tbuckley/cabot-search huggingface dataset:
Antenatal screening for Down's syndrome in assisted reproductive pregnancies
Authors: R Maymon
Journal: Human Reproduction Update (1999)

The wide use of assisted conception methods has risen dramatically. The greater proportion of singletons, twins and high order of multiplicity conceived by those methods have already focused the medical community to various obstetric complications. Recently, there have been suggestions that the levels of mid-gestation serum markers, particularly human chorionic gonadotrophin (HCG), might be affected by assisted conception, leading to higher false-positive results. Furthermore, women who conceived after assisted reproduction methods are on average older, and in many cases their current pregnancy was achieved after long-standing infertility and might even be their last one. This is why they are extremely wary of any invasive fetal karyotyping. Therefore, every effort should be made to provide them with the most accurate screening of Down's syndrome (DS) risk. In this respect, nuchal translucency (NT) measurement, which has been reported to be another effective screening method, might be a more reliable marker in these pregnancies. This review explores the problematic issue of antenatal DS screening in assisted conception pregnancies. For the singletons and twins, a sequential NT and second-trimester serum marker screening can be offered, thus producing a single risk estimation which seems to be more accurate. For the high order of multiplicity, the NT offers additional important data, which can be taken in consideration both as a screening tool for DS and if fetal reduction is planned.
An Atypical Variant of Fabry's Disease in Men with Left Ventricular Hypertrophy
Authors: Shoichiro Nakao, Toshihiro Takenaka, Masato Maeda, Chihaya Kodama, Akihiro Tanaka, Minoru Tahara, Aichi Yoshida, Masaru Kuriyama, Hidemasa Hayashibe, Hitoshi Sakuraba, Hiromitsu Tanaka
Journal: New England Journal of Medicine (1995)

fabry's disease is an x-linked recessive disorder that results from a deficiency of α-galactosidase. Left ventricular hypertrophy is one of the common manifestations in men with classic hemizygous disease. Recently, several cases of an atypical variant of hemizygous Fabry's disease, with manifestations limited to the heart, have been reported. Therefore, we assessed the incidence of hemizygosity for Fabry's disease among male patients with left ventricular hypertrophy.
Ethambutol induced bullous and lichenoid skin eruptions
Authors: Inés Akrout, Eya Tangour, Souraya Fenniche, Hela Hassene, Leila Feki, Dorra Greb, Haifa Zaibi, Med Lamine Megdiche
Journal: European Respiratory Journal (2011)

Introduction:  Ethambutol is an essential drug for tuberculosis treatment. It has been in use since 1961. Its major side effect is on visual system, cutaneous side effects are rarely descripted in the literature including purpura, pruritic erythematous papules and exfoliative dermatitis.   Materials and methods:  We report one case of ethambutol induced bullous and lichenoid skin rashes confirmed by provocation test.   Results:  It9s about 73 years old woman, diabetic,treated of lung tuberculosis with Isoniazid, Rifampicin, pyrazinamid and ethambutol. After 25 days for treatment she reported generalised itching. Cutaneous examination revealed vesiculo-bullous eruptions on chest and abdominal wall, hyperpigmented face and diffuse desquamation on the limbs. All anti tuberculosis drugs were stopped and patient was put on local corticosteroid therapy for two weeks. The lesions cleared completely. Because of its low risk of entraining skin side effect, ethambutol was introduced the first drug in a dose of 20 mg/kg. 24 hours later this provocation test, generalised itching and erythematovisicular skin eruptions more marked on the extremities were appeared, further administration of ethambutol was stopped. Patch tests will be programmed when lesions disappeared.  Clinician should be alerted to consider ethambutol also as one of possible drug causing cutaneous eruptions.
Inhibition of AMPK signalling by doxorubicin: at the crossroads of the cardiac responses to energetic, oxidative, and genotoxic stress
Authors: Séverine Gratia, Laurence Kay, Lucia Potenza, Amal Seffouh, Valérie Novel-Chaté, Coralie Schnebelen, Piero Sestili, Uwe Schlattner, Malgorzata Tokarska-Schlattner
Journal: Cardiovascular Research (2012)

AimsCardiotoxic side effects of anthracyclines, the most widely used anticancer drugs, are well documented, while mechanisms involved are not fully elucidated. The cellular energy sensor and regulator AMP-activated protein kinase (AMPK) was suggested as a putative mediator of cardiotoxicity of doxorubicin, the leading anthracycline drug, by our earlier work. Here, we study the interference of doxorubicin with AMPK signalling and potentially involved mechanisms.
Lung cancer risk based on visual assessment of emphysema and interstitial abnormalities in low dose chest CT
Authors: Mathilde Winkler Wille, Laura Thomsen, Asger Dirksen, Saher Shaker, Jesper Holst Pedersen
Journal: European Respiratory Journal (2014)

Introduction  – Screening for lung cancer should be limited to a high risk population, and CT findings may be relevant for predicting the risk of lung cancer.   Aims and objectives  – To compare the occurrence of visually detected emphysema and interstitial abnormalities in subjects with and without lung cancer.   Methods and materials  – Baseline low dose CT scans of 1990 participants from The Danish Lung Cancer Screening Trial were evaluated. Participants had a smoking history of at least 20 pack years, a FEV 1  of at least 30% of predicted, and were aged 50-75 years. Two blinded observers independently scored emphysema and various interstitial abnormalities as present or absent, and furthermore the degree of emphysema was scored as 0: 0%, 1:1-5%, 2:6-25%, 3:26-50%, 4:51-75% or 5:76-100%. Furthermore, emphysema was measured quantitatively as: 15 th  percentile density (PD15), low attenuation area percentages with a threshold of -910 Hounsfield Units (HU) (LAA%-910) and -950 HU (LAA%-950).   Results  - Visual evaluations: emphysema present: OR 1.9 (p= 0.009). Mean emphysema grade 1.4 (SD 0.6) versus 1.2 (SD 0.5), p=0.010 in groups with and without lung cancer, respectively. Interstitial abnormality present: OR 4.5 (p   Conclusion  – In a lung cancer screening cohort of current and former heavy smokers visual assessment of even early signs of emphysema and interstitial abnormalities can be used for predicting lung cancer as these findings are significantly overrepresented in lung cancer patients. Quantitative measurements of emphysema—regardless of type—did not have the same predictive value.
Impact of Vascular Endothelial Growth Factor-C and -D Expression in Human Pancreatic Cancer
Authors: Hiroshi Kurahara, Sonshin Takao, Kousei Maemura, Hiroyuki Shinchi, Shoji Natsugoe, Takashi Aikou
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The aim of this study was to evaluate the expression of vascular endothelial growth factor (VEGF)-C and -D in pancreatic cancer and to reveal its relation to lymph node metastasis. Experimental Design: Formalin-fixed, paraffin-embedded blocks were obtained from 58 patients with pancreatic head cancer. All of the patients underwent a curative resection. The total number of resected lymph nodes was 1,058. The expressions of VEGF-C and -D were evaluated by immunohistochemical staining. To evaluate the relation to lymph node metastasis, the expressions of VEGF-C and -D between the marginal and central portions in the tumor were compared. When &amp;gt;25% of the tumor cells showed distinct staining, the portion was judged as high expression. Results: The two groups with high expression of VEGF-C (P = 0.015) and VEGF-D (P = 0.020) in the marginal portion had a significantly higher incidence of lymph node metastasis compared with the groups with low expression, respectively. Furthermore, the group with high expression of both VEGF-C and -D in the marginal portion had a higher incidence of lymph node metastasis compared with the group with low expression (P = 0.007). The 5-year survival rate of patients with high expression of both VEGF-C and -D in the marginal portion was significantly lower than that of patients with low expression of both VEGF-C and -D (P = 0.017). Conclusions: VEGF-C and -D expression in tumor cells in the marginal portion of the tumor significantly associated with lymphatic metastasis and prognosis in patients with pancreatic head cancer.
3D-MAGMA: A novel way of measuring gastrointestinal motility in patients with infectious diarrhoea
Authors: J. Felber, S. Paetzold, H. Richert, A. Stallmach
Journal: Gut (2011)

<h3>Introduction</h3> The current means of measuring gut motility are limited. Manometry and scintigraphic transit tests are the two most commonly used tests to investigate small bowel motility. Diarrhoeal symptoms are a frequent problem in clinical practise. They can be explained by abnormalities in the absorption and secretion of fluids but also by changes in the motility of the small and large intestine. <h3>Methods</h3> 20 healthy volunteers and 7 patients with infectious diarrhoea (ID) caused by salmonella spec. underwent motility testing of the small bowel by a high-resolution three-dimensional magnetic detection system called 3D-MAGMA. A new technique that allows the tracking of a magnetic capsule in three-dimensional space with high accuracy in position and orientation by sensors placed above a supine patient. <h3>Results</h3> The pacemaker frequency in patients with infectious diarrhoea (median: 10.6; min-max: 8.4−11.8; (cpm)) did not differ from that in healthy controls (median: 10.7; min-max: 8.4−12.9). There was a tendency of the capsule in patients with diarrhoeal symptoms to cover a greater distance in the first hour after leaving the stomach (controls: median: 150; min-max: 82−262; ID: median: 175; min-max: 135−315; (cm)). The time proportion of spike-wave activity (&gt;0.2 cm/s) in the duodenum was higher in all participants compared to the jejunum as was the velocity of the capsule in the duodenum. However, while patients with infectious diarrhoea showed an increase of strong spike-wave activity (&gt;0.5 cm/s) in the jejunum compared to the duodenum, strong spike-wave activity was absent in the jejunum of controls. For both groups a negative correlation could be found for the time proportion of spike-wave activity (&gt;0.2 cm/s) and the length of time the capsule spent in the duodenum (controls: rs=−0.95; p&lt;0.0001; ID: rs=−0.91; p=0.004). While this could also be shown in the jejunum for controls the correlation was lost in diarrhoea sufferers (controls: rs=−0.91; p&lt;0.0001; ID: rs=−0.62; p=0.14). <h3>Conclusion</h3> Abnormalities in small bowel motility play an important part in developing diarrhoeal symptoms in patients with gastroenteritis. Especially the distal small bowel appears to be of importance in the development of symptoms. Small bowel testing with magnetic marker monitoring enhances the understanding of the underlying pathophysiology in these patients.
Low-Volume Insulin Degludec 200 Units/mL Once Daily Improves Glycemic Control Similarly to Insulin Glargine With a Low Risk of Hypoglycemia in Insulin-Naïve Patients With Type 2 Diabetes
Authors: Stephen C.L. Gough, Anuj Bhargava, Rajeev Jain, Henriette Mersebach, Søren Rasmussen, Richard M. Bergenstal
Journal: Diabetes Care (2013)

The 200 units/mL formulation of insulin degludec (IDeg 200 units/mL) contains equal units of insulin in half the volume compared with the 100 units/mL formulation. We compared the efficacy and safety of IDeg 200 units/mL once daily with 100 units/mL insulin glargine (IGlar) in insulin-naïve subjects with type 2 diabetes (T2DM) inadequately controlled with oral antidiabetic drugs.In this 26-week, open-label, treat-to-target trial, subjects (n = 457; mean HbA1c 8.3% [67 mmol/mol], BMI 32.4 kg/m(2), and fasting plasma glucose [FPG] 9.6 mmol/L [173.2 mg/dL]) were randomized to IDeg 200 units/mL or IGlar, both given once daily in combination with metformin with or without a dipeptidyl peptidase-4 inhibitor. Basal insulin was initiated at 10 units/day and titrated weekly to an FPG target of <5 mmol/L (<90 mg/dL) according to mean prebreakfast self-measured blood glucose values from the preceding 3 days.By 26 weeks, IDeg reduced HbA1c by 1.30% and was not inferior to IGlar. Mean observed FPG reductions were significantly greater with IDeg than IGlar (-3.7 vs. -3.4 mmol/L [-67 vs. -61 mg/dL]; estimated treatment difference: -0.42 [95% CI -0.78 to -0.06], P = 0.02). Despite this difference, rates of overall confirmed hypoglycemia were not higher with IDeg than with IGlar (1.22 and 1.42 episodes/patient-year, respectively), as were rates of nocturnal confirmed hypoglycemia (0.18 and 0.28 episodes/patient-year, respectively). Mean daily basal insulin dose was significantly lower by 11% with IDeg 200 units/mL compared with IGlar. IDeg was well-tolerated, and the rate of treatment-emergent adverse events was similar across groups.In this treat-to-target trial in insulin-naïve patients with T2DM, IDeg 200 units/mL improved glycemic control similarly to IGlar with a low risk of hypoglycemia.
An Iron Regulatory Gene Signature Predicts Outcome in Breast Cancer
Authors: Lance D. Miller, Lan G. Coffman, Jeff W. Chou, Michael A. Black, Jonas Bergh, Ralph D'Agostino, Suzy V. Torti, Frank M. Torti
Journal: Cancer Research (2011)

Abstract Changes in iron regulation characterize the malignant state. However, the pathways that effect these changes and their specific impact on prognosis remain poorly understood. We capitalized on publicly available microarray datasets comprising 674 breast cancer cases to systematically investigate how expression of genes related to iron metabolism is linked to breast cancer prognosis. Of 61 genes involved in iron regulation, 49% were statistically significantly associated with distant metastasis-free survival. Cases were divided into test and training cohorts, and the supervised principal component method was used to stratify cases into risk groups. Optimal risk stratification was achieved with a model comprising 16 genes, which we term the iron regulatory gene signature (IRGS). Multivariable analysis revealed that the IRGS contributes information not captured by conventional prognostic indicators (HR = 1.61; 95% confidence interval: 1.16–2.24; P = 0.004). The IRGS successfully stratified homogeneously treated patients, including ER+ patients treated with tamoxifen monotherapy, both with (P = 0.006) and without (P = 0.03) lymph node metastases. To test whether multiple pathways were embedded within the IRGS, we evaluated the performance of two gene dyads with known roles in iron biology in ER+ patients treated with tamoxifen monotherapy (n = 371). For both dyads, gene combinations that minimized intracellular iron content [anti-import: TFRCLow/HFEHigh; or pro-export: SLC40A1 (ferroportin)High/HAMPLow] were associated with favorable prognosis (P &amp;lt; 0.005). Although the clinical utility of the IRGS will require further evaluation, its ability to both identify high-risk patients within traditionally low-risk groups and low-risk patients within high-risk groups has the potential to affect therapeutic decision making. Cancer Res; 71(21); 6728–37. ©2011 AACR.
Trends in the Use of Percutaneous Ventricular Assist Devices
Authors: Rohan Khera, Peter Cram, Xin Lu, Ankur Vyas, Alicia Gerke, Gary E. Rosenthal, Phillip A. Horwitz, Saket Girotra
Journal: JAMA Internal Medicine (2015)

Percutaneous ventricular assist devices (PVADs) provide robust hemodynamic support compared with intra-aortic balloon pumps (IABPs), but clinical use patterns are unknown.To examine contemporary patterns in PVAD use in the United States and compare them with use of IABPs.Retrospective study of adults older than 18 years who received a PVAD or IABP while hospitalized in the United States (2007-2012).Temporal trends in utilization, patient and hospital characteristics, in-hospital mortality, and cost of PVAD use compared with IABP.During 2007 through 2012, utilization of PVADs increased 30-fold (4.6 per million discharges in 2007 to 138 per million discharges in 2012; P for trend < .001) while utilization of IABPs decreased from 1738 per million discharges in 2008 to 1608 per million discharges in 2012 (P for trend = .02). In 2007, an estimated 72 hospitals used PVADs, increasing to 477 in 2011 (P for trend < .001). The number of hospitals with an annual volume of 10 or more PVAD procedures per year increased from 0 in 2007 to 102 in 2011 (21.4% of PVAD-using hospitals; P for trend < .001). Among PVAD recipients, 67.3% had a diagnosis of cardiogenic shock or acute myocardial infarction (AMI). There was a temporal increase in the use of PVADs in older patients and patients with AMI, hypertension, diabetes mellitus, and chronic kidney disease (P for trend < .001 for all). Overall, mortality in PVAD recipients was 28.8%, and mean (SE) hospitalization cost was $85,580 ($4165); both were significantly higher in PVAD recipients with cardiogenic shock (mortality, 47.5%; mean [SE] cost, $113,695 [$6260]; P < .001 for both). The PVAD recipients were less likely than IABP recipients to have cardiogenic shock (34.3% vs 41.2%; P = .001), AMI (48.0% vs 68.6%; P < .001), and undergo coronary artery bypass graft surgery (6.2% vs 43.2%; P < .001), but more likely to undergo percutaneous coronary intervention (70.9% vs 40.4%; P < .001). In propensity-matched analysis, PVADs were associated with higher mortality compared with IABP (odds ratio, 1.23 [95% CI, 1.06-1.43]; P = .007).There has been a substantial increase in the use of PVADs in recent years with an accompanying decrease in the use of IABPs. Given the high mortality, associated cost, and uncertain evidence for a clear benefit, randomized clinical trials are needed to determine whether use of PVADs leads to improved patient outcomes.
Lansley denies plan to create "super quango" to control the NHS
Authors: A. O'Dowd
Journal: BMJ (2011)

Health secretary Andrew Lansley has denied allegations that the NHS Commissioning Board could be reshaped as a new “super quango” with greater central power over local commissioners.

MPs on the parliamentary health select committee quizzing Mr Lansley on 5 July asked about an as yet unpublished Department of Health document leaked to the Health Service Journal about a proposal to rename the NHS Commissioning Board as NHS England, suggesting its power would encompass much more than commissioning and overseeing the new clinical commissioning groups.

The evidence session was held as part of an inquiry into the NHS Future Forum—the independent body set up by the government to review the planned …
The Regulation of AMPK β1, TSC2, and PTEN Expression by p53: Stress, Cell and Tissue Specificity, and the Role of These Gene Products in Modulating the IGF-1-AKT-mTOR Pathways
Authors: Zhaohui Feng, Wenwei Hu, Elisa de Stanchina, Angelika K. Teresky, Shengkan Jin, Scott Lowe, Arnold J. Levine
Journal: Cancer Research (2007)

The insulin-like growth factor 1 (IGF-1)-AKT-mTOR pathways sense the availability of nutrients and mitogens and respond by signaling for cell growth and division. The p53 pathway senses a variety of stress signals which will reduce the fidelity of cell growth and division, and responds by initiating cell cycle arrest, senescence, or apoptosis. This study explores four p53-regulated gene products, the beta1 and beta2 subunits of the AMPK, which are shown for the first time to be regulated by the p53 protein, TSC2, PTEN, and IGF-BP3, each of which negatively regulates the IGF-1-AKT-mTOR pathways after stress. These gene products are shown to be expressed under p53 control in a cell type and tissue-specific fashion with the TSC2 and PTEN proteins being coordinately regulated in those tissues that use insulin-dependent energy metabolism (skeletal muscle, heart, white fat, liver, and kidney). In addition, these genes are regulated by p53 in a stress signal-specific fashion. The mTOR pathway also communicates with the p53 pathway. After glucose starvation of mouse embryo fibroblasts, AMPK phosphorylates the p53 protein but does not activate any of the p53 responses. Upon glucose starvation of E1A-transformed mouse embryo fibroblasts, a p53-mediated apoptosis ensues. Thus, there is a great deal of communication between the p53 pathway and the IGF-1-AKT and mTOR pathways.
Novel Prognostic Value of Nuclear Epidermal Growth Factor Receptor in Breast Cancer
Authors: Hui-Wen Lo, Weiya Xia, Yongkun Wei, Mohamed Ali-Seyed, Shiu-Feng Huang, Mien-Chie Hung
Journal: Cancer Research (2005)

Epidermal growth factor receptor (EGFR) has been detected in the nucleus of cancer cells and primary tumors for decades. While localized in the nucleus, EGFR functions as a transcriptional regulator resulting in the activation of the cyclin D1 gene. Despite nuclear accumulation of EGFR is linked to increased DNA synthesis and proliferative potential, the pathological significance of nuclear EGFR, however, remains uninvestigated. Furthermore, expression of EGFR has not provided a consistent predictive value for survival of breast cancer patients. Here, we analyzed 130 breast carcinomas via immunohistochemical analyses for the levels of nuclear and non-nuclear EGFR. We found 37.7% of the cohort immunostained positively for nuclear EGFR and 6.9% with high levels of expression. Importantly, Kaplan-Meier survival analysis and log-rank test revealed a significant inverse correlation between high nuclear EGFR and overall survival (P = 0.009). Expression of nuclear EGFR correlated positively with increased levels of cyclin D1 and Ki-67, both are indicators for cell proliferation. In contrast, expression of non-nuclear EGFR did not significantly correlate with those of cyclin D1 and Ki-67 or the overall survival rate. In addition, we analyzed 37 oral squamous carcinomas for EGFR expression and found 24.3% of the cases to contain moderate/high levels of nuclear EGFR. Taken together, our findings indicate pathological significance of nuclear EGFR and may have important clinical implication.
Future directions for rhodopsin structure and function studies
Authors: Paul A. Hargrave
Journal: Behavioral and Brain Sciences (1995)

Abstract To understand how the photoreceptor protein rhodopsin performs in its role as a receptor, its structure needs to be determined at the atomic level. Upon receiving a photon of light, rhodopsin undergoes a change in conformation that allows it to bind and activate the C-protein, transducin. An important future goal should be to determine the structure of both the inactive and the photoactivated state of rhodopsin, R*. This should provide the groundwork necessary for experiments on how rhodopsin achieves its signaling state R*, and how R* functions to activate transducin. To do this, the crystal structure of both rhodopsin and R* must be determined. Few membrane proteins have been successfully crystallized, so this is not a trivial undertaking. Two- or three dimensional crystals of rhodopsin must be prepared that are well ordered, to produce a high-resolution structure. Rhodopsin must be purified to homogeneity and the appropriate detergent(s) selected for crystallization experiments. Long-term thermal stability of the rhodopsin-detergent complex must be achieved in the presence of a precipitant. Two-dimensional crystals may offer advantages in investigating the structure of R*, but the structure obtained may be limited in resolution. It is necessary to work with rhodopsin in the dark, unless suitable light-stable retinal derivatives are developed. Protein engineering of rhodopsin offers attractive opportunities to improve its ability to crystallize, but is presently hindered by the absence of a high-yielding expression system. Knowledge of the structure of rhodopsin will have general importance. Because rhodopsin is a member of the family of C-protein-coupled receptors, knowledge of the structure and the mechanism of action of rhodopsin suggests by analogy how other members of the receptor family may function.