tbuckley/cabot-search huggingface dataset:
Bad medicine: motherhood
Authors: Des Spence
Journal: BMJ (2013)

Holding hands and drinking beers, cigarette in mouth, whooping as the sun comes up, best friends forever, piercing, tattoos, mosh pits, vodka, rock festivals, and recreational drugs—this is youth. Never going to conform, to become our neurotic parents, and never trapped in the open prison of the suburbs. Mother Earth-types, free and alive, and happy to give birth under a bush in moonlight. But this isn’t how life works, because we grow up. Friends pair off, and stop going out. Anxiety, once abstract, begins to stalk us—constantly whispering, “What if?” The biological …
Involvement of Sphingolipids in Apoptin-Induced Cell Killing
Authors: Xiang Liu, Youssef H. Zeidan, Saeed Elojeimy, David H. Holman, Ahmed M. El-Zawahry, Gui-wen Guo, Alicja Bielawska, Jacek Bielawski, Zdzislaw Szulc, Semyon Rubinchik, Jian-Yun Dong, Thomas E. Keane, Mahvash Tavassoli, Yusuf A. Hannun, James S. Norris
Journal: Molecular Therapy (2006)

The potential anti-tumor agent Apoptin activates apoptosis in many human cancers and transformed cell lines, but is believed to be less potent in primary cells. Although caspase 3 is activated during apoptin-induced apoptosis, the mechanism of tumor cell killing remains elusive. We now show that apoptin-mediated cell death involves modulation of the sphingomyelin–ceramide pathway. Treating cells with Ad-GFPApoptin resulted in increased ceramide accumulation and enhanced expression of acid sphingomyelinase (ASMase) with a concomitant increase in ASMase activity and decreased sphingomyelin. Using confocal microscopy, ASMase, normally present in the endosomal/lysosomal compartment, was observed to translocate to the cell's periphery. Cotreatment of Ad-GFPApoptin-infected cells with the ASMase inhibitor desipramine (2.5 μM) attenuated (30%; P<0.01) apoptin-induced cell death. Apoptin was also able to induce a significant decline in sphingosine content by inhibition of ceramide deacylation through down-regulation of acid ceramidase at the protein level. Supporting the role of ceramide in apoptin action, treatment of cells with the combination of an exogenous cell-permeable ceramide analog (C6-ceramide) and Ad-GFPApoptin infection yielded a significant increase (P<0.01) in apoptosis over either treatment modality alone. Together, these data suggest that apoptin modulates ceramide/sphingolipid metabolism as part of its mechanism of action.
Monitoring serum hepatitis C virus (HCV) RNA in patients with HCV‐infected CD20‐positive B‐cell lymphoma undergoing rituximab combination chemotherapy
Authors: Daisuke Ennishi, Yasuhito Terui, Masahiro Yokoyama, Yuko Mishima, Shunji Takahashi, Kengo Takeuchi, Hiroaki Okamoto, Mitsune Tanimoto, Kiyohiko Hatake
Journal: American Journal of Hematology (2007)

Abstract Several studies have shown that the frequency of hepatitis C virus (HCV) infection is high in patients with B‐cell non‐Hodgkin's lymphoma (NHL). In these studies, liver dysfunction during chemotherapy has been demonstrated, but changes in HCV ribonucleic acid (RNA) levels during chemotherapy have not been well documented. In this study, we monitored serum HCV RNA levels and liver function in five HCV‐infected patients with B‐cell NHL undergoing treatment with rituximab‐combination chemotherapy. Increased HCV RNA levels during or after the chemotherapy were observed in all five patients, and a significant increase in transaminases was seen in one case. In this case, serum HCV RNA level dramatically decreased at the time of the increase of transaminases, and this suggested that the cause of liver damage was an immune reaction against hepatocytes with HCV and not any anticancer drug induced liver toxicity. Monitoring of serum HCV RNA levels and transaminases may be helpful to understand the cause of liver dysfunction in patients receiving chemotherapy. However, increases of HCV viral load were not associated with the occurrence of liver dysfunction in this study. Further studies will be necessary to investigate more fully the relationship between changes in HCV viral load and liver function during chemotherapy for HCV‐infected patients. Am. J. Hematol., 2008. © 2007 Wiley‐Liss, Inc.
Modification of the human allergic immune response by allergen-DNA–transfected dendritic cells in vitro☆
Authors: Bettina Klostermann, Iris Bellinghausen, Ingo Böttcher, Arnd Petersen, Wolf-Meinhard Becker, Jürgen Knop, Joachim Saloga
Journal: Journal of Allergy and Clinical Immunology (2004)
Clinical Depression Versus Distress Among Patients With Type 2 Diabetes: Not Just a Question of Semantics
Authors: Lawrence Fisher, Marilyn M. Skaff, Joseph T. Mullan, Patricia Arean, David Mohr, Umesh Masharani, Russell Glasgow, Grace Laurencin
Journal: Diabetes Care (2007)

Given the findings of our recently published report (1) and their earlier study (2), Hermanns et al. (3) suggest that because screening for multiple conditions is not always feasible, it may make sense to use diabetes distress measures to assess both depression and diabetes-specific distress. Both studies concluded that measures of diabetes distress captured both the negative affect associated with depression and the negative affect associated with diabetes-related distress. Hermanns et al. support their view by presenting cogent arguments that are based on the sensitivity of distress measures in capturing both kinds of negative affect. We used the Center for Epidemiology Depression Scale (CESD) (4) to assess depressive affect and the Diabetes Distress Scale (DDS) (5) to measure diabetes distress. We also used a structured interview, the Composite International Diagnostic Interview (CIDI), to assess clinical depression or …
Sustained benefit of interferon-alpha therapy and oral hyposensitization in severe atopic dermatitis
Authors: A. Michils, C.-M. Farber, J.-P. Vookkn, J.-C. Yernault, J. Duchateau
Journal: British Journal of Dermatology (1994)

Journal Article Sustained benefit of interferon‐alpha therapy and oral hyposensitization in severe atopic dermatitis Get access A. Michils, A. Michils Chest Department, Erasme University Hospital, Belgium Search for other works by this author on: Oxford Academic Google Scholar C.‐M. Farber, C.‐M. Farber Department of Clinical Immunology, Erasme University Hospital, Belgium Search for other works by this author on: Oxford Academic Google Scholar J.‐P. Van Vookkn, J.‐P. Van Vookkn Chest Department, Erasme University Hospital, Belgium Search for other works by this author on: Oxford Academic Google Scholar J.‐C. Yernault, J.‐C. Yernault Chest Department, Erasme University Hospital, Belgium Search for other works by this author on: Oxford Academic Google Scholar J. Duchateau J. Duchateau Immunology Department, St Pierre University Hospital Brussels, Belgium Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 130, Issue 1, 1 January 1994, Pages 134–135, https://doi.org/10.1111/j.1365-2133.1994.tb06908.x Published: 01 January 1994
Diet, Obesity, and Cardiovascular Risk
Authors: Robert O. Bonow, Robert H. Eckel
Journal: New England Journal of Medicine (2003)

The growing prevalence of obesity and type 2 diabetes in the United States has attracted the attention and concern of the medical profession, the media, policymakers, and the American public. Recent statistics from the Centers for Disease Control and Prevention indicate that nearly two thirds of American adults are overweight (body-mass index [the weight in kilograms divided by the square of the height in meters], greater than 25) and more than 30 percent are frankly obese (body-mass index, greater than 30), that nearly 8 percent are diabetic, and that 24 percent have the metabolic syndrome. The metabolic syndrome is an . . .
Relation Between Hospital Specialization With Primary Percutaneous Coronary Intervention and Clinical Outcomes in ST-Segment Elevation Myocardial Infarction
Authors: Brahmajee K. Nallamothu, Yongfei Wang, David J. Magid, Robert L. McNamara, Jeph Herrin, Elizabeth H. Bradley, Eric R. Bates, Charles V. Pollack, Harlan M. Krumholz
Journal: Circulation (2006)

Hospitals with primary percutaneous coronary intervention (PPCI) capability may choose to predominately offer PPCI to their patients with ST-segment elevation myocardial infarction (STEMI), or they may selectively offer PPCI or fibrinolytic therapy based on patient and hospital-level factors. Whether a greater level of hospital specialization with PPCI is associated with better quality of care is unknown.We analyzed data from the National Registry of Myocardial Infarction-4 to compare in-hospital mortality and times to treatment in STEMI across different levels of hospital specialization with PPCI. We divided 463 hospitals into quartiles of PPCI specialization based on the relative proportion of reperfusion-treated patients who underwent PPCI (< or =34.0%, >34.0 to 62.5%, >62.5 to 88.5%, >88.5%). Hierarchical multivariable regression assessed whether PPCI specialization was associated with better outcomes, after adjusting for patient and hospital characteristics, including PPCI volume. We found that greater PPCI specialization was associated with a lower relative risk of in-hospital mortality in patients treated with PPCI (adjusted relative risk comparing the highest and lowest quartiles, 0.64; P=0.006) but not in those treated with fibrinolytic therapy. Compared with patients at hospitals in the lowest quartile of PPCI specialization, adjusted door-to-balloon times in the highest quartile were significantly shorter (99.6 versus 118.3 minutes; P<0.001), and the likelihood of door-to-balloon times exceeding 90 minutes was significantly lower (relative risk, 0.78; P<0.001). Adjusting for PPCI specialization diminished the association between PPCI volume and clinical outcomes.Greater specialization with PPCI is associated with lower in-hospital mortality and shorter door-to-balloon times in STEMI patients treated with PPCI.
Letter: Splenectomy and susceptibility to malaria and babesia infection.
Authors: P G Shute
Journal: BMJ (1975)

sPecial consideration concerming suscepti- bility to malaria and infection with some species of babesia in patients who have undergone ;splenectomy for haematological disorders.Research work on apes and monkeys has shown that when these animals have acquired immuunity to malaria they can be reinfected with the same .strain of tthe same species of parasite if, before reinfection, the recommence a drug which he rightly believes could have killed him.-Iam, etc.,
New ethical framework for pharmaceutical physicians
Authors: Rubin Minhas
Journal: BMJ (2006)

EDITOR—Lenzer highlighted the helping hand that some US news organisations give to pharmaceutical companies in circumventing the Food and Drug Administration's requirements for fair balance in video news releases.1 An ethical framework of guiding principles for pharmaceutical physicians has recently been published.2 Pharmaceutical physicians should “ensure that expectations are not inappropriately raised as a result of media briefings” …
Intradermal B.C.G. Vaccination by Jet Injection
Authors: M. I. Griffiths, M. C. Davitt, T. W. Brindle, T. Holme
Journal: BMJ (1965)

Intradermal vaccination with B.C.G. has been an accepted prophylactic measure against tuberculosis in Great Britain since 1950.When given to schoolchildren it has been shown con- sistently to produce tuberculin sensitivity (Miller and Kinsley, 1961), to protect against tuberculosis (Sutherland, 1959; Medical Research Council, 1963), and to be relatively free from complications (Medical Research Council, 1958).The intra- dermal method is still the most accurate and reliable means of administering B.C.G. vaccine.It has, however, disadvantages in that considerable skill is required if subcutaneous inoculation is to be avoided; highly trained vaccinators need to spend a long time over the injections, and the fact that a needle has to be inserted into the skin makes the technique unacceptable to many schoolchildren and unsophisticated adults.Progress in B.C.G. vaccination techniques must therefore be towards efficiency combined with simplicity, and a search is still con- tinuing for a method which is accurate and effective, which causes few complications, which requires little skill in administration, and which is economical in manpower and materials.Jet injection, if it could be adapted to administer a small
Standard flow-time waveforms for testing of PEF meters.
Authors: J L Hankinson, R O Crapo
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

The American Thoracic Society (ATS) has recommended the use of 24 volume-time waveforms for the testing of spirometers. Although these waveforms include values of peak expiratory flow (PEF), they were not originally intended to test PEF meters, but, rather, volume parameters for spirometers. In addition, the practice of using ATS volume-time Waveform 24 with varying multiplying factors does not provide the range of flow-time waveform shapes (rise times) needed to evaluate PEF meters. Accordingly, we have developed a set of 26 flow-time waveforms specifically selected to evaluate PEF meters. PEF and other flow parameters (rise time and time to PEF) can be directly measured from these flow-time waveforms. When PEF determined directly from the flow-time curve was compared with PEF determined indirectly from a volume-time curve (ATS-recommended algorithm with an 80 ms time segment), as much as a 10.7% difference between the two methods was observed using a waveform with a fast rise time. In contrast, there was very little difference between the various methods of deriving PEF for waveforms with slower rise times. These 26 flow-time waveforms provide a means of defining PEF for the testing of software algorithms and the testing of PEF meters with computer-driven mechanical pumps.
Survival after early treatment for carbamyl phosphate synthetase (CPS) I deficiency associated with increase of intramitochondrial CPS I
Authors: K-P. Zimmer, H.G. Koch, R. Rossi, T. Deufel, K. Ullrich, E. Harms, K.W. Schmid, H.Y. Naim, J-P. Colombo
Journal: The Lancet (1995)
Supply-Demand Mismatch Transients in Susceptible Peri-infarct Hot Zones Explain the Origins of Spreading Injury Depolarizations
Authors: Daniel von Bornstädt, Thijs Houben, Jessica L. Seidel, Yi Zheng, Ergin Dilekoz, Tao Qin, Nora Sandow, Sreekanth Kura, Katharina Eikermann-Haerter, Matthias Endres, David A. Boas, Michael A. Moskowitz, Eng H. Lo, Jens P. Dreier, Johannes Woitzik, Sava Sakadžić, Cenk Ayata
Journal: Neuron (2015)
Physical Activity During Daily Life and Mortality in Patients With Peripheral Arterial Disease
Authors: Parveen K. Garg, Lu Tian, Michael H. Criqui, Kiang Liu, Luigi Ferrucci, Jack M. Guralnik, Jin Tan, Mary M. McDermott
Journal: Circulation (2006)

We determined whether patients with lower-extremity peripheral arterial disease (PAD) who are more physically active during daily life have lower mortality rates than PAD patients who are less active.
Re: Christian G. Stief, Hartmut Porst, Dieter Neuser, et al. A Randomised, Placebo-Controlled Study to Assess the Efficacy of Twice-Daily Vardenafil in the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia. Eur Urol 2008;53:1236–44
Authors: Mauro Gacci, Mario Maggi, Marco Carini
Journal: European Urology (2008)
The Art and Science of Nondisease
Authors: Clifton K. Meador
Journal: New England Journal of Medicine (1965)

FOR the physician accustomed to dealing only with pathologic entities, terms such as "nondisease entity" or "nondisease" are foreign and difficult to comprehend. This paper will present the background for the development of this new science, a classification of nondisease and finally the important therapeutic principles based on this concept.Since disease is an abnormal state that lends itself to classification into syndromes and entities, one tends to think of health or nondisease as all encompassing and without specificity. This is not the case, since it is now clear that "nondisease" may be used in quite a specific manner; furthermore, . . .
Linkage analysis of the hemoglobin F determinant(s) in an australian hemoglobin lepore (Boston) kindred
Authors: Penelope I. Motum, Jennifer A. Donald, Ronald J. Trent
Journal: American Journal of Hematology (1993)

Abstract Genetic determinants that influence the levels of fetal hemoglobin (Hb F) in a single Australian kindred with heterozygous Hb Lepore (Boston) were sought. There were 22 affected individuals, some of whom had high Hb F and others with Hb F levels within the normal range. Family members were typed for restriction fragment length polymorphisms (RFLPs) associated with the β‐globin gene complex and the nearby genetic markers D11S12, INS, HRAS, and PTH. Prior to linkage analysis, a cohort of 54 unrelated Hb Lepore heterozygotes was analyzed to establish the distribution of Hb F levels measured by alkaline denaturation (Hb F AD ). An Hb F level of &gt;2.0% was used as the cutoff point for linkage analysis of the putative hereditary persistence of fetal hemoglobin (HPFH) determinant(s) in this kindred. Positive peak lod scores were obtained for the entire pedigree between the HPFH determinant and Hb Lepore (Z m+1 = 2.35 at θ = 0.15) and the β‐globin cluster (HBBC) (Z m+1 = 2.38 at θ = 0.20) marker loci, indicating the possibility of an independent HPFH gene at some distance from the β‐globin gene cluster. However, most of these lod scores result from the non‐Hb Lepore members of the family who, with one exception, do not have high Hb F, and when only those affected with Hb Lepore were analyzed the lod score values at these loci fell to small positive values (&lt;1.0). These data do not support an independent cosegregating HPFH determinant separate from the Hb Lepore locus in this pedigree. The results favor a pleiotropic effect of the Hb Lepore lesion itself influencing Hb F levels by genetic or environmental factors not yet elucidated.
A phase 1/2, dose-escalation trial of deferasirox for the treatment of iron overload in HFE-related hereditary hemochromatosis
Authors: Pradyumna Phatak, Pierre Brissot, Mark Wurster, Paul C Adams, Herbert L. Bonkovsky, John Gross, Peter Malfertheiner, Gordon D. McLaren, Claus Niederau, Alberto Piperno, Lawrie W. Powell, Mark W. Russo, Ulrich Stoelzel, Wolfgang Stremmel, Louis Griffel, Nicola Lynch, Yiyun Zhang, Antonello Pietrangelo
Journal: Hepatology (2010)

Hereditary hemochromatosis (HH) is characterized by increased intestinal iron absorption that may result in iron overload. Although phlebotomy is widely practiced, it is poorly tolerated or contraindicated in patients with anemias, severe heart disease, or poor venous access, and compliance can vary. The once-daily, oral iron chelator, deferasirox (Exjade) may provide an alternative treatment option. Patients with HH carrying the HFE gene who were homozygous for the Cys282Tyr mutation, serum ferritin levels of 300-2000 ng/mL, transferrin saturation ≥45%, and no known history of cirrhosis were enrolled in this dose-escalation study to characterize the safety and efficacy of deferasirox, comprising a core and an extension phase (each 24 weeks). Forty-nine patients were enrolled and received starting deferasirox doses of 5 (n = 11), 10 (n = 15), or 15 (n = 23) mg/kg/day. Adverse events were generally dose-dependent, the most common being diarrhea, headache, and nausea (n = 18, n = 10, and n = 8 in the core and n = 1, n = 1, and n = 0 in the extension, respectively). More patients in the 15 mg/kg/day than in the 5 or 10 mg/kg/day cohorts experienced increases in alanine aminotransferase and serum creatinine levels during the 48-week treatment period; six patients had alanine aminotransferase &gt;3× baseline and greater than the upper limit of normal range, and eight patients had serum creatinine &gt;33% above baseline and greater than upper limit of normal on two consecutive occasions. After receiving deferasirox for 48 weeks, median serum ferritin levels decreased by 63.5%, 74.8%, and 74.1% in the 5, 10, and 15 mg/kg/day cohorts, respectively. In all cohorts, median serum ferritin decreased to &lt;250 ng/mL. Conclusion: Deferasirox doses of 5, 10, and 15 mg/kg/day can reduce iron burden in patients with HH. Based on the safety and efficacy results, starting deferasirox at 10 mg/kg/day appears to be most appropriate for further study in this patient population. (Hepatology 2010)
Serum immunoreactive cationic trypsinogen: a useful indicator of severe exocrine dysfunction in the paediatric patient without cystic fibrosis.
Authors: D J Moore, G G Forstner, C Largman, G J Cleghorn, S S Wong, P R Durie
Journal: Gut (1986)

We evaluated serum cationic trypsinogen as a marker of exocrine pancreatic function in children without cystic fibrosis. The ability of this test to determine steatorrhoea of pancreatic origin, and its relationship to a wide range of exocrine pancreatic function were assessed. Serum trypsinogen was measured in 32 children with steatorrhoea, 10 with pancreatic and 22 with non-pancreatic causes. In patients with pancreatic steatorrhoea, serum cationic trypsinogen was 4.9 +/- 4.9 micrograms/l (mean +/- SD), significantly below values in patients with non-pancreatic steatorrhoea (47.0 +/- 22.1 micrograms/l, p less than 0.001) and 50 control subjects (31.4 +/- 7.4 micrograms/l, p less than 0.001). Serum cationic trypsinogen values in patients with pancreatic steatorrhoea all fell below the lower limit of our control range and below all values for patients with non-pancreatic steatorrhoea. Serum cationic trypsinogen was also evaluated against pancreatic trypsin output in 47 patients (range 0.2-17.0 yr who underwent a hormonal pancreatic stimulation test. In 17 patients, serum cationic trypsinogen was low (less than -2SD or less than 16.6 micrograms/l), and associated with greatly impaired pancreatic trypsin output, ranging from 0-8% of mean normal trypsin output. Five of these 17 patients did not have steatorrhoea. In 30 patients with normal or raised serum cationic trypsinogen (greater than or equal to 16.6 micrograms/l), pancreatic trypsin output ranged from 15-183% of mean normal values. In conclusion, low serum cationic trypsinogen suggests severely impaired exocrine pancreatic function, with sensitivity extending above the steatorrhoeic threshold. In the presence of steatorrhoea, low serum cationic trypsinogen indicates a pancreatic aetiology. Normal serum cationic trypsinogen, however, does not exclude impaired pancreatic function, above the steatorrhoeic threshold.
Genome-wide screening reveals that miR-195 targets the TNF-α/NF-κB pathway by down-regulating IκB kinase alpha and TAB3 in hepatocellular carcinoma
Authors: Jie Ding, Shenglin Huang, Ying Wang, Qi Tian, Ruopeng Zha, Haibing Shi, Qifeng Wang, Chao Ge, Taoyang Chen, Yingjun Zhao, Linhui Liang, Jinjun Li, Xianghuo He
Journal: Hepatology (2013)

Nuclear factor kappa B (NF-κB) is an important factor linking inflammation and tumorigenesis. In this study we experimentally demonstrated through a high-throughput luciferase reporter screen that NF-κB signaling can be directly targeted by nearly 29 microRNAs (miRNAs). Many of these miRNAs can directly target NF-κB signaling nodes by binding to their 3' untranslated region (UTR). miR-195, a member of the miR-15 family, is frequently down-regulated in gastrointestinal cancers, especially in hepatocellular carcinoma (HCC). The expression level of miR-195 is inversely correlated with HCC tumor size. We further show that miR-195 suppresses cancer cell proliferation and migration in vitro and reduces tumorigenicity and metastasis in vivo. Additionally, miR-195 may exert its tumor suppressive function by decreasing the expression of multiple NF-κB downstream effectors by way of the direct targeting of IKKα and TAB3.Multiple miRNAs are involved in the NF-κB signaling pathway and miR-195 plays important inhibitory roles in cancer progression and may be a potential therapeutic target.