Factors Present on Admission Associated with Increased Mortality in Children Admitted to a Paediatric Intensive Care Unit (PICU)

Background. The admission of children to an intensive care unit (ICU) necessitates the selection of children who will benefit most from scarce ICU resources. Decisions should be based on objective data available on outcomes related to particular conditions and resource availability. Objective. To determine which sociodemographic factors and paediatric scoring systems can be used on admission to identify patients who would derive the most benefit.Methods. A retrospective review was undertaken of the charts of children admitted to a paediatric ICU (PICU) over a 6-month period. Charts were analysed according to health status; biographical and demographic data; as well as Pediatric Risk of Mortality (PRISM); Pediatric Logistic Organ Dysfunction (PELOD) and Paediatric Index of Mortality 3 (PIM3) scores to determine which factors were associated with an increased mortality risk.Results. Two hundred and two children were admitted during the study period. Ninety-six children were included in the study; 79 files were not found and 27 children were ineligible. The median age was 14 months and the mortality rate was 15.6%. The significant factor associated with mortality was severe malnutrition. In total 88% of required data were available for the calculation of both the PRISM and PELOD scores and 95% for PIM3 score. The PRISM; PELOD and PIM3 standardised mortality ratios were 2.5; 4.8 and 2.9; respectively. P-values for PRISM; PELOD and PIM3 were 0.05.Conclusion. Severe malnutrition is a statistically significant factor in predicting mortality. This possibly reflects the social context in which the children live. PRISM; PELOD and PIM3 underpredict mortality in our setting. A larger sample is required to verify these outcomes and to determine whether other factors play a role

A search for varying fundamental constants using hertz-level frequency measurements of cold CH molecules.

Many modern theories predict that the fundamental constants depend on time, position or the local density of matter. Here we develop a spectroscopic method for pulsed beams of cold molecules, and use it to measure the frequencies of microwave transitions in CH with accuracy down to 3 Hz. By comparing these frequencies with those measured from sources of CH in the Milky Way, we test the hypothesis that fundamental constants may differ between the high- and low-density environments of the Earth and the interstellar medium. For the fine structure constant we find Δα/α=(0.3 ± 1.1) × 10⁻7, the strongest limit to date on such a variation of α. For the electron-to-proton mass ratio we find Δµ/µ=(-0.7 ± 2.2) × 10⁻7. We suggest how dedicated astrophysical measurements can improve these constraints further and can also constrain temporal variation of the constants.

Characterization of a cryogenic beam source for atoms and molecules.

We present a combined experimental and theoretical study of beam formation from a cryogenic buffer gas cell. Atoms and molecules are loaded into the cell by laser ablation of a target, and are cooled and swept out of the cell by a flow of cold helium. We study the thermalization and flow dynamics inside the cell and measure how the speed, temperature, divergence and extraction efficiency of the beam are influenced by the helium flow. We use a finite element model to simulate the flow dynamics and use the predictions of this model to interpret our experimental results.

Herpes keratitis.

Herpes simplex virus-1 (HSV-1) infects the majority of the world's population. These infections are often asymptomatic, but ocular HSV-1 infections cause multiple pathologies with perhaps the most destructive being herpes stromal keratitis (HSK). HSK lesions, which are immunoinflammatory in nature, can recur throughout life and often cause progressive corneal scaring resulting in visual impairment. Current treatment involves broad local immunosuppression with topical steroids along with antiviral coverage. Unfortunately, the immunopathologic mechanisms defined in animal models of HSK have not yet translated into improved therapy. Herein, we review the clinical epidemiology and pathology of the disease and summarize the large amount of basic research regarding the immunopathology of HSK. We examine the role of the innate and adaptive immune system in the clearance of virus and the destruction of the normal corneal architecture that is typical of HSK. Our goal is to define current knowledge of the pathogenic mechanisms and recurrent nature of HSK and identify areas that require further study.

Franck-Condon factors and radiative lifetime of the A2Π(1/2)-X2Σ+ transition of ytterbium monofluoride, YbF.

The fluorescence spectrum resulting from laser excitation of the A(2)Π(1/2)←X(2)Σ(+) (0,0) band of ytterbium monofluoride, YbF, has been recorded and analyzed to determine the Franck-Condon factors. The measured values are compared with those predicted from Rydberg-Klein-Rees (RKR) potential energy curves. From the fluorescence decay curve the radiative lifetime of the A(2)Π(1/2) state is measured to be 28 ± 2 ns, and the corresponding transition dipole moment is 4.39 ± 0.16 D. The implications for laser cooling YbF are discussed.

Patients' perspective on the comprehensive preventive health evaluation in veterans with spinal cord injury.

STUDY DESIGN: Survey research methods. OBJECTIVES: To assess patient satisfaction with the annual comprehensive preventative health evaluation (CPHE) and to determine if the patient's needs were being met. SETTING: Department of Veterans Affairs National Survey, United States. METHODS: A total of 853 subjects with spinal cord injuries participated in a mailed survey regarding the annual CPHE. Subjects were asked about satisfaction with the examination, preferences on how the examination is conducted and whether their needs were being met with the examination. RESULTS: In all, 76% of the subjects that responded to the survey had completed a CPHE within the previous year. Subjects cited getting their medication and supplies refilled and talking to the doctor as the top two reasons for completing the evaluation. Subjects indicated that they would most like to discuss their muscle strength and weakness, bladder care, chronic pain, digestion and bowel care issues, and equipment problems during their evaluation. The majority of subjects (81%) indicated that they were satisfied with the CPHE. Subjects that were satisfied with the CPHE were also more satisfied with other aspects of care as well. CONCLUSION: The majority of respondents had completed a CPHE within the previous year. Most respondents cite health issues related to the spinal cord injury as areas they would most like to discuss during the evaluation. The majority of subjects were satisfied with the conduct of the CPHE.

Lactams as EP4 prostanoid receptor agonists. 3. Discovery of N-ethylbenzoic acid 2-pyrrolidinones as subtype selective agents.

Two distinct synthetic schemes were applied to access heteroatom-containing alpha-chain lactams or lactams terminated as aryl acids. The latter lactams were devised using a pharmacophore for EP(4) receptor activity. gamma-Lactams were characterized for their prostanoid EP receptor affinities and EP(4) activity and found to be selective for the EP(2) and EP(4) receptors or selective for the EP(4) subtype. Benzoic acid 17 displayed enhanced in vivo exposure relative to 3.

Gamma interferon can prevent herpes simplex virus type 1 reactivation from latency in sensory neurons.

We recently demonstrated that CD8(+) T cells could block herpes simplex virus type 1 (HSV-1) reactivation from latency in ex vivo trigeminal ganglion (TG) cultures without destroying the infected neurons. Here we establish that CD8(+) T-cell prevention of HSV-1 reactivation from latency is mediated at least in part by gamma interferon (IFN-gamma). We demonstrate that IFN-gamma was produced in ex vivo cultures of dissociated latently infected TG by CD8(+) T cells that were present in the TG at the time of excision. Depletion of CD8(+) T cells or neutralization of IFN-gamma significantly enhanced the rate of HSV-1 reactivation from latency in TG cultures. When TG cultures were treated with acyclovir for 4 days to insure uniform latency, supplementation with recombinant IFN-gamma blocked HSV-1 reactivation in 80% of cultures when endogenous CD8(+) T cells were present and significantly reduced and delayed HSV-1 reactivation when CD8(+) T cells or CD45(+) cells were depleted from the TG cultures. The effectiveness of recombinant IFN-gamma in blocking HSV-1 reactivation was lost when its addition to TG cultures was delayed by more than 24 h after acyclovir removal. We propose that when the intrinsic ability of neurons to inhibit HSV-1 gene expression is compromised, HSV-specific CD8(+) T cells are rapidly mobilized to produce IFN-gamma and perhaps other antiviral cytokines that block the viral replication cycle and maintain the viral genome in a latent state.

Alpha-1-antitrypsin and a broad spectrum metalloprotease inhibitor, RS113456, have similar acute anti-inflammatory effects.

There is increasing evidence that antiproteases are able to affect the inflammatory response. To further examine this question, we administered human alpha-1-antitrypsin (alpha1AT) or a synthetic metalloprotease inhibitor (RS113456) to C57 mice followed by a single intratracheal dose of quartz, a dust that evokes a marked, lasting, polymorphonuclear leukocyte (PMN) infiltrate. At 2 hours after dust administration, both antiproteases completely suppressed silica-induced PMN influx into the lung and macrophage inflammatory protein-2 (MIP-2)/monocyte chemotactic protein-1 (MCP-1) (neutrophil/macrophage chemoattractant) gene expression, partially suppressed nuclear transcription factor kappaB (NF-kappaB) translocation, and increased inhibitor of NF-kappaB (IkappaB) levels. By 24 hours, PMN influx and connective tissue breakdown measured as lavage desmosine or hydroxyproline were still at, or close to, control levels after antiprotease treatment, and increases in NF-kappaB translocation and MIP-2/MCP-1 gene expression were variably suppressed. At both time points, neither agent prevented silica-induced increases in amount of whole lung MIP-2 or MCP-1 protein, but both did prevent increases in whole lung intercellular adhesion molecule-1 (ICAM-1) at 24 hours. Inactivating the alpha1AT by oxidation to the point that it no longer possessed antiproteolytic properties did not affect its ability to suppress inflammation. Both antiproteases also prevented the silica-induced acute inflammatory response in mice with knocked out genes for macrophage metalloelastase (MME -/-), mice that develop inflammation, but not connective tissue breakdown, and the pattern of alpha1AT breakdown fragments was identical in control and MME -/- animals. These findings suggest that, in this model of acute PMN mediated inflammation, a serine protease inhibitor and a metalloprotease inhibitor have similar anti-inflammatory properties, that inflammation is not mediated by proteolysis with generation of chemotactic matrix fragments, and that classic antiproteolysis (complexing of protease to antiprotease) probably does not play a role in suppression of inflammation. The antiproteolytic effects of these agents do not seem to be mediated by protection of endogenous alpha1AT.

Comparison of subacute rehabilitative care with outpatient primary medical care.

PURPOSE: Prior rehabilitation outcome studies have had many weaknesses. but they gradually observe a lack of long-term benefits from inpatient care alone. The goal of this study was to measure the additive effect of outpatient, subacute rehabilitation (compared with usual outpatient primary medical care) for adults diagnosed with a disabling disorder in four major diagnostic groups (nervous, circulatory, musculoskeletal and injury). METHOD: A randomized clinical trial was conducted to determine the effects of outpatient, subacute rehabilitative care on: (1) physical function; (2) health; (3) well being; (4) family function; and (5) social support. Patients hospitalized for the first time with a disabling condition (n = 180) were provided inpatient rehabilitation and then were randomly assigned to either outpatient, subacute rehabilitation at home (n = 90) or to usual outpatient follow-up (n = 90) in which only primary care medical services were provided. To compare the two groups, univariate analyses of covariance were conducted for the outcome variables. RESULTS: The major finding of this study was that of no significant effect of the intervention on any outcome variable. CONCLUSIONS: Based on current study results, we conclude that any long term additive benefit of outpatient, subacute rehabilitation may not be detectable across disability categories and may require closer evaluation in studies with a more homogeneous population than in the current study. Providing complex follow-up case management services to all clients is apparently not beneficial and might better be provided using selection criteria based on need. Future studies should determine if services are more effective when provided to those with the most unmet rehabilitative needs. Further outpatient, subacute care rehabilitation studies should address the specific needs of the patients and be adapted individually to those needs.

Department of Veterans Affairs Quality Enhancement Research Initiative for spinal cord injury.

Spinal cord injury (SCI) is a lifelong condition, requiring ongoing efforts by multiple disciplines to stabilize, diminish, or prevent impairments; avoid or limit secondary complications; and improve or maintain social role functioning and quality of life for the individual throughout his or her life. There are approximately 200,000 persons with SCI in the United States, of whom roughly 22% are veterans. The estimated national economic impact of SCI is approximately $9.73 billion per year. These figures illustrate why SCI is an important topic for the Department of Veterans Affairs Quality Enhancement Research Initiative (QUERI). The SCI QUERI will identify gaps in knowledge of SCI treatment and management, develop research efforts to address these gaps, identify best practices for care and management of SCI, and assess whether best practices lead to improved outcomes, including health-related quality of life.

CD8(+) T cells can block herpes simplex virus type 1 (HSV-1) reactivation from latency in sensory neurons.

Recurrent herpes simplex virus type 1 (HSV-1) disease usually results from reactivation of latent virus in sensory neurons and transmission to peripheral sites. Therefore, defining the mechanisms that maintain HSV-1 in a latent state in sensory neurons may provide new approaches to reducing susceptibility to recurrent herpetic disease. After primary HSV-1 corneal infection, CD8(+) T cells infiltrate the trigeminal ganglia (TGs) of mice, and are retained in latently infected ganglia. Here we demonstrate that CD8(+) T cells that are present in the TGs at the time of excision can maintain HSV-1 in a latent state in sensory neurons in ex vivo TG cultures. Latently infected neurons expressed viral genome and some expressed HSV-1 immediate early and early proteins, but did not produce HSV-1 late proteins or infectious virions. Addition of anti-CD8alpha monoclonal antibody 5 d after culture initiation induced HSV-1 reactivation, as demonstrated by production of viral late proteins and infectious virions. Thus, CD8(+) T cells can prevent HSV-1 reactivation without destroying the infected neurons. We propose that when the intrinsic capacity of neurons to inhibit HSV-1 reactivation from latency is compromised, production of HSV-1 immediate early and early proteins might activate CD8(+) T cells aborting virion production.

The effect of diabetes self-management education with frequent follow-up on the health outcomes of African American men.

PURPOSE: This study was conducted to determine whether objective clinical, patient performance, quality-of-life, and subjective outcomes are significantly different among African American men with type 2 diabetes who received follow-up at either monthly or 3-month intervals after participating in a structured diabetes self-management education program. METHODS: Prior to the diabetes self-management education program, 30 African American men with type 2 diabetes were randomly assigned to 2 groups to receive telephone follow-up at either monthly or 3-month intervals over a 6-month period. Information obtained at follow-up contact included HbA1c level, perception of general health, and present diabetes knowledge. In addition, daily foot care, dietary, exercise, and medication compliance measures were assessed postprogram. RESULTS: There were no significant differences between the participants who received follow-up at monthly and 3-month intervals on any measures of the selected clinical, patient performance, quality-of-life, and subjective outcomes. CONCLUSIONS: This cross-sectional study showed that telephone follow-up at 3-month intervals following a structured program of diabetes self-management education may be just as effective in contributing to favorable diabetes health outcomes as monthly follow-up.

The Diabetes Day Treatment experiment: a preliminary report on what we learned.

PURPOSE: This paper presents data on the efficacy of a diabetes day treatment program to modify the healthcare behavior of elderly African Americans with diabetes. METHODS: African American patients with Type 1 or Type 2 diabetes who were referred by their certified diabetes educator were eligible to participate in the day treatment program. The program was designed to serve eight patients for 4 hours 1 day a week over 9 months. Participants engaged in informal discussions, low-impact armchair exercises, and discussions of various diabetes issues. A flow sheet was initiated and maintained by the investigators to record information pertaining to each participant's blood pressure, blood sugar, and weight at each session. Attendance and reasons for not attending sessions were recorded. To obtain more in-depth information, the group leaders used a technique known as participant observation. RESULTS: Having CDEs administer a blood sugar test, take blood pressure, and weigh each patient at each clinic visit promotes patient adherence to the diabetes treatment regimen. Memory loss was observed to be especially prevalent among the subjects. CONCLUSIONS: The Diabetes Day Treatment Program may be used as a model for working with elderly persons with diabetes from different ethnic groups.

Suppression of experimental abdominal aortic aneurysms by systemic treatment with a hydroxamate-based matrix metalloproteinase inhibitor (RS 132908).

BACKGROUND: Abdominal aortic aneurysms (AAAs) are associated with chronic inflammation, disruption of medial elastin, and increased local production of elastolytic matrix metalloproteinases (MMPs). The purpose of this study was to investigate how treatment with a hydroxamate-based MMP antagonist (RS 132908) might affect the development of experimental AAAs. METHODS: Male Wistar rats underwent intraluminal perfusion of the abdominal aorta with 50 units of porcine pancreatic elastase followed by treatment for 14 days with RS 132908 (100 mg/kg/day subcutaneously; n = 8) or with vehicle alone (n = 6). The external aortic diameter (AD) was measured in millimeters before elastase perfusion and at death, with AAA defined as an increase in AD (DeltaAD) of at least 100%. Aortic wall elastin and collagen concentrations were measured with assays for desmosine and hydroxyproline, and fixed aortic tissues were examined by light microscopy. RESULTS: AAAs developed in all vehicle-treated rats, with a mean AD (+/- SE) that increased from 1.60 +/- 0.03 mm before perfusion to 5.98 +/- 1.02 mm on day 14 (DeltaAD = 276.4 +/- 67.7%). AAAs developed in only five of eight animals (62.5%) after MMP inhibition, with a mean AD that increased from 1.56 +/- 0.05 mm to 3.59 +/- 0.34 mm (DeltaAD = 128.1 +/- 18.7%; P <.05, vs vehicle). The overall inhibition of aortic dilatation attributable to RS 132908 was 53.6 +/- 6.8%. Aortic wall desmosine fell by 85.4% in the vehicle-treated rats (1210.6 +/- 87.8 pmol/sample to 176.7 +/- 33.4 pmol/sample; P <.05) but only by 65.6% in the animals treated with RS 312908 (416.2 +/- 120.5 pmol/sample). In contrast, hydroxyproline was not significantly affected by either elastase perfusion or drug treatment. Microscopic examination revealed the preservation of pericellular elastin and a greater degree of fibrocollagenous wall thickening after MMP inhibition, with no detectable difference in the extent of inflammation. CONCLUSIONS: Systemic MMP inhibition suppresses aneurysmal dilatation in the elastase-induced rodent model of AAA. Consistent with its direct inhibitory effect on various MMPs, RS 132908 promotes the preservation of aortic elastin and appears to enhance a profibrotic response within the aortic wall. Hydroxamate-based MMP antagonists may therefore be useful in the development of pharmacologic approaches to the suppression of AAAs.

Crystal structures of MMP-1 and -13 reveal the structural basis for selectivity of collagenase inhibitors.

The X-ray crystal structures of the catalytic domain of human collagenase-3 (MMP-13) and collagenase-1 (MMP-1) with bound inhibitors provides a basis for understanding the selectivity profile of a novel series of matrix metalloprotease (MMP) inhibitors. Differences in the relative size and shape of the MMP S1' pockets suggest that this pocket is a critical determinant of MMP inhibitor selectivity. The collagenase-3 S1' pocket is long and open, easily accommodating large P1' groups, such as diphenylether. In contrast, the collagenase-1 S1' pocket must undergo a conformational change to accommodate comparable P1' groups. The selectivity of the diphenylether series of inhibitors for collagenase-3 is largely determined by their affinity for the preformed S1' pocket of collagenase-3, as compared to the induced fit in collagenase-1.