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The organization and management of a pediatric dialysis unit is a multi-faceted endeavor which requires a unique mindset and perspective for services provided. The environment of care is not an outpatient clinic or a critical care ward, but rather a merging of the two. Providing safe and effective patient care that enhances the life experiences of patients, their families, and staff is the ultimate goal of care and treatment in the pediatric dialysis unit. This chapter will review operational management – culture, organization, regulatory, physical space, human factors influences, and staffing – as well as components of care implementation, modality selection, patient/family education, patient care plans, patient/family support, quality improvement, infection prevention, and safety.

The preferred vascular access for hemodialysis recipients is an arteriovenous fistula in the nondominant arm. Prior placement of a peripheral intravenous (PIV) catheter can lead to vascular injury and limit options for arteriovenous fistula creation, a particular problem for children, who may need hemodialysis for their entire lifetime. We instituted an initiative to increase the frequency of PIV catheter placement in the dominant arm for hospitalized pediatric patients with advanced chronic kidney disease (CKD).Quality improvement initiative.Children with CKD stage 3-5, receiving dialysis, and/or following kidney transplantation who were hospitalized at one children's hospital between September 2018 and August 2020.Retrospective data on PIV catheter location for patients from January 1 to June 30, 2017, served as baseline data. Quality improvement activities consisted of: 1) education of the multidisciplinary treatment team, patients, and parents regarding importance of vein preservation; 2) placement of individualized notes in the electronic medical record identifying the preferred arm for PIV catheter placement; 3) use of "restricted extremity" arm bands; and 4) vascular access team participation to minimize attempts for PIV catheter placement.Monthly compliance with placement of PIV catheters in dominant arms.Location of PIV catheter placements were determined monthly and used to create run charts describing compliance.At baseline and before institution of this initiative, 34 of 72 (47%) PIV catheters were placed in patients' dominant arms, with only 2 of 8 (25%) PIV catheters placed in the dominant arm for children aged5 years. After instituting the initiative, 345 of 371 (93%) PIV catheters were placed in the dominant arm of 93 children; in children aged5 years, 58 of 62 (94%) PIV catheters were placed in the dominant arm. Only 38 of 371 (10%) PIV catheters were placed in the antecubital vein.Single-center study.Education regarding the importance of vein preservation, along with implementation of a standardized process for identifying children for whom vein preservation is important, can help direct PIV catheter placement and potentially preserve vasculature in pediatric patients with CKD.

Objective Activated (CD38HLA-DR) PD-1 CD4 T cells are strongly associated with virus replication and disease progression in untreated HIV-1 infection, and viral persistence in individuals on ART. Few studies have examined cell-associated viral load (CAVL) in different activated CD4 T-cell populations to measure relative contributions to viral reservoirs. Design Longitudinal assessment of HIV-1 chronically infected Ugandans initiating ART, to investigate activated CD4 T-cell populations and their contribution to viral reservoirs. Methods We followed 32 HIV-1 chronically infected individuals from Kampala, Uganda, and determined their CD4 T-cell counts and viral load at baseline, 6, and 12 months after the initiation of ART. T-cell populations were sorted based on activation profiles and gag DNA was measured to determine CAVL within these populations. Soluble factors associated with inflammation were measured in plasma using a multiplexed platform. Results Concomitant with viral load decline and CD4 T-cell count rebound, the activated PD-1 CD4 T-cell population contracted upon initiation of ART. Baseline levels of activated PD-1 CD4 T cells correlated with plasma levels of IP-10 and TNFRII. Interestingly, a higher baseline level of activated PD-1 CD4 T cells was associated with poorer CD4 T-cell recovery after 12 months of ART. This population contributed significantly to the cell-associated HIV DNA load at baseline, whereas their contribution declined on ART, indicating high turnover. Conclusion Activated PD-1 CD4 T cells are predictors of poor immunologic recovery on ART and may represent a short-lived component of HIV-1 reservoirs.

HIV DNA is a marker of HIV persistence that predicts HIV progression and remission, but its kinetics in early acute HIV infection (AHI) is poorly understood. We longitudinally measured the frequency of peripheral blood mononuclear cells harboring total and integrated HIV DNA in 19 untreated and 71 treated AHI participants, for whom 50 were in the earliest Fiebig I/II (HIV IgM −) stage, that is ≤ 2 weeks from infection. Without antiretroviral therapy (ART), HIV DNA peaked at 2 weeks after enrollment, reaching a set-point 2 weeks later with little change thereafter. There was a marked divergence of HIV DNA values between the untreated and treated groups that occurred within the first 2 weeks of ART and increased with time. ART reduced total HIV DNA levels by 20-fold after 2 weeks and 316-fold after 3 years. Therefore, very early ART offers the opportunity to significantly reduce the frequency of cells harboring HIV DNA., Highlights • The HIV DNA set-point is established early in acute HIV infection. • Over three years without antiretroviral therapy, persons with acute HIV infection have total HIV DNA in peripheral blood mononuclear cells that is 300-fold and integrated HIV DNA that is 100-fold higher than those on treatment. • Early antiretroviral therapy provides an opportunity to markedly reduce proviral HIV DNA burden, HIV is difficult to cure because it infects long-lived cells in the body, also called “reservoirs”. Having a small HIV reservoir size may benefit health. We show that HIV DNA in peripheral blood cells, a marker of the HIV reservoir size, establishes a set-point level during the first 6 weeks of infection and changes little over time without HIV medications. However, if HIV medications are started early, the reservoir size declines rapidly, and is 300-fold lower than that seen in untreated persons. Currently the most effective way to significantly lower the HIV reservoir size is with very early treatment.

Resume Le terme tumeurs orbitaires recouvre un large spectre de pathologies benignes et malignes, touchant les composants orbitaires ou developpees a leur contact. Elles sont decouvertes de maniere fortuite ou recherchees dans le bilan d’une affection generale ou devant des signes orbitaires (exophtalmie, douleurs…). Le scanner, l’IRM et l’echographie avec Doppler couleur (EDC) jouent un role qui varie en fonction de la presentation clinique et de la pathologie recherchee. Cet article, fruit d’une longue experience dans un centre referent, n’a pas la volonte d’etre exhaustif. Nous avons prefere aborder ces tumeurs sous l’angle de leur presentation usuelle, en insistant sur les causes les plus frequentes et les tableaux radiocliniques qui permettent d’y penser (exophtalmie progressive ou brutale, enfant ou adulte, lesions des glandes lacrymales, lesions periorbitaires, enophtalmie). Nous detaillerons en particulier les atteintes musculaires (maladie de Basedow, tumeurs), les lesions vasculaires (hemangiome caverneux, varices, lymphangiome kystique), les lesions de l’enfant, les hematomes orbitaires. Nous proposons des protocoles d’exploration simples et des diagnostics differentiels utiles. Les references bibliographiques permettront a ceux qui veulent aller plus loin de completer leurs connaissances dans ce domaine passionnant.

The term orbital tumor covers a wide range of benign and malignant diseases affecting specific component of the orbit or developing in contact with them. They are found incidentally or may be investigated as part of the assessment of a systemic disorder or because of orbital signs (exophthalmos, pain, etc.). Computed tomography, MRI and Color Doppler Ultrasound (CDU), play a varying role depending on the clinical presentation and the disease being investigated. This article reflects long experience in a reference center but does not claim to be exhaustive. We have chosen to consider these tumors from the perspective of their usual presentation, emphasizing the most common causes and suggestive radiological and clinical presentations (progressive or sudden-onset exophthalmos, children or adults, lacrimal gland lesions, periorbital lesions and enophthalmos). We will describe in particular muscle involvement (thyrotoxicosis and tumors), vascular lesions (cavernous sinus hemangioma, orbital varix, cystic lymphangioma), childhood lesions and orbital hematomas. We offer straightforward useful protocols for simple investigation and differential diagnosis. Readers who wish to go further to extend their knowledge in this fascinating area can refer to the references in the bibliography.

RADIOLOGIE ET IMAGERIE MEDICALE : Musculosquelettique - Neurologique - Maxillofaciale - 31-680-C-10

Orbito-palpebral vascular pathology represents 10% of all the diseases of this area. The lesion may be discovered during a brain CT scan or MRI, or because it causes clinical symptoms such as orbital mass, visual or oculomotor alteration, pain, proptosis, or acute bleeding due to a complication of the lesion (hemorrhage, thrombosis). We present these lesions using an anatomical, clinical, imaging and therapeutic approach. We distinguish four different entities. Vascular tumors have common imaging characteristics (hypersignal on T2 sequence, contrast enhancement, abnormal vascularization well depicted with ultrasound and Doppler, and possible bleeding). The main lesions are cavernous hemangiomas, the most frequent lesion of that type during adulthood; infantile hemangiomas, the most frequent vascular tumor in children; and more seldomly, hemangioperitcytomas. True vascular malformations are divided according to their flow. Low flow lesions are venous (orbital varix), capillarovenous or lymphatic (lymphangioma). High flow malformations, more rare, are either arteriovenous or arterial malformations (aneurisms). Complex malformations include both low and high flow elements. Lesions leading to modifications of the orbito-palpebral blood flow are mainly due to cavernous sinus abnormalities, either direct carotid-cavernous fistula affecting young adults after severe head trauma, or dural fistula, more insidious, found in older adults. The last section is devoted to congenital syndromic vascular malformations (Sturge-Weber, Rendu-Olser…). This classification allows for a better understanding of these pathologies and their specific imaging features.

OBJECTIVES To better understand the gene expression patterns in tumor-associated stroma, laser-capture-microdissections from clinical specimens were analyzed by genome-wide-expression microarray technology. The epithelial-stromal interaction plays a critical role in prostate development, reactive changes, and tumorigenesis. Diverse microarray technologies have been used to characterize the molecular changes in prostate cancer. Even though these gene expression studies are compromised by the heterogeneity of the tumor, as well as by the difficulty associated with collecting appropriate counterparts to represent normal prostate cells, the gene array data from tumors have shown promising results. Currently, little is known about the tumor-associated stromal gene expression profile in prostate cancer. METHODS Matching benign and malignant epithelial cell-related stroma cells were subjected to microarray platforms. RESULTS The prostatatic stroma expressed several osteogenic molecules. In particular, one of the genes, OSF2, was upregulated in tumor-associated stroma compared with benign epithelial cell associated stroma, which was further validated by immunohistochemical examination. CONCLUSIONS These data show that the combination of laser capture dissection with computational enhancement of epithelial and stromal microarray data is a useful tool to assess gene expression changes in prostate cancer stroma.

The high prevalence of TMPRSS2-ERG rearrangements ( approximately 60%) in prostate cancer (CaP) leads to androgenic induction of the ETS-related gene (ERG) expression. However, the biological functions of ERG overexpression in CaP remain to be understood. ERG knockdown in TMPRSS2-ERG expressing CaP cells induced striking morphological changes and inhibited cell growth both in cell culture and SCID mice. Evaluation of the transcriptome and specific gene promoters in ERG siRNA-treated cells and investigation of gene expression signatures of human prostate tumors revealed ERG-mediated activation of C-MYC oncogene and the repression of prostate epithelial differentiation genes (PSA and SLC45A3/Prostein). Taken together, these data combining cell culture and animal models and human prostate tumors reveal that ERG overexpression in prostate tumor cells may contribute to the neoplastic process by activating C-MYC and by abrogating prostate epithelial differentiation as indicated by prostate epithelial specific markers.

To assess the role of colour Doppler flow imaging (CDFI) in the diagnosis and management of lacrimal fossa lesions. Institutional ethical committee approval was obtained. Fifty-one patients with 62 lacrimal fossa lesions were retrospectively included from 2003–2015. All patients underwent conventional ultrasonography and CDFI, with a qualitative and quantitative analysis of the vascularization. All patients had lacrimal gland surgery. Definitive diagnosis was based on pathological examination. The study included 47 non-epithelial lesions (NEL) and 15 epithelial lesions (EL), with 24 (39 %) malignant lesions and 38 (61 %) benign lesions. NEL were significantly more likely to present with septa (p

Transcription factors encoded by the ETS family of genes are central in integrating signals that regulate cell growth and differentiation, stress responses, and tumorigenesis. This study, analysing laser microdissected paired benign and malignant prostate epithelial cells from prostate cancer (CaP) patients (n=114; 228 specimen) by GeneChip and quantitative real-time RT-PCR, identifies ETS-related gene (ERG), a member of the ETS transcription factor family, as the most frequently overexpressed proto-oncogene in the transcriptome of malignant prostate epithelial cells. Combined quantitative expression analysis of ERG with two other genes commonly overexpressed in CaP, AMACR and DD3, revealed overexpression of at least one of these three genes in virtually all CaP specimen (54 of 55). Comprehensive evaluation of quantitative ERG1 expression with clinicopathological features also suggested that ERG1 expression level in prostate tumor cells relative to benign epithelial cells is indicator of disease-free survival after radical prostatectomy.

Evaluations of androgen regulated gene (ARG) repertoire provide new insights into the androgen receptor (AR) mediated signaling at the transcriptional level. Definition of ARGs having critical functions in the biology of normal and malignant prostate should aid in identifying new bio-markers and therapeutic targets for prostate cancer (CaP). Using Affymetrix HuGene FL oligonucleotide arrays, temporal expression profiles of ARGs in widely used hormone responsive LNCaP cells, were analysed by hierarchical clustering methods and functional classification. ARGs in response to different androgen concentrations showed temporal co-regulation of genes involved in specific biochemical pathways. This study focuses on our new observations of the coordinated androgen induction of genes (NDRG1, PDIR, HERPUD1, ORP150) involved in the endoplasmic reticulum (ER) stress response pathway. Expression analysis of the two selected ER stress responsive genes, NDRG1 and HERPUD1 in primary CaPs revealed a significantly reduced tumor associated expression. Intriguing linkage of the androgen signaling to ER stress responsive genes, a protective response to protein unfolding or protein damage resulting from cellular stress signals, suggests that androgens may induce such stress signals in CaP cells. Decreased CaP associated expression of two ER stress responsive genes also suggests that possible abrogation of this pathway in prostate tumorigenesis.

Exploiting the power of high-density gene arrays, the simultaneous expression analysis of 5600 cellular genes was executed on proliferating peripheral blood mononuclear cells (PBMCs) from three normal human donors that were infected in vitro with the T cell tropic laboratory strain of HIV-1, RF. Profiles of expressed genes were assessed at 1, 12, 24, 48, and 72 hr postinfection and compared with those of matched uninfected PBMCs. Viral infection resulted in an overall increase in the number of genes expressed with peaks of expression at 1, 12, and 48 hr postinfection. Functional clustering of genes whose expression level in infected PBMCs varied by 2-fold or greater from levels in the controls indicated that cellular activation markers, proteins associated with immune cell function and with transcription and translation, exhibited increased expression subsequent to viral infection. Gene families exhibiting a decline in gene expression were confined to the 72 hr time point and included genes associated with catabolism and a subset of genes involved with cell signaling and synthetic pathways. Self-organizing map (SOM) cluster analysis identified temporal patterns of coordinated gene expression in infected PBMCs including genes associated with the immune response, the cytoskeleton, and ribosomal subunit structural proteins required for protein synthesis.

HIV-1 envelope-specific CD4+ T cell lines were established simultaneously from PBMC and lymph node mononuclear cells of two HIV-1-infected patients. Three recombinant envelope proteins were used to establish the CD4+ T cell lines: gp160NL4-3, gp120IIIB, and gp120MN. Six T cell lines were established from the first patient, one for each Ag from each compartment, and four T cell lines, two per compartment, were established from the second patient. Each line was challenged with a panel of overlapping peptides spanning the entire gp120 sequence to define its T cell epitope specificity. The pattern of recognition for all the lines from any given patient was similar between compartments. Each patient had a different pattern of peptide recognition. TCR analysis showed a heterogeneous usage of Vbeta between lines with same peptide specificity and established from different compartments. These data suggest that the cellular immune response does not phenotypically vary between the peripheral blood and lymph node compartments, but demonstrates genotypic heterogeneity, showing possible redundancy of the immune response to HIV-1 gp160.

In HIV infection, CD4 responses to opportunistic pathogens such as Candida albicans are lost early, but CMV-specific CD4 response persists. Little is currently known about HIV infection of CD4 T cells of different pathogen/antigen specificities. CFSE-labeled PBMCs were stimulated with CMV, tetanus toxoid (TT), and C albicans antigens and subsequently exposed to HIV. HIV infection was monitored by intracellular p24 in CFSE(low) population. We found that although TT- and C albicans-specific CD4 T cells were permissive, CMV-specific CD4 T cells were highly resistant to both R5 and X4 HIV. Quantification of HIV DNA in CFSE(low) cells showed a reduction of strong-stop and full-length DNA in CMV-specific cells compared with TT- and C albicans-specific cells. β-Chemokine neutralization enhanced HIV infection in TT- and C albicans-specific cells, whereas HIV infection in CMV-specific cells remained low despite increased entry by β-chemokine neutralization, suggesting postentry HIV restriction by CMV-specific cells. Microarray analysis (Gene Expression Omnibus accession number: GSE42853) revealed distinct transcriptional profiles that involved selective up-regulation of comprehensive innate antiviral genes in CMV-specific cells, whereas TT- and C albicans-specific cells mainly up-regulated Th17 inflammatory response. Our data suggest a mechanism for the persistence of CMV-specific CD4 response and earlier loss of mucosal Th17-associated TT- and C albicans-specific CD4 response in AIDS.

Background Patterns of expressed genes in the peripheral blood mononuclear cells of persons who were receiving RTS,S/AS01 or RTS,S/AS02 malaria vaccine and were undergoing experimental challenge with mosquito-borne falciparum malaria were examined to identify markers associated with protection. Methods Thirty-nine vaccine recipients were assessed at study entry; on the day of the third vaccination; at 24 h, 72 h, and 2 weeks after vaccination; and on day 5 after challenge. Of 39 vaccine recipients, 13 were protected and 26 were not. Eleven vaccine recipients exhibited delayed onset of parasitemia. All infectivity control subjects developed parasitemia. Prediction analysis of microarrays identified genes corresponding with protection. Gene set enrichment analysis identified sets of genes associated with protection after the third vaccination and before challenge. Results After the third vaccination and before challenge, differential expression of genes in the immunoproteasome pathway distinguished protected and nonprotected persons. At 5 days after challenge, differential expression of genes associated with programmed cell death distinguished between subjects protected and not protected from malaria blood-stage infection. Conclusions The up-regulation of genes associated with the efficient processing of major histocompatibility complex peptides suggests a potential role of the vaccine in conferring major histocompatibility complex class 1-mediated protection and may represent a useful surrogate marker of vaccine efficacy without the need for challenge.

Patterns of expressed genes examined in cryopreserved peripheral blood mononuclear cells (PBMCs) of seropositive persons electing to stop antiretroviral therapy in the AIDS Clinical Trials Group Study A5170 were scrutinized to identify markers capable of predicting the likelihood of CD4+ T-cell depletion after cessation of antiretroviral therapy (ART). A5170 was a multicenter, 96-week, prospective study of HIV-infected patients with immunological preservation on ART who elected to interrupt therapy. Study entry required that the CD4 count was greater than 350 cells/mm(3) within 6 months of ART initiation. Median nadir CD4 count of enrollees was 436 cells/mm(3). Two cohorts, matched for clinical characteristics, were selected from A5170. Twenty-four patients with an absolute CD4 cell decline of less that 20% at week 24 (good outcome group) and 24 with a CD4 cell decline of20% (poor outcome group) were studied. The good outcome group had a decline in CD4+ Tcell count that was 50% less than the poor outcome group. Significance analysis of microarrays identified differential gene expression (DE) in the two groups in data obtained from Affymetrix Human FOCUS GeneChips. DE was significantly higher in the poor outcome group than in the good outcome group. Prediction analysis of microarrays (PAM-R) identified genes that classified persons as to progression with greater than 80% accuracy at therapy interruption (TI) as well as at 24 weeks after TI. Gene set enrichment analysis (GSEA) identified a set of genes in the Ras signaling pathway, associated with the downregulation of apoptosis, as significantly upregulated in the good outcome group at cessation of ART. These observations identify specific host cell processes associated with differential outcome in this cohort after TI.

Ten patients with orbital fractures and optic nerve trauma are reported. Fractures of the optic canal could be demonstrated by computed tomography in six cases and fractures of the orbital apex in another three cases. Surgical decompression of the optic canal was performed in seven cases. Computed tomography enhanced decision for surgery in cases of intraorbital haematoma with exophthalmus and narrowing of the canal by bony fragments, especially in those patients presenting with incomplete or progressive visual disturbance. Language: de

Es wird uber die physikalisch-chemischen Charakteristika von geformtem Aluminiumoxid auf Basis von Bohmit berichtet, der aus Natriumaluminatlosung mit Salpetersaure kontinuierlich gefallt, nach Filtrieren bei 110deg;C getrocknet und vor der Formgebung gemahlen wurde. In zweifacher Abhangigkeit von der Mahlintensitat und den Fallbedingungen werden die Veranderungen der Morphologie und Textur des Bohmithydrogels untersucht. Dem Dualismus in der Morphologie entsprechend erfolgt die Zerkleinerung der das gefallte Bohmithydrogel konstituierenden Teilchen zweistufig. Bei der Abriebfestigkeit des geformten Aluminiumoxids wird fur die Abhangigkeit von der Mahlintensitat eine Maximumbeziehung beobachtet. Preparation and Properties of Formed Aluminium Oxide. II. Influence of the Mechanical Comminution of Precipitated Boehmite Hydrogel on the Pore Structure and Abrasion Resistance of the Aluminium Oxide A report is given on the physical-chemical characteristics of formed aluminium oxide on the basis of boehmite which had been continuously precipitated with nitric acid from sodium aluminate solution, subsequently filtrated, dried at 110°C and ground prior to moulding. In double dependence on the grinding intensity (type of mill, grinding time) and on the precipitation conditions (pH value, temperature) the changes of the morphology and the texture of the boehmite hydrogel are investigated. According to the particles constituting the precipitated boehmite hydrogel is made in two stages. In dependence on the grinding intensity a maximum correlation is observed for the abrasion resistance.

Formalin-fixed paraffin-embedded (FFPE) prostate specimens are rich sources of molecular pathological information. However, FFPE-based microarray analysis of tissue samples may be hampered by the degradation and chemical alteration of RNA molecules due to the preservation procedure. In this report, we employed a probe analyses of Affymetrix oligonucleotide arrays at individual probe level to compensate for the potential loss of gene identifications associated with compromised mRNA quality in FFPE preparations. Furthermore, to increase the sample quality, we utilized laser capture microdissection of prostate tumor and benign epithelial cells. Remarkably, combination of these approaches recapitulated the common prostate cancer-associated gene expression alteration. Identification of prostate cancer associated-gene expression alterations such as AMACR, Kallikrein gene family and genes associated with androgen signaling such as PDEF and STEAP were consistent with previous findings reported in prostate cancer. These data suggest that combination of laser capture dissection with computational enhancement of microarray data may be useful for the assessment of gene expression changes in FFPE prostate cancer specimens.

Cancer cells gain selection advantages by the coordinated silencing of protective and by the activation of cell proliferation/cell survival genes. Evaluations of epithelial cell transcriptome of benign and malignant prostate glands by laser capture microdissection (LCM) identified Lactotransferrin (LTF) as the most significantly downregulated gene in prostate cancer (CaP) cells (p10(-6)). Frequent downregulation, significant association of LTF with PSA recurrence-free survival in CaP patients and the established anti-tumorigenic effects of LTF in experimental cancer models have provided impetus to evaluate LTF expression features and mechanisms in CaP specimens.LTF mRNA expression analysis was performed in LCM derived benign and malignant prostate epithelial cells by using Affymetrix GeneChip and QRT-PCR. LTF protein expression was assessed in tissue specimens by immunohistochemistry and in serum samples from CaP patients compared to healthy male control by using ELISA. Mechanism of LTF downregulation was analyzed in 5-azadeoxycytidine treated LNCaP and LAPC4 cells using MALDI-TOF MS. Proliferation and cell cycle analysis of CaP cells by FACS flow cytrometry was assessed in LNCaP cell cultures.Quantitative analysis of LTF mRNA expression in tumor cells revealed marked downregulation of LTF with significant associations to decreased PSA recurrence-free survival of CaP patients (n = 100, por = 0.0322). Moreover, low levels of LTF protein expression was observed in tumor tissues as well as in sera from CaP patients (por = 0.0001). LTF promoter downstream CpG island methylation was found in LNCaP and LAPC4 cells. Furthermore, replenishing of LTF by supplementing growth media with LTF protein resulted in reduced cell growth. Cell cycle analysis revealed robust increases in apoptosis in response to LTF treatment.This study highlights the potential for LTF in chemoprevention and to become a biologically relevant prognostic marker of CaP, suggesting that silencing of the LTF gene may be causally linked to CaP progression.

BACKGROUND A survey of gene expression in peripheral blood mononuclear cells from cynomolgus macaques infected with SIVmac251 was conducted to ascertain the impact of viral infection and successful antiretroviral (ARV) intervention on gene transcription at peak seroconversion, viral set point, and after treatment with 9-R 2 phosphonomethoxypropyl adenine and beta -2'3' dideoxy-3'-thia-5 fluorocytidine. METHODS Robust multichip average-normalized data sets generated on Affymetrix GeneChips were analyzed using Significance Analysis of Microarrays (SAM), to determine differential gene expression. Unsupervised learning algorithms and gene-ontology tools were used to elucidate hierarchical relationships and to define the function of significantly enriched biological categories of differentially regulated genes. Gene networks associated with immune response and inflammation impacted by ARV treatment were derived by use of Pathway Architect software. RESULTS Viral infection results in down-regulation of gene expression, which is greatest by the viral set point. Of the 3647 genes down-regulated at the viral set point, 1033 were up-regulated as the result of successful ARV treatment. There is significant overlap in the identity of these genes. CONCLUSIONS Intervention with successful ARV treatment in macaques infected with SIVmac251 results in the partial reversal of the down-regulated gene expression characteristic of early viral infection.

The assessment of viral load in the blood, tissues, and bodily fluids of persons infected with human immunodeficiency virus is fundamental to defining the stage of disease (1-3), the effect of antiviral treatments to abate disease (4, 5), disease progression (6-8), and propensity for the transmission of disease (9,10) as well. Now accepted as a surrogate for all of these features of HIV-1 disease, specific guidelines have been adopted for the use of viral load measures in the clinical management of the disease (11).

Using the Affymetrix HuGeneFL GeneChip, the global expression patterns of genes in the peripheral blood mononuclear cells (PBMCs) of rhesus macaques, infected with SIVmac251 and exhibiting rapid, typical, or slow rates of disease progression, were examined. Assessments of the change in gene expression (fold change), the temporal coordination of gene expression (self-organizing map analysis), and the similarities and significant differences in gene expression across the groups were performed on samples taken before infection and 3 and 7 weeks postinfection. An upregulation of the p27 interferon-inducible gene and of genes associated with cellular activation and immune response was observed in all three groups. Rapidly progressing animals exhibited a modest number of genes with a change in expression of 3-fold or greater, typically progressing animals exhibited the greatest number, and slowly progressing animals exhibited the fewest. Self-organizing map cluster analysis indicated that rapidly progressing animals exhibited the least coordinated gene expression over the three study time points, typically progressing animals exhibited a moderate degree, and animals with slow progression exhibited the most coordinated gene expression. Mann-Whitney U analysis indicated that differences in gene expression were most pronounced between the rapidly and slowly progressing groups and least pronounced between the rapidly and typically progressing animals. These observations elucidate distinct features of gene expression in animals with different rates of disease progression.

Chloroquine (CQ) is commonly used for treatment of malaria; however, its mode of action and the mechanism of resistance are still not fully understood. Better knowledge of CQ's mode of action may make it possible to identify new drugs that target similar pathways or to reverse existing resistant phenotypes. CQ has been shown to interact in both mammalian cells and Plasmodium spp. with a number of different pathways, including changes in vacuolar (or lysosomal) pH (9, 22, 39, 56), binding to DNA and RNA (3, 11, 41, 53), binding to heme and β-hematin in Plasmodium falciparum (1, 55; reviewed in reference 20). In the case of P. falciparum, CQ was an effective drug whose efficacy has been severely compromised by the emergence of drug-resistant parasites (8, 20). To analyze the mechanism of CQ action, we used transcriptional profiling in a model eukaryotic system, Saccharomyces cerevisiae. Differential transcriptional profiling using microarray analysis is based on detecting differences in expression of mRNAs in cells treated under different conditions. No information other than the genomic sequence and the open reading frame (ORF) predictions is necessary to assay mRNA expression. Such whole-genome analysis allows the determination of expression profiles without preselection of genes. For the experiments described here, we used the Affymetrix Yeast Chip YE6100, which is based on the oligonucleotide array method. We published the adaptation of this system to the wild-type S. cerevisiae strain YPH499 and derivatives previously (38). From this transcriptional profile analysis, we identified a number of genes whose products are involved in metal acquisition and metabolism that have increased mRNA levels during challenge with CQ. Increased expression of genes involved in iron (Fe) availability suggested that CQ toxicity might, in part, result from interference with iron uptake or metabolism. Although CQ has been demonstrated to disrupt iron trafficking in several cell types, including pathogenic yeasts (9, 22, 39), the observation of altered expression of iron metabolism genes in S. cerevisiae was surprising. In all these cases, CQ disrupts iron trafficking by increasing pH in lysosomes and preventing the release of iron from the carrier proteins. No iron carrier protein system has been identified in S. cerevisiae, and thus, this mechanism of CQ action is very unlikely in S. cerevisiae. Therefore, we initiated a more thorough investigation of genes involved in metal transport and availability, with particular interest in those involved with iron transport. In this study, we investigated the role of CQ in iron trafficking using a variety of approaches involving pharmacological, genetic, and biochemical techniques. One of the advantages of the S. cerevisiae system is the availability not only of the whole genome sequence but also of mutants deficient in specific genes or combinations of genes, thus allowing genetic dissection of pathways. For these experiments, we utilized yeast lacking the major iron uptake pathways (Fet3 and Fet4) as well as yeast deficient in SIT1, the major iron siderophore transporter that is induced under CQ pressure.

The performance of a silica chip-based resequencing method, the Affymetrix HIV PRT 440 assay (hereafter referred to as the Affymetrix assay), was evaluated on a panel of well-characterized nonclade B viral isolates and on isolates exhibiting length polymorphisms. Sequencing of human immunodeficiency virus type 1 (HIV-1) pol cDNAs from clades A, C, D, E, and F resulted in clade-specific regions of base-calling ambiguities in regions not known to be associated with resistance polymorphisms, as well as a small number of spurious resistance polymorphisms. The Affymetrix assay failed to detect the presence of additional serine codons distal to reverse transcriptase (RT) codon 68 that are associated with multinucleoside RT inhibitor resistance. The increasing prevalence of non-clade B HIV-1 strains in the United States and Europe and the identification of clinically relevant pol gene length polymorphisms will impact the generalizability of the Affymetrix assay, emphasizing the need to accommodate this expanding pool of pol genotypes in future assay versions.

This study examined the fate of axon terminals of one of the major sources of hypoglossal afferents, the spinal V nucleus, after XIIth nerve resection in adult Sprague-Dawley rats. In order to anterogradely label trigemino-hypoglossal projections, small quantities of horse radish peroxidase were pressure-injected into the ipsilateral dorsal (mandibular) portion of the spinal V nucleus two days before the animals were killed. Survival periods ranged from 5 to 33 days after nerve injury (dpo). Axonal injury produced relative changes in the association of labelled axon terminals to structures in the hypoglossal nucleus on the injured side. The proportion of horse radish peroxidase-labelled spinal V nucleus terminals with spherical vesicles (S-terminals) that were unapposed to hypoglossal somata or dendrites increased rapidly and reached maximal levels by 11 dpo. By contrast, the isolation of labelled terminals with pleomorphic/flattened vesicles (P/F-terminals) from postsynaptic structures began later, advanced at a slower rate and did not attain maximal levels until 20 dpo. S-terminals not apposed to neuronal cell parts increased at a rate of 2.2 times greater than unapposed P/F-terminals. In addition, at peak levels, the proportion of labelled S-terminals that were detached from somata and dendrites was significantly greater than unapposed, labelled P/F-terminals. Axotomy did not alter the caliber of the labelled axon terminals. However, by 29 days after axotomy, the average diameter of dendrites remaining in contact with SPVN terminals was 1/3 the diameter of dendrites of uninjured neurons apposed to labelled axon terminals. These findings provide the morphological correlate for physiological and pharmacological evidence that the effectiveness of excitatory and inhibitory synapses are down-regulated in a coordinated manner after hypoglossal nerve injury.

Twenty-two patients suffering from syringomyelia were treated operatively. Different shunt procedures were performed. Most often syringo-subarachnoid shunt (seven cases) and syringopleural shunt (eight cases) were used. Operative findings and complications were discussed. Postoperative improvement was observed in five patients, twelve were stable-unchanged, four showed further deterioration and one died. Operative treatment should be performed before gross neurological deficit is established.

The value of visual evoked potentials (VEP) in the control and therapy of processes afflicting the visual pathways is not clear. The response can be altered by a number of factors which hinder an accurate interpretation (Barnett et al. 1980; Blom et al. 1980; Dustman and Beck 1969; Harter and White 1968; Hawkes and Stow 1981; Sokol et al. 1981). Such factors include check size, luminescence, visual field, state of refraction, and pupillary diameter. Their influence on the various VEPs — pattern reversal (PREP) and flash-evoked potentials (FEP), half- or full-field stimulation — is well known but difficult to distinguish from other influences, e.g., from pathological influences on the visual response. Differing results have therefore been published concerning especially the validity of side differences in localizing the pathological process. Some authors recommend VEP as the most sensitive procedure in the control of tumor patients, even in preserving visual acuity during operation (Feinsod et al. 1976).

Depending on the surgical approach, involving either total or subtotal extirpation of pituitary tumors, the recurrence rates have varied from 10.4% (intra- and suprasellar tumors without parasellar enlargement) to 35% (large tumors with parasellar configuration) in patients examined by us (Rauhut et al. 1986). In the literature there are many reports of a high risk of tumor recurrence in cases of a primary supra- and parasellar tumor configuration with infiltration of the neighboring structures (Fahlbusch et al. 1978; Guiot 1978; Wilson 1984).

Objectifs Rechercher des criteres distinctifs entre les tumeurs epi-theliales (necessitant une exerese) et les lesions lymphoides (lymphomes, hyperplasies lymphoides, dacryoadenites) qui necessitent une biopsie suivie d’un traitement medical. Materiels et methodes Les echographies Doppler de 33 patients (avec 36 lesions) ont ete revues et analysees de facon prospective. Tous les patients ont ensuite beneficie d’une intervention chirurgicale ou d’une biopsie suivie d’un traitement. Les quelques lesions non epitheliales (ex : metastase) avaient ete pealablement exclues de la serie. Resultats Vingt-trois lesions lymphoides etaient retrouvees : elles apparaissaient le plus souvent hypoechogenes (87 %) et hypervascularisees sous forme de septas conjonctivo-vasculaires (57 %). Les lymphomes vrais presentaient ces caracteristiques dans 80 % (hypoechogeneicite) et 100 % des cas (hypervascularisation avec septas). L’index de resistance etait bas (0,64 en moyenne). Les tumeurs epitheliales (13 cas) etaient plutot echogenes ou heterogenes (69 %), faiblement vascularisees (77 %) de facon anarchique (sans jamais de septas), avec index de resistance eleve (0,84 en moyenne). Conclusion Les donnees de l’echographie et du Doppler permettent de separer de facon fiable les lesions epitheliales des lesions lymphoides.

The odontogen brain abscess is a relatively rare, but very serious complication of an infection of the teeth. Frequently the bacteria found by aspiration of the brain abscess are the only indication of a dental focus. The diagnostic problems in confirming a covert dental infection as the cause of the brain abscess are illustrated.

Ten patients with orbital fractures and optic nerve trauma are reported. Fractures of the optic canal could be demonstrated by computed tomography in six cases and fractures of the orbital apex in another three cases. Surgical decompression of the optic canal was performed in seven cases. Computed tomography enhanced decision for surgery in cases of intraorbital haematoma with exophthalmus and narrowing of the canal by bony fragments, especially in those patients presenting with incomplete or progressive visual disturbance.

This paper deals with the histological alterations found in the ischiadic nerve of the domestic fowl after compression with aneurysm clips. The corresponding clinical and electrophysiological findings are described elsewhere in this volume (Nau et al.).