Biomedical subjects

M R Powell

Publications and source records attributed to M R Powell.

At least 37 records · Page 2Linked to original sources

PubMed1997

Modeling the effects of exercise during 100% oxygen prebreathe on the risk of hypobaric decompression sickness.

BACKGROUND: Several previous studies indicated that exercise during prebreathe with 100% O2 decreased the incidence of hypobaric decompression sickness (DCS). We report a meta-analysis of these investigations combined with a new study in our laboratory to develop a statistical model as a predictive tool for DCS. HYPOTHESIS: Exercise during prebreathe increases N2 elimination in a theoretical 360-min half-time compartment decreasing the incidence of DCS. METHODS: A dose-response probability tissue ratio (TR) model with 95% confidence limits was created for two groups, prebreathe with exercise (n = 113) and resting prebreathe (n = 113), using nonlinear regression analysis with maximum likelihood optimization. RESULTS: The model predicted that prebreathe exercise would reduce the residual N2 in a 360-min half-time compartment to a level analogous to that in a 180-min compartment. This finding supported the hypothesis. The incidence of DCS for the exercise prebreathe group was significantly decreased (Chi-Square = 17.1, p < 0.0001) from the resting prebreathe group. CONCLUSIONS: The results suggested that exercise during prebreathe increases tissue perfusion and N2 elimination approximately 2-fold and markedly lowers the risk of DCS. Based on the model, the prebreathe duration may be reduced from 240 min to a predicted 91 min for the protocol in our study, but this remains to be verified. The model provides a useful planning tool to develop and test appropriate prebreathe exercise protocols and to predict DCS risks for astronauts.

Clinical Protocols↗

PubMed1996

Use of melengestrol acetate-based treatments to induce and synchronize estrus in seasonally anestrous ewes.

Ten experiments utilizing 1,659 ewes were conducted to determine the potential of melengestrol acetate (MGA)-based treatments in inducing and synchronizing estrous activity in ewes during the nonbreeding season. In May or June, ewes were given .25 mg of MGA.ewe-1.d-1 or control diet and(or) a subsequent i.m. injection of zeranol, estradiol-17 beta, or oil vehicle. Fertile rams were introduced, and estrous and(or) lambing responses were determined. In Exp. 1, more (P < .01) ewes given MGA for 14 d followed by 5 mg of zeranol (i.m.) were in estrus than controls. Melengestrol acetate and zeranol independently induced estrus in Exp. 2, with MGA-treated ewes exhibiting the greatest lambing response (P < .05). The optimum duration of feeding MGA was 8 d vs 11 or 14 d (Exp. 3). In Exp. 4, as the dose of zeranol increased, synchrony of estrus increased but lambing response decreased. A dose of 1.25 mg of zeranol represented a compromise in estrous and lambing response and was determined to be optimally effective when given 54 h after the last feeding of MGA (Exp. 5). Shortcomings in lambing responses were treated in Exp. 6 by supplementing ewes with MGA after breeding, which proved unsuccessful, and in Exp. 7 by substituting estradiol-17 beta for zeranol, which proved effective when given 54 h after the last feeding of MGA (Exp. 8). In Exp. 9, use of MGA + estradiol increased (P < .05) the estrous and subsequent lambing response of 30-d postpartum ewes temporarily weaned of their lambs. In contrast, lambing response of 90-d postpartum ewes treated with MGA + estradiol was not increased by temporary removal of lambs (Exp. 10). These data collectively support the hypothesis that treatment of ewes with MGA + estradiol is an effective and practical approach for inducing and synchronizing a fertile estrus in ewes during the non-breeding season.

Anestrus↗

PubMed1996

Anti-Trypanosoma cruzi antibody isotype profiles in patients with different clinical manifestations of Chagas' disease.

Chagas' disease results from infection with the protozoan hemoflagellate Trypanosoma cruzi. Patients in the chronic phase of infection can be categorized into four groups based on the presence of cardiac abnormalities (CARD), gastrointestinal involvement (DIGEST), a combination of both presentations (BOTH), or indeterminate (IND) if Chagas' related pathology is not apparent. Previous studies have indicated that parasite-specific antibody production is important in both resistance to and pathogenesis of disease. The anti-T. cruzi epimastigote stage antibody isotype profiles in the sera of Brazilian patients from each clinical category, as well as from uninfected individuals (UNINF) from the same endemic area were analyzed. Anti-epimastigote immunoglobulin G (IgG)1 and IgG3 levels were strikingly high with titers > or = 1:100,000. Sera from patients in the CARD group had higher levels of IgM than either UNINF or IND individuals, which is consistent with the theory that autoimmunity may contribute to chagasic cardiomyopathy. The IgA levels were higher in sera from patients with gastrointestinal involvement when compared with individuals from any of the other clinical categories as well as from uninfected controls. Interestingly, patients with both digestive and cardiac involvement did not express high serum levels of IgA. However, like patients with cardiac involvement alone, persons with both clinical manifestations produced elevated levels of IgG2 compared with the IND or UNINF groups. These data suggest the presence of complex immunoregulatory processes, most likely related to differential cytokine involvement, which can influence the expression of antibody isotypes and possibly the course of disease.

Adolescent↗

PubMed1996

Host genetics and resistance to acute Trypanosoma cruzi infection in mice: profiles and compartmentalization of IL-2-, -4-, -5-, -10-, and IFN-gamma-producing cells.

Survival of acute Trypanosoma cruzi infection by mice is influenced by genes inside and outside the major histocompatibility complex (MHC) and genes associated with resistance must be expressed in both the MHC and the genetic background or the host will die within a few weeks of infection. Both the levels and the kinetics of cytokine production have also been implicated as important factors for resistance. Antigen-stimulated spleen cells from mice that express the resistant H-2q MHC haplotype produced significantly more interferon (IFN)-gamma than did cells from mice that share the susceptible H-2k haplotype. But, spleen cells from susceptible and resistant mice produce similar levels of IFN-gamma when stimulated with concanavalin A. The kinetics of interleukin (IL)- 10 production by ConA (ConA)-stimulated spleen cell were inversely correlated with IFN-gamma levels throughout the course of acute infection in all mouse strains. Levels of IL-2 produced by ConA-stimulated spleen cells were also initially high (day 0) then decreased as acute infection progressed. Conversely, IL-4 production by ConA-stimulated spleen cells increased during infection, and mice that express the susceptible C3H background produced significantly more IL-4 than those that share the resistant B10 background. IL-2 production by lymph node cells from mice that express the susceptible C3H genetic background also declined during infection, while lymph node cells from B10 background mice showed a moderate increase in IL-2 secretion. These data suggest that both the levels and the kinetics of cytokine production may be genetically regulated and that cytokine responses are compartmentalized in the T. cruzi-infected host.

Animals↗

PubMed1996

A probabilistic model of hypobaric decompression sickness based on 66 chamber tests.

One consequence of the NASA tissue ratio (TR) model is that calculated probability of decompression sickness [P(DCS)] is constant in tests at different ambient pressures so long as the ratio of P1N2 to P2 is the same in each test; P1N2 is N2 pressure in the 360 minute half-time compartment, and P2 is ambient pressure after decompression. We test the hypothesis that constant P(DCS) is better described by TRs that decrease as P2 decreases. Data were from 66 NASA and USAF hypobaric chamber tests resulting in 211 cases of DCS in 1075 exposures. The response variable was presence or absence of DCS while at P2. Explanatory variables were P1N2, P2, exercise at P2, (yes or no), time to DCS (failure time), and time to end of test in those without DCS (censored time). Probability models were fitted using techniques from survival analysis. The log likelihood for the two parameter log logistic survival model was -846 with only failure and censored times, -801 when TR [P1N2/P2] plus exercise were added, and -663 when modified TR [(((P1N2+cl)/P2)-1)c2] plus exercise were added, where c1 and c2 are fitted parameters in the five parameter model. Constant P(DCS) was better described by TRs that decrease as P2 decreases; a conclusion supported by additional empirical observations, and bubble growth models that are independent of DCS data. Exercise increased the P(DCS) at P2. As a description of decompression "dose", the modified TR was superior to TR over a wider range of experimental conditions.

Adult↗

PubMed1996

Relationship of the time course of venous gas bubbles to altitude decompression illness.

The correlation is low between the occurrence of gas bubbles in the pulmonary artery, called venous gas emboli (VGE), and subsequent decompression illness (DCI). The correlation improves when a "grade" of VGE is considered; a zero to four categorical classification based on the intensity and duration of the VGE signal from a Doppler bubble detector. Additional insight about DCI might come from an analysis of the time course of the occurrence of VGE. Using the NASA Hypobaric Decompression Sickness Databank, we compared the time course of the VGE outcome between 322 subjects who exercised and 133 Doppler technicians who did not exercise to evaluate the role of physical activity on the VGE outcome and incidence of DCI. We also compared 61 subjects with VGE and DCI with 110 subjects with VGE but without DCI to identify unique characteristics about the time course of the VGE outcome to try to discriminate between DCI and no-DCI cases. The VGE outcome as a function of time showed a characteristic short lag, rapid response, and gradual recovery phase that was related to physical activity at altitude and the presence or absence of DCI. The average time for DCI symptoms in a limb occurred just before the time of the highest fraction of VGE in the pulmonary artery. It is likely, but not certain, that an individual will report a DCI symptom if VGE are detected early in the altitude exposure, the intensity or grade of VGE rapidly increases from a limb region, and the intensity or grade of VGE remains high.

Adult↗

PubMed1996

Cardiovascular deconditioning and venous air embolism in simulated microgravity in the rat.

BACKGROUND: Astronauts conducting extravehicular activities undergo decompression to a lower ambient pressure, potentially resulting in gas bubble formation within the tissues and venous circulation. Additionally, exposure to microgravity produces fluid shifts within the body leading to cardiovascular deconditioning. A lower incidence of decompression illness in actual spaceflight compared with that in ground-based altitude chamber flights suggests that there is a possible interaction between microgravity exposure and decompression illness. HYPOTHESIS: The purpose of this study was to evaluate the cardiovascular and pulmonary effects of simulated hypobaric decompression stress using a tail suspension (head-down tilt) model of microgravity to produce the fluid shifts associated with weightlessness in conscious, chronically instrumented rats. METHODS: Venous bubble formation resulting from altitude decompression illness was simulated by a 3-h intravenous air infusion. Cardiovascular deconditioning was simulated by 96 h of head-down tilt. Heart rate, mean arterial blood pressure, central venous pressure, left ventricular wall thickening and cardiac output were continuously recorded. Lung studies were performed to evaluate edema formation and compliance measurement. Blood and pleural fluid were examined for changes in white cell counts and protein concentration. RESULTS: Our data demonstrated that in tail-suspended rats subjected to venous air infusions, there was a reduction in pulmonary edema formation and less of a decrease in cardiac output than occurred following venous air infusion alone. Mean arterial blood pressure and myocardial wall thickening fractions were unchanged with either tail-suspension or venous air infusion. Heart rate decreased in both conditions while systemic vascular resistance increased. CONCLUSIONS: These differences may be due in part to a change or redistribution of pulmonary blood flow or to a diminished cellular response to the microvascular insult of the venous air embolization.

Animals↗

PubMed1995

A potential strategy for decreasing milk production in the ewe at weaning using a growth hormone release blocker.

Following the loss or removal of ewes' lambs, ewes frequently continue to lactate for a short time, which potentially predisposes them to mastitis. Therapies that stop or reduce milk production in such situations would be beneficial. Milk production in ruminants is positively correlated with serum concentrations of growth hormone (GH). We sought to determine whether methscopolamine bromide (MB), an anticholinergic agent reported to block GH secretion, would selectively and reversibly reduce milk yield in lactating ewes. White-face ewes (n = 24) that were nursing lambs were assigned on d 59 +/- 2 postpartum (d 0) to receive s.c. injections of 96 mg of MB on d 2, 3, and 4 (1630). On d 0, 2, 5, and 7 (0900), ewes were sequentially separated from their lambs, treated with 40 IU oxytocin, and 30 s later were milked. Ewes remained separated from their lambs for 6 h, after which (1500) ewes were again milked and quantity of milk was determined. Milk yields at d 0, 2, 5, and 7 were 267 +/- 16.9, 266 +/- 15.5, 225 +/- 11.9, and 244 +/- 13.4 g, respectively. It was concluded that treatment of ewes with MB reduced milk yield (P < .01), and the effect was reversible. A second experiment was performed to determine the acute effects of MB on serum concentrations of GH. Hampshire ewes (n = 14) that were nursing lambs were assigned on d 55 +/- 1 postpartum to receive a.s.c. injection of saline (n = 7) or 96 mg of MB (n = 7) at min 0.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Blood donors in a vector-free zone of Ecuador potentially infected with Trypanosoma cruzi.

Chagas' disease is a serious health problem for the population of South and Central America. Blood transfusion is the second most common way in which this disease is transmitted. Several studies have reported finding Trypanosoma cruzi-infected blood in blood banks in endemic areas. Serum samples were taken from the Red Cross blood bank in Quito, a nonendemic and vector free zone of Ecuador, in December 1992 and May 1993 and analyzed by enzyme-linked immunosorbent assay using crude epimastigote extract from the Brazil strain of T. cruzi. Of 162 samples examined in December 1992, 12.1%, 13.9%, and 74% were seropositive, indeterminate, and seronegative, respectively. Of 173 samples taken in May 1993, 6.2%, 17.9%, 75.9% were seropositive, indeterminate, and seronegative, respectively. Western blot analysis of these sera using sodium dodecyl sulfate-polyacrylamide gel electrophoresis with 7.5% gels separated T. cruzi epimastigote antigen proteins, and revealed a reaction with a 205-kD doublet antigen with most of the seropositive samples. These results indicate the necessity for long-term screening of blood bank donors to reduce the risk of transfusion transmission of the disease even in areas of endemic countries where the vector is not present.

Animals↗

PubMed1995

Inverted immersion as a novel gravitoinertial environment.

BACKGROUND: Inverted immersion (II) offers a unique opportunity to swing the orientation of the gravity vector 180 degrees from its usual configuration with vestibular end organs. During II, extrathoracic fluid dynamics are identical to those of upright immersion (UI). II exposes individuals to a novel gravitoinertial environment and, therefore, should produce motion sickness (MS). HYPOTHESIS: II is more provocative of signs and symptoms of MS than UI. METHODS: Nine subjects were exposed once to II and UI. Conventional SCUBA gear was worn. In II, the subject wore a wetsuit which provided 5-7 kg force of positive buoyancy and, with no weight belt, caused him to float while inverted against the underside of a platform. An experiment with UI was identical except that a weight belt was worn which provided 5-7 kg force of negative buoyancy, and the subject stood upright against the bottom of the pool. The experiment was terminated after 3 hours or "upon the onset of the first, clear, persistent feeling of nausea", whichever came first. Throughout the experiment the subject rotated through a series of tasks: assembly of a pipe puzzle, performance of a series of head movements, and ambulation. Immediately post-dive, postural stability was assessed with tandem standing with and without eyes closed and with and without the neck extended 45 degrees. A questionnaire regarding susceptibility to motion sickness was completed pre-dive. RESULTS: No subject terminated the test because of MS during UI; seven subjects terminated the test during II (p < 0.025, McNemar's test). Posture was less stable after II than after UI (p < 0.05, sign test). MS questionnaire results did not predict susceptibility to II. CONCLUSION: II is provocative of MS and postural instability.

Adult↗

PubMed1995

Patent foramen ovale and hypobaric decompression.

Gas microbubbles were detected in the left ventricle of a supine subject being screened for an atrial septal defect as a participant of a hypobaric decompression study. This determination was made using the saline echocontrast procedure. We found provocation by a Valsalva maneuver not to be necessary in this individual for right-to-left passage of contrast microbubbles into the left heart and middle cerebral artery. When this same individual underwent hypobaric decompression to a simulated altitude of 21,000 ft, numerous gas microbubbles were detected in the right heart, but no gas bubbles were detected in either the left ventricular outflow tract or in the middle cerebral artery. This observation appears to be a novel finding, not previously reported.

Cerebral Arteries↗

PubMed1994

Early stopping of aerospace medical trials: application of sequential principles.

A two-period, crossover trial was conducted in the hypobaric chamber on human subjects to compare the influence of inflight exercise (experimental) and restricted activity (control) on altitude decompression sickness (DCS) during simulated extravehicular activities. Out of 39 pairs (total of 78 exposures), 4 cases of DCS occurred under control and 5 occurred under experimental conditions. Analysis of the crossover results showed that the P values for differences in DCS occurrence was 0.56. Under these circumstances, it was necessary to decide whether additional information would be obtained by accruing more subjects. This problem was examined by using a skew sequential design in which the "stopping rule" was based on an alpha of 0.05 (one-sided) and power of 80%. The result of this analysis was in favor of the null hypothesis, and the trial was terminated. The authors recommend the use of similar stopping rules in aerospace trials to optimize sample size without compromising statistical validity.

Adult↗

PubMed1994

Survivorship models for estimating the risk of decompression sickness.

Several approaches have been used for modeling the incidence of decompression sickness (DCS) such as Hill's dose-response and logistic regression. Most of these methods do not include the time-to-onset information in the model. Survival analysis (failure time analysis) is appropriate when the time to onset of an event is of interest. The applicability of survival analysis for modeling the risk of DCS is illustrated by using data obtained from hypobaric chamber exposures simulating extravehicular activities (n = 426). Univariate analysis of incidence-free survival proportions were obtained for Doppler-detectable circulating microbubbles (CMB), symptoms of DCS and test aborts. A log-linear failure time regression model with 360-min half-time tissue ratio (TR) as covariate was constructed, and estimated probabilities for various TR values were calculated. Further regression analysis by including CMB status in this model showed significant improvement (p < 0.05) in the estimation of DCS over the previous model. Since DCS is dependent on the exposure pressure as well as the duration of exposure, we recommend the use of survival analysis for modeling the risk of DCS.

Computer Simulation↗

PubMed1993

Host genetics and resistance to acute Trypanosoma cruzi infection in mice. I. Antibody isotype profiles.

Some strains of inbred mice survive acute infection with Trypanosoma cruzi while others die within a few weeks after infection. Mice which express B10 background genes and either the H-2q or H-2d haplotypes are resistant and survive. However, mice which share the B10 genetic background but express H-2k alleles die, usually within 4 weeks following infection. These data confirm that at least 1 gene in the major histocompatibility complex can determine whether an animal lives or dies during the acute phase. Expression of the H-2q haplotype on the B10 genetic background or in DBA/1 mice is associated with resistance, but H-2q mice expressing the C3H background are susceptible. Therefore, at least 1 gene in the genetic background also influences resistance. Our data suggest that genes associated with resistance must be present in both the MHC and the genetic background or the animal will die. The isotypes and specificities of parasite reactive antibodies found in the serum of different inbred mouse strains were assessed during acute infection. Levels of IgM were higher in sera from mice which express the resistant B10 background than in sera from mice expressing the susceptible C3H background. Conversely, mice which share the C3H background genes produced high levels of anti-parasite IgG2a when compared to B10 congenic strains. Antigen specificity, however, may be influenced by both background and MHC genes, as congenic strains expressing different MHC haplotypes recognized different constellations of T. cruzi antigens.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1993

Epidemiology of decompression sickness under simulated space extravehicular activities.

Several ground-based trials were conducted by NASA at the Lyndon B. Johnson Space Center, Houston, TX, during 1982-90 to examine the risk of altitude decompression sickness (DCS) during space extravehicular activities. There were 22 different pressure profiles involving single and staged decompression procedures, each lasting from 180 to 360 min at the final altitude. A total of 164 healthy subjects participated in 426 exposures to altitude. Symptoms of DCS occurred in 17% (74/426) and circulating microbubbles by precordial Doppler ultrasound were detected in 42% (179/426) of all exposures. About 27% (20/74) of exposures with symptoms resulted in test abort, and one-third of all test aborts required treatment in the hyperbaric chamber. There was about 3.20 times (95% Confidence Interval [95% CI] = 1.56-6.66) higher risk of symptoms in the presence of Doppler-detectable microbubbles. Examination of individual risk factors showed that there was about 4.3 times (95% CI = 1.62-11.50) higher risk of symptoms with increasing number of exposures. These findings emphasize the importance of evaluating risk factors from ground-based trials for application in operational decision-making and treatment strategies.

Adult↗

PubMed1992

Preliminary report: modification of cardiac contraction rate by pulsed magnetic fields.

Isolated rat hearts and excised canine cardiac tissues were subjected to pulsed magnetic fields. The fields excited in coils by tandem pairings of sinusoidal pulses were presented at various inter-pair delays and repetition rates. The waveform of the magnetic field was a single or multiple sinusoid followed after a variable delay by another single or multiple sinusoid. Small but reliable increases in the beating rate of rat heart were observed. Similar increases occurred in contraction rates of canine tissues. Both preparations exhibited a contraction-rate dependency on the repetition rate of the paired magnetic pulses: 4.5-6 rep/s for canine tissue, and 20-25 and 40-55 reps/s for rat heart. Flux-density thresholds for both preparations approximated 10 mT (100 gauss) rms.

Animals↗

PubMed1992

Time to detection of circulating microbubbles as a risk factor for symptoms of altitude decompression sickness.

This study investigated the association between time at onset of circulating microbubbles (CMB) and symptoms of altitude decompression sickness (DCS), using Cox proportional hazard regression models. The study population consisted of 125 individuals who participated in direct ascent, simulated extravehicular activities profiles. Using individual CMB status as a time-dependent variable, we found that the hazard for symptoms increased significantly (at the end of 180 min at altitude) in the presence of CMB (Hazard Ratio = 29.59; 95% confidence interval [95% CI] = 7.66-114.27), compared to no CMB. Further examination was conducted on the subgroup of individuals who developed microbubbles during the test (n = 49), by using Cox regression. Individuals with late onset of CMB (> 60 min at altitude) showed a significantly reduced risk of symptoms (hazard ratio = 0.92; 95% CI = 0.89-0.95), compared to those with early onset (< or = 60 min), while controlling for other risk factors. We conclude that time to detection of circulating microbubbles is an independent determinant of symptoms of DCS.

Adult↗

PubMed1991

Trypanosoma cruzi: flow cytometric analysis of lymphocyte subsets in susceptible and protected C3H/He mice.

Inbred strains of mice vary widely in their ability to survive infection with Trypanosoma cruzi. C3H/He mice are highly susceptible to infection with the Brazil strain T. cruzi, but can be protected by immunization with avirulent Corpus Christi strain parasites. We have examined, during the course of infection, the changes in lymphocyte populations in C3H/He mice that were infected but protected by immunization, infected but not immunized, immunized but not infected, and normal age-matched controls. Immunization- and/or infection-induced changes in lymphocyte populations in lymph nodes were unremarkable except for an increase in the percentage of Ig+ cells. Conversely, in the spleen the percentages of mu+ cells decreased and T cells increased in all manipulated animals. The increase in splenic T cell subsets in immunized only controls occurred simultaneously and thus the CD4:CD8 ratio remained similar to that of normal animals (approximately 2.2). Twenty days after infection, mice that were infected but not immunized (and thus would be expected to die 4-8 days later) showed a dramatic increase in the percentage of CD8+ cells which resulted in a decline in the CD4:CD8 ratio to 0.85. Mice protected by immunization had a CD4:CD8 ratio of 1.7 at this critical time point, which did, however, decline to 1.0 by Day 60. The percentages of all cell phenotypes examined in all mice had returned to normal levels 155 days after infection. These data suggest that alterations in the splenic CD4:CD8 ratio may be important in determining whether or not an animal can survive infection with the Brazil strain of T. cruzi.

Animals↗