Feldkamp and circle-and-line cone-beam reconstruction for 3D micro-CT of vascular networks

Detailed morphometric knowledge of the microvascular network is needed for studies relating structure to haemodynamic function in organs like the lung. Clinical volumetric CT is limited to millimetre-order spatial resolution. Since evidence suggests that small arterioles (50 to 300 micrometres) dominate pulmonary haemodynamics, we built a micro-CT scanner, capable of imaging excised lungs in 3D with 100 microm resolution, for basic physiology research. The scanner incorporates a micro-focal (3 microm) x-ray source, an xyz theta stage and a CCD-coupled image intensifier detector. We imaged phantoms and contrast-enhanced rat lungs, reconstructing the data with either the Feldkamp or the circle-and-line cone-beam reconstruction algorithm. We present reconstructions using 180 views over 360 degrees for the circular trajectory, augmented with views from a linear scan for the circle-and-line algorithm. Especially for platelike features perpendicular to the rotation axis and remote from the midplane, the circle-and-line algorithm produces superior reconstructions compared with Feldkamp's algorithm. We conclude that the use of nonplanar source trajectories to perform micro-CT on contrast-enhanced, excised lungs can provide data useful for morphometric analysis of vascular trees, currently down to the 130 microm level.     

Analysis of clustered data in receiver operating characteristic studies

Clustered data is not simply correlated data, but has its own unique aspects. In this paper, various methods for correlated receiver operating characteristic (ROC) curve data that have been extended specifically to clustered data are reviewed. For those methods that have not yet been extended, suggestions for their application to clustered ROC studies are provided. Various methods with respect to their ability to meet either of two objectives of the analysis of clustered ROC data are compared to consider a variety of ROC indices and their accessibility to researchers. The available statistical methods for clustered data vary in the range of indices that can be considered and in their accessibility to researchers. Parametric models permit all indices to be considered but, owing to computational complexity, are the least accessible of available methods. Nonparametric methods are much more accessible, but only permit estimation and inference about ROC curve area. The jackknife method is the most accessible and permits any index to be considered. Future development of methods for clustered ROC studies should consider the continuation ratio model, which will permit the application of widely available software for the analysis of mixed generalized linear models. Another area of development should be in the adoption of bootstrapping methods to clustered ROC data.     

Interleukin-12 and interleukin-18 synergistically induce murine tumor regression which involves inhibition of angiogenesis

The antitumor effect and mechanisms activated by murine IL-12 and IL-18, cytokines that induce IFN-gamma production, were studied using engineered SCK murine mammary carcinoma cells. In syngeneic A/J mice, SCK cells expressing mIL-12 or mIL-18 were less tumorigenic and formed tumors more slowly than control cells. Neither SCK.12 nor SCK.18 cells protected significantly against tumorigenesis by distant SCK cells. However, inoculation of the two cell types together synergistically protected 70% of mice from concurrently injected distant SCK cells and 30% of mice from SCK cells established 3 d earlier. Antibody neutralization studies revealed that the antitumor effects of secreted mIL-12 and mIL-18 required IFN-gamma. Interestingly, half the survivors of SCK.12 and/or SCK.18 cells developed protective immunity suggesting that anti-SCK immunity is unlikely to be responsible for protection. Instead, angiogenesis inhibition, assayed by Matrigel implants, appeared to be a property of both SCK.12 and SCK.18 cells and the two cell types together produced significantly greater systemic inhibition of angiogenesis. This suggests that inhibition of tumor angiogenesis is an important part of the systemic antitumor effect produced by mIL-12 and mIL-18.     

A model for improving medication use in home health care patients

OBJECTIVES: (1) To develop a model for the identification and resolution of problems associated with suboptimal medication use in elderly patients receiving home health care; (2) To select the most important identifiable problems and develop structured procedures for their resolution. DESIGN: Expert panel review, problem selection, and development of a problem resolution model and guidelines. SETTING: Home health care. PARTICIPANTS: A panel with expertise in home health nursing, pharmacy, clinical pharmacology, gerontology, pharmacoepidemiology, and health services research. INTERVENTIONS: A list of potential problems associated with the most frequently used classes of drugs was compiled for review by the panel. Problems that were controversial or that could not be identified in the home care setting were excluded. Panel members individually ranked the remainder. Detailed procedures for identification and resolution of the 15 top-ranking problems were developed. MAIN OUTCOME MEASURES: Not applicable. RESULTS: Potential medication problems were defined by both drug use and symptoms or clinical signs associated with specific adverse effects, to ensure that clinically relevant problems would be identified. The model developed for problem assessment and resolution was centered on the drug utilization review (DUR) coordinator and the attending home health nurse. Following guidelines developed by the panel, the DUR coordinator advises the home health nurse about identified problems and how to resolve them. One of these practitioners, usually the nurse, then contacts the attending physician to explain their concerns, offer potential solutions, and request instructions. CONCLUSION: A potentially useful model for the identification and resolution of medication problems in the home health care setting was developed. This model is currently being evaluated in a randomized controlled trial.     

Hydroxyl radical production in the brain after CO hypoxia in rats

Reactive oxygen species (ROS) have been implicated in the pathogenesis of neuronal injury after carbon monoxide (CO) poisoning. Severe CO poisoning is treated with hyperbaric oxygen (HBO), which eliminates CO quickly from hemoglobin and body tissue stores, but has a potential to increase ROS generation. In this study, the effects of HBO on generation of highly reactive hydroxyl radical (HO.) in the brain after CO poisoning in rats was investigated using nonenzymatic hydroxylation of salicylic acid to 2,3 dihydroxybenzoic acid (2,3-DHBA) as a probe. In control studies, the concentrations of 2,3-DHBA after HBO in brain mitochondria and postmitochondrial supernatant (cytosol) were similar to air-exposed animals. After CO poisoning, 2,3-DHBA concentration increased in brain mitochondria but not in the cytosol. After CO exposure and HBO administration at 1.5 atmospheres absolute (ATA), a decrease in 2,3-DHBA production was detected in brain mitochondria. After CO and HBO at 2.5 ATA, 2,3-DHBA concentration increased in both mitochondria and cytosol. The oxidant scavenger dimethylthiourea (DMTU) and the monoamine oxidase (MAO) inhibitor pargyline, administered to CO poisoned rats after HBO at 2.5 ATA, diminished 2,3-DHBA production in both subcellular compartments. These findings indicate that brain HO. production can be either diminished or accelerated after severe CO poisoning depending on the oxygen partial pressure employed during therapy.     

Leukocyte transfusion-associated granulocyte responses in a patient with X-linked hyper-IgM syndrome

X-linked hyper-IgM syndrome (XHIM) is a severe congenital immunodeficiency caused by mutations in CD154 (CD40 ligand, gp39), the T cell ligand for CD40 on B cells. Chronic or cyclic neutropenia is a frequent complicating feature that heightens susceptibility to severe infections. We describe a patient with a variant of XHIM who produced elevated levels of serum IgA as well as IgM and suffered from chronic severe neutropenia. Eight of ten leukocyte transfusions with cells from a maternal aunt, performed because of mucosal infections, resulted in similar episodes of endogenous granulocyte production. Transfection studies with the mutant CD154 protein indicate that the protein is expressed at the cell surface and forms an aberrant trimer that does not interact with CD40. The data suggest that allogeneic cells from the patient's aunt, probably activated T cells bearing functional CD154, may interact with CD40+ recipient cells to produce maturation of myeloid precursors in the bone marrow.     

Activation of complement by mannose-binding lectin on isogenic mutants of Neisseria meningitidis serogroup B

Mannose-binding lectin (MBL) is a serum protein that has been demonstrated to activate the classical complement pathway and to function directly as an opsonin. Although MBL deficiency is associated with a common opsonic defect and a predisposition to infection, the role of the protein in bacterial infection remains unclear. We have investigated MBL binding to Neisseria meningitidis serogroup B1940 and three isogenic mutants, and the subsequent activation of the two major isoforms of C4 (C4A and C4B) by an associated serine protease, MASP. The mutants lacked expression of the capsular polysaccharide (siaD-), the lipo-oligosaccharide (LOS) outer core that prevented LOS sialylation (cpsD-), or both capsule and LOS outer core (cps-). Using flow cytometry, it was possible to detect strong MBL binding to the cps- and cpsD- mutants over a wide range of concentrations. In contrast, minimal or no MBL binding was detected on the parent organism, with binding to siaD- only at higher MBL concentrations. C4 was activated and bound by mutants that had previously bound MBL/MASP, but there was no significant difference in the amounts of C4A and C4B bound. When sialic acid residues were removed from the parent organism by neuraminidase treatment, the binding of both MBL and C4 increased significantly. Our results suggest that MBL may bind to and activate complement on these encapsulated organisms, and the major determinants of these effects are the LOS structure and sialylation.     

An object-oriented SECS programming environment

An object-oriented programming (OOP) environment for developing SEMI Equipment Communication Standard (SECS) applications with the C++ and C programming languages in a Unix workstation environment is described. The system defines a set of programming objects corresponding to the standard SECS-II item types, messages and headers as well as a number of support classes and operations. Conversion between standard program datatypes and SECS-II items is transparent or explicitly managed by the developer. Within a standard framework using standard C++ input/output methods, SECS-II messages may be created, analyzed, transmitted and received between internal buffers, external files and communication channels. Classes corresponding to specific SECS stream and function codes are also available and can be incorporated easily into application code with little or no modification