tbuckley/cabot-search huggingface dataset:
An Echocardiographic Study of Valvular Heart Disease Associated with Systemic Lupus Erythematosus
Authors: Carlos A. Roldan, Bruce K. Shively, Michael H. Crawford
Journal: New England Journal of Medicine (1996)

Valvular heart disease is the most important cardiac manifestation of systemic lupus erythematosus. We performed a study to determine the relation of valvular disease to other clinical features of lupus, whether or not the valve disease progresses, and the associated morbidity and mortality.We performed transesophageal echocardiography and rheumatologic evaluations in 69 patients with systemic lupus erythematosus. The echocardiographic findings were compared with those in 56 healthy volunteers. Fifty-eight patients (84 percent) had second evaluations a mean (+/-SD) period of 29 +/- 13 months later. The patients and controls were followed for 57 months.Valvular abnormalities were common on the initial and the follow-up echocardiograms (in 61 and 53 percent of the patients, respectively). Valvular thickening was the predominant finding initially and on follow-up (in 51 and 52 percent of the patients, respectively), followed by vegetations (in 43 and 34 percent), valvular regurgitation (in 25 and 28 percent), and stenosis (in 4 and 3 percent). Valvular abnormalities frequently resolved, appeared for the first time, or persisted but changed in appearance or size between the two studies. Mild or moderate valvular regurgitation did not progress to become severe, and new stenoses did not develop. Neither the presence of valvular disease nor changes in the echocardiographic findings were temporally related to the duration, activity, or severity of lupus or to its treatment. The combined incidence of stroke, peripheral embolism, heart failure, infective endocarditis, and the need for valve replacement was 22 percent in the patients with valvular disease, but only 8 percent in those without it. A total of seven patients died during follow-up, in most cases as a result of valvular disease. Valvular abnormalities and complications were uncommon in the controls (occurring in 9 and 2 percent, respectively).Valvular heart disease is common in patients with systemic lupus erythematosus, frequently changes over time, appears to be temporally unrelated to other clinical features of lupus, and is associated with substantial morbidity and mortality.
P11.07 * BLOOD-BRAIN BARRIER DISRUPTION AND INTRA-ARTERIAL METHOTREXATE-BASED THERAPY FOR NEWLY DIAGNOSED PRIMARY CNS LYMPHOMA: A SINGLE-INSTITUTION EXPERIENCE
Authors: G. L. Kobyakov, M. S. Aronov, A. Y. Lubnin, S. B. Yakovlev, N. K. Serova, O. F. Tropinskaya, L. V. Shishkina, M. V. Ryzhova, A. A. Poddubsky, M. V. Inozemtceva
Journal: Neuro-Oncology (2014)

INTRODUCTION: Primary CNS lymphoma (PCNSL) is confined to the CNS and/or the eyes at presentation and is usually initially treated with intravenous methotrexate-based chemotherapy and whole-brain radiotherapy (WBRT). However, the intact blood-brain barrier (BBB) can limit diffusion of methotrexate into brain and tumor and so very high doses of methotrexate are needed for intravenous treatment. With BBB disruption (BBBD), enhanced drug delivery to the tumor can be achieved. Both methods are well known and are using in different clinics in the World. PATIENTS AND METHODS: This report summarizes the single institutional (Burdenko Neurosurgical Institute, Moscow, Russia) experience of 104 newly diagnosed patients with PCNSL treated with osmotic BBBD and intra-arterial (IA) methotrexate from 2000 to 2013. There were 57 female and 47 male at age from 25 to 75 (median 57,6 and 40,1% > or = 60). 51.3% had Karnofsky performance score (KPS) less than 70 at diagnosis. Diagnosis was verified by stereotactic biopsy (STB) in 76,7 % of cases and by tumor removing in 21,1% and by open biopsy in 2,2%. RESULTS: The overall response rate was 86.4% (63.8% complete; 21.6% partial). Median overall survival (OS) was 35 months. Median progression-free survival (PFS) was 24 months, with 5-year PFS of 29,4%. In 20 of 104 patients ophthalmological signs of intraocular lymphoma were registered (19.2%). Procedures were generally well tolerated and there were no cases of technique associated deaths in our series. CONCLUSION: Our results of treating large series of PCNSL patients using BBBD/IA methotrexate-based chemotherapy confirmed successful and durable tumor control and outcomes that were reported early. BBBD/IA technique are comparable to other PCNSL treatment regimens.
Risk factors for recurrence of artificial gastric ulcers after endoscopic submucosal dissection
Authors: Y. Huang, N. Kakushima, K. Takizawa, M. Tanaka, H. Ikehara, Y. Yamaguchi, H. Matsubayashi, H. Ono, T. Oishi, T. Nakajima
Journal: Endoscopy (2010)

It has been reported previously that artificial gastric ulcers caused by endoscopic submucosal dissection (ESD) would heal within 8 weeks, irrespective of their size and location. The aim of this retrospective study was to describe long-term outcomes of gastric ESD ulcers. Check-up of ulcers was performed by periodic endoscopy. The rate of ESD ulcer recurrence and clinicopathological factors that may relate to recurrence were assessed. During the median observation period of 33 months, a benign ulcer recurrence occurred in 10 lesions in 10 patients (2.1 %). Univariate analysis showed that Helicobacter pylori infection and presence of pathological ulcer findings within the ESD specimen were significantly related to the risk of ESD ulcer recurrence. Although the frequency is low, there is a possibility of ESD ulcer recurrence in patients with H. pylori infection and in patients who undergo ESD for a lesion with ulceration.
Torsion of the Spermatic Cord
Authors: John S. Wheeler, Frederick B. Clark
Journal: New England Journal of Medicine (1952)

TORSION of the spermatic cord resulted in loss of the involved testis in approximately 75 per cent of cases reviewed in the literature by Riba and Schmidlapp.1 Indifference on the part of the physician causes such a loss. With early diagnosis and surgical correction, potentially all involved testes could be saved. These facts have prompted us to review the cases treated at the Veterans Administration Hospital, West Roxbury, Massachusetts.The condition is uncommon, occurring in 9 of 40,000 patients admitted to this hospital from 1946 through 1952. The average age of the patients was twenty-two years.Etiology and PathologyEmbryologically, . . .
Immunomonitoring of a phase I/II study of AGS-003, a dendritic cell immunotherapeutic, as first-line treatment for metastatic renal cell carcinoma.
Authors: D. Healey, A. H. Gamble, A. Amin, V. Cohen, T. Logan, C. A. Nicolette
Journal: Journal of Clinical Oncology (2010)

e13006 Background: AGS-003 is an autologous immunotherapy prepared from matured monocyte-derived dendritic cells (DCs) co- electroporated with the subject's own amplified total tumor and synthetic CD40 ligand RNA. Immune monitoring analyses were performed by interferon (IFN)g and interleukin (IL)-2 ELISpot on 14 newly diagnosed renal cell carcinoma (RCC) subjects administered AGS-003. Methods: Peripheral blood was drawn from subjects prior to tumor excision, at first dose with AGS-003, and after 3 and 5 doses of AGS-003, each dose given once every 2wk. Immunomonitoring utilized the autologous AGS-003 product and autologous DCs electroporated with RNA encoding the RCC tumor-associated antigens (TAA) G250, survivin, and hTERT. Enhanced green fluorescent protein (eGFP) RNA and flu matrix protein RNA electroporated DCs were used as negative and positive control targets, respectively. Overall immunocompetence was determined by stimulating responder cells with staphylococcus enterotoxin B (SEB) superantigen. Results: 13 of 14 subjects showed positive per protocol immunity to at least one RCC tumor-associated antigen. 9 of 14 subjects demonstrated de novo IFNg responses to RCC TAAs that were not present prior to immunotherapy. 7 of 14 subjects displayed IL-2 and IFNg responses to the same target antigen only after immunotherapy. Responses tended to be maximal after 3 doses of AGS-003 rather than 5. Conclusions: The immune monitoring results for the majority of subjects demonstrated improvements in IL-2 and/or IFNg antitumor immune responses to at least one RCC TAA after AGS-003 immunotherapy. In vitro studies showed that prototype AGS-003 products induced a CD8 T-cell response associated with the expression of the tissue homing chemokine receptor CXCR3. The apparent loss of immune reactivity in the blood after 5 doses of AGS- 003 may correlate with selective homing of the induced antitumor immune response to target tissues. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Argos Therapeutics Bristol-Myers Squibb, Genentech, Novartis, Pfizer, Wyeth Bristol-Myers Squibb, Genentech, Novartis, Pfizer, Wyeth Argos Therapeutics
Oral Cavity Cancer in Non-Users of Tobacco
Authors: S. K.C. Ng, G. C. Kabat, E. L. Wynder
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Oral Cavity Cancer in Non-Users of Tobacco Get access Stephen K.C. Ng, Stephen K.C. Ng American Health Foundation320 East 43rd St., New York, N.Y. * Correspondence to: Stephen K. C. Ng, M.D., Dr.PH., American Health Foundation, 320 East 43rd St.. New York, NY 10017. Search for other works by this author on: Oxford Academic PubMed Google Scholar Geoffrey C. Kabat, Geoffrey C. Kabat American Health Foundation320 East 43rd St., New York, N.Y. Search for other works by this author on: Oxford Academic PubMed Google Scholar Ernst L. Wynder Ernst L. Wynder * American Health Foundation320 East 43rd St., New York, N.Y. * Correspondence to: Stephen K. C. Ng, M.D., Dr.PH., American Health Foundation, 320 East 43rd St.. New York, NY 10017. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 9, 5 May 1993, Pages 743–745, https://doi.org/10.1093/jnci/85.9.743 Published: 05 May 1993
Abstract P2-09-26: Circadian Clock Genes in Primary Breast Cancer: Strong Predictors of Pathologic Response on Neoadjuvant Chemotherapy
Authors: I Iurisci, F Valet, S Giacchetti, JY Pierga, F André, P De Cremoux, B Asselain, S Delaloge, H de Thé, F Spyratos, E Brain, B Sigal-Zifrani, L Mignot, M Marty, F. Levi
Journal: Cancer Research (2010)

Abstract Background: Circadian clocks involve 15 specific genes, which control cell cycle, apoptosis, DNA repair and metabolism. Circadian disruption is associated with both an increased risk of breast cancer, and poor survival in patients (pts) with metastatic cancer (IARC#98; Innominato et al. Cancer Res 2009). Objective: to provide first evidence of clinical relevance of clock genes expression for the therapeutic sensitivity of primary breast cancer. Method: Affymetrix Hgu133plus2 microarrays data were derived from 189 primary breast cancers. All the pts had non metastatic disease and were registered in multicenter Phase II trial of neoadjuvant chemotherapy with epirubicin-cyclophosphamide (4 courses) then docetaxel ± herceptin (4 courses). In this study, negative hormonal receptor status and limited tumor size predicted for pathological complete response rate (pCR) (Pierga JY, et al Breast Cancer Res Treat. 2010).The expression data of 15 core clock genes, within the whole tumor transcriptome, were related both to tumor mitotic index (MI) and estrogen receptors (ESR1), and to chemotherapy-induced pCR. Statistical validation involved T-test statistics, with corrections for multiple testing. Results: In the tumor biopsy obtained before treatment onset, both Per2 and Cry2 expressions correlated positively with ESR1 (r≥0.43; P&amp;lt;0.001) and inversely with (MI (r≤−0.28; P&amp;lt;0.007). In addition, a positive correlation was found for Dec 1 with ESR1 (r=0.65, P&amp;lt;0.001). The mean expressions of Per2, Cry2 and Dec 1 before chemotherapy were lower in the 32 pts who subsequently achieved pathologic complete response (pCR) as compared to the 157 who did not (P&amp;lt;0.001). No other clock gene expression was significantly related to pCR. The odds ratio confirmed the decreased chance of achieving pCR with increased expression of clock genes Per2, Cry2 or Dec1. Clock gene expression and pCR Conclusion: Low expressions of three core genes in the negative loop of the molecular circadian clock strongly predicted for the induction of a pathologic complete response of primary breast cancer with neoadjuvant chemotherapy. While circadian clock disruption seems to constitute a poor prognostic factor in cancer patients, our data suggest that the downregulation of core circadian genes in tumors significantly enhances susceptibility to chemotherapy. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-09-26.
Abstract 635: Triggering cancer cell death using light-inactivation of the Ki-67 protein
Authors: Ramtin Rahmanzadeh, Prakash Rai, Imran Rizvi, Jonathan Celli, Adnan Abu-Yousif, Bettina Baron-Lühr, Johannes Gerdes, Tayyaba Hasan
Journal: Cancer Research (2010)

Abstract INTRODUCTION: Specific destruction of cancer cells can reduce the acute systemic toxicity associated with current treatments. This can be achieved by targeting key molecular markers implicated in cancer cell growth. One such marker associated with cell proliferation is the Ki-67 protein (pKi-67) and is highly expressed in cancer cells. However it is a protein that resides inside the nuclei of cells and thus targeting it has been a challenge so far. Here, we show an innovative proof-of-principle approach for efficient killing of proliferating ovarian cancer cells by photoinactivation of pKi-67 with nanotechnology-based photodynamic therapy (PDT). METHODS: Anti pKi-67 antibodies were conjugated to fluorescein isothiocyanate (FITC) which is used as a photoactivatable agent. These conjugates were then encapsulated inside liposomes for intracellular delivery. The efficacy of Ki-67 targeting was evaluated using two in vitro models of ovarian cancer, monolayer cultures and 3D cultures established in our lab. Cell viability after irradiation with laser light at 488 nm was assessed using MTT viability assay for monolayer cultures while a Live/Dead assay kit was used for analyzing 3D cultures. RESULTS: First we demonstrated the delivery of pKi-67 antibodies to the nucleoli of ovarian cancer cells with liposomal constructs. Irradiation of these cells with a 488 nm laser led to a significant loss of viability when pKi-67 was targeted with the TuBB-9-FITC antibodies. The antibody TuBB-9 recognizes a fraction of pKi-67, which is involved in ribosomal RNA synthesis. The efficacy of this approach was also demonstrated in a 3D culture model of OVCAR-5 cells. Incubation of 3D cultures with the liposomal constructs followed by light irradiation led to destruction of their acinar structures over 72 h following treatment. Analysis of cell killing with dependence on acinar size showed that largest acini responded best to the treatment. The specificity of this approach was demonstrated in confluent human lung fibroblasts (MRC-5) where only a small population expresses pKi-67 and consistent with our hypothesis, minimal cell death was observed here. CONCLUSIONS: Our findings suggest that pKi-67 is an attractive therapeutic target in cancer. This approach allows destruction of the most aggressive cancer cells and holds promise as an effective alternative treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 635.
Effect of ketoconazole (KET) on the pharmacokinetics (PK) of atrasentan (ABT-627, ATN)
Authors: T. Zhu, A. Andre, I. Facey, W. Chiu, P. Wang, N. McCracken, D. A. Katz, R. A. Carr, T. Doan, A. Allen
Journal: Journal of Clinical Oncology (2004)

4727 Background: ATN is an oral selective endothelin A receptor antagonist, currently in phase 3 clinical development for the treatment of hormone-refractory prostate cancer. In humans, extensive ATN metabolism is equally distributed between oxidation and glucuronidation. In vitro, CYP3A was the predominant isozyme involved in oxidative metabolism. The antifungal KET is a potent and selective CYP3A inhibitor, and is a probe of choice to determine the maximal inhibitory effect against a CYP3A-metabolized drug. Methods: To assess the effect of KET on ATN PK, a phase 1 open label study was conducted in 12 healthy subjects (11 M and 1 F; mean±SD 35±9 yrs, 80±8 kg). Subjects received ATN 10 mg PO on Days 1 and 8, and KET 200 mg PO BID from Day 4 through 10. Blood samples for ATN assay were collected predose and over 72 h after each ATN dose. Plasma concentrations of ATN were determined using a validated LC/MS/MS method. Results: ATN PK data are summarized (mean±SD; N=12) in the following table. ATN t1/2 increased most in the 2 subjects heterozygous for a low activity variant of UGT2B4; changes in ATN t1/2 and AUC did not significantly vary by UGT1A1, UGT2B15, CYP3A5, ABCB1, SLC21A6 or SLC22A2 genotype. ATN with KET was generally well tolerated. The most common AE possibly related to study drug was headache. All AEs were mild. Conclusions: KET inhibited the systemic clearance of ATN but had little effect on ATN bioavailability. Predicted steady-state ATN concentrations in the presence of KET are within the range previously shown to be well-tolerated in cancer patients. These results suggest ATN can be safely co-administered with KET, a potent inhibitor of CYP3A and Pgp. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories Abbott Laboratories Abbott Laboratories
A new fluorescence-based optical imaging method to non-invasively monitor hepatic myofibroblasts in vivo
Authors: Saimir Luli, Daniela Di Paolo, Patrizia Perri, Chiara Brignole, Stephen J. Hill, Helen Brown, Jack Leslie, H.L. Marshall, Matthew C. Wright, Derek A. Mann, Mirco Ponzoni, Fiona Oakley
Journal: Journal of Hepatology (2016)

Currently, staging of fibrosis in preclinical rodent liver fibrosis models is achieved histologically. Many animals are used at multiple time-points to assess disease progression or therapeutic responses. Hepatic myofibroblasts promote liver fibrosis therefore quantifying these cells in vivo could assess disease or predict therapeutic responses in mice. We fluorescently labelled a single chain antibody (C1-3) that binds hepatic myofibroblasts to monitor fibrogenesis in vivo.CCl4 was used to induce acute liver injury in WT and cRel(-/-) mice. Bile duct ligation was used to model chronic fibrosis. Hepatic myofibroblasts were depleted using a liposome-drug delivery system or chemically with sulfasalazine. An IVIS® spectrum visualised fluorophore-conjugated C1-3 in vivo.IVIS detection of fluorescently labelled-C1-3 but not a control antibody discriminates between fibrotic and non-fibrotic liver in acute and chronic liver fibrosis models. cRel(-/-) mice have a fibro-protective phenotype and IVIS signal is reduced in CCl4 injured cRel(-/-) mice compared to wild-type. In vivo imaging of fluorescently labelled-C1-3 successfully predicts reductions in hepatic myofibroblast numbers in fibrotic liver disease in response to therapy.We report a novel fluorescence imaging method to assess murine hepatic myofibroblast numbers in vivo during liver fibrosis and after therapy. We also describe a novel liposomal antibody targeting system to selectively deliver drugs to hepatic myofibroblasts in vivo. C1-3 binds human hepatic myofibroblast therefore imaging labelled-C1-3 could be used for clinical studies in man to help stage fibrosis, demonstrate efficacy of drugs that promote hepatic myofibroblast clearance or predict early therapeutic responses.In response to damage and injury scars develop in the liver and the main cell that makes the scar tissue is the hepatic myofibroblast (HM). C1-3 is an antibody fragment that binds to the scar forming HM. We have fluorescently labelled C1-3 and given it to mice that have either normal or scarred livers (which contain HM) and then used a machine called an in vivo imaging system (IVIS) that takes pictures of different wavelengths of light, to visualise the antibody binding to HM inside the living mouse. Using fluorescently labelled C1-3 we can assess HM numbers in the injured liver and monitor response to therapy. We have also used C1-3 to target drugs encapsulated in lipid carriers (liposomes) to the HM to kill the HM and reduce the liver disease.
Case 16-1983
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Gary R. Epler, Eugene J. Mark
Journal: New England Journal of Medicine (1983)

Presentation of CaseA 52-year-old woman was admitted to the hospital because of multiple pulmonary infiltrates.She was well until four months earlier, when she experienced the abrupt onset of left-sided pleuritic pain. She came to the clinic, where the temperature was 36.1°C. The lungs were clear, and the heart was normal. An electrocardiogram was normal. X-ray films and tomograms of the chest (Fig. 1) revealed a normal appearance of the heart; nonhomogeneous consolidations were observed in the anterior segment of the right upper lobe, the right middle lobe, and the lingula; there was no pleural effusion. Acetaminophen was advised. . . .
532 SIGNIFICANT GENOTYPE-SPECIFIC ASSOCIATION OF HEPATITIS B SURFACE ANTIGEN LEVEL AND SEVERITY OF LIVER DISEASE IN PATIENTS WITH CHRONIC HEPATITIS B
Authors: M. Martinot-Peignoux, R. Carvalho-Filho, A.C. Ferreira, Netto Cardoso, M. Lapalus, O. Lada, T. Asselah, F. Krause, P. Marcellin
Journal: Journal of Hepatology (2012)
Effect of Bilateral Carotid-Body Resection on Ventilatory Control at Rest and during Exercise in Man
Authors: Robert Lugliani, Brian J. Whipp, Charles Seard, Karlman Wasserman
Journal: New England Journal of Medicine (1971)

Abstract To investigate the role of the carotid bodies in the control of ventilation during rest and moderate exercise, seven asthmatic subjects who had undergone bilateral carotid-body resection (the barostatic reflexes remained intact) were studied while they were breathing air and hypoxic, hypercapnic, and hyperoxic gas. During breathing of air and 25 per cent oxygen, ventilation was not different between this group and control subjects either at rest or during exercise. The hyperpnea of hypoxia was absent, and the ventilatory response to increased arterial carbon dioxide tension was reduced 30 per cent after carotid-body resection. These studies indicate that ventilation with the subject breathing air during rest and steady-state exercise is not affected by the operation, the carotid bodies appear to be responsible for the hyperpnea of hypoxia, and this response is not enhanced by moderate exercise, and the ventilatory response to increased arterial carbon dioxide tension is reduced after bilateral ca...
EFFECTIVENESS OF BIVALIRUDIN VERSUS UNFRACTIONATED HEPARIN DURING PERCUTANEOUS CORONARY INTERVENTION AMONG PATIENTS WITH ACUTE MYOCARDIAL INFARCTION IN THE UNITED STATES
Authors: Eric Alexander Secemsky, Ajay Kirtane, Sripal Bangalore, Enrico Ferro, Neil Wimmer, Matthew Roe, Dadi (David) Dai, Laura Mauri, Robert Yeh
Journal: Journal of the American College of Cardiology (2016)