tbuckley/cabot-search huggingface dataset:
High Prevalence of Diabetes and Cardiovascular Risk Factors Associated With Urbanization in India
Authors: Ambady Ramachandran, Simon Mary, Annasami Yamuna, Narayanasamy Murugesan, Chamukuttan Snehalatha
Journal: Diabetes Care (2008)

OBJECTIVE—To compare prevalence of diabetes, impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and cardiovascular risk factors between a city, a town, and periurban villages (PUVs) in southern India and to look for temporal changes in the city and PUVs. RESEARCH DESIGN AND METHODS—Subjects aged ≥20 years were studied in Tamilnadu, India, in Chennai (city, n = 2,192; 1,053 men and 1,138 women), Kanchipuram (town, n = 2,290; 988 men and 1,302 women), and Panruti (PUVs, n = 2,584; 1,280 men and 1,304 women) in 2006. Demographic, socioeconomic, and anthropometric details; blood pressure; physical activity; diet habits; and lipids were studied. Risk associations with diabetes were analyzed using multiple logistic regression analyses. Present and previous data in the city and the PUVs were compared. RESULTS—Mean BMI, waist circumference, and family history of diabetes were significantly lower in the PUVs. The PUVs had a lower prevalence of diabetes (9.2 [95% CI 8.0–10.5], P &amp;lt; 0.0001) than the city (18.6 [16.6–20.5]) and town (16.4 [14.1–18.6]). Approximately 40% of subjects were newly diagnosed. Prevalence of impaired glucose tolerance (IGT) was higher (P &amp;lt; 0.0001) in the city (7.4 [6.2–8.5]) than in the town (4.3 [3.3–5.3]) and the PUVs (5.5 [4.6–6.5]). Prevalence of IFG was generally low. Age, family history, and waist circumference were significantly associated with diabetes, while physical activity was not. Overweight, elevated waist circumference, hypertension, and dyslipidemia were more prevalent in the city. CONCLUSIONS—In the city, diabetes increased from 13.9 to 18.6% in 6 years and IGT decreased significantly. The town and city had similar prevalences; the PUVs had lower diabetes prevalence, but prevalence had increased compared with that in a previous survey. Cardiometabolic abnormalities were more prevalent in urban populations.
Phase I Study of Navitoclax (ABT-263), a Novel Bcl-2 Family Inhibitor, in Patients With Small-Cell Lung Cancer and Other Solid Tumors
Authors: Leena Gandhi, D. Ross Camidge, Moacyr Ribeiro de Oliveira, Philip Bonomi, David Gandara, Divis Khaira, Christine L. Hann, Evelyn M. McKeegan, Elizabeth Litvinovich, Philip M. Hemken, Caroline Dive, Sari H. Enschede, Cathy Nolan, Yi-Lin Chiu, Todd Busman, Hao Xiong, Andrew P. Krivoshik, Rod Humerickhouse, Geoffrey I. Shapiro, Charles M. Rudin
Journal: Journal of Clinical Oncology (2011)

Resistance to chemotherapy-induced apoptosis represents a major obstacle to cancer control. Overexpression of Bcl-2 is seen in multiple tumor types and targeting Bcl-2 may provide therapeutic benefit. A phase I study of navitoclax, a novel inhibitor of Bcl-2 family proteins, was conducted to evaluate safety, pharmacokinetics, and preliminary efficacy in patients with solid tumors.Patients enrolled to intermittent dosing cohorts received navitoclax on day -3, followed by dosing on days 1 to 14 of a 21-day cycle. Patients on continuous dosing received a 1-week lead-in dose of 150 mg followed by continuous daily administration. Blood samples were collected for pharmacokinetic analyses, biomarker analyses, and platelet monitoring.Forty-seven patients, including 29 with small-cell lung cancer (SCLC) or pulmonary carcinoid, were enrolled between 2007 and 2008, 35 on intermittent and 12 on continuous dosing cohorts. Primary toxicities included diarrhea (40%), nausea (34%), vomiting (36%), and fatigue (34%); most were grade 1 or 2. Dose- and schedule-dependent thrombocytopenia was seen in all patients. One patient with SCLC had a confirmed partial response lasting longer than 2 years, and eight patients with SCLC or carcinoid had stable disease (one remained on study for 13 months). Pro-gastrin releasing peptide (pro-GRP) was identified as a surrogate marker of Bcl-2 amplification and changes correlated with changes in tumor volume.Navitoclax is safe and well tolerated, with dose-dependent thrombocytopenia as the major adverse effect. Preliminary efficacy data are encouraging in SCLC. Efficacy in SCLC and the utility of pro-GRP as a marker of treatment response will be further evaluated in phase II studies.
Musings on genome medicine: cancer genetics and the promise of effective treatment
Authors: David G Nathan, Stuart H Orkin
Journal: Genome Medicine (2009)

Cancer is the most common acquired genetic disease. Great progress has been made in documenting the genetic abnormalities that cause the disease, and in the future each tumor will be subjected to genetic analysis and the appropriate combination of drugs selected. Although there are serious technological and cost hurdles to surmount and resistance and continued mutation will be a constant problem, the way is clear to rational therapy.
Sympathetic Joint Effusion in Septic Arthritis
Authors: Stuart B. Baker
Journal: JAMA (1978)

SYMPATHETIC joint effusions have not received much attention in the rheumatologic literature; in fact, we have been unable to find a general discussion of this phenomenon. A sympathetic effusion may be defined as a transudative, noninflammatory synovial fluid in a joint adjacent to a site of inflammation. The clinical picture is that of an acute arthritis or periarthritis; with synoviocentesis, a noninflammatory fluid is found. A variety of diseases are associated with this combination, including sarcoidosis, erythema nodosum, calcific periarthritis, apatite arthritis, gout, systemic lupus erythematosus, hypertrophic pulmonary osteoarthropathy, and an acute arthritis associated with chronic hemodialysis. In these entities, the supposition is that the primary inflammatory process occurs adjacent to the joint, in the periarticular structures, and the synovial fluid represents a secondary or sympathetic response. A similar phenomenon can occur between two adjacent joints. In particular, a focus of sepsis in one joint can cause a sympathetic effusion
Lipopolysaccharide (LPS)-binding protein and soluble CD14 function as accessory molecules for LPS-induced changes in endothelial barrier function, in vitro.
Authors: S E Goldblum, T W Brann, X Ding, J Pugin, P S Tobias
Journal: Journal of Clinical Investigation (1994)

Bacterial LPS induces endothelial cell (EC) injury both in vivo and in vitro. We studied the effect of Escherichia coli 0111:B4 LPS on movement of 14C-BSA across bovine pulmonary artery EC monolayers. In the presence of serum, a 6-h LPS exposure augmented (P < 0.001) transendothelial 14C-BSA flux compared with the media control at concentrations > or = 0.5 ng/ml, and LPS (10 ng/ml) exposures of > or = 2-h increased (P < 0.005) the flux. In the absence of serum, LPS concentrations of up to 10 micrograms/ml failed to increase 14C-BSA flux at 6 h. The addition of 10% serum increased EC sensitivity to the LPS stimulus by > 10,000-fold. LPS (10 ng/ml, 6 h) failed to increase 14C-BSA flux at serum concentrations < 0.5%, and maximum LPS-induced increments could be generated in the presence of > or = 2.5%. LPS-binding protein (LBP) and soluble CD14 (sCD14) could each satisfy this serum requirement; either anti-LBP or anti-CD14 antibody each totally blocked (P < 0.00005) the LPS-induced changes in endothelial barrier function. LPS-LBP had a more rapid onset than did LPS-sCD14. The LPS effect in the presence of both LBP and sCD14 exceeded the effect in the presence of either protein alone. These data suggest that LBP and sCD14 each independently functions as an accessory molecule for LPS presentation to the non-CD14-bearing endothelial surface. However, in the presence of serum both molecules are required.
Understanding Cancer Centers
Authors: Joseph V. Simone
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.07.574 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12454105 Understanding Cancer Centers Joseph V. SimonexJoseph V. SimoneSearch for articles by this author Show More Huntsman Cancer Institute, University of Utah School of Medicine, Simone Consulting, Dunwoody, GA https://doi.org/10.1200/JCO.2002.07.574 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
A simplified model of screening questionnaire and home monitoring for obstructive sleep apnoea in primary care
Authors: C. L. Chai-Coetzer, N. A. Antic, L. S. Rowland, P. G. Catcheside, A. Esterman, R. L. Reed, H. Williams, S. Dunn, R. D. McEvoy
Journal: Thorax (2011)

<h3>Background</h3> To address the growing burden of disease and long waiting lists for sleep services, a simplified two-stage model was developed and validated for identifying obstructive sleep apnoea (OSA) in primary care using a screening questionnaire followed by home sleep monitoring. <h3>Methods</h3> 157 patients aged 25–70 years attending their primary care physician for any reason at six primary care clinics in rural and metropolitan regions of South Australia participated. The first 79 patients formed the development group and the next 78 patients the validation group. A screening questionnaire was developed from factors identified from sleep surveys, demographic and anthropometric data to be predictive of moderate to severe OSA. Receiver operating characteristic (ROC) curve analysis was used to validate the two-channel ApneaLink device against full polysomnography. The diagnostic accuracy of the overall two-stage model was then evaluated. <h3>Results</h3> Snoring, waist circumference, witnessed apnoeas and age were predictive of OSA and incorporated into a screening questionnaire (ROC area under curve (AUC) 0.84, 95% CI 0.75 to 0.94, p&lt;0.001). ApneaLink oximetry with a 3% dip rate was highly predictive of OSA (AUC 0.96, 95% CI 0.91 to 1.0, p&lt;0.001). The two-stage diagnostic model showed a sensitivity of 0.97 (95% CI 0.81 to 1.00) and specificity of 0.87 (95% CI 0.74 to 0.95) in the development group, and a sensitivity of 0.88 (95% CI 0.60 to 0.98) and specificity of 0.82 (95% CI 0.70 to 0.90) in the validation group. <h3>Conclusion</h3> A two-stage model of screening questionnaire followed by home oximetry can accurately identify patients with OSA in primary care and has the potential to expedite care for patients with this common sleep disorder.
Kinetics of interaction of the lidocaine metabolite glycylxylidide with the cardiac sodium channel. Additive blockade with lidocaine.
Authors: D J Wendt, C F Starmer, A O Grant
Journal: Circulation Research (1992)

The recovery of the sodium channel from blockade by local anesthetic antiarrhythmic drugs is voltage dependent. Recovery from lidocaine-induced blockade is accelerated by hyperpolarization, whereas that from glycylxylidide (GX) blockade has been reported to be slowed by hyperpolarization. This striking difference occurs despite similarities in chemical structure. The fast recovery from GX block at depolarized potentials may lead to a partial reversal of lidocaine blockade when the two drugs are combined. We have examined the kinetics of interaction of GX with the cardiac sodium channel over a range of membrane potentials by measuring whole-cell currents in isolated rabbit myocytes under voltage clamp at 15 degrees C. In the absence of drug, slow inactivation developed with a time constant of 10.7 +/- 5.1 seconds (n = 6). During exposure to 74 mumol/l GX, block developed with a time constant of 7.0 +/- 3 seconds (n = 6). Because of the similar time course of slow inactivation and block, we used a high concentration of GX to induce a level of block sufficient for analysis. The onset of block was slower than that induced by lidocaine and was unaffected by variation of external sodium from 20 to 75 mmol/l. Use-dependent blockade of sodium channels was greater when pulse trains were applied from a holding potential of -100 than -140 mV. This suggested that recovery from GX block might be slower at -100 than -140 mV. Direct measurements gave time constants of recovery of 10.3 +/- 4.2 seconds at -100 mV (n = 6) and 4.1 +/- 0.4 seconds at -140 mV (n = 4). The combination of GX with lidocaine produced only additive blocking effects when pulse trains were applied from both holding potentials. Computer simulations of the requirements for the competitive displacement of a sodium channel blocker with slow kinetics by one with fast kinetics suggest that the recovery time constant of the fast drug must be 10-100-fold smaller than that of the slow drug. Rapid association kinetics effected by a large binding rate constant or a higher concentration of the fast blocking drug is also important. The simulations suggest that, for the interaction of GX and lidocaine, only additive blocking action should be observed over the range of stimulus frequencies used in these experiments.
Idarubicin and ATRA Is as Effective as MRC Chemotherapy in Patients with Acute Promyelocytic Leukaemia with Lower Toxicity and Resource Usage: Preliminary Results of the MRC AML15 Trial.
Authors: Alan K. Burnett, Robert K. Hills, David Grimwade, Anthony H. Goldstone, Ann Hunter, Don Milligan, Archie G. Prentice, Nigel H. Russell, Keith Wheatley
Journal: Blood (2007)
Crizotinib Therapy for Advanced Lung Adenocarcinoma and a <i>ROS1</i> Rearrangement: Results From the EUROS1 Cohort
Authors: Julien Mazières, Gérard Zalcman, Lucio Crinò, Pamela Biondani, Fabrice Barlesi, Thomas Filleron, Anne-Marie C. Dingemans, Hervé Léna, Isabelle Monnet, Sacha I. Rothschild, Federico Cappuzzo, Benjamin Besse, Luc Thiberville, Damien Rouvière, Rafal Dziadziuszko, Egbert F. Smit, Jurgen Wolf, Christian Spirig, Nicolas Pecuchet, Frauke Leenders, Johannes M. Heuckmann, Joachim Diebold, Julie D. Milia, Roman K. Thomas, Oliver Gautschi
Journal: Journal of Clinical Oncology (2015)

Approximately 1% of lung adenocarcinomas are driven by oncogenic ROS1 rearrangement. Crizotinib is a potent inhibitor of both ROS1 and ALK kinase domains.In the absence of a prospective clinical trial in Europe, we conducted a retrospective study in centers that tested for ROS1 rearrangement. Eligible patients had stage IV lung adenocarcinoma, had ROS1 rearrangement according to fluorescent in situ hybridization, and had received crizotinib therapy through an individual off-label use. Best response was assessed locally using RECIST (version 1.1). All other data were analyzed centrally.We identified 32 eligible patients. One patient was excluded because next-generation sequencing was negative for ROS1 fusion. Median age was 50.5 years, 64.5% of patients were women, and 67.7% were never-smokers. Thirty patients were evaluable for progression-free survival (PFS), and 29 patients were evaluable for best response. We observed four patients with disease progression, two patients with stable disease, and objective response in 24 patients, including five complete responses (overall response rate, 80%; disease control rate, 86.7%). Median PFS was 9.1 months, and the PFS rate at 12 months was 44%. No unexpected adverse effects were observed. Twenty-six patients received pemetrexed (either alone or in combination with platinum and either before or after crizotinib) and had a response rate of 57.7% and a median PFS of 7.2 months.Crizotinib was highly active at treating lung cancer in patients with a ROS1 rearrangement, suggesting that patients with lung adenocarcinomas should be tested for ROS1. Prospective clinical trials with crizotinib and other ROS1 inhibitors are ongoing or planned.
Comparison of Unitary Displacements and Forces Between 2 Cardiac Myosin Isoforms by the Optical Trap Technique
Authors: Seiryo Sugiura, Naoshi Kobayakawa, Hideo Fujita, Hiroshi Yamashita, Shin-ichi Momomura, Shigeru Chaen, Masao Omata, Haruo Sugi
Journal: Circulation Research (1998)

Abstract —To provide information on the mechanism of cardiac adaptation at the molecular level, we compared the unitary displacements and forces between the 2 rat cardiac myosin isoforms, V 1 and V 3 . A fluorescently labeled actin filament, with a polystyrene bead attached, was caught by an optical trap and brought close to a glass surface sparsely coated with either of the 2 isoforms, so that the actin-myosin interaction took place in the presence of a low concentration of ATP (0.5 μmol/L). Discrete displacement events were recorded with a low trap stiffness (0.03 to 0.06 pN/nm). Frequency distribution of the amplitude of the displacements consisted of 2 gaussian curves with peaks at 9 to 10 and 18 to 20 nm for both V 1 and V 3 , suggesting that 9 to 10 nm is the unitary displacement for both isoforms. The duration of the displacement events was longer for V 3 than for V 1 . On the other hand, discrete force transients were recorded with a high trap stiffness (2.1 pN/nm), and their amplitude showed a broad distribution with mean values between 1 and 2 pN for V 1 and V 3 . The durations of the force transients were also longer for V 3 than for V 1 . These results indicate that both the unitary displacements and forces are similar in amplitude but different in duration between the 2 cardiac myosin isoforms, being consistent with the reports that the tension cost is higher in muscles consisting mainly of V 1 than those consisting mainly of V 3 .
Randomized Controlled Trial of Early Zoledronic Acid in Men With Castration-Sensitive Prostate Cancer and Bone Metastases: Results of CALGB 90202 (Alliance)
Authors: Matthew R. Smith, Susan Halabi, Charles J. Ryan, Arif Hussain, Nicholas Vogelzang, Walter Stadler, Ralph J. Hauke, J. Paul Monk, Philip Saylor, Nirmala Bhoopalam, Fred Saad, Ben Sanford, W. Kevin Kelly, Michael Morris, Eric J. Small
Journal: Journal of Clinical Oncology (2014)

Purpose Zoledronic acid decreases the risk for skeletal-related events (SREs) in men with castration-resistant prostate cancer and bone metastases but its role earlier in the natural history of the disease is unknown. This phase III study evaluated the efficacy and safety of earlier treatment with zoledronic acid in men with castration-sensitive metastatic prostate cancer. Patients and Methods Men with castration-sensitive prostate cancer and bone metastases whose androgen-deprivation therapy was initiated within 6 months of study entry were randomly assigned in a blinded 1:1 ratio to receive zoledronic acid (4 mg intravenously every 4 weeks) or a placebo. After their disease progressed to castration-resistant status, all patients received open-label treatment with zoledronic acid. The primary end point was time to first SRE, defined as radiation to bone, clinical fracture, spinal cord compression, surgery to bone, or death as a result of prostate cancer. Target accrual was 680 patients. Primary analysis was planned after 470 SREs. The study was discontinued prematurely (645 patients; 299 SREs) after the corporate supporter withdrew study drug supply. Results Early zoledronic acid was not associated with increased time to first SRE. The median time to first SRE was 31.9 months in the zoledronic acid group (95% CI, 24.2 to 40.3) and 29.8 months in the placebo group (95% CI, 25.3 to 37.2; hazard ratio, 0.97; 95% CI, 0 to 1.17; one-sided stratified log-rank P = .39). Overall survival was similar between the groups (hazard ratio, 0.88; 95% CI, 0.70 to 1.12; P = .29). Rates of adverse events were similar between the groups. Conclusion In men with castration-sensitive prostate cancer and bone metastases, early treatment with zoledronic acid was not associated with lower risk for SREs.
THE MENACE OF HEREDITARY BLINDNESS
Authors: J. M. Bickerton
Journal: BMJ (1934)

IEIA ORA remain obscure it -is a matter for coimfort that it lies within our power to recognize that some of the more alarming episodes of medical practice need not, in fact, occasion any fear of an unhappy endinig.* Column 1 is mlodified fromn Harman, and the other figures are my own estimlates.
CLINICAL UTILITY OF BIOCHEMICAL ASSAYS IN PSYCHIATRY
Authors: J M Davis
Journal: Annual Review of Medicine (1987)

Biological abnormalities are found almost consistently in schizophrenia and affective disease. While most remain as research leads, some are sufficiently well studied that they are now or may soon enter in routine medical practice. The dexamethasone test (DST) has been investigated thoroughly enough so it should pass into practice.
Family Structure in Three Cases of Anorexia Nervosa: The Role of the Father
Authors: PATRICIA WOLD
Journal: American Journal of Psychiatry (1973)

The family structure in three cases of anorexia nervosa is described. Each parent placed a daughter (the patient) in the position of his or her own mother, toward whom neither parent could express hostility. This conflict was focused on the child, blocking any expression of aggression or sexuality in the child. The actual weight loss seemed closely related to the patient's relationship with her father.
Spontaneous Cytomegalovirus Mononucleosis
Authors: M. COLIN JORDAN
Journal: Annals of Internal Medicine (1973)

Nine cases of cytomegalovirus mononucleosis in previously healthy persons were seen during a 10-month period. All were women between 19 and 28 years of age. Their illnesses were characterized by malaise, myalgia, fever, atypical lymphocytosis, and abnormal liver functions. Five patients noted sore throat, but none had exudative pharyngitis. Generalized lymphadenopathy was present in two patients and splenomegaly in three. Heterophil agglutination and ox cell hemolysin tests were uniformly negative. Seven patients had mild illnesses, one developed ascending polyneuritis (Guillain-Barré syndrome), and another had a prolonged illness complicated by splenic infarction. Persistent viruria was noted in all patients; cytomegalovirus was also recovered from oropharyngeal secretions in five patients and other sites in one patient. Cytomegalovirus mononucleosis may be common among young adults. This diagnosis should be considered in all patients with heterophil-antibody-negative mononucleosis, including those with lymphadenopathy and splenomegaly.
Biomarkers for predicting COPD exacerbations
Authors: Ruth Pais
Journal: Thorax (2013)

Biomarkers for predicting COPD exacerbationsThis Danish prospective cohort study compared frequency of exacerbations in stable chronic obstructive pulmonary disease (COPD) patients with chronically raised inflammatory biomarkers to those with normal inflammatory biomarkers over a 5-year follow-up.It measured baseline levels of C-reactive protein (CRP), leucocytes and fibrinogen levels.An exacerbation was defined as requiring a short course of treatment with oral corticosteroids and/or antibiotics, or requiring hospital treatment due to COPD.Frequent exacerbations were defined as having two or more per year and each being more than 4 weeks apart.This study found that simultaneously elevated levels of CRP, fibrinogen and leucocytes positively correlated with an increased risk of frequent exacerbations in stable COPD, which was statistically significant.The relative risk remained consistent when multivariable factors, such as previous exacerbations, symptom burden, disease severity and Body Mass Index were included, indicating that inflammatory biomarkers give additional information when riskstratifying patients.Although this was a large prospective study with 100% follow-up rate, a large percentage of patients suffered with mild COPD, and were not on regular inhaled therapy.Therefore, the numbers with frequent exacerbations were small, decreasing the statistical power of the results.Currently, the main predictors for frequent exacerbations are previous exacerbation and disease severity.This study suggests that measuring inflammatory biomarkers in stable disease enables clinicians to further risk-stratify their patients and potentially provide high-risk patients with preventative medication.However, further investigation is needed to determine the clinical value of these biomarkers for risk stratification.