tbuckley/cabot-search huggingface dataset:
Repeated latex aeroallergen challenges employing a hooded exposure chamber: safety and reproducibility
Authors: K. M. Kurtz, R. G. Hamilton, J. A. Schaefer, M. N. Primeau, N. F. Adkinson Jr
Journal: Allergy (2001)

Background: Bronchial, nasal, and conjunctival challenges are useful for clarifying discordant clinical history (Hx) and skin and/or serologic tests and in assessing semiquantitative changes in biologic sensitivity over time. The objective of this study was to determine the safety and reproducibility of repeated latex‐allergen challenges with a hooded exposure chamber (HEC). Methods: The HEC system comprises a powered forced‐air respirator with a fitted face shield and hood that uses glove‐derived latex‐allergen associated cornstarch particles (LAC) to expose simultaneously the conjunctiva, nose, and lungs. Serial control and incremental LAC challenges are conducted until an endpoint based on upper and/or lower respiratory tract symptoms and peak expiratory flow rates is reached. Six latex‐allergic (Hx and puncture skin test [PST]‐ and 5/6 radioallergosorbent test [RAST]‐positive) subjects were challenged on three separate occasions at least 2 weeks apart. Serial latex PST midpoints and serum anti‐latex IgE by RAST were monitored at each visit and at a fourth follow‐up visit. Results: All subjects responded to LAC, but not to air or control cornstarch administered as controls. All responses were confined to mild symptoms of allergic rhinoconjunctivitis and/or asthma that either resolved spontaneously or were reversed with inhaled albuterol. No subject experienced a systemic or delayed reaction. There were no significant changes in the endpoint LAC doses over the three challenge visits ( P &gt;0.2). The mean coefficient of variation for log 2 endpoints within‐subjects was 17.3±17.2% (SD). The serum latex‐specific IgE was not significantly boosted by the three challenges ( P &gt;0.2). The concentration of latex extract necessary to produce an 8‐mm wheal by PST was not significantly changed during the study ( P &gt;0.1), indicating that latex sensitivity was not affected by the repeated LAC exposures. Conclusions: The results of this study indicate that repeated HEC latex‐allergen challenges are both reproducible and safe, and do not increase latex sensitivity.
New Strategies in the Treatment of the Thalassemias
Authors: Stanley L. Schrier, Emanuele Angelucci
Journal: Annual Review of Medicine (2004)

In addition to the severe beta thalassemias, hematologists have begun to recognize the more severe forms of alpha thalassemia, namely hemoglobin (Hb) H disease and Hb H/Hb Constant Spring, as well as the beta compound heterozygote, beta thalassemia/HbE. Clinically, variably severe anemia becomes apparent in the first year accompanied by occasionally massive expansion of erythropoiesis. The most anemic patients require regular red blood cell transfusions to avoid death from cardiac failure. However, the inevitable iron accumulation leads to dysfunction, primarily involving the heart, liver, and endocrine system; thus, regularly transfused patients require iron chelation. A major discovery was that allogeneic bone marrow (stem cell) transplantation in severely affected subjects with both alpha and beta thalassemia could result in cure. Current work deals with specific complications, such as iron overload and endocrine, cardiopulmonary, thrombophilic, and osteopenic problems. The thalassemias are likely to benefit in the future from specific gene therapy. There are also important advances in genetic counseling based on results of early fetal diagnosis.
Dizziness after sports-related concussion: Can physiotherapists offer better treatment than just ‘physical and cognitive rest’?
Authors: Jennifer C Reneker, Chad E Cook
Journal: British Journal of Sports Medicine (2014)

Examination and treatment of concussed athletes is a complex endeavour. Three notable position papers: the International Conference on Concussion in Sport (Zurich) Consensus Statement,1 the American Academy of Neurology (AAN) Guideline,2 and American Medical Society for Sports Medicine Position paper,3 advocate for a multifactorial assessment to diagnose sports-related concussion (‘concussion’ in this paper) and determine the degree of functional disturbance. These papers also provide guidelines to manage recovery, the cornerstone of which is cognitive and physical rest. Rest is a well-established practice pattern even though it has only very low-level evidence. Strikingly absent from concussion management are specific treatment strategies which are underpinned by anatomical-symptom correlates.4 ,5

Symptoms such as dizziness are very common among concussed individuals, present in nearly 80% of concussions,6 second only to headaches.3 For the most part after concussion, non-dizziness oriented symptoms are transient, whereas the natural course of recovery from dizziness often lingers, in some cases for years after the initial event.6 Considering the mechanism associated with concussion and …
Induction of a cross-reactive idiotype dextran-positive antibody response in two IgH-Cb mouse strains treated with anti-J558 cross-reactive idiotype antibodies.
Authors: J Pène, F Bekkhoucha, C Desaymard, H Zaghouani, M Stanislawski
Journal: The Journal of Experimental Medicine (1983)

The effect of IdX-specific rabbit and allogeneic antiidiotype antibodies (Ab2) was investigated in vivo in Igh-Cb mouse strains with respect to the induction of a cross-reactive idiotype (IdX)-positive anti-alpha (1-3) Dextran (Dex) response. These C.B20 and C57Bl/6 mice have an allotype-linked incapacity to respond with IdX-positive anti-alpha (1-3) Dex antibodies upon conventional immunization with Dex B1355. 7 d after the rabbit Ab2 injections, IdX-positive Ig (Ab3) and IdX-positive anti-alpha (1-3) Dex antibodies (Ab1') were detected in the sera of each tested mouse. The affinity-purified Ab1' were idiotypically indistinguishable from reference BALB/c IdX-positive myeloma proteins and BALB/c anti-alpha (1-3) Dex antibodies (Ab1) in a competitive inhibition radioimmunoassay, while Ab3 Ig appeared idiotypically deficient and did not bind to Dex. The response to the alpha (1-6) linkage of Dex was not affected in these mice. A large fraction of the Ab1' and Ab3 responses of both mouse strains were of the IgG1 class. The Ab1' antibodies differed from BALB/c Ab1 by lower relative binding to five of eight tested Dex, and by expressing the Igh4b allotype determinants on the IgG1 antibodies. This study identifies the products of a VHDex gene that appears to be under regulatory control in the Ighb mice. Its association with the b haplotype suggests that this gene may differ structurally from the BALB/c VHDex gene.
Evidence of a Graft-Versus-Leukemia Effect in Chronic Lymphocytic Leukemia After Reduced-Intensity Conditioning and Allogeneic Stem-Cell Transplantation: The Cooperative German Transplant Study Group
Authors: J. Schetelig, C. Thiede, M. Bornhäuser, R. Schwerdtfeger, M. Kiehl, J. Beyer, H.G. Sayer, N. Kröger, M. Hensel, C. Scheffold, T.K. Held, K. Höffken, A.D. Ho, J. Kienast, A. Neubauer, A.R. Zander, A.A. Fauser, G. Ehninger, W. Siegert
Journal: Journal of Clinical Oncology (2003)

To study whether hematopoietic stem-cell transplantation (HSCT) after reduced-intensity conditioning is effective and tolerable in patients with advanced chronic lymphocytic leukemia (CLL).Thirty patients with advanced B-cell CLL were included into the study. After reduced-intensity conditioning with fludarabine, busulfan, and antithymocyte globulin, patients received a transplant from related (n = 15) or unrelated donors (n = 15). Minimal residual disease (MRD) was monitored with a clone-specific polymerase chain reaction.After a median follow-up of 2 years, 23 patients are alive (to date). Neutrophil and platelet engraftment occurred after a median of 17.5 and 15 days, respectively. Acute graft-versus-host disease (GVHD) grade 2 to 4 was observed in 17 patients (56%), and chronic GVHD was observed in 21 patients (75%). Twelve patients (40%) achieved a complete remission (CR), and 16 patients (53%) achieved a partial remission. Late CR occurred up to 2 years after transplantation. MRD was monitored in eight patients with CR. All patients achieved a molecular CR. At last follow-up, six patients were in ongoing molecular CR. Causes of death were treatment-related complications in four patients and progressive disease in three patients. The probability of overall survival, progression-free survival, and nonrelapse mortality at 2 years was 72% (95% confidence interval [CI], 54% to 90%), 67% (95% CI, 49% to 85%), and 15% (95% CI, 1% to 29%), respectively.Treatment-related mortality after reduced-intensity conditioning followed by allogeneic HSCT was low. The procedure induced molecular remissions in patients with advanced CLL. The observation of late remissions provided evidence of a graft-versus-leukemia effect.
Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study
Authors: Ian McKeith, Teodoro Del Ser, PierFranco Spano, Murat Emre, Keith Wesnes, Ravi Anand, Ana Cicin-Sain, Roberto Ferrara, René Spiegel
Journal: The Lancet (2000)
Use of antipolymer antibody assay in recipients of silicone breast implants
Authors: Scott A Tenenbaum, Janet C Rice, Luis R Espinoza, Malta L Cuéllar, Douglas R Plymale, David M Sander, Linda L Williamson, Allyson M Haislip, Oscar S Cluck, John RP Tesser, Leigh Nogy, Kathleen M Stribrny, Julie Á Bevan, Robert F Garry
Journal: The Lancet (1997)
A systematic review and meta-analysis of the cardioprotective effects of remote ischaemic preconditioning in open cardiac surgery
Authors: Janine M Pilcher, Paul Young, Mark Weatherall, Ishtiaq Rahman, Robert S Bonser, Richard W Beasley
Journal: Journal of the Royal Society of Medicine (2012)

To investigate the cardioprotective efficacy of remote ischaemic preconditioning (RIPC) in cardiac surgery.We have performed a systematic search of MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials to identify randomized controlled trials involving RIPC.Randomized controlled trials of RIPC in open cardiac surgery patients.Meta-analysis was performed with the primary outcome the standardized mean difference between intervention and control groups in 12 hour postoperative troponin concentration. Heterogeneity was examined by fixed effects meta-regression.Ten studies with a total of 693 participants were included in the meta-analysis. RIPC reduced troponin levels 12 hours after surgery compared with control. The fixed and random effects differences were 0.35 (95% CI 0.19 to 0.51) and 0.53 (95% CI 0.18-0.88) respectively. However, important heterogeneity was present. Fixed effects meta-regression partially accounted for heterogeneity based on whether studies had full blinding, comprising blinding of patients, surgeons, anaesthetists and investigators. Studies with incomplete or no blinding demonstrated a larger estimate of effect, 0.74 (95% CI 0.47 to 1.00) compared to those with full blinding, 0.13 (95% CI - 0.07 to 0.33).Although our analysis suggests RIPC may result in cardiac protection during cardiac surgery, the effect was most marked in studies without full blinding, with a smaller and statistically non-significant effect in fully blinded studies. We propose that further double blind randomized controlled trials investigating the cardioprotective effects of RIPC in cardiac surgery are required to resolve the current clinical uncertainty.
Occupational and environmental risk factors for respiratory symptoms in rural Beijing, China
Authors: L-X. Zhang, D.A. Enarson, G-X. He, B. Li, M. Chan-Yeung
Journal: European Respiratory Journal (2002)

The aim of the present study was to determine the effects of occupational and environmental exposure on respiratory symptoms in adults in rural Beijing, China. Thirty randomly selected villages in the counties of Shunyi and Tongxian, 50 km north and east, respectively, of the city of Beijing, China, participated in this study. Village doctors interviewed all residents aged > or = 15 yrs and completed the International Union Against Tuberculosis and Lung Disease Questionnaire on Bronchial Symptoms translated into Chinese with added questions on smoking and occupational and environmental exposure. Of the eligible population, 22,528 adults (98%) took part. The prevalence of all respiratory symptoms, i.e. asthma-like symptoms, asthma attacks in the last 12 months, chronic cough and chronic phlegm, was low. Significant determinants for respiratory symptoms were age, sex, smoking and county of residence. A dose-dependent relationship was found between cumulative cigarette consumption and prevalence of respiratory symptoms. After adjusting for these variables, exposure to insecticides and fertilisers significantly increased the risk of most of the respiratory symptoms, whereas exposure to indoor air pollution from domestic fuels did not. Exposure to chemicals such as insecticides and fertilisers contributed independently to the risk of respiratory symptoms in rural Beijing, China.
Physical illness in patients with severe mental disorders. I. Prevalence, impact of medications and disparities in health care
Authors: MARC DE HERT, CHRISTOPH U. CORRELL, JULIO BOBES, MARCELO CETKOVICH‐BAKMAS, DAN COHEN, ITSUO ASAI, JOHAN DETRAUX, SHIV GAUTAM, HANS‐JURGEN MÖLLER, DAVID M. NDETEI, JOHN W. NEWCOMER, RICHARD UWAKWE, STEFAN LEUCHT
Journal: World Psychiatry (2011)

The lifespan of people with severe mental illness (SMI) is shorter compared to the general population. This excess mortality is mainly due to physical illness. We report prevalence rates of different physical illnesses as well as important individual lifestyle choices, side effects of psychotropic treatment and disparities in health care access, utilization and provision that contribute to these poor physical health outcomes. We searched MEDLINE (1966 - August 2010) combining the MeSH terms of schizophrenia, bipolar disorder and major depressive disorder with the different MeSH terms of general physical disease categories to select pertinent reviews and additional relevant studies through cross-referencing to identify prevalence figures and factors contributing to the excess morbidity and mortality rates. Nutritional and metabolic diseases, cardiovascular diseases, viral diseases, respiratory tract diseases, musculoskeletal diseases, sexual dysfunction, pregnancy complications, stomatognathic diseases, and possibly obesity-related cancers are, compared to the general population, more prevalent among people with SMI. It seems that lifestyle as well as treatment specific factors account for much of the increased risk for most of these physical diseases. Moreover, there is sufficient evidence that people with SMI are less likely to receive standard levels of care for most of these diseases. Lifestyle factors, relatively easy to measure, are barely considered for screening; baseline testing of numerous important physical parameters is insufficiently performed. Besides modifiable lifestyle factors and side effects of psychotropic medications, access to and quality of health care remains to be improved for individuals with SMI.
Incidence and implications of natural deaths of road users.
Authors: M. S. Christian
Journal: BMJ (1988)

A prospective study was carried out over the 10 years 1978-87 to determine the incidence and implications of sudden death in road users--that is, drivers, pedestrians, cyclists, and motorcyclists. During the study period 30,000 patients were seen in the same accident and emergency departments of East Berkshire after road traffic incidents or accidents, of whom 267 either were brought in dead or died within two hours after arrival. Of these patients, 64 (24%) were found to have died of natural causes due to pre-existing disease or to have been killed in an incident that occurred as a result of a medical or psychiatric condition. Twelve of the patients sustained physical injury; all 64 came to necropsy. Only one incident resulted in the death of another person in addition to the natural death of a patient. It is concluded that sudden natural death occurring in road users does not present an appreciable hazard to other road users.
c-<b> <i>erb</i> </b>B-2 Related Aggressiveness in Breast Cancer Is Hypoxia Inducible Factor-1α Dependent
Authors: Alexandra Giatromanolaki, Michael I. Koukourakis, Costantinos Simopoulos, Alexandros Polychronidis, Kevin C. Gatter, Adrian L. Harris, Efthimios Sivridis
Journal: Clinical Cancer Research (2004)

c-erbB-2-positive breast carcinomas are highly aggressive tumors. In vitro data on breast cell lines showed that c-erbB-2 enhanced translational efficiency of hypoxia inducible factor-1alpha (HIF1alpha) production (Laughner et al., Mol Cell Biol 2001;21:3995-4005). We investigated the clinical correlate of this observation to assess whether c-erbB-2 expression was related to HIF1alpha expression, angiogenesis, and prognosis. A series of 180 breast carcinomas of known c-erbB-2 status (90 c-erbB-2-positive and 90 c-erbB-2-negative carcinomas) were stained immunohistochemically for HIF1alpha and CD31 endothelial cell antigen. c-erbB-2 positivity was clearly related to HIF1alpha protein expression and high angiogenesis. However, prognosis was decreased only in cases with simultaneous c-erbB-2 and HIF1alpha expression. If activation of c-erbB-2 in humans results in overexpression of HIF1alpha independently of conditions of hypoxia, as occur in experimental studies, this interaction may represent a main pathway conferring clinical aggressiveness to c-erbB-2-positive breast tumors.
Novel Risk Factors and the Prediction of Type 2 Diabetes in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: L.A. Raynor, James S. Pankow, Bruce B. Duncan, Maria I. Schmidt, Ron C. Hoogeveen, Mark A. Pereira, J. Hunter Young, Christie M. Ballantyne
Journal: Diabetes Care (2012)

OBJECTIVE The objective of this study was to determine potential added value of novel risk factors in predicting the development of type 2 diabetes beyond that provided by standard clinical risk factors. RESEARCH DESIGN AND METHODS The Atherosclerosis Risk in Communities (ARIC) Study is a population-based prospective cohort study in four U.S. communities. Novel risk factors were either measured in the full cohort or in a case-control sample nested within the cohort. We started with a basic prediction model, previously validated in ARIC, and evaluated 35 novel risk factors by adding them independently to the basic model. The area under the curve (AUC), net reclassification index (NRI), and integrated discrimination index (IDI) were calculated to determine if each of the novel risk factors improved risk prediction. RESULTS There were 1,457 incident cases of diabetes with a mean of &amp;gt;7.6 years of follow-up among 12,277 participants at risk. None of the novel risk factors significantly improved the AUC. Forced expiratory volume in 1 s was the only novel risk factor that resulted in a significant NRI (0.54%; 95% CI: 0.33–0.86%). Adiponectin, leptin, γ-glutamyl transferase, ferritin, intercellular adhesion molecule 1, complement C3, white blood cell count, albumin, activated partial thromboplastin time, factor VIII, magnesium, hip circumference, heart rate, and a genetic risk score each significantly improved the IDI, but net changes were small. CONCLUSIONS Evaluation of a large panel of novel risk factors for type 2 diabetes indicated only small improvements in risk prediction, which are unlikely to meaningfully alter clinical risk reclassification or discrimination strategies.
Identification of Novel Diagnostic Biomarkers for Asthma and Chronic Obstructive Pulmonary Disease
Authors: Nicole M. Verrills, Jennifer A. Irwin, Xiao Yan He, Lisa G. Wood, Heather Powell, Jodie L. Simpson, Vanessa M. McDonald, Alistair Sim, Peter G. Gibson
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Proteomics may identify a useful panel of biomarkers for identification of asthma and chronic obstructive pulmonary disease (COPD).To conduct an unsupervised analysis of peripheral blood proteins in well-characterized subjects with asthma and COPD, and identify and validate a biomarker panel for disease discrimination.Two-dimensional difference gel electrophoresis was used to separate plasma proteins from healthy control subjects, stable patients with asthma, and individuals with COPD. Candidate protein markers were identified by matrix assisted laser desorption ionization time of flight mass spectrometry and subsequently validated in two populations via immunoassay. A panel of four biomarkers was selected and their ability to distinguish between groups was assessed in isolation and in combination in two separate validation populations.Seventy-two protein spots displayed significantly different expression levels between the three subject groupings (P < 0.05). Fifty-eight were positively identified, representing 20 unique proteins. A panel of four biomarkers (α(2)-macroglobulin, haptoglobin, ceruloplasmin, and hemopexin) was able to discriminate with statistical significance between the clinical groups of patients with asthma, patients with COPD, and control subjects, and these results were confirmed in a second clinical population of older adults with airflow obstruction.Proteomics has identified novel biomarkers for asthma and COPD, and shown that the iron metabolism pathways and acute-phase response may be involved in the pathogenesis of airway disease. The panel of peripheral blood biomarkers has the potential to become an extremely useful addition to the clinical diagnosis and management of respiratory disease.
Delivery of a Liposomal <b> <i>c-raf-1</i> </b> Antisense Oligonucleotide by Weekly Bolus Dosing in Patients with Advanced Solid Tumors
Authors: Charles M. Rudin, John L. Marshall, Chao Hui Huang, Hedy L. Kindler, Chuanbo Zhang, Deepak Kumar, Prafulla C. Gokhale, Joyce Steinberg, Steve Wanaski, Usha N. Kasid, Mark J. Ratain
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Rapid cleavage in vivo and inefficient cellular uptake limit the clinical utility of antisense oligonucleotides (AON). Liposomal formulation may promote better intratumoral AON delivery and inhibit degradation in vivo. We conducted the first clinical evaluation of this concept using a liposomal AON complementary to the c-raf-1 proto-oncogene (LErafAON). Experimental Design: A dose escalation study was done to determine the maximum tolerated dose and to characterize the toxicities of LErafAON given as weekly intravenous infusion for 8 weeks to adults with advanced solid tumors. Pharmacokinetic analysis and evaluation of c-raf-1 target suppression in peripheral blood mononuclear cells were included. Results: Twenty-two patients received LErafAON (median 7 infusions; range 1–27) at doses of 1, 2, 4, and 6 mg/kg/week. Across all dose cohorts patients experienced infusion-related hypersensitivity reactions including flushing, dyspnea, hypoxia, rigors, back pain, and hypotension. Prolonged infusion duration and pretreatment with acetaminophen, H1- and H2-antagonists, and corticosteroids reduced the frequency and severity of these reactions. Progressive thrombocytopenia was dose-limiting at 6 mg/kg/week. No objective responses were observed. Two patients treated at the maximum tolerated dose of 4 mg/kg/week had evidence of stable disease, with dosing extended beyond 8 weeks. Pharmacokinetic analysis revealed persistence of detectable circulating rafAON at 24 hours in 7 of 10 patients in the highest 2 dose cohorts. Suppression of c-raf-1 mRNA was noted in two of five patients analyzed. Conclusions: Dose-independent hypersensitivity reactions and dose-dependent thrombocytopenia limited tolerance of LErafAON. Future clinical evaluation of this approach will depend on modification of the liposome composition.