tbuckley/cabot-search huggingface dataset:
Case 53-1987
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, R. James Klingenstein, Louis P. Lamarre
Journal: New England Journal of Medicine (1987)

Presentation of Case First admission. A 54-year-old woman was admitted to the hospital because of diarrhea and weight loss.She was well until three months earlier, when diarrhea developed, with the passage of six large, pale, soft stools daily, accompanied by nausea, vague abdominal pain, and a loss of 9 kg in weight. A barium-enema examination, upper gastrointestinal study, sigmoidoscopic examination, and microscopical examination of a stool specimen for ova and parasites, performed elsewhere, were reported to be negative. Her symptoms persisted, and two weeks before admission carpopedal spasm appeared. She was admitted to this hospital.There was no . . .
Morphology of the Development of Type B Virus Particles in a Transplantable Mammary Tumor of ICR/Ha Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Dolowy, William C.
Journal: JNCI Journal of the National Cancer Institute (1965)

Journal Article Morphology of the Development of Type B Virus Particles in a Transplantable Mammary Tumor of ICR/Ha Mice Get access William C. Dolowy, M.S., D.V.M. William C. Dolowy, M.S., D.V.M. Medical Research Laboratory, The University of Illinois, Chicago, Illinois Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 34, Issue 6, June 1965, Pages 815–825, https://doi.org/10.1093/jnci/34.6.815 Published: 01 June 1965 Article history Received: 09 October 1964 Published: 01 June 1965
Abstract 3096: CDK4/6 as a therapeutic target in malignant melanoma
Authors: Jessica L. Teh, Andrew Aplin
Journal: Cancer Research (2015)

Abstract Melanoma is the most deadly form of skin cancer and FDA-approved therapies such as vemurafenib and ipilimumab are associated with short-term responses and/or severe toxicities for patients. Recent favorable clinical data with cyclin-dependent kinase (CDK) 4/6 inhibitor, palbociclib (PD’991) in ER+ breast cancer has rekindled an interest in targeting cell cycle progression to stop aberrant cell growth. Thus, we set out to analyze the potential use of CDK4/6 inhibitors in melanoma. Due to the inability of CDK4/6 inhibitors to induce apoptosis as a single agent, we explored viable combinatorial strategies that will trigger both pro-senescent and pro-apoptotic pathways that may lead to an effective treatment modality for melanoma patients. Here, we demonstrate the benefit of combining a MEK inhibitor, trametinib (GSK’212) with PD’991 both in vitro and in vivo. We did not observe any enhanced effects of combining both GSK’212 and PD’991 in cells that are wild-type for BRAF and NRAS or an RB1-null BRAF mutant line. However, B-RAF and N-RAS mutant cells exhibited an enhanced response to the combinatorial agents as compared to single agents. Furthermore, we observed a dramatic increase in apoptosis in cell lines that are sensitive to combined GSK’212 and PD’991 treatment. Expression of Inhibitor-of-Apoptosis (IAP) protein, survivin, was associated with response. Finally, because it is important to understand how resistance develops, we have validated a novel E2F reporter system in vivo to quantitatively and temporally measure the efficacy of CDK4/6 inhibitors and possible re-activation of the pathway during acquired drug resistance. Citation Format: Jessica L. Teh, Andrew Aplin. CDK4/6 as a therapeutic target in malignant melanoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3096. doi:10.1158/1538-7445.AM2015-3096
A Controlled Trial Comparing Continued Zidovudine with Didanosine in Human Immunodeficiency Virus Infection
Authors: James O. Kahn, Stephen W. Lagakos, Douglas D. Richman, Anne Cross, Carla Pettinelli, Song-heng Liou, Michael Brown, Paul A. Volberding, Clyde S. Crumpacker, Gildon Beall, Henry S. Sacks, Thomas C. Merigan, Mohan Beltangady, Laurie Smaldone, Raphael Dolin
Journal: New England Journal of Medicine (1992)

Although zidovudine is effective in patients with human immunodeficiency virus (HIV) infection, its efficacy may decline with prolonged use. Didanosine is another inhibitor of HIV reverse transcriptase. We evaluated the effectiveness of changing anti-HIV treatment from zidovudine to didanosine.
Case 2-2014
Authors: W. Scott McDougal, Richard J. Lee, Jason A. Efstathiou, Mukesh Harisinghani, Chin-Lee Wu
Journal: New England Journal of Medicine (2014)

A 44-year-old man was seen in the urology clinic because of a penile lesion that had been enlarging for 6 months. Examination and imaging revealed an ulcerated mass and enlarged inguinal lymph nodes. A diagnostic procedure was performed, and management decisions were made.
Dementia Associated with the Acquired Immunodeficiency Syndrome
Authors: Stuart A. Lipton, Howard E. Gendelman
Journal: New England Journal of Medicine (1995)

Approximately one third of adults and half of children with the acquired immunodeficiency syndrome (AIDS) eventually have neurologic complications, which are directly attributable to infection of the brain by the human immunodeficiency virus type 1 (HIV-1).1,2 Neurologic problems occur even in the absence of opportunistic infection or secondary cancer.3 Important clinical manifestations include impaired mental concentration, slowness of hand movements, and difficulty in walking. This malady has been called the AIDS dementia complex by Price and colleagues3; a more recent term is HIV-1–associated cognitive–motor complex.Pathologically, the signs of HIV-1 infection in the central nervous system (or HIV . . .
Third-generation inhibitors targeting EGFR T790M mutation in advanced non-small cell lung cancer
Authors: Shuhang Wang, Shundong Cang, Delong Liu
Journal: Journal of Hematology & Oncology (2016)

The tyrosine kinase inhibitors (TKI) against epidermal growth factor receptor (EGFR) are widely used in patients with non-small cell lung cancer (NSCLC). However, EGFR T790M mutation leads to resistance to most clinically available EGFR TKIs. Third-generation EGFR TKIs against the T790M mutation have been in active clinical development. These agents include osimertinib, rociletinib, HM61713, ASP8273, EGF816, and PF-06747775. Osimertinib and rociletinib have shown clinical efficacy in phase I/II trials in patients who had acquired resistance to first- or second-generation TKIs. Osimertinib (AZD9291, TAGRISSO) was recently approved by FDA for metastatic EGFR T790M mutation-positive NSCLC. HM61713, ASP8237, EGF816, and PF-06747775 are still in early clinical development. This article reviews the emerging data regarding third-generation agents against EGFR T790M mutation in the treatment of patients with advanced NSCLC.
Abstract 2400: Circulating tumor DNA as a non-invasive substitute to metastasis biopsy for targeted sequencing in a prospective randomized trial for personalized treatment in all tumor type: The SHIVA study
Authors: Jean-Yves Pierga, Charles Decraene, Virginie Bernard, Maud Kamal, Anthony Blin, Quentin Leroy, Thomas Rio Frio, Gaëlle Pierron, Céline Callens, Ivan Bieche, Adrien Saliou, Jordan Madic, Etienne Rouleau, François-Clément Bidard, Olivier Lantz, Marc-Henri Stern, Ronald Lebofsky, Christophe Le Tourneau
Journal: Cancer Research (2015)

Abstract Rationale: The noninvasive biomarker circulating cell-free tumor DNA (ctDNA) has the potential to enable noninvasive diagnostic tests for personalized medicine in providing similar molecular information as that derived from invasive tumor biopsies. The ongoing large multicentric randomized histology-independent phase II trial (SHIVA, NCT01771458) compares molecularly targeted therapy based on tumor molecular profiling versus conventional therapy in patients with any type of refractory cancer. The screening phase consists of the invasive biopsy of metastatic tumor tissue and downstream analysis using Ion Torrent's Ampliseq hotspot cancer panel. We evaluated whether ctDNA analysis would identify the same mutations as those obtained through invasive biopsy. Patients and methods: de novo detection of somatic mutations using ctDNA in 34 patients covering 18 different tumor types, scanning ∼50 genes and more than 2500 mutations with a multiplexed next generation sequencing panel. Results: In 27 patients, 27 of 28 actionable mutations identified in metastasis biopsies (96%) were detected in matched ctDNA. Among these 27 patients, two additional mutations were found in ctDNA only. In the seven other patients, mutation detection from metastasis biopsy failed due to inadequate biopsy material, but was successful in all plasma DNA samples providing three more potential actionable mutations. Conclusion; These results suggest that ctDNA analysis is a cheaper, safer and quicker alternative to invasive biopsy of metastasis, irrespective of cancer type and metastatic site, for multiplexed mutation detection in selecting personalized therapies based on the patient's tumor genetic content. Citation Format: Jean-Yves Pierga, Charles Decraene, Virginie Bernard, Maud Kamal, Anthony Blin, Quentin Leroy, Thomas Rio Frio, Gaëlle Pierron, Céline Callens, Ivan Bieche, Adrien Saliou, Jordan Madic, Etienne Rouleau, François-Clément Bidard, Olivier Lantz, Marc-Henri Stern, Ronald Lebofsky, Christophe Le Tourneau. Circulating tumor DNA as a non-invasive substitute to metastasis biopsy for targeted sequencing in a prospective randomized trial for personalized treatment in all tumor type: The SHIVA study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2400. doi:10.1158/1538-7445.AM2015-2400
Prolonged Immune Suppression after Rituximab Use in Children
Authors: Susanne LaBarba, Blanka M. Kaplan, Barbara Eberhard
Journal: Journal of Allergy and Clinical Immunology (2016)

Rituximab is an anti-CD20 chimeric antibody that is used to treat B cell neoplasms and autoimmune disease. It induces the depletion of B lymphocytes in peripheral blood, with an average recovery time of 6-9 months. There is evidence that some patients have prolonged hypogammaglobulinemia and B-cell deficiency following Rituximab treatment (RT). We examined 10 children who received Rituximab to determine if there immune status fully recovered after treatment. A retrospective chart review was performed in 10 children that underwent RT for various autoimmune disorders. CBC, immunoglobulins, T and B cells were obtained at least 1 year after the last dose of Rituximab. The mean follow-up time was 1-4 years. 20 % (2/10) patients had low IgG 1 year or more after the RT. 50% (5/10) patients had low IgM and one patient had low IgA. 50% (5/10) had low CD19 levels 2 years after the last Rituximab dose. 20% (2/10) also had low CD3, CD4 and CD8 levels up to two years after. After RT, most patients have full recovery of B cells with no residual immune dysfunction. There is limited data in the literature regarding immune dysfunction after RT in children. In our patient sample, 8 children demonstrated some type of immune suppression 1 year or greater after treatment. Obtaining baseline studies prior to RT and close monitoring is important to differentiate RT-induced from an undiagnosed underlying immune dysfunction in these children.
A phase I dose-escalation study of LDE225, a smoothened (Smo) antagonist, in patients with advanced solid tumors.
Authors: J. Rodon Ahnert, J. Baselga, H. A. Tawbi, Y. Shou, C. Granvil, J. Dey, M. M. Mita, A. L. Thomas, D. D. Amakye, A. C. Mita
Journal: Journal of Clinical Oncology (2010)

2500 Background: LDE225 is a potent and selective inhibitor of Smo, a key signaling protein in the hedgehog (Hh) pathway. Activation of the Hh pathway is implicated in the pathogenesis of a wide range of malignancies. This first-in-human study aims to determine the maximum tolerated dose of LDE225, with additional assessments of its pharmacokinetics (PK), pharmacodynamics (PD), and potential efficacy. Methods: Patients (pts) age ≥18 with advanced solid tumors are treated with LDE225 orally once daily on a continuous 28-day dosing schedule. A single-dose 7-day PK run-in is performed prior to the first treatment cycle. A minimum of 3 patients is enrolled at each dose level, and dose escalation decisions are guided by a Bayesian logistic regression model. Hair follicles and skin biopsies are collected for PD analysis. Results: To date 25 pts have been treated across dose levels of 100, 200, 400, and 800 mg. LDE225 has been well tolerated and no DLTs have been observed. CTC grade 1–2 adverse events considered possibly treatment-related have included fatigue, nausea, vomiting, anorexia, muscle cramps, and dysgeusia. The PK of LDE225 has been dose-proportional, with a mean half-life of 60 hours. There is a 2-fold increase in Cmax and a 4-fold increase in AUC0–24h at steady-state on day 15 compared with day 1. Dose-dependent reductions in Gli1 mRNA expression in skin have been detected on day 28, with mean (95% CI) fold changes from baseline of 1.13 (−6.38, 4.91), −3.17 (−11.41, 1.14), and −7.36 (−53.45, −1.01) at 100, 200, and 400 mg/day, respectively. One pt (medulloblastoma, 200 mg/day) achieved an objective partial response (PR) that was maintained for ∼f4 months and five patients (lung adenocarcinoma, basal cell carcinoma, spindle cell sarcoma, osteosarcoma and breast cancer) have received LDE225 for more than 4 months. Conclusions: LDE225 is well tolerated and has a favorable PK profile. Continued clinical development of LDE225 is supported by the early evidence for its activity, including decreases in Gli-1 mRNA expression in skin and an objective response observed in medulloblastoma. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Institutes for Biomedical Research Novartis Novartis Novartis
Can Ticks Be Vectors for Hepatitis C Virus?
Authors: Lois Gitlin Wurzel, Ritchard G. Cable, David A. Leiby
Journal: New England Journal of Medicine (2002)

Although the study by Moseley et al. (July 11 issue) 1 was based on sound scientific principles and included a dramatic control (a sham operation), it was flawed because of the selection of patients.The study group comprised veterans, 75 years of age or younger, almost all of whom were men.This cohort of patients does not truly represent the general population.Osteoarthritis does not suddenly appear late in life, when increasing symptoms are accompanied by radiologic changes.Osteoarthritis is a degenerative process that starts with the earliest changes in the articular cartilage seen at arthroscopy and progresses to the secondary changes that can finally be identified by plain-film radiography.Although I am in full agreement with the authors that arthroscopy is of little value in the more advanced stages of osteoarthritic degeneration, it is my experience that arthroscopic lavage and débridement can dramatically improve symptoms in the early stages of osteoarthritis and can do so for several years.To cast doubt on all arthroscopic surgery for osteoarthritis, with the implication that it is worthless, does a disservice to the increasing number of people in our population who have early stages of arthritis and might deprive them of this treatment.
Case report: Fulminant pneumococcal sepsis in an unvaccinated asplenic patient in Italy
Authors: M Chironna, A Sallustio, A De Robertis, M Quarto, C Germinario
Journal: Eurosurveillance (2010)

We report a fatal case of overwhelming pneumococcal infection in an asplenic young adult not vaccinated against Streptococcus pneumoniae (S. pneumoniae). Post-mortem microbiological investigations revealed the presence of S. pneumoniae in blood samples and lungs. Serotyping by molecular methods identified the presence of a 6C serotype not comprised in the current 23-valent pneumococcal vaccine, highlighting that a risk of fatal infections may persist even in vaccinated splenectomised individuals.
ATPS-94THIRD GENERATION mTOR INHIBITORS IN GLIOBLASTOMA
Authors: QiWen Fan, Robyn Wong, Chris Novotny, Masanori Okaniwa, Theodore Nicolaides, Kevan Shokat, William Weiss
Journal: Neuro-Oncology (2015)

The mTOR serine-theronine kinase exists in two distinct multi-protein mTORC complexes. First generation allosteric inhibitors of mTOR (rapalogs) block mTORC1, whereas second generation mTOR kinase inhibitors (MLN128) inhibit both mTORC1 and mTORC2. Although rapalogs and mTOR kinase inhibitors are in clinical trials, rapalogs are inefficient mTORC1 blockers, while blockade of mTORC2 by mTORCi is poorly tolerated by normal cells, perhaps due to components of mTORC2 being essential genes. We synthesized and here characterize third generation mTOR kinase inhibitors that show improved efficacy in glioblastoma, tied to highly efficient blockade of mTORC1, with relative mTORC2 sparing. Compared to rapamycin, MLN128, and the AKT inhibitor MK-2206, third generation mTOR inhibitors were 10-100 fold more active as antiprolfierative agents, driving arrest in G1 without appreciable induction of apoptosis. Third generation mTOR inhibitors demonstrated efficacy in cells wild-type and mutant for PTEN, a negative regulator of PI3K signaling. We demonstrate that third generation efficiently blocked the mTORC1 targets S6K and EIF4E, and traced the increased activity of these agents mTOR inhibitors to higher affinity for mTORC1, in comparison with rapamycin and MLN128. We also demonstrated that third generation mTOR inhibitors cross the blood brain barrier. In vivo testing in orthotopic PDX models is underway, and will be discussed.
Treatment of Children with Port-Wine Stains Using the Flashlamp-Pulsed Tunable Dye Laser
Authors: Oon Tian Tan, Karen Sherwood, Barbara A. Gilchrest
Journal: New England Journal of Medicine (1989)

Thirty-five children, three months to 14 years of age, with disfiguring port-wine stains were treated with a flashlamp-pulsed tunable dye laser. All had complete clearing of the stains after an average of 6.5 laser treatments to each lesional area; skin over bony prominences required approximately half as many sessions as skin on the cheek. Children less than seven years old required fewer sessions (mean ±SD, 5.8±1.1) than older children (7.1±1.1; P<0.05). Treated skin was identical in texture and color to adjacent normal skin in 33 (94.3 percent) of the children, whereas 2 (5.7 percent) had small, isolated, depressed scars in areas accidentally traumatized soon after laser treatment. The only other side effect was transient hyperpigmentation, which occurred in 20 patients (57 percent). These results can be attributed to two distinguishing characteristics of the flashlamp-pulsed tunable dye laser: an emission wavelength of 577 nm, theoretically ideal for selective absorption by the intravascular target oxyhemoglobin, and a pulse duration of 360 μsec, which closely matches the thermal relaxation time for dermal blood vessels and hence avoids diffuse nonspecific thermal necrosis with subsequent scarring of the treated skin. (N Engl J Med 1989;320:416–21.)
Problems of Spectrum and Bias in Evaluating the Efficacy of Diagnostic Tests
Authors: David F. Ransohoff, Alvan R. Feinstein
Journal: New England Journal of Medicine (1978)

Abstract To determine why many diagnostic tests have proved to be valueless after optimistic introduction into medical practice, we reviewed a series of investigations and identified two major problems that can cause erroneous statistical results for the "sensitivity" and "specificity" indexes of diagnostic efficacy. Unless an appropriately broad spectrum is chosen for the diseased and nondiseased patients who comprise the study population, the diagnostic test may receive falsely high values for its "rule-in" and "rule-out" performances. Unless the interpretation of the test and the establishment of the true diagnosis are done independently, bias may falsely elevate the test's efficacy. Avoidance of these problems might have prevented the early optimism and subsequent disillusionment with the diagnostic value of two selected examples: the carcinoembryonic antigen and nitro-blue tetrazolium tests. (N Engl J Med 299:926–930, 1978)
Hypercalcemia and Increased Parathyroid-Hormone Activity in a Primary Hepatoma
Authors: R. P. Knill-Jones, Richard M. Buckle, Victor Parsons, R. Y. Calne, Roger Williams
Journal: New England Journal of Medicine (1970)

A patient with hypercalcemia associated with a carcinoma of the intrahepatic bile ducts showed some decrease in serum calcium after a course of prednisone. Orthotopic liver transplantation was followed by a further fall in serum calcium, and the urinary excretion of calcium and hydroxyproline returned to normal. The circulating concentration of immunoassayable parathyroid hormone was elevated before and fell to normal after transplantation. Parathyroid hormone was demonstrated in extracts of the resected tumor. At operation arteriovenous and venovenous gradients across the liver suggested that the hepatic tumor was actively secreting a parathyroid-hormone–like polypeptide into the circulation.
A preliminary study of the personality of the nightmare sufferer: relationship to schizophrenia and creativity?
Authors: E Hartmann, D Russ, B van der Kolk, R Falke, M Oldfield
Journal: American Journal of Psychiatry (1981)

Through psychiatric interviews and psychological tests the authors studied 38 adults who reported experiencing at least one nightmare per week. Nearly all of the subjects had a lifelong history of frequent nightmares. Four of the subjects met DSM-III criteria for schizophrenia, 9 met the criteria for borderline personality, and 6 met the criteria for schizotypal personality. The others had no specific diagnosis, and none of the subjects had a diagnosis of typical neurosis. Many had mentally ill relatives. Most had artistic interests and talents. These nightmare sufferers may be seen as unusually vulnerable, with a potential for mental illness--especially schizophrenia--as well as a potential for artistic achievement.
End-Stage Renal Failure in Primary Hyperoxaluria Type 2
Authors: Martino Marangella, Michele Petrarulo, Domenico Cosseddu
Journal: New England Journal of Medicine (1994)

To the Editor: Primary hyperoxaluria with l-glyceric aciduria (primary hyperoxaluria type 2) is caused by a deficiency of d-glycerate dehydrogenase,1 which catalyzes the conversion of hydroxypyruva...