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Warren, David K., Katelin B. Nickel, Anna E. Wallace, Daniel Mines, Victoria J. Fraser e Margaret A. Olsen. "Can Additional Information Be Obtained from Claims Data to Support Surgical Site Infection Diagnosis Codes?" Infection Control & Hospital Epidemiology 35, S3 (outubro de 2014): S124—S132. http://dx.doi.org/10.1086/677830.
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Objective.International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes are increasingly used to identify healthcare-associated infections, often with insufficient evidence demonstrating validity of the codes used. Absent medical record verification, we sought to confirm a claims algorithm to identify surgical site infections (SSIs) by examining the presence of clinically expected SSI treatment.Methods.We performed a retrospective cohort study, using private insurer claims data from persons less than 65 years old with ICD-9-CM procedure or Current Procedure Terminology (CPT-4) codes for anterior cruciate ligament (ACL) reconstruction from January 2004 through December 2010. SSIs occurring within 90 days after ACL reconstruction were identified by ICD-9-CM diagnosis codes. Antibiotic utilization, surgical treatment, and microbiology culture claims within 14 days of SSI codes were used as evidence to support the SSI diagnosis.Results.Of 40,702 procedures, 401 (1.0%) were complicated by SSI, 172 (0.4%) of which were specifically identified as septic arthritis. Most SSIs were associated with an inpatient admission (232/401 [58%]), and/or surgical procedure(s) for treatment (250/401 [62%]). Temporally associated antibiotics, surgical treatment procedures, and cultures were present for 84% (338/401), 61% (246/401), and 59% (238/401), respectively. Only 5.7% (23/401) of procedures coded for SSI after the procedure had no antibiotics, surgical treatments, or cultures within 14 days of the SSI claims.Conclusions.More than 94% of patients identified by our claims algorithm as having an SSI received clinically expected treatment for infection, including antibiotics, surgical treatment, and culture, suggesting that this algorithm has very good positive predictive value. This method may facilitate retrospective SSI surveillance and comparison of SSI rates across facilities and providers.
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Zelenetz, Andrew David, Deepa Jagadeesh, Nishitha M. Reddy, Anastasios Stathis, Huda S. Salman, Adam Steven Asch, Vaishalee Padgaonkar Kenkre et al. "Results of the PI3Kδ inhibitor ME-401 alone or with rituximab in relapsed/refractory (R/R) follicular lymphoma (FL)." Journal of Clinical Oncology 37, n.º 15_suppl (20 de maio de 2019): 7512. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.7512.
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7512 Background: ME-401, a potent and selective oral PI3kδ inhibitor, is being evaluated in a Phase 1b study in patients (pts) with R/R B-cell malignancies (NCT02914938). 70 pts were treated; we report here results in FL. Methods: Pts with ECOG ≤2, no prior PI3K therapy and progression of disease (POD) after ≥1 prior therapy were initially enrolled in a dose escalation phase (60-180 mg) then in 60 mg expansion cohorts as monotherapy or in combination with rituximab. ME-401 was given initially on a daily continuous schedule (CS) until POD or unacceptable toxicity. An intermittent schedule (IS) on days 1-7 of a 28-day cycle was then evaluated after 2 cycles (n = 18) or ≥3 cycles (n = 9) of CS. Toxicity on CS managed by switch to IS. POD on IS managed by switch to CS. Results: 48 FL pts received ME-401 alone (n = 39) or with rituximab (n = 9). Median age 64.5 yrs. (range 38-81), median prior therapies 2 (range 1-10), 30 had ≥3 prior therapies and 25 were POD24. 28 pts remain on therapy with median follow-up of 9.3 months (range 0.5-22.5) and 20 discontinued: 9 POD, 4 adverse events (AEs), 4 withdrew consent, and 3 for stem cell transplant. Delayed (> Cycle 2) grade 3 immune related AEs (irAEs), primarily diarrhea/colitis and rash, reported in 9/30 (30%) on CS and 2/18 (11%) switched to IS after 2 cycles, with irAEs noted 15 and 18 days after switch. 4 pts with grade 3 irAEs had a drug holiday and corticosteroids then resumed ME-401 on IS without AE recurrence. Objective responses in 34/43 pts (79%) with follow-up disease assessment: 79% with ME-401 alone (including 26% morphologic/metabolic CR), 78% with ME-401 plus rituximab, 91% in POD24, and 75% in ≥3rd line therapy. 24/27 (89%) IS pts continue therapy, 20 on IS and 4 who switched to CS due to POD on IS, and 3 pts discontinued due to persistent POD after switch to CS. Conclusions: ME-401 achieves a high rate of durable responses in R/R FL. IS appears to reduce the incidence of irAEs and maintains responses. POD on IS can be salvaged by reverting to CS. A randomized study to evaluate ME-401 given by IS or CS is enrolling pts with R/R FL, with switch to IS for irAEs and switch to CS if POD on IS. Clinical trial information: NCT02914938. [Table: see text]
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Rajagopalan, Prasanna, e Harish C. Chandramoorthy. "(2E)-2-Benzylidene-4,7-dimethyl-2,3-dihydro-1H-inden-1-one (MLT-401), a novel arylidene indanone derivative, scavenges free radicals and exhibits antiproliferative activity of Jurkat cells". Asian Biomedicine 13, n.º 4 (31 de março de 2020): 131–39. http://dx.doi.org/10.1515/abm-2019-0052.
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AbstractBackgroundThe arylidene indanone scaffold has contributed many lead molecules in chemotherapeutic anticancer agent research.ObjectivesTo determine the oxidant-scavenging activities and antiproliferative activity of (2E)-2-benzylidene-4,7-dimethyl-2,3-dihydro-1H-inden-1-one (MLT-401), an arylidene indanone derivative.MethodsJurkat cells, primary lymphocytes, and Vero cells were treated with MLT-401. Antioxidant properties of MLT-401 were determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH)-based, 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS)-based, and ferric-reducing antioxidant potential (FRAP) assays. Inhibition of cell proliferation was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide-based assay. Nuclear status was determined using a DNA fragmentation assay, and cell cycle stage was analyzed by flow cytometry. Mitochondrial membrane enzyme activities were measured using colorimetric methods.ResultsThe antioxidant assays gave MLT-401 half maximal inhibitory concentration (IC50) values of 1611 nM (DPPH-based assay), 2115 nM (ABTS-based assay), and 1586 nM (FRAP assay). MLT-401 inhibited proliferation of Jurkat cells with a concentration for 50% of maximal inhibition of cell proliferation (GI50) of 341.5 nM, being 12- and 9-fold less than GI50 concentrations for normal lymphocytes and Vero cells, respectively. MLT-401 caused nuclear fragmentation and DNA laddering as seen by electrophoresis. Jurkat cells showed a time-dependent accumulation of sub G0/G1 cells after MLT-401 treatment. Mitochondrial membrane-bound Na+/K+ ATPase, Ca2+ ATPase, and Mg2+ ATPase activities were inhibited by MLT-401 in a dose-dependent manner.ConclusionMLT-401 possesses significant antiproliferative activity and scavenges free radicals released through mitochondrial membrane damage in a Jurkat cell line model of cancer cells. Further investigation of MLT-401 as a chemotherapeutic anticancer agent and development of other arylidene indanone analogues are warranted. A detailed elucidation of mechanistic pathways is required for further development.
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Forlini, Francesca. "Adaptation in the Age of Media Convergence, Johannes Fehrle and Werner Schäfke-Zell (eds) (2019)". Journal of Adaptation in Film & Performance 14, n.º 1 (1 de março de 2021): 125–28. http://dx.doi.org/10.1386/jafp_00046_5.
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Review of: Adaptation in the Age of Media Convergence, Johannes Fehrle and Werner Schäfke-Zell (eds) (2019)Amsterdam: Amsterdam University Press, 232 pp.,ISBN 978-9-46298-366-3, h/bk, €99.00ISBN 978-9-04853-401-2, e/bk, €98.99
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Lawlor, Hannie. "Following Franco: Spanish Culture and Politics in Transition, Duncan Wheeler (2020)". International Journal of Iberian Studies 35, n.º 2 (1 de junho de 2022): 210–12. http://dx.doi.org/10.1386/ijis_00075_5.
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Coll-Vinent, Sílvia. "Fólica, Laura; Roig-Sanz, Diana; Caristia, Stefania (eds.). Literary Translation in Periodicals: Methodological challenges for a transnational approach". Quaderns. Revista de traducció 29 (12 de maio de 2022): 212–15. http://dx.doi.org/10.5565/rev/quaderns.75.
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Fólica, Laura; Roig-Sanz, Diana; Caristia, Stefania (eds.)Literary Translation in Periodicals: Methodological challenges for a transnational approachAmsterdam; Filadèlfia: John Benjamins, 2020, 401 p.ISBN 978-90-272-0773-9
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Kachinsky, A. M., J. A. Dominov e J. B. Miller. "Intermediate filaments in cardiac myogenesis: nestin in the developing mouse heart." Journal of Histochemistry & Cytochemistry 43, n.º 8 (agosto de 1995): 843–47. http://dx.doi.org/10.1177/43.8.7542682.
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By using immunohistology combined with immunoblotting, cell culture, and RT-PCR, we show that the intermediate filament protein nestin is transiently expressed in the midembryonic mouse heart. Monoclonal antibody (MAb) Rat-401, known to react with nestin in neural and skeletal muscle cells, was also found to react with ventricular and atrial cells throughout the mouse heart from embryonic day 9 (E9) through E10.5. Both before (E8.5) and after (E11-adult) this brief period, staining with Rat-401 was absent from atrial and ventricular myocytes. To evaluate the specificity of staining with MAb Rat-401 in the heart, we used immunoblotting, cell culture, and RT-PCR to verify that the authentic nestin protein and mRNA were expressed in cardiomyocytes of the E10 mouse. Nestin expression is the first molecular marker for this distinct midembryonic period of heart development.
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Angelot-Delettre, Fanny, Arthur E. Frankel, Jen Sing Liu, Estelle Seilles, Sabeha Biichle, Bernard Drenou, Mark L. Jacobson et al. "The IL-3Rα-Targeted Drug SL-401 Selectively Kills Blastic Plasmacytoid Dendritic Cell Neoplasm Cells". Blood 118, n.º 21 (18 de novembro de 2011): 2588. http://dx.doi.org/10.1182/blood.v118.21.2588.2588.
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Abstract Abstract 2588 Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive neoplasm derived from plasmacytoid dendritic cell precursors that involves the skin and invariably leads to aggressive leukemic dissemination (Garnache Ottou et al., 2007). The incidence is more frequent in men and elderly subjects, but BPDCN may occur in young adults and even in children. Current treatment options are not codified, and although conventional chemotherapy often induces an initial response, relapse is frequent and rapid. The prognosis is poor, with a median overall survival of 9–13 months whatever the initial presentation was. Allogeneic hematopoietic transplantation is currently the only potentially curative treatment, but this is not an option for most elderly patients. Therefore, there is an urgent need to develop novel therapies that can specifically target this tumor type. Since BPDCN cells express high levels of the interleukin-3 receptor (IL-3R) α-chain (CD123), we tested SL-401, a novel biologic conjugate that targets IL-3Rα (Konopleva et al. 2010 and Frolova et al. 2010), against 2 BPDCN cell lines (GEN2.2 and CAL-1) and 6 primary BPDCN cells isolated from 5 patients (P#1-5). Cells from P#2 were tested at diagnosis (#2d) and at relapse (#2r). A CD123+ cell line (TF-1/H-ras) sensitive to SL-401 and a CD123− cell line (Daudi) were used as controls. Cytotoxicity was assessed by MTT assay as well as flow cytometry (FC) after Annexin-V (AV) and 7-AAD staining. Primary BPDCN cells were cultured with IL-3 alone (to maintain survival) or IL-3 in combination with SL-401 for 24 h (FC) or 48 h (MTT) (Figure 1). All BPDCN cell lines and primary cells were found to be sensitive to SL-401 by MTT assay (Figure 1A). These results were confirmed by FC with a dose-dependent decrease in cell viability observed for the GEN2.2 and CAL-1 lines, (47 ± 10 to 2 ± 2%, n = 4, and 90 ± 7 to 11 ± 5%, n = 4, respectively) when treated with SL-401 compared to untreated cells (48 ± 9% and 88 ± 5%, for GEN2.2 and CAL-1 respectively). Cell viability decreased for all the 6 primary cells tested by FC (Figure 1B). The Daudi negative control cell line was resistant to SL-401 (Figure 1A), which confirmed SL-401 specificity.Figure 1.In vitro sensitivity of BPDCN cell lines (CAL-1 and GEN2.2) and primary cells from 5 BPDCN patients to SL-401 assessed by FC and MTT assays.Figure 1. In vitro sensitivity of BPDCN cell lines (CAL-1 and GEN2.2) and primary cells from 5 BPDCN patients to SL-401 assessed by FC and MTT assays. This is the first study evaluating the in vitro sensitivity of BPDCN using the IL-3R targeted drug candidate, SL-401, which is currently being evaluated in clinical trials of patients with acute myeloid leukemia (AML), myelodysplastic syndrome, and chronic myeloid leukemia. Importantly, the highest concentration of SL-401 evaluated in these in vitro studies was ten times lower than the peak plasma concentration achieved in AML patients (Frankel et al, 2008). Since all BPDCN patients evaluated to date express high levels of CD123 (Garnache Ottou et al, 2009), these results suggest that BPDCN patients may clinically benefit from SL-401 therapy. This new strategy should be evaluated in a clinical trial. A. Percentage of viable cells from BPDCN patients (#1, #4, and #5, n = 1) or of viable CAL-1 and GEN 2.2 cells (n = 3) assessed by MTT assay after incubation with different concentrations of SL-401 or without drug (cells only). Untreated cells were considered as 100% viable cells. The Daudi cell line (CD123−) was used as a negative control (n = 3). B. Percentage of viable cells (AV and 7-AAD negative, as measured by FC) after incubation with different concentrations of SL-401 or without drug (cells only) for 24 h. The histogram represents a mean of 3 (P#1), 4 (P#2d), and 6 (P#2r) independent experiments. Samples (P#3- 4, and- 5) were each tested once. Disclosures: Frankel: Stemline Therapeutics: Patents & Royalties, Research Funding. Jacobson:Stemline Therapeutics, Inc: Employment, stock Options. Cirrito:Stemline Therapeutics, Inc: Employment, Equity Ownership, Patents & Royalties. Brooks:Stemline Therapeutics, Inc: Employment, equity options.
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Miegel, Annekathrin, e Pius Engelbert. "Rezension von: Engelbert, Pius (Hrsg.), Willehelmi abbatis Constitutiones Hirsaugienses". Zeitschrift für Württembergische Landesgeschichte 72 (11 de abril de 2022): 665–66. http://dx.doi.org/10.53458/zwlg.v72i.2484.
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Willehelmi abbatis Constitutiones Hirsaugienses. Hg. von Pius Engelbert unter Mitwirkung von Candida Elvert (Corpus consuetudinum monasticarum 15,1–2). Siegburg: Schmitt 2010. CLIII u. 1020 S. ISBN 978-3-87710-401-9. Geb. mit Umschlag. € 284,–
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Lane, Andrew A., Kendra L. Sweet, Eunice S. Wang, William B. Donnellan, Roland B. Walter, Anthony S. Stein, David A. Rizzieri et al. "Results from Ongoing Phase 2 Trial of SL-401 As Consolidation Therapy in Patients with Acute Myeloid Leukemia (AML) in Remission with High Relapse Risk Including Minimal Residual Disease (MRD)". Blood 128, n.º 22 (2 de dezembro de 2016): 215. http://dx.doi.org/10.1182/blood.v128.22.215.215.
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Abstract Background: SL-401 is a novel targeted therapy directed to the interleukin-3 receptor (CD123), a target overexpressed on acute myeloid leukemia (AML) blasts and AML cancer stem cells (CSCs), and a variety of additional hematologic malignancies. While conventional chemotherapy can induce remission in a majority of treatment-naive AML patients, relapse rates remain high. Outcomes are particularly poor when minimal residual disease (MRD), as determined by genetic and/or flow cytometric analyses, remains after therapy, with high rates of relapse and short disease-free survival. Conceivably, a therapy directed at lowering MRD burden may improve long-term outcomes. Given the association of MRD with CD123+ AML CSCs, SL-401 is being evaluated in patients with AML in first or second complete remission (CR1 or CR2, respectively) with high risk of relapse including persistent MRD. Preliminary results are reported here. Methods & Results: This multicenter, single-arm Phase 2 trial of AML patients in CR1 or CR2 with high risk of relapse includes a lead-in (stage 1) and expansion (stage 2). In stage 1, patients (MRD+ or MRD-) receive SL-401 as a daily IV infusion at 7, 9, or 12 ug/kg/day for days 1- 5 of a 28 day cycle in a 3x3 design. In stage 2, patients (MRD+ only) receive SL-401 at the dose determined in stage 1. Presence of MRD for eligibility requires either molecular (by cytogenetics, FISH, PCR, or next-generation sequencing of AML-associated mutations) or multiparameter flow cytometry (MFC) evidence of persistent abnormalities in the setting of morphologic CR. In stage 2, MRD assessment will include MFC of bone marrow aspirates conducted at a central laboratory for uniformity. Objectives include characterization of SL-401 safety with determination of the maximum tolerated or tested dose, and preliminary assessment of efficacy including changes in MRD burden and response duration. As of 7/27/16, stage 1 has been completed and stage 2 is open for enrollment. Nine patients (stage 1) received SL-401 (7 ug/kg, n=3; 9 ug/kg, n=3; 12ug/kg, n=3). The median age was 63 years (range: 51-78 years); 6 males and 3 females were treated; 8 patients were in CR1 and 1 patient was in CR2 at enrollment. The 12 ug/kg dose level was the highest tested dose with no DLTs; MTD was not reached. The most common treatment-related AEs, all grades, were thrombocytopenia (3/9; 33%) and hypoalbuminemia (3/9; 33%); the most common ≥ grade 3 treatment-related AE was thrombocytopenia (1/9; 11%); there was no DLT. Patients treated at all doses received 1+ to 5+ cycles (ongoing) of SL-401, including 3 MRD+ patients treated at 7 ug/kg (n=1) or 9 ug/kg (n=2) who received 1-5 cycles, and 1 MRD+ patient treated at 12 ug/kg who is receiving ongoing SL-401 for 4+ cycles. For all 3 patients treated at 12 ug/kg (MRD+, n=1; MRD-, n=2), 2 patients remain on SL-401 and have received 1+ and 4+ cycles (both ongoing); one other patient treated at 12 ug/kg discontinued the study because of infection unrelated to study drug. Notably, the one MRD+ patient treated at 12 ug/kg (ongoing at 4+ cycles) had marked MRD reduction as determined by MFC at the local institution; this patient is being considered for stem cell transplant (SCT). Conclusions: Stage 1 is complete without DLT or MTD, and stage 2 (expansion) is open to enroll AML patients in CR1 or CR2 who are MRD+ at the highest tested dose of 12 ug/kg. The safety profile has been similar to that observed in other SL-401 clinical studies, with no unexpected AEs. Targeting MRD with SL-401 has the potential to reduce this chemo-resistant cell population and offer improved long-term outcomes for AML patients in remission with high risk of relapse. Updated data will be presented. Clinical trial information: NCT02270463. Disclosures Lane: N-of-1: Consultancy; Stemline Therapeutics: Research Funding. Sweet:Pfizer: Speakers Bureau; Karyopharm: Honoraria, Research Funding; Incyte Corporation: Research Funding; Novartis: Consultancy, Speakers Bureau; Ariad: Consultancy, Speakers Bureau. Wang:Immunogen: Research Funding; Incyte: Speakers Bureau. Stein:Seattle Genetics: Research Funding; Amgen: Consultancy, Research Funding, Speakers Bureau; Stemline Therapeutics: Consultancy, Research Funding; Argios: Research Funding; Celgene: Research Funding. Carraway:Incyte: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding, Speakers Bureau; Baxalta: Speakers Bureau. Prebet:celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Chen:Stemline Therapeutics, Inc.: Employment, Equity Ownership. Lindsay:Stemline Therapeutics, Inc.: Employment, Equity Ownership. Shemesh:Stemline Therapeutics: Employment, Equity Ownership. Brooks:Stemline Therapeutics, Inc.: Employment, Equity Ownership, Patents & Royalties. Stone:Novartis: Consultancy; Juno Therapeutics: Consultancy; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy; Amgen: Consultancy; Celator: Consultancy; Karyopharm: Consultancy; Jansen: Consultancy; Pfizer: Consultancy; ONO: Consultancy; Merck: Consultancy; Roche: Consultancy; Seattle Genetics: Consultancy; Sunesis Pharmaceuticals: Consultancy; Xenetic Biosciences: Consultancy. Jabbour:ARIAD: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Research Funding; BMS: Consultancy. Konopleva:Cellectis: Research Funding; Calithera: Research Funding.
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Htut, Myo, Cristina Gasparetto, Jeffrey Zonder, Thomas G. Martin, Emma C. Scott, Janice Chen, Shay Shemesh et al. "Results from Ongoing Phase 1/2 Trial of SL-401 in Combination with Pomalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma". Blood 128, n.º 22 (2 de dezembro de 2016): 5696. http://dx.doi.org/10.1182/blood.v128.22.5696.5696.
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Abstract Background: The bone marrow microenvironment of many multiple myeloma (MM) patients harbors high quantities of plasmacytoid dendritic cells (pDCs), which are specialized immune cells that express the interleukin-3 receptor (CD123). These pDCs have been shown to augment MM growth and contribute to drug resistance, suggesting that targeting pDCs may offer clinical benefit for MM patients. SL-401, a novel targeted therapy directed to CD123, has previously demonstrated potent preclinical in vitro and in vivo activity against MM cell lines and primary tumor samples via both a direct anti-MM effect and an indirect effect by targeting neighboring pDCs. SL-401 has also demonstrated synergy in these systems when used in combination with traditional MM therapies including pomalidomide (POM). Clinically, SL-401 has demonstrated high levels of anti-tumor activity in patients with an aggressive CD123+ malignancy of pDC origin, namely blastic plasmacytoid dendritic cell neoplasm (BPDCN). SL-401 is currently being evaluated in combination with POM and dexamethasone (DEX) in relapsed or refractory (r/r) MM patients. Preliminary results are reported here. Methods and Results: This multicenter, single arm Phase 1/2 trial of patients with r/r MM includes a lead-in (stage 1) and expansion (stage 2). In stage 1, patients receive SL-401 as a daily IV infusion at 7, 9, or 12 ug/kg/day for days 1-5 of a 28 day cycle as a single agent for the initial run-in cycle (cycle 0) and in combination with standard doses/administration of POM+DEX in cycles 1 and beyond, in a 3x3 design. In stage 2, patients receive SL-401 in combination with POM+DEX at the dose and regimen determined in stage 1. Objectives include characterization of the safety profile of SL-401 in combination with POM+DEX, including determination of the maximum tolerated or tested dose, and detection of efficacy signals including evaluation of tumor response based on International Myeloma Working Group criteria, duration of response, progression-free survival, and translational evaluation of changes in BM microenvironmental pDCs. As of 7-25-16, 2 patients with r/r MM received SL-401 at 7 ug/kg in combination with POM+DEX. The median age was 65 years (range: 63-67 years). The most common treatment-related AEs, all grades, were thrombocytopenia (2/2, both grade 1) and hypoalbuminemia (2/2, both grade 2); there has been no DLT. Rapid onset decrease in a set of myeloma-related laboratory values from pre-SL-401 treatment was observed in both patients after the first combination cycle of SL-401 and POM+DEX. In one patient, serum M-protein decreased from 2.34 to 1.19 g/dL (cycle 1), free light chain kappa decreased from 40.1 to 8.27 mg/dL (cycle 1), and free light chain kappa/lambda ratio decreased from 58.12 to 41.35 (cycle 1). In the other patient, serum M-protein decreased from 1.88 to 0.87 (cycle 1) and then was 0.96 (cycle 3) g/dL, free light chain kappa decreased from 134 to 49.4 (cycle 1) and then was 92.5 (cycle 3) mg/dL, and free light chain kappa/lambda ratio decreased from 638.1 to 76 (cycle 1) and then was 111.45 (cycle 3). Both patients remain on study receiving ongoing SL-401 at 2+ and 4+ months. Dose escalation to 9 ug/kg is planned if a third patient clears the 7 ug/kg cohort. Conclusions:This is the first clinical study to evaluate SL-401 in combination with other agents. SL-401 thus far has been well-tolerated in combination with POM+DEX in r/r MM patients, with no unexpected AEs observed. After the first cycle of SL-401 and POM+DEX combination therapy, 2 of 2 patients experienced a rapid decrease in serum M-protein and remain on SL-401 therapy. Given CD123 expression on microenvironmental immune pDCs and the potential synergy of SL-401 with certain current MM agents including POM, SL-401 may offer a novel therapeutic approach in MM. This Phase 1/2 trial continues to enroll and updated data will be presented. Clinical trial information: NCT02661022. Disclosures Zonder: Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria; Prothena: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Pharmacyclics: Other: DSMC membership. Martin:Sanofi: Research Funding; Amgen: Research Funding. Chen:Stemline Therapeutics, Inc.: Employment, Equity Ownership. Shemesh:Stemline Therapeutics: Employment, Equity Ownership. Brooks:Stemline Therapeutics, Inc.: Employment, Equity Ownership, Patents & Royalties. Chauhan:Stemline Therapeutics: Consultancy. Anderson:Oncopep: Other: Scientific Founder; Acetylon: Other: Scientific Founder; Gilead: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Sonofi Aventis: Membership on an entity's Board of Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory committees. Richardson:Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees.
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Ruth Acham, Winfred, Aisha Nalugya, Ricky Nyatia e Nelson Bunani. "Virologic re-suppression and the associated factors among children aged 1-9 years on Antiretroviral Therapy in The Aids Support Organization Soroti Region, Uganda: a retrospective cohort analysis". African Health Sciences 24, n.º 2 (11 de julho de 2024): 1–9. http://dx.doi.org/10.4314/ahs.v24i2.2.
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Background: Children living with HIV experience low viral load re-suppression after a high viral load compared to the rest of the population. We determined the proportion with re-suppressed viral load and associated factors among children 1-9 years on Antiretroviral Therapy (ART) in The Aids Support Organization (TASO) Soroti Region. Methods: We conducted a retrospective cohort analysis of 401 records of children that initially had high viral load > 1000copies/ml for the period January 2016 to December 2018. Modified Poisson regression was performed to determine factors associated with virologic re-suppression. Results: The prevalence of virologic re-suppression was 97/401 (24.2%). More than half, 213 (53.1%) of the children were females and 197/401 (49%) were aged between 8 and 9 years. Factors associated with virologic re-suppression were; being on protease inhibitor (PI) based regimen [APR 2.87, 95% CI 1.76-4.79], good adherence [APR1.71, 95% CI 1.22-2.51] and caregiver HIV seropositive status [APR 2.56, 95% CI 1.69-3.91]. Conclusion: Virologic re-suppression was low compared to the UNAIDS target. Taking PI-based regimen, good adherence and HIV seropositive status of the caregiver were predictors of virologic re-suppression. Close viral load monitoring of children on ART and intensified targeted adherence support to caregivers is vital to improving virologic re-suppression. Keywords: Virologic re-suppression; Human Immunodeficiency Virus; children.
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Pemmaraju, Naveen, Andrew A. Lane, Kendra L. Sweet, Anthony S. Stein, Sumithira Vasu, William Blum, David A. Rizzieri et al. "Results from Phase 2 Trial Ongoing Expansion Stage of SL-401 in Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)". Blood 128, n.º 22 (2 de dezembro de 2016): 342. http://dx.doi.org/10.1182/blood.v128.22.342.342.
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Abstract Background: SL-401 is a targeted therapy directed to the interleukin-3 receptor (CD123), a target overexpressed on blastic plasmacytoid dendritic cell neoplasm (BPDCN) and other hematologic malignancies. BPDCN is an aggressive hematologic malignancy of unmet medical need that often presents in bone marrow and skin, and may also involve lymph nodes and viscera. Long-term outcomes after treatment with chemotherapy have been very poor, with median overall survival from diagnosis of ~12 months, highlighting the need for novel therapies. Results from the Phase 2 trial of SL-401 in patients with BPDCN are reported here. Methods:This multicenter, single-arm Phase 2 trial of patients with BPDCN includes a lead-in (stage 1) and expansion (stage 2). In stage 1, patients with BPDCN or relapsed or refractory (r/r) AML received SL-401 as a daily IV infusion at 7, 9, 12, or 16 ug/kg/day for days 1-5 of a 21 day cycle. In stage 2, patients with BPDCN receive SL-401 at the dose determined in stage 1. Results: As of 7/25/16, 29 patients with BPDCN have received SL-401, including 16 first-line and 10 relapsed/refractory (r/r) adults and 3 pediatric patients (under compassionate use). The 26 adult patients (9+17 in stages 1&2) received SL-401 at 7 ug/kg (n=3 [stage 1]) or 12 ug/kg (n=23 [6+17 in stages 1&2]). The median adult age was 69 years (range: 29-82 years). In stage 1, 12 ug/kg was the highest tested dose for BPDCN; MTD was not reached in BPDCN. Results in AML (r/r) patients will be reported separately. The most common treatment-related AEs, all grades, were transient transaminase elevation (54%) and hypoalbuminemia (38%). Transient thrombocytopenia was also noted (19%). The most common ≥ Grade 3 treatment-related AEs were transient transaminase elevation (42%) and thrombocytopenia (19%). Two stage 1 patients developed capillary leak syndrome (CLS): gr 5 (7 ug/kg) and gr 4 (12 ug/kg). Safety precautions, including monitoring of albumin levels and body weight, were successfully implemented to minimize risk of severe CLS, which has not occurred in patients with BPDCN since adoption. Twenty-one of 26 adult patients were evaluable for response (response assessment from 3 recently treated patients are pending; 1 patient was discontinued for as yet unspecified reasons; and 1 patient treated at 7 ug/kg was not evaluable for response due to AE); median follow-up for evaluable patients was 6.9 months (range: 0.6-17.6 months). An 86% (18/21) ORR was observed in evaluable adult BPDCN patients. ORR in evaluable patients was 100% (14/14) in first-line and 57% (4/7) in r/r BPDCN. Of these, 92% (11/12) of first-line patients treated at 12 ug/kg had a CR (n=8) or clinical CR (CRc: a CR in non-skin organs with gross reduction in cutaneous lesions and residual microscopic skin disease) (n=3). 75% (9/12) of these patients remain progression free for 3+ to 16+ months (ongoing), including 4 patients who remain on SL-401 in remission (for 3+ to 12+ months [up to 16+ cycles], ongoing) and 5 additional patients who experienced a major response on SL-401 (3 CR, 1 CRc, 1 PR) and were then successfully bridged to stem cell transplant (SCT; 3 auto-SCT and 2 allo-SCT) and all remain progression free for 3+ to 16+months (ongoing) since first SL-401 dose. Notably, a patient with r/r BPDCN was recently bridged to allo-SCT following CRc on SL-401. Conclusions: SL-401 demonstrates robust single agent activity in BPDCN, including 86% ORR in all-lines, with multiple CRs, in evaluable patients. Six patients, including 1 r/r patient, have proceeded to SCT after achieving a major response from SL-401, and an additional 7 patients remain on SL-401 for up to 12+ months, ongoing. The SL-401 side effect profile remains manageable, and no unexpected AEs have emerged with increased treatment duration, drug exposure, and patient enrollment. Response duration, progression-free and overall survival data continue to be encouraging and updated data will be presented. Clinical trial information: NCT02113982. Disclosures Lane: N-of-1: Consultancy; Stemline Therapeutics: Research Funding. Sweet:Ariad: Consultancy, Speakers Bureau; Incyte Corporation: Research Funding; Pfizer: Speakers Bureau; Karyopharm: Honoraria, Research Funding; Novartis: Consultancy, Speakers Bureau. Stein:Seattle Genetics: Research Funding; Amgen: Consultancy, Research Funding, Speakers Bureau; Stemline Therapeutics: Consultancy, Research Funding; Argios: Research Funding; Celgene: Research Funding. Wang:Immunogen: Research Funding; Incyte: Speakers Bureau. Chen:Stemline Therapeutics, Inc.: Employment, Equity Ownership. Shemesh:Stemline Therapeutics: Employment, Equity Ownership. McDonald:Stemline Therapeutics: Employment, Equity Ownership. Brooks:Stemline Therapeutics, Inc.: Employment, Equity Ownership, Patents & Royalties. Lancet:Quantum First: Consultancy; Pfizer: Research Funding; Seattle Genetics: Consultancy; Novartis: Consultancy; Biopath Holdings: Consultancy; ERYtech: Consultancy; Karyopharm: Consultancy; Baxalta: Consultancy; Kalo Bios: Consultancy; Celgene: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy; Boehringer-Ingelheim: Consultancy; Amgen: Consultancy. Kantarjian:Bristol-Myers Squibb: Research Funding; Amgen: Research Funding; ARIAD: Research Funding; Pfizer Inc: Research Funding; Delta-Fly Pharma: Research Funding; Novartis: Research Funding. Konopleva:Reata Pharmaceuticals: Equity Ownership; Abbvie: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Stemline: Consultancy, Research Funding; Eli Lilly: Research Funding; Cellectis: Research Funding; Calithera: Research Funding.
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Ray, Arghya, Deepika Sharma DAS, Yan Song, Vincent Macri, Christopher L. Brooks, Eric K. Rowinsky, Paul G. Richardson, Dharminder Chauhan e Kenneth C. Anderson. "A Novel Agent SL-401 Triggers Anti-Myeloma Activity By Targeting Plasmacytoid Dendritic Cells: Implications for a Novel Immune-Associated Mechanism". Blood 126, n.º 23 (3 de dezembro de 2015): 3000. http://dx.doi.org/10.1182/blood.v126.23.3000.3000.
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Abstract Introduction Multiple myeloma (MM) remains incurable despite novel therapies, highlighting the need for further identification of factors mediating disease progression and resistance. Our studies have identified an integral role of bone marrow (BM) plasmacytoid dendritic cells (pDCs) in MM pathogenesis. The functional significance of increased numbers of pDCs in MM BM is evident from our observations that pDCs: are relatively resistant to novel and conventional therapies; protect tumor cells from therapy-induced cytotoxicity; promote tumor growth and survival; and suppress immune responses (Chauhan et al, Cancer Cell 2009, 16:309-323). Aberrant pDC function is evidenced in their interactions not only with MM cells, but also with other immune effector T cells and NK cells in the MM BM milieu (Ray et al, Leukemia 2015, 29:1441-1444). Directly targeting pDC interactions with MM and immune effector cells in the MM BM milieu will be required to enhance both anti-tumor immunity and cytotoxicity. However, therapies targeting pDCs are lacking. We found that IL-3R is highly expressed on pDCs, and that pDC-MM interactions trigger secretion of IL-3, which in turn, promotes both pDC survival and osteolytic bone disease. Recent efforts have led to the development of a novel therapeutic agent SL-401, which specifically targets IL-3R-expressing pDCs. Here we examined the effect of SL-401 on pDC-induced MM cell growth both in vitro and in vivo, as well as on IL-3R-expressing osteoclasts. Methods Patient MM cells, pDCs, and MNCs were obtained from normal donors or MM patients. Cell growth/viability was analyzed using MTT/WST assays. OCL function and bone resorption were measured using the OsteoAssays and TRAP staining. The RPMI-8226 cell line was used to isolate MM-SPs by flow-cytometry based Hoechst 33342 staining. SL-401 is a recombinant protein expressed in E. coli. The hybrid gene is comprised of human IL-3 fused to truncated diphtheria toxin (DT). The IL-3 domain of SL-401, which replaces the native binding domain of DT, targets SL-401 to cells that overexpress IL-3R. SL-401 was obtained from Stemline Therapeutics, NY; bortezomib, lenalidomide, pomalidomide, and melphalan were purchased from Selleck Chemicals. For animal model studies, SL-401 (16.5 μg/kg) was administered intravenously daily for 2 weeks. Results SL-401 triggered significant apoptosis in pDCs (>95%) at low picomolar concentrations that are well within clinically achievable doses.Higher concentrations of SL-401 trigger a modest apoptosis (30%± 1.3% apoptosis at 83 ng/ml or 1.3 nM) in MM cells due to lower IL-3R expression versus pDCs. Moreover, SL-401 did not significantly induce apoptosis of normal PBMCs (8% ± 0.5% apoptosis at 83 ng/ml), suggesting a favorable therapeutic index for SL-401. SL-401 inhibited pDC-induced growth of MM cell lines and patient MM cells in a dose-dependent manner. Moreover, 6 of 9 MM samples were obtained from patients whose disease was progressing while on bortezomib, dexamethasone, and lenalidomide therapies. Combinations of SL-401 with melphalan, bortezomib, lenalidomide, or pomalidomide induced synergistic anti-MM activity (Combination index < 1). SL-401 blocked monocyte-derived osteoclast formation in a dose-dependent fashion, as well as restored MM patient BM-derived osteoblast formation. Having defined the efficacy of SL-401 in targeting pDCs and pDC-triggered MM cell growth in vitro, we validated these findings in vivo using our murine xenograft model of human MM, under auspices of protocols approved by our institutional animal protection committee. SL-401 inhibited pDC-induced MM cell growth in vivo and prolonged survival in a murine xenograft model of human MM. We also evaluated the efficacy of SL-401 in vivo using our SCID-human (SCID-hu) mouse model, which reflects the human BM milieu with human cytokines and extracellular matrix proteins. SL-401 significantly abrogated pDC-triggered MM cell growth in vivo in SCID-hu model. Conclusions Our data provide the basis for using SL-401 to directly target pDCs and inhibit the pDC-MM interaction as well as target osteolytic bone disease in novel therapeutic strategies in order to enhance MM cytotoxicity, overcome drug resistance, and improve patient outcome. The interactions of immune effector cells in the MM tumor microenvironment also provide a rationale for combining SL-401 with checkpoint inhibitors. Correspondence: Dharminder Chauhan Disclosures Macri: Stemline Therapeutics, Inc., New York, NY USA: Employment. Brooks:Stemline Therapeutics, Inc.: Employment, Equity Ownership, Patents & Royalties. Rowinsky:Stemline Therapeutics: Employment, Equity Ownership. Richardson:Millennium Takeda: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gentium S.p.A.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees. Chauhan:Stemline Therapeutics: Consultancy.
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Sperling, Joy. "Dressed for Freedom: The Fashionable Politics of American Feminism, Einav Rabinovitch-Fox (2021)". Fashion, Style & Popular Culture 9, n.º 3 (1 de julho de 2022): 418–22. http://dx.doi.org/10.1386/fspc_00137_5.
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Review of: Dressed for Freedom: The Fashionable Politics of American Feminism, Einav Rabinovitch-Fox (2021)Urbana, IL, Chicago, IL and Springfield, IL: University of Illinois Press, 248 pp.,ISBN 978-0-25204-401-4, h/bk, $110.00ISBN 978-0-25208-606-9, p/bk, $24.95ISBN 978-0-25205-294-1, e-book, $14.95
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Patnaik, Mrinal M., Vikas Gupta, Jason R. Gotlib, Hetty E. Carraway, Martha Wadleigh, Gary J. Schiller, Moshe Talpaz et al. "Results from Ongoing Phase 2 Trial of SL-401 in Patients with Advanced, High-Risk Myeloproliferative Neoplasms Including Chronic Myelomonocytic Leukemia". Blood 128, n.º 22 (2 de dezembro de 2016): 4245. http://dx.doi.org/10.1182/blood.v128.22.4245.4245.
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Abstract Background: SL-401 is a novel targeted therapy directed to the interleukin-3 receptor (CD123), a target overexpressed by many hematologic malignancies. SL-401 is currently being advanced through clinical trials in patients with a variety of CD123+ malignancies including blastic plasmacytoid dendritic cell neoplasm (BPDCN), acute myeloid leukemia (AML) in remission with high relapse risk, and multiple myeloma. CD123 has been shown to be expressed on myeloproliferative neoplasm (MPN) cells as well as microenvironmental immune cells, namely plasmacytoid dendritic cells (pDCs), in the bone marrows of some patients with MPN including chronic myelomonocytic leukemia (CMML). Microenvironmental pDCs have been implicated in promoting plasma cell disorders and preliminary data suggest that pDCs could play a related role in some myeloid neoplasms. Accordingly, a therapy directed at both CD123-expressing myeloid cells and neighboring CD123-expressing pDCs could provide therapeutic benefit. SL-401 is being evaluated in patients with advanced, high-risk MPN, including systemic mastocytosis (SM), myelofibrosis (MF), primary eosinophilic disorders (PED), and CMML. Preliminary results are reported here. Methods & Results: This multicenter, single-arm Phase 2 trial of patients with advanced, high risk MPN includes a lead-in (stage 1) and expansion (stage 2). In stage 1, patients receive SL-401 as a daily IV infusion at 7, 9, 12 ug/kg/day, or higher for days 1-3 of a 21-28 day cycle in a 3x3 design. In stage 2, patients receive SL-401 at the dose determined in stage 1. Study objectives include characterization of the safety profile, including determination of the maximum tolerated or tested dose, and detection of preliminary efficacy signals including evaluation of tumor response and progression free survival by standard criteria. As of 7/20/16, 6 patients with MPN (MF, n=3; CMML-2, n=2; CMML-1, n=1) received SL-401 (7 ug/kg, n=3; 9 ug/kg, n=3). The median age was 66 years (range: 42-81 years). Patients treated at all doses received 1+ to 2+ cycles (ongoing) of SL-401. The most common treatment-related adverse events (AEs) were thrombocytopenia (2/6; 33%) and fatigue (2/6; 33%); the most common ≥ Grade 3 treatment-related AEs were thrombocytopenia (2/6; 33%) and anemia (1/6; 17%); there has been no DLT. Efficacy assessments are ongoing. Patients are currently enrolling in the 12 ug/kg/day cohort. Conclusions: Initial dosing of SL-401 appears to be well-tolerated in patients with MPN and CMML, with no unexpected AEs observed. Given CD123 expression on myeloid neoplastic cells as well as microenvironmental immune cells (namely, pDCs), SL-401 may offer a novel, targeted therapeutic approach in patients with high-risk MPN and CMML of unmet medical need. Enrollment continues in stage 1 of this ongoing Phase 2 trial and updated safety and efficacy data will be presented. Clinical trial information: NCT02268253. Disclosures Gupta: Novartis: Consultancy, Honoraria, Research Funding; Incyte Corporation: Consultancy, Research Funding. Carraway:Incyte: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Baxalta: Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees. Schiller:Incyte Corporation: Research Funding. Talpaz:Incyte Corporation: Other: Travel expense reimbursement, Research Funding; Ariad: Other: Expense reimbursement, travel accomodation expenses, Research Funding; Novartis: Research Funding; Pfizer: Consultancy, Other: travel accomodation expenses, Research Funding. McCloskey:Novartis: Speakers Bureau; Incyte: Consultancy; Ariad: Consultancy, Speakers Bureau; Amgen: Speakers Bureau. Lee:Alexion Pharmaceuticals: Consultancy; Amgen: Consultancy; Baxalta: Consultancy; Boehringer Ingelheim: Consultancy; Pfizer Inc: Consultancy. Yacoub:Alexion: Honoraria; Seattle Genetics: Consultancy, Honoraria, Speakers Bureau; Incyte: Consultancy, Honoraria, Speakers Bureau. Ali:Incyte Corporation: Research Funding. Chen:Stemline Therapeutics, Inc.: Employment, Equity Ownership. Shemesh:Stemline Therapeutics: Employment, Equity Ownership. Brooks:Stemline Therapeutics, Inc.: Employment, Equity Ownership, Patents & Royalties.
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Sánchez-Gutiérrez, Ricardo A., Alejandro Espinoza-Canales, Alberto Muro-Reyes e Héctor Gutiérrez-Bañuelos. "CRECIMENTO Y PRODUCCIÓN DE FORRAJE DE CANOLA (Brassica napus L.) DE OTOÑO-INVIERNO EN ZACATECAS, MÉXICO". Revista Fitotecnia Mexicana 41, n.º 2 (7 de junho de 2018): 211–16. http://dx.doi.org/10.35196/rfm.2018.2.211-216.
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La canola (Brassica napus L.) puede representar una alternativa como cultivo forrajero para el ciclo otoño-invierno (O-I); sin embargo, se desconoce el momento de cosecha para lograr los máximos rendimientos de materia seca. El objetivo del estudio fue determinar en dos variedades de canola la acumulación de la materia seca y sus componentes morfológicos durante 10 fechas de corte, y así poder identificar el momento óptimo de cosecha para el ciclo O-I en Zacatecas, México. Las variedades Canorte 2010 y Hyola 401 fueron evaluadas en un diseño experimental completamente al azar con tres repeticiones. La cosecha de las plantas se realizó manualmente los días 9, 16, 23, 30, 42, 49, 56, 63, 70 y 77 después de la siembra. Las variables medidas fueron rendimiento de forraje seco, producción de materia seca de hoja verde, tallo, flor/botón, silicua y hoja muerta. La dinámica de crecimiento en la producción de forraje seco en las dos variedades de canola presentó un incremento constante y significativo (P ≤ 0.05) a partir del día 23 hasta el 63, donde Hyola 401 tuvo una mayor producción (P ≤ 0.05). El valor máximo de la tasa de crecimiento se presentó al día 63 después de la siembra, con un promedio de 69.2 y 59.3 kg MS ha-1 d-1, respectivamente, para Hyola 401 y Canorte 2010. Se concluye que la fecha óptima de corte para incrementar el rendimiento de forraje seco es el día 63 después de la siembra, y que la variedad Hyola 401 muestra mayores rendimientos de materia seca.
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Frankel, Arthur E., Jung H. Woo, Jeremy P. Mauldin, Hetty E. Carraway, Olga Frankfurt, Stephen J. Forman, Sumithira Vasu et al. "An Update On The Robust Clinical Activity Of SL-401, a Targeted Therapy Directed To The Interleukin-3 Receptor On Cancer Stem Cells and Tumor Bulk, In Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)". Blood 122, n.º 21 (15 de novembro de 2013): 2682. http://dx.doi.org/10.1182/blood.v122.21.2682.2682.
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Abstract Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) is an aggressive hematologic malignancy derived from plasmacytoid dendritic cells. The clinical presentation of BPDCN typically involves the skin at outset and invariably progresses to a leukemic phase with or without lymph node and splenic involvement. BPDCN blasts have a distinctive phenotypic appearance with ubiquitous overexpression of CD4, CD56, and CD123 (interleukin-3 receptor [IL-3R]). Although rare, BPDCN has been estimated to affect at least two thousand patients in the United States and Europe annually. There is no standard therapy for BPDCN, but treatment usually incorporates intensive combination chemotherapy, occasionally with allogeneic stem cell transplant. Treatment-naïve patients generally respond to these measures, but disease-free survival is brief, and most patients relapse with chemo-resistant disease. Despite aggressive upfront therapies, BPDCN has a dismal prognosis with estimated median survival of 9-14 months. SL-401, a novel biologic targeted therapy directed to IL-3R, is being developed to treat BPDCN, acute myeloid leukemia (AML), and several other IL-3R-expressing hematologic malignancies. SL-401, which is comprised of IL-3 conjugated to a truncated diphtheria toxin, a potent inhibitor of protein synthesis, has demonstrated ultra-high anti-tumor potency against BPDCN cell lines and primary BPDCN tumor cells, with IC50 values in the femtomolar (10-15 M) range and robust activity after treatment of an in vivo model of human primary BPDCN cell engraftment (Angelot-Delettre et al; ASH 2013). This report serves to update the results of SL-401 treatment in BPDCN patients who are participating in a Phase 1/2 study of SL-401 administered as a single cycle (15 minute infusion daily for 5 days). To date, 6 subjects with BPDCN (5 male/1 female; ages 35-72 years) received a single cycle of SL-401. The BPDCN blasts of all 6 patients expressed CD123 (IL-3R) as well as CD4 and CD56. Five patients had failed previous chemotherapy regimens, with 3 of these subjects also having received allogeneic stem cell transplantation, whereas one patient was treatment naïve. There have been no serious adverse events. Two patients had SL-401-related Grade 3 liver function test (LFT) elevations that recovered to Grade ≤2 within 24 hours and one patient had a brief episode of SL-401-related Grade 3 neutropenia and thrombocytopenia; all other SL-401-related adverse events (AEs) were Grade ≤2. One patient was not evaluable for response. To date, 5 (100%) of the 5 evaluable patients have had major responses. All five responding patients were treated with SL-401 at 12.5 µg/kg/day for 5 days, and experienced either a complete response (CR; 4 patients) or a partial response (1 patient). The CRs included disappearance of BPDCN in the skin, bone marrow, peripheral blood, spleen, and lymph nodes. As of August 2013, CR durations following a single cycle of SL-401 treatment are 11+ (ongoing), 5, 3, and 1 months; the PR duration is 1 month. Given these promising clinical responses to this targeted therapy, additional BPDCN patients are being accrued to this study and a pivotal program will begin in 2014. Disclosures: Frankel: Stemline Therapeutics: Research Funding. Woo:Angimmune: Patents & Royalties, Research Funding. Brooks:Stemline Therapeutics: Employment, Equity Ownership. Szarek:Stemline Therapeutics: Employment, Equity Ownership. Bergstein:Stemline Therapeutics: Employment, Equity Ownership, Patents & Royalties. Rowinsky:Stemline Therapeutics: Employment, Equity Ownership, Membership on an entity’s Board of Directors or advisory committees.
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Porter, John, Kris Kowdley, Ali Taher, Jeffrey Vacirca, Zancong Shen, Steve Chen, Lakhmir Chawla e George Tidmarsh. "Effect of Ljpc-401 (synthetic human hepcidin) on Iron Parameters in Healthy Adults". Blood 132, Supplement 1 (29 de novembro de 2018): 2336. http://dx.doi.org/10.1182/blood-2018-99-110885.
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Abstract Background: Iron overload is a significant complication in patients with hereditary hemochromatosis and hereditary hemolytic anemia (esp. sickle cell disease and thalassemia). LJPC-401, a synthetically produced peptide identical to endogenous human hepcidin, is being developed as a therapeutic intervention for iron overload in these conditions. Methods: Phase 1, randomized, double-blind, two-arm, placebo-controlled, single dose escalation, and multiple dose study to assess the safety, tolerability, and pharmacokinetics (PK) /pharmacodynamics (PD) of LJPC-401 in healthy adults. Eligible healthy adults were randomized in a 3:1 ratio to receive either LJPC-401 or placebo as a subcutaneous (SC) injection in single-dose cohorts (Arm A) or a multiple-dose cohort (Arm B, twice weekly for two weeks). Subjects were assigned to receive LJPC-401 at doses of 4, 10, or 20 mg. Serial blood samples were collected up to one-week post dose in the single-dose cohort and up to two weeks in the multiple-dose cohort for PK and PD assessments. PD assessments included effects on serum iron, ferritin, unsaturated iron binding capacity (UIBC), and transferrin saturation (TSAT). Results: Twenty-one healthy adults were randomized and included in analyses (12 from Arm A and 9 from Arm B). In Arm A, dose-related increases in mean baseline-corrected LJPC-401 concentrations were observed following single SC doses of 4, 10, and 20 mg LJPC-401. Peak concentrations were observed at approximately 2 hours postdose for all doses. LJPC-401 concentrations returned to near baseline by approximately 1 day postdose for the 4- and 10-mg dose groups and by 7 days postdose for all groups. In Arm A, dose-dependent decreases in serum iron were observed in all LJPC-401 dose groups, beginning at 2 hours postdose. The largest percent decrease in serum iron for the LJPC-401 groups occurred at the 12-hour postdose timepoint and was a mean (SD) of−56.0% (16.9%) in the 4-mg group, −66.9% (6.1%) in the 10-mg group, and −79.7% (4.1%) in the 20-mg group. Serum iron levels returned to baseline within approximately 24 hours in the 4-mg dose group and within approximately 48 hours after dosing in the 10 and 20 mg dose groups. In Arm B (10 mg dose twice weekly), decreases in mean serum iron from baseline were observed after each dose of LJPC-401. The largest percent decreases in serum iron for the LJPC-401 group was observed at Hours 8 and 12 for the Day 1 dose (mean (SD): −69.1% [9.6%] and −69.2% [17.8%], respectively) and at Hour 12 for the Day 11 dose (−73.0% [13.1%]). Dose-related increases in UIBC were observed, along with dose-related decreases in TSAT, which were similar to those observed for serum iron. Dose-related prolonged increases in serum ferritin were observed. Diurnal variation patterns were seen in endogenous hepcidin and baseline iron levels in placebo subjects. No treatment-emergent serious adverse events were reported. One subject discontinued treatment due to a TEAE (exacerbation of pre-existing atopic dermatitis) two days after initial 10 mg dose. No trends were observed in clinical laboratory data, vital signs, ECGs, or concomitant medications. No subjects tested positive for antibodies specific to LJPC-401. Conclusion: LJPC-401 was well tolerated at single doses between 4 and 20 mg (the highest dose tested), and at doses of 10 mg twice weekly in healthy adults, and resulted in decreases in serum iron levels compared with baseline. Serum ferritin increased over the time course of observations, consistent with an increased distribution of iron into the macrophage compartment, secondary to decreased iron egress into the plasma transferrin compartment. These results warrant further research in longer-term studies. Disclosures Porter: Agios: Honoraria; Novartis: Consultancy; Cerus: Honoraria. Taher:Celgene Corp.: Research Funding; Protagonist Therapeutics: Consultancy; Novartis: Consultancy, Honoraria, Research Funding; La Jolla Pharmaceutical: Research Funding; Ionis Pharmaceuticals: Consultancy. Shen:La Jolla Pharmaceutical Company: Employment, Equity Ownership. Chen:La Jolla Pharmaceutical Company: Employment, Equity Ownership. Chawla:La Jolla Pharmaceutical Company: Employment, Equity Ownership. Tidmarsh:La Jolla Pharmaceutical Company: Employment, Equity Ownership.
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Bigirimana, J., R. Fontaine e M. Höfte. "Bean Anthracnose: Virulence of Colletotrichum lindemuthianum Isolates from Burundi, Central Africa". Plant Disease 84, n.º 4 (abril de 2000): 491. http://dx.doi.org/10.1094/pdis.2000.84.4.491c.
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The diversity of Colletotrichum lindemuthianum is a major limiting factor in control of anthracnose on bean (Phaseolus vulgaris), and race characterization of this pathogen is an important tool in breeding programs. Race characterization has been carried out on isolates from North, Central, and South America; Europe; and Asia, but little or no information exists on the diversity of C. lindemuthianum in Africa. In this work, 12 isolates from the major bean-growing areas of Burundi, Central Africa, were characterized. Their virulence was tested on 12 bean differential cultivars (1) and on 4 bean cultivars commonly grown in Burundi: 2 from local germ plasm (Muyinga-1 and Urubonobono) and 2 from Colombia (A 321 and Calima). Detached unifoliate bean leaves from 8-day-old plants were placed on a humid surface in trays and sprayed until runoff with a suspension of 106 spores ml-1. Trays covered with transparent plastic sheets to keep a minimum relative humidity of 92% were incubated at 20°C. Seven days after inoculation, symptoms were evaluated for severity on a scale of 1 to 9. Leaves scored as 1 to 3 were considered resistant. Races were characterized according to a numerical binary system (1). Nine races were identified: 9, 69, 87, 384, 385, 401, 448, 449, and 485. Seven of these races (9, 69, 87, 384, 401, 448, and 485) were described for the first time in Africa. Races 401 and 485 have not yet been reported in the literature. The most susceptible differential cultivars were Michelite, PI 207262, To, and Mexico 222. Muyinga-1, Urubonobono, and A 321 were sensitive to nine, six, and five races, respectively. There is a high diversity of C. lindemuthianum in Burundi, and the local germ plasm tested is very susceptible to the characterized races. Breeding programs in Burundi should focus on lines and cultivars, such as Tu, AB 136, G 2333, and Calima, that are resistant to all the races characterized in this study. Reference: (1) M. A. Pastor-Corrales. Phytopathology 81:694, 1991.
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Ogudov, Sergey A. "Diegesis and grotesque: the film adaptation of The Overcoat by Yu.N. Tynyanov". Vestnik Tomskogo gosudarstvennogo universiteta, n.º 401 (1 de dezembro de 2015): 63–68. http://dx.doi.org/10.17223/15617793/401/9.
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Miura, Toshihiro, e Atsushi Kato. "Hypoglycemic Action of Embelia madagascariensis in Normal and Diabetic Mice". American Journal of Chinese Medicine 25, n.º 02 (janeiro de 1997): 169–73. http://dx.doi.org/10.1142/s0192415x97000196.
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The hypoglycemic effect of Embelia madagascariensis (Myrsinaceae) was investigated in both normal and streptozotocin-induced diabetic mice. The methanol extract of leaves of Embelia madagascariensis (EL)(500 mg/kg) reduced the blood glucose of normal mice from 206 ± 9 to 137 ± 10 mg/100 ml 4 hours after intraperitoneal administration (P<0.001), and also significantly lowered the blood glucose of streptozotocin-induced diabetic mice from 570 ± 29 to 401 ± 59 mg/100 ml under similar conditions (P<0.05). EL also suppressed epinephrine-induced hyperglycemia in mice (control vs EL, P<0.01).
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Dors, Arkadiusz, Ewelina Czyżewska-Dors e Grzegorz Woźniakowski. "A survey on the occurrence of Brachyspira pilosicoli and Brachyspira hyodysenteriae in growing-finishing pigs". F1000Research 8 (1 de abril de 2021): 1702. http://dx.doi.org/10.12688/f1000research.20639.3.
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Background: The major pathogenic intestinal spirochetes affecting pigs during the growing- finishing stage of production include Brachyspira hyodysenteriae and Brachyspira pilosicoli. The aim of this study was to assess the current occurrence of B. hyodysenteriae and B. pilosicoli in Polish pig herds. Moreover, associations between the presence of diarrhea or other intestinal pathogens and occurrence of B. hyodysenteriae and B. pilosicoli in pigs were investigated. Methods: Between January 2017 and August 2019, a total of 401 samples of pig feces from 95 different herds were submitted to the National Veterinary Research Institute of Poland. These samples were obtained from pigs older than 7 weeks. All the received fecal samples were examined for the presence of B. hyodysenteriae, B. pilosicoli and Lawsonia intracellularis by real-time PCR. Results: B. pilosicoli was detected in 4.5% (95% CI, 2.5–7.0%) (18/401) of pig fecal samples. At the herd level 13.7% (95% CI, 7.5–22.3%) (13/95) of herds were positive for B. pilosicoli. B. hyodysenteriae was detected in 7.0% (95% CI, 4.7–9.9%) (28/401) of pig fecal samples and 18.9% (95% CI, 11.6–28.3%) (18/95) of pig herds were positive. Out of 18 B. pilosicoli positive samples, this pathogen was detected alone in 5 samples; simultaneously with L. intracellularis in 9 samples; simultaneously with B. hyodysenteriae in 1 sample and in 3 samples was detected simultaneously with both of these bacteria. The presence of B. hyodysenteriae in fecal samples was associated with the presence of diarrhea in pigs. Conclusions: This study confirmed that B. pilosicoli infections occur in Polish pig herds, but the prevalence is at a low level and the presence of B. pilosicoli is not associated with the development of diarrhea in pigs. B. hyodysenteriae is still a common cause of diarrhea among pigs from Polish herds.
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Dors, Arkadiusz, Ewelina Czyżewska-Dors e Grzegorz Woźniakowski. "A survey on the occurrence of Brachyspira pilosicoli and Brachyspira hyodysenteriae in growing-finishing pigs". F1000Research 8 (13 de março de 2020): 1702. http://dx.doi.org/10.12688/f1000research.20639.2.
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Background: The major pathogenic intestinal spirochetes affecting pigs during the growing- finishing stage of production include Brachyspira hyodysenteriae and Brachyspira pilosicoli. The aim of this study was to assess the current occurrence of B. hyodysenteriae and B. pilosicoli in Polish pig herds. Moreover, associations between the presence of diarrhea or other intestinal pathogens and occurrence of B. hyodysenteriae and B. pilosicoli in pigs were investigated. Methods: Between January 2017 and August 2019, a total of 401 samples of pig feces from 95 different herds were submitted to the National Veterinary Research Institute of Poland. These samples were obtained from pigs older than 7 weeks. All the received fecal samples were examined for the presence of B. hyodysenteriae, B. pilosicoli and Lawsonia intracellularis by real-time PCR. Results: B. pilosicoli was detected in 4.5% (95% CI, 2.5–7.0%) (18/401) of pig fecal samples. At the herd level 13.7% (95% CI, 7.5–22.3%) (13/95) of herds were positive for B. pilosicoli. B. hyodysenteriae was detected in 7.0% (95% CI, 4.7–9.9%) (28/401) of pig fecal samples and 18.9% (95% CI, 11.6–28.3%) (18/95) of pig herds were positive. Out of 18 B. pilosicoli positive samples, this pathogen was detected alone in 5 samples; simultaneously with L. intracellularis in 9 samples; simultaneously with B. hyodysenteriae in 1 sample and in 3 samples was detected simultaneously with both of these bacteria. The presence of B. hyodysenteriae in fecal samples was associated with the presence of diarrhea in pigs. Conclusions: This study confirmed that B. pilosicoli infections occur in Polish pig herds, but the prevalence is at a low level and the presence of B. pilosicoli is not associated with the development of diarrhea in pigs. B. hyodysenteriae is still a common cause of diarrhea among pigs from Polish herds.
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Belleguic, Chantal, Marianne Corbel, Noëlla Germain, Elisabeth Boichot, Philippe Delaval e Vincent Lagente. "Reduction of matrix metalloproteinase-9 activity by the selective phosphodiesterase 4 inhibitor, RP 73-401 in sensitized mice". European Journal of Pharmacology 404, n.º 3 (setembro de 2000): 369–73. http://dx.doi.org/10.1016/s0014-2999(00)00638-5.
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STELLIN, G. P., J. R. LILLY e J. H. GITHENS. "On Partial Splenectomy in Gaucher's Disease". Pediatrics 77, n.º 4 (1 de abril de 1986): 618–19. http://dx.doi.org/10.1542/peds.77.4.618c.
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To the Editor.— In a recent issue of Pediatrics (1985;76:398-401), Bar-Maor and Govrin-Yehudain describe three children with Gaucher's disease who had a partial splenectomy for hypersplenism and mechanical problems. Neither hypersplenism nor massive splenomegaly recurred in clinical follow-up that was 4, 3, and ½ years, respectively. We warn that partial splenectomy in patients with Gaucher's disease may not always be so long-lasting. Hypersplenism and splenomegaly recurred in our patient within 9 months. Our patient was a 4-year-old girl with the diagnosis of type III Gaucher's disease which was made at 2 years of age.
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Choi, Rihwa, Wonseo Park, Gayoung Chun, Jiwon Lee, Sang Gon Lee e Eun Hee Lee. "Recent information on test utilization and intraindividual change in anti-glutamic acid decarboxylase antibody in Korea: a retrospective study". BMJ Open Diabetes Research & Care 10, n.º 3 (junho de 2022): e002739. http://dx.doi.org/10.1136/bmjdrc-2021-002739.
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IntroductionThis study aimed to evaluate the test utilization and intraindividual changes of anti-glutamic acid decarboxylase antibody (GADA), a biomarker for autoimmune diabetes in Korean adults.Research design and methodsWe retrospectively investigated longitudinally measured GADA test results to assess test utilization and intraindividual changes through a laboratory information system.ResultsDuring the 3-year study period, 11 668 GADA tests were performed in 11 184 Korean adults. The overall rate of GADA positivity at initial measurement was 7.8%. Among the 11 668 test results, 871 GADA test results from 401 Korean patients (228 men and 173 women) requested by 54 hospitals were analyzed for intraindividual changes. Among these 401 patients, 80 (20.0%) had positive (≥2.0 U/mL) and 35 (8.7%) had gray zone GADA (1.0–1.9 U/mL) level at initial measurement. The prevalence of GADA-positive patients based on initial measurement was significantly different by type of medical institution. Among 80 patients with initial positive results, 5 (6.3%) experienced qualitative GADA changes during follow-up. Among the 321 patients with initially negative or gray zone GADA, 9 (2.8%) changed to GADA positive at least once during follow-up.ConclusionsAlthough most patients had stable GADA results, some exhibited qualitative changes during follow-up. This study can help to understand the variation in GADA positivity in the monitored patients.
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Gioulounta, Kleio, Ioannis Kosmadakis, Costas Elmasides, Vasileios Diamantis, Arsenis Piskilopoulos, Iosif Amiridis e Katerina Stamatelatou. "Energy valorisation of the residual biomass from greenhouses in the framework of a circular economy". IOP Conference Series: Earth and Environmental Science 1123, n.º 1 (1 de dezembro de 2022): 012016. http://dx.doi.org/10.1088/1755-1315/1123/1/012016.
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Abstract Thrace Greenhouses S.A. cultivates 5000 t y−1 cucumbers and 3500 t y−1 tomatoes hydroponically on 170,000 m2 of land. During cultivation (from February to November), suckers and leaves are removed regularly, producing 7,000 – 8,000 t y−1 residual green biomass. The anaerobic digestion technology was applied at laboratory scale, to explore the potential of valorising the generated residues for biogas production. The latter ranged between 18 and 30 NL methane per kg of fresh biomass (suckers or leaves, respectively). Considering a typical mixture of suckers and leaves produced during the cultivating season, the methane produced annually was estimated at 140,000 m3. The biogas can be used as a fuel in a combined heat and power (CHP) system (cogeneration). CHP was considered the central unit in a hybrid energy system (HES) integrated with batteries, aiming to provide energy autonomy to the greenhouses. Moreover, the flue gas from the CHP containing 10% CO2 and 9% O2 could be used as a source of CO2 in the greenhouses. In this case, trace gases (NOx: 401±37 ppm, NO:168±15 ppm, NO2: 150±18ppm, CO: 401±60, SO2: 1.4±2.2) present in the flue gas should be removed and/or diluted with air before entering the greenhouses.
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Katz, A. "Calcium and the heart Ed. GA Langer, Raven Press NY, 1990. 401 pp. ISBN: 0-88167-617-9 $80.00". Journal of Molecular and Cellular Cardiology 23, n.º 4 (abril de 1991): 519. http://dx.doi.org/10.1016/0022-2828(91)90175-l.
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Sweet, Kendra L., Naveen Pemmaraju, Andrew A. Lane, Anthony S. Stein, Sumithira Vasu, William Blum, David A. Rizzieri et al. "Lead-in Stage Results of a Pivotal Trial of SL-401, an Interleukin-3 Receptor (IL-3R) Targeting Biologic, in Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) or Acute Myeloid Leukemia (AML)". Blood 126, n.º 23 (3 de dezembro de 2015): 3795. http://dx.doi.org/10.1182/blood.v126.23.3795.3795.
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Abstract Background: SL-401 is a novel biologic delivering a truncated diphtheria toxin, a highly potent protein synthesis inhibitor, to the IL-3R that is overexpressed on cancer stem cells and tumor bulk in BPDCN, AML and other hematologic malignancies. The agent is being further evaluated in relapsed/refractory (r/r) BPDCN based on robust activity in BPDCN pts treated with a single cycle at 12 µg/kg/day x 5 (78% ORR, 55% CR; Frankel, Blood 2014). The objectives of the lead-in stage of this trial, which includes a pivotal evaluation in r/r BPDCN, were to evaluate the safety, pharmacokinetics (PK), and preliminary activity of multiple cycles, and confirm the dose for the BPDCN study and further AML studies. Methods & Results: To date, 17 adults (9 BPDCN; 8 AML; median ages: All 63; BPDCN 69; AML 53), 15 of whom are evaluable for dose-limiting toxicity (DLT), have received 57+ cycles (range, 1-12+) of SL-401 as a 15 min infusion daily for up to 5 days every 3 weeks at 7 (6 pts/29+ cycles), 9 (3 pts/9 cycles) & 12 µg/kg/day (8 pts/19+ cycles). Two BPDCN pts had DLTs of capillary leak syndrome (CLS; Gr 5 [7 µg/kg/d]; Gr 4 [12 µg/kg/d]) in cycle 1 as manifested by decreased serum albumin during treatment followed by symptomatic CLS; both had rapid improvement of skin only disease but did not complete formal end-of-cycle assessments and are not evaluable for response. No other DLTs have occurred and the maximum tolerated dose (MTD) has not been identified. Measures, successful to date in preventing CLS, have been implemented to suspend dosing within a cycle for early CLS (manifested by weight gain and/or decreased albumin) and have allowed those pts to proceed to full 5-day dosing in subsequent cycles. Transient Gr 3 transaminase elevations, largely limited to cycle 1, have also occurred. Cumulative side effects have not been observed over multiple cycles. Five (71%) of 7 evaluable BPDCN pts had major objective responses, including complete responses. Four of 5 BPDCN pts with bone marrow involvement (range 15-80% blast count) had normalization to ≤ 5% blasts, and robust resolution of extensive, symptomatic skin lesions, lymphadenopathy, and soft tissue disease have also been noted, often within days of starting treatment. Several BPDCN pts with objective responses are receiving continued therapeutic benefit with successive cycles. Three r/r AML pts had stable disease for 6-12+ cycles, one of whom resolved transfusion dependence. Preliminary PK studies indicate inter-subject variability, increasing exposure from day 1 to 5 of cycle 1, and generally increased exposure in BPDCN relative to AML pts. Conclusions: Multiple cycles of SL-401 are feasible and confer an acceptable safety profile at doses up to 12 µg/kg/day, which, along with safety measures to prevent CLS, will be used in a pivotal stage of this study in r/r BPDCN. Because of limited toxicity and evidence of protracted disease stabilization (up to 9+ mo) in several AML pts, further SL-401 dose escalation in AML is ongoing. Major responses in BPDCN and stabilization in AML indicate that targeting of IL-3R expressing cells via SL-401 has potential for sustained anticancer activity in aggressive myeloid malignancies. Disclosures Pemmaraju: Stemline: Research Funding; Incyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; LFB: Consultancy, Honoraria. Lane:Stemline Therapeutics, Inc.: Research Funding. Stein:Amgen: Speakers Bureau. Blum:Celator: Consultancy; Celgene: Consultancy; Boerhinger Ingelheim: Consultancy. Rizzieri:Teva: Other: ad board, Speakers Bureau; Celgene: Other: ad board, Speakers Bureau. Wang:Immunogen: Research Funding. Rowinsky:Stemline Therapeutics: Employment, Equity Ownership. Szarek:Stemline Therapeutics: Employment. Brooks:Stemline Therapeutics, Inc.: Employment, Equity Ownership, Patents & Royalties. Disalvatore:Stemline Therapeutics: Employment. Liu:Stemline Therapeutics: Employment. Duvic:Cell Medica Ltd: Consultancy; Array Biopharma: Consultancy; Oncoceutics: Research Funding; Spatz Foundation: Research Funding; Rhizen Pharma: Research Funding; Allos (spectrum): Research Funding; Soligenics: Research Funding; Eisai: Research Funding; MiRagen Therapeutics: Consultancy; Huya Bioscience Int'l: Consultancy; Therakos: Research Funding, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kyowa Hakko Kirin, Co: Membership on an entity's Board of Directors or advisory committees, Research Funding; Innate Pharma: Research Funding; Tetralogics SHAPE: Research Funding. Schwartz:Stemline Therapeutics, Inc.: Employment, Equity Ownership. Konopleva:Novartis: Research Funding; AbbVie: Research Funding; Stemline: Research Funding; Calithera: Research Funding; Threshold: Research Funding.
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Zucareli, Claudemir, Cristian Rafael Brzezinski, Josiane Marlle Guiscem, Fernando Augusto Henning e João Nakagawa. "Qualidade fisiológica de sementes de milho doce classificadas pela espessura e largura". Pesquisa Agropecuária Tropical 44, n.º 1 (março de 2014): 71–78. http://dx.doi.org/10.1590/s1983-40632014000100009.
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As sementes de milho doce apresentam qualidade fisiológica inferior à das sementes de milho comum, devido à influência de várias características, como o tamanho e a forma das sementes. Diante disto, este estudo objetivou avaliar a qualidade fisiológica de sementes de duas cultivares de milho doce (BR-401 e BR-402), classificadas, separadamente, quanto à espessura, por meio de peneiras de crivos oblongos (8/64" x 3/4, 9/64" x 3/4, 10/64" x 3/4, 11/64" x 3/4, 12/64" x 3/4 e 13/64" x 3/4), e quanto à largura, em peneiras de crivos redondos (17/64", 18/64", 19/64", 20/64", 21/64" e 22/64"). Para cada cultivar, os lotes classificados foram comparados com o lote sem classificação, seguindo delineamento inteiramente casualizado, em esquema fatorial 2x7, com quatro repetições. Os parâmetros biométricos avaliados foram: retenção em peneira, massa de 100 sementes e teor de água. A qualidade fisiológica foi determinada por meio da primeira contagem, germinação, teste de frio, envelhecimento acelerado, condutividade elétrica e emergência de plântulas no campo. A classificação em peneiras melhorou a qualidade fisiológica das sementes de milho doce. As sementes com espessura intermediária, para ambas as cultivares, em geral, apresentaram maior vigor. Quanto à largura, sementes maiores, para a cultivar BR-401, e de largura intermediária, para a cultivar BR-402, apresentaram melhor qualidade fisiológica.
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Stucki, David, Marie Ballif, Matthias Egger, Hansjakob Furrer, Ekkehardt Altpeter, Manuel Battegay, Sara Droz et al. "Standard Genotyping Overestimates Transmission of Mycobacterium tuberculosis among Immigrants in a Low-Incidence Country". Journal of Clinical Microbiology 54, n.º 7 (18 de maio de 2016): 1862–70. http://dx.doi.org/10.1128/jcm.00126-16.
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Immigrants from regions with a high incidence of tuberculosis (TB) are a risk group for TB in low-incidence countries such as Switzerland. In a previous analysis of a nationwide collection of 520Mycobacterium tuberculosisisolates from 2000 to 2008, we identified 35 clusters comprising 90 patients based on standard genotyping (24-locus mycobacterial interspersed repetitive-unit–variable-number tandem-repeat [MIRU-VNTR] typing and spoligotyping). Here, we used whole-genome sequencing (WGS) to revisit these transmission clusters. Genome-based transmission clusters were defined as isolate pairs separated by ≤12 single nucleotide polymorphisms (SNPs). WGS confirmed 17/35 (49%) MIRU-VNTR typing clusters; the other 18 clusters contained pairs separated by >12 SNPs. Most transmission clusters (3/4) of Swiss-born patients were confirmed by WGS, as opposed to 25% (4/16) of the clusters involving only foreign-born patients. The overall clustering proportion was 17% (90 patients; 95% confidence interval [CI], 14 to 21%) by standard genotyping but only 8% (43 patients; 95% CI, 6 to 11%) by WGS. The clustering proportion was 17% (67/401; 95% CI, 13 to 21%) by standard genotyping and 7% (26/401; 95% CI, 4 to 9%) by WGS among foreign-born patients and 19% (23/119; 95% CI, 13 to 28%) and 14% (17/119; 95% CI, 9 to 22%), respectively, among Swiss-born patients. Using weighted logistic regression, we found weak evidence of an association between birth origin and transmission (adjusted odds ratio of 2.2 and 95% CI of 0.9 to 5.5 comparing Swiss-born patients to others). In conclusion, standard genotyping overestimated recent TB transmission in Switzerland compared to WGS, particularly among immigrants from regions with a high TB incidence, where genetically closely related strains often predominate. We recommend the use of WGS to identify transmission clusters in settings with a low incidence of TB.
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Parthasarathy, M. "The Far-Infrared (IRAS) Excess in Roberts 22 and Related Objects". Highlights of Astronomy 8 (1989): 399–401. http://dx.doi.org/10.1017/s1539299600008054.
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ABSTRACTFrom an analysis of the IRAS data of Roberts 22,Ml-92,M2-9,OH 231.8+4.2,M1-91,MWC 922,Hen 401,Mz-3,OH 19.2-1.0 and OH 26.5+0.6 it is found that the characteristics of the dust shells or disks around these objects are similar to that observed in planetary nebulae. These ten objects may be described as transition objects evolving from the tip of AGB towards left in the HR diagram. The bipolar and disk geometry of the dust envelopes around these objects may be the result of large angular momentum of the progenitor star or the central objects may be evolved binary systems embedded in thick disks formed from severe mass loss.
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Stern, Fábio L., e Leonardo Breno Martins. "Religião e humor na Nova Era". REVER: Revista de Estudos da Religião 23, n.º 1 (27 de julho de 2023): 173–94. http://dx.doi.org/10.23925/1677-1222.2023vol23i1a11.
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O presente estudo objetivou analisar a produção humorística da página de Facebook “Humor New Age”. Foram analisadas todas as publicações de 1º de junho de 2020 a 27 de março de 2022, totalizando 401 memes únicos. Os memes foram classificados em nove categorias de temas de piadas: (1) orientalismos, (2) moral e política, (3) natureza e corpo, (4) cultura pop, (5) sacralização da psicologia e psicologização da religião, (6) esoterismo europeu cristão, (7) mitologias de ciência, (8) magia, bruxaria e paganismo, e (9) teorias de conspiração. Baseado nas considerações sobre ethos de Bateson, o estudo demonstrou que estudar o humor de um grupo religioso também permite captar elementos centrais de seu ethos.
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Gill, J. "Inherited Hematologic and Oncologic Syndromes". Pediatrics in Review 32, n.º 9 (1 de setembro de 2011): 401–4. http://dx.doi.org/10.1542/pir.32-9-401.
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Zichner, R., e R. R. Baumann. "3-D transponder antennas for future SHF RFID applications". Advances in Radio Science 9 (8 de dezembro de 2011): 401–5. http://dx.doi.org/10.5194/ars-9-401-2011.
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Abstract. The radio frequency identification (RFID) technology is omnipresent since a few years. Some of the most popular fields of application are the use for security tasks, for logistics and for the consumer segment. For example, chip card or key ring sized RFID transponders can allow wireless access to secured rooms. The number of applications for wireless data transmission for the identification and tracking of objects increases every year. There is a large development need for highly functional and inexpensive RFID transponders due to the ever-increasing demand on improved reliability, higher data rates and read and write ranges of the RFID systems. Therefore, research was performed on new 3-D transponder antennas for the Super High Frequency Band around 5.8 GHz. Additionally, wave propagation effects and the influence of different dielectric environments were considered. Parallel to the design of the novel antenna structures, the printing process for inexpensive manufacturing was investigated. The gained results are the basis for prospective RFID applications.
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Cowie, Robert, e Stephen Field. "Non-cystic fibrosis bronchiectasis". Clinical Medicine 9, n.º 4 (agosto de 2009): 401–2. http://dx.doi.org/10.7861/clinmedicine.9-4-401.
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Han, Lianyi, Yanli Wang e Stephen H. Bryant. "Developing and validating predictive decision tree models from mining chemical structural fingerprints and high–throughput screening data in PubChem". BMC Bioinformatics 9, n.º 1 (2008): 401. http://dx.doi.org/10.1186/1471-2105-9-401.
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Li, Haobing, René Vaillancourt, Neville Mendham e Meixue Zhou. "Comparative mapping of quantitative trait loci associated with waterlogging tolerance in barley (Hordeum vulgare L.)". BMC Genomics 9, n.º 1 (2008): 401. http://dx.doi.org/10.1186/1471-2164-9-401.
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Achouch, Samia, Fakhita Regragui e Mourad Gharbi. "Improvement of the performance of a capacitive relative pressure sensor: case of large deflections". Journal of Sensors and Sensor Systems 9, n.º 2 (27 de novembro de 2020): 401–9. http://dx.doi.org/10.5194/jsss-9-401-2020.
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Abstract. Capacitive pressure sensors are widely used in a variety of applications and are built using a variety of processes, including 3D printing technology. The use of this technology could lead us to a situation of large deflections, depending on the mechanical properties of the materials and the resolution of the machines used. This aspect is rarely reported in previous research works that focus on improving the performance in terms of linearity and sensitivity of these sensors. This paper describes the realization of relative pressure sensors designed as two different structures; the first one is the classical design composed of a single capacitor, while the second one is composed of two capacitors, designed in such a way that they both vary according to the applied pressure but in opposite senses to each other. The purpose is to study in particular the performance of the second structure in the case of large deflections for the context of educational use. Polylactic acid (PLA) is used as the manufacturing material to print the sensors by means of a printer based on fused deposing modeling, while conductive materials are used to provide the electrical conductivity required for the printed sensors. The manufactured sensors were tested under pressure in the range of [0; 9] KPa. Compared to the performance obtained with the first structure, simulation and experimental results show that the second structure improves linearity and allows the sensitivity to be increased from a minimum of 9.98×10-2 pF/hPa to a minimum of 3.4×10-1 pF/hPa.
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Marchetti, G. "Cinema Frames, Videoscapes, and Cyberspace: Exploring Shu Lea Cheang's Fresh Kill". positions: east asia cultures critique 9, n.º 2 (1 de setembro de 2001): 401–22. http://dx.doi.org/10.1215/10679847-9-2-401.
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Rath, Padmalaya, Shweta Gautam, Shruti Jain, Anurag Bajpai, Mohan Singh e Subhash Kaushik. "Impact of third wave of COVID-19 pandemic on mental health and its related lifestyle: a cross sectional survey". International Journal Of Community Medicine And Public Health 10, n.º 2 (27 de janeiro de 2023): 766–75. http://dx.doi.org/10.18203/2394-6040.ijcmph20230235.
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Background: The coronavirus outbreak has a detrimental impact on human life. Various measures have been taken to reduce socioeconomic impact, but many problems still persist especially mental health, in particular anxiety. The aim of this study was to examine the prevalence and contributing factors of anxiety among the people aged 18 and above, residents of Noida, during the third wave of COVID-19. Methods: This was descriptive cross-sectional study with semi structured questionnaire, completed by 401 participants. The questionnaire covered four parts: dysfunctional anxiety, mental health-related lifestyle changes, the indicators of negative mental health impact, and social and family support. Results: The mean age of participants was 36.9±11.5, and 34.2%, aged between 18 and 30 years. Of 401 participants, only 29 participants (i.e., 7.2%) reported CAS≥9 indicating anxiety. CAS is significantly higher in females, housewives and non-working group. Also, 53% of respondents reported that the pandemic had worsened their financial burden. There was an association between some of the sociodemographic variables and anxiety, different responses of lifestyle choices, negative health impact and social and family support. Conclusions: The pandemic had some positive results such as impact on social and family support, awareness of mental health issues and lifestyle changes. These positive results might operate as effective defences against the adverse COVID-19 effect. Further studies are required to investigate the positive impacts attributed to COVID-19 which can be supported.
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Maurer, Matthew J., Thomas E. Witzig, William R. Macon, Sergei I. Syrbu, James R. Cerhan, Cristine Allmer, Patrick B. Johnston, Brian K. Link e Thomas M. Habermann. "Diffuse Large B-Cell Lymphoma (DLBCL) Patients with Composite Histology Have Improved Early Outcome Compared to De Novo DLBCL When Treated with R-CHOP". Blood 112, n.º 11 (16 de novembro de 2008): 2819. http://dx.doi.org/10.1182/blood.v112.11.2819.2819.
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Abstract Background: A significant percentage of DLBCL patients present with a composite histology, often seen as a node containing both follicular lymphoma and DLBCL or DLBCL in the node and discordant indolent lymphoma in the bone marrow. Literature from the pre-rituximab era suggests DLBCL patients with transformed lymphoma or composite histology have worse outcome than de novo DLBCL. Here we report on early events in a cohort of R-CHOP treated patients. Goal: To determine whether patients with composite lymphoma have an inferior event free survival (EFS) and overall survival (OS) compared to de novo diffuse large B-cell lymphoma when treated with R-CHOP. Methods: Newly diagnosed patients treated with an R-CHOP containing regimen were prospectively enrolled in our Lymphoma SPORE registry from 9/2002 through 6/2007. Pathology was centrally reviewed. All patients were followed for retreatment, disease progression, and death. Results: 401 DLBCL patients were enrolled; 14% (57/401) had a composite histology. 33 patients had DLBCL and another histology, predominantly follicular lymphoma (n=29), in the same node. 20 patients had a non-DLBCL histology in a distinct location from the DLBCL; this was primarily indolent lymphoma in the bone marrow (n=15). 4 patients had both. 19% (75/401) of patients died during follow-up and 30% (121/401) had an event (death due to any cause, progression, or retreatment). Median follow-up for living patients was 34 months (range, 5–73). Composite DLBCL patients had higher event-free (3 year EFS = 79%) and overall (3 year OS = 93%) survival then de novo DLBCL (3 year OS = 66%, 3 year EFS 79%), p=0.05 and p=0.005 respectively. These differences remained statistically significant after adjusting for the International Prognostic Index (IPI): EFS HR = 0.53, 95% CI: 0.29–0.97, p=0.02; OS HR=0.28, 95% CI: 0.10–0.76, p=0.002. OS and EFS for composite DLBCL more closely resembled R-CHOP treated grade III follicular lymphoma (A,B) from the same cohort (3 year EFS = 81%, 3 year OS = 93%). Improved outcome for composite DLBCL was consistent whether the additional histology was in the same node or distinct from the DLBCL. Conclusions: R-CHOP treated DLBCL patients with indolent discordant bone marrow involvement or other composite histology have improved early OS and EFS compared to de novo DLBCL. Further follow-up is needed to assess the long-term prognosis of composite DLBCL in the rituximab era. Histology N Age > 60 Stage III/IV LDH > ULN PS > 1 >2 EN Sites 3 YR EFS 3 YR OS * Denotes statistically significant difference at p=0.05 de novo DLBCL 344 58% 56% 56% 17% 22% 66% 78% Composite DLBCL 57 65% 77%* 34%* 18% 32% 79%* 93%* Figure Figure
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LOPES, A. P., J. P. DUBEY, O. MOUTINHO, M. J. GARGATÉ, A. VILARES, M. RODRIGUES e L. CARDOSO. "Seroepidemiology of Toxoplasma gondii infection in women from the North of Portugal in their childbearing years". Epidemiology and Infection 140, n.º 5 (31 de agosto de 2011): 872–77. http://dx.doi.org/10.1017/s0950268811001658.
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SUMMARYSeroprevalence of Toxoplasma gondii infection and associated risk factors were investigated in 401 women of childbearing age from the North of Portugal. Of the 98 (24·4%) seropositive women, 92 (93·9%) only had immunoglobulin (Ig)G, two (2·0%) only had IgM, and four (4·1%) others had both IgG and IgM. Risk factors for T. gondii infection in women were: engaging in soil-related activities without gloves [odds ratio (OR) 8·4], consumption of unwashed raw vegetables or fruit (OR 7·6), and consumption of smoked or cured (non-cooked) processed pork products (OR 2·5). Most women of childbearing age from the North Portugal are susceptible to primary infection with T. gondii and, therefore, the risk of congenital toxoplasmosis remains high.
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Miner, Alan C. "A Chronological Setting for the Epistles of Mormon to Moroni". Journal of Book of Mormon Studies (1992-2007) 3, n.º 2 (1 de outubro de 1994): 94–113. http://dx.doi.org/10.2307/44758746.
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Abstract Although chapters 8 and 9 of the book of Moroni (Mormon’s epistles to Moroni) were placed with Mormon and Moroni’s abridgment by Moroni sometime between the years A.D. 401 and 421, these chapters were not written at that time. The insertion into the text of these epistles was done for doctrinal reasons; however, mixed in with the doctrinal message are certain facts and phrases which deal with their historical-chronological setting. By analyzing the specific chronological clues contained within Mormon’s epistles, and comparing them with his abridged record of the final years of the Nephite nation, we can create a set of chronological time frames which then can be compared to construct a reasonable historical setting of A.D. 375 to 376.
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Zelenetz, Andrew D., Jacob D. Soumerai, Deepa Jagadeesh, Nishitha Reddy, Anastasios Stathis, Adam S. Asch, Huda S. Salman et al. "Preliminary Safety and Efficacy Results with an Intermittent Schedule of the PI3kδ Inhibitor ME-401 Alone or in Combination with Rituximab for B-Cell Malignancies". Blood 132, Supplement 1 (29 de novembro de 2018): 2893. http://dx.doi.org/10.1182/blood-2018-99-115670.
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Abstract Background: ME-401, a potent and selective oral PI3kδ inhibitor, achieved a high rate of early and durable responses in patients with follicular lymphoma (FL), chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) when administered once daily in 28-day cycles on a continuous schedule (CS) in a dose escalation Phase 1b study (Soumerai et al, ASCO 2018:#7519). The most common adverse events (AEs) were the delayed onset (beyond Cycle 2) of grade 3 diarrhea and rash, which were reversible with drug interruption and/or corticosteroids. These delayed AEs were thought to be due to pathway inhibition in regulatory T cells (Treg) leading to a disruption in immune homeostasis. We hypothesized that an intermittent schedule (IS) beyond Cycle 2 might mitigate or reduce the incidence of significant delayed AEs. The IS tested was selected based on the kinetics of Treg repopulation, and consists of ME-401 administered on days 1-7 of a 28-day cycle. We report preliminary results of this strategy. Methods: Group 1 included 31 patients with relapsed FL (n = 22) or CLL/SLL (n = 9) who received ME-401 on a CS at doses ≥60 mg per day. 11/29 patients (38%) who received >2 cycles of therapy had developed delayed grade 3 AEs on CS and could be re-challenged with either the CS or IS (from December 2017 onward) following recovery from toxicity. The other 18/29 patients (62%) had not developed a grade 3 AEs of interest on CS and, beginning in December 2017, were switched to IS after a median of 26 weeks (range, 8-49) of daily dosing. Group 2 included 15 patients with relapsed FL (n = 9), diffuse large B-cell lymphoma (n = 4), marginal zone lymphoma (MZL, n = 1), and CLL (n = 1) who received rituximab 375 mg/m2 x 8 doses over 6 months and ME-401 at 60 mg daily x 2 cycles then switched to the IS. Group 3 includes 30 patients with relapsed FL/CLL/SLL enrolling in an expansion cohort of ME-401 alone at 60 mg daily x 2 cycles then switching to IS. Results: Group 1: Of the 11 patients who developed a delayed grade 3 AE on CS, 6 were never re-challenged, 2 were re-challenged with CS with recurrence of their AE, and 3 were re-challenged with IS without recurrence of their AE. Of the 18 patients switched to the IS, and with a median follow-up of 5.2 months (range, 2.3-6.6) on IS, 3 developed grade 3 diarrhea on IS, 2 in the first cycle and 1 in the second cycle after the switch to IS, of whom 2 have been re-treated with IS for 1+ and 5+ months without recurrence of the AE. One patient was not evaluable for response due to discontinuation on Day 28 for personal reasons and 27/30 (90%) evaluable patients achieved an objective response. With a median follow-up of 9.4 months (range, 2.2-17.5) from enrollment, only 2/27 (7%) responders had disease progression (PD) on CS and were discontinued. Of the 18 patients who were switched to IS, only 1 SLL patient with a partial response (PR) achieved on CS developed PD on IS and was successfully rescued with switch back to CS. Another CLL patient in PR on CS had 10% increase in SPD from nadir in Cycle 5 on the IS and was switched back to CS. Group 2: 10/15 patients have completed 2 cycles of daily dosing at the time of analysis and were systematically switched to IS. With a median follow-up of 3.4 months (range, 1.5-5.7) on IS, only 1/10 patients developed delayed grade 3 diarrhea in the first cycle after switch to IS. 7/10 patients (70%) with FL/MZL achieved an objective response and no PD was reported with a median follow-up of 5.2 months (range, 3.1-7.5) from enrollment. Conclusions: Preliminary data suggest that switching to an intermittent schedule consisting of ME-401 administered on days 1-7 of a 28-day cycle following 2 cycles of continuous daily dosing was associated with a low rate of delayed grade 3 AEs and was associated with preservation of response in the vast majority of patients. All delayed grade 3 AEs of interest on IS occurred within 1-2 cycles of switching from CS to IS, suggesting that these might have represented a delayed effect of daily dosing. IS may also be a suitable re-treatment strategy in patients with delayed AEs on CS. Safety and efficacy data for the expansion cohort of 30 patients treated with ME-401 at 60 mg for 2 cycles then switched to IS will be presented at the meeting. A randomized study comparing CS and IS in FL is planned. Disclosures Zelenetz: Abbvie: Research Funding; Celgene: Consultancy; AstraZeneca: Consultancy; Novartis/Sandoz: Consultancy; Amgen: Consultancy; Gilead: Consultancy, Research Funding; Genentech/Roche: Consultancy, Research Funding. Reddy:MEI Pharma: Research Funding. Stathis:Oncology Therapeutic Development: Research Funding. Ghalie:MEI Pharma: Employment, Equity Ownership; Viracta Therapeutics: Membership on an entity's Board of Directors or advisory committees. Pagel:Pharmacyclics, an AbbVie Company: Consultancy; Gilead: Consultancy.
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TIJSSE-KLASEN, E., L. J. JAMESON, M. FONVILLE, S. LEACH, H. SPRONG e J. M. MEDLOCK. "First detection of spotted fever group rickettsiae inIxodes ricinusandDermacentor reticulatusticks in the UK". Epidemiology and Infection 139, n.º 4 (19 de novembro de 2010): 524–29. http://dx.doi.org/10.1017/s0950268810002608.
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SUMMARYA preliminary study was conducted to determine the presence of spotted fever rickettsiae in two species of British tick (Ixodes ricinusandDermacentor reticulatus). The 16S rRNA gene ofRickettsiaspp. was detected in 39/401 (9·7%) of ticks tested, including 22/338 (6·5%)I. ricinusand 17/63 (27%)D. reticulatus. Some positiveI. ricinussamples showed 100% homology withRickettsia helvetica(10/22), and most positiveD. reticulatusshowed 100% homology withR. raoultii(13/17). Five otherRickettsiaspp. were detected exhibiting 96–99% homology. Ticks positive for rickettsiae were collected from various hosts and from vegetation from eight counties across Great Britain. The distribution ofR. helveticain various engorged and unfed stages ofI. ricinussuggests thatR. helveticais widespread.R. raoultiiwas found in questing adultD. reticulatusin Wales and England. This is the first evidence of potentially pathogenic spotted fever rickettsiae in British ticks.
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Lock, Sally, e Paula M. Barrett. "A Longitudinal Study of Developmental Differences in Universal Preventive Intervention for Child Anxiety". Behaviour Change 20, n.º 4 (1 de dezembro de 2003): 183–99. http://dx.doi.org/10.1375/bech.20.4.183.29383.
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AbstractThe present paper presents the results of a longitudinal study evaluating the effects of a universal school-based intervention for child anxiety at two developmental stages. The study involved a cohort of 733 children enrolled in grade 6 (n = 336, 45.6%) aged between 9 and 10 years, and grade 9 (n = 401, 54.4%) aged between 14 and 16 years. Participants were allocated to either a school-based cognitive-behavioural intervention or to a monitoring group, and completed standardised measures of anxiety, depression and coping style. Young people identified as “at risk” of an anxiety disorder were assessed for a clinical diagnosis with a structured diagnostic interview. Findings showed universal intervention as potentially successful in reducing symptoms of anxiety and increasing coping skills in children. Primary school children reported the greatest changes in anxiety symptoms, suggesting earlier preventive intervention was potentially more advantageous than later intervention. Developmental differences in anxiety, depression and coping strategies are discussed in addition to the implications and limitations of this study and directions for future research.
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Kinnaird, Anne A. A., e Ricky Y. K. Man. "The effect of lidocaine compared with verapamil on the enhanced ventricular rhythm in the infarcted canine heart". Canadian Journal of Physiology and Pharmacology 64, n.º 4 (1 de abril de 1986): 472–76. http://dx.doi.org/10.1139/y86-076.
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Myocardial ischemia was produced in dogs by the occlusion of the left anterior descending (LAD) coronary artery for 24 or 48 h. After complete atrioventricular block was produced, enhanced ventricular rhythm was observed in all animals. The enhanced ventricular rhythm showed multiple QRS configurations and had spontaneous cycle lengths (SCL) of 397 ± 18 ms (n = 20) after 24 h of LAD occlusion and 446 ± 23 ms (n = 20) after 48 h of LAD occlusion. Overdrive pacing did not result in the termination of the enhanced ventricular rhythm in any experiment. Propranolol, as a cumulative dose of 1.5–2.0 mg/kg i.v., also did not abolish the enhanced ventricular rhythm. In 24-h infarcted hearts, lidocaine abolished the enhanced ventricular rhythm in 1 of 11 experiments. In the remaining 10 experiments, the ventricular SCL was increased from 401 ± 22 to 491 ± 26 ms after a cumulative dose of 8.8 ± 0.7 mg/kg of lidocaine. In the presence of verapamil, given as a cumulative dose of 0.60 ± 0.11 mg/kg, the ventricular SCL was increased from 401 ± 33 to 482 ± 64 ms (n = 9). In 48-h infarcted hearts, lidocaine abolished the enhanced ventricular rhythm in 5 of 11 experiments. Both lidocaine and verapamil increased the SCL of hearts in which the enhanced ventricular rhythm persisted. Analysis of variance showed that only the increase in SCL by lidocaine in 48-h infarcted hearts was statistically significant. The atrial and idioventricular rhythms in noninfarcted hearts responded differently to lidocaine and verapamil. The results suggest that some electrophysiological effects of antiarrhythmic drugs in the normal heart may not be applicable to those in the diseased situation.
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Norbury, D. "Book reviewFoundations on rock. (2nd Edition) WyllieD. C.. London: E&FN Spon, 1999, xviii + 401 pp. 0-419-23210-9. £90". Géotechnique 52, n.º 2 (março de 2002): 155. http://dx.doi.org/10.1680/geot.2002.52.2.155.
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