Volatiles or TIVA: Which is the standard of care for pediatric airway procedures? A pro‐con discussion

Anesthesia for pediatric airway procedures constitutes a true art form that requires training and experience. Communication between anesthetist and surgeon to establish procedure goals is essential in determining the most appropriate anesthetic management. But does the mode of anesthesia have an impact? Traditionally, inhalational anesthesia was the most common anesthesia technique used during airway surgery. Introduction of agents used for total intravenous anesthesia (TIVA) such as propofol, short‐acting opioids, midazolam, and dexmedetomidine has driven change in practice. Ongoing debates abound as to the advantages and disadvantages of volatile‐based anesthesia versus TIVA. This pro‐con discussion examines both volatiles and TIVA, from the perspective of effectiveness, safety, cost, and environmental impact, in an endeavor to justify which technique is the best specifically for pediatric airway procedures.     

Angiostatin overexpression in Morris hepatoma results in decreased tumor growth but increased perfusion and vascularization.

Growth of malignant tumors is dependent on sufficient blood supply. Thus, inhibition of tumor angiogenesis is emerging as a promising target in the treatment of malignancies. Human angiostatin (hANG) is one of the most potent inhibitors of endothelial cell proliferation, angiogenesis, and tumor growth in vivo. However, its mechanisms operating in vivo are not well understood. METHODS: To obtain more information about functional changes in the angiogenic process, we established Morris hepatoma (MH3924A) cell lines expressing hANG (hANG-MH3924A). The effects of hANG expression on proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs) were measured in coculture experiments in vitro. To evaluate changes in tumor perfusion and blood volume, H2 15O and 68Ga-DOTA-albumin (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N',N'-tetraacetic acid) were used for PET studies in vivo. Additionally, immunohistologic quantification of vascularization, apoptosis, and proliferation as well as gene array analyses were performed. RESULTS: Our in vitro experiments demonstrate reduced proliferation and increased apoptosis in HUVECs when being cocultured with hANG-MH3924A. In support, tumor growth of hANG-MH3924A is diminished by 95% in vivo. However, tumor perfusion and blood volume are increased in hANG-MH3924A corresponding to an increased microvessel density. Furthermore, hANG-transfected tumors show changes in expression of genes related to apoptosis, stress, signal transduction, and metabolism. CONCLUSION: hANG expression leads to inhibition of tumor growth, increased apoptosis, and changes in the expression of multiple genes involved in stress reactions, signal transduction, and apoptosis, which indicates a multifactorial reaction of tumors. An enhanced microvessel density is seen as part of these reactions and is associated with increased perfusion as measured by PET.     

Immunologic privilege in the central nervous system and the blood–brain barrier

The brain is in many ways an immunologically and pharmacologically privileged site. The blood–brain barrier (BBB) of the cerebrovascular endothelium and its participation in the complex structure of the neurovascular unit (NVU) restrict access of immune cells and immune mediators to the central nervous system (CNS). In pathologic conditions, very well-organized immunologic responses can develop within the CNS, raising important questions about the real nature and the intrinsic and extrinsic regulation of this immune privilege. We assess the interactions of immune cells and immune mediators with the BBB and NVU in neurologic disease, cerebrovascular disease, and intracerebral tumors. The goals of this review are to outline key scientific advances and the status of the science central to both the neuroinflammation and CNS barriers fields, and highlight the opportunities and priorities in advancing brain barriers research in the context of the larger immunology and neuroscience disciplines. This review article was developed from reports presented at the 2011 Annual Blood-Brain Barrier Consortium Meeting.     

TrkC Is Essential for Nephron Function and Trans-Activates Igf1R Signaling

BackgroundInjury to kidney podocytes often results in chronic glomerular disease and consecutive nephron malfunction. For most glomerular diseases, targeted therapies are lacking. Thus, it is important to identify novel signaling pathways contributing to glomerular disease. Neurotrophic tyrosine kinase receptor 3 (TrkC) is expressed in podocytes and the protein transmits signals to the podocyte actin cytoskeleton.MethodsNephron-specific TrkC knockout (TrkC-KO) and nephron-specific TrkC-overexpressing (TrkC-OE) mice were generated to dissect the role of TrkC in nephron development and maintenance.ResultsBoth TrkC-KO and TrkC-OE mice exhibited enlarged glomeruli, mesangial proliferation, basement membrane thickening, albuminuria, podocyte loss, and aspects of FSGS during aging. Igf1 receptor (Igf1R)–associated gene expression was dysregulated in TrkC-KO mouse glomeruli. Phosphoproteins associated with insulin, erb-b2 receptor tyrosine kinase (Erbb), and Toll-like receptor signaling were enriched in lysates of podocytes treated with the TrkC ligand neurotrophin-3 (Nt-3). Activation of TrkC by Nt-3 resulted in phosphorylation of the Igf1R on activating tyrosine residues in podocytes. Igf1R phosphorylation was increased in TrkC-OE mouse kidneys while it was decreased in TrkC-KO kidneys. Furthermore, TrkC expression was elevated in glomerular tissue of patients with diabetic kidney disease compared with control glomerular tissue.ConclusionsOur results show that TrkC is essential for maintaining glomerular integrity. Furthermore, TrkC modulates Igf-related signaling in podocytes.     

Upper Limb Pain in Anational Sample of Veterans With Paraplegia

Abstract

Background and Objectives: The purpose of this survey study was to examine the prevalence and intensity of pain and associated patient characteristics in a national sample of veterans with paraplegia. Of particular interest were upper limb (UL) pain conditions, which pose unique challenges to individuals who use a wheelchair for mobility. Because the risk for UL pain conditions appears to increase over time, the associations among age, duration of wheelchair use, and UL pain were evaluated.

Methods: A group of 1 ,6 7 5 individuals between the ages of 1 8 and 65 with a lesion between T2 and L2 and a mailing address on file were selected randomly from the Veteran's Affairs Spinal Cord Dysfunction Registry and mailed a survey packet. Of the deliverable packets, -46% were completed and returned.

Results: Approximately 81% of the respondents reported at least a minimal Ievei of ongoing unspecified pain and 69'7'o experienced current UL pain. Shoulder pain intensity was most severe du ring the performance of wheelchair-related mobility and transportation activities, suggesting that UL pain may have a significant impact on functional independence. Duration of wheelchair use modestly predicted shoulder pain prevalence and intensity, but age and the interaction between age and duration of wheelchair use did not.

Condusion: The data of the present study suggest that the development, persistence, and exacerbation of UL pain conditions in persans with paraplegia aremultidimensional processes. A comprehensive theoretic model is needed to integrate the existing empiric Iiterature in this area.     

Impact of cognitive-psychoeducational interventions in bipolar patients and their relatives.

BACKGROUND: In recent years, several controlled studies could show that psychoeducational interventions have been effective for relapse prevention in bipolar disorders. We therefore established a cognitive-psychoeducational group intervention with 14 sessions providing information about the illness, early warning signs, cognitive and behavioural strategies for stress management and social rhythm. Additionally we offered a group intervention for the patients' relatives. The objective of this study was to describe the outcome associated with our psychoeducational intervention in bipolar patients and their relatives. METHODS: Sixty-two bipolar patients attended 14 sessions (à 90 min) of cognitive-psychoeducational group therapy. Patients' knowledge of bipolar disorder and their satisfaction with the treatment were assessed using self-developed questionnaires before and after the group intervention. Additionally, 49 relatives of bipolar patients received two psychoeducational workshops of 4 hours each. We assessed demographic variables, burden, high expressed emotion and depressive symptoms of the relatives before and after the two workshops and at 1-year follow-up. RESULTS: Patients significantly improved their knowledge of bipolar disorder. They also have benefited from the discussions and the exchange of useful coping strategies. Burden and high expressed emotions showed no significant reductions at post-assessment, however they were significantly reduced at 1-year follow-up. Relatives also felt significantly better informed about the illness. CONCLUSIONS: These findings show that psychoeducational interventions in bipolar patients and their relatives improve patients' and their relatives' knowledge of the illness and the burden of the disorder as well as high expressed emotions are reduced in relatives at 1-year follow-up.     

Anosognosia in mild cognitive impairment: Relationship to activation of cortical midline structures involved in self-appraisal.

Awareness of cognitive dysfunction shown by individuals with Mild Cognitive Impairment (MCI), a condition conferring risk for Alzheimer's disease (AD), is variable. Anosognosia, or unawareness of loss of function, is beginning to be recognized as an important clinical symptom of MCI. However, little is known about the brain substrates underlying this symptom. We hypothesized that MCI participants' activation of cortical midline structures (CMS) during self-appraisal would covary with level of insight into cognitive difficulties (indexed by a discrepancy score between patient and informant ratings of cognitive decline in each MCI participant). To address this hypothesis, we first compared 16 MCI participants and 16 age-matched controls, examining brain regions showing conjoint or differential BOLD response during self-appraisal. Second, we used regression to investigate the relationship between awareness of deficit in MCI and BOLD activity during self-appraisal, controlling for extent of memory impairment. Between-group comparisons indicated that MCI participants show subtly attenuated CMS activity during self-appraisal. Regression analysis revealed a highly significant relationship between BOLD response during self-appraisal and self-awareness of deficit in MCI. This finding highlights the level of anosognosia in MCI as an important predictor of response to self-appraisal in cortical midline structures, brain regions vulnerable to changes in early AD.     

Reductions in postdischarge suicide after deinstitutionalization and decentralization: a nationwide register study in Finland

OBJECTIVE: This study analyzed trends in suicides occurring after a psychiatric hospitalization during more than a decade of significant structural changes in mental health services in Finland-that is, deinstitutionalization, downsizing of inpatient care, and decentralization. METHODS: Retrospective register data on completed suicides and psychiatric inpatient treatments were collected for the periods 1985-1991 and 1995-2001, representing service provision before and after significant structural changes. The data were used to produce an estimate for a change in postdischarge suicide risk. RESULTS: In both periods, a fifth of suicide victims had been psychiatrically hospitalized within the preceding year. Among persons hospitalized, the risk of suicide was greater in 1985-1991 than in 1995-2001 for both one week after discharge (risk ratio [RR]=1.50, 95% confidence interval [CI]=1.38-1.62) and one year after discharge (RR=1.25, CI=1.19-1.30). When types of disorders were analyzed separately, the relative risk of suicide one year postdischarge for those hospitalized in the earlier period was greater for patients with schizophrenia (RR=1.26, CI=1.17-1.36) and patients with affective disorders (RR=1.60, CI=1.48-1.73). In parallel with general development of inpatient psychiatric services, in 1995-2001 the inpatient treatment periods preceding suicides were significantly shorter (a mean+/-SD of 45+/-340 days in 1995-2001, compared with a mean of 98+/-558 days in 1985-1991), the number of individual patients treated in the hospital for schizophrenia spectrum disorders was lower (26% compared with 36%), and the number treated for affective disorders was higher (45% compared with 35%). CONCLUSIONS: The restructuring and downsizing of mental health services was not associated with any increase in suicides immediately (one week) or one year postdischarge. Instead, the risk of these suicides decreased significantly between the two time periods among several diagnostic categories. Although the role of psychiatric hospitalization in general may have changed over time, patients who are hospitalized now may be less suicidal after discharge. Our results indicate, in terms of postdischarge suicides, that the downsizing of psychiatric hospitals has been a success. However, there is still a substantial need for better recognition of suicidal risk among psychiatric patients.