A comparison of radiosensitization by etanidazole and pimonidazole in mouse tumors.

Radiosensitization by pimonidazole (Ro 03-8799) was tested in three murine tumors, EMT6/SF using the excision assay, SCC-VII/SF using the excision and growth delay assays, and MDAH-MCa-4 using TCD50 assays with both single doses and 6 fractions of radiation with a 24-hr interfraction interval. Results were compared with those using etanidazole (SR-2508), both at equitoxic doses and at doses giving tumor concentrations similar to those achievable in the clinic. In excision assays with EMT6/SF and SCC-VII/SF tumors, pimonidazole and etanidazole gave similar radiosensitization at similar concentrations in the tumors. Pimonidazole, however, did not demonstrate radiosensitization in SCC-VII/SF tumors in the growth delay assay, despite tumor concentrations that gave maximum sensitization in the excision assay. Furthermore, pimonidazole gave less than expected sensitization in single dose and 6-fraction TCD50 assays with MDAH-MCa-4 tumors, and less sensitization than comparable levels of etanidazole in this tumor line. When the concentration of pimonidazole in the tumors was approximately 0.36 mumoles/g the dose modification factor (DMF = dose without sensitizer/dose with sensitizer to give an isoeffect) was 1.56 (1.40-1.74, 95% c.l.) in single dose TCD50 assays. Etanidazole, however, gave a DMF of 1.92 (1.59-2.32) with a tumor concentration of approximately 0.32 mumoles/g and 1.69 (1.46-1.96) with a tumor concentration of approximately 0.21 mumoles/g. Thus, etanidazole gave more consistent sensitization for different tumors and different endpoints than did pimonidazole. The results appear to confirm the disappointing performance of pimonidazole in the clinic.     

Mood and spatial memory: emotion and right hemisphere contribution to spatial cognition.

Depressed persons show an impairment of spatial cognition that may reflect the influence of affective arousal on right hemisphere cognition. We examined normal university students to determine whether individual differences in mood and arousal levels would be related to performance on a spatial memory task. Right-hemisphere specialization for this spatial memory task was confirmed by a left field advantage for the targets and this field asymmetry was enhanced as task difficulty was increased. Event-related brain potentials (ERPs), assessed with a 64-channel sensor array, showed a processing negativity contralateral to the target in the P300 interval (300-500 ms after the target appeared). This effect increased as task difficulty was increased. A stronger posterior negativity for good (rather than bad) targets may suggest that attention was allocated toward the good locations. A suggestion of right hemisphere sensitivity to mood in this normal sample was a tendency for the subjects high in Negative Arousal not to show the normal right hemisphere (left field) superiority for the spatial memory task. Interestingly, a medial frontal lobe negativity was elicited in the ERPs by the bad targets, perhaps paralleling the error-related negativity observed in other paradigms. This medial frontal negativity was also seen in response to the feedback stimulus for the bad targets. Motivation may be important to this frontal effect: It was enhanced for subjects describing themselves as high in either positive or negative affective arousal during the task.     

Effect of standard doses of epinephrine on myocardial oxygen delivery and utilization during cardiopulmonary resuscitation

This preliminary study was conducted to evaluate the effects of 0.02 mg/kg of epinephrine (E) on myocardial blood flow (MBF), myocardial oxygen consumption (MVO2), and delivery (MDO2) when administered during CPR after 10-min cardiopulmonary arrest. Five miniature swine were instrumented for MBF measurements using tracer microspheres. Ventricular fibrillation was induced. After 10 min, CPR was begun with a pneumatic compressor. Measurements of MBF, arterial, and coronary sinus blood gases were made. After 3 min of CPR, each animal received 0.02 mg/kg of E. The measurements were repeated and defibrillation was attempted. During CPR, MDO2 and MVO2 were 0.2 +/- 0.3 and 0.2 +/- 0.3 ml/min/100 g tissue, respectively. The myocardial oxygen extraction ratio (ER) was 94.2 +/- 3.0%. After 0.02 mg/kg of E, MDO2 was 1.1 +/- 1.4, MVO2 was 1.0 +/- 1.3, and ER was 93.9 +/- 0.7% (p greater than .05). There were no successful defibrillations. These data indicate that MDO2 improves slightly during CPR after 0.02 mg/kg of E, but it does not meet the oxygen demands of the fibrillating heart.     

Publication trends in telesupervision: A content analysis study

Thirty-five empirical studies from 25 peer-reviewed journals and one book chapter were analyzed through a content analysis for trends in publication, methodological, and research foci in telesupervision between 1990 and 2016. The most significant increase in publications occurred in the past decade. Methodological trends revealed that video-conferencing, webcam, and cybersupervision were frequent terminologies used to describe telesupervision. Studies were focused on supervisee experiences, used an individual supervision method, a videoconferencing medium of supervision delivery, and a qualitative methodology with both male-female samples. Studies examined three topics: effectiveness of telesupervision, counselor development, and supervisory relationship. Implications and future research directions are discussed.     

Hiatal hernia repair with mesh: a survey of SAGES members

Background  

Primary repair of large hiatal hernia is associated with a high recurrence rate. The use of mesh may reduce this recurrence rate. The indication for mesh use, the type of mesh to use, and the placement technique are controversial. A survey of surgeon practice was undertaken to obtain a better understanding of the controversies surrounding this clinical problem.     

Role of p21‐activated kinase in cell polarity and directional mesendoderm migration in the Xenopus gastrula

The p21 activated kinases (Paks) are prominently involved in the regulation of cell motility. Using a kinase‐dead mutant of xPak1, we show that during Xenopus gastrulation, the kinase activity of Pak1 is required upstream of Cdc42 for the establishment of cell polarity in the migrating mesendoderm. Overactivation of Pak1 function by the expression of constitutively active xPak1 compromises the maintenance of cell polarity, by indirectly inhibiting RhoA function. Inhibition of cell polarization does not affect the migration of single mesendoderm cells. However, Pak1 inhibition interferes with the guidance of mesendoderm migration by directional cues residing in the extracellular matrix of the blastocoel roof, and with mesendoderm translocation in the embryo. Developmental Dynamics 238:1709–1726, 2009. © 2009 Wiley‐Liss, Inc.     

Bordetella pertussis binds human C1 esterase inhibitor during the virulent phase, to evade complement-mediated killing

C1 esterase inhibitor (C1inh) is a major inhibitor of several pathways of inflammation in humans. In this study, we show that virulent-phase cultures of Bordetella pertussis, the etiological agent for whooping cough, but not other Bordetella species specifically recruit C1inh from human serum. Using a spontaneous mutant of B. pertussis that was deficient in C1inh binding, we demonstrate that the ability of B. pertussis to acquire high levels of human C1inh and wild-type levels of serum resistance are well correlated, suggesting that, in addition to and independent of BrkA expression, acquisition of C1inh is vital to B. pertussis resistance to complement-mediated killing.