[Hypercapnia under controlled mechanical ventilation in patients with high-risk acute pulmonary thromboembolism].

Objective: To evaluate the variation of arterial partial pressure of carbon dioxide (PaCO2) in patients with high-risk pulmonary embolism under mechanical ventilation. Methods: We retrospectively analyzed the cases of high-risk pulmonary embolism who underwent intravenous thrombolysis in Peking Union Medical College Hospital from January 1, 2012, to May 1, 2022. The enrolled patients were divided into a mechanical-ventilated group and an active-breathing group according to whether they received invasive mechanical ventilation or not. The level of PaCO2 under active breathing between the two groups, the changes in PaCO2 before intubation, after intubation and after thrombolysis in the mechanical-ventilated group were compared. The 14-day all-cause mortality of the two groups was calculated and compared. Results: A total of 49 patients with high-risk pulmonary embolism were enrolled, including 22 patients in the mechanical-ventilated group and 27 patients in the active-breathing group. Before intubation, PaCO2 in both groups was lower than normal without statistically significant difference between the two groups. After effective thrombolysis therapy, PaCO2 in both groups recovered to the normal range. In the mechanical-ventilated group, PaCO2 significantly increased 11-147 min after intubation and returned to the normal range after thrombolysis therapy. The 14-day mortality in the mechanical-ventilated group was 54.5%, while all patients in the active-breathing group survived. Conclusions: Under mechanical controlled ventilation, patients with high-risk pulmonary embolism could represent hypercapnia which resolved after effective thrombolytic therapy. In mechanical ventilated patients with sudden-onset hypoxemia and hypercapnia, the possibility of high-risk pulmonary embolism should be considered.

Model-based calculations of off-axis ratio of conic beams for a dedicated 6 MV radiosurgery unit.

PURPOSE: Because the small-radius photon beams shaped by cones in stereotactic radiosurgery (SRS) lack lateral electronic equilibrium and a detector's finite cross section, direct experimental measurement of dosimetric data for these beams can be subject to large uncertainties. As the dose calculation accuracy of a treatment planning system largely depends on how well the dosimetric data are measured during the machine's commissioning, there is a critical need for an independent method to validate measured results. Therefore, the authors studied the model-based calculation as an approach to validate measured off-axis ratios (OARs). METHODS: The authors previously used a two-component analytical model to calculate central axis dose and associated dosimetric data (e.g., scatter factors and tissue-maximum ratio) in a water phantom and found excellent agreement between the calculated and the measured central axis doses for small 6 MV SRS conic beams. The model was based on that of Nizin and Mooij ["An approximation of central-axis absorbed dose in narrow photon beams," Med. Phys. 24, 1775-1780 (1997)] but was extended to account for apparent attenuation, spectral differences between broad and narrow beams, and the need for stricter scatter dose calculations for clinical beams. In this study, the authors applied Clarkson integration to this model to calculate OARs for conic beams. OARs were calculated for selected cones with radii from 0.2 to 1.0 cm. To allow comparisons, the authors also directly measured OARs using stereotactic diode (SFD), microchamber, and film dosimetry techniques. The calculated results were machine-specific and independent of direct measurement data for these beams. RESULTS: For these conic beams, the calculated OARs were in excellent agreement with the data measured using an SFD. The discrepancies in radii and in 80%-20% penumbra were within 0.01 cm, respectively. Using SFD-measured OARs as the reference data, the authors found that the calculated OARs were more accurate than those measured with a microchamber or film dosimetry. CONCLUSIONS: The model produces sufficiently accurate conic beam dosimetric data that can be used to validate direct measurement results for such beams.

Plasminogen activator system in osteoclasts.

To determine which genes of the plasminogen activator (PA) system were expressed in osteoclasts, RNA extracted from microisolated mouse osteoclasts was used as template for reverse transcribed polymerase chain reaction (RT-PCR) with gene-specific primer pairs. Using this approach, the expression of RNAs for tissue-type plasminogen activator, urokinase-type plasminogen activator, plasminogen activator inhibitor-1, plasminogen activator inhibitor-2, protease nexin, and urokinase receptor isoform 1 (uPAR1) were detected in mouse osteoclasts. The expression of uPAR RNA in osteoclasts was confirmed by in situ hybridization with a uPAR1 probe. RNA encoding the uPAR isoform 2 was not detected in mouse osteoclasts, but a novel unspliced uPAR RNA variant was detected in these cells. The novel uPAR variant and uPAR1 RNA were also detected in mouse calvarial osteoblasts, kidney, muscle, and the mouse macrophage cell line J774A.1 by RT-PCR. The presence of RNAs for most of the components of the PA system in osteoclasts suggests that it may have a functional role in this cell type.

Role of the epithelium in airway smooth muscle responses to relaxant agonists.

We studied the role of the guinea pig tracheal epithelium in modulating tracheal smooth muscle responses to the relaxant agonists albuterol, sodium nitroprusside, and theophylline. We used an in vitro preparation that allowed separation of the fluids bathing the luminal (internal) and serosal (external) surfaces of the trachea, and bronchodilators were administered to either surface of carbachol-contracted tracheae. All three drugs produced dose-dependent relaxation. However, albuterol and nitroprusside were less potent (concentration that produced half-maximal effect increased by 100- and 32-fold, respectively) when given to the epithelial side with the epithelium intact compared with the epithelium denuded or compared with serosal administration with the epithelium intact. These differences were not observed for theophylline, where smooth muscle responses were independent of either the side of stimulation or of the presence or absence of the epithelium. Direct measurements of the diffusion of theophylline across the tracheal wall in the presence or absence of epithelium showed that after 5 h of incubation with a fixed luminal concentration of theophylline, only 1.7% had diffused across the tracheal wall with the epithelium intact. This increased to only approximately 3.3% when the epithelium was denuded. These results suggest that the epithelial is a relatively weak barrier for lipophilic agents but has a major role as a diffusion barrier to hydrophilic substances.

Effect of pH on pulmonary vascular tone, reactivity, and arachidonate metabolism.

We studied the effects of perfusate pH on pulmonary vascular tone, reactivity, and thromboxane and prostacyclin synthesis in isolated buffer-perfused rabbit lungs. Extracellular acidosis did not affect base-line vascular tone, but alkalosis had a biphasic effect. Increasing the perfusate pH from 7.40 to 7.65 caused vasodilation, whereas raising pH to 7.70-8.10 caused vasoconstriction. Removing calcium (Ca2+) from the perfusate completely prevented the vasoconstriction caused by alkalosis. Perfusate pH strikingly affected pulmonary vascular reactivity. Acidosis inhibited the vasoconstriction caused by thromboxane and potassium chloride (KCl) but did not affect the response to angiotensin II. Alkalosis, in contrast, augmented the vasoconstriction caused by thromboxane and angiotensin II but reduced the vasoconstriction caused by KCl. Changes in pH also altered thromboxane and prostacyclin synthesis after the infusion of exogenous arachidonic acid (AA) or the endogenous release of AA by the lipid peroxide tert-butyl hydroperoxide.

An investigation of tomotherapy beam delivery.

Experimental simulations for tomotherapy beam delivery were performed using a computer-controlled phantom positioner, a cylindrical phantom, and a 6 MV x-ray slit beam. Both continuous helical beam and sequential segmented tomotherapy (SST) beam deliveries were evaluated. Beam junctioning problem due to couch indexing error or field width errors presented severe dose uniformity perturbations for SST, while the problem was minimized for helical beam delivery. Longitudinal breathing motions were experimentally simulated for helical and SST beam delivery. While motions reduced the dose uniformity perturbations for SST, small artifacts in dose uniformity can be introduced for helical beam delivery. With typical breath frequency and magnitude, for a slit beam of 2.0 cm width at 4 rpm, the dose uniformity perturbation was not significant. A running start/stop technique was implemented with helical beam delivery to sharpen the 20%-80% longitudinal dose fall-off from 1.5 to 0.5 cm. The latter was comparable to the corresponding dose penumbra of a conventional 6 MV 10 x 10 cm2 field. All together, helical beam delivery showed advantages over SST for tomotherapy beam delivery under similar delivery conditions.

Illuminant cues in surface color perception: tests of three candidate cues.

Many recent computational models of surface color perception presuppose information about illumination in scenes. The models differ primarily in the physical process each makes use of as a cue to the illuminant. We evaluated whether the human visual system makes use of any of three of the following candidate illuminant cues: (1) specular highlight, (2) full surface specularity [Lee, H. C. (1986). Method for computing the scene-illuminant chromaticity from specular highlights. Journal of the Optical Society of America A, 3(10), 1694-1699; D'Zmura, M., & Lennie, P. (1986). Mechanisms of color constancy. Journal of the Optical Society of America A, 3(10), 1662-1672], and (3) uniform background. Observers viewed simulated scenes binocularly in a computer-controlled Wheatstone stereoscope. All simulated scenes contained a uniform background plane perpendicular to the observer's line of sight and a small number of specular, colored spheres resting on the uniform background. Scenes were rendered under either standard illuminant D65 or standard illuminant A. Observers adjusted the color of a small, simulated test patch to appear achromatic. In a series of experiments we perturbed the illuminant color signaled by each candidate cue and looked for an influence of the changed cue on achromatic settings. We found that the specular highlight cue had a significant influence, but that the influence was asymmetric: greater when the base illuminant, CIE standard Illuminant A, was perturbed in the direction of Illuminant D65 than vice versa. Neither the full surface specularity cue nor the background cue had any observable influence. The lack of influence of the background cue is likely due to the placement of the test patch in front of the background rather than, as is typical, embedded in the background.

Interpersonal underpinnings of request strategies: general principles and differences due to culture and gender.

Several hypotheses derived from P. Brown and Levinson's (1987) politeness theory were tested with Ss from the United States and Korea. Ss imagined themselves in situations in which they were to make a request. They then indicated exactly what they would say in each situation and what their perceptions of the request size, the hearer's power, and the closeness of their relationship with the hearer were. Consistent with P. Brown and Levinson's theory, power, distance, and size contributed significantly to politeness. Significant predictor variable interactions suggested that an additive model is not appropriate. Finally, there was evidence of cultural and gender differences in the weighting of these predictor variables. These differences can partially account for cultural and gender differences in language use.

Use of microcomputers in medical practice management: a practical guide.

The decreasing cost and increasing availability of computers have created both concern and desire on the part of the non-computer professional. This article provides basic information to use in the selection of microcomputer hardware and software. It is slanted toward the small practitioner, one to four physicians, and provides practical guidelines, definitions, and examples relevant for a small practice.

Statins excert neuroprotection on cerebral ischemia independent of their lipid-lowering action: the potential molecular mechanisms.

Cerebral ischemia is a major neurological disorder and a leading cause of death and disability in the world. Statins are a widely used group of cholesterol-lowering agents that act by inhibiting the enzyme 3-hydroxy 3-methylglutaryl CoA (HMG CoA) reductase, which catalyses the rate-limiting step of cholesterol biosynthesis. In addition to their cholesterol-lowering properties, however, statins exert a number of so-called 'pleiotropic' actions. Data has emerged largely from thromboembolic animal models of stroke and cultivated cells. It is suggested that statins which have efficacy in preventing the stroke pretreatedly may have a positive effect even given post ischemia possibly through their pleiotropic effects. Mechanisms of the protective actions on cerebral ischemia include the inhibition of inflammatory responses, the improvement of endothelial dysfunction, the regulation of apoptosis proteins, the reduction of oxidative damage and the control of other relative endogenous signal pathways. Attempting to review these properties of statins is an exciting work that will improve our understanding on stroke and thus enable us to better use clinically this type of drugs. The present review summarizes available evidences on the effects and the potential molecular mechanisms of statins on cerebral ischemia.

Adenosine A(3) receptors regulate heart rate, motor activity and body temperature.

AIM: To examine the phenotype of mice that lack the adenosine A(3) receptor (A(3)R). METHODS: We examined the heart rate, body temperature and locomotion continuously by telemetry over several days. In addition, the effect of the adenosine analogue R-N(6)-phenylisopropyl-adenosine (R-PIA) was examined. We also examined heat production and food intake. RESULTS: We found that the marked diurnal variation in activity, heart rate and body temperature, with markedly higher values at night than during day time, was reduced in the A(3)R knock-out mice. Surprisingly, the reduction in heart rate, activity and body temperature seen after injection of R-PIA in wild type mice was virtually eliminated in the A(3)R knock-out mice. The marked reduction in activity was associated with a decreased heat production, as expected. However, the A(3)R knock-out mice, surprisingly, had a higher food intake but no difference in body weight compared to wild type mice. CONCLUSIONS: The mice lacking adenosine A(3) receptors exhibit a surprisingly clear phenotype with changes in diurnal rhythm and temperature regulation. Whether these effects are due to a physiological role of A(3) receptors in these processes or whether they represent a role in development remains to be elucidated.

Adenosine A(1) receptors and vascular reactivity.

AIM: Blood pressure is higher in A(1) receptor knock-out (A(1)R-/-) mice than in wild type litter mates (A(1)R+/+) and we have examined if this could be related to altered vascular functions. METHODS: Contraction of aortic rings and mesenteric arteries were examined. To examine if the adenosine A(1) receptor-mediated contraction of aortic muscle was functionally important we examined pulse pressure (PP) and augmentation index (AIX) using a sensor that allows measurements of rapid pressure transients. RESULTS: Contraction of aortic rings to phenylephrine and relaxation to acetylcholine were similar between genotypes. The non-selective adenosine receptor agonist N-ethyl carboxamido adenosine (NECA) enhanced the contractile response, and this was eliminated in aortas from A(1)R-/- mice. However, in mesenteric arteries no contractile response was seen and adenosine-mediated relaxation was identical between studied genotypes. A(2B) adenosine receptors, rather than A(2A) receptors, may be mainly responsible for the vasorelaxation induced by adenosine analogues in the examined mouse vessels. PP was higher in A(1)R-/- mice, but variability was unaltered. AIX was not different between genotypes, but the NECA-induced fall was larger in A(1)R-/- mice. CONCLUSIONS: The role of adenosine A(1) receptors in regulating vessel tone differs between blood vessels. Furthermore, contractile effects on isolated vessels cannot explain the blood pressure in A(1) knock-out mice. The A(1) receptor modulation of blood pressure is therefore mainly related to extravascular factors.

Sex differences in mouse heart rate and body temperature and in their regulation by adenosine A1 receptors.

AIM: To examine cardiac function, body temperature and locomotor behaviour in the awake adenosine A(1) receptor knock out mouse of both sexes. METHODS: Male and female A(1)R (+/+) and (-/-) mice, instrumented with telemetric devices, were recorded during basal conditions and after drug administration. RESULTS: Female mice had higher heart rate, body temperature and locomotion, both during daytime and during the night. Awake A(1)R (-/-) mice had a slightly elevated heart rate, and this was more clear-cut in males. Heart rate was also higher in Langendorff-perfused denervated A(1)R (-/-) hearts. Body temperature was higher in A(1)R (-/-) males and females; locomotor activity was higher in A(1)R (-/-) females, but not in males. The adenosine receptor agonist R-PIA (0.2 mg kg(-1)) decreased heart rate and body temperature, but less in A(1)R (-/-) animals than in A(1)R (+/+) mice (P < 0.001 in both parameters). The unselective adenosine receptor antagonist caffeine had a minor stimulatory effect on heart rate in lower doses, but depressed it at a dose of 75 mg kg(-1). Body temperature was increased after a low dose (7.5 mg kg(-1)) of caffeine in both sexes and genotypes, and markedly reduced after a high dose (75 mg kg(-1)) of caffeine. An intermediary dose of caffeine 30 mg kg(-1) increased or decreased body temperature depending on genotype and sex. Locomotor responses to caffeine were variable depending both on genotype and sex. CONCLUSION: Thus, the adenosine A(1) receptor is involved in the regulation of heart rate, body temperature and locomotor activity, but the magnitude of the involvement is different in males and females.

Eliminating the antilipolytic adenosine A1 receptor does not lead to compensatory changes in the antilipolytic actions of PGE2 and nicotinic acid.

AIM: We examined whether compensatory changes after adenosine A(1) receptor knockout [A(1)R (-/-)] eliminate the antilipolytic actions mediated by this receptor. METHODS: Lipolysis experiments were performed on adipocytes prepared from the wild type A(1)R (+/+), A(1)R (-/-) and heterozygous mice. Gene expression was assayed with cDNA microarray technique and real-time PCR; protein expression with immunoblotting. RESULTS: The A(1)R was the only adenosine receptor involved in lipolysis. The effects of adenosine deaminase and 2-chloroadenosine were abolished in A(1)R (-/-) mice. The IC(50) value of 2-chloroadenosine doubled from 16.6 to 33.6 nm when half of the A(1)Rs were eliminated. Adrenergic alpha(2) agonists had no effects on lipolysis. Prostaglandin E(2) (PGE(2)) inhibited lipolysis with an IC(50) value of 5.8 nm (4.7-7.2 nm) in the A(1)R (+/+) mice and 10.6 nm (9.0-12.6 nm) in the A(1)R (-/-) mice. Nicotinic acid inhibited lipolysis with an IC(50) value of 0.30 microm (0.19-0.46 microm) in the A(1)R (+/+) mice and 0.24 microm (0.16-0.37 microm) in the A(1)R (-/-) mice. G(i)alpha(1) mRNA was significantly up-regulated in adipose tissue from A(1)R (-/-) mice. However, immunoblotting showed that G(ialpha1) was not up-regulated at the protein level. CONCLUSION: The A(1)R mediates the antilipolytic actions of adenosine. Deletion of the A(1)R in mice does not result in compensatory increases in G-protein-mediated antilipolytic actions of PGE(2) or nicotinic acid.

Endogenous Mtv-8 or a closely linked sequence stimulates rearrangement of the downstream V kappa 9 gene.

Mtv-8 is an endogenous retrovirus located 4.6 kb upstream of a V kappa region gene (called V kappa 9M) within the kappa-Ig locus. The proximity of these two genes resulted in several effects. Using a newly developed RNase protection assay for measuring transcription from a single endogenous provirus, we found that Mtv-8 transcription could be detected after juxtaposition of the kappa-enhancers to the normally silent provirus. Reciprocally, using the polymerase chain reaction we observed that the frequency of V kappa 9M rearrangement was 5- to 10-fold higher in spleens from Mtv-8-positive mice (BALB/c, C58.C, A/J, and B6) compared to spleens from mice that lacked the Mtv-8 provirus (C58, C.C58, NZB, and PERA/Ei). Molecular cloning and sequencing of the V kappa 9M gene from C.C58 mice (containing the kappa-locus from C58 mice on a BALB/c background) indicated that at least some Mtv-8-negative strains have a functional V kappa 9M gene. Together these data suggest that Mtv-8 or a closely linked gene enhances V kappa 9M rearrangement. Since Mtv-8 also reportedly produces a superantigen, it appears that Mtv-8 may influence both the T cell and B cell repertoires.

The endogenous Mtv-8 provirus resides within the V kappa locus.

The endogenous Mtv-8 provirus previously has been mapped within approximately 0.52 centimorgan from several V kappa markers on mouse chromosome 6. Using Southern blotting and DNA from a recombinant backcross mouse from the C57BL/6 (Mtv-8 positive) and C58 (Mtv-8 negative) strains, Mtv-8 was localized to the same side of the crossover point as immunoglobulin kappa (Ig kappa)-V24 but on the opposite side of the crossover from Ig kappa-V10 and Ig kappa-V21. Molecular cloning and characterization of cellular DNA adjacent to Mtv-8 revealed a functional V kappa 9 gene approximately 4.6 kb downstream and in the same transcriptional orientation as the provirus. These data suggest that Mtv-8 is within the centromere-proximal portion of the V kappa locus.

The endogenous retrovirus Mtv-8 on mouse chromosome 6 maps near several kappa light chain markers.

Endogenous retroviruses are known to affect expression of cellular genes in the vicinity of their integration sites. The endogenous mouse mammary tumor provirus (Mtv-8) previously has been reported to reside on mouse chromosome 6 near the immunoglobulin kappa chain locus. Using pairs of mouse strains on the BALB/c (Mtv-8 positive) and C58 (Mtv-8 negative) backgrounds which are congenic for chromosome 6 genetic markers, we have confirmed the chromosome assignment of this provirus. Moreover, we have analyzed the N1 progeny of a (B6 X C58) X C58 backcross to determine the segregation of the Mtv-8 provirus with respect to polymorphisms in the Igk-VSer and Igk-J loci. The results with congenic and backcross mice together with results of others suggest that Mtv-8 is located approximately 0.52 cM from several closely linked kappa markers on chromosome 6.

Mammalian osteoclasts express a transient potassium channel with properties of Kv1.3.

Previous studies have revealed that expression of K+ channels in osteoclasts correlates with cell morphology and is influenced by interaction with the extracellular matrix. In this study, we investigated the electrophysiological properties of an outwardly rectifying K+ channel in rat and mouse osteoclasts using patch-clamp techniques. Cell-attached patch recordings revealed a channel of approximately 14 pS conductance that opened upon depolarization, and had a reversal potential close to that predicted for a K+ channel. Channel activity was transient; inactivation of ensemble currents, like that of whole-cell currents, occurred as a single exponential process. Both single-channel and macroscopic currents exhibited use-dependent inactivation in response to repetitive depolarizations. Two scorpion toxins, margatoxin and charybdotoxin, blocked this transient K+ channel, with half-maximal inhibition at 200 pM and 5 nM, respectively. In contrast, dendrotoxin (500 nM) had little effect. In summary, the outwardly rectifying K+ channel in osteoclasts resembles the Shaker-related K+ channel, Kv1.3. When membrane potential was recorded in whole-cell configuration, charybdotoxin (50 nM) caused a depolarization of 5 to 10 mV from resting levels of -50 mV or more positive; therefore this K+ channel contributes to the membrane potential of osteoclasts under some conditions. To investigate the molecular nature of osteoclast K+ channels, we performed RT-PCR on osteoclast RNA using primers for Kv1.3 and the inward rectifier, IRK1. mRNA encoded by Kv1.3 and IRK1 was detected and message identity confirmed by restriction enzyme digestion and sequence analysis. We conclude that osteoclasts exhibit, in addition to the previously described inward rectifier, an outwardly rectifying K+ conductance with properties of the Kv1.3. channel.

A method for in vitro mapping of ultrasonic speed and density in breast tissue.

A method has been developed for mapping density and ultrasonic speed in 1 mm thick slices of soft tissue with a resolution of about 1 mm. Tests using phantom sections have verified the accuracy and resolution of the ultrasonic speed maps. The method has been applied to breast tissues of three patients including tumors and surrounding tissue. Fixing a specimen in 5% formaldehyde did not change the degree of local variation in ultrasonic speeds, and raised mean speeds by less than 0.8%. The densities with fixing remained almost unchanged at low tissue densities (0.93 g/cm3), but rose 1.5% for higher tissue density (greater than 1.00 g/cm3).