[Antenatal Prediction of Pulmonary Hypoplasia and Intrauterine Treatment by Endoscopic Fetal Tracheal Occlusion in Severe Isolated Congenital Diaphragmatic Hernia]

Bulletin De L'Académie Nationale De Médecine. Nov, 2008  |  Pubmed ID: 19445375

Congenital diaphragmatic hernia (CDH) affects one in 2500 to 5000 births and can be detected in utero by means of ultrasound screening Associated structural problems aggravate the prognosis. The survival rate is 70% or more for cases managed in tertiary care centers. The commonest causes of neonatal death in this setting are pulmonary hypoplasia and pulmonary hypertension. Prenatal imaging findings can now accurately predict postnatal outcome, based mainly on ultrasound determination of the lung-to-head ratio and liver position. This information can be used to counsel patients. In severe cases, prenatal intervention can reverse pulmonary hypoplasia. We review current data on prenatal prediction of neonatal survival. We also discuss experimental and clinical data on the benefits of fetal tracheal occlusion. The TOTAL trial (Tracheal Occlusion To Accelerate Lung growth) is currently ongoing in Europe.

Biochemical Control and Toxicity After Intensity-modulated Radiation Therapy for Prostate Cancer

Technology in Cancer Research & Treatment. Jun, 2009  |  Pubmed ID: 19445537

Intensity modulated radiation therapy (IMRT) has achieved widespread use for prostate cancer; however, in relation to this use, outcomes studies are still relatively sparse. We report a single-institutional experience in outcomes analysis with the use of IMRT for the primary management of prostate cancer. One hundred thirty consecutive patients with adenocarcinoma of the prostate were treated at a single institution using IMRT with curative intent. Thirty-six (28%) patients were classified as low-risk, 69 (53%) as intermediate-risk, and 25 (19%) as high-risk. The median dose prescription was 76 Gy to the planning target volume. Sixty-five (50%) patients received androgen deprivation therapy (ADT) for a median 4 months, starting 2 months prior to IMRT. Biochemical failure was defined as PSA < post-treatment nadir+2. Gastrointestinal (GI) and Genitourinary (GU) toxicity were defined by RTOG criteria. Median follow-up was 53 months. By NCCN risk category, 4-year biochemical control was 97%, 94%, and 87% for low, intermediate, and high-risk patients, respectively. Among disease factors, multivariable analysis demonstrated the strongest association between biochemical control and Gleason score < or =6 (p=0.0371). Therapy was well tolerated with no Grade 4 toxicity and limited grade 3 GI or GU toxicity. Acute Grade 3+ GI and GU toxicity rates were 0% and 2%, and maximal late Grade 3+ GI and GU toxicity rates were 5% and 6%, respectively. Late rectal toxicity was associated with higher volumes of RT to the rectum. By last follow-up late Grade 3+ toxicity was 2% for both GI and GU systems. In conclusion, patients treated with IMRT for prostate cancer have excellent rates of biochemical control and low rates of severe toxicity of treatment.

Regulated Transcription of the Saccharomyces Cerevisiae Phosphatidylinositol Biosynthetic Gene, PIS1, Yields Pleiotropic Effects on Phospholipid Synthesis

FEMS Yeast Research. Jun, 2009  |  Pubmed ID: 19456874

Phosphatidylinositol is an important membrane lipid in Saccharomyces cerevisiae and other eukaryotes. Phosphatidylinositol and its metabolites (phosphoinositides, inositol polyphosphates, etc.) affect many cellular processes with implications in human diseases. Phosphatidylinositol synthesis in S. cerevisiae requires the essential PIS1 gene. Recent studies reveal that PIS1 expression is regulated at the level of transcription in response to carbon source, oxygen, and zinc. However, the consequence of this regulation on phosphatidylinositol levels and functions has not been thoroughly studied. To investigate this, we created a strain with a galactose-inducible GAL1-PIS1 gene. In this strain, the amount of phosphatidylinositol correlated with PIS1 expression but did not exceed c. 25% of the total phospholipid composition. Interestingly, we found that 4% phosphatidylinositol was sufficient for cell growth. We also found that reduced PIS1 expression yielded derepression of two phospholipid biosynthetic genes (INO1 and CHO1) and the INO2 regulatory gene. Consistent with this derepression, reduced PIS1 expression also yielded an overproduction of inositol (Opi(-)) phenotype. The effect on transcription of the INO1, CHO1, and INO2 genes is consistent with the accepted model that phosphatidic acid (PA) is the signal for regulation of these genes because decreased phosphatidylinositol synthesis would affect PA levels.

Lymphadenectomy for Patients with Cervical Cancer: is It of Value?

Journal of Surgical Oncology. Oct, 2009  |  Pubmed ID: 19760670

Discovery of positive lymph nodes (LNs) in patients with cervix cancer is important prognostically, may direct adjuvant therapy, and may have therapeutic benefit. The purpose of this Surveillance Epidemiology and End Results (SEER) analysis was to assess the value of lymphadenectomy (LND) in patients with cervical cancer.

Synthesis and Photophysics of Core-substituted Naphthalene Diimides: Fluorophores for Single Molecule Applications

Chemistry, an Asian Journal. Oct, 2009  |  Pubmed ID: 19760701

The synthesis and photophysics of two new aminopropenyl naphthalene diimide (SANDI) dyes are reported. A general and convenient method for the synthesis of the precursor mono-, di-, and tetrabrominated 1,4,5,8-naphthalene tetracarboxylic dianhydrides is described. The two core-substituted SANDIs exhibit many of the photophysical properties required for fluorescence labeling applications including high photostability and high fluorescence quantum yields (>0.5) in the visible region of the spectrum. The emission wavelength is sensitive to the number of substituents on the NDI core, and the fluorescence decay times are in the range of approximately 8-12 ns for both compounds in the solvents investigated. Preliminary fluorescence emission data from single molecules of the compounds embedded in poly(methyl methacrylate) films are also reported and show that single molecules have very low yields of photobleaching, particularly the di-substituted system. Furthermore, only a small proportion (<10 %) of the single molecules studied display fluorescence intermittencies or "blinks" in their photon trajectory. The compounds appear to be excellent candidates for applications at the single molecule level, for example, as FRET labels.

A Simple and Efficient Agrobacterium-mediated Procedure for Transformation of Tomato

Journal of Biosciences. Sep, 2009  |  Pubmed ID: 19805904

We describe a highly efficient and reproducible Agrobacterium-mediated transformation protocol applicable to several varieties of tomato (Solanum lycopersicum, earlier known as Lycopersicum esculentum). Conditions such as co-cultivation period, bacterial concentration, concentration of benzyl amino purine (BAP), zeatin and indole acetic acid (IAA) were optimized. Co-cultivation of explants with a bacterial concentration of 108 cells/ml for three days on 2 mg/l BAP, followed by regeneration on a medium containing 1 mg/ml zeatin resulted in a transformation frequency of 41.4%. Transformation of tomato plants was confirmed by Southern blot analysis and beta-glucuronidase (GUS) assay. The protocol developed showed very high efficiency of transformation for tomato varieties Pusa Ruby, Arka Vikas and Sioux. The optimized transformation procedure is simple, efficient and does not require tobacco, Petunia, tomato suspension feeder layer or acetosyringone.

Diffusion-weighted MRI in Lungs of Normal Fetuses and Those with Congenital Diaphragmatic Hernia

Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. Dec, 2009  |  Pubmed ID: 19866446

To prospectively determine apparent diffusion coefficient (ADC) values of normally developing fetal lungs over gestation, as obtained by diffusion-weighted (DW) magnetic resonance imaging (MRI) and to investigate its potential application in fetuses with congenital diaphragmatic hernia (CDH).

Risk of Extended Viral Resistance in Human Immunodeficiency Virus-1-infected Mozambican Children After First-line Treatment Failure

The Pediatric Infectious Disease Journal. Dec, 2009  |  Pubmed ID: 19907359

Resistant virus may be selected by sub-optimal control of HIV-1 replication during antiretroviral treatment. The incidence and profile of resistance in children receiving World Health Organization-recommended treatment remains to be evaluated on a large scale.

A Multi-institutional Acute Gastrointestinal Toxicity Analysis of Anal Cancer Patients Treated with Concurrent Intensity-modulated Radiation Therapy (IMRT) and Chemotherapy

Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology. Nov, 2009  |  Pubmed ID: 19717198

Using previous dosimetric analysis methods, we identified the volume of bowel receiving 30 Gy (V(30)) correlated with acute gastrointestinal (GI) toxicity in anal cancer patients treated with intensity-modulated radiation therapy and concurrent chemotherapy. For V(30)>450 cc and < or =450 cc, acute GI toxicity was 33% and 8%, respectively (p=0.003).

Loss of Correlation Between HIV Viral Load and CD4+ T-cell Counts in HIV/HTLV-1 Co-infection in Treatment Naive Mozambican Patients

International Journal of STD & AIDS. Dec, 2009  |  Pubmed ID: 19948902

Seven hundred and four HIV-1/2-positive, antiretroviral therapy (ART) naïve patients were screened for HTLV-1 infection. Antibodies to HTLV-1 were found in 32/704 (4.5%) of the patients. Each co-infected individual was matched with two HIV mono-infected patients according to World Health Organization clinical stage, age +/-5 years and gender. Key clinical and laboratory characteristics were compared between the two groups. Mono-infected and co-infected patients displayed similar clinical characteristics. However, co-infected patients had higher absolute CD4+ T-cell counts (P = 0.001), higher percentage CD4+ T-cell counts (P < 0.001) and higher CD4/CD8 ratios (P < 0.001). Although HIV plasma RNA viral loads were inversely correlated with CD4+ T-cell-counts in mono-infected patients (P < 0.0001), a correlation was not found in co-infected individuals (P = 0.11). Patients with untreated HIV and HTLV-1 co-infection show a dissociation between immunological and HIV virological markers. Current recommendations for initiating ART and chemoprophylaxis against opportunistic infections in resource-poor settings rely on more readily available CD4+ T-cell counts without viral load parameters. These guidelines are not appropriate for co-infected individuals in whom high CD4+ T-cell counts persist despite high HIV viral load states. Thus, for co-infected patients, even in resource-poor settings, HIV viral loads are likely to contribute information crucial for the appropriate timing of ART introduction.

Co-infection by Human Immunodeficiency Virus Type 1 (HIV-1) and Human T Cell Leukemia Virus Type 1 (HTLV-1): Does Immune Activation Lead to a Faster Progression to AIDS?

BMC Infectious Diseases. 2009  |  Pubmed ID: 20028500

Recent data have shown that HTLV-1 is prevalent among HIV positive patients in Mozambique, although the impact of HTLV-1 infection on HIV disease progression remains controversial. Our aim was to determine the phenotypic profile of T lymphocytes subsets among Mozambican patients co-infected by HIV and HTLV-1.

Mitochondrial Reactive Oxygen Species Generation in Obese Non-diabetic and Type 2 Diabetic Participants

Diabetologia. Apr, 2009  |  Pubmed ID: 19183935

The aim of this study was to measure mitochondrial reactive oxygen species (ROS) production directly from skeletal muscle biopsies obtained from obese insulin-resistant non-diabetic and type 2 diabetic participants.

Dose-escalated Radiation Therapy for Intermediate-risk Prostate Cancer: Patient Selection for Androgen Deprivation Therapy Using Percentage of Positive Cores

Cancer. Apr, 2009  |  Pubmed ID: 19208426

Randomized trials supported the use of androgen deprivation therapy (ADT) with radiation therapy (RT) for intermediate-risk prostate cancer. However, the value of concurrent ADT was less certain with dose-escalated RT. Better methods of stratifying patients in this risk group may help select patients who are most likely to benefit.

Serologic and Molecular Typing of Human T-lymphotropic Virus Among Blood Donors in Maputo City, Mozambique

Transfusion. Jun, 2009  |  Pubmed ID: 19222818

Screening for human T-lymphotropic virus-1/2 (HTLV-1/2) infection is not performed in blood banks in Mozambique. The aim was to determine the prevalence of HTLV-1/2 among blood donors of the Maputo Central Hospital Blood Bank and measure the coinfection rate of HTLV-1/2 with human immunodeficiency virus (HIV), hepatitis B virus (HBV), and syphilis.

Kinetic Characterization of Sulfasalazine Transport by Human ATP-binding Cassette G2

Biological & Pharmaceutical Bulletin. Mar, 2009  |  Pubmed ID: 19252303

The pharmacokinetics of sulfasalazine, an anti-inflammatory drug is influenced by ATP-binding cassette G2 (ABCG2) (breast cancer resistance protein (BCRP), mitoxantrone resistance protein (MXR)) both in vitro and clinically. Due to its low passive permeability, the intracellular concentration of sulfasalazine is dependent on uptake transporters, rendering the characterization of transporter specific interactions in cell based experimental systems difficult. Applying membrane assays a detailed kinetic analysis of sulfasalazine ABCG2 interaction was conducted and Km values of 0.70 +/- 0.03 microM and 0.66 +/- 0.08 microM were obtained at pH 7.0 and pH 5.5, respectively.

Mutational Uncoupling of the Role of Sus1 in Nuclear Pore Complex Targeting of an MRNA Export Complex and Histone H2B Deubiquitination

The Journal of Biological Chemistry. May, 2009  |  Pubmed ID: 19269973

Sus1 is an evolutionary conserved protein that functions both in transcription and mRNA export and has been proposed to contribute to coupling these processes in yeast. Sus1 mediates its different roles as a component of both the histone H2B deubiquitinating module (Sus1-Sgf11-Ubp8-Sgf73) of the SAGA (Spt-Ada-Gcn5 acetyltransferase) transcriptional co-activator and the mRNA export complex, TREX-2 (Sus1-Sac3-Thp1-Cdc31). We have dissected the different functions of Sus1 with respect to its partitioning in transcription and export complexes using a mutational approach. Here we show that the sus1-10 (E18A, S19A, and G20A) and sus1-12 (V73A and D75A) alleles of Sus1 can be dissociated from TREX-2 while leaving its interaction with SAGA largely intact. Conversely, the binding to both TREX-2 and SAGA was impaired in the sus1-11 allele (G37A and W38A), in which two highly conserved residues were mutated. In vitro experiments demonstrated that dissociation of mutant Sus1 from its partners is caused by a reduced affinity toward the TREX-2 subunit, Sac3, and the SAGA factor, Sgf11, respectively. Consistent with the biochemical data, these sus1 mutant alleles showed differential genetic relationships with SAGA and mRNA export mutants. In vivo, all three sus1 mutants were impaired in targeting TREX-2 (i.e. Sac3) to the nuclear pore complexes and exhibited nuclear mRNA export defects. This study has implications for how Sus1, in combination with distinct interaction partners, can regulate diverse aspects of gene expression.

Successive Radiations, Not Stasis, in the South American Primate Fauna

Proceedings of the National Academy of Sciences of the United States of America. Apr, 2009  |  Pubmed ID: 19321426

The earliest Neotropical primate fossils complete enough for taxonomic assessment, Dolichocebus, Tremacebus, and Chilecebus, date to approximately 20 Ma. These have been interpreted as either closely related to extant forms or as extinct stem lineages. The former hypothesis of morphological stasis requires most living platyrrhine genera to have diverged before 20 Ma. To test this hypothesis, we collected new complete mitochondrial genomes from Aotus lemurinus, Saimiri sciureus, Saguinus oedipus, Ateles belzebuth, and Callicebus donacophilus. We combined these with published sequences from Cebus albifrons and other primates to infer the mitochondrial phylogeny. We found support for a cebid/atelid clade to the exclusion of the pitheciids. Then, using Bayesian methods and well-supported fossil calibration constraints, we estimated that the platyrrhine most recent common ancestor (MRCA) dates to 19.5 Ma, with all major lineages diverging by 14.3 Ma. Next, we estimated catarrhine divergence dates on the basis of platyrrhine divergence scenarios and found that only a platyrrhine MRCA less than 21 Ma is concordant with the catarrhine fossil record. Finally, we calculated that 33% more change in the rate of evolution is required for platyrrhine divergences consistent with the morphologic stasis hypothesis than for a more recent radiation. We conclude that Dolichocebus, Tremacebus, and Chilecebus are likely too old to be crown platyrrhines, suggesting they were part of an extinct early radiation. We note that the crown platyrrhine radiation was concomitant with the radiation of 2 South American xenarthran lineages and follows a global temperature peak and tectonic activity in the Andes.

Sus1, Cdc31, and the Sac3 CID Region Form a Conserved Interaction Platform That Promotes Nuclear Pore Association and MRNA Export

Molecular Cell. Mar, 2009  |  Pubmed ID: 19328066

The yeast Sac3:Cdc31:Sus1:Thp1 (TREX-2) complex facilitates the repositioning and association of actively transcribing genes with nuclear pores (NPCs)-"gene gating"-that is central to integrating transcription, processing, and mRNA nuclear export. We present here the crystal structure of Sus1 and Cdc31 bound to a central region of Sac3 (the CID domain) that is crucial for its function. Sac3(CID) forms a long, gently undulating alpha helix around which one Cdc31 and two Sus1 chains are wrapped. Sus1 has an articulated helical hairpin fold that facilitates its wrapping around Sac3. In vivo studies using engineered mutations that selectively disrupted binding of individual chains to Sac3 indicated that Sus1 and Cdc31 function synergistically to promote NPC association of TREX-2 and mRNA nuclear export. These data indicate Sac3(CID) provides a scaffold within TREX-2 to integrate interactions between protein complexes to facilitate the coupling of transcription and mRNA export during gene expression.

Laparoscopic Surgery Was More Effective Than Medical Management for GORD Disease

Evidence-based Medicine. Apr, 2009  |  Pubmed ID: 19332610

New Frontiers in the Therapy of Tuberculosis: Fighting with the Global Menace

Mini Reviews in Medicinal Chemistry. Apr, 2009  |  Pubmed ID: 19356120

Tuberculosis has remained an enemy of humankind since its inception. It has affected all facets of human life and remained leading cause of mortality and morbidity despite of availability of effective chemotherapy and BCG vaccine in 21st century. This has exposed the frailties of the current drug armamentarium. No new drug is available acting through novel mechanism of action for last 40 years. This has culminated into resistant strain of TB, MDR-TB and XDR-TB. Concomitant occurrence of TB and HIV presents a lethal combination. The availability of the M. tuberculosis genome sequence and mycobacterial genetic tools, such as transposon mutagenesis, gene knockout and gene transfer, greatly facilitate target identification. This review provides a comprehensive literature compilation on the present research paradigm of anti-TB drug discovery including advances in the new structural classes analogs reported in last decade.

Prognostic Relevance of 6q Deletion in Waldenström's Macroglobulinemia: a Multicenter Study

Clinical Lymphoma & Myeloma. Mar, 2009  |  Pubmed ID: 19362968

The deletion of the long arm of chromosome 6 is the most common cytogenetic abnormality in Waldenstrom's macroglobulinemia (WM), but its prognostic significance is unclear. We investigated 77 patients with WM by interphase cytoplasmic immunoglobulin M fluorescence in situ hybridization (cIgM-FISH) and correlated the 6q status with the patients' clinical features and survival. cIg-FISH detected hemizygous 6q deletions in 32 patients (41.6%). The 6q deletions were correlated with higher C-reactive protein levels (P = .02) and CD23 expression (P = .03) but not with other clinical laboratory features of WM. There was no significant difference in time to the initial treatment between deleted and non-deleted groups (median, 5.6 months vs. 2.6 months; P = .46), or overall survivals in patients with and without del (6q) (163 months vs. not reached; P = .83). Our study confirms that the 6q deletion is a frequent event, but it does not appear to affect the clinical outcome of WM.

The Effect of Maternal Betamethasone and Fetal Tracheal Occlusion on Pulmonary Vascular Morphometry in Fetal Rabbits with Surgically Induced Diaphragmatic Hernia: a Placebo Controlled Morphologic Study

Prenatal Diagnosis. Jul, 2009  |  Pubmed ID: 19365875

We studied the vascular effects of betamethasone (BM) and/or tracheal occlusion (TO) in fetal rabbits with surgically induced congenital diaphragmatic hernia (CDH).

Case Study of Anti-1-amino-3-F-18 Fluorocyclobutane-1-carboxylic Acid (anti-[F-18] FACBC) to Guide Prostate Cancer Radiotherapy Target Design

Clinical Nuclear Medicine. May, 2009  |  Pubmed ID: 19387202

Anti-1-amino-3-F-18 fluorocyclobutane-1-carboxylic acid (FACBC) is a novel radiotracer, which has shown some promise for use with positron emission tomography (PET)/computed tomography (CT) for visualizing prostate cancer. Here we describe a case of a prostate cancer patient who underwent radiation treatment and had an FACBC scan obtained as part of a pilot study.

Mineral Content of Complementary Foods

Indian Journal of Pediatrics. Jan, 2009  |  Pubmed ID: 19391001

To document mineral contents iron, zinc, calcium, energy contents and nutrient densities in complementary foods commonly given to young urban slum children.

A 220-nucleotide Deletion of the Intronic Enhancer Reveals an Epigenetic Hierarchy in Immunoglobulin Heavy Chain Locus Activation

The Journal of Experimental Medicine. May, 2009  |  Pubmed ID: 19414554

A tissue-specific transcriptional enhancer, Emu, has been implicated in developmentally regulated recombination and transcription of the immunoglobulin heavy chain (IgH) gene locus. We demonstrate that deleting 220 nucleotides that constitute the core Emu results in partially active locus, characterized by reduced histone acetylation, chromatin remodeling, transcription, and recombination, whereas other hallmarks of tissue-specific locus activation, such as loss of H3K9 dimethylation or gain of H3K4 dimethylation, are less affected. These observations define Emu-independent and Emu-dependent phases of locus activation that reveal an unappreciated epigenetic hierarchy in tissue-specific gene expression.

Design, Synthesis and Antimycobacterial Activity of Some Novel Imidazo[1,2-c]pyrimidines

European Journal of Medicinal Chemistry. Oct, 2009  |  Pubmed ID: 19423196

Tuberculosis, due to its relentless nature, is now a major public health threat. The concomitant resurgence of TB with the MDR- or XDR-TB and HIV/AIDS pandemic has exposed the frailties of the current drug armatorium. Based on isosteric replacement and good 3D structural similarity between PA-824, a novel antimycobacterial agent undergoing clinical trials, and imidazo[1,2-c]pyrimidines, we have designed novel imidazo[1,2-c]pyrimidines. The designed molecules were synthesized by nucleophilic displacement of chloro group of various substituted 4-chloropyrimidines by ethanolamine followed by cyclisation of these 4-(2-hydroxyethyl)aminopyrimidines to imidazo[1,2-c]pyrimidines in good yield. All the compounds were screened for their antimycobacterial activity on Mycobacterium tuberculosis H37Rv strain by 1% proportion method. Some of the synthesized compounds exhibited potent antimycobacterial activity with MIC values in the range of 2-20 microg/mL.

Costs of Neonatal Care for Low-birthweight Babies in English Hospitals

Acta Paediatrica (Oslo, Norway : 1992). Jul, 2009  |  Pubmed ID: 19432825

To estimate mean costs of neonatal care for babies with birthweights

Pelvic Shape and Prostate Motion: Implications for Target Volume Design and Analysis of Acute Toxicity

American Journal of Clinical Oncology. Jun, 2009  |  Pubmed ID: 19433967

To study the impact of pelvic shape on prostate motion and the implications for radiotherapy target design and treatment outcomes.

Molecular Mechanisms of Mechanosensing in Muscle Development

Developmental Dynamics : an Official Publication of the American Association of Anatomists. Jun, 2009  |  Pubmed ID: 19441055

Mechanical forces are crucial to muscle development and function, but the mechanisms by which forces are sensed and transduced remain elusive. Evidence implicates the sarcolemmal lattice of integrin adhesion and the Z-disk components of the contractile machinery in such processes. These mechanosensory devices report changes in force to other cellular compartments by self-remodeling. Here we explore how their structural and functional properties integrate to regulate muscle development and maintenance. Developmental Dynamics 238:1526-1534, 2009. (c) 2009 Wiley-Liss, Inc.

Evidence and Patterns in Lung Response After Fetal Tracheal Occlusion: Clinical Controlled Study

Radiology. Aug, 2009  |  Pubmed ID: 19508989

To prospectively assess changes in lung volume in fetuses with isolated severe congenital diaphragmatic hernia (CDH) after fetoscopic endoluminal tracheal occlusion (FETO) compared with those in fetuses with CDH of variable severity who were expectantly managed.

Performance Evaluation of Calypso 4D Localization and Kilovoltage Image Guidance Systems for Interfraction Motion Management of Prostate Patients

TheScientificWorldJournal. 2009  |  Pubmed ID: 19526184

Prostate cancer represents a model site for advances in understanding inter- and intrafraction motion for radiotherapy. In this study, we examined the correlation of the electromagnetic transponder system/Calypso 4D Localization System with conventional on-board imaging (OBI) using kilovoltage imaging. Initially using a quality assurance (QA) phantom and subsequently using data of seven patients, the vector distances between Calypso- and OBI-recorded shifts were compared using the t-test. For the 30 phantom measurements, the average differences between the measured Calypso offset and the calculated OBI shift were 0.4 +/- 0.4, 0.2 +/- 0.3, and 0.4 +/- 0.3 mm in the lateral, longitudinal, and vertical directions, respectively (p = 0.73, p = 0.91, and p = 0.99, respectively), and the average difference vector for all sessions was 0.8 +/- 0.4 mm. For the 259 patient measurements, the average differences between the measured Calypso offset and the calculated OBI shift were 0.7 +/- 0.5, 1.1 +/- 0.9, and 1.2 +/- 0.9 mm in the lateral, longitudinal, and vertical directions, respectively (p = 0.45, p = 0.28, and p = 0.56, respectively), and the average difference vector for all sessions was 2.1 +/- 1.0 mm. Our results demonstrated good correlation between Calypso and OBI. While other studies have explored the issue of Calypso/OBI correlation, our analysis is unique in our use of phantom validation and in our performing the patient analysis on an initial population prior to routine setup using Calypso without OBI. Implications for Calypso's role as a QA tool are discussed.

Lanthanide Complexes on Ag Nanoparticles: Designing Contrast Agents for Magnetic Resonance Imaging

Journal of Colloid and Interface Science. Sep, 2009  |  Pubmed ID: 19527906

This paper describes colloidal particles that are designed to induce hyper-intensity contrast (T(1) relaxation) in MRI. The contrast agents consist of discrete gadolinium complexes tethered to 10 nm diameter silver nanoparticles. The gadolinium complexes (1) [Gd(DTPA-bisamido cysteine)](2-) and (2) [Gd(cystine-NTA)(2)](3-), undergo chemisorption to particle surfaces through thiol or disulfide groups, respectively, to form two new contrast agents. The resulting nanoparticulate constructs are characterized on the basis of their syntheses, composition, spectra and contrast enhancing power. The average r(1) relaxivities of the of the surface bound complexes (obtained at 9.4 T and 25 degrees C) are 10.7 and 9.7 s(-1) mM(-1), respectively, as compared to 4.7 s(-1) mM(-1) for the clinical agent Magnevist. Correspondingly, the respective whole particle relaxivities are 27927 and 13153 s(-1) mM(-1).

Chromatin Remodeling Complex in Treg Function

International Immunopharmacology. May, 2009  |  Pubmed ID: 19539570

Regulatory T cells (Treg), formerly known as suppressor T cells, are essential for maintaining self-tolerance as well as immune homeostasis. Lack of Treg or normal function of Treg often leads to lymphoproliferative syndrome and autoimmunity in human and mouse. The chromatin remodeling BAF complex regulates gene expression through the activity of Brg. Genetic ablation of Brg gene in mouse resulted in early embryonic lethality. T cell failed to develop in the thymus when Brg is deleted at DN stage. Using a Brg conditional KO mouse model, we deleted Brg at the DP stage in the thymus. Unexpectedly, T cells developed and matured normally. However, these mice displayed lympho-proliferative syndrome 2-4 months of age with enlarged peripheral lymphoid organs and leukocyte infiltration in non-lymphoid organs. T cells from these mice turned into effector cells producing increased amounts of effector cytokines as early as 4 weeks after birth. Further analysis revealed that the Treg population was specifically affected by Brg deletion. In this mini-review, we will discuss in detail the properties of Tregs controlled by Brg and the potential underlying mechanisms for an unanticipated, specific role of the Brg-containing BAF complex in controlling Treg functions.

Evaluation of the Bactec MGIT 960 TB System for Recovery and Identification of Mycobacterium Tuberculosis Complex in a High Through Put Tertiary Care Centre

Indian Journal of Medical Microbiology. Jul-Sep, 2009  |  Pubmed ID: 19584501

To evaluate the performance of an automated BACTEC MGIT 960, a non-radioactive, non-invasive liquid culture system for cultivation of M. tuberculosis complex in terms of recovery rate and time.

A Rare Case of Chondromyxoid Fibroma of the Scapula

American Journal of Orthopedics (Belle Mead, N.J.). May, 2009  |  Pubmed ID: 19585000

Can Prompt Treatment of Childhood UTI Prevent Kidney Scarring?

Pediatric Nephrology (Berlin, Germany). Oct, 2009  |  Pubmed ID: 19588169

The aim of the study reported here was to determine whether kidney scarring after urinary tract infections (UTI) in children can be prevented and to identify the risk factors for developing scars. We identified children in the Northern health region of the UK who had been seen to develop scars, identified as new defects on dimercapto-succinic acid (DMSA) scanning. Risk factors were sought by reviewing case-notes and interviews with parents. Twenty girls were identified whose new scarring was strongly associated with having both vesicoureteric reflux (VUR) and a UTI (p = 0.0001); 19/23 (83%) of kidneys exposed to both of these factors developed scars. Children were much more likely to be febrile (94 vs. 30%, p < 0.0001) or unwell (82 vs. 10%, p < 0.0001) during their earlier UTIs when they were of median age 2.8 years (range 0.3-5.0 years) and did not scar, compared to their later UTIs at age 7.3 years (1.2-12.5 years), when they did scar. However, most patients were treated within 1 day of their symptoms for their early UTIs, compared to a wait >or=7 days for later UTIs (p = 0.001). Being febrile or unwell during a UTI does not predict the development of scars, but prompt treatment appears to prevent scarring in children with VUR.

Unilateral Breast Oedema in a Case of Non-rheumatic Giant Left Atrium

Age and Ageing. Sep, 2009  |  Pubmed ID: 19589811

Giant left atrium (GLA) is a well-described entity in association with rheumatic heart disease. However, mitral valve prolapse is an extremely unusual cause of GLA, especially without the compressive symptoms it can often accompany. We discuss a case of a 78-year-old lady with no prior history of rheumatic heart disease with these findings with the unusual presentation of accompanied unilateral breast oedema as a manifestation of heart failure. This case illustrates the investigations and treatment options for GLA and the need for prompt assessment as it increases the risk of sudden death; therefore, its presence warrants careful evaluation and surgical intervention when appropriate.

Microfabricated Arrays of Cylindrical Wells Facilitate Single-molecule Enzymology of Alpha-chymotrypsin

Biotechnology Progress. Jul-Aug, 2009  |  Pubmed ID: 19610052

Single-molecule enzymology allows scientists to examine the distributions of kinetic rates among members of a population. We describe a simple method for the analysis of single-molecule enzymatic kinetics and provide comparisons to ensemble-averaged kinetics. To isolate our model enzyme, alpha-chymotrypsin, into single molecules, we use an array of cylindrical poly(dimethylsiloxane) wells 2 microm in diameter and 1.35 microm in height. Inside the wells, a protease assay with a profluorescent substrate detects alpha-chymotrypsin activity. We hold the concentration of alpha-chymotrypsin at 0.39 nM in a given well with an enzyme-to-substrate ratio of 1:6,666 molecules. Fluorescence emitted by the substrate is proportional to enzyme activity and detectable by a charge-coupled device. This method allows for the simultaneous real-time characterization of hundreds of individual enzymes. We analyze single-molecule kinetics by recording and observing their intensity trajectories over time. By testing our method with our current instruments, we confirm that our methodology is useful for the analysis of single enzymes for extracting static inhomogeneity.

Retroperitoneoscopic Lumbar Sympathectomy for Plantar Hyperhidrosis

Journal of the American College of Surgeons. Aug, 2009  |  Pubmed ID: 19632589

Reference Ranges for Middle Cerebral Artery Peak Systolic Velocity in Monochorionic Diamniotic Twins: a Longitudinal Study

Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. Aug, 2009  |  Pubmed ID: 19644951

The role of middle cerebral artery (MCA) peak systolic velocity (PSV) has become established in the management of fetal anemia. To date, singleton reference ranges have also been used in twin pregnancies. However, in monochorionic twin pregnancies, normal ranges for cerebral blood flow may differ from those in singletons owing to intertwin blood exchange. We aimed to establish gestational age-specific reference ranges for MCA-PSV in monochorionic diamniotic (MCDA) twin pregnancies, to compare them with previously reported singleton reference ranges, and to establish terms for calculating conditional reference intervals appropriate for individual serial measurements.

PET Lesion Segmentation Using Automated Iso-intensity Contouring in Head and Neck Cancer

Technology in Cancer Research & Treatment. Aug, 2009  |  Pubmed ID: 19645517

To improve the objectivity of the integration of positron emission tomography (PET), we used the conformality index (CI) to measure the goodness of fit of a given PET iso-SUV (standardized uptake value) level with the GTV defined on PET (GTV(PET)) and CT (GTV(CT)). Twenty-two datasets involving 20 head and neck cancer patients were identified. GTV(PET) and GTV(CT) were delineated manually.An iso-intensity method was developed to automatically segment GTV(PET-ISO) using (a) SUV and (b) maximum intensity thresholding (% Max), over a range of intensities. For each intensity, GTV(PET-ISO) was compared to GTV(PET) using the conformality index CI(PET) (and, similarly, to GTV(CT) using CICT). Comparing GTV(PET) to GTV(PET-ISO) vs comparing GTV(CT) to GTV(PET-ISO), the average peak CI was 0.68 +/- 0.09 vs 0.49 +/- 0.12 (p < 0.001), the optimum iso-SUV was 2.7 +/- 0.7 vs 2.9 +/- 1.0 (p=0. 253), and the % Max SUV was 21.8% +/- 7.6% vs 23.8% +/- 8.6% (p=0. 310), respectively. The radiation oncologist's volumes corresponded to a lower iso-SUV (3.02 +/- 0.58 vs 4.36 +/- 0.77, p< 0.001) and lower % Max SUV (24.1 +/- 9.1% vs 34.3 +/- 11.2%, p<0.001) than those drawn by the nuclear medicine physician. Though manual editing may still be necessary, PET iso-contouring is one method to improve the objectivity of GTV definition in head and neck cancer patients. Iso-SUV's can also be used to study the differences between PET's role as a nuclear medicine diagnostic test versus a radiation oncology treatment planning tool.

Severe Diaphragmatic Hernia Treated by Fetal Endoscopic Tracheal Occlusion

Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. Sep, 2009  |  Pubmed ID: 19658113

To examine operative and perinatal aspects of fetal endoscopic tracheal occlusion (FETO) in congenital diaphragmatic hernia (CDH).

Rheumatic Heart Disease Screening by Echocardiography: the Inadequacy of World Health Organization Criteria for Optimizing the Diagnosis of Subclinical Disease

Circulation. Aug, 2009  |  Pubmed ID: 19667239

Early case detection is vital in rheumatic heart disease (RHD) in children to minimize the risk of advanced valvular heart disease by preventive measures. The currently utilized World Health Organization (WHO) criteria for echocardiographic diagnosis of subclinical RHD emphasize the presence of pathological valve regurgitation but do not include valves with morphological features of RHD without pathological regurgitation. We hypothesized that adding morphological features to diagnostic criteria might have significant consequences in terms of case detection rates.

B-cell Depletion with Rituximab for Refractory Head and Neck Wegener's Granulomatosis: a Cohort Study

Clinical Otolaryngology : Official Journal of ENT-UK ; Official Journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery. Aug, 2009  |  Pubmed ID: 19673980

This study aimed to evaluate the response of refractory Wegener's granulomatosis affecting the ear, nose and throat and granulomatous eye disease to B-cell depletion with rituximab.

Influence of Demographic Factors on Outcome of Collecting Duct Carcinoma: a Surveillance, Epidemiology, and End Results (SEER) Database Analysis

Clinical Genitourinary Cancer. Aug, 2009  |  Pubmed ID: 19692318

Collecting duct carcinoma (CDC) is a rare tumor that is difficult to analyze in a single-institution setting. The Surveillance, Epidemiology, and End Results (SEER) database was used to examine demographics and outcomes of CDC.

Oxygen Cylinders: "life" or "death"?

African Health Sciences. Mar, 2009  |  Pubmed ID: 20842245

Oxygen is crucial to maintain and save human life. Other than medical purposes it is widely used for manufacture of mineral water, fabrication works and other industrial activities. If adequate precautionary measures are not adopted while handling, storage or transport of oxygen cylinder or container, accidental blast may claim human life and other damage as well. The case involving three victims is presented to highlight various relevant aspects i.e. autopsy findings, cause/s of blast and recommended precautions are discussed in the light of oxygen cylinder blast case in an" oxygen filling factory", claiming three human lives.

A Quality Management Systems Approach for CD4 Testing in Resource-poor Settings

American Journal of Clinical Pathology. Oct, 2010  |  Pubmed ID: 20855636

Quality assurance (QA) is a systematic process to monitor and improve clinical laboratory practices. The fundamental components of a laboratory QA program include providing a functional and safe laboratory environment, trained and competent personnel, maintained equipment, adequate supplies and reagents, testing of appropriate specimens, internal monitoring of quality, accurate reporting, and external quality assessments. These components are necessary to provide accurate and precise CD4 T-cell counts, an essential test to evaluate start of and monitor effectiveness of antiretroviral therapy for HIV-infected patients. In recent years, CD4 testing has expanded dramatically in resource-limited settings. Information on a CD4 QA program as described in this article will provide guidelines not only for clinical laboratory staff but also for managers of programs responsible for supporting CD4 testing. All agencies involved in implementing CD4 testing must understand the needs of the laboratory and provide advocacy, guidance, and financial support to established CD4 testing sites and programs. This article describes and explains the procedures that must be put in place to provide reliable CD4 determinations in a variety of settings.

Renal and Metabolic Effects of Three Months of Decarbonated Cola Beverages in Rats

Experimental Biology and Medicine (Maywood, N.J.). Nov, 2010  |  Pubmed ID: 20921275

Epidemiological studies have shown an association between the intake of cola beverages and chronic kidney diseases. Experimental evidence for the negative effects of cola intake on kidneys is lacking. Male Wistar rats had ad libitum access to water (control group) or three different sugar-sweetened cola beverages for three months. Despite very high cola intake (daily cca 140 mL), no differences were found in body weight, kidney weight, glomerular morphology, oxidative and carbonyl stress or expression of selected marker genes in the renal cortex. Interestingly, all groups consuming cola beverages had lower blood glucose levels during an oral glucose tolerance test, suggesting improved insulin sensitivity. Despite hyperfiltration (5-6-fold increase in diuresis), cola beverages had no effect on assessed parameters of renal function, histology, gene expression or oxidative stress. Moreover, cola intake seems to increase creatinine clearance and to decrease plasma levels of urea. In our study increased insulin sensitivity and altered renal functional parameters were observed in rats receiving cola beverages for three months. Whether the findings are due to the short duration of the study or interspecies metabolic differences should be uncovered in further studies. Even more interesting might be the analysis of effects of cola intake in animal models of diabetes.

Mucocele--a Study of 36 Cases

Indian Journal of Dental Research : Official Publication of Indian Society for Dental Research. Jul-Sep, 2010  |  Pubmed ID: 20930340

Mucocele is one of the most common benign soft tissue tumor present in the oral cavity. They are of two types - one is extravasation and second one is retention type but the majority are extravasation type.

A Review of Low-dose-rate Prostate Brachytherapy--techniques and Outcomes

Journal of the National Medical Association. Jun, 2010  |  Pubmed ID: 20575216

Prostate cancer is the most common male cancer in the United States and the second leading cause of male cancer death. The main therapeutic modalities for the treatment of prostate cancer are surgery, external beam radiation therapy, hormonal therapy, and brachytherapy. In recent years, brachytherapy has been increasingly utilized for the treatment of early-stage prostate cancer. Technological advances, including improvements in imaging, planning, and postimplant quality assessment by dosimetry have led to widespread use of brachytherapy. Outcomes for prostate brachytherapy have been shown to be equivalent, in selected patients, to those of other treatment modalities for prostate cancer, including radical prostatectomy and external beam radiation therapy. Further, prostate brachytherapy has quality-of-life benefits in comparison to these other treatment modalities, particularly in the domain of sexual function. This paper describes the history of low-dose rate brachytherapy; current techniques for brachytherapy implantation and postoperative dosimetric evaluation; recent outcomes studies; recent quality-of-life analyses; and current and future prostate brachytherapy developments, including open clinical trials. As research in prostate brachytherapy continues, it is likely that this modality will play an increasingly important role in the treatment of early-stage prostate cancer patients in the future.

Human Leukocyte Antigen-A, -B, and -DRB1 Allele and Haplotype Frequencies in the Mozambican Population: a Blood Donor-based Population Study

Human Immunology. Oct, 2010  |  Pubmed ID: 20600444

Human leukocyte antigen (HLA) has been used for several decades as genetic markers for analyzing diversity of gene pool origin, platelet transfusion, tissue transplantation, disease susceptibility or resistance, and forensic and anthropological studies. In the present study, the allele and haplotype frequencies of HLA-A, -B, and -DRB1 were studied in 250 unrelated Mozambican individuals (black African from south of Mozambique Basin) by using a low-medium resolution polymerase chain reaction-Luminex typing method. A total of 18 A, 25 B, and 13 DRB1 alleles were identified. The most frequent HLA-A, -B, and -DRB1 alleles were HLA-A*30 (23.9%), HLA-B*15 (15.6%), and HLA-DRB1*13 (19.8%), respectively. The most frequent two-locus haplotypes were HLA-A*30-B*42 (7.4%) and HLA-B*42-DRB1*03 (5.4%), and three-locus haplotypes were HLA-A*30-B*42-DRB1*03 (4.9%), and HLA-A*02-B*58-DRB1*11 (4.1%). Allele distribution and haplotype analysis demonstrated that Mozambican population shares HLA patterns with sub-Saharan populations.

Morphologic Changes and Methodological Issues in the Rabbit Experimental Model for Diaphragmatic Hernia

Histology and Histopathology. Sep, 2010  |  Pubmed ID: 20607652

Fetal lung development may be impaired by some congenital anomalies or in utero events. Animal models are used to understand the pathophysiology of these diseases and explore therapeutic strategies. Our group has an interest in the prenatal management of congenital diaphragmatic hernia (CDH). Isolated CDH remains associated with a 30% mortality because of lung hypoplasia and pulmonary hypertension. On day 23 of gestation (pseudoglandular stage) CDH was created in both ovarian-end fetuses (n= 28) in 14 time-mated pregnant white rabbits (hybrid of Dendermonde and New-Zealand White). At term (day 30) all survived operated fetuses and size-matched controls were harvested. Fetuses/lungs were assigned randomly to formalin fixation either under pressure of 25 cm H2O (CDH25 n=5; CTR25 n=5) or without (0 cm H2O (CDH0 n=7; CTR0 n=7). Fetuses and lungs were first weighed, and then the lungs were processed for morphometry. Pulmonary development was evaluated by lung-to-body weight ratio (LBWR) and airway and vascular morphometry. Surgical induction of CDH does reduce the LBWR to hypoplastic levels. The contralateral lung weight is 81% of what is expected, whereas the ipsilateral lung is only 46% of the normal. This was accompagnied by a loss of conducting airway generations, precisely, terminal bronchioles (TB), which were surrounded by less alveoli. The ipsilateral CDH lung demonstrated a thickened media in the peripheral arteries as well. As a result, in the severely hypoplastic ipsilateral lung, an airway fixation pressure of 25 H2O has no significant effect on the morphometric indices. The contralateral lung has a normal amount of alveoli around a single TB, which also behave like alveoli of the normal lung, i.e. expand under pressure fixation. The present study on severely hypoplastic lungs that never respirated, shows that in contrast to normal lungs, the morphometric indices are not significantly influenced by a difference in fixation pressure. Increasing fixation pressure seems to expand the lung only when sufficient alveolated parenchyma is present.

Stage IV Prostate Cancer: Survival Differences in Clinical T4, Nodal and Metastatic Disease

The Journal of Urology. Aug, 2010  |  Pubmed ID: 20620410

In the prostate specific antigen era most prostate cancer presents at an early stage. However, a significant number of patients have advanced disease, including those with stage IV disease. Assignment to stage IV prostate cancer may occur by different modes, namely as T4N0M0 vs N1 vs M1 disease. We hypothesize that patients with clinical T4 disease have better outcomes than those with N1 or M1 disease.

Type VI Secretion: Not Just for Pathogenesis Anymore

Cell Host & Microbe. Jul, 2010  |  Pubmed ID: 20638635

Type VI secretion systems (T6SS) have been studied primarily in the context of pathogenic bacteria-host interactions. Recent data suggest, however, that these versatile secretion systems may also function to promote commensal or mutualistic relationships between bacteria and eukaryotes or to mediate cooperative or competitive interactions between bacteria.

Role of Endoscopic Ultrasound/SpyScope in Diagnosis and Treatment of Choledocholithiasis in Pregnancy

World Journal of Gastroenterology : WJG. Jul, 2010  |  Pubmed ID: 20653072

Cholelithiasis and choledocholithiasis occur frequently in pregnancy and their management can be complicated. Traditional endoscopic retrograde cholangiopancreatography (ERCP) is the first line treatment for choledocholithiasis, but in addition to its baseline risks, fluoroscopy poses an additional radiation risk to the fetus. Endoscopic ultrasound (EUS) is an accurate modality for detecting common bile duct stones, but its role has not been defined in pregnancy. We describe an alternative management strategy to conventional ERCP in a pregnant patient with choledocholithiasis and cholangitis detected using EUS and choledochoscopy.

An Ellipsoidal Model for Studying Response of Head Impacts

Acta of Bioengineering and Biomechanics / Wrocław University of Technology. 2010  |  Pubmed ID: 20653325

The objective of this study was to propose a new analytical model for studying response of head impacts. Head is modeled by fluidfilled ellipsoidal shell of inconstant thickness impacted by a solid elastic sphere. Modeling the head as an ellipsoid is more realistic than modeling it as a sphere, the previous model existing in the literature [3]-[8]. In this model, the effect of Hertzian contact stiffness and local shell stiffness are combined to derive explicit equations for impact duration, the peak force transmitted to head, and the head injury criterion. One of the advantages of the model presented is sensitivity to the site of impact. A comparison between the present analytical results with the analytical data from spherical model [8] has been done to verify the validation of the present model.

Comparison of Commercial Histamine Release Test and Autologous Serum Skin Test in the Diagnosis of Autoimmune Urticaria

Indian Journal of Dermatology, Venereology and Leprology. Jul-Aug, 2010  |  Pubmed ID: 20657128

Serum Fructosamine Versus Glycosylated Hemoglobin As an Index of Glycemic Control, Hospitalization, and Infection in Diabetic Hemodialysis Patients

Kidney International. Supplement. Aug, 2010  |  Pubmed ID: 20671744

Diabetes is the most common cause of end-stage renal disease and an important risk factor for morbidity and mortality in dialysis patients. Glycemic control, utilizing serial measurement of glycosylated hemoglobin (HbA1c), is generally recommended to limit end-organ damage, including cardiovascular morbidity and mortality. We, along with others, have previously suggested that HbA1c may not be a reliable measure of glycemic control in dialysis patients, and have therefore explored the use of serum fructosamine (SF) as an alternative marker. The objective of this study was to compare HbA1c levels with SF in monitoring glycemic control and associated morbidity (infection and hospitalization) in diabetic patients in a large urban hemodialysis (HD) center. We enrolled 100 diabetic HD patients and followed them up prospectively for 3 years. Data on demographics, as well as biochemical and clinical data, including hospitalizations and infections, were recorded. The mean age was 63 years. In all 54% were women and the majority were African Americans (72%). As expected, HbA1c and albumin-corrected fructosamine (AlbF) levels were highly correlated and both were significantly associated with serum glucose. AlbF, however, was more highly correlated with mean glucose values when less than 150 mg/dl and was a more useful predictor of morbidity. By univariate logistic regression and by Poisson regression analysis, AlbF, but not HbA1c, was a significant predictor of hospitalization. Additionally, in patients dialyzed by arteriovenous (AV) access (that is, excluding those dialyzed via vascular catheters), AlbF, but not HbA1c, was a significant predictor of infection. In conclusion, AlbF is as reliable a marker as HbA1c for glycemic control in diabetic patients on HD, and may be advantageous for patients with serum glucose in a desirable therapeutic range (<150 mg/dl). In addition, AlbF, but not HbA1c, is associated with morbidity (hospitalizations and infections) in diabetic patients on HD.

Paediatric Dosing Errors Before and After Electronic Prescribing

Quality & Safety in Health Care. Aug, 2010  |  Pubmed ID: 20693222

To compare the incidence and severity rating of dose prescribing errors before and after the implementation of a commercially available electronic prescribing system at a tertiary care children's hospital.

ATP-binding Cassette B1 Transports Seliciclib (R-roscovitine), a Cyclin-dependent Kinase Inhibitor

Drug Metabolism and Disposition: the Biological Fate of Chemicals. Nov, 2010  |  Pubmed ID: 20699410

Seliciclib, a cyclin-dependent kinase inhibitor, is a promising candidate to treat a variety of cancers. Pharmacokinetic studies have shown high oral bioavailability but limited brain exposure to the drug. This study shows that seliciclib is a high-affinity substrate of ATP-binding cassette B1 (ABCB1) because it activates the ATPase activity of the transporter with an EC(50) of 4.2 μM and shows vectorial transport in MDCKII-MDR1 cells, yielding an efflux ratio of 8. This interaction may be behind the drug's limited penetration of the blood-brain barrier. ABCB1 overexpression, on the other hand, does not confer resistance to the drug in the models tested. These findings should be considered when treatment strategies using seliciclib are designed.

Retroperitoneal Hematoma After Percutaneous Coronary Intervention: Prevalence, Risk Factors, Management, Outcomes, and Predictors of Mortality: a Report from the BMC2 (Blue Cross Blue Shield of Michigan Cardiovascular Consortium) Registry

JACC. Cardiovascular Interventions. Aug, 2010  |  Pubmed ID: 20723857

This study sought to evaluate the prevalence, risk factors, outcomes, and predictors of mortality of retroperitoneal hematoma (RPH) following percutaneous coronary intervention.

American Radium Society 92nd Annual Meeting

Expert Review of Anticancer Therapy. Aug, 2010  |  Pubmed ID: 20735305

We provide a summary of the 92nd Annual Meeting of the American Radium Society (ARS), the oldest organization devoted to the study of cancer. This May 2010 meeting included a postgraduate course/contouring laboratory, seven scientific sessions, two keynote lectures, one Janeway lecture, four Panel presentations, one debate, one satellite symposium and 107 poster presentations--details of each of these activities are provided. All of these academic activities revolved around the major meeting theme of 'Improved Outcomes Through Judicious Applications of Advanced Technology'.

Implementation and Adoption of Nationwide Electronic Health Records in Secondary Care in England: Qualitative Analysis of Interim Results from a Prospective National Evaluation

BMJ (Clinical Research Ed.). 2010  |  Pubmed ID: 20813822

To describe and evaluate the implementation and adoption of detailed electronic health records in secondary care in England and thereby provide early feedback for the ongoing local and national rollout of the NHS Care Records Service.

Cochlear Implants in Otosclerosis

Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. Oct, 2010  |  Pubmed ID: 20814344

COCHLEAR IMPLANTATION IN OTOSCLEROSIS

Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. Sep, 2010  |  Pubmed ID: 20818289

Learning Lessons from Electronic Prescribing Implementations in Secondary Care

Studies in Health Technology and Informatics. 2010  |  Pubmed ID: 20841684

This paper reports a study undertaken in the UK to gather lessons learned from hospital sites that have implemented electronic prescribing systems. The work was commissioned by NHS Connecting for Health, the UK Department of Health agency responsible for the implementation of the National Programme for Information Technology. The aim was to capture front-line experience of the project and systems implementation, and to share it with staff who will in the future participate in other implementations. Data were drawn from detailed interviews with staff and a survey in 13 hospitals in England, as well as a review of published studies of implementations. The study output is a report and six user-facing briefing documents targeted at key stakeholder groups; nurses, pharmacist, doctors, senior executives, implementation team members and IM&T staff.

Metastatic Renal Cell Cancer and a Gastric Mass: An Unusual Finding

Case Reports in Gastroenterology. 2010  |  Pubmed ID: 21060712

Renal cell cancer (RCC) accounts for approximately 3% of all adult malignancies. RCC has a metastasis rate of approximately 25%, which is most commonly to the lungs (>50%). On the contrary, RCC metastasis to the gastrointestinal tract (excluding the liver) is very uncommon and ranges from 0.2 to 0.7%. Thus, a gastric cancer in a patient with known metastatic RCC would most likely be secondary to metastasis. We present the first reported case of a metastatic RCC coexisting with a new-onset primary gastric cancer and a review of management using guidelines from metastatic RCC to the stomach. An 82-year-old African American male with papillary RCC status post left nephrectomy with recurrence of liver metastasis presented with failure to thrive shortly after his third cycle of chemotherapy despite stable disease by imaging studies. He had received 7 chemotherapy cycles of Gemzar, Nexavar, and Avastin prior to admission. He subsequently had a drop in his hemoglobin and was found to have hemoccult positive stool in the setting of recent Avastin. Endoscopic evaluation showed a 3 cm ulcerated mass in the cardia which was biopsied. The biopsy showed invasive and poorly differentiated gastric adenocarcinoma unrelated to his RCC. The patient subsequently underwent partial gastrectomy with loop gastrojejunostomy for resection of his stage 1 primary gastric adenocarcioma. The surgery also facilitated future chemotherapy (Avastin), which could not be given prior to surgery due to its side effect of bleeding. The patient did not receive adjuvant chemoradiation for his gastric cancer due to his comorbidities at the time and was doing well at a one month follow-up. Metastatic RCC and primary gastric cancer can coexist, especially when there is an overlap of risk factors such as smoking or nitrosamines. The management of a gastric cancer in the setting of metastatic RCC is similar to the management of solitary primary gastric carcinoma. Treatment of the primary gastric cancer can facilitate future chemotherapy such as Avastin, which has been recently approved for the treatment of metastatic RCC.

Laparoscopic Paracolostomy Hernia Repair: a Retrospective Case Series at a Tertiary Care Center

Surgical Laparoscopy, Endoscopy & Percutaneous Techniques. Dec, 2010  |  Pubmed ID: 21150417

Paracolostomy hernias are one of the most common complications of stomas. Primary repair is associated with a high rate of recurrence. The choice is between mesh-reinforced repair of the defect and relocation of the stoma to another position. The laparoscopic approach seems attractive, as it is minimally invasive, requires shorter hospitalization, and the entry is through a noncontaminated part of the abdomen.

Regulation of Polar Peptidoglycan Biosynthesis by Wag31 Phosphorylation in Mycobacteria

BMC Microbiology. 2010  |  Pubmed ID: 21190553

Sensing and responding to environmental changes is a central aspect of cell division regulation. Mycobacterium tuberculosis contains eleven Ser/Thr kinases, two of which, PknA and PknB, are key signaling molecules that regulate cell division/morphology. One substrate of these kinases is Wag31, and we previously showed that partial depletion of Wag31 caused morphological changes indicative of cell wall defects, and that the phosphorylation state of Wag31 affected cell growth in mycobacteria. In the present study, we further characterized the role of the Wag31 phosphorylation in polar peptidoglycan biosynthesis.

The Need for Systematic Evaluations of Diagnostic Tests

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. Sep, 2010  |  Pubmed ID: 20649435

Oral in Vivo Bactofection in Dextran Sulfate Sodium Treated Female Wistar Rats

Folia Biologica. 2010  |  Pubmed ID: 20968181

Salmonella typhimurium SL7207 carrying Cu-Zn superoxide dismutase and an N-terminal deletion mutant of monocyte chemoattractant protein-1 genes was applied to dextran sodium sulfate treated female Wistar rats. Stool quality, food and water intake were monitored. Markers of oxidative stress, interleukin 1, interleukin 6 and tumor necrosis factor alpha were quantified. No differences were found in body weights, markers of oxidative stress in plasma and inflammatory markers in colon homogenates. Plasma concentrations of I11, I16 were lower in the treatment groups than in the dextran sodium sulfate group. However, dextran sodium sulfate induced inflammation could not be confirmed by plasma levels of I11, I16 and TNFalpha. Although some parameters showed a tendency to improve, the inflammation caused by administration of 4% dextran sodium sulfate during 7 days was low and contradictory to other studies. Results showed the potential synergic effect of combined bacteria-mediated antioxidative and anti-inflammatory gene therapy.

Laparoscopic Truncal Vagotomy with Gastrojejunostomy

Journal of the Indian Medical Association. Oct, 2010  |  Pubmed ID: 21510547

Surgery still remains the treatment of choice for patients of peptic ulceration with gastric outlet obstruction. With the advent of minimal access surgery, laparoscopic truncal vagotomy with gastrojejunostomy is an attractive option. Between September 2006 and May 2010, 18 patients underwent laparoscopic truncal vagotomy with gastrojejunostomy for gastric outlet obstruction with peptic ulcer. Four patients underwent stapled gastrojejunostomy and 14 patients had a sutured anasotomosis. There were no major intra-operative and postoperative complications. We conclude that the laparoscopic approach is beneficial and, with sufficient expertise, a sutured gastrojejunostomy can be safely performed, thus saving on the costs.

Flavokavain B from the Rhizome of Alpinia Mutica Roxb

Acta Crystallographica. Section E, Structure Reports Online. 2010  |  Pubmed ID: 21589048

THE TITLE COMPOUND [SYSTEMATIC NAME: (E)-1-(2-hydroxy-4,6-dimethoxyphenyl)-3-phenylprop-2-en-1-one], C(17)H(16)O(4), has an aromatic ring at both ends of the -CH= CH-C(=O)- fragment with the -CH=CH- bond in a trans configuration. The phenyl ring is nearly coplanar with this fragment [dihedral angle 4.8 (3) °] as is the hy-droxy-ldimeth-oxy-lphenyl unit [dihedral angle 6.3 (3) °]. The hy-droxy group is the donor in an intra-molecular hydrogen bond to the double-bonded O atom.

Dose-escalated Radiotherapy for High-risk Prostate Cancer: Outcomes in Modern Era with Short-term Androgen Deprivation Therapy

International Journal of Radiation Oncology, Biology, Physics. May, 2010  |  Pubmed ID: 19695789

Randomized data have supported the use of long-term androgen deprivation therapy (ADT) combined with radiotherapy (RT) for men with high-risk prostate cancer. The present study reviewed the outcomes of intermediate- and high-risk men treated with RT and short-term ADT.

Endogenous Thrombin Potential in the Assessment of Hypercoagulability in Systemic Lupus Erythematosus

American Journal of Hematology. Jan, 2010  |  Pubmed ID: 20029948

External Beam Radiation Therapy After Transurethral Resection of the Prostate: a Report on Acute and Late Genitourinary Toxicity

International Journal of Radiation Oncology, Biology, Physics. Jul, 2010  |  Pubmed ID: 20045267

To describe genitourinary (GU) toxicity in men with a history of transurethral resection of the prostate (TURP) treated with external beam radiation therapy (EBRT) for prostate cancer.

A Surveillance, Epidemiology, and End Results Registry Analysis of Prostate Cancer Modality Time Trends by Age

American Journal of Clinical Oncology. Dec, 2010  |  Pubmed ID: 20051808

To use the Surveillance, Epidemiology, and End Results (SEER) registry to analyze age-specific time trends in the use of radiotherapy (RT) (external beam radiotherapy [EBRT], brachytherapy [brachy], and combination therapy [combo]) as first-line treatment for prostate cancer.

Diffusion-weighted Magnetic Resonance Imaging: Its Uses in Otolaryngology

The Journal of Laryngology and Otology. Mar, 2010  |  Pubmed ID: 20053311

Transgenic Labeling of Hair Cells in the Zebrafish Acousticolateralis System

Gene Expression Patterns : GEP. Feb-Mar, 2010  |  Pubmed ID: 20085825

The zebrafish provides a useful experimental system for investigations of aural development. To permit the controlled expression of transgenes in developing hair cells, we isolated the genomic control regions of the parvalbumin 3a (pvalb3a) and parvalbumin 3b (pvalb3b) genes. Deletion analysis and somatic-cell transgenesis restricted the cis-acting control regions for hair cells to as little as 484base pairs for pvalb3a and 650base pairs for pvalb3b. Using both meganuclease-mediated and standard methods, we produced transgenic animals that transmit transgenes through their germ lines. These fish express GFP in hair cells in the inner ear and lateral line. Two stable transgenic lines express GFP prior to hair-bundle formation, so the associated promoter constructs are suitable for manipulating gene expression during bundle development. We additionally identified a transgenic line that offers variable labeling of supporting cells.

Off-label Use of Medical Products in Radiation Therapy: Summary of the Report of AAPM Task Group No. 121

Medical Physics. May, 2010  |  Pubmed ID: 20527564

Medical products (devices, drugs, or biologics) contain information in their labeling regarding the manner in which the manufacturer has determined that the products can be used in a safe and effective manner. The Food and Drug Administration (FDA) approves medical products for use for these specific indications which are part of the medical product's labeling. When medical products are used in a manner not specified in the labeling, it is commonly referred to as off-label use. The practice of medicine allows for this off-label use to treat individual patients, but the ethical and legal implications for such unapproved use can be confusing. Although the responsibility and, ultimately, the liability for off-label use often rests with the prescribing physician, medical physicists and others are also responsible for the safe and proper use of the medical products. When these products are used for purposes other than which they were approved, it is important for medical physicists to understand their responsibilities. In the United States, medical products can only be marketed if officially cleared, approved, or licensed by the FDA; they can be used if they are not subject to or specifically exempt from FDA regulations, or if they are being used in research with the appropriate regulatory safeguards. Medical devices are either cleared or approved by FDA's Center for Devices and Radiological Health. Drugs are approved by FDA's Center for Drug Evaluation and Research, and biological products such as vaccines or blood are licensed under a biologics license agreement by FDA's Center for Biologics Evaluation and Research. For the purpose of this report, the process by which the FDA eventually clears, approves, or licenses such products for marketing in the United States will be referred to as approval. This report summarizes the various ways medical products, primarily medical devices, can legally be brought to market in the United States, and includes a discussion of the approval process, along with manufacturers' responsibilities, labeling, marketing and promotion, and off-label use. This is an educational and descriptive report and does not contain prescriptive recommendations. This report addresses the role of the medical physicist in clinical situations involving off-label use. Case studies in radiation therapy are presented. Any mention of commercial products is for identification only; it does not imply recommendations or endorsements of any of the authors or the AAPM. The full report, containing extensive background on off-label use with several appendices, is available on the AAPM website (http://www.aapm.org/pubs/reports/).

Evaluation of Selective Gamma-secretase Inhibitor PF-03084014 for Its Antitumor Efficacy and Gastrointestinal Safety to Guide Optimal Clinical Trial Design

Molecular Cancer Therapeutics. Jun, 2010  |  Pubmed ID: 20530712

Aberrant regulation of Notch signaling has been implicated in tumorigenesis. Proteolytic release of the Notch intracellular domain (NICD) by gamma-secretase plays a key role in Notch-dependent nuclear signaling. gamma-Secretase is an attractive pharmaceutical target for therapeutic intervention in cancer. We describe the potent antitumor effects of PF-03084014, a small molecule that is a reversible, noncompetitive, and selective gamma-secretase inhibitor. The ability of PF-03084014 to inhibit gamma-secretase activity was shown by the reduction of endogenous NICD levels and by the downregulation of Notch target genes Hes-1 and cMyc in the T-cell acute lymphoblastic leukemia (T-ALL) cell line HPB-ALL. PF-03084014 caused cell growth inhibition of several T-ALL cell lines via cell cycle arrest and induction of apoptosis. PF-03084014 treatment also resulted in robust NICD reduction in HBP-ALL xenograft models. Broad antitumor efficacy at well-tolerated dose levels was observed in six Notch-dependent models. Additional mechanism-of-action studies showed inhibition of tumor cell proliferation and induction of apoptosis in HPB-ALL tumors, suggesting that the antitumor activity of PF-03084014 may be mediated by its direct effects on tumor cell growth or survival. Further studies on PF-03084014-induced gastrointestinal toxicity identified an intermittent dosing schedule that displayed reduced body weight loss and sustained antitumor efficacy. We also showed that glucocorticoids abrogated PF-03084014-induced gastrointestinal toxicity and delayed administration of glucocorticoids did not compromise its protection effect. Collectively, the results show that inhibition of Notch signaling by PF-03084014 while minimizing gastrointestinal toxicity presents a promising approach for development of therapies for Notch receptor-dependent cancers. This compound is being investigated for the treatment of T-ALL and advanced solid tumors in phase I clinical trials.

Melt-induced Fluorescent Signature in a Simple Naphthalenediimide

Chemical Communications (Cambridge, England). Jul, 2010  |  Pubmed ID: 20544080

The synthesis and fluorescence properties of a naphthalenediimide ditosylate are presented. The fluorescence is highly solvent and morphology dependent with a dramatic change in fluorescence output occurring following melting from a crystalline form. This observation is attributed to thermal disruption of the crystal structure allowing the formation of emissive dimers within the amorphous melt.

Extensive Inguinal Lymphadenectomy Improves Overall 5-year Survival in Penile Cancer Patients: Results from the Surveillance, Epidemiology, and End Results Program

Cancer. Jun, 2010  |  Pubmed ID: 20564401

European Urological Association guidelines recommend potentially curative inguinal lymphadenectomy for certain cases of penile cancer such as grade 3 and pT2-4 lesions, among others. Anecdotally, the authors have noticed that few patients undergo inguinal lymphadenectomy. Therefore, they assessed the frequency of inguinal lymphadenectomy and the impact of dissection extent on survival using the Surveillance, Epidemiology, and End Results (SEER) database.

Solvophobic Control of Core-substituted Naphthalene Diimide Nanostructures

Chemical Communications (Cambridge, England). Feb, 2010  |  Pubmed ID: 20107668

The requirements for the self-assembly of 2,3-annulated core-substituted NDIs into discrete worm-like nanostructures are explored in MeOH-CHCl(3) solutions. AFM was used to visualize and characterize the structures formed at precise proportions of solvent mixes.

Novel Fe (III) Heterochelates: Synthesis, Structural Features and Fluorescence Studies

Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy. Apr, 2010  |  Pubmed ID: 20133183

Fluorescence properties of five 4-acyl pyrazolone based hydrazides (H(2)SB(n)) and their Fe (III) heterochelates of the type [Fe(SB(n))(L)(H(2)O)].mH(2)O [H(2)SB(n)=nicotinic acid [1-(3-methyl-5-oxo-1-phenyl-4,5-di hydro-1H-pyrazol-4yl)-acylidene]-hydrazide; where acyl=-CH(3), m=4 (H(2)SB(1)); -C(6)H(5), m=2 (H(2)SB(2)); -CH(2)-CH(3), m=3 (H(2)SB(3)); -CH(2)-CH(2)-CH(3), m=1.5 (H(2)SB(4)); -CH(2)-C(6)H(5), m=1.5 (H(2)SB(5)) and HL=1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid] were studied at room temperature. The fluorescence spectra of heterochelates show red shift, which may be due to the chelation by the ligands to the metal ion. It enhances ligand ability to accept electrons and decreases the electron transition energy. The kinetic parameters such as order of reaction (n), energy of activation (E(a)), entropy (S*), pre-exponential factor (A), enthalpy (H*) and Gibbs free energy (G*) have been reported.

The Use of Anticoagulants Improves Biochemical Control of Localized Prostate Cancer Treated with Radiotherapy

Cancer. Apr, 2010  |  Pubmed ID: 20143436

: Substantial experimental evidence suggests that anticoagulants (ACs) may inhibit cancer growth and metastasis, although the limited data from clinical trials have been inconsistent. The potential antineoplastic effect of ACs was investigated in patients who received radiotherapy for localized prostate cancer.

Antenatal Fetal VEGF Therapy to Promote Pulmonary Maturation in a Preterm Rabbit Model

Early Human Development. Feb, 2010  |  Pubmed ID: 20181445

To assess the effects of fetal tracheal administration of VEGF on pulmonary maturation in a preterm rabbit model.

PF-03814735, an Orally Bioavailable Small Molecule Aurora Kinase Inhibitor for Cancer Therapy

Molecular Cancer Therapeutics. Apr, 2010  |  Pubmed ID: 20354118

The Aurora family of highly related serine/threonine kinases plays a key role in the regulation of mitosis. Aurora1 and Aurora2 play important but distinct roles in the G(2) and M phases of the cell cycle and are essential for proper chromosome segregation and cell division. Overexpression and amplification of Aurora2 have been reported in different tumor types, including breast, colon, pancreatic, ovarian, and gastric cancer. PF-03814735 is a novel, potent, orally bioavailable, reversible inhibitor of both Aurora1 and Aurora2 kinases that is currently in phase I clinical trials for the treatment of advanced solid tumors. In intact cells, the inhibitory activity of PF-03814735 on the Aurora1 and Aurora2 kinases reduces levels of phospho-Aurora1, phosphohistone H3, and phospho-Aurora2. PF-03814735 produces a block in cytokinesis, resulting in inhibition of cell proliferation and the formation of polyploid multinucleated cells. Although PF-03814735 produces significant inhibition of several other protein kinases, the predominant biochemical effects in cellular assays are consistent with inhibition of Aurora kinases. Once-daily oral administration of PF-03814735 to mice bearing human xenograft tumors produces a reduction in phosphohistone H3 in tumors at doses that are tolerable and that result in significant inhibition of tumor growth. The combination of PF-03814735 and docetaxel in xenograft mouse tumor models shows additive tumor growth inhibition. These results support the clinical evaluation of PF-03814735 in cancer patients. Mol Cancer Ther; 9(4); 883-94. (c)2010 AACR.

GeneMesh: a Web-based Microarray Analysis Tool for Relating Differentially Expressed Genes to MeSH Terms

BMC Bioinformatics. 2010  |  Pubmed ID: 20359363

An important objective of DNA microarray-based gene expression experimentation is determining inter-relationships that exist between differentially expressed genes and biological processes, molecular functions, cellular components, signaling pathways, physiologic processes and diseases.

Testicular Seminoma Metastasis to Pancreas: a Rare Cause of Obstructive Jaundice

The New Zealand Medical Journal. Mar, 2010  |  Pubmed ID: 20360785

Neonatal Tracheal Changes Following in Utero Fetoscopic Balloon Tracheal Occlusion in Severe Congenital Diaphragmatic Hernia

Journal of Pediatric Surgery. Apr, 2010  |  Pubmed ID: 20385271

To report postnatal tracheal changes after in utero fetoscopic balloon tracheal occlusion in severe congenital diaphragmatic hernia (CDH).

Bladder Cancer Metastasis to Duodenum: an Unusual Presentation of Obscure GI Bleed

Digestive Diseases and Sciences. Jun, 2010  |  Pubmed ID: 20397049

Inhibition of NF-kappaB Signaling by Quinacrine is Cytotoxic to Human Colon Carcinoma Cell Lines and is Synergistic in Combination with Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) or Oxaliplatin

The Journal of Biological Chemistry. Jun, 2010  |  Pubmed ID: 20424169

Colorectal cancer is the third most common malignancy in the United States. Modest advances with therapeutic approaches that include oxaliplatin (L-OHP) have brought the median survival rate to 22 months, with drug resistance remaining a significant barrier. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is undergoing clinical evaluation. Although human colon carcinomas express TRAIL receptors, they can also demonstrate TRAIL resistance. Constitutive NF-kappaB activation has been implicated in resistance to TRAIL and to cytotoxic agents. We have demonstrated constitutive NF-kappaB activation in five of six human colon carcinoma cell lines; this activation is inhibited by quinacrine. Quinacrine induced apoptosis in colon carcinomas and potentiated the cytotoxic activity of TRAIL in RKO and HT29 cells and that of L-OHP in HT29 cells. Similarly, overexpression of IkappaBalpha mutant (IkappaBalphaM) or treatment with the IKK inhibitor, BMS-345541, also sensitized these cells to TRAIL and L-OHP. Importantly, 2 h of quinacrine pretreatment resulted in decreased expression of c-FLIP and Mcl-1, which were determined to be transcriptional targets of NF-kappaB. Extended exposure for 24 h to quinacrine did not further sensitize these cells to TRAIL- or L-OHP-induced cell death; however, exposure caused the down-regulation of additional NF-kappaB-dependent survival factors. Short hairpin RNA-mediated knockdown of c-FLIP or Mcl-1 significantly sensitized these cells to TRAIL and L-OHP. Taken together, data demonstrate that NF-kappaB is constitutively active in colon cancer cell lines and NF-kappaB, and its downstream targets may constitute an important target for the development of therapeutic approaches against this disease.

Haemostasis in Head and Neck Surgical Procedures: Valsalva Manoeuvre Versus Trendelenburg Tilt

Annals of the Royal College of Surgeons of England. May, 2010  |  Pubmed ID: 20501015

The aim of the study was to identify whether Trendelenburg position helps detect any further bleeding points following Valsalva manoeuvre in order to achieve adequate haemostasis in head and neck surgery.

Discovery and Initial Optimization of 5,5'-disubstituted Aminohydantoins As Potent Beta-secretase (BACE1) Inhibitors

Bioorganic & Medicinal Chemistry Letters. Jan, 2010  |  Pubmed ID: 19959359

8,8-Diphenyl-2,3,4,8-tetrahydroimidazo[1,5-a]pyrimidin-6-amine (1) was identified through HTS, as a weak (micromolar) inhibitor of BACE1. X-Ray crystallographic studies indicate the 2-aminoimidazole ring forms key H-bonding interactions with Asp32 and Asp228 in the catalytic site of BACE1. Lead optimization using structure-based focused libraries led to the identification of low nanomolar BACE1 inhibitors such as 20b with substituents which extend from the S(1) to the S(3) pocket.

Structural Basis for the Interaction Between Yeast Spt-Ada-Gcn5 Acetyltransferase (SAGA) Complex Components Sgf11 and Sus1

The Journal of Biological Chemistry. Feb, 2010  |  Pubmed ID: 20007317

Sus1 is a central component of the yeast gene gating machinery, the process by which actively transcribing genes such as GAL1 become associated with nuclear pore complexes. Sus1 is a component of both the SAGA transcriptional co-activator complex and the TREX-2 complex that binds to nuclear pore complexes. TREX-2 contains two Sus1 chains that have an articulated helical hairpin fold, enabling them to wrap around an extended alpha-helix in Sac3, following a helical hydrophobic stripe. In SAGA, Sus1 binds to Sgf11 and has been proposed to provide a link between SAGA and TREX-2. We present here the crystal structure of the complex between Sus1 and the N-terminal region of Sgf11 that forms an extended alpha-helix around which Sus1 wraps in a manner that shares some similarities with the Sus1-Sac3 interface in TREX-2. However, the Sus1-binding site on Sgf11 is somewhat shorter than on Sac3 and is based on a narrower hydrophobic stripe. Engineered mutants that disrupt the Sgf11-Sus1 interaction in vitro confirm the importance of the hydrophobic helical stripe in molecular recognition. Helix alpha1 of the Sus1-articulated hairpin does not bind directly to Sgf11 and adopts a wide range of conformations within and between crystal forms, consistent with the presence of a flexible hinge and also with results from previous extensive mutagenesis studies (Klöckner, C., Schneider, M., Lutz, S., Jani, D., Kressler, D., Stewart, M., Hurt, E., and Köhler, A. (2009) J. Biol. Chem. 284, 12049-12056). A single Sus1 molecule cannot bind Sgf11 and Sac3 simultaneously and this, combined with the structure of the Sus1-Sgf11 complex, indicates that Sus1 forms separate subcomplexes within SAGA and TREX-2.

Prostate Cancer Modality Time Trend Analyses from 1973 to 2004: a Surveillance, Epidemiology, and End Results Registry Analysis

American Journal of Clinical Oncology. Apr, 2010  |  Pubmed ID: 19745696

Although specialized (urology/radiotherapy [RT]) databases have been used to measure practice patterns in nonmetastatic prostate cancer, the Surveillance, Epidemiology, and End Results (SEER) registry has not yet been employed for this task in detail. Our objectives were to analyze time trends in the use of surgery and RT and type of RT (external beam RT [EBRT], brachytherapy [Brachy] or combination EBRT + Brachy [Combo]).

Asexual Endophytes and Associated Alkaloids Alter Arthropod Community Structure and Increase Herbivore Abundances on a Native Grass

Ecology Letters. Jan, 2010  |  Pubmed ID: 19912292

Despite their minute biomass, microbial symbionts of plants potentially alter herbivory, diversity and community structure. Infection of grasses by asexual endophytic fungi often decreases herbivore loads and alters arthropod diversity. However, most studies to date have involved agronomic grasses and often consider only infection status (infected vs. uninfected), without explicitly measuring endophyte-produced alkaloids, which vary among endophyte isolates and may impact consumers. We combined field experiments and population surveys to investigate how endophyte infection and associated alkaloids influence abundances, species richness, evenness and guild structure of arthropod communities on a native grass, Achnatherum robustum (sleepygrass). Surprisingly, we found that endophyte-produced alkaloids were associated with increased herbivore abundances and species richness. Our results suggest that, unlike what has been found in agronomic grass systems, high alkaloid levels in native grasses may not protect host grasses from arthropod herbivores, and may instead more negatively affect natural enemies of herbivores.

The Effect of Wag31 Phosphorylation on the Cells and the Cell Envelope Fraction of Wild-type and Conditional Mutants of Mycobacterium Smegmatis Studied by Visible-wavelength Raman Spectroscopy

Biochemical and Biophysical Research Communications. Jan, 2010  |  Pubmed ID: 19932688

Non-surface-enhanced Raman spectroscopy using a 514.5 nm wavelength laser has been used to measure the molecular difference of conditional mutants of Mycobacterium smegmatis expressing three different alleles: wild-type wag31(Mtb), phosphoablative wag31T73A(Mtb), and phosphomimetic wag31T73E(Mtb). This study demonstrates that the phosphorylation of Wag31, a key cell-division protein, causes significant differences in the quantity of amino acids associated with peptidoglycan precursor proteins and lipid II which are observable in the Raman spectra of these cells. Raman spectra were also acquired from the isolated P60 cell envelope fraction of the cells expressing wag31T73A(Mtb) and wag31T73E(Mtb). A significant number of the molecular vibrational differences observed in the cells were also observed in the cell envelope fraction, indicating that these differences are indeed localized in the cell envelope. Principal component analyses and discriminant function analyses were conducted on these data to demonstrate the ease of spectral classification and the reproducibility of the data.

Late Rectal Toxicity After Prostate Brachytherapy: Influence of Supplemental External Beam Radiation on Dose-volume Histogram Analysis

Brachytherapy. Apr-Jun, 2010  |  Pubmed ID: 19853533

To describe the rate of gastrointestinal (GI) toxicity after prostate brachytherapy and describe how external beam radiation therapy (EBRT) may influence the association of rectal dose-volume histogram (DVH) parameters with rectal toxicity.

Renal Masses Herniating into the Hilum: Technical Considerations of the "ball-valve Phenomenon" During Nephron-sparing Surgery

Urology. Mar, 2010  |  Pubmed ID: 19854478

To describe our technique to recognize and resect renal tumors "ball-valving" into the sinus. Partial nephrectomy (PN) offers a functional advantage over radical nephrectomy for many cases of localized renal cell carcinoma. However, PN is underutilized particularly in anatomically challenging cases. Often unrecognized is the tendency for central renal tumors to herniate into the renal sinus.

Effect of Short-term Free Fatty Acids Elevation on Mitochondrial Function in Skeletal Muscle of Healthy Individuals

The Journal of Clinical Endocrinology and Metabolism. Jan, 2010  |  Pubmed ID: 19864449

Mitochondrial dysfunction has been proposed as an underlying mechanism in the pathogenesis of insulin resistance and type 2 diabetes mellitus.

External Beam Radiotherapy for Prostate Cancer Patients on Anticoagulation Therapy: How Significant is the Bleeding Toxicity?

International Journal of Radiation Oncology, Biology, Physics. Mar, 2010  |  Pubmed ID: 19464123

To characterize the bleeding toxicity associated with external beam radiotherapy for prostate cancer patients receiving anticoagulation (AC) therapy.

Clinical and Laboratory Factors Associated with Shear-dependent Platelet Hyper-reactivity in Patients on Chronic Aspirin Therapy

Thrombosis Research. Nov, 2010  |  Pubmed ID: 19501388

Prostate-specific Antigen Halving Time While on Neoadjuvant Androgen Deprivation Therapy is Associated with Biochemical Control in Men Treated with Radiation Therapy for Localized Prostate Cancer

International Journal of Radiation Oncology, Biology, Physics. Mar, 2011  |  Pubmed ID: 20510547

To assess whether the PSA response to neoadjuvant androgen deprivation therapy (ADT) is associated with biochemical control in men treated with radiation therapy (RT) for prostate cancer.

Ivermectin Interacts with Human ABCG2

Journal of Pharmaceutical Sciences. Jan, 2011  |  Pubmed ID: 20574995

Ivermectin is an antiparasitic drug frequently administered to humans. It has a limited brain exposure that is attributed to the efflux activity of ABCB1/Abcb1. ABCG2/Abcg2 is also a major transporter present in most pharmacologically important barriers. However, interaction of ivermectin with Abcg2 shows species specificity and in many studies was confounded by the masking effect of ABCB1/Abcb1. In this study using cellular and membrane assays we show that ivermectin displays a high-affinity interaction with human ABCG2 with IC(50) values in the 1-1.5  µM range. This interaction may have implications in human ABCG2-mediated drug-drug interactions of ivermectin.

Toxicity Analysis of Dose Escalation from 75.6 Gy to 81.0 Gy in Prostate Cancer

American Journal of Clinical Oncology. Feb, 2011  |  Pubmed ID: 20101167

Several randomized trials have demonstrated a biochemical control advantage to an increase from the "conventional" 66 to 70 Gy range to the "high-dose" 75 to 81 Gy range; these trials have also, however, demonstrated a toxicity disadvantage. Our objective was to perform a toxicity analysis of a minor dose escalation (from 75.6 to 81.0 Gy) within this "high-dose" range.

HIV Infection and Cocaine Use Induce Endothelial Damage and Dysfunction in African Americans

International Journal of Cardiology. May, 2011  |  Pubmed ID: 21600668

BACKGROUND: Clinical and epidemiological evidence suggests that HIV infection and cocaine use are associated with an increased risk of premature atherosclerosis. The underlying mechanisms linking HIV infection and cocaine use with early atherosclerosis remain elusive. METHODS AND RESULTS: Endothelin-1 (ET-1) levels in 360 African American participants in Baltimore, Maryland were measured. Quantile regression analysis was performed to examine the associations between ET-1, HIV infection, cocaine use, and other relevant clinical factors. The median of ET-1 in plasma, (1.05pg/mL with interquartile range: 0.73, 1.40) for those with HIV infection was significantly higher than values for those without HIV infection (0.74pg/mL with interquartile range: 0.61, 0.93). The median of ET-1 was markedly higher in chronic cocaine users (0.96pg/mL with interquartile range: 0.71, 1.36) than that in non-cocaine users (0.72pg/mL with interquartile range: 0.58, 1.06). Multivariate quantile regression suggested that HIV infection and duration of cocaine use were independently associated with plasma ET-1 levels after controlling for potential confounding factors. CONCLUSIONS: This study may provide insight into the mechanism of premature atherosclerosis in HIV-infected cocaine users and suggest that measurement of ET-1 in plasma can be used as a marker of early atherosclerosis in HIV infected patients and cocaine users.

Stimulus-responsiveness and Drug Release from Porous Silicon Films ATRP-grafted with Poly(N-isopropylacrylamide)

Langmuir : the ACS Journal of Surfaces and Colloids. Jun, 2011  |  Pubmed ID: 21604788

In this report, we employ surface-initiated atom transfer radical polymerization (SI-ATRP) to graft a thermoresponsive polymer, poly(N-isopropylacrylamide) (PNIPAM), of controlled thickness from porous silicon (pSi) films to produce a stimulus-responsive inorganic-organic composite material. The optical properties of this material are studied using interferometric reflectance spectroscopy (IRS) above and below the lower critical solution temperature (LCST) of the PNIPAM graft polymer with regard to variation of pore sizes and thickness of the pSi layer (using discrete samples and pSi gradients) and also the thickness of the PNIPAM coatings. Our investigations of the composite's thermal switching properties show that pore size, pSi layer thickness, and PNIPAM coating thickness critically influence the material's thermoresponsiveness. This composite material has considerable potential for a range of applications including temperature sensors and feedback controlled drug release. Indeed, we demonstrate that modulation of the temperature around the LCST significantly alters the rate of release of the fluorescent anticancer drug camptothecin from the pSi-PNIPAM composite films.

Seroprevalence of Transfusion-transmissible Infections and Evaluation of the Pre-donation Screening Performance at the Provincial Hospital of Tete, Mozambique

BMC Infectious Diseases. 2011  |  Pubmed ID: 21605363

The World Health Organization recommends universal and quality-controlled screening of blood donations for the major transfusion-transmissible infections (TTIs): human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and syphilis. The study objectives were to determine the seroprevalence of these TTIs among blood donors at the Provincial Hospital of Tete, Mozambique, and to assess the local pre-donation screening performance.

Citric Acid Modified Kenaf Core Fibres for Removal of Methylene Blue from Aqueous Solution

Bioresource Technology. Aug, 2011  |  Pubmed ID: 21620692

Chemically modified kenaf core fibres were prepared via esterification in the presence of citric acid (CA). The adsorption kinetics and isotherm studies were carried out under different conditions to examine the adsorption efficiency of CA-treated kenaf core fibres towards methylene blue (MB). The adsorption capacity of the kenaf core fibres increased significantly after the citric acid treatment. The values of the correlation coefficients indicated that the Langmuir isotherm fitted the experimental data better than the Freundlich isotherm. The maximum adsorption capacity of the CA-treated kenaf core fibres was found to be 131.6mg/g at 60°C. Kinetic models, pseudo-first-order, pseudo-second-order and intraparticle diffusion, were employed to describe the adsorption mechanism. The kinetic data were found to fit pseudo-second-order model equation as compared to pseudo-first-order model. The adsorption of MB onto the CA-treated kenaf core fibres was spontaneous and endothermic.

Sub-hepatic Cholesterol Stones Indicate a Sinister Underlying Diagnosis

QJM : Monthly Journal of the Association of Physicians. Jun, 2011  |  Pubmed ID: 21642362

Chemical Compositions of the Rhizome Oils of Two Alpinia Species of Malaysia

Natural Product Research. Jun, 2011  |  Pubmed ID: 21644178

The essential oils obtained by hydrodistillation of the rhizomes of Alpinia aquatica Rosc. syn. Alpinia melanocarpa and Alpinia malaccensis Roscoe were analysed by capillary gas chromatography and gas chromatography-mass spectrometry. Eighteen compounds, representing 98.4% of the essential oil were identified in A. aquatica rhizome oil, with β-sesquiphellandrene in 36.5% being the major constituent, while 20 compounds representing 99.7% of the rhizome oil of A. malaccensis were identified, among which methyl (E)-cinnamate (78.2%) was the major constituent.

Tracheal Diameter at Birth in Severe Congenital Diaphragmatic Hernia Treated by Fetal Endoscopic Tracheal Occlusion

Prenatal Diagnosis. Jul, 2011  |  Pubmed ID: 21671461

To investigate tracheal dimensional differences seen at birth following fetal endoscopic tracheal occlusion (FETO) in cases of severe congenital diaphragmatic hernia (CDH) and to report on their clinical follow-up.

Cryptococcal Meningitis in an HIV-negative Patient with Rheumatoid Arthritis Treated with Rituximab

Rheumatology (Oxford, England). Sep, 2011  |  Pubmed ID: 21700684

Resident-directed Long-term Care: Staff Provision of Choice During Morning Care

The Gerontologist. Dec, 2011  |  Pubmed ID: 21719629

To develop an observational protocol to assess the quality of staff-resident communication relevant to choice and describe staff-resident interactions as preliminary evidence of the usefulness of the tool to assess current nursing home practices related to offering choice during morning care provision.

Nasogastric Tube Insertion in Difficult Cases with the Aid of a Flexible Nasendoscope

The Journal of Laryngology and Otology. Sep, 2011  |  Pubmed ID: 21729448

Nasogastric tube insertion is often difficult, due to a variety of reasons, e.g. skewed laryngeal anatomy. We present a previously unreported method of facilitating nasogastric tube insertion, using a flexible nasendoscope.

Solitary Extra-skeletal Sinonasal Metastasis from a Primary Skeletal Ewing's Sarcoma

The Journal of Laryngology and Otology. Aug, 2011  |  Pubmed ID: 21729453

Ewing's sarcoma is a rare, malignant tumour predominantly affecting young adolescent males. We describe a unique case of an isolated extra-skeletal metastasis from a skeletal Ewing's sarcoma primary, arising in the right sinonasal cavity of a young man who presented with severe epistaxis and periorbital cellulitis.

Treatment of Kaposi Sarcoma in Human Immunodeficiency Virus-1-infected Mozambican Children with Antiretroviral Drugs and Chemotherapy

The Pediatric Infectious Disease Journal. Oct, 2011  |  Pubmed ID: 21730886

AIDS-associated Kaposi sarcoma occurs in children, but treatment experience reports are very scarce. A retrospective analysis of 28 children treated with highly active antiretroviral therapy and monthly paclitaxel showed unexpected results with 19 children in complete and sustainable remission, including those with the most severe form. Tolerance and feasibility were good, despite a lack of skilled staff in a low-resource setting.

[Congenital Diaphragmatic Hernia: Antenatal Care]

Revue Des Maladies Respiratoires. Jun, 2011  |  Pubmed ID: 21742241

The prenatal evaluation of the postnatal prognosis of fetuses displaying congenital diaphragmatic hernia (CDH) has improved over the past five years. Although the accuracy of these outcome predictions remains a matter of debate, it seems important that all teams in charge of those fetuses use the same prognostic factors in order to be able to improve and compare their practice. Prediction will be based on Lung over Head Ratio (LHR) between 22 and 28 weeks or the LHR observed/expected whatever the gestational age, (the measurement of which relies on very strict criteria), the position of the liver and lung volumes measured by MRI. These factors allow the identification of a group of fetuses likely to have a poor outcome. In the group with LHR less than 1 or LHR o/e less than 25% and where the liver is in the thorax, survival is less than 20%. In utero treatment could be offered to these fetuses. A balloon can be placed in the trachea, under the vocal cords, by foetoscopy between 28 and 30 weeks of pregnancy. The balloon is retrieved at 34 weeks. The preliminary results show that survival in this group increases from 20% to up to 50%. The morbidity does not seem to be increased but is currently under evaluation.

Absolute and Percent CD4+ T-cell Enumeration by Flow Cytometry Using Capillary Blood

Journal of Immunological Methods. Sep, 2011  |  Pubmed ID: 21787779

CD4+ T-cell counting is usually performed on whole blood obtained from standard venipuncture. Venipuncture requires expertise, results in discomfort and generates biological waste. Capillary blood could be used to measure the levels of CD4+ T-cell in children, elderly and very ill patients. We studied the agreement between CD4+ T-cell counts and percent generated using venous blood with those obtained with capillary blood in HIV-infected adults and children in a resource-limited tropical setting.

Republished Error Management: Paediatric Dosing Errors Before and After Electronic Prescribing

Postgraduate Medical Journal. Aug, 2011  |  Pubmed ID: 21788235

To compare the incidence and severity rating of dose prescribing errors before and after the implementation of a commercially available electronic prescribing system at a tertiary care children's hospital.

Antenatal Ultrasound Prediction of Pulmonary Hypoplasia in Congenital Diaphragmatic Hernia: Correlation with Pathology

Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. Sep, 2011  |  Pubmed ID: 21520476

To examine the relationship between observed to expected (o/e) lung to head circumference ratio (LHR) and lung-to-body weight ratio (LBWR) in fetuses with congenital diaphragmatic hernia (CDH).

Improving Performance in Single-incision Laparoscopy

Journal of the American College of Surgeons. May, 2011  |  Pubmed ID: 21530854

Genetic Characterization of Human T-cell Lymphotropic Virus Type 1 in Mozambique: Transcontinental Lineages Drive the HTLV-1 Endemic

PLoS Neglected Tropical Diseases. 2011  |  Pubmed ID: 21532745

Human T-Cell Lymphotropic Virus Type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It has been estimated that 10-20 million people are infected worldwide, but no successful treatment is available. Recently, the epidemiology of this virus was addressed in blood donors from Maputo, showing rates from 0.9 to 1.2%. However, the origin and impact of HTLV endemic in this population is unknown.

Gold Nanoparticle-decorated Keggin Ions/TiO2 Photococatalyst for Improved Solar Light Photocatalysis

Langmuir : the ACS Journal of Surfaces and Colloids. Jun, 2011  |  Pubmed ID: 21534553

We demonstrate a facile localized reduction approach to synthesizing a Au nanoparticle-decorated Keggin ion/TiO(2) photococatalyst for improved solar light photocatalysis application. This has been achieved by exploiting the ability of TiO(2)-bound Keggin ions to act as a UV-switchable, highly localized reducing agent. Notably, the approach proposed here does not lead to contamination of the resultant cocatalyst with free metal nanoparticles during aqueous solution-based synthesis. The study shows that for Keggin ions (phosphotungstic acid, PTA), being photoactive molecules, the presence of both Au nanoparticles and PTA on the TiO(2) surface in a cocatalytic system can have a dramatic effect on increasing the photocatalytic performance of the composite system, as opposed to a TiO(2) surface directly decorated with metal nanoparticles without a sandwiched PTA layer. The remarkable increase in the photocatalytic performance of these materials toward the degradation of a model organic Congo red dye correlates to an increase of 2.7-fold over that of anatase TiO(2) after adding Au to it and 4.3-fold after introducing PTA along with Au to it. The generalized localized reduction approach to preparing TiO(2)-PTA-Au cocatalysts reported here can be further extended to other similar systems, wherein a range of metal nanoparticles in the presence of different Keggin ions can be utilized. The composites reported here may have wide potential implications toward the degradation of organic species and solar cell applications.

Supramolecular Construction of Vesicles Based on Core-substituted Naphthalene Diimide Appended with Triethyleneglycol Motifs

Chemical Communications (Cambridge, England). Aug, 2011  |  Pubmed ID: 21552619

The self-assembly of core-substituted naphthalene diimides bearing triethylene glycol motifs leads to the formation of stable vesicles in DMSO and CHCl(3)/MeOH (6 : 4, v/v) solvents. The vesicles were evaluated by means of UV/vis and fluorescence spectroscopy, transmission electron microscopy, atomic force microscopy and dynamic light scattering.

Primary Stent Revascularization for Critical Flow-limiting Middle Cerebral Artery Stenosis Presenting with Rapid Neurologic Decline

The American Journal of Emergency Medicine. Oct, 2011  |  Pubmed ID: 20970285

Maternal Hyperoxygenation Test in Fetuses Undergoing FETO for Severe Isolated Congenital Diaphragmatic Hernia

Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. Mar, 2011  |  Pubmed ID: 20652932

To predict neonatal survival and pulmonary hypertension by measurement of fetal pulmonary artery reactivity to maternal hyperoxygenation in fetuses with severe congenital diaphragmatic hernia treated by fetoscopic endoluminal tracheal occlusion (FETO).

Perfusion Storage Reduces Apoptosis in a Porcine Kidney Model of Donation After Cardiac Death

Transplantation. Jan, 2011  |  Pubmed ID: 21200363

Donation after cardiac death (DCD) kidneys suffer a high incidence of delayed graft function attributable to warm ischemia and cold ischemia (CI). Neither the mechanism of injury nor type of cell death has been described. Clinical studies suggest that perfusion storage (PS) of DCD kidneys may reduce injury although the mechanism of protection is unknown. In a porcine model of DCD, we hypothesized that DCD kidneys have increased caspase-1 due to warm ischemia (WI) and increased caspase-3 and apoptosis due to CI.

Evidence of Human Papillomavirus in the Placenta

The Journal of Infectious Diseases. Feb, 2011  |  Pubmed ID: 21208925

Human papillomavirus (HPV) is an epitheliotropic virus typically infecting keratinocytes but also possibly epithelial trophoblastic placental cells. In the present study, we set out to investigate whether HPV can be recovered from transabdominally obtained placental cells to avoid any confounding contamination by HPV-infected cervical cells. Thirty-five placental samples from women undergoing transabdominal chorionic villous sampling were analyzed, and we detected HPV-16 and HPV-62 in 2 placentas. This study suggests that HPV infection of the placenta can occur early in pregnancy. The overall clinical implication of these results remains to be elucidated.

Technical Aspects of Fetal Endoscopic Tracheal Occlusion for Congenital Diaphragmatic Hernia

Journal of Pediatric Surgery. Jan, 2011  |  Pubmed ID: 21238635

In isolated congenital diaphragmatic hernia, prenatal prediction is made based on measurements of lung size and the presence of liver herniation into the thorax. A subset of fetuses likely to die in the postnatal period is eligible for fetal intervention that can promote lung growth. Rather than anatomical repair, this is now attempted by temporary fetal endoscopic tracheal occlusion (FETO). Herein we describe purpose-designed instruments that were developed thanks to a grant from the European Commission. The feasibility and safety of FETO have now been demonstrated in several active fetal surgery programs. The most frequent complication of the procedure is preterm premature rupture of the membranes, which is probably iatrogenic in nature. It does have an impact on gestational age at delivery and complicates balloon removal. FETO is associated with an apparent increase in survival compared with same severity controls, although this needs to be evaluated in a formal trial. The time has come to do so.

Hypoxia-inducible Factor-1α (HIF-1α) and Autophagy in Polycystic Kidney Disease (PKD)

American Journal of Physiology. Renal Physiology. May, 2011  |  Pubmed ID: 21270095

Cyst expansion in polycystic kidney disease (PKD) results in localized hypoxia in the kidney that may activate hypoxia-inducible factor-1α (HIF-1α). HIF-1α and autophagy, a form of programmed cell repair, are induced by hypoxia. The purposes were to determine HIF-1α expression and autophagy in rat and mouse models of PKD. HIF-1α was detected by electrochemiluminescence. Autophagy was visualized by electron microscopy (EM). LC3 and beclin-1, markers of autophagy, were detected by immunoblotting. Eight-week-old male heterozygous (Cy/+) and 4-wk-old homozygous (Cy/Cy) Han:SPRD rats, 4-wk-old cpk mice, and 112-day-old Pkd2WS25/- mice with a mutation in the Pkd2 gene were studied. HIF-1α was significantly increased in massive Cy/Cy and cpk kidneys and not smaller Cy/+ and Pkd2WS25/- kidneys. On EM, features of autophagy were seen in wild-type (+/+), Cy/+, and cpk kidneys: autophagosomes, mitophagy, and autolysosomes. Specifically, autophagosomes were found on EM in the tubular cells lining the cysts in cpk mice. The increase in LC3-II, a marker of autophagosome production and beclin, a regulator of autophagy, in Cy/Cy and cpk kidneys, followed the same pattern of increase as HIF-1α. To determine the role of HIF-1α in cyst formation and/or growth, Cy/+ rats, Cy/Cy rats, and cpk mice were treated with the HIF-1α inhibitor 2-methoxyestradiol (2ME2). 2ME2 had no significant effect on kidney volume or cyst volume density. In summary, HIF-1α is highly expressed in the late stages of PKD and is associated with an increase in LC3-II and beclin-1. The first demonstration of autophagosomes in PKD kidneys is reported. Inhibition of HIF-1α did not have a therapeutic effect.

Three-dimensional Ultrasound Fetal Lung Volumes and Infant Respiratory Outcome: a Prospective Observational Study

BJOG : an International Journal of Obstetrics and Gynaecology. Apr, 2011  |  Pubmed ID: 21291507

To determine if fetal lung volumes (FLVs), determined by three-dimensional rotational ultrasound and virtual organ computer-aided analysis software (vocal), correlated with neonatal respiratory outcomes in surviving infants who had a high risk [fetuses with congenital diaphragmatic hernia (CDH)], lower risk [fetuses with anterior wall defects (AWDs)] and no risk (controls) of abnormal antenatal lung growth.

Salmonella-mediated Gene Therapy in Experimental Colitis in Mice

Experimental Biology and Medicine (Maywood, N.J.). Feb, 2011  |  Pubmed ID: 21321314

Bacterial gene therapy - bactofection is a simple and effective method to deliver plasmid DNA into target tissue. We hypothesize that oral in vivo bactofection can be an interesting approach to influence the course of inflammatory bowel diseases. The aim of this study was to prove the effects of antioxidative and anti-inflammatory bactofection in dextran sulfate sodium (DSS)-treated mice. Attenuated bacteria Salmonella Typhimurium SL7207 carrying plasmids with genes encoding Cu-Zn superoxide dismutase and an N-terminal deletion mutant of monocyte chemoattractant protein-1 were prepared. Male Balb/c mice had ad libitum access to 1% DSS solution in drinking water during 10 days (mild model of colitis). The animals were daily fed with 200 Mio bacteria via gastric gavage during the experiment. Fecal consistency, clinical status, food and water intake were monitored. After 10 days samples were taken and markers of oxidative stress and inflammatory cytokine levels were measured. Colonic tissue was scored histologically by a blinded investigator. DSS treatment significantly increased the levels of inflammatory cytokines and malondialdehyde as a marker of lipoperoxidation in the colon. Anti-inflammatory gene therapy improved the total antioxidative capacity. In comparison with the untreated group, bacterial gene therapy lowered the histological colitis score. Salmonella-mediated antioxidative and anti-inflammatory gene therapy alleviated colitis in mice. The effect seems to be mediated by increased antioxidative status. Further studies will show whether recombinant probiotics expressing therapeutic gene might be used for the therapy of inflammatory bowel diseases.

HIV-infected Hospitalized Patients with 2009 Pandemic Influenza A (pH1N1)--United States, Spring and Summer 2009

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. Jan, 2011  |  Pubmed ID: 21342893

We describe the clinical findings of HIV-infected patients hospitalized with 2009 pandemic influenza A (pH1N1). Data were derived from 3 separate case series in the United States. Among 911 adults hospitalized with pH1N1 influenza, 31 (3.4%) were HIV infected compared with an HIV prevalence of 0.45% in the general US adult population. HIV-infected influenza patients experienced similar rates of intensive care unit admission (29% vs 34%) and death (13% vs 13%) compared with non-HIV-infected patients. Among HIV-infected patients with available data, 14 (50%) of 28 patients had a CD4 cell count <200 cells/μL, which was not associated with an increased risk of an intensive care unit admission or death. Overall, 25 (81%) HIV-infected patients received influenza antiviral therapy, but treatment was initiated within 48 h of illness onset in only 33% of cases. Clinicians should consider early empiric influenza antiviral treatment in HIV-infected patients presenting with suspected influenza.

Gastrointestinal Stromal Tumor (GIST) Presenting with Acute Pancreatitis

Endoscopy. 2011  |  Pubmed ID: 21370224

Accurate CD4 T-cell Enumeration and Antiretroviral Drug Toxicity Monitoring in Primary Healthcare Clinics Using Point-of-care Testing

AIDS (London, England). Mar, 2011  |  Pubmed ID: 21378535

To evaluate the accuracy of point-of-care tests (POCTs) for CD4 cell, clinical chemistry and hemoglobin in primary healthcare clinics in Mozambique.

T2 Quantifications of Fetal Lungs at MRI-normal Ranges

Prenatal Diagnosis. Jul, 2011  |  Pubmed ID: 21425299

To prospectively determine the pattern of lung intensities and T2 values in fetuses with normally developing lungs as obtained with T2-weighted single-shot turbo spin echo magnetic resonance (TSE MR) imaging. This should serve as a reference to which images from fetuses with lung development disorders are compared.

An International Perspective on Interest in a General Surgery Career Among Final-year Medical Students

American Journal of Surgery. Sep, 2011  |  Pubmed ID: 21457938

The level of interest in general surgery among US seniors has been declining; however, it may be perceived as a more attractive career outside the United States.

Prenatal Presentation of Transient Central Diabetes Insipidus

European Journal of Pediatrics. May, 2011  |  Pubmed ID: 21072537

Nephrogenic diabetes insipidus (DI) in the foetus has been described as a rare presentation of severe polyhydramnios.

Antioxidant and Antitumor Activities of Artemisia Campestris and Thymelaea Hirsuta from Southern Tunisia

Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association. Feb, 2011  |  Pubmed ID: 21075159

The essential oil of Artemisia campestris and the ethanol-water, hexane and water extracts of A. campestris and Thymelaea hirsuta collected in southern of Tunisia were investigated for their antioxidant (DPPH, ABTS and beta-carotene methods) and antitumor growth inhibition of human colon cancer HT-29 cells using MTT test activities. All the A. campestris extracts tested at high concentrations (100 μg/ml) showed activity ranging from 19.5% for essential oil to 64.4% of negative control growth for infusion extract, except the hexane extract. With T. hirsuta, all the extracts tested (hexane and ethanol-water), except the infusion extract, also exhibited antitumor activity (58.2% and 65.5% of control growth respectively). The ethanol-water and infusion extracts of A. campestris showed higher antioxidant activity, polyphenol and flavonoid contents than those of T. hirsuta. These results show that there is a positive correlation between the antitumor activity and the antioxidant activity, and of these two activities and with the levels of polyphenols and flavonoids. The essential oil and the other extracts of A. campestris, which exhibited significant antitumor activity against the HT-29 cells deserve further research into the chemoprevention and treatment of colon cancer.

Long-term Damage to the ENT System in Wegener's Granulomatosis

European Archives of Oto-rhino-laryngology : Official Journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : Affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. May, 2011  |  Pubmed ID: 21085976

The objectives of the study are to describe long-term ENT damage and assess risk factors in patients with newly diagnosed and treated Wegener's granulomatosis (WG) using the vasculitis damage index (VDI). Data from four randomised controlled trials carried out by the European Vasculitis Study Group was used. Patients newly diagnosed with WG with complete data at 5 years were included. Patients enrolled into the trials without 5-year data were excluded. Total and ENT VDI scores were recorded at 12 months and after at least 5 years. Logistic regression models were constructed to assess risk factors using total ENT and overall VDI score over the follow-up period, the proportion of patients with increased VDI score and the presence or absence of damage as the main outcomes. One hundred and thirty-eight patients were included. Ninety patients (65%) had long-term damage and 81% of these (73/90) developed some damage in the first 12 months. Positive ENT activity score (BVAS) at baseline and relapses were associated with higher ENT VDI scores long-term (OR = 6.90, 95% CI 2.01-23.75; OR = 2.65, 95% CI 1.20-5.82). Increasing BVAS score showed a trend towards lower VDI scores (OR = 0.93, 95% CI 0.88-0.99). Only ENT relapses and number of relapses were associated with an increase in VDI over time (OR = 8.38, 95% CI 3.10-22.68; OR = 1.79, 95% CI 1.24-2.58). In conclusion, most of the ENT damage in these patients was accrued within 12 months of diagnosis. We have shown an association between later ENT damage and the presence of ENT disease at baseline; lower initial BVAS and higher rate of disease relapse.

External Beam Radiotherapy for Prostate Cancer: Urinary Outcomes for Men with High International Prostate Symptom Scores (IPSS)

International Journal of Radiation Oncology, Biology, Physics. Jul, 2011  |  Pubmed ID: 20643513

To report the urinary outcome of men treated for prostate cancer with external beam radiotherapy (EBRT) who have pretreatment obstructive urinary symptoms (International Prostate Symptom Score [IPSS] ≥ 15).

Examining the Relationship Between the Lung-to-head Ratio Measured on Ultrasound and Lung Volumetry by Magnetic Resonance in Fetuses with Isolated Congenital Diaphragmatic Hernia

Fetal Diagnosis and Therapy. 2011  |  Pubmed ID: 20962504

In fetuses with isolated congenital diaphragmatic hernia (CDH), lung development can be measured by the lung-to-head ratio (LHR) using ultrasound as well as by lung volumetry determined by fetal magnetic resonance imaging (MRI). We aimed to investigate their relationship as well as to analyze the factors that may have an impact on it.

Magnetic Resonance Imaging in the Normal Fetal Heart and in Congenital Heart Disease

Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. Aug, 2011  |  Pubmed ID: 21837757

OBJECTIVE: To evaluate prospectively the feasibility of magnetic resonance imaging (MRI) for assessment of the fetal heart for congenital heart disease (CHD). METHODS: This was a cross-sectional study, including 66 fetuses with a normal heart and 40 with CHD. The fetal heart was examined on MRI using axial steady-state free precession (SSFP) sequences. Regression analysis was used to investigate the effect on the ability to visualize cardiac anatomy of gestational age at examination, maternal body mass index, presence of fetal cardiac abnormality, fetal movements, fetal lie and twinning. The sensitivity and specificity of detecting cardiac defects were calculated. RESULTS: The four-chamber view was visualized in 98.1% of fetuses. The sensitivity of detecting a cardiac defect on the four-chamber view was 88% and the specificity 96%. The ability to visualize the left and right outflow tracts was only influenced by the presence of fetal movements: for the left outflow tract 94.4 vs. 50.0% visualization and for the right outflow tract 92.6 vs. 53.8% visualization without and with fetal movements, respectively. The sensitivity of detecting a cardiac defect of the left outflow tract was 63% and the specificity 100%, while sensitivity and specificity were 59 and 97%, respectively, for the right outflow tract. CONCLUSIONS: Despite the use of SSFP sequences, MRI in the fetal heart remains of limited value. It can only be used as a second-line approach for abnormalities of the four-chamber view suspected at prenatal ultrasound. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.

Frequency of Human Immunodeficiency Virus Type-2 in Hiv Infected Patients in Maputo City, Mozambique

Virology Journal. 2011  |  Pubmed ID: 21849066

The HIV/AIDS pandemic is primarily caused by HIV-1. Another virus type, HIV-2, is found mainly in West African countries. We hypothesized that population migration and mobility in Africa may have facilitated the introduction and spreading of HIV-2 in Mozambique. The presence of HIV-2 has important implications for diagnosis and choice of treatment of HIV infection. Hence, the aim of this study was to estimate the prevalence of HIV-2 infection and its genotype in Maputo, Mozambique.HIV-infected individuals (N = 1,200) were consecutively enrolled and screened for IgG antibodies against HIV-1 gp41 and HIV-2 gp36 using peptide-based enzyme immunoassays (pepEIA). Specimens showing reactivity on the HIV-2 pepEIA were further tested using the INNO-LIA immunoblot assay and HIV-2 PCR targeting RT and PR genes. Subtype analysis of HIV-2 was based on the protease gene.After screening with HIV-2 pepEIA 1,168 were non-reactive and 32 were reactive to HIV-2 gp36 peptide. Of this total, 30 specimens were simultaneously reactive to gp41 and gp36 pepEIA while two samples reacted solely to gp36 peptide. Only three specimens containing antibodies against gp36 and gp105 on the INNO-LIA immunoblot assay were found to be positive by PCR to HIV-2 subtype A.The proportion of HIV-2 in Maputo City was 0.25% (90%CI 0.01-0.49). The HIV epidemic in Southern Mozambique is driven by HIV-1, with HIV-2 also circulating at a marginal rate. Surveillance program need to improve HIV-2 diagnosis and consider periodical survey aiming to monitor HIV-2 prevalence in the country.

Digoxin is Not a Substrate for Organic Anion-transporting Polypeptide Transporters OATP1A2, OATP1B1, OATP1B3, and OATP2B1 but is a Substrate for a Sodium-dependent Transporter Expressed in HEK293 Cells

Drug Metabolism and Disposition: the Biological Fate of Chemicals. Nov, 2011  |  Pubmed ID: 21849517

Digoxin, an orally administered cardiac glycoside cardiovascular drug, has a narrow therapeutic window. Circulating digoxin levels (maximal concentration of ∼1.5 ng/ml) require careful monitoring, and the potential for drug-drug interactions (DDI) is a concern. Increases in digoxin plasma exposure caused by inhibition of P-glycoprotein (P-gp) have been reported. Digoxin has also been described as a substrate of various organic anion-transporting polypeptide (OATP) transporters, posing a risk that inhibition of OATPs may result in a clinically relevant DDI similar to what has been observed for P-gp. Although studies in rats have shown that Oatps contribute to the disposition of digoxin, the role of OATPs in the disposition of digoxin in humans has not been clearly defined. Using two methods, Boehringer Ingelheim, GlaxoSmithKline, Pfizer, and Solvo observed that digoxin is not a substrate of OATP1A2, OATP1B1, OATP1B3, and OATP2B1. However, digoxin inhibited the uptake of probe substrates of OATP1B1 (IC(50) of 47 μM), OATP1B3 (IC(50) > 8.1 μM), and OATP2B1 (IC(50) > 300 μM), but not OATP1A2 in transfected cell lines. It is interesting to note that digoxin is a substrate of a sodium-dependent transporter endogenously expressed in HEK293 cells because uptake of digoxin was significantly greater in cells incubated with sodium-fortified media compared with incubations conducted in media in which sodium was absent. Thus, although digoxin is not a substrate for the human OATP transporters evaluated in this study, in addition to P-gp-mediated efflux, its uptake and pharmacokinetic disposition may be partially facilitated by a sodium-dependent transporter.

Muscle Type-specific Expression of Zasp52 Isoforms in Drosophila

Gene Expression Patterns : GEP. Dec, 2011  |  Pubmed ID: 21867777

Zasp52 is a member of the PDZ-LIM domain protein family in Drosophila, which comprises Enigma, ENH, ZASP, Alp, CLP36, RIL, and Mystique in vertebrates. Drosophila Zasp52 colocalizes with integrins at myotendinous junctions and with α-actinin at Z-disks, and is required for muscle attachment as well as Z-disk assembly and maintenance. Here we document 13 Zasp52 splice variants giving rise to six different LIM domains. We demonstrate stage- and tissue-specific expression in different muscle types for Zasp52 isoforms encoding different LIM domains. In particular, LIM1b is expressed only in heart muscle and certain somatic muscles, implying muscle-specific functions in Z-disk assembly or maintenance.

Effects of Upper Body Resistance Training on Pulmonary Functions in Sedentary Male Smokers

Lung India : Official Organ of Indian Chest Society. Jul, 2011  |  Pubmed ID: 21886949

Cigarette smoking is well correlated with lung diseases such as chronic obstructive pulmonary disease. It is common among men than women in India. In addition, sedentary lifestyle is associated with less efficient pulmonary function. Effectiveness of upper body resistance training (UBRT) in improving pulmonary function is unclear. Keeping all these factors in view, this study aims to examine the effect of UBRT on pulmonary function in male sedentary smokers.

Characteristics of Clinical Decision Support Alert Overrides in an Electronic Prescribing System at a Tertiary Care Paediatric Hospital

The International Journal of Pharmacy Practice. Oct, 2011  |  Pubmed ID: 21899617

CONTEXT  Electronic prescribing (EP) systems are advocated as a solution to minimise medication errors. Benefits in patient safety are often as a result of some clinical decision support (CDS) within the system. OBJECTIVE  To study the characteristics of the CDS alerts generated within a commercially available EP system in use at a tertiary care paediatric hospital in the UK. METHODS  Retrospective review and characterisation of CDS alerts recorded in the EP system over 1 year. RESULTS  A total of 16 182 conflict alerts were recorded when ordering 26 836 items, of which 3507 (13 alerts per 100 prescription orders (95% confidence interval, 12.8 to 13.6)) were visible to the user. Eighty nine percent (3119/3507) of all visible alerts were overridden by the user at point of prescribing. Drug-allergy conflict alerts were the most accepted, and exact drug duplication alerts the least. CONCLUSION  We found a high incidence of alert override, which is undesirable but consistent with that reported in the literature. The results suggest that the underlying algorithms for alert generation in many EP systems are not specific and need to be reviewed.

Diagnosis and Management of Cystic Lesions of the Pancreas

Diagnostic and Therapeutic Endoscopy. 2011  |  Pubmed ID: 21904442

Pancreatic cysts are challenging lesions to diagnose and to treat. Determining which of the five most common diagnoses-pancreatic pseudocyst, serous cystic neoplasm (SCN), solid pseudopapillary neoplasm (SPN), mucinous cystic neoplasm (MCN), and intraductal mucinous papillary neoplasm (IPMN)-is likely the correct one requires the careful integration of many historical, radiographic, laboratory, and other factors, and management is markedly different depending on the type of cystic lesion of the pancreas. Pseudocysts are generally distinguishable based on historical, clinical and radiographic characteristics, and among the others, the most important differentiation is between the mucin-producing MCN and IPMN (high risk for cancer) versus the serous SCN and SPN (low risk for cancer). EUS with FNA and cyst-fluid analysis will continue to play an important role in diagnosis. Among mucinous lesions, those that require treatment (resection currently) are any MCN, any MD IPMN, and BD IPMN larger than 3 cm, symptomatic, or with an associated mass, with the understanding that SCN or pseudocysts may be removed inadvertently due to diagnostic inaccuracy, and that a certain proportion of SPN will indeed be malignant at the time of removal. The role of ethanol ablation is under investigation as an alternative to resection in selected patients.

Acceptance, Reliability and Confidence of Reporting Fetal and Neonatal Virtuopsy As Compared to Conventional Necropsy: a Prospective Study

Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. Sep, 2011  |  Pubmed ID: 21919100

PURPOSE: To prospectively compare the acceptance of both virtuopsy and conventional autopsy and to determine the confidence with which magnetic resonance(MR) virtuopsy can report on various fetal organs. MATERIALS AND METHODS: Informed consent was obtained for this ethics committee approved study. In 96 patients and 102 fetuses following termination of pregnancy(TOP) or neonatal death, MR and/or Computer Tomography(CT) virtuopsy and conventional autopsy was offered to parents. Regression analysis was used to investigate the effect on the acceptance by parents for a virtuopsy and/or conventional autopsy of the age of the mother, gestation at termination, twinning, parity, religion, care giver taking consent and reason for death. In cases where parents consented for both MR virtuopsy and conventional autopsy, where fetuses were above or equal to 20 weeks of gestation, confidence of MR virtuopsy was determined on a scale where conventional autopsy is considered gold standard. Autopsy was classified as either "normal" or "abnormal" organs; groups were analysed separately. At virtuopsy, we used a scale (0 = definitely abnormal, 0-50 = probably abnormal, 50 = unable to comment, 50-100 = probably normal, 100 = definitely normal) to indicate confidence of each anatomical structure in both groups defined at postmortem autopsy. RESULTS: Ninety-nine % (95/96) of patients consented for virtuopsy and 62.5% (60/96) for conventional autopsy & virtuopsy. In total, 36 patients consented for virtuopsy alone. Acceptance for conventional autopsy was independently positively related to singleton pregnancies, non-Moslem patients, earlier gestation at TOP and a maternal fetal medicine specialist taking the consent. Thirty-three fetuses were at 20 weeks of gestation or more and had both conventional & MR autopsy among which 19 had full autopsy including the brain. For fetuses with normal organs at conventional autopsy, MR virtuopsy showed high confidence scores (>80) for the brain, skeleton, thoracic organs except the heart, abdominal organs except the pancreas, ureters, bladder and genitals. For abnormal fetal organs at necropsy, MR virtuopsy detected these anomalies with high confidence scores below 20 for the same organs where confidence was high when they were normal. However, in three cases, virtuopsy diagnosed additional brain anomalies than what could be seen at conventional necropsy. CONCLUSIONS: MR virtuopsy is accepted by nearly all patients while conventional autopsy is accepted by about two-third of patients and refusal depends mainly on factors on which we cannot act. Although conventional autopsy remains the gold standard, the high acceptance of virtuopsy makes it an acceptable alternative when the former is declined. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

IL-33 Exacerbates Acute Kidney Injury

Journal of the American Society of Nephrology : JASN. Nov, 2011  |  Pubmed ID: 21949094

Inflammation contributes to the pathogenesis of acute kidney injury (AKI). IL-33 is a proinflammatory cytokine, but its role in AKI is unknown. Here we observed increased protein expression of full-length IL-33 in the kidney following induction of AKI with cisplatin. To determine whether IL-33 promotes injury, we administered soluble ST2 (sST2), a fusion protein that neutralizes IL-33 activity by acting as a decoy receptor. Compared with cisplatin-induced AKI in untreated mice, mice treated with sST2 had fewer CD4 T cells infiltrate the kidney, lower serum creatinine, and reduced acute tubular necrosis (ATN) and apoptosis. In contrast, administration of recombinant IL-33 (rIL-33) exacerbated cisplatin-induced AKI, measured by an increase in CD4 T cell infiltration, serum creatinine, ATN, and apoptosis; this did not occur in CD4-deficient mice, suggesting that CD4 T cells mediate the injurious effect of IL-33. Wildtype mice that received cisplatin and rIL-33 also had higher levels of the proinflammatory chemokine CXCL1, which CD T cells produce, in the kidney compared with CD4-deficient mice. Mice deficient in the CXCL1 receptor also had lower serum creatinine, ATN, and apoptosis than wildtype mice following cisplatin-induced AKI. Taken together, IL-33 promotes AKI through CD4 T cell-mediated production of CXCL1. These data suggest that inhibiting IL-33 or CXCL1 may have therapeutic potential in AKI.

Effect of Point-of-care CD4 Cell Count Tests on Retention of Patients and Rates of Antiretroviral Therapy Initiation in Primary Health Clinics: an Observational Cohort Study

Lancet. Oct, 2011  |  Pubmed ID: 21951656

Loss to follow-up of HIV-positive patients before initiation of antiretroviral therapy can exceed 50% in low-income settings and is a challenge to the scale-up of treatment. We implemented point-of-care counting of CD4 cells in Mozambique and assessed the effect on loss to follow-up before immunological staging and treatment initiation.

Novel Paramagnetic AT1 Receptor Antagonists

Chemical Communications (Cambridge, England). Nov, 2011  |  Pubmed ID: 21963998

Novel paramagnetic selective angiotensin AT(1) receptor antagonists (sartans) bearing nitroxides (3, 4) have been prepared and their pharmacology evaluated in vitro as well as in vivo. Compounds 3, 4 proved to be effective sartans with pK(B) estimates in the range 6.2-9.1. In addition, the sodium salt (11) of 4 (R = Bu) is able to protect against vascular injury in hypertensive rats as determined by its ability to attenuate the development of intimal thickening caused by balloon injury of the carotid artery.

Implementation and Adoption of Nationwide Electronic Health Records in Secondary Care in England: Final Qualitative Results from Prospective National Evaluation in "early Adopter" Hospitals

BMJ (Clinical Research Ed.). 2011  |  Pubmed ID: 22006942

To evaluate the implementation and adoption of the NHS detailed care records service in "early adopter" hospitals in England.

Hypergastrinemia and Recurrent Type 1 Gastric Carcinoid in a Young Indian Male: Necessity for Antrectomy?

World Journal of Gastroenterology : WJG. Sep, 2011  |  Pubmed ID: 22046097

Carcinoid tumors are the most common neuroendocrine tumors. Gastric carcinoids represent 2% of all carcinoids and 1% of all gastric masses. Due to the widespread use of Esophagogastroduodenoscopy for evaluating a variety of upper gastrointestinal symptoms, the detection of early gastric carcinoids has increased. We highlight an alternative management of a young patient with recurrent type 1 gastric carcinoids with greater than 5 lesions, as well as lesions intermittently greater than 1 cm. Gastric carcinoids have a variable presentation and clinical course that is highly dependent on type. Type 1 gastric carcinoids are usually indolent and have a metastasis rate of less than 2%, even with tumors larger than 2 cm. There are a number of experts as well as organizations that recommend endoscopic resection for all type 1 gastric carcinoid lesions less than 1 cm, with a follow-up every 6-12 mo. They also recommend antrectomy for type 1 gastric carcinoids with greater than 5 lesions, lesions 1 cm or greater, or refractory anemia. However, the American Society of Gastrointestinal Endoscopy guidelines state that type 1 gastric carcinoid surveillance is controversial based on the evidence and could not make an evidence-based position statement on the best treatment modality. Our report illustrates a rare cause of iron deficiency anemia in a young male (without any medical history) due to multiple recurrent gastric carcinoid type 1 lesions in the setting of atrophic gastritis causing hypergastrinemia, and in the absence of a vitamin B12 deficiency. Gastric carcinoid type 1 can present in young males without an autoimmune history, despite the known predilection for women aged 50 to 70 years. Type 1 gastric carcinoids can be managed by endoscopic resection in patients with greater than 5 lesions, even with lesions larger than 1 cm. This course of treatment enabled the avoidance of early antrectomy in our patient, who expressed a preference against more invasive measures at his young age.

Managing Eczema in Children--a Treatment Update

The Journal of Family Practice. Nov, 2011  |  Pubmed ID: 22049348

What's the best way to manage pediatric atopic dermatitis? Do alternative remedies work? This evidence-based review--and easy-to-use treatment formula--answers these questions.

Incremental Prognostic Value of Echocardiography in Patients with Prior Mitral Valve Surgery

The Journal of Heart Valve Disease. Sep, 2011  |  Pubmed ID: 22066361

Patients with prior mitral valve surgery are at increased risk for events late after surgery. The study aim was to investigate the value of assessing clinical variables, and left and right heart anatomy and function, to predict outcome in these patients.

Renal Protection from Prolonged Cold Ischemia and Warm Reperfusion in Hibernating Squirrels

Transplantation. Dec, 2011  |  Pubmed ID: 22082817

We have previously shown that cold ischemia (CI) results in massive increases in caspase-3 activity, tubular apoptosis, and brush border injury (BBI) in mouse kidneys. During hibernation, the 13-lined ground squirrel (GS) cycles through repeated CI during torpor, followed by warm ischemia/reperfusion (WI) during interbout arousal (IBA). We sought to determine whether CI and WI during hibernation caused caspase-3 activation, tubular apoptosis, acute tubular necrosis, or BBI, and reduced renal function. We also determined whether protection was dependent on the stage of hibernation.

Matched Cohort Analysis of Outcomes of Definitive Radiotherapy for Prostate Cancer in Human Immunodeficiency Virus-Positive Patients

International Journal of Radiation Oncology, Biology, Physics. Nov, 2011  |  Pubmed ID: 22104362

PURPOSE: To compare the biochemical outcome and toxicity scores of men with human immunodeficiency virus (HIV) and prostate cancer with a matched control population with negative or unknown HIV status when treated with external-beam radiotherapy (EBRT). METHODS AND MATERIALS: A single-institution database of men with prostate cancer treated with EBRT from 1999 to 2009 was reviewed. Thirteen men with HIV were identified and matched to 2 control patients according to age, race, T stage, prostate-specific antigen level, Gleason score, RT dose, intensity-modulated RT vs. three-dimensional conformal RT, and whole-pelvis vs. prostate-only RT, for a total of 39 cases. The median follow-up time was 39 months (range, 3-110 months). RESULTS: The 4-year biochemical failure (BF)-free survival rate was 87% in the HIV-positive group vs. 89% in the controls (p = 0.94). Pre- and post-RT viral loads were found to be predictive of BF (p = 0.04 and p = 0.04, respectively). No men with HIV died, whereas 2 in the control group died of causes unrelated to prostate cancer. Acute and chronic genitourinary and gastrointestinal toxicity were less in the HIV-positive patients than in controls (p < 0.001, p < 0.001, p = 0.003, and p < 0.001, respectively). The HIV-positive men experienced an average decline in CD4 count of 193 cells/mm(3). CONCLUSIONS: Our findings suggest that men with HIV treated with EBRT have a similar risk of BF; however, high viral loads may contribute to an increased risk. This analysis supports that HIV-positive men with prostate cancer can be treated with definitive EBRT with similar disease control and toxicity outcomes as in the general population.

BSEP Inhibition - In Vitro Screens to Assess Cholestatic Potential of Drugs

Toxicology in Vitro : an International Journal Published in Association with BIBRA. Nov, 2011  |  Pubmed ID: 22120137

Bile salt export pump (BSEP, ABC11) is a membrane protein that is localized in the cholesterol-rich canalicular membrane of hepatocytes. Its function is to eliminate unconjugated and conjugated bile acids/salts from hepatocyte into the bile. In humans there is no compensatory mechanism for the loss of this transporter. Mutations of BSEP result in a genetic disease, called progressive familial intrahepatic cholestasis type 2 (PFIC2), that is characterized with decreased biliary bile salt secretion, leading to decreased bile flow and accumulation of bile salts inside the hepatocyte, inflicting damage. BSEP inhibitor drugs produce similar bile salt retention that may lead to severe cholestasis and liver damage. Drug-induced liver injury is a relevant clinical issue, in severe cases ending in liver transplantation. Therefore, measurement of BSEP inhibition by candidate drugs has high importance in drug discovery and development. Although several methods are suitable to detect BSEP-drug interactions, due to interspecies differences in bile acid composition, differences in hepatobiliary transporter modulation, they have limitations. This review summarizes appropriate in vitro methods that could be able to predict BSEP-drug candidate interactions in humans before the start of clinical phases.

ABCG2 Modulates Chlorothiazide Permeability in Vitro - Characterization of the Interaction

Drug Metabolism and Pharmacokinetics. Nov, 2011  |  Pubmed ID: 22123130

We are showing that chlorothiazide, a diuretic is an ABCG2 substrate. It is a Biopharmaceutics Classification System / Biopharmaceutics Drug Distribution and Classification System (BCS / BDDCS) Class IV drug with low bioavailability. Therefore, we tested if chlorothiazide interacts with major apically located intestinal efflux transporters. Our data show that chlorothiazide is transported by ABCG2 with a K(m) value of 334.6 µM and does not interact with ABCB1, ABCC2. The chlorothiazide - ABCG2 interaction results in a vectorial transport in MDCKII-BCRP and Caco-2 cells with efflux ratios of 36 and 8.1 respectively. Inhibition of ABCG2 in Caco-2 cells reduced the efflux ratio to 1.4 suggesting that ABCG2 plays a role in limiting chlorothiazide bioavailability in humans.

D2-40 is Expressed on the Luminal Surface of Pulmonary Airspaces in Normal Developing and Adult Lung but is Lost in Conditions Associated with Intra-alveolar Infiltrates

Pediatric and Developmental Pathology : the Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society. Dec, 2011  |  Pubmed ID: 22150577

Abstract The D2-40 antigen is a glycosylated sialomucin that is strongly expressed by lymphatic endothelial cells. Recently we also observed the expression of D2-40 on the luminal surface of pulmonary airspaces in sections of lung. The aim of the study was to assess the expression of D2-40 antigen in normal lung development and in various pathological conditions in which abnormal alveolar infiltrates were present. Formalin-fixed lung tissue was selected from 42 fetal/neonatal autopsy cases ranging in gestational age from 12 to 41 weeks and from 10 adult lungs. In the fetal/neonatal group, 22 cases were histologically normal, whereas 20 were abnormal (including cases of pneumonia, alveolar hemorrhage, meconium aspiration, pulmonary hypoplasia and pulmonary interstitial emphysema). In the adult group, 5 cases were histologically normal and 5 had pneumonia. Immunohistochemical staining was performed on all cases using antibody to D2-40. All cases of normal fetal/neonatal lung and normal adult lung showed diffuse strong expression of D2-40 on the luminal surface of the alveolar lining cells. D2-40 expression was also noted on the bronchiolar lining cells of normal fetal/neonatal lung. In all cases where there was an abnormal infiltrate or foreign material within the airspaces, expression of D2-40 was lost in the alveolar lining. The production of the D2-40 antigen in the alveolar lining occurs as early as 12 weeks gestation and continues to be present throughout all other stages of lung development as well as in adult lung. These results suggest that D2-40 may have a cell membrane protective function.

Multifunctional PEGylated 2C5-immunoliposomes Containing PH-sensitive Bonds and TAT Peptide for Enhanced Tumor Cell Internalization and Cytotoxicity

Journal of Controlled Release : Official Journal of the Controlled Release Society. Dec, 2011  |  Pubmed ID: 22182771

pH-sensitive PEGylated (with PEG-PE) long-circulating liposomes (HSPC:cholesterol and Doxil®), modified with cell-penetrating TAT peptide (TATp) moieties and cancer-specific mAb 2C5 were prepared. A degradable pH-sensitive hydrazone bond between a long shielding PEG chains and PE (PEG(2k)-Hz-PE) was introduced. TATp was conjugated with a short PEG(1k)-PE spacer and mAb 2C5 was attached to a long PEG chain (2C5-PEG(3.4k)-PE). The "shielding" effect of TATp by long PEG chains was investigated using three liposomal models. At normal pH, surface TATp moieties are "hidden" by the long PEG chains. Upon the exposure to lowered pH, this multifunctional carrier exposes TATp moieties after the degradation of the hydrazone bond and removal of the long PEG chains. Enhanced cellular uptake of the TATp-containing immunoliposomes was observed in vitro after pre-treatment at lowered pH (using flow cytometry and fluorescence microscopy techniques). The presence of mAb 2C5 on the liposome surface further enhanced the interaction between the carrier and tumor cells but not normal cells. Furthermore, multifunctional immuno-Doxil® preparation showed increased cellular cytotoxicity of B16-F10, HeLa and MCF-7 cells when pre-incubated at lower pH, indicating TATp exposure and activity. In conclusion, a multifunctional immunoliposomal nanocarrier containing a pH-sensitive PEG-PE component, TATp, and the cancer cell-specific mAb 2C5 promotes enhanced cytotoxicity and carrier internalization by cancer cells and demonstrates the potential for intracellular drug delivery after exposure to lowered pH environment, typical of solid tumors.

Respiratory Infections Increase the Risk of Granulation Tissue Formation Following Airway Stenting in Patients with Malignant Airway Obstruction

Chest. Dec, 2011  |  Pubmed ID: 22194585

Abstract BACKGROUND:The most serious complications of airway stenting are long term, including infection and granulation tissue formation. However, no studies have quantified the incidence rate of long term complications for different stents. METHODS:To compare the incidence of complications of different airway stents, we conducted a retrospective cohort study of all patients at our institution that had airway stenting for malignant airway obstruction from January 2005 to August 2010. Patients were excluded if more than one type of stent was in place at the same time. Complications recorded were lower respiratory tract infections, stent migration, granulation tissue, mucus plugging requiring intervention, tumor overgrowth, and stent fracture.Measurements and Main RESULTS:One hundred seventy-two patients with 195 stent procedures were included. Aero® stents were associated with an increased risk of infection (HR=1.98; 95% CI, 1.03-3.81; P=0.041). Dumon™ silicone tube stents had an increased risk of migration (HR=3.52; 95% CI, 1.41-8.82; P=0.007). Silicone stents (HR=3.32; 95% CI, 1.59-6.93; P=0.001) and lower respiratory tract infections (HR=5.69; 95% CI, 2.60-12.42; P<0.001) increased the risk of granulation tissue. Lower respiratory tract infections were associated with decreased survival (HR=1.57; 95% CI, 1.11-2.21; P=0.011). CONCLUSIONS:Significant differences exist among airway stents in terms of infection, migration, and granulation tissue formation. These complications, in turn, are associated with significant morbidity and mortality. Granulation tissue formation develops because of repetitive motion trauma and infection.

Increased Mortality Among Hispanic Testis Cancer Patients Independent of Neighborhood Socioeconomic Status: a SEER Study

Journal of Immigrant and Minority Health / Center for Minority Public Health. Oct, 2011  |  Pubmed ID: 21140218

Testis cancer-specific survival (CSS) varies by Hispanic ethnicity. Our goal was to assess whether neighborhood socioeconomic status (SES) accounts for elevated testis CSS among Hispanic patients. We queried the Surveillance, Epidemiology, and End Results (SEER) database for Hispanic (HW) and Non-Hispanic white (NHW) patients. Multivariate Cox regression analyses evaluated Hispanic ethnicity's impact on tCSS while adjusting for neighborhood socioeconomic status (education and income levels). HWs constituted 14.3% of the 26,258 patients in the cohort. Neighborhood SES factors such as county income (P < 0.001) and education level (P < 0.001) were significant predictors of testis cancer-specific survival (tCSS). Controlling for SES and other variables, Hispanic ethnicity remained a significant predictor of tCSS. Compared to NHWs, HWs experienced a 41% greater cancer-specific mortality (HR: 1.406, 95% CI: 1.178-1.678, P < 0.001). The mechanism underlying the increased testis cancer mortality experienced by Hispanic patients remains unknown.

Microsecond Scale Replica Exchange Molecular Dynamic Simulation of Villin Headpiece: an Insight into the Folding Landscape

Journal of Biomolecular Structure & Dynamics. Jun, 2011  |  Pubmed ID: 21469746

Reaching the experimental time scale of millisecond is a grand challenge for protein folding simulations. The development of advanced Molecular Dynamics techniques like Replica Exchange Molecular Dynamics (REMD) makes it possible to reach these experimental timescales. In this study, an attempt has been made to reach the multi microsecond simulation time scale by carrying out folding simulations on a three helix bundle protein, Villin, by combining REMD and Amber United Atom model. Twenty replicas having different temperatures ranging from 295 K to 390 K were simulated for 1.5 µs each. The lowest Root Mean Square Deviation (RMSD) structure of 2.5 Å was obtained with respect to native structure (PDB code 1VII), with all the helices formed. The folding population landscapes were built using segment-wise RMSD and Principal Components as reaction coordinates. These analyses suggest the two-stage folding for Villin. The combination of REMD and Amber United Atom model may be useful to understand the folding mechanism of various fast folding proteins.

The Neglected and Often Ignored: Nontuberculous Mycobacteria

Journal of Global Infectious Diseases. Jan, 2011  |  Pubmed ID: 21572618

Apoptosis and Autophagy in Cold Preservation Ischemia

Transplantation. Jun, 2011  |  Pubmed ID: 21577181

Prolonged cold ischemia (CI) is a risk factor for the development of delayed graft function that predicts reduced 5-year kidney transplant survival. CI results in caspase-3 activation, tubular injury, and apoptosis. Autophagy, a highly conserved pathway that permits recycling of nutrients within the cell during stress, is linked to apoptosis. We hypothesized that CI during kidney preservation would induce autophagy. We sought to determine apoptosis and autophagic flux in CI.

The ABCD and ABCD2 Scores and the Risk of Stroke Following a TIA: A Narrative Review

ISRN Neurology. 2011  |  Pubmed ID: 22389822

The California, ABCD, and ABCD2 risk scores (ABCD system) were developed to help stratify short-term stroke risk in patients with TIA (transient ischemic attack). Beyond this scope, the ABCD system has been extensively used to study other prognostic information such as DWI (diffusion-weighted imaging) abnormalities, large artery stenosis, atrial fibrillation and its diagnostic accuracy in TIA patients, which are independent predictors of subsequent stroke in TIA patients. Our comprehensive paper suggested that all scores have and equivalent prognostic value in predicting short-term risk of stroke; however, the ABCD2 score is being predominantly used at most centers. The majority of studies have shown that more than half of the strokes in the first 90 days, occur in the first 7 days. The majority of patients studied were predominantly classified to have a higher ABCD/ABCD2 > 3 scores and were particularly at a higher short-term risk of stroke or TIA and other vascular events. However, patients with low risk ABCD2 score < 4 may have high-risk prognostic indicators, such as diffusion weighted imaging (DWI) abnormalities, large artery atherosclerosis (LAA), and atrial fibrillation (AF). The prognostic value of these scores improved if used in conjunction with clinical information, vascular imaging data, and brain imaging data. Before more data become available, the diagnostic value of these scores, its applicability in triaging patients, and its use in evaluating long-term prognosis are rather secondary; thus, indicating that the primary significance of these scores is for short-term prognostic purposes.

High-Dose Radiotherapy With or Without Androgen Deprivation Therapy for Intermediate-Risk Prostate Cancer: Cancer Control and Toxicity Outcomes

International Journal of Radiation Oncology, Biology, Physics. Jan, 2012  |  Pubmed ID: 22245201

PURPOSE: To evaluate the impact of short-course androgen deprivation therapy (ADT) on cancer control outcomes and toxicity in intermediate-risk prostate cancer treated with dose-escalated external beam radiotherapy (high-dose radiotherapy [HDRT]). METHODS AND MATERIALS: Demographic, disease, and treatment characteristics of prostate cancer patients at 2 institution consortiums were charted. Of 296 men with intermediate-risk prostate cancer (defined as ≥T2b, prostate-specific antigen level >10 ng/mL, or Gleason score [GS] of 7, with none of the following: ≥T3, prostate-specific antigen level >20 ng/mL, GS ≥8, or positive nodes) treated with HDRT to a dose of 72 Gy or greater, 123 received short-course ADT and 173 did not. Univariate and multivariate analyses on biochemical failure-free survival (BFFS) (including subset analysis by disease factors) and on overall survival (OS) were performed, as were comparisons of gastrointestinal (GI) and genitourinary (GU) toxicity rates. RESULTS: For the whole group, the median dose was 75.6 Gy; the minimum follow-up was 2 years, and the median follow-up was 47.4 months. For ADT vs. no ADT, the 5-year BFFS rate was 86% vs. 79% (p = 0.138) and the 5-year OS rate was 87% vs. 80% (p = 0.159). On multivariate analysis, percent positive cores (PPC) (p = 0.002) and GS (p = 0.008) were significantly associated with BFFS, with ADT showing a trend (p = 0.055). The impact of ADT was highest in the subsets with PPC greater than 50% (p = 0.019), GS 4+3 (p = 0.078), and number of risk factors greater than 1 (p = 0.022). Only intensity-modulated radiotherapy use (p = 0.012) and GS (p = 0.023) reached significance for OS, and there were no significant differences in GU or GI toxicity. CONCLUSIONS: Although the use of ADT with HDRT did not influence BFFS, our study suggests a benefit in patients with PPC greater than 50%, GS 4+3, or multiple risk factors. No OS benefit was shown, and ADT was not associated with additional radiotherapy-related GI or GU toxicity.

Ultrasound-guided Core-needle Biopsy and Magnetic Resonance Imaging in the Accurate Diagnosis of Intramuscular Haemangiomas of the Head and Neck

The Journal of Laryngology and Otology. Apr, 2012  |  Pubmed ID: 22258504

Introduction:Intramuscular haemangiomas of the digastric muscle are often misdiagnosed due to their low incidence and non-specific manifestation. Only two out of six previously reported cases were diagnosed correctly before excision. Ultrasound may not reveal their vascularity, and fine-needle aspiration biopsy is unhelpful as it reveals only blood.Methods:A case of intramuscular haemangioma of the posterior belly of the digastric muscle is described. Previously reported cases are reviewed. Investigations used to diagnose the lesions and reasons for their common failure are discussed.Results:Core-needle biopsy led to the correct histological diagnosis, and magnetic resonance imaging precisely located the lesion within the digastric muscle.Conclusion:Core-needle biopsy was safely used in the diagnosis of an intramuscular haemangioma. The combination of core-needle biopsy and meticulous review of magnetic resonance imaging enables accurate diagnosis pre-operatively.

Evaluation of a High-Throughput Diagnostic System for Detection of HIV-1 in Dried Blood Spot Samples from Infants in Mozambique

Journal of Clinical Microbiology. Apr, 2012  |  Pubmed ID: 22278838

We performed a comparative analysis between Roche Amplicor HIV-1 DNA test and CAPTAQ assay for the detection of HIV in 830 dried blood spot (DBS) pediatric samples collected in Mozambique. Our results demonstrated no statistical difference between these assays. The CAPTAQ assay approached nearly 100% repeatability/accuracy. The increased throughput of testing with minimal operator interference in performing the CAPTAQ assay clearly demonstrated that this method is an improvement over the Roche Amplicor HIV-1 DNA test, version 1.5.

Depletion of Macrophages and Dendritic Cells in Ischemic Acute Kidney Injury

American Journal of Nephrology. 2012  |  Pubmed ID: 22286667

Background: Inflammation is thought to play a role in ischemic acute kidney injury (AKI). We have demonstrated that macrophage and dendritic cell depletion, using liposome-encapsulated clodronate (LEC), is protective against ischemic AKI. Methods: To determine whether macrophages or dendritic cells or both play a role in ischemic AKI, we performed ischemic AKI in CD11b-DTR mice that have a diphtheria toxin (DT)-induced depletion of CD11b cells (macrophages) and CD11c-DTR mice that have a DT-induced depletion of CD11c cells (dendritic cells). Results: While LEC-treated animals had a significant functional protection from AKI, CD11b-DTR and CD11c-DTR mice were not protected against AKI despite a similar degree of renal macrophage and dendritic cell depletion. Proinflammatory cytokines are known to play a role in ischemic AKI. To determine the possible reasons for the lack of protection in CD11b-DTR and CD11c-DTR mice compared to LEC-treated mice, 32 cytokines/chemokines were measured in these mice. Of the cytokines/chemokines measured, IL-6, MCP-1, GMCSF, IL-1β and CXCL1 (also known as IL-8 in humans or KC in mice) showed significant differences in the LEC-treated, CD11b-DTR and CD11c-DTR mice. MCP-1 and CXCL1 (known mediators of AKI), and also GMCSF and IL-1β were increased in AKI and decreased in LEC-treated AKI but not AKI in CD11b-DTR or CD11c-DTR mice. Conclusions: These findings suggest that LEC-mediated protection from AKI is not simply mediated by depletion of renal macrophage or dendritic cell subpopulations. Protection against AKI in LEC-treated compared to CD11b-DTR or CD11c-DTR mice may be partially explained by differences in proinflammatory cytokine profiles.

Patient Enablement Requires Physician Empathy: a Cross-sectional Study of General Practice Consultations in Areas of High and Low Socioeconomic Deprivation in Scotland

BMC Family Practice. Feb, 2012  |  Pubmed ID: 22316293

ABSTRACT: BACKGROUND: Patient 'enablement' is a term closely aligned with 'empowerment' and its measurement in a general practice consultation has been operationalised in the widely used patient enablement instrument (PEI), a patient-rated measure of consultation outcome. However, there is limited knowledge regarding the factors that influence enablement, particularly the effect of socio-economic deprivation. The aim of the study is to assess the factors influencing patient enablement in GP consultations in areas of high and low deprivation. METHODS: A questionnaire study was carried out on 3,044 patients attending 26 GPs (16 in areas of high socio-economic deprivation and 10 in low deprivation areas, in the west of Scotland). Patient expectation (confidence that the doctor would be able to help) was recorded prior to the consultation. PEI, GP empathy (measured by the CARE Measure), and a range of other measures and variables were recorded after the consultation. Data analysis employed multi-level modelling and multivariate analyses with the PEI as the dependant variable. RESULTS: Although numerous variables showed a univariate association with patient enablement, only four factors were independently predictive after multilevel multivariate analysis; patients with multimorbidity of 3 or more long-term conditions (reflecting poor chronic general health), and those consulting about a long-standing problem had reduced enablement scores in both affluent and deprived areas. In deprived areas, emotional distress (GHQ-caseness) had an additional negative effect on enablement. Perceived GP empathy had a positive effect on enablement in both affluent and deprived areas. Maximal patient enablement was never found with low empathy. CONCLUSIONS: Although other factors influence patient enablement, the patients' perceptions of the doctors' empathy is of key importance in patient enablement in general practice consultations in both high and low deprivation settings.

Lung Function at Follow-up of Infants with Surgically Correctable Anomalies

Pediatric Pulmonology. Feb, 2012  |  Pubmed ID: 22328362

Infants with congenital diaphragmatic hernia (CDH) or anterior wall defects (AWD) can suffer abnormal antenatal lung growth, the risk, however, may be greater for CDH infants. The objectives of this study were to test the hypothesis that following surgical correction, CDH infants would have worse lung function at follow-up than AWD infants and to determine whether fetal lung volume (FLV) results correlated with the lung function results at follow-up. Thirteen infants with CDH and 13 infants with AWD had lung function measurements at a median age of 11 (range 6-24) months; 17 of the infants had had their FLV assessed. Lung function was assessed by plethysmographic measurement of lung volume (FRCpleth) and airway resistance (Raw). In addition, functional residual capacity was assessed by a helium gas dilution technique (FRCHe); tidal breathing parameters (T(PTEF) :Te) and compliance and resistance of the respiratory system (Crs and Rrs, respectively) were also determined. FLV was assessed using three-dimensional (3D) ultrasound and virtual organ computer aided analysis. The CDH compared to the AWD infants had a higher median FRCpleth (41 ml/kg vs. 37 ml/kg, P = 0.043) and a lower median Crs (1.45 ml/cm H(2) O/kg vs. 2.78 ml/cm H(2) O/kg, P = 0.041). FRCpleth results correlated significantly with FLV results (r = 0.721, P < 0.001). In conclusion, infants with CDH had significantly different lung function at follow-up than AWD infants. Our findings suggest FLV results may predict lung function abnormalities at follow-up in infants with surgically correctable anomalies. Pediatr Pulmonol. © 2012 Wiley Periodicals, Inc.

Referral Proformas Improve Compliance to National Colorectal Two-week Wait Targets: Does This Impact on Cancer Detection Rates?

Colorectal Disease : the Official Journal of the Association of Coloproctology of Great Britain and Ireland. Feb, 2012  |  Pubmed ID: 22360704

Aim:  To facilitate implementation of National Institute for Health and Clinical Excellence (NICE) guidelines for urgent colorectal cancer referral, local cancer networks have promoted the use of standardised proformas in primary care. This clinical audit assessed proforma use within the Thames Valley Cancer Network (TVCN) to see whether increased proforma use was associated with higher compliance to NICE guidelines and higher cancer detection rates. Method:  All lower bowel cancer two-week wait referrals to the six Acute NHS Trusts in the TVCN received during the month of June 2010 were identified, anonymised and analysed in relation to colorectal cancer detection rates. Results:  Of the 586 referrals audited, proforma usage varied significantly across the six Acute NHS Trusts from 18% to 96%. Referral letters from primary care had NICE compliance ranging from 30%-50%.In those which receiced a referral protocol, 50%-90% were NICE compliant. Proforma use was associated with higher cancer detection rates (P=0.03). Conclusion:  These results have wide-ranging implications since they suggest that the adoption of a simple proforma in primary care can improve the effectiveness of referral for suspected cancer. © 2012 The Authors Colorectal Disease © 2012 The Association of Coloproctology of Great Britain and Ireland.

Direct Drug Susceptibility Testing of Mycobacterium Tuberculosis for Rapid Detection of Multidrug Resistance Using the Bactec MGIT 960 System: a Multicenter Study

Journal of Clinical Microbiology. Feb, 2012  |  Pubmed ID: 22162558

Conventional indirect drug susceptibility testing of Mycobacterium tuberculosis with liquid medium is well established and offers time-saving and reliable results. This multicenter study was carried out to evaluate if drug susceptibility testing (DST) can be successfully carried out directly from processed smear-positive specimens (direct DST) and if this approach could offer substantial time savings. Sputum specimens were digested, decontaminated, and concentrated by the laboratory routine procedure and were inoculated in Bactec MGIT 960 as well as Lowenstein-Jensen (LJ) medium for primary isolation. All the processed specimens which were acid-fast bacterium (AFB) smear positive were used for setting up direct DST for isoniazid (INH) and rifampin (RIF). After the antimicrobial mixture of polymyxin B, amphotericin B, nalidixic acid, trimethoprim, and azlocillin (PANTA) was added, the tubes were entered in the MGIT 960 instrument using the 21-day protocol (Bactec 960 pyrazinamide [PZA] protocol). Results obtained by direct DST were compared with those obtained by indirect DST to establish accuracy and time savings by this approach. Of a total of 360 AFB smear-positive sputum specimens set up for direct DST at four sites in three different countries, 307 (85%) specimens yielded reportable results. Average reporting time for direct DST was 11 days (range, 10 to 12 days). The average time savings by direct DST compared to indirect DST, which included time to isolate a culture and perform DST, was 8 days (range, 6 to 9 days). When results of direct DST were compared with those of indirect DST, there was 95.1% concordance with INH and 96.1% with rifampin. These findings indicate that direct DST with the Bactec MGIT 960 system offers further time savings and is a quick method to reliably detect multidrug resistance (MDR) cases.

The Effects of Anti-inflammatory and Anti-angiogenic DNA Vaccination on Diabetic Nephropathy in Rats

Human Gene Therapy. Feb, 2012  |  Pubmed ID: 21939398

Inflammation and angiogenesis play a crucial role in the pathomechanism of diabetic nephropathy. Monocyte chemoattractant protein 1 (MCP) is a key regulator of the immune system in kidneys, and its inhibition with a dominant-negative mutant lacking the N-terminal amino acids 2-8 (7ND) reduces renal fibrosis. Angiomotin (Amot) is a novel angiogenesis modulator. We studied the effects of inhibition of Amot and MCP using DNA vaccination on incipient diabetic nephropathy in rats. Plasmid DNA (with either 7ND or human Amot) was electroporated twice into hind-limb muscles of rats with streptozotocin-induced diabetes mellitus. Sham-electroporated diabetic rats and healthy animals served as controls. After 4 months, renal histology and biochemical analyses were performed. In sham-electroporated diabetic rats, glomerular histology revealed pathological changes. 7ND and Amot treatments reduced glomerular hypertrophy and periodic acid-Schiff positivity. In both treated groups, the expression of profibrotic (transforming growth factor-β, collagen 1), proinflammatory (interleukin-6, tumor necrosis factor-α), and proangiogenic (vascular endothelial growth factor) genes in the renal cortex was lower than in the diabetic group without treatment. The mentioned renoprotective effects could be mediated via higher total antioxidant capacity and improved glycemic control. Anti-angiogenic and anti-inflammatory DNA vaccination ameliorates the progression of glomerular pathology in an animal model of diabetic nephropathy.

Prostate Intrafraction Translation Margins for Real-time Monitoring and Correction Strategies

Prostate Cancer. 2012  |  Pubmed ID: 22111005

The purpose of this work is to determine appropriate radiation therapy beam margins to account for intrafraction prostate translations for use with real-time electromagnetic position monitoring and correction strategies. Motion was measured continuously in 35 patients over 1157 fractions at 5 institutions. This data was studied using van Herk's formula of (αΣ + γσ') for situations ranging from no electromagnetic guidance to automated real-time corrections. Without electromagnetic guidance, margins of over 10 mm are necessary to ensure 95% dosimetric coverage while automated electromagnetic guidance allows the margins necessary for intrafraction translations to be reduced to submillimeter levels. Factors such as prostate deformation and rotation, which are not included in this analysis, will become the dominant concerns as margins are reduced. Continuous electromagnetic monitoring and automated correction have the potential to reduce prostate margins to 2-3 mm, while ensuring that a higher percentage of patients (99% versus 90%) receive a greater percentage (99% versus 95%) of the prescription dose.

Lung-to-head Ratio: a Need to Unify the Technique

Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. Jan, 2012  |  Pubmed ID: 22213615

Fetal Surgery for Severe Congenital Diaphragmatic Hernia?

Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. Jan, 2012  |  Pubmed ID: 22213616

An Unusual Cause of Abdominal Pain

Journal of Pediatric Gastroenterology and Nutrition. Jan, 2012  |  Pubmed ID: 22258290

Functional and Structural Characterization of the Mammalian TREX-2 Complex That Links Transcription with Nuclear Messenger RNA Export

Nucleic Acids Research. Feb, 2012  |  Pubmed ID: 22307388

Export of messenger RNA (mRNA) from the nucleus to the cytoplasm is a critical step in the gene expression pathway of eukaryotic cells. Here, we report the functional and structural characterization of the mammalian TREX-2 complex and show how it links transcription/processing with nuclear mRNA export. Mammalian TREX-2 is based on a germinal-centre associated nuclear protein (GANP) scaffold to which ENY2, PCID2 and centrins bind and depletion of any of these components inhibits mRNA export. The crystal structure of the GANP:ENY2 complex shows that two ENY2 chains interact directly with GANP, but they have different orientations from those observed on yeast Sac3. GANP is required to recruit ENY2 to nuclear pore complexes (NPCs), but ENY2 is not necessary to recruit GANP, which requires both its CID and MCM3AP domains, together with nucleoporin Nup153. GANP and ENY2 associate with RNA polymerase II and inhibition of mRNA processing redistributes GANP from NPCs into nuclear foci indicating that mammalian TREX-2 is associated with transcription. Thus, we implicate TREX-2 as an integral component of the mammalian mRNA export machinery where it links transcription and nuclear export by facilitating the transfer of mature mRNPs from the nuclear interior to NPCs.

Signaling Molecules in the Fetal Rabbit Model for Congenital Diaphragmatic Hernia

Pediatric Pulmonology. Feb, 2012  |  Pubmed ID: 22328320

RATIONALE AND OBJECTIVES: Little is known about molecular changes in lungs of fetal rabbits with surgically induced diaphragmatic hernia (DH). Therefore, we examined in this model gene expressions of pivotal molecules for the developing lung. METHODS: At day 23 of gestation, DH was created in 12 fetuses from 4 does. Both lungs from six live DH fetuses and from six unoperated controls were harvested and weighed at term. Transcription of 15 genes involved in alveolarization, angiogenesis, regulation of vascular tone, or epithelial maturation was investigated by real-time quantitative polymerase chain reaction. MAIN RESULTS: DH decreased lung-to-body weight ratio (P < 0.001). A bilateral downregulation was seen for genes encoding for tropoelastin (P < 0.01), lysyl oxidase (P < 0.05), fibulin 5 (P < 0.05), and cGMP specific phosphodiesterase 5 (P < 0.05). Lower mRNA levels for endothelial nitric oxide synthase occurred in the ipsilateral lung (P < 0.05). CONCLUSIONS: Experimental DH in fetal rabbits disrupted transcription of genes implicated in lung growth and function. Similarities with the human disease make this model appropriate for investigation of new prenatal therapies. Pediatr Pulmonol. © 2012 Wiley Periodicals, Inc.

A Comprehensive Review of Incidence and Survival in Patients with Rare Histological Variants of Prostate Cancer in the United States from 1973 to 2008

Prostate Cancer and Prostatic Diseases. Feb, 2012  |  Pubmed ID: 22349984

Background:The American Joint Commission on Cancer (AJCC) identifies five rare variants of prostate adenocarcinoma: mucinous, ductal, signet ring cell, adenosquamous and neuroendocrine including small cell. No prior study has comprehensively detailed incidence and outcomes for all AJCC variants of prostate cancer.Methods:We used the Surveillance, Epidemiology and End Results (SEER) program to analyze prostate cancers diagnosed from 1973 to 2008. Cases of mucinous, ductal, signet ring cell, adenosquamous and neuroendocrine carcinoma were identified, along with cases of non-variant adenocarcinoma for comparison. Age-adjusted incidence rates (IRs) and overall survival (OS) were evaluated and stratified by race, age, stage and PSA. All IRs represent the number of cases per million people per year.Results:Each variant is rare, with IRs between 0.03 (adenosquamous) and 0.61 (mucinous). There was a significant difference in incidence between Caucasian and African American patients with mucinous adenocarcinoma. Median OS varied ranged from 10.0 months in neuroendocrine carcinoma to 125.0 months in mucinous adenocarcinoma. In all, 5-year OS ranged from 12.6% in neuroendocrine carcinoma to 75.1% in mucinous adenocarcinoma. There was a significant difference in survival between Caucasian and African American patients for mucinous adenocarcinoma (median survival 144.0 vs 99.0 months, P<0.01). African American patients with mucinous adenocarcinoma also presented with more advanced stage disease compared with Caucasian patients. Multivariate analysis demonstrated that African American race was not associated with worse survival when corrected for stage.Conclusions:There are differences in IRs and OS among rare variants of prostate cancer. For mucinous adenocarcinoma, there are significant differences in incidence and survival between Caucasian and African American patients. These differences should be considered in clinical decision making for patients with these malignancies.Prostate Cancer and Prostatic Diseases advance online publication, 21 February 2012; doi:10.1038/pcan.2012.4.

Comment on "Tracing the Sources of Water Using Stable Isotopes: First Results Along the Mangalore-Udupi Region, South-west Coast of India"

Rapid Communications in Mass Spectrometry : RCM. Apr, 2012  |  Pubmed ID: 22368069

Abatacept in the Long-term Treatment of Rheumatoid Arthritis

Expert Review of Clinical Immunology. Mar, 2012  |  Pubmed ID: 22390487

Evaluation of: Kremer JM, Russell AS, Emery P et al. Long-term safety, efficacy and inhibition of radiographic progression with abatacept treatment in patients with rheumatoid arthritis and an inadequate response to methotrexate: 3-year results from the AIM trial. Ann. Rheum. Dis. 70(10), 1826-1830 (2011). The last decade has been an era of exciting and innovative therapeutic targets in the treatment of moderate-to-severe rheumatoid arthritis. One such treatment that acts by disrupting T-cell activation is abatacept, which is currently used in patients who have had an inadequate clinical response to traditional disease-modifying drugs or anti-TNF therapies. As newer therapies emerge, issues that need addressing include: long-term drug tolerance, adverse events, sustained clinical response, prevention of progression in structural damage and retention rates. In this article we discuss a recently published paper by Kremer et al. that reported 3-year data on safety, efficacy and radiographic progression in patients enrolled in a clinical trial of abatacept, as well as the advantages and limitations of long-term extension studies.

Early Dynamic PET/CT and 18F-FDG Blood Flow Imaging in Bladder Cancer Detection: A Novel Approach

Clinical Nuclear Medicine. Apr, 2012  |  Pubmed ID: 22391706

: The standard PET/CT and F-FDG scanning protocols for patients with cancer call for data acquisitions to start 50 to 60 minutes postinjection (PI) of the radiopharmaceutical. This prolonged incubation period allows the concentration of high activity tracer to accumulate in the urinary bladder rendering identification of bladder lesions very difficult, if not impossible. The objective of this study was to identify bladder cancer using a novel PET/CT and F-FDG scanning protocol that takes advantage of the angiogenesis observed in malignancies and the kidneys' physiology of delayed excretion of F-FDG into the urinary bladder.

Efflux Transporters in the Blood-brain Interfaces - in Vitro and in Vivo Methods and Correlations

Expert Opinion on Drug Metabolism & Toxicology. Apr, 2012  |  Pubmed ID: 22394316

Introduction: Sufficient brain exposure is crucial to the success of CNS drugs. The twofold greater attrition rate in clinical development of CNS drugs over the respective attrition rate of non-CNS drugs is due to lack of efficacy. It is generally thought that poor brain exposure is at least partly responsible for this, as the concentration-time profile at the brain target site is critical for efficacy. Efflux transporters in the blood-brain interfaces play a crucial role in modulation of permeability of drugs across these interfaces. Validation of preclinical tools to correctly predict brain exposure in humans is essential. Areas covered: This review summarizes in vitro and in vivo tools to detect and characterize interactions of drugs with efflux transporters relevant to blood-brain interfaces. Furthermore, the article discusses the strengths and weaknesses of these methods and the limitations of their application, in addition to covering in vitro - in vivo correlations. Expert opinion: A more detailed validation of in vitro efflux transporter assays employing primary brain endothelial cultures is needed. This should go along with mapping uptake transporters expressed in the blood-brain interfaces. With the availability of specific inhibitors, utilization of in vivo methods such as brain microdialysis is increasing. Once transporter-humanized mice are available, we may witness a further increase in applications of in vivo methods.

Computational Design of Targeted Inhibitors of Polo-like Kinase 1 (plk1)

Bioinformatics and Biology Insights. 2012  |  Pubmed ID: 22399850

Computational design of small molecule putative inhibitors of Polo-like kinase 1 (Plk1) is presented. Plk1, which regulates the cell cycle, is often over expressed in cancers. Down regulation of Plk1 has been shown to inhibit tumor progression. Most kinase inhibitors interact with the ATP binding site on Plk1, which is highly conserved. This makes the development of Plk1-specific inhibitors challenging, since different kinases have similar ATP sites. However, Plk1 also contains a unique region called the polo-box domain (PBD), which is absent from other kinases. In this study, the PBD site was used as a target for designed Plk1 putative inhibitors. Common structural features of several experimentally known Plk1 ligands were first identified. The findings were used to design small molecules that specifically bonded Plk1. Drug likeness and possible toxicities of the molecules were investigated. Molecules with no implied toxicities and optimal drug likeness values were used for docking studies. Several molecules were identified that made stable complexes only with Plk1 and LYN kinases, but not with other kinases. One molecule was found to bind exclusively the PBD site of Plk1. Possible utilization of the designed molecules in drugs against cancers with over expressed Plk1 is discussed.

Structural Basis for the Assembly and Disassembly of MRNA Nuclear Export Complexes

Biochimica Et Biophysica Acta. Mar, 2012  |  Pubmed ID: 22406340

Most of the individual components of the nuclear elements of the gene expression pathway have been identified and high-resolution structural information is becoming available for many of them. Information is also starting to become available on the larger complexes they form and is beginning to give clues about how the dynamics of their interactions generate function. Although the translocation of export-competent messenger ribonucleoprotein particles (mRNPs) through the nuclear pore transport channel that is mediated by interactions with nuclear pore proteins (nucleoporins) is relatively well understood, the precise molecular mechanisms underlying the assembly of export-competent mRNPs in the nucleus and their Dbp5-mediated disassembly in the cytoplasm is less well defined. Considerable information has been obtained on the structure of Dbp5 in its different nucleotide-bound states and in complex with Gle1 or Nup159/NUP214. Although the precise manner by which the Dbp5 ATPase cycle is coupled to mRNP remodelling remains to be established, current models capture many key details of this process. The formation of export-competent mRNPs in the nucleus remains an elusive component of this pathway and the precise nature of the remodelling that generates these mRNPs as well as detailed understanding of the molecular mechanisms by which this step is integrated with the transcriptional, splicing and polyadenylation machinery by the TREX and TREX-2 complexes remain obscure. This article is part of a Special Issue entitled: Nuclear Transport and RNA Processing.

Virtuopsy by CT Angiography of Fetal Heart: a Feasibility Study

Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. Mar, 2012  |  Pubmed ID: 22407734

Purpose: Postmortem magnetic resonance imaging has been proposed as an alternative to classical postmortem autopsy and has proven to be useful in the detection of soft-tissue lesions, but has limitations when examining the fetal heart. Our study aimed to determine the feasibility of pm-CT angiography for fetal heart evaluations. Methods: Following Termination of Pregnancy (TOP) beyond 18 weeks of gestation, 8 fetuses underwent contrast medium injection through the umbilical cord while 25 were directly injected into the heart. Regression analysis was used to investigate the effect on the ability to visualize on pm-CT angiography cardiac structures of gestational age at TOP, the time delay between fetal death and examination, the technique used for contrast medium injection, the presence of cardiac abnormality and whether or not there was an intrauterine fetal death. The diagnostic accuracy of pm-CT angiography for the evaluation of fetal cardiac structures was also evaluated. Results: Cardiac anatomy including heart situs, a 4-chamber view and great vessels could be visualized on pm-CT angiography in 29 (87.9%) out of 33 fetuses. Regression analysis showed that the ability to visualize cardiac structures on pm-CT angiography was positively correlated only to contrast medium injected directly into the heart. Twenty-five out of the 33 fetuses underwent conventional autopsy. There were 5 cases with suspected major cardiac abnormality at prenatal ultrasound and one with minor cardiac abnormality. In one case, severe leakage into the pleural cavity did not allow for visualization of any heart structure on pm-CT angiography. In the remaining 4 cases, the findings of the pm-CT angiography and the invasive autopsy were in agreement. None of the 27 cases with normal hearts were falsely classified as abnormal using pm-CT angiography. Conclusions: Pm-CT angiography by direct injection into the heart seems to offer a feasible evaluation of the fetal heart. The extent in which such a technique could be used for the evaluation of congenital heart disease as an alternative to classical postmortem autopsy, remains to be determined. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.

Estimating Various Fetal Organ Weight by Post-mortem High-field Magnetic Resonance Imaging Before 20 Weeks of Gestation

Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. Mar, 2012  |  Pubmed ID: 22407748

Objective: To examine whether high-field magnetic resonance (MR) imaging allows accurate estimation of various fetal organ weight in fetuses below 20 weeks of gestation. Methods: Twenty-three fetuses at 9-20 weeks and 207 various fetal organs were evaluated on high-field MR imaging at 9.4T prior to conventional autopsy. Fetal organ density was calculated by correlating necropsy volume and necropsy weight using linear regression analysis and served to estimate fetal organ weight by MR imaging. The relative error in MRI estimation of organ weight was calculated as following: (|MRI weight - necropsy weight| / necropsy weight) x 100 (%). Regression analysis was used to investigate the effect on the relative error of MRI organ weight estimates of gestational age at termination of pregnancy (TOP), necropsy weight, fetal organ examined, in utero fetal death (IUFD) and fetal maceration. Results: Of the 207 organs evaluated, 133 organs (64%) were examined for fetal organ density and 155 organs (75%) for fetal organ weight. Fifty-two organs were excluded from our analysis deriving from fetuses at a median of 12.0 (range 9.0-16.0) weeks. Forty-one of these organs derived from fetuses with IUFD with 39 organs macerated. In 32 cases, exclusion from analysis was due to our inability to visualize and delineate the corresponding organ on MRI but also to dissect it on conventional autopsy. Necropsy volume and necropsy weight correlated significantly following the linear equation: necropsy volume (mm(3) ) = 0.9947 mm(3) /mg x necropsy weight (mg) - 4.7556 mm(3) (r = 0.99; p<0.001(. Overall the relative error in the MR estimation of organ weight was 68%. Regression analysis showed that the relative error of MRI organ weight was significantly associated with gestational age at TOP and fetal maceration but not with the necropsy weight, fetal organ examined or IUFD. In the subgroup of non-macerated organs and for fetuses above 14 weeks of gestation, the MRI relative error in the estimation of organ weight was 34%. Conclusion: In fetuses before 20 weeks of gestation, non-invasive estimation of organ weights is feasible using high-field MR, however with a constant over-estimation. Limitations mainly occur in case of small macerated fetuses before 14 weeks of gestation. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.

Hyperbaric Oxygen Therapy for Radiation-Induced Cystitis and Proctitis

International Journal of Radiation Oncology, Biology, Physics. Mar, 2012  |  Pubmed ID: 22440041

PURPOSE: To provide a retrospective analysis of the efficacy of hyperbaric oxygen therapy (HBOT) for treating hemorrhagic cystitis (HC) and proctitis secondary to pelvic- and prostate-only radiotherapy. METHODS AND MATERIALS: Nineteen patients were treated with HBOT for radiation-induced HC and proctitis. The median age at treatment was 66 years (range, 15-84 years). The range of external-beam radiation delivered was 50.0-75.6 Gy. Bleeding must have been refractory to other therapies. Patients received 100% oxygen at 2.0 atmospheres absolute pressure for 90-120 min per treatment in a monoplace chamber. Symptoms were retrospectively scored according to the Late Effects of Normal Tissues-Subjective, Objective, Management, Analytic (LENT-SOMA) scale to evaluate short-term efficacy. Recurrence of hematuria/hematochezia was used to assess long-term efficacy. RESULTS: Four of the 19 patients were lost to follow-up. Fifteen patients were evaluated and received a mean of 29.8 dives: 11 developed HC and 4 proctitis. All patients experienced a reduction in their LENT-SOMA score. After completion of HBOT, the mean LENT-SOMA score was reduced from 0.78 to 0.20 in patients with HC and from 0.66 to 0.26 in patients with proctitis. Median follow-up was 39 months (range, 7-70 months). No cases of hematuria were refractory to HBOT. Complete resolution of hematuria was seen in 81% (n = 9) and partial response in 18% (n = 2). Recurrence of hematuria occurred in 36% (n = 4) after a median of 10 months. Complete resolution of hematochezia was seen in 50% (n = 2), partial response in 25% (n = 1), and refractory bleeding in 25% (n = 1). CONCLUSIONS: Hyperbaric oxygen therapy is appropriate for radiation-induced HC once less time-consuming therapies have failed to resolve the bleeding. In these conditions, HBOT is efficacious in the short and long term, with minimal side effects.

Use of a High-frequency Linear Transducer and MTI Filtered Color Flow Mapping in the Assessment of Fetal Heart Anatomy at the Routine 11 to 13 + 6-week Scan: a Randomized Trial

Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. Feb, 2012  |  Pubmed ID: 21465608

To prospectively assess the contribution of a high-frequency linear transducer and of moving target indicator (MTI) filtered color flow mapping in the visualization of cardiac fetal anatomy at the routine 11 to 13 + 6-week scan.

Advanced Glycation End Products in Myocardial Reperfusion Injury

Heart and Vessels. Mar, 2012  |  Pubmed ID: 21562777

Advanced glycation end products (AGEs) are associated with cardiovascular diseases. Whether the AGE levels change during myocardial reperfusion injury is currently unknown. The aim of our study was to investigate the dynamics of AGEs in myocardial reperfusion injury and to discuss potential reasons for these changes. The dynamics of AGEs, pentosidine and neopterin in the plasma of patients with acute myocardial infarction (AMI) treated using thrombolysis (n = 40) were analyzed. In addition, AGEs were measured in patients with open heart surgery (n = 12) and rabbits with induced AMI (n = 9). In all three studies of myocardial reperfusion injury, a significant decrease of AGEs was observed (by 26 ± 19% in patients with AMI, by 23 ± 14% in patients with open heart surgery and by 39 ± 10% in rabbits with AMI within 1 day of reperfusion; p < 0.05 in all studies). In additional studies, an association between lower AGEs and an activated immune system (R (2) = 0.09; p < 0.01) and fasting (decrease by 38%; p < 0.01) was shown. AGEs decrease in reperfusion injury of the heart. Indices pointing towards the involvement of immune system activation and fasting are presented. Further studies focusing on the underlying mechanism and on the clinical value of the observed dynamics of AGEs are needed.

The Association of Autism Diagnosis with Socioeconomic Status

Autism : the International Journal of Research and Practice. Mar, 2012  |  Pubmed ID: 21810908

Background: In 2007 the Centers for Disease Control and Prevention (CDC) reported a higher prevalence of autism spectrum disorder (ASD) in New Jersey, one of the wealthiest states in the United States, than in other surveillance regions. Objective: To examine the association of socioeconomic status (SES) with ASD prevalence. Methods: Information on eight-year-olds with ASD from four counties was abstracted from school and medical records. US Census 2000 provided population and median household income data. Results: 586 children with ASD were identified: autism prevalence was 10.2/1000, higher in boys than girls (16 vs. 4/1000); higher in white and Asian non-Hispanics than in black non-Hispanics and Hispanics (12.5, 14.0, 9.0, and 8.5/1000, respectively); and higher (17.2/1000 (95% CI 14.0-21.1)) in tracts with median income >US$90,000 than in tracts with median income ≤US$30,000 (7.1 (95% CI 5.7-8.9)). Number of professional evaluations was higher, and age at diagnosis younger, in higher income tracts (p < .001), but both measures spanned a wide overlapping range in all SES levels. In multivariable models race/ethnicity did not predict ASD, but the prevalence ratio was 2.2 (95% CI 1.5-3.1) when comparing highest with lowest income tracts. Conclusions: In the US state of New Jersey, ASD prevalence is higher in wealthier census tracts, perhaps due to differential access to pediatric and developmental services.