tbuckley/cabot-search huggingface dataset:
High Risk of Symptomatic Cardiac Events in Childhood Cancer Survivors
Authors: Helena J. van der Pal, Elvira C. van Dalen, Evelien van Delden, Irma W. van Dijk, Wouter E. Kok, Ronald B. Geskus, Elske Sieswerda, Foppe Oldenburger, Caro C. Koning, Flora E. van Leeuwen, Huib N. Caron, Leontien C. Kremer
Journal: Journal of Clinical Oncology (2012)

To evaluate the long-term risk for validated symptomatic cardiac events (CEs) and associated risk factors in childhood cancer survivors (CCSs).We determined CEs grade 3 or higher: congestive heart failure (CHF), cardiac ischemia, valvular disease, arrhythmia and/or pericarditis (according to Common Terminology Criteria for Adverse Events [CTCAE], version 3.0) in a hospital-based cohort of 1,362 5-year CCSs diagnosed between 1966 and 1996. We calculated both marginal and cause-specific cumulative incidence of CEs and cause-specific cumulative incidence of separate events. We analyzed different risk factors in multivariable Cox regression models.Overall, 50 CEs, including 27 cases of CHF, were observed in 42 survivors (at a median attained age of 27.1 years). The 30-year cause-specific cumulative incidence of CEs was significantly increased after treatment with both anthracyclines and cardiac irradiation (12.6%; 95% CI, 4.3% to 20.3%), after anthracyclines (7.3%; 95% CI, 3.8% to 10.7%), and after cardiac irradiation (4.0%; 95% CI, 0.5% to 7.4%) compared with other treatments. In the proportional hazards analyses, anthracycline (dose), cardiac irradiation (dose), combination of these treatments, and congenital heart disease were significantly associated with developing a CE. We demonstrated an exponential relationship between the cumulative anthracycline dose, cardiac irradiation dose, and risk of CE.CCSs have a high risk of developing symptomatic CEs at an early age. The most common CE was CHF. Survivors treated with both anthracyclines and radiotherapy have the highest risk; after 30 years, one in eight will develop severe heart disease. The use of potentially cardiotoxic treatments should be reconsidered for high-risk groups, and frequent follow-up for high-risk survivors is needed.
Effects of supramaximal exercise on the electromyographic signal
Authors: A M Hunter, A St Clair Gibson, M I Lambert, L Nobbs, T D Noakes
Journal: British Journal of Sports Medicine (2003)

To determine the neuromuscular recruitment characteristics during supramaximal exercise.Ten healthy subjects completed the Wingate anaerobic test (WAT) cycling protocol. Electromyographic (EMG) data and rate of fatigue were recorded throughout the cycling.The mean (SD) rate of fatigue (decrease in power output) was 44.5 (8.6)%. No significant change was found in EMG amplitude. A significant decrease (p<0.01) in mean power frequency spectrum was found over the 30 second period.During WAT, mean power frequency spectrum was attenuated with no decline in EMG amplitude, which may be caused by an accumulation of metabolites in the periphery. However, it is also possible that the feedback loop from intramuscular metabolism to the central nervous system is unable, within the 30 second period of the WAT, to affect neural recruitment strategy.
Peptide and Dendritic Cell Vaccines
Authors: Craig L. Slingluff, Victor H. Engelhard, Soldano Ferrone
Journal: Clinical Cancer Research (2006)

Abstract There has been a rush to convert discovery of new melanoma antigens into cancer vaccines for the therapy of melanoma. The result has been disappointing from a clinical standpoint. The premise behind rapid pursuit of peptide vaccines for melanoma therapy was that the spontaneous tumor-associated immune response was too weak to be effective. However, it is increasingly clear that the host-tumor relationship is a complex interplay of immune response, immune escape, and immune adaptation, with multiple layers of regulatory control and modulation of responses over time. The lesion in the immune response to cancer is much more complex than simply a weak immune response to defined antigens. Current results should serve as a call to take a closer look at immune regulatory processes and principles and to develop more comprehensive and multiagent approaches to modulate the host-tumor relationship. Development of effective immune therapy for cancer will require (a) more comprehensive and real-time immune monitoring in various tissue compartments and (b) patient-specific modulation of immune responses, informed by the real-time monitoring. Peptide antigens associated with MHC class I or class II molecules are the molecular targets for T-cell recognition of cancer. To characterize the host-tumor relationship and to optimize cancer vaccines, clinical studies using defined peptide antigens offer special opportunities to advance the field and thus have an important place in the ongoing development of effective immune therapy of melanoma.
A phase II study of dacetuzumab (SGN-40) in patients with relapsed diffuse large B-cell lymphoma (DLBCL) and correlative analyses of patient-specific factors
Authors: Sven de Vos, Andres Forero-Torres, Stephen M Ansell, Brad Kahl, Bruce D Cheson, Nancy L Bartlett, Richard R Furman, Jane N Winter, Henry Kaplan, John Timmerman, Nancy C Whiting, Jonathan G Drachman, Ranjana Advani
Journal: Journal of Hematology & Oncology (2014)

Patients with DLBCL who are ineligible for or have relapsed after aggressive salvage chemotherapy have a poor prognosis. CD40 is expressed on multiple B-cell neoplasms including DLBCL and is a potential target for immunotherapy. Dacetuzumab (SGN-40), a non-blocking, partial agonist, humanized IgG1, anti-CD40 monoclonal antibody, has previously demonstrated anti-lymphoma activity in a phase I study. A phase II study was undertaken to evaluate the rate and duration of objective responses and safety of single-agent dacetuzumab in relapsed DLBCL. Forty-six adult patients with relapsed/refractory DLBCL received up to 12 cycles of intravenous dacetuzumab using intrapatient dose-escalation to a target dose of 8 mg/kg/week in an initial 5-week cycle, followed by 4-week cycles of 8 mg/kg/week. Study endpoints included rate and duration of objective responses, safety, survival, pharmacokinetics, immunogenicity, and exploratory correlative studies. Overall response rate was 9% and disease control rate (complete remission + partial remission + stable disease) was 37%. Common non-hematologic adverse events (AEs) included fatigue, headache, chills, fever, and nausea. The most frequent Grade 3–4 non-hematologic AE was deep venous thrombosis (3 patients). Grade 3–4 lymphopenia (41%), neutropenia (13%), or thrombocytopenia (19%) occurred without associated infection or bleeding. Reversible ocular events, including conjunctivitis and ocular hyperemia, occurred in 8 patients (17%). Patient-specific factors, including Fc-gamma-RIIIa polymorphism, did not appear to correlate with antitumor activity. Single-agent dacetuzumab has modest activity and manageable toxicity in unselected patients with relapsed DLBCL. Combination regimens and robust methods of patient selection may be necessary for further development. ClinicalTrials.gov identifier NCT00435916 .
Effect of Liver Damage on Experimental Renal Hypertension in the Rat
Authors: H. F. LOYKE, J. J. PLUCINSKY, T. L. CRAWFORD
Journal: Circulation Research (1960)

Renal hypertension was produced in 26 test rats and fell to normal levels when they received CCl 4 . Our data indicate that this is due to liver damage and not to general inanition. These changes are reversible, since cessation of CCl 4 injections led to blood pressure rise. Morphologically, only a moderate degree of fatty metamorphosis is necessary to cause the blood pressure to fall from hypertensive levels to normotension. The biochemical change involved variable changes in albumin and globulin.
Coexistence of Dual Systemic Allergic Rhinitis and Local Allergic Rhinitis
Authors: Miguel Blanca, Paloma Campo, Carmen Rondon, Esther Barrionuevo Sanchez, Natalia Blanca-López, Maria Auxiliadora Guerrero, Veronique Godineau, Maria J. Torres
Journal: Journal of Allergy and Clinical Immunology (2015)
Congenital Malformation of the Hands and Feet Transmitted through Four Generations
Authors: W. Anderson
Journal: BMJ (1886)

Tam subjoinled cases of congenital Inalformation bear great resemblance to tho series reported by Mr. H.A.YFotherby, in the JOURNAL of May 22nd, and will serve as a further illustration of the possibility of a repetition, generation after generatio.n, of abnormalities of develop.ment that were probably, in a certain sense, accidental iii their 9rigin.The history of the defect commences, in 1798, with J. G., an only child, of healthy parentage, who was born at fllteirm, with a peculiar pincer-like conformation of the hands and feet, which is said to ,cor- respond exactly in appearance with that figured below, from his grand- soniji,E.G.He was well developed in ;all other, respects, and no ptevious example of deformity of any kiud is known to have e64sted in the family of his mother or father.The -strange aspect of the affected,members was attributed by the mother to an alarm in the early period of her pregnancy, caused by the sight of a parcel of,, living lobster; J. O. married early, and had fourteen children.Of these, eleven were malformed in the.hands' and feet, like their father, one tin the feet only, and twowere -perfect.All exceptithree,of the number died before the age of puberty, and no further information cani be obtained with regard to them.The survivors were the '1fq lowing.i.J. H. G
Antibody-dependent cell-mediated antibacterial activity of human mononuclear cells. I. K lymphocytes and monocytes are effective against meningococi in cooperation with human imune sera.
Authors: G H Lowell, L F Smith, M S Artenstein, G S Nash, R P MacDermott
Journal: The Journal of Experimental Medicine (1979)

In cooperation with human heat-inactivated antisera from adults immunized with group C meningococcal polysaccharide, normal human peripheral blood mononuclear cells significantly decreased the viability of group C meningococci (Mgc) in vitro. K lymphocytes (Null cells) and monocytes, (but not T or B lymphocytes) were capable of effecting antibody-dependent cell-mediated (ADC) antibacterial activity in this system. The degree to which meningococcal viability was decreased was a function of the length of the test incubation, the concentration of effector cells, and the amount of antiserum used in the assay. When specific antibodies directed against Mgc were adsorbed from the antiserum, cell-mediated antibacterial activity was abolished. ADC antibacterial activity was also abrogated by performing the assay at 4 degrees C or by heating effector cells to 46 degrees C for 15 min before the assay, Similarities between the ADC antibacterial system and previously described ADCC assays are discussed. The data suggest the K cells (as well as monocytes) may play a role in host immune defense against pathogenic bacteria.
The reconstitution of cell-mediated immunity in the cutaneous lesions of lepromatous leprosy by recombinant interleukin 2.
Authors: G Kaplan, R Kiessling, S Teklemariam, G Hancock, G Sheftel, C K Job, P Converse, T H Ottenhoff, M Becx-Bleumink, M Dietz
Journal: The Journal of Experimental Medicine (1989)

Human rIL-2 (10-30 micrograms) was injected intradermally into the skin of patients with lepromatous leprosy with high bacillary loads. All patients responded to the lymphokine with local areas of induration that peaked at 24 h and persisted for 4-7 d irrespective of whether the site was "normal skin" or a nodular lesion. Within 24 h there was an extensive emigration of T cells and monocytes into the site. The percentage of the dermis infiltrated by mononuclear cells increased by more than sevenfold, peaking at 4 d and persisting for greater than 15 d. Both CD4+ and CD8+ T cells entered the site. T cells of CD4+ phenotype predominated at 2-7 d but by 11 d, CD8+ cells were predominant. Considerable numbers of T6+ Langerhans' cells appeared in the dermis by 72 h and persisted for 3 wk. By 4 d the thickness of the overlying epidermis had increased twofold, and keratinocytes were expressing MHC class II antigen and the IFN-gamma-induced peptide IP-10. Starting at 48 h, there was an extensive destruction of mononuclear phagocytes that contained structurally intact or fragmented M. leprae observed at the electron microscope level. The organisms, either free or contained within endocytic vacuoles, were discharged into the extracellular space and then reingested by blood-borne monocytes. This was followed by marked reductions in the number of acid-fast organisms in the injected site, evident as early as 4-7 d and more marked at 2-3 wk after injection. 13 of 15 patients exhibited a disposal of acid-fast bacilli ranging from 5- to 1,000-fold with a mean value of approximately 100-fold. The administration of IL-2 leads to the generation of an effective cell-mediated immune response, recapitulating an antigen-driven event and leading to striking local reductions in M. leprae. In comparison with the purified protein derivative of tuberculin reaction, bacilli are cleared more promptly, although emigratory cells persist for a shorter time.
Effect of hypoxia on fluid filtration rate during forward and reverse perfusion of isolated rabbit lungs
Authors: R S. DE LEON, C H ORCHARD, M K CHAKRABARTI, M K SYKES
Journal: Cardiovascular Research (1982)

Fluid filtration rate (FFR) was measured under predominantly zone 3 conditions in isolated rabbit lungs perfused at constant flow. During forward perfusion, alveolar hypoxia produced a significant increase in mean pulmonary artery pressure and a significant decrease in FFR. During reverse perfusion, alveolar hypoxia produced a similar increase in the pressure gradient across the lung, but a significant increase in FFR. It is concluded that the pulmonary vasoconstriction induced by alveolar hypoxia occurs predominantly on the arterial side of the pulmonary circulation.
Hypertension in patients with sleep apnoea, a combined effect?
Authors: E C FLETCHER
Journal: Thorax (2000)

Studies in both humans and animal show beyond doubt that obstructive apnoea produces an acute rise in systemic blood pressure. Such increases are well characterised with regard to timing and peripheral events such as changes in oxyhaemoglobin saturation, pulse rate, and autonomic activity. However, following early reports of sustained hypertension in patients with sleep apnoea, it has been argued that this long term haemodynamic abnormality is related to obesity rather than to nightly repetitive apnoeas. Since obesity is so common in obstructive sleep apnoea, it is nearly impossible to accumulate chronic blood pressure data on non-obese apnoeic individuals. In the past few months, including the current issue of Thorax , four fairly definitive studies have been published. The authors of these studies conclude that there is an independent relationship between the presence of obstructive sleep apnoea and chronic hypertension, considering other risk factors including obesity.1-4 

Obesity associated hypertension5 is believed to result from a combination of mechanisms mainly centering around insulin resistance. Obesity and high caloric intake are associated with activation of the sympathetic nervous system (as evidenced by high rates of muscle sympathetic nerve activity) through hyperinsulinaemia. High insulin levels are associated with increased tubular sodium reabsorption resulting in sodium retention. Hyperinsulinaemia is further implicated in vascular hypertrophy, as well as attenuated vasodilation in skeletal muscle of obese patients. That all of these mechanisms can exist in obese patients with sleep apnoea goes without saying. Thus, in part there can be no argument that obesity, in and of itself, can contribute to hypertension in some or even many patients with sleep apnoea. The question is whether obesity and hyperinsulinaemia account for all of the blood pressure changes in these patients.

Several early publications examining this question attempted to control for weight as a variable, but were probably …
Fibronectin mediates adherence of rat alveolar type II epithelial cells via the fibroblastic cell-attachment domain.
Authors: R A Clark, R J Mason, J M Folkvord, J A McDonald
Journal: Journal of Clinical Investigation (1986)

The lung alveolar surface is composed of types I and II epithelial cells. Extremely attenuated type I cells cover 90% of the surface and are prone to necrosis during acute lung injury. After denudation of type I cells, the alveolar epithelium is restored by proliferation of type II cells. During reepithelialization in vivo the type II cells have been observed to reorganize on an extracellular matrix that contains fibronectin. We thus sought to determine whether type II cells would adhere to purified fibronectin. Adherence assays of primary rat type II cells were performed in protein-coated bacteriologic microtiter wells for 24 h at 37 degrees C. Concentrations of fibronectin from 1 to 300 micrograms/ml mediated type II cell adherence, 10 micrograms/ml gave maximal adherence, and 4 micrograms/ml gave 50% maximal adherence. Adherence progressively increased from 1 to 72 h. Adherence on fibronectin was at least 50% greater than adherence on laminin, types I and III collagen, or IV collagen. Little or no adherence was observed on bacteriologic plastic or albumin. Spreading on these various substrata paralleled adherence. Adherence to fibronectin, laminin, and fibrinogen was specifically blocked by their respective polyclonal antibodies. Monoclonal antibodies (MoAb) to the fibronectin cell-attachment domain blocked adherence to fibronectin, whereas MoAb to other domains did not. From the data reported here and the previously mentioned in vivo study we propose that fibronectin is an important functional component of the extracellular matrix that supports type II cells during alveolar reepithelialization.
The Impact of the Polymerase Chain Reaction in Clinical Medicine
Authors: J C Post, G D Ehrlich
Journal: JAMA (2000)

netic information (elucidated by PCR) already forms the basis of some clinical testing and will do so increasingly in the future. Thus, physicians need to understand how PCR-based diagnostics are used to detect the presence of infectious disease agents and mutations associated with simple genetic diseases. Moreover, many diseases not traditionally thought of as genetic are now being evaluated in terms of inherited susceptibilities, or as genetically mediated maladaptive responses to external stimuli. In the future, molecular diagnostics that evaluate constellations of complex genetic factors may be used to assess medical risks, based on patients’ occupation, lifestyle, and family history. An enzymatic in vitro DNA amplification method, 1,2 PCR can be coupled with a number of detection methods to identify any gene (by DNA) or its expression (by messenger RNA [mRNA]) directly from clinical samples, no mat
Burden of Type 2 Diabetes in Young Korean Adults Owing to Obesity
Authors: Yeong Sook Yoon, Soon-Ae Shin, Jung-Hyun Noh, Sang Woo Oh
Journal: Diabetes Care (2005)

Previous large-scale surveys reported that magnitudes of increase in type 2 diabetes and obesity are more remarkable among young adults than older ones, whereas prevalences of these are lower in young adults (1,2). These epidemiological findings have very important implications in clinical practice and public health policies. Despite its significance, however, there are few reports on the effects of obesity on the risk of disease in younger generations compared with older people.

We investigated the effects of BMI on the development of type 2 diabetes according to age-group in a …
Adjustment to Diabetes Mellitus in Preschoolers and Their Mothers
Authors: Tim Wysocki, Karen Huxtable, Thomas R Linscheid, Wynola Wayne
Journal: Diabetes Care (1989)

Although preschool-aged children with diabetes might be at increased risk for both general and disease-specific psychological adjustment difficulties, this issue has not been investigated. We evaluated both general and diabetes-related adjustment of 20 preschool-aged children and their mothers. The mothers completed the Child Behavior Checklist, Parenting Stress Index, Parents' Diabetes Opinion Survey, and the Preschool Diabetes Behavior Checklist. The latter measure was constructed specifically for this study to measure the frequency of oppositional and avoidance behaviors of children regarding diabetes management tasks. Mothers reported that their children displayed significantly more internalizing behavior problems (anxiety, depression, withdrawal) and were a significantly greater source of parental stress compared with corresponding nondiabetic normative group samples. Also, certain maternal attitudes about diabetes and its treatment were correlated with the children's disease-specific behavior problems. The children's general psychological adjustment, however, was not predictive of these diabetes-specific behavior problems.
Epidemiology and disease burden from allergic disease in Scotland: analyses of national databases
Authors: C Anandan, R Gupta, CR Simpson, C Fischbacher, A Sheikh
Journal: Journal of the Royal Society of Medicine (2009)

Summary Background There are ongoing concerns about the quality of care provided to patients with allergic disorders in Scotland, but there are relatively few reliable data on the overall disease burden. We sought to: (1) describe the incidence, prevalence and outcome of allergic disorders; (2) estimate healthcare burden and costs; and (3) investigate ethnic variations in the epidemiology and outcomes from allergic disorders in Scotland. Methods Data sources: national surveys; primary care data; prescribing and medication data; hospital admissions data and mortality data. Results Allergic disorders are extremely common in Scotland, affecting about one in three of the population at some time in their lives. Incidence was highest for eczema (10.2 per 1000 registered patients). Over 4% of all GP consultations and 1.5% of hospital admissions were for allergic disorders. There were 100 asthma deaths in 2005 (20 per million people). Direct healthcare costs for allergic disorders were an estimated £130 million per year, the majority of these being incurred in primary care and related to asthma. Conclusions Allergic disorders are common in Scotland and given the very high proportion of children now affected, the high disease burden associated with these conditions is likely to persist for many decades.