tbuckley/cabot-search huggingface dataset:
ET-53 * IPILIMUMAB FOR RECURRENT GLIOBLASTOMA (GBM)
Authors: L. R. Schaff, A. B. Lassman, S. A. Goldlust, T. Cloughesy, S. Singer, G. K. Schwartz, F. M. Iwamoto
Journal: Neuro-Oncology (2014)

Available treatments for recurrent glioblastoma (GBM) are inadequate, and median survival is approximately 6 months. Ipilimumab (ipi) is an immune modulator that inhibits CTLA-4 and is active in refractory melanoma, including brain metastases. We retrospectively reviewed records of patients treated with ipi for recurrent GBM, and explored safety, response, and survival using Kaplan-Meier methodology. There were 10 patients (6 men), median age 55 years (range 41-65). All received prior radiotherapy and temozolomide, and 9 received prior bevacizumab. Ipi (3mg/kg/dose) was administered for 1st (1), 2nd (4), 3rd (4), or 6th (1) recurrence. Bevacizumab was administered concurrently to all patients to reduce corticosteroid requirements that can blunt ipi effect. Other concurrent therapies included GM-CSF (8), nitrosoureas (5), carboplatin (1), temozolomide (1), or lapatinib (1). Corticosteroids (dexamethasone, 0.75 - 4.0 mg/day) were administered concurrently in 4. All patients were evaluated for toxicity. One experienced fever, elevated LDH, and transaminitis. One experienced rash and fatigue. There were no other significant toxicities, specifically no endocrinopathies or electrolyte abnormalities. Responses included stable disease (5) and progressive disease (5). Median progression-free survival (PFS) was 2.8 months and overall survival (OS) was 5.1 months, although 5 patients remain alive. Results were the same for those (9) treated for bevacizumab-refractory disease. Historical control suggests results are similar in bevacizumab-failure patients treated with salvage chemotherapy (PFS 1-3 moths, OS 4-6 months), and superior to those in patients who receive no further treatment following progression on bevacizumab. Comparison of immunologic effects in pre-ipi and post-ipi tumor tissue for one case is underway. Ipi can be administered safely to patients with GBM concurrently with GM-CSF, bevacizumab, nitrosoureas, and other therapies. In patients treated for bevacizumab-refractory disease, ipi may prolong PFS and OS as compared to historical controls. Concurrent bevacizumab may reduce corticosteroid requirements. Treatment earlier in the disease course merits investigation.
Letter: Treatment of genital herpes.
Authors: S M Laird, R B Roy
Journal: BMJ (1974)

recent reports.2It is recommended that potentially lethal infection with Str.pneumoniae or H. influenzae be seriously considered in any asplenic patient with pyrexia which is not readily explaned and, if leucocytosis is found, that treatment with ampicillin be commenced inmmediately after obtaining blood for culture.Asplenuic patients presenting with meningitis or Waterhouse- Friderichsen syndromle should be treated with a regimean including an antibiotic effec- tive against boith Str.pneumoniae and H. influenzae-for example, intravenous am- picillin-until the causal organism has been cldarly identified.
Sugar and ischemic heart disease.
Authors: R W Howell, D G Wilson
Journal: BMJ (1969)

ITISHit cannot be too strongly emphasized that this study was not designed to discover varia- tions in intake levels of low statistical signi- ficance.Not only is Professor Yudkin's questionary too blunt an instrument for this, but interpretation of such circumstances is difficult because of statistical variation and the intrusion of minor variables, known and unknown The object, with no preconceived ideas to advance or defend, was to confirm or refute, with larger numbers and using a fairly " normal " population, Professor Yudkin's earlier finding of a very significant difference in sucrose intake between I.H.D. and control groups.Mean Sugar Intake (g.iweek) in 1,158 Controls and 170 I.H.D. Patients by Age Groupzng and Social Class Controls I.H.D.
Chylothorax Following Translumbar Aortogram
Authors: Charles J. Fagan
Journal: JAMA (1971)

<h3>To the Editor.—</h3> Chylothorax is a significant complication of translumbar arotography which has been documented in medical literature previously,<sup>1-3</sup>but infrequently compared to the other more common renal, neurological, and hemorrhagic complications. Occurrence solely on the left side, as opposed to the usual right-sided location, appears not to have been reported. <h3>Report of a Case.—</h3> A 64-year-old white woman exhibited complaints and physical findings consistent with severe arterial insufficiency of the lower extremities. Severe intermittent claudication and coldness of the feet were of several years' duration. A bilateral lumbar sympathectomy in 1967 resulted in temporary relief of symptoms. The blood pressure was 180/100 mm Hg, a tender, pulsatile mass was present in the area of the umbilicus, popliteal pulses were not obtained bilaterally, and dorsalis pedis pulses were very weak. The diagnosis was generalized arteriosclerosis and possibly an aneurysm of the abdominal aorta. An abdominal aortogram (Fig 1) revealed
Measurement of left ventricular stroke volume using continuous wave doppler echocardiography of the ascending aorta and M-mode echocardiography of the aortic valve
Authors: Alain Bouchard, Steven Blumlein, Nelson B. Schiller, Steven Schlitt, Benjamin F. Byrd, Thomas Ports, Kanu Chatterjee
Journal: Journal of the American College of Cardiology (1987)
Phase II Trial of Imatinib in AIDS-Associated Kaposi's Sarcoma: AIDS Malignancy Consortium Protocol 042
Authors: Henry B. Koon, Susan E. Krown, Jeannette Y. Lee, Kord Honda, Suthee Rapisuwon, Zhenghe Wang, David Aboulafia, Erin G. Reid, Michelle A. Rudek, Bruce J. Dezube, Ariela Noy
Journal: Journal of Clinical Oncology (2013)

Kaposi's sarcoma (KS) is a disease of multifocal vascular proliferation that requires infection with KS herpes virus (KSHV/HHV-8). Activation of the c-kit and platelet-derived growth factor (PDGF) receptors by autocrine/paracrine mechanisms follows endothelial cell KSHV infection. In a pilot study, imatinib, a c-kit/PDGF-receptor inhibitor, induced partial regression of AIDS-associated KS (AIDS-KS) in five of 10 patients.This multicenter phase II study was designed to estimate the response rate to imatinib in AIDS-KS. Secondary objectives included investigation of predictors of response and imatinib pharmacokinetics in patients on antiretrovirals. Patients received imatinib 400 mg/day by mouth for up to 12 months with dose escalation up to 600 mg/day at 3 months if their disease was stable.Thirty patients were treated at 12 AIDS Malignancy Consortium sites. Ten patients (33.3%) achieved partial response, six (20%) had stable disease, and seven (23.3%) exhibited KS progression. Nine patients completed 52 weeks of imatinib therapy. The median treatment duration was 22.5 weeks. Only five patients (16.7%) discontinued therapy owing to adverse events. Antiretroviral regimens did not significantly alter imatinib metabolism. Activating mutations in PDGF-R and c-kit were not found at baseline or at disease progression. We found no correlation with response with changes in any of the candidate cytokines.Imatinib has activity in AIDS-KS. Pharmacokinetic interactions with antiretroviral drugs did not correlate with toxicity. Thirty percent of patients showed long-term clinical benefit and remained on imatinib for the entire year. These results suggest imatinib is well tolerated and may be an alternative therapy for some patients with AIDS-KS.
Scapular Osteomyelitis as a Rare Complication of Staphylococcus aureus Endocarditis
Authors: Jeroen Mertens, Véronique Van Gaever, Hamphrey Ham, Christophe Van De Wiele
Journal: Clinical Nuclear Medicine (2010)

Spondylodiscitis and septic arthritis of the large joints are well-known complications of infective endocarditis. In contrast, osteomyelitis of the appendicular skeleton as a complication of infective endocarditis has not yet well been established in the medical literature. We report a case of scapular osteomyelitis in a 27-year-old woman with Staphylococcus aureus endocarditis, which was detected by 3-phase Tc-99m MDP bone scintigraphy. Although the initial complaint of the patient was right shoulder pain, there was a significant delay in diagnosis, because the initial conventional radiograph was negative.
Effect of glutathione S-transferase M1 polymorphisms on biomarkers of exposure and effects.
Authors: R J Srám
Journal: Environmental Health Perspectives (1998)

Genotypes responsible for interindividual differences in ability to activate or detoxify genotoxic agents are recognized as biomarkers of susceptibility. Among the most studied genotypes are human glutathione transferases. The relationship of genetic susceptibility to biomarkers of exposure and effects was studied especially in relation to the genetic polymorphism of glutathione S-transferase M1 (GSTM1). For this review papers reporting the effect of GSTM1 genotype on DNA adducts, protein adducts, urine mutagenicity, Comet assay parameters, chromosomal aberrations, sister chromatid exchanges (SCE), micronuclei, and hypoxanthine-guanine phosphoribosyl transferase mutations were assessed. Subjects in groups occupationally exposed to polycyclic aromatic hydrocarbons, benzidine, pesticides, and 1,3-butadiene were included. As environmentally exposed populations, autopsy donors, coal tar-treated patients, smokers, nonsmokers, mothers, postal workers, and firefighters were followed. From all biomarkers the effect of GSTM1 and N-acetyl transferase 2 was seen in coke oven workers on mutagenicity of urine and of glutathione S-transferase T1 on the chromosomal aberrations in subjects from 1,3-butadiene monomer production units. Effects of genotypes on DNA adducts were found from lung tissue of autopsy donors and from placentas of mothers living in an air-polluted region. The GSTM1 genotype affected mutagenicity of urine in smokers and subjects from polluted regions, protein adducts in smokers, SCE in smokers and nonsmokers, and Comet assay parameters in postal workers. A review of all studies on GSTM1 polymorphisms suggests that research probably has not reached the stage where results can be interpreted to formulate preventive measures. The relationship between genotypes and biomarkers of exposure and effects may provide an important guide to the risk assessment of human exposure to mutagens and carcinogens.
Deaf in America: Voices From a Culture
Authors: Burton C. Einspruch
Journal: JAMA (1989)

Historically, medical schools have seldom prepared an emerging physician to deal with problems so fundamental as nutrition, much less such complex political and ethical issues as the subcultures of poverty, minorities, or the "handicapped." Authors Padden and Humphries have undertaken the task of clarifying the cultural "uniqueness" of the deaf. Being deaf was regarded as a separate but very undesirable culture as early as medieval times, when "the position of the deaf was especially difficult because they were thought to be 'possessed by the devil' or, at least, morally deficient. The deaf could not obtain 'the true faith' since in the Holy Scriptures is written fides ex auditu (faith comes from hearing)."<sup>1</sup> Although Padden and Humphries write with compassion and understanding, their approach is less rigorous than traditional approaches by cultural anthropologists or linguists, and this in some ways detracts from the structured scholarship that such credentials afford. The
Pathways to sociopathy: Twin analyses offer direction
Authors: Nancy L. Segal
Journal: Behavioral and Brain Sciences (1995)

Abstract Understanding the bases of complex behavioral phenotypes, such as sociopathy, is assisted by an evolutionary approach, in addition to other theoretical perspectives. Unraveling genetic and environmental factors underlying variant forms of sociopathy remains a key challenge for behavioral science investigators. Twin research methods (e.g., longitudinal analyses; twins reared apart) offer informative means of assessing novel hypotheses relevant to sociopathic behaviors.
Prophylaxis for Venous Thromboembolism in Cancer Patients With a Central Vein Catheter: New Tones for an Old Song
Authors: Giuseppe Curigliano, Marco Colleoni, Mario Mandalà, Tommaso De Pas, Gianluca Spitaleri, Filippo de Braud, Aron Goldhirsch
Journal: Journal of Clinical Oncology (2005)
Abstract 1847: Molecular profiles of microRNA in endometrial carcinoma using paraffin-embedded (FFPE) specimens.
Authors: Taek Sang Lee, Hye-Won Jeon, Yong-Beom Kim
Journal: Cancer Research (2013)

Abstract MicroRNAs (miRNAs) are small non-coding RNAs that regulate mRNA stability and protein expression at post-transcriptional level. Certain miRNAs have been demonstrated to act either as oncogenes or tumor suppressors. The specific expression profiles of miRNAs have been found in many human cancers, but the role of miRNAs in endometrioid endometrial cancer (EEC) remains poorly understood. Most miRNA profiling studies have used fresh tissue samples. This study was to provide the candidate miRNAs for further confirming the role of miRNAs in carcinogenesis of EEC and to explore whether FFPE material would be suitable for miRNA profiling. We found the differences in miRNA expression profile using human miRNA microarray in EECs and normal endometrium. Of those, the miR-200a*, miR-200b*, miR-141, miR-182, and miR-205 were greatly enriched. The expressions of these 5 miRNAs were validated using quantitative real time reverse transcription-PCR (qRT-PCR). Then, we performed qRT-PCR profiling of miR expression in 30 microdissected formalin-fixed paraffin-embedded (FFPE) specimens (20 EECs, 10 non-tumor specimens) and reconfirmed the results of differential expression between cancer and normal tissue. We next tested whether specific inhibition of overexpressed microRNAs would alter the chemosensitivity. In in vitro cell viability assay, anti-miR200b* slightly enhanced cisplatin cytotoxicity compared with negative control although it showed marginal statistical significance (p=0.07). This information provided the candidate miRNAs for further confirming the role of miRNAs in carcinogenesis of EEC and potentially serving as a diagnostic or therapeutic tool. FFPE specimens of endometrial tissues are suitable as a source for miRNA microarray profiling. Citation Format: Taek Sang Lee, Hye-Won Jeon, Yong-Beom Kim. Molecular profiles of microRNA in endometrial carcinoma using paraffin-embedded (FFPE) specimens. [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 1847. doi:10.1158/1538-7445.AM2013-1847
Beta-adrenergic antagonists in the prevention of gastrointestinal rebleeding in patients with cirrhosis: A meta-analysis
Authors: B Bernard
Journal: Hepatology (1997)

A meta-analysis of 12 selected randomized trials was performed to assess the efficacy of beta-blockers in the prevention of rebleeding and the effect on long-term survival in patients with cirrhosis. Five end points were assessed: rebleeding, variceal rebleeding, death, death from bleeding, and adverse events. Analyses were performed according to the intention-to-treat method. For each end point, heterogeneity and treatment efficacy were assessed by the Der Simonian and Peto methods. When a significant difference was observed, sensitivity analyses were performed by successive stratifications according to treatment duration, cause of initial bleeding, use of placebo, type of beta-blocker, type of publication, certainty of randomization, severity of cirrhosis, interval between index bleed and randomization, and methodological quality. Beta-blockers significantly increased the mean percentage of patients free of rebleeding (21% mean improvement rate, CI 95%: 10%-32%, P < .001, relative risk 1.42), the mean percentage of patients free of variceal rebleeding (20% mean improvement rate, CI 95%: 11%-28%, P < .001), the mean survival rate (5.4% mean improvement rate, CI 95%: 0%-11%, P = .05, relative risk 1.27), the mean percentage of patients free of bleeding death (7.4%, CI 95%: 2%-13%, P < .01, relative risk 1.50). Five patients would need to be treated with beta-blockers to prevent one rebleeding episode, 14 treated to prevent one death, and 13 treated to prevent one death from bleeding. There was no significant heterogeneity among studies by both methods of analysis. In patients with esophageal varices, beta-blockers significantly increase the mean percentage of patients free of rebleeding and the mean survival rate at 2 years.
Chelation Therapy for Ischemic Heart Disease
Authors: Merril L. Knudtson
Journal: JAMA (2002)

ContextChelation therapy using EDTA is an unproven but widely used alternative therapy for ischemic heart disease.ObjectiveTo determine if current EDTA protocols have a favorable impact on exercise ischemia threshold and quality of life measures in patients with stable ischemic heart disease.DesignDouble-blind, randomized, placebo-controlled trial conducted between January 1996 and January 2000.SettingParticipants were recruited from a cohort of cardiac catheterization patients and the practices of cardiologists in Calgary, Alberta.ParticipantsWe screened 3140 patients, performed a qualifying treadmill test in 171, and enrolled 84. Entry criteria included age at least 21 years with coronary artery disease proven by angiography or a documented myocardial infarction and stable angina while receiving optimal medical therapy. The required treadmill test used a gradual ramping protocol and patients had to demonstrate at least 1-mm ST depression.InterventionsPatients were randomly assigned to receive infusion with either weight-adjusted (40 mg/kg) EDTA chelation therapy (n = 41) or placebo (n = 43) for 3 hours per treatment, twice weekly for 15 weeks and once per month for an additional 3 months. Patients in both groups took oral multivitamin therapy as well.Main Outcome MeasureChange from baseline to 27-week follow-up in time to ischemia (1-mm ST depression).ResultsThirty-nine patients in each group completed the 27-week protocol. One chelation patient had therapy discontinued for a transient rise in serum creatinine. The mean (SD) baseline exercise time to ischemia was 572 (172) and 589 (176) seconds in the placebo and chelation groups, respectively. The corresponding mean changes in time to ischemia at 27 weeks were 54 seconds (95% confidence interval [CI], 23-84 seconds; P<.001) and 63 seconds (95% CI, 29-95 seconds; P<.001), for a difference of 9 seconds (95% CI, −36 to 53 seconds; P = .69). Exercise capacity and quality of life scores improved by similar degrees in both groups.ConclusionBased on exercise time to ischemia, exercise capacity, and quality of life measurements, there is no evidence to support a beneficial effect of chelation therapy in patients with ischemic heart disease, stable angina, and a positive treadmill test for ischemia.
All Heat, No Light — The States' Medicaid Claims before the Supreme Court
Authors: Sara Rosenbaum, Timothy Stoltzfus Jost
Journal: New England Journal of Medicine (2012)

In appealing to the Supreme Court, 26 states are arguing that the Affordable Care Act unconstitutionally coerces them into expanding their Medicaid programs. But although states may face a hard choice about participating in Medicaid, that's not a constitutional matter.
Protracted, But Not Acute, Hepatitis A Virus Infection Is Strongly Associated With Hla–Drb1*1301, A Marker for Pediatric Autoimmune Hepatitis
Authors: Leonardo Fainboim, Maria Cristina Cañero Velasco, Cintia Y. Marcos, Mirta Ciocca, Adriana Roy, Graciela Theiler, Monica Capucchio, Silvia Nuncifora, Livio Sala, Marta Zelazko
Journal: Hepatology (2001)

HLA alleles are known to be associated with susceptibility to develop autoimmune hepatitis (AH), and hepatitis A virus (HAV) infection is postulated as a putative trigger for AH. We investigated whether HLA may influence the outcome of the HAV infection by studying 67 children with self-limited and 39 children with protracted forms of this infection. HLA typing of the uncomplicated forms showed no significant increase of any HLA class I or II alleles. In contrast, DRB1*1301 was present in 46.1% of the children with protracted forms (vs. 9.8% in healthy controls; relative risk [RR]: 7.6; chi(2) = 33.3; P = 2 x 10(-9)). In uncomplicated hepatitis, 45% developed anti-smooth muscle antibody (SMA)/actin antibodies, but only 1 child had detectable antibodies after 3 months of infection onset. In contrast, after 1 year, 69% of the patients suffering protracted forms had titers of anti-SMA/actin antibodies that ranged between 1:40 and 1:160. Within their follow-up, 2 patients developed a Hashimoto's thyroiditis, but the remaining patients showed no signs of developing autoimmune hepatitis. We conclude that the DRB1*1301 haplotype is strongly associated with the protracted forms of HAV infection and suggest that the infection allows a sustained release of liver self-antigens. However, other still-unknown susceptibility genes are required for the full development of pediatric AH.
Primary prevention of cardiovascular disease using validated risk scores: A systematic review
Authors: Andrew Willis, Melanie Davies, Thomas Yates, Kamlesh Khunti
Journal: Journal of the Royal Society of Medicine (2012)

Objectives The high prevalence of cardiovascular disease (CVD) and the increased cost of treatment have prompted strategies for the primary prevention of CVD in the UK to move towards the use of validated CVD risk scores to identify individuals at the highest risk. There are no reviews evaluating the effectiveness of this strategy as a means of reducing CVD risk or mortality. This review summarizes current evidence for and against the use of validated CVD risk scores for the primary prevention of CVD. Design We utilized an in depth search strategy to search MEDLINE, EMBASE and the Cochrane database of clinical trials, expert opinions were sought and reference lists of identified studies and relevant reviews were checked. Due to a lack of homogeneity in outcomes and risk scores used it was not possible to conduct a meta-analysis of the identified studies. Setting The majority of included trials were carried out in a primary care setting. 2 trials were carried out in North America, 2 in Scandinavia and 1 in the UK. Participants 31,651 participants in total were recruited predominantly from a primary care setting. Participants were aged 18-65 years old and were free from CVD at baseline. Main outcome measures Outcome measures used in the included studies were change in validated CVD risk score and CVD/All-cause mortality. Results We identified 16 papers which matched the inclusion criteria reporting 5 unique trials. Due to a lack of homogeneity in outcomes and risk scores used it was not possible to conduct a meta-analysis of the identified studies. Only one study reported a significant difference in risk score at follow up and one study reported a significant difference in total mortality, however significant differences in individual risk factors were reported by the majority of identified studies. Conclusions This review demonstrates the potential for multifactorial interventions aimed at individuals selected by CVD risk scores for lowering CVD risk and mortality. However, the majority of studies in this area do not provide an intensity of intervention which is sufficient in significantly reducing CVD mortality or validated CVD risk.
Comparison of early and late clinical events in coiled vs. tubular slotted stents
Authors: A.S. Abizaid, J.J. Popma, A. Abizaid, R. Mehran, J.F. Saucedo, A.J. Lansky, A.D. Pichard, L.F. Satler, K.M. Kent, M.B. Leon
Journal: Journal of the American College of Cardiology (1998)