tbuckley/cabot-search huggingface dataset:
Serum type III procollagen peptide concentrations in severe chronic active hepatitis: Relationship to cirrhosis and disease activity
Authors: Arthur J. McCullough, William N. Stassen, Russell H. Wiesner, Albert J. Czaja
Journal: Hepatology (1987)

To analyze the correlations between the presence of cirrhosis and hepatocellular inflammation and the serum concentrations of the amino-terminal peptide of procollagen type III in chronic liver disease, we measured procollagen type III concentrations in paired serum samples from 46 patients (17 had cirrhosis) with severe chronic active hepatitis during a therapeutic treatment trial. Coded sera were analyzed for procollagen type III concentrations using both a standard and a recently described Fab radioimmunoassay to compare their relative diagnostic accuracy. Mean procollagen type III levels were elevated to the same extent in the cirrhotic and noncirrhotic groups at entry into the study. In response to immunosuppressive therapy, the initially elevated procollagen type III levels improved to normal values at remission in both groups. Qualitatively, the results were similar using either assay, but the standard assay was more sensitive for identifying the clinical stage of disease (i.e., active disease vs. disease in remission) than the Fab assay. Since both procollagen type III levels and standard liver function tests correlated well individually with the presence or absence of active disease, they also correlated with each other when both entry and remission values were considered. However, procollagen type III levels correlated poorly with indicators of inflammation (histologic grade and serum transaminase levels) during active disease. It is concluded that procollagen type III levels change in concert with standard liver function tests but do not quantitatively reflect inflammation or static measurements of hepatic fibrosis in severe chronic active hepatitis. However, these preliminary results suggest that procollagen type III can distinguish active disease from chronic active hepatitis in remission. Consequently, this test may be useful for monitoring disease activity and therapeutic response in severe chronic active hepatitis. For this purpose, the standard procollagen type III radioimmunoassay has greater diagnostic accuracy than the Fab radioimmunoassay.
Selective Targeting of TGF-β Activation to Treat Fibroinflammatory Airway Disease
Authors: Shunsuke Minagawa, Jianlong Lou, Robert I. Seed, Anthony Cormier, Shenping Wu, Yifan Cheng, Lynne Murray, Ping Tsui, Jane Connor, Ronald Herbst, Cedric Govaerts, Tyren Barker, Stephanie Cambier, Haruhiko Yanagisawa, Amanda Goodsell, Mitsuo Hashimoto, Oliver J. Brand, Ran Cheng, Royce Ma, Kate J. McKnelly, Weihua Wen, Arthur Hill, David Jablons, Paul Wolters, Hideya Kitamura, Jun Araya, Andrea J. Barczak, David J. Erle, Louis F. Reichardt, James D. Marks, Jody L. Baron, Stephen L. Nishimura
Journal: Science Translational Medicine (2014)

Therapeutic targeting of an extended-closed conformation of the integrin αvβ8 inhibits TGF-β activation and ameliorates symptoms of experimental airway disease in mice.
The Death-Rate of Anaesthesia
Authors: R. M. Gunn
Journal: BMJ (1883)

The most commonly used mode of noninvasive mechanical ventilation (NMV) is volume-controlled intermittent positive pressure ventilation (IPPV). Pressure support ventilation has recently become increasingly popular, but its merits have not been clearly defined. In an open, nonrandomized follow-up study, we evaluated two modes of NMV, volume-controlled (IPPV) and pressure-controlled ventilation (PCV) over 6 months in 30 consecutive patients (24 males and 6 females, aged 49 +/- 19 yrs) with chronic respiratory failure (CRF). The baseline assessments comprised both physiological and subjective data. In all cases, nasal IPPV was initially administered for 1 month, followed by a second month of nasal PCV. Thereafter, responders or nonresponders to PCV were defined according to the patients9 subjective symptom score and/or the recurrence of hypercapnia. During the IPPV phase, in all but two patients the subjective and objective parameters improved significantly. During the following 1 month PCV phase, stabilization was maintained in 18 patients ("responders"), while 10 patients were defined as "nonresponders". In nonresponders, hypercapnia increased (arterial carbon dioxide tension (Pa,CO2): 5.7 +/- 0.4 to 6.6 +/- 0.5 kPa; p &lt; 0.05) and symptom scores decreased. Compared with responders, nonresponders had a lower mean nocturnal arterial oxygen saturation (Sa,O2) (p &lt; 0.05) and a higher daytime Pa,CO2 (p &lt; 0.05) at baseline. We con clude that the majority of patients suffering from chronic respiratory failure who are initially satisfactorily ventilated with intermittent positive pressure ventilation may also be adequately maintained with pressure-controlled ventilation. However, there is a subgroup with more severe chronic respiratory failure at baseline, in whom pressure-controlled ventilation is inadequate. After 4 weeks of treatment with pressure-controlled ventilation, the subjective scores and the arterial carbon dioxide tension values reliably distinguished between long-term responders and nonresponders to pressure-controlled ventilation.
Hypothalamic-pituitary-gonadal axis and cortisol in young women with primary fibromyalgia: the potential roles of depression, fatigue, and sleep disturbance in the occurrence of hypocortisolism
Authors: A Gur
Journal: Annals of the Rheumatic Diseases (2004)

To investigate abnormalities of the hypothalamic-pituitary-gonadal (HPG) axis and cortisol concentrations in young women with primary fibromyalgia (FM); and to determine whether depression, fatigue, and sleep disturbance affect these hormones.Follicle stimulating hormone (FSH), luteinising hormone (LH), oestradiol, progesterone, prolactin, and cortisol concentrations in 63 women with FM were compared with those in 38 matched healthy controls; all subjects aged <35 years. The depression rate was assessed by the Beck Depression Inventory (BDI) and patients with high and low BDI scores were compared. Additionally, patients were divided according to sleep disturbance and fatigue and compared both with healthy controls and within the group.No significant differences in FSH, LH, oestradiol, prolactin, and progesterone levels were found between patients with FM and controls, but cortisol levels were significantly lower in patients than in controls (p<0.05). Cortisol levels in patients with high BDI scores, fatigue, and sleep disturbance were significantly lower than in controls (p<0.05). Correlation between cortisol levels and number of tender points in all patients was significant (r = -0.32, p<0.05).Despite low cortisol concentrations in young women with FM, there is no abnormality in HPG axis hormones. Because fatigue, depression rate, sleep disturbance, and mean age of patients affect cortisol levels, these variables should be taken into account in future investigations.
Mass spectrometric identification of a naturally processed melanoma peptide recognized by CD8+ cytotoxic T lymphocytes.
Authors: C Castelli, W J Storkus, M J Maeurer, D M Martin, E C Huang, B N Pramanik, T L Nagabhushan, G Parmiani, M T Lotze
Journal: The Journal of Experimental Medicine (1995)

We and others have previously reported that melanoma-specific, cytotoxic T lymphocytes (CTL) define a minimum of six class I-presented peptide epitopes common to most HLA-A2+ melanomas. Here we show that three of these peptide epitopes are coordinately recognized by a CTL clone obtained by limiting dilution from the peripheral blood of an HLA-A2+ melanoma patient. Tandem mass spectrometry was used to characterize and sequence one of these three naturally processed melanoma peptides. One of the potential forms of the deduced peptide sequence (XXTVXXGVX, X = I or L) matches positions 32-40 of the recently identified melanoma gene MART-1/Melan-A. This peptide (p939; ILTVILGVL) binds to HLA-A2 with an intermediate-to-low affinity and is capable of sensitizing the HLA-A2+ T2 cell line to lysis by CTL lines and clones derived from five different melanoma patients. A relative high frequency of anti-p939-specific effector cells appear to be present in situ in HLA-A2+ melanoma patients, since p939 is also recognized by freshly isolated tumor infiltrating lymphocytes. p939 represents a good candidate for the development of peptide-based immunotherapies for the treatment of patients with melanoma.
Adaptive Therapy for Androgen-Independent Prostate Cancer: A Randomized Selection Trial of Four Regimens
Authors: P. F. Thall, C. Logothetis, L. C. Pagliaro, S. Wen, M. A. Brown, D. Williams, R. E. Millikan
Journal: JNCI Journal of the National Cancer Institute (2007)

BackgroundPhysicians typically switch therapies unless clinically relevant thresholds of response are observed, and treatments that produce high-quality responses and that are active in the salvage setting are generally felt to be promising. With the goal of efficiently selecting promising regimens for more advanced trials, we conducted a randomized selection trial of four regimens to identify promising treatments for androgen-independent prostate cancer.
Investigation of multipotent postnatal stem cells from human periodontal ligament
Authors: Byoung-Moo Seo, Masako Miura, Stan Gronthos, Peter Mark Bartold, Sara Batouli, Jaime Brahim, Marian Young, Pamela Gehron Robey, Cun Yu Wang, Songtao Shi
Journal: The Lancet (2004)
Insulin, Insulin-Like Growth Factor-I (IGF-I), IGF Binding Proteins, Their Biologic Interactions, and Colorectal Cancer
Authors: M. S. Sandhu
Journal: JNCI Journal of the National Cancer Institute (2002)

Secular changes and worldwide variations in incidence rates of colorectal cancer, along with results from twin and migrant studies, provide compelling evidence that environmental factors influence the risk of this disease. Among the most important of these factors are diet and associated factors, such as physical activity and body size. Recent data suggest that dietary and related factors may influence colorectal cancer risk via their effects on serum insulin concentrations and on the bioavailability of insulin-like growth factor-I (IGF-I). Epidemiologic studies have shown that IGF-I is positively associated with the risk of colorectal cancer, and experimental studies have shown that IGF-I has mitogenic and antiapoptotic actions on colorectal cancer cells. IGF-I bioactivity is regulated in part by its six binding proteins (IGFBP-1 to IGFBP-6); insulin inhibits the production of IGFBP-1 and perhaps IGFBP-2. As a result, chronically elevated fasting and postprandial insulin levels may lead to a decrease in circulating IGFBP-1 and IGFBP-2 concentrations and, consequently, an increase in IGF-I bioavailability. Insulin may also increase the circulating IGF-I/IGFBP-3 ratio by increasing hepatic growth hormone sensitivity. The increased IGF-I bioavailability may, over time, increase the risk of colorectal cancer. This new evidence for biologic interactions among insulin, IGF-I, and IGFBPs in the context of colorectal carcinogenesis provides a potential mechanism through which diet and associated factors may increase the risk of this cancer.
Use of Pressure Offloading Devices in Diabetic Foot Ulcers
Authors: Stephanie C. Wu, Jeffrey L. Jensen, Anna K. Weber, Daniel E. Robinson, David G. Armstrong
Journal: Diabetes Care (2008)

Pressure mitigation is crucial for the healing of plantar diabetic foot ulcers. We therefore discuss characteristics and considerations associated with the use of offloading devices.A diabetic foot ulcer management survey was sent to foot clinics in all 50 states and the District of Columbia in 2005. A total of 901 geographically diverse centers responded. The survey recorded information regarding usage frequency and characteristics of assessment and treatment of diabetic foot ulcers in each center.Of the 895 respondents who treat diabetic foot ulcers, shoe modifications (41.2%, P < 0.03) were the most common form of pressure mitigation, whereas total contact casts were used by only 1.7% of the centers.This study reports the usage and characteristics of offloading devices in the care of diabetic foot ulcers in a broadly distributed geographic sample. Less than 2% of specialists use what has been termed the "gold standard" (total contact cast) for treating the majority of diabetic foot ulcers.
Transient Ischemic Attacks
Authors: C Miller Fisher
Journal: New England Journal of Medicine (2002)

The occurrence of fleeting episodes of numbness or paralysis was known to early physicians. One referred to them as “straws which show how the intracranial wind is blowing.” In 1950, a patient with a left-sided paralysis reported that before his stroke he had several brief spells of blindness in his right eye. “Isn't it funny, it was in the wrong eye? I went blind in the right eye and got paralyzed on the left side.” The patient had metastatic colorectal cancer and died shortly afterward. Autopsy disclosed occlusion of the right internal carotid artery in the neck (see Figure). Transient . . .
Normal, Autoimmune, and Malignant CD5+ B Cells: The LY-1 B Lineage?
Authors: K Hayakawa, R R Hardy
Journal: Annual Review of Immunology (1988)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
First official citywide electronic record system for patients is launched in London
Authors: A. O'Dowd
Journal: BMJ (2009)

Dengue virus (DENV) is a mosquito-borne flavivirus that causes serious global human disease and mortality. Skin immune cells are an important component of initial DENV infection and systemic spread. Here, we show that mast cells are a target of DENV in human skin and that DENV infection of skin mast cells induces degranulation and alters cytokine and growth factor expression profiles. Importantly, to our knowledge, we also demonstrate for the first time that DENV localizes within secretory granules in infected skin mast cells. In addition, DENV within extracellular granules was infectious in vitro and in vivo, trafficking through lymph to draining lymph nodes in mice. We demonstrate an important role for human skin mast cells in DENV infection and identify a novel mechanism for systemic spread of DENV infection from the initial peripheral mosquito injection site.
Peripheral Naive B-Cell Phenotype in X-Linked Severe Combined Immunodeficiency (XSCID) Patients with Hypogammaglobulinemia After Bone Marrow Transplantation
Authors: J. Chinen, D. Moratto, M.R. Kirby, G.F. Linton, H.L. Malech, J.M. Puck
Journal: Journal of Allergy and Clinical Immunology (2006)
Pulmonary hypertension in a patient with Abt-Letterer-Siwe syndrome and episodes of HAPE
Authors: C. Corvinus, P. Bärtsch, C. Dehnert, F.J. Herth, E. Grünig
Journal: European Respiratory Journal (2010)

To the Editors:

Abt–Letterer–Siwe syndrome, which is a disseminated form of Langerhans' cell histiocytosis (LCH), was diagnosed in the patient at the age of 6 months, affecting the inguinal lymph nodes and skin, and recurred at the age of 21 yrs, affecting lungs and arcus pubis 1. After two chemotherapy sessions, including vinblastine, etoposide and corticosteroids, complete remission was reached. At the age of 25 yrs the first high-altitude oedema occurred during a ski vacation at 2,400 m followed by the second episode 3 yrs later at an altitude of 2,800 m, which was confirmed by chest radiograph. After the second episode of high-altitude pulmonary oedema (HAPE) the patient was referred to the Division of Sports Medicine at the University Hospital of Heidelberg, Heidelberg, Germany, where he was assessed as described before 2. Estimated systolic pulmonary artery pressure ( P pa) was normal at rest (25 mmHg), increased to 50 mmHg after 30 min (oxygen saturation 74%) and to 60 mmHg (saturation 65%) after 90 min of exposure to normobaric hypoxia (inspiratory oxygen fraction ( F I,O2) of 12%). Stress Doppler echocadiography revealed systolic P pa values up to 95 mmHg during normoxic exercise of 125 W. The patient had a normal systemic blood pressure at rest and during exercise and no signs of left ventricular dysfunction. Maximum exercise capacity was 1.95 W·kg−1 (70% of normal), maximum oxygen consumption ( V ′O2) was 2.6 L·min−1 (80% of normal), body plethysmography showed patterns of obstructive and restrictive lung disease (airway resistance 158% of normal, forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) ratio was 60% (70% predicted), vital capacity was 70%, residual volume 166%, total lung capacity 95%) and a reduced diffusion capacity for carbon monoxide (48% pred). Despite shortness of breath, the …
Contribution of Na <sup>+</sup> -Ca <sup>2+</sup> Exchange to Stimulation of Transient Inward Current by Isoproterenol in Rabbit Cardiac Purkinje Fibers
Authors: Xinqiang Han, Gregory R. Ferrier
Journal: Circulation Research (1995)

Abstract Cellular mechanisms underlying β-adrenergic stimulation of the arrhythmogenic transient inward current (TI) were investigated by using a two-microelectrode voltage-clamp technique in rabbit cardiac Purkinje fibers. TI induced by elevating [Ca 2+ ] o to 30 mmol/L and substituting [Na + ] o with N -methyl- d -glucamine (NMG) chloride had a distinct reversal potential (E REV ) of −25 mV, suggesting that Na + -Ca 2+ exchange was not the charge carrier for TI. In the absence of [Na + ] o , isoproterenol (ISO, 0.01 to 5.0 μmol/L) had no effect on either inward or outward TI or on the current-voltage relation of TI. However, ISO (0.1 μmol/L) significantly increased both inward and outward TIs without affecting the E REV of TI, if [Na + ] o was present. Pretreatment with propranolol (0.2 μmol/L) or atenolol (0.2 μmol/L) abolished the stimulatory effects of ISO. Addition of propranolol (0.2 to 0.5 μmol/L) after the effects of ISO had developed caused only partial reversal of TI stimulation. This indicates persistence of stimulatory effects downstream from the initial agonist-receptor interaction. Forskolin (1 μmol/L), a direct adenylate cyclase activator, also strongly increased both inward and outward TI in the presence of [Na + ] o . These effects also were abolished when [Na + ] o was substituted by NMG. Inward and outward TIs enhanced by either ISO or forskolin were reversed by two putative Na + -Ca 2+ exchange blockers, dodecylamine (20 μmol/L) and quinacrine (20 μmol/L). These results suggest that β-adrenergic stimulation of TI is mediated by the Na + -Ca 2+ exchange; stimulation likely involves phosphorylation of the exchanger or some factor that modulates exchanger activity.
Validation and comparison of several published prognostic systems for patients with small cell lung cancer
Authors: M. Paesmans, J.J. Lafitte, J. Lecomte, T. Berghmans, A. Efremidis, V. Giner, O. Van Cutsem, A. Scherpereel, A.P. Meert, N. Leclercq, P. Van Houtte, J.P. Sculier
Journal: European Respiratory Journal (2011)

The aim of the present study was to validate and compare published prognostic classifications for predicting the survival of patients with small cell lung cancer. We pooled data from phase III randomised clinical trials, and used Cox models for validation purposes and concordance probability estimates for assessing predictive ability. We included 693 patients. All the classifications impacted significantly on survival, with hazard ratios (HRs) in the range 1.57-1.68 (all p<0.0001). Median survival times were 16-19 months for the best predicted groups, while they were 6-7 months for the most poorly predicted groups. Most of the paired comparisons were statistically significant. We obtained similar results when restricting the analysis to patients with extensive disease. Multivariate Cox models for fitting survival data were also performed. The HRs for a single covariate were 8.23 (95% CI 5.88-11.69), and 9.46 (6.67-13.50), and for extensive disease were 5.60 (3.13-9.93), 12.49 (5.57-28.01) and 8.83 (4.66-16.64). Concordance probability estimates ranged 0.55-0.65 (overlapping confidence intervals). Published classifications were validated and suitable for use at a population level. As expected, prediction at an individual level remains problematic. A specific model designed for extensive-disease patients did not appear to perform better.
Feeding Artery of a Left Atrial Myxoma Demonstrated by Three-Dimensional Volume-Rendering Images With Multislice Computed Tomography
Authors: Nobusada Funabashi, Nobuyuki Komiyama, Hiroshi Hasegawa, Hideyuki Kato, Yutaka Yamamoto, Katsuya Yoshida, Issei Komuro
Journal: Circulation (2002)
Tuberculosis Recurrence and Mortality after Successful Treatment: Impact of Drug Resistance
Authors: Helen Cox, Yared Kebede, Sholpan Allamuratova, Gabit Ismailov, Zamira Davletmuratova, Graham Byrnes, Christine Stone, Stefan Niemann, Sabine Rüsch-Gerdes, Lucie Blok, Daribay Doshetov
Journal: PLoS Medicine (2006)

Background The DOTS (directly observed treatment short-course) strategy for tuberculosis (TB) control is recommended by the World Health Organization globally. However, there are few studies of long-term TB treatment outcomes from DOTS programs in high-burden settings and particularly settings of high drug resistance. A DOTS program was implemented progressively in Karakalpakstan, Uzbekistan starting in 1998. The total case notification rate in 2003 was 462/100,000, and a drug resistance survey found multidrug-resistant (MDR) Mycobacterium tuberculosis strains among 13% of new and 40% of previously treated patients. A retrospective, observational study was conducted to assess the capacity of standardized short-course chemotherapy to effectively cure patients with TB in this setting. Methods and Findings Using routine data sources, 213 patients who were sputum smear-positive for TB, included in the drug resistance survey and diagnosed consecutively in 2001–2002 from four districts, were followed up to a median of 22 months from diagnosis, to determine mortality and subsequent TB rediagnosis. Valid follow-up data were obtained for 197 (92%) of these patients. Mortality was high, with an average of 15% (95% confidence interval, 11% to 19%) dying per year after diagnosis (6% of 73 pansusceptible cases and 43% of 55 MDR TB cases also died per year). While 73 (74%) of the 99 new cases were "successfully" treated, 25 (34%) of these patients were subsequently rediagnosed with recurrent TB (13 were smear-positive on rediagnosis). Recurrence ranged from ten (23%) of 43 new, pansusceptible cases to six (60%) of ten previously treated MDR TB cases. MDR M. tuberculosis infection and previous TB treatment predicted unsuccessful DOTS treatment, while initial drug resistance contributed substantially to both mortality and disease recurrence after successful DOTS treatment. Conclusions These results suggest that specific treatment of drug-resistant TB is needed in similar settings of high drug resistance. High disease recurrence after successful treatment, even for drug-susceptible cases, suggests that at least in this setting, end-of-treatment outcomes may not reflect the longer-term status of patients, with consequent negative impacts for patients and for TB control.