tbuckley/cabot-search huggingface dataset:
Von Hippel-Lindau Disease: Genetics and Role of Genetic Counseling in a Multiple Neoplasia Syndrome
Authors: Sarah M. Nielsen, Lindsay Rhodes, Ignacio Blanco, Wendy K. Chung, Charis Eng, Eamonn R. Maher, Stéphane Richard, Rachel H. Giles
Journal: Journal of Clinical Oncology (2016)

Von Hippel-Lindau disease (VHL) is one of the most common inherited neoplasia syndromes and is characterized by highly vascular tumors of the eyes, brain, and spine, as well as benign and malignant tumors and/or cysts of the kidneys, adrenal medullae and sympathetic paraganglia, endolymphatic sac, epididymis, and broad ligament. Since the discovery of the VHL gene in 1993, more than 900 families with VHL have been identified and examined. Genetic testing for VHL is widely available and will detect a disease-causing mutation in rate 95% to 100% of individuals who have a clinical diagnosis of VHL, making it the standard of care for diagnosis of VHL. Furthermore, genetic testing for VHL is indicated in some individuals with seemingly sporadic VHL-related tumor types, as ≤ 10% of pheochromocytoma or early-onset renal cell carcinoma and ≤ 40% of CNS hemangioblastoma harbor germline VHL mutations without a family history or additional features of VHL disease. The majority of VHL mutations are private, but there are also well-characterized founder mutations. VHL is a complex, multiorgan disease that spans the breadth of oncology subspecialties, and, as such, providers in these subspecialties should be aware of when to consider a diagnosis of VHL, when to refer a patient to a genetics specialist for consideration of gene testing, and, perhaps most importantly, how to communicate this sensitive information in an age-appropriate manner to at-risk families. This review will provide state-of-the-art information regarding the genetics of VHL and will serve as a key reference for nongenetics professionals who encounter patients with VHL.
Case 35-1971
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. McNeely, Franz J. Ingelfinger, Benjamin Castleman
Journal: New England Journal of Medicine (1971)

Presentation of Case First admission. A 60-year-old woman was admitted to the hospital because of fever.She had been well until six years previously, when arthralgia developed in multiple joints; she was treated with aspirin and indomethacin. Six months before admission she had a shaking chill and fever, which recurred once or twice monthly until the time of entry, lasting for a few hours on each occasion and followed by fatigue. During the two months before entry she experienced malaise, and chills and fever occurred as often as three times weekly, usually at night.Thirty-four years earlier the patient's . . .
Evaluation of routine radiation boost following breast conservation therapy in young patient
Authors: J. P. Lamont, M. Faynsod, D. Smith, R. Pezner, J. D. I. Ellenhorn
Journal: Journal of Clinical Oncology (2004)

709 Background: A recent trial compared local radiation boost (RB) to no local boost (NB) following breast conservation therapy. Fewer local recurrences (LR) occurred in the RB group, most pronounced in patients ≤ 40 years old. The current study evaluates LR in young patients at an institution where RB is not routine. Methods: A retrospective review was performed on patients ≤ 40 years with primary breast cancer who underwent adjuvant breast radiation from 1980–1999. RB was added to patients at high risk for LR (close margins, multifocal tumors). Results: Seventy-five patients with a median age of 37 years (range 24–40) were followed for a median 7.6 years (range 0.5–17.7). Twenty-six patients received a RB while 49 patients were treated with uniform breast radiation only. Multifocal tumors, were more prevalent in the RB group (19% vs. 2%, p=0.03). LR occurred in 8 of 75 patients (11%). There was no difference in LR between NB group (3/49, 6.1%) and RB group (5/26, 19.2%)(p=0.18). LR in the same quadrant as the primary tumor was found in 2 patients in the NB group (4%) and 3 patients in the RB group (n=12%)(p=0.23). There were no significant differences in overall survival, disease-free survival, and same quadrant disease-free survival between the two groups. The addition of a radiation boost was not predictive of local recurrence by univariate and multivariate analyses. Conclusions: Uniform breast irradiation resulted in low ipsilateral and same quadrant recurrence rates. Routine RB does not appear to be justified in young patients. No significant financial relationships to disclose.
Cardiac Fibro-Adipocyte Progenitors Express Desmosome Proteins and Preferentially Differentiate to Adipocytes Upon Deletion of the Desmoplakin Gene
Authors: Raffaella Lombardi, Suet Nee Chen, Alessandra Ruggiero, Priyatansh Gurha, Grazyna Z. Czernuszewicz, James T. Willerson, Ali J. Marian
Journal: Circulation Research (2016)

Rationale: Mutations in desmosome proteins cause arrhythmogenic cardiomyopathy (AC), a disease characterized by excess myocardial fibroadipocytes. Cellular origin(s) of fibroadipocytes in AC is unknown. Objective: To identify the cellular origin of adipocytes in AC. Methods and Results: Human and mouse cardiac cells were depleted from myocytes and flow sorted to isolate cells expressing platelet-derived growth factor receptor-α and exclude those expressing other lineage and fibroblast markers (CD32, CD11B, CD45, Lys76, Ly −6c and Ly 6c , thymocyte differentiation antigen 1, and discoidin domain receptor 2). The PDGFRA pos :Lin neg :THY1 neg :DDR2 neg cells were bipotential as the majority expressed collagen 1 α-1, a fibroblast marker, and a subset CCAAT/enhancer-binding protein α, a major adipogenic transcription factor, and therefore, they were referred to as fibroadipocyte progenitors (FAPs). FAPs expressed desmosome proteins, including desmoplakin, predominantly in the adipogenic but not fibrogenic subsets. Conditional heterozygous deletion of Dsp in mice using Pdgfra-Cre deleter led to increased fibroadipogenesis in the heart and mild cardiac dysfunction. Genetic fate mapping tagged 41.4±4.1% of the cardiac adipocytes in the Pdgfra-Cre : Eyfp:Dsp W /F mice, indicating an origin from FAPs. FAPs isolated from the Pdgfra-Cre : Eyfp:Dsp W /F mouse hearts showed enhanced differentiation to adipocytes. Mechanistically, deletion of Dsp was associated with suppressed canonical Wnt signaling and enhanced adipogenesis. In contrast, activation of the canonical Wnt signaling rescued adipogenesis in a dose-dependent manner. Conclusions: A subset of cardiac FAPs, identified by the PDGFRA pos :Lin neg :THY1 neg :DDR2 neg signature, expresses desmosome proteins and differentiates to adipocytes in AC through a Wnt-dependent mechanism. The findings expand the cellular spectrum of AC, commonly recognized as a disease of cardiac myocytes, to include nonmyocyte cells in the heart.
Graduate medical education
Authors: C Ragan
Journal: JAMA (1992)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Abstract 1244: Hyperthermia and chemotherapy mediated effects on tumor cell proliferation and heat shock protein expression in human colon cancer
Authors: Tanja Grimmig, Rebeca Thumm, Romana Moench, Eva M. Moll, Christoph T. Germer, Ana Maria Waaga-Gasser, Martin Gasser
Journal: Cancer Research (2015)

Abstract In patients with peritoneal carcinomatosis (PC) of gastrointestinal cancer hyperthermic intraperitoneal chemotherapy (HIPEC) represents a promising treatment option integrated into multimodal concepts. Heat shock proteins (HSP) play a major role in cellular stress response conferring increased resistance in tumor cells. Therefore we analyzed HSP expression profiles in tumor cells exposed to hyperthermic and chemotherapeutic stress. To mimic HIPEC-like conditions HT29 colon cancer cells were exposed to varying hyperthermic conditions for 60 min with additional 5-fluorouracil (5-FU) treatment. HSP expression was analyzed 30 min, 24 h, 48 h and 72 h after treatment using Western Blot and RT-qPCR. Untreated cells cultivated at 37°C served as controls. Additionally, effects on tumor cell proliferation were determined 24 h, 48 h and 72 h after treatment by MTS-assay. Hyperthermia caused temperature dependent upregulation of HSP27, HSP70, HSP72, and HSP90 gene and protein expression that was further increased by additional cytotoxic 5-FU treatment. 5-FU initiated progressive rise in HSP gene expression up to 72 h after 1 h exposure at normothermia as well as under hyperthermia. After isolated hyperthermia tumor cell proliferation was recovered at 72 h. Antiproliferative effects of 5-FU could not be enhanced by further increased hyperthermia. Antiproliferative effects of hyperthermia induced during HIPEC therapy seem to be negatively influenced by highly conserved HSP mechanisms. Our findings suggest that HSP27, HSP70/72, and HSP90 are significantly involved in hyperthermia and chemotoxicity mediated cell stress repair mechanisms. While initial increase in HSP expression can counteract cytotoxic effects during HIPEC therapy long-term elevated expression levels may cause lasting resistance to cellular stress. Note: This abstract was not presented at the meeting. Citation Format: Tanja Grimmig, Rebeca Thumm, Romana Moench, Eva M. Moll, Christoph T. Germer, Ana Maria Waaga-Gasser, Martin Gasser. Hyperthermia and chemotherapy mediated effects on tumor cell proliferation and heat shock protein expression in human colon cancer. [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 1244. doi:10.1158/1538-7445.AM2015-1244
Memory Enhancement and Deep-Brain Stimulation of the Entorhinal Area
Authors: Andres H Neuhaus, Malek Bajbouj
Journal: New England Journal of Medicine (2012)

n engl j med 366;20 nejm.org may 17, 2012 1945 To the Editor: The study by Suthana and coworkers (Feb. 9 issue)1 involved patients with pharmacoresistant epilepsy who underwent implantation of intracranial depth electrodes before possible surgical resection. The authors found that stimulation of the entorhinal cortex, but not of the hippocampus proper, during the learning phase of a spatial-navigation task resulted in more efficient performance. This finding may serve as a starting point for future neuromodulatory interventions aimed at treating disorders with medial temporal-lobe dysfunction and associated cognitive dysfunction. In the context of identification of therapeutic targets, a more precise description of electrode localization, especially along the anterior-posterior axis, would considerably strengthen the findings. Spatial navigation, as tested in the current study, is functionally associated with the posterior hippocampus, as shown by long-standing evidence obtained from studies involving various species, including monkeys2 and humans.3 Electrical conduction could have affected structures that were not directly targeted by the electrodes of interest; this further underscores the importance of clarifying electrode positions in three-dimensional space for every patient.
MDM2 inhibition rescues neurogenic and cognitive deficits in a mouse model of fragile X syndrome
Authors: Yue Li, Michael E. Stockton, Ismat Bhuiyan, Brian E. Eisinger, Yu Gao, Jessica L. Miller, Anita Bhattacharyya, Xinyu Zhao
Journal: Science Translational Medicine (2016)

The MDM2 inhibitor Nutlin-3 rescues neurogenic and cognitive deficits in mice with fragile X syndrome.
Evolution of the Expression of Fetal Acinar Antigens During Carcinogenesis of the Pancreas in Hamsters: Individual Follow-up by Open Biopsy
Authors: M Eriguchi, A Carré-Llopis, S Orbach-Arbouys, J Escribano
Journal: JNCI Journal of the National Cancer Institute (1987)

Individual lesions in the pancreas and the presence of fetal acinar antigens along with carcinogenesis induced by N-nitrosobis(2-oxopropyl)amine (CAS: 60599-38-4) were studied by open biopsy in 16 Syrian golden hamsters 13, 22, and 40 weeks after initiation of treatment. At 13 weeks, cystadenoma and regular ductal hyperplasia were noted in 3 animals and 1 animal, respectively. Staining for fetal acinar antigens in the pancreas was found in 69% of the hamsters. At 22 weeks, cystadenoma and hyperplastic ducts were common (60 and 53%), and 3 hamsters developed pancreatic adenocarcinoma. Fetal acinar antigens persisted in the acini and extended to irregular hyperplastic ducts and tumor cells. At 40 weeks, ductal proliferation was the main lesion in all pancreatic tissue, and 9 animals had adenocarcinoma. Acinar antigens were found in the remaining acini, in irregular hyperplastic ducts, and in tumor cells. Thus, once reexpressed, fetal acinar antigens persist in pancreatic lesions and pancreatic carcinomas in the hamster.
PTH-138 Indication for splenectomy: a 12 year review of splenectomy in a district general hospital: Abstract PTH-138 Table 1
Authors: M Mason, T Roe, M Vipond
Journal: Gut (2015)

<h3>Introduction</h3> Splenectomy is undertaken for a heterogenous range of conditions by a wide variety of surgeons. The management of splenic disorders continues to evolve and we have therefore undertaken a review of the indications for splenectomy in our institution. <h3>Method</h3> A retrospective review of the indications for splenectomy in a large district general hospital over a twelve year period, 2003–2014. All patients undergoing splenectomy were identified from the histopathology database. Hospital records were reviewed to identify the indications for splenectomy. <h3>Results</h3> The commonest indication for splenectomy was trauma with 56 cases (41%), including 15 cases of iatrogenic trauma. All indications are shown below in two 6 year periods. Open splenectomy was undertaken in trauma and laparoscopic splenectomy in elective cases where the spleen was less than 1000g. There has been a change in the indications for splenectomy in the 12 year period: in the last six years splenectomy for trauma represents only 12 cases compared with 29 cases in the first six years. Similarly, there has been a decline in referral of patients with ITP in the second six years of the study. <h3>Conclusion</h3> This series shows that the indications for splenectomy covers a diverse range of disorders. The decline in splenectomy for trauma may represent an increasing use of conservative management in recent years. Thrombopoetin-receptor agonists are being increasingly used in the management of refractory ITP in place of splenectomy. Overall, elective splenectomy is infrequently performed and is best managed by a specialist team. <h3>Disclosure of interest</h3> None Declared.
Current Quandaries in Cancer-Associated Anemia
Authors: Jeffrey A. Gilreath, George M. Rodgers
Journal: Journal of the National Comprehensive Cancer Network (2014)

Anemia remains ubiquitous among patients with cancer.Despite a preponderance of positive data on the use of erythropoietic stimulating agents (ESAs) and intravenous (IV) iron, these agents have failed to reach their full treatment potential. 1Is this because clinicians believe that alternative therapies are safer?ESAs present a risk of thrombosis and possibly cancer progression (when high hemoglobin [Hb] values are targeted), 2 but these risks are also present with red blood cell transfusions. 3,4dditionally, difficulty in interpreting iron studies may prevent clinicians from giving IV iron, when vast benefits could be realized.And although not every patient will respond to IV iron with the same vigor, those with less severe functional iron deficiency may still derive benefit.Cancer treatments are becoming more targeted, but data suggest that many new agents have the potential to produce severe anemia. 5ecognizing that present-day anemia management (using ESAs) has been vitiated by certain insurers and regulatory agencies, this editorial discusses current quandaries in managing cancer-associated anemia (CAA) that clinicians should, but may not be, aware of.
The IRAK-ERK-p67phox-Nox-2 axis mediates TLR4, 2-induced ROS production for IL-1β transcription and processing in monocytes
Authors: Ankita Singh, Vishal Singh, Rajiv L. Tiwari, Tulika Chandra, Ashutosh Kumar, Madhu Dikshit, Manoj K. Barthwal
Journal: Cellular and Molecular Immunology (2015)
Case 8-1989
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, David N. Levine, Edward P. Richardson
Journal: New England Journal of Medicine (1989)

Presentation of Case First admission. A 46-year-old woman was admitted to the hospital because of cognitive impairment and cerebrospinal fluid pleocytosis.She was well until four months earlier, when her relatives began to notice progressive loss of memory and decrease in intellectual functioning. Two months later she was admitted to another hospital because of alcohol abuse. No localizing neurologic signs were detected. While at that hospital the patient was observed to have increasing difficulty with memory, writing, calculation, comprehension, and attention; she slept poorly and appeared depressed. A cranial computed tomographic (CT) scan, performed without the intravenous injection of . . .
A phase III trial of adjuvant chemotherapy following chemoradiation as primary treatment for locally advanced cervical cancer compared to chemoradiation alone: Outback (ANZGOG0902/GOG0274/RTOG1174).
Authors: Linda R. Mileshkin, Kailash Narayan, Kathleen N. Moore, Danny Rischin, Madeleine King, Ilka Kolodziej, Julie Martyn, Michael Friedlander, Michael Quinn, William Small, Gillian Thomas, Anthony W. Fyles, Val Gebski, Martin R. Stockler
Journal: Journal of Clinical Oncology (2014)

TPS5632 Background: Cervical cancer is a global health problem and the most common cause of cancer-related death among women in developing nations. Despite the recently developed cervical cancer vaccine, many women will continue to die from cervical cancer for many decades unless existing treatments can be improved. Unscreened women often present with locally-advanced disease that has a 5-year overall survival (OS) rate of 60% or less following standard chemo-radiation. Although some evidence suggests that adjuvant chemotherapy following chemo-radiation may be of value, its role remains controversial. Methods: OUTBACK is a randomised phase III Gynecologic Cancer InterGroup (GCIG) trial designed and led by the Australia New Zealand Gynaecological Oncology Group (ANZGOG) in collaboration with the NHMRC Clinical Trials Centre. Participating countries (groups) include Australia & New Zealand (ANZGOG), the USA (GOG, RTOG), Saudi Arabia, and Canada (RTOG). OUTBACK is suitable for women with locally advanced cervical cancer (FIGO stage IB1 & node positive, IB2, II, IIIB or IVA). The primary objective is to determine if the addition of adjuvant chemotherapy to standard cisplatin-based chemo-radiation improves OS. Women are randomized to either (A) standard cisplatin-based chemo-radiation or (B) standard cisplatin-based chemo-radiation followed by 4 cycles of carboplatin and paclitaxel chemotherapy. Secondary objectives are to compare progression-free survival, treatment-related toxicity, patterns of disease recurrence, quality of life and psycho-sexual health, and the association between radiation protocol compliance and outcomes. Blood and tumour samples are collected from consenting patients for future translational studies. 780 women will be enrolled to determine if the addition of adjuvant chemotherapy can improve the 5-year OS rate by ≥ 10%. OUTBACK opened in Australia & New Zealand in 2011 and in early 2012 the trial opened in the USA. 285 patients have been recruited from 145 active sites. The IDMC last reviewed the trial in September 2013 and recommended that the trial continue as planned. Clinical trial information: ACTRN12610000732088.
Cost effectiveness of telehealth for patients with long term conditions (Whole Systems Demonstrator telehealth questionnaire study): nested economic evaluation in a pragmatic, cluster randomised controlled trial
Journal: BMJ (2013)

Cost effectiveness of telehealth for patients with long term conditions (Whole Systems Demonstrator telehealth questionnaire study): nested economic evaluation in a pragmatic, cluster randomised controlled trialThe authors of this paper, Catherine Henderson and colleagues, have told us of some transcription errors they made in the tables (BMJ 2013;346:f1035, doi:10.1136/bmj.f1035).In table 1⇓ the raw differences for use of "GP (home)", "GP (surgery)", and "GP (telephone)" services are incorrect.In table 5⇓ there are errors in the QALY value for the primary outcome in the telehealth group; the ICER for CESD-10; and the footnote text.There are also errors scattered throughout table 4⇓.The three corrected tables are here.
Vegf and Vegfrs Polymorphisms Analysis in Advanced Renal Cell Carcinoma Tissues: is Heterogeneity Ever the Answer?
Authors: M. Bianconi, M. Scartozzi, L. Faloppi, A. Zizzi, M. D'Anzeo, M. Del Prete, R. Giampieri, L. Burattini, R. Montironi, S. Cascinu
Journal: Annals of Oncology (2014)