Current Online-pharmacy-dictionary- News Results

Barth syndrome: an X-linked cause of fetal cardiomyopathy and stillbirth.

Prenat Diagn. 2010 Sep 1;
Steward CG, Newbury-Ecob RA, Hastings R, Smithson SF, Tsai-Goodman B, Quarrell OW, Kulik W, Wanders R, Pennock M, Williams M, Cresswell JL, Gonzalez IL, Brennan P

OBJECTIVE: Barth Syndrome (BTHS) is an X-linked multisystem disorder (OMIM 302060) usually diagnosed in infancy and characterized by cardiac problems [dilated cardiomyopathy (DCM) +/- endocardial fibroelastosis (EFE) +/- left ventricular non-compaction (LVNC)], proximal myopathy, feeding problems, growth retardation, neutropenia, organic aciduria and variable respiratory chain abnormalities. We wished to determine whether BTHS had a significant impact on fetal and perinatal health in a large cohort of family groups originating from a defined region. METHOD: Case note review on 19 families originating from the UK and known to the Barth Syndrome Service of the Bristol Royal Hospital for Children. RESULTS: Details are presented on six kindreds (32%) with genetically and biochemically proven BTHS that demonstrate a wider phenotype including male fetal loss, stillbirth and severe neonatal illness or death. In these families, 9 males were stillborn and 14 died as neonates or infants but there were no losses of females. BTHS was definitively proven in five males with fetal onset of DCM +/- hydrops/EFE/LVNC. CONCLUSION: These findings stress the importance of considering BTHS in the differential diagnosis of unexplained male hydrops, DCM, EFE, LVNC or pregnancy loss, as well as in neonates with hypoglycemia, lactic acidosis and idiopathic mitochondrial disease. Copyright (c) 2010 John Wiley & Sons, Ltd.

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Hepatology. 2010 Sep; 52(3): 1169-70
Liu H, Kim Y, Sharkis S, Ye Z, Jang YY

MicroRNA-151 and its hosting gene FAK (focal adhesion kinase) regulate tumor cell migration and spreading of hepatocellular carcinoma.

Hepatology. 2010 Sep; 52(3): 1162-4
Luedde T

Recurrent chromosomal aberrations are often observed in hepatocellular carcinoma (HCC), but little is known about the functional non-coding sequences, particularly microRNAs (miRNAs), at the chromosomal breakpoints in HCC. Here we show that 22 miRNAs are often amplified or deleted in HCC. MicroRNA-151 (miR-151), a frequently amplified miRNA on 8q24.3, is correlated with intrahepatic metastasis of HCC. We further show that miR-151, which is often expressed together with its host gene FAK, encoding focal adhesion kinase, significantly increases HCC cell migration and invasion in vitro and in vivo, mainly through miR-151-5p, but not through miR-151-3p. Moreover, miR-151 exerts this function by directly targeting RhoGDIA, a putative metastasis suppressor in HCC, thus leading to the activation of Rac1, Cdc42 and Rho GTPases. In addition, miR-151 can function synergistically with FAK to enhance HCC cell motility and spreading. Thus, our findings indicate that chromosome gain of miR-151 is a crucial stimulus for tumour invasion and metastasis of HCC.

Innate immune genetic profile to predict infection risk and outcome after liver transplant.

Hepatology. 2010 Sep; 52(3): 814-21
Razonable RR

Beta-blockers in cirrhosis: Friend and foe?

Hepatology. 2010 Sep; 52(3): 811-3
Wong F, Salerno F

Emerging genes associated with the progression of nonalcoholic fatty liver disease.

Hepatology. 2010 Sep; 52(3): 807-11
Koutsari C, Lazaridis KN

Predicting factors of unexpected peritoneal seeding in locally advanced gastric cancer: Indications for staging laparoscopy.

J Surg Oncol. 2010 Sep 1;
Hur H, Lee HH, Jung H, Song KY, Jeon HM, Park CH

BACKGROUND AND OBJECTIVES: The aim of this study is to investigate predictive factors for unexpected peritoneal seeding from clinically resectable advanced gastric cancers to suggest the indications for staging laparoscopy (SL). METHODS: A total of consecutive 589 gastric cancer patients who were clinically diagnosed with advanced gastric cancer with no metastatic disease underwent operations at Seoul St. Mary's Hospital. RESULTS: A total of 72 patients (including 35 patients with seeding to distant peritoneum) were surgically diagnosed with peritoneal seeding. Borrmann type 3 (OR: 4.475) or type 4 (OR: 8.243) cancer, tumor invasion of T3 (OR: 2.794) or T4 (OR: 6.841) and tumor size (4 cm

Adenocarcinoma arising from colonic duplication cyst with metastasis to omentum: A case report.

J Clin Ultrasound. 2010 Sep 1;
Hsu H, Gueng MK, Tseng YH, Wu CC, Liu PH, Chen CC

Gastrointestinal tract duplications are uncommon congenital abnormalities. Carcinoma arising from duplication cyst is extremely rare, not to mention metastasis to other organs. We present a case of adenocarcinoma arising from a colonic duplication cyst with invasion of the serosa and metastasis to the omentum in a 40-year-old man. Duplication cysts should be included in the differential diagnosis of cystic masses of the gastrointestinal tract. Because these lesions occur so infrequently, they are often not suspected until encountered intraoperatively. The specific findings and advantages of sonography are reviewed. (c) 2010 Wiley Periodicals, Inc. J Clin Ultrasound, 2010.

Choice of pulse sequences for MRI-based semiquantitative assessment of cartilage defects in osteoarthritis research: Comment on the article by Doré et al.

Arthritis Rheum. 2010 Sep 1;
Hayashi D, Roemer FW, Guermazi A

Matrilysin-1 (MMP7) cleaves galectin-3 and inhibits wound healing in intestinal epithelial cells.

Inflamm Bowel Dis. 2010 Sep 1;
Puthenedam M, Wu F, Shetye A, Michaels A, Rhee KJ, Kwon JH

BACKGROUND:: Galectin-3 is an animal lectin that has been implicated in wound healing and is decreased in inflammatory bowel disease (IBD). Matrix metalloproteinase-7 (MMP7), also known as matrilysin-1, a protease shown to cleave extracellular matrix proteins, is highly expressed in IBD tissues, especially at the leading edge of gastrointestinal ulcers. The ability of MMP7 to cleave galectin-3 and influence wound healing has not been reported previously. The aim was to determine whether MMP7 cleaves galectin-3 and modulates wound healing in intestinal epithelial cells. METHODS:: The cleaved fragments of galectin-3 were identified by N-terminal sequencing and mass spectrometry. Western blotting was used to detect the cleaved galectin-3 products in a colonic epithelial cell line (T84 cells). Cell migration was studied by the in vitro scratch method. RESULTS:: We demonstrate for the first time that MMP7 cleaves galectin-3 in vitro, resulting in three cleaved fragments (20.2 kDa, 18.9 kDa, and 15.5 kDa). Exogenous treatment of T84 cells with recombinant MMP7 resulted in the appearance of secreted galectin-3 cleavage fragments in the supernatant. MMP7 inhibited cell migration and resulted in wound retraction and the addition of MMP7 to galectin-3 abrogated the wound healing and cell migration induced by galectin-3. CONCLUSIONS:: We have demonstrated that galectin-3 is a substrate for MMP7. Cleavage of galectin-3 may be one mechanism by which MMP7 inhibits wound healing. This study has significance in understanding delayed wound healing in chronic intestinal diseases like intestinal ulcers and IBD, where MMP7 protein expression is elevated with a decreased galectin-3 protein expression. (Inflamm Bowel Dis 2010;).

Physician assessment of ulcerative colitis activity correlates poorly with endoscopic disease activity.

Inflamm Bowel Dis. 2010 Sep 1;
Regueiro M, Rodemann J, Kip KE, Saul M, Swoger J, Baidoo L, Schwartz M, Barrie A, Binion D

BACKGROUND:: Subjective physician assessment is the cornerstone of routine ulcerative colitis (UC) management. Endoscopic and histologic assessment of UC provides objective measures of inflammatory disease activity. The level of agreement between physician impression of UC activity and endoscopic disease activity has not been evaluated. The aim was to assess the level of agreement between physician's clinical impression of UC disease activity and endoscopic and histologic findings of inflammation. METHODS:: Using the Medical Archival Retrieval System at the University of Pittsburgh Medical Center, we reviewed clinical information on all UC patients between 1995 and 2008 who had clinic visits recorded prior to colonoscopy. Clinical UC disease activity was defined by the physician's clinical impression and the endoscopic and histologic activity by colonoscopy with biopsy. The level of agreement between colonoscopy assessment of UC with histologic and clinical assessment was determined by sensitivity, specificity, positive and negative predictive values, and the kappa coefficient. RESULTS:: There were 369 UC patients who had a clinic visit proximate to a colonoscopy. The mean age of patients was 46 +/- 16 years (50% female). The performance of clinical impression in recognizing disease activity, as determined by endoscopy, was relatively poor: sensitivity = 56.0%, predictive value negative = 56.8%, kappa coefficient = 0.35. In contrast, the performance of histological evaluation in recognizing disease activity was markedly better: sensitivity = 93.5%, predictive value negative = 89.1%, kappa coefficient = 0.70. CONCLUSIONS:: The physician's clinical impression of UC activity shows poor agreement with endoscopy and histology, with over one-third of patients with chronic inflammation underrecognized by clinical impression. The consequences of underestimated UC activity by clinical assessment may include undertreatment of active disease and uncontrolled chronic inflammation. (Inflamm Bowel Dis 2010;).

Peripheral blood MicroRNAs distinguish active ulcerative colitis and Crohn's disease.

Inflamm Bowel Dis. 2010 Sep 1;
Wu F, Guo NJ, Tian H, Marohn M, Gearhart S, Bayless TM, Brant SR, Kwon JH

BACKGROUND:: Crohn's disease (CD) and ulcerative colitis (UC) result from pathophysiologically distinct dysregulated immune responses, as evidenced by the preponderance of differing immune cell mediators and circulating cytokine expression profiles. MicroRNAs (miRNAs) are small, noncoding RNAs that act as negative regulators of gene expression and have an increasingly recognized role in immune regulation. We hypothesized that differences in circulating immune cells in CD and UC patients are reflected by altered miRNA expression and that miRNA expression patterns can distinguish CD and UC from normal healthy individuals. METHODS:: Peripheral blood was obtained from patients with active CD, inactive CD, active UC, inactive UC, and normal healthy adults. Total RNA was isolated and miRNA expression assessed using miRNA microarray and validated by mature miRNA quantitative reverse-transcription polymerase chain reaction. RESULTS:: Five miRNAs were significantly increased and two miRNAs (149* and miRplus-F1065) were significantly decreased in the blood of active CD patients as compared to healthy controls. Twelve miRNAs were significantly increased and miRNA-505* was significantly decreased in the blood of active UC patients as compared to healthy controls. Ten miRNAs were significantly increased and one miRNA was significantly decreased in the blood of active UC patients as compared to active CD patients. CONCLUSIONS:: Peripheral blood miRNAs can be used to distinguish active CD and UC from healthy controls. The data support the evidence that CD and UC are associated with different circulating immune cells types and that the differential expression of peripheral blood miRNAs may form the basis of future diagnostic tests for inflammatory bowel disease. (Inflamm Bowel Dis 2010).

Clinical usefulness of therapeutic drug monitoring of thiopurines in patients with inadequately controlled inflammatory bowel disease.

Inflamm Bowel Dis. 2010 Sep 1;
Haines ML, Ajlouni Y, Irving PM, Sparrow MP, Rose R, Gearry RB, Gibson PR

BACKGROUND:: Circulating concentrations of 6-thioguanine nucleotide (6-TGN) and 6-methyl mercaptopurine (6-MMP) are associated with thiopurine efficacy and may predict toxicity. This study aimed to examine retrospectively the utility of measuring metabolite concentrations in patients with inflammatory bowel disease (IBD) who had continuing symptoms despite stable thiopurine treatment. METHODS:: Concentrations of 6-TGN and 6-MMP were measured in lysates of washed red cells by high-performance liquid chromatography in peripheral blood drawn from 63 symptomatic patients with IBD (63% men, mean age 37, range 14-74 years, 67% Crohn's disease, 33% ulcerative colitis) treated with azathioprine or 6-mercaptopurine. Short-term clinical outcomes were examined. RESULTS:: 6-TGN concentrations weakly correlated with the thiopurine dose (r = 0.28, P = 0.08). On weight-based criteria, 50% of patients were underdosed. However, metabolite patterns suggested 7 (11%) patients were noncompliant, 18 (29%) were being underdosed, 33 (52%) were refractory to treatment with either appropriate (41%) or elevated (11%) metabolite concentrations, and 6 (10%) had a raised 6-MMP:6-TGN ratio consistent with aberrant thiopurine metabolism. The clinical outcome improved in 40 of 46 (87%) of patients in whom the course of action taken was as recommended by a metabolite-directed algorithm, while 3 of 17 patients (18%) improved where discordant actions were taken (P = 0.0001; Fisher's exact test). Fifteen patients (24%) avoided inappropriate escalation of therapy. CONCLUSIONS:: Dose-optimization or toxicity-avoidance strategies frequently result from metabolite testing in patients with inadequate efficacy from thiopurines, with evidence of better outcomes. Thiopurine metabolite testing is a potentially powerful tool for optimizing thiopurine usage in IBD. (Inflamm Bowel Dis 2010;).

Competitive dopamine receptor antagonists increase the equiactive cocaine concentration during self-administration.

Synapse. 2010 Sep 1;
Norman AB, Norman MK, Tabet MR, Tsibulsky VL, Pesce AJ

Competitive dopamine receptor antagonists increase the rate of cocaine self-administration. As the rate of self-administration at a particular unit dose is determined by the satiety threshold and the elimination half-life (t(1/2)) of cocaine, we investigated whether dopamine receptor antagonists altered these parameters. The plasma cocaine concentration at the time of each self-administration was constant during a session demonstrating that this satiety threshold concentration represents an equiactive cocaine concentration. The plasma cocaine concentration at the time of self-administration was increased by SCH23390, consistent with pharmacological theory. In rats trained to reliably self-administer cocaine, SCH23390 had no effect on the plasma steady-state cocaine concentration produced by constant infusions of cocaine. Therefore, this antagonist had no effect on cocaine t(1/2) at a dose that accelerated cocaine self-administration. A continuous cocaine infusion at a rate that maintained steady state concentrations above the satiety threshold stopped self-administration. SCH23390, or the D(2) dopamine receptor antagonist (-)eticlopride, reinstated self-administration in the presence of the constant cocaine infusion. This is consistent with SCH23390 and eticlopride raising the satiety threshold above the steady state level produced by the constant cocaine infusion. It is concluded that the antagonist-induced acceleration of cocaine self-administration is the result of a pharmacokinetic/pharmacodynamic interaction whereby the rate of cocaine elimination is faster at the higher concentrations, as dictated by first-order kinetics, so that cocaine levels decline more rapidly to the elevated satiety threshold. This results in the decreased inter-injection intervals. Synapse, 2010. (c) 2010 Wiley-Liss, Inc.

Increased natural killer cell cytotoxicity and NKp30 expression protects against hepatitis C virus infection in high-risk individuals and inhibits replication in vitro.

Hepatology. 2010 Aug 19;
Golden-Mason L, Cox AL, Randall JA, Cheng L, Rosen HR

CD56(pos) natural killer (NK)/natural T (NT) cells are important innate effectors providing the first line of defense against viral infection. Enhanced NK activity has been shown to protect from human immunodeficiency virus-1 infection. However, the role played by these innate effectors in protection against or development of hepatitis C virus (HCV) infection is unknown. We characterized CD56(pos) populations in 11 injection drug users (IDUs) who remained uninfected despite being repeatedly exposed to HCV. NK profiles in exposed but uninfected (EU) individuals were compared with preinfection samples (median 90 days prior to HCV seroconversion) collected from 14 IDUs who were exposed and subsequently became infected (EI) and unexposed normal control subjects (n = 8). Flow cytometric analysis of CD56(pos) populations demonstrated that EUs had a higher proportion of CD56(low) mature (P = 0.0011) NK cells compared with EI subjects. Bead-isolated NKs (>90% purity) from EUs had significantly higher interleukin-2 (IL-2)-induced cytolytic activity against the NK-sensitive cell line K562 at an effector-to-target ratio of 10:1 (P < 0.0001). NKp30, a natural cytotoxicity receptor involved in NK activation, is highest on NK/NT cells in EUs relative to infected subjects. Using the JFH-1 infection system, we demonstrated that NKp30(high) cells in the absence of exogenous stimulation significantly reduce infection of hepatocytes. Conclusion: CD56(pos) populations in EUs are enriched for effector NKs displaying enhanced IL-2-induced cytolytic activity and higher levels of the natural cytotoxicity receptor NKp30-activating receptor. In addition, NKp30(high) cells are more effective in preventing infection of Huh-7.5 cells than their NKp30(low/neg) counterparts. These data support the hypothesis that NK cells contribute to anti-HCV defense in vivo in the earliest stages of infection, providing innate protection from HCV acquisition. (HEPATOLOGY 2010).

Diabetes in pregnancy: scanning the wrong horizon?

Ultrasound Obstet Gynecol. 2010 Sep; 36(3): 266-7
Kiserud T

Excellence, innovation and impact factor of Ultrasound in Obstetrics & Gynecology.

Ultrasound Obstet Gynecol. 2010 Sep; 36(3): 263-265
Romero R

Distributed lag non-linear models.

Stat Med. 2010 Sep 20; 29(21): 2224-34
Gasparrini A, Armstrong B, Kenward MG

Environmental stressors often show effects that are delayed in time, requiring the use of statistical models that are flexible enough to describe the additional time dimension of the exposure-response relationship. Here we develop the family of distributed lag non-linear models (DLNM), a modelling framework that can simultaneously represent non-linear exposure-response dependencies and delayed effects. This methodology is based on the definition of a 'cross-basis', a bi-dimensional space of functions that describes simultaneously the shape of the relationship along both the space of the predictor and the lag dimension of its occurrence. In this way the approach provides a unified framework for a range of models that have previously been used in this setting, and new more flexible variants. This family of models is implemented in the package dlnm within the statistical environment R. To illustrate the methodology we use examples of DLNMs to represent the relationship between temperature and mortality, using data from the National Morbidity, Mortality, and Air Pollution Study (NMMAPS) for New York during the period 1987-2000. Copyright (c) 2010 John Wiley & Sons, Ltd.

SPECT/CT hybrid imaging; with which CT?

Contrast Media Mol Imaging. 2010 Jul; 5(4): 208-12
Bach-Gansmo T, Schwarzlmüller T, Jøraholmen V, Salbu J, Biermann M, Naum A, Kleven-Madsen N

AIM: The aim of this study is to show the practical use of, and to discuss the rationale for, high-end computed tomography (CT) integrated with intrinsic low-resolution single-photon emission tomography (SPECT). MATERIALS AND METHODS: All examinations performed on three new SPECT/CT systems with diagnostic CT capabilities were recorded retrospectively. The use of CT was classified as low-dose, using the CT with restraint as to the tube current and radiation dose, or diagnostic, with an optimum use of the CT, using CT protocols as used in ordinary radiological practice. The number of low-dose CT was compared with the number of diagnostic CT examinations. The report is based on 436 patient examinations from three hospitals in Norway with recently installed SPECT/CT systems, the time of use varying from 6 months to 2 years. The examinations performed were myocardial perfusion (45%), various tumors (thyroid, parathyroid, neuroendocrine 37%), malignant skeletal disease (12%), brain perfusion (4%), sentinel nodes in breast cancer (1%) and gastrointestinal bleeding (1%). RESULTS: Of the 436 patients, 431 had a low-dose CT for attenuation correction, anatomic localisation and, also for diagnosis, whereas five patients had a diagnostic CT. In these series, as was found in recent literature, the diagnostic potential of the CT was seldom used to its capacity and always in predetermined diagnostic situations. CONCLUSION: There is a low degree of utilization of the diagnostic capabilities of the CT in the SPECT/CT context, for a number of reasons. This raises questions about the cost-benefit of investing in high-end CT for SPECT/CT applications. Copyright (c) 2010 John Wiley & Sons, Ltd.

Multimodality imaging techniques.

Contrast Media Mol Imaging. 2010 Jul; 5(4): 180-9
Martí-Bonmatí L, Sopena R, Bartumeus P, Sopena P

In multimodality imaging, the need to combine morphofunctional information can be approached by either acquiring images at different times (asynchronous), and fused them through digital image manipulation techniques or simultaneously acquiring images (synchronous) and merging them automatically. The asynchronous post-processing solution presents various constraints, mainly conditioned by the different positioning of the patient in the two scans acquired at different times in separated machines. The best solution to achieve consistency in time and space is obtained by the synchronous image acquisition. There are many multimodal technologies in molecular imaging. In this review we will focus on those multimodality image techniques more commonly used in the field of diagnostic imaging (SPECT-CT, PET-CT) and new developments (as PET-MR). The technological innovations and development of new tracers and smart probes are the main key points that will condition multimodality image and diagnostic imaging professionals' future. Although SPECT-CT and PET-CT are standard in most clinical scenarios, MR imaging has some advantages, providing excellent soft-tissue contrast and multidimensional functional, structural and morphological information. The next frontier is to develop efficient detectors and electronics systems capable of detecting two modality signals at the same time. Not only PET-MR but also MR-US or optic-PET will be introduced in clinical scenarios. Even more, MR diffusion-weighted, pharmacokinetic imaging, spectroscopy or functional BOLD imaging will merge with PET tracers to further increase molecular imaging as a relevant medical discipline. Multimodality imaging techniques will play a leading role in relevant clinical applications. The development of new diagnostic imaging research areas, mainly in the field of oncology, cardiology and neuropsychiatry, will impact the way medicine is performed today. Both clinical and experimental multimodality studies, in humans and animals, will have to demonstrate an efficient use of the imaging information provided by the modalities to affect the future of medical imaging. Copyright (c) 2010 John Wiley & Sons, Ltd.