tbuckley/cabot-search huggingface dataset:
Africa can solve its own health problems
Authors: B. B Afolabi
Journal: BMJ (2002)

All you need is cognitive behaviour therapy? Critical appraisal of evidence base must be understood and respectedEditor-The article by Holmes and the accompanying commentaries essentially aim to explore the evidence for the efficacy and effectiveness of the psychotherapies and how this should be applied in everyday clinical practice. 1It is ironic that the arguments against cognitive therapy include numerous instances of idiosyncratic use of research evidence.Firstly, for example, in his commentary Bolsover selects three studies to support his view that the evidence base for cognitive therapy is weak.We would challenge him to apply his arguments to the seven systematic reviews of cognitive therapy in the Cochrane Database and the Database of Abstracts of Reviews of Effectiveness. 2 Holmes and also Bolsover cite a single paper to suggest that cognitive therapy is less effective in the real world of clinical practice than in university based clinical trials.This caricature may have applied to some trials conducted 30 years ago but is irrelevant now.To give just two examples, recent trials of cognitive therapy for chronic depression specifically recruited individuals who were depressed despite adequate trials of pharmacotherapy and psychotherapy. 3Also, the Cochrane review of cognitive therapy for schizophrenia includes examples of "real world" interventions. 4 Holmes argues that leading cognitive therapists are starting to question aspects of their discipline.However, these critiques are quoted out of context; the criticisms actually refer to the need to adapt the basic cognitive model to enhance its effectiveness for other disorders.Far from being a weakness, the critical appraisal of cognitive therapy by its practitioners is an important reason why it has been systematically evaluated in such a wide range of conditions.We agree with Holmes that it is unhelpful to evaluate psychotherapies by using only the research methods applied to drug trials.If clinicians and researchers aspire to an evidence based health service, however, they must accept two challenges.First is the challenge of evaluating what they think they do.We look forward to the evidence base of the psychodynamic psychotherapies developing, to allow more valid comparisons between the different approaches.Until then there is no escaping the robust evidence that exists for the use of cognitive therapy across clinical conditions and settings and the fact that much of this research is clearly applicable to the NHS.The second challenge is for clinicians and commentators to understand and respect the critical appraisal of the evidence base.Regrettably, some of the contributors to this series of articles have failed in this.
A revised model of platelet aggregation
Authors: Suhasini Kulkarni, Sacha M. Dopheide, Cindy L. Yap, Catherine Ravanat, Monique Freund, Pierre Mangin, Kathryn A. Heel, Alison Street, Ian S. Harper, Francois Lanza, Shaun P. Jackson
Journal: Journal of Clinical Investigation (2000)

In this study we have examined the mechanism of platelet aggregation under physiological flow conditions using an in vitro flow-based platelet aggregation assay and an in vivo rat thrombosis model. Our studies demonstrate an unexpected complexity to the platelet aggregation process in which platelets in flowing blood continuously tether, translocate, and/or detach from the luminal surface of a growing platelet thrombus at both arterial and venous shear rates. Studies of platelets congenitally deficient in von Willebrand factor (vWf) or integrin αIIbβ3 demonstrated a key role for platelet vWf in mediating platelet tethering and translocation, whereas integrin αIIbβ3 mediated cell arrest. Platelet aggregation under flow appears to be a multistep process involving: (a) exposure of vWf on the surface of immobilized platelets; (b) a reversible phase of platelet aggregation mediated by the binding of GPIbα on the surface of free-flowing platelets to vWf on the surface of immobilized platelets; and (c) an irreversible phase of aggregation dependent on integrin αIIbβ3. Studies of platelet thrombus formation in vivo demonstrate that this multistep adhesion mechanism is indispensable for platelet aggregation in arterioles and also appears to promote platelet aggregate formation in venules. Together, our studies demonstrate an important role for platelet vWf in initiating the platelet aggregation process under flow and challenge the currently accepted view that the vWf-GPIbα interaction is exclusively involved in initiating platelet aggregation at elevated shear rates.
Detection of alloantigens during preimplantation development and early trophoblast differentiation in the mouse by immunoperoxidase labeling.
Authors: R F Searle, M H Sellens, J Elson, E J Jenkinson, W D Billington
Journal: The Journal of Experimental Medicine (1976)

An immunoperoxidase-labeling technique allowing visualization of antibody binding to the cell surface at the electron microscopical level has been employed an an analysis of H-2 and non-H-2 alloantigen expression on the early mouse embryo. The presence of non-H-2 antigenic determinants has been confirmed on eight-cell, morula, and blastocyst stages of development. Contrary to previous reports, however, low levels of H-2 antigen have also been detected on the blastocyst. This is the earliest stage at which H-2 has been shown to be expressed on the fertilized mouse egg and may reflect the greater resolution of the immunoperoxidase technique. Using two different models to study the critical peri-implantation stages, those of experimentally induced blastocyst activation and blastocyst outgrowth in vitro, it has been demonstrated that antigen loss occurs on the trophectoderm at the time of implantation, and that this is not necessarily dependent upon maternal influence. It is suggested that the loss may be an important factor in the prevention of maternal immune rejection during the establishment of the fetal allograft. The two major components of the early postimplantation conceptus display a striking differential in antigenic status. The embryonic sac shows a high degree of peroxidase labeling, while the ectoplacental cone trophoblast is unlabeled. These findings add support to the concept of antigenic neutrality of the early trophoblast and its role in the maintenance of a normal fetomaternal immunological equilibrium.
Sniff nasal inspiratory pressure: simple or too simple?
Authors: J-W. Fitting
Journal: European Respiratory Journal (2006)

Respiratory muscle weakness, be it of acute or chronic onset, is a potentially threatening condition. Weakness of inspiratory muscles generates an imbalance between muscle load and capacity that, when severe enough, leads to hypercapnic respiratory failure. Conversely, weakness of expiratory muscles impairs cough and airway clearance and favours lung atelectasis and infection. Dysfunction of both respiratory muscle groups commonly precipitates acute respiratory failure in neuromuscular disorders. In recent years, the importance of respiratory muscle assessment has been recognised and a variety of tests has been proposed 1, 2.

The strength of inspiratory muscles can be assessed either by volitional or by nonvolitional tests. The volitional tests are simple, portable and inexpensive. Their main limitation lies in their dependence on maximal voluntary neuromuscular activation, which, in practice, is difficult to ascertain. In contrast, the cortical motor command is bypassed by nonvolitional tests such as phrenic nerve magnetic stimulation 3. Phrenic nerve stimulation offers the most reliable measure of diaphragm contractility, but is not widely available because it requires expensive equipment. It must be added that phrenic nerve stimulation may overestimate the diaphragm strength that is actually available to the patient in case of upper motor neuron lesions 4. Thus, notwithstanding their limitations, volitional tests remain on the first line and must be best exploited.

Maximum inspiratory pressure ( P I,max) is the classic volitional test of inspiratory muscle strength. It is measured as the highest mouth pressure sustained for 1 s during a maximum inspiratory effort against a quasi occlusion. Although simple in principle, the P I,max manoeuvre is difficult for many and requires a hermetic seal around the mouthpiece. As a consequence, low values may be due to true muscle weakness, a submaximal effort, or air leaks in the case of facial muscle weakness. The sniff is an …
Characterization and comparative profiling of the small RNA transcriptomes in two phases of locust
Authors: Yuanyuan Wei, Shuang Chen, Pengcheng Yang, Zongyuan Ma, Le Kang
Journal: Genome biology (2009)

Abstract Background All the reports on insect small RNAs come from holometabolous insects whose genome sequence data are available. Therefore, study of hemimetabolous insect small RNAs could provide more insights into evolution and function of small RNAs in insects. The locust is an important, economically harmful hemimetabolous insect. Its phase changes, as a phenotypic plasticity, result from differential gene expression potentially regulated at both the post-transcriptional level, mediated by small RNAs, and the transcriptional level. Results Here, using high-throughput sequencing, we characterize the small RNA transcriptome in the locust. We identified 50 conserved microRNA families by similarity searching against miRBase, and a maximum of 185 potential locust-specific microRNA family candidates were identified using our newly developed method independent of locust genome sequence. We also demonstrate conservation of microRNA*, and evolutionary analysis of locust microRNAs indicates that the generation of miRNAs in locusts is concentrated along three phylogenetic tree branches: bilaterians, coelomates, and insects. Our study identified thousands of endogenous small interfering RNAs, some of which were of transposon origin, and also detected many Piwi-interacting RNA-like small RNAs. Comparison of small RNA expression patterns of the two phases showed that longer small RNAs were expressed more abundantly in the solitary phase and that each category of small RNAs exhibited different expression profiles between the two phases. Conclusions The abundance of small RNAs in the locust might indicate a long evolutionary history of post-transcriptional gene expression regulation, and differential expression of small RNAs between the two phases might further disclose the molecular mechanism of phase changes.
Advanced therapeutic approach for the treatment of malignant pleural mesothelioma via the intrapleural administration of liposomal pemetrexed
Authors: Hidenori Ando, Sakiko Kobayashi, Amr S. Abu Lila, Noha Essam Eldin, Chihiro Kato, Taro Shimizu, Masami Ukawa, Kazuyoshi Kawazoe, Tatsuhiro Ishida
Journal: Journal of Controlled Release (2015)
Minimum urine flow rate during water deprivation
Authors: S D Soroka, S Chayaraks, S Cheema-Dhadli, J A Myers, S Rubin, H Sonnenberg, M L Halperin
Journal: Journal of the American Society of Nephrology (1997)

Antidiuretic hormone leads to an increase in the permeability for water and urea in the inner medullary collecting duct. Hence, urea may not be an "effective" osmole in the inner medulla during maximal renal water conservation. Accordingly, the purpose of this study was to evaluate whether differences in the rate of urea excretion would influence maximum renal water conservation in humans. In water-deprived rats, the concentration of urea and total osmolality were somewhat higher in the urine exiting the inner medullary collecting duct than in interstitial fluid obtained from the entire papillary tip. Nevertheless, the "nonurea" (total osmolality minus urea in millimolar terms) osmolality was virtually identical in both locations. Chronically fasted human subjects that were water-deprived for 16 h had a lower rate of urea excretion (71 +/- 7 versus 225 +/- 14 mumol/min) and a somewhat lower urine osmolality (745 +/- 53 versus 918 +/- 20 mosmol/kg H2O). Nevertheless, they had identical urine flow rates (0.5 +/- 0.01 and 0.5 +/- 0.02 ml/min, respectively), and their nonurea osmolality also was similar (587 +/- 25 and 475 +/- 14 mosmol/kg H2O, respectively) to the water-deprived normal subjects. The composition of their urine differed in that the principal nonurea osmoles became NH4+ and beta-hydroxybutyrate rather than Na and C1. During water deprivation in normal subjects, the ingestion of urea caused a twofold rise in urine flow rate, a fall in the nonurea osmolality, and a rise in the rate of excretion of nonurea osmoles. The nonurea osmolality of the urine, and presumably the medullary interstitial fluid as well, was inversely related to the urea excretion rate. In chronic fasting, the nature, but not the quantity, of nonurea osmoles changed. The similar minimum urine volume was predictable from an analysis based on nonurea osmole considerations.
Proteomic Mucin Profiling for the Identification of Cystic Precursors of Pancreatic Cancer
Authors: Karolina S. Jabbar, Caroline Verbeke, Anders G. Hyltander, Henrik Sjövall, Gunnar C. Hansson, Riadh Sadik
Journal: JNCI Journal of the National Cancer Institute (2014)

BackgroundPancreatic cystic lesions (PCLs) are increasingly frequent radiological incidentalomas, with a considerable proportion representing precursors of pancreatic cancer. Better diagnostic tools are required for patients to benefit from this development.
Radioimmunotherapy with [131I]cG250 in Patients with Metastasized Renal Cell Cancer: Dosimetric Analysis and Immunologic Response
Authors: Adrienne H. Brouwers, Wilhelmina C.A.M. Buijs, Peter F.A. Mulders, Pieter H.M. de Mulder, Wim J.M. van den Broek, Carola Mala, Egbert Oosterwijk, Otto C. Boerman, Frans H.M. Corstens, Wim J.G. Oyen
Journal: Clinical Cancer Research (2005)

Abstract Purpose: A study was designed to define the therapeutic efficacy, safety, and toxicity of two sequential high-dose treatments of radioimmunotherapy with [131I]cG250 in patients with metastasized renal cell carcinoma. Here, we report the dosimetric analysis and the relationship between the development of a human antichimeric antibody response and altered pharmacokinetics. Experimental Design: Patients (n = 29) with progressive metastatic renal cell carcinoma received a low dose (222 MBq) of [131I]cG250 for dosimetric analysis, followed by the first radioimmunotherapy with 2,220 MBq/m2 [131I]cG250 (n = 27) 1 week later. If no grade 4 hematologic toxicity was observed, a second low dose of [131I]cG250 (n = 20) was given 3 months later. Provided that no accelerated blood clearance was observed, a second radioimmunotherapy of [131I]cG250 was administered at an activity-dose level of 1,110 MBq/m2 (n = 3) or 1,665 MBq/m2 (n = 16). After each administration, whole-body images were obtained and the pharmacokinetics and the development of human antichimeric antibody responses were determined. Radiation-absorbed doses were calculated for whole body, red marrow, organs, and metastases. Results: No correlation was found between hematologic toxicity and radiation-absorbed dose to the whole body or bone marrow, nor administered activity (MBq and MBq/kg). The tumor-absorbed doses varied largely. An inverse relation between tumor size and radiation-absorbed dose was found. Most tumor lesions received &amp;lt;10 Gy, whereas only lesions &amp;lt;5 g absorbed &amp;gt;50 Gy. A relatively high number of patients developed a human antichimeric antibody response (8 of 27) with altered pharmacokinetics, hampering additional radioimmunotherapies in four of these patients. Conclusions: Dosimetric analysis did not adequately predict the degree of bone marrow toxicity. When human antichimeric antibody developed, the rapid clearance of radioactivity from the blood and body prohibited further treatment. According to the calculated absorbed dose in metastatic lesions, future radioimmunotherapy studies with radiolabeled cG250 should aim at treatment of small-volume disease or treatment in an adjuvant setting.
The impact of carcinoembryonic antigen flare in patients with advanced colorectal cancer receiving first-line chemotherapy
Authors: A.S. Strimpakos, D. Cunningham, C. Mikropoulos, I. Petkar, Y. Barbachano, I. Chau
Journal: Annals of Oncology (2009)

Background: Carcinoembryonic antigen (CEA) flare may have a favourable response to chemotherapy, but its impact on survival is unknown. This study aimed to evaluate the incidence of CEA flare and its impact on objective response rate (ORR), progression-free survival (PFS) and overall survival (OS).Patients and methods: Patients with histologically proven advanced colorectal cancer undergoing first-line chemotherapy with three or more serial CEA measurements (one at baseline and two or more during treatment) were included. Patients were grouped according to CEA kinetic as flare (F), decreasing CEA, normal baseline CEA, stable CEA and increasing CEA (I).Results: From January 2000 to February 2008, 837 patients were screened of whom 670 were eligible. CEA flare occurred in 78 (11.6%) patients. On multivariate analysis, compared with patients with increasing CEA, patients with CEA flare had a significantly better ORR [I versus F: 11% versus 73%; risk ratio (RR): 27.96; 95% confidence interval (CI): 9.55–81.88; P < 0.001], PFS (median 3.1 versus 8.3 months; RR: 0.38; 95% CI: 0.26–0.56; P < 0.001) and OS (median 10.9 versus 17.7 months; RR: 0.53; 95% CI: 0.34–0.82; P < 0.001).Conclusions: Compared with patients with rising CEA, flare was an independent favourable predictive and prognostic factor for tumour response and survival.
Smoking is associated with an age-related decline in exhaled nitric oxide
Authors: J. S. Sundy, D. W. Hauswirth, S. Mervin-Blake, C. A. Fernandez, K. B. Patch, K. M. Alexander, S. Allgood, P. D. McNair, M. C. Levesque
Journal: European Respiratory Journal (2007)

Age-related declines in forced expiratory volume in one second are accelerated in smokers. Smoking is associated with decreased exhaled nitric oxide fraction ( F eNO ). The aim of the present study was to determine the impact of age on F eNO in otherwise healthy smokers and nonsmokers. F eNO and serum cotinine levels were measured in 994 healthy subjects aged 18–40 yrs. American Thoracic Society questionnaire data on smoking habits was used to validate serum cotinine levels as a surrogate marker for categorisation of smokers and nonsmokers in the cohort. Serum cotinine levels were a good discriminator of smokers (n = 99) and nonsmokers (n = 895). F eNO levels were significantly lower in otherwise healthy smokers compared with nonsmokers. There was an inverse correlation of serum cotinine levels with F eNO . No correlation of age with F eNO was found in nonsmokers but an inverse correlation of F eNO with age in smokers was found. F eNO was significantly lower in smokers aged 21–40 yrs compared with nonsmokers aged 21–40 yrs, but was not lower in smokers aged 18–20 yrs compared with nonsmokers of the same age. Smoking was associated with decreased exhaled nitric oxide. The greatest smoking-related declines in exhaled nitric oxide occurred in older subjects. This suggests that smoking is associated with age-related declines in exhaled nitric oxide and justifies future mechanistic studies that address the impact of exhaled nitric oxide decline on lung function.
Compensation for Vaccine Injury
Authors: Max Bader
Journal: JAMA (1985)

<h3>To the Editor.—</h3> The recommendations for vaccine injury compensation published in the Dec 7 issue ofThe Journal<sup>1</sup>are both necessary and generally sound.<i>All</i>claims of injury should first be funneled through a no-fault federal compensation program. However, when the claimant finds the disposition of his claim by the program to be unsatisfactory, there probably deserves to be a limited appeals process involving petition for a rehearing or appeal to a federal court, where a contention as to fact could be heard by a judge without jury. This is most apt to be needed when a claim is turned down. In addition, health insurers should not be permitted to exclude these injuries from medical care coverage, and compensation should be limited to cases of serious injury only to the extent that a family's health insurance does not provide such coverage. Pain and suffering compensation should be excluded. In
A multicentre study of percentage change in venous leg ulcer area as a prognostic index of healing at 24 weeks
Authors: J. Kantor, D.J. Margolis
Journal: British Journal of Dermatology (2000)

Journal Article A multicentre study of percentage change in venous leg ulcer area as a prognostic index of healing at 24 weeks Get access J. Kantor, J. Kantor Biostatistics and Epidemiology (Room 110), Blockley Hall, 423 Guardian Drive, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, U.S.A. J.Kantor. E‐mail: jkantor@cceb.med.upenn.edu Search for other works by this author on: Oxford Academic Google Scholar D.J. Margolis D.J. Margolis Biostatistics and Epidemiology (Room 110), Blockley Hall, 423 Guardian Drive, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, U.S.A.Departments of Dermatology (Room 815) and Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 142, Issue 5, 1 May 2000, Pages 960–964, https://doi.org/10.1046/j.1365-2133.2000.03478.x Published: 01 May 2000
Natural killer (NK) cell stimulatory factor increases the cytotoxic activity of NK cells from both healthy donors and human immunodeficiency virus-infected patients.
Authors: J Chehimi, S E Starr, I Frank, M Rengaraju, S J Jackson, C Llanes, M Kobayashi, B Perussia, D Young, E Nickbarg
Journal: The Journal of Experimental Medicine (1992)

Natural killer cell stimulatory factor (NKSF), or interleukin 12 (IL-12), is a heterodimeric lymphokine produced by B cells that has multiple effects on T and NK cell functions. NKSF at concentrations as low as 0.4 pM enhances the spontaneous cytotoxic activity of peripheral blood lymphocytes (PBL) against a variety of tumor-derived target cell lines and virus-infected target cells. The combined treatment of PBL with NKSF and IL-2 results in a less than additive enhancement of cytotoxicity. NKSF enhances the cytotoxic activity of spontaneously cytotoxic CD16+CD5- NK cells and does not confer cytotoxic activity to CD16-CD5+ T cells. PBL from patients infected with human immunodeficiency virus (HIV) have significantly lower cytotoxic activity against tumor-derived target cells and virus-infected target cells than PBL from control healthy donors. Treatment of PBL from HIV-infected patients with NKSF and/or IL-2 results in an increase of NK cell cytotoxicity against both types of target cells to levels similar to or higher than those of untreated PBL from healthy donors. PBL from HIV-infected patients produce interferon gamma in response to NKSF and/or IL-2, although at levels 5- or 10-fold lower than those produced by PBL from healthy donors. The multiple biological effects of NKSF, its activity at very low molar concentrations, and its ability to synergize with other physiological stimuli suggest that NKSF/IL-12 is a lymphokine likely to have physiological importance and considerable therapeutic potential.