tbuckley/cabot-search huggingface dataset:
Treatment of Acute Respiratory Distress Syndrome with Recombinant Surfactant Protein C Surfactant
Authors: Roger G. Spragg, James F. Lewis, Wilhelm Wurst, Dietrich Häfner, Robert P. Baughman, Mark D. Wewers, James J. Marsh
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

We performed a phase I/II trial in North America of a recombinant surfactant protein C–based surfactant (Venticute) as treatment for the acute respiratory distress syndrome. Patients were prospectively randomized to receive either standard therapy or standard therapy plus one of two doses of exogenous surfactant given four times over 24 hours. Surfactant administration was well tolerated. No significant treatment benefit was associated with surfactant treatment. Bronchoalveolar lavage of treated patients at 48 hours reflected the presence of exogenous surfactant components, did not show evidence of improved surface tension lowering function, and had interleukin-6 concentrations that were significantly lower than control group values, consistent with an antiinflammatory treatment effect. The presence of exogenous surfactant was not detected in lavage fluid obtained at 120 hours. Future studies might rationally employ larger surfactant doses and a more prolonged dosing schedule.
I have taken my umbrella, so of course it does not rain: Figure 1
Authors: D S Postma, G Brusselle, A Bush, J W Holloway
Journal: Thorax (2011)

Spirometry is used worldwide to diagnose respiratory disease, and it is a validated measure to assess airway obstruction. Irreversible airway obstruction is the defining feature of chronic obstructive pulmonary disease (COPD). Thus, an FEV(1)/FVC ratio <70% is used to diagnose COPD, and the severity is thereafter based on the level of FEV(1). This definition is widely used in clinical practice and research, yet may lead to confusion with respect to the diagnosis associated with the presence of airway obstruction. The three main reasons are the following: (1) fixed airflow obstruction may be the result of specific diagnoses such as cystic fibrosis; (2) FEV(1)/FVC ratio changes with ageing, and it is therefore inappropriate to use the same ratio at 40 and 90 years, leaving aside gender differences; (3) even when specific diagnoses are excluded, fixed airflow obstruction may be the end-stage of many different underlying processes. The authors believe that they have strong arguments that a COPD diagnosis based solely on spirometric values is nonsense. More sophisticated lung function tests, such as plethysmography, forced oscillation and lung clearance index, may help further to delineate the characteristics of low lung function. However, these are not feasible in most clinical contexts and in epidemiologic studies. Therefore, the authors throw down the gauntlet: spirometry is an essential tool in patient evaluation but dangerous for disease diagnosis, and the term COPD should only be used in the appropriate clinical (diagnostic) context.
Prevalent Rain-bearing Winds and the Milk Supply of Manchester during the Years 1896-1909
Authors: W. Gordon
Journal: BMJ (1911)

ZIX OM ](M RH 4 911-value, as it causes relaxation of the pylorus in addition to inhibiting the secretion of the gastric juice.As there is certain to be more or less continuous gastric secretion, the stomach should be washed out with an alkaline solution every evening.If the symptoms do not disappear after four weeks, or if they recur in spite of carefal dieting, an operation should be advised.
Immunologic Response to Xenogeneic gp100 DNA in Melanoma Patients: Comparison of Particle-Mediated Epidermal Delivery with Intramuscular Injection
Authors: Brian A. Ginsberg, Humilidad F. Gallardo, Teresa S. Rasalan, Matthew Adamow, Zhenyu Mu, Sapna Tandon, Barrett B. Bewkes, Ruth-Ann Roman, Paul B. Chapman, Gary K. Schwartz, Richard D. Carvajal, Katherine S. Panageas, Stephanie L. Terzulli, Alan N. Houghton, Jianda D. Yuan, Jedd D. Wolchok
Journal: Clinical Cancer Research (2010)

Prior studies show that i.m. injection of xenogeneic orthologues of melanosomal antigens (tyrosinase, gp100) induces CD8(+) T-cell responses to the syngeneic protein. To further define the optimal vaccination strategy, we conducted a pilot clinical trial comparing i.m. injection with particle-mediated epidermal delivery (PMED).Human leukocyte antigen (HLA)-A*0201(+) disease-free melanoma patients were randomized to the PMED or i.m. arm, receiving eight vaccinations over 4 months. Patients received 4 microg or 2,000 microg per injection, respectively, of mouse gp100 DNA. Peripheral blood mononuclear cells were collected, cultured with gp100 peptides, and analyzed by tetramer and intracellular cytokine staining for responses to HLA-A*0201-restricted gp100 epitopes [gp100(209-217) (ITDQVPFSV) and gp100(280-288) (YLEPGPVTA)].Twenty-seven patients with stage IIB-IV melanoma were analyzable for immune response. The only common toxicity was grade 1 injection site reaction in nine patients with no intergroup difference, and one dose-limiting toxicity of acute hypersensitivity occurred in a PMED patient with undiagnosed gold allergy. Four of 27 patients produced gp100 tetramer(+)CD8(+) T cells, all carrying the CCR7(lo)CD45RA(lo) effector-memory phenotype. Five of 27 patients generated IFN-gamma(+)CD8(+) T cells, one who was also tetramer-positive. Overall, vaccination induced a response in 30% of patients, which was not significantly associated with study arm or clinical outcome. However, the PMED group showed a trend toward increased IFN-gamma(+)CD8(+) T-cell generation (P = 0.07).A comparable efficacy and safety profile was shown between the i.m. and PMED arms, despite a significantly decreased dose of DNA used for PMED injection.
Auditors criticise FDA for failing to track adverse events and workload
Authors: J. Hopkins Tanne
Journal: BMJ (2009)

The US medical regulation and safety body, the Food and Drug Administration, has been criticised by auditors for failing to track its workload, which has rendered it unable to estimate what resources it needs to fulfil its responsibilities.

A report by the US Government Accountability Office says, “The FDA reports that it cannot do all that is asked of it and our analysis of the agency’s activities confirm this.”

The report calls on the FDA commissioner “to establish a comprehensive and reliable basis to substantiate the agency’s estimates of its current and future resources.” It called on the commissioner to take four actions: assess the agency’s staffing, including its workforce of contractors; gather data on the work the agency conducts to fulfil …
Précis of Gallistel's<i>The organization of action: A new synthesis</i>
Authors: C. R. Gallistel
Journal: Behavioral and Brain Sciences (1981)

Abstract The book describes three elementary units of action – the reflex, the oscillator, and the servomechanism – and the principles by which they are combined to make complex units. The combining of elementary units to make complex units gives behavior and the neural circuitry underlying behavior a hierarchical structure. Circuits at higher levels govern the operation of lower circuits by selective potentiation and depotentiation: by regulating the potential for operation in lower circuits – raising the potential for some and lowering it for others – a higher unit establishes the overall pattern to be exhibited in the combined operations of the lower units, while leaving it to the lower units to determine the details of the implementation of this pattern. A theory of motivation of the kind long championed by ethologists and physiological psychologists grows out of the notion of the selective potentiation and depotentiation of hierarchically structured units of behavior. The question then becomes how this conception of motivation may be integrated with a conception of a learned representation of the world to yield a theory of how animals produce novel motivated behavioral sequences based on learned representations. The representation of space, which is central to the behavior of organisms at least as lowly as the digger wasp, is a promising domain for the investigation of this question. Another promising area is the representation of skilled movements, such as handwriting. A number of issues in cognitive and developmental psychology are illumined by this theory about the organization of action. Among these are the degrees-of-freedom problem, the role of practice in development and in the learning of skilled action, and the role of mental rotation of spatial representations.
The Italian multicentre study on noninvasive ventilation in chronic obstructive pulmonary disease patients
Authors: E. Clini, C. Sturani, A. Rossi, S. Viaggi, A. Corrado, C.F. Donner, N. Ambrosino
Journal: European Respiratory Journal (2002)

Chronic obstructive pulmonary disease (COPD) patients with chronic ventilatory failure (CVF) are more likely to develop exacerbations, which are an important determinant of health-related quality of life (HRQL). Long-term noninvasive positive-pressure ventilation (NPPV) has been proposed in addition to long-term oxygen therapy (LTOT) to treat CVF but little information is available on its effects on HRQL and resource consumption. Therefore, the current authors undertook a 2-yr multicentric, prospective, randomised, controlled trial to assess the effect of NPPV+LTOT on: 1) severity of hypercapnia; 2) use of healthcare resources, and 3) HRQL, in comparison with LTOT alone. One hundred and twenty-two stable hypercapnic COPD patients on LTOT for ≥6 months were consecutively enrolled. After inclusion and 1-month run-in, 90 patients were randomly assigned to NPPV+LTOT (n=43) or to LTOT alone (n=47). Arterial blood gases, hospital and intensive care unit (ICU) admissions, total hospital and ICU length of stay and HRQL were primary outcome measures; survival and drop-out rates, symptoms (dyspnoea and sleep quality) and exercise tolerance were secondary outcome measures. Follow-up was performed at 3-month intervals up to 2 yrs. Lung function, inspiratory muscle function, exercise tolerance and sleep quality score did not change over time in either group. By contrast the carbon dioxide tension in arterial blood on usual oxygen, resting dyspnoea and HRQL, as assessed by the Maugeri Foundation Respiratory Failure Questionnaire, changed differently over time in the two groups in favour of NPPV+LTOT. Hospital admissions were not different between groups during the follow-up. Nevertheless, overall hospital admissions showed a different trend to change in the NPPV+LTOT (decreasing by 45%) as compared with the LTOT group (increasing by 27%) when comparing the follow-up with the follow-back periods. ICU stay decreased over time by 75% and 20% in the NPPV+LTOT and LTOT groups, respectively. Survival was similar. Compared with long-term oxygen therapy alone, the addition of noninvasive positive-pressure ventilation to long-term oxygen therapy in stable chronic obstructive pulmonary disease patients with chronic ventilatory failure: 1) slightly decreased the trend to carbon dioxide retention in patients receiving oxygen at home and 2) improved dyspnoea and health-related quality of life. The results of this study show some significant benefits with the use of nocturnal, home noninvasive positive-pressure ventilation in patients with chronic ventilatory failure due to advanced chronic obstructive pulmonary disease patients. Further work is required to evaluate the effect of noninvasive positive-pressure ventilation on reducing the frequency and severity of chronic obstructive pulmonary disease exacerbation.
Estimation of the Age of Extant Ephedra Using Chloroplast rbcL Sequence Data
Authors: J. Huang
Journal: Molecular Biology and Evolution (2003)

The distinctive gymnosperm genus Ephedra is sometimes considered to have originated over 200 million years (Myr) ago on the basis of "ephedroid" fossil pollen. In this article we estimate the age of extant Ephedra using chloroplast rbcL gene sequences. Relative rate tests fail to reject the null hypothesis of equal rates of nucleotide substitution of the rbcL sequences among three landmark lineages (Gnetales, Pinaceae, and Ginkgo). The most divergent sequences we have found in Ephedra differ by only 7 bp for an 1,110 bp region of rbcL sequence, whereas the differences among genera range from 92 to 107 bp in Gnetales and from 35 to 92 bp in Pinaceae. Using three landmark events, the age of extant Ephedra is estimated to be approximately 8–32 Myr. Our result is consistent with the current distribution of many Ephedra species in geologically recent habitats and points out difficulties in the identification of older ephedroid pollen fossils with the modern genus Ephedra.
CHK1 plays a critical role in the anti-leukemic activity of the wee1 inhibitor MK-1775 in acute myeloid leukemia cells
Authors: Wenxiu Qi, Chengzhi Xie, Chunhuai Li, J Timothy Caldwell, Holly Edwards, Jeffrey W Taub, Yue Wang, Hai Lin, Yubin Ge
Journal: Journal of Hematology & Oncology (2014)

Acute myeloid leukemia (AML) remains a difficult disease to treat and requires new therapies to improve treatment outcome. Wee1 inhibitors have been used to prevent activation of the G2 cell cycle checkpoint, thus enhancing the antitumor activity of DNA damaging agents. In this study, we investigated MK-1775 in AML cell lines and diagnostic blast samples to identify sensitive subtypes as well as possible mechanisms of resistance. In vitro MK-1775 cytotoxicities of AML cell lines and diagnostic blasts were measured using MTT assays. The effects of MK-1775 on cell cycle progression and related proteins were determined by propidium iodide (PI) staining and flow cytometry analysis and Western blotting. Drug-induced apoptosis was determined using annexin V/PI staining and flow cytometry analysis. We found that newly diagnosed and relapsed patient samples were equally sensitive to MK-1775. In addition, patient samples harboring t(15;17) translocation were significantly more sensitive to MK-1775 than non-t(15;17) samples. MK-1775 induced apoptosis in both AML cell lines and diagnostic blast samples, accompanied by decreased phosphorylation of CDK1 and CDK2 on Tyr-15 and increased DNA double-strand breaks (DSBs). Time-course experiments, using AML cell lines, revealed a time-dependent increase in DNA DSBs, activation of CHK1 and subsequent apoptosis following MK-1775 treatment, which could be attenuated by a CDK1/2 inhibitor, Roscovitine. Simultaneous inhibition of CHK1 and Wee1 resulted in synergistic anti-leukemic activity in both AML cell lines and primary patient samples ex vivo. Our study provides compelling evidence that CHK1 plays a critical role in the anti-leukemic activity of MK-1775 and highlights a possible mechanism of resistance to MK-1775. In addition, our study strongly supports the use of MK-1775 to treat both newly diagnosed and relapsed AML, especially cases with t(15;17) translocation, and supports the development of combination therapies with CHK1 inhibitors.
Phosphatase-1 inhibitor-1 in physiological and pathological -adrenoceptor signalling
Authors: K. Wittkopper, D. Dobrev, T. Eschenhagen, A. El-Armouche
Journal: Cardiovascular Research (2011)

Control of protein phosphorylation–dephosphorylation events occurs through regulation of protein kinases and phosphatases. Phosphatase type 1 (PP-1) provides the main activity of serine/threonine protein phosphatases in the heart. Inhibitor-1 (I-1) was the first endogenous molecule found to inhibit PP-1 specifically. Notably, I-1 is activated by cAMP-dependent protein kinase A (PKA), and the subsequent prevention of target dephosphorylation by PP-1 provides distal amplification of β-adrenoceptor (β-AR) signalling. I-1 was found to be down-regulated and hypo-phosphorylated in human and experimental heart failure but hyperactive in human atrial fibrillation, implicating I-1 in the pathogenesis of heart failure and arrhythmias. Consequently, the therapeutic potential of I-1 in heart failure and arrhythmias has recently been addressed by the generation and analysis of several I-1 genetic mouse models. This review summarizes and discusses these data, highlights partially controversial issues on whether I-1 should be therapeutically reinforced or inhibited and suggests future directions to better understand the functional role of I-1 in physiological and pathological β-AR signalling.
Islet Transplantation Is Associated with Improvement of Renal Function among Uremic Patients with Type I Diabetes Mellitus and Kidney Transplants
Authors: Paolo Fiorina, Franco Folli, Gianpaolo Zerbini, Paola Maffi, Chiara Gremizzi, Valerio Di Carlo, Carlo Socci, Federico Bertuzzi, Michael Kashgarian, Antonio Secchi
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. The potential effects of islet transplantation on the renal function of 36 patients with type I diabetes mellitus and kidney transplants were studied with 4 yr of follow-up monitoring. Kidney-islet recipients were divided into two groups, i.e., patients with successful islet transplants (SI-K group) (n = 24, fasting C-peptide levels of >0.5 ng/ml for >1 yr) and patients with unsuccessful islet transplants (UI-K group) (n = 12, fasting C-peptide levels of <0.5 ng/ml). Kidney graft survival rates and function, urinary albumin excretion rates, and sodium handling were compared. Na+/K+-ATPase activity in protocol kidney biopsies and in red blood cells was cross-sectionally analyzed. The SI-K group demonstrated better kidney graft survival rates (100, 83, and 83% at 1, 4, and 7 yr, respectively) than did the UI-K group (83, 72, and 51% at 1, 4, and 7 yr, respectively; P = 0.02). The SI-K group demonstrated reductions in exogenous insulin requirements and higher C-peptide levels, compared with the UI-K group, whereas GFR values were similar. Microalbuminuria (urinary albumin index) increased significantly in the UI-K group only (UI-K, from 92.0 ± 64.9 to 183.8 ± 83.8, P = 0.05; SI-K, from 108.5 ± 53.6 to 85.0 ± 39.0, NS). In the SI-K group, but not in the UI-K group, natriuresis decreased at 2 and 4 yr (P < 0.01). The SI-K group demonstrated greater Na+/K+-ATPase immunoreactivity in renal tubular cells (P = 0.05) and higher activity in red blood cells (P = 0.03), compared with the UI-K group. The Na+/K+-ATPase activity in red blood cells was positively correlated with circulating C-peptide levels but not with glycated hemoglobin levels. Successful islet transplantation was associated with improvements in kidney graft survival rates and function among uremic patients with type I diabetes mellitus and kidney grafts. E-mail: [email protected]
Multinucleate cell angiohistiocytoma: a clinicopathological, immunohistochemical and ultrastructural study
Authors: J. SMOLLE, L. AUBOECK, I. GOGG-RETZER, H-P. SOYER, H. KERL
Journal: British Journal of Dermatology (1989)

The term 'multinucleate cell angiohistiocytoma'was first introduced by Smith and Wilson Jones in 1985. We report the clinicopathological, immunohistological and ultrastructural findings observed in two patients. Multinucleate cell angiohistiocytoma occurs mainly in middle‐aged women and is usually located at acral sites, particularly the distal extremities. Grouped, brown‐red, slightly elevated, asymptomatic papules slowly develop over several months until further growth ceases. There is no evidence of systemic disease. Histologically, the dermis shows numerous well developed capillaries with prominent endothelia, large bizarre basophilic and often multinucleate cells with a sparse lymphohistiocytic infiltrate. The immunohistological and ultrastructural findings suggest a fibroblastic differentiation of the large multinucleate cells.
Immunoglobulins and α1-acid glycoprotein do not contribute to the cholesterol crystallization—promoting effect of concanavalin a—binding biliary protein
Authors: Marianne A.C. De Bruijn, Kam S. Mok, Tiny Out, Guido N.J. Tytgat, Albert K. Groen
Journal: Hepatology (1994)

Human bile contains cholesterol crystallization-stimulating proteins that can be isolated by concanavalin A-Sepharose chromatography. In the past few years an increasing number of different pronucleating proteins have been identified in the concanavalin A-binding fraction. In this study we attempted to estimate the relative contribution of a number of these proteins to total concanavalin A-binding pronucleating activity. For this purpose, concanavalin A-binding glycoproteins were isolated from gallbladder bile samples from 12 patients with gallstones. The role of IgA, IgG and IgM and alpha 1-acid glycoprotein was investigated by means of immunoextraction. No decrease in crystallization-promoting activity was observed after precipitation of more than 98% of the different immunoglobulins. In addition, removal of more than 95% of alpha 1-acid glycoprotein from different concanavalin A-binding fractions had no significant effect on cholesterol crystallization-promoting activity. The influence of fibronectin was estimated by addition of physiological concentrations to a model bile system. At these concentrations fibronectin did not promote crystallization. From these data we conclude that immunoglobulins, alpha 1-acid glycoprotein and probably also fibronectin do not significantly contribute to total concanavalin A-binding activity.
The Prevalence Of AERD In a Tertiary Care Center
Authors: Whitney Wyatt Stevens, Anju T. Peters, Kathryn E. Hulse, Leslie C. Grammer, Joy Hsu, Pedro C. Avila, James Norton, Lydia Suh, Rakesh Chandra, David Conley, Robert C. Kern, Bruce K. Tan, Robert P. Schleimer
Journal: Journal of Allergy and Clinical Immunology (2014)
Remarks on ACUTE HAEMORRHAGIC NEPHRITIS
Authors: H. L. Tidey
Journal: BMJ (1928)

IN acute haemorrhagic niephritis tlle olltstanidilug, and frequenitly tlle sole immiiiiediate, characteristic is the occur- rence of gross renial haem.orrhage;oftenl this is directly related to infectionis in or arlo-und tlme throat.Otlmern-ise there is lno marked constant feature.This condition is somewlhat nwsterious, and in textbocks of miiedicinie it is practically unmiiientioned.Tllere is, how- ever, a considerable liter ature on tlhe subject, mainly, until recently, by Continental and American authors.Hale- White, writing in 1911 under the titlo " essenitial renial haeimaturia," gave references to 120 articles.Among children it has been studied in riecent years especially by Patersoni, Wylie, Moncrieff, amid L. G. Parsoins.Many cases i'n adults pass into oblivionl witlh a dia-gn-osis of "essential haematuria."
4D hyperspherical harmonic (HyperSPHARM) representation of surface anatomy: A holistic treatment of multiple disconnected anatomical structures
Authors: A. Pasha Hosseinbor, Moo K. Chung, Cheng Guan Koay, Stacey M. Schaefer, Carien M. van Reekum, Lara Peschke Schmitz, Matt Sutterer, Andrew L. Alexander, Richard J. Davidson
Journal: Medical Image Analysis (2015)