186 research outputs found
Effect of pancreatic and/or renal transplantation on diabetic autonomic neuropathy
Thirty-nine Type 1 (insulin-dependent) diabetic patients were studied prospectively after simultaneous pancreas and kidney (n=26) and kidney grafting alone (n=13) by measuring heart rate variation during various manoeuvers and answering a standardized questionnaire every 6 to 12 months post-transplant. While age, duration of diabetes, and serum creatinine (168.1±35.4 vs 132.7±17.7 mgrmol/l) were comparable, haemoglobin A1 levels were significantly lower (6.6±0.2 vs 8.5±0.3%; p<0.01) and the mean observation time longer (35±2 vs 25±3 months; p<0.05) in the pancreas recipients when compared with kidney transplanted patients. Heart rate variation during deep breathing, lying/standing and Valsalva manoeuver were very similar in both groups initially and did not improve during follow-up. However, there was a significant reduction in heart rate in the pancreas recipient group. Autonomic symptoms of the gastrointestinal and thermoregulatory system improved more in the pancreas grafted subjects, while hypoglycaemia unawareness deteriorated in the kidney recipients. This study suggests that long-term normoglycaemia by successful pancreatic grafting is able to halt the progression of autonomic dysfunction
Binary and Millisecond Pulsars at the New Millennium
We review the properties and applications of binary and millisecond pulsars.
Our knowledge of these exciting objects has greatly increased in recent years,
mainly due to successful surveys which have brought the known pulsar population
to over 1300. There are now 56 binary and millisecond pulsars in the Galactic
disk and a further 47 in globular clusters. This review is concerned primarily
with the results and spin-offs from these surveys which are of particular
interest to the relativity community.Comment: 59 pages, 26 figures, 5 tables. Accepted for publication in Living
Reviews in Relativity (http://www.livingreviews.org
Extragalactic Radio Continuum Surveys and the Transformation of Radio Astronomy
Next-generation radio surveys are about to transform radio astronomy by
discovering and studying tens of millions of previously unknown radio sources.
These surveys will provide new insights to understand the evolution of
galaxies, measuring the evolution of the cosmic star formation rate, and
rivalling traditional techniques in the measurement of fundamental cosmological
parameters. By observing a new volume of observational parameter space, they
are also likely to discover unexpected new phenomena. This review traces the
evolution of extragalactic radio continuum surveys from the earliest days of
radio astronomy to the present, and identifies the challenges that must be
overcome to achieve this transformational change.Comment: To be published in Nature Astronomy 18 Sept 201
Cirrhosis: Morphologic dynamics for the nonmorphologist
Cirrhosis is an irreversible end-stage liver disease characterized by septate scars dividing a distorted liver into nodules. It generates through a sequence of dynamic changes and once it develops, it may alter its appearance through variations in secondary factors, such as injury and nutrition. The different classification schemes have, unfortunately, only served to make cirrhosis static in our thinking. Stationary morphologic characteristics are of value only if they can be correlated with etiology.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44380/1/10620_2005_Article_BF02231300.pd
Primary biliary cirrhosis and autoimmune cholangitis are not associated with coeliac disease in Crete
BACKGROUND: An increased prevalence of coeliac disease in patients with primary biliary cirrhosis has been recently reported. However, in other studies the association has not been confirmed. There have been no formal attempts to systematically evaluate patients with autoimmune cholangitis for coeliac disease. METHODS: Sera from 62 patients with primary biliary cirrhosis, 17 with autoimmune cholangitis and 100 blood donors were screened for anti-gliadin, anti-endomysial, anti-reticulin, and IgA class antibodies to guinea pig liver-derived tissue transglutaminase. Eighteen untreated coeliacs served as methodological controls. Analyses were performed by using the χ(2) and Fischer's exact tests. RESULTS: Anti-gliadin antibodies were detected in 21% of patients with primary biliary cirrhosis, 35% of patients with autoimmune cholangitis, and 3% of controls (p < 0.001). IgA class gliadin antibodies positivity was more pronounced in patients with Scheuer's stage III-IV disease (p < 0.05). Anti-transglutaminase antibodies were detected in 10% and in 18% of patients with primary biliary cirrhosis and autoimmune cholangitis respectively (p < 0.001). Anti-reticulin and anti-endomysial antibodies were negative in all patients. Duodenal biopsies were performed in 59% and 71% of patients with primary biliary cirrhosis and autoimmune cholangitis respectively, tested positive for at least one antibody class. No histological features of coeliac disease were found. CONCLUSIONS: We were unable to demonstrate an increased risk of coeliac disease in patients with primary biliary cirrhosis and autoimmune cholangitis. Our results confirm the previously reported high prevalence of false-positive anti-gliadin and guinea pig liver-derived anti-tissue transglutaminase antibodies in patients with chronic liver disease
Beyond trastuzumab: novel therapeutic strategies in HER2-positive metastatic breast cancer
The use of trastuzumab, a monoclonal antibody that targets the human epidermal growth factor receptor 2 (HER2) alteration present in 25 to 30% of breast cancers, has been associated with improved survival outcomes in both the adjuvant and metastatic settings. However, despite the robust clinical efficacy of trastuzumab in HER2-positive metastatic breast cancer (MBC), primary and secondary resistance remains a clinical challenge. Although lapatinib has demonstrated modest activity in this setting, trials reported to date have yet to demonstrate improvements in overall survival with its use. Novel therapeutic strategies to circumvent trastuzumab resistance are warranted, and agents targeting the HER, vascular endothelial growth factor, heat shock protein 90, phosphoinositide 3 kinase/Akt/mammalian target of rapamycin, and insulin-like growth factor-1 receptor pathways represent rational approaches in the management of HER2-positive disease. In this review, early-phase and emerging trial data surrounding the use of these promising agents in HER2-positive MBC will be discussed
HER2-family signalling mechanisms, clinical implications and targeting in breast cancer.
Approximately 20 % of human breast cancers (BC) overexpress HER2 protein, and HER2-positivity is associated with a worse prognosis. Although HER2-targeted therapies have significantly improved outcomes for HER2-positive BC patients, resistance to trastuzumab-based therapy remains a clinical problem. In order to better understand resistance to HER2-targeted therapies in HER2-positive BC, it is necessary to examine HER family signalling as a whole. An extensive literature search was carried out to critically assess the current knowledge of HER family signalling in HER2-positive BC and response to HER2-targeted therapy. Known mechanisms of trastuzumab resistance include reduced receptor-antibody binding (MUC4, p95HER2), increased signalling through alternative HER family receptor tyrosine kinases (RTK), altered intracellular signalling involving loss of PTEN, reduced p27kip1, or increased PI3K/AKT activity and altered signalling via non-HER family RTKs such as IGF1R. Emerging strategies to circumvent resistance to HER2-targeted therapies in HER2-positive BC include co-targeting HER2/PI3K, pan-HER family inhibition, and novel therapies such as T-DM1. There is evidence that immunity plays a key role in the efficacy of HER-targeted therapy, and efforts are being made to exploit the immune system in order to improve the efficacy of current anti-HER therapies. With our rapidly expanding understanding of HER2 signalling mechanisms along with the repertoire of HER family and other targeted therapies, it is likely that the near future holds further dramatic improvements to the prognosis of women with HER2-positive BC
Binary and Millisecond Pulsars
We review the main properties, demographics and applications of binary and
millisecond radio pulsars. Our knowledge of these exciting objects has greatly
increased in recent years, mainly due to successful surveys which have brought
the known pulsar population to over 1700. There are now 80 binary and
millisecond pulsars associated with the disk of our Galaxy, and a further 103
pulsars in 24 of the Galactic globular clusters. Recent highlights have been
the discovery of the first ever double pulsar system and a recent flurry of
discoveries in globular clusters, in particular Terzan 5.Comment: 77 pages, 30 figures, available on-line at
http://www.livingreviews.org/lrr-2005-
Estrogen receptor transcription and transactivation: Basic aspects of estrogen action
Estrogen signaling has turned out to be much more complex and exciting than previously thought; the paradigm shift in our understanding of estrogen action came in 1996, when the presence of a new estrogen receptor (ER), ERβ, was reported. An intricate interplay between the classical ERα and the novel ERβ is of paramount importance for the final biological effect of estrogen in different target cells
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