tbuckley/cabot-search huggingface dataset:
Hospital-acquired pneumonia: coverage and treatment adequacy of current guidelines
Authors: M. Ioanas, M. Cavalcanti, M. Ferrer, M. Valencia, C. Agusti, J. Puig de la Bellacasa, A. Torres
Journal: European Respiratory Journal (2003)

The American Thoracic Society (ATS) guideline for hospital-acquired pneumonia (HAP) released in 1996 and the Trouillet classification published in 1998 supply different rational foundations for the classification of patients with HAP and for the selection of initial antibiotic therapy. The aims of this study were to assess the level of bacterial coverage and to assess and validate the adequacy of antibiotic strategy of each of these classifications. Intensive care unit-admitted patients (n=71) with suspicion of HAP were evaluated. The ATS and Trouillet classifications demonstrated an accuracy to predict the causative microorganism of 91% and 83% respectively. The ATS and Trouillet antibiotic treatment recommendations were adequate in 79% and 80% of the patients, respectively. The microorganisms implicated in the treatment inadequacy of the ATS guideline were Pseudomonas aeruginosa (n=3), Acinetobacter baumanii (n=1), Stenotrophomonas maltophilia (n=1) and methicillin-resistant Staphylococcus aureus (n=1). P. aeruginosa was implicated with Trouillet treatment inadequacy. The current recommendations for empirical antibiotic treatment of hospital-acquired pneumonia (American Thoracic Society and Trouillet) showed a good ability to predict the involved pathogen. However, considering the resistance pattern of the isolated pathogens, both classifications demonstrated a rather lower treatment adequacy; the main reason was the failure to treat highly resistant strains.
Vasoactive Potential of the B <sub>1</sub> Bradykinin Receptor in Normotension and Hypertension
Authors: Irena Duka, Ekaterina Kintsurashvili, Irene Gavras, Conrado Johns, Margaret Bresnahan, Haralambos Gavras
Journal: Circulation Research (2001)

Abstract —The B 1 type receptor of bradykinin (Bk B 1 R) is believed to be physiologically inert but highly inducible by inflammatory mediators and tissue damage. To explore the potential participation of the Bk B 1 R in blood pressure (BP) regulation, we studied mice with deleted Bk B 2 R gene with induced experimental hypertension, either salt-dependent (subtotal nephrectomy with 0.5% NaCl as drinking water) or renin/angiotensin-dependent (renovascular 2-kidney–1-clip). Compared with the wild-type controls, the B 2 R gene knockout mice had a higher baseline BP (109.7±1.1 versus 101.1±1.3 mm Hg, P =0.002), developed salt-induced hypertension faster (in 19.3±2.3 versus 27.7±2.4 days, P =0.024), and had a more severe end point BP (148±3.7 versus 133±3.1 mm Hg, P &lt;0.05). On the contrary, renovascular hypertension developed to the same extent (149.7±4.3 versus 148±3.6 mm Hg) and in the same time frame (14±2.2 versus 14±2.1 days). A bolus infusion of a selective B 1 R antagonist at baseline produced a significant hypertensive response (by 11.4±2 mm Hg) in the knockout mice only. Injection of graded doses of a selective B 1 R agonist produced a dose-dependent hypotensive response in the knockout mice only. Assessment of tissue expression of B 1 R and B 2 R genes by reverse transcription–polymerase chain reaction techniques revealed significantly higher B 1 R mRNA levels in the B 2 R knockout mice at all times (normotensive baseline and hypertensive end points). At the hypertensive end points, there was always an increase in B 1 R gene expression over the baseline values. This increase was significant in cardiac and renal tissues in all hypertensive wild-type mice but only in the clipped kidney of the renovascular knockout mice. The B 2 R gene expression in the wild-type mice remained unaffected by experimental manipulations. These results confirm the known vasodilatory and natriuretic function of the Bk B 2 R; they also indicate that in its absence, the B 1 R can become upregulated and assume some of the hemodynamic properties of the B 2 R. Furthermore, they indicate that experimental manipulations to produce hypertension also induce upregulation of the B 1 R, but not the B 2 R, in cardiac and renal tissues.
Associated Alterations of Striatal Dopamine D<sub>2</sub>/D<sub>3</sub>Receptor and Transporter Binding in Drug-Naive Patients With Schizophrenia: A Dual-Isotope SPECT Study
Authors: Yen Kuang Yang, Lung Yu, Tzung Lieh Yeh, Nan Tsing Chiu, Po See Chen, I Hui Lee
Journal: American Journal of Psychiatry (2004)

In vivo imaging studies have revealed deregulated presynaptic or postsynaptic function of the midbrain dopaminergic system in patients with schizophrenia. To further delineate the neuropathological involvement of the presynaptic and postsynaptic dopamine neurons in schizophrenia, the authors examined brain D(2)-family receptor and dopamine transporter binding simultaneously in patients with drug-naive schizophrenia using the dual-isotope single photon emission computed tomography (SPECT) imaging technique.Eleven patients with schizophrenia and 12 healthy comparison subjects were recruited. Striatal dopamine D(2)/D(3) receptor was measured with SPECT and [(123)I]iodobenzamide ([(123)I]IBZM), while dopamine transporter was measured with SPECT and [(99m)Tc]TRODAT-1.Striatal D(2)/D(3) receptor and dopamine transporter binding were unaltered in these drug-naive patients with schizophrenia. Nonetheless, D(2)/D(3) receptor binding measures were positively correlated with dopamine transporter binding measures in these patients but not in the comparison subjects.The associated presynaptic and postsynaptic disturbances of midbrain dopamine neurons could be clinically relevant in drug-naive patients with schizophrenia.
Ethical, Legal, and Counseling Challenges Surrounding the Return of Genetic Results in Oncology
Authors: Martijn P. Lolkema, Christa G. Gadellaa-van Hooijdonk, Annelien L. Bredenoord, Peter Kapitein, Nancy Roach, Edwin Cuppen, Nine V. Knoers, Emile E. Voest
Journal: Journal of Clinical Oncology (2013)

In the last decade, an overwhelming number of genetic aberrations have been discovered and linked to the development of treatment for cancer. With the rapid advancement of next-generation sequencing (NGS) techniques, it is expected that large-scale DNA analyses will increasingly be used to select patients for treatment with specific anticancer agents. Personalizing cancer treatment has many advantages, but sequencing germline DNA as reference material for interpreting cancer genetics may have consequences that extend beyond providing cancer care for an individual patient. In sequencing germline DNA, mutations may be encountered that are associated with increased susceptibility not only to hereditary cancer syndromes but also to other diseases; in those cases, disclosing germline data could be clinically relevant and even lifesaving. In the context of personal autonomy, it is necessary to develop an ethical and legal framework for how to deal with identified hereditary disease susceptibilities and how to return the data to patients and their families. Because clear legislation is lacking, we need to establish guidelines on disclosure of genetic information and, in the process, we need to balance privacy issues with the potential advantages and drawbacks of sharing genetic data with patients and their relatives. Importantly, a strong partnership with patients is critical for understanding how to maximize the translation of genetic information for the benefit of patients with cancer. This review discusses the ethical, legal, and counseling issues surrounding disclosure of genetic information generated by NGS to patients with cancer and their relatives. We also provide a framework for returning these genetic results by proposing a design for a qualified disclosure policy.
Response to immunization with Haemophilus influenzae type b polysaccharide-pertussis vaccine and risk of Haemophilus meningitis in children with the Km(1) immunoglobulin allotype.
Authors: D M Granoff, J P Pandey, E Boies, J Squires, R S Munson, B Suarez
Journal: Journal of Clinical Investigation (1984)

In experimental animals, immune responses to certain antigens are regulated by immunoglobulin allotype-linked genes. In an effort to detect such genes in humans, we examined the antibody responses of 74 healthy children with different Km(1) or Gm(23) allotypes to a Haemophilus influenzae type b vaccine (type b polysaccharide capsule-pertussis vaccine). The anticapsular antibody responses of black or white children with the Km(1) allotype were 4.6- to 9.5-fold higher than those of children who lacked this determinant (P less than 0.004). No significant differences were found in antibody response with respect to the Gm(23) allotype. The frequencies of Km(1) and Gm(23) also were examined in 170 patients with Haemophilus meningitis, 71 patients with epiglottitis, and 173 control children. Km(1) was detected less frequently in black patients with meningitis (38%) than in those with epiglottitis (81%, P less than 0.002) or in controls (66%, P less than 0.0007). The relative risk of meningitis thus was 3.2-fold lower among black children with the Km(1) allotype than in those who lacked this allotype (odds ratio = 0.3, 95% confidence interval 0.2 to 0.6). However, the risk of meningitis was not decreased in white children with the Km(1) allotype (odds ratio = 1.0). There were no significant differences in the frequency of Gm(23) among the patient groups and controls. The Km(1) allotype but not the Gm(23) thus defines a subpopulation of children of both races who are high responders to this vaccine, and black children but not white children with the Km(1) allotype are at decreased risk of developing Haemophilus meningitis. These data indicate that in blacks, genes associated with Km(1) may affect immune response to a prototype type b Haemophilus vaccine, and perhaps interact with another factor related to race to affect susceptibility to Haemophilus meningitis.
Narrative Review: Lack of Evidence for Recommended Low-Density Lipoprotein Treatment Targets: A Solvable Problem
Authors: Rodney A. Hayward, Timothy P. Hofer, Sandeep Vijan
Journal: Annals of Internal Medicine (2006)

Recent national recommendations have proposed that physicians should titrate lipid therapy to achieve low-density lipoprotein (LDL) cholesterol levels less than 1.81 mmol/L (<70 mg/dL) for patients at very high cardiovascular risk and less than 2.59 mmol/L (<100 mg/dL) for patients at high cardiovascular risk. To examine the clinical evidence for these recommendations, the authors sought to review all controlled trials, cohort studies, and case-control studies that examined the independent relationship between LDL cholesterol and major cardiovascular outcomes in patients with LDL cholesterol levels less than 3.36 mmol/L (<130 mg/dL). For those with LDL cholesterol levels less than 3.36 mmol/L (<130 mg/dL), the authors found no clinical trial subgroup analyses or valid cohort or case-control analyses suggesting that the degree to which LDL cholesterol responds to a statin independently predicts the degree of cardiovascular risk reduction. Published studies had avoidable limitations, such as a reliance on ecological (aggregate) analyses, use of analyses that ignore statins' other proposed mechanisms of action, and failure to account for known confounders (especially healthy volunteer effects). Clear, compelling evidence supports near-universal empirical statin therapy in patients at high cardiovascular risk (regardless of their natural LDL cholesterol values), but current clinical evidence does not demonstrate that titrating lipid therapy to achieve proposed low LDL cholesterol levels is beneficial or safe.
Does exercise training during pregnancy affect gestational age? A randomised controlled trial
Authors: R Barakat, J R Stirling, A Lucia
Journal: British Journal of Sports Medicine (2008)

Background: Some controversy exists over the possibility that exercise during pregnancy might increase the risk of preterm delivery. Objective: This study aimed to determine the possible cause–effect relationship between regular exercise performed during the second and third trimesters of pregnancy by previously sedentary, healthy gravidae and gestational age at the moment of delivery. Methods: Caucasian (Spanish) women with singleton gestation were assigned to either a training (n = 72) or a control (n = 70) group. The supervised training programme focused mainly on very light resistance and toning exercises and included ∼80 sessions (three times/week, 35 min/session from weeks 12–13 to weeks 38–39 of pregnancy). Results: No significant differences were found (p&gt;0.05) between the groups in those maternal characteristics (age, smoking habits, number of hours standing or prior parity history) that could potentially influence gestational age. The mean gestational age did not differ (p = 0.745) between the training (39 weeks,3 days (SD 1 day)) and the control group (39 weeks,4 days (SD 1 day)). Conclusions: Previously sedentary, healthy gravidae with singleton gestation can safely engage in moderate, supervised exercise programmes until the end of gestation as this would not affect gestational age.
Brief Physician-Initiated Quit-Smoking Strategies for Clinical Oncology Settings: A Trial Coordinated by the Eastern Cooperative Oncology Group
Authors: Robert A. Schnoll, Bin Zhang, Montserrat Rue, James E. Krook, Wayne T. Spears, Alfred C. Marcus, Paul F. Engstrom
Journal: Journal of Clinical Oncology (2003)

Although tobacco use by cancer patients increases the risk of relapse, diminishes treatment efficacy, and worsens quality of life, about one third of patients who smoked before their diagnosis continue to smoke. Because patients have regular contact with oncologists, the efficacy of a physician-based smoking cessation treatment was evaluated.Cancer patients (n = 432) were randomly assigned to either usual care or a National Institutes of Health (NIH) physician-based smoking intervention. The primary outcome was 7-day point prevalence abstinence at 6 and 12 months after study entry.At the 6-month follow-up, there was no significant difference in quit rates between the usual care (11.9%) and intervention (14.4%) groups, and there was no significant difference between the usual care (13.6%) and intervention (13.3%) groups at the 12-month follow-up. Patients were more likely to have quit smoking at 6 months if they had head and neck or lung cancer, began smoking after the age of 16, reported at baseline using a cessation self-help guide or treatment in the last 6 months, and showed greater baseline desire to quit. Patients were more likely to have quit smoking at 12 months if they smoked 15 or fewer cigarettes per day, had head and neck or lung cancer, tried a group cessation program, and showed greater baseline desire to quit. Finally, there was greater adherence among physicians to the NIH model for physician smoking treatment for patients in the intervention versus the usual care group.While training physicians to provide smoking cessation treatment to cancer patients can enhance physician adherence to clinical practice guidelines, physician smoking cessation interventions fail to yield significant gains in long-term quit rates among cancer patients.
Collagen deposition in liver disease
Authors: J. OD. McGee
Journal: Annals of the Rheumatic Diseases (1977)

Collagen forms a small component of the total protein of normal liver, but in diseases which lead to cirrhosis and in cirrhosis itself it is deposited in large amounts throughout the organ.This leads to structural disruption of normal liver architecture (Fig. 1).The effects of this are the creation of portosystemic shunts within the liver (Hase, 1968) and perhaps the formation of a connective tissue diffusion barrier in the space of Disse between hepatocytes and their vascular supply.This paper presents evidence that collagen deposition in liver disease is due, at least in part, to increased collagen synthesis.Those liver cells which are responsible for collagen synthesis and the regulation of the synthesis of this protein in the diseased liver are also briefly discussed.FIG. 1 Percutaneous needle biopsy of liver showing alcoholic cirrhosis with pronounced connective tissue deposition throughout the liver parenchyma.Reticulin stain.
Possible Role of Brain-Derived Neurotrophic Factor in the Pathogenesis of Coronary Artery Disease
Authors: Junya Ejiri, Nobutaka Inoue, Seiichi Kobayashi, Rio Shiraki, Kazunori Otsui, Tomoyuki Honjo, Motonori Takahashi, Yoshitaka Ohashi, Shinobu Ichikawa, Mitsuyasu Terashima, Takao Mori, Kojiro Awano, Toshiro Shinke, Junya Shite, Ken-ichi Hirata, Hiroshi Yokozaki, Seinosuke Kawashima, Mitsuhiro Yokoyama
Journal: Circulation (2005)

The neurotrophin (NT) family, including nerve growth factor NT-3 and brain-derived neurotrophic factor (BDNF), has a critical role in the survival, growth, maintenance, and death of central and peripheral neurons. NTs and their receptors are expressed in atherosclerotic lesions; however, their significance in cardiovascular disease remains unclear.To clarify the role of NTs in the pathogenesis of coronary artery disease, NT plasma levels in the aorta, coronary sinus, and peripheral veins of patients with unstable angina (n=38), stable effort angina (n=45), and non-coronary artery disease (n=24) were examined. In addition, regional expression of BDNF in coronary arteries was examined in autopsy cases and patients with angina pectoris by directional coronary atherectomy. The difference in BDNF levels, but not NT-3, between the coronary sinus and aorta was significantly greater in the unstable angina group compared with the stable effort angina and non-coronary artery disease groups. Immunohistochemical investigations demonstrated BDNF expression in the atheromatous intima and adventitia in atherosclerotic coronary arteries. BDNF expression was enhanced in macrophages and smooth muscle cells in atherosclerotic coronary arteries. Stimulation with recombinant BDNF significantly enhanced NAD(P)H oxidase activity and the generation of reactive oxygen species in cultured human coronary artery smooth muscle cells.BDNF has an important role in atherogenesis and plaque instability via the activation of NAD(P)H oxidase.
Manganese Superoxide Dismutase Enhances the Invasive and Migratory Activity of Tumor Cells
Authors: Kip M. Connor, Nadine Hempel, Kristin K. Nelson, Ganary Dabiri, Aldo Gamarra, James Belarmino, Livingston Van De Water, Badar M. Mian, J. Andres Melendez
Journal: Cancer Research (2007)

Abstract Clinically significant elevations in the expression of manganese superoxide dismutase (Sod2) are associated with an increased frequency of tumor invasion and metastasis in certain cancers. The aim of this study was to examine whether increases in Sod2 activity modulate the migratory potential of tumor cells, contributing to their enhanced metastatic behavior. Overexpression of Sod2 in HT-1080 fibrosarcoma cells significantly enhanced their migration 2-fold in a wound healing assay and their invasive potential 3-fold in a transwell invasion assay. Severity of invasion was directly correlated to Sod2 expression levels and this invasive phenotype was similarly observed in 253J bladder tumor cells, in which Sod expression resulted in a 3-fold increase in invasion compared with controls. Further, migration and invasion of the Sod2-expressing cells was inhibited following overexpression of catalase, indicating that the promigratory/invasive phenotype of Sod2-expressing cells is H2O2 dependent. Sod2 overexpression was associated with a loss of vinculin-positive focal adhesions that were recovered in cells coexpressing catalase. Tail vein injections of Sod2-GFP–expressing HT-1080 cells in NCR nude mice led to the development of pulmonary metastatic nodules displaying high Sod2-GFP expression. Isolated tumors were shown to retain high Sod2 activity in culture and elevated levels of the matrix degrading protein matrix metalloproteinase-1, and a promigratory phenotype was observed in a population of cells growing out from the tumor nodule. These findings suggest that the association between increased Sod2 activity and poor prognosis in cancer can be attributed to alterations in their migratory and invasive capacity. [Cancer Res 2007;67(21):10260–67]
Interferon Effect on Cytotoxicity of Peripheral Blood and Tumor-Associated Lymphocytes Against Human Ovarian Carcinoma Cells&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: Paola Allavena, Martino Introna, Cristiana Sessa, Costantino Mangioni, Alberto Mantovani
Journal: JNCI Journal of the National Cancer Institute (1982)

A study was done to investigate the tumoricidal activity of peripheral blood lymphocytes (PBL) and tumor-associated lymphoid cells (TAL) against freshly isolated tumor cells in human ovarian carcinoma. TAL and carcinoma cells were purified by density and velocity sedimentation on discontinuous Ficoll-Hypaque gradients and fetal bovine serum. Purified carcinoma cells from 23 ascitic and 3 solid tumors were used as targets in a 4- or a 20-hour 51Cr release assay. K562 cells were used to measure natural killer (NK) activity. Freshly purified ovarian carcinoma cells were relatively resistant to lysis by normal unstimulated PBL. Cytolytic activity of ovarian cancer PBL and TAL did not exceed that of control PBL: Only one PBL preparation had high levels of cytotoxicity (36.2 and 42.9% specific lysis after 4 and 20 hr at an effector-to-target cell ratio of 50:1) against autologous cancer cells but not against allogeneic targets (<5% specific lysis). TAL and, to a lesser extent, ovarian cancer PBL showed impaired NK activity against K562 compared to the activity seen in controls. In vitro exposure to partially purified human fibroblast interferon (IFN) (1,000 U/ ml for 1–18 hr) augmented NK activity against K562 of PBL and TAL. When ovarian carcinoma cells were used as targets, IFN enhanced the cytotoxicity of normal PBL in a 4- and 20-hour assay; stimulation by IFN was less frequently observed with ovarian cancer PBL and TAL in a 4-hour assay, but after 20 hours effector cells from tumor-bearing subjects showed IFN-boosted cytotoxicity against carcinoma cells similar to the degree of cytotoxicity seen in controls. IFN enhanced the cytotoxicity of PBL and TAL against both autologous and allogeneic carcinoma cells. Thus PBL and TAL are rarely cytotoxic against 51Cr-labeled fresh autologous carcinoma cells, but in vitro exposure to IFN induced low levels of killing of ovarian tumor cells.
Biomarkers for determining the prognosis in chronic myelogenous leukemia
Authors: Kendra Sweet, Ling Zhang, Javier Pinilla-Ibarz
Journal: Journal of Hematology & Oncology (2013)

Abstract The introduction of BCR-ABL1 tyrosine kinase inhibitors (TKIs) for treatment of chronic myelogenous leukemia in chronic phase (CML-CP) has revolutionized therapy, altering the outcome from one of shortened life expectancy to long-term survival. With over 10 years of long-term treatment with imatinib and several years of experience with the next generation of TKIs, including nilotinib, dasatinib, bosutinib, and ponatinib, it is becoming clear that many clinical parameters have great impact on the prognosis of patients with CML. Emerging novel gene expression profiling and molecular techniques also provide new insights into CML pathogenesis and have identified potential prognostic markers and therapeutic targets. This review presents the supporting data and discusses how certain clinical characteristics at diagnosis, the depth of early response, the presence of certain kinase domain mutations, and additional molecular changes serve as prognostic factors that may guide individualized treatment decisions for patients with CML-CP.