tbuckley/cabot-search huggingface dataset:
Patients on Atypical Antipsychotic Drugs
Authors: Michael E.J. Lean, Frank-Gerald Pajonk
Journal: Diabetes Care (2003)

Patients with schizophrenia are more likely than the general population to develop diabetes, which contributes to a high risk of cardiovascular complications; individuals with schizophrenia are two to three times more likely to die from cardiovascular disease than the general population. The risk of diabetes, and hence cardiovascular disease, is particularly increased by some of the new atypical antipsychotic drugs. Individuals taking an atypical antipsychotic drug, particularly younger patients under 40 years of age (odds ratio 1.63, 95% CI 1.23–2.16), represent an underrecognized group at high risk of type 2 diabetes. The mechanisms responsible for antipsychotic-induced diabetes remain unclear. Hypotheses include these drugs’ potential to cause weight gain, possibly through antagonism at the H1, 5-HT2A, or 5-HT2C receptors. Other mechanisms independent of weight gain lead to elevation of serum leptin and insulin resistance. Patients with psychoses have difficulties with diet and lifestyle interventions for diabetes and weight management. If hyperglycemia develops, withdrawal from antipsychotic medication will often be inappropriate, and a change to an atypical antipsychotic drug with lower diabetogenic potential should be considered, especially in younger patients. Management of psychoses should routinely include body weight and blood glucose monitoring and steps to promote exercise and minimize weight gain. Careful collaboration between the psychiatric and diabetology teams is essential to minimize the risk of diabetes in patients taking atypical antipsychotic medication and for effective management when it develops. This collaboration will also help minimize the already high risk of cardiovascular disease in individuals with schizophrenia.
Arterial expression of the plasminogen activator system early after cardiac transplantation
Authors: M Garvin
Journal: Cardiovascular Research (1997)

Recent studies suggest that alterations in tissue thrombolysis as well as the inward migration of cells may be specific events that contribute to coronary artery narrowing after cardiac transplantation. Plasminogen activators and inhibitors play a central role in governing not only tissue thrombolysis, but also vascular cell migration. The purpose of this study was to examine arterial wall expression of the plasminogen activation system in coronary arteries during graft vascular disease initiation and progression.Using in situ hybridization and immunocytochemistry, the expression patterns of uPA and PAI-1 in coronary arteries from cardiac allografts were compared to those of young individuals without disease.Both PAI-1 and uPA were over-expressed early after transplantation and as late as 27 months post grafting. Over-expression of these molecules preceded morphological evidence of graft vascular disease. Of special note was the adventitial expression of uPA and PAI-1 in microvessels and myofibroblasts. In contrast, the expression of uPA and PAI-1 in normal coronary arteries was confined to endothelial cells of the central lumen, as well as low levels of expression in intimal and medial smooth muscle cells.Despite morphologic similarities between normal and transplant coronary arteries, differences were noted in the vascular expression pattern of uPA and PAI-1. The exact role of these molecules in graft vascular disease requires further study; however, it is intriguing to consider that a local imbalance in the plasminogen system may contribute to arterial wall thrombosis and/or excessive cell migration and the genesis of complex vascular lesions.
Human Parvovirus Infections
Authors: Harley A. Rothart
Journal: Annual Review of Medicine (1990)

The B19 strain ofparvovirus causes several distinct and important clinical diseases in humans. Aplastic crisis in patients with chronic hemolytic anemia, persistent bone marrow depression in immunocompromised individuals, and hydrops fetalis all result from direct infection of hematopoietic cells by the virus. Erythema infectiosum, arthritis, and purpuric vasculitis are postinfectious manifestations of B19 parvovirus infection.
TRANSPLANTATION OF THE HEART AND LUNGS IN CHILDREN
Authors: Thomas L. Spray, M.D
Journal: Annual Review of Medicine (1994)

▪ Abstract Heart transplantation in children with complex congenital heart disease or cardiomyopathies has become an effective form of therapy for patients with no other surgical options. Because pediatric pulmonary transplantation is a relatively new procedure, long-term follow-up data are not yet available. However, the intermediate-term results of pediatric lung transplantation appear similar to those for heart and lung transplantation. Children represent a particularly difficult patient group for transplant of thoracic organs, and recipients must be selected carefully. Additionally, physicians must pay close attention to multiple medical conditions relating to the underlying disease process in order to achieve optimal results.
Chronic progressive pressure overload of the cat right ventricle.
Authors: G Cooper, R J Tomanek, J C Ehrhardt, M L Marcus
Journal: Circulation Research (1981)

When an abrupt, fixed increase in afterload induces hypertrophy, the myocardium exhibits normal pump function in vivo, depressed muscle function in vitro, and paradoxically increased oxygen consumption. Such abnormalities may be either a transient response to a reversible myocardial injury or instead may be a persistent characteristic of hypertrophy contributing to eventual heart failure. To distinguish between these alternatives, we developed a model of chronic progressive pressure overload. Kittens had either a sham operation or pulmonary banding for 25 (group I) or 60 (group II) weeks. Banding produced a gradually increasing pressure overload with growth, maximum at 16 weeks after operation. The ratio of right ventricular to body weight increase from 0.54 +/- 0.03 to 0.82 +/0.04 g/kg (P less than 0.01) in group I and from 0.50 +/- 0.03 to 0.72 +/- 0.03 (P less than 0.01) in group II. In vivo right ventricular pump function (cardiac output and ejection fraction) was normal in both groups. In vitro contractile function and metabolism were measured in papillary muscles from the same right ventricles. Both experimental groups showed marked contractile abnormalities: preloaded shortening velocity was reduced from 0.80 +/- 0.05 to 0.53 +/- 0.05 muscle length/sec (P less than 0.01) in group I and from 0.84 +/- 0.04 to 0.60 +/- 0.06 (P less than ).01) in group II. Maximum isometric active tension was reduced from 60 +/- 7 to 35 +/- 5 mN/mm2 (P less than 0.01) in group I and from 56 +/- 5 to 27 +/- 4 (P less than 0.01) in group II. Metabolism was normal in both experimental groups. Thus, under conditions relevant to the study of clinical cardiac hypertrophy that are unlikely to cause acute injury, hypertrophy produces persistently abnormal intrinsic contractile function
Downregulation of dystroglycan glycosyltransferases LARGE2 and ISPD associate with increased mortality in clear cell renal cell carcinoma
Authors: Michael R. Miller, Deqin Ma, James Schappet, Patrick Breheny, Sarah L. Mott, Nadine Bannick, Eric Askeland, James Brown, Michael D. Henry
Journal: Molecular Cancer (2015)

Dystroglycan (DG) is a cell-surface laminin receptor that links the cytoskeleton to the extracellular matrix in a variety of epithelial tissues. Its function as a matrix receptor requires extensive glycosylation of its extracellular subunit αDG, which involves at least 13 distinct genes. Prior work has shown loss of αDG glycosylation in an assortment of carcinomas, including clear cell renal cell carcinoma (ccRCC) though the cause (s) and functional consequences of this loss are still unclear. Using The Cancer Genome Atlas (TCGA) database, we analyzed the DG glycosylation pathway to identify changes in mRNA expression and correlation with clinical outcomes. We validated our findings with a cohort of 65 patients treated with radical nephrectomy by analyzing DG glycosylation via immunohistochemistry and gene expression via qRT-PCR. Analysis of TCGA database revealed frequent dysregulation of a subset of DG glycosyltransferases. Most notably, there was a frequent, significant downregulation of GYLTL1B (LARGE2) and ISPD. DG glycosylation is frequently impaired in ccRCC patient samples and most strongly associates with downregulation of GYLTL1B. Reduced levels of GYLTL1B and ISPD mRNA associated with increased patient mortality and are the likely cause of αDG hypoglycosylation in ccRCC.
Play down protein to play up metabolism?
Authors: Timo D. Müller, Matthias H. Tschöp
Journal: Journal of Clinical Investigation (2014)

Who among us hasn't fantasized about a diet that allows ingestion of a surfeit of calories that are burned off effortlessly by ramping up energy expenditure? In this issue of the JCI, research led by Christopher Morrison suggests that this dream may become a reality; however, a complete understanding of the molecular interface that connects nutrient choices with our cellular metabolism will be required. Laeger et al. show that the expression and secretion of the weight-reducing hormone fibroblast growth factor 21 (FGF21) is regulated by dietary proteins and not, as has been heretofore assumed, simply triggered by reduced caloric intake. This study not only sheds new light on the role of FGF21 in systems metabolism, but also on the ways our bodies cope with the ever-changing availability of different dietary macronutrients.
Improved Metabolic Control in Children and Adolescents With Type 1 Diabetes
Authors: Joachim Rosenbauer, Axel Dost, Beate Karges, Andreas Hungele, Anna Stahl, Christina Bächle, Eva Maria Gerstl, Christian Kastendieck, Sabine E. Hofer, Reinhard W. Holl
Journal: Diabetes Care (2011)

To investigate the temporal trend of metabolic control and potential predictors in German and Austrian children and adolescents with type 1 diabetes.This study is based on a large, multicenter database for prospective longitudinal documentation of diabetes care in Germany and Austria. Data from 30,708 patients documented in 305 diabetes centers between 1995 and 2009 were analyzed. Generalized linear mixed regression models were used to adjust trend analysis for relevant confounders.Unadjusted mean HbA(1c) decreased from 8.7 ± 1.8% in 1995 to 8.1 ± 1.5% in 2009. In multiple regression analysis, treatment year, age, sex, diabetes duration, migration background, BMI-SDS, and daily insulin dose were significant predictors of metabolic control (P < 0.001). After multiple adjustment, mean HbA(1c) decreased significantly by 0.038% per year (95% CI 0.032-0.043%), average odds ratio (OR) per year for HbA(1c) >7.5% (>9.0%) was 0.969 (95% CI 0.961-0.977) (0.948, 95% CI 0.941-0.956). Intensified insulin regimen was associated with lower frequency of poor metabolic control (HbA(1c) >9%; P = 0.005) but not with average HbA(1c) (P = 0.797). Rate of severe hypoglycemia and hypoglycemic coma decreased significantly (relative risk [RR] per year 0.948, 95% CI 0.918-0.979; RR 0.917, 95% CI 0.885-0.950) over the study period. Diabetic ketoacidosis rate showed no significant variation over time.This study showed a significant improvement in metabolic control in children and adolescents with type 1 diabetes during the past decade and a simultaneous decrease in hypoglycemic events. The improvement was not completely explained by changes in the mode of insulin treatment. Other factors such as improved patient education may have accounted for the observed trend.
The Polarity Protein Par6 Induces Cell Proliferation and Is Overexpressed in Breast Cancer
Authors: Marissa E. Nolan, Victoria Aranda, Sangjun Lee, Balasubramanian Lakshmi, Srinjan Basu, D. Craig Allred, Senthil K. Muthuswamy
Journal: Cancer Research (2008)

Abstract The polarity protein complex Par6/atypical protein kinase (aPKC)/Cdc42 regulates polarization processes during epithelial morphogenesis, astrocyte migration, and axon specification. We, as well as others, have shown that this complex is also required for disruption of apical-basal polarity during the oncogene ErbB2-induced transformation and transforming growth factor β–induced epithelial-mesenchymal transition of mammary epithelial cells. Here, we report that expression of Par6 by itself in mammary epithelial cells induces epidermal growth factor–independent cell proliferation and development of hyperplastic three-dimensional acini without affecting apical-basal polarity. This is dependent on the ability of Par6 to interact with aPKC and Cdc42, but not Lgl and Par3, and its ability to promote sustained activation of MEK/ERK signaling. Down-regulation of Cdc42 or aPKC expression suppresses the ability of Par6 to induce proliferation, demonstrating that Par6 promotes cell proliferation by interacting with aPKC and Cdc42. We also show that Par6 is overexpressed in breast cancer–derived cell lines and in both precancerous breast lesions and advanced primary human breast cancers, suggesting that Par6 overexpression regulates tumor initiation and progression. Thus, in addition to regulating cell polarization processes, Par6 is an inducer of cell proliferation in breast epithelial cells. [Cancer Res 2008;68(20):8201–9]
A correlation between Paco2 and body temperature in febrile patients
Authors: G. Chapot, M. Muller, N. Barrault, N. Dargnat, J.-M. Languillat
Journal: Thorax (1974)

<b>Chapot, G., Muller, Michèle, Barrault, Nicole, Dargnat, Nicole, and Languillat, J-M. (1974).</b><i>Thorax</i>, <b>29</b>, 104-105. <b>A correlation between Pa</b>co<sub>2</sub><b>and body temperature in febrile patients.</b> Paco<sub>2</sub> has been measured in 49 patients with normal and raised body temperature. Within the temperature range 35·5°C-41·4°C, there was an inversely proportional relationship between Paco<sub>2</sub> and body temperature with a highly significant correlation coefficient.
Phase III Study of Molecularly Targeted Adjuvant Therapy in Locally Advanced Urothelial Cancer of the Bladder Based on p53 Status
Authors: Walter M. Stadler, Seth P. Lerner, Susan Groshen, John P. Stein, Shan-Rong Shi, Derek Raghavan, David Esrig, Gary Steinberg, David Wood, Laurence Klotz, Craig Hall, Donald G. Skinner, Richard J. Cote
Journal: Journal of Clinical Oncology (2011)

Introduction Retrospective studies suggest that p53 alteration is prognostic for recurrence in patients with urothelial bladder cancer and predictive for benefit from combination methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) adjuvant chemotherapy. Patients and Methods Patients with pT1/T2N0M0 disease whose tumors demonstrated ≥ 10% nuclear reactivity on centrally performed immunohistochemistry for p53 were offered random assignment to three cycles of adjuvant MVAC versus observation; p53-negative patients were observed. By using a log-rank test with one-sided α = .05 and β = .10, 190 p53-positive patients were planned to be randomly assigned to detect an absolute improvement in probability of recurring by 3 years from 0.50 to 0.30. Results A total of 521 patients were registered, 499 underwent p53 assessment, 272 (55%) were positive, and 114 (42%) were randomly assigned. Accrual was halted on the basis of the data and safety monitoring board review of a futility analysis. Overall 5-year probability of recurring was 0.20 (95% CI, 0.16 to 0.24) with no difference on the basis of p53 status. Only 67% of patients randomly assigned to MVAC received all three cycles with 12 patients receiving no treatment. There was no difference in recurrence in the randomly assigned patients (hazard ratio, 0.78; 95% CI, 0.29 to 2.08; P = .62). Conclusion Neither the prognostic value of p53 nor the benefit of MVAC chemotherapy in patients with p53-positive tumors was confirmed, but the high patient refusal rate, lower than expected event rate, and failures to receive assigned therapy severely compromised study power.
Disruption of Cadherin-Related Junctions Triggers Autocrine Expression of Vascular Endothelial Growth Factor in Bovine Aortic Endothelial Cells
Authors: M. Angeles Castilla, Maria Victoria Alvarez Arroyo, Esther Aceituno, Paloma Aragoncillo, Francisco R. González-Pacheco, Emma Texeiro, Rafael Bragado, Carlos Caramelo
Journal: Circulation Research (1999)

The mechanisms involved in the blockade of proliferation in confluent endothelial cells are insufficiently understood. In this regard, the continuity of intercellular junctions appears to be critical to the regulation of endothelial monolayer cell growth. The present study examined the hypothesis that the disruption of the intercellular adherens junctions will trigger both endothelial cell proliferation and autocrine production of growth factors. With this purpose, we assessed the changes in growth, death resistance, and expression of vascular endothelial growth factor (VEGF) under conditions of disruption of the intercellular junctions between endothelial cells. Disruption of cell junctions was produced by means of a specific anti-vascular endothelial cadherin monoclonal antibody, EGTA, or cytochalasin D. Our results disclosed that these maneuvers induce an increase in VEGF mRNA production, with transcription of the 121-, 165-, and 189-amino acid isoforms of VEGF. Further evidence of the relationship between endothelial cells monolayer continuity and VEGF protein expression was obtained by the demonstration of an increase in VEGF protein, as determined by Western blot, induced by the aforementioned maneuvers, as well as by immunocytochemical detection of increased VEGF staining in the areas surrounding a mechanical endothelial injury and in endothelial cells at subconfluence. In functional terms, the autocrine expression of VEGF was associated with growth-promoting and cytoprotective effects, as assessed by [(3)H]thymidine uptake, (51)Cr release, and flow cytometry. In conclusion, our results reveal that disruption of homophilic interendothelial junctions induces VEGF expression. Under these conditions, autocrine VEGF appears to have a relevant role in death inhibition and proliferation of endothelial cells.
Duration of antibiotic therapy in hospitalised patients with community-acquired pneumonia
Authors: S. Aliberti, F. Blasi, A.M. Zanaboni, P. Peyrani, P. Tarsia, S. Gaito, J.A. Ramirez
Journal: European Respiratory Journal (2009)

Recent guidelines suggest that duration of antibiotic therapy for hospitalized patients with community-acquired pneumonia (CAP) can be reduced by individualising treatment based on patient's clinical response. However, the degree of application of this principle in clinical practice is unknown. Duration of therapy was analysed in patients identified from the Community-Acquired Pneumonia Organization database and evaluated with respect to severity of the disease on admission and time to clinical stability (TCS). Among the 2,003 patients enrolled, mean duration of total antibiotic therapy was 11 days. Neither the pneumonia severity index (r(2) = 0.005) nor the CRB-65 (r(2) = 0.004) scores were related to total duration of therapy. Duration of intravenous antibiotic therapy was related to TCS (r(2) = 0.198). Conversely, TCS was not related to duration of either oral (r(2) = 0.014) or total (r(2) = 0.02) antibiotic therapy. Neither TCS nor other characteristics were found to be significantly associated with duration of total therapy by logistic regression analysis (r(2)<0.09). The individualised approach suggested by recent guidelines has not been adopted in current clinical practice. Duration of therapy is not influenced by either the severity of disease at the time of hospitalisation or the clinical response to therapy.
Expression of multiple cytokines and CCR4 in adult T-cell leukemia/lymphoma cells infiltrating the skin
Authors: Shoko Nakayama-Ichiyama, Taiji Yokote, Nobuya Hiraoka, Kazuki Iwaki, Ayami Takayama, Kichinosuke Kobayashi, Toshikazu Akioka, Satoko Oka, Takuji Miyoshi, Takayuki Takubo, Motomu Tsuji, Toshiaki Hanafusa
Journal: Journal of the American Academy of Dermatology (2011)
Clinical response to peroral endoscopic myotomy in patients with idiopathic achalasia at a minimum follow-up of 2 years
Authors: Yuki B Werner, Guido Costamagna, Lee L Swanström, Daniel von Renteln, Pietro Familiari, Ahmed M Sharata, Tania Noder, Guido Schachschal, Jan F Kersten, Thomas Rösch
Journal: Gut (2015)

The recently developed technique for peroral endoscopic myotomy (POEM) has been shown to be effective in several short-term studies. Longer term outcome data are largely non-existent.To systematically report clinical outcome with a minimum post-POEM follow-up of 2 years.All patients treated consecutively by POEM for achalasia at three centres were retrospectively analysed, with a minimum follow-up of 2 years. The main outcome was the rate of POEM failures (Eckardt score >3) related to follow-up time.Of 85 patients treated, five (5.9%) cases were excluded due to protocol violation or loss to follow-up; the remaining 80 patients (mean age 44.9 years, 54% men) were followed clinically for 29 months (range 24-41). Initial clinical response was observed in 77 cases (96.3%). Clinical recurrences (later failures) were seen in a further 14 cases (17.7%), accounting for a total failure rate of 21.5%. In a multivariate analysis, age and endoscopic reflux signs were independent predictors of treatment success. Of the 17 failures, eight were among the first 10 cases treated in the participating centres. Reflux-associated sequelae included one case of a severe reflux-associated stricture requiring dilatation, and two patients with minor transient Eckardt score elevations curable by proton pump inhibitor (PPI) treatment. Endoscopic signs of reflux oesophagitis, mostly Los Angeles grade A/B, were seen in 37.5% (37/72) at the 2-year control.In this multicentre retrospective analysis, a high initial success rate of POEM is followed by a mid-term recurrence rate of 18%. Reflux oesophagitis, albeit mild, is frequent and should probably be treated by regular low-dose PPI therapy.NCT 01405417 (UKE study).
Budget cuts have worsened quality of mental healthcare, think tank warns
Authors: G. Iacobucci
Journal: BMJ (2015)

Changes to mental health services in England driven by budget cuts are negatively affecting the care of patients, a report from a leading think tank has warned.

In a briefing published on 12 November the King’s Fund said that the sector was under huge strain, with around 40% of mental health trusts having had their income cut in 2013-14 and 2014-15.1 In contrast, more than 85% of trusts in the acute care sector saw their income rise over the same period.

The briefing said that the cuts had prompted many trusts to embark on large scale transformation programmes aimed at shifting demand away from acute care services towards recovery …