-9,9'-aminoacridine, 1,4-butane-9,9'-aminoacridine, and THA were 1.1 x 10(8), 1.4 x 10(8), and 3.5 x 10(7) M-1 sec-1, respectively, at a holding potential of -80 mV. The unblocking rate constants for the bis-9-aminoacridines were similar and in the range of 7 sec-1, whereas THA had an unblocking rate constant of approximately 6.2 x 10(3) sec-1. In the presence of Mg2+ (approximately 5 microM), the predictions of the model for open-channel blockade by the 9-aminoacridines were invalid, because the relationships between the channel lifetimes and 9-aminoacridine concentrations were not linear. The effects of Mg2+ (approximately 0-50 microM) on the open-channel blockade of the NMDA receptor by the 9-aminoacridines were evaluated further by measuring the burst times in the presence of 1,2-propane-bis-9,9'-aminoacridine (5 microM). The results suggested that the interactions of 9-aminoacridines and Mg2+ with the ion channel of the NMDA receptor were not mutually exclusive. Simultaneous occupancy of the NMDA receptor ion channel by Mg2+ and a channel-blocking organic cation could be a common mechanism of channel blockade for this receptor under physiological conditions.

Aminacrine↗