tbuckley/cabot-search huggingface dataset:
Lung cancer resection rate is related to survival
Authors: Kelvin K W Lau, David A Waller, Sridhar Rathinam, Richard Page, Mick D Peake
Journal: Thorax (2012)

Treasure and colleagues1 provided a welcomed counterpoint to the belief that resection rate should go up in England. However, we feel the editorial is intentionally controversial and biased against the role of surgery. In particular, the authors question the relationship between resection rate and outcome but fail to cite the recent evidence that relates resection rate to survival in the UK: that the small excess mortality from operating in higher-risk groups was more than justified by the increase in overall survival from lung cancer.2

In terms of treatment, …
Obstructive Sleep Apnea in Young Lean Men
Authors: Sushmita Pamidi, Kristen Wroblewski, Josiane Broussard, Andrew Day, Erin C. Hanlon, Varghese Abraham, Esra Tasali
Journal: Diabetes Care (2012)

OBJECTIVE To assess whether the presence of obstructive sleep apnea (OSA) affects glucose metabolism in young, lean individuals who are healthy and free of cardiometabolic disease. RESEARCH DESIGN AND METHODS In a prospective design, 52 healthy men (age 18–30 years; BMI 18–25 kg/m2) underwent laboratory polysomnogram followed by a morning oral glucose tolerance test (OGTT). We stratified all subjects according to the presence or absence of ethnicity-based diabetes risk and family history of diabetes. We then used a frequency-matching approach and randomly selected individuals without OSA, yielding a total of 20 control men without OSA and 12 men with OSA. Indices of glucose tolerance, insulin sensitivity, and insulin secretion (early phase and total) were compared between men with OSA and control subjects. The incremental areas under the glucose (incAUCglu) and insulin (incAUCins) curves were calculated using the trapezoidal method from 0 to 120 min during the OGTT. RESULTS Men with OSA and control subjects were similar in terms of age, BMI, ethnicity-based diabetes risk, family history of diabetes, and level of exercise. Both groups had normal systolic and diastolic blood pressure and fasting lipid levels. After ingestion of a glucose load, men with OSA had 27% lower insulin sensitivity (estimated by Matsuda index) and 37% higher total insulin secretion (incAUCins) than the control subjects, despite comparable glucose levels (incAUCglu). CONCLUSIONS In young, lean, and healthy men who are free of cardiometabolic disease, the presence of OSA is associated with insulin resistance and a compensatory rise in insulin secretion to maintain normal glucose tolerance. Thus, OSA may increase the risk of type 2 diabetes independently of traditional cardiometabolic risk factors.
Huntington's disease: the case for genetic modifiers
Authors: James F Gusella, Marcy E MacDonald
Journal: Genome Medicine (2009)

For almost three decades, Huntington's disease has been a prototype for the application of genetic strategies to human disease. HD, the Huntington's disease gene, was the first autosomal defect mapped using only DNA markers, a finding in 1983 that helped to spur similar studies in many other disorders and contributed to the concept of the human genome project. The search for the genetic defect itself pioneered many mapping and gene-finding technologies, and culminated in the identification of the HD gene, its mutation and its novel protein product in 1993. Since that time, extensive investigations into the pathogenic mechanism have utilized the knowledge of the disease gene and its defect but, with notable exceptions, have rarely relied for guidance on the genetic findings in human patients to interpret the relevance of findings in non-human model systems. However, the human patient still has much to teach us through a detailed analysis of genotype and phenotype. Such studies have implicated the existence of genetic modifiers - genes whose natural polymorphic variation contributes to altering the development of Huntington's disease symptoms. The search for these modifiers, much as the search for the HD gene did in the past, offers to open new entrées into the process of Huntington's disease pathogenesis by unlocking the biochemical changes that occur many years before diagnosis, and thereby providing validated target proteins and pathways for development of rational therapeutic interventions.
SHORT TERM EFFECT OF SILDENAFIL ON PULMONARY ARTERIAL PRESSURE AND PLATELET ACTIVITY THALASSEMIA PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION
Authors: Navy Tanjararak, Suporn Chuncharunee, Sirada Srihirun, Nathawut Sibmooh, Sukit Yamwong, Somruthai Wattanachai, Piyamitr Sritara
Journal: Journal of the American College of Cardiology (2014)
An Altered Repolarizing Potassium Current in Rat Cardiac Myocytes after Subtotal Nephrectomy
Authors: PAUL DONOHOE, BRUCE M. HENDRY, OMAL V. WALGAMA, FEDERICA BERTASO, DEBORAH J. HOPSTER, MICHAEL J. SHATTOCK, ANDREW F. JAMES
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Renal failure in humans is associated with electrocardiographic changes including altered QT interval dispersion, which suggests that cardiac myocyte repolarization is abnormal and which appears to correlate with cardiac prognosis. In this study, cardiac myocyte repolarizing currents have been studied in isolated cells from rats 8 wk after subtotal nephrectomy (SNx), using sham-operated animals as controls. In addition, monophasic cardiac action potentials were recorded from the epicardial surface of the left ventricle (LV) apex, LV base, and the right ventricle of isolated perfused hearts paced at 320/min. SNx was associated with cardiac hypertrophy and histologic evidence of myocardial fibrosis, but SNx rats were not hypertensive. Repolarizing K + currents were measured using whole-cell patch-clamp, and 4-aminopyridine (4-AP)-sensitive transient outward ( I to ) and 4-AP-insensitive sustained outward ( I so ) components were quantified. After SNx, I to was increased by two to threefold at voltages from -30 to +60 mV and showed increased heterogeneity. For example, at 0 mV voltage clamp pulse, the median I to was increased from 3.23 pA/pF in control myocytes (interquartile range 3.20 pA/pF, n = 24) to 5.86 pA/pF in SNx myocytes (interquartile range 7.32 pA/pF, n = 21, P &lt; 0.005). The kinetics of inactivation of I to were altered after SNx with slowing both of the onset and the recovery from inactivation. The mean time constant of inactivation at +30 mV after SNx was 14.2 ± 1.6 ms ( n = 20) compared with control values of 9.8 ± 0.6 ms ( n = 23, P &lt; 0.05). Neither I so nor inward rectifier K + currents were altered after SNx. The action potential duration (APD 50 ) at the left ventricular base was approximately 20% shorter ( P &lt; 0.02) in hearts from SNx rats compared with controls. 4-AP (2 mM) prolonged the APD 50 in all regions in hearts from both SNx and control rats and abolished the APD 50 shortening in SNx. These results indicate that abnormalities of the cardiac transient outward K + current contribute to alterations in the cardiac action potential in renal failure and warrant further investigation because they may contribute to altered repolarization and arrythmogenesis.
Total T lymphocytes in primary bronchial carcinoma.
Authors: H L Roberts, W T Donohoe, S Hewitt, D A Price Evans
Journal: Thorax (1977)

Percentage and absolute levels of circulating T lymphocytes were measured in 48 patients with bronchial carcinoma. These were compared with control values from nine healthy adults and 19 age-matched patients with benign disorders. A further 20 patients who had been given postoperative immunotherapy after complete resection of bronchial carcinoma were also studied. There was no significant difference in the mean percentage T cells between the groups. Lymphopenia, however, was a feature of the bronchial cancer patients with metastatic disease. This resulted in a significant diminution of absolute T cells in this group. There is no evidence, with the technique employed in this study, of a total T-cell deficiency in early bronchial carcinoma.
RAGE: A New Target for the Prevention and Treatment of the Vascular and Inflammatory Complications of Diabetes
Authors: Ann Marie Schmidt, David M Stern
Journal: Trends in Endocrinology and Metabolism (2000)

Although the underlying causes of hyperglycemia are multiple, a common thread associated with high levels of blood sugar is the development of a range of vascular and inflammatory complications that might seriously limit the quality and duration of life in affected individuals. Despite multiple aggressive efforts to prevent complications, diabetes remains the leading disease consuming healthcare dollars in the USA. This review focuses on the role of advanced glycation endproducts (AGEs) and their interaction with their signal-transduction AGE receptor (RAGE), in vascular and inflammatory cell perturbation and the chronic activation that underlies diabetes. Our studies provide mechanistic insights into complications within the macrovasculature and those ensuing from an exaggerated host response to invading bacteria, and suggest that blockade of RAGE might provide a potent and safe strategy for the prevention of complications that typify long-term diabetes.
Thiazolidinediones and the Risk of Lung, Prostate, and Colon Cancer in Patients With Diabetes
Authors: Rangaswamy Govindarajan, Luke Ratnasinghe, Debra L. Simmons, Eric R. Siegel, Madhu V. Midathada, Lawrence Kim, Peter J. Kim, Randall J. Owens, Nicholas P. Lang
Journal: Journal of Clinical Oncology (2007)

Peroxisome proliferator-activated receptor gamma (PPARgamma) mediates cell cycle arrest and adipocyte differentiation; has tumor suppressor activity in liposarcoma, lung, and prostate cancers; and suppresses colonic polyp formation in adenomatous polyposis coli (APC)min/+ mice. To assess the influence of thiazolidinediones (TZDs), which are PPAR ligands used to treat diabetes mellitus, a retrospective analysis of a database from 10 Veteran Affairs medical centers was conducted.Data on male patients 40 years and older diagnosed to have diabetes mellitus between 1997 and 2003 were obtained from the Veterans Integrated Services Network 16 (VISN 16) data warehouse. Subsequent diagnoses of colorectal, lung, and prostate cancer and use of TZD, other antidiabetic agents, and insulin were identified. Cox regression with time-dependent covariates was used to estimate the association between TZD use and cancer risk. Relative risks were adjusted for confounders (age, race/ethnicity, body mass index, use of insulin, and other oral antidiabetic agents).Of 87,678 individuals, 1,137 had colorectal cancer, 3,246 had prostate cancer, and 1,371 had lung cancer. We observed a 33% reduction in lung cancer risk among TZD users compared with nonusers after adjusting for confounder interactions (relative risk, 0.67; 95% CI, 0.51 to 0.87). The risk reduction for colorectal and prostate cancers did not reach statistical significance.TZD use was associated with reduced risk of lung cancer. Further studies are warranted to confirm our findings.
Elevation of troponin I levels in patients without evidence of myocardial injury
Authors: S. A. Wright
Journal: JAMA (1997)

To the Editor.  —The cardiac isoform of troponin I (TnI) has been touted as 100% specific for myocardial injury.1-3While serving on the consult service of a large teaching hospital, we occasionally have evaluated patients with chest pain and elevations of TnI levels in whom we were unable to find any evidence of myocardial injury. We reviewed consecutive patients evaluated at our hospital between January and June 1996 who had elevated serum TnI levels to determine the specificity of this assay for myocardial injury in clinical practice.  Troponin I levels were obtained as part of routine clinical practice when myocardial injury was suspected, and 343 patients had 1 or more TnI values of 1.0 ng/mL or greater. Cardiac TnI was measured on the Stratus II analyzer (Baxter Dade, Miami, Fla) with a commercial immunoassay procedure that uses 2 monoclonal antibodies directed against different epitopes on TnI.4  Of the
Cardiac Transgenic and Gene Transfer Strategies Converge to Support an Important Role for Troponin I in Regulating Relaxation in Cardiac Myocytes
Authors: So-ichiro Yasuda, Pierre Coutu, Sakthivel Sadayappan, Jeffrey Robbins, Joseph M. Metzger
Journal: Circulation Research (2007)

Elucidating the relative roles of cardiac troponin I (cTnI) and phospholamban (PLN) in beta-adrenergic-mediated hastening of cardiac relaxation has been challenging and controversial. To test the hypothesis that beta-adrenergic phosphorylation of cTnI has a prominent role in accelerating cardiac myocyte relaxation performance we used transgenic (Tg) mice bearing near complete replacement of native cTnI with a beta-adrenergic phospho-mimetic of cTnI whereby tandem serine codons 23/24 were converted to aspartic acids (cTnI S23/24D). Adult cardiac myocytes were isolated and contractility determined at physiological temperature under unloaded and loaded conditions using micro-carbon fibers. At baseline, cTnI S23/24D myocytes had significantly faster relaxation times relative to controls, and isoproterenol stimulation (Iso) had only a small effect to further speed relaxation in cTnI S23/24D myocytes (delta Iso: 7.2 ms) relative to the maximum Iso effect (31.2 ms) in control. The Ca(2+) transient decay rate was similarly accelerated by Iso in Tg and nontransgenic (Ntg) myocytes. Gene transfer of cTnI S23/24D to myocytes in primary culture showed comparable findings. Gene transfer of cTnI with both serines 23/24 converted to alanines (cTnI S23/24A), or gene transfer of slow skeletal TnI, both of which lack PKA phosphorylation sites, significantly blunted Iso-mediated enhanced relaxation compared with controls. Gene transfer of wild-type cTnI had no effect on relaxation. These findings support a key role of cTnI in myocyte relaxation and highlight a direct contribution of the myofilaments in modulating the dynamics of myocardial performance.
TEN-YEAR FOLLOW-UP STUDY OF ISLET-CELL ANTIBODIES AND CHILDHOOD DIABETES MELLITUS
Authors: G.J. Bruining, D.E. Grobbee, G.J. Scheffer, A.M. De Bruyn, J.L. Molenaar, A. Hofman, H.A. Bruining, H.A. Valkenburg
Journal: The Lancet (1989)
Clinical Lecture on a Case of Chronic Cerebral Meningitis: Chronic Abscess of Brain: Limited Peritonitis: Obstruction of the Portal and Splenic Veins: And Acute Cerebro-Spinal Meningitis
Authors: A. H. Bennett
Journal: BMJ (1882)

TiE subject was M. M., aged 37, of no occupation.The father of the patient, who was otherwise a healthy man, was said to have had several attacks of temporary paralysis affecting the right leg and both arms.These seizures came on suddenly, and their effects lasted from a few days -to several months.Otherwise, the family history was healthy.The patient himself, a gentleman of large property, appeared to have enjoyed perfectly robust general health all his life till the present illness.He was born in Australia, and remained there till a few years ago, engaged in active and healthy pursuits.Since his resi- dence in England, he had passed his time in country and outdoor occupations, and had always been noted for his activity and strength, as well as for intellectual acumen.At the age of fifteen, on awaking one morning, the patient discovered weakness in one of his arms; this soon passed away.Since then, he had been liable to attacks of a similar nature.Being in his usual good health at night, next morning he would find one or more of his limbs on the left side weak.This paresis lasted from a few days to some weeks, and on one occasion as long as six months.The paralysis was not complete; and, when it affected the leg, did not prevent the patient from walking, but only caused him to be lame and drag the toes along the ground.When the arm was attacked, it was weak; and there was numbness, especially on the ulnar side.In the intervals between these seizures, he was perfectly well, and there was no trace of impaired motion.Even when the paresis was present, he could, as a rule, take a great amount of exercise; but on several occasions, when it was severe, he was com- pletely laic up.He had never had syphilis or or any other cerebral symptoms, and was not aware of having had " fits" or attacks of any kind.About the middle of September i88o, the patient, being inI his usual
Phase II Trial of Gefitinib in Recurrent Glioblastoma
Authors: Jeremy N. Rich, David A. Reardon, Terry Peery, Jeannette M. Dowell, Jennifer A. Quinn, Kara L. Penne, Carol J. Wikstrand, Lauren B. Van Duyn, Janet E. Dancey, Roger E. McLendon, James C. Kao, Timothy T. Stenzel, B.K. Ahmed Rasheed, Sandra E. Tourt-Uhlig, James E. Herndon, James J. Vredenburgh, John H. Sampson, Allan H. Friedman, Darell D. Bigner, Henry S. Friedman
Journal: Journal of Clinical Oncology (2003)

To evaluate the efficacy and tolerability of gefitinib (ZD1839, Iressa; AstraZeneca, Wilmington, DE), a novel epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma.This was an open-label, single-center phase II trial. Fifty-seven patients with first recurrence of a glioblastoma who were previously treated with surgical resection, radiation, and usually chemotherapy underwent an open biopsy or resection at evaluation for confirmation of tumor recurrence. Each patient initially received 500 mg of gefitinib orally once daily; dose escalation to 750 mg then 1,000 mg, if a patient received enzyme-inducing antiepileptic drugs or dexamethasone, was allowed within each patient.Although no objective tumor responses were seen among the 53 assessable patients, only 21% of patients (11 of 53 patients) had measurable disease at treatment initiation. Seventeen percent of patients (nine of 53 patients) underwent at least six 4-week cycles, and the 6-month event-free survival (EFS) was 13% (seven of 53 patients). The median EFS time was 8.1 weeks, and the median overall survival (OS) time from treatment initiation was 39.4 weeks. Adverse events were generally mild (grade 1 or 2) and consisted mainly of skin reactions and diarrhea. Drug-related toxicities were more frequent at higher doses. Withdrawal caused by drug-related adverse events occurred in 6% of patients (three of 53 patients). Although the presence of diarrhea positively predicted favorable OS from treatment initiation, epidermal growth factor receptor expression did not correlate with either EFS or OS.Gefitinib is well tolerated and has activity in patients with recurrent glioblastoma. Further study of this agent at higher doses is warranted.
Revision of BTS guidelines for treatment of asthma
Authors: G. Strube
Journal: Thorax (2003)

Revision of BTS guidelines for treatment of asthmaThe paper by Ward et al 1 confirms the findings of Laitinen et al 2 showing that airways inflammation is present even in patients with mild asthma.This emphasises the importance of using anti-inflammatory drugs (steroids) as soon as the diagnosis of asthma has been confirmed, even in patients thought to have only "mild asthma".Without antiinflammatory treatment, symptoms resulting from bronchial hyperresponsiveness are never controlled and optimal lung function is never attained.Over time, structural changes (remodelling) occur leading to a progressive decline in lung function 3 and the risk of fixed obstruction (chronic obstructive pulmonary disease).The present widespread dependence on bronchodilators in the UK may contribute to the fact that we have one of the highest respiratory death rates in Europe. 4The use of bronchodilators alone as in step 1 of the BTS guidelines should be discouraged, and treatment started at step 2 with regular inhaled corticosteroids to control symptoms and maximise peak flow rate.Bronchodilators should be used only as necessary for breakthrough wheezing.These principles have been used in Finland since 1994 with remarkable success in treating asthma. 5 The new BTS guidelines would do well to follow their example.
Is Pesticide Use Related to Parkinson Disease? Some Clues to Heterogeneity in Study Results
Authors: Marianne van der Mark, Maartje Brouwer, Hans Kromhout, Peter Nijssen, Anke Huss, Roel Vermeulen
Journal: Environmental Health Perspectives (2011)

Previous systematic reviews have indicated that pesticide exposure is possibly associated with Parkinson disease (PD). However, considerable heterogeneity has been observed in study results.We aimed at providing an update of the literature published on PD and exposure to pesticides by performing a systematic review and meta-analysis. In addition, we investigated whether methodological differences between studies could explain the heterogeneity in study results.We identified studies through a systematic literature search. We calculated summary risk ratios (sRRs) for pesticide exposure and subcategories using random effects meta-analyses and investigated sources of heterogeneity by meta-regression and stratified analyses.Thirty-nine case-control studies, four cohort studies, and three cross-sectional studies were identified. An sRR of 1.62 [95% confidence interval (CI): 1.40, 1.88] for pesticide exposure (ever vs. never) was found. Summary estimates for subclasses of pesticides indicated a positive association with herbicides and insecticides, but not with fungicides. Heterogeneity in individual study results was not related to study design, source of control population, adjustment of results for potential confounders, or geographical area. However, results were suggestive for heterogeneity related to differences in the exposure assessment. Job title-based exposure assignment resulted in a higher sRR (2.5; 95% CI: 1.5, 4.1) than did assignment based on self-reported exposure (e.g., for self-reported ever/never exposure, sRR = 1.5; 95% CI: 1.3, 1.8).This review affirms the evidence that exposure to herbicides and insecticides increase the risk of PD. Future studies should focus on more objective and improved methods of pesticide exposure assessment.
Social consequences. The public health implications of the 1995 'pill scare'
Authors: A Furedi
Journal: Human Reproduction Update (1999)

The warning issued by the UK Committee on Safety Medicines in October 1995, followed by their 'Dear Doctor' letter of October 18, 1995, that oral contraceptive pills containing gestodene or desogestrel were associated with a higher risk of venous thromboembolism has had a negative impact on public heath. A significant number of women either switched brands or ceased contraception altogether following the announcement. National data suggest a strong association between the pill scare and a substantial increase in the number of unintended pregnancies, particularly significant among younger women, with use of oral contraception falling from 40 to 27% of under 16s between 1995-1996 and 1996-1997. The resulting cost of the increase in births and abortions to the National Health Service has been estimated at about Pound Sterling 21 million for maternity care and from Pound Sterling 46 million for abortion provision. The level of risk should, in future, be more carefully assessed and advice more carefully presented in the interests of public health.
The illusion of repressed memory
Authors: George A. Bonanno
Journal: Behavioral and Brain Sciences (2006)

Erdelyi's unified theory includes the idea that traumatic memories can be unconsciously repressed so that they are enduringly inaccessible to deliberate recall. I argue here that clinical evidence for repressed memory is illusory, and illustrate this claim by examining previous studies of putative repressed memories and also recent research on nonverbal behaviors among survivors of childhood sexual abuse.