tbuckley/cabot-search huggingface dataset:
A Novel and Rapid Whole-Blood Assay for D-Dimer in Patients With Clinically Suspected Deep Vein Thrombosis
Authors: Philip S. Wells, Patrick Brill-Edwards, Pamela Stevens, Akbar Panju, Ameen Patel, James Douketis, M. Patricia Massicotte, Jack Hirsh, Jeffrey I. Weitz, Clive Kearon, Jeffrey S. Ginsberg
Journal: Circulation (1995)

Background The clinical utility of using a novel whole blood assay for D-dimer (SimpliRED), alone or in combination with impedance plethysmography (IPG), was investigated in a two-center, prospective cohort study of 214 consecutive patients with clinically suspected deep vein thrombosis (DVT). Methods and Results All patients underwent the SimpliRED D-dimer assay, contrast venography, and IPG. According to the results of venography, 43 patients had proximal DVT (popliteal and/or more proximal veins), 10 had isolated calf DVT, and 161 had DVT ruled out. The D-dimer had a sensitivity of 93% for proximal DVT and of 70% for calf DVT, an overall specificity of 77%, and a negative predictive value of 98% for proximal DVT. The sensitivity and specificity of IPG for proximal DVT were 67% and 96%, respectively. When analyzed in combination with the IPG results, it was determined that (1) the combination of a negative D-dimer and a normal IPG had a negative predictive value of 97% for all DVT and of 99% for proximal DVT and occurred in 58% of patients (likelihood ratio, 0.1) and (2) the combination of a positive D-dimer and an abnormal IPG had a positive predictive value of 93% for any DVT and of 90% for proximal DVT and occurred in 14% of patients (likelihood ratio, 42.6). When the D-dimer and IPG results were discordant, it was not possible to exclude or diagnose DVT reliably; discordant results occurred in 28% of patients. Conclusions The SimpliRED D-dimer assay, which can be performed and interpreted at the bedside within 5 minutes, has great potential in patients with clinically suspected DVT, especially for ruling out DVT, and is complementary to IPG. The assay should be evaluated in large clinical management studies.
Genetic Testing in an Ethnically Diverse Cohort of High-Risk Women
Authors: Rita Nanda, L. Philip Schumm, Shelly Cummings, James D. Fackenthal, Lise Sveen, Foluso Ademuyiwa, Melody Cobleigh, Laura Esserman, Noralane M. Lindor, Susan L. Neuhausen, Olufunmilayo I. Olopade
Journal: JAMA (2005)

Ten years after BRCA1 and BRCA2 were first identified as major breast cancer susceptibility genes, the spectrum of mutations and modifiers of risk among many ethnic minorities remain undefined.To characterize the clinical predictors, spectrum, and frequency of BRCA1 and BRCA2 mutations in an ethnically diverse high-risk clinic population and to evaluate the performance of the BRCAPRO statistical model in predicting the likelihood of a mutation.Comparative analysis of families (white, Ashkenazi Jewish, African American, Hispanic, Asian) with 2 or more cases of breast and/or ovarian cancer among first- and second-degree relatives. Families were identified at US sites between February 1992 and May 2003; in each family, the individual with the highest probability of being a mutation carrier was tested.Frequency of BRCA1 and BRCA2 mutations and area under the receiver operating characteristic curve for the BRCAPRO model.The mutation spectrum was vastly different between families of African and European ancestry. Compared with non-Hispanic, non-Jewish whites, African Americans had a lower rate of deleterious BRCA1 and BRCA2 mutations but a higher rate of sequence variations (27.9% vs 46.2% and 44.2% vs 11.5%; P<.001 for overall comparison). Deleterious mutations in BRCA1 and BRCA2 were highest for Ashkenazi Jewish families (69.0%). Early age at diagnosis of breast cancer and number of first- and second-degree relatives with breast and ovarian cancer were significantly associated with an increased likelihood of carrying a BRCA1 or BRCA2 mutation. In discriminating between mutation carriers, BRCAPRO performed as well in African American families as it did in white and Jewish families, with an area under the curve of 0.77 (95% confidence interval, 0.61-0.88) for African American families and 0.70 (95% confidence interval, 0.60-0.79) for white and Jewish families combined.These data support the use of BRCAPRO and genetic testing for BRCA1 and BRCA2 mutations in the management of high-risk African American families. Irrespective of ancestry, early age at diagnosis and a family history of breast and ovarian cancer are the most powerful predictors of mutation status and should be used to guide clinical decision making.
Mouse and computational models link Mlc2v dephosphorylation to altered myosin kinetics in early cardiac disease
Authors: Farah Sheikh, Kunfu Ouyang, Stuart G. Campbell, Robert C. Lyon, Joyce Chuang, Dan Fitzsimons, Jared Tangney, Carlos G. Hidalgo, Charles S. Chung, Hongqiang Cheng, Nancy D. Dalton, Yusu Gu, Hideko Kasahara, Majid Ghassemian, Jeffrey H. Omens, Kirk L. Peterson, Henk L. Granzier, Richard L. Moss, Andrew D. McCulloch, Ju Chen
Journal: Journal of Clinical Investigation (2012)

Actin-myosin interactions provide the driving force underlying each heartbeat. The current view is that actin-bound regulatory proteins play a dominant role in the activation of calcium-dependent cardiac muscle contraction. In contrast, the relevance and nature of regulation by myosin regulatory proteins (for example, myosin light chain-2 [MLC2]) in cardiac muscle remain poorly understood. By integrating gene-targeted mouse and computational models, we have identified an indispensable role for ventricular Mlc2 (Mlc2v) phosphorylation in regulating cardiac muscle contraction. Cardiac myosin cycling kinetics, which directly control actin-myosin interactions, were directly affected, but surprisingly, Mlc2v phosphorylation also fed back to cooperatively influence calcium-dependent activation of the thin filament. Loss of these mechanisms produced early defects in the rate of cardiac muscle twitch relaxation and ventricular torsion. Strikingly, these defects preceded the left ventricular dysfunction of heart disease and failure in a mouse model with nonphosphorylatable Mlc2v. Thus, there is a direct and early role for Mlc2 phosphorylation in regulating actin-myosin interactions in striated muscle contraction, and dephosphorylation of Mlc2 or loss of these mechanisms can play a critical role in heart failure.
Phase I trial of taxol given as a 24-hour infusion every 21 days: responses observed in metastatic melanoma.
Authors: P H Wiernik, E L Schwartz, A Einzig, J J Strauman, R B Lipton, J P Dutcher
Journal: Journal of Clinical Oncology (1987)

Taxol, a plant product, has significant activity against certain rodent and human xenograft tumors. It promotes microtubule assembly in vitro, in contrast to vinca alkaloids, which inhibit assembly. In this phase I study, taxol was administered as a 24-hour continuous intravenous (IV) infusion in 65 courses to 26 patients. A premedication regimen of dexamethasone, cimetidine, and diphenhydramine was used to prevent the acute hypersensitivity reactions observed in previous studies of taxol. Only one episode of mild stridor occurred in this study. Peripheral neuropathy was the dose-limiting toxicity and was observed in 40% of patients treated at a dose of 250 mg/m2. Significant neutropenia of brief duration was also common. Pharmacokinetic studies by a high-performance liquid chromatography (HPLC) method demonstrated that drug plasma concentrations increased during the 24-hour infusion and then declined rapidly. Peak plasma concentrations correlated with dose, and less than 5% of taxol was excreted in the urine. Most of the drug was bound to serum components. Partial responses of more than 3 months' duration were observed in four of 12 melanoma patients treated. The recommended phase II dose of taxol on this schedule is 250 mg/m2. Priority should be given to the study of taxol in melanoma.
Contribution and Risks of Left Ventricular Endomyocardial Biopsy in Patients With Cardiomyopathies
Authors: Cristina Chimenti, Andrea Frustaci
Journal: Circulation (2013)

Background— Use of left ventricular (LV) endomyocardial biopsy (EMB) to investigate cardiomyopathies is currently discouraged because it is considered riskier than and as contributive as right ventricular (RV) biopsy. The aim of our study is to report our experience with this option and to discuss its advantages and disadvantages. Methods and Results— In our center from 1983 to 2010, 4221 patients underwent diagnostic EMB. In particular, 2396 (56.8%) underwent biventricular EMB, 1153 (27.3%) underwent selective LVEMB, and 672 (15.9%) underwent selective RVEMB. The rate of complications and histological findings were retrospectively analyzed. The periprocedural major complication rate (perforation with or without cardiac tamponade, embolization) was 0.33% for LVEMB and 0.45% for RVEMB, with a significant decrease in the rate of major complications with time (from 1.6% and 1.9% in 1983–1988 to 0% and 0.3% in 2007–2013, respectively; P &lt;0.001 for both), denoting a steep learning curve. No patients died. When the structural and functional abnormalities affected exclusively the LV, the diagnostic yield of LVEMB was 97.8% compared with 53% for RVEMB. Conversely, when the echocardiographic presence of increased wall thickness, local or global ventricular dilation, or dysfunction also involved the RV, the diagnosis was reached in 98.1% of LVEMBs and 96.5% of RVEMBs. This discrepancy was particularly evident for myocarditis, whereas in infiltrative and storage diseases, the histological abnormalities were always detectable in both ventricles. Conclusions— LVEMB is a safe procedure with very low transient complications, comparable to RVEMB. It appears diagnostically more contributive than RVEMB in patients with cardiomyopathies and clinically preserved RV.
TREATMENT OF ASTHMA BY RADIATION
Authors: S. G. Scott
Journal: BMJ (1929)

TIrI JOUBRN 9 b)owel, anid miiay even be absenit in acute obstruction of the nsinall intestinee wvlien ganigrenie quickly followN-s obstruction it is niot ai constant syniptoini in the ruptlure of ani ectopic gestation.ATauisea is more constant, but niot so strikinig a snipt'tonm.Di.stelsiono muist never be waited for, and slhould not be presenit in the early stages excelt in obstruction of the large intestine.I well rememiber a man being sent to St. Mary's Hospital some years ago by a doctor who 'Wrote:Last niglht 1 thoughlt this mani very likely had a per- for-ated ulcer, but he was niot distended, so I left him alonie; this miiorninig le is distended, so I send hillm up to vont.''Alteration of the pulse rate is of value when noted, but nearly 1evefy kind of acute abdominal disorder may be epiesent without an appreciable alteration of the pulse.In some of the acute colics the pulse may be slowed; in p)erforated gastric or duodenal ulcer the pulse after two or thlree lhourI's generally becomlies quite normal; in intestinal obstruction of either the small or-large intestine the pulse is frequently normal or slowed unitil toxaemia begins or unless there is severe shock oni accouint of str angulation.In appendicitis I expect to filnd a noormal pulse, unless (a) there is comnmencing l)eritonitis, or (b) the appendix is distended with toxic material.I liave even known a niormal pulse with acute pancreatitis, tlhough I must admit that this is very exceptional.1. need hardly dwell on the rr(li(Ibility of temperature in acute abdominal disease.A drop of several degrees accom- panied by acute pain in the abdomiieni at once proclaims the occurr-ence of a catastrophe, however quickly the patient may regain a normal appearalice.But many conditions cause no fall in temperature.Fever is absent in the acute obstructions, is moderate in amnount and rather slow in onset in the peritoneal inflammations, and is high only in those conditions where infection is ocecurring in small cavities such as tho pelvis of thte ki(dney and the biliary duicts.I imiake it a rule, in any case of acuite abdomen witlh .aeimperature of 1040 or 105°to turni first to the kidneys and thlien to thie lulngs aid l)leura.C(OIstipa-tion is too vague a syinptoni to be of muhelulse in early diagnosis.The same remark applies to furred tougue, though it is often p)ossible to lear-n a lot by looking at the tongue.
Comprehensive mapping of HLA-A*0201-restricted CD8 T-cell epitopes on PDC-E2 in primary biliary cirrhosis
Authors: Shuji Matsumura, Hiroto Kita, Xiao-Song He, Aftab A. Ansari, Zhe-Xiong Lian, Judy van de Water, Kazuhide Yamamoto, Takao Tsuji, Ross L. Coppel, Marshall Kaplan, Eric M. Gershwin
Journal: Hepatology (2002)

Growing evidence has implicated the involvement of autoreactive T lymphocytes in the pathogenesis of primary biliary cirrhosis (PBC). We have recently taken advantage of motif prediction analysis of HLA-A*0201 and identified the first major histocompatibility complex (MHC) class I restricted epitope, amino acids 159 to 167 on E2 components of pyruvate dehydrogenase complexes (PDC-E2), the major mitochondrial antigens in PBC. The mechanisms involved in the selection of epitope peptide(s) that comprise the PDC-E2-specific autoreactive cytotoxic T lymphocytes (CTLs) are unknown and likely involve other epitopes on PDC-E2 restricted by MHC class I molecules. To address this issue, a comprehensive mapping of the CTL epitope repertoire on the PDC-E2 molecule that binds HLA-A*0201 was performed to provide further clues regarding the role of CTLs. We used the T2 cell line to screen 79 overlapping 15mer peptides, spanning the entire PDC-E2 molecule. Six of the 79 peptides exhibited significantly higher binding activity to HLA-A*0201 than the other 15mer peptides. Two of these 6 peptides induced CTL lines from patients with PBC. Fine mapping with N-terminus or C-terminus truncated peptides identified 10mer peptide, PDC-E2 amino acids 165 to 174, which is a novel CD8 epitope restricted by HLA-A*0201. In conclusion, using a combination of the 15mer peptide library screening with the T2 binding assay and also the induction of CTL lines with candidate peptides, we have defined a novel HLA-A*0201-restricted epitope PDC-E2 165 to 174 in patients with PBC. These data will become important in the development of altered peptide ligands to modulate disease activity.
Industrial Food Animal Production, Antimicrobial Resistance, and Human Health
Authors: Ellen K. Silbergeld, Jay Graham, Lance B. Price
Journal: Annual Review of Public Health (2008)

Antimicrobial resistance is a major public health crisis, eroding the discovery of antimicrobials and their application to clinical medicine. There is a general lack of knowledge of the importance of agricultural antimicrobial use as a factor in antimicrobial resistance even among experts in medicine and public health. This review focuses on agricultural antimicrobial drug use as a major driver of antimicrobial resistance worldwide for four reasons: It is the largest use of antimicrobials worldwide; much of the use of antimicrobials in agriculture results in subtherapeutic exposures of bacteria; drugs of every important clinical class are utilized in agriculture; and human populations are exposed to antimicrobial-resistant pathogens via consumption of animal products as well as through widespread release into the environment.
Phase II Study of Cetuximab in Combination With Chemoradiation in Patients With Stage IIIA/B Non–Small-Cell Lung Cancer: RTOG 0324
Authors: George R. Blumenschein, Rebecca Paulus, Walter J. Curran, Francisco Robert, Frank Fossella, Maria Werner-Wasik, Roy S. Herbst, Philip O. Doescher, Hak Choy, Ritsuko Komaki
Journal: Journal of Clinical Oncology (2011)

Non-small-cell lung cancer (NSCLC) commonly expresses the epidermal growth factor receptor (EGFR), which is associated with poor clinical outcome. Cetuximab is a chimerized monoclonal antibody that targets the EGFR and, in preclinical models, it demonstrates radiosensitization properties. We report a phase II trial testing the combination of cetuximab with chemoradiotherapy (CRT) in unresectable stage III NSCLC.Eligibility criteria included unresectable stage III NSCLC, Zubrod performance status ≤ 1, weight loss ≤ 5%, forced expiratory volume in 1 second ≥ 1.2 L, and adequate organ function. Patients received an initial dose of cetuximab (400 mg/m(2)) on day 1 of week 1 and then weekly doses of cetuximab (250 mg/m(2)) until completion of therapy (weeks 2 through 17). During week 2, patients started CRT (63 Gy in 35 fractions) with weekly carboplatin at area under the [concentration-time] curve (AUC) 2 and six doses of paclitaxel at 45 mg/m(2) followed by carboplatin (AUC 6) and two cycles of paclitaxel (200 mg/m(2)) during weeks 12 through 17. Primary end points included safety and compliance of concurrent cetuximab and CRT.In all, 93 patients were enrolled and 87 were evaluable. Median follow-up was 21.6 months. Response rate was 62% (n = 54), median survival was 22.7 months, and 24-month overall survival was 49.3%. Adverse events related to treatment included 20% grade 4 hematologic toxicities, 8% grade 3 esophagitis, and 7% grade 3 to 4 pneumonitis. There were five grade 5 events.The combination of cetuximab with CRT is feasible and shows promising activity. The median and overall survival achieved with this regimen were longer than any previously reported by the Radiation Therapy Oncology Group.
Clinical Implications of Traumatic Stress from Birth to Age Five
Authors: Ann T. Chu, Alicia F. Lieberman
Journal: Annual Review of Clinical Psychology (2010)

Children aged birth to five years are exposed to a disproportionately increased amount of potentially traumatic events compared to older children. This review examines the prevalence of traumatic exposure in the birth-to-five age range, the indicators and diagnostic criteria of early traumatic stress, and the contextual issues associated with the experience of early trauma. The article also selectively reviews the impact of trauma on the biological, emotional, social, and cognitive functioning of young children's development along with some promising clinical treatment and service interventions that target the parent-child relationship as a vehicle of trauma recovery. Despite extensive documentation of the negative impact of trauma on the normal development of young children, research, clinical, and policy efforts to address the psychological repercussions of early victimization remain remarkably limited. Future directions in research and clinical practice as well as implications for policy are discussed.
Enhancement of Cognitive Performance in Schizophrenia by Addition of Tandospirone to Neuroleptic Treatment
Authors: Tomiki Sumiyoshi, Mié Matsui, Shigeru Nohara, Ikiko Yamashita, Masayoshi Kurachi, Chika Sumiyoshi, Karu Jayathilake, Herbert Y. Meltzer
Journal: American Journal of Psychiatry (2001)

The goal of this study was to evaluate the effects of the addition of tandospirone, a serotonin-1A (5-HT(1A)) agonist, to ongoing treatment with typical antipsychotic drugs, on two cognitive domains that are relevant to functional outcome in patients with schizophrenia.Twenty-six patients with schizophrenia who were receiving stable doses of typical antipsychotics were randomly assigned to adjunctive treatment with 30 mg/day of tandospirone or placebo for 6 weeks. Executive function and verbal memory as well as psychopathology were assessed at baseline and after 6 weeks.Both cognitive measures improved significantly in the patients who received tandospirone; subjects who did not receive tandospirone showed no change. There was no significant change in psychopathology ratings in either group.The results suggest the usefulness of 5-HT(1A) agonists for enhancing some types of cognitive performance and possibly social and work function in patients with schizophrenia.
Cough and upper airway disorders in elite athletes: a critical review
Authors: Louis-Philippe Boulet
Journal: British Journal of Sports Medicine (2012)

Respiratory diseases such as asthma, chronic cough, recurrent respiratory infections and various upper airways conditions are common in elite athletes, but these conditions are often underdiagnosed and undertreated. Recurrent cough, often observed after exercise, is the most commonly reported symptom in athletes, particularly winter athletes, but it does not predict airway function; its intensity correlates with the dryness of inspired air but may not be associated with airway hyper-responsiveness. Rhinitis, either allergic or not, is highly prevalent in athletes, particularly non-allergic rhinitis in swimmers. Finally, dysfunctional breathing, including vocal cord dysfunction, may mimic or accompany asthma in a significant number of athletes. These conditions should be recognised and treated properly according to current guidelines, although how these last apply in the athlete is uncertain. Furthermore, regulatory agencies' restrictions on the type of drugs allowed for therapeutic use of these conditions in competitive athletes should be checked.
Multidimensional Dyspnea Profile: an instrument for clinical and laboratory research
Authors: Robert B. Banzett, Carl R. O'Donnell, Tegan E. Guilfoyle, Mark B. Parshall, Richard M. Schwartzstein, Paula M. Meek, Richard H. Gracely, Robert W. Lansing
Journal: European Respiratory Journal (2015)

There is growing awareness that dyspnoea, like pain, is a multidimensional experience, but measurement instruments have not kept pace. The Multidimensional Dyspnea Profile (MDP) assesses overall breathing discomfort, sensory qualities, and emotional responses in laboratory and clinical settings. Here we provide the MDP, review published evidence regarding its measurement properties and discuss its use and interpretation. The MDP assesses dyspnoea during a specific time or a particular activity (focus period) and is designed to examine individual items that are theoretically aligned with separate mechanisms. In contrast, other multidimensional dyspnoea scales assess recalled recent dyspnoea over a period of days using aggregate scores. Previous psychophysical and psychometric studies using the MDP show that: 1) subjects exposed to different laboratory stimuli could discriminate between air hunger and work/effort sensation, and found air hunger more unpleasant; 2) the MDP immediate unpleasantness scale (A1) was convergent with common dyspnoea scales; 3) in emergency department patients, two domains were distinguished (immediate perception, emotional response); 4) test-retest reliability over hours was high; 5) the instrument responded to opioid treatment of experimental dyspnoea and to clinical improvement; 6) convergent validity with common instruments was good; and 7) items responded differently from one another as predicted for multiple dimensions.