No description available.

No description available.

Background: Idiopathic inflammatory myopathies (IIM) constitute a heterogeneous group of diseases with severe consequences for the life of affected patients. Dermatomyositis, polymyositis and inclusion body myositis (IBM) are the classical representatives of this group. The treatments given today often have limited effects, and are taken at the cost of side effects. Major obstacles in the search for more effective treatments are; (1) an incomplete understanding of the disease mechanisms, (2) difficulties to delineate homogeneous disease groups for clinical studies and (3) the sometimes challenging task to diagnose these diseases. Aims: We addressed a number of “loose ends” in the areas of pathogenesis, classification and diagnosis; mechanisms of muscle fiber degeneration in IIM, with a focus of programmed cell death (apoptosis) and invasion of muscle  fibers by inflammatory cells (partial invasion); protecting and mediating factors present in muscle; the association of other diseases with IIM, in particular celiac disease ; the evaluation of two classification systems and laboratory methods for increased diagnostic performance. The studies: We included 106 patients, diagnosed at the Neuromuscular unit in Linköping, Sweden, with pathological muscle findings consistent with IIM. The incidence in the county of Östergötland (during 5 years) was 7.3 per million/year (3 patients each year). Of 88 patients with confirmed IIM 4 (4.5 %) had celiac disease, 33 (38%) had an associated systemic inflammatory disease and 5 (5.7 %) had a malignancy. Ninety-nine patients were included for a comparison of two classification systems using criteria of the European Neuromuscle Centre (Amato/ENMC), and the widely used Bohan and Peter classification, both with the addition of IBM according to Griggs et al. Using the Amato/ENMC criteria the most prevalent diagnostic group after IBM (30%) was nonspecific myositis (23%), followed by polymyositis (20%) and dermatomyositis 17%). A substantial number of patients meeting Bohan and Peter (or Griggs) criteria were excluded by Amato/ENMC criteria, most (21/23) due to lack of detectable muscle weakness. Extended muscle sectioning increased the sensitivity of a muscle biopsy by 15 % and the specificity by 22%, and showed an overlap between disease groups. Muscle biopsies from patients with IIM and controls were used to investigate pathological findings considered specific for disease groups, and for the presence of programmed cell death (apoptosis) and disease protecting and mediating factors in muscle. The presence of apoptotic muscle fiber nuclei was detected in muscle with partial invasion (however not in the invaded fibers) in the presence of granzyme B and CD8+ cytotoxic T cells. The major apoptosis inhibiting protein Bcl-2 was shown to be constitutionally expressed in healthy muscle but weakened in IIM. Conclusion: We present apoptosis as a possible disease mechanism in parallel with partial invasion of fibers. Furthermore, partial invasion may not be a suitable distinguishing feature in the pathogenesis, or for classification and diagnosis of IIM. We also introduce the anti-apoptotic Bcl-2 as a possible relevant muscle fiber protecting factor. A more extensive pathological work-up improves classification and diagnosis of IIM. The proposed Amato/ENMC creates a substantial portion of patients with non-specific or unclassified myositis. Associated diseases are common in IIM, and also include celiac disease.

No description available.

acase@tulane.edu

MiR-17-92 is an oncogenic miRNA cluster implicated in the development of several human cancers; however, it remains unknown whether miR-17-92 cluster is able to regulate hepatobiliary carcinogenesis. This study was designed to investigate the biological functions and molecular mechanisms of miR-17-92 cluster in primary liver cancer.<br>In-situ hybridization and qRT-PCR analysis showed that miR-17-92 cluster is highly expressed in human cholangiocarcinoma cells compared to the non-neoplastic biliary epithelial cells. Forced overexpression of the miR-17-92 cluster or its members, miR-92a and miR-19a, in cultured human cholangiocarcinoma cells enhanced tumor cell proliferation, colony formation and invasiveness, in vitro. Overexpression of miR-17-92 cluster or miR-92a also enhanced cholangiocarcinoma growth in vivo in SCID hairless outbred mice. The tumor suppressor PTEN was identified as a bona fide target of both miR-92a and miR-19a in cholangiocarcinoma cells. Accordingly, overexpression of PTEN open reading frame protein (devoid of 3’UTR) prevented miR-92a- or miR-19a-induced cholangiocarcinoma cell growth. Microarray analysis revealed additional targets of miR-17-92 cluster in human cholangiocarcinoma cells, including APAF-1 and PRDM2. Moreover, we observed that the expression of miR-17-92 cluster is regulated by IL-6/Stat3, a key oncogenic signaling pathway pivotal in cholangiocarcinogenesis. Taken together, our findings in this study disclose a novel IL-6/Stat3 miR-17-92 cluster PTEN signaling axis that is crucial for cholangiocarcinogenesis and tumor progression.<br>We also found the miR-17-92 is highly expressed in tumor tissue compared to non-tumor adjacent tissue in hepatocellular carcinoma patient tissue. Forced overexpression of the miR-17-92 cluster in cultured human hepatocellular carcinoma cells enhanced tumor growth in vitro; on contrast, inhibition of miR-17-92 cluster inhibited cell growth. MiR-17-92 cluster promote diethylnitrosamine-induced hepatocarcinogenesis in liver-specific miR-17-92 cluster transgenic mice. Binding sequence and mice whole genome microarray analysis revealed about 300 possible targets. RNA-sequencing data analysis showed both individual miRNAs and the host gene of miR-17-92 cluster was highly expressed in hepatocellular carcinoma patients and had negative correlation with several genes (CREBL2, PRRG1, and NTN4), among which, CREBL2 may play an important role in the hepatocarcinogenesis. / acase@tulane.edu

Objective: To assess the feasibility of applying Quality Management philosophies and techniques to pathology laboratories. Design: Series of case studies. Setting: Two tertiary referral pathology laboratories in Australian University teaching hospitals. Intervention: Application of Continuous Quality Improvement techniques to complex laboratory processes; Implementation of formal Quality Systems into laboratories; Introduction of a new Laboratory Information System. Measurement: Measurement of changes in key performance indicators. Results: Statistically significant improvements in a variety of key performance indicators, reduction in frequency of incidents, and improvement in surrogate clinical outcomes were achieved using Quality Management approaches in pathology laboratories. Comparison of environments associated with introduction of a new Laboratory Information System identified the presence of a formal Quality System as a key factor associated with superior laboratory performance. Conclusion: Quality Management can be applied successfully to a variety of pathology laboratory environments, and can result in significant improvements in product and service quality. A key success factor in implementing Quality Management may be the introduction of a formal Quality System.

Enligt Socialstyrelsens föreskrifter om ledningssystem för kvalitet och patientsäkerhet i hälso- och sjukvården, SOSFS 2005:12, krävs det av vårdgivaren att denne arbetar efter mål. Att formulera mål inom hälso- och sjukvården kräver eftertanke. Målen måste vara mätbara och inkludera flera olika delar av verksamheten. Varje förbättringsprojekt är unikt och bör relateras till de resurser som avsatts. Ett stort problem vid kontinuerlig uppföljning är att välja ut parametrar som ger tillräcklig information och är lätta att skapa. Här krävs mer utvecklade datasystem och även integrering mellan befintliga datasystem  I uppsatsen diskuteras med vilka parametrar man kan utvärdera ett förbättringsprojekt inom laboratoriemedicin. Det finns för närvarande inte några standardiserade kvalitetsparametrar inom klinisk kemi. De parametrar som i denna undersökning visade sig vara mest lämpliga att använda kontinuerligt i det korta perspektivet var svarstider, personalresurser och reagenskostnader. I det längre perspektivet kan ovanstående data kombineras till indikatorer som visar kostnad per analyspoäng och analyspoäng per årsarbetare. De indikatorer som kan få användning först när datasystem utvecklas är data från avvikelsesystem och analyskommentarer som visar t.ex. att svar inte har kunnat lämnas ut. / According to the National Board of Health and Welfare, SOSFS 2005:12, it is required that the caregiver adheres to his work through following stated objectives. Formulating goals in health care requires careful consideration. Goals must be measurable and include many different aspects of the project. Each improvement project is unique and should be directly related to the resources allocated to the project. A major problem for continuous monitoring is to select parameters that provide sufficient information and are easy to produce. This requires more advanced computer systems and integration with existing computer systems. The paper discusses the parameters an improvement project in laboratory medicine can evaluate its results after. There are currently no standardized quality parameters in clinical chemistry. The parameters used in this study that proved to be the most suitable to be used continuously in the short term was the response times, staffing and reagent costs. In the long term, the above data are combined with indicators that show cost per analysis score and analysis points per full-time employees. The indicator that may be used when the computer system is developed is deviation systems and analytical comments that show for example that a response has not been disclosed.

Objective: To assess the feasibility of applying Quality Management philosophies and techniques to pathology laboratories. Design: Series of case studies. Setting: Two tertiary referral pathology laboratories in Australian University teaching hospitals. Intervention: Application of Continuous Quality Improvement techniques to complex laboratory processes; Implementation of formal Quality Systems into laboratories; Introduction of a new Laboratory Information System. Measurement: Measurement of changes in key performance indicators. Results: Statistically significant improvements in a variety of key performance indicators, reduction in frequency of incidents, and improvement in surrogate clinical outcomes were achieved using Quality Management approaches in pathology laboratories. Comparison of environments associated with introduction of a new Laboratory Information System identified the presence of a formal Quality System as a key factor associated with superior laboratory performance. Conclusion: Quality Management can be applied successfully to a variety of pathology laboratory environments, and can result in significant improvements in product and service quality. A key success factor in implementing Quality Management may be the introduction of a formal Quality System.

Primary aldosteronism (PA) is a common form of secondary hypertension with an international prevalence rates between 5 and 10 %. It is characterized by a high autonomous aldosterone production that causes cardiovascular damage, renin suppression, hypertension, sodium retention, potassium excretion and hypokalemia. The screening of PA is a simple test measuring aldosterone to renin ratio (ARR) with immunoassay method. This test is currently considered as the most reliable screening tool for PA.     The main objective of the study was to evaluate an ELISA-method, for detection of aldosterone and renin in blood plasma, to be used for routine analysis in the laboratory. The second aim was to investigate the effect of refreezing samples, considering that cryoactivation of prorenin might occur.     One hundred blood samples were analysed, in regard to aldosterone and renin, by using two commercial ELISA assays (DRG ELISA from DRG Diagnostics, Germany) on a Dynex DS2 instrument. In addition, the accuracy and precision of the methods were calculated. The effect of refreezing was investigated with a series of eight samples, which were analyzed twice on the same instrument.     Both assays performed well. The resulting data showed good precision and accuracy. The correlation between the original and refreezed samples was good, r = 0.989 and r = 1.0 for aldosterone and renin respectively. Considering that the study only included eight samples, further investigation is recommended.     Evaluation showed that both immunoassays are reliable in diagnostic use and the ELISA-method is suitable to implement in the laboratory for routine analysis.