tbuckley/cabot-search huggingface dataset:
An Anomaly of Neutrophil Morphology with Impaired Function
Authors: Ronald G. Strauss, Kevin E. Bove, James F. Jones, Alvin M. Mauer, Vincent A. Fulginiti
Journal: New England Journal of Medicine (1974)

Neutrophils from a boy with recurrent bacterial infections since infancy were found to have unique morphologic abnormalities. The nuclei were bilobed, and the cytoplasm appeared nearly devoid of granules in blood smears subjected to Wright-Giemsa stain. Neutrophil alkaline phosphatase activity was absent by histochemical staining. In ultrastructural studies of bone marrow, specific granules were found to be delayed in appearance and abnormal in structure. After the ingestion of Staphylococcus aureus by the cell, abnormal phagolysosomes were formed, and bactericidal function was impaired. The basic abnormality in this patient appears to be a congenital abnormality of specific granule formation. (N Engl J Med 290:478–484, 1974)
Case 11-1993
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Bartolome R. Celli, Eugene J. Mark
Journal: New England Journal of Medicine (1993)

Presentation of CaseA 52-year-old man with cardiomyopathy and interstitial lung disease was admitted to the hospital in extremis.Asthma began at the age of 10 years. A coarctation of the aorta was repaired at the age of 22 years. At the age of 36 years progressive exertional dyspnea developed, with orthopnea and paroxysmal nocturnal dyspnea. Furosemide was prescribed, with improvement.At 37 years of age the patient was admitted to this hospital for cardiac catheterization. He consumed one or two bottles of wine and smoked 1 1/2 packs of cigarettes daily. On physical examination the blood pressure was 120/80 . . .
Abstract P3-12-06: Active breathing control in the management of left-sided breast cancer with irradiation: A dosimetric analysis of cardiac and lung dose
Authors: ES Gogineni, JD Kehrer, GC Jones, C Premo, S Stinson
Journal: Cancer Research (2016)

Abstract Purpose: Deep inspiratory breath hold (DIBH) is a technique that has been increasingly utilized over the past several years for the purpose of reducing the radiation dose received by the heart and ipsilateral lung during radiotherapy (RT) for breast cancer. The purpose of this study was to provide a comparative analysis of cardiac and lung dose in patients treated with and without moderate DIBH with an active breathing control (ABC) device during RT for left-sided breast cancer at a community radiation oncology center. Methods: From June 2013 to December 2014, 83 patients with stages 0-III left-sided breast cancer were treated with RT. Of these, 45 patients underwent CT simulation with an ABC device and the remaining 38 patients underwent standard free-breathing CT simulation for RT planning. Twenty-eight patients in the ABC cohort were treated with standard tangent fields and 18 were treated with locoregional RT. The non-ABC cohort included 26 patients treated with standard tangents and 12 treated with locoregional RT. A 4- or 5-field technique was utilized in all locally advanced patients to allow for coverage of the supraclavicular fossa and internal mammary lymph nodes with inclusion of low axillary coverage based on individual risk factors. All patients were treated with 3D-conformal techniques utilizing multi-leaf collimators to block the heart. Comparisons were made between mean heart dose, heart V5, mean lung dose, and lung V5 with and without the use of ABC. Kruskal-Wallis tests were used to determine significance between groups with α for significance set at p ≤0.05. Results: On combined analysis, the use of DIBH with ABC resulted in a reduction in heart V5 (1.5 versus 5.4%; p=0.018). Mean heart dose, mean lung dose, and lung V5 were not significantly improved with the use of ABC. On subgroup analysis, patients treated with locoregional RT had reduced mean heart dose (161 cGy versus 309 cGy; p=0.014) and heart V5 (2.3% versus 14.8%; p&amp;lt;0.001) compared to patients treated with a standard free-breathing technique. Conclusions: The use of ABC provided a significant reduction in heart V5 in all patients with left-sided breast cancer and in mean heart dose and heart V5 in patients treated with locoregional RT. This retrospective, single-institution analysis demonstrates the feasibility of implementing moderate DIBH with ABC technology in the treatment of left-sided breast cancer in a community radiation oncology center. Citation Format: Gogineni ES, Kehrer JD, Jones GC, Premo C, Stinson S. Active breathing control in the management of left-sided breast cancer with irradiation: A dosimetric analysis of cardiac and lung dose. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-12-06.
Letrozole (L) with bevacizumab (B) is feasible in patients (pts) with hormone receptor-positive metastatic breast cancer (MBC)
Authors: T. A. Traina, H. Rugo, J. Caravelli, B. Yeh, K. Panageas, J. Bruckner, L. Norton, J. Park, C. Hudis, M. Dickler
Journal: Journal of Clinical Oncology (2006)

3050 Background: Bevacizumab added to chemotherapy (CRx) prolongs PFS in pts with MBC. Data suggest that estrogen (E 2 ) modulates VEGF-induced angiogenesis in physiologic and pathologic conditions. E 2 -induced VEGF expression may promote breast cancer growth therefore combination therapy with an aromatase inhibitor (AI) and an antibody to VEGF may be more effective than either agent alone. We performed a feasibility study testing B with L for the treatment (tx) of hormone receptor-positive MBC. Methods: Eligible pts have MBC and are candidates for AI therapy. Prior non-steroidal AI (NSAI) use without progression is permitted. Premenopausal pts undergo ovarian suppression/oophorectomy prior to tx. Therapy consists of L (2.5 mg daily) and B (15 mg/kg IV q3 weeks). The primary endpoint is frequency of Grade (Gr) 4 toxicity. Secondary endpoints include response rate, stable disease (SD) ≥ 6 mo and time to tumor progression. Using a two-stage design, 19 pts were accrued. Because &lt;3 pts had Gr 4 toxicity, the 2 nd stage is now enrolling an additional 23 pts. If &lt;5 of the 42 pts have Gr 4 toxicity, the regimen will be considered feasible. Results: Thirty two pts are currently accrued and 28 are now evaluable. Medians: Age 49.5 yrs (32–77) and ECOG PS 0 (0–1). Sites of MBC: bone only 11/28, visceral 16/28, chest wall/soft tissue/lymph nodes 11/28. All are ER and/or PR (+); none are HER2 (+). Prior therapy: adjuvant CRx 20; adjuvant tamoxifen 14. Twenty five pts received an NSAI as first-line tx of MBC, starting a median of 23 wks (1–213) before B. Three pts received first-line tamoxifen; one pt had prior CRx for MBC. After a median of 8 cycles (1–20), tx-related toxicities: Gr 2: hypertension (HTN) 4, headache (HA) 4, proteinuria 3, fatigue 6, joint pain 5, hot flashes 1, epistaxis 1; Gr 3: HTN 5, HA 1, proteinuria 1. There has been no tx-related Gr 4/5 toxicity. Tx-related withdrawals: HTN 1 and headache 1. Twenty five pts are evaluable for response: PR 2, SD ≥ 6 mo 13, SD 4, progression 6. Conclusions: Combination L and B is well tolerated and will be studied in a randomized CALGB trial. Circulating endothelial and tumor cell data is reported separately. Supported in part by Genentech and Novartis. [Table: see text]
Recent Advances in Dermatology
Authors: Tania J. Phillips, Jeffrey S. Dover
Journal: New England Journal of Medicine (1992)

THE past decade has witnessed important advances in the field of dermatology, several of which we have selected for review in this paper.Acne VulgarisAcne vulgaris, the most common skin disease seen in dermatologic practice, affects approximately 17 million people in the United States.1 Its precise cause is unknown, although abnormal keratin production with obstruction of the follicular opening, increased production of sebum (lipids secreted by the androgen-sensitive sebaceous glands), and proliferation of Propionibacterium acnes (anaerobic follicular diphtheroids) leading to inflammation play a part.1Topical treatments for mild and moderate cases of acne include comedolytic agents, such as tretinoin . . .
Mortality Rates and Risk Factors for Coronary Disease in Black as Compared with White Men and Women
Authors: Julian E. Keil, Susan E. Sutherland, Rebecca G. Knapp, Daniel T. Lackland, Peter C. Gazes, Herman A. Tyroler
Journal: New England Journal of Medicine (1993)

Currently recognized risk factors for coronary artery disease have been identified primarily from investigations of white populations. In this investigation, we estimated mortality rates for coronary disease and for any cause and identified risk factors for death from coronary disease among whites and blacks.
Adjuvant Trastuzumab Benefit in Patients Diagnosed With Triple-Positive Breast Cancer
Authors: Anne F. Schott
Journal: JAMA Oncology (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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Oncology journal
Abstract A52: Investigation of p53 restoration therapy in a mouse model of pineoblastoma
Authors: Mohammad Harajly, Hassan Zalzali, Zafar Nawaz, Raya Saab
Journal: Cancer Research (2016)

Abstract Background: Pineoblastoma is a malignant childhood tumor with poor outcomes. We have previously characterized a mouse model of pineoblastoma induced by transgenic expression of Cyclin D1 in a p53 null background. We showed that Cyclin D1 expression in the setting of intact p53 results in pineal hyperplasia, but no onset of invasive tumors, reminiscent of pineal enlargement seen in a subset of children with RB haploinsufficiency. In the setting of p53 loss, pineoblastoma occurs with 100% penetrance. We now investigated the role of p53 restoration therapy in prevention and treatment of pineoblastoma using this mouse model. Results: We found that restoration of p53 in mouse pre-malignant proliferating pineal tumors results in tumor prevention, shown by effective cell cycle exit and induction of cellular senescence, a tumor suppressor mechanism. Conversely, p53 reactivation in established malignant pineal tumors had no effect cell proliferation, unless paired with DNA damaging therapy. The response to p53 restoration did not correlate with levels of p19Arf expression. Interestingly, in premalignant lesions, p53 restoration was associated with secondary amplification of MAPK signaling and induction of p19Arf expression. Subsequent inactivation of p53 after senescence resulted in diffuse re-entry into the cell cycle and rapid tumor progression. Evaluation of a panel of human supratentorial primitive neuroectodermal tumors showed low activity of the p53 pathway, while only one of 6 tumors had p53 deletion or mutation. Conclusion: Our data shows that, in a mouse model of Cyclin D1-driven pineoblastoma, restoration of p53 has different effects in premalignant versus invasive pineal tumors, where it may need to be paired with DNA damaging agents for effective tumor suppression. Furthermore, p53 activation may need to be continually sustained in such lesions undergoing senescence. Finally, p53 restoration approaches may be worth exploring in sPNET, where the p53 gene seems to be intact but the pathway inactive in the majority of examined tumors. Citation Format: Mohammad Harajly, Hassan Zalzali, Zafar Nawaz, Raya Saab. Investigation of p53 restoration therapy in a mouse model of pineoblastoma. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr A52.
P286 Correlations of functional multi-nuclear MR imaging indices with pulmonary function tests in the assessment of idiopathic pulmonary fibrosis
Authors: ND Weatherley, NJ Stewart, H Marshall, G Collier, K Hart, F Horn, G Norquay, MK Whyte, S Bianchi, JM Wild
Journal: Thorax (2015)

<h3></h3> Disease progression in idiopathic pulmonary fibrosis (IPF) is variable and unpredictable. Declining forced vital capacity (FVC) and transfer factor (TLCO) of 10% and 15% respectively are common markers of deterioration, but may be insufficiently sensitive to prognosticate and rely on serial measurements. Echocardiography provides screening for pulmonary artery hypertension (PAH), but is insensitive to pulmonary haemodynamic change before PAH is already apparent. Recently established Magnetic Resonance Imaging (MRI) techniques may provide insight into evaluating IPF. Greater septal thickness as measured by hyperpolarised xenon in patients with IPF compared with with healthy volunteers was previously demonstrated.<sup>1</sup> Here, we investigate the correlation between MRI indices, including hyperpolarised gas ventilation and gadolinium-enhanced perfusion, with pulmonary function parameters in a pilot cohort of subjects with IPF. Six subjects with IPF were recruited. T1 mapping was performed in all subjects. Imaging sequences following inhalation of hyperpolarised 3-Helium was used to calculate estimates for ventilated volume percentage (VV%) and coefficient of variation of ventilation (CoV). Dynamic contrast-enhanced lung perfusion MRI was performed for pulmonary haemodynamic assessment All subjects underwent pulmonary function testing (PFTs). VV% strongly correlated with transfer coefficient (KCO) with R = 0.955; p = 0.003, but also FEV (forced vital capacity)/FVC ratio. CoV is a measure of regional ventilation heterogeneity and trended to correlation with transfer factor TLCO (R = -0.775; p = 0.108). Time to peak (TTP) of the gadolinium perfusion signal showed negative correlation with FVC (R = -0.909 with p &lt; 0.05) and trended to a negative correlation with TLCO (R = -0.766, p = 0.131). All p values two-tailed. TTP correlation with PFT values suggests that changes in pulmonary haemodynamics may be detectable at an early stage of the disease process. VV% and helium mapping may provide information about regional airways ventilation in IPF. MRI based assessments could prove useful in assessing different aspects of lung structure-function for use in future research and potentially in clinical assessment of patients with IPF. Sequential imaging with concurrent PFT and echocardiography would help to further assess the applicability of evolving MRI techniques. <h3>Reference</h3> 1 Stewart NJ, <i>et al</i>.<i> Magn Reson Med</i>. 2015;<b>74</b>(1):196–207
Mutation position in BRCA-associated breast cancers.
Authors: F. Meric-Bernstam, A. Gutierrez-Barrera, J. K. Litton, L. Mellor-Crummey, K. Ready, A. M. Gonzalez-Angulo, K. H. Lu, G. N. Hortobagyi, B. Arun
Journal: Journal of Clinical Oncology (2010)

1542 Background: Individuals with germline BRCA1 or 2 mutations are at high risk for breast cancer; studies are ongoing to determine subgroups that may be at lower risk. For BRCA1, a trend of increasing risk has been associated with increasing downstream (3′) location of mutations compared to the upstream (i.e., 5’) mutations. For BRCA2, compared with no mutation, an increased risk of breast cancer has been associated with mutations outside of the “ovarian cancer cluster region” (OCCR). We sought to determine the mutation position in BRCA- associated breast cancers and whether there was a genotype-phenotype correlation. Methods: Patients with breast cancer with BRCA1 or 2 mutations were identified by a search of a prospectively maintained database at a major cancer center. BRCA mutation site, patient and tumor characteristics were determined through retrospective review. Results: One hundred and sixty patients with BRCA1-associated breast cancers and 102 patients with BRCA2-associated breast cancer were identified. Of 160 patients with BRCA1-associated cancers, 85 (53%) had mutations in the 5’ half of the gene. There was no difference in median age, tumor size, ER/PR status and nodal status between patients with 5’ vs. 3’ mutations. Of the 102 patients with BRCA2-associated breast cancers, 37 (36%) had OCCR mutations. There was no difference in median age, tumor size, ER/PR status and nodal status between patients with OCCR vs non-OCCR mutations. Conclusions: In this single institution study, over half of BRCA1-associated breast cancers and over a third of BRCA2-associated breast cancers were associated with putative lower risk mutation positions. Although we cannot exclude that patients with mutations in these regions have a lower relative risk for breast cancer, vigilance in cancer screening and prevention remains necessary. Further studies in genotype/phenotype correlation are needed to individualize cancer prevention strategies. No significant financial relationships to disclose.
Clinical Relevance Of VEGF-C/VEGF-D/VEGFR-3 Axis In Diffuse Large B-Cell Lymphoma
Authors: Dariusz Wolowiec, Anna Wosztyl, Ewelina Ziolkowska, Ewa Robak, Marcin Pasiarski, Tadeusz Robak, Anna Korycka-Wolowiec
Journal: Blood (2013)
Venous Thrombosis and Pulmonary Embolism
Authors: John Homans
Journal: New England Journal of Medicine (1947)

PULMONARY embolism, once regarded as an unavoidable accident of surgery, today preoccupies the minds of many clinicians, physicians and surgeons alike. For it is recognized as a threatened complication in the great field of serious diseases, injuries and operations that depress the patient and enforce life in bed.In the last decade, pathologists have shown that when post-mortem examinations of the legs are thoroughly made, thrombosis is found in the deep veins of the calf in nearly 50 per cent of all cases at autopsy. Much of this thrombosis is terminal and in no sense a cause of death. Yet . . .
Circulating Virus, Interferon and Antibody after Vaccination with the 17-D Strain of Yellow-Fever Virus
Authors: E. Frederick Wheelock, William A. Sibley
Journal: New England Journal of Medicine (1965)

CIRCULATING interferon has been induced in laboratory animals by the inoculation of several different viruses.1 , 2 In man circulating interferon has been detected after the intravenous administration of viruses to a patient with acute leukemia3 as well as in a number of patients with naturally occurring clinical viral infections.4 In the latter the lack of virus isolations precluded the establishment of any relation between the type of virus, time of infection and virus, interferon and antibody production. In an attempt to establish these relations recent studies both in this laboratory and elsewhere have been concerned with infections produced by live-virus vaccines, . . .
Autoantibodies to a 128-kd Synaptic Protein in Three Women with the Stiff-Man Syndrome and Breast Cancer
Authors: Franco Folli, Michele Solimena, Roxanne Cofiell, Mario Austoni, Giovanni Tallini, Giuliano Fasseta, David Bates, Niall Cartlidge, Gian Franco Bottazzo, Giovanni Piccolo, Pietro De Camilli
Journal: New England Journal of Medicine (1993)

The stiff-man syndrome is a rare disease of the central nervous system characterized by progressive rigidity of the body musculature. Autoantibodies directed against glutamic acid decarboxylase are present in about 60 percent of patients with the syndrome. In this group, there is a striking association of the stiff-man syndrome with organ-specific autoimmune diseases, primarily insulin-dependent diabetes mellitus.
Hemangioma of Cervical Vertebras with Spinal-Cord Compression
Authors: Leonard R. Robbins, Edmund M. Fountain
Journal: New England Journal of Medicine (1958)

A NUMBER of conditions, relatively common at autopsy, only rarely become of clinical importance. An example involving the nervous system is cyst of the septum pellucidum, or fifth ventricle, which can be a common incidental finding at autopsy, especially in infants. Several autopsy series have been reported1 2 3 in which detailed search of the spine discloses the frequency of vertebral hemangioma to be 10 to 12 per cent, mostly in the dorsal and lumbar regions. Only rarely, however, does such a hemangioma cause spinal-cord compression. Myelocompression by hemangioma of the cervical vertebral bodies is particularly unusual. Since early recognition and prompt . . .
Phase II study of bevacizumab and nitrosourea in patients with recurrent malignant glioma: A multicenter Italian study
Authors: R. Soffietti, R. Rudà, E. Trevisan, E. Picco, D. Guarneri, M. Caroli, M. Fabrini, V. Scotti
Journal: Journal of Clinical Oncology (2009)

2012 Background: Bevacizumab (BV) has shown a promising activity in recurrent malignant gliomas (MG) in combination with irinotecan. Few data are available on the combination of bevacizumab and nitrosoureas, that represent the standard cytotoxic option at recurrence. Methods: In this ongoing phase II study patients with MG recurrent after surgery, radiation therapy, and temozolomide are eligible. The treatment consists of an induction phase with BV at 10 mg/kg intravenously on day 1 and 15 and fotemustine (FTM) (a nitrosourea with elevated lipophilic properties) at 75 mg/m 2 intravenously on day 1 and 8, followed after a 3-week interval by a maintenance phase with BV at 10 mg/kg i.v. and FTM 75 mg/m 2 i.v. every 3 weeks until tumor progression or unacceptable toxicity. Patients undergo clinical and MRI assessment 1 month after the start of treatment and thereafter every 2 months. Monitoring of CBV with perfusion MRI is performed in selected centers. The co-primary endpoints are objective response rate (ORR), based on Mc Donald's criteria (CR + PR) and progression-free survival at 6 months (PFS6), with secondary endpoints of safety time to tumor progression (TTP) and overall survival. Results: From April 2008 to December 2008, 34 patients were enrolled and 31 (22 glioblastomas and 9 anaplastic gliomas) are evaluable for response. Overall response rate (2 CR and 9 PR) was 35% (glioblastomas 33%, anaplastic gliomas 41.5%). Median time to maximal response was 1 month. Steroids were reduced in 50% of patients. Sixteen of 31 patients progressed with a TTP of 2.6 months (1–8.5). Patterns of progression were local in 10/16, local + leptomeningeal spread in 3/16 and gliomatosis in 3/16. Fifteen patients are free of tumor progression (from 2 to 8 months). Toxicities included grade III-IV neutropenia in three patients, grade III-IV piastrinopenia in five, and grade III thrombosis in two. Seventeen patients developed mild to moderate fatigue, six arterial hypertension, and three grade I intratumoral haemorrhage. Conclusions: Combination of bevacizumab and fotemustine in recurrent malignant gliomas is safe and promising. Updated results, monitoring of CBV with perfusion MRI, and correlations between MGMT promoter methylation and response/outcome will be presented. No significant financial relationships to disclose.