tbuckley/cabot-search huggingface dataset:
Predictors of progression of HRCT diagnosed fibrosing alveolitis in patients with rheumatoid arthritis
Authors: J K Dawson
Journal: Annals of the Rheumatic Diseases (2002)

Fibrosing alveolitis (FA) is the most serious pleuropulmonary extra-articular feature of rheumatoid arthritis (RA). Features that predict progression of FA in patients with RA have not yet been determined.To identify clinical features that predict progressive FA in patients with RA.An unselected cohort of 29 patients with RA and FA confirmed by high resolution computed tomography (HRCT) were studied prospectively for 24 months. Three monthly clinical assessment, four monthly pulmonary function tests, and yearly HRCT scanning was undertaken on these patients. Progressive FA was defined as >15% fall in carbon monoxide transfer factor (TLCO) with evidence of increasing FA on HRCT or death as a result of FA.During 24 months of follow up 10/29 (34%) patients had progressive FA. Progression on HRCT was seen as acute ground glass exacerbations or increasing reticular pattern lung involvement. Progressive FA was associated with the presence of bibasal crackles (p=0.041), TLCO (p=0.001), and extent (p=0.026) and distribution (p=0.031) of lung involvement on HRCT at initial presentation. When multiple logistic regression was used, only TLCO remained significant. Receiver operator curve analysis was employed to identify presenting TLCO of progressive FA. A TLCO <54% of the predicted value demonstrated 80% sensitivity and 93% specificity in predicting progressive FA.A TLCO <54% of the predicted value is a highly specific predictor of disease progression.
Hodgkin’s lymphoma in Chinese migrants to British Columbia:a 25-year survey
Authors: W.Y. Au, R.D. Gascoyne, R.E. Gallagher, N. Le, R.D. Klasa, R.H.S. Liang, C. Choy, W. Foo, J.M. Connors
Journal: Annals of Oncology (2004)
The In Vitro Activity, Human Pharmacology, and Clinical Effectiveness of New beta-Lactam Antibiotics
Authors: Harold C. Neu
Journal: The Annual Review of Pharmacology and Toxicology (1982)

There have been many factors which have caused proliferation of new ,B-Iactam compounds. The increasing resistance of gram-negative enteric bacteria to existing compounds has been a world wide phenomenon which has accelerated in the decade of the 1970s (1-3). There has been an in­ creased awareness of the toxic properties of the aminoglycosides and antibi­ otics of other classes (4). Finally, penicillins and cephalosporins are agents which lend themselves to modification which alters both microbiological activity as well as pharmacologic properties. Many structural modifications of the cephem nucleus have been produced since 1970. Moreover, new ,B-Iactam antibiotics with different ring systems have been isolated from natural sources (5) and others have been totally synthesized. This article will consider those cephalosporin agents about which there is sufficient information to determine their future clinical utility.
Thyroxine-induced left ventricular hypertrophy in the rat. Anatomical and physiological evidence for angiogenesis.
Authors: W M Chilian, R D Wangler, K G Peters, R J Tomanek, M L Marcus
Journal: Circulation Research (1985)

We examined anatomical and physiological responses of the left coronary vascular system to thyroxine-induced myocardial hypertrophy. Wistar-Kyoto rats (1 and 5 months old) were administered thyroxine (0.25 mg/kg per day) or the saline vehicle (sham-treated controls) for 2 months. At the ages of 3 and 7 months, each group of animals was used for one of three experimental protocols: determination of numerical capillary density in perfusion-fixed hearts, measurement of coronary reactive hyperemic responses following a 20-second coronary occlusion (peak-to-resting blood flow velocity) as an index of coronary reserve, and assessment of myocardial perfusion under resting conditions and during maximum coronary dilation (dipyridamole infusion) for the calculation of minimum coronary resistance per unit weight of the left ventricle or minimum coronary resistance of the total left ventricle. In both groups of thyroxine-treated animals, the left ventricular weight-to-body weight ratio increased by 35-40%. Capillary density of the 3- and 7-month-old Wistar Kyoto controls was 4467 +/- 352 (mean +/- SEM) and 4029 +/- 143 capillaries/mm2, respectively, but was increased significantly in the thyroxine-treated animals to 6052 +/- 409 capillaries/mm2 (3-month) and 4654 +/- 201 capillaries/mm2 (7-month). In both age control groups, the peak-to-resting blood flow velocity ratio was about 2.2. This index of coronary reserve was not changed in the thyroxine-treated animals. Myocardial perfusion measurements were limited to the 7-month-old animals.(ABSTRACT TRUNCATED AT 250 WORDS)
The Evolving Diabetes Burden in the United States
Authors: Michael M. Engelgau, Linda S. Geiss, Jinan B. Saaddine, James P. Boyle, Stephanie M. Benjamin, Edward W. Gregg, Edward F. Tierney, Nilka Rios-Burrows, Ali H. Mokdad, Earl S. Ford, Giuseppina Imperatore, K. M. Venkat Narayan
Journal: Annals of Internal Medicine (2004)

A diabetes epidemic emerged during the 20th century and continues unchecked into the 21st century. It has already taken an extraordinary toll on the U.S. population through its acute and chronic complications, disability, and premature death. Trend data suggest that the burden will continue to increase. Efforts to pre- vent or delay the complications of diabetes or, better yet, to prevent or delay the development of diabetes itself are urgently needed.
Docetaxel Plus Gemcitabine or Docetaxel Plus Cisplatin in Advanced Pancreatic Carcinoma: Randomized Phase II Study 40984 of the European Organisation for Research and Treatment of Cancer Gastrointestinal Group
Authors: Manfred P. Lutz, Eric Van Cutsem, Theo Wagener, Jean-Luc Van Laethem, Udo Vanhoefer, Jacques A. Wils, Eric Gamelin, Claus H. Koehne, Jean P. Arnaud, Emmanuel Mitry, Faress Husseini, Peter Reichardt, Mustafa El-Serafi, Pierre-Luc Etienne, Thomas Lingenfelser, Michel Praet, Bruno Genicot, Muriel Debois, Bernard Nordlinger, Michel P. Ducreux
Journal: Journal of Clinical Oncology (2005)

To define the efficacy and toxicity of docetaxel plus gemcitabine or docetaxel plus cisplatin for advanced pancreatic carcinoma.Chemotherapy-naive patients with measurable disease and WHO performance status less than 2 were randomly assigned to receive 21-day cycles of gemcitabine 800 mg/m2 on days 1 and 8 plus docetaxel 85 mg/m2 on day 8 (arm A) or docetaxel 75 mg/m2 on day 1 plus cisplatin 75 mg/m2 on day 1 (arm B). Primary end points were tumor response and rate of febrile neutropenia grade.Of 96 randomly assigned patients (49 patients in arm A and 47 patients in arm B), 70 patients were analyzed for response (36 in arm A and 34 in arm B) and 89 patients were analyzed for safety (45 in arm A and 44 in arm B). Confirmed responses were observed in 19.4% (95% CI, 8.2% to 36.0%) of patients in arm A and 23.5% (95% CI, 10.7% to 41.2%) in arm B. In arm A, the median progression-free survival (PFS) was 3.9 months (95% CI, 3.0 to 4.7 months), median survival was 7.4 months (95% CI, 5.6 to 11.0 months), and 1-year survival was 30%. In arm B, the median PFS was 2.8 months (95% CI, 2.6 to 4.6 months), median survival was 7.1 months (95% CI, 4.8 to 8.7 months), and 1-year survival was 16%. Febrile neutropenia occurred in 9% and 16% of patients in arms A and B, respectively.Both regimens are well tolerated and show activity in advanced pancreatic carcinoma. The safety profile and survival analyses favor docetaxel plus gemcitabine for further evaluation.
Effects of a Reduced Dose Schedule and Intramuscular Administration of Anthrax Vaccine Adsorbed on Immunogenicity and Safety at 7 Months&lt;subtitle&gt;A Randomized Trial&lt;/subtitle&gt;
Authors: Nina Marano, Brian D. Plikaytis, Stacey W. Martin, Charles Rose, Vera A. Semenova, Sandra K. Martin, Alison E. Freeman, Han Li, Mark J. Mulligan, Scott D. Parker, Janiine Babcock, Wendy Keitel, Hana El Sahly, Gregory A. Poland, Robert M. Jacobson, Harry L. Keyserling, Stephen D. Soroka, Sarah P. Fox, John L. Stamper, Michael M. McNeil, Bradley A. Perkins, Nancy Messonnier, Conrad P. Quinn
Journal: JAMA (2008)

In 1999, the US Congress directed the Centers for Disease Control and Prevention to conduct a pivotal safety and efficacy study of anthrax vaccine adsorbed (AVA).To determine the effects on serological responses and injection site adverse events (AEs) resulting from changing the route of administration of AVA from subcutaneous (s.q.) to intramuscular (i.m.) and omitting the week 2 dose from the licensed schedule.Assessment of the first 1005 enrollees in a multisite, randomized, double-blind, noninferiority, phase 4 human clinical trial (ongoing from May 2002).Healthy adults received AVA by the s.q. (reference group) or i.m. route at 0, 2, and 4 weeks and 6 months (4-SQ or 4-IM; n = 165-170 per group) or at a reduced 3-dose schedule (3-IM; n = 501). A control group (n = 169) received saline injections at the same time intervals.Noninferiority at week 8 and month 7 of anti-protective antigen IgG geometric mean concentration (GMC), geometric mean titer (GMT), and proportion of responders with a 4-fold rise in titer (%4 x R). Reactogenicity outcomes were proportions of injection site and systemic AEs.At week 8, the 4-IM group (GMC, 90.8 microg/mL; GMT, 1114.8; %4 x R, 97.7) was noninferior to the 4-SQ group (GMC, 105.1 microg/mL; GMT, 1315.4; %4 x R, 98.8) for all 3 primary end points. The 3-IM group was noninferior for only the %4 x R (GMC, 52.2 microg/mL; GMT, 650.6; %4 x R, 94.4). At month 7, all groups were noninferior to the licensed regimen for all end points. Solicited injection site AEs assessed during examinations occurred at lower proportions in the 4-IM group compared with 4-SQ. The odds ratio for ordinal end point pain reported immediately after injection was reduced by 50% for the 4-IM vs 4-SQ groups (P < .001). Route of administration did not significantly influence the occurrence of systemic AEs.The 4-IM and 3-IM regimens of AVA provided noninferior immunological priming by month 7 when compared with the 4-SQ licensed regimen. Intramuscular administration significantly reduced the occurrence of injection site AEs. Trial Registration clinicaltrials.gov Identifier: NCT00119067.
Nicotine Gum to Help Stop Smoking
Authors: John R. Hughes
Journal: JAMA (1984)

A nicotine gum has been approved as a prescription drug to help smokers stop smoking. This article reviews the rationale, pharmacology, efficacy, adverse effects, and method of use of the gum. Several randomized trials, including double-blind placebo-controlled studies, indicate nicotine gum improves long-term quit rates. The efficacy of the gum seems to be due to its ability to relieve withdrawal symptoms. Successful use of the gum depends on appropriate instructions, expectancies, and adjunct therapies. How effective the gum will be when used in general medical practice, to whom it is best to prescribe the gum, and what proportion of smokers will become dependent on the gum are still unclear.
Measuring red blood cell oxygenation in vivo using hyperpolarized 129Xe MRI
Authors: General Leung, Graham Norquay, Juan Parra Robles, Jim Wild
Journal: European Respiratory Journal (2012)

Introduction  Red blood cell (RBC) oxygenation plays an important role in cell survival. However, measuring this parameter in deep tissues is difficult. We report a method of detecting RBC oxygenation  in vivo  using MRI chemical shift (CS) of hyperpolarized (HP) 129Xe dissolved in RBCs explored previously  in vitro  (Mag Res Med 43;4(491) 2000).   Methods  400mL of HP 129Xe mixed with 600mL N 2  was delivered to 3 healthy volunteers who inhaled the gas and held their breath. Spectroscopy was performed on a 3T Philips Intera every 3 seconds for the length of the breath hold. CS was extracted from fits to the spectra. Surrogate oxygenation was measured using an SpO 2  monitor.   Results  Example spectra from one volunteer early(red) and at end of breath hold(blue) are shown in Fig 1(left). The CS change between the tissue/plasma and the RBC peak are plot as a function of time(green) in the panel right along with measured SpO 2 (blue). A decrease in the separation between these two peaks is seen over the course of the breath hold corresponding with a measured decrease in SpO 2 . Similar trends are seen in data from all subjects.   Discussion  The CS decrease with breath hold time correlates with  in vitro  data showing CS decrease with RBC deoxygenation. To our knowledge, this is the first demonstration in humans of the effect of RBC oxygenation on the CS of dissolved 129Xe. Localisation of this technique may provide insight into regional RBC oxygen non invasively.
Receptor-Dependent Mechanisms of Cell Stimulation by Bacterial Endotoxin
Authors: R J Ulevitch, P S Tobias
Journal: Annual Review of Immunology (1995)

In humans and experimental animals the presence of bacterial lipopolysaccharide (endotoxin, LPS) signals the presence of gram-negative bacteria. Recognition of LPS triggers gene induction by myeloid and nonmyeloid lineage cells. These inducible genes encode proteins that include cytokines, adhesive proteins, and enzymes that produce low molecular weight proinflammatory mediators. Together the products of these inducible genes upregulate host defense systems that participate in eliminating the bacterial infection. Unfortunately, these same mediators contribute to a serious human disease known as septic shock. Considerable progress has been made during the past decade in determining the sources, identities, and sequence of release of these mediators. In contrast, until recently, marked gaps in our knowledge existed regarding the identity of the LPS receptor and intracellular signaling pathways responsible for LPS-induced cell activation. The discovery in 1986 of a plasma protein termed LPS binding protein (LBP) led to the discovery of unanticipated mechanisms of LPS-induced cell activation. CD14 was found as a soluble serum protein or as a glycosylphosphatidylinositol (GPI)-anchored protein of myeloid lineage cells; it now occupies a key role in LPS-induced cell activation as we understand it today. Here we discuss how LBP enables LPS binding to CD14 and how complexes of LPS and soluble or GPI-anchored CD14 participate in cell activation. We also review the evidence supporting a model for a functional LPS receptor of myeloid cells, which is multimeric, comprised of GPI-anchored CD14 and a presently unidentified transmembrane protein that together bind LPS and initiate cell activation via kinase cascades.
Dietary fat increases high density lipoprotein (HDL) levels both by increasing the transport rates and decreasing the fractional catabolic rates of HDL cholesterol ester and apolipoprotein (Apo) A-I. Presentation of a new animal model and mechanistic studies in human Apo A-I transgenic and control mice.
Authors: T Hayek, Y Ito, N Azrolan, R B Verdery, K Aalto-Setälä, A Walsh, J L Breslow
Journal: Journal of Clinical Investigation (1993)

In humans, diets high in saturated fat and cholesterol raise HDL-cholesterol (HDL-C) levels. To explore the mechanism, we have devised a mouse model that mimics the human situation. In this model, HuAITg and control mice were studied on low fat (9% cal)-low cholesterol (57 mg/1,000 kcal) (chow) and high fat (41% cal)-high cholesterol (437 mg/1,000 kcal) (milk-fat based) diets. The mice responded to increased dietary fat by increasing both HDL-C and apo A-I levels, with a greater increase in HDL-C levels. This was compatible with an increase in HDL size observed by nondenaturing gradient gel electrophoresis. Turnover studies with doubly labeled HDL showed that dietary fat both increase the transport rate (TR) and decreased the fractional catabolic rate of HDL cholesterol ester (CE) and apo A-I, with the largest effect on HDL CE TR. The latter suggested that dietary fat increases reverse cholesterol transport through the HDL pathway, perhaps as an adaptation to the metabolic load of a high fat diet. The increase in apo A-I TR by dietary fat was confirmed by experiments showing increased apo A-I secretion from primary hepatocytes isolated from animals on the high fat diet. The increased apo A-I production was not associated with any increase in hepatic or intestinal apo A-I mRNA, suggesting that the mechanism of the dietary fat effect was posttranscriptional, involving either increased translatability of the apo A-I mRNA or less intracellular apo A-I degradation. The dietary fat-induced decrease in HDL CE and apo A-I fractional catabolic rate may have been caused by the increase in HDL particle size, as was suggested by our previous studies in humans. In summary, a mouse model has been developed and experiments performed to better understand the paradoxical HDL-raising effect of a high fat diet.
Are we losing control?
Authors: Gerd Gigerenzer
Journal: Behavioral and Brain Sciences (2001)

Most students are trained in using but not in actively choosing a research methodology. I support Hertwig and Ortmann's call for more rationality in the use of methodology. I comment on additional practices that sacrifice experimental control to the experimenter's convenience, and on the strange fact that such laissez-faire attitudes and rigid intolerance actually co-exist in psychological research programs.
Risk factors for lower extremity injury: a review of the literature
Authors: D F Murphy, D A J Connolly, B D Beynnon
Journal: British Journal of Sports Medicine (2003)

Prospective studies on risk factors for lower extremity injury are reviewed. Many intrinsic and extrinsic risk factors have been implicated; however, there is little agreement with respect to the findings. Future prospective studies are needed using sufficient sample sizes of males and females, including collection of exposure data, and using established methods for identifying and classifying injury severity to conclusively determine additional risk factors for lower extremity injury.
Localized and generalized forms of blistering in junctional epidermolysis bullosa due to COL17A1 mutations in the Netherlands
Authors: A.M.G. Pasmooij, H.H. Pas, G.H.L. Jansen, H.H. Lemmink, M.F. Jonkman
Journal: British Journal of Dermatology (2007)

Mutations in the gene COL17A1 coding for type XVII collagen cause non-Herlitz junctional epidermolysis bullosa (nH-JEB).Here we give an overview of the genotype-phenotype correlation in 12 patients from the Netherlands with type XVII collagen-deficient nH-JEB.Family and personal history and clinical presentation were recorded from each patient, and skin biopsies of intact and bullous skin were taken for immunofluorescence and electron microscopy. The mutations were identified by analysing the patient's DNA isolated from peripheral blood cells.DNA analysis identified five novel deletions: 1284delA, 1365delC, 3236delT, 3600-3601delCT and 4425delT. Interestingly, we identified a new patient, homozygous for 4425delT, with an exceptionally mild blistering phenotype. All together, three patients had more localized blistering confined to hands, lower legs and face, absent or very mild nail dystrophy, normal primary hair and sparse secondary hair. Nine patients had generalized blistering, nail dystrophy, sparse primary and absent secondary hair. All 12 patients had amelogenesis imperfecta (enamel pitting). Immunofluorescence (IF) antigen mapping with monoclonal antibodies 1A8C and 1D1 that bind to type XVII collagen, but not to its 97-kDa fragment was completely negative in patients with generalized blistering, whereas reduced in patients with localized blistering.Our data reveal that in patients with COL17A1 mutations a localized nH-JEB phenotype can be differentiated from a generalized nH-JEB phenotype by IF antigen mapping. The data are important for genetic counselling at early age when the clinical phenotype is not yet clear.
Detection of antigens specific for B-lymphoid cultured cell lines with human alloantisera.
Authors: D L Mann, L Abelson, S Harris, D B Amos
Journal: The Journal of Experimental Medicine (1975)

Human sera were tested for cytotoxicity to pairs of long-term tissue-cultured cell lines. Each pair had been derived from the same individual and one of the pairs possessed the characteristics of either "T" or "B" cells. The alloantisera used were HL-A-typing reagents or sera obtained from Amish multiparas. Selected cytotoxicity was found against the B-cell lines by direct testing. Cytotoxicity was abolished by absorption with B-cell line but not by absorption with the T-cell lines. The results suggest that a group of allotypic antigens may be expressed exculsively on human B cells.
Tubular and Glomerular Injury in Diabetes and the Impact of ACE Inhibition
Authors: Stine E. Nielsen, Takeshi Sugaya, Lise Tarnow, Maria Lajer, Katrine J. Schjoedt, Anne Sofie Astrup, Tsuneharu Baba, Hans-Henrik Parving, Peter Rossing
Journal: Diabetes Care (2009)

OBJECTIVE We studied tubular and glomerular damage in type 1 diabetic patients by measuring urinary–liver fatty acid binding protein (U-LFABP) and albuminuria. Subsequently, we evaluated the effect of ACE inhibition on U-LFABP in patients with diabetic nephropathy. RESEARCH DESIGN AND METHODS We studied Caucasians with type 1 diabetes: 58 with normoalbuminuria (urinary albumin &amp;lt;30 mg/24 h), 45 with persistent microalbuminuria (30–300 mg/24 h), and 45 with persistent macroalbuminuria (≥300 mg/24 h). A control group consisted of 57 healthy individuals. The groups were matched by sex and duration of diabetes. In addition, U-LFABP was measured in 48 type 1 diabetic patients with diabetic nephropathy in a randomized crossover trial consisting of 2 months of treatment with 20, 40, and 60 mg lisinopril once daily in random order. RESULTS In the cross-sectional study, levels of U-LFABP were significantly higher in normoalbuminuric patients versus those in the control group (median 2.6 [interquartile range 1.3–4.1] vs. 19 [0.8–3.0] μg/g creatinine, P = 0.02) and increased with increasing levels of albuminuria (microalbuminuric group 4.2 [1.8–8.3] μg/g creatinine and nephropathy group 71.2 [8.1–123.4], P &amp;lt; 0.05 for all comparisons). U-LFABP correlates with the urinary albumin-to-creatinine ratio (R2 = 0.54, P &amp;lt; 0.001). In the intervention study, all doses of lisinopril significantly reduced urinary albumin excretion rate and U-LFABP from baseline. The reductions in U-LFABP were 43, 46, and 40% with increasing doses of lisinopril (NS). CONCLUSIONS An early and progressive increase in tubulointerstitial damage as reflected by increased U-LFABP levels occurs in type 1 diabetic patients and is associated with albuminuria. Furthermore, ACE inhibition reduces the tubular and glomerular damage and dysfunction.
Cirrhotic cardiomyopathy: Getting to the heart of the matter
Authors: Z Ma, S S Lee
Journal: Hepatology (1996)

In cirrhosis, cardiac contractile function has been extensively documented to be abnormal. At baseline, cardiac output is increased, and this is one of the characteristics of hyperdynamic circulation. However, when cirrhotic patients are challenged by pharmacological or physiological stress, ventricular hyporesponsiveness is revealed. Similar patterns have been noted in cirrhotic animal models. This phenomenon has been termed “cirrhotic cardiomyopathy.” Although alcohol abuse may contribute to some cases of cirrhotic cardiomyopathy, it has been clearly documented to occur even in the absence of alcohol ingestion. Diminished myocardial β–adrenergic receptor signal transduction function, possibly caused by a persistent elevation in norepinephrine content, has been shown to play an important role. Alternation in cardiac plasma membrane properties due to impaired lipid metabolism is also crucial. Other possible pathogenic factors are reviewed, including accumulation of cardiodepressant substances caused by hepatocellular insufficiency, and ventricular overload secondary to increased blood volume and hyperdynamic circulation. Because the cardiac reserve function is borderline in patients with cirrhosis, cardiovascular status should be carefully monitored, especially when patients undergo stresses such as liver transplantation or portosystemic shunting procedures.