tbuckley/cabot-search huggingface dataset:
Reduction of Cancer-Related Fatigue With Dexamethasone: A Double-Blind, Randomized, Placebo-Controlled Trial in Patients With Advanced Cancer
Authors: Sriram Yennurajalingam, Susan Frisbee-Hume, J. Lynn Palmer, Marvin O. Delgado-Guay, Janet Bull, Alexandria T. Phan, Nizar M. Tannir, Jennifer Keating Litton, Akhila Reddy, David Hui, Shalini Dalal, Lisa Massie, Suresh K. Reddy, Eduardo Bruera
Journal: Journal of Clinical Oncology (2013)

Purpose Cancer-related fatigue (CRF) is the most common symptom in patients with advanced cancer. The primary objective of this prospective, randomized, double-blind, placebo-controlled study was to compare the effect of dexamethasone and placebo on CRF. Patients and Methods Patients with advanced cancer with ≥ three CRF-related symptoms (ie, fatigue, pain, nausea, loss of appetite, depression, anxiety, or sleep disturbance) ≥ 4 of 10 on the Edmonton Symptom Assessment Scale (ESAS) were eligible. Patients were randomly assigned to either dexamethasone 4 mg or placebo orally twice per day for 14 days. The primary end point was change in the Functional Assessment of Chronic Illness–Fatigue (FACIT-F) subscale from baseline to day 15. Secondary outcomes included anorexia, anxiety, depression, and symptom distress scores. Results A total of 84 patients were evaluable (dexamethasone, 43; placebo, 41). Mean (± standard deviation) improvement in the FACIT-F subscale at day 15 was significantly higher in the dexamethasone than in the placebo group (9 [± 10.3] v 3.1 [± 9.59]; P = .008). The improvement in FACIT-F total quality-of-life scores was also significantly better for the dexamethasone group at day 15 (P = .03). The mean differences in the ESAS physical distress scores at day 15 were significantly better for the dexamethasone group (P = .013, respectively). No differences were observed for ESAS overall symptom distress (P = .22) or psychological distress score (P = .76). Frequency of adverse effects was not significantly different between groups (41 of 62 v 44 of 58; P = .14). Conclusion Dexamethasone is more effective than placebo in improving CRF and quality of life in patients with advanced cancer.
Effects of Na+/H+ exchanger inhibitors on subcellular localisation of endocytic organelles and intracellular dynamics of protein transduction domains HIV–TAT peptide and octaarginine
Authors: Marjan Fretz, Jing Jin, Robin Conibere, Neal A. Penning, Saly Al-Taei, Gert Storm, Shiroh Futaki, Toshihide Takeuchi, Ikuhiko Nakase, Arwyn T. Jones
Journal: Journal of Controlled Release (2006)
Comparison of three faecal occult blood tests in the detection of colorectal neoplasia.
Authors: R L Hope, G Chu, A H Hope, R G Newcombe, P E Gillespie, S J Williams
Journal: Gut (1996)

METHODS AND AIMS: For the detection of colorectal neoplasia, 192 consecutive patients had colonoscopy to evaluate the sensitivity and specificity of three faecal occult blood tests (FOBT). Of 160 evaluable patients (96 female, mean age 51.9), 21 patients (13.1%) had adenomas and three patients (1.9%) had colorectal carcinoma. RESULTS: When comparing all three faecal occult blood tests for the detection of colorectal neoplasia, the sensitivity of Monohaem (43.8%) was superior to both Hemoccult II (25%) and to BM-Test colon albumin (25%). The specificity of Monohaem (94.6%) was greater than both Hemoccult II (88%) and BM-Test colon albumin (89%). Using McNemar9s test, Monohaem was a more accurate FOBT than Hemoccult II and BM-Test albumin (p &lt; 0.05). In the 21 patients with adenomatous polyps, FOBT sensitivity seemed to be dependent on polyp size, but not polyp site. CONCLUSIONS: Monohaem, a feacal occult blood test that uses a monoclonal antibody that is specific for human haemoglobin, is a more accurate test in the detection of colorectal neoplasia and should possibly be used in colorectal cancer screening programmes.
CXCL-12/Stromal Cell–Derived Factor-1α Transactivates HER2-neu in Breast Cancer Cells by a Novel Pathway Involving Src Kinase Activation
Authors: Neslihan Cabioglu, Justin Summy, Claudia Miller, Nila U. Parikh, Aysegul A. Sahin, Sitki Tuzlali, Kevin Pumiglia, Gary E. Gallick, Janet E. Price
Journal: Cancer Research (2005)

Abstract Experimental evidence suggests that CXCR4, a Gi protein–coupled receptor for the ligand CXCL12/stromal cell–derived factor-1α (SDF-1α), plays a role in breast cancer metastasis. Transactivation of HER2-neu by G protein–coupled receptor activation has been reported as a ligand-independent mechanism of activating tyrosine kinase receptors. We found that SDF-1α transactivated HER2-neu in the breast cancer cell lines MDA-MB-361 and SKBR3, which express both CXCR4 and HER2-neu. AMD3100, a CXCR4 inhibitor, PKI 166, an epidermal growth factor receptor/HER2-neu tyrosine kinase inhibitor, and PP2, a Src kinase inhibitor, each blocked SDF-1α–induced HER2-neu phosphorylation. Blocking Src kinase, with PP2 or using a kinase-inactive Src construct, and inhibiting epidermal growth factor receptor/HER2-neu signaling with PKI 166 each inhibited SDF-1α–stimulated cell migration. We report a novel mechanism of HER2-neu transactivation through SDF-1α stimulation of CXCR4 that involves Src kinase activation.
Depression in developing countries: lessons from Zimbabwe
Authors: V. Patel
Journal: BMJ (2001)

Depression is one of the most important causes of morbidity and disability in developing countries. 1Zimbabwe, in common with other developing nations, has absolute poverty, economic reform programmes, limited public health services, widespread private and traditional healthcare services, civil unrest, cultural diversity, and sex inequality.We have conducted research on depression in Zimbabwe over the past 15 years, covering ethnographic and epidemiological studies in a range of populations.We compared our findings with research from other developing countries and with evidence from industrialised countries.In the context of developing countries we examined the validity of World Health Organization classifications and medical concepts of depression, the public health implications of depression, and the implications for clinical practice and research.
Plasma levels of elastase-specific fibrinopeptides correlate with proteinase inhibitor phenotype. Evidence for increased elastase activity in subjects with homozygous and heterozygous deficiency of alpha 1-proteinase inhibitor.
Authors: J I Weitz, E K Silverman, B Thong, E J Campbell
Journal: Journal of Clinical Investigation (1992)

There is indirect evidence that unopposed human neutrophil elastase (HNE) is responsible for emphysema in patients with alpha 1-proteinase inhibitor (Pi) deficiency. To directly explore this possibility, we developed an assay for fibrinopeptide A alpha 1-21 and its degradation products and used it to measure HNE activity in 128 subjects of known Pi phenotype. The mean elastase-specific fibrinopeptide (ESF) level in 49 deficient PiZ individuals is significantly higher than that in 56 PiMZ heterozygotes (4.5 and 1.5 nM, respectively; P less than 0.01), while the mean ESF value in heterozygotes is significantly elevated over that in 23 normal PiM subjects (1.5 and 0.6 nM, respectively; P less than 0.01), consistent with increased HNE activity in those deficient in the major regulator of the enzyme. These results are not due to differences in smoking history because after correction for pack-years of smoking, ESF values in PiZ subjects are fourfold higher than those in PiMZ individuals (P = 0.005), while the ESF levels in heterozygotes are threefold higher than those in PiM subjects (P = 0.02). In addition, this analysis suggests that cigarette smoking and alpha 1-proteinase inhibitor deficiency have additive effects on ESF levels thereby explaining why PiZ and some PiMZ individuals are at especially high risk for the development of lung disease if they smoke. Finally, the observation that ESF levels in nonsmoking PiZ subjects are inversely related to the percent of predicted forced expiratory volume in 1 s (FEV 1%) provides direct support for the concept that unregulated HNE activity causes alveolar septal destruction in patients with alpha 1-proteinase inhibitor deficiency.
Ixabepilone (Epothilone B Analogue BMS-247550) Is Active in Chemotherapy-Naive Patients With Hormone-Refractory Prostate Cancer: A Southwest Oncology Group Trial S0111
Authors: Maha Hussain, Catherine M. Tangen, Primo N. Lara, Ulka N. Vaishampayan, Daniel P. Petrylak, A. Dimitrios Colevas, Wael A. Sakr, E. David Crawford
Journal: Journal of Clinical Oncology (2005)

The epothilones are a new class of tubulin-polymerizing agents with activity in taxane-sensitive and resistant tumor models. We evaluated ixabepilone (BMS-247550) in patients with metastatic hormone-refractory prostate cancer (HRPC).Eligible patients had chemotherapy-naive metastatic HRPC, a Zubrod performance status of 0 to 2, and adequate organ function. All patients received BMS-247550 at 40 mg/m2 over 3 hours every 3 weeks. The primary end point was proportion of patients achieving a prostate-specific antigen (PSA) response.Forty-eight patients with metastatic HRPC were registered. Forty-two patients were eligible, with a median age of 73 years and a median PSA level of 111 ng/mL; 78% had bone-only or bone and soft tissue metastases, and 88% had objective radiologic disease progression at registration. Grade 3 and 4 adverse events (AEs) occurred in 16 and three patients, respectively. All grade 4 toxicities were neutropenia or leukopenia. The most frequent grade 3 AEs were neuropathy (eight patients), hematologic toxicity (seven patients), flu-like symptoms, and infection (five patients each). There were no grade 3/4 thrombocytopenia or grade 5 AEs. There were 14 confirmed PSA responses (33%; 95% CI, 20% to 50%); 72% of PSA responders had declines greater than 80%, and two patients achieved an undetectable PSA. The estimated median progression-free survival is 6 months (95% CI, 4 to 8 months), and the median survival is 18 months (95% CI, 13 to 24 months).Ixabepilone has demonstrated activity in patients with chemotherapy-naive metastatic HRPC. Major toxicities were neutropenia and neuropathy. Further testing to define its activity relative to standard therapy is warranted.
A new disposable probe for recording intraluminal pressure and electric potentials in the human gastrointestinal tract.
Authors: S Dorph, A Oigaard, M Kragsholm
Journal: Gut (1972)

Patients with type 2 diabetes are prone to hypertension and persistent protein leakage from the kidney (microalbuminuria or macroalbuminuria). A progressive decline in renal function can lead to overt diabetic nephropathy and ESRD. The likelihood of cardiovascular disease also is increased. Control of hypertension is paramount to prevent these life-threatening complications. Agents that target the renin-angiotensin system—angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers—have been shown to be renoprotective. The groundbreaking Diabetics Exposed to Telmisartan And enalaprIL (DETAIL) trial was designed to address the absence of comparative data on the long-term effects of an angiotensin II receptor blocker <i>versus</i> an angiotensin-converting enzyme inhibitor on renoprotection and survival in 250 patients with hypertension and early type 2 diabetic nephropathy. The primary purpose of the 5-yr double-blind, double-dummy, randomized study was to establish whether 40 to 80 mg of telmisartan conferred similar (<i>i.e.</i>, noninferior) renoprotection to 10 to 20 mg of enalapril as determined by the change from baseline in GFR, measured by the plasma clearance of iohexol. Secondary end points included the emergence of ESRD and all-cause mortality. Telmisartan was not inferior to enalapril in reducing the decline in GFR: Mean annual declines in GFR were 3.7 and 3.3 ml/min per 1.73 m<sup>2</sup> with telmisartan and enalapril, respectively. During the 5-yr study period, no patient developed a serum creatinine &gt;200 μmol/L, and none required dialysis. There were only six deaths in each treatment group during the study, with half being due to cardiovascular events.
An association between fine particles and asthma emergency department visits for children in Seattle.
Authors: G Norris, S N YoungPong, J Q Koenig, T V Larson, L Sheppard, J W Stout
Journal: Environmental Health Perspectives (1999)

Asthma is the most common chronic illness of childhood and its prevalence is increasing, causing much concern for identification of risk factors such as air pollution. We previously conducted a study showing a relationship between asthma visits in all persons < 65 years of age to emergency departments (EDs) and air pollution in Seattle, Washington. In that study the most frequent zip codes of the visits were in the inner city. The Seattle-King County Department of Public Health (Seattle, WA) subsequently published a report which showed that the hospitalization rate for children in the inner city was over 600/100,000, whereas it was < 100/100,000 for children living in the suburbs. Therefore, we conducted the present study to evaluate whether asthma visits to hospital emergency departments in the inner city of Seattle were associated with outdoor air pollution levels. ED visits to six hospitals for asthma and daily air pollution data were obtained for 15 months during 1995 and 1996. The association between air pollution and childhood ED visits for asthma from the inner city area with high asthma hospitalization rates were compared with those from lower hospital utilization areas. Daily ED counts were regressed against fine particulate matter (PM), carbon monoxide (CO), sulfur dioxide, and nitrogen dioxide using a semiparametric Poisson regression model. Significant associations were found between ED visits for asthma in children and fine PM and CO. A change of 11 microg/m3 in fine PM was associated with a relative rate of 1.15 [95% confidence interval (CI), 1.08-1.23]. There was no stronger association between ED visits for asthma and air pollution in the higher hospital utilization area than in the lower utilization area. These findings were seen when estimated PM2.5 concentrations were below the newly adopted annual National Ambient Air Quality Standard of 15 microg/m3.
Risk of suicide after suicide attempt according to coexisting psychiatric disorder: Swedish cohort study with long term follow-up
Authors: D. Tidemalm, N. Langstrom, P. Lichtenstein, B. Runeson
Journal: BMJ (2008)

<b>Objective</b> To investigate the impact of coexistent psychiatric morbidity on risk of suicide after a suicide attempt. <b>Design</b> Cohort study with follow-up for 21-31 years. <b>Setting</b> Swedish national register based study. <b>Participants</b> 39 685 people (53% women) admitted to hospital for attempted suicide during 1973-82. <b>Main outcome measure</b> Completed suicide during 1973-2003. <b>Results</b> A high proportion of suicides in all diagnostic categories took place within the first year of follow-up (14-64% in men, 14-54% in women); the highest short term risk was associated with bipolar and unipolar disorder (64% in men, 42% in women) and schizophrenia (56% in men, 54% in women). The strongest psychiatric predictors of completed suicide throughout the entire follow-up were schizophrenia (adjusted hazard ratio 4.1, 95% confidence interval 3.5 to 4.8 in men, 3.5, 2.8 to 4.4 in women) and bipolar and unipolar disorder (3.5, 3.0 to 4.2 in men, 2.5, 2.1 to 3.0 in women). Increased risks were also found for other depressive disorder, anxiety disorder, alcohol misuse (women), drug misuse, and personality disorder. The highest population attributable fractions for suicide among people who had previously attempted suicide were found for other depression in women (population attributable fraction 9.3), followed by schizophrenia in men (4.6), and bipolar and unipolar disorder in women and men (4.1 and 4.0, respectively). <b>Conclusion</b> Type of psychiatric disorder coexistent with a suicide attempt substantially influences overall risk and temporality for completed suicide. To reduce this risk, high risk patients need aftercare, especially during the first two years after attempted suicide among patients with schizophrenia or bipolar and unipolar disorder.
Age-related changes in ploidy levels and biochemical parameters in cardiac myocytes isolated from spontaneously hypertensive rats.
Authors: G L Engelmann, J C Vitullo, R G Gerrity
Journal: Circulation Research (1986)

Postnatal growth of the mammalian ventricular myocyte is characterized by a brief period of hyperplasia followed by an extensive period of physiological hypertrophy. Using myocytes isolated from both Wistar-Kyoto and spontaneously hypertensive rats from fetus to 10 months old, we analyzed morphological, biochemical, and ploidy changes. Fetal myocytes from both spontaneously hypertensive and Wistar-Kyoto rats were mononuclear, diploid cells. By 4 weeks, adult binucleation levels (84% binuclear) were found, and myocytes pooled from both ventricles demonstrated nuclear ploidy shifts to tetraploid levels. However, analysis of myocytes isolated from left ventricle, right ventricle, and septum showed that nuclear polyploidation was confined to the right ventricle and septum, with few polyploid nuclei detected in the left ventricle. This pattern remained relatively constant through 10 months of age, although spontaneously hypertensive myocytes showed significantly more polyploidation than Wistar-Kyoto in all regions. Biochemical analysis of isolated myocytes substantiated the nuclear ploidy changes and demonstrated elevated protein and ribonucleic acid content in left ventricular myocytes without extensive polyploidation. Since cardiac hypertrophy, both physiological and pathological, is associated primarily with the left ventricle and occurs in the absence of significant ploidy changes, these findings suggest that a unique pattern of gene regulation may be ongoing in the left ventricle myocytes that is not present in the septum and right ventricle. These variations may be essential for cellular hypertrophy under normal and pathological conditions.
Vesicular Trafficking of Tyrosine Kinase Receptors and Associated Proteins in the Regulation of Signaling and Vascular Function
Authors: Sanchita Mukherjee, Mathewos Tessema, Angela Wandinger-Ness
Journal: Circulation Research (2006)

Receptor tyrosine kinases (RTKs) play a pivotal role in the development and function of the cardiovascular system. Ligand-activated RTKs promote numerous downstream signal transduction pathways that lead to vascular permeability, as well as proliferation, migration, and differentiation of vascular endothelia and smooth muscle cells. Ligand binding also promotes internalization of the activated receptors either to downregulate the signaling via degradation of the ligand/receptor complex or to signal from endosomes. However, the outcomes of receptor internalization via clathrin-dependent or caveolar pathways and trafficking mechanisms are incompletely clarified in vascular systems. Activity modulation through endocytosis and vesicular trafficking significantly impacts downstream targets of RTKs such as endothelial nitric oxide synthase (eNOS) and VE-cadherin. RTKs and their associated targets are also transported to the nucleus, where they may directly impact nuclear signaling. Although the nuclear transport pathways are just beginning to be unraveled, it appears that endocytosis and vesicular trafficking are involved. In this review, we discuss the mechanisms by which activated RTKs and the downstream targets eNOS and VE-cadherin may be internalized and transported to various intracellular compartments. How localization and interacting proteins impact protein function and influence signaling is an important theme, as is the potential for modulating signaling through therapeutic targeting of activated receptors and components of the endocytic machinery.
Detection of <i>Trypanosoma cruzi</i><scp>DNA</scp> in blood by <scp>PCR</scp> is associated with Chagas cardiomyopathy and disease severity
Authors: E. C. Sabino, A. L. Ribeiro, T. H Lee, C. L. Oliveira, A. B. Carneiro‐Proietti, A. P. Antunes, M. M. Menezes, B. M. Ianni, V. M. Salemi, L. Nastari, F. Fernandes, V. Sachdev, D. M. Carrick, X. Deng, D. Wright, T. T. Gonçalez, E. L. Murphy, B. Custer, M.P. Busch
Journal: European Journal of Heart Failure (2015)
Renin Excretion in Patients with Renal Disease
Authors: ACHILLE C. PESSINA, BARRY HULME, ALESSANDRO RAPPELLI, W. STANLEY PEART
Journal: Circulation Research (1970)

The renal handling of renin was studied in normal subjects and in patients with predominant tubular and glomerular damage. The renin in plasma and urine was assayed in the blood pressure preparation of the rat. Excessive renin excretion occurred only in patients with proximal tubular dysfunction and was not related to creatinine clearance, proteinuria or plasma renin levels. However, a significant correlation was found between renin clearance and clearances of other low molecular weight proteins which pass freely through the glomerular membrane and are normally reabsorbed by the tubules. All the evidence points to the important role played by tubular reabsorption in the control of renin urinary excretion.
Evolution of Insect Olfaction
Authors: Bill S. Hansson, Marcus C. Stensmyr
Journal: Neuron (2011)

Neuroethology utilizes a wide range of multidisciplinary approaches to decipher neural correlates of natural behaviors associated with an animal's ecological niche. By placing emphasis on comparative analyses of adaptive and evolutionary trends across species, a neuroethological perspective is uniquely suited to uncovering general organizational and biological principles that shape the function and anatomy of the nervous system. In this review, we focus on the application of neuroethological principles in the study of insect olfaction and discuss how ecological environment and other selective pressures influence the development of insect olfactory neurobiology, not only informing our understanding of olfactory evolution but also providing broader insights into sensory processing. Neuroethology utilizes a wide range of multidisciplinary approaches to decipher neural correlates of natural behaviors associated with an animal's ecological niche. By placing emphasis on comparative analyses of adaptive and evolutionary trends across species, a neuroethological perspective is uniquely suited to uncovering general organizational and biological principles that shape the function and anatomy of the nervous system. In this review, we focus on the application of neuroethological principles in the study of insect olfaction and discuss how ecological environment and other selective pressures influence the development of insect olfactory neurobiology, not only informing our understanding of olfactory evolution but also providing broader insights into sensory processing.