tbuckley/cabot-search huggingface dataset:
Necroinflammation in Kidney Disease
Authors: Shrikant R Mulay, Andreas Linkermann, Hans-Joachim Anders
Journal: Journal of the American Society of Nephrology (2015)

The bidirectional causality between kidney injury and inflammation remains an area of unexpected discoveries. The last decade unraveled the molecular mechanisms of sterile inflammation, which established danger signaling via pattern recognition receptors as a new concept of kidney injury–related inflammation. In contrast, renal cell necrosis remained considered a passive process executed either by the complement-related membrane attack complex, exotoxins, or cytotoxic T cells. Accumulating data now suggest that renal cell necrosis is a genetically determined and regulated process involving specific outside-in signaling pathways. These findings support a unifying theory in which kidney injury and inflammation are reciprocally enhanced in an autoamplification loop, referred to here as necroinflammation. This integrated concept is of potential clinical importance because it offers numerous innovative molecular targets for limiting kidney injury by blocking cell death, inflammation, or both. Here, the contribution of necroinflammation to AKI is discussed in thrombotic microangiopathies, necrotizing and crescentic GN, acute tubular necrosis, and infective pyelonephritis or sepsis. Potential new avenues are further discussed for abrogating necroinflammation-related kidney injury, and questions and strategies are listed for further exploration in this evolving field.
Mechanisms of Immunity to Sarcoma I Allografts in the C57BL/Ks Mouse. I. Passive Transfer Studies With Immune Peritoneal Macrophages in X-Irradiated Hosts&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Mang-So Tsoi, Russell S. Weiser
Journal: JNCI Journal of the National Cancer Institute (1968)

Passive transfer of immunity to Sarcoma I (Sal) allografts was demonstrated by sublethal inoculation of X-irradiated C57BL/Ks mice subcutaneously with mixtures of immune peritoneal macrophages and Sal cells. The degree of suppression of tumor growth was directly related to the number of immune macrophages added to the tumor inoculum. When inocula containing tumor cells and macrophages in ratios of 5:1, 2:1, and 1:1 were used, tumor growth was suppressed significantly. Tumor growth was unaffected when cells in the ratio of 10:1 were used. When immune macrophages were injected intraperitoneally and tumor cells were inoculated subcutaneously, no inhibition of tumor growth was noted. We studied the growth of the ascites form of Sal by mixing the inoculum of tumor cells with immune macrophages in ratios of 10:1, 4:1, 2:1, and 1:1. Tumor suppression was obtained only with inocula in which the tumor cells and immune macrophages were in ratios of 2:1 and 1:1. The results indicate that macrophages contribute significantly to the rejection of Sal allografts in the C57BL/Ks mouse. Moreover, they support the concept that the tumor-suppressive action of macrophages demands contact with the tumor cells.
11q23/MLL rearrangement confers a poor prognosis in infants with acute lymphoblastic leukemia.
Authors: C H Pui, F G Behm, J R Downing, M L Hancock, S A Shurtleff, R C Ribeiro, D R Head, H H Mahmoud, J T Sandlund, W L Furman
Journal: Journal of Clinical Oncology (1994)

PURPOSE Leukemic cell characteristics were analyzed in infants less than 1 year of age with acute lymphoblastic leukemia (ALL) to determine adverse prognostic factors that might explain the poor prognosis of this group. PATIENTS AND METHODS Treatment outcomes were analyzed according to the presenting clinical and laboratory features of 30 infants treated between May 1979 and April 1993. A stepwise multivariate regression model was used to identify the most important prognostic indicator with respect to event-free survival. RESULTS Infant ALL cases were characterized by high presenting leukocyte count (median, 87 x 10(9)/L), increased frequency of CNS leukemia (50%), and blast cells with a CD10- phenotype (67%), myeloid-associated antigen expression (48%), and 11q23/MLL rearrangement (68%). The 11q23/MLL involvement was correlated with age less than 6 months, CD10- phenotype, myeloid-associated antigen expression, and high leukocyte count. Although 11q23/MLL involvement, age less than 6 months, myeloid-associated antigen expression, and female sex were each significantly associated with an inferior treatment outcome, only rearranged 11q23/MLL emerged as an independent predictor of prognosis in multivariate analysis (P = .01). Infants with this genetic abnormality had a 4.7-fold (95% confidence interval, 1.3- to 17.0-fold) increased risk in adverse events compared to other infants. CONCLUSION The 11q23/MLL involvement of blast cells identifies a major subgroup of infant ALL cases that require an innovative treatment approach. Infants who lack this genetic abnormality have an intermediate prognosis and could be treated accordingly on risk-directed protocols.
Abstract 1015: Human Heart Contains A Stem Cell Population With Mesenchymal Properties
Authors: Alessandra Rossini, Alessandro Scopece, Ombretta Pozzoli, Giulio Pompilio, Carlo Gaetano, Maurizio C. Capogrossi, Antonia Germani
Journal: Circulation (2007)

Background Mesenchymal Stem Cells (MSC) were initially isolated from the bone marrow (BM) and identified as plastic adherent cells with a typical immunophenotype (negative for CD45, CD34, CD117 and HLA-DR and positive for CD105, CD90, CD44, CD73 and CD13), and able to differentiate into mesodermal lineages in vitro . Recently, MSC have been isolated from different adult tissues, i.e. liver, fat, kidney and thymus. Aim of the present study was to search for Cardiac Mesenchymal Stem Cells (C-MSC) in the adult human heart. Methods and Results : Auricle fragments were obtained from adult patients undergoing cardiac surgery. From these specimens we isolated a high proliferating plastic adherent cell population that, by FACS analysis, expressed mesenchymal markers (CD105, CD44, CD73, CD13 ) and was negative for hematopoietic markers (CD45, CD34) and HLA-DR. Further, in appropriate differentiating media, these cells exhibited osteogenic and adipogenic differentiation as cultures were positive for Oil Red O and Von Kossa staining used to mark intracellular lipid droplets and calcium salts deposits, respectively. Quantitative Real Time (qRT) -PCR analysis revealed that cells were negative for the early cardiac markers Nkx2.5 and Tbx5 and for the adult cardiac markers α-Myosin Heavy Chain and Myosin Light Chain-2a. Interestingly, in standard culture conditions, cells were positive for the early cardiac marker GATA4; in contrast, BM-MSC expressed GATA4 only after dexamethasone treatment. Additionally, when injected into the zebrafish blastula (about 100 –200 cells, n=70), C-MSC specifically homed in the cardiac region, as found at 24 –28 hpf (hours post fertilization). In contrast, transplanted BM-MSCs, were found not only in proximity of the heart, but throughout several mesodermal derivatives of the embryo (n=25). Conclusions: The adult human heart contains C-MSCs that can be easily expanded in vitro and may represent a useful population for autologous cell therapy of some cardiac diseases.
P-195 SPRY2 and response to FOLFOX/CAPOX in metastatic KRAS mutated colorectal cancer
Authors: R. Montal, M.-V. Merche, B. Anta, N. Martínez, C. Santos, X. Sanjuan, M.J. Paúles, F.J. Pérez Martín, D. Azuara, R. Salazar, J.M. Rojas
Journal: Annals of Oncology (2015)
Clinically prescribed sunscreen (sun protection factor 15) does not decrease serum vitamin D concentration sufficiently either to induce changes in parathyroid function or in metabolic markers
Authors: None Farrerons, None Barnadas, None RodrÍguez, None Renau, None Yoldi, None LÓpez-Navidad, None Moragas
Journal: British Journal of Dermatology (1998)

Some studies have suggested that the use of sunscreens to prevent skin cancer may put the population at risk of vitamin D deficiency. We followed 24 sunscreen users and 19 controls over 2 years, including two summers, two winters and a basal period (winter). Vitamin D, parathormone and bone biological markers were evaluated each season. Mean levels of 25-hydroxyvitamin D rose in summer, with the increments being significantly higher for the second year in the control group. Levels decreased in winter in both groups, and were significantly lower in sunscreen users. We did not observe any significant change in parathormone, tartrate resistant phosphatase, total alkaline phosphatase, osteocalcin, urine hydroxyproline or urine calcium. Clinically prescribed sunscreen creams (sun protection factor 15) caused a minor decrease in 25-hydroxyvitamin D levels, which did not induce secondary hyperparathyroidism or an increment in bone biological markers.
Abstract 8947: A Meta-Analysis of Cardiovascular Outcomes in Clinical Trials of Dapagliflozin
Authors: Anna Maria Langkilde, Jennifer Sugg, Peter Johannson, Lisa Ying, James List, Shamik Parikh
Journal: Circulation (2011)

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular (CV) disease. Dapagliflozin (DAPA), a selective SGLT2 inhibitor, is currently under evaluation for the treatment of T2DM. DAPA reduces hyperglycemia by promoting renal glucose excretion, independent of insulin secretion or action, also reducing weight and blood pressure. In response to FDA recommendations for new T2DM therapies, a pre-specified meta-analysis was conducted of data from 14 phase 2/3 studies (n=6228) to assess the CV safety of all DAPA doses (2.5 to &gt;10mg/d) pooled (n=4287), relative to all comparators (active or placebo) pooled (n=1941). CV events were systematically identified from investigator reports of adverse events and adjudicated by an independent committee. Adjudication was blinded to treatment allocation and conducted prospectively for the majority of trials. The primary end point was a composite of time to first event of CV death, myocardial infarction (MI), stroke, or hospitalization for unstable angina. The secondary end point included the primary end point, unplanned coronary revascularization, and hospitalization for heart failure. Baseline characteristics were balanced between groups: mean age=56 years, body mass index=31.5 kg/m 2 , and T2DM duration=6 years. Characteristics mirrored CV risk in the general T2DM population and included hypertension (62%), dyslipidemia (49%), smoking history (40%), and CV disease history (19%). A total of 78 primary end point events were confirmed with a stratified event rate (subjects with events/1000 subject years) of 11.3 for DAPA vs 16.6 for comparators. The estimated hazard ratio (HR) using a Cox proportional hazards method was 0.674 (98% CI: 0.385, 1.178; 95% CI: 0.421, 1.078). Analyses of the secondary end point (HR: 0.632; 95% CI: 0.416, 0.959) and of a composite CV death, MI, and stroke end point (HR: 0.596; 95% CI: 0.357, 0.996) were consistent with primary results. Analyses by dose (DAPA 2.5, 5 and 10 mg) were comparable to overall results. Review of data from the 4-month safety update confirmed the conclusions from the initial pre-specified analysis. The results suggest that DAPA is not associated with an increase in CV risk, and are consistent with a potential reduction in CV risk.
Abstract 2578: Acceleration and Deceleration Slope of Longitudinal Early Mitral Annulus Velocity Distinguishes Primary from Secondary Constrictive Pericarditis
Authors: Jacob P Dal-Bianco, Lieng H Ling, Diego Bellavia, Marion E Barnes, Jae K Oh
Journal: Circulation (2007)

Background: Assessment of coexisting pericardial and myocardial disease in constrictive pericarditis (CP) remains a diagnostic challenge and decision for pericardiectomy depends on the degree of pericardial versus myocardial restraint limiting left ventricular (LV) filling. Early diastolic longitudinal mitral annulus velocity (Ea) can help to differentiate CP from restrictive cardiomyopathy. Recently, acceleration rate of Ea has been shown to be an index of LV myocardial relaxation. We therefore assessed acceleration (Ea-AR) and deceleration (Ea-DR) rate of Ea in patients with CP before and after pericardiectomy. Methods: We retrospectively studied patients (n=42) with surgically confirmed CP who underwent radical pericardiectomy between 2003–2006 at Mayo Clinic Rochester. Ea-AR and Ea-DR slopes were measured before (pre-Echo) and after (post-Echo) pericardiectomy. Patients were divided into primary CP (idiopathic &amp; acute pericarditis with presumed normal myocardial function) and secondary CP (cardiac surgery &amp; chest irradiation with presumed abnormal myocardial function). Results: Ea-AR and Ea-DR changed significantly after pericardiectomy in primary CP patients, however remained similar in secondary CP patients. Diagnostic accuracy of Ea-AR, Ea-DR and Ea to discriminate primary versus secondary CP by ROC analysis was 0.88, 0.80 and 0.81 respectively. Conclusion: Assessment of Ea-AR and Ea-DR in patients with CP is useful to discriminate primary from secondary CP and may help to predict coexistence of myocardial disease: Prepericardiectomy Ea-AR and Ea-DR appear to reflect the interaction of intrinsic myocardial relaxation with enhanced early LV filling. The lack of decrease of Ea-AR and Ea-DR in patients with secondary CP seems to indicate a primarily restrictive component. The significant decrease of Ea-DR in patients with primary CP after pericardiectomy could reflect abolition of a predominant pericardial limitation to LV filling. Early Diastolic Longitudinal Mitral Annulus Motion before and after Pericardiectomy
Sudden-Onset Dystonia in a Patient Taking Asenapine: Interaction Between Ciprofloxacin and Asenapine Metabolism
Authors: Kathryn K. Ridout, Samuel J. Ridout, Loreen F. Pirnie, Sharath P. Puttichanda
Journal: American Journal of Psychiatry (2015)

treatment.Results are consistent with research indicating that the VMPFC, and its connectivity with the DLPFC and amygdala, is critical to optimizing goal-directed choices during value-based decision-making and can be modulated using rTMS (e.g., 2).Replication of our results is needed using controlled designs, and generalization of treatment effects to other clinical populations characterized by decision-making deficits (e.g., obesity, addiction) should be explored.
Pulmonary tumour thrombotic microangiopathy: unclassifiable pulmonary hypertension?
Authors: Neelam Kumar, Laura C. Price, M. Angeles Montero, Konstantinos Dimopoulos, Athol U. Wells, S. John Wort
Journal: European Respiratory Journal (2015)

Pulmonary hypertension (PH) is defined as a mean pulmonary artery pressure ≥25 mmHg, and can be associated with multiple conditions. The diagnostic strategy and treatment of PH is heavily reliant on accurately classifying patients [1]. We recently identified two patients presenting with rapidly fatal PH of unknown aetiology, who were subsequently diagnosed at post mortem with pulmonary tumour thrombotic microangiopathy (PTTM). This is a rare, albeit likely under-diagnosed cause of PH, characterised by a remodelling pulmonary vasculopathy rather than simple tumoural obstruction. At present, it is unclear where PTTM fits within the current classification system. PTTM is a rare, likely under-diagnosed cause of PH, which is related to, but distinct from PTE <http://ow.ly/OQad5>
Influence of smoking on symptoms, comorbidities and severity in a population with obstructive sleep apnea (OSA) versus control
Authors: Oana Claudia Deleanu, Diana Pocora, Andra Elena Malaut, Ana Maria Nebunoiu, Ion Mirelus-Mazilu, Florin Dumitru Mihaltan
Journal: European Respiratory Journal (2011)

Rationale:  The association of smoking with OSA is uncertain, even is an association with increased upper airway resistance and predisposition to cardiovascular complications.   Method:  We analyzed 129 OSA patients (65% active smokers, 35% never smokers) with normal lung function, without diurnal hipercapnia, successfully titrated with autoCPAP in lab and a control group of 17 active smokers with ronchopathy, regarding anthropometrical, functional lung data, OSA symptoms, severity, comorbidities and parameters after titration. We used SPSS (T, Chi, Pearsons tests).   Results:  For OSA group: 22.5% female, 77.5% male, mean values: age 49.6±11.7, body mass index (BMI) 33.6±7, apnea hipopnea index (AHI) 43.1±25.1; for smokers group: index package year (PY) 21±14.4, Fagerstrom score (FS) 3.6±2.5; for control group: 11.8% female, 88.2% male, age 40±12.1, PY 20.7±13.7, FS 4.9±2.5, BMI 29±5.3.  Significant differences: OSA patients are less fatigue (p=0.04), have a poorer lung function (FEV1,p=0.036, FVC,p=0.04) (justified by the effects of smoking), are fatter (p=0.025), with apneas more difficult to correct (p=0.018) related to PY (r=0.251, p=0.01). In control group was no difference in terms of smoking, BMI, neck circumference but was a smaller percentage of tonsillar hypertrophy (p=0.043) and diastolic blood pressure (p=0.002).   Conclusions:  Smoking appears not to influence symptoms, severity, and comorbidities in OSA patients, except a difficult CPAP correction of apneas. Also, smoking does not seem to contribute to the appearance of OSA and tonsilar hypertrophy (cause of OSA). Studies are needed to thoroughly into the mechanisms by which smoking could influence OSA.
Engraftment Kinetics After Nonmyeloablative Allogeneic Peripheral Blood Stem Cell Transplantation: Full Donor T-Cell Chimerism Precedes Alloimmune Responses
Authors: R. Childs, E. Clave, N. Contentin, D. Jayasekera, N. Hensel, S. Leitman, E.J. Read, C. Carter, E. Bahceci, N.S. Young, A.J. Barrett
Journal: Blood (1999)
Factors related to discontinuous use of inhaled drugs in COPD patients: A population-based cohort study in Lazio (Italy)
Authors: Lisa Bauleo, Nera Agabiti, Ursula Kirchmayer, Riccardo Pistelli, Vittoria Colamesta, Silvia Cascini, Marina Davoli
Journal: European Respiratory Journal (2012)

Inhaled therapy is essential to control symptoms in COPD, but information on real-life clinical practice is limited.  We measured treatment discontinuity and its predictors among COPD patients.  A cohort of residents in Lazio discharged after COPD exacerbation in 2006-7 was enrolled. The two-years follow-up was segmented in six months time-windows, in order to dynamically evaluate prescriptions of long-acting beta-agonists (LABA), tiotropium and inhaled corticosteroids (ICS). Patients were classified in two groups: “ regularly treated ” (at least one prescription of LABA and/or tiotropium in each time-window); “ not regularly treated ” (defined as those never treated or with late onset of treatment or with any interruption of treatment for at least six months). Multivariate logistic regression was performed.  A total of 7982 patients were included, 55% males, mean age (SD) 74 (10) years. Only 33% patients were regularly treated during follow-up. Old people (OR=1.01), females (OR=1.7) and those with comorbidities (diabetes OR=1.4, heart failure OR=1.3, psychiatric OR=2.1, nephropathy OR=1.6, cerebrovascular OR=1.4, obesity OR=1.4) were more likely to have discontinuity. Risk of discontinuity was lower among more severe patients (respiratory failure OR=0.7). Large heterogeneity in discontinuity was observed across areas of residence.  This observational study evidences that discontinuity of COPD therapy is influenced not only by demographic factors and COPD severity, but also by the presence of comorbidities. This information may be an important input for clinicians caring COPD patients.   Partially funded by National Medicines Agency; Prot.   FARM8ZBT93 .
Problems in Diagnosis of Popliteal Aneurysms
Authors: R Downing, F Ashton, R P Grimley, G Slaney
Journal: Journal of the Royal Society of Medicine (1985)

Clinical features and errors in diagnosis have been assessed in a retrospective study of 62 popliteal aneurysms in 40 patients, 22 of whom had bilateral aneurysms. Only 29% of patients complained of pain or swelling behind the knee, while 31% of aneurysms had produced distal ischaemia presenting as intermittent claudication, 9 aneurysms had thrombosed producing ischaemic rest pain in 6 legs, and 4 aneurysms had ruptured. Although 94% of aneurysms were suspected or confidently diagnosed by palpation alone, only 43% of patients had had the correct diagnosis made at the time of initial referral. Treatment was delayed in 12 patients, 8 of whom subsequently required amputation. Popliteal aneurysm should be suspected in patients with a prominent popliteal pulse who present with intermittent claudication, and in patients with acute ischaemia of the leg who may have a thrombosed aneurysm requiring surgical exploration.
The Family and Disability - Some Reflections on Culture: Discussion Paper
Authors: A O Frank
Journal: Journal of the Royal Society of Medicine (1989)

Severe congenital impairments in one child will affect the whole family, possibly for a generation if the child remains at home as an adult. Disability acquired in adult life will affect both partners as roles are gained or relinquished. For children this may result in a loss of parenting. The adjustment process to any psychological or personality changes may be very painful, particularly if children have no one outside the family to provide informed support. Acquired illness or disability in children may have enormous consequences for siblings, the health of the parents and the whole fabric of family life, often resulting in family isolation. In some Asian families, the feeling that the extended family unit is self sufficient and able to provide care may conflict with the ideal of increasing independence fostered by the professionals, and limit the possibility of support from social workers or psychologists. The extended family may reduce the need for statutory support. The expectation that care will be provided to old people by their daughters or daughters-in-law may be frustrated if the younger generation of women are disabled or otherwise engaged, resulting in possible family strife or rejection.
High genetic identity within the C:2b:P1.2,5 meningococcal epidemic strain in Galicia (Spain)
Authors: L. Arreaza, S. Berrón, J.A. Gómez, M.I. Sánchez-Romero, S. Fernández, M.I. Santiago, J.A. Vázquez
Journal: Clinical Microbiology and Infection (1999)
Short-form Sun-style Tai Chi as an exercise training modality in people with COPD: A randomised controlled trial
Authors: Regina Wai Man Leung, Zoe McKeough, Matthew Peters, Jennifer Alison
Journal: European Respiratory Journal (2012)

The aims of the study were, in people with COPD to: determine the effect of short-form Sun-style Tai Chi (SSTC) compared to usual medical care on exercise capacity, balance and quality of life (Part A) and investigate the exercise intensity of SSTC (Part B). Methods: Part A was a single blinded, randomised controlled trial with concealed, random allocation of participants to either the Tai Chi Group (TCG) or Control Group (CG) (usual medical care only) after confirmation of eligibility. Participants in the TCG trained for one hour, twice weekly for 12 weeks at a moderate dyspnoea or exertion level (score = 3 in a 10 point scale). Part B was a repeated measures design where participants who had completed training in TCG performed incremental shuttle walk test and SSTC while wearing a portable metabolic system. Exercise intensity of SSTC was determined by the percent of oxygen consumption (VO2) reserve. Results: Of 42 participants (mean (SD) age 73 (8) years, FEV1% 59 (16)% predicted), 38 completed Part A of the study (19 in each group) and 15 completed Part B. Compared to control, SSTC significantly increased incremental shuttle walk distance (mean difference, 95% CI 55 metres, 31 to 80) and endurance shuttle walk time (384 seconds, 186 to 510); reduced medial-lateral body sway in semi-tandem stand (-12.4 mm, -21 to -3); and increased total score on the chronic respiratory disease questionnaire (11 points, 4 to 18). The exercise intensity of SSTC in COPD was 53 (18)% of VO2 reserve. Conclusion: Short-form Sun-style Tai Chi was an effective training modality in people with COPD and the exercise intensity was moderate which met the recommendation for training in COPD.