tbuckley/cabot-search huggingface dataset:
Chemical Disinfection of Creutzfeldt–Jakob Disease Virus
Authors: Paul Brown, Clarence J. Gibbs, Herbert L. Amyx, David T. Kingsbury, Robert G. Rohwer, Michael P. Sulima, D. Carleton Gajdusek
Journal: New England Journal of Medicine (1982)

RECOMMENDATIONS for the disinfection of virus-contaminated tissues from patients with Creutzfeldt–Jakob disease (CJD), published five years ago in the Journal, 1 relied heavily on data from experiments using mouse-adapted scrapie virus — at that time a more conveniently studied member of the same group of spongiform encephalopathy viruses. We have now accumulated sufficient data on guinea-pig and mouse-adapted viral isolates from two patients with CJD to be able to present current recommendations based on studies of the CJD virus itself. Autoclaving for one hour at a temperature of at least 121°C (15 psi) remains the method of choice for the sterilization . . .
Fatal Adult Respiratory Distress Syndrome in a Patient With Lyme Disease
Authors: Michael Kirsch
Journal: JAMA (1988)

A dry cough, fever, generalized maculopapular rash, and myositis developed in a 67-year-old woman; she also had markedly abnormal liver function test results. Serologic tests proved that she had an infection of recent onset with Borrelia burgdorferi, the agent that causes Lyme disease. During a two-month course of illness, her condition remained refractory to treatment with antibiotics, salicylates, and steroids. Ultimately, fatal adult respiratory distress syndrome developed; this was believed to be secondary to Lyme disease.
On the Origin of Cancer
Authors: W. Cramer
Journal: BMJ (1938)

Why does a patient get cancer?That is a question which summarizes the problem of cancer and which must have often occurred to you when a patient presents himself or herself, apparently in good health except for some obscure and not necessarily painful symptoms, and on examination a malignant growth is found, sometimes in an early stage but possibly already in an advanced stage, although the patient may have presented himself as soon as he noticed that something was wrong.It is this insidious onset of cancer-striking a patient like a bolt from the blue-which has given the disease the air of a grim mystery. Interpretation of Age IncidenceIf I were asked in what respect the experimental investi- gation of cancer of the last fifteen years has most pro- foundly altered our outlook on the cancer problem, I would say it lies in the correct interpretation of the age incidence.The frequency of cancer increases with in- creasing rapidity as age advances.This can be readily seen from the following table, which gives the mortality rate per million people from cancer of all sites in decennial age groups in England and Wales: Age Groups: 0-15-25-35-45- 55-65-75-
Recurrent localised pneumonia due to bronchial infiltration in a patient with chronic lymphocytic leukaemia.
Authors: A Desjardins, G Ostiguy, S Cousineau, M Gyger
Journal: Thorax (1990)

A woman with chronic lymphocytic leukaemia developed pneumonia on five occasions in the right middle lobe in the course of 27 months. Bronchoscopy disclosed concentric narrowing of the middle lobe bronchus by leukaemic infiltration.
Krox20/EGR2 deficiency accelerates cell growth and differentiation in the monocytic lineage and decreases bone mass
Authors: Yankel Gabet, Sanjeev K. Baniwal, Nathalie Leclerc, Yunfan Shi, Alice E. Kohn-Gabet, Jon Cogan, Alexis Dixon, Marilyn Bachar, Lixin Guo, Jack E. Turman, Baruch Frenkel
Journal: Blood (2010)
987. Foamy Virus Vectors That Block HIV Infection
Authors: Jason Taylor, Ingrid Bahner, Lucia Vojtech, Erik Olson, James Allen, Dorothee von Laer, Donald B. Kohn, David W. Russell, Robert E. Richard
Journal: Molecular Therapy (2005)

Foamy virus (FV) vectors have been demonstrated to transduce human hematopoietic stem cells with a high frequency. We have developed FV vectors that can block HIV infection with the intention of developing a therapeutic vector. Additional features of FV vectors that support their use in clinical gene therapy include: a) no evidence of disease from the prototypic FV in infected humans and in non-human primates, b) reduced recombination potential with HIV in infected patients, c) FV vectors are self-inactivating vectors, and d) relative to lentivirus vectors, FV vector production does not share molecular pathways with HIV.
Differences in lipopolysaccharide- and lipoteichoic acid-induced cytokine/chemokine expression
Authors: Simon J. Finney, Susannah K. Leaver, Timothy W. Evans, Anne Burke-Gaffney
Journal: Intensive Care Medicine (2011)

To investigate differences in cytokine/chemokine release in response to lipoteichoic acid (LTA) or lipopolysaccharide (LPS) and contributing cellular mechanisms, in order to improve understanding of the pathogenesis of sepsis.Levels of cytokines/chemokines were measured in plasma and peritoneal lavage fluid of 10-week-old male mice (C57/B16) following intraperitoneal injection of LTA or LPS (250 µg), and in supernatants of murine J774.2 cells, immortalised blood monocytes, or isolated human monocytes treated with LTA or LPS (0-10 µg/ml). The role of cytokine/chemokine messenger RNA (mRNA) stability versus nuclear factor-kappaB (NF-κB) and activator protein-1 (AP-1) in mediating cytokine/chemokine release in J774 cells was also assessed.In mice, plasma levels of keratinocyte-derived chemokine (KC), macrophage inflammatory protein (MIP)-2, interleukin (IL)-10, interferon (IFN)-γ and tumour necrosis factor-alpha (TNF-α) and peritoneal lavage fluid levels of KC, MIP-2 and TNF-α increased significantly 1 h after LPS. Only KC and MIP-2 levels increased 1 h after LTA. LPS-treated (10 μg/ml) J774 cells released MIP-2, IL-10, IFN-γ and TNF-α but not KC (24 h), whereas cells treated with 10 μg/ml LTA released only MIP-2. LPS-stimulated human monocytes released IL-10 and IL-8 (24 h); by contrast, LTA-treated cells released only IL-8. LPS and LTA activated NF-κB and AP-1 in J774 cells. The protein synthesis inhibitor cycloheximide abolished LPS-induced IL-10 mRNA expression and increased LTA- and LPS-induced mRNA for MIP-2 in J774 cells.LTA and LPS, at clinically relevant concentrations, induced differential cytokine/chemokine release in vitro and in vivo, via effects distal to activation of NF-κB/AP-1 that might include chromatin remodelling or mRNA stability.
Nephropathy associated with the diffuse infiltrative lymphocytosis syndrome
Authors: L. Zafrani, P. Coppo, S. Dettwiler, V. Molinier-Frenkel, F. Agbalika, J.-B. Guiard-Schmid, G. Pialoux, Y.-C. Xu-Dubois, E. Rondeau, A. Hertig
Journal: Kidney International (2007)
American Society of Hematology/American Society of Clinical Oncology clinical practice guideline update on the use of epoetin and darbepoetin in adult patients with cancer
Authors: J. Douglas Rizzo, Melissa Brouwers, Patricia Hurley, Jerome Seidenfeld, Murat O. Arcasoy, Jerry L. Spivak, Charles L. Bennett, Julia Bohlius, Darren Evanchuk, Matthew J. Goode, Ann A. Jakubowski, David H. Regan, Mark R. Somerfield
Journal: Blood (2010)

To update American Society of Hematology/American Society of Clinical Oncology recommendations for use of erythropoiesis-stimulating agents (ESAs) in patients with cancer.An Update Committee reviewed data published between January 2007 and January 2010. MEDLINE and the Cochrane Library were searched.The literature search yielded one new individual patient data analysis and four literature-based meta-analyses, two systematic reviews, and 13 publications reporting new results from randomized controlled trials not included in prior or new reviews.For patients undergoing myelosuppressive chemotherapy who have a hemoglobin (Hb) level less than 10 g/dL, the Update Committee recommends that clinicians discuss potential harms (eg, thromboembolism, shorter survival) and benefits (eg, decreased transfusions) of ESAs and compare these with potential harms (eg, serious infections, immune-mediated adverse reactions) and benefits (eg, rapid Hb improvement) of RBC transfusions. Individual preferences for assumed risk should contribute to shared decisions on managing chemotherapy-induced anemia. The Committee cautions against ESA use under other circumstances. If used, ESAs should be administered at the lowest dose possible and should increase Hb to the lowest concentration possible to avoid transfusions. Available evidence does not identify Hb levels ≥ 10 g/dL either as thresholds for initiating treatment or as targets for ESA therapy. Starting doses and dose modifications after response or nonresponse should follow US Food and Drug Administration-approved labeling. ESAs should be discontinued after 6 to 8 weeks in nonresponders. ESAs should be avoided in patients with cancer not receiving concurrent chemotherapy, except for those with lower risk myelodysplastic syndromes. Caution should be exercised when using ESAs with chemotherapeutic agents in diseases associated with increased risk of thromboembolic complications. Table 1 lists detailed recommendations.
Preconditioning causes improved wall motion as well as smaller infarcts after transient coronary occlusion in rabbits.
Authors: M V Cohen, G S Liu, J M Downey
Journal: Circulation (1991)

A brief coronary occlusion before a more prolonged occlusion results in less myocardial infarction than the longer occlusion alone. However, the effects of this preconditioning on recovery of systolic function after coronary occlusion have not been determined.Ultrasonic crystals implanted in rabbit myocardium measured segment length in the distribution of a branch of the left coronary artery that was fitted with a snare occluder. Rabbits were randomly allocated to either nonpreconditioned or preconditioned groups. Rabbits in the latter group underwent preconditioning with a 5-minute coronary occlusion followed by 10 minutes of reperfusion. Then the coronary artery was occluded for 20 minutes in all rabbits, after which it was allowed to reperfuse for 90 minutes. The hearts were then excised, and infarct size was measured by staining with triphenyltetrazolium chloride. During coronary occlusion, all hearts except one demonstrated either akinesis or paradoxical bulging. Five minutes after release of the 20-minute occlusion, active shortening had returned in the preconditioned rabbits and averaged 27.9 +/- 16.6% of baseline shortening. At the same time, paradoxical lengthening persisted in nonpreconditioned rabbits (-15.5 +/- 19.8% of baseline). By the end of the 90-minute reperfusion period, segment shortening averaged 40.1 +/- 8.4% of baseline in preconditioned rabbits and only 6.2 +/- 12.0% in nonpreconditioned rabbits (p less than 0.05). Infarct size as a percentage of risk area was significantly smaller in preconditioned rabbits as well (3.0 +/- 1.6% versus 28.8 +/- 7.0%, p less than 0.002) and likely accounted for the improved shortening.We conclude that a brief coronary occlusion before a more prolonged occlusion results in not only reduced infarct size but also significantly better recovery of systolic function.
Response of chronic constipation symptoms to prucalopride treatment and relationship with patient satisfaction
Authors: R. Kerstens, L. Vandeplassche, D. Dubois, L. Wouters
Journal: Gut (2011)

<h3>Introduction</h3> Prucalopride (PRU) is a selective 5-HT<sub>4</sub> agonist, effective and approved in EU for treatment of chronic constipation (CC) in females in whom laxatives do not provide adequate relief. The aim of this study was to assess the meaningfulness of changes in constipation symptoms and patient satisfaction after 4 weeks of treatment with placebo, PRU 2 mg or 4 mg. In addition, the relationships between changes in symptom scores and patient satisfaction were explored. <h3>Methods</h3> Symptoms of CC were assessed in 1552 female subjects of 3 identical pivotal trials. Subjects were selected if treated for at least 21 days and with data at baseline (BL) and 4 weeks of treatment. Symptom severity was evaluated by the Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire, a 12-item self-report instrument with abdominal (4 items), rectal (3 items) and stool (5 items) symptom subscales. Patient satisfaction with bowel habit and treatment was evaluated by the 5-item subscale of the Patient Assessment of Constipation Quality of Life questionnaire (PAC-QOL). The meaningfulness of changes in the PAC-SYM items and patient satisfaction was assessed by the effect size (ES), that is, mean change from BL divided by the SD of the BL value. The relationship between changes after treatment with PRU in PAC-SYM items and patient satisfaction was evaluated using partial least squares path modelling (PLSPM). <h3>Results</h3> At BL the mean symptom severity score was ‘moderate’ for abdominal symptoms, ‘severe’ for stool symptoms and ‘mild’ for rectal symptoms. Treatment with PRU 2–4 mg resulted in a substantial relief of all symptoms with ES varying from moderate (ES: 0.5–0.8) to large (ES&gt;0.8) and with the largest ES for the abdominal bloating and discomfort symptoms for both doses of PRU. Analysis of the 3 subscales showed that the ES of PRU were large (&gt;0.8) for both the abdominal and stool symptoms. Comparison between placebo and PRU of the cumulative distributions of the changes from baseline showed that PRU provides a consistent benefit among patients. PRU treatment also resulted in large ES of patient satisfaction, with regularity of bowel movement frequency as the most responsive item. PLSPM showed that improvement in patient satisfaction can largely be attributed to relief of abdominal and stool related symptoms (r=0.6). <h3>Conclusion</h3> Prucalopride is highly effective in relief of abdominal and stool related symptoms. Relief of these symptoms is associated with a substantial improvement in patient satisfaction with bowel habit and treatment.
Metobolic Imaging of Brain Tumors
Authors: FCL Wong, E E Kim, M Korkmaz, W H Wong, K Hicks, R Tilbury, A Yung, W Tansey, T P Haynie
Journal: Clinical Nuclear Medicine (1993)

Wong, FCL; Kim, E E; Korkmaz, M; Wong, W H; Hicks, K; Tilbury, R; Yung, A; Tansey, W; Haynie, T PAuthor Information
British Poliomyelitis Vaccine
Authors: W. L. M. Perry
Journal: BMJ (1956)

MEDICAL JOURLNALwrite the instructions down so that there can be no doubt about what should be done and what must be avoided.The diet should be normal, but very hot or cold things omitted." A nice hot cup of tea," hot soup, or ice-cream should not be taken, as by their temperature they may cause reflex uterine contraction from overactive peristalsis.Luke- warm should be the order ot the day.Apart from liquid paraffin, say 2 dr.(7 ml.) twice a day, no aperient of any kind should be given, and above all no enemas; it does not matter if the patient's bowels do not open for a week or even longer, provided she is not un- comfortable.The overenthusiastic nurse, by the giving of an enema, may cause a threatened to become an inevitable abortion.It cannot be too strongly stressed that the patient mulist not go to the ordinary lavatory; a bed-pan or chamber must always be used, and if any blood, clot, or other abnormal product be passed then this must be saved for medical inspection.All soiled pads, bed-linen, clothing, etc., must be similarly saved and not thrown away.Unless these rules are obeyed it is impossible for the doctor in charge of the case to know what is happening to the pregnancy.Vaginal douching must certainly never be performed in cases of threatened abortion, but the removal of any
Delta-like1-induced Notch1 signaling regulates the human plasmacytoid dendritic cell versus T-cell lineage decision through control of GATA-3 and Spi-B
Authors: Wendy Dontje, Remko Schotte, Tom Cupedo, Maho Nagasawa, Ferenc Scheeren, Ramon Gimeno, Hergen Spits, Bianca Blom
Journal: Blood (2005)
Politically correct references
Authors: P. V Scott
Journal: BMJ (2000)

In my day we were not stupid enough to suppose that references were the key to getting a hospital consultant job. They were just one more worry. Given a fair wind at interview we knew perfectly well that telephone calls would long ago have been made, discussions at the 19th hole would have taken place, and the chosen candidate's on-call roster would be into the third draft. We knew, too, that references for the also rans would have been taken up, made available to the advisory appointments committee, and read out, or better still read—all of them—after the interviews but before crunch time.

> References do not seem to mean what they used to mean 

References (and the choice of referees) were important. Without them the appointments committee could rely only on candidates' opinions of themselves from self serving curricula vitae or from self confident interviews. Some doctors who excel at their job do not always excel at interview; a referee can say that. References gave honest …
New twist on the regulation of NKG2D ligand expression
Authors: Adelheid Cerwenka
Journal: The Journal of Experimental Medicine (2009)

The NK cell–activating receptor NKG2D plays a prominent role in antitumor immune responses. Expression of the multiple NKG2D ligands must be tightly controlled to guarantee that NK cells attack tumors but not healthy cells. New data reveal a novel mechanism of posttranslational regulation of the mouse NKG2D ligand MULT1, in which MULT1 is ubiquitinated and degraded in healthy cells. In response to UV stress or heat shock, ubiquitination of MULT1 decreases and cell surface expression increases. Thus, targeting the ubiquitination machinery in cancer cells might increase the susceptibility of tumors to NK cell–mediated killing.
Insulin deficiency exacerbates cerebral amyloidosis and behavioral deficits in an Alzheimer transgenic mouse model
Authors: Xu Wang, Wei Zheng, Jing-Wei Xie, Tao Wang, Si-Ling Wang, Wei-Ping Teng, Zhan-You Wang
Journal: Molecular Neurodegeneration (2010)

Although increasing evidence has indicated that brain insulin dysfunction is a risk factor for Alzheimer disease (AD), the underlying mechanisms by which insulin deficiency may impact the development of AD are still obscure. Using a streptozotocin (STZ)-induced insulin deficient diabetic AD transgenic mouse model, we evaluated the effect of insulin deficiency on AD-like behavior and neuropathology.Our data showed that administration of STZ increased the level of blood glucose and reduced the level of serum insulin, and further decreased the phosphorylation levels of insulin receptors, and increased the activities of glycogen synthase kinase-3α/β and c-Jun N-terminal kinase in the APP/PS1 mouse brain. We further showed that STZ treatment promoted the processing of amyloid-β (Aβ) precursor protein resulting in increased Aβ generation, neuritic plaque formation, and spatial memory deficits in transgenic mice.Our present data indicate that there is a close link between insulin deficient diabetes and cerebral amyloidosis in the pathogenesis of AD.
Comparison of Magnetic Resonance Imaging and Radionuclide Bone Imaging of Vertebral Fractures
Authors: STEPHEN N. WIENER, DONALD R. NEUMANN, MARK S. RZESZOTARSKI
Journal: Clinical Nuclear Medicine (1989)

The following report summarizes the authors' initial experience with detecting and aging vertebral fractures in elderly patients with osteoporosis, emphasizing the use of an inversion recovery sequence with a short time to inversion (STIR) and comparing these results to that achieved using RBI.
Children with obsessive compulsive disorder
Authors: I. Heyman
Journal: BMJ (1997)

Obsessive compulsive disorder in young people is common and under-recognised. Estimated prevalence rates in children and adolescents are about 1%.1 The distress to young people caused by the characteristic intrusive, unwanted, and often unpleasant thoughts or fears is often hidden, as children identify these symptoms as peculiar or embarrassing and keep them secret, sometimes for years. Likewise, compulsive behaviours such as washing or checking are usually perceived as unnecessary and often ridiculous, and children may go to great lengths to conceal them.

The psychopathology is strikingly similar to that seen in the adult disorder, and many adults diagnosed with obsessive compulsive disorder report that their symptoms first began in childhood.2 Parents, teachers, and primary care practitioners, as well as paediatricians and child psychiatrists, may well be familiar with the symptoms, …
Tumorigenicity and genetic profiling of circulating tumor cells in small-cell lung cancer
Authors: Cassandra L Hodgkinson, Christopher J Morrow, Yaoyong Li, Robert L Metcalf, Dominic G Rothwell, Francesca Trapani, Radoslaw Polanski, Deborah J Burt, Kathryn L Simpson, Karen Morris, Stuart D Pepper, Daisuke Nonaka, Alastair Greystoke, Paul Kelly, Becky Bola, Matthew G Krebs, Jenny Antonello, Mahmood Ayub, Suzanne Faulkner, Lynsey Priest, Louise Carter, Catriona Tate, Crispin J Miller, Fiona Blackhall, Ged Brady, Caroline Dive
Journal: Nature Medicine (2014)
Do we need GPs?
Authors: D. Spence
Journal: BMJ (2013)

Everyone is prejudiced; we merely have different prejudices. There are widely held prejudices against general practitioners (GPs). And, like most prejudices, these are unspoken and denied. But the anonymity of online communities means these views come spilling forth. GPs are the failed doctors: the thick, the lazy, and the useless. Forum members have even suggested that all GPs be sacked, with receptionists simply making appointments with hospital specialists. Generalism means less; everyone wants the expert.⇑

So I perennially find myself promoting or defending generalism (depending on your perspective). …
Inhibition of Hsp90 Down-regulates Mutant Epidermal Growth Factor Receptor (EGFR) Expression and Sensitizes EGFR Mutant Tumors to Paclitaxel
Authors: Ayana Sawai, Sarat Chandarlapaty, Heidi Greulich, Mithat Gonen, Qing Ye, Carlos L. Arteaga, William Sellers, Neal Rosen, David B. Solit
Journal: Cancer Research (2008)

Abstract Mutations in the kinase domain of the epidermal growth factor receptor (EGFR) are found in a subset of patients with lung cancer and correlate with response to EGFR tyrosine kinase inhibitors (TKI). Resistance to these agents invariably develops, and current treatment strategies have limited efficacy in this setting. Hsp90 inhibitors, such as 17-allylamino-17-demethoxygeldanamycin (17-AAG), induce the degradation of EGFR and other Hsp90 interacting proteins and may thus have utility in tumors dependent upon sensitive Hsp90 clients. We find that the EGFR mutations found most commonly in patients with lung adenocarcinoma who respond to EGFR TKIs are potently degraded by 17-AAG. Although the expression of wild-type EGFR was also down-regulated by 17-AAG, its degradation required higher concentrations of drug and a longer duration of drug exposure. In animal models, a single dose of 17-AAG was sufficient to induce degradation of mutant EGFR and inhibit downstream signaling. 17-AAG treatment, at its maximal tolerated dose, caused a significant delay in H3255 (L858R EGFR) xenograft growth but was less effective than the EGFR TKI gefitinib. 17-AAG alone delayed, but did not completely inhibit, the growth of H1650 and H1975 xenografts, two EGFR mutant models which show intermediate and high levels of gefitinib resistance. 17-AAG could be safely coadministered with paclitaxel, and the combination was significantly more effective than either drug alone. These data suggest that Hsp90 inhibition in combination with chemotherapy may represent an effective treatment strategy for patients whose tumors express EGFR kinase domain mutations, including those with de novo and acquired resistance to EGFR TKIs. [Cancer Res 2008;68(2):589–96]
Absence of antiphospholipid and anti-endothelial cell antibodies in malignant atrophic papulosis: A study of 15 cases
Authors: H Assier, O Chosidow, J.C Piette, M.C Boffa, P Youinou, L Thomas, F Caux, B Cribier, J.M Bonnet-Blanc, G Guillet, P Plantin, R Triller, A Cosnes, E Delaporte, M Dandurand, C Francès
Journal: Journal of the American Academy of Dermatology (1995)