tbuckley/cabot-search huggingface dataset:
GP commissioning and the NHS reforms: what lies behind the hard sell?
Authors: Lucy Reynolds, Martin McKee
Journal: Journal of the Royal Society of Medicine (2012)

General practitioners (GPs) are divided on the government's proposed changes to the NHS, in which Primary Care Trusts (PCTs) will be replaced by commissioning consortia that promise to allow them a greater role. Some, such as members of the National Association of Primary Care, have been enthusiastic advocates of the government's proposals, at least as set out in the initial Health and Social Care Bill prior to the ‘pause’. They see an opportunity to exert greater control over the services to which they refer their patients. Others are highly critical, seeing the changes as portending the break-up of the NHS; according to a recent poll, only a small minority (14%) have confidence in the Health Secretary in respect of the reform.1 Critics include Clare Gerada, chair of the Royal College of General Practitioners, who has drawn attention to the profound risks to GPs and patients.2 Here we reflect on some of the practical consequences for GPs if the proposed changes become law.
Defining chronic Q fever: A matter of debate
Authors: L.M. Kampschreur, P.C. Wever, M.C.A. Wegdam-Blans, C.E. Delsing, C.P. Bleeker-Rovers, T. Sprong, M.E.E. van Kasteren, R.A. Coutinho, P.M. Schneeberger, D.W. Notermans, H.A. Bijlmer, M.P.G. Koopmans, M.H. Nabuurs-Franssen, J.J. Oosterheert
Journal: Journal of Infection (2012)
The Mitotic Kinase Aurora-A Induces Mammary Cell Migration and Breast Cancer Metastasis by Activating the Cofilin-F-actin Pathway
Authors: Li-hui Wang, Jin Xiang, Min Yan, Yan Zhang, Yan Zhao, Cai-feng Yue, Jie Xu, Fei-meng Zheng, Jin-na Chen, Zhuang Kang, Tong-sheng Chen, Da Xing, Quentin Liu
Journal: Cancer Research (2010)

The mitotic kinase Aurora-A (Aur-A) is required to form the bipolar spindle and ensure accurate chromosome segregation before cell division. Aur-A dysregulation represents an oncogenic event that promotes tumor formation. Here, we report that Aur-A promotes breast cancer metastasis. Aur-A overexpression enhanced mammary cell migration by dephosphorylation and activation of cofilin, which facilitates actin reorganization and polymerization. Cofilin knockdown impaired Aur-A-driven cell migration and protrusion of the cell membrane. Conversely, overexpression of activated cofilin abrogated the effects of Aur-A knockdown on cell migration. Moreover, Aur-A overexpession increased the expression of the cofilin phosphatase Slingshot-1 (SSH1), contributing to cofilin activation and cell migration. We found that phosphatidylinositol 3-kinase (PI3K) inhibition blocked Aur-A-induced cofilin dephosphorylation, actin reorganization, and cell migration, suggesting crosstalk with PI3K signaling and a potential benefit of PI3K inhibition in tumors with deregulated Aur-A. Additionally, we found an association between Aur-A overexpression and cofilin activity in breast cancer tissues. Our findings indicate that activation of the cofilin-F-actin pathway contributes to tumor cell migration and metastasis enhanced by Aur-A, revealing a novel function for mitotic Aur-A kinase in tumor progression.
Precocious puberty and statural growth
Authors: J.-C. Carel
Journal: Human Reproduction Update (2004)

Precocious puberty results mostly from the precocious activation of the gonadotropic axis. Although the age limits have recently been discussed, most physicians consider that onset of pubertal development before the age of 8 years in a girl or 9 years in a boy warrants at least a clinical and bone age evaluation by a paediatric endocrinologist. The major concern in precocious puberty is the underlying condition, and central nervous system or gonadal neoplasm have to be formally excluded as a first step in the diagnosis. A secondary concern is height, since precocious puberty leads to accelerated growth, accelerated bone maturation and ultimately reduced stature. Precocious puberty is heterogeneous and strict criteria should be used to define it, both in terms of age and in terms of potential for progression. Depot forms of GnRH agonists are now the standard treatment for progressive central precocious puberty and aim at alleviating the clinical symptoms of early pubertal development, their psychological consequences and the effects on growth. Here, we review the consequences of both central and gonadotropin-independent precocious puberty on adult stature and the information available on outcomes using the therapeutic regimens currently available. In girls with progressive precocious puberty, all published evidence indicates a gain of adult height over height predicted before treatment or over untreated historical controls. However, the apparent height gain (derived from the comparison of predicted and actual heights) is very variable, in large part due to the inaccuracy of height prediction methods. In girls with onset of puberty at the lower half of the normal age (8-10 years) distribution, trials using GnRH agonists have given negative results (no benefit of treatment). In boys, precocious puberty is rare and fewer results are available but point in the same direction. The most appropriate time for interrupting the treatment is still controversial. In conclusion, GnRH agonists restore adult height in children when it is compromised by precocious puberty.
Increased mortality among sleepy snorers: a prospective population based study
Authors: E. Lindberg, C. Janson, K. Svardsudd, T. Gislason, J. Hetta, G. Boman
Journal: Thorax (1998)

The long term health consequences of snoring and sleep apnoea syndrome are still uncertain. This study was conducted to assess the mortality risk associated with snoring and excessive daytime sleepiness (EDS), the two main symptoms of sleep apnoea syndrome, in men.In 1984 a sample of 3100 men aged 30-69 responded to a postal questionnaire including questions about snoring, EDS, and the prevalence of various diseases (response rate 77.1%). Mortality data for the period 1985-1995 were collected for the complete sample.During the 10 year follow up period 213 men died, 88 of cardiovascular diseases. Compared with subjects with no snoring or EDS in 1984, men with isolated snoring or EDS displayed no significantly increased mortality. The combination of snoring and EDS was associated with a significant increase in mortality. However, the relative rates decreased with increasing age, and in men aged 60 and above no effect on mortality was found. Men below the age of 60 with both snoring and EDS had an age adjusted total death rate which was 2.7 times higher than men with no snoring or EDS (95% CI 1.6 to 4.5). The corresponding age adjusted hazard ratio for cardiovascular mortality was 2.9 (95% CI 1.3 to 6.7) for subjects with both snoring and EDS. Further adjustment for body mass index and reported hypertension, cardiac disease, and diabetes reduced the relative mortality risk associated with the combination of snoring and EDS to 2.2 (95% CI 1.3 to 3.8) and the relative risk of cardiovascular mortality to 2.0 (95% CI 0.8 to 4.7).Snoring without EDS does not appear to carry an increased risk of mortality. The combination of snoring and EDS appears to be associated with an increased mortality rate, but the effects seems to be age dependent. The increased mortality is partly explained by an association between "snoring and EDS" and cardiovascular disease.
Considerable Time From the Onset of Plaque Rupture and/or Thrombi Until the Onset of Acute Myocardial Infarction in Humans
Authors: Shinsuke Ojio, Hisato Takatsu, Tsutomu Tanaka, Katsumi Ueno, Koichi Yokoya, Tetsuo Matsubara, Takahiko Suzuki, Sachiro Watanabe, Norihiko Morita, Masanori Kawasaki, Toshihiko Nagano, Itsuki Nishio, Kazuyoshi Sakai, Kazuhiko Nishigaki, Genzou Takemura, Toshiyuki Noda, Shinya Minatoguchi, Hisayoshi Fujiwara
Journal: Circulation (2000)

Background —It has been thought that the thrombi and bleeding in plaques that occur after plaque rupture or endothelial damage from vessels with mild stenosis suddenly occlude the lumen and cause acute myocardial infarction (AMI). However, our hypothesis is that thrombi and bleeding may not suddenly occlude the lumen. Methods and Results —The study group consisted of 20 patients who had coronary angiograms performed within 1 week (3±3 days) before AMI and 20 control patients who had coronary angiograms performed 6 to 18 months (282±49 days) before AMI. The features of infarct-related coronary segments (IRCS) at 3 days before AMI were the presence of a significant stenosis of &gt;50% (95% in incidence and 71±12% diameter stenosis) and Ambrose’s type II eccentric lesions (plus multiple irregularities), an indicator of plaque rupture and/or thrombi (60% [70%]), and the features at 1 year before AMI were mild stenosis of &lt;50% (95% incidence and 30±18% diameter stenosis) with rare Ambrose’s type II eccentric lesions (plus multiple irregularities) (10% [10%]). The same relation was observed in each of the 4 subgroups with Q-wave infarction, non–Q-wave infarction, preceding effort angina within 1 month before AMI, and no preceding effort angina. Conclusions —The appearance of marked progression and Ambrose’s type II eccentric lesion on coronary angiograms 3 days before AMI suggests the presence of a considerable time from the onset of plaque rupture and/or thrombi until the onset of AMI. These features may be predictors of AMI. The concept provides new insight into the mechanism and prevention of human AMIs.
Repolarization Phase at Various Sites of the Right Atrium
Authors: HIROSHI IRISAWA, ISHIO NINOMIYA, ISSEI SEYAMA
Journal: Circulation Research (1966)

By means of a suction electrode method, the time course of depolarization and repolarization was observed in the in situ exposed right atrium of dogs. Under normal conditions the end of repolarization at various sites on the atrium occurred after the QRS spikes, and therefore, the T a wave should be inscribed after and not during the QRS spikes. The concentric spread of activation originating from the S-A node has been confirmed. The region of inital excitation does not become the initial focus of repolarization. The initial focus of repolarization is different from animal to animal, and this focus cannot be associated with any special cardiac tissue. The process of repolarization occurs concentrically from an initial focus that is not limited to any specific region of the atrium.
Vascular Endothelial Growth Factor-A Specifies Formation of Native Collaterals and Regulates Collateral Growth in Ischemia
Authors: Jason A. Clayton, Dan Chalothorn, James E. Faber
Journal: Circulation Research (2008)

The density of native (preexisting) collaterals and their capacity to enlarge into large conduit arteries in ischemia (arteriogenesis) are major determinants of the severity of tissue injury in occlusive disease. Mechanisms directing arteriogenesis remain unclear. Moreover, nothing is known about how native collaterals form in healthy tissue. Evidence suggests vascular endothelial growth factor (VEGF), which is important in embryonic vascular patterning and ischemic angiogenesis, may contribute to native collateral formation and arteriogenesis. Therefore, we examined mice heterozygous for VEGF receptor-1 (VEGFR-1(+/-)), VEGF receptor-2 (VEGFR-2(+/-)), and overexpressing (VEGF(hi/+)) and underexpressing VEGF-A (VEGF(lo/+)). Recovery from hindlimb ischemia was followed for 21 days after femoral artery ligation. All statements below are P<0.05. Compared to wild-type mice, VEGFR-2(+/-) showed similar: ischemic scores, recovery of hindlimb perfusion, pericollateral leukocytes, collateral enlargement, and angiogenesis. In contrast, VEGFR-1(+/-) showed impaired: perfusion recovery, pericollateral leukocytes, collateral enlargement, worse ischemic scores, and comparable angiogenesis. Compared to wild-type mice, VEGF(lo/+) had 2-fold lower perfusion immediately after ligation (suggesting fewer native collaterals which was confirmed by angiography) and blunted recovery of perfusion. VEGF(hi/+) mice had 3-fold greater perfusion immediately after ligation, more native collaterals, and improved recovery of perfusion. These differences were confirmed in the cerebral pial cortical circulation where, compared to VEGF(hi/+) mice, VEGF(lo/+) formed fewer collaterals during the perinatal period when adult density was established, and had 2-fold larger infarctions after middle cerebral artery ligation. Our findings indicate VEGF and VEGFR-1 are determinants of arteriogenesis. Moreover, we describe the first signaling molecule, VEGF-A, that specifies formation of native collaterals in healthy tissues.
Cutaneous chylous reflux
Authors: L-C. CHERN, C-S. LIN, C-K. WONG
Journal: British Journal of Dermatology (1989)

Two cases of cutaneous chylous reflux are described. Both patients had many translucent white vesicles from which milk-like fluid wept intermittently. Lymphangiogram revealed dilated, tortuous lymphatic vessels and dermal backflow. Electron microscopic studies showed an abnormal ultrastructure of the dilated lymphatics.
Visual Pigment Molecular Evolution in the Trinidadian Pike Cichlid (Crenicichla frenata): A Less Colorful World for Neotropical Cichlids?
Authors: Cameron J. Weadick, Ellis R. Loew, F. Helen Rodd, Belinda S. W. Chang
Journal: Molecular Biology and Evolution (2012)

The Trinidadian pike cichlid (Crenicichla frenata) is a major predator of the guppy (Poecilia reticulata), a model system for visual ecology research, and visual predation by the pike cichlid is known to select for male guppies with reduced short-wavelength reflectance. However, an early study of the pike cichlid's visual system suggested a lack of short-wavelength–sensitive cone photoreceptors, a surprising finding as many African cichlids have highly developed short-wavelength vision. In this study, we found evidence for only four expressed cone opsins (LWS, RH2a, SWS2a, and SWS2b), plus one pseudogene (RH2b). Taken together with our microspectrophotometry data, which revealed the presence of three types of cone photoreceptor, including one sensitive to short-wavelength light, this would indicate a broader spectral capacity than previously believed from earlier visual studies of this fish. Relative to the highly diverse African cichlids, however, this Neotropical cichlid appears to have a greatly reduced opsin complement, reflecting both gene loss along the Neotropical lineage (lacking functional RH2b and, possibly, SWS1 opsins) and gene duplication within the African clade (which possesses paralogous RH2aα and RH2aβ opsins). Molecular evolutionary analyses show that positive selection has shaped the SWS2b and RH1 opsins along the Neotropical lineage, which may be indicative of adaptive evolution to alter nonspectral aspects of opsin biology. These results represent the first molecular evolutionary study of visual pigments in a Neotropical cichlid and thus provide a foundation for further study of a morphologically and ecologically diverse clade that has been understudied with respect to the link between visual ecology and diversification.
Methods for Gene Expression Profiling in Clinical Trials of Adjuvant Breast Cancer Therapy
Authors: Soonmyung Paik
Journal: Clinical Cancer Research (2006)

Although endocrine therapy is highly effective in the treatment of endocrine receptor-positive breast cancer, chemotherapy has been shown to provide clinical benefit when added to tamoxifen. However, baseline risk after tamoxifen treatment is so low, especially in patients who are axillary node negative, that significant overtreatment will result if chemotherapy is given to every patient. Robust prognostic and predictive markers need to be developed to identify those at high risk of treatment failure. Although comprehensive gene expression profiling methods do offer promise, they require fresh or frozen tumor samples. To take advantage of existing archived tissue blocks with clinical follow-up collected from finished clinical trials, such as National Surgical Adjuvant Breast and Bowel Project trials B-20 and B-14, technologies that allow interrogation of archived blocks for gene expression profiling need to be realized. Recent developments in gene expression profiling technologies are discussed with their implications in clinical management of endocrine receptor-positive breast cancer.
Reactive oxygen species signaling in vascular smooth muscle cells
Authors: R CLEMPUS, K GRIENDLING
Journal: Cardiovascular Research (2006)

Reactive oxygen species (ROS) have been shown to function as important signaling molecules in the cardiovascular system. Vascular smooth muscle cells (VSMCs) contain several sources of ROS, among which the NADPH oxidases are predominant. In VSMCs, ROS mediate many pathophysiological processes, such as growth, migration, apoptosis and secretion of inflammatory cytokines, as well as physiological processes, such as differentiation, by direct and indirect effects at multiple signaling levels. Therefore, it becomes critical to understand the different roles ROS play in the physiology and pathophysiology of VSMCs.
PTU-092 The Management of Alcohol Withdrawal in Patients with advanced Liver Disease: Abstract PTU-092 Table
Authors: E Forrest, A Ahmed, G Benson
Journal: Gut (2013)

<h3>Introduction</h3> Alcohol withdrawal syndrome (AWS) is a common reason for hospital admission. However a significant number of these patients have co-existent liver disease or other medical problems. There is little information regarding the management of these patients. <h3>Methods</h3> Patients were assessed for hazardous drinking using the FAST score. Data was collected prospectively on FAST positive patients with regards to their subsequent treatment using a unified AWS guideline. Patients with known liver disease or presenting with decompensated liver disease were identified (Group 1) and compared with patients admitted with non-hepatic primary alcohol-related diagnoses (Group 2) and patients with admitted primarily non-alcohol related medical diagnoses (Group 3). Results are expressed as median (95% confidence). <h3>Results</h3> 53 patients had significant liver disease (Group 1), with 153 in Group 2 and 106 in Group 3. Median MELD score in Group 1 was 15.4 [12.8, 17.6]. The three groups had similar FAST scores: 14 [12, 15], 14 [13, 14] and 13 [12, 14] respectively. Fewer patients in Group 1 and Group 3 required benzodiazepine (BZD) treatment compared with Group 2. When required, the median BZD prescription (mg diazepam equivalent) during admission was greater for Group 2 patients compared with Group 1 and Group 3 (Table). More patients in Group 1 were treated with lorazepam rather than diazepam; 13% <i>cf</i> 5% in Group 2 (p = 0.1, –1, 20.4) and 3% in Group 3 (p = 0.04; 0.7, 22.3). The proportion of patients requiring parenteral treatment for breakthrough symptoms were similar: Group 1: 5.6%, Group 2: 4.6%, Group 3 4.7%. There were correlations between the FAST score and subsequent amount of diazepam prescribed for Group 2 (p = 0.002; 0.09, 0.4) and Group 3 (p = 0.03; 0.02, 0.41), but not for Group 1 (p = 0.26; –0.12, 0.43). Overall survival until 33 months was less in Group 1 (64%) compared with Group 2 (84%; p = 0.0007 HR 0.29 [0.14, 0.60] and Group 3 (81%; p = 0.016 HR 2.30 [1.17, 4.55]). <h3>Conclusion</h3> Compared to patients admitted with primarily AWS or alcohol related seizures, patients with chronic liver disease and those with other medical problems were less likely to require any benzodiazepine therapy and require lesser amounts of such treatment. The expected association between indicators of harmful/dependent drinking and BZD requirement was lost in liver disease patients. Care should be taken to avoid unnecessary over-treatment of these patients. <h3>Disclosure of Interest</h3> None Declared
Lack of association of intermediate CPK-MB elevation and late mortality in patients treated with intracoronary stents
Authors: J.F. Saucedo, J.J. Popma, R. Mehran, T. Bucher, A.S. Abizaid, M. Curran, M. Mastoor, K.M. Kent, A. Pichard, L. Satler, M.B. Leon
Journal: Journal of the American College of Cardiology (1998)
Errors in the Processing of Dye Dilution Curves
Authors: G. Richard Kelman
Journal: Circulation Research (1966)

Errors of two kinds occur in the processing of dye dilution curves: 1) Individual estimates of the decay constant of a dye curve are subject to random errors causing a variability of up to 10% in the calculated cardiac output, and of up to 4% in the estimated vascular volume. 2) The use of an inappropriate numerical integration formula can cause an additional error of up to 5% in the calculated cardiac output. This may be avoided by using either the trapezoid rule or Simpson's rule. The planimeter measures areas with sufficient accuracy for routine determination of cardiac output.
DNA synthesis in human rheumatoid and nonrheumatoid synovial lining.
Authors: L A Coulton, B Henderson, L Bitensky, J Chayen
Journal: Annals of the Rheumatic Diseases (1980)

The DNA content per nucleus has been measured in the lining cells of 12 specimens of rheumatoid and 12 of nonrheumatoid synovial tissue. Optimal conditions for this reaction on these cells have been defined, and an index of DNA synthesis has been applied to give a quantitative measure of the degree of synthesis. This has given evidence of some DNA synthesis in both types of synoviocytes, compatible with the amount found in a slowly self-replacing tissue. There was no difference in the amount of synthesis in the rheumatoid and nonrheumatoid synoviocytes.
Allelic Imbalance on 12q22-23 in Serum Circulating DNA of Melanoma Patients Predicts Disease Outcome
Authors: Akihide Fujimoto, Steven J. O’Day, Bret Taback, David Elashoff, Dave S. B. Hoon
Journal: Cancer Research (2004)

Abstract Allelic imbalance (AI) encompassing the apoptotic protease-activating factor 1 (APAF-1) locus (12q22-23) is found frequently in metastatic melanoma. Circulating DNA with AI on 12q22-23 in serum was evaluated as a surrogate marker to predict biochemotherapy (BC) treatment response in melanoma patients. Sera were collected from 49 American Joint Committee on Cancer stage IV melanoma patients treated with BC. Serum AI of the 12q22-23 region was demonstrated to be present before and/or after BC. BC responders showed a significantly lower frequency of AI (5 of 24, 21%) compared with nonresponders (11 of 20, 55%; Fisher’s exact test, P &amp;lt; 0.029). Serum AI on 12q22-23 was associated with worse prognosis (log-rank test, P &amp;lt; 0.046). These findings indicate that serial serum genetic analysis of tumor-related AI on 12q22-23 may have clinical use in predicting tumor response to therapy.
Complex Genetics of Obesity in Mouse Models
Authors: Daniel Pomp, Derrick Nehrenberg, Daria Estrada-Smith
Journal: Annual Review of Nutrition (2008)

Traits related to energy balance and obesity are exceptionally complex, with varying contributions of genetic susceptibility and interacting environmental factors. The use of mouse models has been a powerful driving force in understanding the genetic architecture of polygenic traits such as obesity. However, the use of mouse models for analysis of complex traits is at an important crossroad. Genome-wide association studies in humans are now leading to direct identification of obesity genes. In this review, we focus on three areas representing the current and future roles of mouse models regarding genetics of complex obesity. First, we summarize increasingly powerful ways to harness the strength of mouse models for discovery of genes affecting polygenic obesity. Second, we examine the status of using a systems biology approach to dissect the genetic architecture of obesity. And third, we explore the effects of recent findings indicating increasing levels of complexity in the nature of variation underlying, and the heritability of, complex traits such as obesity.