Influence of glucose kinetics on plasma lactate concentration and energy expenditure in severely burned patients

BACKGROUND: In critically ill patients, elevation in the plasma lactate concentration has traditionally been interpreted as indicating a deficiency in oxygen availability and is often an impetus to increase oxygen delivery clinically. However, another possible basis for increased lactate concentrations may be simply a mass effect from increased pyruvate availability (i.e., accelerated glycolysis). METHODS: In six hypermetabolic burned patients, the rates of glucose production and oxidation were quantified using a tracer infusion of 6,6 d2 glucose combined with indirect calorimetry. Measurements were obtained after a 9-hour fast and after a 3-hour infusion of unlabeled glucose at 30 micromol/kg/min. No patient was overtly septic, hypoxic, or hypovolemic. RESULTS: The infusion of glucose significantly increased the arterial glucose concentration and rate of glucose oxidation, with a corresponding increase in the arterial plasma concentration of lactate and pyruvate. Resting energy expenditure and oxygen consumption were not affected by the infusion of glucose. CONCLUSIONS: These findings show that elevations in plasma lactate in severely injured patients may, in part, be related to increases in glucose flux and not entirely a reflection of any deficit in oxygen availability. Such findings highlight a potential pitfall for interpreting plasma lactate concentrations as an index of tissue oxygen availability in hypermetabolic patients.     

High-dose therapy and autologous hematopoietic stem-cell transplantation does not increase the risk of second neoplasms for patients with Hodgkin's lymphoma: a comparison of conventional therapy alone versus conventional therapy followed by autologous hematopoietic stem-cell transplantation.

PURPOSE: To determine the incidence of second malignancies among patients with Hodgkin's lymphoma (HL) treated with autologous hematopoietic stem cell transplantation (AHSCT) compared with patients receiving conventional therapy alone and to identify potential risk factors for their occurrence. PATIENTS AND METHODS: We analyzed data on 1,732 consecutive patients with HL treated at the British Columbia Cancer Agency from 1976 to 2001, including 202 patients undergoing AHSCT. The median follow-up duration was 9.8 years for the whole cohort, 9.7 years for those patients treated with conventional therapy, and 7.8 years from AHSCT. RESULTS: The cumulative incidence of developing any second malignancy 15 years after therapy for HL was 9% (risk ratio = 3.5; P < .001); however, the incidence did not differ between those patients receiving conventional therapy alone compared with those undergoing AHSCT (10% and 8%, respectively; P = .48). In multivariate analysis, the only factor significantly associated with an increased risk of developing any second neoplasm or solid tumor was age > or = 35 years (P < .0001). An increased risk of therapy-induced acute myeloid leukemia and therapy-induced myelodysplastic syndrome was seen for patients aged > or = 35 years (P = .03) and stage III/IV (P = .04). CONCLUSION: Patients with HL are at increased risk of developing a second neoplasm. However, those patients undergoing AHSCT do not seem to be at greater risk compared with those patients receiving conventional therapy alone, at least during the first decade after therapy.     

Preclinical pharmacology of desloratadine, a selective and nonsedating histamine H1 receptor antagonist. 2nd communication: lack of central nervous system and cardiovascular effects

Desloratadine (descarboethoxyloratadine, CAS 100643-71-8) is a selective histamine H1 antagonist that exhibits qualitatively similar pharmacodynamic activity to its parent, loratadine (CAS 79794-75-5), but is 2.5-4 times more potent orally. In studies of central nervous system (CNS) effects that might lead to sedation, desloratadine had no behavioral, neurological or autonomic effects in the conscious mouse and rat. At large multiples of the antihistaminic dose in the mouse, it did not inhibit convulsions caused by electroconvulsive shock and inhibited acetic acid-induced writhing only at a dose approximately 1,000 times the antihistaminic dose in the mouse. Desloratadine had no effects on blood pressure, heart rate or electrocardiographic parameters in the rat or guinea pig or on electrocardiographic parameters in the monkey. Notably, there was no effect on the corrected Q-wave to T-wave (QTc) interval. Desloratadine did not inhibit IKr channel human ether-a-go-go-related gene (HERG)-induced current in a study in which HERG was expressed in Xenopus oocytes. In the rat, desloratadine did not cause effects in urine volume, electrolytes or creatinine, or inhibit gastric emptying or intestinal transit, or cause any harmful effects on gastric mucosa. The results of these preclinical studies provide evidence that desloratadine is a safe antihistamine without CNS or cardiovascular effects.     

The Past as a Lens for Biodiversity Conservation on a Dynamically Changing Planet: A resilient and connected network of sites to sustain biodiversity under a changing climate

Motivated by declines in biodiversity exacerbated by climate change, we identified a network of conservation sites designed to provide resilient habitat for species, while supporting dynamic shifts in ranges and changes in ecosystem composition. Our 12-y study involved 289 scientists in 14 study regions across the conterminous United States (CONUS), and our intent was to support local-, regional-, and national-scale conservation decisions. To ensure that the network represented all species and ecosystems, we stratified CONUS into 68 ecoregions, and, within each, we comprehensively mapped the geophysical settings associated with current ecosystem and species distributions. To identify sites most resilient to climate change, we identified the portion of each geophysical setting with the most topoclimate variability (high landscape diversity) likely to be accessible to dispersers (high local connectedness). These “resilient sites” were overlaid with conservation priority maps from 104 independent assessments to indicate current value in supporting recognized biodiversity. To identify key connectivity areas for sustaining species movement in response to climate change, we codeveloped a fine-scale representation of human modification and ran a circuit-theory-based analysis that emphasized movement potential along geographic climate gradients. Integrating areas with high values for two or more factors, we identified a representative, resilient, and connected network of biodiverse lands covering 35% of CONUS. Because the network connects climatic gradients across 250,000 biodiversity elements and multiple resilient examples of all geophysical settings in every ecoregion, it could form the spatial foundation for targeted land protection and other conservation strategies to sustain a diverse, dynamic, and adaptive world.

Conservationists in the United States are not winning the battle to sustain biological diversity. Despite broad public support and unprecedented bipartisan agreement on Earth Day 1970, followed by landmark environmental laws, expanded regulatory efforts, and the establishment of hundreds of private conservation organizations, the species and ecosystems that characterize the natural world continue to decline. In North America, the abundance of birds has fallen 29% since 1970 (1); 32% of insect taxa are in decline (2); and 56% of mammalian carnivore and ungulates have shown notable range contractions since 1950 (3). Amphibians have declined an average (avg.) of 33% since 2002 (4). Of the 51,936 species of plants, vertebrates, and macroinvertebrates tracked by NatureServe for the conterminous United States (CONUS), 9% are ranked vulnerable, 12% imperiled, and 1% possibly extinct (5).^*Changes in climate are exacerbating species declines, especially for small, isolated populations. As temperature and moisture regimes change, species ranges are shifting with speed and magnitude unprecedented in recent millennia. In the eastern United States, trees have shifted their centers of distribution 10 km north and 11 km west per decade since 1980 (6). Southern bird ranges have shifted northward by an avg. of 23.5 km per decade (7). These changes are on par with global shifts of 10 km north and 11 m upslope per decade across taxa groups (8).A primary driver of biodiversity decline is habitat loss and degradation resulting from land-use change (9, 10). Land- and water-conservation efforts can reverse these trends when strategically located and enabled by the necessary investments. In North America, billions of dollars spent on wetland restoration and management, combined with more stringent hunting regulations, reversed bird-abundance declines in wetlands (1). Globally, conservation investment from 1996 to 2008 reduced the extinction risk for mammals and birds by a median value of 29% (10). However, the effectiveness of land and water conservation in sustaining biodiversity depends on the representativeness of the conserved area network, the resilience and condition of the sites, and the connectivity between sites to allow for movement and adaptation (11, 12).To sustain biodiversity and facilitate adaptation of species to a changing climate, the Convention on Biological Diversity (CBD) Target 2 (13) calls for the protection of well-connected and effective systems of protected areas covering at least 30% of the planet. However, as climate change drives changes in species distributions and ecosystem composition, conservation plans based on current biodiversity patterns may become less effective at sustaining species (14). In particular, the current configuration of protected areas may fail to adequately provide access to the diverse climatic conditions needed for species populations to persist amid changing regional climates (12, 15, 16). Accordingly, conservation planners are beginning to focus on conserving sites that represent the earth’s eco-physiographic regions (hereafter “ecoregions”) and the spectrum of geophysical variation and a diversity of connected topographic microclimates (hereafter “topoclimates”) to allow species to adapt in situ or move to newly favorable areas, an approach known as Conserving Nature’s Stage (CNS) (15–19).Most studies of climate effects on biota use regional-scale climate-projection models combined with species vulnerability assessments to identify areas of relatively high threat or stability at a coarse scale. Here, we take a different approach. By focusing on geophysical diversity that shapes species distributions and fine-scale climate variation directly relevant to species persistence (20, 21), we aimed to identify enduring climate strongholds relevant under many climate scenarios and to map them at scales appropriate for land-conservation decisions.For species in topographically diverse locations, variability in temperature locally may exceed the degree of warming expected over the next century (22, 23). These areas have the potential to provide species with microclimatic buffering from regional climatic change by allowing local dispersal to more favorable microclimates or providing stepping stones to facilitate longer-distance range shifts (24, 25). Paleoecological records highlight the dynamic nature of species responses to Quaternary climate change, including the role of topography in creating climate refugia (26–28), and suggest that the CNS strategy may be appropriate for many taxa if it is purposefully designed to accommodate species responses to climate change (29).Species persisted under past climatic changes through in situ refugia combined with range shifts to track suitable climates (30–32). Rapid warming projected for the next century will likely require many species to adapt in a similar way (33–35), and many species’ ranges are already shifting (8). However, high levels of habitat loss and fragmentation due to anthropogenic activities are isolating populations and creating barriers to species movement that were not present during past periods of rapid climate change (29, 36, 37). Thus, conservation actions that maintain or increase connectivity are essential for effective conservation under climate change, as connectivity facilitates movement and gene flow, bolstering adaptive capacity by maintaining genetic diversity (38–40).To sustain biodiversity, a conservation network must also include sites that support living biotic assemblages reflecting each ecoregion’s geophysical properties, such as dominant habitats, unique communities, and viable examples of rare and specialist species populations. We refer to these as sites with “recognized biodiversity value.” Including them in a conservation network ensures that it is embedded with species and habitats that provide the capacity for adapting to climate change (41, 42). In the United States, state agencies and nongovernment organizations (NGOs) have identified over a thousand areas with recognized biodiversity value through comprehensive ecoregional or state-based assessments specifically targeting viable rare species populations, exemplary natural communities, and intact ecosystems. Integrating the footprint of these sites with spatial information on connected topoclimates and representative geophysical features helps confirm that the sites are collectively distributed across all abiotic “stages” needed to sustain biodiversity into the future.     

The influence of variations in blood flow on pulsed doppler ultrasonic heating of the cerebral cortex of the neonatal pig

Pulsed Doppler ultrasound examination of the fetal cerebral circulation may cause potentially harmful temperature elevations in brain tissue immediately beneath the insonated segment of the skull. This study measured the effect of variations in cerebral blood flow on ultrasonic heating of the cerebral cortex of anaesthetised, neonatal pigs. Wide and narrow ultrasound beams were used. Pulsed ultrasound exposures were delivered in 90 s bursts at 5.8 micros pulse length, pulse repetition frequency 8 kHz and centre frequency 3.5 MHz. Studies were performed with the target at the focus of a fixed, stationary beam of 0.3 cm -6 dB beam width (narrow beam) and I(spta) 1.4 W/cm(2) (n = 11), or with the target in the near field of a fixed, stationary beam of 1.6 cm -6 dB beam width (wide beam) and I(spta) 3.6 W/cm(2)(n = 5). The 90 s ultrasound exposures were performed under three different conditions of ambient cerebral blood flow: baseline (during normocarbic, normoxic conditions), increased (during hypercarbic, hypoxic conditions) and absent (postmortem). Cerebral blood flow was measured using the radiolabelled microsphere technique. In the narrow beam studies, cerebral blood flow during baseline was 34 +/- 4 ml/min/100 g, rising to 109 +/- 32 ml/min/100 g during the increased phase (p < 0.001); in the wide beam studies baseline flows were 29 +/- 9 ml/min/100 g, whereas flows in the increased phase were 128 +/- 32 ml/min/100 g (p < 0.001). There was no difference in the heating curves for normal, increased and absent cerebral blood flow for exposure to the narrow beam, when mean temperature increases of 1.5 degrees C at 90 s were recorded in each case (p > 0.21, power > 0.8). However, the heating curves for the wide beam were significantly different for the three rates of blood flow with mean temperature increases of 1.9 degrees C (normal flow), 1.7 degrees C (increased flow) and 2.4 degrees C (no flow) recorded at 90 s (p < 0.05).     

应用功能磁共振成像分析脑卒中患者康复治疗前后大脑再塑机制

目的:应用功能磁共振成像观察脑卒中后及康复过程中,在相应脑内运动功能区激活的变化情况,探讨不同运动模式下皮质功能再塑的表现。方法:选取2003-02/10大庆油田总医院康复科住院的皮质下脑梗死患者8例,在发病后1周始进行连续两个月的康复。在康复前、康复1,2个月时运用Brunnstrom分级、Caroll上肢功能量表(0￣100分,评分越高功能越好)对其手功能进行评价,并采用GEMR/iHiSpeed1.5超导磁共振扫描机进行磁共振成像功能激发检查。患者用病手执行简单运动(快速连续的拇指与其他各指的对指动作)、随意运动(用病手摸不同形状的木块),获得脑功能激发图像,观察脑内相关功能区的激活情况。结果:8例受试者均进入结果分析。①康复后所有患者Brunnstrom分级和Caroll上肢功能评分均较康复前有明显改善。②病手简单运动时脑内相关功能区的激活情况:8例受试者7例在损伤后早期手指不能对指,所以没有激活;M1,SMA,PMA脑区和小脑呈现单侧激活-双侧激活-单侧激活的变化过程;随着运动功能恢复,脑内激活数目随时间呈下降趋势,几乎接近正常人脑功能表现。③病手随意运动时脑内相关功能区的激活情况:实验中发现引起的运动相关功能区的激发情况变化多样,规律性较差,但其中5例受试者表现出损伤后激发数目明显减少,许多对运动起决定性支配作用的功能区亦不激活;随着运动功能恢复,激发区数目呈上升趋势,同损伤后简单运动的激活表现。结论:①脑卒中后病手经过康复治疗简单运动恢复较好,康复治疗2个月后脑内运动功能相关区域激活的规律已同正常人。②脑卒中后病手随意运动恢复较困难,康复治疗后不如简单运动恢复好,脑内相关运动功能区激活无明显的规律性。随着运动功能的恢复,脑内相应的运动功能区激活增多。     

Round window ultrasonic treatment of Meniere disease.

The neurosensory structures within the vestibular labyrinth of the inner ear are selectively irradiated with ultrasonic energy to alleviate the vertiginous symptoms of Meniere disease. However, correct application and coupling of the ultrasonic transducer to the inner ear is essential for maximum transmission of energy into the vestibule. The importance of assessing the results of long-term postoperative treatment is demonstrated by a change in the success rate that decreased by approximately 10% when the results obtained within the first 12 months of treatment were compared with those after four years. In this investigation, 32 patients were treated by the round window approach between 1970 and 1972, and after four years it was found that 72% of these were successful in relieving the giddiness symptoms.