tbuckley/cabot-search huggingface dataset:
Thyroid abnormalities in patients treated with lenalidomide for hematological malignancies: Results of a retrospective case review
Authors: M. Kathleen Figaro, Warren Clayton, Chinenye Usoh, Kara Brown, Adetola Kassim, Vipul T. Lakhani, Shubhada Jagasia
Journal: American Journal of Hematology (2011)

Lenalidomide is an antiangiogenic drug associated with hypothyroidism. We describe a case-series of lenalidomide use in hematological cancers and the prevalence of thyroid abnormalities. We reviewed medical records of patients treated with lenalidomide at a single center form 2005 to 2010 and extracted demographic, clinical, and laboratory data. Of 170 patients with confirmed lenalidomide use (age 64.9 ± 15 years), 148 were treated for multiple myeloma and 6% had thyroid abnormalities attributable only to lenalidomide. In patients with a previous diagnosis of thyroid dysfunction, the addition of lenalidomide therapy was associated with a higher incidence of subsequent TFTF abnormality (17%) as compared to patients with no previous diagnosis of thyroid dysfunction (6%) (P=0.0001). Many patients (44%) with pre-existing disease and a change in thyroid function before or while on lenalidomide had no further follow-up of their thyroid abnormalities, Of 20 patients who did not undergo any thyroid function testing either before starting or while on lenalidomide for a median of 9.4 months (± 6.5), 35% developed new symptoms compatible with hypothyroidism, including worsened fating, constipation or cold intolerance. Symptoms of thyroid dysfunction overlap with side effects of lenalidomide. Thyroid hormone levels are not regularly evaluated in patients on lenalidomide. While on this treatment, thyroid abnormalities can occur in patients with no previous diagnoses and in patients with pre-existing abnormalities. Because symptoms of thyroid dysfunction could be alleviated by appropriate treatment, thyroid function should be evaluated during the course of lenalidomide to improve patients quality of life.
On the Physical Death of Jesus Christ
Authors: William D. Edwards
Journal: JAMA (1986)

Jesus of Nazareth underwent Jewish and Roman trials, was flogged, and was sentenced to death by crucifixion. The scourging produced deep stripelike lacerations and appreciable blood loss, and it probably set the stage for hypovolemic shock, as evidenced by the fact that Jesus was too weakened to carry the crossbar (patibulum) to Golgotha. At the site of crucifixion, his wrists were nailed to the patibulum and, after the patibulum was lifted onto the upright post (stipes), his feet were nailed to the stipes. The major pathophysiologic effect of crucifixion was an interference with normal respirations. Accordingly, death resulted primarily from hypovolemic shock and exhaustion asphyxia. Jesus' death was ensured by the thrust of a soldier's spear into his side. Modern medical interpretation of the historical evidence indicates that Jesus was dead when taken down from the cross.
Induction of Immune Responses and Clinical Efficacy in a Phase II Trial of IDM-2101, a 10-Epitope Cytotoxic T-Lymphocyte Vaccine, in Metastatic Non–Small-Cell Lung Cancer
Authors: Minal Barve, James Bender, Neil Senzer, Casey Cunningham, F. Anthony Greco, David McCune, Ronald Steis, Hung Khong, Donald Richards, Joe Stephenson, Prasanthi Ganesa, Jackie Nemunaitis, Glenn Ishioka, Beena Pappen, Michael Nemunaitis, Michael Morse, Bonnie Mills, Phillip B. Maples, Jeffrey Sherman, John J. Nemunaitis
Journal: Journal of Clinical Oncology (2008)

Purpose Generation of broad cytotoxic T-lymphocyte responses against multiple epitopes and tumor-associated antigens (TAAs) may provide effective immunotherapy in patients with cancer. We evaluated a single-vial peptide vaccine consisting of nine HLA-A2 supertype-binding epitopes (two native and seven analog epitopes modified for optimal HLA binding or T-cell receptor stimulation) covering five TAAs and the universal helper pan-DR epitope, formulated as a stable emulsion with incomplete Freund's adjuvant (Montanide ISA 51; Seppic SA, Paris, France). The clinical efficacy, safety, and multiepitope immunogenicity of IDM-2101 was evaluated in patients with stage IIIB or IV non–small-cell lung cancer (NSCLC). Patients and Methods A total of 63 patients were enrolled who were positive for HLA-A2. End points included survival, safety, and immune response. IDM-2101 (previously EP-2101) was administered every 3 weeks for the first 15 weeks, then every 2 months through year 1, then quarterly through year 2, for a total of 13 doses. Epitope-specific cytotoxic and helper T-lymphocyte immunogenic responses were measured by the interferon gamma enzyme-linked immunosorbent spot assay. Results No significant adverse events were noted. Low-grade erythema and pain at the injection site were the most common adverse effects. One-year survival in the treated patients was 60%, and median survival was 17.3 months. One complete and one partial response were identified. Survival was longer in patients demonstrating an immune response to epitope peptides (P &lt; .001). Conclusion IDM-2101 was well tolerated, and evidence of efficacy was suggested.
582 MELD-SCORE PREDICTS OUTCOME OF LUNG TRANSPLANTATION IN CYSTIC FIBROSIS PATIENTS
Authors: A. Wree, N. Kumarasamy, U. Sommerwerck, C. Jochum, H. Jakob, H.A. Baba, G. Gerken, M. Kamler, A. Canbay
Journal: Journal of Hepatology (2011)
When should the umbilical cord be clamped?
Authors: Lelia Duley, Jon Dorling, Gill Gyte
Journal: BMJ (2015)

#### The bottom line 

At birth, if the umbilical cord is not clamped immediately blood flow between the baby and placenta continues for a short time; this continued placental transfusion is part of the physiological transition from fetal to neonatal circulation.1 Clamping the cord too quickly may restrict the infant’s ability to cope with this transition.2 3 Healthy babies at term usually adapt without major consequences, but this may affect wellbeing in those born preterm or with an impaired cardiorespiratory circulation. A brief delay in cord clamping may increase neonatal blood volume, but a longer delay may have other advantages, such as a smoother cardiorespiratory transition and more stable blood pressure, irrespective of net change in blood volume. For very preterm infants (<32 weeks’ gestation), improved blood pressure stability may reduce the risk of intraventricular haemorrhage.4 Concerns about deferring (delaying) cord clamping include exacerbation of jaundice, increased blood viscosity owing to greater red cell mass, delayed respiratory support, and hypothermia.

There is no agreement on what constitutes early or deferred cord clamping. At term, placental transfusion is usually complete by two minutes but may continue for up to five minutes,5 and it contributes up to a …
Raloxifene for prevention of glucocorticoid-induced bone loss: a 12-month randomised double-blinded placebo-controlled trial
Authors: C. C. Mok, K. Y. Ying, C. H. To, L. Y. Ho, K. L. Yu, H. K. Lee, K. M. Ma
Journal: Annals of the Rheumatic Diseases (2010)

AIM: To establish whether infection with Epstein-Barr virus (EBV) contributed to the development of coronary artery lesions in a six year old child with an aneurysm and stenoses of the coronary arteries and suspected Kawasaki disease. METHODS: Postmortem paraffin wax sections of the coronary artery and myocardium were examined by in situ hybridisation for expression of EBER-1 (EBV-encoded RNA-1). Positive controls consisted of an EBV positive case of Hodgkin disease and a case of posttransplantation lymphoma. RESULTS: No EBER-1 positive cells were identified in either myocardium or walls of the coronary artery. CONCLUSIONS: Although EBV has been implicated in the aetiology of Kawasaki disease and development of coronary artery lesions, this process was not confirmed in this patient. It is likely that an unusual immunological reaction to a primary EBV infection with suspected deregulation of T helper cell activity leads to severe coronary artery damage in early childhood.
Pharmacologic Biomarkers in the Development of Stratified Cancer Medicine
Authors: William Douglas Figg, David R. Newell
Journal: Clinical Cancer Research (2014)

Abstract Clinical pharmacologic research plays a vital role in cancer drug development. In recent years, biomarker studies have become integral to this process, specifically the use of pharmacologic biomarkers in the development of targeted therapies and their translation to clinical practice. In this overview, we discuss the validation of pharmacodynamics (PD) biomarkers and highlight the circulating tumor DNA as a promising cancer biomarker to illustrate how PD biomarkers can be powerful tools for guiding treatment strategies. We provide insights into PD biomarker approaches for future development of novel therapies and their role in cancer medicine. See all articles in this CCR Focus section, “Progress in Pharmacodynamic Endpoints.” Clin Cancer Res; 20(10); 2525–9. ©2014 AACR.
Severe Myocardial Fibrosis Caused by a Deletion of the 5’ End of the Lamin A/C Gene
Authors: J. Peter van Tintelen, Rene A. Tio, Wilhelmina S. Kerstjens-Frederikse, Jop H. van Berlo, Ludolf G. Boven, Albert J.H. Suurmeijer, Stefan J. White, Johan T. den Dunnen, Gerard J. te Meerman, Yvonne J. Vos, Annemarie H. van der Hout, Jan Osinga, Maarten P. van den Berg, Dirk J. van Veldhuisen, Charles H.C.M. Buys, Robert M.W. Hofstra, Yigal M. Pinto
Journal: Journal of the American College of Cardiology (2007)
Polycomb Protein EZH2 Regulates Tumor Invasion via the Transcriptional Repression of the Metastasis Suppressor RKIP in Breast and Prostate Cancer
Authors: Gang Ren, Stavroula Baritaki, Himangi Marathe, Jingwei Feng, Sungdae Park, Sandy Beach, Peter S. Bazeley, Anwar B. Beshir, Gabriel Fenteany, Rohit Mehra, Stephanie Daignault, Fahd Al-Mulla, Evan Keller, Ben Bonavida, Ivana de la Serna, Kam C. Yeung
Journal: Cancer Research (2012)

Epigenetic modifications such as histone methylation play an important role in human cancer metastasis. Enhancer of zeste homolog 2 (EZH2), which encodes the histone methyltransferase component of the polycomb repressive complex 2 (PRC2), is overexpressed widely in breast and prostate cancers and epigenetically silences tumor suppressor genes. Expression levels of the novel tumor and metastasis suppressor Raf-1 kinase inhibitor protein (RKIP) have been shown to correlate negatively with those of EZH2 in breast and prostate cell lines as well as in clinical cancer tissues. Here, we show that the RKIP/EZH2 ratio significantly decreases with the severity of disease and is negatively associated with relapse-free survival in breast cancer. Using a combination of loss- and gain-of-function approaches, we found that EZH2 negatively regulated RKIP transcription through repression-associated histone modifications. Direct recruitment of EZH2 and suppressor of zeste 12 (Suz12) to the proximal E-boxes of the RKIP promoter was accompanied by H3-K27-me3 and H3-K9-me3 modifications. The repressing activity of EZH2 on RKIP expression was dependent on histone deacetylase promoter recruitment and was negatively regulated upstream by miR-101. Together, our findings indicate that EZH2 accelerates cancer cell invasion, in part, via RKIP inhibition. These data also implicate EZH2 in the regulation of RKIP transcription, suggesting a potential mechanism by which EZH2 promotes tumor progression and metastasis.
Results of national registration of familial adenomatous polyposis
Authors: S Bulow
Journal: Gut (2003)

<b>Background and aims:</b> The Danish Polyposis Register was established in 1971 with the aim of improving the poor prognosis of familial adenomatous polyposis (FAP), and in 1975 the register became national. The aim of the present study was to evaluate the prevalence of colorectal cancer and survival rate in FAP patients before and after the establishment of the Danish Polyposis Register. <b>Patients and methods:</b> The Danish Polyposis Register was established by collecting information on probands and construction of their pedigrees. Family members at risk were offered prophylactic endoscopic and molecular genetic examination, and affected individuals were treated by colectomy. <b>Results:</b> At the end of 2001, the Danish Polyposis Register included 434 patients from 165 families. The incidence rate was 1.90×10<sup>−6</sup> and the prevalence rate 4.65×10<sup>−5</sup>. Colorectal cancer on the basis of FAP constituted 0.07% of all colorectal cancers in the 1990s. Colorectal cancer was diagnosed in 170/252 probands (67%) and in 5/182 call-up patients (3%) (p&lt;0.001). The cumulative crude survival was 94% in call-up patients compared with 44% in probands (p&lt;0.0001). A comparison of two periods, 1900–1975 and 1976–2001, demonstrated a decreased prevalence of colorectal cancer from 60% to 27% (p&lt;0.0001), and an increased use of colectomy from 52% to 93% (p&lt;0.00001). The cumulative crude survival in FAP showed substantial improvement with time (p&lt;0.00001). <b>Conclusion:</b> Since the establishment of the Danish Polyposis Register, the prevalence of colorectal cancer has decreased considerably and the prognosis has improved substantially. The work of the Danish Polyposis Register is probably the main cause of this improvement.
A phase I study of topotecan as a radiosensitizer for brainstem glioma of childhood: First report of the Children's Cancer Group-0952
Authors: Seema N. Sanghavi, Michael N. Needle, Mark D. Krailo, J. Russell Geyer, Joann Ater, Minesh P. Mehta
Journal: Neuro-Oncology (2003)

Our purpose was to establish the maximum tolerated dosage (MTD) of daily i.v. topotecan with conventionally fractionated radiotherapy (XRT) for patients with intrinsic pontine glioma of childhood. Topotecan was given as a 30-min i.v. infusion 30-60 min before each XRT treatment given daily for 33 days. Total XRT dose was 59.4 Gy. Dose escalation of topotecan was carried out using a standard phase I design. Dose limiting toxicity (DLT) was defined as an absolute neutrophil count (ANC) of < or =500/mm(3) for > or =7 days; platelets of < or =50,000/mm(3) for > or =7 days; >7 days platelet transfusions; fever and neutropenia (ANC < or =500/mm(3) for > or =7 days); and/or any > or=grade 3 non-hematologic toxicity. In this multi-institutional phase I study, 17 patients <21 years with intrinsic pontine glioma were enrolled. Sixteen patients completed treatment. An ANC < or =500/mm(3) for > or =7 days occurred in 2/5 patients at 0.50 mg/m(2) of topotecan, which was the DLT. The remaining 14 patients received topotecan without experiencing DLT. One patient at 0.40 mg/m(2) died of disease progression while on treatment. There were 6 other grade 4 hematologic events (5 ANCs <500/mm(3), 1 hemoglobin <6. 5 g/dl) not meeting DLT criteria. No significant non-hematologic toxicities were seen. The actuarial median survival time is 15 months (95% confidence interval, 9.6-19 months); 1-year survival is 53%. DLT of daily topotecan with cranial XRT is grade 4 neutropenia for > or =7 days at 0.50 mg/m(2) x 33 (total dosage = 16.5 mg/m(2)); the recommended safe MTD of daily topotecan for further phase II testing is 0.40 mg/m(2) x 33 (total dosage = 13.2 mg/m(2)).
Diabetic Retinopathy and Diabetic Neuropathy
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2007)

Perspectives on the News commentaries are now part of a new, free monthly CME activity. The Mount Sinai School of Medicine, New York, New York, is designating this activity for 2.0 AMA PRA Category 1 credits. If you wish to participate, review this article and visit www.diabetes.procampus.net to complete a posttest and receive a certificate. The Mount Sinai School of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. 

This is the sixth in a series of articles on presentations at the American Diabetes Association’s 66th Scientific Sessions, Washington, DC, 9–13 June 2006, reviewing aspects of diabetic retinopathy and neuropathy and lower extremity vascular disease.

Maria Grant (Gainesville, FL) discussed the treatment of diabetic retinopathy with insulin-like growth factor (IGF)-1 antagonists, reviewing a number of lines of evidence. There is evidence of hypersecretion of growth hormone in diabetes. Furthermore, diabetic retinopathy has been seen following administration of growth hormone to individuals without diabetes (1); there is evidence of reduction in diabetic retinopathy in growth hormone–deficient individuals (2), and pituitary ablation has been shown to have a benefit in reducing diabetic retinopathy progression (3). A number of studies have addressed the potential benefit of somatostatin and its analogs in the treatment of diabetic retinopathy (4). IGF-1 causes a phosphatidylinositol 3-kinase–mediated increase in vascular endothelial growth factor (VEGF) expression by retinal pigment epithelial cells leading to effects on retinal endothelial cells. Somatostatin reduces circulating IGF-1, as well as acting directly in the retina to reduce VEGF production and to decrease retinal neovascularization, with three of the five somatostatin receptor subtypes having been identified in the retina.

Octreotide is an eight–amino acid synthetic peptide acting at somatostatin receptors. In a 15-month study of the effect of administration of octreotide to diabetic individuals with …
Two novel mutations in the β‐myosin heavy chain gene associated with dilated cardiomyopathy
Authors: Satu Kärkkäinen, Tiina Heliö, Pertti Jääskeläinen, Raija Miettinen, Petri Tuomainen, Kari Ylitalo, Maija Kaartinen, Eeva Reissell, Lauri Toivonen, Markku S. Nieminen, Johanna Kuusisto, Markku Laakso, Keijo Peuhkurinen
Journal: European Journal of Heart Failure (2004)
Human immunodeficiency virus-infected macrophages produce soluble factors that cause histological and neurochemical alterations in cultured human brains.
Authors: L Pulliam, B G Herndier, N M Tang, M S McGrath
Journal: Journal of Clinical Investigation (1991)

We wanted to establish an in vitro human model for AIDS-associated dementia and pursue the hypothesis that this disease process may be a result of soluble factors produced by HIV-infected macrophages. Human brain aggregates were prepared from nine different brain specimens, and were treated with supernatants from in vitro HIV-infected macrophages (SI), uninfected macrophages (SU), infected T cells, or macrophage-conditioned media from four AIDS patients. Seven of nine treated brains exposed to SI showed peripheral rarefaction after 1 wk of incubation that by ultrastructural analysis showed cytoplasmic vacuolation. Aggregates from two of three brain cultures treated with SI for 3 wk became smaller, an approximately 50% decrease in size. The degree of apparent toxicity in brains exposed to patient-derived macrophage supernatants paralleled the proportion of macrophages found to be expressing HIV p24. Ultrastructural abnormalities were not observed in brains treated with supernatants from HIV-infected T cells, uninfected macrophages, or LPS-activated macrophages. Levels of five neurotransmitter amino acids were decreased in comparison to the structural amino acid leucine. These findings suggest that HIV-infected macrophages, infected both in vitro as well as derived from AIDS patients' peripheral blood, produce factors that cause reproducible histochemical, ultrastructural, and functional abnormalities in human brain aggregates.
Is COPD in adulthood really so far removed from early development?
Authors: W. Shi, D. Warburton
Journal: European Respiratory Journal (2009)

Chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema, is commonly thought of as an adult onset lung disease most often seen in aging people with a tobacco smoking history 1. Yet, conversely, only ∼20% of cigarette smokers develop full-blown emphysema, while COPD may also be seen in nonsmokers. Therefore, genetic susceptibility is a hot topic in recent COPD research. A wealth of information has been accumulating regarding genetic polymorphisms and the incidence and severity of COPD in patients. However, the mechanisms by which these genetic alterations contribute to COPD pathogenesis are as yet barely understood. Accumulated research evidence from gene knockout and transgenic mouse models suggest that some of these genetic mutations may affect lung developmental processes in early life, which may later function as an antecedent of apparently adult onset COPD. For example, conventional gene knockout of latent transforming growth factor-β binding protein 4 or Smad3 results in retarded lung alveogenesis during early postnatal life with further subsequent alveolar enlargement 2, 3 …
Survival in Patients With Idiopathic, Familial, and Anorexigen-Associated Pulmonary Arterial Hypertension in the Modern Management Era
Authors: Marc Humbert, Olivier Sitbon, Ari Chaouat, Michèle Bertocchi, Gilbert Habib, Virginie Gressin, Azzedine Yaïci, Emmanuel Weitzenblum, Jean-François Cordier, François Chabot, Claire Dromer, Christophe Pison, Martine Reynaud-Gaubert, Alain Haloun, Marcel Laurent, Eric Hachulla, Vincent Cottin, Bruno Degano, Xavier Jaïs, David Montani, Rogério Souza, Gérald Simonneau
Journal: Circulation (2010)

Background— Novel therapies have recently become available for pulmonary arterial hypertension. We conducted a study to characterize mortality in a multicenter prospective cohort of patients diagnosed with idiopathic, familial, or anorexigen-associated pulmonary arterial hypertension in the modern management era. Methods and Results— Between October 2002 and October 2003, 354 consecutive adult patients with idiopathic, familial, or anorexigen-associated pulmonary arterial hypertension (56 incident and 298 prevalent cases) were prospectively enrolled. Patients were followed up for 3 years, and survival rates were analyzed. For incident cases, estimated survival (95% confidence intervals [CIs]) at 1, 2, and 3 years was 85.7% (95% CI, 76.5 to 94.9), 69.6% (95% CI, 57.6 to 81.6), and 54.9% (95% CI, 41.8 to 68.0), respectively. In a combined analysis population (incident patients and prevalent patients diagnosed within 3 years before study entry; n=190), 1-, 2-, and 3-year survival estimates were 82.9% (95% CI, 72.4 to 95.0), 67.1% (95% CI, 57.1 to 78.8), and 58.2% (95% CI, 49.0 to 69.3), respectively. Individual survival analysis identified the following as significantly and positively associated with survival: female gender, New York Heart Association functional class I/II, greater 6-minute walk distance, lower right atrial pressure, and higher cardiac output. Multivariable analysis showed that being female, having a greater 6-minute walk distance, and exhibiting higher cardiac output were jointly significantly associated with improved survival. Conclusions— In the modern management era, idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension remains a progressive, fatal disease. Mortality is most closely associated with male gender, right ventricular hemodynamic function, and exercise limitation.