tbuckley/cabot-search huggingface dataset:
Phase II prospective study of weekly topotecan and bevacizumab in platinum refractory ovarian cancer or peritoneal cancer (OC)
Authors: K. F. McGonigle, H. G. Muntz, J. L. Vuky, P. J. Paley, D. S. Veljovich, H. J. Gray, T. W. Malpass
Journal: Journal of Clinical Oncology (2008)

5551 Background: Patients (pts) with platinum refractory OC have limited treatment options. Bevacizumab, an anti- angiogenesis agent has demonstrated efficacy in recurrent ovarian cancer. Bevacizumab combined with chemotherapy in other solid tumors has improved efficacy compared with bevacizumab or chemotherapy alone. Topotecan, an active drug in recurrent OC has been used in a weekly fashion with less toxicity and more acceptability than a standard 5 day regimen. Topotecan and bevacizumab have non-overlapping toxicities. We studied the efficacy and tolerability of weekly topotecan and bevacizumab in patients with platinum refractory OC. Methods: The primary objectives of this study were to evaluate time to progression, overall survival, response rate and toxicity of this combination regimen. Eligible pts included those with platinum refractory OC (recurrence < 6 months of platinum therapy) who had received a maximum of 2 prior chemotherapy regimens. Pts had measurable disease or elevated CA-125 (>100). Treatment regimen was topotecan: 4 mg/m2 day 1, 8, 15 and bevacizumab: 10 mg/kg IV day 1, 15 of a 28 day cycle. Treatment continued until progression or severe toxicity. Results: Twenty-two pts have been enrolled to date, with 11 remaining on study and 18 now evaluable. Best responses for the 18 evaluable pts were: 22.2% partial response (n=4), 27.8% stable disease (n=5), and 50% progressive disease (n=9). Eleven pts went off study due to progressive disease (based on CT scan RECIST criteria [n=6] or general deterioration and/or bowel obstruction [n=5]). Median duration on study for the 18 evaluable pts was 15 wks (5–63). Four pts have had progression free survival >5 months. The 18 evaluable pts received a total of 91 treatment cycles. No pt went off study due to treatment related toxicity or suffered a bowel perforation. Conclusions: Combination bevacizumab and topotecan administered in a weekly fashion demonstrate good activity in platinum refractory OC with acceptable toxicity. G3–4 Hematologic or Hypertensive Toxicities (n=18 evaluable pts) Toxicity Treatment cycles (n=91) with toxicity: n (%) Pts with toxicity: n (%) G3 thrombocytopenia 1 (1.1 ) 1 (5.5)* G3 leukopenia 2 ( 2.2) 2 (11.1)* G4 leukopenia 1 ( 1.1) 1 (5.5) G3 hypertension 3 (3.3 ) 3 (16.7) All G3–4 7 (7.7) 6 (33.3) * one pt had both toxicities in one cycle No significant financial relationships to disclose.
Correlation between the activity of different fluoroquinolones and the presence of mechanisms of quinolone resistance in epidemiologically related and unrelated strains of methicillin-susceptible and -resistant Staphylococcus aureus
Authors: J.M. Sierra, F. Marco, J. Ruiz, M.T. Jiménez de Anta, J. Vila
Journal: Clinical Microbiology and Infection (2002)
Abstract 14832: Immunologic Targeting of CD30 Eliminates Tumorigenic Human Pluripotent Stem Cells (iPSC) Allowing Safer Clinical Application of hiPSC-Based Therapy
Authors: Nagako Sougawa, Shigeo Masuda, Shigeru Miyagawa, Satsuki Fukushima, Emiko Ito, Atsuhiro Saito, Yoshiki Sawa
Journal: Circulation (2014)

Background:  Human induced pluripotent stem cells (hiPSCs) are considered to be invaluable for regenerative medicine. However, they carry the risk of teratoma formation by residual undifferentiated cells, and it is important to develop a means of eliminating all residual tumorigenic cells before clinical application. Cell surface markers of hiPSCs can be useful for selective removal of undifferentiated hiPSCs from differentiated cultures. Although cell sorting strategies may be feasible, they are time-consuming and reduce cell viability. In this study, we hypothesized that cell selection using an antibody-cytotoxic drug conjugate may be clinically useful for immunologic targeting of undifferentiated cells.   Methods and Results:  We first compared CD antigen expression patterns between undifferentiated and differentiated cells and found that CD30, CD50, TRA-1-60, and TRA-1-81 were highly expressed on undifferentiated cells. The CD30-negative fraction was less positive for Lin28, a pluripotent marker. To eliminate the CD30-positive fraction, we applied an anti-CD30 antibody-drug conjugate (brentuximab vedotin, Adcetris, SGN-35) that has been shown to be potent for selectively eliminating CD30-positive cells and has been already approved by the FDA for lymphoma therapy. Brentuximab vedotin treatment at 100 μg/ml for 72 hours blocked proliferation of hiPSCs, leading to cell death in vitro, but did not affect differentiated cells (fibroblasts and cardiomyocytes) (iPS and NHDF: 35-75% and 100% survival compared to untreated cells, respectively). Furthermore, hiPSC-derived cardiomyocytes treated with brentuximab vedotin showed reduced Lin28 expression compared to untreated hiPSC-derived cardiomyocytes (96 h, 100 μg/ml: 71.6%, 200 μg/ml: 26.6%; 120 h, 100 μg/ml: 46.7%, 200 μg/ml: 16.3%).   Conclusion:  An anti-CD30 antibody-drug conjugate (brentuximab vedotin) eliminates residual undifferentiated hiPSCs from culture, which may enable safer clinical application of hiPSC-based cell therapy.
Abstract 656: A bispecific HER2/CD3 targeting FynomAb with excellent tumor killing and favorable pharmacokinetic properties
Authors: Ulrich Wuellner, Fabian Buller, Kristina Klupsch, Simon Brack, Irene Zbinden, Roger Santimaria, Isabella Attinger-Toller, Susann König-Friedrich, Julian Bertschinger, Dragan Grabulovski
Journal: Cancer Research (2014)

Abstract There is increasing evidence that T cells are able to control tumor growth and increase survival of cancer patients. However, tumor-specific T cell responses are difficult to mount and sustain in cancer patients, and are limited by numerous immune escape mechanisms of tumor cells. A promising approach in the immunotherapy of cancer is to engage T cells to target tumor cells using bispecific therapeutics targeting a tumor-associated surface antigen and CD3e on T cells. Such therapeutics elicit T cell mediated lysis of tumor cells independent of T cell specificity. Fynomers are small 7 kDa globular proteins derived from the SH3 domain of the human Fyn kinase (Fyn SH3) that can be engineered to bind with antibody-like affinity and specificity to virtually any target of choice. Fynomers can be fused to N-terminal and/or C-terminal ends of antibodies to generate multispecific therapeutics (FynomAbs) with tailored architectures. FynomAbs can be produced using standard antibody technology (GMP production yield of 3.3 g/L at 1000 L scale achieved), and show IgG-like biophysical properties and pharmacokinetic profiles. We have generated a novel bispecific FynomAb which can simultaneously bind HER2 on tumor cells and CD3 on T cells. The bispecific HER2/CD3 targeting FynomAb COVA420 potently redirected T cells to HER2 expressing tumor cells showing picomolar tumor cell lysis activity. We present for the first time that a tailored architecture of the FynomAb leads to optimal tumor cell killing properties. The activity of COVA420 was found to be highly specific, as no lysis of cells was observed in the absence of HER2 expression. In addition, COVA420 demonstrated an antibody-like pharmacokinetic profile in mice. We anticipate that the increased half-life of T cell recruiting FynomAbs compared to other bispecific formats translates into a significant benefit for patients, since it circumvents the need for continuous infusion and prolongs the intervals between successive treatments. In summary, bispecific T cell recruiting FynomAbs represent a novel platform technology to redirect T cells to tumor cells with optimal biophysical properties, long-half lives and tailored architectures. Citation Format: Ulrich Wuellner, Fabian Buller, Kristina Klupsch, Simon Brack, Irene Zbinden, Roger Santimaria, Isabella Attinger-Toller, Susann König-Friedrich, Julian Bertschinger, Dragan Grabulovski. A bispecific HER2/CD3 targeting FynomAb with excellent tumor killing and favorable pharmacokinetic properties. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 656. doi:10.1158/1538-7445.AM2014-656
Reduced risk of life‐threatening ventricular tachyarrhythmias with cardiac resynchronization therapy: relationship to left ventricular ejection fraction
Authors: Valentina Kutyifa, Arthur J. Moss, Scott D. Solomon, Scott McNitt, Mehmet K. Aktas, Alon Barsheshet, Bela Merkely, Wojciech Zareba, Ilan Goldenberg
Journal: European Journal of Heart Failure (2015)
Ombudsman criticises deputising service
Authors: Zosia Kmietowicz
Journal: BMJ (2000)

General practitioners in England have been advised to monitor the deputising service they use more closely after complaints to the health service ombudsman, Michael Buckley, showed that the biggest of the private companies provided a “totally unacceptable” service.

Although Mr Buckley's office received only three complaints about Healthcall, which provides out of hours cover for more than 7000 GPs, investigations showed the service to be substandard.

In one case a woman in Gateshead had to wait nearly three …
A 11.7-kb deletion triggers intersexuality and polledness in goats
Authors: Eric Pailhoux, Bernard Vigier, Stéphane Chaffaux, Nathalie Servel, Sead Taourit, Jean-Pierre Furet, Marc Fellous, François Grosclaude, Edmond P. Cribiu, Corinne Cotinot, Daniel Vaiman
Journal: Nature Genetics (2001)
NIH Ethics Rules Revisited
Authors: Tracy Hampton
Journal: JAMA (2005)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Thymomas alter the T-cell subset composition in the blood: a potential mechanism for thymoma-associated autoimmune disease
Authors: Viola Hoffacker, Anja Schultz, James J. Tiesinga, Ralf Gold, Berthold Schalke, Wilfred Nix, Reinhard Kiefer, Hans Konrad Müller-Hermelink, Alexander Marx
Journal: Blood (2000)
Association between CCR5 Genotype and the Clinical Course of HIV-1 Infection
Authors: Ana-Maria de Roda Husman
Journal: Annals of Internal Medicine (1997)

Background: Heterozygosity for a 32-nucleotide deletion in the C-C chemokine receptor 5 gene (CCR5 delta32) is associated with delayed disease progression in persons infected with HIV-1. Objective: To compare the predictive value of CCR5 genotype with that of established markers in the clinical course of HIV-1 infection. Design: Retrospective longitudinal study and nested case–control study. The latter included only long-term survivors, who were individually matched with progressors. Setting: Amsterdam, the Netherlands. Participants: 364 homosexual men with HIV-1 infection. Measurements: Polymerase chain reaction was used for CCR5 genotyping. Univariate and multivariate Cox proportional-hazard analyses were done for disease progression with CCR5 genotype, CD4+ T-lymphocyte counts, T-lymphocyte function, HIV-1 biological phenotype (syncytium-inducing or non-syncytium-inducing HIV-1), and viral RNA load in serum as covariates. Results: In the case–control study, 48% of long-term survivors were heterozygous for CCR5 delta32 compared with 9% of progressors (odds ratio, 6.9 [95% CI, 1.9 to 24.8]). In the total study sample, CCR5 delta32 heterozygotes had significantly delayed disease progression (P < 0.001; relative hazard, 0.4 [CI, 0.3 to 0.6]), a 1.5-fold slower decrease in CD4+ T-lymphocyte count (P = 0.01), and a 2.6-fold lower viral RNA load (P = 0.01) at approximately 2.3 years after seroconversion compared with CCR5 wild-type homozygotes. At the end of the study, both groups showed the same prevalence of syncytium-inducing HIV-1, but CCR5 delta32 heterozygotes had a delayed conversion rate. The protective effect of CCR5 delta32 heterozygosity was stronger in the presence of only non-syncytium-inducing HIV-1. The CCR5 genotype predicted disease progression independent of viral RNA load, CD4 T-lymphocyte counts, T-lymphocyte function, and HIV-1 biological phenotype. Conclusions: The addition of CCR5 genotype to currently available laboratory markers may allow better estimation of the clinical course of HIV-1 infection.
Station (577-2)
Authors: M. Therese Southgate
Journal: JAMA (2003)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Periarthritis: Another Duration-Related Complication of Diabetes Mellitus
Authors: Mohammed Abdul Sattar, Wijdan Ali Luqman
Journal: Diabetes Care (1985)

The association between periarthritis of the shoulder and diabetes mellitus is well recognized. A study of 100 hospitalized patients with diabetes was performed, comparing them with 100 control subjects. The mean +/- SEM age of the subjects was 47 +/- 2 yr. Nineteen percent of the patients with diabetes had periarthritis. The afflicted subjects had a higher incidence of retinopathy (P less than 0.005) and albuminuria (P less than 0.005). The duration of shoulder pain correlated with the duration of the diabetes mellitus (P less than 0.001). However, the presence of other complications in subjects with periarthritis was not as well correlated with the duration of the diabetes mellitus. These data emphasize the common occurrence of periarthritis in subjects with diabetes mellitus and its extension to people of diverse backgrounds.
Abstract 12211: Exosomal Transfer of Mir-130a Excreted From Gata-4-Modified Mesenchymal Progenitor Cells Promotes Angiogenesis
Authors: Min Gong, Bin Yu, Jingcai Wang, Yigang Wang, Ronald W Millard, Muhammad Ashraf, Meifeng Xu
Journal: Circulation (2014)

Background:  It is well known that exosomes play an important role in cell-cell communication and cellular functions. Bioactive molecules, components of exosomes released from stem cells may regulate angiogenesis. Here, we investigated the involvement of microRNAs excreted from GATA-4-modified mesenchymal progenitor cells (MPC GATA-4 ) on the angiogenesis.   Methods and Results:  MPC GATA-4  was constructed using retrovirus carrying GATA-4 gene. MPC GFP  was used as counterpart to MPC GATA-4 . The conditioned medium (CdM) was collected from MPC and human umbilical vein endothelial cells (HUVEC) were incubated with CdM. [[Unable to Display Character: ⑴]] Concentrated CdM from MPC GATA-4  (CdM GATA-4 ) exerted greater potent pro-angiogenic effects than CdM obtained from MPC GFP  (CdM GFP ). The total tube length in HUVEC treated with CdM GATA-4  was 44.0 ± 4.8 mm/14.8 mm 2  field, whereas it was only 31.3 ± 3.6 mm/14.8 mm 2  field in the CdM GFP  treated group. Similarly, the cumulative sprout length per HUVEC spheroid treated with CdM GATA-4  was significantly longer than that of the CdM GFP  treated group. [[Unable to Display Character: ⑵]] Pro-angiogenic miR-130a expression level in CdM GATA-4  was 2.6 fold higher than that in CdM GFP . To confirm the pro-angiogenic effect of miR-130a from CdM GATA-4 , we overexpressed miR-130a in MPC and collected the CdM (CdM miR-130a ). The pro-angiogenic capacity of CdM miR-130a  was significantly greater than its negative control, CdM sramble , assessed by both tube formation and spheroid-based angiogenesis assay. [[Unable to Display Character: ⑶]] The expression of miR-130a in CdM GATA-4  was decreased dramatically when MPC GATA-4  treated with GW4869 (10μM), an exosome release inhibitor. The total tube length in HUVEC treated with CdM GATA-4+GW4869  was significantly shorter than that of CdM GATA-4  treated group. Then, exosomes were isolated from CdM GATA-4  and CD63-GFP Cyto-Tracers™ lentivirus was used to label exosomes in MPC (exo CD63-GFP ). Exo CD63-GFP  were internalized by HUVEC and the expression of CD63 was detectable in HUVEC. Finally, the exosomes in CdM miR-130a  (exo miR-130a ) exerted more pronounced pro-angiogenic effects than those in CdM sramble  (exo sramble ).   Conclusion:  Exosome-mediated transfer of miR-130a from MPC GATA-4  to HUVEC promoted angiogenesis. Exosomes may be therapeutically used in various cardiovascular diseases.
Abstract 20443: Differential Effect of Ticagrelor vs Thienopyridine Loading on Fractional Flow Reserve: Possible Implications for Clinical Practice
Authors: Dimitrios Alexopoulos, Ioanna Xanthopoulou, Grigorios Tsigkas, Nikolaos Koutsogiannis, Athena Hassapi, Dionusios Ktenas, Christos Schortsanitis, Periklis Davlouros
Journal: Circulation (2014)

Background: Ticagrelor increases adenosine plasma levels and enhances coronary blood flow velocity during adenosine infusion, actions not possessed by thieonopyridines. It has been hypothesized tha...
SPONTANEOUS BULLA FORMATION IN THE SKIN IN DIABETES MELLITUS
Authors: R L COPE
Journal: Annals of Internal Medicine (1950)

Case Reports1 May 1950SPONTANEOUS BULLA FORMATION IN THE SKIN IN DIABETES MELLITUSR. LOUIS COPE, M.D., F.A.C.P.R. LOUIS COPE, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-32-5-964 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe sudden appearance of bullae in the skin without apparent cause is not uncommon in patients with diabetes mellitus. The prevailing opinion concerning the etiology appears to be that the bulla results from an occlusion of the arteriole supplying that particular area of the skin with resulting localized necrosis. Such an explanation is plausible in view of the pathologic changes known to occur in the arterial vessels in diabetes. That another factor or factors may be involved was suggested by the following two cases observed during the past year.CASE REPORTSCase 1. A white male, age 63, was admitted...Bibliography1. Kramer DW: Early or warning signs of impending gangrene in diabetes, M. J. and Rec. 132: 338, 1930. Google Scholar2. Kramer DW: Peripheral vascular diseases, 1948, F. A. Davis Company, Philadelphia. Google Scholar3. JordanRandallBloor WRLOWR: Neuropathy in diabetes mellitus, Arch. Int. Med. 55: 26, 1935. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Houston, Texas*Received for publication November 16, 1948.From the Department of Medicine, Baylor University College of Medicine and Jefferson Davis Hospital, Houston, Texas. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byIncidence of bullosis diabeticorum - a controversial cause of chronic foot ulcerationDiabetic bullae: 12 cases of a purportedly rare cutaneous disorderLa bullose des diabétiques. A propos d'un nouveau casEndocrine-skin interactionsBullosis diabeticorumBullosis diabeticorum: A case reportHaut und DiabetesBULLOUS LESIONS OF THE SKIN IN DIABETES (BULLOSIS DIABETICORUM) 1 May 1950Volume 32, Issue 5Page: 964-967KeywordsArteriolesBlistersDiabetes mellitusEtiologyHospital medicineNecrosis Issue Published: 1 May 1950 PDF downloadLoading ...
Daclatasvir plus asunaprevir for chronic HCV genotype 1b infection
Authors: Hiromitsu Kumada, Yoshiyuki Suzuki, Kenji Ikeda, Joji Toyota, Yoshiyasu Karino, Kazuaki Chayama, Yoshiiku Kawakami, Akio Ido, Kazuhide Yamamoto, Koichi Takaguchi, Namiki Izumi, Kazuhiko Koike, Tetsuo Takehara, Norifumi Kawada, Michio Sata, Hidetaka Miyagoshi, Timothy Eley, Fiona McPhee, Andrew Damokosh, Hiroki Ishikawa, Eric Hughes
Journal: Hepatology (2014)

All-oral combinations of direct-acting antivirals may improve efficacy and safety outcomes for patients with hepatitis C virus (HCV) infection, particularly those who are poor candidates for current interferon/ribavirin-based regimens. In this open-label, phase 3 study, 135 interferon-ineligible/intolerant and 87 nonresponder patients with chronic HCV genotype 1b infection were enrolled at 24 centers in Japan. Patients received daclatasvir 60 mg once daily plus asunaprevir 100 mg twice daily for 24 weeks. The primary endpoint was sustained virologic response 24 weeks after treatment (SVR 24 ). This study is registered with ClinicalTrials.gov (NCT01497834). SVR 24 was achieved by 87.4% of interferon-ineligible/intolerant patients and 80.5% of nonresponder (null and partial) patients; rates were similar in cirrhosis (90.9%) and noncirrhosis (84.0%) patients, and in patients with IL28B CC (84.5%) or non-CC (84.8%) genotypes. Fourteen patients in each group (12.6%) discontinued dual therapy, mainly due to adverse events or lack of efficacy. Nine nonresponder patients received additional treatment with peginterferon/ribavirin per protocol-defined criteria. The rate of serious adverse events was low (5.9%) and varied among patients. The most common adverse events were nasopharyngitis, increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST), headache, diarrhea, and pyrexia. Conclusion : Interferon-free, ribavirin-free all-oral therapy with daclatasvir and asunaprevir for 24 weeks is well tolerated and can achieve a high rate of SVR in patients with HCV genotype 1b who were ineligible, intolerant, or had not responded to prior interferon-based therapy. (Hepatology 2014;59:2083–2091)