tbuckley/cabot-search huggingface dataset:
Blood Lead Level and Measured Glomerular Filtration Rate in Children with Chronic Kidney Disease
Authors: Jeffrey J. Fadrowski, Alison G. Abraham, Ana Navas-Acien, Eliseo Guallar, Virginia M. Weaver, Susan L. Furth
Journal: Environmental Health Perspectives (2013)

Background: The role of environmental exposure to lead as a risk factor for chronic kidney disease (CKD) and its progression remains controversial, and most studies have been limited by a lack of direct glomerular filtration rate (GFR) measurement.Objective: We evaluated the association between lead exposure and GFR in children with CKD.Methods: In this cross-sectional study, we examined the association between blood lead levels (BLLs) and GFR measured by the plasma disappearance of iohexol among 391 participants in the Chronic Kidney Disease in Children (CKiD) prospective cohort study.Results: Median BLL and GFR were 1.2 µg/dL and 44.4 mL/min per 1.73 m2, respectively. The average percent change in GFR for each 1-µg/dL increase in BLL was –2.1 (95% CI: –6.0, 1.8). In analyses stratified by CKD diagnosis, the association between BLL and GFR was stronger among children with glomerular disease underlying CKD; in this group, each 1-µg/dL increase in BLL was associated with a –12.1 (95% CI: –22.2, –1.9) percent change in GFR. In analyses stratified by anemia status, each 1-µg/dL increase in BLL among those with and without anemia was associated with a –0.3 (95% CI: –7.2, 6.6) and –4.6 (95% CI: –8.9, –0.3) percent change in GFR, respectively.Conclusions: There was no significant association between BLL and directly measured GFR in this relatively large cohort of children with CKD, although associations were observed in some subgroups. Longitudinal analyses are needed to examine the temporal relationship between lead and GFR decline, and to further examine the impact of underlying cause of CKD and anemia/hemoglobin status among patients with CKD.
Better clinician access will help government halve smoking by 2010
Authors: A. O'Dowd
Journal: BMJ (2010)

Doctors will be required to provide more smoking cessation services as part of a new government target to halve the number of smokers in England.

The Department of Health this week announced a new tobacco control strategy that aims to halve the number of smokers in the population from 21% to 10% by 2020.

The guidance will build on efforts over the past decade that cut the number of people who smoke by a quarter. 

Under A smokefree future: a comprehensive tobacco control strategy for England , smokers will be encouraged to get support from the NHS, where professional help will be more accessible and wider range of options available.

As part of …
Breast Cancer Prevention: Lessons to be Learned from Mechanisms of Early Pregnancy–Mediated Breast Cancer Protection
Authors: Fabienne Meier-Abt, Mohamed Bentires-Alj, Christoph Rochlitz
Journal: Cancer Research (2015)

Pregnancy at early, but not late age, has a strong and life-long protective effect against breast cancer. The expected overall increase in breast cancer incidence demands the development of a pharmaceutical mimicry of early-age pregnancy-mediated protection. Recently, converging results from rodent models and women on molecular and cellular mechanisms underlying the protective effect of early-age pregnancy have opened the door for translational studies on pharmacologic prevention against breast cancer. In particular, alterations in Wnt and TGFβ signaling in mammary stem/progenitor cells reveal new potential targets for preventive interventions, and thus might help to significantly reduce the incidence of breast cancer in the future.
Mechanical versus manual chest compression for out-of-hospital cardiac arrest (PARAMEDIC): a pragmatic, cluster randomised controlled trial
Authors: Gavin D Perkins, Ranjit Lall, Tom Quinn, Charles D Deakin, Matthew W Cooke, Jessica Horton, Sarah E Lamb, Anne-Marie Slowther, Malcolm Woollard, Andy Carson, Mike Smyth, Richard Whitfield, Amanda Williams, Helen Pocock, John J M Black, John Wright, Kyee Han, Simon Gates
Journal: The Lancet (2014)

BackgroundMechanical chest compression devices have the potential to help maintain high-quality cardiopulmonary resuscitation (CPR), but despite their increasing use, little evidence exists for their effectiveness. We aimed to study whether the introduction of LUCAS-2 mechanical CPR into front-line emergency response vehicles would improve survival from out-of-hospital cardiac arrest.MethodsThe pre-hospital randomised assessment of a mechanical compression device in cardiac arrest (PARAMEDIC) trial was a pragmatic, cluster-randomised open-label trial including adults with non-traumatic, out-of-hospital cardiac arrest from four UK Ambulance Services (West Midlands, North East England, Wales, South Central). 91 urban and semi-urban ambulance stations were selected for participation. Clusters were ambulance service vehicles, which were randomly assigned (1:2) to LUCAS-2 or manual CPR. Patients received LUCAS-2 mechanical chest compression or manual chest compressions according to the first trial vehicle to arrive on scene. The primary outcome was survival at 30 days following cardiac arrest and was analysed by intention to treat. Ambulance dispatch staff and those collecting the primary outcome were masked to treatment allocation. Masking of the ambulance staff who delivered the interventions and reported initial response to treatment was not possible. The study is registered with Current Controlled Trials, number ISRCTN08233942.FindingsWe enrolled 4471 eligible patients (1652 assigned to the LUCAS-2 group, 2819 assigned to the control group) between April 15, 2010 and June 10, 2013. 985 (60%) patients in the LUCAS-2 group received mechanical chest compression, and 11 (<1%) patients in the control group received LUCAS-2. In the intention-to-treat analysis, 30 day survival was similar in the LUCAS-2 group (104 [6%] of 1652 patients) and in the manual CPR group (193 [7%] of 2819 patients; adjusted odds ratio [OR] 0·86, 95% CI 0·64–1·15). No serious adverse events were noted. Seven clinical adverse events were reported in the LUCAS-2 group (three patients with chest bruising, two with chest lacerations, and two with blood in mouth). 15 device incidents occurred during operational use. No adverse or serious adverse events were reported in the manual group.InterpretationWe noted no evidence of improvement in 30 day survival with LUCAS-2 compared with manual compressions. On the basis of ours and other recent randomised trials, widespread adoption of mechanical CPR devices for routine use does not improve survival.FundingNational Institute for Health Research HTA – 07/37/69.
Targeted Delivery of Tumor Necrosis Factor-α to Tumor Vessels Induces a Therapeutic T Cell–Mediated Immune Response that Protects the Host Against Syngeneic Tumors of Different Histologic Origin
Authors: Enrica Balza, Lorenzo Mortara, Francesca Sassi, Stefano Monteghirfo, Barbara Carnemolla, Patrizia Castellani, Dario Neri, Roberto S. Accolla, Luciano Zardi, Laura Borsi
Journal: Clinical Cancer Research (2006)

Abstract Purpose: We sought to demonstrate that a single systemic administration of L19mTNFα (a fusion protein constituted by the scFv L19 specific for the oncofetal ED-B domain of fibronectin and tumor necrosis factor α, TNFα) in combination with melphalan induced complete and long-lasting tumor eradication in tumor-bearing mice and triggered the generation of a specific T cell–based immune response that protects the animals from a second tumor challenge, as well as from challenges with syngeneic tumor cells of different histologic origin. Experimental Design and Results: Treatment with L19mTNFα, in combination with melphalan, induced complete tumor regression in 83% of BALB/c mice with WEHI-164 fibrosarcoma and 33% of animals with C51 colon carcinoma. All cured mice rejected challenges with the same tumor cells and, in a very high percentage of animals, also rejected challenges with syngeneic tumor cells of different histologic origin. In adoptive immunity transfer experiments, the splenocytes from tumor-cured mice protected naive mice both from C51 colon carcinoma and from WEHI-164 fibrosarcoma. Similar results were also obtained in adoptive immunity transfer experiments using severely immunodepressed mice. Experiments using depleted splenocytes showed that T cells play a major role in tumor rejection. Conclusions: The results show that the selective targeting of mTNFα to the tumor enhances its immunostimulatory properties to the point of generating a therapeutic immune response against different histologically unrelated syngeneic tumors. These findings predicate treatment approaches for cancer patients based on the targeted delivery of TNFα to the tumor vasculature.
Phase II study of low-dose recombinant leukocyte A interferon in disseminated malignant melanoma.
Authors: E T Creagan, D L Ahmann, S J Green, H J Long, S Frytak, J R O'Fallon, L M Itri
Journal: Journal of Clinical Oncology (1984)

Thirty patients with disseminated malignant melanoma received intramuscular recombinant leukocyte A interferon (rIFN-alpha A), 12 X 10(6) U/m2, three times weekly for a planned treatment duration of three months. This dose was selected in view of our prior phase II data indicating that 50 X 10(6) U/m2 three times weekly produced excessive toxicity. In this current trial we observed three objective partial regressions (20%) among the 15 better-risk patients (performance score 0, 1, and no prior chemotherapy) with times to disease progression of 1.9, 9.6, and 12.9+ months. There were also three regressions (one complete and two partial) among the 15 poor-risk patients (performance score 2, 3, or prior chemotherapy) with progression times of 3, 3.2, and 9.6+ months. For all patients, the median survival time was 4.2 months. One half of the patients were observed to have progressive disease within one month of commencing treatment. Responding metastatic lesions were limited to soft tissue, although one patient also had a partial response of a lung nodule. The most substantial toxicities were moderate-to-severe myalgias (27%), nausea (33%), anorexia (47%), and fatigue (50%). Among the 22 patients with weight loss, the median was 2.3 kg (range, 0.6 to 8.4 kg). Hematologic and hepatic toxicity was transient and of little clinical significance. Our study indicates that rIFN-alpha A in the dose and schedule that we used is clinically tolerable and has antitumor activity in malignant melanoma. The response rate was similar to results observed in our previous study of a higher dose regimen.
A Two-Dimensional Ballistocardiographic Study of 59 Apparently Normal Persons
Authors: GWENDOLYN L. MORRIS, JOHN R. BRAUNSTEIN
Journal: Circulation (1955)

Simultaneous longitudinal and transverse ballistocardiograms were obtained from 59 apparently normal persons. A highly significant correlation was found to exist between body surface area and basal longitudinal "IJ" amplitude. The significance of this is discussed. The transverse IJ amplitude is shown to be related to the rotation of the heart about the anteroposterior axis of the body.
Computed tomography in staging for lung cancer
Authors: J.A. Verschakelen, J. Bogaert, W. De Wever
Journal: European Respiratory Journal (2002)

Computed tomography (CT) provides the most detailed imaging information, hence it is generally used as a routine imaging procedure in the tumour, node, metastasis (TNM)-staging of patients with lung cancer. However, despite the continuously ongoing process of improvement in CT scanning in which today's CT scanners combine fast acquisition, fast data reconstruction and high detail, the technique has important limitations. CT can, in some cases, very accurately show tumour extent within, and predict spread beyond the lung. However, the question of whether the tumour has invaded the chest wall or the mediastinum and, if so, whether it is still potentially surgically curable often remains unanswered. In addition, the only sign for predicting lymph node involvement using CT is enlargement. Many studies have shown that this sign is not very reliable. CT is also, with success, being used to evaluate distant metastases although other techniques such as ultrasound and magnetic resonance imaging can have similar or higher accuracies. Despite these well-known limitations, computed tomography will most likely stay the routine imaging procedure for determining resectability and for assessing intra- and extrathoracic spread of lung cancer. The improvement in technology will probably result a better T-staging. The role of computed tomography in nodal staging remains important. It offers the surgeon a road map of the lymph nodes and guides towards the nodes that need biopsy. Combining computed tomography with positron emission tomography, when it becomes more widely available, will add functional images to the detail of computed tomography and will not only improve nodal staging but will probably also allow a better evaluation of distant metastasis and reduce the number of unnecessary interventional procedures.
Role of red blood cells in the coronary microcirculation during cold blood cardioplegia
Authors: A. SAKAI, J. MIYA, Y. SOHARA, H. MAETA, N. OHSHIMA, M. HORI
Journal: Cardiovascular Research (1988)

The role of red blood cells during cold blood cardioplegia was studied using an intravital microscope in 13 isolated canine hearts perfused with diluted blood containing potassium chloride. The coronary microcirculation on the left ventricular epicardial surface was observed while the perfusate temperature was varied between 37°C and 10°C. Considerable sludging of red blood cells occurred during hypothermia. The percentage of capillaries perfused by red blood cells (percentage change) significantly decreased as perfusate temperature was reduced (100, 56, and 31% at 37, 20, and 10°C respectively). This was caused by occlusion of microvessels due to sludging and by functional closure due to hypothermia. There was incomplete recovery of perfusion of capillaries at the end of rewarming (60%). The diameters of venules were reduced to 76% of control value at 10°C because of the decrease in the numbers of feeding capillaries, but this value returned to 91 % at the end of rewarming. Coronary vascular resistance (mmHg·ml−1·min−1 (kPa·s·litre−1)) significantly decreased from 2.0(0.2) at 37°C to 1.2(0.12) at 10°C, but it increased to 2.4(0.24) at the end of rewarming. The finding in this study that sludging occurred which was slow to clear is a definite disadvantage of perfusion with red blood cells during hypothermia.
iPSC-derived β cells model diabetes due to glucokinase deficiency
Authors: Haiqing Hua, Linshan Shang, Hector Martinez, Matthew Freeby, Mary Pat Gallagher, Thomas Ludwig, Liyong Deng, Ellen Greenberg, Charles LeDuc, Wendy K. Chung, Robin Goland, Rudolph L. Leibel, Dieter Egli
Journal: Journal of Clinical Investigation (2013)

Diabetes is a disorder characterized by loss of β cell mass and/or β cell function, leading to deficiency of insulin relative to metabolic need. To determine whether stem cell-derived β cells recapitulate molecular-physiological phenotypes of a diabetic subject, we generated induced pluripotent stem cells (iPSCs) from subjects with maturity-onset diabetes of the young type 2 (MODY2), which is characterized by heterozygous loss of function of the gene encoding glucokinase (GCK). These stem cells differentiated into β cells with efficiency comparable to that of controls and expressed markers of mature β cells, including urocortin-3 and zinc transporter 8, upon transplantation into mice. While insulin secretion in response to arginine or other secretagogues was identical to that in cells from healthy controls, GCK mutant β cells required higher glucose levels to stimulate insulin secretion. Importantly, this glucose-specific phenotype was fully reverted upon gene sequence correction by homologous recombination. Our results demonstrate that iPSC-derived β cells reflect β cell-autonomous phenotypes of MODY2 subjects, providing a platform for mechanistic analysis of specific genotypes on β cell function.
P2Y1 Gene Deficiency Protects from Renal Disease Progression and Capillary Rarefaction during Passive Crescentic Glomerulonephritis
Authors: Bernd Hohenstein, Sindy Renk, Kathrin Lang, Christoph Daniel, Monique Freund, Catherine Léon, Kerstin U. Amann, Christian Gachet, Christian P.M. Hugo
Journal: Journal of the American Society of Nephrology (2007)

The metabotropic receptor P2Y1 is necessary for full ADP-induced platelet activation and is localized on various intrinsic renal cells, including mesangial cells, podocytes, and endothelial cells. To date, nothing is known about the role of the P2Y1 receptor during inflammatory renal disease. The role of the P2Y1 receptor was investigated using 22 P2Y1 gene-deficient (-/-) and 27 wild-type (wt) mice during the time course of passive crescentic nephrotoxic glomerulonephritis. Six P2Y1 -/- and six wt mice served as undiseased controls. Renal tissues were harvested on days 1, 10, and 28 after disease induction. No renal phenotype was found in P2Y1 -/- versus wt mice. In contrast, during crescentic glomerulonephritis, approximately 50% of all wt mice died, whereas all P2Y1 -/- mice survived. Renal function as assessed by creatinine clearance measurements, glomerulosclerosis, and tubulointerstitial injury indices as well as glomerular and interstitial matrix expansion were improved significantly in P2Y1 -/- compared with wt mice. These changes were preceded by reduced glomerular and peritubular capillary rarefaction indices in P2Y1 -/- compared with wt mice. The alteration of the rates of both peritubular apoptosis and endothelial cell proliferation suggests improved capillary preservation in P2Y1 -/- mice early in disease (day 10) and an additional enhanced repair reaction in P2Y1 -/- mice at the late time point (day 28), whereas injury on day 1 seemed to be equivalent in both groups. It is concluded that loss of P2Y1 receptor function safeguards against capillary loss, fibrosis, and death by renal failure during experimental crescentic glomerulonephritis.
Does the type of competing interest statement affect readers' perceptions of the credibility of research? Randomised trial
Authors: Sara Schroter, Julie Morris, Samena Chaudhry, Richard Smith, Helen Barratt
Journal: BMJ (2004)

diabetes in the past 30 years.Because methods for glycaemic control and the delivery of insulin therapy have improved over time, the proportion of people admitted with diabetes whose condition is difficult to control is unlikely to have increased.Survival of young people with type 1 diabetes whose disease was serious enough to warrant admission is therefore not likely to have improved much.Leicester Gill, Glenys Bettley, and Myfanwy Griffith built the database.
Role of different proton-sensitive channels in releasing calcitonin gene-related peptide from isolated hearts of mutant mice
Authors: T STRECKER, K MESSLINGER, M WEYAND, P REEH
Journal: Cardiovascular Research (2004)

Calcitonin gene-related peptide (CGRP), a potent vasodilator released from a subset of sensory Adelta- and C-fiber afferents, has been suggested to play a beneficial role in myocardial ischemia. The aim of the present study was to investigate some receptors possibly involved in the proton-mediated CGRP release from the heart.CGRP release from freshly isolated hearts of mice lacking the capsaicin receptor (TRPV1-/-), the bradykinin receptor type 2 (B2-/-), or the acid-sensing ion channel type 3 (ASIC3-/-) and their wild-type littermates (TRPV1+/+, B2+/+, ASIC3+/+) were compared. Hearts were passed through a series of solutions based on oxygenated synthetic interstitial fluid (SIF). SIF buffered to pH 5.7 or 5.2 was used as an acidic test stimulus, and capsaicin (5x10(-7) M) was finally applied as a positive control. All eluates were processed using an enzyme immunoassay (EIA) for measurement of CGRP concentrations.SIF at pH 5.7 and 5.2 caused significant increases in CGRP release in TRPV1+/+ but not in mice lacking the TRPV1 receptor. The same acid stimuli caused no significant differences in CGRP release between ASIC3+/+ and ASIC3-/- or between B2+/+ and B2-/-, respectively. Capsaicin caused massive CGRP release in all mouse genotypes with the exception of TRPV1-/-.We conclude that cardiac acidosis is a strong stimulus to release CGRP from the mouse heart. This effect seems to be primarily mediated through activation of TRPV1 receptors that are known to be expressed by slowly conducting nociceptive primary afferent nerve fibers.
Dating Violence Against Adolescent Girls and Associated Substance Use, Unhealthy Weight Control, Sexual Risk Behavior, Pregnancy, and Suicidality
Authors: Jay G. Silverman
Journal: JAMA (2001)

ContextIntimate partner violence against women is a major public health concern. Research among adults has shown that younger age is a consistent risk factor for experiencing and perpetrating intimate partner violence. However, no representative epidemiologic studies of lifetime prevalence of dating violence among adolescents have been conducted.ObjectiveTo assess lifetime prevalence of physical and sexual violence from dating partners among adolescent girls and associations of these forms of violence with specific health risks.Design, Setting, and ParticipantsFemale 9th through 12th-grade students who participated in the 1997 and 1999 Massachusetts Youth Risk Behavior Surveys (n = 1977 and 2186, respectively).Main Outcome MeasuresLifetime prevalence rates of physical and sexual dating violence and whether such violence is independently associated with substance use, unhealthy weight control, sexual risk behavior, pregnancy, and suicidality.ResultsApproximately 1 in 5 female students (20.2% in 1997 and 18.0% in 1999) reported being physically and/or sexually abused by a dating partner. After controlling for the effects of potentially confounding demographics and risk behaviors, data from both surveys indicate that physical and sexual dating violence against adolescent girls is associated with increased risk of substance use (eg, cocaine use for 1997, odds ratio [OR], 4.7; 95% confidence interval [CI], 2.3-9.6; for 1999, OR, 3.4; 95% CI, 1.7-6.7), unhealthy weight control behaviors (eg, use of laxatives and/or vomiting [for 1997, OR, 3.2; 95% CI, 1.8-5.5; for 1999, OR, 3.7; 95% CI, 2.2-6.5]), sexual risk behaviors (eg, first intercourse before age 15 years [for 1997, OR, 8.2; 95% CI, 5.1-13.4; for 1999, OR, 2.4; 95% CI, 1.4-4.2]), pregnancy (for 1997, OR, 6.3; 95% CI, 3.4-11.7; for 1999, OR, 3.9; 95% CI, 1.9-7.8), and suicidality (eg, attempted suicide [for 1997, OR, 7.6; 95% CI, 4.7-12.3; for 1999, OR, 8.6; 95% CI, 5.2-14.4]).ConclusionDating violence is extremely prevalent among this population, and adolescent girls who report a history of experiencing dating violence are more likely to exhibit other serious health risk behaviors.
Anaphylactic shock by rupture of hydatid hepatic cyst
Authors: B. Saenz de San Pedro, J. L. Cazaña, J. Cobo, C. L. Serrano, J. Quiralte, J. Contreras, F. Martinez
Journal: Allergy (1992)

Total and specific serum IgE antibodies were estimated in a 68‐year‐old woman with anaphylactic shock due to spontaneous rupture of hydatid cyst of the liver. After she had recovered, an abdominal ultrasonography showed a cyst, 10×15 cm, in the right hepatic lobe. The cyst was surgically removed. Antihydatid IgE in the acute phase and periodically after surgical intervention, determined by Phadezym RAST, Pharmacia, and Pharmacia CAP system (a new solid‐phase immunoassay, fully automated, for the titration of specific IgE with greater sensitivity in the detection of low IgE antibody levels), showed decreasing antihydatid IgE antibodies on day 10 after surgical intervention and may thus serve to monitor the evolution of hydatid disease.