Relationship between land use classification and grass shrimp Palaemonetes spp. population metrics in coastal watersheds.

Estuaries in the southeastern USA have experienced increased loading of contaminants from nonpoint source runoff as well as changes in habitat (e.g., loss of wetlands) due to urbanization. These changes may pose significant risks to estuarine fauna, including crustaceans. Several studies have shown relationships between land use classification and levels of stress in estuarine populations. The grass shrimp of the genus Palaemonetes is one of the dominant species found in estuarine tidal creeks, accounting for more than 50 % of all macropelagic fauna. Grass shrimp populations were sampled monthly for 3 years at six estuarine creeks on Kiawah Island, SC. Creek watersheds were estimated using National Aerial Photograph Program color infrared and low-altitude true color aerial photography combined with in situ differentially corrected global positioning system mapping of engineered features. Land classifications delineated included water, marsh, buildings, roads, and lawns. Pairwise comparisons for grass shrimp densities among sites showed significant differences on an annual and seasonal basis. Significant relationships (p < 0.05) between land class variables and grass shrimp density were identified both annually and seasonally. These findings suggest an influence of land use on Palaemonetes spp. populations.

Human physiology at extreme altitudes on Mount Everest.

Extreme altitude presents an enormous physiological challenge to the human body because of severe oxygen deprivation. The American Medical Research Expedition to Everest was specifically designed to study man under these conditions, and successfully obtained physiological data above 8000 meters, including a few measurements on the summit itself. The results show that man can tolerate the extreme hypoxia only by an enormous increase in ventilation, which results in an alveolar partial pressure of carbon dioxide of 7.5 torr on the summit and an arterial pH of over 7.7. Even so, the arterial partial pressure of oxygen is apparently less than 30 torr, and maximum oxygen uptake is about 1 liter per minute. Additional measurements of ventilation, blood physiology, and metabolic and psychometric changes clarified how man responds to this hostile environment.

Continuous distributions of ventilation-perfusion ratios in normal subjects breathing air and 100 per cent O2.

A new method has been developed for measuring virtually continuous distributions of ventilation-perfusion ratios (V(A)/Q) based on the steadystate elimination of six gases of different solubilities. The method is applied here to 12 normal subjects, aged 21-60. In nine, the distributions were compared breathing air and 100% oxygen, while in the remaining three, effects of changes in posture were examined. In four young semirecumbent subjects (ages 21-24) the distributions of blood flow and ventilation with respect to V(A)/Q were virtually log-normal with little dispersion (mean log standard deviations 0.43 and 0.35, respectively). The 95.5% range of both blood flow and ventilation was from V(A)/Q ratios of 0.3-2.1, and there was no intrapulmonary shunt (V(A)/Q of 0). On breathing oxygen, a shunt developed in three of these subjects, the mean value being 0.5% of the cardiac output. The five older subjects (ages 39-60) had broader distributions (mean log standard deviations, 0.76 and 0.44) containing areas with V(A)/Q ratios in the range 0.01-0.1 in three subjects. As for the young subjects, there was no shunt breathing air, but all five developed a shunt breathing oxygen (mean value 3.2%), and in one the value was 10.7%. Postural changes were generally those expected from the known effects of gravity, with more ventilation to high V(A)/Q areas when the subjects were erect than supine. Measurements of the shunt while breathing oxygen, the Bohr CO(2) dead space, and the alveolar-arterial oxygen difference were all consistent with the observed distributions. Since the method involves only a short infusion of dissolved inert gases, sampling of arterial blood and expired gas, and measurement of cardiac output and minute ventilation, we conclude that it is well suited to the investigation of pulmonary gas exchange in man.

Ventilation-perfusion inequality in chronic obstructive pulmonary disease.

A multiple inert gas elimination method was used to study the mechanism of impaired gas exchange in 23 patients with advanced chronic obstructive pulmonary disease (COPD). Three patterns of ventilation-perfusion (Va/Q) inequality were found: (a) A pattern with considerable regions of high (greater than 3) VA/Q, none of low (less than 0.1) VA/Q, and essentially no shunt. Almost all patients with type A COPD showed this pattern, and it was also seen in some patients with type B. (b) A pattern with large amounts of low but almost none of high VA/Q, and essentially no shunt. This pattern was found in 4 of 12 type B patients and 1 of type A. (c) A pattern with both low and high VA/Q areas was found in the remaining 6 patients. Distributions with high VA/Q areas occurred mostly in patients with greatly increased compliance and may represent loss of blood-glow due to alveolar wall destruction. Similarly, well-defined modes of low VA/Q areas were seen mostly in patients with severe cough and sputum and may be due to reduced ventilation secondary to mechanical airways obstruction or distortion. There was little change in the VA/Q distributions on exercise or on breathing 100% O2. The observed patterns of VA/Q inequality and shunt accounted for all of the hypoxemia at rest and during exercise. There was therefore no evidence for hypoxemia caused by diffusion impairment. Patients with similar arterial blood gases often had dissimilar VA/Q patterns. As a consequence the pattern of VA/Q inequality could not necessarily be inferred from the arterial PO2 and PCO2.

Endotypes of difficult-to-control asthma in inner-city African American children.

African Americans have higher rates of asthma prevalence, morbidity, and mortality in comparison with other racial groups. We sought to characterize endotypes of childhood asthma severity in African American patients in an inner-city pediatric asthma population. Baseline blood neutrophils, blood eosinophils, and 38 serum cytokine levels were measured in a sample of 235 asthmatic children (6-17 years) enrolled in the NIAID (National Institute of Allergy and Infectious Diseases)-sponsored Asthma Phenotypes in the Inner City (APIC) study (ICAC (Inner City Asthma Consortium)-19). Cytokines were quantified using a MILLIPLEX panel and analyzed on a Luminex analyzer. Patients were classified as Easy-to-Control or Difficult-to-Control based on the required dose of controller medications over one year of prospective management. A multivariate variable selection procedure was used to select cytokines associated with Difficult-to-Control versus Easy-to-Control asthma, adjusting for age, sex, blood eosinophils, and blood neutrophils. In inner-city African American children, 12 cytokines were significant predictors of Difficult-to-Control asthma (n = 235). CXCL-1, IL-5, IL-8, and IL-17A were positively associated with Difficult-to-Control asthma, while IL-4 and IL-13 were positively associated with Easy-to-Control asthma. Using likelihood ratio testing, it was observed that in addition to blood eosinophils and neutrophils, serum cytokines improved the fit of the model. In an inner-city pediatric population, serum cytokines significantly contributed to the definition of Difficult-to-Control asthma endotypes in African American children. Mixed responses characterized by TH2 (IL-5) and TH17-associated cytokines were associated with Difficult-to-Control asthma. Collectively, these data may contribute to risk stratification of Difficult-to-Control asthma in the African American population.

A strategy for reducing neonatal mortality at high altitude using oxygen conditioning.

Neonatal mortality increases with altitude. For example, in Peru the incidence of neonatal mortality in the highlands has been shown to be about double that at lower altitudes. An important factor is the low inspired PO2 of newborn babies. Typically, expectant mothers at high altitude will travel to low altitude to have their babies if possible, but often this is not feasible because of economic factors. The procedure described here raises the oxygen concentration in the air of rooms where neonates are being housed and, in effect, this means that both the mother and baby are at a much lower altitude. Oxygen conditioning is similar to air conditioning except that the oxygen concentration of the air is increased rather than the temperature being reduced. The procedure is now used at high altitude in many hotels, dormitories and telescope facilities, and has been shown to be feasible and effective.

Human limits for hypoxia. The physiological challenge of climbing Mt. Everest.

Climbing Mt. Everest without supplementary oxygen presents a fascinating physiological challenge because, at the summit, humans are very near the limit of tolerance to hypoxia. It was not until 1978 that the feat was accomplished, and this was after many unsuccessful attempts over a period of more than 50 years, and several physiological studies that suggested that it would be impossible. An analysis shows that the critical factors for reaching the summit are the enormous hyperventilation which is necessary to maintain the alveolar PO2 at viable levels, the fact that the barometric pressure is substantially higher than predicted by the Standard Atmosphere, and the severe respiratory alkalosis that assists loading of oxygen by the blood in the lung. Even so the maximal oxygen consumption on the summit is extremely low with the result that climbers are critically vulnerable to unexpected setbacks such as changes in the weather.

T.H. Ravenhill and his contributions to mountain sickness.

Thomas Holmes Ravenhill (1881-1952) was an important pioneer in high-altitude medicine but almost nothing has been published about him. He wrote a landmark paper in 1913 that included the classification of high-altitude sickness that is still in use, and it also contained the first accurate descriptions of high-altitude pulmonary edema and high-altitude cerebral edema, although he used different terms. The work was done while he was medical officer at the Collahuasi and Poderosa mines in northern Chile at altitudes he gave as 4,690-4,940 m. Remarkably, the paper was then forgotten until it was rediscovered over 50 yr later, but it is now cited in any comprehensive study of high-altitude illness. Ravenhill graduated in medicine from the University of Birmingham, Birmingham, UK, in 1905 and 4 yr later went to the mines where he spent 2 yr. Subsequently, he served in the Royal Army Medical Corps in the 1914-1918 war and was awarded the Military Cross. He returned to general practice but after a few years gave up medicine altogether. He then made important contributions to archeology and spent the last third of his life in London as a painter, mainly in watercolors. It is unclear to what extent his war experiences brought about his dramatic career change.

Prediction of barometric pressures at high altitude with the use of model atmospheres.

It would be valuable to have model atmospheres that allow barometric pressures (PB) to be predicted at high altitudes. Attempts to do this in the past using the International Civil Aviation Organizations or United States Standard Atmosphere model have brought such models into disrepute because the predicted pressures at high altitudes are usually much too low. However, other model atmospheres have been developed by geophysicists. The critical variable is the change of air temperature with altitude, and, therefore, model atmospheres have been constructed for different latitudes and seasons of the year. These different models give a large range of pressures at a given altitude. For example, the maximum difference of pressure at an altitude of 9 km is from 206 to 248 Torr, i.e., approximately 20%. However, the mean of the model atmospheres for latitude of 15 degrees (in all seasons) and 30 degrees (in the summer) predicts PB at many locations of interest at high altitude very well, with predictions within 1%. The equation is PB (Torr) = exp (6.63268 - 0.1112 h - 0.00149 h2), were h is the altitude in kilometers. The predictions are good because many high mountain sites are within 30 degrees of the equator and also many studies are made during the summer. Other models should be used for latitudes of 45 degrees and above. Model atmospheres have considerable value in predicting PB at high altitude if proper account is take of latitude and season of the year.

Alexander M. Kellas and the physiological challenge of Mt. Everest.

Alexander M. Kellas (1868-1921) was a British physiologist who made pioneering contributions to the exploration of Everest and to the early physiology of extreme altitudes, but his physiological contributions have been almost completely overlooked. Although he had a full-time faculty position at the Middlesex Hospital Medical School in London, he was able to make eight expeditions to the Himalayas in the first two decades of the century, and by 1919 when the first official expedition to Everest was being planned, he probably knew more about the approaches than anybody else. But his most interesting contributions were made in an unpublished manuscript written in 1920 and entitled "A consideration of the possibility of ascending Mount Everest." In this he discussed the physiology of acclimatization and most of the important variables including the summit altitude and barometric pressure, and the alveolar PO2, arterial oxygen saturation, maximal oxygen consumption, and maximal ascent rate near the summit. On the basis of this extensive analysis, he concluded that "Mount Everest could be ascended by a man of excellent physical and mental constitution in first-rate training, without adventitious aids [supplementary oxygen] if the physical difficulties of the mountain are not too great." Kellas was one of the first physiologists to study extreme altitude, and he deserves to be better known.

Invited review: pulmonary capillary stress failure.

The pulmonary blood-gas barrier is an extraordinary bioengineering structure because of its vast area but extreme thinness. Despite this, almost no attention has been given to its mechanical properties. The remarkable area and thinness come about because gas exchange occurs by passive diffusion. However, the barrier also needs to be immensely strong to withstand the very high stresses in the capillary wall when capillary pressure rises during exercise. The strength of the thin region of the barrier comes from type IV collagen in the basement membranes. When the stresses in the capillary walls rise to high levels, ultrastructural changes occur in the barrier, a condition known as stress failure. Physiological conditions that alter the properties of the barrier include severe exercise in elite human athletes. Animals that have been selectively bred for high aerobic activity, such as Thoroughbred racehorses, consistently break their pulmonary capillaries during galloping. Pathophysiological conditions causing stress failure include high-altitude pulmonary edema and overinflation of the lung, which frequently occurs with mechanical ventilation. Remodeling of the capillary wall occurs in response to increased wall stress in diseases such as mitral stenosis. The barrier is able to maintain its extreme thickness with sufficient strength as a result of continual regulation of its wall structure. How it does this is a central problem in lung biology.

Physiology in microgravity.

Studies of physiology in microgravity are remarkably recent, with almost all the data being obtained in the past 40 years. The first human spaceflight did not take place until 1961. Physiological measurements in connection with the early flights were crude, but, in the past 10 years, an enormous amount of new information has been obtained from experiments on Spacelab. The United States and Soviet/Russian programs have pursued different routes. The US has mainly concentrated on relatively short flights but with highly sophisticated equipment such as is available in Spacelab. In contrast, the Soviet/Russian program concentrated on first the Salyut and then the Mir space stations. These had the advantage of providing information about long-term exposure to microgravity, but the degree of sophistication of the measurements in space was less. It is hoped that the International Space Station will combine the best of both approaches. The most important physiological changes caused by microgravity include bone demineralization, skeletal muscle atrophy, vestibular problems causing space motion sickness, cardiovascular problems resulting in postflight orthostatic intolerance, and reductions in plasma volume and red cell mass. Pulmonary function is greatly altered but apparently not seriously impaired. Space exploration is a new frontier with long-term missions to the moon and Mars not far away. Understanding the physiological changes caused by long-duration microgravity remains a daunting challenge.

Historical aspects of the early Soviet/Russian manned space program.

Human spaceflight was one of the great physiological and engineering triumphs of the 20th century. Although the history of the United States manned space program is well known, the Soviet program was shrouded in secrecy until recently. Konstantin Edvardovich Tsiolkovsky (1857-1935) was an extraordinary Russian visionary who made remarkable predictions about space travel in the late 19th century. Sergei Pavlovich Korolev (1907-1966) was the brilliant "Chief Designer" who was responsible for many of the Soviet firsts, including the first artificial satellite and the first human being in space. The dramatic flight of Sputnik 1 was followed within a month by the launch of the dog Laika, the first living creature in space. Remarkably, the engineering work for this payload was all done in less than 4 wk. Korolev's greatest triumph was the flight of Yuri Alekseyevich Gagarin (1934-1968) on April 12, 1961. Another extraordinary feat was the first extravehicular activity by Aleksei Arkhipovich Leonov (1934-) using a flexible airlock that emphasized the entrepreneurial attitude of the Soviet engineers. By the mid-1960s, the Soviet program was overtaken by the United States program and attempts to launch a manned mission to the Moon failed. However, the early Soviet manned space program has a preeminent place in the history of space physiology.

The original presentation of Boyle's law.

The original presentation of what we know as Boyle's law has several interesting features. First, the technical difficulties of the experiment were considerable, because Boyle used a glass tube full of mercury that was nearly 2.5 m long, and the large pressures sometimes shattered the glass. Next, Boyle's table of results contains extremely awkward fractions, such 10/13, 2/17, 13/19, and 18/23, which look very strange to us today. This was because he calculated the pressure for a certain volume of gas by using simple multiplication and division, keeping the vulgar fractions. Boyle was not able to express the numbers as decimals because this notation was not in common use at the time. Finally, his contention that pressure and volume were inversely related depended on the reader's comparing two sets of numbers in adjacent columns to see how well they agreed. Today we would plot the data, but again orthogonal graphs were not in general use in 1662. When Boyle's data are plotted by using modern conventional methods, they strongly support his hypothesis that the volume and pressure of a gas are inversely related.

Barometric pressures on Mt. Everest: new data and physiological significance.

Barometric pressures (PB) near the summit of Mt. Everest (altitude 8, 848 m) are of great physiological interest because the partial pressure of oxygen is very near the limit for human survival. Until recently, the only direct measurement on the summit was 253 Torr, which was obtained in October 1981, but, despite being only one data point, this value has been used by several investigators. Recently, two new studies were carried out. In May 1997, another direct measurement on the summit was within approximately 1 Torr of 253 Torr, and meteorologic data recorded at the same time from weather balloons also agreed closely. In the summer of 1998, over 2,000 measurements were transmitted from a barometer placed on the South Col (altitude 7,986 m). The mean PB values during May, June, July, and August were 284, 285, 286, and 287 Torr, respectively, and there was close agreement with the PB-altitude (h) relationship determined from the 1981 data. The PB values are well predicted from the equation PB = exp (6.63268 - 0.1112 h - 0.00149 h2), where h is in kilometers. The conclusion is that on days when the mountain is usually climbed, during May and October, the summit pressure is 251-253 Torr.

Deposition and dispersion of 1-micrometer aerosol boluses in the human lung: effect of micro- and hypergravity.

We performed bolus inhalations of 1-micrometer particles in four subjects on the ground (1 G) and during parabolic flights both in microgravity (microG) and in approximately 1.6 G. Boluses of approximately 70 ml were inhaled at different points in an inspiration from residual volume to 1 liter above functional residual capacity. The volume of air inhaled after the bolus [the penetration volume (Vp)] ranged from 200 to 1,500 ml. Aerosol concentration and flow rate were continuously measured at the mouth. The deposition, dispersion, and position of the bolus in the expired gas were calculated from these data. For Vp >/=400 ml, both deposition and dispersion increased with Vp and were strongly gravity dependent, with the greatest deposition and dispersion occurring for the largest G level. At Vp = 800 ml, deposition and dispersion increased from 33.9% and 319 ml in microG to 56.9% and 573 ml at approximately 1.6 G, respectively (P < 0.05). At each G level, the bolus was expired at a smaller volume than Vp, and this volume became smaller with increasing Vp. Although dispersion was lower in microG than in 1 G and approximately 1.6 G, it still increased steadily with increasing Vp, showing that nongravitational ventilatory inhomogeneity is partly responsible for dispersion in the human lung.

Dispersion of 0.5- to 2-micron aerosol in microG and hypergravity as a probe of convective inhomogeneity in the lung.

We used aerosol boluses to study convective gas mixing in the lung of four healthy subjects on the ground (1 G) and during short periods of microgravity (microG) and hypergravity ( approximately 1. 6 G). Boluses of 0.5-, 1-, and 2-micron-diameter particles were inhaled at different points in an inspiration from residual volume to 1 liter above functional residual capacity. The volume of air inhaled after the bolus [the penetration volume (Vp)] ranged from 150 to 1,500 ml. Aerosol concentration and flow rate were continuously measured at the mouth. The dispersion, deposition, and position of the bolus in the expired gas were calculated from these data. For each particle size, both bolus dispersion and deposition increased with Vp and were gravity dependent, with the largest dispersion and deposition occurring for the largest G level. Whereas intrinsic particle motions (diffusion, sedimentation, inertia) did not influence dispersion at shallow depths, we found that sedimentation significantly affected dispersion in the distal part of the lung (Vp >500 ml). For 0.5-micron-diameter particles for which sedimentation velocity is low, the differences between dispersion in microG and 1 G likely reflect the differences in gravitational convective inhomogeneity of ventilation between microG and 1 G.

Limitation of maximal O2 uptake and performance by acute hypoxia in dog muscle in situ.

The factors that determine maximal O2 uptake (VO2max) and muscle performance during severe, acute hypoxemia were studied in isolated, in situ dog gastrocnemius muscle. Our hypothesis that VO2max is limited by O2 diffusion in muscle predicts that decreases in VO2max, caused by hypoxemia, will be accompanied by proportional decreases in muscle effluent venous PO2 (PvO2). By altering the fraction of inspired O2, four levels of arterial PO2 (PaO2) [21 +/- 2, 28 +/- 1, 44 +/- 1, and 80 +/- 2 (SE) Torr] were induced in each of eight dogs. Muscle arterial and venous circulation was isolated and arterial pressure held constant by pump perfusion. Each muscle worked maximally (3 min at 5-6 Hz, isometric twitches) at each PaO2. Arterial and venous samples were taken to measure lactate, [H+], PO2, PCO2, and muscle VO2. Muscle biopsies were taken to measure [H+] (homogenate method) and lactate. VO2max decreased with PaO2 and was linearly (R = 0.99) related to both PVO2 and O2 delivery. As PaO2 fell, fatigue increased while muscle lactate and [H+] increased. Lactate release from the muscle did not change with PaO2. This suggests a barrier to lactate efflux from muscle and a possible cause of the greater fatigue seen in hypoxemia. The gas exchange data are consistent with the hypothesis that VO2max is limited by peripheral tissue diffusion of O2.

Ventilation-perfusion relationships during induced normovolemic polycythemia in dogs.

Previous studies on normal subjects and patients with polycythemia have given conflicting results of the effect of polycythemia on pulmonary gas exchange. We studied acutely induced normovolemic polycythemia in the dog and measured arterial blood gases and ventilation-perfusion (VA/Q) relationships using the multiple inert gas elimination technique. The mean base-line hematocrit of 43 +/- 5% was increased to 57 +/- 4 and 68 +/- 8%, respectively, after two exchange transfusions of packed erythrocytes. Subsequent plasma exchange transfusions returned the mean hematocrit to 44 +/- 4%. Polycythemia caused no significant arterial hypoxemia; indeed there was a slight improvement in the alveolar-arterial PO2 difference. The multiple inert gas elimination measurements showed no increase in VA/Q inhomogeneity with no increase in log SD ventilation (V) or log SD blood flow (Q). There was a shift of mean V and mean Q to high VA/Q areas because of a decrease in cardiac output, presumably caused by increased blood viscosity. This study showed no deleterious effects on pulmonary gas exchange within the hematocrit range of 36-76%.

Effect of microgravity and hypergravity on deposition of 0.5- to 3-micron-diameter aerosol in the human lung.

We measured intrapulmonary deposition of 0. 5-, 1-, 2-, and 3-micron-diameter particles in four subjects on the ground (1 G) and during parabolic flights both in microgravity (microG) and at approximately 1.6 G. Subjects breathed aerosols at a constant flow rate (0.4 l/s) and tidal volume (0.75 liter). At 1 G and approximately 1.6 G, deposition increased with increasing particle size. In microG, differences in deposition as a function of particle size were almost abolished. Deposition was a nearly linear function of the G level for 2- and 3-micron-diameter particles, whereas for 0.5- and 1.0-micron-diameter particles, deposition increased less between microG and 1 G than between 1 G and approximately 1.6 G. Comparison with numerical predictions showed good agreement for 1-, 2-, and 3-micron-diameter particles at 1 and approximately 1.6 G, whereas the model consistently underestimated deposition in microG. The higher deposition observed in microG compared with model predictions might be explained by a larger deposition by diffusion because of a higher alveolar concentration of aerosol in microG and to the nonreversibility of the flow, causing additional mixing of the aerosols.