tbuckley/cabot-search huggingface dataset:
Secret Insulin-Injection Syndrome among Adolescents with Type 1 Diabetes
Authors: Pierre Bougnères, Pascal Boileau, Brigitte Aboumrad
Journal: New England Journal of Medicine (2005)

to the editor: In Case 28-2005 (Sept.15 issue), 1 the authors describe a 42-year-old man who had a systemic necrotizing vasculitis secondary to the Churg-Strauss syndrome with rapidly progressive glomerulonephritis (with a serum creatinine level of 5.7 mg per deciliter at admission), systemic symptoms, eosinophilia, asthma, hemoptysis, sinusitis, purpura, and peripheral-nerve disease.The patient was successfully treated with corticosteroids and oral cyclophosphamide, with normalization of the serum creatinine level, erythrocyte sedimentation rate, urine sediment, and blood eosinophil count.The patient felt well, he was able to return to work, and tests for antineutrophil cytoplasmic antibodies became negative.Yet the patient continued to receive cyclophosphamide well over a year after treatment was begun.In view of the potential toxicity of cyclophosphamide, this approach is no longer the norm for the treatment of a systemic necrotizing vasculitis. 2,3The preferred current approach is to induce remission with three to six months of cyclophosphamide therapy and then to use a less toxic maintenance regimen of azathioprine, methotrexate, or mycophenolate mofetil.Since relapses are common, the current induction-maintenance approach, by mini-mizing the initial exposure to cyclophosphamide, allows for further cyclophosphamide treatment for late relapses.
Anti-B Lymphocytotoxins in Renal-Allograft Rejection
Authors: Robert B. Ettenger, Paul I. Terasaki, Alan Ting, Mohammed H. Malekzadeh, Alfred J. Pennisi, Christel Uittenbogaart, Robert Garrison, Richard N. Fine
Journal: New England Journal of Medicine (1976)

To determine the possible role of the B lymphocyte alloantigen system in renal-transplant rejection, we examined serum specimens from 81 allograft recipients for cytotoxic activity against a panel of normal B lymphocytes. Specimens from 22 of 25 recipients undergoing allograft rejection demonstrated strong B-lymphocyte cytotoxicity whereas only 13 of 56 recipients with normal allograft function showed similar B lymphocyte cytotoxocitiy (P less than 0.0001). In the serum samples of recipients with graft rejection who were followed sequentially, B-lymphocyte cytotoxicity preceded or was concurrent with the onset of functional impairment. The results show that anti-B-lymphocyte antibodies are associated with rejection, but it is quite possible that they are the products of rejection rather than the cause.
Development of Resistance to MOPC-315 Plasmacytoma After Intralesional and Intraperitoneal Melphalan Therapy of Tumor-Bearing BALB/c Mice. II. Enhancement of In Vitro Cell-Mediated Cytotoxicity by Combined Chemotherapy-Immunotherapy&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A Adler, Y Keisari, R Ofir
Journal: JNCI Journal of the National Cancer Institute (1985)

As previously reported, tumor-bearing BALB/c mice can be cured by split-course melphalan therapy, with 40-60% of the treated animals developing resistance to subsequent challenge with viable MOPC-315. The present study deals with the identification of effector-cytotoxic cells that may be developed as a result of chemotherapy-induced tumor regression and their possible potentiation by active, specific immunization with melphalan- and glutaraldehyde-treated MOPC-315 plasmacytoma cells. The cytotoxic potential of spleen-derived lymphocytes in treated animals could be demonstrated only after in vitro sensitization against mitomycin-treated MOPC-315 cells. Lymphocyte-mediated cytotoxicity, as measured against syngeneic 51Cr-labeled MOPC-315, could be detected in melphalan-cured animals and was significantly enhanced by active immunization as compared to the cytotoxicity seen in normal and tumor-bearing mice. With the use of M109 syngeneic, unrelated tumor cells as control targets in the assay, no cytotoxicity was detected. Macrophage cytotoxicity was not significantly enhanced in any of the treatment groups described, with these assays performed 6-8 weeks following treatment and cure. When in vitro killing of MOPC-315 targets was tested with the use of peritoneal macrophages harvested shortly following cure of ascitic tumor by ip injected melphalan, the cytotoxic response was significantly enhanced. In conclusion, following chemotherapy-mediated cure of established MOPC-315 tumors, splenic lymphocytes exhibited enhanced antitumor cytotoxicity, which was further augmented by active immunization. Macrophage activation, as measured by direct cytotoxicity against MOPC-315 targets, was found to occur locally and early following the event of melphalan-induced tumor regression.
Runx1 downregulates stem cell and megakaryocytic transcription programs that support niche interactions
Authors: Kira Behrens, Ioanna Triviai, Maike Schwieger, Nilgün Tekin, Malik Alawi, Michael Spohn, Daniela Indenbirken, Marion Ziegler, Ursula Müller, Warren S. Alexander, Carol Stocking
Journal: Blood (2016)
S17 Do pre-school lung ventilation scans predict outcome by 6 years of age in children with Cystic Fibrosis (CF)?
Authors: R Yahia, L Viviani, S Carr, A Bush
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> Progressive respiratory disease accounts for most of the mortality and morbidity in CF. Identification of early lung disease is imperative to recognise young patients who are at high risk of developing future lung damage. The London CF collaboration has shown that infant pulmonary function at one and at two years is essentially normal, and one year HRCT has mild abnormalities only, so new markers need to be identified. We have used ventilation scans (VS) at the CF annual assessment in infants too young to perform standard pulmonary function tests; VS are more sensitive than chest radiography, and have been used to guide immediate management. We hypothesised that an abnormal pre-school lung VS predicted worse spirometry by age six years in CF children. <h3>Methods</h3> Data from children born after 2000 under the care of the RBH were retrieved from hospital databases and Port CF. We recorded demographics (gender, age, CFTR genotype, weight, height, ethnicity) and spirometry nearest to 6 years of age because repeatable measurements in a clinical context are feasible at this age. The primary outcome was FEV<sub>1</sub>% predicted (%p) (GLI reference equation (http://www.lungfunction.org/); and VS at annual assessment. Between 1–5 scans were performed prior to the age 6 year spirometry, and were independently reported as normal or abnormal (at least one abnormal VS). Statistical analysis was performed using Student t test. P &lt; 0.05 was considered significant. <h3>Results</h3> 143/217 children (72 females, 71 males) had data on VS and spirometry available; mean age at first spirometry was 6.36 (range 5.0–7.6). The remaining 73 were excluded due to late diagnosis, moving away before the first reliable spirometry, or first being seen later than the window for ventilation scans (1–5 years). Children with ≥1 abnormal VS had a statistically significant reduction in lung function (mean FEV1% p 83.4%) when compared with children with normal ventilation scans (mean FEV1% p%89.6), P = 0.03 (Figure 1). <h3>Conclusion</h3> Although abnormal VS predict abnormal first spirometry, the overlap between the two groups means that VS are not a useful clinical tool to delineate a high risk group.
Trends in systemic management (SM) for the treatment of locally advanced breast cancer: Data from a regional cancer centre
Authors: S. F. Dent, S. Verma, J. Azzi, L. Vandermeer, J. Spaans
Journal: Journal of Clinical Oncology (2006)

10728 Background: Locally advanced breast cancer (LABC) accounts for less than 5% of women diagnosed with breast cancer in North America each year. The scarcity of clinical trials addressing the SM of these women continues to represent a challenge for clinicians. Methods: A retrospective database was developed using the American Joint Committee on Cancer (AJCC) 2002 staging classification for all women who presented to TOHRCC with LABC between Jan 1/02-April 1/05. Information was obtained from clinic charts and patient self-reported questionnaires. Results: Outcomes reflect the SM of the first 50 women entered into our database. Median age at presentation was 57 years (range 28–88); 62% were post-menopausal; and hormonal status was 52% estrogen receptor (ER) positive and 54% progesterone receptor (PR) positive. Surgery was performed prior to chemotherapy in 50% of patients (pts).The majority (90%) of pts received SM as follows: 38% anthracyclines (A) alone (52% epirubicin, 26% adriamycin, 2% both); 7% taxanes (T) alone (33% paclitaxel, 66% docetaxel), 53% received both T and A regimens, and 2% received other types of chemotherapy (gemcitabine,vinorelbine,capecitabine). The addition of trastuzumab to the SM of HER2-positive pts has also been observed. Hormone therapy was given to 22 pts (44%) of whom 82% were ER or PR-positive: tamoxifen (27%); aromatase inhibitors (AIs; 50%); both tamoxifen and AIs (23%). Pts were treated with AIs as follows: anastrozole (73%); fulvestrant (9%), and atemestane (9%). In pts with measurable disease receiving neoadjuvant SM; 7(35%) had a complete clinical response and 13 (65%) had a partial response; mean tumour size decreased from 7.5 cm (range 2–22) to 2.8 cm (range 0–8). Pathological complete response rates and improved survival rates have been observed and will be reported in detail. Conclusions: These results represent our first analysis of treatment outcomes in women with LABC using the new AJCC system. This database highlights the increased utilization of T and AIs in the SM of these pts, which seems to translate into the increasingly observed improvements in overall survival. Microarray studies to further explore predictability of treatment outcomes are planned. No significant financial relationships to disclose.
Role of Toll-like receptor 9 (TLR-9) in acute graft-versus-host disease
Authors: A. Balsari, C. Calcaterra, L. Sfondrini, A. Rossini, S. Ménard
Journal: Journal of Clinical Oncology (2008)

7037 Background: Graft-versus-host disease (GVHD) requires a signal from co-stimulatory molecules expressed by host antigen- presenting cells (APC) for activation of donor T cells. Expression of co-stimulatory molecules might be induced by Toll-like receptors (TLRs) stimulated by intestinal bacterial breakdown products produced by myeloablative conditioning regimens. Using knockout mice, we evaluated the role of TLR4 and TLR9 in the GVHD associated with allogeneic bone marrow transplantation. Methods: Female wild type C57BL/6, TLR9-/- or TLR4-/- mice (8–12 weeks of age) that received myeloablative total body irradiation (900 cGy, 137Cs source) in two doses with a 2-hour interval to minimize gastrointestinal toxicity, followed by intravenous infusion of 1 × 107 donor BALB/c bone marrow cells and 4 × 107 BALB/c splenocytes as a source of allogeneic T cells, were evaluated for survival, body weights and GVHD clinical scores. In vivo expansion of alloreactive donor cells in transplanted mice was evaluated ex vivo by flow cytometry after labeling with CFSE. Mixed lymphocyte reaction (MLR) assays were performed to evaluate the stimulatory activity of MHC class II+ antigen presenting cells (APCs) obtained from spleen of C57BL/6, TLR9-/- or TLR4-/- mice not irradiated or irradiated 24 h before with myeloablative conditioning regimen on proliferation of CD19- BALB/c-derived responder cells. Results: When myeloablative irradiated TLR9-/- mice, instead of wild-type mice, were used as graft recipients, survival and clinical score of acute GVHD severity were improved: 18/30 vs 1/31 mice still alive at day 70, while no significant differences were observed using recipient TLR4-/- mice. The reduced mortality and morbidity in TLR9-/- mice were associated with reduced proliferation of allogeneic donor cells transplanted in these mice. Moreover, MLR assays revealed a significantly reduced proliferation of allogeneic T cells in the presence of APCs from TLR9-/- as compared with APCs from wild-type irradiated mice, while in the presence of APCs from TLR9-/- and wild-type non-irradiated mice proliferation was comparable. Conclusions: These data reveal a novel function of TLR9 in GVHD, a finding that might provide tools to reduce this complication of allogeneic transplantation. No significant financial relationships to disclose.
Improved light microscopy counting method for accurately counting <i>Plasmodium parasitemia</i> and reticulocytemia
Authors: Caeul Lim, Ligia Pereira, Pritish Shardul, Anjali Mascarenhas, Jennifer Maki, Jordan Rixon, Kathryn Shaw‐Saliba, John White, Maria Silveira, Edwin Gomes, Laura Chery, Pradipsinh K. Rathod, Manoj T. Duraisingh
Journal: American Journal of Hematology (2016)

Even with the advances in molecular or automated methods for detection of red blood cells of interest (such as reticulocytes or parasitized cells), light microscopy continues to be the gold standard especially in laboratories with limited resources. The conventional method for determination of parasitemia and reticulocytemia uses a Miller reticle, a grid with squares of different sizes. However, this method is prone to errors if not used correctly and counts become inaccurate and highly time-consuming at low frequencies of target cells. In this report, we outline the correct guidelines to follow when using a reticle for counting, and present a new counting protocol that is a modified version of the conventional method for increased accuracy in the counting of low parasitemias and reticulocytemias. Am. J. Hematol. 91:852-855, 2016. © 2016 Wiley Periodicals, Inc.
P110 A review of persistent hypercapnia and subsequent referral for obese patients admitted into an Intensive Care Unit
Authors: K Manalan, K Sanderson, T Akhtar, N Hart, P Murphy
Journal: Thorax (2015)

<h3>Introduction</h3> Obesity hypoventilation syndrome (OHS) is increasingly common but data detailing the prevalence, outcome and long-term management, in patients admitted to the ICU, are limited. Indeed, we aimed to assess the prevalence of persistent hypercapnia in obese patients admitted to ICU and subsequent referral rate for specialist long-term management of sleep disordered breathing. <h3>Methods</h3> A retrospective analysis of data that was prospectively entered into an electronic patient record was conducted, from May 2011 to May 2014, at a University Hospital. Obesity was defined as a body mass index (BMI) (&gt;35 kg/m<sup>2</sup>) and hypercapnia as an arterial partial pressure of carbon dioxide (PaCO<sub>2</sub>) &gt;6 kPa. All patients meeting both criteria were reviewed to assess whether these patients were referred to the regional sleep and ventilation unit. <h3>Results</h3> A total of 5014 patients were ventilated in critical care of which 240 (5%) had obesity with persistent hypercapnia (age 49 ± 14 years, BMI 41.5 ± 6.7 kg/m<sup>2</sup>, PaCO<sub>2</sub> 7.5 kPa). 27% percent (65/240) were referred for assessment of sleep disordered breathing. Referred patients were more likely to have respiratory comorbidity (p &lt; 0.001) and were more obese (ΔBMI 3.1 kg/m<sup>2</sup>, p &lt; 0.001) but of similar age (p = 0.977) and degree of hypercapnia (p = 0.474). Patients referred for assessment of sleep disordered breathing had improved survival compared to those who were not referred (980 days v 1271 days, log rank test p = 0.004, Figure 1). <h3>Conclusions</h3> Rates of obesity and persistent hypercapnia are high in survivors of critical illness. However, patients are frequently not referred for specialist respiratory assessment. Survival is increased in patients referred for long-term management, although this data needs to be interpreted with caution as this could be the result of referral bias and a prospective study is now required.
Salinomycin and paclitaxel silk fibroin nanoparticles incorporated silk fibroin hydrogel for superior inhibition of cancer stem cells and tumor growth.
Authors: Puyuan Wu, Rutian Li, Qin Liu, Baorui Liu
Journal: Journal of Clinical Oncology (2015)

e13565 Background: Cancer stem cells (CSCs), a small population of tumor cells responsible for tumor seeding and recurrence, are considered to be chemotherapy resistant and have been reported to be sensitive to salinomycin (Sal) instead of paclitaxel (Ptx). Here we report a novel silk fibroin (SF) hydrogel loading Sal and Ptx by incorporating drug loaded silk fibroin nanoparticles (SF-NPs) to kill CSCs and non-CSCs simultaneously. Methods: We prepared Sal loaded SF-NPs using the method we have previously reported to prepare Ptx loaded SF-NPs (Ptx-SF-NPs). The drug loaded SF-NPs were dispersed in the ultrasound processed SF solution before gelation. After characterization, we conducted in vivo degradation study in ICR mice for 28 days. Anti-tumor efficacy studies were carried out on the murine hepatic carcinoma H22 subcutaneous tumor model. Results: Sal-SF-NPs with a diameter of 120nm were fabricated under mild and non-toxic condition. The resulting SF hydrogel (Sal-Ptx-NP-Gel) retained its injectable property, showed no swelling, exhibited bio-degradability and demonstrated homogenous drug distribution compared to the non-NP incorporated hydrogel. Ptx was released from the hydrogel in a sustained manner, while Sal demonstrated a burst release followed by sustained release. The in vivo degradation study proved the slow degradation of Sal-Ptx-NP-Gel for longer than 28 days after subcutaneous injection with mild immunogenicity. Sal-Ptx-NP-Gel increased the maximum tolerated dose of Sal in ICR mice. Sal-Ptx-NP-Gel showed significantly better inhibition of tumor growth compared to single drug loaded hydrogel and systemic dual drug administration. Sal-Ptx-NP-Gel also significantly reduced CD44+CD133+ tumor cells and demonstrated the least tumor formation in the in vivo tumor seeding experiment, indicating the superior inhibition of cancer stem cells. Conclusions: These results suggest that SF-NPs incorporated SF hydrogel is a promising drug delivery platform, and Sal-Ptx-NP-Gel could be a novel and powerful locoregional tumor treatment regimen in the future.
A randomized phase III comparison of standard-dose (60 Gy) versus high-dose (74 Gy) conformal chemoradiotherapy with or without cetuximab for stage III non-small cell lung cancer: Results on radiation dose in RTOG 0617.
Authors: Jeffrey D Bradley, Rebecca Paulus, Ritsuko Komaki, Gregory A. Masters, Kenneth Forster, Steven E. Schild, Jeffrey Bogart, Yolanda I. Garces, Samir Narayan, Vivek Kavadi, Lucien Alexander Nedzi, Jeff M. Michalski, Douglas Johnson, Robert Malcolm MacRae, Walter John Curran, Hak Choy
Journal: Journal of Clinical Oncology (2013)

7501 Background: The first objective of RTOG 0617 was to compare the overall survival(OS) of patients(pts) treated with standard-dose(SD)(60Gy) versus high-dose(HD)(74Gy) radiotherapy with concurrent chemotherapy(CT). Methods: This Phase III Intergroup trial randomized 464 pts with Stage III NSCLC to the SD(60Gy) vs. HD(74Gy) arms prior to closure of the HD arm. Concurrent CT included weekly paclitaxel(45 mg/m2) and carboplatin(AUC=2). Pts randomized to cetuximab received a 400 mg/m2 loading dose on Day 1 followed by weekly doses of 250 mg/m2. All pts were to receive consolidation CT. We are reporting the final results on radiation dose. Results: 464 pts were accrued prior to closure of the HD arm in 6/11, of which 419 were eligible for analysis. Median follow up was 17.2 months. There were 2 and 10 grade 5 treatment-related adverse events(AEs) on the SD and HD arms, respectively. Grade 3+AEs were 74.2% and 78.2% on SD and HD arms, respectively (p=0.34). The median survival times and 18-month OS rates for the SD and HD arms were 28.7 vs 19.5 months, and 66.9% vs 53.9% respectively (p=0.0007). The primary cause of death was lung cancer (72.2% vs 73.5%)(p=0.84). Local failure rates at 18 months were 25.1% vs 34.3% for SD and HD patients, respectively(p=0.03). Local-regional and distant failures at 18 months were 35.3% vs 44%(p=0.04) and 42.4% vs 47.8%(p=0.16) for SD and HD arms, respectively. Factors predictive of less favorable OS on multivariate analysis were higher radiation dose, higher esophagitis/dysphagia grade, greater gross tumor volume, and heart volume &gt;5 Gy. Conclusions: In this setting of chemoradiation for locally-advanced Stage III NSCLC, 60 Gy is superior to 74 Gy in terms of OS and local-regional control. The effect of the anti-EGFR antibody (cetuximab) awaits further follow up. This project was supported by RTOG grant U10 CA21661, CCOP grant U10 CA37422, and ATC U24 CA 81647 from the National Cancer Institute (NCI) and Eli Lilly and Company. Clinical trial information: NCT00533949.
Monosomy 7 in Granulocytes and Monocytes in Myelodysplastic Syndrome
Authors: Juha Kere, Tapani Ruutu, Albert de la Chapelle
Journal: New England Journal of Medicine (1987)

Monosomy for all or part of chromosome 7 in bone marrow mitoses of some patients with myelodysplastic syndrome or acute nonlymphocytic leukemia has been associated with a defect in granulocyte function. To study which blood-cell lineages are affected by the monosomy, we used chromosome 7-specific DNA probes in Southern blotting experiments on DNA derived from specific cell fractions isolated from the blood of five patients. As judged by the presence or absence of two different alleles for restriction-fragment-length polymorphisms, lymphocytes of all five patients were shown to have two different chromosomes 7. Granulocytes were affected by the chromosomal abnormality in four patients (No. 1, 2, 4, and 5) and unaffected in one (No. 3). Chemotaxis was normal in Patient 3 and impaired in Patients 4 and 5. Monocytes were affected by the monosomy in two of three patients (No. 2 and 3) and mainly unaffected in one (No. 1). Thus, the granulocytes and monocytes were affected differently in different patients. We conclude that mature blood cells are derived from abnormal progenitors and that there may be heterogeneity in the involvement of different cell lineages in different patients with myelodysplastic syndrome or acute nonlymphocytic leukemia. There is an association between DNA loss and functional impairment.
Case 15-2005
Authors: Laura M. Dember, Jo-Anne O. Shepard, Francesca Nesta, James R. Stone
Journal: New England Journal of Medicine (2005)

An 80-year-old man was admitted to the hospital because of shortness of breath. He had pleural effusions, edema of the legs, and a history of atrial fibrillation, several episodes of congestive heart failure, and increasing proteinuria. Laboratory studies revealed nephrotic-range proteinuria and an IgG paraprotein. A diagnostic procedure was performed.
Case 10-1966
Authors: William H. Baker, Benjamin Castleman
Journal: New England Journal of Medicine (1966)

Presentation of Case First admission. A fifty-three-year-old man was admitted to the hospital because of dyspnea. He had been well until seven months previously, when a "rattling noise" and a sensation of pressure developed in the left side of the chest, accompanied by a cough productive of a small amount of yellow sputum. Two months before entry an x-ray film of the chest showed an abnormality within the left lung. Penicillin was given, but the symptoms and radiologic pattern persisted.He had smoked 1 package of cigarettes daily for thirty years. A brother had been treated for tuberculosis many years . . .