tbuckley/cabot-search huggingface dataset:
Derivation and Validation of a Composite Index of Severity in Chronic Obstructive Pulmonary Disease
Authors: Rupert C. Jones, Gavin C. Donaldson, Niels H. Chavannes, Kozui Kida, Maria Dickson-Spillmann, Samantha Harding, Jadwiga A. Wedzicha, David Price, Michael E. Hyland
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Chronic obstructive pulmonary disease (COPD) is increasingly recognized as a multicomponent disease with systemic consequences and effects on quality of life. Single measures such as lung function provide a limited reflection of how the disease affects patients. Composite measures have the potential to account for many of the facets of COPD.To derive and validate a multicomponent assessment tool of COPD severity that is applicable to all patients and health care settings.The index was derived using data from 375 patients with COPD in primary care. Regression analysis led to a model explaining 48% of the variance in health status as measured by the Clinical COPD Questionnaire with four components: dyspnea (D), airflow obstruction (O), smoking status (S), and exacerbation frequency (E). The DOSE Index was validated in cross-sectional and longitudinal samples in various health care settings in Holland, Japan, and the United Kingdom.The DOSE Index correlated with health status in all data sets. A high DOSE Index score (> or = 4) was associated with a greater risk of hospital admission (odds ratio, 8.3 [4.1-17]) or respiratory failure (odds ratio, 7.8 [3.4-18.3]). The index predicted exacerbations in the subsequent year (P < or = 0.014).The DOSE Index is a simple, valid tool for assessing the severity of COPD. The index is related to a range of clinically important outcomes such as health care consumption and predicts future events.
Limited-Field Radiation Therapy in the Management of Early-Stage Breast Cancer
Authors: F. A. Vicini, L. Kestin, P. Chen, P. Benitez, N. S. Goldstein, A. Martinez
Journal: JNCI Journal of the National Cancer Institute (2003)

Several phase III trials have demonstrated equivalent long-term survival between breast conserving surgery plus radiation therapy and mastectomy in patients with early-stage breast cancer but have not provided information on the optimal volume of breast tissue requiring post-lumpectomy radiation therapy. Therefore, we examined the 5-year results of a single institution's experience with radiation therapy limited to the region of the tumor bed (i.e., limited-field radiation therapy) in selected patients treated with breast-conserving therapy and compared them with results of matched breast-conserving therapy patients who underwent whole-breast radiation therapy.A total of 199 patients with early-stage breast cancer were treated prospectively with breast-conserving therapy and limited-field radiation therapy using interstitial brachytherapy. To compare potential differences in local recurrence rates based on the volume of breast tissue irradiated, patients in the limited-field radiation therapy group were matched with 199 patients treated with whole-breast radiation therapy. Match criteria included tumor size, lymph-node status, patient age, margins of excision, estrogen receptor status, and use of adjuvant tamoxifen therapy. Local-regional control and disease-free and overall survival were analyzed using the Kaplan-Meier method, and the statistical significance of differences between treatment groups was calculated using the log-rank test. All statistical tests were two-sided.Median follow-up for surviving patients was 65 months (range = 12-115 months). Five ipsilateral breast failures (i.e., recurrences) were observed in patients treated with limited-field radiation therapy. The cumulative incidence of local recurrence was 1% (95% confidence interval [CI] = 0% to 2.8%). On matched-pair analysis, the rate of local recurrence was not statistically significantly different between the patient groups (1% [95% CI = 0% to 2.4%] for the whole-breast radiation therapy patients versus 1% [95% CI = 0% to 2.8%] for the limited-field radiation therapy patients; P =.65).Limited-field radiation therapy administered to the region of the tumor bed has comparable 5-year local control rates to whole-breast radiation therapy in selected patients.
A Phylogenetic Analysis of the Lipocalin Protein Family
Authors: María D. Ganfornina, Gabriel Gutiérrez, Michael Bastiani, Diego S
Journal: Molecular Biology and Evolution (2000)

The lipocalins are a family of extracellular proteins that bind and transport small hydrophobic molecules. They are found in eubacteria and a great variety of eukaryotic cells, in which they play diverse physiological roles. We report here the detection of two new eukaryotic lipocalins and a phylogenetic analysis of 113 lipocalin family members performed with maximum-likelihood and parsimony methods on their amino acid sequences. Lipocalins segregate into 13 monophyletic clades, some of which are grouped in well-supported superclades. An examination of the G + C content of the bacterial lipocalin genes and the detection of four new conceptual lipocalins in other eubacterial species argue against a recent horizontal transfer as the origin of prokaryotic lipocalins. Therefore, we rooted our lipocalin tree using the clade containing the prokaryotic lipocalins. The topology of the rooted lipocalin tree is in general agreement with the currently accepted view of the organismal phylogeny of arthropods and chordates. The rooted tree allows us to assign polarity to character changes and suggests a plausible scenario for the evolution of important lipocalin properties. More recently evolved lipocalins tend to (1) show greater rates of amino acid substitutions, (2) have more flexible protein structures, (3) bind smaller hydrophobic ligands, and (4) increase the efficiency of their ligand-binding contacts. Finally, we found that the family of fatty-acid-binding proteins originated from the more derived lipocalins and therefore cannot be considered a sister group of the lipocalin family.
A Phase I/II, Multiple-Dose, Dose-Escalation Study of Siltuximab, an Anti-Interleukin-6 Monoclonal Antibody, in Patients with Advanced Solid Tumors
Authors: Eric Angevin, Josep Tabernero, Elena Elez, Steven J. Cohen, Rastilav Bahleda, Jean-Luc van Laethem, Christian Ottensmeier, Jose A. Lopez-Martin, Sally Clive, Florence Joly, Isabelle Ray-Coquard, Luc Dirix, Jean-Pascal Machiels, Neil Steven, Manjula Reddy, Brett Hall, Thomas A. Puchalski, Rajesh Bandekar, Helgi van de Velde, Brenda Tromp, Jessica Vermeulen, Razelle Kurzrock
Journal: Clinical Cancer Research (2014)

This phase I/II study evaluated safety, efficacy, and pharmacokinetics of escalating, multiple doses of siltuximab, a chimeric anti-interleukin (IL)-6 monoclonal antibody derived from a new Chinese hamster ovary (CHO) cell line in patients with advanced/refractory solid tumors.In the phase I dose-escalation cohorts, 20 patients with advanced/refractory solid tumors received siltuximab 2.8 or 5.5 mg/kg every 2 weeks or 11 or 15 mg/kg every 3 weeks intravenously (i.v.). In the phase I expansion (n = 24) and phase II cohorts (n = 40), patients with Kirsten rat sarcoma-2 (KRAS)-mutant tumors, ovarian, pancreatic, or anti-EGF receptor (EGFR) refractory/resistant non-small cell lung cancer (NSCLC), colorectal, or H&N cancer received 15 mg/kg every 3 weeks. The phase II primary efficacy endpoint was complete response, partial response, or stable disease >6 weeks.Eighty-four patients (35 colorectal, 29 ovarian, 9 pancreatic, and 11 other) received a median of three (range, 1-45) cycles. One dose-limiting toxicity occurred at 5.5 mg/kg. Common grade ≥3 adverse events were hepatic function abnormalities (15%), physical health deterioration (12%), and fatigue (11%). Ten percent of patients had siltuximab-related grade ≥3 adverse events. Neutropenia (4%) was the only possibly related adverse event grade ≥3 reported in >1 patient. Serious adverse events were reported in 42%; most were related to underlying disease. The pharmacokinetic profile of CHO-derived siltuximab appears similar to the previous cell line. No objective responses occurred; 5 of 84 patients had stable disease >6 weeks. Hemoglobin increased ≥1.5 g/dL in 33 of 47 patients. At 11 and 15 mg/kg, completely sustained C-reactive protein suppression was observed.Siltuximab monotherapy appears to be well tolerated but without clinical activity in solid tumors, including ovarian and KRAS-mutant cancers. The recommended phase II doses were 11 and 15 mg/kg every 3 weeks.
A secret revealed
Authors: L. Farrell
Journal: BMJ (2003)

Two months ago I went to France for the European rugby semi-final between Munster and Toulouse. As francophile as Belloc (every civilised man has two native countries, his own and France), I wanted to look like a local, so I wore a pair of stylish shorts.

At half time, like the other 40 000 in attendance, I had to visit the bathroom, and it was there that I had a most revealing and refreshing experience. As we stood shoulder …
Bioluminescence Assays for Bile Acids in the Detection and Follow-Up of Experimental Liver Injury
Authors: Jürgen SchÖLmerich, Marlene Deluca, Mario Chojkier
Journal: Hepatology (1984)

We evaluated the usefulness of recently developed bioluminescence assays for serum bile acids (BA) in the detection and follow-up of experimental liver injury. Liver damage was induced in rats by either D-galactosamine or CC1 4 , and BA were compared to SGPT and aminopyrine breath test (ABT). In severe liver injury, following D-galactosamine administration, all three methods revealed a significant difference from control values. The degree of abnormality was, however, far greater with SGPT and BA than with ABT. In moderate liver injury, induced by CC1 4 , the increase in BA was not significant. Values of SGPT and BA showed a very good correlation (3α1-OH: r = 0.88; 7α1-OH: r = 0.90; 12α1-OH: r = 0.83; p &lt; 0.001 for all correlations). Application of different assays for 3α1-OH, 7α1-OH and 12α1-OH BA allowed us to assess changes in individual BA. A 96-hr follow-up study in D-galactosamine-treated animals showed an increase in BA up to 48 hr and a decrease thereafter. The bioluminescence assays for BA are simple, rapid and require only 10 μl of serum. Thus, these assays may be the method of choice in detecting and monitoring liver injury in small laboratory animals.
Gained in translation: the importance of biologically relevant models of<i>Helicobacter pylori</i>-induced gastric cancer
Authors: Richard M Peek, Ernst J Kuipers
Journal: Gut (2011)

The attributable risk of gastric cancer conferred by Helicobacter pylori ranges from 75% to more than 90% depending on H pylori prevalence; however, only a fraction of colonised persons ever develop neoplasia.1 2 Disease risk involves well-choreographed interactions between pathogen and host, which are dependent upon strain-specific bacterial factors as well as host genotypic traits, each of which can be amplified by the environment. In their paper published in Gut , Kwon et al provide fresh insights into the role of a tumour suppressor, vitamin D3 upregulated protein 1 (VDUP1), in H pylori -associated gastric carcinogenesis ( in press ).3 Importantly, these investigators used multiple model systems to demonstrate that VDUP1 negatively regulates carcinogenesis induced by the combination of H pylori and N-methyl-N-nitrosourea (MNU) via dissociating proliferation from apoptosis and suppression of tumour necrosis factor α (TNFα)-dependent nuclear factor κB (NF-κB) activation and subsequent cyclooxygenase-2 (COX-2) expression.

Using a genetic model of VDUP1 deficiency, Kwon and colleagues observed that the incidence and severity of gastric premalignant and malignant lesions was increased in vdup1−/− mice compared with wild-type mice.3 This was accompanied by hyperproliferation that was not balanced by a corresponding increase in apoptosis. Contact between H pylori and epithelial cells in vitro dysregulates signalling pathways that influence oncogenesis, which mirrors interactions between H pylori and epithelial cells that occur within infected tissue. Kwon et al therefore also used an in vitro …
AIDS Serology Testing in Low- and High-Risk Groups
Authors: James R. Carlson, Martin L. Bryant, Steven H. Hinrichs, Janet K. Yamamoto, Norman B. Levy, JoAnn Yee, Joanne Higgins, Alexandra M. Levine, Paul Holland, Murray B. Gardner, Niels C. Pedersen
Journal: JAMA (1985)

The performance characteristics of the acquired immunodeficiency syndrome (AIDS)-retrovirus serological tests including enzyme-linked immunosorbent assay (ELISA), Western blot, and immunofluorescence assay were defined in a clinical laboratory setting by testing 1,257 serum specimens from low- and high-risk groups for AIDS. The three prototype AIDS retroviruses (lymphadenopathy-associated virus, human T-lymphotropic virus III, and AIDS-associated retrovirus) were equally suitable as target antigen for these assays. Sera from six of 74 laboratory and health care personnel and 91 of 1,014 unselected blood donors were falsely positive by ELISA (positive to negative ratio [P/N], greater than or equal to 2) based on the lack of Western blot confirmation. Only two true-positives (two [0.2%] of 1,014 blood donors) were detected in these low-risk groups. In contrast, 106 of 108 specimens with ELISA P/N ratios of 2 or greater from the high-risk groups including asymptomatic homosexual men, hemophiliacs, AIDS-related complex patients, and AIDS patients were positive by Western blot and immunofluorescence assay. Four false-negative ELISA results based on positive immunofluorescence assay and Western blot were found in the AIDS patient group. Ten of 69 AIDS patients were negative by all three serological tests. The consequence of maintaining high sensitivity for the ELISA (P/N ratio, greater than or equal to 2) as a screening test was a loss of specificity. The number of false-positive results necessitated the use of a confirmation test with greater specificity.
Increased Arterial Wall Stiffness Limits Flow Volume in the Lower Extremities in Type 2 Diabetic Patients
Authors: Eiji Suzuki, Atsunori Kashiwagi, Yoshihiko Nishio, Katsuya Egawa, Shinya Shimizu, Hiroshi Maegawa, Masakazu Haneda, Hitoshi Yasuda, Shigehiro Morikawa, Toshiro Inubushi, Ryuichi Kikkawa
Journal: Diabetes Care (2001)

OBJECTIVE—To document an association between arterial wall stiffness and reduced flow volume in the lower-extremity arteries of diabetic patients. RESEARCH DESIGN AND METHODS—We recruited 60 consecutive type 2 diabetic patients who had no history or symptoms of peripheral arterial disease (PAD) in the lower extremities and normal ankle/brachial systolic blood pressure index at the time of the study (non-PAD group) and 20 age-matched nondiabetic subjects (control group). We used an automatic device to measure pulse wave velocity (PWV) in the lower extremities as an index of arterial wall stiffness. At the popliteal artery, we evaluated flow volume and the resistive index as an index of arterial resistance to blood flow using gated two-dimensional cine-mode phase-contrast magnetic resonance imaging. RESULTS—Consistent with previous reports, we confirmed that the non-PAD group had an abnormally higher PWV compared with that of the control group (P &amp;lt; 0.001). To further demonstrate decreased flow volume and abnormal flow pattern at the popliteal artery in patients with a higher degree of arterial wall stiffness, we assigned the 60 non-PAD patients to tertiles based on their levels of PWV. In the highest group, magnetic resonance angiograms of the calf and foot arteries showed decreased intravascular signal intensity, indicating the decreased arterial inflow in those arteries. The highest group was also characterized by the lowest late diastolic and total flow volumes as well as the highest resistive index among the groups. From stepwise multiple regression analysis, PWV and autonomic function were identified as independent determinants for late diastolic flow volume (r2 = 0.300; P &amp;lt; 0.001). CONCLUSIONS—Arterial wall stiffness was associated with reduced arterial flow volume in the lower extremities of diabetic patients.
Thromboxane synthesis inhibition increases renal prostacyclin and prevents renal disease progression in rats with remnant kidney.
Authors: C Zoja, N Perico, D Corna, A Benigni, M Gabanelli, M Morigi, T Bertani, G Remuzzi
Journal: Journal of the American Society of Nephrology (1990)

Previous studies have demonstrated that inhibition of thromboxane A2-dependent platelet aggregation by the thromboxane A2 synthase inhibitor, OKY 1581, ameliorated the progressive kidney disease of rats with subtotal renal ablation. OKY 1581 also decreased the excessive renal thromboxane A2 synthesis and lowered systemic blood pressure. In the same model, a low dose aspirin and a specific thromboxane A2 receptor antagonist failed to influence proteinuria, glomerulosclerosis, and hypertension, thus excluding a role for either platelet or renal thromboxane A2 in renal disease progression. The aims of this study were to establish (1) whether a thromboxane A2 synthase inhibitor different from OKY 1581 could retard the progression of glomerular disease in rats with remnant kidney and (2) whether this effect was associated with an increase in renal synthesis of the vasodilatory prostacyclin. Treatment of rats with renal mass ablation with FCE 22178 (100 mg/kg by gavage and 200 mg/kg in the drinking water) for 35 days starting 10 days after surgical ablation was associated with an improvement in renal function in comparison with rats receiving the vehicle alone. Proteinuria was significantly lower, and rats were partially protected from the development of glomerulosclerosis. Systolic blood pressure was significantly lower than in animals given the vehicle. Urinary thromboxane B2 excretion was significantly decreased, and urinary 6-keto-prostaglandin F1 alpha increased in respect to vehicle-treated rats. We conclude that FCE 22178 limits glomerular injury in rats with remnant kidney.
Fluctuations in End-Expiratory Lung Volume during Cheyne-Stokes Respiration
Authors: Thomas Brack, Amal Jubran, Franco Laghi, Martin J. Tobin
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

We hypothesized that patients with Cheyne-Stokes respiration exhibit periodic increases in end-expiratory lung volume, mediated by changes in breath components, postinspiratory inspiratory muscle activity, or both. Calibrated inductive plethysmography revealed that 12 of 12 patients with Cheyne-Stokes respiration experienced increases in end-expiratory volume during hyperpnea: maximum 412 +/- 112 (SE) ml (range 75-1,543 ml). Compared with quiet breathing, the breath with largest increase in end-expiratory volume had larger tidal volume (867 +/- 107 vs. 567 +/- 38 ml, p < 0.01) and shorter expiratory time (1.25 +/- 0.11 vs. 1.66 +/- 0.15 seconds, p < 0.05). During decrescendo, the breath with largest decrease in end-expiratory volume had smaller tidal volume (p < 0.01) and longer expiratory time (p < 0.01). Cross-correlation of time series revealed that end-expiratory volume was related to both breath components (p < 0.0001). Bipolar needle electrodes revealed that scalene muscle activity at end-expiration was 50.7 +/- 14.0% higher at highest increase in lung volume than during preceding apnea (p < 0.05). Time series for scalene activity and end-expiratory volume were cross-correlated (p < 0.008). Increase in tonic scalene activity at end-expiration, however, was equivalent during crescendo and decrescendo phases: 50.6 +/- 22.1 versus 42.0 +/- 12.9% (p = 0.48). In conclusion, patients with Cheyne-Stokes respiration exhibit fluctuations in end-expiratory lung volume, primarily because of alterations in tidal volume and expiratory time rather than postinspiratory inspiratory muscle activity.
Depressive symptoms predict the future risk of severe pruritus in haemodialysis patients: Japan Dialysis Outcomes and Practice Patterns Study
Authors: Y. Yamamoto, Y. Hayashino, S. Yamazaki, T. Akiba, T. Akizawa, Y. Asano, A. Saito, K. Kurokawa, Y. Miyachi, S. Fukuhara
Journal: British Journal of Dermatology (2009)

Recent reports suggest a cross-sectional association between psychiatric distress and pruritus in patients on haemodialysis (HD). However, no study has examined the likelihood of developing severe pruritus in patients on HD with depressive symptoms.To evaluate the relationship between baseline depressive symptoms and subsequent risk of developing severe pruritus.A longitudinal study with a 0.5-2.5-year follow-up period was performed using 1799 patients on HD who had no/mild pruritus at baseline, based on the Japan Dialysis Outcomes and Practice Patterns Study (1996-2004), a cohort study composed of a representative sample of patients on HD. We assessed pruritus after the follow-up period using a self-reported questionnaire and depressive symptoms using scores from the five-item version of the Mental Health Inventory (MHI-5).The 1799 patients had a mean age of 56.9 years, 59.5% were men, and 23.6% presented depressive symptoms. Multivariable analysis revealed that patients with depressive symptoms had significantly higher odds of developing severe pruritus during the 0.5-2.5-year follow-up period [adjusted odds ratio (AOR) 1.57, 95% confidence interval 1.22-2.01, P < 0.001]. In addition, a significant linear trend was observed between baseline MHI-5 scores and risk of developing severe pruritus, with AORs for third, second and first MHI-5 score quartiles of 1.08, 1.51 and 1.95, respectively (P for trend < 0.0001).Our results suggest that depressive symptoms measured by MHI-5 may predict the future risk of developing severe pruritus in patients on HD.
Human Tyrosine Kinase 2 Deficiency Reveals Its Requisite Roles in Multiple Cytokine Signals Involved in Innate and Acquired Immunity
Authors: Yoshiyuki Minegishi, Masako Saito, Tomohiro Morio, Ken Watanabe, Kazunaga Agematsu, Shigeru Tsuchiya, Hidetoshi Takada, Toshiro Hara, Nobuaki Kawamura, Tadashi Ariga, Hideo Kaneko, Naomi Kondo, Ikuya Tsuge, Akihiro Yachie, Yukio Sakiyama, Tsutomu Iwata, Fumio Bessho, Tsutomu Ohishi, Kosuke Joh, Kohsuke Imai, Kazuhiro Kogawa, Miwa Shinohara, Mikiya Fujieda, Hiroshi Wakiguchi, Srdjan Pasic, Mario Abinun, Hans D. Ochs, Eleonore D. Renner, Annette Jansson, Bernd H. Belohradsky, Ayse Metin, Norio Shimizu, Shuki Mizutani, Toshio Miyawaki, Shigeaki Nonoyama, Hajime Karasuyama
Journal: Immunity (2006)
Sucralfate in the treatment and prevention of gastric ulcer: multicentre double blind placebo controlled study.
Authors: A L Blum, H Bethge, J C Bode, W Domschke, G Feurle, K Hackenberg, B Hammer, W Huttemann, M Jung, G Kachel
Journal: Gut (1990)

A randomised controlled multicentre trial was performed in 160 patients with gastric ulcer, proved by endoscopy and biopsy, to compare ulcer healing with sucralfate and ranitidine (double blind double dummy design) and to assess the effect of maintenance treatment with sucralfate on ulcer recurrence (double blind placebo controlled design). The healing rates were similar with 4 g sucralfate suspension per day and 300 mg ranitidine per day (82% and 88% after 12 weeks, respectively). Of the 109 patients with healed ulcers, 92 were entered into the maintenance trial and treated with sucralfate tablets (2 g per day) or placebo tablets. Maintenance treatment with sucralfate delayed symptoms of gastric ulcer recurrence. Lifetable analysis showed significant differences between sucralfate and placebo, both after six months (p = 0.018) and after 12 months (p = 0.044). The rates of symptom recurrences were 13% and 34% after six months and 34% and 55% after 12 months for sucralfate and placebo, respectively. The rate of asymptomatic recurrences after 12 months was similar in the two groups (9% and 10%, respectively). The recurrence rate was higher in patients who had never taken non-steroidal anti-inflammatory drugs than in those who had but had stopped on admission to the study. It was also higher in patients with recurrent ulcer and in those with scarring deformation and narrowing of the pylorus. Maintenance treatment with sucralfate slowed the appearance of symptom recurrences of gastric ulcer.