tbuckley/cabot-search huggingface dataset:
Hydroxyethyl Starch or Saline for Fluid Resuscitation in Intensive Care
Authors: John A. Myburgh, Simon Finfer, Rinaldo Bellomo, Laurent Billot, Alan Cass, David Gattas, Parisa Glass, Jeffrey Lipman, Bette Liu, Colin McArthur, Shay McGuinness, Dorrilyn Rajbhandari, Colman B. Taylor, Steven A.R. Webb
Journal: New England Journal of Medicine (2012)

The safety and efficacy of hydroxyethyl starch (HES) for fluid resuscitation have not been fully evaluated, and adverse effects of HES on survival and renal function have been reported.We randomly assigned 7000 patients who had been admitted to an intensive care unit (ICU) in a 1:1 ratio to receive either 6% HES with a molecular weight of 130 kD and a molar substitution ratio of 0.4 (130/0.4, Voluven) in 0.9% sodium chloride or 0.9% sodium chloride (saline) for all fluid resuscitation until ICU discharge, death, or 90 days after randomization. The primary outcome was death within 90 days. Secondary outcomes included acute kidney injury and failure and treatment with renal-replacement therapy.A total of 597 of 3315 patients (18.0%) in the HES group and 566 of 3336 (17.0%) in the saline group died (relative risk in the HES group, 1.06; 95% confidence interval [CI], 0.96 to 1.18; P=0.26). There was no significant difference in mortality in six predefined subgroups. Renal-replacement therapy was used in 235 of 3352 patients (7.0%) in the HES group and 196 of 3375 (5.8%) in the saline group (relative risk, 1.21; 95% CI, 1.00 to 1.45; P=0.04). In the HES and saline groups, renal injury occurred in 34.6% and 38.0% of patients, respectively (P=0.005), and renal failure occurred in 10.4% and 9.2% of patients, respectively (P=0.12). HES was associated with significantly more adverse events (5.3% vs. 2.8%, P<0.001).In patients in the ICU, there was no significant difference in 90-day mortality between patients resuscitated with 6% HES (130/0.4) or saline. However, more patients who received resuscitation with HES were treated with renal-replacement therapy. (Funded by the National Health and Medical Research Council of Australia and others; CHEST ClinicalTrials.gov number, NCT00935168.).
Training Physicians in Counseling about Smoking Cessation
Authors: S R Cummings, T J Coates, R J Richard, B Hansen, E G Zahnd, R VanderMartin, C Duncan, B Gerbert, A Martin, M J Stein
Journal: Annals of Internal Medicine (1989)

Study Objective: To test whether physicians who receive a continuing education program ("Quit for Life") about how to counsel smokers to quit would counsel smokers more effectively and have higher rates of long-term smoking cessation among their patients who smoke. Design: Randomized trial with blinded assessment of principal outcomes. Setting: Four health maintenance organization medical centers in northern California. Subjects: Eighty-one internists assigned by blinded randomization to receive training (40) or serve as controls (41). Consecutive samples of smokers visiting each physician (mean, 25.6 patients per experimental and 25.2 per control physician). Interventions: Internists received 3 hours of training about how to help smokers quit. Physicians and their office staff also were given self-help booklets to distribute free to smokers and were urged to use a system of stickers on charts to remind physicians to counsel smokers about quitting. Measurements and Main Results: On the basis of telephone interviews with patients after visiting the physician, we determined that internists who attended the Quit for Life program discussed smoking with more patients who smoked, spent more time counseling them about smoking, helped more patients set dates to quit smoking, gave out more self-help booklets, and made more follow-up appointments to discuss smoking than did internists in the control group. One year later, the rate of biochemically confirmed, long-term (≥ 9 months) abstinence from smoking was 1% higher among all patients of trained internists than among patients of controls (95% CI, -0.1% to -+2.3%), and 2.2% (+0.2% to +4.3%) higher among the patients who most wanted to quit smoking. Conclusions: This continuing education program substantially changed the way physicians counseled smokers. As a result, a few more patients who wanted to quit smoking achieved long-term abstinence.
Clinical Response to a Lapatinib-Based Therapy for a Li-Fraumeni Syndrome Patient with a Novel <i>HER2</i>V659E Mutation
Authors: Violeta Serra, Ana Vivancos, Xose S. Puente, Enriqueta Felip, Daniel Silberschmidt, Ginevra Caratù, Josep-Lluís Parra, Leticia De Mattos-Arruda, Judit Grueso, Javier Hernández-Losa, Joaquín Arribas, Ludmila Prudkin, Paolo Nuciforo, Maurizio Scaltriti, Joan Seoane, José Baselga
Journal: Cancer Discovery (2013)

Genomic characterization of recurrent breast and lung tumors developed over the course of 10 years in a 29-year-old patient with a germline TP53 mutation (Li-Fraumeni Syndrome) identified oncogenic alterations in the HER2 and EGFR genes across all tumors, including HER2 amplifications, an EGFR-exon 20 insertion, and the first-in-humans HER2V659E mutation showing a phenotypic convergent evolution toward HER2 and EGFR alterations. Following the identification of HER2-activating events in the most recent lung carcinoma and in circulating tumor cells, we treated the reminiscent metastatic lesions with a lapatinib-based therapy. A symptomatic and radiologic clinical response was achieved. HER2V659E sensitivity to lapatinib was confirmed in the laboratory.The precise knowledge of the genomic alterations present in tumors is critical to selecting the optimal treatment for each patient. Here, we report the molecular characterization and clinical response to a lapatinib-based therapy for the tumors of a Li-Fraumeni patient showing prevalence of HER2 and EGFR genomic alterations.
Bone loss caused by iron overload in a murine model: importance of oxidative stress
Authors: Jaime Tsay, Zheiwei Yang, F. Patrick Ross, Susanna Cunningham-Rundles, Hong Lin, Rhima Coleman, Philipp Mayer-Kuckuk, Stephen B. Doty, Robert W. Grady, Patricia J. Giardina, Adele L. Boskey, Maria G. Vogiatzi
Journal: Blood (2010)
Comparative analysis of transposed element insertion within human and mouse genomes reveals Alu's unique role in shaping the human transcriptome
Authors: Noa Sela, Britta Mersch, Nurit Gal-Mark, Galit Lev-Maor, Agnes Hotz-Wagenblatt, Gil Ast
Journal: Genome biology (2007)

Abstract Background Transposed elements (TEs) have a substantial impact on mammalian evolution and are involved in numerous genetic diseases. We compared the impact of TEs on the human transcriptome and the mouse transcriptome. Results We compiled a dataset of all TEs in the human and mouse genomes, identifying 3,932,058 and 3,122,416 TEs, respectively. We than extracted TEs located within human and mouse genes and, surprisingly, we found that 60% of TEs in both human and mouse are located in intronic sequences, even though introns comprise only 24% of the human genome. All TE families in both human and mouse can exonize. TE families that are shared between human and mouse exhibit the same percentage of TE exonization in the two species, but the exonization level of Alu , a primate-specific retroelement, is significantly greater than that of other TEs within the human genome, leading to a higher level of TE exonization in human than in mouse (1,824 exons compared with 506 exons, respectively). We detected a primate-specific mechanism for intron gain, in which Alu insertion into an exon creates a new intron located in the 3' untranslated region (termed 'intronization'). Finally, the insertion of TEs into the first and last exons of a gene is more frequent in human than in mouse, leading to longer exons in human. Conclusion Our findings reveal many effects of TEs on these two transcriptomes. These effects are substantially greater in human than in mouse, which is due to the presence of Alu elements in human.
The Health Care Costs of Smoking
Authors: Jan J. Barendregt, Luc Bonneux, Paul J. van der Maas
Journal: New England Journal of Medicine (1997)

Although smoking cessation is desirable from a public health perspective, its consequences with respect to health care costs are still debated. Smokers have more disease than nonsmokers, but nonsmokers live longer and can incur more health costs at advanced ages. We analyzed health care costs for smokers and nonsmokers and estimated the economic consequences of smoking cessation.
Docetaxel (Taxotere®)-cisplatin (TC): An effective drug combination in gastric carcinoma
Authors: A.D. Roth, R. Maibach, G. Martinelli, N. Fazio, M.S. Aapro, O. Pagani, R. Morant, M.M. Borner, R. Herrmann, H. Honegger, F. Cavalli, P. Alberto, M. Castiglione, A. Goldhirsch
Journal: Annals of Oncology (2000)
Defective Expression of Fas Messenger RNA and Fas Receptor on Pulmonary T Cells from Patients with Asthma
Authors: F Spinozzi, M Fizzotti, E Agea, S Piattoni, S Droetto, A Russano, N Forenza, G Bassotti, F Grignani, A Bertotto
Journal: Annals of Internal Medicine (1998)

Background: Inflammation at sites of target organs seems to be the pathologic hallmark of respiratory allergic diseases, but why this response cannot be turned off in atopic persons is not known. Programmed cell death (apoptosis) mediated by Fas/APO-1 (CD95), a 45-kD surface protein belonging to the tumor necrosis factor receptor family, is important in the resolution of all inflammatory immune responses. Objective: To test whether the expression of Fas receptor is defective in allergen-specific pulmonary T lymphocytes from persons with asthma. Design: 12-month prospective study. Setting: University allergy and immunology clinic. Patients: 12 untreated persons with newly diagnosed allergic asthma who underwent bronchoalveolar lavage. Ten normal persons served as controls. Measurements: Fas receptor expression was studied by using surface double-color cytofluorometry on pulmonary and circulating T lymphocytes. Fas messenger RNA (mRNA) was searched for in bronchoalveolar lavage cells from patients and controls by reverse transcription polymerase chain reaction (PCR). In vitro induction of DNA fragmentation, as an expression of cell death induced by an IgM anti-Fas monoclonal antibody, was assessed by propidium iodide staining and agarose gel electrophoresis. In vitro modulation of surface Fas receptor was studied on pulmonary T lymphocytes stimulated with anti-CD3 monoclonal antibody and interleukin-2 or interleukin-4. Results: Pulmonary T lymphocytes from patients as opposed to controls did not undergo DNA fragmentation after in vitro exposure to IgM anti-Fas. Other activation markers (CD25, HLA-DR, and CD45R0) were displayed, but surface Fas expression was always negative. A remarkable proportion of T cells from controls showed a clear double-staining pattern. Reverse transcription PCR for Fas mRNA yielded the same results. Circulating T lymphocytes from patients and controls included similar percentages of CD3 (+) Fas+ cells. Pulmonary T cells from both patients and controls showed upregulation of Fas receptor expression after in vitro anti-CD3 stimulation; co-culturing with interleukin-4 downmodulated surface Fas receptor expression on T cells from patients; it was less effective in controls. Conclusions: Hypoexpression of Fas mRNA and surface Fas receptor on pulmonary CD3+ T lymphocytes may explain the persistence of inflammatory cellular infiltrates in allergic bronchial asthma.
Absorption capacity of fructose in healthy adults. Comparison with sucrose and its constituent monosaccharides.
Authors: J J Rumessen, E Gudmand-Hoyer
Journal: Gut (1986)

The capacity to absorb fructose in 10 healthy adults was investigated by means of hydrogen breath analysis. Fructose absorption was quantified with lactulose standards. Significant hydrogen production (greater than or equal to 20 ppm rise of breath hydrogen) was found after challenge with 10% solutions of 50, 37.5, 25, 20, and 15 g fructose in eight, seven, five, four and one subjects, respectively. One subject showed malabsorption after a 10 g dose and possibly also 5 g fructose. In contrast, no malabsorption could be detected in any of the 10 subjects after ingestion of 100 g, 75 g, or 50 g sucrose or a mixture of 50 g glucose and 50 g fructose. After ingestion of mixtures of 50 g fructose +25 g glucose and 50 g fructose +12.5 g glucose malabsorption was present in three and seven subjects, respectively. Symptoms during all challenges were mild, or absent. It is concluded that in the healthy state the absorption capacity of fructose given alone ranges from less than 5 g to more than 50 g. The absorption capacity of fructose given as sucrose is much higher. Glucose stimulates fructose uptake in a dose dependent fashion. The possible existence of more than one intestinal transport system for fructose is considered. The elucidation of the clinical relevance of the findings is important.
Rtog 0436: A Phase III Trial of Cisplatin, Paclitaxel and Radiation with or Without Cetuximab in the Nonoperative Treatment of Esophageal Cancer
Authors: D. Ilson, K. Winter, M. Suntharalingham, A. Dicker, L. Kachnic, A. Konski, A. Chakravarthy, C. Anker, H. Thakrar, N. Horiba, V. Kavadi, J. Giguere, M. Deutsch, A. Raben, K. Roof, G. Videtic, J. Pollock, H. Safran, C. Crane
Journal: Annals of Oncology (2014)
Mitochondrial permeability transition pore opening during myocardial reperfusion—a target for cardioprotection
Authors: A Halestrap
Journal: Cardiovascular Research (2003)

Reperfusion of the heart after a period of ischaemia leads to the opening of a nonspecific pore in the inner mitochondrial membrane, known as the mitochondrial permeability transition pore (MPTP). This transition causes mitochondria to become uncoupled and capable of hydrolysing rather than synthesising ATP. Unrestrained, this will lead to the loss of ionic homeostasis and ultimately necrotic cell death. The functional recovery of the Langendorff-perfused heart from ischaemia inversely correlates with the extent of pore opening, and inhibition of the MPTP provides protection against reperfusion injury. This may be mediated either by a direct interaction with the MPTP [e.g., by Cyclosporin A (CsA) and Sanglifehrin A (SfA)], or indirectly by decreasing calcium loading and reactive oxygen species (ROS; key inducers of pore opening) or lowering intracellular pH. Agents working in this way may include pyruvate, propofol, Na+/H+ antiporter inhibitors, and ischaemic preconditioning (IPC). Mitochondrial KATP channels have been implicated in preconditioning, but our own data suggest that the channel openers and blockers used in these studies work through alternative mechanisms. In addition to its role in necrosis, transient opening of the MPTP may occur and lead to the release of cytochrome c and other proapoptotic molecules that initiate the apoptotic cascade. However, only if subsequent MPTP closure occurs will ATP levels be maintained, ensuring that cell death continues down an apoptotic, rather than a necrotic, pathway.
Growth Hormone and the Insulin-Like Growth Factor System in Myogenesis*
Authors: JAMES R. FLORINI, DAINA Z. EWTON, SHARON A. COOLICAN
Journal: Endocrine Reviews (1996)

THE general characterization of the growth hormone/insulin-like growth factor-I (GH/IGF-I) system has been established for a considerable length of time, and we will not repeat the many detailed descriptions of these proteins. Specifics of GH structure and general actions are presented in reviews such as those by Li (1) and by Laron (2). A later review (3) summarizes much of the early literature on biological effects of GH, with some emphasis on effects on isolated muscles. Carter-Su et al. (4, 5) have summarized more recent findings on the mechanisms of GH interactions with its receptor and subsequent intracellular signals; virtually all of this has been done in nonmuscle systems. The induction of hepatic IGF gene expression by GH has been well established for a long time, and we will not cover this area here, as we are concerned with actions of the IGFs rather than their secretion by liver. Information on the structures of the IGFs and their binding proteins, as well as their actions in nonmuscle systems, is presented in a number of recent comprehensive reviews (6–19). For this review, we simply specify that GH is a simple protein (containing only one intrachain S-S bond, and relatively unstable) of 22 kDa, and the IGFs (IGF-I and IGF-II) are single chains with three intrachain disulfides (and quite high stability in neutral or acid conditions) of about 7.5 kDa. In addition, six IGF-specific binding proteins (IGFBP-1 to -6) have been characterized. The IGFBPs include numerous disulfides and are remarkably stable, retaining substantial IGF-binding activity after precipitation with trichloroacetic acid and separation by SDS gel electrophoresis (10). A cartoon summarizing a current view of the GH/IGF system is presented in Fig. 1.
In vivo cartilage deformation after different types of activity and its dependence on physical training status
Authors: F Eckstein
Journal: Annals of the Rheumatic Diseases (2005)

Knowledge of the deformational behaviour of articular cartilage in vivo is required to understand the pathogenesis of osteoarthritis and the mechanical target environment of prospective cartilage transplant recipients.To study the in vivo deformational behaviour of patellar and femorotibial cartilage for different types of physiological activities; and to test the hypothesis that in vivo deformation of cartilage is modified by intense physical exercise.Magnetic resonance imaging and 3D digital image analysis were used to determine cartilage volume before and after physical activity in the patella of 12 volunteers (knee bends, squatting, normal gait, running, cycling). Deformation of femorotibial cartilage was investigated in 10 subjects (knee bends, static compression, high impact loading). Patellar cartilage deformation after knee bends was compared in seven professional weight lifters, seven sprinters, and 14 untrained volunteers.Patellar cartilage deformation was -5.9% after knee bends, -4.7% after squatting, -2.8% after normal walking, -5.0% after running, and -4.5% after cycling. The pattern of patellar cartilage deformation corresponded to the range of motion involved in the particular activity. Tibial cartilage deformation was greatest under high impact loading (-7%), but small for other activities. No significant difference was found between athletes and non-athletic controls.Patellar cartilage deformation shows a "dose dependent" response, where more intense loading leads to greater deformation. Relatively little deformation was observed in the femorotibial joint, except during high impact activities. The findings provide no evidence that adult human cartilage properties are amendable to training effects in vivo.
Re: Dominant Negative ATM Mutations in Breast Cancer Families
Authors: H. Lei
Journal: JNCI Journal of the National Cancer Institute (2002)

Breast cancer is the most frequent malignancy in women in the
world, with a cumulative lifetime risk estimated to be 10-12%.
Cytogenic and molecular genetic analyses of breast tumor cells
suggest that the development of human breast cancer involves
the accumulation of alterations in genes which normally serve
to control growth and differentiation. One type of this
alteration is loss of heterozygosity (LOH), which is detected
in many cases of breast cancer. LOH of tumor suppressor genes
are associated with cancerogenesis. Several studies have
indicated that the genes harbors on long arm of chromosome 11,
could be detected during tumorogenesis. Deletions at 11q23 were
detected in variety of human neoplasma, including breast. In
this region can be harbor at least one tumor suppressor gene,
which is inactivated during the establishment or progression of
several types of tumors. Evidence for the existence of a tumor
suppresor gene(s) in this region came from the observation that
tumorgenicity of the MCF-7 cell line is inhibited by the
introduction of the segment 11q13-q23 of the normal human
chromosome 11. One of the candidate gene is A-T
(ataxia-teleangiectasia) gene, located at chromosomal region
11q22-q23. Patients carrying two mutant alleles (ATM) and
affected by A-T a 100-fold higher risk of developing cancer,
moustly leukemias and lymphomas, than unaffected age-matched
subjects. Heterozygous A-T carriers have a 3,1 and 2,3 (females
and males) fold increases risk of cancer, in particular breast
cancer, compared to the normal population. IT is estimated,
that asuch as 8% of sporadic breast cancer could possibly
develop in carriers of ATM gene predisposition mutations. It
seems that inherited mutations in ATM gene are responsible for
a certain proportion of breast cancer cases, and that LOH of
other allele will unmask such a recessive mutation. The ATM
gene spans - 150kb genomic sequence and contains 66 exons. It
is expressed as 12 kb transcript in all tissues and cell types.
This gene is implicated in cell cycle regulation, control of
telomere length, and response to DNA danage. The enzyme
cooperates with many protein in cell. Its inactivation could be
influenced repair process in cell. We interested in catalytic
domain as candidate region for inactivation of kinase activity.
This part of protein corresponds with last 16 exons on DNA of
this gene. Tumor DNA from 42 patients with primary breast
cancer were studied. This samples were choosen after analyzed
for lost of one alele (part of chromosome) in region 11q22-q23
by methods which detected polymorphic makers on pair of
chromosomes. For LOH detection we used SSCP (single-strand
conformation polymorphism) and silver staining method. We did
not found any unique SSCP variants.
Comment on Steck et al. Early Hyperglycemia Detected by Continuous Glucose Monitoring in Children at Risk for Type 1 Diabetes. Diabetes Care 2014;37:2031–2033
Authors: Davide Brancato, Vincenzo Provenzano
Journal: Diabetes Care (2015)

We read with great interest the article by Steck et al. (1) demonstrating that continuous glucose monitoring (CGM) can detect early hyperglycemia in children with positive islet autoantibodies (Ab+) who are at high risk for type 1 diabetes. In fact, the CGM data derived from the group of five subjects who developed type 1 diabetes (Ab+ progressors) showed more impaired glycemia, with percentage of time spent above 140 mg/dL of 31% compared with 12% in Ab+ nonprogressors; Ab+ progressors also had larger SD and …
Drug-related deaths
Authors: R. H. De Jong
Journal: JAMA (1977)

In this issue, members of the Boston Collaborative Drug Surveillance Program report on 24 drug-related deaths in hospitalized medical patients. The five-year study monitored more than 26,000 acutely ill patients, spanning seven countries. In this sense, the report represents an overview of therapeutic practices, and their attendant hazards, in the Western world.  A death rate of nearly one per thousand (0.9 per 1,000, to be exact) may seem disquietingly high at first sight. A closer look at the study protocol, however, makes it clear that the outlook isn't all that bleak. For one, the five deaths from intravenous fluid overload weight the data unfavorably, inasmuch as the drug (ie, water plus additives) is less at fault than the mode of administration (ie, too much, too fast).  Then too, the majority of drug-related deaths occurred in patients so sick as to require hospital admission; and of these, most were severely or