tbuckley/cabot-search huggingface dataset:
Using CT colonography as a triage technique after a positive faecal occult blood test in colorectal cancer screening
Authors: M H Liedenbaum, A F van Rijn, A H de Vries, H M Dekker, M Thomeer, C J van Marrewijk, L Hol, M G W Dijkgraaf, P Fockens, P M M Bossuyt, E Dekker, J Stoker
Journal: Gut (2009)

<h3>Objective:</h3> The purpose of this study was to evaluate the effectiveness of CT colonography (CTC) as a triage technique in faecal occult blood test (FOBT)-positive screening participants. <h3>Methods:</h3> Consecutive guaiac (G-FOBT) and immunochemical (I-FOBT) FOBT-positive patients scheduled for colonoscopy underwent CTC with iodine tagging bowel preparation. Each CTC was read independently by two experienced observers. Per patient sensitivity, specificity and positive and negative predictive values (PPV and NPV) were calculated based on double reading with different CTC cut-off lesion sizes using segmental unblinded colonoscopy as the reference standard. The acceptability of the technique to patients was evaluated with questionnaires. <h3>Results:</h3> 302 FOBT-positive patients were included (54 G-FOBT and 248 I-FOBT). 22 FOBT-positive patients (7%) had a colorectal carcinoma and 211 (70%) had a lesion ⩾6 mm. Participants considered colonoscopy more burdensome than CTC (p&lt;0.05). Using a 6 mm CTC size cut-off, per patient sensitivity for CTC was 91% (95% CI 85% to 91%) and specificity was 69% (95% CI 60% to 89%) for the detection of colonoscopy lesions ⩾6 mm. The PPV of CTC was 87% (95% CI 80% to 93%) and NPV 77% (95% CI 69% to 85%). Using CTC as a triage technique in 100 FOBT-positive patients would mean that colonoscopy could be prevented in 28 patients while missing ⩾10 mm lesions in 2 patients. <h3>Conclusion:</h3> CTC with limited bowel preparation has reasonable predictive values in an FOBT-positive population and a higher acceptability to patients than colonoscopy. However, due to the high prevalence of clinically relevant lesions in FOBT-positive patients, CTC is unlikely to be an efficient triage technique in a first round FOBT population screening programme.
Advances and challenges in malaria vaccine development
Authors: Peter D. Crompton, Susan K. Pierce, Louis H. Miller
Journal: Journal of Clinical Investigation (2010)

Malaria caused by Plasmodium falciparum remains a major public health threat, especially among children and pregnant women in Africa. An effective malaria vaccine would be a valuable tool to reduce the disease burden and could contribute to elimination of malaria in some regions of the world. Current malaria vaccine candidates are directed against human and mosquito stages of the parasite life cycle, but thus far, relatively few proteins have been studied for potential vaccine development. The most advanced vaccine candidate, RTS,S, conferred partial protection against malaria in phase II clinical trials and is currently being evaluated in a phase III trial in Africa. New vaccine targets need to be identified to improve the chances of developing a highly effective malaria vaccine. A better understanding of the mechanisms of naturally acquired immunity to malaria may lead to insights for vaccine development.
Role of Central and Peripheral Adrenergic Mechanisms in Neurogenic Hypertension Produced by Brainstem Lesions in Rat
Authors: NOBUTAKA DOBA, DONALD J. REIS
Journal: Circulation Research (1974)

Bilateral lesions of the nucleus tractus solitarius (NTS) in rats result in acute fulminating hypertension (NTS hypertension) as a consequence of central deafferentation of baroreceptors. The hypertension is due to increased peripheral resistance and decreased cardiac output. The hypertension is blocked and cardiac output is increased by phentolamine, trimethaphan (Arfonad), and reserpine but not by propranolol. In the present experiment, systemically administered 6-hydroxydopamine (6-OH-DA) did not alter NTS hypertension if the adrenal glands were intact. Adrenalectomy, however, blocked the lesion-induced rise in blood pressure in 6-OH-DA-treated rats. Intracisternally administered 6-OH-DA (600 µg) lowered the concentration of norepinephrine only in the spinal cord and blocked the development of NTS hypertension. Local injection of 6-OH-DA into the lateral hypothalamus did not affect the hypertension. Injection of 6-OH-DA into the NTS resulted in a mild, transient elevation in blood pressure. The results of these experiments demonstrate that (1) NTS hypertension is due to increased sympathetic neural discharge, (2) during NTS hypertension sufficient adrenomedullary catecholamines are released to produce hypertension when sympathetic terminals are destroyed, (3) central noradrenergic neurons participate in the expression of NTS hypertension, and (4) baroreceptors can inhibit the release of adrenal catecholamines.
Cardiac gap junction channels: modulation of expression and channel properties
Authors: T van Veen
Journal: Cardiovascular Research (2001)

In the heart, intercellular gap junction channels constructed from connexin molecules are crucial for conduction of the electric impulse. Cardiomyocytes can be interconnected by channels composed of three types of connexin proteins: Cx40, Cx43 or Cx45. In mammalian hearts, these three isoforms are regionally differently expressed and even between the species differences exist. Each of these channel-types possesses specific properties and are susceptible to modulation by various mechanisms. In this paper we compare the differences in properties of these channels as deduced from studies on transfected cells and isolated cardiomyocytes and discuss the factors involved in modulation of channel properties. Next, we evaluate the consequences of alterations in expression and modulation of channel properties for cardiac function. Therefore, we have compared reports on genetically engineered animals and discuss this information in relation to various pathophysiological disorders.
Tissue Growth and Remodeling
Authors: Stephen C. Cowin
Journal: Annual Review of Biomedical Engineering (2004)

The growth and remodeling of a tissue depends on certain features in the history of its mechanical environment as well as its genetic makeup. The mechanical environment influences the tissue's developing morphology, the process of simply increasing the size of existing morphological structures, and the formation of the proteins of which the tissue is constructed. The relationships between genetic information, various epigenetic mechanisms and tissue development are discussed. The developmental growth and remodeling of most structural tissues are enhanced by the use of those tissues and retarded by their disuse. The mechanical or mathematical modeling of tissue growth and development using cellular automata models and continuum mechanical models is reviewed.
The mechanism of deep inspiration-induced bronchoprotection: evidence from a mouse model
Authors: Russell S. Wong, Alexander N. Larcombe, Lynette B. Fernandes, Graeme R. Zosky, Peter B. Noble
Journal: European Respiratory Journal (2012)

In healthy individuals, deep inspirations (DIs) taken prior to a bronchial challenge reduce the bronchoconstrictor response, which is termed "bronchoprotection". The mechanism(s) of DI-induced bronchoprotection is unclear. The forced oscillation technique was used to assess the effect of prior DI on subsequent bronchoconstriction to methacholine (MCh) in BALB/c mice. We assessed likely mechanisms for the bronchoprotective effects of DI including reduced airway narrowing (from changes in airway resistance) and/or closure (changes in tissue elastance) and enhanced bronchodilation to a subsequent DI (% reversal in airway narrowing). DI prior to MCh challenge: 1) did not reduce but instead enhanced airway narrowing (p<0.05); 2) increased ventilation heterogeneity (p<0.05); 3) enhanced the subsequent bronchodilatory response to DI (p<0.05); and 4) reduced tissue elastance (p<0.05), suggesting opening of closed airways or alveoli units. Our findings suggest that DI prior to MCh challenge may elicit a series of changes, some of which are beneficial to respiratory function (enhanced bronchodilation), while others place greater load on the system (enhanced bronchoconstriction and ventilation heterogeneity). It is proposed that the relative magnitudes of these opposing physiological and mechanical effects will determine the net effect on respiratory function in health and disease.
Therapeutic Efficacy of Endostatin Exhibits a Biphasic Dose-Response Curve
Authors: Ilhan Celik, Oguzkan Sürücü, Carsten Dietz, John V. Heymach, Jeremy Force, Iris Höschele, Christian M. Becker, Judah Folkman, Oliver Kisker
Journal: Cancer Research (2005)

Abstract We show here that recombinant endostatin protein has a biphasic effect on the inhibition of endothelial cell migration in vitro. In tumor-bearing animals, there is a similar biphasic effect on the inhibition of tumor growth and on circulating endothelial cells after once-daily s.c. injections. This biphasic effect is revealed as a U-shaped curve in which efficacy is optimal between very low and very high doses depending on the tumor type. This result may be applicable to other inhibitors of endothelial growth and to angiogenesis. Furthermore, these results have important implications for clinicians who administer angiogenesis inhibitors for cancer or other angiogenesis-dependent diseases. When these results are taken together with two previous reports of angiogenesis inhibitors with a U-shaped dose-response, they suggest that other regulators of endothelial growth may display a similar pattern.
Ventilator-induced Lung Injury. Similarity and Differences between Children and Adults
Authors: Martin C. J. Kneyber, Haibo Zhang, Arthur S. Slutsky
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

It is well established that mechanical ventilation can injure the lung, producing an entity known as ventilator-induced lung injury (VILI). There are various forms of VILI, including volutrauma (i.e., injury caused by overdistending the lung), atelectrauma (injury due to repeated opening/closing of lung units), and biotrauma (release of mediators that can induce lung injury or aggravate pre-existing injury, potentially leading to multiple organ failure). Experimental data in the pediatric context are in accord with the importance of VILI, and appear to show age-related susceptibility to VILI, although a conclusive link between use of large Vts and mortality has not been demonstrated in this population. The relevance of VILI in the pediatric intensive care unit population is thus unclear. Given the physiological and biological differences in the respiratory systems of infants, children, and adults, it is difficult to directly extrapolate clinical practice from adults to children. This Critical Care Perspective analyzes the relevance of VILI to the pediatric population, and addresses why pediatric patients might be less susceptible than adults to VILI.
Current Hypotheses for the Biochemical Basis of Diabetic Retinopathy
Authors: Lawrence J Mandarino
Journal: Diabetes Care (1992)

Diabetic retinopathy is one of the leading causes of vision loss in industrialized countries. Despite recent advances, the biochemical basis for the development of this diabetic complication is uncertain. Although retinal circulation is unique in that it is readily observable noninvasively, retinal tissue is extremely difficult to study in humans because of the problems inherent in obtaining fresh, appropriate biopsy material. Moreover, because of the difficulties in working with animal models of diabetic retinopathy, such as the dog, many investigators have turned to cell-culture models, especially those using primary cultures of retinal capillary endothelial cells and pericytes. Diabetic retinopathy involves both morphological and functional changes in the retinal capillaries. Morphological changes include basement membrane thickening and pericyte disappearance; functional changes include one important early change—increased permeability—which may be attributable to endothelial cell changes and basement membrane leakiness. Investigators have described major biochemical changes in cellular signaling pathways, including myo-inositol, inositol phosphates, and DAG metabolism, as well as decreased Na+-K+-ATPase and increased PKC activity. These defects may be related to the way endothelial cells and pericytes synthesize and interact with the extracellular matrix. Abnormalities in endothelial cell or pericyte interaction with the basement membrane may in turn lead to functional abnormalities, such as increased permeability.
Rejection of bone marrow allografts by mice with severe combined immune deficiency (SCID). Evidence that natural killer cells can mediate the specificity of marrow graft rejection.
Authors: W J Murphy, V Kumar, M Bennett
Journal: The Journal of Experimental Medicine (1987)

C.B-17 scid (H-2d) mice are homozygous for the gene that causes severe combined immune deficiency (SCID). These mice have no T or B cell function, yet display normal natural killer (NK) activity. Irradiated SCID mice were challenged with marrow grafts to determine if antibodies are necessary for marrow allograft rejection. SCID mice rejected H-2/Hh-1 allogeneic marrow grafts. Moreover, this rejection capability could be adoptively transferred using SCID marrow as a source of NK progenitors infused into irradiated B6 (H-2b) hosts. We conclude that NK cells can mediate marrow allograft reactivity in the absence of immunoglobulin. It follows that NK cells probably have specific receptors for Hh antigens.
Enhanced Cardiac Regenerative Ability of Stem Cells After Ischemia-Reperfusion Injury
Authors: Darukeshwara Joladarashi, Venkata Naga Srikanth Garikipati, Rajarajan A. Thandavarayan, Suresh K. Verma, Alexander R. Mackie, Mohsin Khan, Anna M. Gumpert, Arvind Bhimaraj, Keith A. Youker, Cesar Uribe, Sahana Suresh Babu, Prince Jeyabal, Raj Kishore, Prasanna Krishnamurthy
Journal: Journal of the American College of Cardiology (2015)
Linear accelerator-based stereotaxic radiosurgery for brain metastases:the influence of number of lesions on survival.
Authors: J Joseph, J R Adler, R S Cox, S L Hancock
Journal: Journal of Clinical Oncology (1996)

To evaluate the influence of the number of brain metastases on survival after stereotaxic radiosurgery and factors that affect the risk of delayed radiation necrosis after treatment.Between March 1989 and December 1993, 120 consecutive patients underwent linear accelerator-based stereotaxic radiosurgery for brain metastases identified by computed tomography (CT) or magnetic resonance imaging (MRI) scans. The influence of various clinical factors on outcome was assessed using Kaplan-Meier plots of survival from the date of radiosurgery, and univariate and multivariate analyses.The median survival time was 32 weeks. Progressive brain metastases, both local and regional, caused 25 of 104 deaths. Patients with two metastases (n = 30) or a solitary metastasis (n = 70) had equivalent actuarial survival times (P = .07; median, 37 weeks; maximum, 211+ weeks). Patients treated to three or more metastases (n = 20) had significantly shorter survival times (P < .002; median, 14 weeks; maximum, 63 weeks). Prognostic factors associated with prolonged survival included a pretreatment Karnofsky performance status > or = 70% and fewer than three metastases. Delayed radiation necrosis at the treated site developed in 20 patients and correlated with prior or concurrent delivery of whole-brain irradiation and the logarithm of the tumor volume.Survival duration is equivalent for patients with one or two brain metastases and is similar to that reported for patients with a solitary metastasis managed by surgical resection and whole-brain irradiation. Survival after radiosurgery for three or more metastases was similar to that reported for whole-brain irradiation.
Predictors for incidence and remission of NAFLD in the general population during a seven-year prospective follow-up
Authors: Shira Zelber-Sagi, Roni Lotan, Amir Shlomai, Muriel Webb, Gil Harrari, Assaf Buch, Dorit Nitzan Kaluski, Zamir Halpern, Ran Oren
Journal: Journal of Hepatology (2012)
Risk Adjustment for Case Mix and the Effect of Surgeon Volume on Morbidity
Authors: Matthew B. Maas, Michael R. Jaff, Guy A. Rordorf
Journal: JAMA Surgery (2013)

Retrospective studies of large administrative databases have shown higher mortality for procedures performed by low-volume surgeons, but the adequacy of risk adjustment in those studies is in doubt.To determine whether the relationship between surgeon volume and outcomes is an artifact of case mix using a prospective sample of carotid endarterectomy cases.Observational cohort study from January 1, 2008, through December 31, 2010, with preoperative, immediate postoperative, and 30-day postoperative assessments acquired by independent monitors.Urban, tertiary academic medical center.All 841 patients who underwent carotid endarterectomy performed by a vascular surgeon or cerebrovascular neurosurgeon at the institution.Carotid endarterectomy without another concurrent surgery.Stroke, death, and other surgical complications occurring within 30 days of surgery along with other case data. A low-volume surgeon performed 40 or fewer cases per year. Variables used in a comparison administrative database study, as well as variables identified by our univariate analysis, were used for adjusted analyses to assess for an association between low-volume surgeons and the rate of stroke and death as well as other complications. RESULTS The rate of stroke and death was 6.9% for low-volume surgeons and 2.0% for high-volume surgeons (P = .001). Complications were similarly higher (13.4% vs 7.2%, P = .008). Low-volume surgeons performed more nonelective cases. Low-volume surgeons were significantly associated with stroke and death in the unadjusted analysis as well as after adjustment with variables used in the administrative database study (odds ratio, 3.61; 95% CI, 1.70-7.67, and odds ratio, 3.68; 95% CI, 1.72-7.89, respectively). However, adjusting for the significant disparity of American Society of Anesthesiologists Physical Status classification in case mix eliminated the effect of surgeon volume on the rate of stroke and death (odds ratio, 1.65; 95% CI, 0.59-4.64) and other complications.Variables selected for risk adjustment in studies using administrative databases appear to be inadequate to control for case mix bias between low-volume and high-volume surgeons. Risk adjustment should empirically analyze for case mix imbalances between surgeons to identify meaningful risk modifiers in clinical practice such as the American Society of Anesthesiologists Physical Status classification. A true relationship between surgeon volume and outcomes remains uncertain, and caution is advised in developing policies based on these findings.
Hepatic 31P MRS in rat models of chronic liver disease: assessing the extent and progression of disease
Authors: I R Corbin, R Buist, J Peeling, M Zhang, J Uhanova, G Y Minuk
Journal: Gut (2003)

<b>Background:</b> Hepatic adenosine triphosphate (ATP) levels are an accurate reflection of functioning hepatic mass following surgical resections and acute liver injury. <b>Objective:</b> To determine whether hepatic ATP levels can serve as a non-invasive means of documenting progression of chronic liver disease to cirrhosis. <b>Methods:</b> In vivo phosphorus-31 magnetic resonance spectroscopy (<sup>31</sup>P MRS) was performed in three animal models of chronic liver disease. Sixty six adult Sprague- Dawley rats were subjected to either thioacetamide, carbon tetrachloride (CCl<sub>4</sub>), or common bile duct ligation (CBDL) to induce liver disease (n=35, 21, and 10, respectively). Serial MRS examinations, blood samples, and liver biopsies (when appropriate) were obtained throughout and/or on completion of the study. <b>Results:</b> Over the course of the chronic liver disease, a progressive decrease in hepatic ATP levels was consistently observed in each model. The findings were most striking when end stage liver disease (cirrhosis) was established. The reduction in hepatic ATP levels correlated with significant changes in serum albumin concentrations (CCl<sub>4</sub> and CBDL models) and the extent of hepatocyte loss seen histologically (all models). <b>Conclusion:</b> The results of this study indicate that during progression of chronic liver disease to cirrhosis, there is a progressive reduction in hepatic ATP levels. In addition, changes in hepatic ATP levels correlate with changes in liver function and histology. Thus hepatic <sup>31</sup>P MRS provides a non-invasive means of documenting the severity and progression of parenchymal and cholestatic models of chronic liver disease in rats.
Inflammatory cell and epithelial characteristics of perennial allergic and nonallergic rhinitis with a symptom history of 1 to 3 years’ duration
Authors: Kawa Amin, Juhani Rinne, Tari Haahtela, Markku Simola, Christer G.B. Peterson, Godfried M. Roomans, Henrik Malmberg, Per Venge, Lahja Sevéus
Journal: Journal of Allergy and Clinical Immunology (2001)
Patient Satisfaction with 20% Subcutaneous Immunoglobulin (Hizentra®) Treatment: Results From a Single-Center Study in Children with Immunodeficiencies
Authors: Clare Malcolmson, Rebecca Gregory, Chetan Patel, Zoya Panahloo, Alison Jones
Journal: Journal of Allergy and Clinical Immunology (2013)

Patients with primary immunodeficiency diseases (PID) receive life-long treatment and thus satisfaction with therapy plays an important role in treatment decisions. Patients with PID who had previously received a 16% subcutaneous immunoglobulin (SCIG) product (Vivaglobin®) were switched to 20% SCIG (Hizentra®). Following treatment switch, satisfaction with 20% SCIG therapy in children and young adults (<19 years) was assessed based on patients/caregivers opinions of treatment, informally gathered during hospital visits or telephone conversations. Results were analyzed with descriptive statistics. Thirty-seven patients aged 1–18.8 years (median age 9.3 years) were evaluated. 20% SCIG was administered weekly (q1w; n=21), every 2 weeks (q2w; n=14), or every 10 days (q10d; n=2) for an average of 9.3 months. 20% SCIG q2w recipients were younger (median age 3.7 years, range 1–10.9) than q1w recipients (median 12.1 years, range 3.5–18.8). Mean (SD) serum IgG levels in these groups were comparable (10.1 [2.6] g/L in q2w patients and 12.1 [3.3] g/L in q1w patients), considering the age difference and associated serum IgG level variations. All patients were satisfied with their therapy (preliminary data, n=25). Of q2w recipients (n=14), four (29%) reported treatment satisfaction improvements attributed to ease of use, shorter infusions, and general health and well being improvement, five (36%) reported no change; data unavailable in five. Corresponding q1w (n=21) data: four (19%), 11 (52%), and six. Compared to previous SCIG therapy, serum IgG levels are maintained with both weekly and biweekly 20% SCIG Hizentra® administration, with a number of patients reporting improved treatment satisfaction.