tbuckley/cabot-search huggingface dataset:
Suggestion for a Cubic Centimetre Measure for Patient's Use
Authors: J. T. Cash
Journal: BMJ (1904)

I__I_______=_a__________The induction of abortion must be considered in those cases which come under the third and fourth divisions of my .classification.The responsibility of such an operation should be a -divided one, and the patient should have the benefit of it before too late, not waiting too leng under the hope that vomiting may suddenly subside, as it sometimes does.Strict antiseptic precautions and anaesthesia are absolutely neces- -sary to ensure a favourable termination.Lloyd Roberts says "in hyperemesis gravidarum he had never regretted the performance of induction."The following is an illustrative Case: CASE VI.I. J., aged 26, belonging to the upper classes, prepossessing in appearance, strong and athletic, and one who prided herself upon being free from women's ordinary ailments, became pregnant for the second time, had persistent vomiting accompanied by great emaciation, which came on in the tenth week; rectal alimentation was not tolerated, so abortion was induced.Recovery, though protracted, was satis- dactory and complete.This was a typical case for operative procedure.Patient could not (have survived if the operation had been longer delayed.The next case I have to record is one of unusual rapidity.CASE VII.M. R., aged 41, cotton operative, was admitted in August last to the Blackburn and East Lancashire Infirmary.Her medical attendant thought there might be intestinal obstruction, but stated she was eight to nine weeks advanced in pregnancy.The vomiting and collapse were very severe, and all the symptoms pointing to pernicious vomiting of pregnancy, abortion was induced.She died from exhaustion pure and simple, verified by post-mortem examination.This was a very rapidly tatal and unfortunate case.CONCLUSIONS.
Intermittent claudication, exercise, and blood rheology.
Authors: E E Ernst, A Matrai
Journal: Circulation (1987)

Forty-two stable patients with claudication were assigned to two groups. Group I (n = 22) was submitted to regular, standardized treadmill exercise for 2 months. During this time the maximal and pain-free walking distances increased significantly (more than 100%). Group II (n = 20) patients did not exercise over the same period of time, and their walking distances remained essentially unchanged. No drugs or other forms of treatment were given in either group. The rheology of blood, as quantified by blood and plasma viscosity, hematocrit, blood filterability, and red cell aggregation, was initially abnormal in patients as compared with matched controls. Blood and plasma viscosity, blood cell filterability, and red cell aggregation normalized significantly in group I, but remained pathologic in group II. The hemorrheologic values of patients after 2 months of exercise did no longer differ significantly from those of healthy controls. The "fluidification" of blood induced by regular exercise was qualitatively and quantitatively similar to that obtainable by hemorrheologically active medications. The results confirm that physical training is clinically effective in patients suffering from claudication. They furthermore suggest that training may be looked on as a form of "hemorrheologic therapy" suitable for increasing the fluidity of blood in patients with ischemic diseases. Part of the benefits of regular exercise in stage II occlusive peripheral arterial disease may result from changes in hemorrheology; further studies are needed to define the mechanism.
Free cholesterol accumulation in hepatic stellate cells: Mechanism of liver fibrosis aggravation in nonalcoholic steatohepatitis in mice
Authors: Kengo Tomita, Toshiaki Teratani, Takahiro Suzuki, Motonori Shimizu, Hirokazu Sato, Kazuyuki Narimatsu, Yoshikiyo Okada, Chie Kurihara, Rie Irie, Hirokazu Yokoyama, Katsuyoshi Shimamura, Shingo Usui, Hirotoshi Ebinuma, Hidetsugu Saito, Chikako Watanabe, Shunsuke Komoto, Atsushi Kawaguchi, Shigeaki Nagao, Kazuo Sugiyama, Ryota Hokari, Takanori Kanai, Soichiro Miura, Toshifumi Hibi
Journal: Hepatology (2013)

Although nonalcoholic steatohepatitis (NASH) is associated with hypercholesterolemia, the underlying mechanisms of this association have not been clarified. We aimed to elucidate the precise role of cholesterol in the pathophysiology of NASH. C57BL/6 mice were fed a control, high-cholesterol (HC), methionine-choline-deficient (MCD), or MCD+HC diet for 12 weeks or a control, HC, high-fat (HF), or HF+HC diet for 24 weeks. Increased cholesterol intake accelerated liver fibrosis in both the mouse models without affecting the degree of hepatocellular injury or Kupffer cell activation. The major causes of the accelerated liver fibrosis involved free cholesterol (FC) accumulation in hepatic stellate cells (HSCs), which increased Toll-like receptor 4 protein (TLR4) levels through suppression of the endosomal-lysosomal degradation pathway of TLR4, and thereby sensitized the cells to transforming growth factor (TGF)β-induced activation by down-regulating the expression of bone morphogenetic protein and activin membrane-bound inhibitor. Mammalian-cell cholesterol levels are regulated by way of a feedback mechanism mediated by sterol regulatory element-binding protein 2 (SREBP2), maintaining cellular cholesterol homeostasis. Nevertheless, HSCs were sensitive to FC accumulation because the high intracellular expression ratio of SREBP cleavage-activating protein (Scap) to insulin-induced gene (Insig) disrupted the SREBP2-mediated feedback regulation of cholesterol homeostasis in these cells. HSC activation subsequently enhanced the disruption of the feedback system by Insig-1 down-regulation. In addition, the suppression of peroxisome proliferator-activated receptor γ signaling accompanying HSC activation enhanced both SREBP2 and microRNA-33a signaling. Consequently, FC accumulation in HSCs increased and further sensitized these cells to TGFβ-induced activation in a vicious cycle, leading to exaggerated liver fibrosis in NASH.These characteristic mechanisms of FC accumulation in HSCs are potential targets to treat liver fibrosis in liver diseases including NASH.
Flow Cytometric Analysis of Doxorubicin Accumulation in Cells From Human and Rodent Cell Lines
Authors: C. K. Luk, I. F. Tannock
Journal: JNCI Journal of the National Cancer Institute (1989)

The correlation between intracellular accumulation of doxorubicin (DOX) and drug cytotoxicity was studied in cells from seven cell lines of rodent and human origin. We used three Chinese hamster ovary cell lines (AuxB1, CHRC5, and UV20), two murine tumor cell lines (KHT-LP1 and EMT6/Ro), and two human tumor cell lines (MGH-U1 and DLD-1). Intracellular DOX was measured by its fluorescence intensity with flow cytometry, and drug cytotoxicity was quantified with clonogenic assays. When data for all of the cell lines were combined, cell killing was correlated with the intracellular concentration of DOX (r = -.88). For the cell line AuxB1 and its DOX-resistant subline CHRC5, in which cells express high levels of P-glycoprotein, the relationship between cell survival and the intracellular concentration of DOX was stronger than that for the other cell lines. These results suggest that differences in intracellular accumulation of DOX account for much of the heterogeneity in response to the drug in cells from different cell lines, although additional mechanisms also contribute to variation in drug sensitivity. Flow cytometric analysis of intracellular DOX fluorescence is a simple assay that should be tested in cells from human tumors as a possible predictor of tumor response. For a given cell line, this technique also provides a rapid way to monitor the development of drug resistance after multiple courses of chemotherapy. [J Natl Cancer Inst 1989;81:55–59]
Wait-and-see policy or laparoscopic cholecystectomy after endoscopic sphincterotomy for bile-duct stones: a randomised trial
Authors: Djemila Boerma, Erik AJ Rauws, Yolande CA Keulemans, Ignace MC Janssen, Clemens JM Bolwerk, Ron Timmer, Egge J Boerma, Huug Obertop, Kees Huibregtse, Dirk J Gouma
Journal: The Lancet (2002)
A 52-Week Placebo-Controlled Trial of Evolocumab in Hyperlipidemia
Authors: Dirk J. Blom, Tomas Hala, Michael Bolognese, Michael J. Lillestol, Phillip D. Toth, Lesley Burgess, Richard Ceska, Eli Roth, Michael J. Koren, Christie M. Ballantyne, Maria Laura Monsalvo, Kate Tsirtsonis, Jae B. Kim, Rob Scott, Scott M. Wasserman, Evan A. Stein
Journal: New England Journal of Medicine (2014)

Evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly reduced low-density lipoprotein (LDL) cholesterol levels in phase 2 studies. We conducted a phase 3 trial to evaluate the safety and efficacy of 52 weeks of treatment with evolocumab.We stratified patients with hyperlipidemia according to the risk categories outlined by the Adult Treatment Panel III of the National Cholesterol Education Program. On the basis of this classification, patients were started on background lipid-lowering therapy with diet alone or diet plus atorvastatin at a dose of 10 mg daily, atorvastatin at a dose of 80 mg daily, or atorvastatin at a dose of 80 mg daily plus ezetimibe at a dose of 10 mg daily, for a run-in period of 4 to 12 weeks. Patients with an LDL cholesterol level of 75 mg per deciliter (1.9 mmol per liter) or higher were then randomly assigned in a 2:1 ratio to receive either evolocumab (420 mg) or placebo every 4 weeks. The primary end point was the percent change from baseline in LDL cholesterol, as measured by means of ultracentrifugation, at week 52.Among the 901 patients included in the primary analysis, the overall least-squares mean (±SE) reduction in LDL cholesterol from baseline in the evolocumab group, taking into account the change in the placebo group, was 57.0±2.1% (P<0.001). The mean reduction was 55.7±4.2% among patients who underwent background therapy with diet alone, 61.6±2.6% among those who received 10 mg of atorvastatin, 56.8±5.3% among those who received 80 mg of atorvastatin, and 48.5±5.2% among those who received a combination of 80 mg of atorvastatin and 10 mg of ezetimibe (P<0.001 for all comparisons). Evolocumab treatment also significantly reduced levels of apolipoprotein B, non-high-density lipoprotein cholesterol, lipoprotein(a), and triglycerides. The most common adverse events were nasopharyngitis, upper respiratory tract infection, influenza, and back pain.At 52 weeks, evolocumab added to diet alone, to low-dose atorvastatin, or to high-dose atorvastatin with or without ezetimibe significantly reduced LDL cholesterol levels in patients with a range of cardiovascular risks. (Funded by Amgen; DESCARTES ClinicalTrials.gov number, NCT01516879.).
Prevalence, Detection, Evaluation and Management of Chronic Kidney Disease
Authors: P. Ackland
Journal: BMJ (2014)

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Host Factors and Cancer Outcome
Authors: Pamela J. Goodwin, Jeffrey A. Meyerhardt, Stephen D. Hursting
Journal: Journal of Clinical Oncology (2010)

It has long been recognized that host factors and exposures play important roles in cancer etiology. However, with the exception of sex hormone–sensitive cancers (such as breast and prostate cancers), there has been less appreciation of the potential these factors have to influence the clinical course of cancer. Ongoing research in both basic and clinical areas has provided increasingly convincing evidence that these host-related factors may be critical determinants of prognosis and treatment efficacy in patients with established cancer. Our goal in this issue ofJournalofClinicalOncology is to update readers with current evidence that links host factors to cancer outcomes, to encourage additional research designed to understand the mechanisms of host-tumor interactions, and to identify areas where sufficient evidence exists that clinical intervention or intervention research is warranted. The authors of the 11 articles included in this issue 1-11 address a variety of types of host-tumor interactions—including tumor-stroma, tumor-marrow or tumor–immune system, tumor-endocrine, tumorgermline, and germline-treatment interactions—providing evidence of their potential roles in human cancer. The relative importance of these interactions appears to vary both across and within tumor types, and some interactions are better characterized than others. In some areas, evidence in established cancer is nascent, and the authors extrapolate from evidence related to cancer risk. 4,9 A few interactions have immediate clinical implications, and the clinical relevance of many other factors is expected to grow as new data become available. For example, the observation that never-smokers with non–small-cell lung cancer have a significantly greater likelihood of benefit from epidermal growth factor receptor tyrosine kinase inhibitors (eg, erlotinib or gefitinib) 12 has had clinical practice– changing implications
Epidemiology of hepatitis E virus infection in Turkey
Authors: D.L. Thomas, T.C. Quinn, R.W. Mahley, K.E. Palaoglu, S. Badur
Journal: The Lancet (1993)

The seroprevalence and risk factors for infection with hepatitis E virus (HEV) were analysed in five regions of Turkey, where one-third of acute hepatitis cases are non-A, non-B. Antibodies to HEV (anti-HEV) were found in 80 (5.9%) of 1350 subjects. Independent predictors of anti-HEV were age over 25 years, less than elementary education, antibodies to hepatitis C virus, and residence in the warmest region (Adana). Whereas none of 105 subjects in the second decade of life were HEV seropositive, 17 (3.7%) of 464 and 28 (9.1%) of 308 of those in the third and fourth decades of life, respectively, had anti-HEV (p < 0.001). These data demonstrate that in Turkey HEV is more prevalent in warmer regions and in adults, beginning in the third decade of life.
Skills Training Versus Psychosocial Occupational Therapy for Persons With Persistent Schizophrenia
Authors: Robert Paul Liberman, Charles J. Wallace, Gayla Blackwell, Alex Kopelowicz, Jerome V. Vaccaro, Jim Mintz
Journal: American Journal of Psychiatry (1998)

The authors compared the community functioning of outpatients with persistent forms of schizophrenia after treatment with psychosocial occupational therapy or social skills training, with the latter conducted by paraprofessionals.Eighty outpatients with persistent forms of schizophrenia were randomly assigned to receive either psychosocial occupational therapy or skills training for 12 hours weekly for 6 months, followed by 18 months of follow-up with case management in the community. Antipsychotic medication was prescribed through "doctor's choice" by psychiatrists who were blind to the psychosocial treatment assignments.Patients who received skills training showed significantly greater independent living skills during a 2-year follow-up of everyday community functioning.Skills training can be effectively conducted by paraprofessionals, with durability and generalization of the skills greater than that achieved by occupational therapists who provide their patients with psychosocial occupational therapy.
ALCOHOLISM A DISEASE.
Authors: A. ENFLELD
Journal: JAMA (1892)

The day of medical theories, which do not have established facts to justify them, belongs to the past. It has taken ages of observation and investigation, by the greatest intellects of the profession, to elevate the science of medicine to the high position it now occupies. We live in an age of light and knowledge, an age in which old isms, theories and fallacies, are fast disappearing before the sweeping progress of this century. The past decade has given us the beginning of a new epoch in the science of life. Medical science is now called upon to defend our bodies from the parasites which prey upon us from without, and physiological and chemical research has taught us the therapeutic application of drugs in the cure of dipsomania and kindred diseases. The power of self-regeneration is one of the great distinctive properties belonging to all organized living bodies; but the
Patients in rheumatology clinics need reassurance
Authors: E. Grogan
Journal: BMJ (2000)

The quality of systematic reviews Review is biasedEditor-In discussing meta-analyses in the treatment of asthma, Jadad et al state that most reviews published in peer reviewed journals or funded by industry have serious methodological flaws. 1 This summary is misleading and could have been put more succinctly as, "most reviews published in peer reviewed journals have serious methodological flaws," since the industry reviews in their paper were a (similar) subset of the published papers.Jadad et al are, however, right in drawing attention to the inherent bias in their Cochrane approved quality index.Cochrane reviews are excellent in many respects but grossly deficient in at least one-namely, the reliance on software, Rev-Man, that is incapable of satisfying an essential and elementary requirement placed by drug regulators on sponsors, that "the particular model chosen should reflect the state of medical knowledge about the variables to be analysed as well as the statistical design of the trial." 2 RevMan cannot deal appropriately with covariates nor with multicentre, cluster randomised, minimised, or crossover trials.It is thus a suitable tool for single centre, randomised, parallel group trials in which no covariates are measured: a type of trial that is rather rare in my experience.On the other hand, the pharmaceutical industry has long employed doctors and statisticians capable of dealing with the complications of real clinical trials.For a good illustration, see the paper by Richardson and Bablok, 3 which Jadad et al did not include.The biased and one sided review by Jadad et al cannot be taken as showing the superiority of Cochrane reviews to pharmaceutical industry reviews.
Why excessive sleepiness may persist in OSA patients receiving adequate CPAP treatment
Authors: C. Vernet, S. Redolfi, V. Attali, E. Konofal, A. Brion, E. Frija-Orvoen, M. Pottier, T. Similowski, I. Arnulf
Journal: European Respiratory Journal (2011)

From the authors:

P. Castiglioni and co-workers suggest that residual excessive sleepiness (RES) in patients with obstructive sleep apnoea (OSA) who are adequately treated with nasal positive airway pressure may be caused by a concomitant, untreated hypercapnia (if OSA overlaps with obesity hypoventilation syndrome or with chronic obstructive pulmonary disease) or by persistent autonomic subcortical arousals. We examined with interest both hypotheses, but neither fits our series [1]. Concomitant chronic obstructive pulmonary disease was a criterion for exclusion (as was any medical disease that could cause sleepiness per se ), after …
Tumor Cell Gene Expression Changes Following Short-term <i>In vivo</i> Exposure to Single Agent Chemotherapeutics are Related to Survival in Multiple Myeloma
Authors: Bart Burington, Bart Barlogie, Fenghuang Zhan, John Crowley, John D. Shaughnessy
Journal: Clinical Cancer Research (2008)

Abstract Changes in global gene expression patterns in tumor cells following in vivo therapy may vary by treatment and provide added or synergistic prognostic power over pretherapy gene expression profiles (GEP). This molecular readout of drug-cell interaction may also point to mechanisms of action/resistance. In newly diagnosed patients with multiple myeloma (MM), microarray data were obtained on tumor cells prior to and 48 hours after in vivo treatment using dexamethasone (n = 45) or thalidomide (n = 42); in the case of relapsed MM, microarray data were obtained prior to (n = 36) and after (n = 19) lenalidomide administration. Dexamethasone and thalidomide induced both common and unique GEP changes in tumor cells. Combined baseline and 48-hour changes in GEP in a subset of genes, many related to oxidative stress and cytoskeletal dynamics, were predictive of outcome in newly diagnosed MM patients receiving tandem transplants. Thalidomide-altered genes also changed following lenalidomide exposure and predicted event-free and overall survival in relapsed patients receiving lenalidomide as a single agent. Combined with baseline molecular features, changes in GEP following short-term single-agent exposure may help guide treatment decisions for patients with MM. Genes whose drug-altered expression were found to be related to survival may point to molecular switches related to response and/or resistance to different classes of drugs.
Gene Expression Profiles Associated with Treatment Response in Oligodendrogliomas
Authors: Pim J. French, Sigrid M.A. Swagemakers, Jord H.A. Nagel, Mathilde C.M. Kouwenhoven, Eric Brouwer, Peter van der Spek, Theo M. Luider, Johan M. Kros, Martin J. van den Bent, Peter A. Sillevis Smitt
Journal: Cancer Research (2005)

Abstract Oligodendrogliomas are a specific subtype of brain tumor of which the majority responds favorably to chemotherapy. In this study, we made use of expression profiling to identify chemosensitive oligodendroglial tumors. Correlation of expression profiles to loss of heterozygosity on 1p and 19q, common chromosomal aberrations associated with response to treatment, identified 376, 64, and 60 differentially expressed probe sets associated with loss of 1p, 19q or 1p, and 19q, respectively. Correlation of expression profiles to the tumors' response to treatment identified 16 differentially expressed probe sets. Because transcripts associated with chemotherapeutic response were identified independent of common chromosomal aberrations, expression profiling may be used as an alternative approach to the tumors' 1p status to identify chemosensitive oligodendroglial tumors. Finally, we correlated expression profiles to survival of the patient after diagnosis and identified 103 differentially expressed probe sets. The observation that many genes are differentially expressed between long and short survivors indicates that the genetic background of the tumor is an important factor in determining the prognosis of the patient. Furthermore, these transcripts can help identify patient subgroups that are associated with favorable prognosis. Our study is the first to correlate gene expression with chromosomal aberrations and clinical performance (response to treatment and survival) in oligodendrogliomas. The differentially expressed transcripts can help identify patient subgroups with good prognosis and those that will benefit from chemotherapeutic treatments. (Cancer Res 2005; 65(24): 11335-44)