tbuckley/cabot-search huggingface dataset:
Detection of bone metastases in non-small cell lung cancer (NSCLC)
Authors: L. Irving
Journal: Journal of Clinical Oncology (2004)

7189 Background: Symptomatic bone metastases (mets) from bronchogenic cancer occur in >1/3 of late-stage NSCLC patients, and 2% present first with bone mets. They cause pain, hypercalcemia, nerve compression syndromes, and are associated with poor prognosis. Bisphosphonates reduce symptomatic bone met progression, and prevent/slow asymptomatic bone met growth, suggesting prophylactic use in earlier stages. Therefore, early detection of bone mets is vital to target patients who may benefit. Aim: To review positron emission tomography (PET) and radionuclide bone scan data for detecting aymptomatic bone mets from lung cancer. Methods: Literature review of PET and bone scan studies. Results: 7-study meta-analysis (Toloza, Chest 2003) comparing clinical assessment to bone scans (n= 633, varied-stage NSCLC and SCLC, 20% with bone mets). Pooled sensitivity for clinical assessment, 0.87 (95% CI, .79-.93). 13% of pts with positive scans were asymptomatic (2.6% of total n). Histologic confirmation not always achieved; false-positive scans common. False-negative scans also occur (ie, 6% of initially negative scans developed bone mets by 1 yr). PET vs bone scan: Study 1 (Bury, Eur J Nucl Med 1998): n=110 NSCLC (43 stage IV). Mets confirmed by biopsy or radiography (n=21; stage IV, 49%). PET/ bone scan sensitivity, .9 ea; specificity, .98/.61; accuracy, 96/66%. Study 2 (Hsia, Neoplasia 2002): n=48 stage IV NSCLC. PET/ bone scan sensitivity, 93.4/93.5%; accuracy, 92.5/72.5%. Study 3 (Gayed, Mol Imaging Biol 2003): retrospective n= 85. PET/ bone scan sensitivity, .73/.81; specificity, .88/.78. Study 4 (MacManus, Int J Radiat Oncol Biol Phys 2001): n=167, stage I/II/III, 39/28/100. PET detected new bone mets in 6% of pre-PET stage III (but no stageI/II). Thorax/upper abdomen PET imaging was used, so asymptomatic bone met (commonly, spine, pelvis, sternum, ribs, skull) incidence may be underestimated. Conclusions: Bone mets are common in lung cancer. PET is the most accurate means for detecting asymptomatic bone mets. Bone scans are sensitive but have poor specificity. PET detected bone mets in 6% with pre-PET stage III NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis
CBIO-32MUTANT IDH EXPRESSION DRIVES hTERT REACTIVATION AS PART OF THE CELLULAR TRANSFORMATION PROCESS
Authors: Shigeo Ohba, Joydeep Mukherjee, Tor-Christian Aase Johannessen, Yuichi Hirose, Tracy Chow, Roxanne Marshall, Kyle Walsh, Arie Perry, Joanna Phillips, Sabrina Ronen, Russell Pieper
Journal: Neuro-Oncology (2015)

IDH1 mutations in lower grade glioma result in the production of 2-hydroxyglutarate (2HG), disrupted patterns of histone methylation, altered gene expression, and cellular transformation. IDH1 mutations, however, are also linked to mutations in the ATRX gene and the hTERT promoter, suggesting that IDH1 mutation contributes to events that stabilize telomeres and help drive the cellular immortalization and transformation processes. To determine if and how IDH1 mutation influences telomeric stabilization and cellular immortalization, pRb/p53-deficient normal human astrocytes (E6/E7 NHA) were lentivirally infected with constructs encoding WT (IDH1 WT) or R132H mutant IDH 1 (IDH1mut). Following selection, the cells were then monitored for 2HG levels, histone modifications, hTERT promoter mutations, ATRX and telomerase expression, and telomere length as they progressed through their lifespan. Introduction of IDH1mut, but not IDH1 WT, resulted in 2HG production and alterations in histone methylation within 20 population doublings (PD). Neither IDH1mut nor IDH1 WT expression, however, had any direct effect on telomerase expression or telomere length, and cells expressing either IDH1 WT or IDH1mut entered a telomere-induced crisis at PD 70. While cells expressing IDH1 WT failed to reactivate telomerase and escape from crisis, cells expressing IDH1mut emerged from crisis after 51 days, grew indefinitely in culture, and formed colonies in soft agar and tumors in vivo. The transformed IDH1mut cells did not exhibit the ALT phenotype or hTERT promoter mutations, but rather exhibited telomerase expression and activity, and shortened but stabilized telomeres. These results show that while IDH1 mutations do not directly contribute to ATRX gene mutation, hTERT promoter mutation, or TERT reactivation, they are permissive for the events that indirectly drive the TERT reactivation that contributes to both the immortalization and transformation of astrocytic cells.
Phenotypical and Functional Characterization of Mesenchymal Stem Cells Derived From Patients Affected by Schwachman-Diamond Syndrome
Authors: Valentina Andrée, Daniela Longoni, Silvia Bresolin, Geertruy Kronnie, Giovanni Cazzaniga, Laura Sainati, Marco Cipolli, Andrea Biondi, Giovanna D'Amico
Journal: Blood (2011)
Effect of PHY906 on capecitabine (CAP)-induced diarrhea in patients with GI malignancies
Authors: C. J. Hoimes, L. Lamb, W. Lok, K. Elligers, R. Carbone, K. Keley, F. Lansigan, S. H. Liu, Y. C. Cheng, M. W. Saif
Journal: Journal of Clinical Oncology (2009)

e20595 Background: 15.4% of pts with GI cancers treated with CAP alone at 1250mg/m 2 BID D1–14 q 3 wks (14/7) develop G3/4 diarrhea (Hoff et al. JCO, 2001). PHY906 composed of 4 herbs, Scutellaria baicalensis Georgi, Glycyrrhiza uralensis Fisch., Ziziphus jujuba Mill., and Paeonia lactiflora Palla, has been used to treat diarrhea since approximately 300AD. Preliminary studies showed synergistic activity of PHY906 with chemotherapeutics and reduction of chemotherapy-induced GI toxicities, especially chemotherapy-induced diarrhea (CID). Methods: We prospectively evaluated 44 pts treated on a clinical study with CAP plus PHY906 for diarrhea (experimental arm) and compared to historical data by Hoff et al., CAP 14/7 alone arm (control arm). Experimental arm consisted of pts with refractory solid tumors in phase I and gemcitabine-refractory advanced pancreatic cancer (APC) in phase II. Ph I pts received PHY906 800mg BID D1–4 with escalating doses of CAP (1000mg/m 2 →1250mg/m 2 →1500 mg/m 2 →1750mg/m 2 BID) D1 -7 q 2 wks (7/7), until MTD. Ph II treated pts with APC at 1500 mg/m 2 and PHY906 800mg BID D1–4. Toxicity was assessed per NCI-CTCAE-v3.0. In addition, correlative chemokine (IL-2, IL-4, IL-5, etc) levels will be quantified by cytometric bead array. Results: 44 pts (30M/14F; median 64yr) received 209 cycles (median:3, r:&lt;1–14) of PHY906 in the four CAP-7/7 escalation cohorts in Phase I (19 pts), then at the MTD of 1500mg/m 2 BID in Phase II (25 pts). Phase I pts had GI malignancies; 15 (63%) had APC and 6 (25%) colorectal. Of all phase I and phase II pts, G3/4 diarrhea was observed in 5 (11.4%) pts, without G3/4 constipation. One pt with APC who received 3 cycles at the 1500mg/m 2 dose level was diarrhea-free until he was removed from the study; he continued on single-agent CAP at 1000mg/m 2 BID and developed G3 diarrhea. Conclusions: In this study, G3/4 diarrhea was reduced by 19.5% in pts treated with PHY906 (experimental arm) when combined with CAP 7/7 compared to historical controls (control arm). As an underlying mechanism of CID may include cytokine activation, evalation of cytokines is ongoing. [Table: see text]
Tissue-Culture Assay of Antibodies to Heat-Labile<i>Escherichia coli</i>Enterotoxins
Authors: Sam T. Donta, David A. Sack, Robert B. Wallace, Herbert L. Dupont, R. Bradley Sack
Journal: New England Journal of Medicine (1974)

Abstract Serums of volunteers challenged orally with either toxigenic or invasive strains of Escherichia coli were analyzed for antibody content by means of an adrenal tumor-cell tissue-culture system and by the standard rabbit ileal-loop method. The tissue-culture assay system depends on the ability of specific antibody to neutralize the morphogenic effects of heat-labile Esch. coli enterotoxins. Six of seven volunteers receiving the toxigenic strains demonstrated fourfold or greater increases in antibody titers to heat-labile Esch. coli enterotoxins by the tissue-culture method, whereas eight of nine receiving the invasive Esch. coli strains did not demonstrate any such increases. These results compared favorably with those obtained by the ileal-loop method. The adrenal cell morphologic assay method can be used in seroepidemiologic and clinical studies designed to assess the importance of heat-labile enterotoxigenic Esch. coli diarrheal disease. (N Engl J Med 291:117–121, 1974)
Collapse phenomenon during Chartis collateral ventilation assessment
Authors: Wolfgang Gesierich, Konstantinos Samitas, Frank Reichenberger, Juergen Behr
Journal: European Respiratory Journal (2016)

Chartis is increasingly used for bronchoscopic assessment of collateral ventilation before endobronchial valve (EBV) treatment for severe emphysema. Its prognostic value is, however, limited by the airway collapse phenomenon. The frequency and clinical significance of the collapse phenomenon remain largely unknown. We performed a retrospective analysis of 92 patients undergoing Chartis evaluation under spontaneous breathing (n=55) or jet ventilation (n=37) from May 2010 to November 2013. Collateral ventilation status (positive/negative/collapse phenomenon/unclear) was reassessed and correlated with high-resolution computed tomography (HRCT) fissure analysis and clinical response. In the absence of the collapse phenomenon, the predictive value of Chartis measurements and HRCT fissural analysis was comparable. The collapse phenomenon was observed in 31.5% of all assessments, and was more frequent in lower lobes (44.9% versus 16.9% in upper lobes) and under jet ventilation (41.4% versus 22.1% under spontaneous breathing). 69.8% of lobes with the collapse phenomenon had complete fissures. Most patients with the collapse phenomenon in the target lobe and complete fissures treated with EBVs were responders (n=11/15). All valve-treated collapse phenomenon patients with fissure defects were nonresponders (n=3). In the absence of the collapse phenomenon Chartis measurement is reliable to predict response to valve treatment. In patients with the collapse phenomenon, treatment decisions should be based on HRCT detection of fissure integrity. Chartis assessment should be performed under spontaneous breathing.
Bone-Marrow Transplantation in Severe Gaucher's Disease
Authors: Joel M. Rappeport, Edward I. Ginns
Journal: New England Journal of Medicine (1984)

We performed allogeneic bone-marrow transplantation of normal cells in an eight-year-old patient with Type 3 Gaucher's disease in an attempt to alter his progressive deterioration. The procedure resulted in complete engraftment of the enzymatically normal donor cells. Donor monocyte precursors were present in the circulation of the recipient by 28 days after transplantation. Post-transplantation beta-glucocerebrosidase activity in mononuclear white cells in peripheral blood exceeded normal levels. Despite these early results no change in Gaucher's-cell infiltration of the bone marrow was noted for at least 111 days, and Gaucher's cells persisted in the marrow for at least 274 days. The plasma glucocerebroside concentration ultimately returned to normal. During the post-transplantation course, until the patient died from an episode of sepsis, there was no important change in his clinical status. However, this case demonstrates that the enzymatic abnormality in hematopoietic cells in Gaucher's disease is correctable by bone-marrow transplantation, leading to normalization of plasma levels of glucocerebroside. We observed the long survival of Gaucher's cells, which was consistent with the lack of clinical improvement. Intervention might have been more effective earlier in the course of the disease.
Immunoglobulin-Gene Rearrangements as Unique Clonal Markers in Human Lymphoid Neoplasms
Authors: Andrew Arnold, Jeffrey Cossman, Ajay Bakhshi, Elaine S. Jaffe, Thomas A. Waldmann, Stanley J. Korsmeyer
Journal: New England Journal of Medicine (1983)

Immunoglobulin genes in their germ-line form are separated DNA subsegments that must be joined by means of recombinations during B-cell development. Individual immunoglobulin-gene rearrangements are specific for a given B cell and its progeny. We show that the detection of such gene rearrangements by Southern hybridization provides a sensitive marker for both clonality and B-cell lineage within lymphoid tissues lacking expression of definitive surface phenotypes. We have used these genetic markers in three ways: to establish a diagnosis of lymphoma in a neoplastic disorder of uncertain cell type, to show that some lymphomas that were previously classified as being of T-cell type in fact contain monoclonal B cells, and to detect clonal B-cell populations within lymphomatous tissues of uncertain immunotype and within an atypical lymphofollicular hyperplasia having no other clonal surface markers. These sensitive and unique indicators of clonality located directly at the DNA level are capable of providing insights into the cellular origin, early detection, and natural history of neoplasia.
Absence of Immunization Effect in Human-Kidney Retransplantation
Authors: Gerhard Opelz, Paul I. Terasaki
Journal: New England Journal of Medicine (1978)

We examined whether rejection of a previous graft rendered a recipient immunized against subsequent kidney transplants in over 1900 retransplants. The one-year survival rate (43 +/- 1 per cent [ +/- S.E.M.]) of second grafts from cadaver donors was only slightly (but statistically significantly) lower than that of first transplant (47 +/- 1 per cent, P less than 0.02). Repeated HLA mismatches in 180 second transplants did not show a lower survival rate than 925 grafts with no repeated HLA incompatibility. We conclude that the danger of immunization by previous grafts has been overemphasized from studies in laboratory animals. Those who rejected the first graft rapidly (high responders) had significantly shorter survival of the second graft compared with those who rejected the initial graft slowly (low responders) (60 +/- 3 versus 31 +/- 3 per cent at one year, P less than 0.00001).
Laser Photocoagulation for the Treatment of Acute Peptic-Ulcer Bleeding
Authors: Guenter J. Krejs, Katherine H. Little, Henrik Westergaard, J. Kent Hamilton, David K. Spady, Daniel E. Polter
Journal: New England Journal of Medicine (1987)

We tested the hypothesis that therapeutic endoscopy using the Nd:YAG (neodymium:yttrium–aluminum–garnet) laser would benefit patients with acute peptic-ulcer bleeding. Over 43 months, 174 patients with active bleeding (n = 32) or stigmata of recent bleeding (n = 142) due to peptic ulcers were randomly assigned during endoscopy to either standard treatment with laser photocoagulation or therapy without photocoagulation. There were no significant differences in a number of outcomes between the group treated with laser photocoagulation and the control group. Continued bleeding or rebleeding was observed in 22 percent of the laser-treated group and in 20 percent of the control group. Urgent surgery was necessary in 16 percent of the laser-treated patients and in 17 percent of the controls. Laser-treated patients spent a mean of 41 hours in the intensive care unit, and controls spent a mean of 32 hours. The mean hospital stay was 12 days in the laser-treated group and 11 days in the control group. One death occurred in each group. When patients with active bleeding were analyzed separately, there was no significant difference in outcome, even though laser photocoagulation stopped active bleeding in 88 percent of cases. Among patients with visible vessels, rebleeding occurred in 5 of 14 (36 percent) who received laser treatment and 2 of 15 (13 percent) who did not. Laser treatment precipitated bleeding in four patients and duodenal perforation in one. We conclude that Nd:YAG-laser photocoagulation does not benefit patients with acute upper gastrointestinal bleeding from peptic ulcers. (N Engl J Med 1987; 316: 1618–21.)
Abstract 90: Inhospital Outcome of 458 Patients with Acute Myocardial Infarction Requiring Mechanical Ventilation. Results of the BEAT Registry of the ALKK.
Authors: Uwe Zeymer, Kleopatra Kouraki, Steffen Schneider, Herzzentrum Ludwigshafen, Rainer Uebis, Klinikum Aschaffenburg, Ulrich Tebbe, Klinikum Lippe-Detmold, Hermann Klein, Klinikum Idar-Oberstein, Uwe Janssens, Jochen Senges, Herzzentrum Ludwigshafen
Journal: Circulation (2007)

Background: There is only limited information about characteristics and clinical outcome of patients with acute myocardial infarction (AMI) requiring endotracheal intubation and mechanical ventilation. Therefore we sought to evaluate the clinical course of a large cohort of patients with AMI and mechanical ventilation. Methods: The BEAT Registry of the ALKK prospectively enrolled all consecutive patients requiring mechanical ventilation, who were admitted to an internal intensiv care unit (ICU) of 45 participating German centers. Patient characteristics, treatment and complications until discharge were collected. For this analysis we created a subgroup of patients admitted with ST-segment elevation or non-ST Segment elevation myocardial infarction. Results : During the 9-month study period 458 consecutive patients with AMI were included. The mean age was 68±8 years and 71% were men. While 40% of the patients were intubated in the prehospital phase, 60% were intubated in the hospital. The initial cause for intubation was in 48% of the cases ventricular fibrillation/ tachycardia or sudden cardiac death, in 39% congestive heart failure and in 13% of the cases non-cardiac. Of the 458 patients 256 (56%) developed cardiogenic shock, 86 (19%) acute renal failure, 76 (17%) coma or brain damage, 64 (14%) severe infection, 46 (10%) sepsis, 28 (6%) MODS and 17 (4%) gastrointestinal bleeding. 204 (45%) patients underwent coronary angiography, 38% were treated with PCI and 5% with coronary artery bypass grafting. The inhospital mortality in the total group was 48% and in the subgroup of patients with cardiogenic shock 69%. Conclusion: Patients requiring mechanical ventilation as complication during the early phase of an AMI constitute a high risk subgroup with a mortality of 50%. Further research is necessary to improve the outcome of these patients.
Cortisone as an Adjunct to Chloramphenicol in the Treatment of Rocky Mountain Spotted Fever
Authors: Joseph B. Workman, John A. Hightower, Francis J. Borges, J. Earle Furman, Robert T. Parker
Journal: New England Journal of Medicine (1952)

THE efficacy of chloramphenicol and other rickettsiostatic agents in the treatment of Rocky Mountain spotted fever is well documented. However, after institution of specific therapy, the febrile period in most reported series has ranged from 2.5 to 4 days.1 2 3 4 The management of severely ill patients who exhibit toxemia, dehydration, hypochloremia, hypoproteinemia and peripheral vascular collapse, characteristic of late cases of Rocky Mountain spotted fever, remains a difficult problem. The reported effectiveness of adrenal cortical hormones in ameliorating the toxemia of certain bacterial diseases5 6 7 prompted a therapeutic trial of cortisone** combined with a specific antibiotic in this rickettsiosis.Method of Study . . .
Systematic review on tuberculosis transmission on aircraft and update of the European Centre for Disease Prevention and Control risk assessment guidelines for tuberculosis transmitted on aircraft (RAGIDA-TB)
Authors: Saara M. Kotila, Lara Payne Hallström, Niesje Jansen, Peter Helbling, Ibrahim Abubakar
Journal: Eurosurveillance (2016)

As a setting for potential tuberculosis (TB) transmission and contact tracing, aircraft pose specific challenges. Evidence-based guidelines are needed to support the related-risk assessment and contact-tracing efforts. In this study evidence of TB transmission on aircraft was identified to update the Risk Assessment Guidelines for TB Transmitted on Aircraft (RAGIDA-TB) of the European Centre for Disease Prevention and Control (ECDC). Electronic searches were undertaken from Medline (Pubmed), Embase and Cochrane Library until 19 July 2013. Eligible records were identified by a two-stage screening process and data on flight and index case characteristics as well as contact tracing strategies extracted. The systematic literature review retrieved 21 records. Ten of these records were available only after the previous version of the RAGIDA guidelines (2009) and World Health Organization guidelines on TB and air travel (2008) were published. Seven of the 21 records presented some evidence of possible in-flight transmission, but only one record provided substantial evidence of TB transmission on an aircraft. The data indicate that overall risk of TB transmission on aircraft is very low. The updated ECDC guidelines for TB transmission on aircraft have global implications due to inevitable need for international collaboration in contract tracing and risk assessment.
Bone Marrow Transplantation without Myeloablation for Sickle Cell Disease
Authors: Lakshmanan Krishnamurti, Bruce R. Blazar, John E. Wagner
Journal: New England Journal of Medicine (2001)

To the Editor: Bone marrow transplantation can eliminate sickle cell disease and halt end-organ damage.1,2 However, the applicability of the procedure is limited because of the toxic effects associated with conventional bone marrow transplantation. Nonmyeloablative conditioning regimens can decrease or eliminate such toxic effects.3–5 An eight-year-old girl with homozygous sickle cell disease had been receiving monthly transfusions and chelation therapy with deferoxamine since having a stroke three years earlier. Before the stroke, she had required three or four hospitalizations per year for vaso-occlusive crises and the acute chest syndrome. We treated the girl with a bone marrow transplant . . .