Galantamine protects against lipopolysaccharide-induced acute lung injury in rats

Lipopolysaccharide (LPS)-induced endotoxemia triggers the secretion of proinflammatory cytokines and can cause acute lung injury (ALI). The high mobility group box 1 (HMGB1) protein plays an important role as a late mediator of sepsis and ALI. Galantamine (GAL) is a central acetylcholinesterase inhibitor that inhibits the expression of HMGB1. This study evaluated the effects of GAL by measuring levels of inflammatory mediators and observing histopathological features associated with LPS-induced ALI. Sixty 8-10 week old male Sprague-Dawley rats (200-240 g) were randomized into three groups as follows: control group, LPS group (7.5 mg/kg LPS), and LPS+GAL group (5 mg/kg GAL before LPS administration). Histopathological examination of lung specimens obtained 12 h after LPS administration was performed to analyze changes in wet-to-dry (W/D) weight ratio, myeloperoxidase (MPO) activity, and HMGB1 expression level. Additionally, plasma concentrations of tumor necrosis factor-α, interleukin-6, and HMGB1 were measured using an enzyme-linked immunosorbent assay at 0 (baseline), 3, 6, 9, and 12 h after LPS administration. Mortality in the three groups was recorded at 72 h. LPS-induced ALI was characterized by distortion of pulmonary architecture and elevation of MPO activity, W/D weight ratio, and levels of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-6, and HMGB1. Pretreatment with GAL significantly reduced the LPS-induced lung pathological changes, W/D weight ratio, levels of pro-inflammatory cytokines and MPO activity (ANOVA). Moreover, GAL treatment significantly decreased the mortality rate (ANOVA). In conclusion, we demonstrated that GAL exerted a protective effect on LPS-induced ALI in rats.     

In search of common ground in handoff documentation in an Intensive Care Unit

ObjectiveHandoff is an intra-disciplinary process, yet the flow of critical handoff information spans multiple disciplines. Understanding this information flow is important for the development of computer-based tools that supports the communication and coordination of patient care in a multi-disciplinary and highly specialized critical care setting. We aimed to understand the structure, functionality, and content of nurses’ and physicians’ handoff artifacts.DesignWe analyzed 22 nurses’ and physicians’ handoff artifacts from a Cardiothoracic Intensive Care Unit (CTICU) at a large urban medical center. We combined artifact analysis with semantic coding based on our published Interdisciplinary Handoff Information Coding (IHIC) framework for a novel two-step data analysis approach.ResultsWe found a high degree of structure and overlap in the content of nursing and physician artifacts. Our findings demonstrated a non-technical, yet sophisticated, system with a high degree of structure for the organization and communication of patient data that functions to coordinate the work of multiple disciplines in a highly specialized unit of patient care.LimitationsThis study took place in one CTICU. Further work is needed to determine the generalizability of the results.ConclusionsOur findings indicate that the development of semi-structured patient-centered interdisciplinary handoff tools with discipline specific views customized for specialty settings may effectively support handoff communication and patient safety.     

Clinical results and issues of acute myeloid leukemia in elderly patients aged 75 years and older

Aim: Clinical outcomes of acute myeloid leukemia (AML) in elderly patients still remain unsatisfactory and the optimal treatment has yet to be clearly established. This report describes the results of a retrospective study of clinical outcomes and prognostic factors of AML in patients aged 75 years and older. In addition, we aimed to elucidate the situation of patients with AML accompanied by dementia, which has been largely ignored in previous studies. Methods: The subjects consisted of 31 patients with untreated AML (including previous myelodysplastic syndrome: AML/MDS). All patients underwent chemotherapy, with 25 undergoing conventional therapy and six undergoing low‐intensity therapy. Results: Complete remission was obtained in 16 of the 31 cases (51.6%), with a 3‐year survival rate of 11.5%. However, in seven cases, Alzheimer's disease (AD) was observed. Although we were able to perform induction therapy in each of these cases, consolidation therapy was difficult in cases of moderate AD. Conclusion: The results of this study suggest that even very elderly patients can benefit from chemotherapy. However, it is thought that the treatment selection for cases which are complicated by moderate to severe dementia should be determined carefully while considering the patient's quality of life. Geriatr Gerontol Int 2011; 11: 290–296 .     

The specific contributions of set‐shifting to freezing of gait in Parkinson's disease

Freezing of gait (FOG) in Parkinson's disease (PD) is common and the pathophysiology of FOG is poorly understood. It has been hypothesized to reflect complementary yet competing frontostriatal pathways that reduce the ability to keep different tasks (motor or cognitive) on‐line. This inability to “set‐shift” has been proposed to trigger a freezing episode. If correct, this hypothesis would predict a differential pattern of executive dysfunction with FOG being most specifically related to attentional set‐shifting. In this study, 31 patients with a range of self‐reported FOG symptom severities were administered tests of executive functioning. The results demonstrate that FOG symptoms were selectively correlated with poorer performance on tasks of set‐shifting, but not with a range of other executive tasks. This was apparent even after controlling for slowed processing speed, disease stage and depressive symptoms. The results support the recently proposed hypothesis for the pathophysiology underlying FOG in PD. © 2010 Movement Disorder Society     

A Surgical Technique for Portal Vein Decompression in Retransplantation

Introduction  

Liver retransplantation is the only option for people who have a failing liver graft, but it can be technically challenging. Intraperitoneal adhesions often form after abdominal operations, which is true in liver retransplantation as well. Also, the liver hilum is scarred, which makes hilar dissection more difficult. In addition, dissection is further complicated in the setting of portal hypertension.     

Behavioral thermoregulation by turtle embryos

Mobile ectothermic animals can control their body temperatures by selecting specific thermal conditions in the environment, but embryos--trapped within an immobile egg and lacking locomotor structures--have been assumed to lack that ability. Falsifying that assumption, our experimental studies show that even early stage turtle embryos move within the egg to exploit small-scale spatial thermal heterogeneity. Behavioral thermoregulation is not restricted to posthatching life and instead may be an important tactic in every life-history stage.     

Respiratory and non-respiratory sinus arrhythmia: implications for heart rate variability

The quantity of blood arriving at the left side of the heart oscillates throughout the breathing cycle due to the mechanics of breathing. Neurally regulated fluctuations in the length of the heart period act to dampen oscillations of the left ventricular stroke volume entering the aorta. We have reported that stroke volume oscillations but not spectral frequency variability stroke volume measures can be used to estimate the breathing frequency. This study investigated with the same recordings whether heart period oscillations or spectral heart rate variability measures could function as estimators of breathing frequency. Continuous 270 s cardiovascular recordings were obtained from 22 healthy adult volunteers in the supine and upright postures. Breathing was recorded simultaneously. Breathing frequency and heart period oscillation frequency were calculated manually, while heart rate variability spectral maximums were obtained using heart rate variability software. These estimates were compared to the breathing frequency using the Bland–Altman agreement procedure. Estimates were required to be <±10% (95% levels of agreement). The 95% levels of agreement measures for the heart period oscillation frequency (supine: −27.7 to 52.0%, upright: −37.8 to 45.9%) and the heart rate variability spectral maximum estimates (supine: −48.7 to 26.5% and −56.4 to 62.7%, upright: −37.8 to 39.3%) exceeded 10%. Multiple heart period oscillations were observed to occur during breathing cycles. Both respiratory and non-respiratory sinus arrhythmia was observed amongst healthy adults. This observation at least partly explains why heart period parameters and heart rate variability parameters are not reliable estimators of breathing frequency. In determining the validity of spectral heart rate variability measurements we suggest that it is the position of the spectral peaks and not the breathing frequency that should be the basis of decision making.     

Immune activation is required for NT-3-induced axonal plasticity in chronic spinal cord injury

After an unilateral lesion of the corticospinal tract (CST) at the level of the medulla over-expression of Neurotrophin-3 (NT-3) in lumbar spinal cord motoneurons induced axonal sprouting of the intact CST in the acutely injured but not uninjured or chronically injured spinal cord in rats. This suggested that processes associated with immune-mediated wound healing may act with NT-3 to induce neuroplasticity. To test whether immune processes were involved we measured NT-3-induced axonal sprouting in immunosuppressed compared to immunocompetent rats. Rats were immunosuppressed with anti-leukocyte antibodies 1 day before receiving a CST lesion and then 2 weeks later NT-3 was over-expressed in the lumbar spinal motoneurons with an adenoviral vector carrying the NT-3 gene targeted to the motoneurons by retrograde transport. At 35 days post-lesion no axonal sprouting was measured in immunosuppressed rats whereas axonal sprouting was measured in the immunocompetent rats. We then tested whether re-evoking an immune response in chronically lesioned rats would induce neuroplasticity. Rats received CST lesions and then 4 months later were treated with systemic injections of lipopolysaccharide (LPS) 7 days before NT-3 was over-expressed in the lumbar spinal motoneurons. Axonal sprouting was observed in the LPS treated rats but not in control animals that were not treated with LPS. Further studies showed that lesioning the CST activated and LPS reactivated microglia and CD4(+) T-cells in the acutely lesioned and chronically lesioned rats, respectively. However, immunosuppression only decreased the number of activated CD4(+) T-cells suggesting they were responsible for the support of axonal growth. These observations demonstrate that processes associated with immune-mediated wound healing play a role in NT-3-induced neuroplasticity after injury.     

Measurement of urinary metanephrines to screen for pheochromocytoma in an unselected hospital referral population

BACKGROUND: Despite the rarity of pheochromocytoma, diagnosis is important because of the dangers of uncontrolled severe hypertension and the availability of very effective surgical treatment. Urinary or plasma catecholamines or catecholamine derivatives are commonly used to screen for pheochromocytomas before imaging, but data from 24-h urinary metanephrine results, patient age, and sex may better predict tumors in populations with a low pretest probability. METHODS: We retrospectively studied outcomes of an unselected population (1819 patients) referred to a tertiary hospital laboratory for urinary metanephrine testing and investigated the usefulness of some simple derivative measures for detecting pheochromocytoma. We normalized values for urinary 24-h excretion of metanephrine, normetanephrine, and 3-methoxytyramine by dividing by an age- and sex-specific reference range. We then compared pheochromocytoma prediction by the use of products of these normalized measures with the gold standard of biopsy-confirmed tumor. RESULTS: The product of the excretion of normalized metanephrine (nMAD) and normalized normetanephrine (nNMT) (nMAD.nNMT) was a highly sensitive (100%) and specific (99.1%) measure, yielding a positive predictive value of 82%. ROC curves were not improved by including the normalized 3-methoxytyramine concentrations in the product. The test for nMAD.nNMT gave higher sensitivity and specificity than the tests for either substance alone. CONCLUSION: The test for nMAD.nNMT is a useful measure for identifying pheochromocytoma in a population with a low pretest probability.