Datasets:

bisectgroup

/

PubMed_TA

like 0

Follow

Biosystems Engineering and Control Group 20

15546015

Digital treatment objectives: procedure and clinical application.

the introduction of digital study models in the orthodontic practice changed the traditional stone gipsotec to a virtual gipsotec and the orthodontist has the possibility to see, immediately on the computer, this basic analysis with a great reduction of space and time. The aim of this study is to extend the use of digital models to the occlusal virtual set-up in 3D and have the orthodontist simulate and visualize the resulting occlusion from a suggested treatment plan for the malocclusion. a case is presented where the treatment plan involvers extractions. The malocclusion is a Class II division 1 in the permanent dentition where an extraction treatment of 1.4, 2.4, 3.5 et 4.5 is planned: the final result shows the new occlusal relationship with proper anchorage management of the extraction spaces. From the primary silicon impression, a digital model is obtained followed by the virtual set up according the prescription of the treatment plan. More digital treatment objectives can be performed for the same malocclusion from the primary digital models, according to different treatment plans and the resulting occlusion visualized. the basic principle for the virtual occlusal set-up is the straight-wire system with the final position of the teeth resulting both from the bracket prescription and the final rectangular wire in a full slot engagement. the resulting dental arches show a correct arch form, arch coordination and a proper dental intercuspation. The results coming from different virtual simulations are analyzed; all these simulations need only one pair of impressions. Limits of this virtual method are that it can be used only in full permanent dentition and for cases of dento-alveolar or dento-dental discrepancy.

15546014

The use of titanium miniscrews for molar protraction in extraction treatment.

Orthodontic space closure in the mandibular arch by protraction of the mandibular second molars, after the extraction of first molars, may sometimes result in loss of incisor anchorage when using conventional orthodontic procedures. The introduction of miniscrews for immediate loading as orthodontic anchorage, has enlarged treatment possibilities. The authors illustrate their clinical experience in an adult patient treated with the extraction of mandibular first molars and the protraction of second and third molars into the extraction sites. Anchorage control was achieved with the surgical insertion of titanium miniscrews for immediate loading in the cortical bone distal to second bicuspids. Space closure was achieved by means of sliding mechanics according to Bidimensional Technique. The position of lower incisors was maintained preventing any detrimental facial effect.

15546013

Clinical applications of the Mini-Screw-Anchorage-System (M.A.S.) in the maxillary alveolar bone.

anchorage control with self-tapping screws has become an important part of the clinical management of the orthodontic patients. Mechanical resistance and sites of insertion of miniscrews as orthodontic anchorage are critical to ensure successful outcomes. Aim of this clinical study was threefold: 1) to measure the mechanical resistance of the M.A.S., 2) to evaluate if the alveolar areas usually selected for mini-screws placement are adequate, 3) to illustrate the most frequent clinical application on the maxillary alveolar bone. two methods were chosen to test these screws mechanically, representing two potential modes of failure during insertion or removal: torsional strenght and bending strenght. Three-dimension images of fifty maxillas have been retrieved from a group of 200 patients, age range between 20 and 40 years with a new type of tomogram called Newtom System. For each area mesio-distal and labio-lingual measurements from four horizontal cuts made at 2-5-8-11 mm below the bone-crest have been evaluated. the mean value of resistance to breakage in torsion is of 48.7 N.cm (around 5 Kg) for the miniscrew of 1.5 diameter, while the mean value of resistance to breakage in torsion is of 23.4 N.cm (around 2 Kg) for the miniscrew of 1.3 diameter.. The mean value of resistance to breakage in flexion is of 120.4 N (around 12 Kg) for the miniscrew of 1.5 diameter, while the mean value of resistance to the flexion is of 63.7 N (around 6 Kg) for the miniscrew of 1.3 diameter. On the maxillary alveolar bone the highest amount of bone was in mesio-distal dimension between 6 and 5 on the palatal side (minimum 1.9 mm at -11 mm cut; maximum 5.5 mm at -5 mm cut). The smallest amount of bone was in the tuber (minimum 0.2 mm; maximum 1.3 mm). Examination of the labio-palatal dimension demonstrated similar high thickness between 5-6 and 6-7 (minimum 3.7 mm at -11 mm cut; maximum 13.2 mm at -2 mm cut). The smallest amount of bone was recorded on the tuber (minimum 0.6 mm; maximum 4.1 mm). The following clinical applications are described: Closure of the extractions space, Symmetric intrusion of the incisors, Correction of the cant of the plane of occlusion and of the dental midline, Molar intrusion of one or two teeth, Molar distalization with the Distal Jet and miniscrews, Molar mesialization, Intermaxillary anchorage. the mechanical resistance of the miniscrews M.A.S. is suitable for their use in orthodontics. The best anatomical zones for their implantation are the interradicular spaces mesial to the first maxillary molars. From our experience to date, the miniscrews are a reliable and convenient system for skeletal anchorage when compared with other more invasive osseo-integrated systems.

15546012

Dental arch analysis system.

The purpose of our research is to describe a computerized method, which enables orthodontists and researchers to analyze variation of dental arch form and dimension. The analysis system is composed of two independent parts: the database, where the images of scanned dental casts are stored, and the software. The operator uses the software to identify some landmarks on dental cast images. Corresponding distances are calculated (interincisive, intercanine and intermolar widths and the curve axis). Then the software algorithms calculate and draw the curves passing trough the selected landmarks (conics, catenary, cubic spline and polynomial curves). In the chosen curves the arch length is measured. The dental cast data, recorded at different times of the subject's life or in different steps of orthodontic treatment, are compared in order to evaluate the change in dimension (arch length and width) and form (shape). The statistical analysis of the data evaluates the variation in form and in dimension separately. The shape change is defined by Euclidean Distance Matrix Analysis (EDMA) and Bootstrap analysis. The computerized method allows orthodontists and researches to evaluate the variation in dimension and form of the dental arch in un-treated subjects and-or orthodontic patients over time. After the analysis of a large sample of patients or subjects, information concerning changes in dental arch dimension and form can be added to previous studies of other authors, distinguishing variation during and after orthodontic treatment, during growth or aging.

15546011

Lower incisor extraction in Class I and Class II malocclusions: case reports.

After a brief discussion of the indications/contraindications of extracting lower incisors as part of orthodontic treatment, five case reports are presented. These cases highlight that extracting lower incisors can be an accepted orthodontic option, not only in compromised class III treatments, but also in Class I and Class II malocclusions.

15546010

Rapid palatal expansion and pharyngeal space. Cephalometric evaluation.

the aim of this study was to evaluate cephalometrically the upper respiratory airway dimensions before and after rapid maxillary expansion. rapid palatal expansion was performed on 24 5-9 year old children with adenotonsillar hypertrophy determined radiographically by means of lateral cephalographs. Also, the subjects were questioned concerning their ability to breath through their noses. there was an increase in upper respiratory width that often coincided with a reported improvement in nasal respiration. Adenoid volume was not reduced. the increase in pharyngeal space and improvement in nasal breathing resulted from an increase in pharyngeal lumen enlargement rather than a reduction in the volume of the adenoid tissue.

15546004

TGF-beta-dependent pathogenesis of mitral valve prolapse in a mouse model of Marfan syndrome.

Mitral valve prolapse (MVP) is a common human phenotype, yet little is known about the pathogenesis of this condition. MVP can occur in the context of genetic syndromes, including Marfan syndrome (MFS), an autosomal-dominant connective tissue disorder caused by mutations in fibrillin-1. Fibrillin-1 contributes to the regulated activation of the cytokine TGF-beta, and enhanced signaling is a consequence of fibrillin-1 deficiency. We thus hypothesized that increased TGF-beta signaling may contribute to the multisystem pathogenesis of MFS, including the development of myxomatous changes of the atrioventricular valves. Mitral valves from fibrillin-1-deficient mice exhibited postnatally acquired alterations in architecture that correlated both temporally and spatially with increased cell proliferation, decreased apoptosis, and excess TGF-beta activation and signaling. In addition, TGF-beta antagonism in vivo rescued the valve phenotype, suggesting a cause and effect relationship. Expression analyses identified increased expression of numerous TGF-beta-related genes that regulate cell proliferation and survival and plausibly contribute to myxomatous valve disease. These studies validate a novel, genetically engineered murine model of myxomatous changes of the mitral valve and provide critical insight into the pathogenetic mechanism of such changes in MFS and perhaps more common nonsyndromic variants of mitral valve disease.

15546009

Orthodontic therapy and third party in Europe.

This paper is an attempt to individuate some principles and guidelines apt to regulate the relationship between orthodontists and financing third parties, applicable to most western European Countries. The concepts of orthodontic treatment need, orthodontic treatment request and orthodontic screening are discussed, alongside with a short overview of some of the most common indexes to assess the severity of the malocclusion and/or the treatment priority. The screening method introduced by the Danish Ministry of Health is presented; its importance lies in the fact that for the first time a direct correlation between health risk and individual malocclusions is recognized and assessed. In the discussion, it is stressed how the screening system tightly depends on the chosen general model for orthodontic care. Different models of orthodontic care organization as presently used in many European countries are presented and shortly discussed; among these, the Norwegian model is described more in details, because of its simplicity. Eventually, some guidelines considered necessary in order to achieve satisfactory standards of quality and efficiency are presented and discussed.

15546008

European orthodontic specialists in 2002.

After clarifying the role and significance of the European Federations of Orthodontic Specialists Associations (EFOSA), the results of a recent survey examining the situation of the Speciality of Orthodontics in Europe are presented. Among the many items included are the recognition and availability of orthodontic specialists, their training, and working conditions, the fees charged, and the present insurance and refunding systems.

15546003

Multiple environmental and genetic factors influence skeletal muscle PGC-1alpha and PGC-1beta gene expression in twins.

Genetic and environmental factors contribute to age-dependent susceptibility to type 2 diabetes. Recent studies have reported reduced expression of PPARgamma coactivator 1alpha (PGC-1alpha) and PGC-1beta genes in skeletal muscle from type 2 diabetic patients, but it is not known whether this is an inherited or acquired defect. To address this question we studied expression of these genes in muscle biopsies obtained from young and elderly dizygotic and monozygotic twins without known diabetes before and after insulin stimulation and related the expression to a Gly482Ser variant in the PGC-1alpha gene. Insulin increased and aging reduced skeletal muscle PGC-1alpha and PGC-1beta mRNA levels. This age-dependent decrease in muscle gene expression was partially heritable and influenced by the PGC-1alpha Gly482Ser polymorphism. In addition, sex, birth weight, and aerobic capacity influenced expression of PGC-1alpha in a complex fashion. Whereas expression of PGC-1alpha in muscle was positively related to insulin-stimulated glucose uptake and oxidation, PGC-1beta expression was positively related to fat oxidation and nonoxidative glucose metabolism. We conclude that skeletal muscle PGC-1alpha and PGC-1beta expression are stimulated by insulin and reduced by aging. The data also suggest different regulatory functions for PGC-1alpha and PGC-1beta on glucose and fat oxidation in muscle cells. The finding that the age-dependent decrease in the expression of these key genes regulating oxidative phosphorylation is under genetic control could provide an explanation by which an environmental trigger (age) modifies genetic susceptibility to type 2 diabetes.

15546002

Severe combined immunodeficiency caused by deficiency in either the delta or the epsilon subunit of CD3.

We investigated the molecular mechanism underlying a severe combined immunodeficiency characterized by the selective and complete absence of T cells. The condition was found in 5 patients and 2 fetuses from 3 consanguineous families. Linkage analysis performed on the 3 families revealed that the patients were carrying homozygous haplotypes within the 11q23 region, in which the genes encoding the gamma, delta, and epsilon subunits of CD3 are located. Patients and affected fetuses from 2 families were homozygous for a mutation in the CD3D gene, and patients from the third family were homozygous for a mutation in the CD3E gene. The thymus from a CD3delta-deficient fetus was analyzed and revealed that T cell differentiation was blocked at entry into the double positive (CD4+CD8+) stage with the accumulation of intermediate CD4-single positive cells. This indicates that CD3delta plays an essential role in promoting progression of early thymocytes toward double-positive stage. Altogether, these findings extend the known molecular mechanisms underlying severe combined immunodeficiency to a new deficiency, i.e., CD3epsilon deficiency, and emphasize the essential roles played by the CD3epsilon and CD3delta subunits in human thymocyte development, since these subunits associate with both the pre-TCR and the TCR.

15546001

Disruption of either the Nfkb1 or the Bcl3 gene inhibits skeletal muscle atrophy.

The intracellular signals that mediate skeletal muscle protein loss and functional deficits due to muscular disuse are just beginning to be elucidated. Previously we showed that the activity of an NF-kappaB-dependent reporter gene was markedly increased in unloaded muscles, and p50 and Bcl-3 proteins were implicated in this induction. In the present study, mice with a knockout of the p105/p50 (Nfkb1) gene are shown to be resistant to the decrease in soleus fiber cross-sectional area that results from 10 days of hindlimb unloading. Furthermore, the marked unloading-induced activation of the NF-kappaB reporter gene in soleus muscles from WT mice was completely abolished in soleus muscles from Nfkb1 knockout mice. Knockout of the B cell lymphoma 3 (Bcl3) gene also showed an inhibition of fiber atrophy and an abolition of NF-kappaB reporter activity. With unloading, fast fibers from WT mice atrophied to a greater extent than slow fibers. Resistance to atrophy in both strains of knockout mice was demonstrated clearly in fast fibers, while slow fibers from only the Bcl3(-/-) mice showed atrophy inhibition. The slow-to-fast shift in myosin isoform expression due to unloading was also abolished in both Nfkb1 and Bcl3 knockout mice. Like the soleus muscles, plantaris muscles from Nfkb1(-/-) and Bcl3(-/-) mice also showed inhibition of atrophy with unloading. Thus both the Nfkb1 and the Bcl3 genes are necessary for unloading-induced atrophy and the associated phenotype transition.

15546000

Foxo1 mediates insulin action on apoC-III and triglyceride metabolism.

The apolipoprotein apoC-III plays an important role in plasma triglyceride metabolism. It is predominantly produced in liver, and its hepatic expression is inhibited by insulin. To elucidate the inhibitory mechanism of insulin in apoC-III expression, we delivered forkhead box O1 (Foxo1) cDNA to hepatocytes by adenovirus-mediated gene transfer. Foxo1 stimulated hepatic apoC-III expression and correlated with the ability of Foxo1 to bind to its consensus site in the apoC-III promoter. Deletion or mutation of the Foxo1 binding site abolished insulin response and Foxo1-mediated stimulation. Likewise, Foxo1 also mediated insulin action on intestinal apoC-III expression in enterocytes. Furthermore, elevated Foxo1 production in liver augmented hepatic apoC-III expression, resulting in increased plasma triglyceride levels and impaired fat tolerance in mice. Transgenic mice expressing a constitutively active Foxo1 allele exhibited hypertriglyceridemia. Moreover, we show that hepatic Foxo1 expression becomes deregulated as a result of insulin deficiency or insulin resistance, culminating in significantly elevated Foxo1 production, along with its skewed nuclear distribution, in livers of diabetic NOD or db/db mice. While loss of insulin response is associated with unrestrained apoC-III production and impaired triglyceride metabolism, these data suggest that Foxo1 provides a molecular link between insulin deficiency or resistance and aberrant apoC-III production in the pathogenesis of diabetic hypertriglyceridemia.

15545999

Defining the pathogenic involvement of desmoglein 4 in pemphigus and staphylococcal scalded skin syndrome.

Desmogleins (Dsgs), cadherin-type cell adhesion molecules, are targeted in skin-blistering diseases such as pemphigus and staphylococcal scalded skin syndrome (SSSS). The role of Dsg4, a new isoform, was investigated in these diseases. Dsg4 was recognized by 30 (77%) of 39 pemphigus sera containing anti-Dsg1 IgG but not by 16 pemphigus sera containing no anti-Dsg1 IgG or by 34 normal control sera. The Dsg4 immunoreactivity of these sera was abolished by removal of anti-Dsg1 IgG. Conversely, the removal of anti-Dsg4 IgG from pemphigus sera reduced the immunoreactivity against Dsg1 only 13.8% +/- 8.8% (n = 23) and did not affect its ability to induce blisters in neonatal mice. IgG that was affinity-purified on Dsg4 recognized Dsg1 but failed to induce blisters, while IgG purified on Dsg1 from the same pemphigus foliaceus sera induced blisters. Thus, pemphigus sera show Dsg4 reactivity due to cross-reactivity of a subset of anti-Dsg1 IgG, and the Dsg4/Dsg1-cross-reacting IgG has no demonstrable pathogenic effect. In addition, Dsg4 was not cleaved by exfoliative toxins that induce blisters in SSSS. These findings suggest that Dsg4 may play a role other than adhesion and that the cross-reactivity of desmoglein autoantibodies should be factored into the framework of future studies of autoimmune mechanisms in pemphigus.

15545998

Nephrin strands contribute to a porous slit diaphragm scaffold as revealed by electron tomography.

Nephrin is a key functional component of the slit diaphragm, the structurally unresolved molecular filter in renal glomerular capillaries. Abnormal nephrin or its absence results in severe proteinuria and loss of the slit diaphragm. The diaphragm is a thin extracellular membrane spanning the approximately 40-nm-wide filtration slit between podocyte foot processes covering the capillary surface. Using electron tomography, we show that the slit diaphragm comprises a network of winding molecular strands with pores the same size as or smaller than albumin molecules, as demonstrated in humans, rats, and mice. In the network, which is occasionally stratified, immunogold-nephrin antibodies labeled individually detectable globular cross strands, about 35 nm in length, lining the lateral elongated pores. The cross strands, emanating from both sides of the slit, contacted at the slit center but had free distal endings. Shorter strands associated with the cross strands were observed at their base. Immunolabeling of recombinant nephrin molecules on transfected cells and in vitrified solution corroborated the findings in kidney. Nephrin-deficient proteinuric patients with Finnish-type congenital nephrosis and nephrin-knockout mice had only narrow filtration slits that lacked the slit diaphragm network and the 35-nm-long strands but contained shorter molecular structures. The results suggest the direct involvement of nephrin molecules in constituting the macromolecule-retaining slit diaphragm and its pores.

15545997

Allelic loss underlies type 2 segmental Hailey-Hailey disease, providing molecular confirmation of a novel genetic concept.

Hailey-Hailey disease (HHD) is an autosomal dominant trait characterized by erythematous and oozing skin lesions preponderantly involving the body folds. In the present unusual case, however, unilateral segmental areas along the lines of Blaschko showing a rather severe involvement were superimposed on the ordinary symmetrical phenotype. Based on this observation and similar forms of mosaicism as reported in other autosomal dominant skin disorders, we postulated that in such cases, 2 different types of segmental involvement can be distinguished. Accordingly, the linear lesions as noted in the present case would exemplify type 2 segmental HHD. In the heterozygous embryo, loss of heterozygosity occurring at an early developmental stage would have given rise to pronounced linear lesions reflecting homozygosity or hemizygosity for the mutation. By analyzing DNA and RNA derived from blood and skin samples as well as keratinocytes of the index patient with various molecular techniques including RT-PCR, real-time PCR, and microsatellite analysis, we found a consistent loss of the paternal wild-type allele in more severely affected segmental skin regions, confirming this hypothesis for the first time, to our knowledge, at the molecular and cellular level.

15545996

Loss of alpha-hemoglobin-stabilizing protein impairs erythropoiesis and exacerbates beta-thalassemia.

Hemoglobin (Hb) A production during red blood cell development is coordinated to minimize the deleterious effects of free alpha- and beta-Hb subunits, which are unstable and cytotoxic. The alpha-Hb-stabilizing protein (AHSP) is an erythroid protein that specifically binds alpha-Hb and prevents its precipitation in vitro, which suggests that it may function to limit free alpha-Hb toxicities in vivo. We investigated this possibility through gene ablation and biochemical studies. AHSP(-/-) erythrocytes contained hemoglobin precipitates and were short-lived. In hematopoietic tissues, erythroid precursors were elevated in number but exhibited increased apoptosis. Consistent with unstable alpha-Hb, AHSP(-/-) erythrocytes contained increased ROS and evidence of oxidative damage. Moreover, purified recombinant AHSP inhibited ROS production by alpha-Hb in solution. Finally, loss of AHSP worsened the phenotype of beta-thalassemia, a common inherited anemia characterized by excess free alpha-Hb. Together, the data support a model in which AHSP binds alpha-Hb transiently to stabilize its conformation and render it biochemically inert prior to Hb A assembly. This function is essential for normal erythropoiesis and, to a greater extent, in beta-thalassemia. Our findings raise the possibility that altered AHSP expression levels could modulate the severity of beta-thalassemia in humans.

15545995

A role for proteinase-activated receptor-1 in inflammatory bowel diseases.

Proteinase-activated receptor-1 (PAR1), a G protein-coupled receptor activated by thrombin, is highly expressed in different cell types of the gastrointestinal tract. The activity of thrombin and of other proteinases is significantly increased in the colon of inflammatory bowel disease (IBD) patients. Since PAR1 activation in tissues other than the gut provoked inflammation, we hypothesized that PAR1 activation in the colon is involved in the pathogenesis of IBD. Here, we demonstrate that PAR1 is overexpressed in the colon of IBD patients. In mice, intracolonic administration of PAR1 agonists led to an inflammatory reaction characterized by edema and granulocyte infiltration. This PAR1 activation-induced inflammation was dependent on B and T lymphocytes. Moreover, PAR1 activation exacerbated and prolonged inflammation in a mouse model of IBD induced by the intracolonic administration of trinitrobenzene sulfonic acid (TNBS), while PAR1 antagonism significantly decreased the mortality and severity of colonic inflammation induced by TNBS and dextran sodium sulfate. In these 2 models, colitis development was strongly attenuated by PAR1 deficiency. Taken together, these results imply an important role for PAR1 in the pathogenesis of experimental colitis, supporting the notion that PAR1 inhibition may be beneficial in the context of IBD and possibly in other chronic intestinal inflammatory disorders.

15545994

Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus.

Polycystin-1, which is encoded by a gene that is mutated in autosomal dominant polycystic kidney disease (ADPKD), is involved in cell-matrix interactions as well as in ciliary signaling. The precise mechanisms by which it functions, however, remain unclear. Here we find that polycystin-1 undergoes a proteolytic cleavage that releases its C-terminal tail (CTT), which enters the nucleus and initiates signaling processes. The cleavage occurs in vivo in association with alterations in mechanical stimuli. Polycystin-2, the product of the second gene mutated in ADPKD, modulates the signaling properties of the polycystin-1 CTT. These data reveal a novel pathway by which polycystin-1 transmits messages directly to the nucleus.

15545993

An uncleavable form of pro-scatter factor suppresses tumor growth and dissemination in mice.

Scatter factor (SF), also known as hepatocyte growth factor, is ubiquitously present in the extracellular matrix of tissues in the form of an inactive precursor (pro-SF). In order to acquire biological activity, pro-SF must be cleaved by specific proteases present on the cell surface. The mature form of SF controls invasive cues in both physiological and pathological processes through activation of its receptor, the Met tyrosine kinase. By substituting a single amino acid in the proteolytic site, we engineered an unprocessable form of pro-SF (uncleavable SF). Using lentivirus vector technology, we achieved local or systemic delivery of uncleavable SF in mice. We provide evidence that (a) uncleavable SF inhibits both protease-mediated pro-SF conversion and active SF-induced Met activation; (b) local expression of uncleavable SF in tumors suppresses tumor growth, impairs tumor angiogenesis, and prevents metastatic dissemination; and (c) systemic expression of uncleavable SF dramatically inhibits the growth of transplanted tumors and abolishes the formation of spontaneous metastases without perturbing vital physiological functions. These data show that proteolytic activation of pro-SF is a limiting step in tumor progression, thus suggesting a new strategy for the treatment or prevention of the malignant conversion of neoplastic lesions.

15545992

Genes and pathophysiology of type 2 diabetes: more than just the Randle cycle all over again.

The Randle cycle, which has been invoked to explain the reciprocal relationship between fatty acid oxidation and glucose oxidation, has long been implicated as a potential mechanism for hyperglycemia and type 2 diabetes mellitus (T2DM). Now genetic, functional genomic, and transgenic approaches have identified PPARgamma coactivators (PGC-1alpha and PGC-1beta) as key regulators of mitochondrial number and function. They regulate adaptive thermogenesis as well as glucose and fat oxidation in muscle and fat tissue, gluconeogenesis in liver, and even glucose-regulated insulin secretion in beta cells. PGC-1alpha and PGC-1beta mRNA levels and the mitochondrial genes they regulate are decreased in muscle of people with prediabetes and T2DM. A new report indicates that PGC-1alpha and PGC-1beta mRNA levels decrease with age in individuals with a genetic variant in PGC-1alpha, and these decreases correlate with alterations in whole-body glucose and fatty acid oxidation. These findings provide insights into how aging modifies genetic susceptibility to alterations in oxidative phosphorylation and T2DM.

15545991

What determines glomerular capillary permeability?

There have been exciting recent advances in our understanding of the structural and molecular biology of the glomerular slit diaphragm, as described in a report in this issue of the JCI. These findings, combined with data on the permeability of the basement membrane and evidence that the endothelium may be a more important barrier than often supposed, are allowing a clearer understanding to emerge of how the 3 parts of the glomerular capillary wall jointly determine its functional properties.

15545990

The multiple causes of human SCID.

SCID, a syndrome characterized by the absence of T cells and adaptive immunity, can result from mutations in multiple genes that encode components of the immune system. Three such components are cytokine receptor chains or signaling molecules, five are needed for antigen receptor development, one is adenosine deaminase--a purine salvage pathway enzyme, and the last is a phosphatase, CD45. In this issue of the JCI, a report describes how complete deficiency of the CD3epsilon chain of the T cell antigen receptor/CD3 complex causes human SCID.

15545988

RIP-ed and ready to dance: new mechanisms for polycystin-1 signaling.

Polycystin-1, the protein encoded by the principal gene involved in autosomal dominant polycystic kidney disease, has been implicated in extracellular sensing as well as in cell-cell and cell-matrix interactions. However, the precise mechanisms involved in polycystin-1 signaling are not well defined. A report in this issue of the JCI demonstrates that the C-terminal tail of polycystin-1 is cleaved from the membrane through regulated intramembrane proteolysis (RIP) and that this domain translocates to the nucleus, where it activates the AP-1 transcription pathway. This translocation appears to be modulated by polycystin-2, with which polycystin-1 is thought to interact. These findings provide what we believe to be the first evidence that polycystin-1 can signal directly to the nucleus and that polycystin-1-polycystin-2 interactions do not require colocalization of these proteins in the same membrane compartment.

15545989

Piecing together the puzzle of cutaneous mosaicism.

Autosomal dominant disorders of the skin may present in a pattern following the lines of embryologic development of the ectoderm. In these cases, the surrounding skin is normal, and molecular studies have shown that the causative mutation is confined to the affected ectodermal tissue (type 1 mosaicism). Rarely, an individual shows skin lesions that follow the pattern of type 1 mosaicism, but the rest of the skin shows a milder form of the disorder (type 2 mosaicism). A new study provides the molecular basis for type 2 mosaicism.

15545986

Tregs and allergic disease.

Allergic diseases such as asthma, rhinitis, and eczema are increasing in prevalence and affect up to 15% of populations in Westernized countries. The description of Tregs as T cells that prevent development of autoimmune disease led to considerable interest in whether these Tregs were also normally involved in prevention of sensitization to allergens and whether it might be possible to manipulate Tregs for the therapy of allergic disease. Current data suggest that Th2 responses to allergens are normally suppressed by both CD4+CD25+ Tregs and IL-10 Tregs. Furthermore, suppression by these subsets is decreased in allergic individuals. In animal models, Tregs could be induced by high- or low-dose inhaled antigen, and prior induction of such Tregs prevented subsequent development of allergen sensitization and airway inflammation in inhaled challenge models. For many years, allergen-injection immunotherapy has been used for the therapy of allergic disease, and this treatment may induce IL-10 Tregs, leading to both suppression of Th2 responses and a switch from IgE to IgG4 antibody production. Improvements in allergen immunotherapy, such as peptide therapy, and greater understanding of the biology of Tregs hold great promise for the treatment and prevention of allergic disease.

15545987

Tregs and transplantation tolerance.

The induction and maintenance of immune tolerance to transplanted tissues constitute an active process involving multiple mechanisms that work cooperatively to prevent graft rejection. These mechanisms are similar to inherent tolerance toward self antigens and have a requirement for active immunoregulation, largely T cell mediated, that promotes specific unresponsiveness to donor alloantigens. This review outlines our current understanding of the Treg subsets that contribute to allotolerance and the mechanisms by which these cells exert their effects as well as their potential for therapy.

15545985

Going both ways: immune regulation via CD1d-dependent NKT cells.

NKT cells are a unique T lymphocyte sublineage that has been implicated in the regulation of immune responses associated with a broad range of diseases, including autoimmunity, infectious diseases, and cancer. In stark contrast to both conventional T lymphocytes and other types of Tregs, NKT cells are reactive to the nonclassical class I antigen-presenting molecule CD1d, and they recognize glycolipid antigens rather than peptides. Moreover, they can either up- or downregulate immune responses by promoting the secretion of Th1, Th2, or immune regulatory cytokines. This review will explore the diverse influences of these cells in various disease models, their ability to suppress or enhance immunity, and the potential for manipulating these cells as a novel form of immunotherapy.

15545984

IL-10-producing and naturally occurring CD4+ Tregs: limiting collateral damage.

Effective immune responses against pathogens are sometimes accompanied by strong inflammatory reactions. To minimize damage to self, the activation of the immune system also triggers anti-inflammatory circuits. Both inflammatory and anti-inflammatory reactions are normal components of the same immune response, which coordinately fight infections while preventing immune pathology. IL-10 is an important suppressive cytokine, produced by a large number of immune cells in addition to the antigen-driven IL-10-producing regulatory and the naturally occurring suppressor CD4+ T cells, which is a key player in anti-inflammatory immune responses. However, additional mechanisms have evolved to ensure that pathogen eradication is achieved with minimum damage to the host. Here we discuss those mechanisms that operate to regulate effector immune responses.

15545983

Stem cells: science, policy, and ethics.

Human embryonic stem cells offer the promise of a new regenerative medicine in which damaged adult cells can be replaced with new cells. Research is needed to determine the most viable stem cell lines and reliable ways to promote the differentiation of pluripotent stem cells into specific cell types (neurons, muscle cells, etc). To create new cell lines, it is necessary to destroy preimplantation blastocysts. This has led to an intense debate that threatens to limit embryonic stem cell research. The profound ethical issues raised call for informed, dispassionate debate.

15545981

Intrathecal drug therapy using the Codman Model 3000 Constant Flow Implantable Infusion Pumps: experience with 17 cases.

The objective of this study was to evaluate the accuracy, reliability, safety, and efficacy of the Codman Model 3000 Constant Flow Implantable Infusion Pump for intrathecal baclofen delivery as a therapeutic option for the treatment of severe spasticity. The distinctive features of this pump include a raised, easily palpable septum, a safety valve protecting the bolus pathway, no programmer needed, and no battery to fail. A total of 17 patients with spinal cord injury, multiple sclerosis, or cerebral palsy were implanted with this pump. The accuracy of the pump and drug treatment efficacy was determined at each visit and adjustments to the dosages were made as required. All the intrathecal drug delivery system complications were reviewed. The expected efficacy was achieved. The accuracy of the implanted pumps ranged from 90-97% (average 94%). There were no complications due to primary pump problems. The complications reported are similar to other implantable infusion devices and include dehiscence of the suture line, pressure ulcer development, formation of seroma, inversion of the pump, baclofen overdose, and catheter failures. The Codman Model 3000 Constant Flow Implantable Infusion Pump is an accurate, reliable, and convenient option for patients needing intrathecal baclofen therapy, with complications similar to other available pumps.

15545980

Health and quality of life of persons with spinal cord lesion in Australia and Sweden.

Cross-sectional questionnaire study. The aim of the study was to demonstrate the value of common general health-related quality of life (HRQL) instruments, readily available for cross-cultural comparisons, in persons with spinal cord lesion (SCL) treated at spinal units in Melbourne, Australia and in Gothenburg, Sweden. Another aim was to determine as to which of the independent variables were the most powerful predictors of global QL in the two SCL groups. Australia and Sweden. Two groups consisting of 89 Australian and 71 Swedish SCL persons were surveyed. The two groups were matched according to sex, age, time since injury and level of injury. The 36-item short-form health survey (SF-36) and the Spinal Cord Injuries Quality of Life-23-item questionnaire were used to cover essential generic and specific domains of health and quality of life. Clinical and sociodemographic data were collected using questionnaires. For interpretation purpose, available general population data were used. The most important predictors of QL perception in the Australian group were the same as for the Swedish group; mood, physical and social functioning and problems regarding injury. In total, 61% (Australian group) and 52% (Swedish group) of the variance was explained by these variables. Despite similarities of health profiles, some areas of the SF-36 differed between the two groups. The demonstrated HRQL profiles in SCL persons have shown that valid measures can provide new information of clinical value beyond the self-evident physical and practical restrictions due to injury. Illustrative comparisons, such as those presented here between Australia and Sweden, may extend our knowledge about areas where the SCL persons themselves are the logical experts, for example, maintenance of personal roles, social interaction and emotional well-being.

15545978

Support for involvement of neuregulin 1 in schizophrenia pathophysiology.

Schizophrenia is a common, multigenic psychiatric disorder. Linkage studies, including a recent meta-analysis of genome scans, have repeatedly implicated chromosome 8p12-p23.1 in schizophrenia susceptibility. More recently, significant association with a candidate gene on 8p12, neuregulin 1 (NRG1), has been reported in several European and Chinese samples. We investigated NRG1 for association in schizophrenia patients of Portuguese descent to determine whether this gene is a risk factor in this population. We tested NRG1 markers and haplotypes for association in 111 parent-proband trios, 321 unrelated cases, and 242 control individuals. Associations were found with a haplotype that overlaps the risk haplotype originally reported in the Icelandic population ("Hap(ICE)"), and two haplotypes located in the 3' end of NRG1 (all P<0.05). However, association was not detected with Hap(ICE) itself. Comparison of NRG1 transcript expression in peripheral leukocytes from schizophrenia patients and unaffected siblings identified 3.8-fold higher levels of the SMDF variant in patients (P=0.039). Significant positive correlations (P<0.001) were found between SMDF and HRG-beta 2 expression and between HRG-gamma and ndf43 expression, suggesting common transcriptional regulation of NRG1 variants. In summary, our results suggest that haplotypes across NRG1 and multiple NRG1 variants are involved in schizophrenia.

15545977

Child temperament does not predict adolescent body composition in girls.

Our previous cross-sectional analysis of MIT Growth and Development (MIT) Study girls showed that activity temperament, as assessed by a nine-item temperament questionnaire, was related to body composition and nonresting energy expenditure (NREE). In girls with lower levels of physical activity, having a high activity temperament was associated with a higher NREE. Percentage body fat was lower in girls with high vs low activity temperament. Based on these results, we hypothesized that, especially in girls with declining levels of physical activity over adolescence, high activity temperament in childhood would be protective against increased adiposity during adolescence. We tested this hypothesis with longitudinal data from the MIT study. A total of 196 nonobese premenarcheal girls 8-12 y old were enrolled between 1990 and 1993. Girls were followed until 4 y postmenarche; average duration of follow-up was 7 y. Activity temperament was assessed at baseline by the girls' mothers with questions modified from those developed by Thomas and Chess that tapped predilection for movement. Temperament, the stylistic component of behavior, is considered relatively stable within an individual. Body composition was assessed by total body water at baseline and study completion (4 y postmenarche), and by bioelectrical impedance (BIA) annually. Physical activity was assessed annually by questionnaire, and by activity diary at baseline only. Child activity temperament was not associated with percentage body fat at 4 y postmenarche in multivariate regression models controlling for baseline percentage body fat, physical activity, parental obesity status, age at menarche, age at baseline, and race-ethnicity. Body composition of girls with low and high activity temperaments who reported declining levels of physical activity over adolescence was not statistically significantly different at study completion. In longitudinal models of percentage body fat by BIA, high activity temperament was not associated with lower adiposity. Although high activity temperament was associated cross-sectionally with lower percentage body fat and higher NREE, we did not find evidence to support our hypothesis that high child activity temperament would be protective for increased adiposity prospectively in our cohort of girls followed over the adolescent period.

15545975

Molecular mechanisms of action and prediction of response to oxaliplatin in colorectal cancer cells.

The platinum compound oxaliplatin has been shown to be an effective chemotherapeutic agent for the treatment of colorectal cancer. In this study, we investigate the molecular mechanisms of action of oxaliplatin to identify means of predicting response to this agent. Exposure of colon cancer cells to oxaliplatin resulted in G2/M arrest and apoptosis. Immunofluorescent staining demonstrated that the apoptotic cascade initiated by oxaliplatin is characterised by translocation of Bax to the mitochondria and cytochrome c release into the cytosol. Oxaliplatin treatment resulted in caspase 3 activation and oxaliplatin-induced apoptosis was abrogated by inhibition of caspase activity with z-VAD-fmk, but was independent of Fas/FasL association. Targeted inactivation of Bax or p53 in HCT116 cells resulted in significantly increased resistance to oxaliplatin. However, the mutational status of p53 was unable to predict response to oxaliplatin in a panel of 30 different colorectal cancer cell lines. In contrast, the expression profile of these 30 cell lines, assessed using a 9216-sequence cDNA microarray, successfully predicted the apoptotic response to oxaliplatin. A leave-one-out cross-validation approach was used to demonstrate a significant correlation between experimentally observed and expression profile predicted apoptosis in response to clinically achievable doses of oxaliplatin (R=0.53; P=0.002). In addition, these microarray experiments identified several genes involved in control of apoptosis and DNA damage repair that were significantly correlated with response to oxaliplatin.

15545976

Predictors of drop-out in overweight and obese outpatients.

To investigate the impact on drop-out rates of several baseline clinical characteristics of a sample of overweight and obese outpatients. Retrospective clinical trial. The charts of 383 patients aged 15-82 y attending an outpatient clinic for the treatment of obesity were examined from the first clinical evaluation until 1 y of diet ambulatory treatment. We characterised the participants at baseline on the basis of their somatic characteristics, socioeconomic status, obesity-related diseases and dietary habits. The most significant factors resulting in univariate statistical analysis (waist, body mass index (BMI), full-time job, depressive syndrome, number of obesity-related diseases, daily frequency of fruit consumption) were then examined as independent variables in direct multiple logistic regression with the dependent variable drop-out. The 1-y drop-out rate was 77.3%. A total of 87 patients completed the follow-up study. The noncompleter patients had slightly lower BMI and waist circumference mean values, and they were further regularly employed in full-time jobs, while the completer patients were principally pensioners and housewives. Drop-outs had a lower number of obesity-related diseases and as a result were less depressed. By the logistic regression, full-time job is the best predictor of premature withdrawal (odds ratio=2.40). Age, gender, anthropometric measurements, lifestyle and dietary habits did not result as significant predictors of drop-out. The overweight and obese outpatients at higher risk of ambulatory treatment drop-out are more likely to work full hours, have less obesity-related complications and be less depressed. In our study, the full-time job condition seems to be the strongest predictor of premature withdrawal.

15545974

Interleukin-8/CXCL8 is a growth factor for human lung cancer cells.

Interleukin-8/CXCL8 (IL-8) is a chemokine and angiogenic factor. Recently, IL-8 was identified as an autocrine growth factor in several human cancers. Here, we investigated the expression and function of IL-8 in lung cancer cells. The expressions of IL-8 and its receptors, CXCR1 and CXCR2, were examined in a panel of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) cell lines. Using reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay, we found that all NSCLC cell lines tested produced modest or high levels of IL-8 (up to 51 ng ml(-1) 10(6) cells(-1)). Expression of CXCR1 and CXCR2 was found by RT-PCR and flow cytometry in two out of three cell lines. In contrast, SCLC cell lines produced very low or undetectable levels of IL-8, but expressed CXCR1 and CXCR2. We next investigated whether IL-8 could act as an autocrine growth factor in two NSCLC cell lines (H460 and MOR/P) expressing both IL-8 and its receptors. We found that cell proliferation was attenuated by anti-IL-8 neutralising antibody to 71 and 76% in H460 and MOR/P, respectively (P<0.05). Exogenous IL-8 significantly stimulated cell proliferation in four SCLC cell lines tested in a dose-dependent fashion. Cell proliferation was increased by between 18% (P<0.05) and 37% (P<0.05). Stimulation of cell proliferation by IL-8 was also demonstrated by analysis of proliferating cell nuclear antigen expression and cell cycle in H69 cells. Furthermore, we investigated which receptor(s) mediated the mitogenic function of IL-8 in lung cancer cells. We found that cell proliferation was significantly reduced by anti-CXCR1 antibody but not by anti-CXCR2 antibody. In conclusion, IL-8 can act as an autocrine and/or paracrine growth factor for lung cancer cells, and the mitogenic function of IL-8 in lung cancer is mediated mainly by CXCR1 receptor.

15545973

Quantifying trade-offs: quality of life and quality-adjusted survival in a randomised trial of chemotherapy in postmenopausal patients with lymph node-negative breast cancer.

We evaluated quality of life (QL) and quality-adjusted survival in International Breast Cancer Study Group Trial IX, a randomised trial including 1669 eligible patients receiving tamoxifen for 5 years or three prior cycles of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) followed by 57 months tamoxifen. During the time with CMF toxicity (Tox), without symptoms and toxicity (TWiST), and following relapse (Rel), patients scored their QL indicators and a utility indicator for subjective health estimation between 'perfect' and 'worst' health. Scores were averaged within Tox, TWiST and Rel and transformed to utilities. Mean durations for the three transition times were weighted with utilities to obtain mean quality-adjusted TWiST (Q-TWiST). Patients receiving CMF reported significantly worse scores for most QL domains at month 3, but less hot flushes. After completing chemotherapy, there were no differences by treatment groups. Benefits evaluated by Q-TWiST favoured the additional chemotherapy. CMF provided 3 more months of Q-TWiST for patients with ER-negative tumours, but CMF provided no benefit in Q-TWiST for patients with ER-positive tumours. Q-TWiST analysis based on patient ratings is feasible in large-scale cross-cultural clinical trials.

15545971

Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis.

Among new biological markers that could become useful prognostic factors for lung carcinoma, Ki-67 is a nuclear protein involved in cell proliferation regulation. Some studies have suggested an association between Ki-67 and poor survival in lung cancer patients. In order to clarify this point, we have performed a systematic review of the literature, using the methodology already described by our Group, the European Lung Cancer Working Party. In total, 37 studies, including 3983 patients, were found to be eligible. In total, 49% of the patients were considered as having a tumour positive for the expression of Ki-67 according to the authors cutoff. In all, 29 of the studies dealt with non-small-cell lung carcinoma (NSCLC), one with small-cell carcinoma (SCLC), two with carcinoid tumours and five with any histology. In terms of survival results, Ki-67 was a bad prognosis factor for survival in 15 studies while it was not in 22. As there was no statistical difference in quality scores between the significant and nonsignificant studies evaluable for the meta-analysis, we were allowed to aggregate the survival results. The combined hazard ratio for NSCLC, calculated using a random-effects model was 1.56 (95% CI: 1.30-1.87), showing a worse survival when Ki-67 expression is increased. In conclusion, our meta-analysis shows that the expression of Ki-67 is a factor of poor prognosis for survival in NSCLC.

15545972

Laminin-5 offsets the efficacy of gefitinib ('Iressa') in hepatocellular carcinoma cells.

Prognosis and survival of patients with hepatocellular carcinoma (HCC) is still very poor, and no therapies are currently available to inhibit tumour growth and metastases. Recently, we reported that the expression of an extracellular matrix component (ECM), namely Laminin-5 (Ln-5), is directly related to poor prognosis in HCC patients. The aim of our study is to investigate the preclinical effect of gefitinib in an in vitro HCC model. We found that the IC(50) of gefitinib in HCC cells ranged from 0.7 to 10.0 muM, whereas Ln-5 inhibited the activity of gefitinib in a dose-dependent manner. Complete inhibition of phosphorylated (p)-EGFR (epidermal growth factor receptor) was obtained within 6 h exposure to gefitinib and complete restoration of the receptor status was obtained after 24 h. A downstream effect yields a decrease in p-Akt and p-Erk 1/2. The addition of exogenous Ln-5 has no effect on p-EGFR, whereas it restores p-Erk 1/2 and p-Akt. Consistently, Ln-5 induces recovery of HCC cells from Gefitinib-induced apoptosis. In conclusion, gefitinib inhibits HCC cell growth and we report for the first time that Ln-5, but not other ECM molecules, reduces the ability of gefitinib to inhibit cell growth via Akt. As patients with HCC have different Ln-5 expression levels, these results may help to better understand which patients might benefit from gefitinib treatment.

15545970

Endostatin expression in pancreatic tissue is modulated by elastase.

Pancreatic tumours are scirrhous, avascular tumours, suggesting that they may produce angiogenesis inhibitors that suppress the growth of the vasculature to the tumour and metastases. We have sought evidence for the angiogenesis inhibitor, endostatin, in normal and cancerous pancreatic tissue. Using Western blotting, we found mature 20 kDa endostatin in cancer tissue but not in normal tissue. Several endostatin-related peptides of higher mol wt were present in both tissues. Extracts from normal tissue were able to degrade exogenous endostatin, whereas extracts from cancer were without effect. Although the exocrine pancreas secretes inactive proenzymes of trypsin, chymotrypsin and elastase, their possible role in this degradation was examined. The trypsin/chymotrypsin inhibitor, Glycine max, did not prevent the degradation of endostatin by normal pancreatic extracts but elastatinal, a specific inhibitor of elastase, reduced the rate of degradation. Extracts of pancreatic tumours did not express any detectable elastase activity, but an elastase (Km 1.1 mM) was expressed by extracts of normal pancreas. We conclude that endostatin is present and stable in pancreatic cancer tissues, which may explain their avascular nature, but that normal pancreatic tissue expresses enzymes, including elastase, which rapidly degrade endostatin. The stability of endostatin may have implications for its therapeutic use.

15545969

Recent trends in cervical cancer mortality in Britain and Ireland: the case for population-based cervical cancer screening.

This study used published mortality data and regression techniques to look at time trends in cervical cancer mortality between 1970 and 2000 in the UK and the Republic of Ireland. Mortality from cancer of the cervix has been declining in the UK for at least the past 30 years. The rate of decrease has been greatest in England, Wales and Scotland and has accelerated in these countries since the reorganisation of screening services in the late 1980s. Mortality in Northern Ireland is also decreasing, but at a lesser rate and without significant change over the same period. In contrast, cervical cancer mortality in the Irish Republic, which, unlike the UK, does not have comprehensive population-based screening, has been increasing by an average of 1.5% per year since 1978. The mortality rate, which was half of that in the UK in the late 1970s, now exceeds that in any of the region of the UK. The absence of population-based screening for cervical cancer in the Republic of Ireland is the most plausible explanation for these differences in trend.

15545968

Genomic imbalances in 70 snap-frozen cervical squamous intraepithelial lesions: associations with lesion grade, state of the HPV16 E2 gene and clinical outcome.

Host genomic abnormalities may determine the natural history of cervical squamous intraepithelial lesions (SILs). We undertook comparative genomic hybridisation analysis of epithelium carefully microdissected from 70 cervical SILs, the largest series to date. In contrast to previous studies, we used frozen sections for optimal DNA quality and examined whether patterns of DNA copy number imbalance (CNI) are characteristic of SIL grade, human papillomavirus (HPV) status and postoperative recurrence. We identified more CNIs in cervical SIL than previously described, with more CNIs per case in high-grade squamous intraepithelial lesion (HG-SIL) than in low-grade squamous intraepithelial lesion (LG-SIL) (P=0.04). While some CNIs were seen at similar frequencies in HG-SIL and LG-SIL, others, including gain on 1q, 3q and 16q, were found frequently in HG-SIL but not in LG-SIL. There were significantly more CNIs per case in HG-SILs showing loss of the HPV16 E2 gene (a repressor of viral oncogene transcription) (P=0.026) and in HG-SILs that subsequently recurred (P=0.04). Our data are consistent with sequential acquisition of CNIs in cervical SIL progression. Higher frequency of CNI in association with E2 gene loss supports in vitro evidence that high-risk HPV integration is associated with genomic instability. Further investigation of the clinical value of specific host genomic abnormalities in cervical SIL is warranted.

15545967

TP53 status determines clinical significance of ERBB2 expression in ovarian cancer.

ERBB2 expression has been found in 19 to 44% of ovarian carcinomas; however, its predictive value has not been demonstrated, and trastuzumab has not found clinical application in ovarian cancer patients. We evaluated clinical significance of ERBB2 expression in relation to TP53 accumulation in ovarian carcinoma patients treated with platinum-based regimens. Immunohistochemical analysis with CB11 and a novel NCL-CBE356 antibody (against the internal and external domains of ERBB2, respectively) was performed on 233 tumours (FIGO stage IIB-IV); the US Food and Drug Administration-approved grading system with 0 to 3+ scale was used for evaluation, and the results were analysed by the Cox and logistic regression models. In all, 42% of the tumours expressed (category 1+, 2+ or 3+) either CB11 or CBE356 or both (CB11/CBE356 parameter). Associations between ERBB2 expression and clinical factors were observed only if tumours with staining category 1+ were grouped together with tumours showing staining categories 2+ and 3+. CB11/CBE356 parameter had a better predictive value than CB11 alone. CB11/CBE356 expression was negatively associated with platinum sensitivity (PS) in the TP53(-) group (P=0.022) and with disease-free survival (DFS) in the TP53(+) group (P=0.009). Our results may suggest that trastuzumab should be given postoperatively to patients with TP53(-)/ERBB2(+) ovarian carcinomas to enhance PS, and after completion of chemotherapy to patients with complete remission and TP53(+)/ERBB2(+) carcinomas to extend DFS time (in total to 30.4% of all patients analysed). Thus, novel criteria for ovarian cancer patient inclusion for clinical trials with trastuzumab should be considered and tested.

15545966

Oral contraceptive use and ovarian cancer risk among carriers of BRCA1 or BRCA2 mutations.

Women with mutations of the genes BRCA1 or BRCA2 are at increased risk of ovarian cancer. Oral contraceptives protect against ovarian cancer in general, but it is not known whether they protect against the disease in carriers of these mutations. We obtained self-reported lifetime histories of oral contraceptive use from 451 women who carried mutations of BRCA1 or BRCA2. We used conditional logistic regression to estimate the odds ratios associated with oral contraceptive use, comparing the histories of 147 women with ovarian cancer (cases) to those of 304 women without ovarian cancer (controls) who were matched to cases on year of birth, country of residence and gene (BRCA1 vs BRCA2). Reference ages for controls had to exceed the ages at diagnosis of their matched cases. After adjusting for parity, the odds-ratio for ovarian cancer associated with use of oral contraceptives for at least 1 year was 0.85 (95 percent confidence interval, 0.53-1.36). The risk decreased by 5% (1-9%) with each year of use (P for trend=0.01). Use for 6 or more years was associated with an odds-ratio of 0.62 (0.35-1.09). These data support the hypothesis that long-term oral contraceptive use reduces the risk of ovarian cancer among women who carry mutations of BRCA1 or BRCA2.

15545965

Additive interaction of gefitinib ('Iressa', ZD1839) and ionising radiation in human tumour cells in vitro.

Cultures of human carcinoma A-431, A-549 and HeLa cells were challenged with gamma-rays without or with concomitant exposure to gefitinib, a potent inhibitor of the tyrosine kinase activity of epidermal growth factor receptor (EGFR). The outcome of treatment was determined from cell and colony count, cell cycle progression and DNA double-strand break formation and rejoining. Apoptosis was measured in parallel from hypodiploid DNA and using an annexin V assay. Gefitinib developed a cytostatic effect in all cell lines, with drug sensitivity correlating the level of EGFR expression. A weak cytotoxicity of gefitinib was observed in HeLa cells only, although the drug was unable to induce significant cell cycle redistribution in this cell line. In contrast, substantial G1 block and S-phase depletion was observed in A-431 and A-549 cells exposed to gefitinib. The drug brought about additive to subadditive interaction with radiation with regard to growth inhibition, clonogenic death and induction of apoptosis. Consistently, gefitinib did not hinder the rejoining of radiation-induced DNA double-strand breaks in any cell line. The results demonstrate that gefitinib may elicit cytotoxicity at high concentration, but does not act as a radiosensitiser in vitro in concomitant association with radiation.

15545958

Choriocarcinoma involving the pancreas as first manifestation of a metastatic regressing mixed testicular germ cell tumor.

We describe an unusual case of metastatic choriocarcinoma of the pancreas arising from a regressing testicular mixed germ cell tumor that clinically mimicked a primary pancreatic tumor. A 54-year-old male presented with a 2-month history of progressive upper abdominal pain, weight loss, and jaundice. He also had a history of recurrent epididymitis associated with the presence of a right testicular mass shown to be cystic by ultrasound and stable for at least 10 years. A computed tomography scan showed an isolated 6 cm mass in the head of the pancreas. A pancreaticoduodenectomy was performed. Upon histological examination, the pancreatic tumor showed extensive hemorrhage and necrosis. In the viable area, the tumor was composed of an intimate mixture of mononuclear cytotrophoblast cells and multinucleated syncytiotrophoblasts with vascular invasion. These characteristic features led to the correct diagnosis on frozen section. The cytology of the tumor was nonspecific and suggested undifferentiated carcinoma of the pancreas. The trophoblastic origin of the tumor cells was confirmed by immunohistochemistry staining. The testicular mass showed a regressed mixed germ cell tumor of predominantly seminoma with focal teratoma but without a choriocarcinoma component. In conclusion, we present a rare and unusual case of a regressing testicular mixed germ cell tumor that presented as a primary pancreatic tumor. Cytological features of the pancreatic mass were not specific and raised the possibility of a primary undifferentiated carcinoma of the pancreas. Characteristic histological features of choriocarcinoma led to the correct diagnosis on frozen section. Subsequent resection of the testicular mass confirmed the presence of a cystic and scarring (regressing) mixed germ cell tumor but without evidence of choriocarcinoma.

15545957

Rapid determination of Epstein-Barr virus latent or lytic infection in single human cells using in situ hybridization.

Epstein-Barr (EBV) virus is associated with malignancies such as lymphoma and carcinoma. Infection of cells with EBV may result in either lytic infection with production of viral particles, characterized by the presence of linear DNA forms, or latent infection, characterized by either episomal or integrated DNA forms. To examine whether the different lytic and latent EBV DNA forms can reliably be distinguished in single human cells, in situ hybridization was performed in EBV-positive cell lines. Immunocytochemistry and Southern blot analysis were performed supplementary to in situ hybridization. In latent infection, three in situ hybridization patterns were observed: large-disperse (episomal), small-punctate (integrated) and combined (both), signal types 1, 2 and 3 respectively. These were associated with expression of latent membrane protein 1, but not with Z fragment of Epstein-Barr replication activator or viral capsid antigen. In lytic infection, three additional in situ hybridization patterns were observed: nuclear membrane associated, bubble (filling up the nucleus) and spillover (covering the lysed cells) signals types 4, 5 and 6 respectively. Signal types 4 and 5 were associated with expression of latent membrane protein 1 and Z fragment of Epstein-Barr replication activator but not viral capsid antigen, whereas type 6 was associated with expression of viral capsid antigen only. Southern blot analysis confirmed these results; however, low copy numbers of integrated virus were often missed by Southern blot, confirming that in situ hybridization is more sensitive in determining the presence of all types of EBV DNA. In situ hybridization may prove useful in rapidly screening large series of tissue microarrays and other clinical specimens for the presence of lytic or latent EBV.

15545956

[Lung carcinosarcoma. A case report].

Carcinosarcoma of the lung is a rare highly malignant tumor of unknown histogenesis. There is an epithelial carcinomatous component and a malignant mesenchmatous component with heterologous tissue. Survival at two years after surgical resection is not greater than 10%. We report a case observed in a 71-year-old man who developed chest pain. Outcome was fatal at three months. Pathology examination of a transparietal biopsy provided the diagnosis which was confirmed by immunohistochemistry on the surgical resection specimen.

15545954

[Solitary fibrous mediastinal tumor. A case report].

Solitary fibrous tumor is a rare tumor, generally located in the pleura. Recently, new sites have been described in the literature, particularly involving the peritoneum and mediastinum, as wekk as te-the bronchopulmonary and orbital regions. The diagnosis is established at pathology, but in some cases may be difficult to differentiate from other tumors. We report the case of a 60-year-old women who had undergone surgery 25 years ago for right pulmonary hydatid cyst and who presented inspiratory dyspnea and dry cough for four months. Physical examination revealed a right cervical tumefaction in the supraclavian region. The AP chest x-ray disclosed an opacity in the right laterotracheal upper cervicomediastinal zone laminating the trachea which was displaced to the left. Thoracic computerized tomography showed a tissular process in the superior and middle mediastinum. Surgical tumor resection was performed and pathology confirmed the diagnosis of solitary fibrous tumor. The postoperative period was uneventful. Frequency of the mediastinal localisation is the same in men and women. The tumor generally develops between the 5th and 7th decades, and is most often asymptomatic. Fortuitous discovery is the rule. The clinical course is unforeseeable.

15545955

[Hyperplasia of the thymus in Graves' disease. A case report].

Graves' disease is rarely associated with hypertrophy of the thymus which takes on a pseudotumor aspect. We observed a case in a 40-year-old woman who presented clinical and biological hyperthyroidism with anti-TSH receptor antibodies, favoring the diagnosis of Graves' disease which was confirmed by scintigraphy. The chest x-ray performed because of chest pain revealed enlargement of the mediastinum. The thoracic CT-scan without contrast injected showed a pseudotumor aspect of the thymus. Medical treatment with anti-thyroid drugs and beta blockers led to regression of the thymus mass. Knowledge of this type of association can avoid unnecessary thymus surgery. The clinical course is favorable irrespective of the type of anti-thyroid drug given.

15545953

[Spontaneous pneumothorax revealing malignant pleural mesothelioma. Three case reports].

Spontaneous pneumothorax is an uncommon inaugural presentation of malignant pleural mesothelioma. We report three cases in men aged 65, 30 and 76 years. The diagnosis was suggested at medical imaging and was confirmed at histological analysis of biopsies obtained by thoracoscopy in two patients and thoracotomy in one. The first patient (age 65 years) died two months after the initial diagnosis. The second patient (age 30 years) was alive 40 months after 15 chemotherapy cycles using a platinim-gemcitabine combination. Complete tumor response was achieved in the third patient (age 76 years) after 9 chemotherapy cycles with the same combination. Since mid-term prognosis is fatal for this type of tumor, we propose thoracoscopy in all patients over 30 years who develop spontaneous pneumothorax with no morphological features increasing the risk of pneumothorax, and particularly in patients with asbestos exposure.

15545952

[An unusual diagnosis of post-traumatic hemothorax].

We report the case of malignant pleural mesothelioma revealed by a post-traumatic hemothorax.

15545951

[An exceptional but serious complication of benign intercostal schwannoma: hemothorax].

Spontaneous serious hemothorax has not been described previously as an inaugural signor secondary complication of benign intercostal schwannoma. We report a case in a 45-year-old woman who was hospitalized in an emergency setting after development of massive left hemothorax. After evacuation of the effusion, imaging demonstrated a voluminous apparently neurogenic tumor in an intercostal position. Thoracotomy was required for hemostasis due to persistent bleeding. Tumor resection was performed. At histology, the surgical specimen was found to be a benign schwannoma presenting hemorrhagic remodeling. Resection provided complete cure with no sequelae. This secondary complication favors resection of benign intercostal schwannoma.

15545950

[Smoking in the African setting (Abidjan, Ivory coast): patient knowledge, attitude and behavior].

Recent studies on smoking conducted in the ivory coast have been sparse despite increasingly aggressive tobacco company campaigns. The purpose of this prospective study was to examine the influence of medical specialty on patient knowledge, attitude and smoking behavior among people consulting three university hospitals in Abidjan. The inquiry was performed with a questionnaire concerning a comparative series of 180 subjects (90 patients in each sample). Overall, the series included 16.10% active smokers, 15.60% former smokers, and 68.30% non-smokers, with no difference between the groups. The well-known feature of smoking with friends was main reason cited for beginning smoking. Three quarters of patients (75.9%) had attempted to stop smoking. Information about smoking was obtained from the media. The hospital was involved little in acquiring knowledge about smoking. Type of specialist consultation (hospital units providing care for smoking-related disease or not) had little influence. Hospital units should become more involved in the anti-smoking campaign. Consultations on cessation of smoking should be instituted in a country with highly aggressive smoking advertisements.

15545949

[Efficacy and acceptability of the fixed fluticasone + salmeterol combination in the treatment of acute asthma attacks. Results of a one-year comparative study].

The objective of an asthma treatment is to control asthma, particularly to prevent exacerbations. To study the efficacy, acceptability and safety of the fluticasone/salmeterol (FP/S) combination in preventing asthma exacerbations in comparison with the continuation of previous treatment (TA). This was a multicentre, randomised, parallel-group study to compare the fixed combination FP/S to TA (treatment with a free combination of an inhaled corticosteroid and a long-acting beta2-agonist) over one year in patients whose asthma was well controlled with their current treatment. Five hundred and twenty patients were randomized and their data analyzed on an intent-to-treat basis. Seventy-four percent of the patients in the FP/S group and 71% in the TA group had no exacerbation. The 3.12% difference in favor of the FP/S group (90% CI: -3.32% to 9.56%) demonstrated that FP/S was at least as effective TA in preventing asthma exacerbations. Treatment acceptability, evaluated by the patient on visual analog scales (inclusion as part of the daily habits, constraint, simplicity) was better with FP/S (p<0.001) than with TA. Clinical safety was good and comparable in the two groups. The fixed fluticasone/salmeterol combination provided a protection as good as that obtained with free combinations over a one-year treatment period, with a significant improvement in treatment acceptability and a good clinical safety.

15545947

[Pulmonary hypertension: from genetics to treatments].

Pulmonary hypertertension (PHT) is a rare disease defined by increased resistance of the pulmonary arteries inevitably leading to right heart failure if specific treatment is not given. This disease can occur sporadically (idiopathic or primary PHT), within a familial context (familial PHT, BMPR2 gene mutation), or occur as a complication of other diseases (connective tissue disease, congenital cardiomyopathy, human immunodeficiency virus infection, portal hypertension, use of anorexigenic agents). The incidence of primary PHT is 2 million cases per year, probably an underestimation due to the low specificity of clinical signs, predominantly exercise-induced dyspnea. Recent therapeutic advances (prostacyclin and endothelin receptor antagonists administered in continuous infusion) have improved the prognosis of this orphan disease. Inhaled iloprost and type 5 phosphodiesterase inhibitors should be evaluated for this indication. Lung transplantation is reserved for patients unresponsive to medical treatment.

15545948

[Limitations of drug prescriptions in patients with chronic obstructive pulmonary disease].

National and international guidelines have described in detail the role of bronchodilators and inhaled corticosteroids for the management of patients with chronic obstructive lung disease (COPD). Such guidelines are identical to marketing approval documents in France. The French marketing approval, which limits use of bronchodilators to reversible COPD, is no longer coherent with recent evidence demonstrating the poor reproducibility of reversibility tests and the absence of correlation between reversibility and dyspnea relief. France has not delivered marketing authorization for any inhaled corticosteroid for the treatment of COPD. Clinical trials versus placebo have demonstrated that inhaled corticosteroids do not slow down the decline in ventilatory function but that they do diminish the risk of exacerbation. Decreased risk of exacerbation could be clinically pertinent in patients with severe COPD who often experience exacerbations requiring to specialist management. Inquiries concerning precriptions for COPD show that the majority of patients are treated by inhaled corticosteroids, demonstrating the gap between medical practice and national and international recommendations and marketing approval documents.

15545946

[Medicolegal aspects in neuroradiologic emergencies].

Naturally, neuroimaging emergencies are a component of the global subject of emergencies that have for several years been a frequent subject in the press. The current situation is the consequence of the evolution of ideas from contractual liability to the frequently discussed principle of precaution. Examples offered by the daily practice allow to emphasize the main difficulties: diagnosis of headaches, seizure episode on public roads, head trauma, stroke... The medical liability of the neuroradiologist is not the same for diagnostic or interventional neuroradiology; it can sometimes be shared with other physicians. This liability includes the indication, the quality of the diagnosis, the information of the patient and relatives, the communication of results with other physicians, the maintenance of the equipment... Knowledge of potential pitfalls allows preventive measures including competence of the neuroradiologist, informed patient consent, and written precise protocols are the most important. However, according to the evolution of our societies, it is likely that it will become increasingly difficult to achieve a professional neuroradiology career without being questioned; it is thus advisable to be prepared for such eventuality.

15545945

[The value of teleradiology in the management of neuroradiologic emergencies].

First, to summarize the results of teleradiology programs on neurosurgical emergency care in France. Second, to compare French data with the international literature. Third, to discuss the likely developments and future of teleneuroradiology and teleneurosurgery. Data on French use of telemedicine applications in neuroradiology come from a survey of telemedicine applications in France, which has been conducted in year 2003 at the request of the French ministry of the Research. Teleradiology clearly has a positive impact on emergency neurosurgical care by reducing the time to correct diagnosis and initiation of treatment of patients who need to be transferred and avoid unnecessary transfers. However, present teleradiology applications have organizational limitations that are summarized and discussed with reference to the literature. Further developments in information and communications technology have the potential to revolutionise neurosurgical emergency care and contribute to improve the training of neuroradiology and neurosurgery staff.

15545943

[Imaging in acute toxic encephalopathy].

Neuroimaging, particularly MR imaging, plays a major role for the diagnosis of many acute toxic encephalopathies. Toxic disorders are related to drugs (immunosuppressive agents, chemotherapeutic agents, anti-epileptic drugs, heroin...), to metals (lead, manganese, mercury...), and to industrial and environmental chemicals (solvent, carbon monoxide...). MR imaging with diffusion and perfusion imaging provides information regarding brain lesions induced by the toxic agents (vasogenic edema, cytotoxic edema, infarction, hemorrhage, demyelination...).

15545944

[Emergency imaging of cerebrovascular accidents].

Over the last 25 years, advances in neuroimaging have significantly changed the evaluation and management of acute stroke syndromes. In the seventies, computed tomography (CT) could differentiate between ischemic and hemorrhagic stroke. Magnetic resonance imaging (MRI) is nowadays the imaging modality of choice in the initial assessment of acute stroke. MRI images can better discriminate acute, subacute and chronic infarcts, differentiate venous from arterial infarcts, detect arterial dissection, stenosis or occlusion. Diffusion-weighted images are highly sensitive and specific to acute infarction and the combination with perfusion technique is suitable to define potentially reversible ischemia (area of cerebral "mismatch" which is thought to represent the so-called ischemic penumbra). This penumbra is a potential therapeutic target of valuable interest for the treating physician.

15545942

[Neuroradiologic emergencies in infectious pathology].

The main goal of urgent imaging evaluation of patients with suspected CNS infection is to differentiate infectious from tumoral or vascular lesions in order to provide appropriate management. MR imaging, including diffusion weighted imaging and spectroscopy, is superior to CT imaging to characterize lesion location and etiology. The CT and MRI features of the more frequent bacterial, viral and parasitic CNS infections will be described.

15545941

[Imaging of neuro-ophthalmological emergencies].

MRI often is mandatory in the diagnostic work-up of visual loss, visual field alterations and oculomotor problems. It is performed emergently in patients with painful diplopia associated to mydriasis, to exclude aneurysm, or in patients with painful Horner syndrome to exclude dissection of the internal carotid artery. CT scan in emergency remains useful in case of acute lateral hemianopsia or acute post traumatic visual loss. Progressive neuro-ophthalmological symptoms may require imaging examination in a short delay to define the therapeutic strategy: monocular transient blindness (dissection or carotid stenosis), progressive visual loss (optic nerve compression), bitemporal hemianopsia (optic chiasm lesion), painful visual loss (optic neuritis). A very precise clinical indication is helpful for the choice of imaging protocol and to improve its diagnosis value.

15545940

[Management of patients after a first seizure].

Neuroimaging evaluation in patients after a first seizure could be easily determined on the basis of seizure history, neurological examination, blood sample analysis and electroencephalography. The main objectives of the initial work-up are to differentiate a true seizure event from seizure-like symptoms, to exclude a single seizure as a manifestation of non organic cause and finally to consider the seizure as a result of cerebral lesion or inaugurate epilepsy. When a new onset seizure is diagnosed, urgent neuroimaging is recommended only in patients with focal neurological deficit, persistent or worsening alteration in the level of consciousness and when clinical and biological data lead to a suspected vascular or infectious etiology. Brain CT scan is usually more available in emergency to identify the cause of seizure. It may have an important role for the therapeutic strategy and may defer MRI investigation. Nevertheless, brain MRI must be performed in emergency when CT scan is not conclusive despite a severe clinical condition or in case of cerebral venous thrombosis. Imaging modalities depend on clinical data, patient age and suspected epilepsy type.

15545939

[Pediatric neuroimaging emergencies].

The notion of emergency with regards to pediatric neuroimaging requires a strong knowledge of clinical indications. In children under 2 years of age, head trauma requires a CT scan in case of repeated or prolonged or rapidly increasing vomiting, focal signs, loss of consciousness, unusual behavior, seizures, clinical signs of skull fracture or polytrauma. The "shaken baby syndrome" is usually suspected in case of loss of consciousness or seizures before 8 months of age. The hematomas that are observed are subdural in location, diffuse and deeply located. Imaging is only mandatory for headache suggesting underlying space occupying lesion: permanent or increasing pain, nocturnal headache, headache during postural changes or efforts, associated to seizures or abnormal neurological examination. No imaging is indicated in case of first epileptic seizure associated to normal neurological examination and without any particular context. The presence of trauma, intracranial hypertension, persisting disturbances of consciousness or associated focal sign necessitates urgent neuroimaging. No imaging is indicated in case of typical febrile seizures, i.e. generalized, brief and occurring between 1 and 5 years of age. Spinal cord symptoms require immediate MRI evaluation. The most frequent tumor is neuroblastoma. In the absence of spinal tumor, brain abnormalities must be excluded (inflammatory disease). In neonates, CT scan or MRI must be readily performed in case of seizures or loss of consciousness to exclude ischemic, traumatic or infectious lesions.

15545938

[Headaches in the emergency context].

Headaches constitute one of the most frequent reason of consultation. Their causes are extremely varied. The first step consists in the analysis of the characteristics of the pain and the associated signs in order to distinguish primary and secondary headaches. Primary headaches, including migraines and tension-type headaches are the most frequent types and do not require imaging evaluation. Secondary headaches are related to an organic cause and require specific investigations. In case of suspected symptomatic or secondary headaches, brain imaging plays an important role in the etiologic work-up. The main purpose of imaging in an emergency setting is to diagnose a life-threatening disease.

15545937

[Evaluation of neurological deficits].

The first step in the evaluation of patients with neurological deficit is to obtain expert clinical evaluation to achieve accurate and complete characterization. The type of neurological deficit, its mode of onset, the presence or absence of associated signs and symptoms, and a differential diagnosis must first be described. This will allow identification of the probable site of CNS involvement and appropriate imaging evaluation to be performed. A multi-disciplinary approach with constant correlation between clinical, imaging and pathological findings will enable clinicians to provide patients accurate diagnoses, appropriate prognostic evaluation and optimal management.

15545936

[Neurologic emergencies].

Neurological symptoms are a very frequent cause of consultation in emergency units and require consultation with neurologists and neuroradiologists. The most frequent diagnoses are stroke syndrome, seizure, headache, confusion, meningitis and meningo-encephalitis, and facial palsy. The morbidity and mortality of neurological emergencies are strongly related to prompt medical management of the patients which often requires neuroimaging studies. The most common neurological emergencies will be reviewed.

15545934

[Extracranial internal carotid artery aneurysm].

Extracranial aneurysm of the internal carotid artery is an exceptional finding. An 89-year-old woman consulted for a peritonsillar mass. Physical examination revealed a parapharyngeal pulsatile mass in the oropharynx. Computed tomography (CT) provided the diagnosis of extracranial internal carotid artery aneurysm. Endovascular or surgical treatment were declined. Anticoagulation medication was given. We reviewed the CT and magnetic resonance imaging findings and the clinical manifestations of extracranial internal artery aneurysm. Endovascular treatment is an alternative to open surgery.

15545933

[Metachronous sinonasal squamous-cell carcinoma after pharyngolaryngectomy].

Three laryngectomized patients developed metachronous sinonasal squamous-cell carcinoma. We reviewed their files to search for clinical features useful for early diagnosis of this localization. Two of the patients, a textile worker and a food processing worker, had occupation exposure risk factors for sinonasal squamous-cell carcinoma. The anatomic modifications created by laryngectomy contributed to late diagnosis of the metachronous tumor at an advanced stage. Surgery was performed in all three patients. Local recurrence was observed at one year in two patients. Sinonasal fibroscopy should be part of the surveillance scheme in laryngectomized patients to enable early diagnosis and treatment of metachronous tumors.

15545932

[Interest of PET/CT scan fusion to assess mandible involvement in oral cavity and oro pharyngeal carcinomas].

The aim of the study is to assess mandible involvement in oral cavity and oropharyngeal carcinomas. To evaluate interest of fusion of Positron Emission Tomography (PET) with Computed Tomography scan (CT scan). Eight patients were included in this prospective study. Each patient underwent PET and CT scan of the head and neck before surgery including tumorectomy and mandibulectomy. We compared results of PET- CT fusion with histologic examinations. Oral cavity (6), oropharyngeal (2) carcinoma: Mandibular invasion was suspected by PET-CT in 3 cases, but was confirmed in histological examination in only 2 cases. In 5 cases, PET-CT did not find mandibular invasion; this was confirmed in histological examination in all cases. Sensibility of PET-CT fusion was 100%, specificity was 83%. Positive predictive value was 66% and negative predictive value was 100%. PET-CT fusion provided maximal sensitivity. Specificity was better than for MRI but less than CT-scan. There were no false negatives and the false positive rate was 33%. PET-CT fusion is interesting to predict mandible involvement. Further studies are necessary to confirm these preliminary results.

15545931

[Mitomycin C: prevention and treatment of anterior glottic synechia].

Topical applications of mitomycin C to the anterior glottis may prevent anterior glottic synechia (prevention group) or restenosis (treatment group). In the prevention group, six patients with glottic carcinoma involving the anterior commissure were treated by transoral laser surgery. Repeated procedures were performed in one patient. For the six patients in the treatment group, the anterior glottic synechia was secondary to frontolateral laryngectomy (three patients), transoral laser therapy for laryngeal papillomatosis (two patients) or bilateral glottic carcinoma (one patient). Mitomycin C (0.4 mg/ml) was used as a topical application on the anterior commissure for a duration of 4 minutes. Outcome was assessed clinically at three months using a visual scale: no synechia (success), micro-synechia (partial failure), and synechia (failure). In the prevention group, there were six successes and one partial failure. In the treatment group, there were two successes, three partial failures, and one failure. No side effects were noted. Topical application of mitomycin C was effective to prevent anterior glottic synechia after transoral laser surgery for glottic carcinoma involving the anterior commissure. It is an alternative to endolaryngeal keel in patients with sequellar synechia. These preliminary results should be further evaluated in a larger series.

15545930

[Endoscopic closure of septal perforations by mucosal rotation flaps].

We present a technique of endoscopic endonasal closure of average sized (0.5 - 2 cm) to large (>2 cm) septal perforations. The surgical technique involves a mucosal rotation flap on a unilateral posterior pedicle without interposition material. We reviewed our experience with eleven patients with average sized and large septal perforations treated over an 8-year period. We based our evaluation on the model proposed by Younger and Blokmanis. Our results were comparable with earlier publications. One-phase closure was achieved in 75% of patients (55% to 90% in the literature reporting all techniques, including external septorhinoplasty and midfacial degloving). Our preliminary series provides a basis for a new approach to this condition. The technique is promising for large perforations. This technique could also be considered for other nasal fossae in the event of failed closure. It also offers a way to obtain excellent closure of the anterior portion of the perforation, relieving the patient of the most annoying symptoms. The technique does not contraindicate other procedures which may be performed during the same operation or later.

15545929

[Ethmoid adenocarcinoma: trans-facial approach for anterior skull base resection. a series of 80 cases].

To present results of a retrospective analysis of eighty cases of ethmoid adenocarcinoma. Carcinologic and surgical results of anterior skull base resection via the transfacial approach are presented. Tumors were classified as 5% T1, 23% T2, 31% T3, 21% T4a and 20% T4b. Thirty-four patients were treated via a paralateronasal approach without skull base resection. Anterior skull bas resections were performed via the transfacial approach for 26 patients and by combined neurosurgical approach for 21. Mean follow-up was 4.8 years. Survival rate was 63.4% at 5 years and 57.9% at 8 years. Forty-two patients were alive and disease-free at last follow-up. Three patients were alive with recurrence. The rate of local recurrence was 38.8%. Complications occurred in 20% of the patients who had a transfacial approach. Complications appeared to be less frequent than with the combined approach. Prognosis is related to local control and could be improved by using skull base resection more systematically. In our experience this can be managed by a transfacial approach with similar carcinological results and less complications than the combined approach.

15545928

[Anatomohistologic study of von Oort's vestibulocochlear anastomosis].

The vestibulocochlear anastomosis was first described in 1918 by von Oort. It is situated deeply at the bottom of the internal acoustic meatus, and spreads from the saccular nerve before its terminal ramifications, to the cochlear nerve before its penetration into the cochlea. Nerve fibers of the cochlear efferent system are thought to pass through it. The aim of our study was to investigate the anatomy of the vestibulocochlear anastomosis and characterize its histological features. [corrected] Ten human temporal bones were dissected. Serial sections were obtained for histological evaluation. The vestibulocochlear anastomosis was found in seven of the specimens, perfectly visualized in six. Average diameter was 0.5 mm with lengths varying from 0.5 to 1 mm. Serial histological sections demonstrated the nervous nature of the anastomosis and its relations with the saccular and cochlear nerves. The epinevrium of the saccular nerve was continuous with the supposed anastomosis in five of the specimens, demonstrating the distinct nature of the anastomosis from the saccular and cochlear nerves. We did not find any evidence linking these fibers to the cochlear efferent system. The vestibulocochlear anastomosis was found in seven of our ten dissections. The anastomosis is probably an anatomic reality composed of nerve fibers. The efferent function of these fibers remains to be demonstrated.

15545925

Inhibition of toll-like receptor and cytokine signaling--a unifying theme in ischemic tolerance.

Cerebral ischemia triggers acute inflammation, which exacerbates primary brain damage. Activation of the innate immune system is an important component of this inflammatory response. Inflammation occurs through the action of proinflammatory cytokines, such as TNF, IL-1 beta and IL-6, that alter blood flow and increase vascular permeability, thus leading to secondary ischemia and accumulation of immune cells in the brain. Production of these cytokines is initiated by signaling through Toll-like receptors (TLRs) that recognize host-derived molecules released from injured tissues and cells. Recently, great strides have been made in understanding the regulation of the innate immune system, particularly the signaling mechanisms of TLRs. Negative feedback inhibitors of TLRs and inflammatory cytokines have now been identified and characterized. It is also evident that lipid rafts exist in membranes and play a role in receptor-mediated inflammatory signaling events. In the present review, using this newly available large body of knowledge, we take a fresh look at studies of ischemic tolerance. Based on this analysis, we recognize a striking similarity between ischemic tolerance and endotoxin tolerance, an immune suppressive state characterized by hyporesponsiveness to lipopolysaccharide (LPS). In view of this analogy, and considering recent discoveries related to molecular mechanisms of endotoxin tolerance, we postulate that inhibition of TLR and proinflammatory cytokine signaling contributes critically to ischemic tolerance in the brain and other organs. Ischemic tolerance is a protective mechanism induced by a variety of preconditioning stimuli. Tolerance can be established with two temporal profiles: (i) a rapid form in which the trigger induces tolerance to ischemia within minutes and (ii) a delayed form in which development of protection takes several hours or days and requires de-novo protein synthesis. The rapid form of tolerance is achieved by direct interference with membrane fluidity, causing disruption of lipid rafts leading to inhibition of TLR/cytokine signaling pathways. In the delayed form of tolerance, the preconditioning stimulus first triggers the TLR/cytokine inflammatory pathways, leading not only to inflammation but also to simultaneous upregulation of feedback inhibitors of inflammation. These inhibitors, which include signaling inhibitors, decoy receptors, and anti-inflammatory cytokines, reduce the inflammatory response to a subsequent episode of ischemia. This novel interpretation of the molecular mechanism of ischemic tolerance highlights new avenues for future investigation into the prevention and treatment of stroke and related diseases.

15545924

Retroviral delivery of homeobox D3 gene induces cerebral angiogenesis in mice.

Angiogenesis is regulated by concerted actions of angiogenic and angiostatic factors. Homeobox D3 gene (HOXD3) is a potent proangiogenic transcription factor that promotes angiogenesis by modulating the expression of matrix-degrading proteinases, integrins, and extracellular matrix components. Application of HOXD3 can promote angiogenesis in the skin, but its role in other vascular beds has not been examined. The authors examined HOXD3 expression in human brain vessels by in situ hybridization. Although little or no HOXD3 mRNA was detected in normal brain vessels, increased levels of HOXD3 and its target gene, alpha V beta 3, were found in angiogenic vessels in human brain arteriovenous malformations. The authors further investigated whether HOXD3 plays a role in cerebral angiogenesis in a murine model. Expression of HOXD3 in mouse brain was achieved through retroviral vector-mediated HOXD3 gene transfer. HOXD3 expression lead to a significant induction of cerebral angiogenesis as shown by quantitative microvessel counting (HOXD3: 241 +/- 19 vessels/mm2 vs. saline: 150 +/- 14 vessels/mm2, P < 0.05). The data also showed that focal cerebral blood flow was increased in the angiogenic region with less vascular leakage. Moreover, expression of HOXD3 led to an increase in the expression of a direct downstream target gene alpha V beta 3 integrin. The data suggest that HOXD3 may play an important role in regulating cerebral angiogenesis, and that gene transfer of HOXD3 may provide a novel and potent means to stimulate angiogenesis.

15545923

Activation of proinflammatory caspases by cathepsin B in focal cerebral ischemia.

Cathepsins and caspases are two families of proteases that play pivotal roles in ischemic cell death. This study investigated the existence of a cross-talk between cathepsin B and proinflammatory caspases in stroke-induced cell death, as recently suggested by in vitro data. Cortical ischemic damage was induced in mice by distal and permanent occlusion of the middle cerebral artery. Cytoplasmic activation of cathepsin B was observed from the early stages of infarction, and displayed an activation pattern parallel to the activation pattern of caspase-1 and -11. Immunohistochemistry revealed the colocalization of cathepsin B with each caspase in cells of the infarct core. The apical position of cathepsin B in both caspase-activation cascades was confirmed by pretreatment of the animals with the cathepsin B inhibitor CA-074, which also potently protected cortical structures from ischemic damage, indicating involvement of the proteases in the lesion process. The results show that cathepsin B release is an early event following occlusion of cerebral arteries, which eventually triggers the activation of proinflammatory caspases in the absence of reperfusion. This new pathway may play a critical role in brain infarction by promoting inflammatory responses, and/or by amplifying the apoptotic process.

15545922

Cerebral hemodynamic reserve and early neurologic deterioration in acute ischemic stroke.

Early neurological deterioration (END) is associated with increased mortality and morbidity. Although several predictive factors have been reported, there are little data about the hemodynamic factors. Our aim was to determine the capacity of cerebral hemodynamic reserve (CHR) to predict END. We studied 100 hospitalized patients with a first ever ischemic stroke of the middle cerebral artery (MCA) within the first 24 hours of symptoms onset. END was defined as a drop of at least one point in the Canadian Stroke Scale between admission and 72 hours. The mean flow velocity (mV) in the MCA and the CHR were measured by means of transcranial Doppler within the first 24 hours of admission. The CHR was expressed as the percentage increase in the MCA mV divided by the absolute increase in the end-tidal CO2 pressure in mm Hg after carbogen inhalation. END was observed in 23 patients. Reduced values of the mV in the symptomatic MCA (P = 0.043) and of the CHR in the symptomatic hemisphere (P < 0.001) were significantly associated with END. A CHR of less than 2%/1 mm Hg was independently associated with END (OR 8.45, 95% CI 1.82-39.2) after adjusting for potential confounders. CHR impairment within the first 24 hours of acute ischemic stroke is associated with a higher risk of END. This technique may be useful in selecting patients requiring a more intensive management.

15545921

Degeneration of the basalocortical pathway from the cortex induces a functional increase in galaninergic markers in the nucleus basalis magnocellularis of the rat.

The present work aimed 1) to evaluate whether an increase in galanin or galanin receptors could be induced in the nucleus basalis magnocellularis (nbm) by degeneration of the basalocortical neurons from the cortex and 2) to analyze the consequences of such an increase on cortical activity. First, a mild ischemic insult to the frontoparietal cortex was performed to induce the degeneration of the basalocortical system; galanin immunoreactivity, galanin binding sites, and cholinergic muscarinic receptors were quantified through immunocytochemistry and autoradiography. Second, galanin infusions in the nbm were undertaken to mimic a local increase of the galaninergic innervation; cortical acetylcholine release, cerebral glucose use, and cerebral blood flow were then measured as indices of cortical activity. As a result of the cortical ischemic lesion, the postsynaptic M1 and presynaptic M2 muscarinic receptors were found to be reduced in the altered cortex. In contrast, galaninergic binding capacity and fiber density were found to be increased in the ipsilateral nbm in parallel with a local decrease in the cholinergic markers such as the muscarinic M1 receptor density. Galanin infusion into the nbm inhibited the cortical acetylcholine release and cerebral blood flow increases elicited by the activation of the cholinergic basalocortical system but failed to affect acetylcholine release, cerebral blood flow, and cerebral glucose use when injected alone in the nbm. These results demonstrate that degeneration of the basalocortical system from the cortex induces an increase in galaninergic markers in the nbm, a result that might suggest that the galaninergic overexpression described in the basal forebrain of patients with Alzheimer's disease can result from a degeneration of the cholinergic basalocortical system from the cortex. Because galanin was found to reduce the activity of the basalocortical cholinergic system only when this one is activated, galanin might exert its role rather during activation deficits than under resting conditions such as the resting cortical hypometabolism, which is characteristic of Alzheimer's disease.

15545920

Does the acute diffusion-weighted imaging lesion represent penumbra as well as core? A combined quantitative PET/MRI voxel-based study.

In acute ischemic stroke, the diffusion-weighted imaging (DWI) lesion is widely held to represent the core of irreversible damage and is therefore crucial in selecting patients for thrombolysis. However, recent research suggests it may also represent penumbra. An illustrative patient was imaged 7 hours after stroke onset with back-to-back 3T diffusion tensor imaging and quantitative positron emission tomography, which showed a DWI lesion and misery perfusion, respectively. Using previously validated voxel-based probabilistic CBF, CMRO2, and Oxygen Extraction Fraction (OEF) thresholds, the authors show that the DWI lesion contained not only core but also substantial proportions of penumbra. Also, severe apparent diffusion coefficient reductions were present within the potentially salvageable penumbra as well as in the core. These findings have potential implications regarding treatment decisions.

15545915

Protein ubiquitination in postsynaptic densities after transient cerebral ischemia.

The mechanisms underlying neurologic deficits and delayed neuronal death after ischemia are not fully understood. In the present study, we report that transient cerebral ischemia induces accumulation of ubiquitinated proteins (ubi-proteins) in postsynaptic densities (PSDs). By immunoelectron microscopy, we demonstrated that ubi-proteins were highly accumulated in PSD structures after ischemia. On Western blots, ubi-proteins were markedly increased in purified PSDs at 30 minutes of reperfusion, and the increase persisted until cell death in the CA1 region after ischemia. In the resistant DG area, however, the changes were transient and significantly less pronounced. Deposition of ubi-proteins in PSDs after ischemia correlates well with PSD structural damage in the CA1 region as viewed by electron microscopy. These results suggest that the ubiquitin-proteasome system fails to repair and remove damaged proteins in PSDs. The changes may demolish synaptic neurotransmission, contribute to neurologic deficits, and eventually lead to delayed neuronal death after transient cerebral ischemia.

15545916

Valproate is neuroprotective against malonate toxicity in rat striatum: an association with augmentation of high-affinity glutamate uptake.

The antiepileptic drug valproate (VPA) may be neuroprotective. We treated rats with VPA for 14 days (300 mg/kg twice daily) before intrastriatal injection of 1.5 micromol (1 M) of the succinate dehydrogenase inhibitor malonate. VPA-treated animals developed smaller lesions than control animals: 10 +/- 2 mm(3) versus 26 +/- 8 mm(3) (means +/- SD; P = 10(-4). Injection of NaCl that was equiosmolar with 1 M malonate caused lesions of only 1.2 +/- 0.4 mm(3) in control animals, whereas physiologic saline produced no lesion. VPA pretreatment reduced the malonate-induced extracellular accumulation of glutamate. This effect paralleled an increase in the striatal level of the glutamate transporter GLT, which augmented high-affinity glutamate uptake by 25%, as determined from the uptake of [(3)H] glutamate into striatal proteoliposomes. Malonate caused a 76% reduction in striatal adenosine triphosphate (ATP) content, but the glial, ATP-dependent formation of glutamine from radiolabeled glucose or glutamate was intact, indicating that glial ATP production supported uptake of glutamate. Striatal levels of HSP-70 and fos were reduced, and the levels of bcl-2 and phosphorylated extracellular signal-regulated kinase remained unaffected, but histone acetylation was increased by VPA treatment. The results suggest that augmentation of glutamate uptake may contribute importantly to VPA-mediated neuroprotection in striatum.

15545914

Human C-reactive protein increases cerebral infarct size after middle cerebral artery occlusion in adult rats.

Human C-reactive protein (CRP), the classic acute phase plasma protein, increases in concentration after myocardial infarction and stroke. Human CRP binds to ligands exposed in damaged tissue and can then activate complement and its proinflammatory functions. In contrast, rat CRP, which binds to similar ligands, does not activate complement. In the present study, systemic complement depletion with cobra venom factor in adult rats subjected to middle cerebral artery occlusion did not affect cerebral infarct size, indicating that circulating complement does not contribute to injury in this model. However, we have previously reported that administration of human CRP to rats undergoing coronary artery ligation caused a marked increase in size of the resulting myocardial infarction, associated with codeposition of human CRP and rat complement in the infarcts. In the present study, we show that adult rats subjected to middle cerebral artery occlusion and then treated with human CRP similarly developed significantly larger cerebral infarcts compared with control subjects receiving human serum albumin. Human CRP can thus contribute to ischemic tissue damage in the brain as well as in the heart, and inhibition of CRP binding may therefore be a promising target for tissue protective acute therapeutic intervention in stroke as well as in myocardial infarction.

15545913

Postischemic intraventricular administration of FGF-2 expressing adenoviral vectors improves neurologic outcome and reduces infarct volume after transient focal cerebral ischemia in rats.

Fibroblast growth factor (FGF)-2 is a potent neurotrophic and angiogenic peptide. To examine possible protective effects of FGF-2 gene expression against transient focal cerebral ischemia in rats, a replication defective, recombinant adenovirus vector expressing FGF-2, was injected intraventricularly 2 hours after middle cerebral artery occlusion (MCAO). The treatment group showed significant recovery compared with the vehicle-treated groups in terms of serial neurologic severity scores over the 35 days after MCAO. Further, 2,3,5-triphenyltetrazolium chloride staining showed that FGF-2 gene transfer decreased infarct volume by 44% as compared with that in the vehicle-treated groups at 2 days after MCAO. The same tendency of gene transfer effects on infarct volume was confirmed at 35 days after MCAO with hematoxylin/eosin staining. Enzyme-linked immunosorbent assay revealed that FGF-2 concentration was increased significantly at 2 days after MCAO, not only in cerebrospinal fluid but also in cerebral substance in the lesioned and treated animals. These results suggested that FGF-2 gene transfer using these adenoviral vectors might be a useful modality for the treatment of occlusive cerebrovascular disease even after the onset of stroke.

15545912

Targeting anti-transferrin receptor antibody (OX26) and OX26-conjugated liposomes to brain capillary endothelial cells using in situ perfusion.

Brain capillary endothelial cells (BCECs) express transferrin receptors. The uptake of a potential drug vector (OX26, or anti-transferrin receptor antibody IgG2a) conjugated to polyethyleneglycol-coated liposomes by BCECs was studied using in situ perfusion in 18-day-old rats in which the uptake of OX26 is almost twice as high as in the adult rat. Using radio-labeling, the uptake of OX26 by BCECs after 15-minute perfusion was approximately 16 times higher than that of nonimmune IgG2a (Ni-IgG2a). OX26 and OX26-conjugated liposomes selectively distributed to BCECs, leaving choroid plexus epithelium, neurons, and glia unlabeled. Ni-IgG2a and unconjugated liposomes did not reveal any labeling of BCECs. The labeling of BCECs by OX26 was profoundly higher than that of transferrin. Perfusion with albumin for 15 minutes did not reveal any labeling of neurons or glia, thus confirming the integrity of the blood-brain barrier. The failure to label neurons and glia shows that OX26 and OX26-conjugated liposomes did not pass through BCECs. The expression of transferrin receptors by endothelial cells selective to the brain qualifies OX26 as a candidate for blood-to-endothelium transport. A specifically designed formulation of liposomes may allow for their degradation within BCECs, leading to subsequent transport of liposomal cargo further into the brain.

15545881

Post I-131 therapy scanning in patients with thyroid carcinoma metastases: an unnecessary cost or a relevant contribution?

In patients with elevated serum thyroglobulin (Tg) and a negative whole-body scan (WBS), posttherapy scanning can reveal metastases in many cases and is therefore recommended. In contrast, the routine use of posttherapy scanning is questioned. One hundred six patients with differentiated thyroid carcinoma had pre- and posttherapy scanning, with metastatic uptake on the diagnostic scan and were divided into 2 groups: 60 patients assessed on first ablation after thyroidectomy and 46 patients with tumor persistence or recurrence after initial ablative therapy. Data modifying the disease stage or treatment were considered to be clinically relevant. Posttherapy scanning on first ablation changed the disease stage in 8.3% of the patients and therapeutic approach in another 15%, and provided clinically relevant information for 26% of patients with 1 previous ablation. Even when excluding cases whose lesions were known by the time of the first postablative scan, the therapeutic approach was influenced by posttherapy scanning in 15.6% of the patients. Only 4 of 211 metastases detected on pretherapy WBS did not appear on postablative scans. Posttherapy scanning provides important information, even in patients whose pretherapy WBS is positive for metastases, with this approach being useful both during the first ablation and subsequent treatment.

15545880

Liver and vertebral uptake of Tc-99m macroaggregated albumin (MAA).

An unusual phenomenon during lung scintigraphy is presented. Besides visualization of the lungs, accumulation of Tc-99m macroaggregated albumin (MAA) was seen in a small part of the liver and in and around several thoracic vertebrae. Contrast-enhanced radiographic computed tomography revealed extensive collateral pathways, which were caused by a partially obstructed superior vena cava. Shunting of systemic venous blood flow through chest wall veins to the portal system was responsible for accumulation of MAA in the liver. Retrograde blood flow through dilated thoracic vertebral veins resulted in visualization of the bone marrow.

15545879

FDG PET in epithelioid hemangioendothelioma.

Epithelioid hemangioendothelioma (EH) is an uncommon tumor of endothelial origin. It can develop in any tissue and can be multicentric or metastatic. The usual course is a slow progression. Imaging techniques are generally useful in determining the extent of the disease. A case of EH involving bone marrow and mediastinum is described. We discuss the use of FDG PET scanning in EH, showing its use in detecting bone marrow involvement and determining the extent of the disease.

15545878

F-18 FDG PET/CT in acute respiratory distress syndrome: a case report.

F-18 FDG PET/CT has become a useful technique in the evaluation of pulmonary lesions. We present a case of markedly increased and diffuse pulmonary F-18 FDG activity in a patient with acute respiratory distress syndrome (ARDS). High rates of glucose utilization by the inflammatory cells involved in the pathogenesis of ARDS might explain the increased pulmonary F-18 FDG uptake we observed. In the proper clinical setting, ARDS should be considered in the differential diagnosis of patients with diffusely increased F-18 FDG activity in the lungs.

15545877

Diagnosis of orthopedic infection in clinical practice using Tc-99m sulesomab (antigranulocyte monoclonal antibody fragment Fab'2).

The aim of the study was to analyze the use of Tc-99m-labeled antigranulocyte monoclonal antibody fragment Fab'2 (SMab, Leukoscan) in the diagnosis of acute osteomyelitis and articular prosthesis infection. One hundred seventeen patients (118 studies) have been included, 92 women and 25 men. Thirty-seven had a suspicion of osteomyelitis and 81 with suspicion of infection of a hip (35 patients) or a knee (45 patients) prosthesis. The mean age was 64 years. A 3-phase bone scan and a SMab scan were obtained in all patients. Antigranulocyte scans were obtained within 3 and 8 hours postinjection of 20 mCi (740 MBq) of Tc-99m-labeled antibody. Diagnosis of infection was based on bone biopsy in 8 cases and on at least 2 positive cultures in the remaining cases. Infection was ruled out with negative cultures or 1-year patient follow up with negative C-reactive protein and normal erythrocyte sedimentation rate. Sensitivity, specificity, accuracy, and negative predictive value of Tc 99m-SMab scintigraphy were: 75%, 95%, 87%, and 92% for long bone osteomyelitis and 80%, 89%, 87%, and 91% for articular prosthesis infection, respectively. Positive predictive values were 83% and 63%, respectively. Tc-99m-antigranulocyte monoclonal antibody fragment Fab'2 scintigraphy seems to be a useful method in the diagnosis of osteoarticular infection.

15545869

Detection of subgroup B respiratory syncytial virus in the cerebrospinal fluid of a patient with respiratory syncytial virus pneumonia.

We report detection of subgroup B respiratory syncytial virus in cerebrospinal fluid from a 4-month-old infant, using a 1-step reverse transcription-polymerase chain reaction assay. The infant was diagnosed with bilateral pneumonia and had a febrile seizure. The patient recovered uneventfully after 9 days in the hospital.

15545868

Pasteurella multocida meningitis and cervical spine osteomyelitis in a neonate.

A 20-day-old male infant presented with fever, decreased alertness and quadriparesis as a result of Pasteurella multocida meningitis and C1-2 vertebral osteomyelitis. Although his household contained 2 pet cats, there was no history of bites, scratches or licks. We speculate that colonization of the nasopharynx was followed by contiguous spread to the retropharyngeal soft tissue, cervical vertebrae and meninges.

15545867

A cluster of early neonatal sepsis and pneumonia caused by nontypable Haemophilus influenzae.

Nine premature infants developed early onset sepsis and/or pneumonia with Haemophilus influenzae during a period of 53 months (January 2000 -May 2004). Their respiratory problems were pneumonia-like rather than classic respiratory distress syndrome. In 8 of the cases, the pathogen was a beta-lactamase-negative, nontypable H. influenzae. In the remaining case, the Haemophilus identified was type d. Before January 2000, no case of beta-lactamase-negative, nontypable H. influenzae sepsis or pneumonia had been recorded.

15545866

Fusarium solani endocarditis successfully treated with liposomal amphotericin B and voriconazole.

Fungal infections caused by Fusarium in the immunocompromised host are highly resistant to all antifungal agents. Fusarium endocarditis is a rare and usually fatal disease. We report an immunocompromised child who survived Fusarium solani endocarditis despite the in vitro resistance of the organism to all available antifungal agents.

15545865

Alternative, age- and viral load-related routes of nelfinavir resistance in human immunodeficiency virus type 1-infected children receiving highly active antiretroviral therapy.

To assess prevalence of nelfinavir resistance mutations in children receiving highly active antiretroviral therapy, sequencing of protease gene from plasma of 53 human immunodeficiency virus-infected children was performed. The prevalence of L90M was similar to that of D30N. There was a significant correlation with a higher viral load and lower age and the occurrence of L90M. These findings suggest differential molecular age- and viral load-related routes for nelfinavir resistance.

15545864

Detection of Helicobacter pylori in the stools of newborn infants.

To investigate the transmission route of Helicobacter pylori, stool specimens of 50 infants 3 days old were studied by a stool antigen immunoassay and polymerase chain reaction (PCR). By PCR, H. pylori DNA was detected in 15 neonates (30%). The stool antigen test was positive in only 1 neonate with a positive PCR. The detection rate of H. pylori DNA in neonates was significantly higher for those with mothers having urines positive for anti-H. pylori IgG antibody (60%) than for those mothers with negative urines (17%) (P < 0.01). A follow-up study was done 24 months later on 8 of the 15 infants with positive PCR results, including the infant with a positive stool antigen test. All infants were negative by both PCR and stool antigen test.

15545863

Live attenuated influenza vaccine induces cross-reactive antibody responses in children against an a/Fujian/411/2002-like H3N2 antigenic variant strain.

Serum antibody titers against the A/Panama/2007/99(H3N2) and A/Fujian/411/2002(H3N2)-like viruses were determined in children 6-35 months of age who received either 1 dose of the inactivated influenza vaccine or the live attenuated influenza vaccine containing the A/Panama strain. Results indicated that the live vaccine induced higher antibody responses than the inactivated vaccine against the A/Panama and A/Fujian-like viruses.

15545860

Vertical dengue infection: case reports and review.

Two vertical dengue infection cases are presented, and 15 others are reviewed. Twelve mothers had fever 0-9 (median, 2) days antepartum. The fevers of 17 neonates occurred at 1-11 (median, 4) days of life and lasted for 1-5 (median, 3) days. Neonatal thrombocytopenia was detected at 1-11 (median, 6) days of life and lasted for 3-18 (median, 6) days; the lowest platelet counts were 5-75 x 10(3) (median, 19 x 10 (3))/mm3. One neonate died.