tbuckley/cabot-search huggingface dataset:
Rheumatic Fever in Siblings
Authors: Mario Spagnuolo, Angelo Taranta
Journal: New England Journal of Medicine (1968)

Most attacks of rheumatic fever have only one or two major clinical manifestations. The possibility that the host is genetically predisposed to individual manifestations was explored by determining whether siblings with rheumatic fever tend to have the same manifestations and sequelae. Sixty-seven sibling pairs were studied. Data of the clinical manifestations during the first attack and of the subsequent sequelae were collected for each member "blindly." The concordance of manifestations and sequelae within sibling pairs was then evaluated statistically. Concordance was significant for chorea (p less than 0.01) and for joint involvement (p less than 0.05). Cardiac involvement was concordant when gauged by the presence of residual heart disease (p less than 0.05) and discordant when gauged by the less reliable method of retrospective diagnosis of carditis. Biases, infectious agent and environment were found to be unlikely reasons for the concordance of manifestations. The exclusion of these factors suggests that the concordance is caused by genetic variation.
P198 Managing Ventilatory Failure in patients on LTOT: A case series of outcomes using NIV
Authors: K Hambleton, J Turner-Wilson, J Riley, J Young, N Gabriel, A Nickol, M Bafadhel, M Hardinge
Journal: Thorax (2015)

<h3>Background</h3> Long term Oxygen therapy (LTOT) has been shown to have survival benefits in patients with COPD when therapeutic levels are achieved (PO<sub>2</sub> &gt;8.0 kPa, saturations &gt;92%). But for some patients, loss of hypoxic ventilatory drive, can lead to development of worsening ventilatory failure and symptomatic hypercapnia during oxygen titration. Current guidelines recommend use of nocturnal NIV in conjunction with LTOT in clinically stable patients who develop a respiratory acidosis and/or a rise in PaCO<sub>2</sub> by &gt;1 kPa (7.5 mmHg) during an LTOT assessment on two repeated occasions, but the evidence for this approach is lacking. We present a case series of patients on LTOT who were commenced on NIV for this indication, and look at arterial blood gas outcomes, survival time and hospital admissions. <h3>Methods</h3> Patients on both LTOT and NIV were identified using our local database and medical notes were reviewed. Results were analysed using a paired T-test and expressed as means with standard deviations. <h3>Results</h3> A case series of 15 patients with COPD on LTOT and NIV were identified. The mean (range) age was 68 (53–83) and mean FEV<sub>1</sub>% predicted was 29%. Mean (SD) pre-treatment pH on LTOT was 7.36 (± 0.67) and post treatment with NIV pH 7.41 (±0.38), p = 0.089. Mean LTOT pCO<sub>2 </sub>was 8.09 kPa (±1.25), and post LTOT/NIV treatment levels dropped to 7.03 kPa (±0.85), p = 0.001; with a significant improvement in PO<sub>2</sub> from 7.26 kPa (±0.64) to 8.87 kPa (±1.15) p &lt; 0.005. PaO<sub>2</sub> increased to therapeutic range (≥ 8.0 kPa) in 80% of patients after commencing NIV with LTOT. Mean (SD) number of hospital admissions in the 12 months before and after the introduction of LTOT/NIV significantly reduced from 0.87 (±0.74) to 0.27 (±0.59), p = 0.023 (Figure 1). In patients with COPD, the mean survival time from starting NIV in addition to LTOT was 30 months. <h3>Conclusion</h3> The addition of NIV to LTOT therapy can facilitate therapeutic oxygen delivery, whilst managing hypercapnia. Concurrent NIV and LTOT use can also reduce hospital admissions and increase survival times.
Case 46-1991
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, R.J. Ginsberg, E.J. Mark
Journal: New England Journal of Medicine (1991)

Presentation of CaseA 64-year-old man was admitted to the hospital because of increasing bouts of hemoptysis, a bronchoesophageal fistula, and broncholithiasis.There was a long history of chronic pulmonary disease characterized by a cough, exertional dyspnea, and hemoptysis of 20 years' duration. The disease was believed to be related to the patient's having worked for 25 years in mines, with exposure to feldspar and mica, and to his having smoked 1 1/2 to 2 packs of cigarettes daily for many years. One year before entry his cough worsened, and the hemoptysis became more frequent. Six weeks before entry, after . . .
A Randomized Trial of Intracoronary Streptokinase in the Treatment of Acute Myocardial Infarction
Authors: Jeffrey L. Anderson, Hiram W. Marshall, Bruce E. Bray, Joan R. Lutz, Philip R. Frederick, Frank G. Yanowitz, Frederick L. Datz, Steven C. Klausner, Arthur D. Hagan
Journal: New England Journal of Medicine (1983)

Fifty patients with acute myocardial infarction were randomly assigned to receive either intracoronary streptokinase or standard (control) therapy within about three hours after the onset of pain. Coronary perfusion was reestablished in 19 of 24 patients receiving streptokinase. Streptokinase alleviated pain (as indicated by differences in subsequent morphine use). The Killip class was significantly improved after therapy with streptokinase, as were changes in radionuclide ejection fraction between Days 1 and 10 in surviving patients (+3.9 vs. -3.0 per cent, P<0.01). The echocardiographic wall-motion index also showed greater improvement after streptokinase treatment (P<0.01). Streptokinase therapy was associated with rapid evolution of electrocardiographic changes, which were essentially complete within three hours after therapy, but loss of R waves, ST elevation, and development of Q waves in the convalescent period were greater in the control group (P<0.01). The time required to reach peak plasma enzyme concentrations was significantly shorter after streptokinase. The incidence of early and late ventricular arrhythmias was not affected by treatment. We conclude that intracoronary streptokinase appears to have a beneficial effect on the early course of acute myocardial infarction. (N Engl J Med 1983; 308:1312–8.)
Interferon Alfa-2b Combined with Cytarabine versus Interferon Alone in Chronic Myelogenous Leukemia
Authors: François Guilhot, Claude Chastang, Mauricette Michallet, Agnès Guerci, Jean-Luc Harousseau, Frédéric Maloisel, Réda Bouabdallah, Denis Guyotat, Nathalie Cheron, Franck Nicolini, Jean-François Abgrall, Joseph Tanzer, Maurice Navarro, Dominique Bordessoule, Patrick Morice, Norbert Ifrah, Henri Rochant, Jean-Pierre Vilque, Martine Delain, Francis Bauters, Joëlle Guilhot
Journal: New England Journal of Medicine (1997)

Treatment with interferon prolongs survival in chronic myelogenous leukemia. We conducted a clinical trial to assess the efficacy of treatment with a combination of interferon and cytarabine.
Transfusion-Reversible Functional Asplenia in Young Children with Sickle-Cell Anemia
Authors: Howard A. Pearson, Eugene A. Cornelius, Allen D. Schwartz, Joseph H. Zelson, Sorrell L. Wolfson, Richard P. Spencer
Journal: New England Journal of Medicine (1970)

We recently defined functional asplenia in children with sickle-cell anemia as impaired splenic reticuloendothelial function despite clinical enlargement of the organ. In three children infusions of fresh plasma did not restore function, indicating that functional asplenia probably is not a consequence of a contracted plasma volume or deficient opsonins or other humoral factors. Transfusions of normal red cells were given, and in five young children, splenic function was restored. Seri al studies suggested that a level of normal red cells of about 50 per cent was necessary for function. The best explanation for functional asplenia is that the high viscosity of sickle-cell blood causes a diversion of splenic blood flow through intrasplenic shunts, thus bypassing the phagocytic reticuloendothelial elements of the organ. When sickled cells are replaced by normal red cells through transfusion, splenic circulation and function are temporarily restored.
Physicians' Use of Mood-Altering Drugs
Authors: George E. Vaillant, Jane R. Brighton, Charles McArthur
Journal: New England Journal of Medicine (1970)

A prospective study carried out over a 20-year period showed that a group of 45 physicians took more tranquilizers, sedatives and stimulants than 90 matched controls. As college sophomores both groups had been selected for the study because of better than average physical and psychologic health. The physicians drank alcoholic beverages and smoked cigarettes to the same extent as the controls.
Horizon of Hope
Authors: Scott D. Young
Journal: Journal of Clinical Oncology (2000)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.8.1808 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10764449 Horizon of Hope Scott D. Young, MD, PhD, FRCP(C)xScott D. YoungSearch for articles by this author Show More Northeastern Ontario Regional Cancer CentreSudburyOntario, Canada https://doi.org/10.1200/JCO.2000.18.8.1808 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical Oncology
Abstract B23: Selective and rapid killing of mixed lineage leukemia and CALM-AF10 leukemia by SM7, a novel small molecule identified by chemical library screening
Authors: Daria Chudakova, Klaartje Somers, Shiloh Middlemiss, Victoria Wen, Alan Kwek, Bing Liu, Molly Clifton, Sukey Pan, Sarah Cruikshank, Marissa Scandlyn, Tim Failes, Wendy Hoang, Ursula Kees, Olga Chernova, Andrei V. Gudkov, Michelle Haber, Murray Norris, Michelle Henderson
Journal: Cancer Research (2016)

Abstract Translocations involving the Mixed Lineage Leukemia (MLL) gene define the major proportion of infant leukemia, a disease that is characterised by a dismal prognosis due to treatment toxicity and therapy resistance. There is an urgent need for the development of less toxic, more selective and targeted therapies for this disease. In this study, we performed a cell-based chemical library screen on an infant MLL cell line, PER-485, in order to identify selective inhibitors of MLL leukemia. After screening initial hits for viability against a panel of 25 cell lines including MLL rearranged and wild-type MLL leukemia, solid tumors and control cells, SM7 was identified as a compound that significantly and selectively decreased the viability of MLL-rearranged (four out of seven) and related CALM-AF10 (two out of two) leukemia cell lines, without killing cell lines derived from wild-type MLL leukemia, solid tumours or normal cells. In contrast to currently developed MLL-inhibitors, the effect of SM7 in suppressing the characteristic MLL-driven gene expression signature in MLL-rearranged cells, with downregulation of leukemogenic HoxA9 and Meis1 expression, occurred within an hour after treatment. The transcript levels of cMyc and Bcl2, important survival proteins regulated by HoxA9, were also rapidly decreased in response to SM7. SM7 induced a rapid caspase-dependent apoptosis, with mitochondrial depolarization within twenty four hours of treatment. This is distinct from the action of other previously described MLL small molecule inhibitors. The rapid and selective toxicity of SM7 towards MLL-rearranged and CALM-AF10 leukemia cell lines suggests an important new avenue in the development of targeted therapies for this disease. Citation Format: Daria Chudakova, Klaartje Somers, Shiloh Middlemiss, Victoria Wen, Alan Kwek, Bing Liu, Molly Clifton, Sukey Pan, Sarah Cruikshank, Marissa Scandlyn, Tim Failes, Wendy Hoang, Ursula Kees, Olga Chernova, Andrei V. Gudkov, Michelle Haber, Murray Norris, Michelle Henderson. Selective and rapid killing of mixed lineage leukemia and CALM-AF10 leukemia by SM7, a novel small molecule identified by chemical library screening. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr B23.
SAT0304 Atorvastatin Inhibits Osteoclast Differentiation and Bone Resorbing Activity by Suppressing NF-κB and Mapk Signaling During IL-1β-Induced Osteoclastogenesis
Authors: W.S. Lee, Y.J. Choi, M.-J. Hong, C.-H. Lee, M.S. Lee, S.-I. Lee, W.-H. Yoo
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) are potent inhibitors of cholesterol biosynthesis. They have been reported to have anti-inflammatory and/or immunomodulatory as well as prophylactic and therapeutic effects in collagen-induced arthritis models. Bone erosion is a central feature of rheumatoid arthritis and is associated with disease severity and poor functional outcome. <h3>Objectives</h3> This study was designed to define the effect of statins on IL-1β-induced osteoclastogenesis and to elucidate the underlying mechanisms. <h3>Methods</h3> Bone marrow cells (BMCs) were obtained from 5-week-old male ICR mice and cultured to differentiate them into osteoclasts with M-CSF and RANKL in the presence or absence of IL-1β or atorvastatin. The formation of osteoclasts was evaluated by tartrate-resistant acid phosphatase (TRAP) staining and resorption pit assay with dentine slice. The molecular mechanisms of the above effects of atorvastatin on osteoclastogenesis were investigated using RT-PCR and immunoblotting for osteoclast specific molecules. <h3>Results</h3> Atorvastatin significantly reduced the number of TRAP-positive multinucleated cells as well as the bone resorption area. Atorvastatin also downregulated the expression of NFATc1 mRNA and inhibited the expression of osteoclast-specific genes. A possible underlying mechanism may be that atorvastatin suppresses the degradation of the inhibitors of NF-κB and blocks the activation of c-JUN N-terminal kinase, extracellular signal-regulated kinase, and p38, thus implicating the NF-κB and MAPK pathway in this process. <h3>Conclusions</h3> These results indicate that atorvastatin is a strong inhibitor of inflammation-induced osteoclastogenesis in inflammatory joint diseases <h3>Disclosure of Interest</h3> None declared
Outcomes of bisphosphonate-related osteonecrosis of the jaw—Importance of staging and management guidelines: A large single institutional update
Authors: B. Mehrotra, J. Fantasia, S. L. Ruggiero
Journal: Journal of Clinical Oncology (2008)

20526 Background: Bisphosphonate (BP) therapy is indicated in the treatment of pts. with symptomatic bony disease secondary to myeloma, solid tumors and in the treatment of osteoporosis. We have previously reported our experience with BP related osteonecrosis of the jaw (ONJ) (J Oral Maxillofac Surg 2004;62:527–34). The reported incidence of this entity in patients receiving IV BP’s is approx. 1–10%. The purpose of our current report is to update our experience and report the clinical outcome of the osteonecrotic lesion, with particular emphasis to clinical stage and after following stage specific management guidelines that we have previously published (Hematology 2006; 356–360). Methods: We performed a retrospective analysis of pts. records that were diagnosed with ONJ at our institution. IRB approval was obtained for this study. Information regarding age, gender, indication for BP treatment, type of BP used, stage of ONJ at time of presentation, outcome of ONJ with appropriate therapy were recorded. Results: Two hundred and seven pts. with ONJ were identified at our institution. Males: n=52; Females: n=155. Underlying frequent diagnoses: Myeloma: n=71; breast ca: n=68; osteoporosis: n=42; prostate ca: n=11; others: n=13. Prior BP therapy included exposure to pamidronate: n=87; zoledronic acid: n=123; oral BP: n=41. Ninety four patients were serially followed for outcome data regarding clinical course of ONJ after cessation of BP therapy. Improvement in ONJ was noted: n=24 (26%), stable disease: n=52 (55%), worsening of ONJ: n=18 (19%). Their initial stage of ONJ was recorded as Stage 1: n=26 (28%), Stage 2: n=45 (48%), Stage 3: n=23 (24%). Outcome by stage: stage 1 pts: improvement 19%; stable disease 73%, worsening 8%; Stage 2 pts: improvement noted in 31%, stable disease 47%, worsening 22%; Stage 3 pts: improvement in 22%, stable disease 52%, worsening 26%. Conclusions: With early detection at a lower stage, and careful conservative management, the large majority (74–92%) of pts. presenting with ONJ will have stabilization or improvement in their clinical presentation after discontinuation of BP therapy. Close coordination of care between oncologists and dental colleagues may optimize treatment outcomes with this entity. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen, Novartis Novartis
Case 29-1979
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Martin A. Samuels, George M. Kleinman
Journal: New England Journal of Medicine (1979)

Presentation of CaseA 51-year-old right-handed man was admitted to the hospital because of neck pain.Three years earlier he experienced aching pain in the left nuchal region. Evaluation, including x-ray films of the neck, led to a diagnosis of cervical arthritis with osteophytes at multiple levels. The administration of anti-inflammatory agents and cervical traction gave little relief. Sixteen months before admission the pain intensified. A cervical myelographic examination was reported to show a ventral extradural abnormality at the C3–C4 level and possibly at the C6–C7 level. Eleven months before entry anterior-disk removal and decompression were performed at the C6–C7 . . .
Neurotoxic Effects of Organohosphorus Insecticides
Authors: Nimal Senanayake, Lakshman Karalliedde
Journal: New England Journal of Medicine (1987)

Acute neurotoxic effects during the cholinergic phase of organophosphorus insecticide poisoning and delayed neurotoxic effects appearing two to three weeks later are well recognized. We observed 10 patients who had paralysis of proximal limb muscles, neck flexors, motor cranial nerves, and respiratory muscles 24 to 96 hours after poisoning, after a well-defined cholinergic phase. The compounds involved were fenthion, monocrotophos, dimethoate, and methamidophos. Four patients urgently required ventilatory support. The paralytic symptoms lasted up to 18 days. A delayed polyneuropathy later developed in one patient. Three patients died. Electromyographic studies showed fade on tetanic stimulation, absence of fade on low-frequency stimulation, and absence of post-tetanic facilitation, suggestive of a postsynaptic defect. This neuromuscular junctional defect may have been the predominant cause of the paralytic symptoms, with neural and central components contributing to various degrees. Our patients appeared to have a distinct clinical entity (a so-called intermediate syndrome) that developed after the acute cholinergic crisis and before the expected onset of the delayed neuropathy.
Echocardiography in Bacterial Endocarditis
Authors: L.S. Wann, J.C. Dillon, A.E. Weyman, Harvey Feigenbaum
Journal: New England Journal of Medicine (1976)

We examined 129 standard M-mode echocardiograms obtained in 65 patients (16 to 73 years old) with bacterial endocarditis. Twenty of the 22 patients with vegetations recognizable by echocargiography died, or underwent cardiac operation (mean interval from admission 22 days, and range two to 120 days). Vegetations were seen on the echocardiograms in 22 (aortic 10, mitral nine and tricuspid three, with anatomic confirmation in 19). Of patients without vegetations on echocardiography none underwent emergency operation or died as a result of cardiac disease (mean follow-up period of 14 months, range of two to 38 months). Other echocardiographic findings in those with vegetations included early mitral-valve closure (six), "flail" aortic leaflet (three), and "flail" mitral leaflet (three). Echocardiography can provide a rapid, reliable noninvasive diagnosis of bacterial vegetations in certain patients with bacterial endocarditis and may identify patients with more severe disease who may require operative intervention.
High Plasma Levels of Factor VIII and the Risk of Recurrent Venous Thromboembolism
Authors: Paul A. Kyrle, Erich Minar, Mirko Hirschl, Christine Bialonczyk, Milena Stain, Barbara Schneider, Ansgar Weltermann, Wolfgang Speiser, Klaus Lechner, Sabine Eichinger
Journal: New England Journal of Medicine (2000)

A high plasma level of factor VIII is a risk factor for venous thromboembolism. We evaluated the risk of a recurrence of thrombosis after an initial episode of spontaneous venous thromboembolism among patients with high plasma levels of factor VIII.
Case 8-2001
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Jo-Anne O. Shepard, Sally H. Ebeling, Stacey M. Ellender, Christine C. Peters, Eric T. Wong, David N. Louis
Journal: New England Journal of Medicine (2001)

Presentation of CaseA 61-year-old man was admitted to the hospital because of transient quadriplegia and apnea.The patient had been well until the morning of admission, when stiffness and pain developed in his neck after he turned his head. The pain was followed by numbness and “electric” sensations in his arms and legs. Within 10 minutes, his arms and legs became paralyzed, and he was unable to speak. Emergency medical technicians found him apneic, pulseless, and unresponsive. Cardiopulmonary resuscitation was successful after one minute. On arrival at a nearby hospital, he was able to move his arms and legs. . . .
Generation of Antigen-Specific Suppressor Cells during Allergy Desensitization
Authors: Ross E. Rocklin, Albert L. Sheffer, Dirk K. Greineder, Kenneth L. Melmon
Journal: New England Journal of Medicine (1980)

We used a suppressor-cell assay to study a possible mechanism of allergy desensitization. Before specific immunotherapy, blood mononuclear cells from 20 patients with ragweed hayfever failed to exhibit suppressor activity in vitro after stimulation by ragweed antigen E. However, when the 10 patients with allergic rhinitis had been desensitized by injections of ragweed extract, their mononuclear cells specifically suppressed a ragweed proliferative response six and 12 months after desensitization was begun (31 per cent and 48 per cent suppression, respectively). Suppressor mononuclear cells were not detected in 10 control subjects of in 10 patients with ragweed hayfever who were not desensitized. When mononuclear cells taken from treated patients were passed over columns containing insolubilized histamine, antigen-specific suppressor cells that could be activated by ragweed antigen were depleted. These results indicate that antigen-specific suppressor cells, probably bearing histamine receptors, are generated during desensitization to allergy and may be partly responsible for the efficacy of this therapy.
Treatment of Severe Atopic Dermatitis with Omalizumab: Experience of a Portuguese Immunoallergology Department
Authors: Ana M. Mendes, Leticia Pestana, Rita Aguiar, Ana Célia Costa, Elisa Pedro, Anabela Lopes, Maria A. Spinola Santos, Estrella Alonso, M.A. Pereira-Barbosa
Journal: Journal of Allergy and Clinical Immunology (2016)