Alkaline phosphatase activity after cardiothoracic surgery in infants and correlation with post-operative support and inflammation: a prospective cohort study

ABSTRACT: INTRODUCTION: Limited evidence suggests that serum alkaline phosphatase activity may decrease after cardiac surgery in adults and children. The importance of this finding is not known. Recent studies, however, have identified a potential role for alkaline phosphatase as modulator of inflammation in multiple settings, including during adult cardiopulmonary bypass. We sought to describe the change in alkaline phosphatase activity after cardiothoracic surgery in infants and to assess for a correlation with intensity and duration of post-operative support, markers of inflammation, and short-term clinical outcomes. METHODS: Sub-analysis of a prospective observational study on the kinetics of procalcitonin in 70 infants ([less than or equal to]90 days old) undergoing cardiothoracic surgery. Subjects were grouped based on the use of cardiopulmonary bypass and delayed sternal closure. Alkaline phosphatase, procalcitonin, and C-reactive protein (CRP) levels were obtained pre-operation and on post-operative day 1. Mean change in alkaline phosphatase activity was determined in each surgical group. Generalized linear modeling and logistic regression were employed to assess for associations between post-operative alkaline phosphatase activity and post-operative support, inflammation, and short term outcomes. Primary endpoints were vasoactive-inotropic score at 24 hours and length of intubation. Secondary endpoints included procalcitonin/CRP levels on post-operative day 1, length of hospital stay, and cardiac arrest or death. RESULTS: Mean decrease in alkaline phosphatase was 30 U/L (p=0.01) in the non-bypass group, 114 U/L (p<0.0001) in the bypass group, and 94 U/L (p<0.0001) in the delayed sternal closure group. On multivariate analysis, each 10 U/L decrease in alkaline phosphatase activity on post-operative day 1 was independently associated with an increase in vasoactive-inotropic score by 0.7 (p<0.0001), intubation time by 6% (p<0.05), hospital stay by 5% (p<0.05), and procalcitonin by 14% (P<0.01), with a trend towards increased odds of cardiac arrest or death (OR 1.3; p=0.06). Post-operative alkaline phosphatase activity was not associated with CRP (p=0.7). CONCLUSIONS: Alkaline phosphatase activity decreases after cardiothoracic surgery in infants. Low post-operative alkaline phosphatase activity is independently associated with increased procalcitonin, increased vasoactive/inotropic support, prolonged intubation time, and prolonged hospital stay. Alkaline phosphatase may serve as a biomarker and potential modulator of post-operative support and inflammation following cardiothoracic surgery in infants.     

A Pseudomonas syringae type III effector suppresses cell wall-based extracellular defense in susceptible Arabidopsis plants

Bacterial effector proteins secreted through the type III secretion system (TTSS) play a crucial role in causing plant and human diseases. Although the ability of type III effectors to trigger defense responses in resistant plants is well understood, the disease-promoting functions of type III effectors in susceptible plants are largely enigmatic. Previous microscopic studies suggest that in susceptible plants the TTSS of plant-pathogenic bacteria transports suppressors of a cell wall-based plant defense activated by the TTSS-defective hrp mutant bacteria. However, the identity of such suppressors has remained elusive. We discovered that the Pseudomonas syringae TTSS down-regulated the expression of a set of Arabidopsis genes encoding putatively secreted cell wall and defense proteins in a salicylic acid-independent manner. Transgenic expression of AvrPto repressed a similar set of host genes, compromised defense-related callose deposition in the host cell wall, and permitted substantial multiplication of an hrp mutant. AvrPto is therefore one of the long postulated suppressors of an salicylic acid-independent, cell wall-based defense that is aimed at hrp mutant bacteria.     

Effects of the home environmental skill-building program on the caregiver-care recipient dyad: 6-month outcomes from the Philadelphia REACH Initiative

PURPOSE: We examine 6-month effects of the Environmental Skill-Building Program on caregiver well-being and care recipient functioning and whether effects vary by caregiver gender, race (White or non-White), and relationship (spouse or nonspouse). DESIGN AND METHODS: We enrolled 255 family caregivers of community-residing persons with Alzheimer's disease or related disorders, of whom 190 participated in a follow-up interview. Caregivers were randomized to a usual care control group or intervention group that received five home contacts and one telephone contact by occupational therapists, who provided education, problem-solving training, and adaptive equipment. Baseline and 6-month follow-up included self-report measures of caregiver objective and subjective burden, caregiver well-being, and care recipient problem behaviors and physical function. RESULTS: Compared with controls (n = 101), intervention caregivers (n = 89) reported less upset with memory-related behaviors, less need for assistance from others, and better affect. Intervention spouses reported less upset with disruptive behaviors; men reported spending less time in daily oversight; and women reported less need for help from others, better affect, and enhanced management ability, overall well-being, and mastery relative to control group counterparts. Statistically significant treatment differences were not found for hours helping with instrumental activities of daily living, upset with providing assistance with instrumental activities of daily living and activities of daily living, perceived change in somatic symptoms, White versus non-White caregivers, or care recipient outcomes. IMPLICATIONS: The Environmental Skill-Building Program reduces burden and enhances caregiver well-being in select domains and has added benefit for women and spouses.     

Diagnostic impact of cerebral transit time in the identification of microangiopathy in dementia: A transcranial ultrasound study.

BACKGROUND AND PURPOSE: The diagnosis and quantification of microangiopathy in dementia is difficult. The assessment of small-vessel disease requires expensive and sophisticated nuclear medicine techniques. This study was performed to identify microangiopathy related to the integrity of cerebral microcirculation by sonographic measurements (arteriovenous cerebral transit time [cTT]). METHODS: We performed transcranial color-coded duplex sonography in 40 patients with vascular dementia, 20 patients with Alzheimer's disease or Lewy body disease, and 25 age-matched controls. The clinical diagnosis was established by history of dementia and neuroimaging findings. Cognitive impairment was assessed by the Mini-Mental State Examination and Alzheimer's Disease Assessment Scale. cTT is defined as the time required by an ultrasound contrast agent to pass from a cerebral artery to a vein. This was measured by recording the power-Doppler intensity curves in the P2 segment of the posterior cerebral artery and the vein of Galen. Previous studies have shown a prolongation of cTT in patients with cerebral microangiopathy. RESULTS: cTT was substantially prolonged in patients with vascular dementia (5.8 seconds; 25th percentile 4.5; 75th percentile 7.5; U test, P<0.001) compared with controls (3.1 seconds; 2.3; 3.4) but not in patients with degenerative dementia (3.7 seconds; 3.7; 4.2). In patients with vascular dementia, cTT was significantly correlated with cognitive impairment. CONCLUSIONS: cTT may be useful tool to disclose small-vessel disease in demented patients. Examination is noninvasive and quickly performed. It may be also useful in follow-up examinations in patients undergoing therapy.     

Opa proteins of pathogenic neisseriae initiate Src kinase-dependent or lipid raft-mediated uptake via distinct human carcinoembryonic antigen-related cell adhesion molecule isoforms

Several pathogenic bacteria exploit human carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) for adhesion to and invasion into their host cells. CEACAM isoforms have characteristic expression patterns on epithelial, endothelial, or hematopoietic cells, providing bacteria with distinct sets of receptors on particular tissues. For example, while CEACAM1 and CEACAM6 have a wide tissue distribution, CEACAM3, CEACAM4, and CEACAM8 are uniquely expressed on primary human granulocytes, whereas CEA and CEACAM7 are limited to epithelia. By reconstitution of a CEACAM-deficient cell line with individual CEACAMs, we have analyzed the requirements for CEACAM-mediated internalization of Neisseria gonorrhoeae. Our results point to two mechanistically different uptake pathways triggered by either epithelial CEACAMs (CEACAM1, CEA, and CEACAM6) or the granulocyte-specific CEACAM3. In particular, CEACAM3-mediated uptake critically depends on Src family protein tyrosine kinase (PTK) activity, and CEACAM3 associates with the SH2 domains of several Src PTKs. In contrast, epithelial CEACAMs require the integrity of cholesterol-rich membrane microdomains and are affected by cholesterol depletion, whereas CEACAM3-mediated uptake by transfected cells or the opsonin-independent phagocytosis by human granulocytes is not altered in the presence of cholesterol chelators. These results allow the subdivision of all human CEACAMs known to be utilized as pathogen receptors into functional groups and point to important consequences for bacterial engagement of distinct CEACAM isoforms.     

Trends in anthropometric measurements among Mescalero Apache Indian preschool children. 1968 through 1988.

OBJECTIVE--To determine if there were trends in underweight, short stature, and obesity among 1- through 5-year-old Mescalero (NM) Apache Indian children from 1968 through 1988. DESIGN--Cross-sectional review of hospital clinic charts for five cohorts. SETTING--General pediatric outpatient clinic at the Mescalero Indian Health Service Hospital. PARTICIPANTS--Sixty-nine patients aged 1 through 5 years in 1968, 1973, 1978, 1983, or 1988 for whom weight and height were recorded during a well-child visit that occurred in the respective year. SELECTION PROCEDURES--Approximately half the charts were screened for eligibility through systematic sampling for all years except 1988; for 1988 all available charts were screened for eligibility for the study. INTERVENTIONS--None. MEASUREMENTS AND RESULTS--We found trends of decreasing prevalence of both underweight (defined as weight-for-height below the fifth percentile) and short stature (defined as height-for-age below the fifth percentile) based on the Centers for Disease Control/World Health Organization growth reference. We found no secular trends in obesity (weight-for-height above the 95th percentile), although the prevalences throughout the 21-year period were as much as two to four times higher than expected when compared with the Centers for Disease Control/World Health Organization reference. There has been an upward shift in both weight-for-height and height-for-age distributions since 1968, indicating that Mescalero children today are, on average, heavier and taller. CONCLUSIONS--Underweight and short stature decreased among Mescalero preschool children from 1968 through 1988, suggesting nutritional improvements. However, given the current high prevalence of obesity, it is recommended that surveillance of nutritional status be continued and appropriate interventions be developed to treat and prevent obesity in this population.     

Depressive symptoms in older African-American and white adults with functional difficulties: the role of control strategies

OBJECTIVES: To examine whether control-oriented strategies buffer effects of functional difficulties on depressive symptoms over time in older African-American and white adults with disability. DESIGN: Community-based, prospective study. SETTING: Baseline and 12-month data from a randomized trial. PARTICIPANTS: One hundred twenty-nine African-American and 151 white older adults with 12-month data from 319 participants in the trial. MEASUREMENTS: Data were obtained for functional difficulties, the extent that respondents reported using control (cognitive and behavioral) strategies to enhance and maintain independence, and baseline and 12-month depressive symptoms (Center for Epidemiologic Studies Depression Scale; CES-D). RESULTS: African Americans reported greater baseline functional difficulty (P=.009), fewer depressive symptoms (P=.002) and higher control strategy use (P=.001) than whites. Functional difficulty was associated with depressive symptoms for both groups at baseline and 12 months. Living alone for whites and low spirituality for African Americans predicted higher 12-month depressive symptom scores. African Americans with baseline functional difficulty and high strategy use had lower 12-month depression than those with similar difficulty levels but low strategy use (P=.04 for interaction), representing a 28.5-point CES-D score differential. Control strategies did not buffer the function-depression relationship over time for whites. CONCLUSION: Control-oriented strategies moderated the experience of depressive symptomatology over time for African Americans with disability but not for whites. This may explain the paradox of greater functional disparities but less reported emotional distress in African Americans than whites. Results suggest that the use and benefits of adaptive resources to attain functional goals and determinants of depression differ by race. Depression prevention programs should be modified to be suitable for different cultural groups.     

鸟氨酸脱羧酶的生理病理特点及其药物研究概况

鸟氨酸脱羧酶(ornithinedecarboxylase,ODC)是多胺代谢中的关键酶,广泛存在于人体和动物各组织细胞内,其中对肠细胞的增生、移行和分化起重要作用.机体调节因素比较复杂.在黏膜损伤性疾病及某些癌前病变等细胞大量增生的病理情况下ODC的表达发生改变,可以作为这些疾病分期、预后及药物作用靶点或疗效的指标.寻找对ODC有作用的药物对于治疗其相关疾病是非常有意义的.