tbuckley/cabot-search huggingface dataset:
Cytokine levels and systemic toxicity in patients undergoing isolated limb perfusion with high-dose tumor necrosis factor, interferon gamma, and melphalan.
Authors: A K Thom, H R Alexander, M P Andrich, W C Barker, S A Rosenberg, D L Fraker
Journal: Journal of Clinical Oncology (1995)

PURPOSE Isolated limb perfusion (ILP) with tumor necrosis factor (TNF), interferon gamma, and melphalan (M) has been reported to result in high response rates for extremity melanoma and sarcoma. We have evaluated the relationship of systemic TNF exposure to induction of several secondary mediators and incidence of systemic toxicity. PATIENTS AND METHODS Nineteen patients with extremity melanoma (n = 16) or sarcoma (n = 3), underwent 90-minute ILP with TNF-alpha, interferon gamma (0.2 mg), and M (10 to 13 mg/L of limb volume) (TNF/IFN/M) (n = 12), or M alone (n = 7). Continuous intraoperative monitoring (CIM) for systemic leak from the perfusion circuit was performed using radioactive iodine-131 albumin. Cytokine levels in the perfusate and systemic circulation during and after ILP were measured by enzyme-linked immunosorbent assay. RESULTS Systemic leaks &gt; or = 1% from the perfusion circuit occurred in six patients who received TNF/IFN/M and in four who received M alone. Hypotension that required vasopressor support occurred in six of six patients with evidence of a leak (&gt; or = 1%) and zero of six patients without a leak (&lt; 1%). These six patients had significantly higher peak systemic TNF levels during and after perfusion than patients without a leak (2.8 and 8.2 ng/mL v 0.7 and 2.0 ng/mL, respectively; P &lt; .05). All patients who received TNF/IFN/M had significantly greater increases in systemic interleukin-6 (IL-6) levels than in patients with M alone (12,395 +/- 10,374 pg/mL v 79.4 +/- 7.2 pg/mL, respectively; P &lt; .001). Intracellular adhesion molecule (ICAM), IL-8, and TNF-R levels were also increased after ILP with TNF/IFN/M. CONCLUSION ILP with TNF/IFN/M can be safely performed, as I131 albumin provides a sensitive measure of systemic leakage from the perfusion circuit. Patients with a measured leak of &gt; or = 1% develop mild and transient postoperative hypotension with significantly higher systemic TNF levels and lower perfusate TNF levels than in patients without leaks.
Comparison of hospital variation in acute myocardial infarction care and outcome between Sweden and United Kingdom: population based cohort study using nationwide clinical registries
Authors: Sheng-Chia Chung, Johan Sundström, Chris P Gale, Stefan James, John Deanfield, Lars Wallentin, Adam Timmis, Tomas Jernberg, Harry Hemingway
Journal: BMJ (2015)

<b>Objective</b> To assess the between hospital variation in use of guideline recommended treatments and clinical outcomes for acute myocardial infarction in Sweden and the United Kingdom. <b>Design</b> Population based longitudinal cohort study using nationwide clinical registries. <b>Setting and participants</b> Nationwide registry data comprising all hospitals providing acute myocardial infarction care in Sweden (SWEDEHEART/RIKS-HIA, n=87; 119 786 patients) and the UK (NICOR/MINAP, n=242; 391 077 patients), 2004-10. <b>Main outcome measures</b> Between hospital variation in 30 day mortality of patients admitted with acute myocardial infarction. <b>Results</b> Case mix standardised 30 day mortality from acute myocardial infarction was lower in Swedish hospitals (8.4%) than in UK hospitals (9.7%), with less variation between hospitals (interquartile range 2.6% <i>v</i> 3.5%). In both countries, hospital level variation and 30 day mortality were inversely associated with provision of guideline recommended care. Compared with the highest quarter, hospitals in the lowest quarter for use of primary percutaneous coronary intervention had higher volume weighted 30 day mortality for ST elevation myocardial infarction (10.7% <i>v</i> 6.6% in Sweden; 12.7% <i>v</i> 5.8% in the UK). The adjusted odds ratio comparing the highest with the lowest quarters for hospitals’ use of primary percutaneous coronary intervention was 0.70 (95% confidence interval 0.62 to 0.79) in Sweden and 0.68 (0.60 to 0.76) in the UK. Differences in risk between hospital quarters of treatment for non-ST elevation myocardial infarction and secondary prevention drugs for all discharged acute myocardial infarction patients were smaller than for reperfusion treatment in both countries. <b>Conclusion</b> Between hospital variation in 30 day mortality for acute myocardial infarction was greater in the UK than in Sweden. This was associated with, and may be partly accounted for by, the higher practice variation in acute myocardial infarction guideline recommended treatment in the UK hospitals. High quality healthcare across all hospitals, especially in the UK, with better use of guideline recommended treatment, may not only reduce unacceptable practice variation but also deliver improved clinical outcomes for patients with acute myocardial infarction. <b>Clinical trials registration</b> Clinical trials NCT01359033.
A useful physiological marker for evaluating the effect of indacaterol in COPD patients
Authors: Yuki Okada, Yuta Kono, Seiko Soeda, Hiroko Hara, Kosuke Araki, Masako To, Yasuo To
Journal: European Respiratory Journal (2013)

[Introduction] Long-acting beta agonist (LABA) is a one of the choices of therapy for COPD. Indacaterol(IND), a new LABA is a LABA with high potency to agonise beta-2 adrenergic receptor so that it is recognized as a strong-partial agonist. It is also known that IND therapy improves lung function and patient’s QOL (Beeh KM et al COPD 2011). However, few data is available about the effect of IND on lung function details including RV and IC. Here we investigated the clinical details including pulmonary function tests before and after IND add-on therapy.  [Methods] COPD patients (mean age 74±10yrs, F:M=0:7, stage I/II/III/IV= 3/3/1/0) were recruited from the outpatient department of The Fraternity Memorial Hospital, a leading teaching hospital in Tokyo. Lung function tests and questionnaire (COPD Assessment Test (CAT)) were carried out before and after 4 weeks of add-on therapy with IND.  [Result]CAT score about dyspnoea during exercise was significantly improved after the therapy (2.8±1.5 before therapy, 1.8±1.7 after therapy, p  [Conclusion] IND clearly improved the symptoms during exercise. Furthermore, VC might be a most sensitive marker to indicate improvement of lung function after IND therapy.
The presence of an extensive intraductal component following a limited excision correlates with prominent residual disease in the remainder of the breast.
Authors: R Holland, J L Connolly, R Gelman, M Mravunac, J H Hendriks, A L Verbeek, S J Schnitt, B Silver, J Boyages, J R Harris
Journal: Journal of Clinical Oncology (1990)

Previous studies of patients with infiltrating ductal breast cancer treated with conservative surgery (ie, limited excision) and radiotherapy have indicated that the presence of an extensive intraductal component (EIC) in the excision specimen is highly associated with subsequent breast recurrence. The reason for this association is not clear, but possible explanations include the presence of more extensive disease in the breast or increased radiation resistance among tumors with an EIC (EIC+) compared with those without (EIC-) tumors. To investigate this association further, we related the presence or absence of an EIC in the primary tumors of 214 women who underwent mastectomy to the likelihood of finding additional foci of cancer in their mastectomy specimens using a correlated pathologic-radiologic mapping technique. Primary tumors that were EIC+ were significantly more likely to have carcinoma in the remainder of the breast than those which were EIC--(74% v 42%; P = .00001). This difference was primarily due to the presence of residual intraductal carcinoma. Seventy-one percent of EIC+ patients had residual intraductal carcinoma compared with 28% of EIC-patients (P less than .00001). In particular, 44% of EIC+ patients had "prominent" residual intraductal carcinoma compared with 3% of EIC-patients (P less than .00001). We conclude that patients whose tumors contain an EIC more frequently have a large subclinical tumor burden in the remainder of the breast compared with patients whose tumors do not contain an EIC. This observation may explain the association between EIC and subsequent breast recurrence when patients are treated with a limited excision before radiotherapy.
Effectiveness of add-on interactive video games exercises in pulmonary rehabilitation programs in chronic respiratory diseases patient
Authors: Giulia Montagnani, Dewi Makhabah, Guido Vagheggini, Fabrizio Mezzasalma, Stefano Mazzoleni, Eugenia Panait, Francesca Moretti, Giulia Farru, Nicolino Ambrosino
Journal: European Respiratory Journal (2013)

Interactive game-based systems, such as Wii Fit™, represent innovative technologies potentially able to increase the effectiveness of Pulmonary Rehabilitation Programmes (PRP).  Aim: to evaluate the effectiveness of interactive game-based exercises in addition to PRP.  Twenty six patients with chronic lung disease (17 COPD), undergoing a 3 week PRP were prospectively enrolled and randomly submitted to the usual PRP (Control Group: CG) or to PRP + 7 sessions of exercises with Wii Fit™ including Yoga, Muscle Exercises, Aerobic Exercises, and Training Plus (Study Group: SG).  Before (T0) and after PRP (T1) we evaluated: maximum inspiratory and expiratory pressure (MIP, MEP), dyspnoea (MRC and Borg Scale), fatigue (Borg Scale), Six-Minute Walking Test (6MWT), leg- and arm-cycle ergometry, Functional Independence Measure (FIM), Baseline (BDI) and Transitional (TDI) dyspnoea index.  As expected, both groups showed a significant improvement in exercise tolerance, dyspnoea and health status.  In SG compared to CG were found:  1) A greater improvement in dyspnoea as assessed by TDI (3.9±1.5 vs. 2.4±1.0, respectively; p=0.01)  2) A reduced dyspnoea (4.5±1.0 vs. 6.3±1.3; p=0.003) and fatigue (5.4±1.6 vs. 6.8±1.4; p=0.04) during arm exercise  Rehabilitation treatment with Wii Fit ™ balance board can be useful as an additional tool to standard PRP in improving dyspnoea and arm exercise tolerance in chronic pulmonary disease. Practical advantages include ability to train at home with or without remote supervision, enjoyability, real-time feedback on performance, healthcare costs reduction. Larger prospective randomized trials are needed to confirm these preliminary results.
An assessment of sex bias in neurodevelopmental disorders
Authors: Andrew Polyak, Jill A. Rosenfeld, Santhosh Girirajan
Journal: Genome Medicine (2015)

Neurodevelopmental disorders such as autism and intellectual disability have a sex bias skewed towards boys; however, systematic assessment of this bias is complicated by the presence of significant genetic and phenotypic heterogeneity of these disorders.To assess the extent and characteristics of sex bias, we analyzed the frequency of comorbid features, the magnitude of genetic load, and the existence of family history within 32,155 individuals ascertained clinically for autism or intellectual disability/developmental delay (ID/DD), including a subset of 8,373 individuals carrying rare copy-number variants (CNVs).We find that girls were more likely than boys to show comorbid features within both autism (P = 2.9 × 10(-6), OR = 1.34) and ID/DD (P = 7.2 × 10(-4), OR = 1.08) cohorts. The frequency of comorbid features in ID/DD was higher in boys (1q21.1 deletion, 15q11.2q13.1 duplication) or girls (15q13.3 deletion, 16p11.2 deletion) carrying specific CNVs associated with variable expressivity while such differences were the smallest for syndromic CNVs (Smith-Magenis syndrome, DiGeorge syndrome). The extent of the male sex bias also varied according to the specific comorbid feature, being most extreme for autism with psychiatric comorbidities and least extreme for autism comorbid with epilepsy. The sex ratio was also specific to certain CNVs, from an 8:1 male:female ratio observed among autistic individuals carrying the 22q11.2 duplication to 1.3:1 male:female ratio in those carrying the 16p11.2 deletion. Girls carried a higher burden of large CNVs compared to boys for autism or ID/DD, and this difference diminished when severe comorbidities were considered. Affected boys showed a higher frequency of neuropsychiatric family histories such as autism (P = 0.01) or specific learning disability (P = 0.03), while affected girls showed a higher frequency of developmental family histories such as growth abnormalities (P = 0.02).The sex bias within neurodevelopmental disorders is influenced by the presence of specific comorbidities, specific CNVs, mutational burden, and pre-existing family history of neurodevelopmental phenotypes.
Abstract 1516: Role of Oxidative Stress in Atrial Tachycardia Remodelling
Authors: Xiao-Yan Qi, Louis R Villeneuve, Balazs Ordog, Denis Chartier, David R Van Wagoner, Stanley Nattel
Journal: Circulation (2008)

Atrial tachycardia remodeling (ATR) promotes atrial fibrillation (AF). Oxidant stress (OxS) occurs in atria of AF patients and antioxidants may be beneficial in AF. This study used a previously validated in vitro paced canine cardiomyocyte model to assess the potential role of OxS in ATR. Cultured canine atrial cardiomyocytes were paced at 1 or 3 Hz (P1, P3) for 24 hrs. I CaL was recorded with whole cell voltage clamp. Single cell superoxide production was assessed by dihydroethidium fluorescence (DHEF) imaging. ATR (3 Hz pacing x 24 hrs) decreased I CaL (Fig. A ) and induced OxS (Fig. B ). Short term induction of OxS (H 2 O 2 100 μM x 10 mins) increased I CaL (Fig. C ) and enhanced Ca 2+ loading (Indo-1 AM). 24-Hr H 2 O 2 100 μ M increased DHEF in P1 cells by 250%* (*P&lt;0.05) and mimicked ATR, decreasing I CaL by 51%* (Fig. C ). H 2 O 2 -mediated DHEF changes were suppressed by inhibiting calmodulin (W7) or CaMKII (KN93). H 2 O 2 -induced I CaL suppression at 1 Hz was prevented by: decreasing Ca 2+ i loading by I CaL blockade (nimodipine) or Ca 2+ chelation (BAPTA-AM); W7 or KN93; antioxidants (2-MPG or N-acetylcysteine, NAC); or suppression of free radical generation via NADPH-oxidase (apocynin). 2-MPG, NAC, and apocynin prevented I CaL downregulation by 3-Hz pacing and W7, KN93 and apocynin abolished ATR-induced DHEF increases. H 2 O 2 mimics ATR by causing Ca 2+ i loading and CaMKII activation coupled to NADPH-oxidase stimulation. ATR-induced I CaL -downregulation is mediated in part by OxS generation. These findings provide insights into the pathways by which OxS contributes to ATR and present a mechanistic framework for understanding the effects of antioxidant interventions in AF.
Neurodevelopmental status of infants and young children treated for brain tumors with preirradiation chemotherapy.
Authors: R K Mulhern, M E Horowitz, E H Kovnar, J Langston, R A Sanford, L E Kun
Journal: Journal of Clinical Oncology (1989)

In an effort to reduce the severity of late neurotoxicities associated with cranial irradiation, 14 infants and young children with malignant brain tumors were given preirradiation chemotherapy for 2 to 22 months (median, 8 months). Prospective neurodevelopmental evaluations were routinely conducted and now extend from 35 to 60 months (median, 41 months) postdiagnosis, and 10 to 52 months (median, 31 months) postirradiation in the 12 surviving children. At the initiation of chemotherapy, less than one fourth of the patients displayed normal performance status or mental functioning on age-corrected tests; the majority remained stable or declined while receiving chemotherapy. Declining mental development and adaptive behavior were noted in six patients following radiation therapy with only two patients now functioning in the normal range for age. The analysis suggests that neurodevelopmental progress is a function of multiple factors, including neurologic and sensorimotor deficits associated with the tumor, surgical intervention, and chemotherapy that antedated radiation therapy. This implies that delaying irradiation will not necessarily improve the patients' functional status. Whether the interval of postponement of irradiation evidenced in this sample will translate into an ultimately better quality of life remains unknown. Given the probable interaction of multiple risk factors, well-controlled prospective clinical trials are needed to definitively analyze this issue.
Susceptibility of Common Marmosets (Callithrix jacchus) to Oncogenic and Attenuated Strains of Herpesvirus saimiri2
Authors: John Wright, Lawrence A. Falk, Lauren G. Wolfe, James Ogden, Friedrich Deinhardt
Journal: JNCI Journal of the National Cancer Institute (1977)

Protein synthesis in the L5178Y mouse lymphoma cell line was stimulated after short-duration heat shock by the addition of dibutyryl cyclic AMP. The stimulation was concentration-dependent (range, 0.01–1.0 mM) and was enhanced by preincubation of the cells in the presence of the cyclic nucleotide before the heat shock. Actinomycin, which blocks the recovery of protein synthesis activity after heat shock, did not block the cyclic AMP stimulation.
Pulmonary involvement in human T-cell lymphotropic virus type-I uveitis: T-lymphocytosis and high proviral DNA load in bronchoalveolar lavage fluid
Authors: M Sugimoto, S Mita, M Tokunaga, K Yamaguchi, I Cho, M Matsumoto, M Mochizuki, S Araki, K Takatsuki, M Ando
Journal: European Respiratory Journal (1993)

The ocular manifestation of human T-cell lymphotropic virus type I (HTLV-I) infection has been recognized as a new clinical entity termed HTLV-I uveitis. In order to determine whether HTLV-I uveitis is associated with lymphocyte alveolitis, bronchoalveolar lavage (BAL) was carried out in 11 patients with HTLV-I uveitis, five asymptomatic HTLV-I carriers, 11 HTLV-I-negative patients with ocular sarcoidosis, and nine normal control subjects seronegative for HTLV-I. Six of the 11 patients with HTLV-I uveitis showed increased total cell counts, and T-lymphocytosis in BAL fluid. CD4+/CD8+ ratios of T-lymphocytes were decreased in three of these patients, and normal in three other patients. Such abnormalities of the lung were not found in asymptomatic HTLV-I carriers, and in normal control subjects. BAL findings in HTLV-I uveitis differed from those of patients with sarcoidosis in terms of the lymphocytic component. Interestingly, it was found that there was an increase of HTLV-I proviral deoxyribonucleic acid (DNA) load in peripheral blood mononuclear cells (PBMC) from seven patients with HTLV-I uveitis, and in the BAL cells from four patients with pulmonary involvement. These results provide further evidence in terms of HTLV-I tropism for the lung, and suggest that a systemic and local increase of HTLV-I proviral DNA load plays an important role in the pathogenesis of lymphocyte alveolitis in patients with HTLV-I uveitis.
Transtracheal lung ventilation with a manual respiratory valve with a variable flow
Authors: Dragan Pavlovic, Wolfgang Fischer
Journal: European Respiratory Journal (2012)

In cannot-intubate, cannot-ventilate situations, a lung ventilation through a thin transtracheal cannula may be attempted. However, it may be impossible to achieve sufficient ventilation if the lungs are spontaneously emptying and dangers of barotrauma may occur. Here we present a valve (*) as a bi-directional manual respiratory pump which low flow during inspiration (by reducing gas supply to the valve) and increased flow during expiration, by increasing gas supply to the valve, permitted more effective venturi effect and efficient expiration, with low gas consumption.  The effectiveness of the valve was tested in vitro. The valve permitted to shorten the expiratory time and achieve higher minute volumes (i.e. volumes of 7L/min of gas or higher), as compared with the ventilation with the similar transtracheal cannula without variable flows (volumes achieved were about 4L/min). Variable flow provided shortening of the inspiratory time and efficient expiratory aid, and permitted I:E ratios of 1:1, or even the inverse ratio ventilation. Satisfactory lung ventilation can be assured with transtracheal ventilation with a bidirectional manual respiration valve with variable gas flow.  *) Konrad Meissner, et al., Successful Transtracheal Lung Ventilation using a Manual Respiration Valve-an in vitro and in vivo Study, Anesthesiology. 2008 Aug;109(2):251-9.
Site-specific immunophenotyping of keloid disease demonstrates immune upregulation and the presence of lymphoid aggregates
Authors: R. Bagabir, R.J. Byers, I.H. Chaudhry, W. Müller, R. Paus, A. Bayat
Journal: British Journal of Dermatology (2012)

Summary Background Keloid disease (KD) is a common fibroproliferative disorder of unknown aetiology. T cells and macrophages are increased in KD and are thought to contribute to its pathogenesis. However, while a link between inflammation and fibrotic disorders is well known for other disorders, it remains undetermined in KD. Objectives Systematically to immunophenotype the inflammatory infiltrate of KD in situ in a site-specific manner, and to compare this with normal skin and scar tissue. Methods Sixty-eight keloid cases were screened for the presence of all three (intralesional, perilesional and extralesional) keloid-associated specific tissue sites. Subsequently, a complete set of 25 keloid biopsies (from different patients) was compared with normal skin (n = 11) and normal scar (n = 11) samples and subjected to systematic, site-specific quantitative immunohistomorphometry and histochemistry, using a range of immunological markers of B cells, T cells, macrophages, mast cells (MCs) and Langerhans cells. Results T cells, B cells, degranulated and mature MCs (coexpressing OX40 ligand) and alternative macrophages (M2) were all significantly increased in intralesional and perilesional KD sites compared with normal skin and scar tissue (P < 0·05). Additionally, 10 of 68 KD cases (15%) showed the presence of distinctive lymphoid aggregates, which resembled mucosa-associated lymphoid tissue (MALT). Conclusions The increased number and activity of MCs and M2 may implicate inflammation in the fibrotic process in KD. The distinct KD-associated lymphoid aggregate resembles MALT, for which we propose the term 'keloid-associated lymphoid tissue' (KALT). It may perpetuate inflammatory stimuli that promote KD growth. KALT, MCs and M2 are promising novel targets for future KD therapy.
Extrapulmonary infections caused by a dominant strain of Mycobacterium massiliense (Mycobacterium abscessus subspecies bolletii)
Authors: A. Cheng, Y.-C. Liu, M.-L. Chen, C.-C. Hung, Y.-T. Tsai, W.-H. Sheng, C.-H. Liao, P.-R. Hsueh, Y.-C. Chen, S.-C. Chang
Journal: Clinical Microbiology and Infection (2013)
Immunofluorescence Tests on Sera of Patients With Osteogenic Sarcoma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Elizabeth S. Priori, J. R. Wilbur, L. Dmochowski
Journal: JNCI Journal of the National Cancer Institute (1971)

Fixed indirect immunofluorescence tests were done on imprints of 8 osteosarcomas and cells of tissue cultures derived from 5 osteosarcomas, with the use of sera from patients with this disease, from their family members, and normal blood-bank donors. Sera of 50% of patients and 30% of their family members contained antibodies to osteosarcoma cells. Sera of patients and their family members also reacted with cells of tissue cultures derived from 2 giant cell tumors, 2 rhabdomyosarcomas, and 1 chondrosarcoma, which suggested the presence of a common antigen in the tumors. Sera from normal donors gave negative reaction when tested against cells of the same tumors. The nature of the antigen demonstrated in cells of the tumors remains to be determined.