tbuckley/cabot-search huggingface dataset:
CD34+ Cells from Acute Myeloid Leukemia, Myelodysplastic Syndromes, and Normal Bone Marrow Display Different Apoptosis and Drug Resistance–Associated Phenotypes
Authors: Lilia Suárez, María-Belén Vidriales, José García-Laraña, Guillermo Sanz, María-José Moreno, Antonio López, Susana Barrena, Rafael Martínez, Mar Tormo, Luis Palomera, Esperanza Lavilla, Ma Consuelo López-Berges, María de Santiago, M. Encarnación Pérez de Equiza, Jesús F. San Miguel, Alberto Orfao
Journal: Clinical Cancer Research (2004)

Abstract Myelodysplastic syndromes and acute myeloid leukemia (AML) are heterogeneous disorders in which conflicting results in apoptosis and multidrug resistance (MDR) have been reported. We have evaluated by multiparameter flow cytometry the expression of apoptosis- (APO2.7, bcl-2, and bax) and MDR-related proteins [P-glycoprotein (P-gp), multidrug resistance protein (MRP), and lung resistance protein (LRP)] specifically on bone marrow (BM) CD34+ cells, and their major CD32−/dim and CD32+ subsets, in de novo AML (n = 90), high-risk myelodysplastic syndrome (n = 9), and low-risk myelodysplastic syndrome (n = 21) patients at diagnosis, and compared with normal BM CD34+ cells (n = 6). CD34+ myeloid cells from AML and high-risk myelodysplastic syndrome patients displayed higher expression of bcl-2 (P &amp;lt; 0.0001) and lower reactivity for APO2.7 (P = 0.002) compared with low-risk myelodysplastic syndrome and normal controls. Similar results applied to the two predefined CD34+ myeloid cell subsets. No significant differences were found in the expression of P-gp, MRP, and LRP between low-risk myelodysplastic syndrome patients and normal BM, but decreased expression of MRP (P &amp;lt; 0.03) in AML and high-risk myelodysplastic syndromes and P-gp (P = 0.008) in high-risk myelodysplastic syndromes were detected. Hierarchical clustering analysis showed that low-risk myelodysplastic syndrome patients were clustered next to normal BM samples, whereas high-risk myelodysplastic syndromes were clustered together and mixed with the de novo AML patients. In summary, increased resistance to chemotherapy of CD34+ cells from both AML and high-risk myelodysplastic syndromes would be explained more appropriately in terms of an increased antiapoptotic phenotype rather than a MDR phenotype. In low-risk myelodysplastic syndromes abnormally high apoptotic rates would be restricted to the CD34− cell compartments.
High-quality care for all children with cancer
Authors: R.R.G Knops, M.E.J.L. Hulscher, R.P.M.G. Hermens, M. Hilbink-Smolders, J.L. Loeffen, W.J.W Kollen, G.J.L Kaspers, H.N. Caron, L.C.M Kremer
Journal: Annals of Oncology (2012)
The Effects of Hypogonadism on Body Composition and Bone Mineral Density in Type 2 Diabetic Patients
Authors: Sandeep Dhindsa, Vishal Bhatia, Gurkiran Dhindsa, Ajay Chaudhuri, Gopalakrishna Murthi Gollapudi, Paresh Dandona
Journal: Diabetes Care (2007)

It is known that type 2 diabetes is frequently associated with hypogonadism in male subjects (1,2). Free testosterone concentrations are negatively related with BMI in type 2 diabetic patients (1,3). However, the relationship of free testosterone with adipose tissue mass and lean body mass in diabetic patients is not well described. Studies examining this relationship have been limited by the fact that they have not measured free testosterone by a reliable method such as equilibrium dialysis (4).

Therefore, we decided to study the body composition of hypogonadal and eugonadal type 2 diabetic patients by using dual-energy X-ray absorptiometry (DEXA) to measure subcutaneous adipose tissue, lean body mass, bone mineral content (BMC), and bone mineral density (BMD).

The study was conducted in two endocrinology practices in Midland, Texas, and Buffalo, New York. It is our practice to screen all diabetic patients for hypogonadism, due to the high prevalence of hypogonadism in diabetic patients. We also routinely evaluate body composition of our diabetic patients by DEXA (done at no cost to our patients). Therefore, informed consent was not obtained.

Data from 164 consecutive male diabetic patients who presented to the endocrinology clinic were prospectively collected for the study. Patients with known history of hypogonadism; panhypopituitarism; a chronic debilitating disease such as renal failure, cirrhosis, HIV, back or hip surgery; or treatment with steroids, bisphosphonates, or recombinant parathyroid hormone were …
The role of UFT in advanced gastric cancer
Authors: N.F. Aykan, E. Idelevich
Journal: Annals of Oncology (2008)

Advanced gastric cancer has a poor prognosis, with a relative 5-year survival rate of 7%-27%. Chemotherapy, which improves overall survival (OS) and quality of life, is the main treatment option. Although numerous regimens have been investigated, there is no standard treatment. Combination chemotherapy, however, is associated with a significant survival benefit compared with monotherapy and i.v. 5-fluorouracil (5-FU) is one of the most widely used agents. UFT (tegafur-uracil) has similar efficacy to continuous infusion 5-FU with improved tolerability and is more convenient for patients.The efficacy and safety of UFT in the treatment of advanced gastric cancer have been demonstrated in a number of phase II studies.UFT with leucovorin (folinic acid) monotherapy shows overall response rates (ORRs) of 16%-29% and median OS of 5.8 months. Combination of UFT with cisplatin, etoposide, or paclitaxel shows ORRs of 35%-51% and median OS of 8.3-10.1 months. UFT-based three-drug combinations show ORRs of 41%-57% and median OS of 8.6-15 months. UFT-based combinations have a good tolerability profile, particularly a low incidence of myelosuppression, mucositis, and hand-foot syndrome.UFT represents a logical replacement for 5-FU in chemotherapy regimens for the treatment of advanced gastric cancer.
Von Willebrand factor could be an index of endothelial dysfunction in patients with cirrhosis: relationship to degree of liver failure and nitric oxide levels
Authors: Liliana Albornoz, Daniel Alvarez, Juan Carlos Otaso, Adrián Gadano, Julieta Salviú, Solange Gerona, Patricia Sorroche, Alejandra Villamil, Ricardo Mastai
Journal: Journal of Hepatology (1999)
Psychiatric disorders and violent reoffending: a national cohort study of convicted prisoners in Sweden
Authors: Zheng Chang, Henrik Larsson, Paul Lichtenstein, Seena Fazel
Journal: The Lancet Psychiatry (2015)

Reoffending and presence of psychiatric disorders are common in prisoners worldwide. However, whether psychiatric disorders are risk factors for reoffending is still unknown. We aimed to examine the association between psychiatric disorders, including substance use disorder, and violent reoffending.
Mapping and Sequencing the Human Genome
Authors: Victor A. McKusick
Journal: New England Journal of Medicine (1989)

IN a 1986 editorial, Renato Dulbecco1 proposed that the best way to speed solution of the fundamental problems of cancer was to sequence the human genome completely — that is, to determine the sequence of nucleotides in each chromosome. (Remarkably, Dulbecco did not mention gene mapping, the process of locating the position of genes on chromosomes.) Large-scale sequencing had been under discussion for some time; indeed, a conference called by the Department of Energy at Los Alamos, New Mexico, to discuss the subject was held the week that Dulbecco's editorial appeared. But perhaps more than any other single factor, the . . .
Superficial femoral vein aneurysm with massive pulmonary embolism
Authors: V. Pandey, J H N Wolfe
Journal: Journal of the Royal Society of Medicine (2003)

Carbon monoxide poisoning is responsible for about 50 deaths and up to 200 severe injuries a year in England. 1 Most cases are accidental.Signs and symptoms of poisoning depend upon exposure, and range from those of a non-specific viral illness to arrhythmias, coma and death. 2 The classic cherry-red lips, cyanosis and retinal haemorrhages rarely occur.Diagnosis is by measurement of carboxyhaemoglobin, although there is poor correlation between severity of symptoms and concentration of carboxyhaemoglobin.Patients may present for imaging studies with unexplained loss of consciousness or neurological abnormalities where carbon monoxide is not initially suspected.The differential diagnosis of the CT and MRI appearances is summarized in Box 1.Treatment requires oxygen to shorten the half-life of carboxyhaemoglobin.A recent double-blind randomized trial demonstrated a reduced incidence of cognitive sequelae at six weeks in patients treated with hyperbaric oxygen, 3 though the optimum number of sessions and the maximum time to therapy were not established.Box 1 Differential diagnosis of the CT and MRI appearances in carbon monoxide poisoning
Contemporary Risk Estimates of Three HbA1c Variables for Myocardial Infarction in 101,799 Patients Following Diagnosis of Type 2 Diabetes
Authors: Marita Olsson, Volker Schnecke, Claudia Cabrera, Stanko Skrtic, Marcus Lind
Journal: Diabetes Care (2015)

OBJECTIVE This study evaluated the risk of myocardial infarction (MI) by impaired glycemic control in a contemporary large cohort of patients with type 2 diabetes followed from diagnosis. RESEARCH DESIGN AND METHODS Patients with type 2 diabetes diagnosed between 1995 and 2011 were retrieved from the Clinical Practice Research Datalink in the U.K., and followed from diagnosis until event of MI or end of study in 2013. Two subcohorts were defined: an early cohort with those diagnosed from 1997 to 2004 and a recent cohort with those diagnosed from 2004 to 2011. Association between each of three HbA1c metrics and MI was estimated using adjusted proportional hazards models. RESULTS In the overall cohort (n = 101,799), the risk increase for MI per 1% (10 mmol/mol) increase in HbA1c was higher for updated latest and updated mean HbA1c of 1.11 (95% CI 1.09–1.13) and 1.15 (1.13–1.18) than for baseline HbA1c of 1.05 (1.03–1.06). In the early subcohort, the corresponding risk estimates were greater than those in the recent subcohort. When categorized, the updated latest variable showed an increased risk for HbA1c &amp;lt;6% (42 mmol/mol), relative category 6–7%, in the recent but not in the early subcohort, with hazard ratios of 1.23 (1.08–1.40) and 1.01 (0.84–1.22), respectively. CONCLUSIONS The two time-updated HbA1c variables show a stronger relation with MI than baseline HbA1c. The risk association between HbA1c and MI has decreased over time. In recently diagnosed patients with type 2 diabetes, an increased risk of MI exists at a current HbA1c of &amp;lt;6.0% (42 mmol/mol).
Phosphatase-Resistant Gap Junctions Inhibit Pathological Remodeling and Prevent Arrhythmias
Authors: Benjamin F. Remo, Jiaxiang Qu, Frank M. Volpicelli, Steven Giovannone, Daniel Shin, Joshua Lader, Fang-yu Liu, Jie Zhang, Danielle S. Lent, Gregory E. Morley, Glenn I. Fishman
Journal: Circulation Research (2011)

Posttranslational phosphorylation of connexin43 (Cx43) has been proposed as a key regulatory event in normal cardiac gap junction expression and pathological gap junction remodeling. Nonetheless, the role of Cx43 phosphorylation in the context of the intact organism is poorly understood.To establish whether specific Cx43 phosphorylation events influence gap junction expression and pathological remodeling.We generated Cx43 germline knock-in mice in which serines 325/328/330 were replaced with phosphomimetic glutamic acids (S3E) or nonphosphorylatable alanines (S3A). The S3E mice were resistant to acute and chronic pathological gap junction remodeling and displayed diminished susceptibility to the induction of ventricular arrhythmias. Conversely, the S3A mice showed deleterious effects on cardiac gap junction formation and function, developed electric remodeling, and were highly susceptible to inducible arrhythmias.These data demonstrate a mechanistic link between posttranslational phosphorylation of Cx43 and gap junction formation, remodeling, and arrhythmic susceptibility.
Long-term effects of two different ventilatory modes on oxygenation in acute lung injury. Comparison of airway pressure release ventilation and volume-controlled inverse ratio ventilation.
Authors: M Sydow, H Burchardi, E Ephraim, S Zielmann, T A Crozier
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

A total of 18 patients with acute lung injury (ALI) were sequentially ventilated with two different modes of mechanical ventilation, each applied for a period of 24 h: (1) volume-controlled inverse ratio ventilation (VC-IRV), (2) airway pressure release ventilation (APRV). The individual sequence of both ventilatory modes was randomized. Ventilatory minute volume was adjusted for a PaCO2 of 35 to 45 mm Hg at the beginning of the study during the first ventilatory mode and then kept constant within preset limits. Hemodynamic variables were stable and similar during the 24-h periods of VC-IRV and APRV as well. Despite the lower sedation and spontaneous breathing during APRV, oxygen uptake was similar during both ventilatory modes. During the 24-h period of VC-IRV there was no relevant change of either airway pressures, alveolo-arterial O2 tension difference (AaDO2)/fraction of inspired oxygen (FIO2) or venous admixture. In contrast, peak airway pressures (Pawmax) during APRV were significantly lower (about 30%; p < 0.01), and decreased further within 24 h (p < 0.05). During APRV AaDO2/FIO2 and venous admixture improved significantly with time after more than 8 h (AaDO2/FIO2: 487 versus 414 mm Hg; p < 0.01; venous admixture: 20.6 versus 13.9%; p < 0.01; medians of onset versus end). The improvement was significantly different between both ventilatory modes (p < 0.01). We conclude that this indicates a progressive alveolar recruitment over time during ventilation with APRV.(ABSTRACT TRUNCATED AT 250 WORDS)
Antidepressant Treatment and Relapse of Depression During Pregnancy—Reply
Authors: Lee S. Cohen, Ruta Nonacs, Adele C. Viguera, Alison M. Reminick, Lori L. Altshuler, Rita Suri, Vivien K. Burt, Victoria Hendrick, Bernard L. Harlow, Allison F. Vitonis, D. Jeffrey Newport, Ada Loughead, Zachary N. Stowe
Journal: JAMA (2006)

To the Editor: In their prospective naturalistic investigation, Dr Cohen and colleagues showed that among women who maintained their antidepressant use throughout the pregnancy, 26% had a relapse of major depression, compared with 68% of those who discontinued taking their antidepressants. They also found that women who increased or decreased their antidepressant use had a rate of relapse between those who maintained and those who discontinued their antidepressants (45% and 35%, respectively). The authors concluded that women with histories of depression who are euthymic while receiving antidepressant therapy should be aware of the association of depressive relapse during pregnancy with antidepressant discontinuation. These findings are very similar to those of lithium treatment for bipolar disorder during pregnancy. First, in the case of lithium continuation, Perlis et al demonstrated that changes in serum lithium level in the maintenance phase (both low to standard and standard to low) were associated with recurrence of bipolar disorder at 36 weeks (rate approximately 50%), whereas unchanged levels were associated with good prognosis (rate approximately 20%). These figures are comparable with the findings of Cohen et al. Second, in the case of lithium discontinuation, Viguera et al showed that the rate of relapse of bipolar disorder in pregnant women following lithium discontinuation was 52%. This rate was dependent on rapidity of lithium discontinuation, with a 63% relapse rate in patients with rapid (1-14 days) discontinuation and 37% relapse with gradual (15-30 days) discontinuation. If the patients in the study by Cohen et al rapidly discontinued their antidepressants within 1 to 2 weeks, their relapse rate of 68% would be comparable. Despite the differences in medication and in diagnoses, the results are very similar. Thus, the conclusion of Cohen et al can be generalized to “women with histories of mood disorder who are euthymic in the context of ongoing antidepressant or lithium therapy should be aware of the association of relapse during pregnancy with the medication discontinuation.”
Detection of Symptoms by Adolescents and Young Adults With Type 1 Diabetes During Experimental Induction of Mild Hypoglycemia
Authors: Christopher M. Ryan, Daisy Dulay, Chittiwat Suprasongsin, Dorothy J. Becker
Journal: Diabetes Care (2002)

To identify hormonal, psychological, and demographic predictors of symptom detection and accuracy of blood glucose estimation during mild hypoglycemia in adolescents and young adults with type 1 diabetes.During an insulin-glucose clamp study, 53 adolescents and 19 young adults estimated blood glucose levels and reported symptoms at euglycemia and after 30 min of mild hypoglycemia (3.3 mmol/l). Epinephrine and pancreatic polypeptide were measured, and both change in anxiety level during hypoglycemia and baseline level of anxiety were measured with the Spielberger Anxiety Inventory. Elevated levels of anxiety during euglycemia were used as an indicator of the psychological trait "negative affectivity." Previous studies have suggested that individuals with higher negative affectivity are more internally focused and, therefore, more likely to report somatic and visceral changes.During mild hypoglycemia, 42% of the sample subjects reported an increase in autonomic symptoms; 29% reported an increase in neuroglycopenic symptoms, and 28% estimated blood glucose levels accurately (within 10% of actual). Hormonal excursions did not predict any outcome, but higher anxiety levels during the euglycemic baseline were associated with better detection of hypoglycemic symptoms and more accurate estimation of blood glucose values after controlling for change in anxiety level during hypoglycemia.Psychological factors such as elevated anxiety levels ("negative affectivity") can influence blood glucose estimation and symptom detection in adolescents and young adults and may explain why some individuals are more adept than others at reducing their risk of severe hypoglycemia after participation in a formal blood glucose awareness training program.
Effect of α-Lipoic Acid on Platelet Reactivity in Type 1 Diabetic Patients
Authors: Roberto Mollo, Francesco Zaccardi, Giancarla Scalone, Giuseppe Scavone, Paola Rizzo, Eliano Pio Navarese, Andrea Manto, Dario Pitocco, Gaetano Antonio Lanza, Giovanni Ghirlanda, Filippo Crea
Journal: Diabetes Care (2012)

OBJECTIVE Type 1 diabetes is associated with increased platelet reactivity. We investigated whether α-lipoic acid (ALA) has any effect on platelet reactivity in these patients. RESEARCH DESIGN AND METHODS We randomly assigned 51 type 1 diabetic patients to ALA (600 mg once daily) or placebo for 5 weeks. Platelet reactivity was evaluated by the PFA-100 method and by measuring CD41 and CD62 platelet expression. C-reactive protein (CRP) and 8-iso-prostaglandin F2α serum levels also were measured. RESULTS Baseline variables were similar in the two groups. After treatment, closure time was longer (P = 0.006) and CD62P platelet expression was lower, both before (P = 0.002) and after (P = 0.009) ADP stimulation in the ALA group compared with the placebo group. CRP and 8-iso-prostaglandin F2α levels showed no differences between the two groups. CONCLUSIONS Our data show that ALA reduces measures of platelet reactivity ex vivo in type 1 diabetic patients, independently of antioxidant or anti-inflammatory effects.
Why UK-trained doctors leave the UK: cross-sectional survey of doctors in New Zealand
Authors: Avinash Sharma, Trevor W Lambert, Michael J Goldacre
Journal: Journal of the Royal Society of Medicine (2012)

To investigate factors which influenced UK-trained doctors to emigrate to New Zealand and factors which might encourage them to return.Cross-sectional postal and Internet questionnaire survey.Participants in New Zealand; investigators in UK. Participants UK-trained doctors from 10 graduation-year cohorts who were registered with the New Zealand Medical Council in 2009.Reasons for emigration; job satisfaction; satisfaction with leisure time; intentions to stay in New Zealand; changes to the UK NHS which might increase the likelihood of return.Of 38,821 UK-trained doctors in the cohorts, 535 (1.4%) were registered to practise in New Zealand. We traced 419, of whom 282 (67%) replied to our questionnaire. Only 30% had originally intended to emigrate permanently, but 89% now intended to stay. Sixty-nine percent had moved to take up a medical job. Seventy percent gave additional reasons for relocating to New Zealand including better lifestyle, to be with family, travel/working holiday, or disillusionment with the NHS. Respondents' mean job satisfaction score was 8.1 (95% CI 7.9-8.2) on a scale from 1 (lowest satisfaction) to 10 (highest), compared with 7.1 (7.1-7.2) for contemporaries in the UK NHS. Scored similarly, mean satisfaction with the time available for leisure was 7.8 (7.6-8.0) for the doctors in New Zealand, compared with 5.7 (5.6-5.7) for the NHS doctors. Although few respondents wanted to return to the UK, some stated that the likelihood of doctors' returning would be increased by changes to NHS working conditions and by administrative changes to ease the process.Emigrant doctors in New Zealand had higher job satisfaction than their UK-based contemporaries, and few wanted to return. The predominant reason for staying in New Zealand was a preference for the lifestyle there.
Cancer Mortality Among Nonsmokers in an Insured Group of U.S. Veterans&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;
Authors: E. Rogot, J. Murray
Journal: JNCI Journal of the National Cancer Institute (1980)

In a 16-year follow-up of insured U.S. veterans, standardized mortality ratios (SMR) for cancer were calculated for nonsmokers (55,049); as the standard, cancer rates of all respondents (248,046) were used. For all cancers, nonsmokers had an SMR of 71%; for lung cancer, they had an SMR of 21%. The data for nonsmokers were further analyzed with risk of cancer assessed according to residence and usual occupation and industry. Among the nonsmokers, SMR were especially low for dentists, carpenters, and lawyers, and for the electric light and power and printing industries. By division of the country, SMR for nonsmokers were especially low for the Mountain States.
Proteinase-activated receptors in fibroproliferative lung disease
Authors: Ricardo J José, Andrew E Williams, Rachel C Chambers
Journal: Thorax (2013)

The coagulation cascade plays a central role in the pathogenesis of fibroproliferative lung diseases such as the acute respiratory distress syndrome (ARDS) and idiopathic pulmonary fibrosis (IPF) through multifaceted effects on haemostasis, inflammation and tissue repair. However, targeting the coagulation cascade using traditional anticoagulant approaches has not resulted in improved outcomes for these patients. The cellular effects of the coagulation cascade are mediated via a family of four proteinase-activated receptors (PAR(1-4)). PARs are G protein-coupled receptors that have a unique method of activation involving proteolytic cleavage. They play key roles in mediating the interplay between coagulation and inflammation and tissue repair and fibrosis. Current evidence suggests a central role for PAR(1) and PAR(2) in influencing these responses, although data from animal models suggest that their contribution is highly dependent on both the nature of the insult and disease status. Nonetheless, these receptors may represent important targets in conditions associated with uncontrolled coagulation signalling responses including IPF, ARDS, asthma and chronic obstructive pulmonary disease.