tbuckley/cabot-search huggingface dataset:
ATPS-68COMBINATION OF TOPOISOMERASE II POISON BERUBICIN WITH STAT3 INHIBITOR WP1066BLOCKS POTENTLY TUMOR GROWTH IN GMB MODELS
Authors: Rafal Zielinski, Stanislaw Skora, Aleksandra Rusin, Izabela Fokt, Amy Heimberger, Raymond Sawaya, Waldemar Priebe
Journal: Neuro-Oncology (2015)

BACKGROUND: Berubicin (WP744) is a DNA binding agent and potent topoisomerase II poison designed and synthesized in our laboratory. Preclinical studies demonstrated that WP744 is a potent anticancer agent with nanomolar potency in glioma cells. WP744 was shown to effectively cross blood-brain barrier (BBB) and displayed antitumor activity in orthotopic glioma models. WP744 gained IND approval and subsequent Phase I clinical trials shows clinical benefits (including complete response) in selected brain tumor patients. Signal Transducer and Activator of Transcription 3 (STAT3) is an oncogenic transcription factor that is activated in numerous tumors including GBM. WP1066, an analog of caffeic acid benzyl ester (CABE, a component of propolis), is a potent inhibitor of activated STAT3 (STAT3-Y705) designed in our laboratory. WP1066 is currently undergoing preclinical development and has demonstrated anticancer activity in multiple cancer models including GBM. WP1066 similarly to WP744 is able to cross BBB. The goal of this study is to assess therapeutic effects of WP744 in combination with WP1066 in the in vitro and in vivo GBM models. RESULTS: WP744 and WP1066 were tested in a panel of GBM cell lines including GSC cell lines. Both, WP744 and WP1066, effectively induce apoptosis and inhibit cells growth at low nanomolar and micromolar concentrations, respectively. Dosing schedule for a combination in vivo therapy was tested in CD-1 mice. The proof-of-principle efficacy study was performed in subcutaneous U87 GBM tumor model and demonstrated superior tumor growth inhibition in a group receiving combination of WP1066 and WP744. CONCLUSION: Proposed novel therapeutic strategy involving two compounds (WP744 and WP1066) with significant CNS uptake that are mechanistically complementary is highly promising and our results warrant further evaluation in different brain tumor models. Consistent activity of WP744 combination with WP1066 in a broader range of tumors would open possibility for its future clinical evaluation.
192TiP: NEPTUNE: A global, phase 3 study of durvalumab (MEDI4736) plus tremelimumab combination therapy versus standard of care (SoC) platinum-based chemotherapy in the first-line treatment of patients (pts) with advanced or metastatic NSCLC
Authors: T. Mok, P. Schmid, O. Arén, O. Arrieta, M. Gottfried, A.R. Jazieh, R. Ramlau, K. Timcheva, C. Martin, S. McIntosh
Journal: Journal of Thoracic Oncology (2016)
Lack of Efficacy of Phenytoin in Recessive Dystrophic Epidermolysis Bullosa
Authors: Dorothea Caldwell-Brown, Robert S. Stern, Andrew N. Lin, D. Martin Carter
Journal: New England Journal of Medicine (1992)

Recessive dystrophic epidermolysis bullosa is an uncommon, severely disabling, heritable disorder characterized by abnormal fragility of the skin. Open trials have suggested that phenytoin is an effective treatment, and this therapy is now widely used.
The Leukotriene E4 Receptor, GPR99 Mediates Mast Cell-Dependent Mucosal Responses to the Mold Allergen, Alternaria alternata
Authors: Lora G. Bankova, Juying Lai, Eri Yoshimoto, K. Frank Austen, Yoshihide Kanaoka, Nora A. Barrett
Journal: Journal of Allergy and Clinical Immunology (2016)
Treatment of Acute Sore Throat in General Practice
Authors: P. A. L. Chapple, L. M. Franklin, J. D. Paulett, E. Tuckman, J. T. Woodall, A. J. H. Tomlinson, J. C. McDonald
Journal: BMJ (1956)

Sore throat is a common complaint in general practice, but doctors do not agree on the best method of treat- ment.Earlier trials of sulphonamide drugs gave con-
Salmonellosis Spread by a Dietary Supplement of Avian Source
Authors: F. Randolf Philbrook, Robert A. MacCready, Henry Van Roekel, E. S. Anderson, C. F. Smyser, F. J. Sanen, William M. Groton
Journal: New England Journal of Medicine (1960)

AS the result of an epidemiologic investigation of an outbreak of salmonellosis in a mental hospital in Massachusetts, an unusual opportunity has presented itself to demonstrate a hidden clue to the spread of the infection and to follow it back to the source, a dietary supplement of avian origin, with exceptionally thorough laboratory confirmation.Description of the OutbreakAn outbreak of 104 cases of salmonellosis occurred in a Massachusetts mental-disease institution among the 1850 inmates between December 5 and 11, 1958. There were 4 deaths directly attributable to the salmonellosis, and 2 other deaths in which the salmonellosis was considered . . .
Diseases or Clinical Conditions Associated with Low Leukocyte Alkaline Phosphatase
Authors: Kouichi R. Tanaka, William N. Valentine, Robert E. Fredrigks
Journal: New England Journal of Medicine (1960)

IT has now been well established that the leukocyte alkaline phosphatase in chronic granulocytic leukemia is very low, whereas in morphologically similar cell populations of polycythemia rubra vera with leukemoid features the activity is elevated. Previous studies have also indicated that it is often increased severalfold in a wide variety of clinical states such as pyogenic infections, myocardial infarction, trauma and diabetic acidosis, which presumably have increased adrenocortical activity as one common denominator.1 , 2 It has also been demonstrated that increased phosphatase activity results from the administration of ACTH or 17-hydroxycorticosteroids to normal subjects in substantial dosage over a three-day period. . . .
Case 37-1997
Authors: Richard P. MacDermott, Fiona M. Graeme-Cook
Journal: New England Journal of Medicine (1997)

Presentation of CaseA 59-year-old man was admitted to the clinic because of anorexia, fatigue, weight loss, and a mediastinal mass.The patient had been well until two years earlier, when his appetite and taste sensation decreased, with an ultimate loss of 16 kg in weight. He felt tired but continued to work as an automobile mechanic. He occasionally had mild headaches and dyspnea. An evaluation elsewhere showed a mediastinal mass; a biopsy revealed only fibrofatty tissue. Mild anemia, hypoalbuminemia, and a polyclonal gammopathy were detected. The patient had visited a Brazilian city for a month on four occasions during . . .
Mesantoin in the Treatment of Epilepsy
Authors: John A. Abbott, Robert S. Schwab
Journal: New England Journal of Medicine (1954)

IN 1950 we reviewed the literature on the serious side effects of anticonvulsants1 and described 11 cases of cytopenia attributed to Mesantoin. Six of the patients treated had died. Since our review, 2 accounts2 , 3 of similar cases, as well as other relevant articles,4 5 6 7 have appeared.The article1 referred to described general safeguards and advocated a routine supervision of blood counts that, it was hoped, would largely prevent such catastrophes. This routine, as we have followed it since then, entails a white-cell count and a differential count with a calculation of the number of neutrophils to be done at the following . . .
P64 Is respiratory protective equipment effective in abolishing the work effect in patients sensitised to metal working fluid?
Authors: A Ilgaz, VC Moore, W Robertson, AS Robertson, PS Burge
Journal: Thorax (2015)

<h3>Background</h3> Removing exposure to the causative agent in workers with occupational asthma or hypersensitivity pneumonitis is the main goal. The effectiveness of Respiratory Protective Equipment (RPE) in sensitised workers with usual exposures in their workplace is not known. We aimed to assess changes in serial peak expiratory flow (PEF) in workers with sensitisation to metal working fluid before and after the introduction of RPE. <h3>Methods</h3> Workers who had been requested to keep 2-hourly PEF measurements before and after the introduction of RPE at a particular engine manufacturing plant were searched for on the Oasys PEF database. Those who had completed a minimum of 1 week before and after the introduction of RPE and had a positive area between curves (ABC) score for occupational effect from Oasys analysis (≥ 15 L/min/hr) on either record were included. All PEF measurements were made outside the working area where the RPE could be removed. Workers who remained symptomatic after cleaning and replacement of the metal-working fluid were only allowed to continue work if they complied with the strict use of respiratory protective equipment (RPE) using powered filtration and external changing facilities. <h3>Results</h3> 19 workers fulfilled the inclusion criteria. The mean ABC score before RPE use was 27.85 L/min/hr (SD 17.69) and after RPE use was 19.65 L/min/hr (SD 22.77) showing a mean overall decrease of 8.20 L/min/hr (SD 28.60). 9 workers (47%) no longer showed an occupational effect on their PEF record once RPE was instated, 7 workers continued to show an occupational effect and 3 workers showed a new occupational effect which was not present before RPE use. <h3>Conclusion</h3> Serial PEF measurements assessed with the ABC score from the Oasys system allowed quantification of the effect of RPE in sensitised workers. The RPE abolished falls in PEF associated with work exposure in 47% of workers, the remaining 10 workers had significant falls in PEF despite rigorously applied RPE. RPE should still remain a last resort in the hierarchy of control for occupational health.
Clinical Value of Liver Photoscanning
Authors: Donald A. Fee, Sylvia O. Fedoruk
Journal: New England Journal of Medicine (1960)

FROM a diagnostic point of view it seems desirable to develop some method of outlining the liver to demonstrate its position, shape, size and, if possible, the presence of tumors or gross disease in its substance.Assessment of the size, shape and position of the liver by x-ray examinations has been described by Fleischner and Sayegh.1 Various reports on detecting liver metastases by means of radioactive isotopes such as rose bengal dye labeled with I131 have appeared, including an excellent survey by Friedell et al.2 This paper presents some of the results obtained from a series of 250 photoscans of . . .
The Pulmonary Macrophage in Acute Leukemia
Authors: David W. Golde, Theodore N. Finley, Martin J. Cline
Journal: New England Journal of Medicine (1974)

Because tissue macrophages are generally thought to arise from bone-marrow precursors via the blood monocyte, the question of maintenance of the alveolar macrophage population in bone-marrow failure was examined in three leukemic patients with long sustained monocytopenia. In all three, morphologically and functionally normal alveolar macrophages existed and were capable of producing colony-stimulating activity and of pre-replicative DNA synthesis. These observations indicate that in monocytopenia, the tissue macrophage population persists and may be self-sustaining. (N Engl J Med 290:875–878, 1974)
Etiology of Cervical Lymphadenitis in Children
Authors: Adnan S. Dajani, Richard E. Garcia, Emanuel Wolinsky
Journal: New England Journal of Medicine (1963)

ALTHOUGH cervical lymphadenitis is a frequent finding in the pediatric age group there is little information concerning this abnormality in standard textbooks, particularly regarding its pathogenesis. The relative frequency with which the various causative agents may produce adenitis has not been well established. Tuberculous cervical lymphadenitis1 2 3 and scrofula caused by the atypical mycobacteria4 5 6 7 have been described in detail. Cat-scratch disease has also received widespread attention as a cause of regional adenitis.8 Adamson9 found a relatively high incidence of Group A streptococci in cervical lymph nodes of children in bacteriologic studies of post-mortem specimens, and cervical lymphadenitis is a frequent finding . . .
The Tumor Necrosis Factor Ligand and Receptor Families
Authors: Flavia Bazzoni, Bruce Beutler
Journal: New England Journal of Medicine (1996)

Tumor necrosis factor (TNF) and lymphotoxin-α were isolated more than 10 years ago, on the basis of their ability to kill tumor cells in vitro and to cause hemorrhagic necrosis of transplantable tumors in mice.1 The complementary DNAs and genes encoding each protein were cloned immediately thereafter.2,3 Concurrently, a factor known as cachectin was isolated from mouse macrophages, sequenced, and shown to be identical to TNF.4,5 Cachectin was identified not as a cytolysin, but as a catabolic hormone that suppressed the expression of lipoprotein lipase and other anabolic enzymes in fat.68 Still other studies demonstrated the powerful . . .
Heterogeneity of “Acquired” or Common Variable Agammaglobulinemia
Authors: Raif S. Geha, Eveline Schneeberger, Ezio Merler, Fred S. Rosen
Journal: New England Journal of Medicine (1974)

Abstract Circulating T (thymus-derived) and B (bone-marrow-derived) lymphocytes were assessed in 19 patients with common variable or acquired agamma-globulinemia. T-cell number and function were concomitantly depressed in five of these patients who had other debilitating illnesses. B-cell number was normal in 10 patients, increased in five, and markedly reduced in four. Transformation of B cells into immunoglobulin (Ig) secretory cells in the presence of a soluble T-cell-derived lymphocyte mitogenic factor (LMF) was studied in the 15 patients with B cells. B cells from nine of these patients, when stimulated with LMF, failed to synthesize Ig. In five other patients, B cells divided and made Ig, but they failed to secrete it. A single patient had a factor in his serum that inhibited activation of both normal and autologous B cells by LMF. Acquired or common variable agammaglobulinemia is a heterogeneous disease caused by defects occurring at various steps in the maturation pathway of the B cell into an...
Diagnostic legitimacy of factitious disorder with psychological symptoms
Authors: R Rogers, R M Bagby, N Rector
Journal: American Journal of Psychiatry (1989)

The authors question the clinical status of factitious disorder with psychological symptoms as a mental disorder. In particular, they argue that unresolved issues regarding the motivational basis of this disorder and the lack of clearly delineated inclusion, exclusion, and outcome criteria seriously compromise its diagnostic legitimacy. Two case reports are presented to illustrate these difficulties. Future studies should consider these empirical and conceptual difficulties in refining the diagnosis of factitious disorder with psychological symptoms for DSM-IV.
Urinary-Tract Infections in Diabetic Women
Authors: Donald M. Barnard, Robert D. Story, Howard F. Root
Journal: New England Journal of Medicine (1953)

THE gravity of urinary-tract infections in diabetes is indicated by past studies1 2 3 4 5 6 and the fact that a recent review of 100 autopsies upon diabetic patients dying in the New England Deaconess Hospital in the years 1945 through 19507 showed that 30 per cent had suffered from significant infection. This presents a serious problem in addition to the effect upon life expectancy when one considers the cost of hospitalization, nursing care, bacteriologic studies and the use of the new antibiotics.As an illustration of this problem, it is pointed out that 51 among the first 52 diabetic patients referred for a . . .
Complications of Endoscopic Sphincterotomy and Their Prevention
Authors: Kees Huibregtse
Journal: New England Journal of Medicine (1996)

Endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy for gallstone removal and the insertion of biliary and pancreatic stents is the most difficult gastrointestinal endoscopic procedure. Success rates depend on the proper training, skills, and experience of the endoscopist and range from 90 to 95 percent, even when the technique is performed by experts.1 Complications cannot always be avoided, with hemorrhage, pancreatitis, perforation of the duodenal wall, and cholangitis being the most frequent. Complications occur in approximately 10 percent of procedures, and about 1 in 100 patients dies.2 It is a surgeon's and an endoscopist's job to know the complications of . . .
Correlation of Maternal Antibody Deficiency with Susceptibility to Neonatal Group B Streptococcal Infection
Authors: Carol J. Baker, Dennis L. Kasper
Journal: New England Journal of Medicine (1976)

We investigated the role of maternal antibody in neonatal Group B streptococcal infection with a radioactive antigen-binding assay employing a purified polysaccharide antigen with both Type III and Group B determinants. Serums from seven women who gave birth to infants who had invasive Group B streptococcal infection with Type III strains were all deficient in antibody. In contrast, serums from 22 of 29 pregnant Type III vaginal carriers whose infants were healthy contained antibody with a prevalence significantly different from that in women delivering infants with Type III disease (P less than 0.01). Three healthy neonates born to women with antibody in serums had demonstrable antibody in umbilical-cord serum. These data suggest that transplacental transfer of maternal antibody protects infants from invasive Group B streptococcal infection with Type III strains.
AB0876 Nonsteroidal Anti-Inflammatory Drugs Had Synergistic Effect on Bone Mineral Density in Bisphosphonate Treatment Osteoarthritis Patients, Compared to Cox-2 Inhibitor
Authors: S.Y. Lee, W.T. Chung, S.W. Lee
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> The use of nonsteroidal anti-inflammatory drugs (NSAIDs) and Cox-2 inhibitor are known to inhibit synthesis of prostaglandins and may prevent bone loss, but there is no study that shown the distinction between NSAIDs and COX-2 inhibitor on bone mineral density (BMD).We hypothesized the subject of NSAIDs use would be associated with increased BMD than the subject of Cox-2 use. <h3>Objectives</h3> The purpose of this study was compared the change of the BMD between NSAID use group and COX-2 inhibitor use group. <h3>Methods</h3> Between January 2005 and September 2011, we identified postmenopausal women with osteoporosis (T score &gt;-2.5) and osteoarthritis treated with Cox-2 inhibitor (Celebrex, n=319) and NSAIDs (aceclofenac, n=104), who underwent a BMD measurement by dual-emission X-ray absorptiometry (DXA) every one year and structured interview in the 5th year of this study. The all subjects were taken bisphosphonate and the outcome measure was present difference in BMD (g/m<sup>2</sup>) and T-score. The affecting factors for elevated BMD evaluated included sex, age, BMI, disease duration, cumulative period of NSAIDs, COX-2 inhibitor and bisphosphonate. After extracting possible affecting factors through univariate analysis, multivariate logistic regression analysis was performed with backward selection to derive affecting model for increased BMD in patients with osteoarthritis. <h3>Results</h3> After adjustment for possible confounders, daily use of NSAIDs users were associated with a higher BMD at whole L-spine (2.54% 1.7-3.1 CI) and both hip (1.21%, 0.6-2.4 CI) than Cox-2 inhibitor users. Also, T-score was higher in NSAIDs users than Cox-2 inhibitor users. Univariate analysis revealed that old age (P=0.008), low BMI (P=0.001), and cumulative period of NSAIDs, COX-2 inhibitor and bisphosphonate (P&lt;0.001) were possible affecting factors. Multivariate logistic regression analysis showed that cumulative period of NSAIDs, COX-2 inhibitor and bisphosphonate [odds ratio (OR) 4.86, 95% CI 1.27 - 18.55, P=0.021) are factors for increased BMD in patients with osteoarthritis and osteoporosis. <h3>Conclusions</h3> Daily use of NSAIDs is synergistic effect on BMD than daily use of Cox-2 inhibitor in postmenopausal women with osteoporosis treated with bisphosphonate. so our results suggest that NSAIDs use is preferred to use cox-2 inhibitor in patients with osteoporosis and osteoarthritis. <h3>References</h3> Osteoporos Int (2006) 17:1410–1419. <h3>Disclosure of Interest</h3> None declared
Reactions to the Stings of the Imported Fire Ant
Authors: Jane F. Desforges, Richard D. deShazo, Brian T. Butcher, W.A. Banks
Journal: New England Journal of Medicine (1990)

COEXISTENCE with the pugnacious imported fire ant has become a necessary evil for residents of both the rural and the urban Gulf South.1 The spread of these insects has produced agricultural problems,2 and their stings have resulted in increasing numbers of persons with hypersensitivity reactions, secondary infections, and neurologic sequelae.1 , 3 , 4 Two recent evolutionary changes in the ants may make the expansion of their geographical range more likely.5 , 6 Imported Fire Ants in the United StatesBoth the black imported fire ant, Solenopsis richteri (native to Argentina and Uruguay), and the red imported fire ant, Solenopsis invicta (native to northern Argentina, Paraguay, . . .
Fibroepithelioma of Pinkus in continuity with a pigmented nodular basal cell carcinoma (BCC): A dermoscopic and histologic correlation
Authors: Rodrigo Roldán-Marín, Lourdes Ramírez-Hobak, Ana Cecilia González-de-Cossio, Sonia Toussaint-Caire
Journal: Journal of the American Academy of Dermatology (2016)
Abnormal brain hemodynamic responses during passive orthostatic challenge in panic disorder
Authors: C Faravelli, M Marinoni, R Spiti, A Ginanneschi, A Serena, C Fabbri, C Di Matteo, M Del Mastio, D Inzitari
Journal: American Journal of Psychiatry (1997)

Autonomic dysregulation and cerebral blood flow (CBF) abnormalities have been reported in patients with anxiety disorders and, more recently, in panic disorder. Variations in the middle cerebral artery velocity (measured by transcranial Doppler technique), heart rate, and blood pressure during a tilting-table test were used as nonanxiogenic procedures to explore these abnormalities.Mean flow velocity in the right middle cerebral artery, heart rate, and blood pressure were monitored at rest and during a 70 degrees tilting-table test. Three groups of patients were studied: 11 patients (eight women and three men; mean age = 31.1 years, SD = 8.0) with a diagnosis of panic disorder within 6 months of the onset of the disorder, nine asymptomatic patients (two men and seven women; mean age = 35.0, SD = 6.3) with a previous diagnosis of panic disorder who were in full remission of symptoms and had been drug free for at least 6 months, and 10 normal comparison subjects (two men and eight women; mean age = 31.1, SD = 5.2).Both patients with acute panic disorder and patients with remitted panic disorder showed a significant percent reduction of right middle cerebral artery mean flow velocity compared with normal subjects following tilting to the upright position. No significant differences were observed for blood pressure and heart rate.Patients with panic disorder, both during the acute phase of the illness and after clinical recovery, show an exaggerated drop in CBF during tilting. Since these findings are similar, although attenuated in intensity, to those which are observed in dysautonomic illnesses, one possible interpretation is that of panic disorder as a subclinical form of autonomic dysreactivity.
Human Immunodeficiency Virus Replication Induces Monocyte Chemotactic Protein-1 in Human Macrophages and U937 Promonocytic Cells
Authors: Manuela Mengozzi, Camilla De Filippi, Pietro Transidico, Priscilla Biswas, Manuela Cota, Silvia Ghezzi, Elisa Vicenzi, Alberto Mantovani, Silvano Sozzani, Guido Poli
Journal: Blood (1999)
Single- vs double-unit cord blood transplantation for children and young adults with acute leukemia or myelodysplastic syndrome
Authors: Gérard Michel, Claire Galambrun, Anne Sirvent, Cecile Pochon, Benedicte Bruno, Charlotte Jubert, Anderson Loundou, Ibrahim Yakoub-Agha, Noel Milpied, Patrick Lutz, Aude Marie-Cardine, Virginie Gandemer, Didier Blaise, Mauricette Michallet, Fanny Rialland, Cecile Renard, Claire Oudin, Sophie Esmiol, Mylene Seux, Karine Baumstarck, Mohamad Mohty, Vanderson Rocha, Jean-Hugues Dalle
Journal: Blood (2016)