tbuckley/cabot-search huggingface dataset:
Effect of peer support on prevention of postnatal depression among high risk women: multisite randomised controlled trial
Authors: C-L Dennis, E Hodnett, L Kenton, J Weston, J Zupancic, D E Stewart, A Kiss
Journal: BMJ (2009)

Objective To evaluate the effectiveness of telephone based peer support in the prevention of postnatal depression. Design Multisite randomised controlled trial. Setting Seven health regions across Ontario, Canada. Participants 701 women in the first two weeks postpartum identified as high risk for postnatal depression with the Edinburgh postnatal depression scale and randomised with an internet based randomisation service. Intervention Proactive individualised telephone based peer (mother to mother) support, initiated within 48-72 hours of randomisation, provided by a volunteer recruited from the community who had previously experienced and recovered from self reported postnatal depression and attended a four hour training session. Main outcome measures Edinburgh postnatal depression scale, structured clinical interview-depression, state-trait anxiety inventory, UCLA loneliness scale, and use of health services. Results After web based screening of 21 470 women, 701 (72%) eligible mothers were recruited. A blinded research nurse followed up more than 85% by telephone, including 613 at 12 weeks and 600 at 24 weeks postpartum. At 12 weeks, 14% (40/297) of women in the intervention group and 25% (78/315) in the control group had an Edinburgh postnatal depression scale score >12 (χ2=12.5, P<0.001; number need to treat 8.8, 95% confidence interval 5.9 to 19.6; relative risk reduction 0.46, 95% confidence interval 0.24 to 0.62). There was a positive trend in favour of the intervention group for maternal anxiety but not loneliness or use of health services. For ethical reasons, participants identified with clinical depression at 12 weeks were referred for treatment, resulting in no differences between groups at 24 weeks. Of the 221 women in the intervention group who received and evaluated their experience of peer support, over 80% were satisfied and would recommend this support to a friend. Conclusion Telephone based peer support can be effective in preventing postnatal depression among women at high risk. Trial registration ISRCTN 68337727.
Four-Year Survival Rate After Second Line Conversion Treatment to Hepatic Resection Using Triplet Hepatic Artery Infusion and Intravenous Cetuximab for KRAS WT Unresectable Metastatic Colorectal Cancer (European Trial Optiliv, NCT00852228)
Authors: Lévi Francis, Ducreux Michel, Bouchahda Mohamed, Smith Denis, Karaboué Abdoulaye, Hebbar Mohamed, Lepère Céline, Focan Christian, Guimbaud Rosine, Innominato Pasquale, Carvalho Carlos, Tumolo Salvatore, Truant Stephanie, Castaing Denis, Boige Valerie, Rougier Philippe, Morere Jean-François, Adam René
Journal: Annals of Oncology (2014)
Expiratory flow limitation and obstruction in the elderly
Authors: C. de Bisschop, M. L. Marty, J. F. Tessier, P. Barberger-Gateau, J. F. Dartigues, H. Guénard
Journal: European Respiratory Journal (2005)

Elderly people commonly suffer from dyspnoea, which may stem from expiratory flow limitation (EFL). The relationship between EFL, as assessed by the negative expiratory pressure method and spirometric indices, was investigated in an elderly French population. Subjects, aged 66–88 yrs, filled in socio-demographic and standardised questionnaires, which dealt with: medical history, smoking status and respiratory symptoms. EFL measurements and forced expiratory manoeuvres were performed. Validated measurements were obtained in 750 out of 1,318 subjects: 47% were EFL+ (EFL &gt;0), with a higher prevalence in females than in males. EFL and forced expiratory volume in one second (FEV 1 ) were correlated with age. A total of 116, from the 750 subjects, with no medical history and no symptoms, served as a healthy group. The prevalence of EFL+ subjects increased with the grade of dyspnoea and was highest in respiratory and cardiac patients when compared with the healthy subjects. EFL did not correlate with FEV 1 /forced vital capacity (FVC), the usual index of obstruction. Some elderly subjects (15%) with dyspnoea but with no medical history, mainly females with small FVC and normal FEV 1 /FVC, had a greater EFL than the healthy subjects. In elderly people, expiratory flow limitation measurements, along with the usual forced expiratory volume in one second/ forced vital capacity ratio, may be of value for the interpretation of dyspnoea.
Screening Pelvic Examinations in Asymptomatic, Average-Risk Adult Women: An Evidence Report for a Clinical Practice Guideline From the American College of Physicians
Authors: Hanna E. Bloomfield, Andrew Olson, Nancy Greer, Amy Cantor, Roderick MacDonald, Indulis Rutks, Timothy J. Wilt
Journal: Annals of Internal Medicine (2014)

Background: Pelvic examination is often included in well-woman visits even when cervical cancer screening is not required. Purpose: To evaluate the diagnostic accuracy, benefits, and harms of pelvic examination in asymptomatic, nonpregnant, average-risk adult women. Cervical cancer screening was not included. Data Sources: MEDLINE and Cochrane databases through January 2014 and reference lists from identified studies. Study Selection: 52 English-language studies, 32 of which included primary data. Data Extraction: Data were extracted on study and sample characteristics, interventions, and outcomes. Quality of the diagnostic accuracy studies was evaluated using a published instrument, and quality of the survey studies was evaluated with metrics assessing population representativeness, instrument development, and response rates. Data Synthesis: The positive predictive value of pelvic examination for detecting ovarian cancer was less than 4% in the 2 studies that reported this metric. No studies that investigated the morbidity or mortality benefits of screening pelvic examination for any condition were identified. The percentage of women reporting pelvic examination–related pain or discomfort ranged from 11% to 60% (median, 35%; 8 studies [n = 4576]). Corresponding figures for fear, embarrassment, or anxiety ranged from 10% to 80% (median, 34%; 7 studies [n = 10 702]). Limitation: Only English-language publications were included; the evidence on diagnostic accuracy, morbidity, and mortality was scant; and the studies reporting harms were generally low quality. Conclusion: No data supporting the use of pelvic examination in asymptomatic, average-risk women were found. Low-quality data suggest that pelvic examinations may cause pain, discomfort, fear, anxiety, or embarrassment in about 30% of women. Primary Funding Source: Department of Veterans Affairs.
Combined Abl Inhibitor Therapy for Minimizing Drug Resistance in Chronic Myeloid Leukemia: Src/Abl Inhibitors Are Compatible with Imatinib
Authors: Thomas O'Hare, Denise K. Walters, Eric P. Stoffregen, Daniel W. Sherbenou, Michael C. Heinrich, Michael W.N. Deininger, Brian J. Druker
Journal: Clinical Cancer Research (2005)

Chronic myeloid leukemia (CML) is effectively treated with imatinib. However, reactivation of Bcr-Abl via kinase domain mutations that reduce sensitivity to imatinib can cause relapse. As combination therapy is frequently used to prevent emergence of resistance, the combination of imatinib with an inhibitor of imatinib-resistant Bcr-Abl mutants (e.g., Src/Abl inhibitors AP23848 and BMS-354825) was investigated.To test this approach, cellular proliferation and Bcr-Abl tyrosine phosphorylation assays were done on Ba/F3 cells expressing wild-type (WT) Bcr-Abl and four common imatinib-resistant mutants (Y253F, E255K, T315I, and M351T). Colony-forming assays with primary CML cells were also done.Both Src/Abl inhibitors retained full inhibitory capacity when coadministered with imatinib at concentrations above typical clinical levels. For cells expressing WT Bcr-Abl or the marginally imatinib-resistant mutant M351T, inclusion of imatinib at therapeutic levels enhanced the effects of the Src/Abl inhibitors. By comparison, for the highly imatinib-resistant mutants Y253F and E255K, inclusion of imatinib at clinical levels resulted in only a slight enhancement beyond the effects of the Src/Abl inhibitors. None of the inhibitors affected Bcr-Abl T315I cells. Colony-forming assays with primary CML cells yielded analogous results.Our results indicate that Src/Abl inhibitors are compatible with imatinib and suggest that combined Abl inhibitor therapy is a feasible treatment strategy for patients with CML.
Robotic-Assisted Laparoscopic Extended Pelvic Lymph Node Dissection for Prostate Cancer: Surgical Technique and Experience with the First 99 Cases
Authors: Antje Feicke, Martin Baumgartner, Scherwin Talimi, Daniel Max Schmid, Hans-Helge Seifert, Michael Müntener, Markus Fatzer, Tullio Sulser, Räto T. Strebel
Journal: European Urology (2008)
Inhibition of Lipopolysaccharide-Induced Inflammatory Responses by an Apolipoprotein AI Mimetic Peptide
Authors: Himanshu Gupta, Lijun Dai, Geeta Datta, David W. Garber, Hernan Grenett, Yanbing Li, Vinod Mishra, Mayakonda N. Palgunachari, Shaila Handattu, Sandra H. Gianturco, William A. Bradley, G.M. Anantharamaiah, C. Roger White
Journal: Circulation Research (2005)

Previous studies suggest that high-density lipoprotein and apoAI inhibit lipopolysaccharide (LPS)-induced inflammatory responses. The goal of the current study was to test the hypothesis that the apoAI mimetic peptide L-4F exerts antiinflammatory effects similar to apoAI. Pretreatment of human umbilical vein endothelial cells (HUVECs) with LPS induced the adhesion of THP-1 monocytes. Incubation of cells with LPS and L-4F (1 to 50 microg/mL) reduced THP-1 adhesion in a concentration-dependent manner. This response was associated with a significant reduction in the synthesis of cytokines, chemokines, and adhesion molecules. L-4F reduced vascular cell adhesion molecule-1 expression induced by LPS or lipid A, whereas a control peptide (Sc-4F) showed no effect. In contrast to LPS treatment, L-4F did not inhibit IL-1beta- or tumor necrosis factor-alpha-induced vascular cell adhesion molecule-1 expression. The inhibitory effect of L-4F on LPS induction of inflammatory markers was associated with reduced binding of LPS to its plasma carrier molecule, lipopolysaccharide binding protein, and decreased binding of LPS to HUVEC monolayers. LPS and L-4F in HUVEC culture medium were fractionated by fast protein liquid chromatography and were localized to the same fractions, suggesting a physical interaction between these molecules. Proinflammatory responses to LPS are associated with the binding of lipid A to cell surface receptors. The current studies demonstrate that L-4F reduces the expression of inflammatory markers induced by LPS and lipid A and suggest that apoAI peptide mimetics may be useful in the treatment of inflammation associated with endotoxemia.
Anaphylactic reactions after use of CT 1341 (althesin).
Authors: J M Watt
Journal: BMJ (1975)

Cutaneous capillary strength was investigated in 12 diabetics, six of whom had symptomatic retinopathy (age range 25-71 years) and 24 controls (age range 21-61 years).The effect on the diabetics of a dietary supplement of vitamin C was studied. Methods and ResultsCutaneous capillary fragility was measured using apparatus described by Hart and Cohen.'We modified the procedure by applying a much lower
Managed care and disease management in the NHS
Authors: M. Lawrence, T. Williams
Journal: BMJ (1996)

What will be the role of the pharmaceutical industry?

“Managed care raises fundamental issues of patient confidentiality and the ethical responsibilities of doctors which makes it an anathema for the medical profession, but it also reduces choice both for the patient and the doctor.”1 Such a comment from the chairman of council of the British Medical Association should encourage us to examine this threat carefully, yet most doctors are ignorant even about what managed care or disease management is. Managed care has been developing rapidly in the United States and is best understood by examining what is happening there.

Faced with increasing health care costs, insurance companies and employers in the United States have supported groups such as health maintenance organisations, which offer care more cheaply in return for the patient surrendering some freedom. Key features include restricting the choice of doctors, providing secondary care only in selected hospitals, modifying clinical behaviour with guidelines, and emphasising primary care. Having developed such controls, organisations can then use the three essential elements of disease management: a knowledge base that quantifies the economic structure of the disease problem and describes care guidelines; a delivery system that coordinates all carers—primary, secondary, and social; and a quality improvement system to audit performance against evolving …
Nitric Oxide–Induced Apoptosis in Lymphoblastoid and Fibroblast Cells Dependent on the Phosphorylation and Activation of p53
Authors: Laura M. McLaughlin, Bruce Demple
Journal: Cancer Research (2005)

When nitric oxide (NO) is produced at micromolar concentrations, as during inflammation, exposure to surrounding cells is potentially cytotoxic. The NO-dependent signaling pathways that initiate cell death are thought to involve the tumor suppressor protein p53, but the degree to which this factor contributes to NO-induced cell death is less clear. Various reports either confirm or negate a role for p53 depending on the cell type and NO donor used. In this study, we have used several pairs of cell lines whose only differences are the presence or absence of p53, and we have treated these cell lines with the same NO donor, spermineNONOate (SPER/NO). Treatment with SPER/NO induced such apoptotic markers as DNA fragmentation, nuclear condensation, poly(ADP-ribose) polymerase cleavage, cytochrome c release, and Annexin V staining. p53 was required for at least 50% of SPER/NO-induced apoptotic cell death in human lymphoblastoid cells and for almost all in primary and E1A-tranformed mouse embryonic fibroblasts, which highlights the possible importance of DNA damage for apoptotic signaling in fibroblasts. In contrast, p53 did not play a significant role in NO-induced necrosis. NO treatment also induced the phosphorylation of p53 at Ser15; pretreatment with phosphoinositide-3 kinase (PI3K) family inhibitors, wortmannin, LY294002, and caffeine, blocked such phosphorylation, but the p38 mitogen-activated protein kinase inhibitor, SB203580, did not. Pretreatment with the PI3K family inhibitors also led to a switch from NO-induced apoptosis to necrosis, which implicates a PI3K-related kinase such as ataxia telangiectasia mutated (ATM) or ATR (ATM and Rad3 related) in p53-dependent NO-induced apoptosis.
Peripheral blood and mesenteric lymph node lymphocytes in Crohn's disease.
Authors: E R Richens, C M Thorp, P W Bland, K R Gough
Journal: Gut (1980)

Analysis of peripheral blood lymphocytes from 44 patients with Crohn's disease showed no difference in the proportions of T- and B-cells from those in 38 healthy controls. Analysis revealed no disturbances in relation to duration or to activity of disease or to drug treatment. Lymphocytes from 18 patients with rheumatoid arthritis also showed normal proportions of T- and B-cells. Lymphocytes taken from gut lymph nodes were studied in five patients with Crohn's disease. On comparison with peripheral blood lymphocytes, significantly decreased proportions of T-cells and significantly increased proportions of B-cells were found in lymph nodes draining areas of diseased bowel. No differences were seen in the proportions of T- and B-cells from lymph nodes taken from apparently healthy bowel of the Crohn's patients and of four control subjects without inflammatory bowel disease, though these were different from those in the peripheral blood in both the Crohn's patients and control subjects.
Factors that Contribute to Variation in Evolutionary Rate among Arabidopsis Genes
Authors: L. Yang, B. S. Gaut
Journal: Molecular Biology and Evolution (2011)

Surprisingly, few studies have described evolutionary rate variation among plant nuclear genes, with little investigation of the causes of rate variation. Here, we describe evolutionary rates for 11,492 ortholog pairs between Arabidopsis thaliana and A. lyrata and investigate possible contributors to rate variation among these genes. Rates of evolution at synonymous sites vary along chromosomes, suggesting that mutation rates vary on genomic scales, perhaps as a function of recombination rate. Rates of evolution at nonsynonymous sites correlate most strongly with expression patterns, but they also vary as to whether a gene is duplicated and retained after a whole-genome duplication (WGD) event. WGD genes evolve more slowly, on average, than nonduplicated genes and non-WGD duplicates. We hypothesize that levels and patterns of expression are not only the major determinants that explain nonsynonymous rate variation among genes but also a critical determinant of gene retention after duplication.
Diabetic Nephropathy in 27,805 Children, Adolescents, and Adults With Type 1 Diabetes
Authors: Klemens Raile, Angela Galler, Sabine Hofer, Antje Herbst, Desiree Dunstheimer, Petra Busch, Reinhard W. Holl
Journal: Diabetes Care (2007)

To give an up-to-date profile of nephropathy and the involvement of risk factors in a large, prospective cohort of patients with type 1 diabetes and largely pediatric and adolescent onset of disease.A total of 27,805 patients from the nationwide, prospective German Diabetes Documentation System survey were included in the present analysis. Inclusion criteria were at least two documented urine analyses with identical classification. Urine analyses, treatment regimens, diabetes complications, and risk factors were recorded prospectively. Baseline characteristics were age at diagnosis 9.94 years (median [interquartile range 5.8-14.3]), age at last visit 16.34 years (12.5-22.2), and follow-up time 2.5 years (0.43-5.3). Cumulative incidence of nephropathy was tested by Kaplan-Meier analysis and association with risk factors by logistic regression.Nephropathy was classified as normal in 26,605, microalbuminuric in 919, macroalbuminuric in 78, and end-stage renal disease (ESRD) in 203 patients. After calculated diabetes duration of 40 years, 25.4% (95% CI 22.3-28.3) had microalbuminuria and 9.4% (8.3-11.4) had macroalbuminuria or ESRD. Risk factors for microalbuminuria were diabetes duration (odds ratio 1.033, P < 0.0001), A1C (1.13, P < 0.0001), LDL cholesterol (1.003, P < 0.0074), and blood pressure (1.008, P < 0.0074), while childhood diabetes onset (1.011, P < 0.0001) was protective. Male sex was associated with the development of macroalbuminuria.Diabetes duration, A1C, dyslipidemia, blood pressure, and male sex were identified as risk factors for nephropathy. Therefore, besides the best possible metabolic control, early diagnosis and prompt treatment of dyslipidemia and hypertension is mandatory in patients with type 1 diabetes.
Delayed phospholamban phosphorylation in post-conditioned heart favours Ca2+ normalization and contributes to protection
Authors: Javier Inserte, Víctor Hernando, Marisol Ruiz-Meana, Marcos Poncelas-Nozal, Celia Fernández, Luis Agulló, Carmem Sartorio, Úrsula Vilardosa, David Garcia-Dorado
Journal: Cardiovascular Research (2014)

It has been shown that sarcoplasmic reticulum calcium ATPase (SERCA) plays a critical role in reperfusion injury. Moreover, ischaemic post-conditioning (PoCo) results in protein kinase G (PKG) activation which has been proposed to modulate phospholamban (PLB) and SERCA. We assessed whether PLB phosphorylation contributes to the cardioprotective effects of PoCo. Isolated Sprague–Dawley rat hearts were submitted to 40 min of ischaemia and reperfusion with and without a PoCo protocol that reduced infarct size by 48%. Reperfusion caused a rapid phosphorylation in PLB at Ser16 and Thr17 that was delayed by PoCo. NO-independent activation of soluble guanylate cyclase (sGC) (ataciguat) and cAMP-dependent protein kinase (PKA) inhibition (KT5720) mimicked the reduction in Ser16 phosphorylation in reperfused control hearts, while in PoCo hearts the inhibitors of PKG (KT5823) and phosphodiesterase 2 (BAY-60-7550) reverted it. CaMKII activity measured by Thr287 phosphorylation was reduced in PoCo. In reperfused control hearts, inhibition of PLB phosphorylation or SERCA (thapsigargin) simulated the cardioprotective effects of PoCo. Ataciguat reduced cytosolic Ca2+ oscillations and improved Ca2+ recovery in cardiomyocytes subjected to anoxia–reoxygenation and infarct size by 32% in rats with 30 min of the left anterior descending coronary artery occlusion and 2 h of reperfusion. Blockade of Na+/Ca2+-exchanger (NCX; KB-R7943) impaired Ca2+ control in cardiomyocytes and abolished cardioprotection in PoCo hearts. PoCo reduces SERCA activity at the onset of reperfusion by delaying PLB phosphorylation through activation of PKG and inhibition of PKA and CaMKII. This effect contributes to PoCo protection by favouring cytosolic Ca2+ extrusion through NCX, and it may be mimicked by pharmacological stimulation of sGC.
Changing the Way We Do Business: Recommendations to Accelerate Biomarker Development in Pancreatic Cancer
Authors: Margaret A. Tempero, David Klimstra, Jordan Berlin, Tony Hollingsworth, Paula Kim, Nipun Merchant, Malcolm Moore, Doug Pleskow, Andrea Wang-Gillam, Andrew M. Lowy
Journal: Clinical Cancer Research (2013)

Pancreatic ductal adenocarcinoma is the most aggressive of all epithelial malignancies. In contrast to the favorable trends seen in most other common malignancies, the five-year survival of patients with this disease remains only 6%, a statistic that has changed minimally for decades. Only two drugs have been approved by the U.S. Food and Drug Administration (FDA) for use in pancreatic cancer in the last 15 years, and there are no established strategies for early detection.
An Adaptive Transposable Element Insertion in the Regulatory Region of the EO Gene in the Domesticated Silkworm, Bombyx mori
Authors: Wei Sun, Yi-Hong Shen, Min-Jin Han, Yun-Feng Cao, Ze Zhang
Journal: Molecular Biology and Evolution (2014)

Although there are many studies to show a key role of transposable elements (TEs) in adaptive evolution of higher organisms, little is known about the molecular mechanisms. In this study, we found that a partial TE (Taguchi) inserted in the cis-regulatory region of the silkworm ecdysone oxidase (EO) gene, which encodes a crucial enzyme to reduce the titer of molting hormone (20-hydroxyecdysone, 20E). The TE insertion occurred during domestication of silkworm and the frequency of the TE insertion in the domesticated silkworm (Bombyx mori) is high, 54.24%. The linkage disequilibrium in the TE inserted strains of the domesticated silkworm was elevated. Molecular population genetics analyses suggest that this TE insertion is adaptive for the domesticated silkworm. Luminescent reporter assay shows that the TE inserted in the cis-regulatory region of the EO gene functions as a 20E-induced enhancer of the gene expression. Further, phenotypic bioassay indicates that the silkworm with the TE insertion exhibited more stable developmental phenotype than the silkworm without the TE insertion when suffering from food shortage. Thus, the inserted TE in the cis-regulatory region of the EO gene increased developmental uniformity of silkworm individuals through regulating 20E metabolism, partially explaining transformation of a domestication developmental trait in the domesticated silkworm. Our results emphasize the exceptional role of gene expression regulation in developmental transition of domesticated animals.