Differential Lung Ventilation with Unilateral PEEP Following Unilateral Hydrochloric Acid Aspiration in the Dog

Differential lung ventilation with positive end expiratory pressure (PEEP) improves pulmonary gas exchange when used in the supportive care of patients with severe unilateral or asymmetrical lung disease. Once the provision of selective PEEP to the two lungs is accomplished, the best method of partitioning the tidal volume between the two lungs is unknown. Twelve mongrel dogs were given a unilateral hydrochloric acid (HCl) aspiration injury. A computer controlled differential lung ventilation system was used to ventilate four dogs with equal volumes to each lung, four dogs with equal driving pressure (end inspiratory pressure-PEEP) to each lung, and four dogs with equal end-tidal CO₂ fraction from each lung. The respiratory rate was feedback controlled to maintain Paco₂ at 4.67 kPa. The dogs were kept supine and ventilated with 30% O₂. Following injury, the PEEP was set at 0 kPa for 1 h. The dogs were then given 1.36 kPa and 2.72 kPa PEEP to the injured lung for 2 h in a cross-over fashion. The assignment of the tidal volume controller, the side of injury, and the PEEP sequence was random. Oxygen tension fell and pulmonary venous admixture increased after giving the HCl injury. In all three groups considered simultaneously, unilateral PEEP improved Pao₂ and venous admixture. The equal tidal volume distribution was the only group to show a significant improvement in Pao₂ at both PEEP increments (0 to 1.36 kPa and 2.72 kPa). There was a significant difference in tidal volume allocation between the three groups with the equal end-tidal and equal pause pressure groups only minimally ventilating the injured lung. With differential lung ventilation and unilateral PEEP, equal partitioning of tidal volume provides the highest Pao₂, compared to the other two methods of partitioning tidal volume.     

Obesity Surgery in the Philippines: Experience in a Private Tertiary Care Hospital for Years 2002 to 2004

Background Information on experience in bariatric surgery in the Asia-Pacific region is minimal: hence the need for more reports from this area. Methods The procedures of bariatric surgery and outcome as part of a weight management program in a tertiary care private hospital in the Philippines is reported from years 2002 to 2004. 50 patients were included, of which 60% underwent laparoscopic adjustable gastric banding (LAGB) and 40% Roux-en- Y gastric bypass (RYGBP). Results There were more females than males (64% vs 36%) with the mean age 38 ± 13.1 years. Initial mean BMI was 46.2 kg/m2, which decreased to 27.0 kg/m² in 1 year. Initial mean weight was 126.7 ± 25.4 kg, of which the 1 year weight loss was 32.3 kg for the morbidly obese and 58.0 kg for the super obese. %EWL at 1 year was 30.2%. There was greater weight loss with RYGBP compared to LAGB at 1 year (43.5 kg vs 30.2 kg). There was no mortality, and early complications were: wound infection (2/50 or 4%), and 1/50 or 2% each for pneumonia, dehydration, gastritis, and leakage. Late complications were: band slippage (2/20 or 10%), stomal stenosis (1/20 or 5%), and ventral hernia (1/5 or 20%). Conclusion Bariatric surgery is safe with a low complication rate and the outcome was similar to the reported data from Asia and the western world.     

MHV68 complement regulatory protein facilitates MHV68 replication in primary macrophages in a complement independent manner

Murine gammaherpesvirus-68 (MHV68) is genetically related to human Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus and provides a tractable model to study gammaherpesvirus-host interactions in vivo and in vitro. The MHV68-encoded v-RCA product inhibits murine complement activation and shares sequence homology with other virus and host regulators of complement activation. Here we show that v-RCA is required for efficient MHV68 replication in primary murine macrophages, but not in murine embryonic fibroblasts. v-RCA-deficient MHV68 mutant viruses display defects in viral DNA synthesis in infected macrophages. Importantly, attenuated growth of v-RCA mutant viruses is not rescued in macrophages lacking critical components of the complement system including C3, indicating that the macrophage-specific role of v-RCA in MHV68 replication is complement-independent. This contrasts with the situation in vivo in which attenuated neurovirulence of v-RCA mutant viruses is rescued in C3-deficient mice. This study shows a novel, complement independent cell-type-specific function of a gammaherpesvirus RCA protein.     

鞘内注射miR-212反义锁核酸对骨癌小鼠痛行为的影响

目的研究骨癌痛发展和维持过程中小鼠脊髓水平miR-212表达的变化规律及连续鞘内注射miR-212反义锁核酸LNA．anti—miR-212对骨癌痛小鼠痛行为的影响。方法本实验分为两个部分：（一）骨癌痛小鼠脊髓水平miR-212表达的变化规律：C3H／HeJ雄性小鼠36只,随机分为假手术组（sham组,n=18）和肿瘤组（T组,n=18）。sham组小鼠在右侧股骨远端骨髓腔注射不含肿瘤细胞的仪一MEM,T组小鼠在右侧股骨远端骨髓腔注射纤维肉瘤细胞NCTC2472,建立骨癌痛模型。在术前1d,术后4d、7d、10d、14d、21d,sham组和T组各随机取三只小鼠处死,取脊髓腰膨大标本,用Real-timePCR的方法检测脊髓水平miR一212的表达情况。（二）连续鞘内注射LNA—anti-miR-212对骨癌痛小鼠痛行为的影响：C3H／HeJ雄性小鼠24只,随机分为四组：L组（鞘内注射LNA-anti—miR一212,n=6）、L’组（鞘内注射LNA＇-negativecontrol,n=6）、C组（鞘内注射溶媒无核酸酶水,n=6）和S组（假手术处理,n=6）。L组、L’组和C组小鼠在右侧股骨远端注射纤维肉瘤细胞NCTC2472,S组小鼠在右侧股骨远端骨髓腔注射不含肿瘤细胞的仪一MEM。所有小鼠于术前1d、术后4d、7d、10d、14d测小鼠痛行为指标,包括自发抬足次数和机械缩足阈值（PWMT）,术后14d,L组、L’组、C组小鼠分别鞘内注射LNA—anti—miR-21212pmol／5山、LNA＇-negativecontrol12pmol／5I＊1和无核酸酶水5I＊1,连续鞘内注射7d,1次／d,每天测小鼠痛行为指标,至术后第21天。结果miR-212的表达变化表现为：与基础值相比,sham组和T组小鼠在术后第4天,脊髓水平miR一212明显升高（P〈0．05）;与基础值和sham组相比,T组小鼠脊髓水平miR-212在术后7d、10d、14d、21d均明显升高（P〈0．05）。连续鞘内注射LNA—anti—miR-212改善骨癌痛小鼠痛行为：术后19d至21d,与L’组和c组相比,L组小鼠PWMT[19d（1．07-4-0．16）g,20d（1．13±0．21）g,21d（1．27±0．21）g）]明显升高（P〈0．05）,自发抬足次数明显降低[19d（6．674-1．04）,20d（6．62±1．39）,21d（6．47±1．17）]（P〈0．05）。与14d给药前相比,L组小鼠术后19d至21d的PWMT明显升高（P〈0．05）,自发抬足次数明显降低（P〈0．05）。结论骨癌痛发展过程中,脊髓水平miR-212表达量升高。连续鞘内注射LNA-anti—miR一212可以缓解骨癌小鼠痛行为。     

Binge Drinking,Marijuana Use,and Friendships: The Relationship Between Similar and Dissimilar Usage and Friendship Quality

Abstract

While it is commonly understood that the substance use of peers influences an individual's substance use, much less is understood about the interplay between substance use and friendship quality. Using a sample of 2,148 emerging adults nested within 1,074 dyadic friendships, this study separately investigates how concordance and discordance in binge drinking and marijuana use between friends is related to each friend's perceptions of friendship quality. Because “friendship quality” is a complex construct, we employ a measure containing five sub-elements – companionship, a lack of conflict, willingness to help a friend, relationship security, and closeness. Results for both binge drinking and marijuana use reveal that individuals in friendship pairs who are concordant in their substance use perceive significantly higher perceptions of friendship quality than individuals in dyads who are dissimilar in substance use. Specifically, concordant binge drinkers estimate significantly higher levels of companionship, relationship security, and willingness to help their friend than concordant non-users, discordant users, and discordant non-users. However, the highest amount of conflict in friendships is found when both friends engage in binge drinking and marijuana use. Several interpretations of these findings are discussed. Overall, concordance between friends’ binge drinking and marijuana use appears to help some elements of friendship quality and harm others.     

A Tiered Approach to Life Stages Testing for Agricultural Chemical Safety Assessment

Aproposal has been developed by the Agricultural Chemical Safety Assessment (ACSA) Technical Committee of the ILSI Health and Environmental Sciences Institute (HESI) for an improved approach to assessing the safety of crop protection chemicals. The goal is to ensure that studies are scientifically appropriate and necessary without being redundant, and that tests emphasize toxicological endpoints and exposure durations that are relevant for risk assessment. The ACSA Life Stages Task Force proposes a tiered approach to toxicity testing that assesses a compound's potential to cause adverse effects on reproduction, and that assesses the nature and severity of effects during development and adolescence, with consideration of the sensitivity of the elderly. While incorporating many features from current guideline studies, the proposed approach includes a novel rat reproduction and developmental study with enhanced endpoints and a rabbit development study. All available data, including toxicokinetics, ADMEdata, and systemic toxicity information, are considered in the design and interpretation of studies. Compared to existing testing strategies, the proposed approach uses fewer animals, provides information on the young animal, and includes an estimation of human exposure potential for making decisions about the extent of testing required.     

Risk Assessment of Toxaphene and its Breakdown Products: Time for a Change?

Technical toxaphene (TT) was last used in commerce in about 1982. Any environmental exposure to toxaphene in this century is to environmentally degraded forms of toxaphene, termed weathered toxaphene. Several hundred chlorinated bornane congeners have been identified in technical toxaphene. The degradation of technical toxaphene to weathered toxaphene can result in various congener mixtures, but the primary mode of degradation is dechlorination. The U.S. Environmental Protection Agency (EPA) presently estimates the risk of exposure to toxaphene by relying upon rat and mouse toxicology studies performed on technical toxaphene. No adjustment is made for the dechlorination of toxaphene in the environment. The European Union (EU), however, has modeled toxaphene risks from eating fish with chlorinated bornane residues through a series of studies on toxaphene degraded by either ultraviolet light, or biodegradation in fish. The EU risk assessment relies upon rat liver studies in vivo and mouse in vitro studies on the inhibition of gap junction intercellular communication (GJIC). This article reviews the current state of knowledge of technical and weathered toxaphene toxicology. We discuss the various current methods and opportunities to advance the risk assessment of weathered toxaphene beyond the existing U.S. EPA assessment of technical toxaphene.     

Public Policy and Headache: Observations of Health Care Policy in the US Congress From a Legislative Fellow's Perspective

Many neurologists and headache specialists are befuddled by inside the Beltway wheelings and dealings as they follow health care politics. A few of us join lobbying efforts, and even fewer become strangers in a strange land.     

A direct comparison of rejection by CD8 and CD4 T cells in a transgenic model of allotransplantation

INTRODUCTION: The relative contributions of CD4+ and CD8+ T cells to transplant rejection remain unknown. The authors integrated a previous model of CD4-mediated graft rejection with a complementary model of CD8-mediated rejection to directly compare the function of graft-reactive CD4+ and CD8+ lymphocytes in vivo in a model where rejection requires transgenic T cells. These studies allow direct comparison of CD4 and CD8 T cell responses to the same antigen without the confounding effects of T cell depletion or homeostatic proliferation. MATERIALS AND METHODS: Clone 4 and TS1 mice possess MHC class I- and II-restricted CD8+ and CD4+ T cells, respectively, which express transgenic T cell receptors that recognize the influenza hemagglutinin antigen (HA). We compared the in vivo response of CFSE-labeled, HA-specific transgenic CD8+ and CD4+ T cells after adoptive transfer into syngeneic BALB/c mice grafted with HA-expressing skin. RESULTS: As in the authors' CD4+ model, HA104 skin was consistently rejected by both Clone 4 mice (n=9, MST: 14.2) and by 5 x 10(5) Clone 4 lymphocytes transferred to naive BALB/c hosts that do not otherwise reject HA+ grafts. Rejection correlated with extensive proliferation of either graft-reactive T cell subset in the draining lymph nodes, and antigen-specific CD4+ and CD8+ cells acquired effector function and proliferated with similar kinetics. CONCLUSIONS: These data extend the authors' unique transgenic transplantation model to the investigation of CD8 T cell function. The initial results confirm fundamental functional similarity between the CD4 and CD8 T cell subsets and provide insight into the considerable redundancy underlying T cell mechanisms mediating allograft rejection.