tbuckley/cabot-search huggingface dataset:
Role of the transjugular intrahepatic portosystemic shunt in the management of severe complications of portal hypertension in idiopathic noncirrhotic portal hypertension
Authors: Julien Bissonnette, Juan Carlos Garcia‐Pagán, Agustín Albillos, Fanny Turon, Carlos Ferreira, Luis Tellez, Jean‐Charles Nault, Nicolas Carbonell, Jean‐Paul Cervoni, Mohamed Abdel Rehim, Annie Sibert, Louis Bouchard, Pierre Perreault, Jonel Trebicka, Félix Trottier‐Tellier, Pierre‐Emmanuel Rautou, Dominique‐Charles Valla, Aurélie Plessier
Journal: Hepatology (2016)

Idiopathic noncirrhotic portal hypertension is a heterogeneous group of diseases characterized by portal hypertension in the absence of cirrhosis. The efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) in this population are unknown. The charts of patients with idiopathic noncirrhotic portal hypertension undergoing TIPS in seven centers between 2000 and 2014 were retrospectively reviewed. Forty-one patients were included. Indications for TIPS were recurrent variceal bleeding (n = 25) and refractory ascites (n = 16). Patients were categorized according to the presence (n = 27) or absence (n = 14) of significant extrahepatic comorbidities. Associated conditions were hematologic, prothrombotic, neoplastic, immune, and exposure to toxins. During follow-up (mean 27 ± 29 months), variceal rebleeding occurred in 7/25 (28%), including three with early thrombosis of the stent. Post-TIPS overt hepatic encephalopathy was present in 14 patients (34%). Eleven patients died, five due the liver disease or complications of the procedure and six because of the associated comorbidities. The procedure was complicated by hemoperitoneum in four patients (10%), which was fatal in one case. Serum creatinine (P = 0.005), ascites as indication for TIPS (P = 0.04), and the presence of significant comorbidities (P = 0.01) at the time of the procedure were associated with death. Mortality was higher in patients with significant comorbidities and creatinine ≥100 μmol/L (P < 0.001).In patients with idiopathic noncirrhotic portal hypertension who have normal kidney function or do not have severe extrahepatic conditions, TIPS is an excellent option to treat severe complications of portal hypertension. (Hepatology 2016;64:224-231).
A study of 10 men charged with patricide
Authors: J M Cravens, J Campion, A Rotholc, F Covan, R A Cravens
Journal: American Journal of Psychiatry (1985)

The authors reviewed the records of 10 men charged with patricide, including one charged with double parricide, all of whom had been examined at the Forensic Psychiatry Service of Bellevue Hospital from 1970 to 1983. Prior psychoses were documented in all subjects; nine were referred to as delusional. Four perceived their fathers as having posed threats of physical or psychological annihilation to them, and five saw paternal threats to their manhood. The 10th man allegedly killed his father during a drunken brawl.
Smoking and Hepatitis B-Negative Primary Hepatocellular Carcinoma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: D Trichopoulos, B MacMahon, L Sparros, G Merikas
Journal: JNCI Journal of the National Cancer Institute (1980)

Smoking histories were obtained from 79 patients with primary hepatocellular carcinoma (PHC) (of whom 40 were negative and 39 positive for serum hepatitis B surface antigen), 39 patients with liver cancer not primary in the liver (LCNP), and 204 hospitalized controls. All subjects were Caucasians of Greek nationality and residence. No significant difference in smoking habits was found between controls and either PHC patients positive for serum hepatitis B surface antigen or LCNP patients. In contrast, there was a highly significant association between smoking and PHC negative for serum hepatitis B surface antigen (P less than 10(-4)); this association was not accounted for by the greater alcohol consumption of smokers. The risk ratios were 1.3, 2.5, 3.7, and 8.4 for current smokers of 1-10, 11-20, 21-30, and 30+ cigarettes per day.
Phase I pharmacokinetic (PK) and pharmacodynamic (PD) study of 17-Allylamino-17-demethoxygeldanamycin (17AAG) in children with solid tumors
Authors: R. Bagatell, L. Gore, M. Egorin, R. Ho, N. Boucher, G. Heller, T. Trippett
Journal: Journal of Clinical Oncology (2006)

9022 Background: 17AAG is a benzoquinone ansamycin that binds to heat shock protein 90 (Hsp90) and alters levels of cancer-associated proteins that are regulated by Hsp90. 17AAG has been well-tolerated in adults, but has not previously been administered to children. Methods: A Phase I study of 17AAG was initiated to define the maximally tolerated dose and toxicity profile of this drug in children. PK and PD were also studied. Cohorts of 3–6 patients with recurrent or refractory solid tumors were treated every 21 days with escalating doses of 17AAG twice weekly for two weeks. Plasma PK of 17AAG and its major metabolite, 17AG, were measured on day 1 by HPLC. Changes in levels of the inducible isoform of Hsp70 were assessed by Western blot using peripheral blood mononuclear cells (PBMCs) obtained 24 h after the 17AAG infusion. Actin was measured for comparison. Because 17AAG is a substrate for CYP3A4/5 and MDR1, pharmacogenetic analyses have been undertaken to determine if genotypes including CYP3A4*1B, CYP3A5*3, and MDR1 G2677T/A and C3435T influence 17AAG disposition. Results: 12 pts (median age 11 years, range 5–18) with neuroblastoma (5), osteosarcoma (4), Ewing’s family tumors (2), and desmoplastic small round cell tumor (1) have been treated with 17AAG. An MTD has yet to be defined though one dose limiting toxicity (Grade 3 hypoxia) was observed at Dose Level 4 (360 mg/m 2 ). The AUC of 17AAG increased with dose, with a linear relationship between end of infusion 17AAG plasma concentration and AUC. The AUC of 17AAG increased with dose, with a linear relationship between end of infusion 17AAG plasma concentration and AUC. Clearance ranged between 12.5 and 29.6 l/hr/m 2 (median, 21.6 l/h/m 2 ) and did not change with increasing doses. Post-treatment increases in Hsp70 in PBMCs have been observed in pts treated with 17AAG doses at or above 150 mg/m 2 . Declines in Akt and IGF1R in PBMCs have been seen in some but not all pts following treatment. Conclusions: 17AAG is well tolerated in children at dose levels studied to date. 17AAG dose escalation continues and at the time of the meeting, updated data will be reported. No significant financial relationships to disclose.
Small intestinal eosinophils regulate Th17 cells by producing IL-1 receptor antagonist
Authors: Reiko Sugawara, Eun-Jung Lee, Min Seong Jang, Eun-Ji Jeun, Chun-Pyo Hong, Jung-Hwan Kim, Areum Park, Chang Ho Yun, Sung-Wook Hong, You-Me Kim, Ju-Young Seoh, YunJae Jung, Charles D. Surh, Masayuki Miyasaka, Bo-Gie Yang, Myoung Ho Jang
Journal: The Journal of Experimental Medicine (2016)

Eosinophils play proinflammatory roles in helminth infections and allergic diseases. Under steady-state conditions, eosinophils are abundantly found in the small intestinal lamina propria, but their physiological function is largely unexplored. In this study, we found that small intestinal eosinophils down-regulate Th17 cells. Th17 cells in the small intestine were markedly increased in the ΔdblGATA-1 mice lacking eosinophils, and an inverse correlation was observed between the number of eosinophils and that of Th17 cells in the small intestine of wild-type mice. In addition, small intestinal eosinophils suppressed the in vitro differentiation of Th17 cells, as well as IL-17 production by small intestinal CD4+ T cells. Unlike other small intestinal immune cells or circulating eosinophils, we found that small intestinal eosinophils have a unique ability to constitutively secrete high levels of IL-1 receptor antagonist (IL-1Ra), a natural inhibitor of IL-1β. Moreover, small intestinal eosinophils isolated from IL-1Ra−deficient mice failed to suppress Th17 cells. Collectively, our results demonstrate that small intestinal eosinophils play a pivotal role in the maintenance of intestinal homeostasis by regulating Th17 cells via production of IL-1Ra.
Abstract 18147: Association of the First Occurrence of Atrial Fibrillation With Short-Term ICD Therapy and Heart Failure Exacerbation
Authors: Heath E Saltzman, JoAnn Lindenfeld, Paul Jones, Vicki Houle, Tim Stivland, Songtao Jiang, Slawomir L Kusmirek
Journal: Circulation (2013)

Background: Atrial fibrillation (AF) predicts inappropriate therapy and mortality in patients (pts) with implantable cardioverter defibrillators (ICDs). The short term effects of AF in pts with ICDs are not known. We sought to determine if AF burden affected 30 day morbidity as defined by heart failure (HF) exacerbations and ICD therapy. Methods: Pts enrolled in the LATITUDE home monitoring system were analyzed. Devices with greater than 1% AF during a 30-day period were included and divided into deciles based on the AF burden. The deciles were compared on number of ICD shocks, blood pressure and heart rate measures, and 6 HF symptom questions from the LATITUDE monitoring system. Symptom questions were scored as “-1” for improved, “0” for same, and “1” for worsened. Results: 4258 pts were identified with an AF burden &gt;1%. Of those, 3197 had heart failure observations recorded before and after the AF episode. Compared with before the 1st AF episode, in the month following, pts had a worsened activity level ( P &lt;0.001), systolic blood pressure ( P &lt;0.001), and heart rate variability ( P =0.005). Pts also reported worsened dizziness ( P &lt;0.001), edema ( P =0.006), exercise capacity ( P =0.01), orthopnea ( P &lt;0.001), and more episodes of nocturnal dyspnea ( P &lt;0.001) The trend for nocturnal dyspnea and fatigue was significant across AF burden deciles (Figure). There was no difference in the mean number of shocks after the analyzed month of AF. Conclusion: Short term AF burden is predictive of worsened HF symptoms but not ICD shocks.
Spontaneous Tumor Cell Killing by Human Blood Monocytes and Human Peritoneal Macrophages: Lack of Alteration by Endotoxin or Quenchers of Reactive Oxygen Species&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: J. Brice Weinberg, Arthur F. Haney
Journal: JNCI Journal of the National Cancer Institute (1983)

Human mononuclear phagocytes (monocytes and macrophages) act as effectors in the destruction of tumor cells. Peritoneal macrophages from normal or infertile women killed a variety of tumor cells in vitro more efficiently than did blood monocytes from the same subjects. Lysis depended on the effector-to-target cell ratio and was neither reproduced by supernatants from nor Iysates of the mononuclear phagocytes. Normal fibroblasts were not lysed. Lipopolysaccharide (101-104 ng/ml) diet not alter the monocyte- or macrophagemediated tumor cell killing. The monocytes and macrophages had equivalent basal and phorbol 12,13-myristate acetate-stimulated H2O2 and O2 production, and the reactive oxygen species scavengers or quenchers catalase, superoxide dismutase, mannitol, and L-histidine did not diminish the killing. These observations suggest that the spontaneous tumor cell killing by human mononuclear phagocytes was not mediated by reactive oxygen species.
Combined modality in advanced Hodgkin's disease.
Authors: M Baumann, T Herrmann, H D Thames
Journal: Journal of Clinical Oncology (1998)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1998.16.8.2893 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 9704747 Combined modality in advanced Hodgkin's disease. M BaumannxM BaumannSearch for articles by this author , T HerrmannxT HerrmannSearch for articles by this author , H D ThamesxH D ThamesSearch for articles by this author https://doi.org/10.1200/JCO.1998.16.8.2893 PDF "Combined modality in advanced Hodgkin's disease.." Journal of Clinical Oncology, 16(8), pp. 2893–2894© 1998 by American Society of Clinical Oncology
Paediatric Rectal Prolapse in Rwanda
Authors: EJ Chaloner, J Duckett, J Lewin
Journal: Journal of the Royal Society of Medicine (1996)

During the 1994 crisis in Rwanda, a high incidence of full-thickness rectal prolapse was noted among the refugee children in the south-west of the country. The prolapses arose as a result of acute diarrhoeal illness superimposed on malnutrition and worm infestation. We used a modification of the Thiersch wire technique in 40 of these cases during two months working in a refugee camp. A catgut pursestring was tied around the anal margin under local, regional or general anaesthesia. This was effective in achieving short-term control of full-thickness prolapse until the underlying illness was corrected. Under the circumstances, no formal follow-up could be arranged; however, no complications were reported and only one patient presented with recurrence.
Brief Communication: Inhibition of Tumor Promotion by a Neutral Fraction of Cigarette Smoke Condensate2
Authors: Frank J. Akin, William J. Chamberlain
Journal: JNCI Journal of the National Cancer Institute (1974)

Cigarette smoke condensate (CSC) and 2 neutral subfractions were applied to mouse skin concurrently with the tumor promoter 12-O-tetradecanoyl phorbol13- acetate (TPA) after initiation with 7,12-dimethylbenz[a] anthracene. The ether-soluble neutral fraction, which has marginal tumor-promoting activity, inhibited the promoting effect of TPA, as measured by a delayed tumor appearance and a reduction in the number of tumor-bearing mice. Neither the benzo[a]pyrene-containing fraction nor crude CSC altered the promoting activity of TPA
Loss of endothelial programmed cell death 10 activates glioblastoma cells and promotes tumor growth
Authors: Yuan Zhu, Kai Zhao, Anja Prinz, Kathy Keyvani, Nicole Lambertz, Ilonka Kreitschmann-Andermahr, Ting Lei, Ulrich Sure
Journal: Neuro-Oncology (2015)

Neo-angiogenesis is a hallmark of glioblastoma (GBM) and is sustained by autocrine and paracrine interactions between neoplastic and nonneoplastic cells. Programmed cell death 10 (PDCD10) is ubiquitously expressed in nearly all tissues and plays crucial roles in regulating angiogenesis and apoptosis. We recently discovered the absence of PDCD10 expression in the tumor vessels of GBM patients. This raised the hypothesis that loss of endothelial PDCD10 affected GBM cell phenotyping and tumor progression. Endothelial PDCD10 was silenced by siRNA and lentiviral shRNA. The tumor cell phenotype was studied in direct and indirect co-culture of endothelial cells (ECs) with U87 or LN229. Angiogenic protein array was performed in the media of PDCD10-silenced ECs. Tumor angiogenesis and tumor growth were investigated in a human GBM xenograft mouse model. Endothelial silence of PDCD10 significantly stimulated tumor cell proliferation, migration, adhesion, and invasion and inhibited apoptosis in co-cultures. Stable knockdown of endothelial PDCD10 increased microvessel density and the formation of a functional vascular network, leading to a 4-fold larger tumor mass in mice. Intriguingly, endothelial deletion of PDCD10 increased (≥2-fold) the release of 20 of 55 tested proangiogenic factors including VEGF, which in turn activated Erk1/2 and Akt in GBM cells. For the first time, we provide evidence that loss of endothelial PDCD10 activates GBM cells and promotes tumor growth, most likely via a paracrine mechanism. PDCD10 shows a tumor-suppressor-like function in the cross talk between ECs and tumor cells and is potentially implicated in GBM progression.
Management of the unstable shoulder
Authors: Tanujan Thangarajah, Simon Lambert
Journal: British Journal of Sports Medicine (2016)

The case is reported of a patient with progressive proximal and distal weakness, dysphagia, respiratory weakness, calcifications, ptosis and ophthalmoparesis with inflammation, rimmed vacuoles and positive amyloid and ubiquitin on muscle biopsy. The histopathological features fit best with inclusion body myositis, but ophthalmoparesis and ptosis have not previously been described. The clinical phenotype fits best with hereditary inclusion body myopathy or distal-oculopharyngeal muscular dystrophy, but the degree of inflammation seen is unusual. None of these are associated with calcinosis.
The antiproteinuric action of angiotensin-converting enzyme is dependent on kinin.
Authors: F N Hutchison, X Cui, S K Webster
Journal: Journal of the American Society of Nephrology (1995)

Converting enzyme inhibitors (CEI) reduce proteinuria in nephrotic humans and animals, but the mediator(s) of this effect has not been identified definitively. To determine whether enhanced kinin activity contributes to the antiproteinuric action of CEI, rats with passive Heymann nephritis were treated with the B2 kinin receptor antagonist HOE 140, 300 micrograms/kg per day, for 3 days and then the CEI enalapril (ENAL), 35 mg/kg per day, was given for another 4 days while HOE 140 was continued (HOE/ENAL). Additional groups of nephrotic rats were untreated (CON), received HOE 140 only (HOE), or received ENAL only. ENAL alone produced a > 60% decrease in albuminuria after 4 days, whereas HOE 140 alone had no effect on albuminuria. In HOE/ENAL, pretreatment with HOE 140 prevented the decrease in albuminuria observed in ENAL. GFR increased significantly over time in all groups but was not different among the groups on any day. The clearance of albumin decreased significantly in ENAL (P < 0.001) and was significantly lower than in CON, HOE, or HOE/ENAL on Day 10. The fractional clearance of albumin decreased in all groups as a result of the increase in GFR but was significantly lower in ENAL compared with the other three groups at Day 10 and was not different between CON, HOE, and HOE/ENAL. Plasma renin activity and concentration were increased significantly in both ENAL and HOE/ENAL, indicating that converting enzyme was effectively inhibited in both groups. It was concluded that enhanced kinin activity contributes to the antiproteinuric action of CEI in this model of nephrotic syndrome.
Primary analysis of the prospective, randomized, phase II trial of GP2+GM-CSF vaccine versus GM-CSF alone administered in the adjuvant setting to high-risk breast cancer patients.
Authors: Erika J Schneble, Sonia A. Perez, James L. Murray, John S. Berry, Alfred F. Trappey, Timothy J. Vreeland, Diane F. Hale, Julia M. Greene, Guy T. Clifton, Alexandros Ardavanis, Jennifer Keating Litton, Sathibalan Ponniah, Nathan M. Shumway, Michael Papamichail, George Earl Peoples, Elizabeth Ann Mittendorf
Journal: Journal of Clinical Oncology (2014)

134 Background: GP2 is a HER2 derived, HLA-A2 + -restricted immunogenic peptide designed to stimulate CD8 + T cells to recognize tumor cells with any level of HER2 expression (IHC 1-3+). Accrual to a prospective, randomized, multi-center, phase II trial of the GP2 vaccine for prevention of breast cancer recurrence has completed. Here, the planned primary analysis of disease-free survival (DFS) is presented. Methods: HLA-A2 + node positive or high-risk node negative breast cancer patients (pts) with any level of HER2 expression rendered disease-free by standard of care therapy (to include trastuzumab where appropriate) were randomized to receive GP2+GM-CSF (VG) or GM-CSF (CG) alone. Pts received 6 monthly inoculations (primary vaccine series = PVS) followed by 4 boosters administered every 6 months. The Kaplan Meier method was used for statistical analysis. The intention-to-treat (ITT) population is defined as the entire randomly assigned population. The per-treatment (PT) group excluded pts who recurred during the PVS or developed a second malignancy. A pre-specified subgroup analysis was performed based on HER2 expression level. HER2 overexpression (OE) is defined as IHC 3 + or FISH &gt;2.2. Results: With 89 VG and 91 CG pts enrolled and vaccinated, there are no differences between groups with respect to age, node positivity, tumor size, grade, ER/PR status, and HER2 expression (p&gt;0.05). The vaccine has been well tolerated with toxicities comparable between the VG and CG. Only one grade 3 local and systemic toxicity reaction has been reported in the VG. At 34 (1-60) month median follow-up, DFS was compared in the ITT (85% VG v 81% CG, p = 0.57) and PT (94% VG v 85% CG, p = 0.17) populations. In OE patients (51 VG and 50 CG) DFS was 94% VG v 89% CG, p = 0.86 (ITT) and 100% VG v 89% CG, p = 0.08 (PT). Conclusions: GP2+GM-CSF is a novel vaccine that is safe and well tolerated. This phase II trial demonstrates potentially greater benefit in pts with HER2 OE tumors, in whom there have been no recurrences in the PT group. This may be due to synergism with trastuzumab therapy, thus justifying a phase III trial evaluating GP2 administered in the adjuvant setting to a HER2 OE population. Clinical trial information: NCT00524277.
Qualitative research can inform clinical practice
Authors: Jenna Panter, Cornelia Guell, David Ogilvie
Journal: BMJ (2016)

We were heartened to read the open letter,1 which echoes our own frustrations, but disappointed by the editors’ response.2

Their suggestion that qualitative research is only pertinent to a specialist audience is incorrect. As outlined in the open letter and corroborated by many responses, we believe that The BMJ …
Abatacept Inhibition of T Cell Priming in Mice by Induction of a Unique Transcriptional Profile That Reduces Their Ability to Activate Antigen‐Presenting Cells
Authors: Agapitos Patakas, Rui‐Ru Ji, William Weir, Sean E. Connolly, Robert A. Benson, Steven G. Nadler, James M. Brewer, Iain B. McInnes, Paul Garside
Journal: Arthritis & Rheumatology (2015)

Objective To determine at the phenotypic, functional, and transcriptional levels whether abatacept, a CTLA‐4Ig molecule that binds with high affinity to CD80/86 on antigen‐presenting cells (APCs) and is used to treat rheumatoid arthritis, induces a state of immunologic tolerance in T cells and dendritic cells in mice. Methods We investigated the capacity of abatacept to regulate the development of antigen‐specific immunologic tolerance in vivo using murine models of priming and tolerance to generate highly purified antigen‐specific T cell populations and CD11c+ APCs. These were combined with detailed immunologic and full genome transcriptional analyses. Results We found that abatacept inhibited T cell activation, but did not render T cells anergic or lead to the generation of Treg cells. However, it induced a sustained inhibition of T cell activation due to the inability of these cells to progress through the cell cycle following T cell receptor stimulation. We also observed that this state was accompanied by an inhibition of dendritic cell activation due to their reduced licensing by T cells. Conclusion This study provides detailed insight into the mode of action of abatacept, demonstrating that its effectiveness is not due to the induction of T cell tolerance, but rather to a sustained inhibition of T cell activation that results in reduced functionality of APCs, with significant implications for its clinical application.