tbuckley/cabot-search huggingface dataset:
Anti-platelet drugs attenuate the expansion of circulating CD14<sup>high</sup>CD16<sup>+</sup>monocytes under pro-inflammatory conditions
Authors: Kerry Layne, Paolo Di Giosia, Albert Ferro, Gabriella Passacquale
Journal: Cardiovascular Research (2016)

Levels of circulating CD14highCD16+ monocytes increase in atherosclerotic patients and are predictive of future cardiovascular events. Platelet activation has been identified as a crucial determinant in the acquisition of a CD16+ phenotype by classical CD14highCD16− cells. We tested the hypothesis that anti-platelet drugs modulate the phenotype of circulating monocytes. Sixty healthy subjects undergoing influenza immunization were randomly assigned to either no treatment or anti-platelet therapy, namely aspirin 300 mg or 75 mg daily, or clopidogrel (300 mg loading dose followed by 75 mg), for 48 h post-immunization (n = 15/group). Monocyte subsets, high-sensitivity C-reactive protein, pro-inflammatory cytokines, and P-selectin were measured at baseline and post-immunization. The CD14highCD16+ monocyte cell count rose by 67.3% [interquartile range (IQR): 35.7/169.2; P = 0.0002 vs. baseline] in untreated participants. All anti-platelet regimes counteracted expansion of this monocytic subpopulation. Although no statistical differences were noted among the three treatments, aspirin 300 mg was the most efficacious compared with the untreated group (−12.5% change from baseline; IQR: −28.7/18.31; P = 0.001 vs. untreated). Similarly, the rise in P-selectin (17%; IQR: −5.0/39.7; P = 0.03 vs. baseline) observed in untreated participants was abolished by all treatments, with aspirin 300 mg exerting the strongest effect (−30.7%; IQR: −58.4/−0.03; P = 0.007 vs. untreated). Changes in P-selectin levels directly correlated with changes in CD14highCD16+ cell count (r = 0.5; P = 0.0002). There was a similar increase among groups in high-sensitivity C-reactive protein (P < 0.03 vs. baseline levels). Anti-platelet drugs exert an immunomodulatory action by counteracting CD14highCD16+ monocyte increase under pro-inflammatory conditions, with this effect being dependent on the amplitude of P-selectin reduction.
A very rare postcholecystectomy complication
Authors: Hugo Guedes, Everson Artifon
Journal: Endoscopy (2016)

A 53-year-old woman underwent elective laparoscopic cholecystectomy for choledocholithiasis. Two days later, she presented abdominal pain, leucocytosis, and subhepatic collection on ultrasonography. The patient was referred for emergency laparoscopy with drainage of the collection.
A multicenter phase I study of DI17E6, a novel de-immunized monoclonal antibody to human αv integrins, in progressive castrate-resistant prostate cancer (CRPC) with bone metastases after chemotherapy.
Authors: M. Wirth, A. Heidenreich, J. E. Gschwend, T. Gil, S. Zastrow, M. Laniado, L. Bernard, T. Vardar, W. Uhl, H. Lannert
Journal: Journal of Clinical Oncology (2011)

e15060 Background: Integrins are cell surface receptors contributing to tumor progression by increasing cell migration, invasion, proliferation, and survival. DI17E6 (EMD 525797) is a de-immunized monoclonal IgG2 antibody specifically targeting αv integrins involved in tumor progression. Methods: This study assessed the safety, tolerability, pharmacokinetics and effect of DI17E6 on e.g. PSA and tumor size (by RECIST 1.0 criteria) in CRPC patients (pts) progressing after chemotherapy. 26 pts were treated with iv infusions of 250, 500, 1,000, or 1,500 mg DI17E6 given over 1 hour. 24 pts (43-80 years) received 3 doses (weeks 1, 3 and 5) prior to response assessment at the end of week 6. Pts without progressive disease could receive further doses every 2 weeks. Dose-limiting toxicities (DLTs) were assessed over the first 6 weeks and pts were followed for safety until 4 weeks after the last administration of DI17E6. Results: At cut-off for analysis, the mean duration on treatment was 95.4 days (26 pts). 4 pts in cohort 2 and 3 pts in cohort 3 had >100 days' on treatment. 7 patients were still being treated (Table). All subjects experienced treatment emergent AEs (TEAEs). Most AEs reflected underlying disease. Among the 26 subjects, 11 reported TEAEs that were possibly DI17E6 related. Of these, only one reported a grade 3 TEAE (septicaemia in cohort 3). 2 pts reported serious TEAEs (one upper GI hemorrhage and the above septicaemia). No DLTs occurred. Pt 1 and 2 of the 500 mg cohort had a marked decrease in PSA. Pt 2 also had primary tumor shrinkage and normalisation of lymph node size. These pts had long term anti-integrin treatment (297 and 380 days respectively). Conclusions: Preliminary signs of activity of DI17E6 in salvage therapy support further investigations in CRPC. DI17E6 is well tolerated without premedication and did not show clinically relevant dose-related changes in safety parameters assessed. Treatment days per cohort. Pt 250 mg 500 mg 1,000 mg 1,500 mg 1 42 297 113 91 2 42 380+ 121 84+ 3 42 85 198+ 72+ 4 42 142 41 64+ 5 56 140 56 77+ 6 98 56 43 57+ 7 14* 8 28* + Ongoing treatment. * Dropped out pts (1 and 2 infusions only).
Allogeneic Stem Cell Transplantation For Primary Refractory Hodgkin's Disease: Ablative Vs Reduced Intensity
Authors: Tulay Ozcelik, Serkan Guvenc, Fehmi Hindilerden, Baris Hasbal, Songul Serefhanoglu, Reyhan Küçükkaya, Mutlu Arat
Journal: Blood (2013)
Poor Prognosis for IKZF1 Intra-Gene Deletions in Pediatric Ph− B-Cell Precursor Acute Lymphoblastic Leukemia,
Authors: Chiara Palmi, Daniela Silvestri, Giulia Longinotti, Elena Vendramini, Valentino Conter, Giuseppe Basso, Andrea Biondi, Maria Grazia Valsecchi, Geertruy te Kronnie, Giovanni Cazzaniga
Journal: Blood (2011)
Reduction of murine osteosarcoma lung metastases using the dipeptidyl peptidase inhibitor talabostat
Authors: S. Y. Kim, S. A. Cohen, J. Epps, J. Smedley, A. Mendoza, C. Khanna, B. Jones, N. Aziz, L. J. Helman
Journal: Journal of Clinical Oncology (2006)

9009 Background: Dipeptidyl peptidases comprise a family of serine proteases that includes the genes dipeptidyl peptidase IV (DPP-IV) and fibroblast activation protein (FAP). FAP is expressed in stromal fibroblasts that surround sites of metastatic carcinomas, but not in the tumor cells themselves. Talabostat (valine-proline-boronic acid) is a potent and long-acting inhibitor of dipeptidyl peptidases. It has previously been shown to have anti-tumor activity in preclinical studies. We utilized this compound to determine whether inhibition of dipeptidyl peptidases leads to a decrease in lung metastases using a murine model of osteosarcoma metastasis. Methods: 1×10 6 K7M3-luciferase murine osteosarcoma cells were injected by tail vein into female Balb/C mice. Mice were then treated by gavage with talabostat (20 ug/dose) twice daily, talabostat once daily, or normal saline twice daily, 5 days on and 2 days off. Half of the mice were analyzed once a week using luminescent imaging. All animals were euthanized on day 24 and the number of lung metastases counted. Results: For the control mice, the average number of surface lung nodules was 75.6 (SD 45.4). Mice treated with talabostat had a ten-fold reduction in the number of nodules (twice daily - average 7.0, SD 6.1, p-value &lt;0.01, once daily - average 3.4, SD 2.4, p-value &lt;0.01). The number of resulting metastatic nodules correlated with luminescent intensity. Conclusions: Mice treated with the dipeptidyl peptidase inhibitor, talabostat, had a ten-fold decrease in the number of visible metastatic lung nodules. Experiments to elucidate the mechanism that links treatment with talabostat and inhibition of metastases are currently being performed. [Table: see text]
CD19 CAR–T cells of defined CD4+:CD8+ composition in adult B cell ALL patients
Authors: Cameron J. Turtle, Laïla-Aïcha Hanafi, Carolina Berger, Theodore A. Gooley, Sindhu Cherian, Michael Hudecek, Daniel Sommermeyer, Katherine Melville, Barbara Pender, Tanya M. Budiarto, Emily Robinson, Natalia N. Steevens, Colette Chaney, Lorinda Soma, Xueyan Chen, Cecilia Yeung, Brent Wood, Daniel Li, Jianhong Cao, Shelly Heimfeld, Michael C. Jensen, Stanley R. Riddell, David G. Maloney
Journal: Journal of Clinical Investigation (2016)

T cells that have been modified to express a CD19-specific chimeric antigen receptor (CAR) have antitumor activity in B cell malignancies; however, identification of the factors that determine toxicity and efficacy of these T cells has been challenging in prior studies in which phenotypically heterogeneous CAR-T cell products were prepared from unselected T cells.We conducted a clinical trial to evaluate CD19 CAR-T cells that were manufactured from defined CD4+ and CD8+ T cell subsets and administered in a defined CD4+:CD8+ composition to adults with B cell acute lymphoblastic leukemia after lymphodepletion chemotherapy.The defined composition product was remarkably potent, as 27 of 29 patients (93%) achieved BM remission, as determined by flow cytometry. We established that high CAR-T cell doses and tumor burden increase the risks of severe cytokine release syndrome and neurotoxicity. Moreover, we identified serum biomarkers that allow testing of early intervention strategies in patients at the highest risk of toxicity. Risk-stratified CAR-T cell dosing based on BM disease burden decreased toxicity. CD8+ T cell-mediated anti-CAR transgene product immune responses developed after CAR-T cell infusion in some patients, limited CAR-T cell persistence, and increased relapse risk. Addition of fludarabine to the lymphodepletion regimen improved CAR-T cell persistence and disease-free survival.Immunotherapy with a CAR-T cell product of defined composition enabled identification of factors that correlated with CAR-T cell expansion, persistence, and toxicity and facilitated design of lymphodepletion and CAR-T cell dosing strategies that mitigated toxicity and improved disease-free survival.ClinicalTrials.gov NCT01865617.R01-CA136551; Life Science Development Fund; Juno Therapeutics; Bezos Family Foundation.
Application of single-cell RNA sequencing in optimizing a combinatorial therapeutic strategy in metastatic renal cell carcinoma
Authors: Kyu-Tae Kim, Hye Won Lee, Hae-Ock Lee, Hye Jin Song, Da Eun Jeong, Sang Shin, Hyunho Kim, Yoojin Shin, Do-Hyun Nam, Byong Chang Jeong, David G. Kirsch, Kyeung Min Joo, Woong-Yang Park
Journal: Genome biology (2016)

Intratumoral heterogeneity hampers the success of marker-based anticancer treatment because the targeted therapy may eliminate a specific subpopulation of tumor cells while leaving others unharmed. Accordingly, a rational strategy minimizing survival of the drug-resistant subpopulation is essential to achieve long-term therapeutic efficacy. Using single-cell RNA sequencing (RNA-seq), we examine the intratumoral heterogeneity of a pair of primary renal cell carcinoma and its lung metastasis. Activation of drug target pathways demonstrates considerable variability between the primary and metastatic sites, as well as among individual cancer cells within each site. Based on the prediction of multiple drug target pathway activation, we derive a combinatorial regimen co-targeting two mutually exclusive pathways for the metastatic cancer cells. This combinatorial strategy shows significant increase in the treatment efficacy over monotherapy in the experimental validation using patient-derived xenograft platforms in vitro and in vivo. Our findings demonstrate the investigational application of single-cell RNA-seq in the design of an anticancer regimen. The approach may overcome intratumoral heterogeneity which hampers the success of precision medicine.
Increased Concentrations of Serum Nickel after Acute Myocardial Infarction
Authors: F. William Sunderman, Shozo Nomoto, Arun M. Pradhan, Howard Levine, Stanley H. Bernstein, Robert Hirsch
Journal: New England Journal of Medicine (1970)

Nickel concentrations were measured by atomic absorption spectrometry in serums collected from 35 patients at intervals after acute myocardial infarction. The highest concentrations were observed during the period from 12 to 36 hours after onset of symptoms (mean serum nickel, 5.4 ± 2.7 μg liter in patients who had had an infarction and 2.6 ± 0.8 μg per liter in 40 healthy controls [p less than 0.001]). During the period from 12 to 36 hours after onset, serum nickel concentrations were increased above the normal range in 72 per cent of patients with myocardial infarction (p versus healthy controls less than 0.0005). No significant alterations in the mean concentrations were found in a group of 17 patients with acute myocardial ischemia without infarction, or in a group of 132 consecutive hospital patients with an assortment of diseases (excluding ischemic heart disease).
Imaging of Bone Sarcomas
Authors: Judd E. Cummings, J. Andrew Ellzey, Robert K. Heck
Journal: Journal of the National Comprehensive Cancer Network (2007)

Identification, staging, and treatment of bone sarcomas rely on both clinical and imaging evaluations. Although conventional radiography remains the primary imaging modality for characterizing bone tumors, bone scintigraphy, computed tomography, magnetic resonance imaging, and positron emission tomography can each add information for staging and treatment planning.
Toward an Integrated Federal Health System
Authors: Dhruv Khullar, Dave A. Chokshi
Journal: JAMA (2016)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Importance of Potassium in Heat Exhaustion in Fibrocystic Disease of the Pancreas
Authors: Seymour J. Harris, Richard L. Lester
Journal: New England Journal of Medicine (1955)

SINCE Kessler and Andersen1 first described the unusual susceptibility of the child with fibrocystic disease to heat exhaustion, a number of investigations have been carried out in an attempt to explain the factors responsible for this phenomenon. Studies have been directed primarily toward the composition of sweat in patients with this disease, for profuse diaphoresis is the chief manifestation of heat exhaustion.2 Subsequent reports suggest that a basic defect in the sweat glands of fibrocystic patients is responsible for an increased excretion of sodium, chloride and potassium.3 , 4 It is our purpose to emphasize the importance of the therapeutic administration of . . .
Pain in the Marriage
Authors: D Mevorach, S N Heyman
Journal: New England Journal of Medicine (1995)

A 78-year-old man had retrosternal and left thoracic pressure-like pain that developed gradually over a four-hour period. He had never had similar symptoms before. Shortness of breath and lassitude began shortly before he was hospitalized.These symptoms are compatible with unstable angina. A ruptured atheromatous plaque with the formation of a thrombus in a coronary vessel is the characteristic pathogenic mechanism, with subsequent myocardial ischemia. Tachyarrhythmias or bradyarrhythmias can also cause a predisposition to myocardial oxygen insufficiency in the presence of a preexisting atheromatous narrowing of a coronary vessel. I would like to know more about predisposing factors . . .
STUDIES ON THE TOTAL BILE
Authors: Philip D. McMaster
Journal: The Journal of Experimental Medicine (1924)

The development of a method for the collection of total bile from dogs in a sterile state and uninfluenced by the gall bladder, day after day for weeks, has rendered possible an accurate study of the influence of diet upon the cholesterol output of the secretion. When a diet rich in cholesterol is given the amount of the substance in the bile greatly increases. Not only this but the concentration per cc. is, in almost every instance, greater. An increase in the total food intake, by the addition to the ordinary ration of a bone mash diet containing only a slight additional amount of cholesterol (200 mg.) produces a similar, though lesser, increase. In the fasting dog, the cholesterol yield is greatly cut down. The increase in the cholesterol after food rich in the substance does not depend on the cholagogue action of this latter, though it is true that the concentration of cholesterol in the bile usually increases with the bile volume. Though fasting cuts down the cholesterol of bile, the concentration of the substance per cc. is greatly increased. On an ordinary diet the yield of it fluctuates abruptly and considerably from day to day. In general the rule holds that an animal eating largely puts out not only much more bile but much more cholesterol. The relation between bile quantity and cholesterol yield is anything but a fixed one, however. The cholesterol yield of the bile does not parallel that of bilirubin. The pigment output from day to day remains relatively constant as compared with that of cholesterol.
Case 34-1994
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Renee M. Rossi, David J. Weissmann
Journal: New England Journal of Medicine (1994)

Presentation of CaseA 38-year-old man was admitted to the hospital because of progressive hoarseness.The patient had been in stable health until six months earlier, when hoarseness developed and gradually worsened, especially during the two months before admission. One month before admission he came to the emergency department, where physical examination showed a left supraglottic mass and irregularity of the right vocal cord; no cervical lymphadenopathy was found. Arrangements were made for his urgent admission to the hospital, but he did not arrive until he was brought in by a friend one month later.The patient was single and . . .
NTCT-01RADIATION NECROSIS IN GLIOBLASTOMA PATIENTS: THE IMPACT OF EXTENT OF RESECTION
Authors: Jong Hee Chang, Hun Ho Park, Tae Hoon Roh, Eui Hyun Kim, Seok Gu Kang, Se Hoon Kim, Sung Soo Ahn, Jaeho Cho, Chang-Ok Suh
Journal: Neuro-Oncology (2015)

NEUROTOXICITY OF CANCER TREATMENT (EFFECTS ON CNS, PNS; PRECLINICAL AND CLINICAL/HUMAN STUDIES) NTCT-01. RADIATION NECROSIS IN GLIOBLASTOMA PATIENTS: THE IMPACT OF EXTENT OF RESECTION JongHee Chang, Hun Ho Park,TaeHoon Roh,EuiHyun Kim, Seok Gu Kang, Se Hoon Kim, Sung Soo Ahn, Jaeho Cho, and Chang-Ok Suh; Yonsei University Health System, Seoul, Republic of Korea BACKGROUND: Radiation necrosis (RN) is a radiation-induced toxicity that has substantial neurological consequence in glioblastoma (GBM) patients. MGMT promoter methylation has been shown to be an important prognostic factor of RN, but the significance of extent of resection (EOR) remains unclear. METHODS: A retrospective analysis was done on newly diagnosed GBM patients with assessable MGMT promoter status who underwent Stupp protocol. EOR was grouped into grossly total resection (GTR), subtotal resection (STR), partial resection (PR) and stereotactic biopsy. Contrast enhancing lesion enlargement was classified as RN or non-RN. RESULTS: 101 patients received GTR, STR, PR and stereotactic biopsy in 57 (56.4%), 34 (33.7%), 9 (8.9%) and 1 patients (1%), respectively. Follow-up imaging done at the end of Stupp protocol was classified 45 patients (44.6%) as RN and 58 patients (55.4%) as non-RN. RN was observed in 24 (61.5%) of 39 methylated MGMT promoter and 21 (33.9%) of 62 unmethylated MGMT promoter patients (p , 0.01). RN was documented in 17 (29.8%), 19 (55.9%), 8 (88.9%) and 1 (100%) patients when EOR was grouped into GTR, STR, PR and stereotactic biopsy (p , 0.01), respectively. On multivariate analysis MGMT promoter status (OR 3.51, 95% CI 1.39-8.87) andEOR(OR 3.30,95% CI1.28-8.49)became independent predictors of RN. A Cox proportional hazards model showed MGMT status (HR 2.51, p , 0.01) and EOR (HR 2.99, p , 0.01) significantly influenced survival. Conclusions: The predictive value of MGMT status and EOR can help understand RN in equivocal situations. GTR can reduce RN and prolong survival. Neuro-Oncology 17:v172–v175, 2015. doi:10.1093/neuonc/nov226.1 Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2015.
Screening for mental problems in people presenting with hypertension and comorbidities
Authors: Helen L Millar, Mohammed Abou-saleh
Journal: BMJ (2016)

The authors provided good guidance on the complexities of managing hypertension with associated chronic comorbid physical conditions, such as kidney disease, diabetes, chronic obstructive pulmonary disease (COPD), and heart failure.1

However, they did not mention the mental health problems that are often seen in these people …
Experimental Whooping Cough
Authors: Chin Chiang Huang, Pin Mein Chen, Jui Kui Kuo, Wen Hsung Chiu, Shou Tien Lin, Hua Shing Lin, Yeng Ching Lin
Journal: New England Journal of Medicine (1962)

MANY questions about the immunologic mechanism responsible for the permanence of immunity after an attack of whooping cough are still obscure, in spite of a large number of clinical and experimental studies. It was considered worthwhile, therefore, to reinvestigate the problem in animals under more uniform conditions. The following is a report on such studies in Taiwan monkeys in which paroxysmal cough developed after an inoculation of Haemophilus pertussis. Materials and MethodsThe animals used in the experiments were normal young Taiwan monkeys, Macaca cyclopsis, weighing from 550 to 1875 gm. All monkeys were kept under preliminary observation to . . .
Primary Acquired Agammaglobulinemia, with a Family History of Collagen Disease and Hematologic Disorders
Authors: John K. Wolf
Journal: New England Journal of Medicine (1962)

PRIMARY agammaglobulinemia was once thought to be an extremely rare condition. However, since Bruton1 first recognized the syndrome in 1952, nearly 200 cases have appeared in the literature. These fall into three pathological categories: primary congenital agammaglobulinemia, which is a sex-linked recessive trait and usually becomes manifest late in the first year of life2 3 4; primary acquired agammaglobulinemia, which has no clear-cut genetic basis and may appear at any time in life; and secondary agammaglobulinemia, which is a symptom, found in certain neoplastic diseases, such as Hodgkin's disease, and other malignant lymphomas, multiple myeloma and chronic lymphatic leukemia.5 6 7 The syndrome . . .
Use of Cortisone during Penicillin Treatment of Secondary Mucocutaneous Syphilis in a Hypersensitive Patient
Authors: Marvin Brodey, Carl T. Nelson
Journal: New England Journal of Medicine (1954)

T)REVIOUS studies1 , 2 have shown that the administration of cortisone to rabbits with untreated experimental syphilis suppresses the usual response of the host to the treponemes and permits the unrestrained proliferation of the micro-organisms in the lesions and blood stream. Apparently, the ability of cortisone to promote the spread of untreated syphilitic infection is comparable to that encountered after the administration of AGTH and cortisone in tuberculous and pneumococcal infections.3 4 5 6 7 8 Although reports on the effect of ACTH and cortisone in the late stages of human syphilis are available9 , 10 there is little information regarding the use of corticosteroids in the early infectious . . .