Neonatal cytokines and coagulation factors in children with cerebral palsy

We explored the association of inflammatory mediators and markers of autoimmune and coagulation disorders with cerebral palsy (CP), examining 53 analytes in dried neonatal blood of 31 children with spastic CP, most born at term, and 65 control children. Ultramicroanalysis was performed by recycling immunoaffinity chromatography coupled with laser-enhanced fluorescence and chemiluminescence detection. Reactive antibodies to lupus anticoagulant, anticardiolipin, antithrombin III, and the translational product of the factor V Leiden mutation were isolated by recycling immunoaffinity chromatography and measured by capillary electrophoresis with chemiluminescence-enhanced immunoassay. Higher concentrations of interleukins (ILs) 1, 8, 9, tumor necrosis factor-alpha, and RANTES were observed in these children with CP than in any control child. There were also substantial elevations of IL-6, 11, 13, and other chemokines and colony-stimulating factors in children with CP. Antiphospholipid antibody was present in a titer of 1:100 or greater in 4 children with CP and no control child. Using cuts empirically chosen by recursive partitioning, we found higher concentrations of antibody to antithrombin III, to a translational product of factor V Leiden mutation, and to proteins C and S in children with CP than in controls. We conclude that inflammation and these coagulation abnormalities, which have interacting pathways, are important in the etiology of CP.     

On the structural changes of native human alpha2-macroglobulin upon proteinase entrapment. Three-dimensional structure of the half-transformed molecule

The reconstructions of an intermediate form of human alpha2-macroglobulin (half-transformed alpha2M) in which two of its four bait regions and thiol ester sites were cleaved by chymotrypsin bound to Sepharose were obtained by three-dimensional electron microscopy from stain and frozen-hydrated specimens. The structures show excellent agreement and reveal a structure with approximate dimensions of 195 (length) x 135 (width) and 130 A (depth) with an internal funnel-shaped cavity. The structure shows that a chisel-shaped body is connected to a broad base at the opposing end by four stands. Four approximately 45 A diameter large openings in the body of the structure result in a central cavity that is more accessible to the proteinase than those associated with the native or fully transformed structures. The dissimilarity in the shapes between the two ends of alpha2M half-transformed and the similarity between its chisel-shaped body and that of native alpha2M indicate that the chymotrypsin has cleaved both bait regions in the bottom-half of the structure. Consequently, its functional division lies on the minor axis. The structural organization is in accord with biochemical studies, which show that the half-transformed alpha2M migrates on native polyacrylamide gels at a rate intermediate to the native and fully transformed alpha2M and is capable of trapping 1 mol of proteinase. Even though its upper portion is similar to the native molecule, significant differences in their shapes are apparent and these differences may be related to its slower reaction with a proteinase than the native structure. These structural comparisons further support the view that the transformation of alpha2M involves an untwisting of its strands with an opening of the cavity for entrance of the proteinase and a retwisting of the strands around the proteinase resulting in its encapsulation.     

Effects of damp and mould in the home on respiratory health: a review of the literature

This review targets the current role of the pathologist in the diagnosis and management of breast disease, a responsibility that evolved along with an increasingly complex approach to human breast cancer. We will focus on the three major areas of this responsibility: premalignancy, highlighting the atypical hyperplasias; the carcinomas in situ, highlighting low grade ductal carcinoma in situ; and the stratification and prognosis of invasive carcinomas. It will be evident that with the advent of an increasingly rich menu of treatment options, the challenge to identify an optimal categorization of breast cancer and its putative precursors is not static.     

Area and depth of surfactant-induced corneal injury correlates with cell death

PURPOSE: In previous studies in which in vivo confocal microscopy (CM) was used, quantifiable differences were identified in the corneal epithelium and stroma for surfactants producing different degrees of ocular irritation. In the present study, in vivo confocal microscopy was used to determine area and depth of the initial corneal changes, and the correlation of the data to cell death was characterized by ex vivo live-dead assay. METHODS: In four groups of rabbits (12 animals each), 10 microl surfactants known to produce slight, mild, moderate, or severe irritation was applied to the central cornea of one eye; 4 untreated rabbits served as controls. Measurements of group total mean epithelial thickness, epithelial cell area, and depth of keratocyte loss in four corneal regions were made by in vivo CM in 6 rabbits of each group and in 4 control animals at 3 hours and in the remaining rabbits at 3 hours and 1 day. Corneas were then removed and fixed for conventional histologic examination (two eyes/treatment/group), or regions were excised and placed in culture media containing 2 microM calcein-acetoxymethyl ester (calcein-AM) and 4 microM ethidium homodimer. Using laser scanning CM, the number of dead epithelial or stromal cells in a 300 x 300 x 170 microm (in the x, y, and z axes, respectively) volume of the cornea was determined. RESULTS: Confocal microscopy showed that application of the slight irritant resulted in decreased epithelial thickness at 3 hours (41.2+/-2.6 microm in treated eyes versus 43.6+/-3 microm in control eyes; n=6 and 4, respectively) and a significant decrease (P < 0.001) in epithelial cell size (630+/-203 microm2 versus 1427.2+/-90.7 microm2). On day 1, mild, moderate, and severe irritants caused complete loss of epithelium and disappearance of keratocytes to a depth of 30.8+/-10.7 microm, 47.2+/-10.4 microm, and 764.6+/-159.6 microm (n=6, 5, and 6), respectively. At 3 hours, live-dead assay detected more dead epithelial cells as a percentage of total surface cells (49.2+/-4.5% in slightly irritated eyes versus 20.9+/-3.2% in control eyes), significantly correlating with the measurement by in vivo CM of average epithelial cell size in each eye (r=-0.96; P < 0.005). On day 1, mild and moderate irritants showed increasing stromal cell death from 9.8+/-16.2 cells to 36.4+/-17.7 cells, which significantly correlated with the depth of stromal injury determined by in vivo CM (r=0.79; P < 0.00001). No surviving keratocytes were detected in severely irritated eyes. CONCLUSIONS: The data support the hypothesis that differences in surfactant-induced ocular irritation are directly related to area and depth of acute corneal injury.     

Effects of ketorolac on bone repair: A radiographic study in modeled demineralized bone matrix grafted rabbits

The treatment of instability of the multiply reoperated knee is a complex problem. The causes for failure are numerous and include repeated trauma, insufficient fixation and non-anatomic placement of the graft, inadequate replacement material, isolated anterior cruciate ligament (ACL) reconstruction in complex knee instability or the use of a ligament prosthesis. With every surgical procedure, however, the anatomical and technical conditions become worse. Problems like degenerative changes, joint stiffness and gait abnormalities occur and often become a more focal point than the instability itself. The purpose of this paper is to present the problems and the dilemma of instability of the multiply reoperated knee and the possible solutions. Between 1976 and 1996, a total of 1752 ACL reconstructions were carried out in Munich and Hannover. Of these, 228 (13%) were revision, mostly of failed ACL reconstructions performed elsewhere. Since 1989, we have chosen the severest cases from this group (more than three operations on the same knee) for this study. Seventeen patients were investigated who had undergone up to 25 operations. The mean number of operations was 7. All primary operations were performed in other hospitals. In 10 cases only the ACL reconstruction was performed as a final procedure, mostly in combination with other procedures like medial meniscus replacement, extra-articular stabilization or arthrolysis. In the other cases operations such as osteotomies, arthrodesis or amputation were necessary. The results present the main dilemma in instability of the multiply reoperated knee since they were not successful in all patients. Finally, 15 patients report still having instability, pain or swelling in isolation or in combination. Nine patients were satisfied with their subjective results. Even after the socalled definitive procedures, certain complications arose. The main goal in the treatment of instability of the multiply reoperated knee is to avoid a series of operations, hospitalization and history of illness. General revision surgery for the entire complaint is not the aim of the treatment. The specific problem of the patient should be extracted from the complex situation, and this should be solved with the most limited procedure possible only.     

Image segmentation by conventional and information-integrating techniques: a synopsis

A synoptic discussion of image segmentation is presented. The aim is to provide an overall understanding of the general problems and issues associated with various segmentation techniques. The discussion has been organized in two parts: the first part is on those conventional techniques which use mainly information from one type of data; the second part is on those which try to combine data from several sources to obtain interpretations that cannot be obtained or would be hard to obtain from any single source of data. The paper stresses the importance, for segmentation, of data integration from several sensors and data integration over time, particularly the use of motion. It further emphasizes the importance of stating clearly the assumptions before developing or using a particular image segmentation algorithm.