tbuckley/cabot-search huggingface dataset:
Progressive multifocal leukencephalopathy and cerebral toxoplasmosis in a patient with CLL
Authors: Ronan Desmond, Karen Lynch, Mary Gleeson, Michael Farrell, Philip Murphy
Journal: American Journal of Hematology (2009)

A 63-year-old man with a 10 year history of Chronic Lymphocytic Leukemia (CLL) presented with apraxia, forgetfulness, and cognitive impairment. He had been treated with single agent fludarabine at diagnosis and combination therapy with fludarabine, cyclophosphamide, and rituximab 8 months previously. MRI showed high signal in the white matter of right frontal, left frontal, and parietal areas. (see Image 1) Cerebrospinal fluid (CSF) analysis was normal with no organisms seen. Brain biopsy showed white matter replacement with oligodendroglial intranuclear inclusions and adjacent ruptured toxoplasmosis cysts. (see Image 2) Immunohistochemistry was positive for JC virus and PCR of CSF confirmed the presence of the virus as well as toxoplasma. He developed progressive ataxia, dysphagia, and dementia and died 4 weeks after diagnosis. Progressive multifocal leukoencephalopathy is associated with the use of purine analogues and rituximab in CLL [1, 2]. The incidental finding of toxoplasma illustrates how markedly immunosuppressive these regimens are. MRI image. Brain biopsy.
Other QRS-T Patterns that May Be Mistaken for Myocardial Infarction
Authors: GORDON B. MYERS
Journal: Circulation (1950)

The electrocardiograms of patients in whom myocardial infarction was excluded at autopsy are presented to bring out (1) differentiation of patterns due to subendocardial ischemia or hypopotassemia from those due to subendocardial infarction; (2) differentiation of cove-plane T inversion associated with subepicardial myocarditis or ischemia from that accompanying myocardial infraction; (3) errors resulting from attempts to draw diagnostic inferences from the registraition of prominent Q waves and/or cove negative T waves in ectopic beats or tachycardias.
Effect of Wine Consumption on Mortality
Authors: John H. Glaser
Journal: JAMA Internal Medicine (2015)

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 Internal Medicine 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 Internal Medicine journal
Sclerotherapy in extrahepatic portal venous obstruction.
Authors: Y K Chawla, J B Dilawari, G N Ramesh, U Kaur, S K Mitra, B N Walia
Journal: Gut (1990)

One hundred and twenty two patients who presented with variceal bleeding as a result of extrahepatic portal vein obstruction (EHPO) were entered into the sclerotherapy programme with a mean follow up of 23.69 months (range four to 60 months). Eighteen (14.7%) patients were lost to follow up, three (2.4%) patients underwent surgery, and six (4.9%) patients died. Variceal obliteration was achieved in the remaining 95 patients requiring 5.4 (2.4) sessions of sclerotherapy (range 2-18). Seventeen episodes of upper gastrointestinal bleed occurred in 15 patients during sclerotherapy. Recurrence of oesophageal varices was seen in 15 patients. Ten patients developed bulbous gastric varices after obliteration. Major complications including perforation and strictures were seen more commonly in children. Sclerotherapy was associated with a significant reduction in the bleeding rate (bleeds/month/patient) as compared with the presclerotherapy period (p less than 0.001). Endoscopic sclerotherapy is an effective and safe modality in the prevention of variceal bleeds in patients with extrahepatic portal vein obstruction.
Race, Treatment, and Long-term Survival From Prostate Cancer in an Equal-Access Medical Care Delivery System
Authors: Scott A. Optenberg
Journal: JAMA (1995)

<h3>Objective.</h3> —To evaluate long-term survival of black and white prostate cancer patients in an equal-access medical care system to help distinguish biological from medical and social explanations of mortality differences. <h3>Design and Setting.</h3> —Retrospective study of US Department of Defense tumor registry patients with prostate cancer. Ethnicity, age, diagnosis, staging, risk factors, treatment, and survival end points were extracted. <h3>Patients.</h3> —Prostate cancer patients (N=1606; 7.5% black, 92.5% white) who were active-duty personnel, dependents, or retirees eligible for care in the military medical system. <h3>Main Outcome Measures.</h3> —Racial differences in tumor stage and grade, risk factors, recurrence, and treatment wait time (time between initial diagnosis and initial treatment); influence of stage, grade, treatment, wait time, age, and race on survival. <h3>Results.</h3> —No differences were found in behavioral risk factors or tumor grade or size, but blacks entered active treatment (<i>P</i>&lt;.001) and exhibited a higher relative risk of cancer (<i>P</i>=.01) in younger age groups, presented with higher stage (<i>P</i>&lt;.001), and demonstrated increased progression in distant metastatic disease (<i>P</i>=.01). No significant differences were detected in overall wait time. When adjusted for stage, no difference was found in type of treatment. Overall, stage, grade, and age were found to affect survival (<i>P</i>=.04 to<i>P</i>&lt;.001), but race did not. When analyzed by stage, blacks demonstrated a clear trend of longer survival for distant metastatic disease (<i>P</i>=.04 to<i>P</i>=.06). This trend was confirmed using Kaplan-Meier estimates (<i>P</i>=.04, likelihood ratio). <h3>Conclusions.</h3> —This analysis suggests that in an equal-access medical care system there are no stage-specific differences in treatment between black and white prostate cancer patients. Survival among blacks is similar to that among whites and may surpass it for high-stage disease. (<i>JAMA</i>. 1995;274:1599-1605)
Abstract 1316: Overactivation of AKT promotes hormone-independent mammary tumors
Authors: Marina Riggio, Laura Polo, Matias Blaustein, Alejandro Colman-Lerner, Claudia Lanari, Virginia Novaro
Journal: Cancer Research (2011)

Abstract Using a mouse mammary tumor model induced by medroxyprogesterone acetate (MPA) that transits through different stages of hormone dependence, we have previously reported that the activation of the PI3K/AKT pathway is critical for the growth of hormone-independent (HI) mammary tumors, but not for the growth of a hormone-dependent (HD) tumor variant. The main aim of this work was to explore whether the activation of the PI3K/AKT pathway per se is responsible for the transition from a HD to a HI tumor phenotype. To answer this question we infected primary cultures of epithelial cells obtained from HD tumors with a retrovirus that directs the expression of a constitutively active form of AKT1 (myristoylated AKT1, myrAKT1), or with the empty vector as control. We inoculated 103 cells in nude mice (n = 6). MyrAKT1 expressing HD-derived cells were able to form mammary tumors even in the absence of MPA, that is, they behaved as HI cells. These tumors were highly differentiated and displayed a ductal phenotype with a pattern of expression of cytokeratin 8 and laminin-1 typical of HI tumors. Ligand-independent phosphorylation of progesterone receptor (PR) in Ser 190 was also increased in myrAKT1 tumors supporting our hypothesis that overactivation of AKT is directly involved in the acquisition of hormone independence. Furthermore, comparing myrAKT tumors with uninfected HD tumors revealed that overactivation of AKT did not increase the incidence of lung metastasis, indicating that AKT1 is involved specifically with tumor differentiation and growth rather than with tumor cell invasiveness. In vitro, primary cultures of mammary tumor cells modified to express myrAKT1 showed similar levels of proliferation determined by Ki67 and H3-tymidine incorporation as compared to control (cells infected with the empty vector), suggesting that the in vivo tumorigenic effect of myrAKT1 cells described above might require cell-cell or cell-matrix interactions absent in vitro. Interestingly, we found that conditioned medium from myrAKT1 tumor cells increase endogenous AKT1 activity when tested in untransfected cells. Moreover, conditioned medium from HI carcinoma associated fibroblasts (CAF-HI) increased the level of activation of the PI3K/AKT pathway in epithelial cells. Altogether, these results indicate that paracrine signals derived from the tumor cells and/or its microenvironment participate in the activation of the PI3K/AKT pathway, ultimately leading to tissue differentiation and ligand-independent mammary tumor growth. Thus, the PI3K/AKT pathway might be a key therapeutic target to prevent progression to autonomous and endocrine resistant breast tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1316. doi:10.1158/1538-7445.AM2011-1316
Elevated Urinary Prostaglandins and the Effects of Aspirin on Renal Function in Lupus Erythematosus
Authors: Robert P. Kimberly, John R. Gill, Robert E. Bowden, Harry R. Keiser, Paul H. Plotz
Journal: Annals of Internal Medicine (1978)

We studied the urinary excretion of immunoreactive prostaglandin E-like material (iPGE) and renal function in seven women with systemic lupus erythematosus to evaluate the relation between urinary iPGE and the increase in serum creatinine in patients taking aspirin. The mean pretreatment excretion of urinary iPGE in patients with lupus erythematosus, 42.7 +/- 6.4 ng/h, was significantly higher than the value of 29.0 +/- 1.9 ng/h for normal subjects (P less than 0.02). With aspirin, the urinary iPGE decreased an average of 45% (P less than 0.001). Increases in serum creatinine and blood urea nitrogen confirmed our previous clinical observations. The concomitant mean fall in creatinine clearance of 18% (P less than 0.001) was accompanied by a 14% decrease in inulin clearance (P less than 0.005); p-aminohippurate clearance fell 29% (P less than 0.005). The decline in urinary iPGE preceded the fall in creatinine clearance but was significantly correlated with it (r = 0.78; P less than 0.001). The observed changes reversed rapidly when aspirin was stopped. These data show that, in these patients with high urinary iPGE excretion, aspirin causes significant changes in renal function that may be mediated by the inhibition of prostaglandin synthesis.
Abstract 2811: Preclinical evaluation of combined TKI258 and RAD001 in hepatocellular carcinoma
Authors: Chi Hang Wong, Winnie Yeo, Vivian Lui, Cecilia P.Y. Lau, Connie W.C. Hui, Anthony T.C. Chan, Stephen L. Chan
Journal: Cancer Research (2012)

Abstract Hepatocellular carcinoma (HCC) is one of the most lethal cancers. Signaling pathways including AKT-mTOR axis is often dysregulated in HCC. RAD001 principally targets at the mTOR complex 1. mTOR inhibition is reportedly associated with activation of feedback loop and parallel pathways. TKI258 is a potent tyrosine kinase inhibitor targeting the FGFRs and VEGFRs, which blocks subsequent PI3K/AKT signaling pathways in cancer cells. In the current study, we aim to study the in-vitro and in-vivo effects of the drug combination with reference to the parallel and upstream pathway of AKT-mTOR axis. We have treated the HCC cell line Hep3B with TKI258 and RAD001. RAD001 could suppress the phosphorylation of down stream signal mediators of mTOR pathway including p70S6 kinase 1 (S6K) and eukaryotic initiation factor binding protein 1 (4E-BP1) and led to G1 phase arrest. The results demonstrated a significant increase in suppression of cell proliferation in vitro with the combination of TKI258 (300nM) and RAD001 (either 200nM or 200pM) compared with either drug alone. Although the addition of the TKI258 only slightly suppressed the AKT positive feedback loop induced by RAD001, the combination of drugs could significantly suppress the phosphorylation of mTOR (Ser2448), ERK1/2 (Ser217/221) and p38 (Thr180/Tyr182) as well as their endogenous protein expression levels. The expression levels of FGFR1 and FGFR2 were also suppressed. The overall protein reduction was due to the synergistic inhibition of p70S6 (Ser240/244) and 4E-BP1 (Ser65) phosphorylation, which indicated a strong suppression in translation and protein synthesis. Pro-caspases 3 and PARP cleavage were not observed at 24 hours and only slightly detected at 48 hours post-treatment, suggesting that the drug combination did not further increase cytotoxic effects but mainly increased in cytostatic arrest ability. In Hep3B derived xenograft model, TKI258 (15mg/ml) and RAD001 (2.5mg/kg) had shown a synergistic inhibition of tumor growth in volume and weight. In addition, there was a significant reduction in microvessel density (MVD) in the xenograft, which indicated an improved effect in angiogenesis inhibition. Our data showed that the combination of RAD001 and TKI258 were active in controlling HCC proliferation via double inhibition of both AKT-mTOR axis and its parallel pathway. Acknowledge: The works are supported by Novartis Oncology. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2811. doi:1538-7445.AM2012-2811
Abstract PR01: H-RasG12V overexpression in the central nervous system leads to expansion of oligodendrocyte precursor cells and neural crest cells
Authors: Martin Distel, David Traver
Journal: Cancer Research (2014)

Abstract Somatic mutations in Ras proto-oncogenes have been found in a large number of different cancers. In addition, germline mutations in the H-Ras gene have been shown to be the causative genetic alteration underlying Costello Syndrome (CS). Costello Syndrome belongs to the large group of Ras/MAPK pathway diseases commonly termed Rasopathies. CS patients exhibit craniofacial and cardiac abnormalities, mental retardation and are prone to develop cancers including neural crest derived neoplasias. Since Costello Syndrome is a rare disease, the effects of H-RasG12V expression on the development of the central nervous system remain largely uncharacterized. Towards this goal, we have established a zebrafish model suitable for live imaging and cost-effective drug screening. Using the Gal4/UAS system we have enforced expression of H-RasG12V in the central nervous system starting at early neurulation stages. H-RasG12V expressing embryos develop hyperplasia of the forebrain and the spinal cord and show an outgrowth in the dorsal tail region around 3 days post fertilization (dpf). In situ hybridisation revealed an increase in oligodendrocyte precursor cells, similar to what has been reported for zebrafish neurofibromin 1 mutants. In addition, cells expressing the neural crest markers Sox10 and FoxD3 accumulate lateral to the neural tube and notochord. Time-lapse imaging revealed that H-RasG12V expressing cells indeed migrate out of the spinal cord. This migration was ectopic, occuring several hours after normal neural crest migration. Furthermore, coinciding with the accumulation of neural crest like cells around the neural tube, the intersomitic vasculature hyperbranches to form new blood vessels towards domains of H-RasG12V expressing cells. Taking advantage of the early onset and obvious phenotypes in our H-RasG12V overexpression model we performed a pilot drug screen to identify potential therapeutic compounds for Costello Syndrome. We found the Mek1/Mek2 inhibitor PD98059 successfully inhibited hyperplasia of the forebrain and the spinal cord, with normal numbers of oligodendrocyte precursor cells and neural crest cells. Thus, this zebrafish model will be a valuable tool to further investigate the mechanisms underlying CNS- abnormalities of Costello Syndrome patients, including the formation of neural crest derived neoplasias and will be useful to identify therapies against this disease. This abstract is also presented as Poster A3. Citation Format: Martin Distel, David Traver. H-RasG12V overexpression in the central nervous system leads to expansion of oligodendrocyte precursor cells and neural crest cells. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr PR01.
Obesity as risk factor for lactic acidosis during nucleoside analogue treatment
Authors: Akif Altınbas, Fuat Ekiz, Osman Yuksel
Journal: Hepatology (2009)

We read with great interest the article by Lange and coworkers.1 It is known that mitochondrial toxicity related to the nucleoside analogues can result in macrovesical hepatic steatosis and lactic acidosis. In vivo, these results were shown as side effects of long-term lamivudine use in patients with human immunodeficiency virus (HIV).2 It was noted that the amount of mitochondrial DNA defects is a predictive marker for the clinical expression of mitochondrial toxicity.2 In case of the severity of the underlying liver dysfunction due to cirrhosis, or acute exacerbation of chronic liver disease, the function of mitochondria in hepatocytes declines immediately. In light of these data, severe mitochondrial dysfunction leading to lactic acidosis can be aggravated by nucleoside analogues in patients with an underlying disease, as discussed above. Moreover, hepatic steatosis may be an additional risk factor for these patients with hyperlactatemia who are using entecavir. Obesity was reported as a possible risk factor for mitochondrial toxicity in patients with HIV who are undergoing highly active antiretroviral therapy.3 So, in spite of the small numbers of patients with lactic acidosis under entecavir, we worry about the effect of body mass index on treatment toxicity. Akif Altınbas MD*, Fuat Ekiz MD*, Osman Yuksel MD, Assoc. Prof.*, * Dışkapı Yıldırım Beyazit, Education and Research Hospital, Department of Gastroenterology, Ankara, Turkey.
974 COMPARING CLINICAL UTILITY AND PREDICTION OF IN-HOSPITAL SURVIVAL OF 3 PROGNOSTIC SCORES FOR ALCOHOLIC HEPATITIS: A MEXICAN COHORT
Authors: J. Altamirano-Gómez, L. Zapata-Irissón, A. Gonzalez Angulo, A. Ortiz-Salgado, S. Andrade
Journal: Journal of Hepatology (2009)
Sherlock and Mycroft Holmes and Heredity
Authors: Frank Batley
Journal: JAMA (1966)

To the Editor:—  D. F. Musto, MD, gives needed recognition to Mycroft Holmes, Sherlock's brother ( 196 :45, 1966 ). As others have indicated before, Mycroft had an unusual genius.  In his capacious mind is filed most of the essential information on which the British Empire operates. Since no other person has so much information or skill on which to base quick decisions, in crisis he takes over, the public unaware.  It is a pity that neither Mycroft nor Sherlock Holmes had offspring because Mycroft's remarkable skills are required much more today with the greater complexities of our times. Sherlock described the hereditary transmission of criminal traits, yet both he and his brother neglected passing down their own talents.  If any reader knows of any unrecorded descendants, The Empire needs their inherited genes today.
Abstract 3215: Detecting low abundance therapeutic targets for ovarian cancer using engineered gold nanoparticles.
Authors: Karuna Giri, Rochelle Arvizo
Journal: Cancer Research (2013)

Abstract Gold nanoparticles (AuNPs) have been widely studied for use in disease therapeutics as targeting and imaging agents, drug delivery vehicles and as self-therapeutics. When AuNPs interact with the biological milieu they form a corona layer, which is predominantly composed of proteins. The outer “soft” layer is dynamic and here proteins are free to exchange over time. The inner “hard” layer on the other hand consists of proteins firmly bound to the NP surface. The Vromans effect predicts that given a limited surface area, low affinity, high abundance proteins, that first attach to the surface, are over time replaced by high affinity, low abundance proteins. Our aim was to enrich low abundance proteins on the AuNP surface to probe for differentially expressed proteins that are not detected by traditional methods of protein identification. We studied the binding of ovarian cell lysates (cancerous and non cancerous) to 10 nm sized positively and negatively charged AuNPs. The formation of corona around the AuNPs was characterized by dynamic light scattering and zeta potential measurements. The composition of the protein corona was identified using mass spectrometry. Proteins were also identified from the cell lysate pool to serve as a control to assess protein enrichment on NP surface. Using this approach, Hepatoma Derived Growth Factor (HDGF) was identified as a low abundance protein that was detected by mass spectrometry in cancer cells only after enrichment on the surface of positively charged AuNPs. HDGF is overexpressed in multiple ovarian cancer cells lines and knock down using siRNA shows decrease in cell proliferation, G2/M arrest and apoptosis. This suggests an important role of HDGF in the tumorigenicity of ovarian cancer, which could serve as an important therapeutic target for the disease. Citation Format: Karuna Giri, Rochelle Arvizo. Detecting low abundance therapeutic targets for ovarian cancer using engineered gold nanoparticles. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3215. doi:10.1158/1538-7445.AM2013-3215