tbuckley/cabot-search huggingface dataset:
Chromosomal Aberrations and Congenital Heart Diseases : I. Congenital Heart Diseases : SYMPOSIUM ON GENE-ENVIRONMENT INTERACTION IN CARDIOVASCULAR DISEASES
Authors: Masuyoshi Naganuma
Journal: Circulation (1978)

1. The incidence of chromosomal aberration with CHD is 10.5% in the autopsy cases. 2. The characteristic major cardiac malformations associated with chromosomal aberration are conal abnormality, abnormal septation and cardiac valve abnormalities. 3. The characteristic association of chromosomal aberration and CHD is CAVO in Down syndrome, triple shunts and multivalvular disease in 18 trisomy, shunts in delition syndrome and coarctation of the aorta in Turner syndrome. 4. Minor cardiac anomalies associated with chromosomal aberration are valve dysplasia such as bicuspid semilunar cusps, parachute A-V valve, thickning, deformity and insufficient differentiation of valve and of chordae tendinae and hypoplastic or immature papillary muscles. 5. Primary target in cardiovascular involvement by chromosomal aberration might be a cement property of the connective tissue which is expected to conseal the foramens and shunts and to develop valve structures in embryonic heart.
Case 8-2003
Authors: Mohamed H. Sayegh, Robert B. Colvin
Journal: New England Journal of Medicine (2003)

Presentation of CaseA 35-year-old man with end-stage renal disease and a history of failed renal transplantation was admitted to the hospital for another transplantation.When the patient was 10 years old, diabetes mellitus type 1 developed, resulting in diabetic retinopathy, neuropathy, vasculopathy, hypertension, and hyperlipidemia. He underwent repeated procedures for a detached retina and was legally blind. Nine years before admission, renal failure occurred, and hemodialysis was begun. One year later, a right-sided nephrectomy and transplantation of a cadaveric kidney into the right iliac fossa were performed. Four years before admission, the patient's base-line creatinine concentration began rising from . . .
The early breast cancer (EBC) biological characteristics from NEMESI, an Italian retrospective, observational study.
Authors: M. Venturini, F. Giotta, A. De Matteis, E. Maiello, L. Manzione, B. Massidda, A. Santoro, S. Siena, S. Rossi, S. De Placido
Journal: Journal of Clinical Oncology (2010)

e11022 Background: The NEMESI study observed the clinical practice adopted in Italian Oncology institutions focusing on ER, ki67, and HER2 status in EBC adjuvant treatment. Methods: NEMESI described adjuvant treatment of EBC in Italy between January 1 and June 30, 2008, involving at least 1,500 cases (30 consecutive in each 50 centers), selected on respect of the Italian oncology units censed by Italian Association of Medical Oncology, representing geographical and institution characteristics. Inclusion criteria: age ≥18 years, operated EBC histological diagnosis (stage I-II TNM AJCC version VI), at least one cycle of adjuvant, chemotherapy, and/or hormone therapy. The negative biological expression definition: ER and PgR <10%, HER2 negative <3+ by IHC and/or FISH not amplified. Results: A total of 1,895 patients from 63 centers have been included. This preliminary analysis is based on 1,542 patients. Biological expression description: HER2 status in 279 (18.1%) were HER2+, 1,228 (79.6%) HER2-, 35 (2.3%) missing; ER status: 1,240 (80.4%) ER+, 298 (19.3%) ER-, 4 (0.3%) missing. The status Ki67/ER/HER2 was matched, showing in 996 cases, 786ER+: 59.9% (Ki67 < 20%), 17.7% (Ki6720-29%), 22.4% (Ki67>29%); in 207 ER-, 17.9% (Ki67<20%), 15.5% (Ki67 20-29%), 66.7% (Ki67>29). ki67/HER2 status matching showed in 175 HER2+: 24% (Ki67<20%), 24% (Ki67 20-29%), 52% (Ki67>29%); in 452 HER2-, 56.6% (Ki67<20%), 15.9% (Ki67 20-29%), 27.6% (Ki67>29). Conclusions: The NEMESI Italian study focused on biological expression and indicates a direct correlation between ki67 expression >29% and ER negative and/or HER2 positive EBC that may have interesting predictive aspects. Sponsored by sanofi-aventis Italy. CMF-like Anthracyclines Anthraycylines + taxanes Taxanes N N % N % N % N % Not Classified 1 10.0 2 20.0 5 50.0 2 20.0 10 ER+, HER2+, Ki67>19 4 6.0 33 49.3 27 40.3 3 4.5 67 ER+, HER2+, Ki67<20 2 8.7 10 43.5 10 43.5 1 4.3 23 ER+, HER2-, Ki67, >19 9 5.7 78 49.7 62 39.5 8 5.1 157 ER-, HER2+, Ki67>19 2 3.6 29 52.7 24 43.6 0 0.0 55 ER+, HER2-, Ki67<20 15 9.1 82 49.7 59 35.8 9 5.5 165 ER-, HER2-, Ki67<20 3 18.8 10 62.5 3 18.8 0 0.0 16 ER-, HER2+, Ki67<20 1 11.1 3 33.3 4 44.4 1 11.1 9 ER-, HER2-, Ki67>20 14 13.5 47 45.2 35 33.7 8 7.7 104 Total 50 8.3 294 48.5 229 37.8 32 5.3 606 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis
Prolonged intralymphatic delivery of dendritic cells through implantable lymphatic ports in patients with advanced cancer
Authors: Michal Radomski, Herbert J. Zeh, Howard D. Edington, James F. Pingpank, Lisa H. Butterfield, Theresa L. Whiteside, Eva Wieckowski, David L. Bartlett, Pawel Kalinski
Journal: Journal for ImmunoTherapy of Cancer (2016)

The currently-used modes of administration of immunotherapeutic agents result in their limited delivery to the lymph nodes and/or require repetitive ultrasound-guided nodal injections or microsurgical lymphatic injections, limiting their feasibility. Here, we report on the feasibility and safety of a new method of long-term repetitive intralymphatic (IL) infusion of immune cells, using implantable delivery ports.Nine patients with stage IV recurrent colorectal cancer underwent complete resection and received autologous dendritic cells (DCs) loaded with killed autologous tumor cells, KLH and PADRE, for up to four monthly cycles. Leg lymphatic vessels were cannulated, connected to 6.6Fr low-profile implantable subcutaneous delivery ports, and used to infuse 12 doses of DC over each 72 h-long cycle (every 6 h), followed by heparin flushes of the cannula-port system (one 72 h-long cycle per month). The patients who opted for alternative route of vaccine administration (2 patients) or whose ports became non-functional between cycles, continued treatment via intranodal (one injection/cycle) or intradermal (four injections/cycle) routes.A total of nine lymphatic cannulations and implantations of subcutaneous delivery ports were attempted in seven patients, with a success rate of eight out of nine (89 %). The average patency of the IL delivery system was 7.5 (±3.2) weeks. All six patients with IL ports successfully completed at least one complete 72 h-long DC infusion cycle (12 injections). Five patients (56 %) completed two full IL cycles (24 IL injections). No patients received more than two IL cycles without replacement of the IL port, due to catheter occlusion and/or local side effects: cellulitis and hematoma. Intranodal and intradermal backup options were used in, respectively, one and two patients. Overall cohort survival was >28 (±25) months. One patient with aggressive recurrent carcinomatosis, who received DC vaccines by intranodal route is alive at > 90 months, without evidence of disease.We conclude that an intermediate-duration IL delivery of multiple doses of immunotherapeutic factors using implantable delivery ports is feasible, highly-tolerable and can be reproducibly performed in cancer patients to administer immune cells, or potentially, other immune factors. However, long-term IL port placement (>7.5 weeks), is not a currently-feasible option.NCT00558051, registered Nov. 13, 2007.
Cardiac device therapy in patients with left ventricular dysfunction and heart failure: ‘real‐world’ data on long‐term outcomes (mortality, hospitalizations, days alive and out of hospital)
Authors: Giuseppe Boriani, Elena Berti, Laura Maria Beatrice Belotti, Mauro Biffi, Rossana De Palma, Vincenzo L. Malavasi, Nicola Bottoni, Luca Rossi, Elia De Maria, Roberto Mantovan, Marco Zardini, Edoardo Casali, Marco Marconi, Alberto Bandini, Corrado Tomasi, Giulio Boggian, Gaetano Barbato, Tiziano Toselli, Mauro Zennaro, Biagio Sassone
Journal: European Journal of Heart Failure (2016)
Replacement Estrogens and Endometrial Cancer
Authors: Hershel Jick, Richard N. Watkins, Judith R. Hunter, Barbara J. Dinan, Sue Madsen, Kenneth J. Rothman, Alexander M. Walker
Journal: New England Journal of Medicine (1979)

We examined the incidence of endometrial cancer in a large prepaid group practice in the Seattle area. From July, 1975, to July, 1977, there was a sharp downward trend in the incidence of endometrial cancer that paralleled a substantial reduction in prescriptions for replacement estrogens. Incidence rates were estimated for estrogen users and nonusers among women 50 to 64 years of age with intact uteri; current long-term users had an annual risk for endometrial cancer between 1 and 3 per cent, whereas nonusers had a risk less than 1/10th as great. These incidence rates remained fairly constant over time among users and nonusers; the drop in overall incidence soon after estrogen use declined suggests that the increased risk associated with estrogens falls quickly after discontinuation. The reduction in incidence of endometrial cancer in this group practice was part of a general decline in the United States after 1975.
First-in-human, dose-escalation, safety, and PK study of a novel 5T4-ADC in patients with advanced solid tumors.
Authors: Geoffrey Shapiro, Patricia LoRusso, Ulka N. Vaishampayan, Muaiad Kittaneh, John Frederick Hilton, James M. Cleary, Karen Velastegui, Dawei Xuan, Steven Hua, Ronald L. Shazer, Hossein Borghaei
Journal: Journal of Clinical Oncology (2015)

TPS2603 Background: PF-06263507 is an anti-5T4 antibody drug conjugate (ADC) comprised of a humanized anti-5T4 IgG1antibody conjugated via cysteine residue to the microtuble disrupting agent monomethylauristatin F (MMAF) with a maleimidocaproyl (mc) linker. 5T4, also known as trophoblast glycoprotein (TPBG) is a cell surface protein, with over-expression observed in a variety of cancers as compared to normal adult tissue. PF-06263507 has demonstrated potent activity in human tumor xenograft models. Methods: PF-06263507 is being evaluated in an open-label study in patients with advanced solid tumors at increasing dose levels in cohorts of 2 to 4 patients. PF-06263507 is given intravenously once every 21 days. A modified continual reassessment method (mCRM) with a target dose limiting toxicity (DLT) rate of 25% is being utilized. Primary objectives include assessing the safety and tolerability of PF-06263507 in order to determine the maximum tolerated dose (MTD). Secondary objectives include evaluating the overall safety profile, characterization of pharmacokinetic (PK), evaluating the immunogenicity, and documenting any preliminary evidence of anti-tumor activity. Standard definitions are being used to classify hematological and non-hematological DLTs. Serum concentrations of ADC, total antibody, and unconjugated payload are measured with validated bioanalytical methods. Immunogenicity evaluation is performed with anti-drug antibody (ADA) assessment. Radiologic assessment of tumor burden is conducted every 6 weeks according to RECIST. Once the MTD is determined, expansion cohorts for patients with 5T4-expressing non-small cell lung cancer, breast cancer and ovarian cancer are planned. Accrual has completed in Cohort 1 (0.05 mg/kg) through Cohort 8 (5.4 mg/kg). The study is continuing to enroll patients at increasing dose levels. Clinical trial information: NCT01891669.
Phase I study of intravenous PI3K inhibitor BAY 80-6946: Activity in patients (pts) with advanced solid tumors and non-Hodgkin lymphoma treated in MTD expansion cohorts.
Authors: Michael T. Lotze, Leonard Joseph Appleman, Ramesh K. Ramanathan, Anthony W. Tolcher, Muralidhar Beeram, Kyriakos P. Papadopoulos, Drew Warren Rasco, Glen J. Weiss, James M Mountz, Frederico G.S. Toledo, Rene J Alvarez, Matthew J Oborski, Prabhu Rajagopalan, Michael Jeffers, Diane Roth, Ronald L. Dubowy, Amita Patnaik
Journal: Journal of Clinical Oncology (2012)

3019 Background: BAY 80-6946 (BAY) is a potent and highly selective reversible pan-Class I PI3K inhibitor, previously reported to be tolerated as a 1-hr infusion at a dose of 0.8 mg/kg on days 1, 8 and 15 every 28 days (MTD). Additional pts were treated in MTD expansion cohorts to assess safety, PK, biomarkers and clinical benefit in selected tumor types, as well as safety in Type 2 diabetics. Methods: To date, 23 nondiabetic pts with solid tumors and 5 with follicular lymphoma (FL) received BAY at the MTD, until disease progression or unacceptable toxicity. Tumor types were selected for high frequency of PIK3CA mutation, including breast cancer (BC; 16), endometrial (3), gastric (2), GU transitional cell (1) and ovarian clear cell (1). Partial enrichment for PIK3CA mutation was achieved by analysis of plasma DNA. 3 diabetic pts have been enrolled, at starting dose of 0.4 mg/kg. PK was done after the 1 st and 3 rd doses. FDG-PET/CT scans were done at baseline and 48 hrs after the 1st dose for pharmacodynamic assessment. Results: Safety and tolerability assessments confirmed MTD. There were no 1 st cycle DLTs. Almost all nondiabetic pts had acute Grade 2/3 hyperglycemia (HG) following each dose; at least 10 of them received insulin for 1-3 days post dose. Hypertension (HTN) lasting &lt; 24 hrs was common in pts with preexisting HTN, and manageable. 2 FL pts developed interstitial pneumonitis (IP) after cycles 2 and 3, both responsive to steroids. Diabetic pts tolerated 0.4 mg/kg. Tumor SUV max consistently fell at 48 hrs. 3 of 4 FL pts had partial response (PR) after 2 cycles, with 2 confirmed PR pts on BAY for 10+ and 8+ mos. 2 BC pts showed PR , 1 confirmed. PIK3CA mutation (n=7) does not appear to correlate with response. Average T 1/2 was 36 hrs. Observation of high C max in very obese pts led to recommended maximum dose of 65 mg. Conclusions: BAY induced PRs in pts with BC and FL. The acute toxicities of HG in most pts and HTN in some are manageable, and IP has been limited to 2 lymphoma pts and is responsive to steroids. The observed clinical activity of BAY, along with its acceptable safety profile, provide a rationale for the ongoing development of BAY in combination with cytotoxic and targeted agents.
Emerging Opportunities and Challenges in Cancer Immunotherapy
Authors: Theresa L. Whiteside, Sandra Demaria, Maria E. Rodriguez-Ruiz, Hassane M. Zarour, Ignacio Melero
Journal: Clinical Cancer Research (2016)

Abstract Immunotherapy strategies against cancer are emerging as powerful weapons for treatment of this disease. The success of checkpoint inhibitors against metastatic melanoma and adoptive T-cell therapy with chimeric antigen receptor T cells against B-cell–derived leukemias and lymphomas are only two examples of developments that are changing the paradigms of clinical cancer management. These changes are a result of many years of intense research into complex and interrelated cellular and molecular mechanisms controling immune responses. Promising advances come from the discovery of cancer mutation-encoded neoantigens, improvements in vaccine development, progress in delivery of cellular therapies, and impressive achievements in biotechnology. As a result, radical transformation of cancer treatment is taking place in which conventional cancer treatments are being integrated with immunotherapeutic agents. Many clinical trials are in progress testing potential synergistic effects of treatments combining immunotherapy with other therapies. Much remains to be learned about the selection, delivery, and off-target effects of immunotherapy used alone or in combination. The existence of numerous escape mechanisms from the host immune system that human tumors have evolved still is a barrier to success. Efforts to understand the rules of immune cell dysfunction and of cancer-associated local and systemic immune suppression are providing new insights and fuel the enthusiasm for new therapeutic strategies. In the future, it might be possible to tailor immune therapy for each cancer patient. The use of new immune biomarkers and the ability to assess responses to therapy by noninvasive monitoring promise to improve early cancer diagnosis and prognosis. Personalized immunotherapy based on individual genetic, molecular, and immune profiling is a potentially achievable future goal. The current excitement for immunotherapy is justified in view of many existing opportunities for harnessing the immune system to treat cancer. Clin Cancer Res; 22(8); 1845–55. ©2016 AACR. See all articles in this CCR Focus section, “Opportunities and Challenges in Cancer Immunotherapy.”
134O_PR: Plasma ctDNA analysis for detection of EGFR T790M mutation in patients (pts) with EGFR mutation-positive advanced non-small cell lung cancer (aNSCLC)
Authors: S. Jenkins, J. Yang, S. Ramalingam, K. Yu, S. Patel, S. Weston, R. Lawrance, M. Cantarini, P. Jänne, T. Mitsudomi
Journal: Journal of Thoracic Oncology (2016)
Prospective molecular profiling of lung cancer patients derived xenografts
Authors: T. Mele, F. Cottino, M. Busso, D. Sardo, F. Guerrera, E. Ruffini, E. Asteggiano, F. Maletta, L. Righi, A. Bertotti, G.V. Scagliotti, L. Trusolino, S. Novello
Journal: Annals of Oncology (2015)
Studies on the Oral and Parenteral Administration of D(+)xylose
Authors: Charles E. Butterworth, Enrique Perez-Santiago, Jose Martinez de Jesus, Rafael Santini
Journal: New England Journal of Medicine (1959)

THE absorption of xylose by the mammalian intestine was studied by Cori1 as long ago as 1925, and has recently been the subject of renewed interest in connection with studies of malabsorption syndromes in human patients. The low levels of xylose absorption reported by Cori were later attributed to the fact that he used L-xylose, which is absorbed much more slowly than its isomer, D-xylose.2 Other investigators substituted D-xylose in testing renal function and found that the urinary excretion of this pentose is proportional to the plasma concentration and is independent of the volume of urine flow.3 , 4 Helmer and Fouts, . . .
Bronchial Response to Beta-Adrenergic Blockade
Authors: Gerald Zaid, Gildon N. Beall
Journal: New England Journal of Medicine (1966)

ASTHMA can be defined as a disease of the bronchi producing diffuse, reversible bronchial obstruction. The bronchial tree of patients with asthma is hypersensitive to the effects of dust, cold air, histamine, methacholine and pollen extracts, so that bronchial obstruction roughly proportional to the severity of the asthma can be demonstrated after such exposures.2 3 4 5 The cause of this bronchial hypersensitivity is not known. Patients with other forms of chronic obstructive pulmonary disease or allergic rhinitis have similar but less marked bronchial sensitivity to these materials.5 , 6 A series of investigations in animals has led to the hypothesis that a partial beta-adrenergic . . .
The Relation of Sex, Pregnancy and Menstruation to Susceptibility in Poliomyelitis
Authors: Louis Weinstein, W. Lloyd Aycock, Roy F. Feemster
Journal: New England Journal of Medicine (1951)

MANY of the general features of the distribution of poliomyelitis are reflections of the widespread dissemination of the virus as it is affected by immunity in the population resulting from previous exposure. Within this broader pattern of distribution there are further restrictions and selectivities in the occurrence of the frank disease that are indicative of the operation of other factors of susceptibility or resistance. Among the many who are exposed to the virus, the preponderant result of which is subclinical immunization, the more frequent occurrence of frank poliomyelitis under particular circumstances and in particular categories of individuals affords some indication . . .
Catechol Amine Metabolism in Essential Hypertension
Authors: Shannon Brunjes
Journal: New England Journal of Medicine (1964)

BECAUSE both norepinephrine and sympathetic stimulation produce vasoconstriction there has been much speculation about the role of norepinephrine in essential hypertension. Hypertensive patients have been shown to be more sensitive to infused norepinephrine than normal persons.1 More recently drugs that affect either the tissue levels or the metabolism of norepinephrine or other catechol amines have been shown to have marked antihypertensive effects.2 The majority of reported studies of catechol amine excretion in hypertensive patients indicate normal or moderately elevated values for urinary catechol amines.2 3 4 5 6 7 8 9 10 11 Several studies have shown significantly lower excretion in hypertensive patients than in normal persons.12 13 14 15 16 vanillyl-mandelic acid . . .
Increased Susceptibility of Livers of Aged F344/NCr Rats to the Effects of Phenobarbital on the Incidence, Morphology, and Histochemistry of Hepatocellular Foci and Neoplasms&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: J M Ward
Journal: JNCI Journal of the National Cancer Institute (1983)

Aged (875 days old) and young 42 days old) male F344/NCr rats were given sodium phenobarbital (PB) in drinking water for periods up to 233 days. Groups of aged rats were killed at 30 or 60 days or allowed to live their normal life-span, and the cause of death was determined. Young rats killed after 30, 60, and 150 days of PB exposure. Hepatocellular foci were classified into basophilic, eosinophilic, or vacuolated types according to morphologic appearance of the hepatocyte cytoplasm and were characterized by histochemical methods for the presence of gamma-glutamyl transpeptidase (GGT). The most common contributing causes of death for rats in both groups were large granular lymphocyte (LGL) leukemia and pituitary tumors. PB decreased the incidence of LGL leukemia but increased the incidence and multiplicity of hepatocellular GGT-positive foci, eosinophilic foci, and eosinophilic hepatocellular adenomas. GGT-positive eosinophilic foci increased in diameter and volume, but not in number, after appearing early in the experiment. Hepatocellular basophilic foci and neoplasms in aged control rats were usually GGT-negative and did not appear to respond to dietary PB. GGT-positive foci were seen in aged control rat livers and were composed of vacuolated amphophilic hepatocytes that differed morphologically from hepatocytes in naturally occurring liver tumors. Young rats given PB had few GGT-positive foci by 150 days on test. Aged rat livers were thus more sensitive to the effects of PB than were livers of young rats.
Modern Concepts in the Treatment of Otitis Media
Authors: Bernard Zonderman
Journal: New England Journal of Medicine (1953)

THE purpose of this paper is to discuss several important aspects of the therapy of otitis media — namely, the use and abuse of antibiotics, the importance of myringotomy, the significance of serous otitis media and the problem of recurrences.ChemotherapyThe advent of chemotherapeutic and antibiotic drugs during the past fifteen years has dramatically changed concepts of the treatment of many diseases caused by bacteria. However, the development of resistance by certain bacteria, the emergence of superinfection by secondary pathogens and the increasing occurrence of undesired side effects have indicated that these drugs are not an unmixed blessing. Failures . . .