Cellular retinoic acid-binding protein 2 is down-regulated in prostate cancer

Prostate cancer is among the most frequent tumours in industrialized nations and many questions remain open concerning the molecular events underlying its development and progression. In the present study we have combined cDNA array hybridization to laser-assisted microdissection (LAM) in order to investigate differences in gene expression between epithelial and stromal cells of prostate cancer and normal peripheral prostate tissue. Results have been verified for selected candidate genes by quantitative real-time RT-PCR. Using this approach and immunohistochemistry we could demonstrate a down-regulation of cellular retinoic acid binding protein 2 (CRABP2) mRNA and protein in carcinoma cells compared to normal glandular cells. CRABP2 is a main regulator of anti-carcinogenic activities of retinoic acid and may become a novel diagnostic marker and experimental therapeutic tool for prostate cancer. In addition, results of cDNA array hybridization suggest an up-regulation of 34 further genes and a down-regulation of 6 genes in cancer tissues compared to normal peripheral prostate tissues. Several of these genes have already been reported to be associated with carcinogenesis in organs such as the prostate.     

Radiologic evaluation of larynx cancer

The authors present the value of imaging for preoperative evaluation of structures that are not assessed or incompletely assessed on physical and endoscopic examination. Discussed are CT, MRI, and positron emission tomography-CT and the appropriate selection of each method to provide information, including the presence or absence of extent of disease to the pre-epiglottic and paraglottic spaces and the subglottis, cartilage invasion, extralaryngeal spread of disease, nodal metastasis, and tumor volume.     

Otologic and leptomeningeal involvements as presenting features in seronegative Wegener granulomatosis

Wegener granulomatosis is an immune-mediated, systemic vasculitis with unknown etiology that can be seen in almost any anatomical site. Positivity for antineutrophil cytoplasmic antigene, which is a serological marker, and presence of granulomatous vasculitis in histopathologic specimens from the lesions are accepted as diagnostic. A case of Wegener granulomatosis whose presenting symptoms and signs are related to otologic and meningeal involvement of the disease is reported. Apart from atypical presentation, histopathological and serological findings from this patient remained negative throughout the course of the disease, and the diagnosis was made on the basis of clinical and secondary laboratory findings. We herewith discuss this unusual case in the light of relevant literature.     

Imaging for functional endoscopic sinus surgery

Radiologic imaging is an essential part of the presurgical evaluation of patients with sinusitis and of the monitoring of difficult-to-treat,recurrent, and postsurgical disease. In patients with noninflammatory sinus pathology and those who "baffle" clinical diagnosis, ima-ging is extremely helpful in differentiating the various pathological entities and determining the extent of disease. Computerized tomography (CT), when deemed clinically necessary, is the current modality of choice to evaluate sinusitis. CT's ability to display bone,mucosa, and air makes it a perfect tool for imaging of the paranasal sinuses. The fine bony architecture of the nasal cavity and the para-nasal sinus drainage pathways are depicted accurately with CT examination.     

Platelet‐Derived CD154: Ultrastructural Localization and Clinical Correlation in Organ Transplantation

CD154 is an immunostimulatory ligand for CD40 that markedly influences alloimmunity. Its presence in platelets suggests that its release and subsequent immune effects are driven by trauma and thus could be relevant following organ transplantation. However, the release of platelet derived CD154 and its consequences have not been investigated in a clinical transplant setting. To better characterize the relationship between platelet activation and CD154 release, we investigated CD154 release by platelets obtained from normal individuals, and patients with two genetic defects that influence platelet granule development. Using these unique patient populations and immune‐electron microscopy, we confirmed that CD154 was an alpha granule and not a cell surface protein, and thereafter optimized the methods for its in vivo measurement in humans. We then investigated plasma CD154 levels in kidney and liver transplant recipients and found no evidence that CD154 levels fluctuated systemically as a result of kidney or liver transplant procedures. Paradoxically, we found that kidney transplant patients had significantly lower systemic CD154 levels during episodes of rejection. These data suggest that the immune effects of CD154 are likely mediated through local and not systemic mechanisms, and discourage the use of CD154 as a peripheral biomarker in organ transplantation.     

Hydroxycarbamide alters erythroid gene expression in children with sickle cell anaemia

Sickle cell anaemia (SCA) is a severe debilitating haematological disorder associated with a high degree of morbidity and mortality. The level of fetal haemoglobin (HbF) is well-recognized as a critical laboratory parameter: lower HbF is associated with a higher risk of vaso-occlusive complications, organ damage, and early death. Hydroxycarbamide treatment can induce HbF, improve laboratory parameters, and ameliorate clinical complications of SCA but its mechanisms of action remain incompletely defined and the HbF response is highly variable. To identify pathways of hydroxycarbamide activity, we performed microarray expression analyses of early reticulocyte RNA obtained from children with SCA enrolled in the HydroxyUrea Study of Long-term Effects (NCT00305175) and examined the effects of hydroxycarbamide exposure in vivo. Hydroxycarbamide affected a large number of erythroid genes, with significant decreases in the expression of genes involved in translation, ribosome assembly and chromosome organization, presumably reflecting the daily cytotoxic pulses of hydroxycarbamide. Hydroxycarbamide also affected expression of numerous genes associated with HbF including BCL11A, a key regulator of baseline HbF levels. Together, these data indicate that hydroxycarbamide treatment for SCA leads to substantial changes in erythroid gene expression, including BCL11A and other potential signalling pathways associated with HbF induction.     

Findings of the International Nosocomial Infection Control Consortium (INICC), Part II: Impact of a multidimensional strategy to reduce ventilator-associated pneumonia in neonatal intensive care units in 10 developing countries

Design.?Before-after prospective surveillance study to assess the efficacy of the International Nosocomial Infection Control Consortium (INICC) multidimensional infection control program to reduce the rate of occurrence of ventilator-associated pneumonia (VAP). Setting.?Neonatal intensive care units (NICUs) of INICC member hospitals from 15 cities in the following 10 developing countries: Argentina, Colombia, El Salvador, India, Mexico, Morocco, Peru, Philippines, Tunisia, and Turkey. Patients.?NICU inpatients. Methods.?VAP rates were determined during a first period of active surveillance without the implementation of the multidimensional approach (phase 1) to be then compared with VAP rates after implementation of the INICC multidimensional infection control program (phase 2), which included the following practices: a bundle of infection control interventions, education, outcome surveillance, process surveillance, feedback on VAP rates, and performance feedback on infection control practices. This study was conducted by infection control professionals who applied National Health Safety Network (NHSN) definitions for healthcare-associated infections and INICC surveillance methodology. Results.?During phase 1, we recorded 3,153 mechanical ventilation (MV)-days, and during phase 2, after the implementation of the bundle of interventions, we recorded 15,981 MV-days. The VAP rate was 17.8 cases per 1,000 MV-days during phase 1 and 12.0 cases per 1,000 MV-days during phase 2 (relative risk, 0.67 [95% confidence interval, 0.50-0.91]; [Formula: see text]), indicating a 33% reduction in VAP rate. Conclusions.?Our results demonstrate that an implementation of the INICC multidimensional infection control program was associated with a significant reduction in VAP rate in NICUs in developing countries.