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Background: Health economics and outcomes research (HEOR) is a growing field that provides important information for making healthcare coverage and access decisions. However, there is no standard process for incorporating HEOR into the decision-making process, and the current use of HEOR by healthcare payers remains unknown., Objectives: To examine how HEOR data are being used by healthcare payers, including managed care organizations today, and how the use of such data is expected to change in the future in relation to access and reimbursement decision-making., Methods: The Managed Care Survey (MCS) and the Pharmacy & Therapeutics (P&T) Committee Survey (PTS) were distributed to decision makers in the United States. A total of 72 managed care decision makers responded to the MCS and 30 P&T Committee members responded to the PTS from US healthcare organizations that cover from tens of thousands to millions of lives. The goal of these surveys was to understand the current use of HEOR data, perceived barriers and limitations in the use of HEOR, and the expectations for future use, and how these and other factors affect formulary decisions. An international perspective was gained by modifying the MCS based on feedback received at a European conference, and a pilot version was given to individuals in emerging markets across Asia, Latin America, and the Middle East and Africa., Results: The majority of US respondents to the MCS (74%; N = 53) and to the PTS (77%; N = 23) indicate that HEOR is currently being used in their decision-making process; but the majority of respondents to the MCS (66%; N = 48) also state that quality assessment is limited (quality assessment was not addressed in the PTS). In addition, the majority of respondents to the MCS (82%; N = 59) expect the use of HEOR to increase in the future. Safety and efficacy were reported in the PTS to be the most important factors in the P&T Committee decision-making process, followed by head-to-head comparisons, and cost. The current use of HEOR in Asia, Latin America, and the Middle East and Africa varied widely across respondents., Conclusion: This study provides an important benchmark of HEOR use in the United States before the implementation of healthcare reform. Between the years 2010 and 2011, HEOR data were used to varying extents across global regions, but their use in the future is likely to increase in relation to access and reimbursement decisions.

This descriptive study assessed dental students' attitudes about computer use as it relates to study habits and use of e-textbook technology. Academic deans and student leaders at all accredited dental education programs in the United States, Puerto Rico, and Canada were asked to forward an e-mail to students explaining the purpose of the study and asking them to participate. The e-mail included an embedded URL link to the survey. A total of 703 complete responses from twenty-four dental schools were received and used in the final analysis. Because the number of students contacted could not be determined, the overall response rate cannot be calculated. Over 65 percent of the respondents reported spending >11 hours per week studying although over 75 percent said they spent little time studying from their textbooks. Over 55 percent were from schools that use e-textbooks exclusively, with 25 percent from schools that exclusively use print textbooks. One-fourth indicated they purchased a traditional printed textbook even when an e-textbook was provided; more than one-third printed information from the e-textbooks rather than reading on the computer. A majority (59 percent) preferred traditional textbook resources over e-textbooks, with over 50 percent reporting not using the required e-textbooks at all. E-textbooks were used by students in this study less frequently than materials/notes provided by dental school faculty. The majority preferred to use traditional resources as references and for augmenting lecture material.

Background: Phase-contrast MRI (PC-MRI) has previously been used for the quantification of CSF and blood flow throughout the body. We propose a new method of semi-automated segmentation for the prepontine cistern based on anatomical and pulsatility information., Methods: Scans were conducted on 48 patients (69.83 ± 14.28 years) ranging in age from 32 to 88 years along with an additional 11 controls (51.91 ± 21.13 years) ranging in age from 22 to 72 years. The segmentation algorithm developed consists of four stages: anatomical, flow quantification for the aqueduct and prepontine cistern, and blood vessel detection., Results: Complete results are presented in Table 1, the 37 preoperative patients and controls had a prepontine cistern stroke volume of 464.32 ± 202.30 and 447.38 ± 75.49 respectively., Conclusion: Reliable quantification of volumetric CSF flow in complex cisternal spaces is possible using a methodology combining known anatomical features with the pulsatile nature of CSF flow.

Medulloblastomas (MB) are highly aggressive primitive neuroectodermal tumors (PNET) usually located in the posterior fossa. Current treatment for MBs, which includes a combination of surgery, chemotherapy and radiation, remain challenging especially in younger patients. However, advances in the understanding of regulatory pathways in cerebellar development have elucidated possible areas of dysfunction involved in tumorigenesis. Multiple studies have demonstrated the importance of the sonic hedgehog, Wnt, and Notch pathways in MB pathogenesis at the molecular level. While staging and prognosis are often based on the Chang classification system, future algorithms will involve identifying molecular markers in order to allow for more specific risk stratifications of various MB subtypes and provide improved correlation with staging and prognosis. Future development of novel therapies that target the heterogeneity of MB and are tailored to the tumor's unique molecular profile may yield improved outcomes for these patients., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Although patients with cerebral cavernous malformations may remain asymptomatic, they often present with neurological symptoms of headache, hemorrhage and, most commonly, seizure. A review of articles published between 1985 and 2009 was performed to elucidate the prognostic factors which may predict post-operative seizure control. The following characteristics were found to consistently correlate with a more favorable post-operative seizure-free outcome: (i) extent of resection of the cavernous malformation and its surrounding hemosiderin rim; (ii) single or sporadic seizures compared to chronic epilepsy; (iii) illness duration less than 1 or 2 years; and (iv) size of cavernous malformation less than 1.5 cm. Radiosurgery may achieve post-operative seizure-free rates ranging from 25% to 64.3%, and may be an alternative to surgical resection for deep or eloquent cavernous malformations, or those in patients with co-morbidities. There was no clear association between post-operative seizures and either lesion location, age, or gender. Prognostic features of cavernous malformations should be utilized for both guidance of lesion treatment, and prediction of post-operative seizure outcomes., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: This study compares open tibia fractures in US Navy and US Marine Corps casualties from the current conflicts with those from a civilian Level I trauma center to analyze the effect of blast mechanism on limb-salvage rates., Methods: Data from the 28,646 records in the University of California San Diego Trauma Registry from 1985 to 2006 was compared with 2,282 records from the US Navy and US Marine Corps Combat Trauma Registry Expeditionary Medical Encounter Database for the period of March 2004 to August 2007. Injuries were categorized by Gustilo-Anderson (G-A) open fracture classification. Independent variables included age, gender, mechanism of injury including blast mechanisms, shock, blood loss, prehospital time, procedures, Injury Severity Score, length of stay, and Mangled Extremity Severity Score (MESS). Dependent variables included early or late amputation and mortality., Results: The civilian group had 850 open tibia fractures with 45 amputations; the military group had 21 amputation patients (3 bilateral) in 115 open tibia fractures. Military group patients were more severely injured, more likely have hypotension, and had a higher amputation rate for G-A IIIB and IIIC fractures then civilian group patients. Blast mechanism was seen in the majority of military group patients and was rare in the civilian group. MESS scores had poor sensitivity (0.46, 95% confidence interval: 0.29-0.64) in predicting the need for amputation in the civilian group; in the military group sensitivity was better (0.67, 95% confidence interval: 0.43-0.85), but successful limb salvage was still possible in most cases with an MESS score of ≥7 when attempted., Conclusion: Despite current therapy, limb salvage for G-A IIIB and IIIC grades are significantly worse for open tibia fractures as a result of blast injury when compared with typical civilian mechanisms. MESS scores do not adequately predict likelihood of limb salvage in combat or civilian open tibia fractures.

We present an application of a socially assistive robotics (SAR) system in a therapeutic setting. We examine the amount of interaction elicited by the robot in a therapeutic setting with individuals post-stroke. We examine the role of various communication modalities, and their affects on the participants' responses. Seven participants of mild to moderate functional impairment due to stroke interacted with our SAR system during three sessions of motor task practice. The robot guided the users as they performed a wire puzzle task, while providing them with feedback about their performance. We evaluated the amount of verbalization and eye contact made with the robot. Our results indicate that users make eye contact more often than they verbalize when interacting with the robot. Further, user interactions are most frequent at the beginning of a practice session, and occur less frequently as the session progresses. When a user observes that the robot is not responding to a certain type of communication, the user limits the use of that communication modality. These insights should be useful in the design of future robot-based therapeutic interventions., (© 2011 IEEE)

Background: Post-transplantation primary central nervous system lymphoma (PT-PCNSL) is a rare neoplasm that can develop within months to years after transplantation, and imaging often reveals multiple lesions with homogeneous or ring enhancement. The clinical and imaging presentation of PT-PCNSL can often be nonspecific and present a diagnostic challenge., Case Description: A 56-year-old woman presented to a tertiary university emergency room with altered mental status 15 months after undergoing renal transplantation. On brain MRI, she was found to have three rim-enhancing mass lesions, and biopsy revealed PT-PCNSL., Conclusion: There has been a steady increase in the number of patients living following organ transplantation in the United States and an increasing likelihood that PT-PCNSL will increasingly be encountered in neurosurgical practice. We present here a case of PT-PCNSL and a brief review of the relevant clinical characteristics, treatment options, and prognosis of PT-PCNSL.

Background: Approximately 30,000 people are diagnosed with oral cancer annually in the United States. Recent evidence suggests that nutrition may play a more complex role in the prevention of oral cancers than previously believed. Proanthocyanidins (PACs) are a class of compounds found in normal dietary foods that exhibit chemopreventive properties and chemotherapeutic potential. Recently preliminary evidence suggests that PACs inhibit the proliferation of oral cancer cell lines. The primary goal of this study was to elucidate the mechanisms responsible for previous observations that grape seed-derived PACs significantly inhibited oral cancer proliferation., Methods: Using the well-characterized oral squamous cell carcinoma cell lines, CAL27 and SCC25, as well as nontumorigenic cell lines, a series of in vitro assays was performed to quantify the temporal and dose-specific growth inhibitory properties of PAC on oral cancers. In addition, quantitative analysis of mRNA from key intracellular signaling pathway molecules, involved in both cell-cycle control and apoptosis, were analyzed using Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)., Results: This study found that oral cancer proliferation was inhibited by 24 hours in the PAC concentration range of 50-70 μg/mL with concomitant decreases in mRNA expression of specific cell-cycle regulators, and increases in the expression of apoptosis-specific molecules, such as caspase-2 and caspase-8., Conclusion: These results may represent the first demonstration of simultaneous, temporal inhibition of cell-cycle signaling pathways with the activation of specific apoptosis-related signaling pathways within oral cancers in response to PAC, lending further support to the concept that PACs may be promising candidates for adjuvant or complementary therapies for oral cancer patients.

Background: Combat injury patterns differ from civilian trauma in that the former are largely explosion-related, comprising multiple mechanistic and fragment injuries and high-kinetic-energy bullets. Further, unlike civilians, U.S. armed forces combatants are usually heavily protected with helmets and Kevlar body armor with ceramic plate inserts. Searchable databases providing actionable, statistically valid knowledge of body surface entry wounds and resulting organ injury severity are essential to understanding combat trauma., Methods: Two tools were developed to address these unique aspects of combat injury: (1) the Surface Wound Mapping (SWM) database and Surface Wound Analysis Tool (SWAT) software that were developed to generate 3D density maps of point-of-surface wound entry and resultant anatomic injury severity; and (2) the Abbreviated Injury Scale (AIS) 2005-Military that was developed by a panel of military trauma surgeons to account for multiple injury etiology from explosions and other high-kinetic- energy weapons. Combined data from the Joint Theater Trauma Registry, Navy/Marine Combat Trauma Registry, and the Armed Forces Medical Examiner System Mortality Trauma Registry were coded in AIS 2005-Military, entered into the SWM database, and analyzed for entrance site and wounding path., Results: When data on 1,151 patients, who had a total of 3,500 surface wounds and 12,889 injuries, were entered into SWM, surface wounds averaged 3.0 per casualty and injuries averaged 11.2 per casualty. Of the 3,500 surface wounds, 2,496 (71%) were entrance wounds with 6,631 (51%) associated internal injuries, with 2.2 entrance wounds and 5.8 associated injuries per casualty (some details cannot be given because of operational security). Crude deaths rates were calculated using Maximum AIS-Military., Conclusion: These new tools have been successfully implemented to describe combat injury, mortality, and distribution of wounds and associated injuries. AIS 2005-Military is a more precise assignment of severity to military injuries. SWM has brought data from all three combat registries together into one analyzable database. SWM and SWAT allow visualization of wounds and associated injuries by region on a 3D model of the body.

Four two-day dental school simulation courses were conducted over a two-year period for the purpose of allowing prospective dental students the opportunity to gain hands-on experience in a dental simulation lab. A total of 292 subjects from thirty-four colleges and universities participated in the courses. The courses were planned and taught by dental students attending the host school, with oversight by faculty members. Participants took pre- and posttests assessing their knowledge of dental practices and completed surveys before and after the course to assess their attitudes toward the dental profession. Student instructors completed a post-course survey of the experience. The simulation course was effective in increasing participants' desire (8 percent increase) to attend the host school. Dental knowledge improved 34 percent following the course. Thirty-four percent of student instructors indicated they were more likely to pursue a career in academics following this experience. Results suggest that a dental school simulation course can be a positive experience for both participants and student instructors.

Topical negative pressure is an effective technique to promote wound healing and the integration of skin graft and synthetic dermal equivalents. We describe an in vitro model to investigate the effect of negative pressure on angiogenesis, a pivotal step. Dermal fibroblasts or human microvascular endothelial cells were cultured on Integra and subjected to intermittent or continuous negative pressure. At fixed intervals of over 120 hours, the Integra was fixed and assessed for cell migration (microscopy), cell viability (MTS assay), and cell proliferation (Ki67 immunostaining). Under control conditions, endothelial cells formed a monolayer and failed to ingress, whereas fibroblasts migrated throughout the Integra within 24 hours. Negative pressure switches endothelial cell to a migratory and proliferative phenotype. Ingress is greatest with intermittent rather than continuous negative pressure. It has no effect on dermal fibroblast function. This study identifies an important, potential pro-angiogenic mechanism by which topical negative pressure promotes wound healing.

The objective of the present analysis was to examine the relationship between vigorous/moderate or strength training exercise, and mental health in a national sample of college females. Secondary data (n = 22,073) from the National College Health Assessment administered during the Spring 2002 and 2003 semesters were used in a cross-sectional design. Depression, anxiety, suicidal ideation, and perceived health were the dependent variables; and two measures of weekly exercise frequency were the independent variables. Vigorous/moderate exercise was associated with positively associated perceived health and modestly negatively associated with depression. Strength training exercise was positively associated with perceived health and modestly negatively associated with depression, anxiety, and suicidal ideation. These findings support an association between two forms of exercise and several indicators of mental health. Additional longitudinal research is needed prior to endorsing exercise as treatment for mental disorders.

The Navy-Marine Corps Combat Trauma Registry is a data repository summarizing information from data sets describing injuries sustained and treatments administered to casualties from the point of injury to rehabilitation. Among the medical facilities contributing data to the Combat Trauma Registry during Operation Iraqi Freedom were the Marine Corps forward surgical companies. The surgical companies offer resuscitative surgery, medical treatment, and temporary holding facilities, in addition to preparing patients for evacuation. This article reviews the types of patients admitted and treatments provided at the surgical companies during the major combat period of Operation Iraqi Freedom. The surgical companies saw an average of 15 to 17 patients per day during this period. Less than 20% of the U.S. casualties seen were wounded in action. In contrast, >75% of the enemy prisoner of war presentations were for battle injuries. Less than 15% of the patients were held at the facilities for >24 hours.

This investigation examined the wounds incurred by 279 U.S. Navy-Marine personnel (97% Marines and 3% sailors) identified as wounded in action during Operation Iraqi Freedom, from March 23 through April 30, 2003. The goal was to assess the potential impact of each causative agent by comparing the differences in anatomical locations, types of injuries caused, and medical specialists needed to treat the casualties. The overall average number of diagnoses per patient was 2.2, and the overall average number of anatomical locations was 1.6. The causative agents were classified into six major categories, i.e., small arms, explosive munitions, motor vehicle accidents, falls, weaponry accidents, and other/unknown. Explosive munitions and small arms accounted for approximately three of four combat-related injuries. Upper and lower extremities accounted for approximately 70% of all injuries, a percentage consistent for battlefield injuries since World War II.

Study Objectives: Idiopathic pulmonary fibrosis (IPF) is a poorly understood chronic respiratory disease of humans, which has no correlate in other animals. Understanding the role that inflammation, alveolar epithelial cells, and myofibroblasts play in the progression of the disease is controversial, and hampered by the lack of an animal model. We have identified spontaneous IPF in domestic cats and hypothesized that this newly identified disease shares the pathology of human IPF; further, this work provides data suggesting that the disease is related to a defect in type II pneumocyte biology., Setting and Subjects: Chronic respiratory disease with pathology consistent with usual interstitial pneumonia (UIP) spontaneously developed in 16 domestic cats., Results: The histopathology of feline IPF consisted of the following: (1) interstitial fibrosis with fibroblast/myofibroblast foci, (2) honeycombing with alveolar epithelial metaplasia and type II pneumocyte hyperplasia, and (3) alveolar interstitial smooth-muscle metaplasia. Interstitial inflammation was not a prominent feature of the disease. alpha-Smooth muscle actin-positive myofibroblasts were prominent in myofibroblast foci, beneath honeycomb and hyperplastic epithelium, and in alveolar septa away from the remodeling. Feline IPF type II pneumocyte ultrastructure is similar to a heritable form of human IPF, with abnormal cytoplasmic lamellar body-like inclusions., Conclusions: We conclude the following: (1) chronic respiratory disease with clinical and pathology features of UIP/IPF occurs in the domestic cat; (2) as in human IPF, the type II pneumocyte and myofibroblasts are important cellular constituents of feline IPF; and (3) type II cell ultrastructure suggests feline IPF is a defect in the type II pneumocyte.

Endothelial interactions with the extracellular matrix (ECM) play important roles in angiogenesis but whether specific ECM signals can determine specific cellular morphologies is unclear. The authors compared in vitro ECM-induced morphological responses of the phenotypically distinct human placental microvascular endothelial cells (HPMECs) with large vessel endothelial cells (HUVECs). HPMECs showed distinct patterns of reorganization in response to collagen-I or collagen-IV (monolayer disruption, sprouting, migration) and Matrigel or laminin-A (intussusception, cord formation, tubulogenesis), and an intermediate response to fibrin; whereas HUVECs responded similarly to collagen-1 and Matrigel (elongation, lattice formation, vacuolation) and showed little response to fibrin. Although the extent of collagen and Matrigel responses of HPMECs were increased by serum, acidic or basic fibroblast growth factor (aFGF, bFGF), or vascular endothelial growth factor (VEGF), and varied with matrix protein concentration, the basic patterns were matrix specific, and were independent of fibronectin. The collagen responses correlated with disruption of adherens and tight junctions and the formation of filopodial protrusions. Matrigel responses were associated with up-regulated junctional localization of VE-cadherin, and tubulogenesis developed mainly through paracellular remodeling rather than intracellular vacuolation. Overall, these findings suggest that distinct ECM interactions stimulate specific morphological responses. These signals may regulate morphological behaviour in the angiogenesis cycle, switching endothelial cells between migratory and vasculogenic phenotypes.

Background: A previous publication indicates a lack of clear guidelines for DNAR orders in Norwegian hospitals. The Norwegian Board of Health has recently published strict requirements for such a procedure., Material and Methods: Patients discharged from a surgical department from 1 March to 31 May 2001 with complicated or advanced cancer and/or a postoperative stay of minimum ten days. The patient files were studied for information on DNAR orders and/or cardiac arrest., Results: 13 out of 69 patients had a DNAR order. In eight of them there was either no explanatory note in the files or no correct signature. Three of the five other patients had taken part in the discussion, so had next-of-kin in two circumstances. Resuscitation was not initiated in any of 14 patients with cardiac arrest. Six of these, who had no DNAR order, all had advanced, inoperable cancer or serious chronic cardiac and respiratory failure. There were no signs that a DNAR order had influenced any other treatment decision., Interpretation: The department had a clear procedure for writing DNAR orders but it was followed in less than half of the cases.

Because managing a laboratory, or any health-care entity, is as much a business as a service, it is important for you to have a good grasp on how you can take opportunities from idea conception to implementation to assessment/revision. Regardless of the size of your proposed project, you need to consider a number of factors, among them: your history and what opportunities you can seize from your strengths and weaknesses; the overall business climate; anticipated costs; staff involvement; how you will market your project; and what measures to use to determine your success. Above all else, you need to set goals, both ultimate and intermediate, to instill focus, incentive, and a sense of achievement. The next time someone on your staff says, "Why don't we try that?," refer to this Template Topic. It can serve as a tool to help you determine whether you should try "that" and be the compass that helps guide your efforts.

The Center for Epidemiologic Study-Depression (CES-D) Scale has been used to assess levels of depressive symptomatology in cancer survivors but has not been validated in African American cancer survivors. The current study assessed the reliability and validity of the CES-D in 216 African American cancer survivors. A Cronbach alpha was calculated to determine internal consistency reliability, and correlations were computed between the CES-D and other measure of mood states (Profile of Mood States-Short Form and Bradburn Positive and Negative Affect Scales) to assess concurrent validity. The CES-D demonstrated acceptable internal consistency (= .90), and the concurrent validity was supported by significant correlations with other measures of mood states. These analyses indicate that the CES-D is a reliable and valid measure for use with African American cancer survivors. The mean CES-D score (M = 15.7, SD = 11.89) further suggests that this sample of African American cancer survivors exhibit significant levels of depressive symptomatology.

Background: Prolonged and complex laparoscopic procedures expose patients to large volumes of cool insufflation gas. The aim of this study was to compare the effects of a conventional room temperature carbon dioxide (CO2) pneumoperitoneum with those of a body temperature pneumoperitoneum., Methods: Patients were randomized to undergo laparoscopic cholecystectomy with a CO2 pneumoperitoneum warmed to either body temperature (n = 15) or room temperature (n = 15). The physiologic and immunologic effects of warming the gas were examined by measuring peroperative core and intraperitoneal temperatures, peritoneal fluid cytokine concentrations, and postoperative pain., Results: The mean duration of surgery was 32 min in both groups. Core temperature was reduced in the room temperature group (mean, 0.42 degrees C; p < 0.05). No reduction in temperature occurred when the gas was warmed. Greater levels of cytokines were detected in peritoneal fluid from the room temperature insufflation group tumor necrosis factor alpha (TNF-alpha): mean, 10.9 pg/ml vs. 0.42, p < 0.05; interleukin 1 beta (IL-1beta): mean, 44.8 pg/ml vs. 15.5, p < 0.05; and IL-6: mean, 60.4 ng/ml vs. 47.2. There was no difference in postoperative pain scores or analgesia consumption between the two groups., Conclusions: The authors conclude that intraoperative cooling can be prevented by warming the insufflation gas, even in short laparoscopic procedures. In addition, warming the insufflation gas leads to a reduced postoperative intraperitoneal cytokine response.

Background: Viable cancer cells may implant at distant sites and cause tumor recurrence. One possible mechanism is the inadvertent exfoliation of viable tumor cells during dissection. The ultrasonically activated scalpel (UAS) uses ultrasonic energy to disrupt tissues by cavitation and produces a dense cloud of cellular debris that may contain viable cells. This study aimed to investigate the viability of airborne cells released during cancer dissection using the UAS and electrosurgery., Methods: Flank tumors (n = 8) measuring 1 cm3 were induced in male WAG rats by subcutaneous injection of 2 x 10(6) CC531s colon cancer cells. Dissection was performed in cutting mode using the maximum power output of the respective devices. Electrosurgery was performed using a standard monopolar electrosurgical unit and a needle probe, and ultrasonic dissection was performed with the Harmonic Scalpel utilising the open surgical handset and the hooked spatula tip. The smoke plume was aspirated by a vacuum pump and bubbled under Hank's balanced salt solution to trap particulate matter. The viability of the cellular material was blindly assessed with the trypan blue test and by in vitro culture. The morphology of the cellular debris was studied by examination of cytospin preparations., Results: Large quantities of cellular debris was trapped in the plume from both devices. However, no viable cells were isolated, nor did in vitro cell growth occur with either device. Examination of the debris from the UAS demonstrated a characteristic mixture of amorphous forms and very few morphologically intact cells. The cauterized tumor produced charred cells and tissue fragments., Conclusions: In conclusion, this study demonstrates that viable airborne cancer cells are not released after tumor ablation with the UAS or electrosurgery.

The effect of early human immunodeficiency virus-1 infection in vitro on proximal signal transduction events in primary peripheral blood lymphocytes was investigated with respect to CD4-mediated costimulation of CD3/T cell-receptor signalling. Tyrosine phosphorylation profiles induced by CD4 and CD3 + CD4 ligation were profoundly abrogated in virally infected cells, although CD4 receptor expression remained intact during early infection. Furthermore, the association of the tyrosine kinase p56lck with the CD4 receptor was reduced in virally infected cells. The downmodulation of CD4-mediated CD3 signalling coincided with the subsequent inhibition of the activity and tyrosine phosphorylation of the downstream kinase ZAP-70 in virally infected cells. The observed virally mediated cosignalling defects during early infection may account for the inhibition of distal signal events and thus contribute to HIV pathogenesis, such as reduced immune response to antigenic exposure, anergy, and apoptosis.

The microfilamentous actin component of the cytoskeleton is crucial to endothelial angiogenesis and vascular permeability. Differences in actin cytoskeletal profiles in cultured human endothelial cells were explored: when first isolated, both primary human umbilical vein endothelial cells (HUVEC) and primary human placental microvascular endothelial cells (HPMEC) expressed F-actin, but not beta-actin or alpha-smooth muscle actin. A similar endothelial actin profile was observed in cryo-sections of freshly delivered term umbilical cord and placenta. In subsequent cell culture, although the actin cytoskeleton of HUVEC remained unchanged, the actin profiles of HPMEC altered after the second passage with the induction of alpha-smooth muscle actin expression, which was intercellularly heterogeneous and increased to 20% at P4. This behaviour occurred in HPMEC monolayers cultured on a variety of extracellular matrices. Comparisons with a spontaneously immortalized human microvascular cell-line, HGTEN 21, revealed that in prolonged passage, both alpha-smooth muscle actin and beta-actin were expressed, whereas HPMEC at P4 showed a lower level of beta-actin expression. Therefore, in comparison with large vessels, microvascular cells are more likely to dedifferentiate. This may reflect the ability of microvascular cells to remodel according to changing requirements for new vessel formation. In conclusion, passage of human microvascular endothelial cells, but not of larger vessel endothelial cells, alters the expression of actin isoforms. This may be important in relation to comparisons of in vitro and in vivo vascular permeability; higher passage microvascular endothelial cells should thus be used with caution in such studies.

Objective: The purpose of this study was to determine if the selective use of low-osmolality contrast material for excretory urography and CT is safe and if it saves money., Materials and Methods: At the University Medical Center in Tucson, a questionnaire was developed to identify high-risk patients who would benefit from the use of a low-osmolality contrast agent. High-risk patients were defined as those with a history of a reaction to contrast material, severe allergies, asthma, severe cardiac disease, multiple myeloma, sickle cell disease, polycythemia, pheochromocytoma, or renal impairment. Beginning in March 1993, the questionnaire was given to all adult outpatients scheduled for daytime excretory urography and routine CT studies of the head and body. Only patients identified as high risk were given a low-osmolality (non-ionic) contrast agent. All other patients received high-osmolality (ionic) contrast material. The contrast agent chosen for a patient was determined by the person administering the questionnaire, usually a radiologic technologist., Results: From March 1993 through December 1993, 1114 adult daytime outpatient excretory urographic and contrast-enhanced CT studies were examined at our institution. In 235 (21%) of the studies, a low-osmolality agent was used and in 879 (79%) studies, a high-osmolality agent was used. This represented a reduction in the use of low-osmolality agents from more than 90% of patients to 21%, an annual cost reduction from $288,000 to $60,480. We observed no untoward reactions to contrast material that could be specifically attributed to the increased use of high-osmolality agents., Conclusions: Selective use of low-osmolality contrast agents during excretory urography and CT can provide substantial cost savings and is not associated with a significant risk of major complications.

Nurses currently use several external measures referenced to the head and chest to predict the insertion distance for orogastric and nasogastric (NG) tubes. The ability of previously published regression equations on height to predict esophageal length for NG tube insertion was evaluated in a sample of 107 children.

1. In an in vitro preparation of the medullary pacemaker nucleus of Apteronotus, the consequences of a variety of ionic and pharmacological manipulations upon both ongoing activity and synaptic modulation of the nucleus were assessed. 2. Spontaneous rhythmicity in the pacemaker nucleus was found to be Na+-, K+-, and Ca(2+)-dependent. The extreme sensitivity to 4-aminopyridine (4-AP) relative to other treatments suggested that the K+ A-current is a critical element in the oscillations. 3. Elevated K+ or 4-AP were titrated to concentrations that suppressed spontaneous oscillations, but allowed modulatory, 'chirp' epsps to persist. The transition to elevated K+ revealed oscillatory properties in some neurons in the form of epsp-induced ringing 4. Threshold concentrations of 4-AP sufficient to halt oscillations, caused epsps to become larger and complex, increased input resistance, and enhanced the effects of current injection on epsp amplitude. A greater degree of voltage-sensitivity was also seen in later components of the complex epsp. 5. Several treatments presumed to increase Ca2+ caused desynchronization of firing and revealed diverging intrinsic frequencies among cells.

Nurses use several external measures referenced to the head and chest to gauge the insertion distance for orogastric and nasogastric (NG) tubes. Few of the measures have been tested. However, in previous studies height was the external measure most correlated with esophageal length both in children and adults. In this study, the ability of previously published regression equations on height to predict esophageal length for NG-tube insertion in 107 children was evaluated. The regression equations were examined for stability, predictive performance, and the likely positions of the tube. The data were heights and esophageal lengths obtained from esophageal manometry records and hospital charts. The predicted values for nasal insertions were biased and averaged 2.4 cm too long (R2prediction = .56, n = 30). Prediction errors greater than 5 cm in absolute value occurred in 25% of the nasally-referenced sample. The predicted values represented overestimates in 18 nasally referenced cases that were 11.5% longer on the average than the measured esophageal lengths. In contrast, the predicted values for the oral insertions were unbiased (R2prediction = .92, n = 77), and gave accurate predictions in the majority of cases. Eighty percent of the oral predictions were within +/- 1.5 cm of the measured esophageal length and represented percentage errors between 0 and 7% (M = 3%, n = 50).

1. Weakly electric fish generate around their bodies low-amplitude, AC electric fields which are used both for the detection of objects and intraspecific communication. The types of modulation in this signal of which the high-frequency wave-type gymnotiform, Apteronotus, is capable are relatively few and stereotyped. Chief among these is the chirp, a signal used in courtship and agonistic displays. Chirps are brief and rapid accelerations in the normally highly regular electric organ discharge (EOD) frequency. 2. Chirping can be elicited artificially in these animals by the use of a stimulus regime identical to that typically used to elicit another behavior, the jamming avoidance response (JAR). The neuronal basis for the JAR, a much slower and lesser alteration in EOD frequency, is well understood. Examination of the stimulus features which induce chirping show that, like the JAR, there is a region of frequency differences between the fish's EOD and the interfering signal that maximally elicits the response. Moreover, the response is sex-specific with regard to the sign of the frequency difference, with females chirping preferentially on the positive and most males on the negative Df. These features imply that the sensory mechanisms involved in the triggering of these communicatory behaviors are fundamentally similar to those explicated for the JAR. 3. Additionally, two other modulatory behaviors of unknown significance are described. The first is a non-selective rise in EOD frequency associated with a JAR stimulus, occurring regardless of the sign of the Df. This modulation shares many characteristics with the JAR. The second behavior, which we have termed a 'yodel', is distinct from and kinetically intermediate to chirping and the JAR. Moreover, unlike the other studied electromotor behaviors it is generally produced only after the termination of the eliciting stimulus.

The relationship between five different suture materials (expanded polytetrafluoroethylene (PTFE), polypropylene, polyglycolic acid, polydioxanone and polyglactin 910) and infection has been studied in 540 guinea-pig wounds contaminated with synergistic enteric organisms. The recently introduced expanded PTFE suture has been studied because, unlike the others, it has not previously been studied under these contaminated conditions. The incidence of wound infection in the control series was 26 per cent and all suture materials increased this figure significantly. The infection rate using expanded PTFE of 51 per cent was similar to all other sutures except polyglycolic acid, which produced an infection rate of 41 per cent. This difference was not statistically significant at the 5 per cent level. This confirms other studies including our own which show that the presence of most suture materials in contaminated wounds increases the incidence of infection. It further demonstrates that expanded PTFE is no different from other materials in this regard.

Previous studies have shown that infusions of propofol, a new intravenous anesthetic, were associated with decreased arterial pressure and slow heart rates. To evaluate the role of baroreflex mechanisms in sustaining these conditions, the effects of two infusion rates of propofol (54 and 108 micrograms.kg-1.min-1) to supplement 66% nitrous oxide in oxygen anesthesia were studied in twelve ASA class I patients having a mean age of 34 years. Baroreflex control of heart rate was studied by perturbing the patients' arterial pressure with phenylephrine or sodium nitroprusside. Valsalva maneuvers were used to assess the response of the systemic arterial system. Steady state anesthesia at both infusion rates was not associated with decreased sensitivity of the baroreflex control of heart rate, but resetting of the reflex occurred to allow lower arterial pressures for a given heart rate than in the awake state. During propofol infusions at either rate, the diastolic pressure overshoot normally associated with the relief of raised airway pressure in the Valsalva maneuver was significantly reduced. It is concluded that propofol/nitrous oxide anesthesia is not associated with impairment of baroreflex sensitivity, but that central sympatholytic and/or vagotonic mechanisms enable low heart rates to be sustained despite decreased arterial pressures.

We have taken advantage of the increasing understanding of glutamate neuropharmacology to probe mechanisms of well-defined vertebrate behaviors. Here we report a set of experiments that suggests distinct roles for two major classes of glutamate receptors in a discrete premotor nucleus of the brainstem. The medullary pacemaker nucleus of weakly electric fish is an endogenous oscillator that controls the electric organ discharge (EOD). Its regular frequency of firing is modulated during several distinct behaviors. The pacemaker nucleus continues firing regularly when isolated in vitro, and modulatory behaviors can be reproduced by stimulating the descending input pathway. Glutamate agonists applied to the pacemaker in vitro produced increases in frequency, while glutamate antagonists selectively blocked stimulus-induced modulations. Experiments with glutamate antagonists in the intact animal resulted in specific effects on two well-characterized behaviors. Our data indicate that these behaviors are separately mediated in the pacemaker by receptors displaying characteristics of the kainate/quisqualate and N-methyl-D-aspartate subtypes of glutamate receptor, respectively.

Direct measurements of systolic, diastolic, and mean arterial blood pressure and electrocardiogram-derived heart rates were compared with indirect arterial blood pressure measurements using the Dinamap 847XT noninvasive monitor. A total of 260 paired comparisons from 16 patients were analyzed. A regression analysis of paired data over a wide range of blood pressure values gave the following results: for heart rate r = 0.97, for systolic arterial pressure r = 0.84, for mean arterial pressure r = 0.73, and for diastolic arterial pressure r = 0.52. The 95% confidence limits for systolic, mean, and diastolic arterial pressure were +/- 16 mm Hg, +/- 18 mm Hg, and +/- 21 mm Hg, respectively. The Dinamap monitor was found to be an accurate trend recorder of heart rate and blood pressure during anesthesia in neonates and small infants.

Severe sepsis leads to depression of the reticulo-endothelial system (RES) with delayed bloodstream clearance of particulate matter and bacteria. Splenectomy results in increased susceptibility to infection with encapsulated organisms but its effect on the resistance to postoperative Gram-negative infection has been little studied. We have investigated the effect of splenectomy on RES function by measurement of plasma fibronectin concentrations and bacterial clearance in the presence and absence of sepsis. In experiment 1, rabbits underwent splenectomy (n = 8) or laparotomy only (n = 8) 4 weeks before a second laparotomy. In experiment 2, animals had either splenectomy (n = 8) or laparotomy only (n = 8) followed 4 weeks later by devascularization of the appendix (sepsis). Plasma fibronectin concentrations and the blood clearance and organ distribution of an intravenous injection of 75Se-labelled viable Escherichia coli (2-3 X 10(8) colony forming units (c.f.u.] were measured 24 h after the second operation. Splenectomy resulted in: (1) a persistent reduction in plasma fibronectin concentration in the presence and absence of sepsis, and (2) a delay in the bloodstream clearance with reduced hepatic (Kupffer cell) uptake of E. coli which was exaggerated in the septic splenectomized animal. It is concluded that the spleen may be important for Gram-negative bacterial clearance, possibly related to its influence on plasma fibronectin concentration and Kupffer cell function.

1. An in vitro preparation of the medullary pacemaker nucleus of the weakly electric fish Apteronotus leptorhynchus was studied which fires regularly and synchronously at the fish's characteristic frequency of electric organ discharge (EOD). Upon bipolar stimulation of tissue regions through which pass prepacemaker nucleus afferents to the pacemaker, a brief, transient increase in discharge frequency ensued at short-latency (Fig. 1A). 2. Intracellular recordings revealed that the acceleration was accompanied by a depolarization and decline in action potential amplitude. The magnitude of these changes was both phase- (Fig. 5) and amplitude-dependent, with the latter showing an evident threshold effect (Figs. 4 and 12). The response was reversibly blocked by high Mg2+ saline (Fig. 1B), and the magnitude of the accelerations showed marked facilitation during repeated stimulation (Fig. 6). 3. Optical and histological identification allowed characteristically different responses in the intracellular recordings to be attributed to the two cell types of the pacemaker nucleus: pacemaker and relay cells (Figs. 2 and 3). Similar responses have been observed at these respective recording locations in the intact animal during chirping (Dye and Heiligenberg 1987). 4. Simultaneous recordings of pairs of cells revealed a transient change in the phase relationship of firing during the accelerations which was most marked between relay and pacemaker cells (Fig. 7). These dual recordings also revealed that the relay cells depolarize and accelerate more than pacemaker cells (Fig. 10), suggesting that they are the principal effectors of this behavioral modulation. 5. Trains of pulses additionally elicited a long-lasting frequency elevation which occurred at a slightly higher threshold than the brief accelerations. This slow frequency change relaxed back to baseline following a biexponential time course which closely resembled that of a distinct behavior seen in intact fish, termed 'yodeling' (Dye 1987).

The cardiovascular effects of induction of anesthesia with minaxolone, a new water soluble steroid agent, have been studied in 12 normotensive patients and 5 patients with treated hypertension. The arterial pressure, heart rate and ECG were continuously recorded before and during induction of anesthesia with Minaxolone 0.5 mg kg-1. Cardiac output measurements were made in the awake patient, at 3 minutes after the induction of anesthesia and 2 minutes after an increment of the drug. In both groups of patients, induction of anesthesia led to a decrease in systolic arterial pressure and a smaller decrease in diastolic arterial pressures. This was coupled with an increase in the heart rate. The decrease in cardiac output was similar in both the normal and treated hypertensive patients. Administration of an increment of minaxolone (0.1 mg kg-1) did not produce further significant changes in the cardiovascular variables. The results of this study show that the changes in hemodynamic variables with minaxolone are comparable with those seen following induction of anesthesia with other intravenous agents, with the one difference in that there was only minimal change in the diastolic arterial pressure.

1. The weakly electric gymnotiform fish, Apteronotus leptorhynchus, can be induced to perform a variety of modulations of its quasi-sinusoidal, electric organ discharge (EOD) in acute physiological preparations. These modulations, many of which are communicatory in function, include the jamming avoidance response (JAR). We have recorded intracellularly from neurons of the medullary pacemaker nucleus which is responsible for maintaining the ongoing EOD frequency during these modulatory behaviors. 2. We have used dye-filled microelectrodes to characterize single cell morphology of the two types of cells in the pacemaker nucleus (relay and pacemaker cells) and to localize anatomically the site of the differing responses we see during frequency modulations. We have also recorded with KCl-filled electrodes and attributed these data to cell type and location on the basis of characteristic behavior during these modulations. 3. Much of our data deals with chirps, brief accelerations of the EOD frequency lasting 10 to 14 ms. We see distinct patterns of activity in the pacemaker nucleus corresponding to different anatomical locations: the relay cell soma and axon, and the pacemaker cell soma and axon. Most of these loci show a marked rise in baseline voltage during the acceleration in spike frequency. The most unusual of these is the pacemaker cell axon which displays an often extreme decline in spike amplitude concurrent with the chirp (Fig. 7A). 4. 'Yodeling' (Dye 1987) appears to involve similar, characteristic changes in the pattern of firing as those seen during chirping. Similar quantitative analyses suggest that the JAR involves a different mechanism, however.