tbuckley/cabot-search huggingface dataset:
Late Recurrence of Childhood T-Cell Acute Lymphoblastic Leukemia Frequently Represents a Second Leukemia Rather Than a Relapse: First Evidence for Genetic Predisposition
Authors: Tomasz Szczepański, Vincent H.J. van der Velden, Esmé Waanders, Roland P. Kuiper, Pieter Van Vlierberghe, Bernd Gruhn, Cornelia Eckert, Renate Panzer-Grümayer, Giuseppe Basso, Hélène Cavé, Udo zur Stadt, Dario Campana, André Schrauder, Rosemary Sutton, Elisabeth van Wering, Jules P.P. Meijerink, Jacques J.M. van Dongen
Journal: Journal of Clinical Oncology (2011)

Purpose Relapse of childhood T-cell acute lymphoblastic leukemia (T-ALL) often occurs during treatment, but in some cases, leukemia re-emerges off therapy. On the basis of previous analyses of T-cell receptor (TCR) gene rearrangement patterns, we hypothesized that some late recurrences of T-ALL might in fact represent second leukemias. Patients and Methods In 22 patients with T-ALL who had late relapses (at least 2.5 years from diagnosis), we studied TCR gene rearrangement status at first and second presentation, NOTCH1 gene mutations, and the presence of the SIL-TAL1 gene fusion. We performed genome-wide copy number and homozygosity analysis by using oligonucleotide- and single nucleotide polymorphism (SNP) –based arrays. Results We found evidence of a common clonal origin between diagnosis and relapse in 14 patients (64%). This was based on concordant TCR gene rearrangements (12 patients) or concordant genetic aberrations, as revealed by genome-wide copy number analysis (two patients). In the remaining eight patients (36%), TCR gene rearrangement sequences had completely changed between diagnosis and relapse, and gene copy number analysis showed markedly different patterns of genomic aberrations, suggesting a second T-ALL rather than a resurgence of the original clone. Moreover, NOTCH1 mutation patterns were different at diagnosis and relapse in five of these eight patients. In one patient with a second T-ALL, SNP analysis revealed a germline del(11)(p12;p13), a known recurrent aberration in T-ALL. Conclusion More than one third of late T-ALL recurrences are, in fact, second leukemias. Germline genetic abnormalities might contribute to the susceptibility of some patients to develop T-ALL.
Pediatric Hodgkin Lymphoma
Authors: Christine Mauz-Körholz, Monika L. Metzger, Kara M. Kelly, Cindy L. Schwartz, Mauricio E. Castellanos, Karin Dieckmann, Regine Kluge, Dieter Körholz
Journal: Journal of Clinical Oncology (2015)

Hodgkin lymphoma (HL) is one of the most curable pediatric and adult cancers, with long-term survival rates now exceeding 90% after treatment with chemotherapy alone or combined with radiotherapy (RT). Of note, global collaboration in clinical trials within cooperative pediatric HL study groups has resulted in continued progress; however, survivors of pediatric HL are at high risk of potentially life-limiting second cancers and treatment-associated cardiovascular disease. Over the last three decades, all major pediatric and several adult HL study groups have followed the paradigm of response-based treatment adaptation and toxicity sparing through the reduction or elimination of RT and tailoring of chemotherapy. High treatment efficacy is achieved using dose-dense chemotherapy. Refinement and reduction of RT have been implemented on the basis of results from collaborative group studies, such that radiation has been completely eliminated for certain subgroups of patients. Because pediatric staging and response criteria are not uniform, comparing the results of trial series among different pediatric and adult study groups remains difficult; thus, initiatives to harmonize criteria are desperately needed. A dynamic harmonization process is of utmost importance to standardize therapeutic risk stratification and response definitions as well as improve the care of children with HL in resource-restricted environments.
Meta-analysis of the use of glyceryl trinitrate ointment after haemorrhoidectomy as an analgesic and in promoting wound healing
Authors: K. Ratnasingham, M. Uzzaman, S.M. Andreani, D. Light, B. Patel
Journal: International Journal of Surgery (2010)

Glyceryl Trinitrate (GTN) ointment has been used to treat anal fissure and pain relief in haemorrhoids, but the value of its use post-haemorrhoidectomy as an analgesic and in wound healing is unclear. The side effect of headache has often been an associated problem. Therefore, a meta-analysis of randomised controlled trials was carried out investigating the role of GTN post-haemorrhoidectomy as an analgesic, its role in would healing and the unwanted incidence of headache. A structured literature search from 1966 to 2009, both paper and online, with no language barrier was carried out. 760 papers were identified and 5 randomised control trials which met the entry criteria were included in this study. A total of 333 patients were included in the meta-analysis. The results revealed that GTN ointment was statistically significant in reducing pain on Day 3 and 7 compared to the placebo group. Day 3 shows a pain score of − 1.51 (p value of 0.029) and Day 7 by − 1.66 (p value of 0.014) respectively. However, it was not significant in reducing pain on Day 1. The Odds ratio for wound healing after GTN treatment at 3 weeks was 3.57 (P < 0.0001) when compared to the placebo group. Side effect of headache was not statistically significant. This meta-analysis has shown that GTN ointment used post-haemorrhoidectomy has a significant analgesic effect in the intermediate time period (ie. Days 3–7). It also significantly improved wound healing at 3 weeks.
Less common "doping" agents and substances encountered during routine screening for drugs.
Authors: P. E. Haywood, P. Chalmers
Journal: British Journal of Sports Medicine (1976)

The chromatographic and spectroscopic properties of several unusual substances which have been detected in the "alkaloidal" chloroform extract from racehorse urine and saliva samples are reported. Some of these substances have been identified by combined gas chromatography-mass spectrometry and the source of the substance is stated where this is known. Other substances whose identity is not known have been detected and their mass spectra show characteristic amine fragments. The occurrence of these unidentified substances is more frequent in aged urine samples and it would therefore appear that they are associated with putrefaction.
Two Cases of Blindness due to Sphenoidal and Ethmoidal Sinus Disease, Both Cases Terminating Fatally: Necropsy
Authors: G. V. Miller
Journal: BMJ (1900)

A NUMBER of cases of the nature indicated by the title of this paper are on record.Sandford, six years ago, brought a case under the notice of the Ophthalmological Society in which there had been double optic atrophy from sphenoidal sinus disease, and was able to show the condition present in the skull after death.McBride mentions a case recorded by Rouge where there was exophthalmos, strabismus, deafness, and blind- ness.Death soon occurred, and the sphenoidal sinus was found diseased.Sphenoidal sinus disease sometimes gives rise to retrobulbar neuritis as described by Holmes.In addi- tion to the above a considerable number of cases of sphenoidal sinus disease have now been placed on record by Schibfer (who first recorded the condition), Grutnwald, Nobel, Mac- donald, Bronner, Heryng, etc.In my two cases, I think the extensive disease in the ethmoid was the chief feature.Added to this were the symptoms of serious brain mischief.CASE I.
Endogenous Testosterone and Mortality Due to All Causes, Cardiovascular Disease, and Cancer in Men
Authors: Kay-Tee Khaw, Mitch Dowsett, Elizabeth Folkerd, Sheila Bingham, Nicholas Wareham, Robert Luben, Ailsa Welch, Nicholas Day
Journal: Circulation (2007)

Background— The relation between endogenous testosterone concentrations and health in men is controversial. Methods and Results— We examined the prospective relationship between endogenous testosterone concentrations and mortality due to all causes, cardiovascular disease, and cancer in a nested case-control study based on 11 606 men aged 40 to 79 years surveyed in 1993 to 1997 and followed up to 2003. Among those without prevalent cancer or cardiovascular disease, 825 men who subsequently died were compared with a control group of 1489 men still alive, matched for age and date of baseline visit. Endogenous testosterone concentrations at baseline were inversely related to mortality due to all causes (825 deaths), cardiovascular disease (369 deaths), and cancer (304 deaths). Odds ratios (95% confidence intervals) for mortality for increasing quartiles of endogenous testosterone compared with the lowest quartile were 0.75 (0.55 to 1.00), 0.62 (0.45 to 0.84), and 0.59 (0.42 to 0.85), respectively ( P &lt;0.001 for trend after adjustment for age, date of visit, body mass index, systolic blood pressure, blood cholesterol, cigarette smoking, diabetes mellitus, alcohol intake, physical activity, social class, education, dehydroepiandrosterone sulfate, androstanediol glucuronide, and sex hormone binding globulin). An increase of 6 nmol/L serum testosterone (≈1 SD) was associated with a 0.81 (95% confidence interval 0.71 to 0.92, P &lt;0.01) multivariable-adjusted odds ratio for mortality. Inverse relationships were also observed for deaths due to cardiovascular causes and cancer and after the exclusion of deaths that occurred in the first 2 years. Conclusions— In men, endogenous testosterone concentrations are inversely related to mortality due to cardiovascular disease and all causes. Low testosterone may be a predictive marker for those at high risk of cardiovascular disease.
Alterations in soluble and leukocyte surface L-selectin (CD 62L) in hemodialysis patients.
Authors: H Rabb, S J Agosti, P A Bittle, M Fernandez, G Ramirez, T F Tedder
Journal: Journal of the American Society of Nephrology (1995)

Hemodialysis (HD) patients can develop acute reactions during treatment as well as increased long-term susceptibility to infections and malignancy. Leukocyte-membrane interactions may contribute to these processes. The effects of a single HD session on L-selectin, a leukocyte adhesion molecule for endothelium, were examined. Serum levels of soluble L-selectin were measured in 23 patients by enzyme-linked immunosorbent assay before and after a 3-h dialysis session. There was a statistically significant increase in soluble L-selectin from 1.36 +/- 0.12 (SE) to 1.57 +/- 0.18 micrograms/mL (P < 0.001). An increase in shed L-selectin was observed for the "venous" compared with the "arterial" part of the dialyser (P < 0.01) 15 min into HD. Soluble L-selectin levels were found to remain increased at 3 h after treatment. Leukocyte-bound L-selectin and CD11b was examined by the use of flow cytometry. Neutrophil L-selectin decreased to 69 +/- 7% at 15 min (P < 0.01) and then rebounded to 98 +/- 7% at 180 min. Monocyte and lymphocyte L-selectin did not decrease. Because L-selectin is important for leukocyte attachment to endothelium at sites of inflammation, alterations of shed L-selectin and cell-surface L-selectin levels may play a role in the immunologic consequences of HD treatment.
Effect Of Human Natural Killer and γδ T Cells on the Growth of Human Autologous Melanoma Xenografts in SCID Mice
Authors: Francesco Lozupone, Daniela Pende, Vito Lelio Burgio, Chiara Castelli, Massimo Spada, Massimo Venditti, Francesca Luciani, Luana Lugini, Cristina Federici, Carlo Ramoni, Licia Rivoltini, Giorgio Parmiani, Filippo Belardelli, Paola Rivera, Stefania Marcenaro, Lorenzo Moretta, Stefano Fais
Journal: Cancer Research (2004)

Abstract Natural killer (NK) cells were first identified for their ability to kill tumor cells of different origin in vitro. Similarly, γδ T lymphocytes display strong cytotoxic activity against various tumor cell lines. However, the ability of both the NK and γδ cells to mediate natural immune response against human malignant tumors in vivo is still poorly defined. Severe combined immunodeficient (SCID) mice have been successfully engrafted with human tumors. In this study, the antitumor effect of local as well as of systemic treatments based on NK cells or Vδ1 or Vδ2 γ/δ T lymphocytes against autologous melanoma cells was investigated in vivo. The results show that all three of the populations were effective in preventing growth of autologous human melanomas when both tumor and lymphoid cells were s.c. inoculated at the same site. However, when lymphoid cells were infused i.v., only NK cells and Vδ1 γ/δ T lymphocytes could either prevent or inhibit the s.c. growth of autologous melanoma. Accordingly, both NK cells and Vδ1 γδ T lymphocytes could be detected at the s.c. tumor site. In contrast, Vδ2 γδ T lymphocytes were only detectable in the spleen of the SCID mice. Moreover, NK cells maintained their inhibitory effect on tumor growth even after discontinuation of the treatment. Indeed they were present at the tumor site for a longer period. These data support the possibility to exploit NK cells and Vδ1 γδ T lymphocytes in tumor immunotherapy. Moreover, our study emphasizes the usefulness of human tumor/SCID mouse models for preclinical evaluation of immunotherapy protocols against human tumors.
IL-17 in lung disease: friend or foe?
Authors: Hui-Leng Tan, Mark Rosenthal
Journal: Thorax (2013)

Interleukin 17 (IL-17) is a key proinflammatory cytokine in the T helper 17 pathway. While it is important in the clearance of certain pathogens, IL-17 has been shown to contribute to the pathogenesis of such inflammatory diseases as rheumatoid arthritis and psoriasis. In the lung, it has been postulated to be involved in the neutrophilic inflammation and airway remodelling of chronic respiratory conditions but the situation is increasingly complex. This review summarises the evidence for its role in several chronic inflammatory lung diseases: asthma, obliterative bronchiolitis, chronic obstructive pulmonary disease, sarcoidosis and cystic fibrosis.
Real-Time Continuous Glucose Monitoring Among Participants in the T1D Exchange Clinic Registry
Authors: Jenise C. Wong, Nicole C. Foster, David M. Maahs, Dan Raghinaru, Richard M. Bergenstal, Andrew J. Ahmann, Anne L. Peters, Bruce W. Bode, Grazia Aleppo, Irl B. Hirsch, Lora Kleis, H. Peter Chase, Stephanie N. DuBose, Kellee M. Miller, Roy W. Beck, Saleh Adi
Journal: Diabetes Care (2014)

OBJECTIVE To assess the frequency of continuous glucose monitoring (CGM) device use, factors associated with its use, and the relationship of CGM with diabetes outcomes (HbA1c, severe hypoglycemia [SH], and diabetic ketoacidosis [DKA]). RESEARCH DESIGN AND METHODS Survey questions related to CGM device use 1 year after enrollment in the T1D Exchange clinic registry were completed by 17,317 participants. Participants were defined as CGM users if they indicated using real-time CGM during the prior 30 days. RESULTS Nine percent of participants used CGM (6% of children &amp;lt;13 years old, 4% of adolescents 13 to &amp;lt;18 years, 6% of young adults 18 to &amp;lt;26 years, and 21% of adults ≥26 years). CGM use was more likely with higher education, higher household income, private health insurance, longer duration of diabetes, and use of insulin pump (P &amp;lt; 0.01 all factors). CGM use was associated with lower HbA1c in children (8.3% vs. 8.6%, P &amp;lt; 0.001) and adults (7.7% vs. 7.9%, P &amp;lt; 0.001). In adults, more frequent use of CGM (≥6 days/week) was associated with lower mean HbA1c. Only 27% of users downloaded data from their device at least once per month, and ≤15% of users reported downloading their device at least weekly. Among participants who used CGM at baseline, 41% had discontinued within 1 year. CONCLUSIONS CGM use is uncommon but associated with lower HbA1c in some age-groups, especially when used more frequently. Factors associated with discontinuation and infrequent use of retrospective analysis of CGM data should be considered in developing next-generation devices and education on CGM use.
Structure-function relationship of immunosuppressive drugs: A cautionary tale
Authors: Laurence A. Turka, Craig B. Thompson
Journal: Hepatology (1991)

The immunosuppressants FK506 and rapamycin bind to the same immunophilin, FK506 binding protein (FKBP), and inhibit distinct signal transduction pathways in T lymphocytes. A nonnatural immunophilin ligand, 506BD, which contains only the common structural elements of FK506 and rapamycin, was synthesized and found to be a high-affinity ligand of FKBP and a potent inhibitor of FKBP rotamase activity. Whereas 506BD does not interfere with T cell activation, it does block the immunosuppressive effects of both FK506 and rapamycin. Thus, the common immunophilin binding element of these immunosuppressants, which is responsible for rotamase inhibition, is fused to different effector elements, resulting in the inhibition of different signaling pathways. Inhibition of rotamase activity is an insufficient requirement for mediating these effects.
Highly Efficient Gene Transfer into Primate Embryonic Stem Cells with a Simian Lentivirus Vector
Authors: Takayuki Asano, Yutaka Hanazono, Yasuji Ueda, Shin-ichi Muramatsu, Akihiro Kume, Hirofumi Suemori, Yutaka Suzuki, Yasushi Kondo, Kiyonori Harii, Mamoru Hasegawa, Norio Nakatsuji, Keiya Ozawa
Journal: Molecular Therapy (2002)

The ability to stably introduce genetic material into primate embryonic stem (ES) cells could allow their broader application. We previously derived ES cell lines from cynomolgus monkey blastocysts. In this study, we examined lentiviral gene transfer into cynomolgus ES cells. When cynomolgus ES cells were transduced once with a simian immunodeficiency virus (SIV)-based lentivirus vector encoding the green fluorescent protein (GFP) gene, most cells (around 90%) fluoresced, and high levels of GFP expression persisted for 5 months without selection procedures. In addition, high levels of GFP expression were observed during embryoid body formation. On the other hand, transduction of mouse ES cells with the SIV-based vector resulted in lower gene transfer rates, implying that SIV vectors can transduce primate ES cells more efficiently than mouse ES cells. The use of GFP as a reporter gene allows direct and simple detection of successfully transduced ES cells and facilitates monitoring of ES cell proliferation and differentiation both in vitro and potentially in vivo. Furthermore, this highly efficient gene transfer method allows faithful gene delivery to primate ES cells with potential for both research and therapeutic application. The ability to stably introduce genetic material into primate embryonic stem (ES) cells could allow their broader application. We previously derived ES cell lines from cynomolgus monkey blastocysts. In this study, we examined lentiviral gene transfer into cynomolgus ES cells. When cynomolgus ES cells were transduced once with a simian immunodeficiency virus (SIV)-based lentivirus vector encoding the green fluorescent protein (GFP) gene, most cells (around 90%) fluoresced, and high levels of GFP expression persisted for 5 months without selection procedures. In addition, high levels of GFP expression were observed during embryoid body formation. On the other hand, transduction of mouse ES cells with the SIV-based vector resulted in lower gene transfer rates, implying that SIV vectors can transduce primate ES cells more efficiently than mouse ES cells. The use of GFP as a reporter gene allows direct and simple detection of successfully transduced ES cells and facilitates monitoring of ES cell proliferation and differentiation both in vitro and potentially in vivo. Furthermore, this highly efficient gene transfer method allows faithful gene delivery to primate ES cells with potential for both research and therapeutic application.
Analysis of cases from an interstitial lung disease (ILD) MDT in a teaching hospital in the West Midlands: Patients with smoking-related disease comprise 11% of cases and have a median age of 50 years
Authors: Stanley Ejiofor, Felix Woodhead, Emma Helm
Journal: European Respiratory Journal (2012)

Introduction 

University Hospitals Coventry and Warwickshire is a large acute teaching NHS trust which serves a population of over 1 million. There has been an ILD MDT since 2006. In July 2010 a consultant with an interest in ILD was appointed. The MDT constitutes a thoracic surgeon, pathologist and radiologist with expressed interest in ILD.

Aim 

To describe the spectrum of ILD presenting in secondary care.

Method 

It is departmental policy to discuss all incident cases of ILD in the MDT. Diagnoses were made according to BTS guidelines, and by consensus. Numbers were compared by χ2, and ages by Mann-Whitney U-test.

Results 

From September 2010 to July 2011, 89 suspected cases were discussed in the ILD MDT, 10 of whom proved not to have significant ILD. The diagnoses of the remaining 79 are given in table below.

View this table:



Definite IPF made up 15% of the cohort, with a median age of 77. Smoking related ILD — Respiratory Bronchiolitis associated ILD and Desquamative Interstitial Pneumonia — account for ( 11% ) of cases. The median age of diagnosis is 27 years younger than those with IPF (p<0.001).

Conclusion 

Smoking related ILD makes a significant proportion of cases discussed at the ILD MDT. Patients are significantly younger than those with IPF. This may reflect an increasing awareness of the radiological and pathological appearance of these diseases.
Cytokines and systemic lupus erythematosus
Authors: Gillian S Dean, Jonathan Tyrrell-Price, Esther Crawley, David A Isenberg
Journal: Annals of the Rheumatic Diseases (2000)

Systemic lupus erythematosus (SLE)SLE is an autoimmune rheumatic disease that principally aVects women in the childbearing years. 1 The prevalence of SLE varies between ethnic groups, being approximately 1:250 among black women, 1:1000 in Chinese women and 1:4300 in white women.SLE aVects the joints, skin and blood in over 80% of patients and the kidneys, central nervous system and cardiopulmonary system in 30%-50% of patients.Between 10% and 30% of patients have anticardiolipin antibodies that are associated with arterial and venous thrombosis.The majority of patients demonstrate systemic manifestations, which may include fatigue, malaise, fever, anorexia, nausea and weight loss.Many cytokines have been implicated in regulating disease activity and in the involvement of diVerent organs in patients with SLE.This article reviews both the role of individual cytokines and discusses possible mechanisms of cytokine action in individual organs. Are cytokines important in SLE?Cytokine production in patients with SLE differs from both healthy controls and patients with other diseases such as rheumatoid arthritis (RA).It is important to note that cytokine production is not only changed in patients with SLE when compared with healthy controls but also changes with diVerent disease phenotypes.For example, interleukin 6 (IL6) seems to be increased in the cerebrospinal fluid (CSF) of patients with central nervous system (CNS) involvement in SLE but not in patients with SLE who lack neurological symptoms. 2It may be that as in other inflammatory diseases, the balance of cytokines is more important in determining disease phenotype or severity rather than in determining disease susceptibility.