tbuckley/cabot-search huggingface dataset:
A pilot study in patients with established advanced liver fibrosis using pirfenidone
Authors: J Armendariz-Borunda, M C Islas-Carbajal, E Meza-Garcia, A R Rincon, S Lucano, A S Sandoval, A Salazar, J Berumen, A Alvarez, A Covarrubias, G Arechiga, L Garcia
Journal: Gut (2006)

Cirrhosis represents the third cause of mortality among Mexican people of productive age.1 Several drugs have been tested in the clinical scenario2,3 although conclusive evidence concerning drug efficacy has proven elusive.

PFD is an orally bioavailable pyridone derivative (5-methyl-1-phenyl-2-(1H)-pyridone) that affects a variety of profibrogenic cytokines and its mechanism of action mostly resides in its anti-inflammatory and antifibrotic activity.4–6 Here we present data obtained from a pilot clinical trial evaluating the safety and efficacy of PFD in 15 patients with established advanced liver disease caused by hepatitis C virus chronic infection. This is the first report showing improvements in liver histology (that is, necrosis, inflammation, steatosis, fibrosis, and cell regeneration) 12 months after PFD therapy. Colour Doppler ultrasound guided liver biopsies were obtained at baseline and after 12 months of PFD treatment and evaluated for stage of fibrosis and grade of activity according to the modified …
Expression of the beta 2 adrenoceptor partial agonist/antagonist activity of salbutamol in states of low and high adrenergic tone.
Authors: A Grove, L C McFarlane, B J Lipworth
Journal: Thorax (1995)

BACKGROUND--Salbutamol exhibits partial agonist/antagonist activity at airway beta 2 receptors in vitro in that it attenuates the bronchorelaxant effect of the full agonist isoprenaline. The aim of the present study was to characterise the partial beta 2 agonist/antagonist activity of salbutamol in vivo during supine rest and exercise, in states of low and high adrenergic tone. METHODS--Eight normal subjects were randomised to receive single oral doses of salbutamol 2 mg, 4 mg, 8 mg (S2, S4, S8), placebo (PL), or propranolol 80 mg (PR). The beta 2 adrenoceptor responses were evaluated after supine rest and subsequently in response to maximal exercise. RESULTS--Salbutamol demonstrated a dose-related increase in resting heart rate and tremor and a fall in serum potassium level consistent with beta 2 agonism. On exercise, the hyperkalaemic response was augmented by propranolol compared with placebo consistent with beta 2 blockade: mean difference for delta response (95% CI) PR v PL was 0.60 (0.02 to 1.27) mmol/l. This effect also occurred with salbutamol in a dose-related fashion: S8 v PL 0.33 (0.01 to 0.71) mmol/l, S8 v S2 0.31 (-0.02 to 0.61) mmol/l. Whilst propranolol blunted exercise heart rate in keeping with beta 1 blockade, salbutamol had no effect. Exercise produced an increase in lymphocyte beta 2 receptor binding density (Bmax) which was not affected by salbutamol. Plasma levels of adrenaline and noradrenaline at peak exercise were also unaltered by salbutamol in comparison with placebo. CONCLUSIONS--In a state of low adrenergic tone at rest salbutamol produces effects consistent with beta 2 agonism. In contrast, in a state of increased adrenergic tone during exercise salbutamol produced beta 2 selective antagonism as evidenced by its effects on exercise-induced hyperkalaemia (beta 2) but not on exercise-induced tachycardia (beta 1). The effects of salbutamol on beta 2 receptor density do not explain its effects on exercise-induced hyperkalaemia since upregulation rather than downregulation was observed. This in vivo phenomenon of partial beta 2 agonist/antagonist activity of salbutamol may be of relevance in the setting of acute asthma if adrenergic tone is increased.
Variation in Hospital Mortality Associated with Inpatient Surgery
Authors: Amir A. Ghaferi, John D. Birkmeyer, Justin B. Dimick
Journal: New England Journal of Medicine (2009)

Hospital mortality that is associated with inpatient surgery varies widely. Reducing rates of postoperative complications, the current focus of payers and regulators, may be one approach to reducing mortality. However, effective management of complications once they have occurred may be equally important.We studied 84,730 patients who had undergone inpatient general and vascular surgery from 2005 through 2007, using data from the American College of Surgeons National Surgical Quality Improvement Program. We first ranked hospitals according to their risk-adjusted overall rate of death and divided them into five groups. For hospitals in each overall mortality quintile, we then assessed the incidence of overall and major complications and the rate of death among patients with major complications.Rates of death varied widely across hospital quintiles, from 3.5% in very-low-mortality hospitals to 6.9% in very-high-mortality hospitals. Hospitals with either very high mortality or very low mortality had similar rates of overall complications (24.6% and 26.9%, respectively) and of major complications (18.2% and 16.2%, respectively). Rates of individual complications did not vary significantly across hospital mortality quintiles. In contrast, mortality in patients with major complications was almost twice as high in hospitals with very high overall mortality as in those with very low overall mortality (21.4% vs. 12.5%, P<0.001). Differences in rates of death among patients with major complications were also the primary determinant of variation in overall mortality with individual operations.In addition to efforts aimed at avoiding complications in the first place, reducing mortality associated with inpatient surgery will require greater attention to the timely recognition and management of complications once they occur.
PERFORMANCE OF TWO SENSITIVE TROPONIN I ASSAYS FOR THE EVALUATION OF SUSPECTED ACS: RESULTS FROM THE MULTICENTER RULE OUT MYOCARDIAL INFARCTION USING COMPUTER ASSISTED TOMOGRAPHY (ROMICAT) II BIOMARKER SUB-STUDY
Authors: James L. Januzzi, Pearl Zakroysky, Quynh Truong, Pamela Woodard, James Hector Pope, Thomas Hauser, John Nagurney, David Schoenfeld, W. Frank Peacock, Stephen Wiviott, Peter Pang, James Udelson, Udo Hoffmann
Journal: Journal of the American College of Cardiology (2013)
Histamine challenge testing: comparison of three methods.
Authors: J Britton, A Mortagy, A Tattersfield
Journal: Thorax (1986)

Non-specific bronchial reactivity is related to the severity of clinical asthma. Histamine challenge testing is increasingly used in association with questionnaires in epidemiological studies of the prevalence and morbidity of asthma in the community. The histamine challenge method described by Cockcroft et al is widely used and well standardised but it has disadvantages for epidemiological studies, being relatively slow and dependent on a supply of pressurised air. In this study we have assessed two simpler methods, one described by Yan et al and one by Mortagy, and compared these with the Cockcroft method. Twenty four adults with asthma were tested with each method in set order in a balanced design, and retested with each method in the same order. The Mortagy and Yan methods recorded PC20 or PD20 values on both occasions in all 24 subjects, but the Cockcroft method only 16 subjects. Repeatability, assessed as the 95% range for a single measurement, did not differ significantly, being +/- 1.94, 2.11, and 2.40 doubling concentrations for the Mortagy, Yan, and Cockcroft methods respectively. The Mortagy and Yan methods required less cumbersome equipment and took under 15 minutes to complete, compared with up to 45 minutes for the Cockcroft technique. The similar repeatability of all three methods in these subjects suggests that the two faster techniques are viable alternatives. The technical problems of standardising the Mortagy method lead us to conclude that, of the three methods compared, the Yan technique offers the greatest advantages for epidemiological studies.
Effects of Adrenal Steroid Withdrawal on Chronic Renovascular Hypertension in Adrenalectomized Sheep
Authors: J. R. BLAIR-WEST, J. P. COGHLAN, D. A. DENTON, J. W. FUNDER, B. A. SCOGGINS, R. D. WRIGHT
Journal: Circulation Research (1968)

Adrenalectomized sheep with a single kidney were maintained chronically hypertensive after renal arterial constriction on a maintenance dosage of desoxycorticosterone acetate and cortisone acetate. This level of steroid support is totally without pressor effects in adrenalectomized animals with normal kidneys. Blood pressure was monitored after steroid withdrawal with (1) no replacement of Na + loss, (2) intravenous replacement of Na + loss, (3) withdrawal of one steroid alone. When cortisone alone was withdrawn, the plasma [Na + ] and [K + ] remained within normal limits, no natriuresis occurred, and the blood pressure remained elevated. When both steroids, or DOCA alone, were withdrawn, a profound natriuresis and alteration in plasma ionic concentrations occurred; the blood pressure, however, remained persistently elevated above the values obtained before renal arterial constriction despite clinical and biochemical evidence of adrenoprival status. This pattern of blood pressure response compared with that following release of the constriction is interpreted as evidence against a causative role for the adrenal cortex in the mechanism of renovascular hypertension.
T cell receptor-major histocompatibility complex class II interaction is required for the T cell response to bacterial superantigens.
Authors: N Labrecque, J Thibodeau, W Mourad, R P Sékaly
Journal: The Journal of Experimental Medicine (1994)

Bacterial and retroviral superantigens (SAGs) stimulate a high proportion of T cells expressing specific variable regions of the T cell receptor (TCR) beta chain. Although most alleles and isotypes bind SAGs, polymorphisms of major histocompatibility complex (MHC) class II molecules affect their presentation to T cells. This observation has raised the possibility that a TCR-MHC class II interaction can occur during this recognition process. To address the importance of such interactions during SAG presentation, we have used a panel of murine T cell hybridomas that respond to the bacterial SAG Staphylococcal enterotoxin B (SEB) and to the retroviral SAG Mtv-7 when presented by antigen-presenting cells (APCs) expressing HLA-DR1. Amino acid substitutions of the putative TCR contact residues 59, 64, 66, 77, and 81 on the DR1 beta chain showed that these amino acids are critical for recognition of the SAG SEB by T cells. TCR-MHC class II interactions are thus required for T cell recognition of SAG. Moreover, Mtv-7 SAG recognition by the same T cell hybridomas was not affected by these mutations, suggesting that the topology of the TCR-MHC class II-SAG trimolecular complex could be different from one TCR to another and from one SAG to another.
Cutaneous Head and Neck Malignancies With Perineural Spread to Contralateral Cranial Nerves: An Argument for Extending Postoperative Radiotherapy Volume
Authors: Catherine M. Barnett, Matthew C. Foote, Benedict Panizza
Journal: Journal of Clinical Oncology (2013)

The incidence of nonmelanoma cutaneous head and neck malignancies is increasing worldwide. In a small percentage of cases, associated perineural spread (PNS) of cranial nerves occurs, resulting in poor prognosis, with a recorded 5-year survival rate of 50% to 64.3%. Patients with clinical PNS from cutaneous head and neck malignancies are treated with surgical resection and postoperative radiotherapy. Recent literature provides few reports of PNS that extends across the facial midline to affect the contralateral cranial nerves. This report describes patients with ipsilateral cranial nerve PNS that has subsequently progressed to contralateral cranial nerves, to both highlight and address the potential implications for the postoperative radiotherapy volume.
Pegfilgrastim in dose-dense, sequential adjuvant chemotherapy for patients with breast cancer (BC)
Authors: E. Stickeler, M. Földi, A. Kummle, A. Hinke, P. C. Hartmann, J. Woll, D. O. Watermann, G. Gitsch
Journal: Journal of Clinical Oncology (2006)

10708 Background: Large randomized trials in the US and Europe have recently shown, that increased dose density of adjuvant chemotherapy leads to a relevant and significant prolongation of disease-free and overall survival in breast cancer. Dose density refers to the administration of drugs with a shortened intertreatment interval. G-CSF support is an essential requirement for increasing dose intensity. We explored the feasibility of pegylated filgrastim (Neulasta) in this setting. Methods: Patients (pts) up to the age of 60 with a confirmed histology of breast cancer and lymph node involvement were recruited into the study. A dose-dense chemotherapy, consisting of 3 x 4 sequential single drug cycles of epirubicin 90 mg/m 2 , paclitaxel 175 mg/m 2 , and cyclophosphamide 600 mg/m 2 was planned on a two-weekly schedule (similar to Citron et al., J Clin Oncol, 21 (2003): 1431–1439). Pegfilgrastim was to be administered on day 2 of each cycle, 24 h after chemotherapy application. Results: Seventeen pts with a mean age of 49 years were enrolled into this feasibility study. 76% of pts had pN2–3 stage, 65% G2 and 35% G3 tumors, 71%/47% a positive estrogen/progesterone receptor status, respectively. All but one pt were HER2-negative. The full number of 12 cytotoxic courses could be administered in all but one patient due to an anaphylactic reaction against paclitaxel. A total of nine weeks of treatment delay was recorded in 6 of the remaining 16 patients (38%), resulting in an overall mean relative dose intensity of 95.9% (range 80– 100%). Pegfilgrastim was given during 85% of the 198 courses. Febrile or grade 4 neutropenia were not recorded, grade 3 neutropenia in one cycle (6%) without G-CSF support. Antibiotic treatment was necessary in only 18% of pts. Median peak WBC count during the complete treatment course was 28,150/μl, no values above 100,000/μl were recorded. Bone pain was reported in 4 patients (24%) and occurred in a total of 6 cycles (3%). Conclusions: Pegfilgrastim can be used safely and seems to achieve the required supportive efficiency in a dose dense sequential chemotherapy schedule for locally advanced BC. [Table: see text]
Microsatellite Instability Predicts Poor Short-Term Survival in Patients with Advanced Breast Cancer after High-Dose Chemotherapy and Autologous Stem-Cell Transplantation
Authors: Peter J. Wild, Albrecht Reichle, Reinhard Andreesen, Georg Röckelein, Wolfgang Dietmaier, Josef Rüschoff, Hagen Blaszyk, Ferdinand Hofstädter, Arndt Hartmann
Journal: Clinical Cancer Research (2004)

The purpose is to define molecular prognostic factors in patients with advanced breast cancer treated with high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT).Thirty-nine patients with breast cancer and extensive lymph node (level III) and/or systemic metastases from a prospective single-center study of sequential HDCT/ASCT were studied. Microsatellite analysis was performed after laser microdissection using 15 markers selected for sensitive detection of microsatellite instability (MSI) in breast cancer. Exons 5-9 of the P53 gene were directly sequenced. Expression of P53, HER-2/neu, and the mismatch repair proteins hMSH2 and hMLH1 was evaluated by immunohistochemistry.MSI of at least three markers was detected in 13 of 39 patients (33%) and was predominantly found at tetranucleotide markers. All MSI-positive tumors showed normal expression of hMSH2 and hMLH1. Complete sequence analysis of exons 5-9 of the P53 gene was successful in 34 cases; 18% (n = 6) revealed a mutation. Overexpression of HER-2/neu and P53 was observed in 7 (22%) and 12 (46%) of 26 evaluated cases, respectively. The presence of MSI strongly correlated with shorter overall survival (OS; P = 0.0004) and progression-free survival (PFS; P = 0.02). None of the other investigated clinical or molecular factors correlated with OS in univariate analyses, with the exception of menopausal status and previous adjuvant chemotherapy. Testing various multivariate Cox regression models, MSI remained a highly significant, independent, and adverse risk factor for OS.MSI is frequent in advanced breast cancer and could be an indicator of chemotherapy resistance and poor prognosis in breast cancer patients treated with HDCT/ASCT.
Ocular Myasthenia
Authors: M. Seth Hochman
Journal: JAMA (1982)

OCULAR myasthenia is a wellknown, localized form of myasthenia gravis frequently limited to the extraocular muscles. It occurs in 20% to 25% of adult patients with this disorder.<sup>1,2</sup>A patient with ocular myasthenia in whom multiple brief recurrences were each followed by rapid spontaneous remission lasting several years is the subject of this report. <h3>Report of a Case</h3> A 54-year-old man noted gradual drooping of the right upper eyelid in July 1980. He noticed that when he looked up, he had vertical diplopia that disappeared when he closed either eye. One day after the onset of the ptosis, the patient had a tensilon test, with negative results. The ophthalmologist noted fasciculations of the eyelids following injection of tensilon, but no change in the moderate ptosis. Fifteen years previously, the patient had had an episode of horizontal diplopia that also disappeared with closure of either eye. Eight years previously, he
CXCR4 promotes B cell egress from Peyer’s patches
Authors: Timothy H. Schmidt, Oliver Bannard, Elizabeth E. Gray, Jason G. Cyster
Journal: The Journal of Experimental Medicine (2013)

Peyer’s patches (PPs) play a central role in supporting B cell responses against intestinal antigens, yet the factors controlling B cell passage through these mucosal lymphoid tissues are incompletely understood. We report that, in mixed chimeras, CXCR4-deficient B cells accumulate in PPs compared with their representation in other lymphoid tissues. CXCR4-deficient B cells egress from PPs more slowly than wild-type cells, whereas CXCR5-deficient cells egress more rapidly. The CXCR4 ligand, CXCL12, is expressed by cells adjacent to lymphatic endothelial cells in a zone that abuts but minimally overlaps with the CXCL13+ follicle. CXCR4-deficient B cells show reduced localization to these CXCL12+ perilymphatic zones, whereas CXCR5-deficient B cells preferentially localize in these regions. By photoconverting KikGR-expressing cells within surgically exposed PPs, we provide evidence that naive B cells transit PPs with an approximate residency half-life of 10 h. When CXCR4 is lacking, KikGR+ B cells show a delay in PP egress. In summary, we identify a CXCL12hi perilymphatic zone in PPs that plays a role in overcoming CXCL13-mediated retention to promote B cell egress from these gut-associated lymphoid tissues.
Human hematopoietic progenitor cells in long-term cultures express HLA-DR antigens and lack HLA-DQ antigens.
Authors: J H Falkenburg, W E Fibbe, H M Goselink, J J Van Rood, J Jansen
Journal: The Journal of Experimental Medicine (1985)

The expression of HLA-DR antigenic determinants on human hematopoietic progenitor cells (HPC) capable of differentiating into mature blood cells, as determined in semisolid cultures, has been demonstrated previously (3-7). Here, we investigated the expression of class II determinants on HPC responsible for the sustained proliferation of colony-forming units of granulocyte/macrophage (CFU-GM), of multilineage HPC (CFU-GEMM, granulocyte/erythrocyte/macrophage/megakaryocyte), and burst-forming units of erythroid cells (BFU-E) in liquid long-term cultures. Using both fluorescence-activated cell sorting and complement-dependent cytotoxicity assays, HLA-DR determinants could be identified on virtually all these HPC capable of proliferating in long-term cultures. Experiments in which the stromal layer had been irradiated provided evidence that the HPC themselves were truly HLA-DR+, and that the sustained proliferation of HPC was not due to activation of HLA-DR- residual HPC in the stromal layer by reinoculated HLA-DR+ accessory cells. Furthermore, it was shown that all HPC recognized in semisolid and liquid long-term cultures were HLA-DQ-. These results suggest that the human true pluripotential stem cell is HLA-DR+. These results open the possibility of studying class II-dependent regulation of hematopoiesis in liquid long-term cultures.
Stress and Depression
Authors: Constance Hammen
Journal: Annual Review of Clinical Psychology (2004)

Improved methods of assessment and research design have established a robust and causal association between stressful life events and major depressive episodes. The chapter reviews these developments briefly and attempts to identify gaps in the field and new directions in recent research. There are notable shortcomings in several important topics: measurement and evaluation of chronic stress and depression; exploration of potentially different processes of stress and depression associated with first-onset versus recurrent episodes; possible gender differences in exposure and reactivity to stressors; testing kindling/sensitization processes; longitudinal tests of diathesis-stress models; and understanding biological stress processes associated with naturally occurring stress and depressive outcomes. There is growing interest in moving away from unidirectional models of the stress-depression association, toward recognition of the effects of contexts and personal characteristics on the occurrence of stressors, and on the likelihood of progressive and dynamic relationships between stress and depression over time-including effects of childhood and lifetime stress exposure on later reactivity to stress.
Robert Dougan Hill
Journal: BMJ (2005)

Former general practitioner Barra, Western Isles (b Dublin 1922; q Aberdeen 1946; MD), died from respiratory failure on 1 July 2004.

During the second world war he served in the Royal Armoured Corps. After the Battle of Alamein he joined the Special Air Service and served the rest of the war in Greece, Yugoslavia, and Italy. He was in general practice in Shetland and Callander before moving to Barra, Western Isles, in 1963. His collaboration with the Medical Research Council genetics unit, Western General Hospital, Edinburgh, on a programme to determine the incidence of inherited disease in island populations resulted in a successful submission for an MD. He bred Eriskay ponies and was instrumental in helping to save the breed. He leaves a wife, Frances; three children; and six grandchildren.
Hepatitis B testing and access to care among racial and ethnic minorities in selected communities across the United States, 2009-2010
Authors: Dale J. Hu, Jian Xing, Rania A. Tohme, Youlian Liao, Henry Pollack, John W. Ward, Scott D. Holmberg
Journal: Hepatology (2013)

Hepatitis B virus (HBV) infection is widely prevalent among racial and ethnic minorities in the United States; however, few data have been available regarding HBV testing and referral to care for these populations. Using survey data collected in 2009-2010 from the Racial and Ethnic Approaches to Community Health (REACH) across the U.S., we assessed rates and determinants of hepatitis B testing and access to care in 28 minority communities in the U.S. Of 53,896 respondents, 21,129 (39.2%) reported having been tested for hepatitis B. Of the 1,235 who reported testing positive, 411 (33.3%) reported currently receiving specialty care. After controlling for demographic and socioeconomic characteristics, the likelihood of having been tested for hepatitis B and receiving care if infected was higher among males, non-English speaking persons, and those having health insurance compared to their counterparts. Compared to college graduates, respondents without a college education were less likely to get tested for hepatitis B.These data indicate that more than half of racial/ethnic minority persons in these communities had not been tested for hepatitis B, and only about one-half of those who tested positive had ever received treatment. More state and federal efforts are needed to screen racial/ethnic minorities, especially foreign-born persons, for HBV and link those with infection to care.