tbuckley/cabot-search huggingface dataset:
CEACAM5-Targeted Therapy of Human Colonic and Pancreatic Cancer Xenografts with Potent Labetuzumab-SN-38 Immunoconjugates
Authors: Serengulam V. Govindan, Thomas M. Cardillo, Sung-Ju Moon, Hans J. Hansen, David M. Goldenberg
Journal: Clinical Cancer Research (2009)

To improve the efficacy and reduce the gastrointestinal toxicity of the cancer prodrug, CPT-11, we have developed immunoconjugates of its active form, SN-38, and an anti-CEACAM5 antibody for targeted chemotherapy.SN-38 conjugates of the anti-CEACAM5 monoclonal antibody, labetuzumab (hMN-14), varying in the nature of the cross-linker attachment at the drug's 20-hydroxyl position, were evaluated in vitro, in metastatic and/or s.c. human colonic and pancreatic cancer xenografts in nude mice using appropriate controls, and in a CEACAM5-negative tumor model.A pilot study in a s.c. LS174T model of human colonic carcinoma established the relative effectiveness of different conjugates. In the lung metastatic model of GW-39 human colonic carcinoma in nude mice, therapy with two specific labetuzumab-SN-38 conjugates, using 0.25 mg SN-38 equivalent/kg, q4d x 8, significantly extended median survival time versus controls (P < 0.002). In an expanded evaluation in the s.c. LS174T xenograft model, specific SN-38 conjugates produced significant tumor growth control and increases in median survival time versus other controls, including CPT-11 at a 33-fold greater cumulative dose (P < 0.01). An improvement was also observed in the therapy of a s.c. human pancreatic tumor xenograft. In a CEACAM5-negative systemic lymphoma xenograft, one labetuzumab-SN-38 conjugate examined was ineffective, whereas the conjugate specific for the tumor model produced 100% survival.The promising labetuzumab-SN-38 conjugates developed showed selective therapeutic efficacy in human tumor models at nontoxic doses that were a fraction of the CPT-11 doses used.
Potential causes of increased long-term mortality after pneumonia
Authors: E. M. Mortensen
Journal: European Respiratory Journal (2011)

Pneumonia, along with influenza, is currently the eighth leading overall cause of death in the USA, and is the leading cause of infectious death [1]. However, this only considers the immediate impact of an episode of pneumonia on mortality. Almost all research on pneumonia has focused on mortality in the first 30–90 days after presentation [2]. However, there is growing interest in the effects of pneumonia after this immediate period. Sir William Osler famously remarked in his Principals and Practices of Medicine , “Pneumonia may well be called the friend of the aged. Taken off by it in an acute, short, not often painful illness, the old male escapes those cold gradations of decay so distressing to himself and to his friends” [3]. Although this may have been the case prior to the advent of antimicrobial therapy in the 1940s, recent studies have cast this assertion into serious doubt.

In 1998, Brancati et al. [4] published a study examining 141 patients hospitalised for pneumonia. They found that 16% died during the initial hospitalisation and that an additional 32% of the cohort, who survived until discharge, died within the next 24 months. Although this increased mortality was associated with …
Blood Pressure and Risk of Secondary Cardiovascular Events in Women
Authors: Peter J. Mason, JoAnn E. Manson, Howard D. Sesso, Christine M. Albert, Marilyn J. Chown, Nancy R. Cook, Philip Greenland, Paul M Ridker, Robert J. Glynn
Journal: Circulation (2004)

In apparently healthy people, the relation between blood pressure and risk of subsequent cardiovascular disease (CVD) is linear. In persons with CVD, the relation is uncertain.We conducted a prospective study of 5218 older women with CVD who reported their blood pressure at baseline in the Women's Antioxidant Cardiovascular Study (WACS), an ongoing double-blind, placebo-controlled secondary prevention trial of the benefits and risks of antioxidant vitamins, folic acid, vitamin B6, and vitamin B12 among women with CVD or > or =3 coronary risk factors. A total of 661 confirmed CVD events (nonfatal myocardial infarction, nonfatal stroke, coronary artery bypass graft procedure, percutaneous coronary angioplasty, or CVD death) occurred during a median follow-up of 6.5 years. After controlling for age, randomized treatment assignment, antihypertensive medication use, and coronary risk factors, we found that systolic blood pressure (SBP) was a strong predictor of CVD events and that the relation between SBP and CVD risk was positive, continuous, and linear (P for linear trend=0.001). For each 10-mm Hg increment in SBP, there was a 9% (95% CI 4% to 15%) increase in risk of secondary CVD events. Diastolic blood pressure, mean arterial pressure, and pulse pressure were weaker predictors of CVD risk in this cohort, and joint consideration of SBP and diastolic blood pressure found that only SBP significantly predicted risk. Use of antihypertensive medication did not modify the relationship of SBP with CVD events.In this population of women with CVD, we observed a strong, continuous, and linear association between SBP and risk of secondary CVD events. SBP was the blood pressure measure most strongly related to CVD risk.
The JAK2V617F activating mutation occurs in chronic myelomonocytic leukemia and acute myeloid leukemia, but not in acute lymphoblastic leukemia or chronic lymphocytic leukemia
Authors: Ross L. Levine, Marc Loriaux, Brian J. P. Huntly, Mignon L. Loh, Miroslav Beran, Eric Stoffregen, Roland Berger, Jennifer J. Clark, Stephanie G. Willis, Kim T. Nguyen, Nikki J. Flores, Elihu Estey, Norbert Gattermann, Scott Armstrong, A. Thomas Look, James D. Griffin, Olivier A. Bernard, Michael C. Heinrich, D. Gary Gilliland, Brian Druker, Michael W. N. Deininger
Journal: Blood (2005)
Relation between humoral pathological changes in multiple sclerosis and response to therapeutic plasma exchange
Authors: Mark Keegan, Fatima König, Robyn McClelland, Wolfgang Brück, Yazmín Morales, Andreas Bitsch, Hillel Panitch, Hans Lassmann, Brian Weinshenker, Moses Rodriguez, Joseph Parisi, Claudia F Lucchinetti
Journal: The Lancet (2005)
NDUFS6 mutations are a novel cause of lethal neonatal mitochondrial complex I deficiency
Authors: Denise M. Kirby, Renato Salemi, Canny Sugiana, Akira Ohtake, Lee Parry, Katrina M. Bell, Edwin P. Kirk, Avihu Boneh, Robert W. Taylor, Hans-Henrik M. Dahl, Michael T. Ryan, David R. Thorburn
Journal: Journal of Clinical Investigation (2004)

Complex I deficiency, the most common respiratory chain defect, is genetically heterogeneous: mutations in 8 nuclear and 7 mitochondrial DNA genes encoding complex I subunits have been described. However, these genes account for disease in only a minority of complex I–deficient patients. We investigated whether there may be an unknown common gene by performing functional complementation analysis of cell lines from 10 unrelated patients. Two of the patients were found to have mitochondrial DNA mutations. The other 8 represented 7 different (nuclear) complementation groups, all but 1 of which showed abnormalities of complex I assembly. It is thus unlikely that any one unknown gene accounts for a large proportion of complex I cases. The 2 patients sharing a nuclear complementation group had a similar abnormal complex I assembly profile and were studied further by homozygosity mapping, chromosome transfers, and microarray expression analysis. NDUFS6, a complex I subunit gene not previously associated with complex I deficiency, was grossly underexpressed in the 2 patient cell lines. Both patients had homozygous mutations in this gene, one causing a splicing abnormality and the other a large deletion. This integrated approach to gene identification offers promise for identifying other unknown causes of respiratory chain disorders.
Lymph Node Density Is Superior to TNM Nodal Status in Predicting Disease-Specific Survival After Radical Cystectomy for Bladder Cancer: Analysis of Pooled Data From MDACC and MSKCC
Authors: Wassim Kassouf, Piyush K. Agarwal, Harry W. Herr, Mark F. Munsell, Philippe E. Spiess, Gordon A. Brown, Louis Pisters, H. Barton Grossman, Colin P. Dinney, Ashish M. Kamat
Journal: Journal of Clinical Oncology (2007)

To compare the utility of lymph node density (LND) with TNM nodal status in predicting disease-specific survival (DSS) after radical cystectomy.We identified 248 patients with nodal metastasis after radical cystectomy (without neoadjuvant chemotherapy): 162 patients from Memorial Sloan-Kettering Cancer Center (MSKCC) and 86 patients from M.D. Anderson Cancer Center (MDACC). We assessed the effect of several variables on DSS.After a median follow-up duration of 24 months, 134 patients died of their disease. The median DSS was 36 months, and the 1-year, 2-year, and 5-year DSS rates were 83.7%, 57.4%, and 36.6%, respectively. The median LND was 20%. The 5-year DSS rate was 54.6% for patients with LND < or = 20% v 15.3% for patients with LND higher than 20% (P < .01). Pathologic nodal (pN) status in patients was 78 for pN1 (32%), 127 for pN2 (51%), and 43 for pN3 (17%). On univariate analysis, pN status and LND were significant predictors of DSS (P < .01). However, when pN status and LND were considered jointly in a multivariate model, only LND higher than 20% predicted decreased DSS (hazard ratio [HR], 2.75; P < .01). In addition, while nonorgan-confined (ie, > pT2) primary tumor (HR, 2.40; P < .01) and adjuvant chemotherapy (HR, 0.47; P < .01) were predictors of DSS, LND remained a predictor of DSS even after accounting for adjuvant chemotherapy.LND is superior to TNM nodal status in predicting DSS for patients with lymph node-positive disease after radical cystectomy, even in the context of adjuvant chemotherapy.
Screening for carriers of cystic fibrosis
Authors: S Raeburn
Journal: BMJ (1994)

At the core of genetic management is the principle that once people have been informed about all the options they can then choose. Clinical geneticists facilitate decision making by confirming the diagnosis, providing information non-directively, and arranging counselling that takes account of emotional aspects. Decision making is not always logical, and geneticists (and other doctors) should know this. People's feelings are as important as the facts; decisions should emerge from both.

Two papers in this week's journal concern screening for carriers of cystic fibrosis, although both use quite different models. Can such studies provide an approach to screening that is applicable to other autosomal recessive conditions? If so, and if health authorities were to introduce screening for carriers of the commoner autosomal recessive diseases, which should be chosen? The feelings of health professionals and of those who allocate resources may contribute (alongside the facts) to such strategic decisions.

Livingstone and colleagues from Edinburgh describe “couple screening” in pregnancy to identify carriers of cystic fibrosis (p 1459).1Following suggestions by Wald et al2,3 they reported back to those at high risk of having a child …
Nursing actions affect the functioning of elderly patients with sepsis during hospitalization
Authors: Lise Notander Clausen
Journal: European Respiratory Journal (2013)

Introduction   In Denmark 12.000 patients are hospitalized due to sepsis yearly. Sepsis is a generalized physical reaction to an infection and divided into; sepsis, severe sepsis and sepsis chock. The literature shows that hospitalization of elderly patients has a negative impact on physical function (Gill, T.M. et al. JAGS 2009; 57:195-201)   Aim   To examine the factors that affect the physical function among hospitalized patients with urosepsis.   Method   The design is a quantitative, retrospective medical record study. Participants were selected on the basis of diagnosis code DA419B, age above 65 years.  Several variables were chosen to examine correlations. Demographic and clinical variables: age, civil status, level of functioning prior to hospitalization, and at discharge, severity of sepsis, co-morbidities and mobilization rate during hospitalization. SPSS Statistics package was used to analyse data.   Results   In the period June 2011 - 2012, 29 patients were admitted with urosepsis at the Department of Infectious Diseases at Hilleroed Hospital. The mean age = 78 years, and the mean length of stay = 9.3 days. We found that 24% of patients loses functionality during hospitalization.  Analyses showed a positive correlation between sufficient mobilization and a stabile physical function. There was no correlation between the severity of sepsis and decline of physical function. Besides, we found no correlation between advanced age and decline in physical function. Data showed a correlation between advanced age and insufficient mobilization during hospitalization.   Conclusion   Mobilization during hospitalization plays a major role in avoiding decline in physical function of elderly patients with urosepsis.
Methicillin-susceptible Staphylococcus aureus clonal complex 398: high prevalence and geographical heterogeneity in bone and joint infection and nasal carriage
Authors: F. Valour, J. Tasse, S. Trouillet-Assant, J.-P. Rasigade, B. Lamy, E. Chanard, P. Verhoeven, J.-W. Decousser, H. Marchandin, M. Bés, C. Chidiac, F. Vandenesch, T. Ferry, F. Laurent
Journal: Clinical Microbiology and Infection (2014)
Fresh evidence confirms links between newer contraceptive pills and higher risk of venous thromboembolism
Authors: S. S. Jick
Journal: BMJ (2015)

Important insights for women and their doctors

In this week’s issue of The BMJ , Vinogradova and colleagues (doi:10.1136/bmj.h2135) report the results of a large study on the effects of combined oral contraceptives on the risk of venous thromboembolism, conducted in two large United Kingdom databases: the Clinical Practice Research Datalink (CPRD) and QResearch. The authors identified over 10 500 cases of VTE in women aged 15-49 years and around 42 000 matched controls to address the inconsistencies and limitations of earlier studies. Older oral contraceptives (those containing levonorgestrel or norethisterone) showed results consistent with previously published findings: current users of oral contraceptives are at increased risk of venous thromboembolism compared with non-users of similar age and health status. Relative to non-users, risks were increased by around 2.5-fold for users of older oral contraceptives. 

Notably, Vinogradova and colleagues also looked at the newer oral contraceptives, such as those containing desogestrel, gestodene, and cyproterone, as well as the newest pill containing drospirenone, where data have been limited and the magnitude of effects on the risks of venous thromboembolism remains controversial. They found that the newer contraceptives increased …
Long-term Intake of Dietary Fiber and Decreased Risk of Coronary Heart Disease Among Women
Authors: Alicja Wolk
Journal: JAMA (1999)

ContextEpidemiological studies of men suggest that dietary fiber intake protects against coronary heart disease (CHD), but data on this association in women are sparse.ObjectiveTo examine the association between long-term intake of total dietary fiber as well as fiber from different sources and risk of CHD in women.Design and SettingThe Nurses' Health Study, a large, prospective cohort study of US women followed up for 10 years from 1984. Dietary data were collected in 1984, 1986, and 1990, using a validated semiquantitative food frequency questionnaire.ParticipantsA total of 68,782 women aged 37 to 64 years without previously diagnosed angina, myocardial infarction (MI), stroke, cancer, hypercholesterolemia, or diabetes at baseline.Main Outcome MeasureIncidence of acute MI or death due to CHD by amount of fiber intake.ResultsResponse rate averaged 80% to 90% during the 10-year follow-up. We documented 591 major CHD events (429 nonfatal MIs and 162 CHD deaths). The age-adjusted relative risk (RR) for major CHD events was 0.53 (95% confidence interval [CI], 0.40-0.69) for women in the highest quintile of total dietary fiber intake (median, 22.9 g/d) compared with women in the lowest quintile (median, 11.5 g/d). After controlling for age, cardiovascular risk factors, dietary factors, and multivitamin supplement use, the RR was 0.77 (95% CI, 0.57-1.04). For a 10-g/d increase in total fiber intake (the difference between the lowest and highest quintiles), the multivariate RR of total CHD events was 0.81 (95% CI, 0.66-0.99). Among different sources of dietary fiber (eg, cereal, vegetables, fruit), only cereal fiber was strongly associated with a reduced risk of CHD (multivariate RR, 0.63; 95% CI, 0.49-0.81 for each 5-g/d increase in cereal fiber).ConclusionsOur findings in women support the hypothesis that higher fiber intake, particularly from cereal sources, reduces the risk of CHD.
Criteria for basic tastes and other sensory primaries
Authors: James E. Cutting
Journal: Behavioral and Brain Sciences (2008)

Abstract Primary, or basic, colors have been discussed for centuries. Over time, three criteria have emerged on their behalf: (a) their physical mixture yielding all other spectral colors, (b) the physiological attunement of receptors or pathways to particular wavelengths, and (c) the etymological history of the color term. These criteria can be applied usefully to taste to clarify issues.
Anakinra treatment in patients with refractory inflammatory myopathies and possible predictive response biomarkers: a mechanistic study with 12 months follow-up
Authors: Mei Zong, Christina Dorph, Maryam Dastmalchi, Helene Alexanderson, Jennifer Pieper, Petra Amoudruz, Sevim Barbasso Helmers, Inger Nennesmo, Vivianne Malmström, Ingrid E Lundberg
Journal: Annals of the Rheumatic Diseases (2013)

Objective To perform a mechanistic study on the effect of interleukin (IL)-1 blockade by anakinra in patients with refractory myositis and to explore possible predictive biomarkers. Methods Fifteen patients with refractory myositis were treated with anakinra for 12 months. Clinical response was assessed by the six-item core set measures of disease activity International Myositis Assessment and Clinical Studies (IMACS) and functional index (FI). Repeated muscle biopsies were investigated for cellular infiltrates, IL-1α, IL-1β, IL-1Ra and major histocompatibility complex-class I by immunohistochemistry. Serum levels of IL-1Ra and granulocyte colony-stimulating factor (G-CSF) were measured by ELISA. T cell phenotype and functional assays were investigated by multicolour flow cytometry. Results Seven patients had clinical response according to IMACS, four of them also showed improved FI. Responders had higher baseline extramuscular score compared with non-responders. In muscle biopsies, baseline CD163 macrophages and IL-1α expression were inversely correlated with muscle performance after 6 months treatment; all responders had IL-1Ra expression in the post-treatment biopsies but only 3/8 non-responders. In serum, IL-1Ra levels were increased and G-CSF was decreased after 6 months treatment, but their levels and changes were not related to clinical response. For T cells, an inverse correlation between baseline frequency of CD4 activated/memory T cells and decreased creatine kinase levels was observed. Five of six patients demonstrated less IL-17A and more IFN-γ secreting CD4 T cells after 6 months treatment. Moreover, anakinra reduced IL-17A secretion in vitro. Conclusions Patients with myositis may respond to anakinra. Extramuscular score, muscle CD163 macrophages and IL-1α expression, blood CD4 activated/memory T cells might associate with anakinra treatment response. Blocking the IL-1 receptor disfavoured Th17 cell differentiation both in vivo and in vitro.
Cardiovascular Mortality Following Short-term Androgen Deprivation in Clinically Localized Prostate Cancer: An Analysis of RTOG 94-08
Authors: Justin C. Voog, Rebecca Paulus, William U. Shipley, Matthew R. Smith, David G. McGowan, Christopher U. Jones, Jean-Paul Bahary, Kenneth L. Zeitzer, Luis Souhami, Mark H. Leibenhaut, Marvin Rotman, Siraj M. Husain, Elizabeth Gore, Adam Raben, Susan Chafe, Howard M. Sandler, Jason A. Efstathiou
Journal: European Urology (2015)
High frequency of helicobacter negative gastritis in patients with Crohn's disease.
Authors: L Halme, P Karkkainen, H Rautelin, T U Kosunen, P Sipponen
Journal: Gut (1996)

The frequency of gastric Crohn9s disease has been considered low. This study was undertaken to determine the prevalence of chronic gastritis and Helicobacter pylori infection in patients with Crohn9s disease. Oesophagogastroduodenoscopy was performed on 62 consecutive patients suffering from ileocolonic Crohn9s disease. Biopsy specimens from the antrum and corpus were processed for both histological and bacteriological examinations. H pylori antibodies of IgG and IgA classes were measured in serum samples by enzyme immunoassay. Six patients (9.7%) were infected with H pylori, as shown by histology, and in five of them the infection was also verified by serology. Twenty one patients (32%) had chronic H pylori negative gastritis (negative by both histology and serology) and one of them also had atrophy in the antrum and corpus. Granulomas were found in four patients. The characteristic appearance of H pylori negative gastritis was focal and mostly mild inflammation resembling the inflammatory changes seen in the gut in Crohn9s disease. Patients with H pylori negative chronic gastritis had a significantly more active disease in their gut than those with normal gastric mucosa (p &lt; 0.01). It is concluded that H pylori positive gastritis is rare, while H pylori negative gastritis is relatively common in patients with Crohn9s disease. H pylori negative 9Crohn9s gastritis9 seems to be associated with active Crohn9s disease.
Medicine and Religion
Authors: Thomas J. O'Donnell
Journal: JAMA (1970)

The respective professions, medicine and religion, are so distinct from one another that in the past they have been sometimes mutually incommunicative. This has warranted an American Medical Association department designed specifically to promote mutual understanding. And yet both professions are deeply concerned with the welfare of the sick, and thus meet in the object of our solicitudes. Moreover, we share certain characteristics in common—certain professional mantles, if you will. And how we bear them very much affects ourselves, and consequently our relationships with each other, and hence our relationships with the patient. To enumerate some of these common characteristics, let me point out that together we share a position of privilege in society and a hierarchy of service. Each of the professions has a moral code and a dogmatic turn of mind. Each of us, with our colleagues, has a responsibility for protecting and enriching the lives of others.
Runner’s stitch and the thoracic spine
Authors: D P Morton, T Aune
Journal: British Journal of Sports Medicine (2004)

The cause of the abdominal pain commonly referred to as “stitch”, but more accurately known as exercise related transient abdominal pain (ETAP), had until recently attracted more speculation than research. Explanations for the pain have included diaphragmatic ischaemia,1 stress on peritoneal ligaments,2 and irritation of the parietal peritoneum.3 Although the exact cause of the pain remains to be elucidated, a neurogenic explanation has not appeared in the literature.

We present the case of an elite runner who, after a thoracic spine trauma, developed severe and recurrent episodes of ETAP which were relieved by localised treatment. As a follow up study, we made observations on 17 other runners who often experience episodes of ETAP and found that palpation of specific facet joints could reproduce symptoms of ETAP shortly after an episode of the pain had been relieved.

The patient was a 25 year old man who had been actively involved in competitive running for about 16 years. During this time, he claimed that he occasionally experienced mild symptoms of ETAP during training and competition, although they were not disruptive to performance. After trauma to the thoracic spine in a trampoline accident, he began to experience ETAP with greater frequency and severity. Subsequently he would develop ETAP …