tbuckley/cabot-search huggingface dataset:
An Immunodeficiency Characterized by Defective Signal Transduction in T Lymphocytes
Authors: Talal Chatila, Richard Wong, Michael Young, Richard Miller, Cox Terhorst, Raif S. Geha
Journal: New England Journal of Medicine (1989)

We studied a nine-year-old boy with severe, recurrent infections. The patient was exposed in utero to azathioprine and prednisone. He had autoimmune hemolytic anemia, bronchiectasis, and Hodgkin's disease. The patient's circulating lymphocytes were normal in number and phenotype, but stimulation of the T-cell receptor by antigens, mitogens, and monoclonal antibodies failed to induce interleukin-2–receptor expression, interleukin-2 synthesis, or lymphocyte proliferation. The early biochemical events necessary to initiate lymphocyte activation — accumulation of the second messenger diacylglycerol, activation of the enzyme protein kinase C, and elevation of the free intracellular calcium concentration — failed to occur in this patient's lymphocytes. The defect in the lymphocyte could be corrected in vitro by two agents that bypass the receptor-mediated signal mechanism (the diacylglycerol analogue phorbol and the calcium ionophore ionomycin). Further studies localized the defect in signal transduction to the interaction between cell-surface receptors and the guanine nucleotide-binding protein. We conclude that this patient's immunodeficiency was caused by a defective coupling of surface receptors to signal-transducing proteins in his T lymphocytes, resulting in failure of lymphocyte activation. (N Engl J Med 1989; 320:696–702.)
Outcome of Myocardial Infarction in Veterans Health Administration Patients as Compared with Medicare Patients
Authors: Laura A. Petersen, Sharon-Lise T. Normand, Jennifer Daley, Barbara J. McNeil
Journal: New England Journal of Medicine (2000)

Some have the opinion that patients cared for in Veterans Health Administration (VHA) hospitals receive care of poorer quality than those cared for in non-VHA institutions. To assess the quality of care in VHA hospitals, we compared the outcome of acute myocardial infarction among patients in VHA and non-VHA institutions while controlling for potential confounders, including coexisting conditions and severity of illness.
Pneumonia Due to<i>Chlamydia trachomatis</i>in an Immunocompromised Adult
Authors: James I. Ito, Keith A. Comess, E. Russell Alexander, H. Robert Harrison, C. George Ray, Jeffrey Kiviat, Richard E. Sobonya
Journal: New England Journal of Medicine (1982)

CHLAMYDIA trachomatis infection has been associated with a wide spectrum of syndromes ranging from ocular to genital-tract diseases. It has been implicated as the cause of a pneumonitis syndrome in infants.1 , 2 Tack et al. have reported on six patients with various underlying conditions (chronic bronchitis, renal allografts, and acute lymphocytic leukemia), most of whom had radiographic evidence of pneumonia.3 C. trachomatis was isolated from sputum, bronchial brushings, or lung tissue in all six. However, the etiologic role of this organism in these patients with respiratory disease remained in question because no antibody to C. trachomatis was demonstrated in the serum . . .
Effects of 25-Hydroxycholecalciferol in Patients with Familial Hypophosphatemia and Vitamin-D-Resistant Rickets
Authors: H. Shelton Earp, Robert L. Ney, Hillel J. Gitelman, Robert Richman, Hector F. DeLuca
Journal: New England Journal of Medicine (1970)

The conversion of vitamin D3 to 25-hydroxycholecalciferol (25-HCC) is quantitatively decreased in some patients with familial hypophosphatemia and vitamin-D-resistant rickets. We tested the responses of five patients with familial vitamin-D-resistant rickets to 25-HCC to determine if their abnormalities in calcium and phosphorus metabolism were due to an inherited defect in the conversion of vitamin D to 25-HCC. Four-week studies of metabolic balance were performed during which 25-HCC was given in a dose of 2500 U daily for the last three weeks. Serum and urinary phosphorus, serum calcium and serum alkaline phosphatase did not change in a consistent manner. Urinary calcium increased slightly in three of five subjects, but in only one subject was a positive effect on calcium balance observed. Thus, a defect in conversion of vitamin D to 25-HCC appears not to be solely responsible for the metabolic abnormalities seen in this disease.
Struck by Lightning
Authors: M Zehender
Journal: New England Journal of Medicine (1994)

Figure 1. Struck by Lightning. A 41-year-old woman in her 26th week of pregnancy was struck by lightning while standing under a tree during a thunderstorm. The lightning entered her body on the right side of the neck through a necklace, went toward the ground, was deflected by the baby's head, and left the woman's body through the left leg, marking its way by a cutaneous “lightning print.” The woman survived, but the baby died.
Leukocyte Activation in Allergen-Induced Late-Phase Asthmatic Reactions
Authors: S.R. Durham, Mary Carroll, G.M. Walsh, A.B. Kay
Journal: New England Journal of Medicine (1984)

Some patients with allergen-induced asthma have both an early and late reaction to allergen (dual asthmatic reactions). To investigate the role of leukocyte activation in dual asthmatic reactions, we measured neutrophil chemotactic activity, percentages of neutrophil and monocyte complement rosettes, and one-second forced expiratory volume (FEV1) in 11 patients with allergen-induced dual asthmatic reactions after a challenge with allergen. To control for the effects of bronchoconstriction, the same studies were done after a challenge with methacholine. In all subjects there was a biphasic increase in neutrophil chemotactic activity and in the percentages of neutrophil and monocyte complement rosettes, accompanied by a reduction in the FEV1. After methacholine, there were no significant changes in neutrophil chemotactic activity or percentages of complement rosettes, despite bronchoconstriction. Six patients with single-phase allergen-induced asthma had similar responses, but they were monophasic. We conclude that allergen-induced early and late asthmatic reactions are accompanied by activation of leukocytes and that these alterations probably reflect the release of mediators from mast cells rather than an effect of bronchoconstriction. (N Engl J Med 1984; 311:1398–1402.)
EPID-33RISK MODELING FOR VASCULAR TOXICITY IN PATIENTS WITH GLIOBLASTOMA (GBM) TREATED ON NRG ONCOLOGY/RTOG 0825
Authors: Renke Zhou, Michael Scheurer, Mark Gilbert, Melissa Bondy, Eric Sulman, Ying Yuan, Yanhong Liu, Elizabeth Vera-Bolanos, Merideth Wendland, David Brachman, James Bearden, Susan McGovern, Steven Wilson, Kevin Judy, H. Ian Robins, Grant Hunter, Ian Crocker, Samuel Chao, Vesna Kaluza, Stephanie Pugh, Terri Armstrong
Journal: Neuro-Oncology (2015)

BACKGROUND: Tumor response and treatment-related toxicities vary greatly among patients despite careful selection criteria and accurate drug dosing. This projects was to evaluate risk and validate prediction models for vascular toxicity in patients with newly diagnosed GBM treated with bevacizumab. METHODS: We tabulated the incidence of cardiac and vascular toxicity in RTOG0525 (standard vs. dose-dense temozolomide) and RTOG0825 (bevacizumab (BEV) vs placebo). Based on the data collected from RTOG0825 BEV containing arm, a risk prediction model for hypertension (Grade 2-4) and thrombosis (Grade 3-4) was built based on known risk factors. Candidate risk factors were screened using univariable logistic regression (significance 0.15), then included in a multivariable model (significance 0.05) to determine the final risk model. RESULTS: In RTOG0825, overall incidence of hypertension was 11% (67/591) and thrombosis (73/591) 12%. Hypertension was higher with BEV (15 vs 8%) and no difference found for thrombosis (12 vs 13%). Men experienced more toxicity than women (12 vs 10% hypertension; 14 vs 9% thrombosis) but this was not significant at 0.05. None of the known risk factors for hypertension and thrombosis with BEV were significant in the final risk prediction model. For comparison, in RTOG0525, the incidence of cardiac toxicity was 4% (27/720) and thrombosis was 6%. CONCLUSIONS: Patients enrolled on these clinical trials had a lower overall incidence of both adverse events than would be expected in this demographic (middle aged or older with underlying glioblastoma where the incidence of hypertension is 30% and thromboembolism of 15%). Previously described risk factors were not confirmed, but may reflect selection by eligibility criteria of a healthier patient cohort compared with a population-based cohort. While clinical risk factors were unrevealing, planned genomic phenotyping focusing on polymorphisms may elucidate informative risk profiles. Supported by NCI grants U10CA21661, U10CA180868, U10CA180822, U10CA37422, U24CA114734, NIH grant 1R01NR013707, and Genentech.
Human Coccidiosis — A Possible Cause of Malabsorption
Authors: Lloyd L. Brandborg, Stanley B. Goldberg, Warren C. Breidenbach
Journal: New England Journal of Medicine (1970)

Nineteen biopsies of the small-bowel mucosa obtained from six patients infected with coccidia (Isospora belli) revealed a spectrum of abnormalities. All the patients had coccidia in their specimens. All the forms of the endogenous life cycle of the organism were identified within the epithelium. Detection of any of these stages of development is diagnostic of coccidiosis. Oocysts were found in the intestinal contents of one patient, and schizonts in another. All the patients had diarrhea and steatorrhea. Three died, one from pulmonary embolism. The therapy given was ineffective. Coccidia may be etiologic in patients with undiagnosed and obscure diarrhea and malabsorption. By careful examination of serially sectioned suction biopsies of small-bowel mucosa and of intestinal contents, additional cases are likely to be detected.
SAT0051 Protein Phosphatase Magnesium-Dependent 1A Regulates Osteoclast Differentiation Through Modulation of Rank Signaling
Authors: S. Hong, S.M. Ahn, D.-H. Lim, S.-H. Bae, E.-J. Chang, C.-K. Lee, B. Yoo, Y.-G. Kim
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Previously, immunity to protein phosphatase magnesium-dependent 1A (PPM1A), which was associated with TGF-β signaling, was reported in patients with ankylosing spondylitis (AS). In addition, PPM1A plays an important role in promotion of osteoblast (OB) differentiation. <h3>Objectives</h3> We try to investigate the role of PPM1A in osteoclast (OC) differentiation, given that AS was associated with OC activation as well as OB differentiation. <h3>Methods</h3> The expression of PPM1A was evaluated in bone-marrow macrophage during OC differentiation after stimulation with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-kB ligand (RANKL). To know the role of PPM1A in OC differentiation, OC differentiation was determined by tartrate-resistant acid phosphatase staining after with or without PPM1A knockdown by siRNA. Further, RANK expression and NF-kB signaling were investigated to see whether RANKL/RANK pathway is responsible for the effects of PPM1A in osteoclastogenesis. <h3>Results</h3> During OC differentiation, PPM1A expression was up-regulated with M-CSF and RANKL stimulation after three days in culture. In addition, RANKL-induced osteoclastogenesis was significantly attenuated by knockdown of PPM1A. However, PPM1A-mediated effects on OC differentiation were not observed when RANK signaling was already triggered before knockdown of PPM1A. Further, we found that silencing of PPM1A showed decrease in RANK expression and increase in IkB expression, indicating the enhancement of RANK/NF-kB pathway by PPM1A. <h3>Conclusions</h3> Our present findings suggested that PPM1A plays an important role in OC differentiation through enhancement of RANK and NF-kB signaling. <h3>References</h3> Role of Protein Phosphatase Magnesium-Dependent 1A and Anti–Protein Phosphatase Magnesium-Dependent 1A Autoantibodies in Ankylosing Spondylitis. Arthritis and Rheumatology, 66(10), 2793-2803, 2014 <h3>Disclosure of Interest</h3> None declared
Coronary Thrombolysis with Tissue-Type Plasminogen Activator in Patients with Evolving Myocardial Infarction
Authors: Frans Van de Werf, Philip A. Ludbrook, Steven R. Bergmann, Alan J. Tiefenbrunn, Keith A. A. Fox, Hilaire de Geest, Marc Verstraete, Desire Collen, Burton E. Sobel
Journal: New England Journal of Medicine (1984)

Tissue-type plasminogen activator is a naturally occurring, clot-selective activator of fibrinolysis. We recently reported that human tissue-type plasminogen activator isolated from a Bowes-melanoma-tissue-culture supernate lysed coronary thrombi in dogs without depleting circulating fibrinogen or alpha 2-antiplasmin, in contrast to the case with streptokinase and urokinase. In the present study coronary thrombolysis, confirmed angiographically, was induced within 19 to 50 minutes with intravenous or intracoronary tissue-type plasminogen activator in six of seven patients with evolving myocardial infarction. Circulating fibrinogen, plasminogen, and alpha 2-antiplasmin were not depleted by this agent, in contrast to the case in the two patients subsequently given streptokinase. In the one patient in whom lysis was not inducible with tissue-type plasminogen activator, it was also not inducible with streptokinase. These observations indicate that clot-selective coronary thrombolysis can be induced in patients with evolving myocardial infarction by means of tissue-type plasminogen activator, without concomitant induction of a systemic lytic state. Definition of its therapeutic benefit must await greater availability of the agent and the performance of appropriate clinical trials.
Day Hospitalization and an Inn Instead of Inpatient Care for Psychiatric Patients
Authors: Jon E. Gudeman, Miles F. Shore, Barbara Dickey
Journal: New England Journal of Medicine (1983)

During the past 25 years (1956 to 1981), there has been major growth in mental health services at virtually all levels, with considerable expansion of outpatient services, psychiatric units in general hospitals, private psychiatric hospitals, and community mental health centers. There has also been a shift in the locus of services and in the manner in which they are delivered. The resident population in state hospitals has decreased dramatically, from 550,000 in 1956 to an estimated 138,000 in 1980.1 An improved ability to treat seriously ill patients with neuroleptic medications, antidepressants, and lithium, and a civil rights movement supporting treatment . . .
Are There Levels of Consciousness?
Authors: Tim Bayne, Jakob Hohwy, Adrian M. Owen
Journal: Trends in Cognitive Sciences (2016)

The notion of a level of consciousness is a key construct in the science of consciousness. Not only is the term employed to describe the global states of consciousness that are associated with post-comatose disorders, epileptic absence seizures, anaesthesia, and sleep, it plays an increasingly influential role in theoretical and methodological contexts. However, it is far from clear what precisely a level of consciousness is supposed to be. This paper argues that the levels-based framework for conceptualizing global states of consciousness is untenable and develops in its place a multidimensional account of global states.
Perturbation of Sodium-Lithium Countertransport in Red Cells
Authors: James W. Woods, John C. Parker, Billie S. Watson
Journal: New England Journal of Medicine (1983)

The rate of sodium-lithium countertransport in red cells is thought to be determined by inheritance and to be constant over years in a given person. We have found that the rate is influenced acutely by ultrafiltration and by hemodialysis. In seven patients with endstage renal disease secondary to essential hypertension, the mean rate of sodium-lithium countertransport (+/- S.E.M.) was reduced from 0.18 +/- 0.02 to 0.09 +/- 0.01 mmol per liter of cells per hour (P less than 0.02) by ultrafiltration and from 0.22 +/- 0.03 to 0.12 +/- 0.03 mmol per liter per hour (P less than 0.001) by hemodialysis. When patients' red cells obtained before dialysis were incubated with plasma obtained afterward, the rate of countertransport fell, and when red cells obtained after dialysis were incubated with plasma obtained beforehand, the rate returned to normal. Whereas the rate in red cells from normal subjects was reduced after incubation in post-dialysis plasma from patients, predialysis plasma from the same patients had no such effect. We conclude that the rate of the countertransport system of red cells is dependent on a dialyzable plasma factor.
Effect of stem cell source on long-term chimerism and event-free survival in children with primary immunodeficiency disorders after fludarabine and melphalan conditioning regimen
Authors: Kanchan Rao, Stuart Adams, Waseem Qasim, Zoe Allwood, Austen Worth, Juliana Silva, Giovanna Lucchini, Robert Chiesa, Paul Veys, Persis Amrolia
Journal: Journal of Allergy and Clinical Immunology (2016)
Observations on the Development of Rheumatic Fever and Glomerulonephritis in Cases of Scarlet Fever Treated with Penicillin
Authors: Louis Weinstein, Louis Bachrach, Norman H. Boyer
Journal: New England Journal of Medicine (1950)

THE clinical course of scarlet fever and of pharyngitis due to the beta-hemolytic streptococcus has undergone remarkable change in the past few years as a result of the widespread use of penicillin. The duration of the fever, discomfort in the pharynx, leukocytosis, elevated sedimentation rate and persistence of the causative organisms in the respiratory tract have been so much reduced that the acute phase of the infection lasts no more than one to three days. Most striking has been the almost complete elimination of the suppurative complications such as otitis media, suppurative lymphadenitis, paronychiae, pneumonia and meningitis, and the ease . . .
JAK2Exon 12 Mutant Allele Burden Study (JETMABS): A European Multicenter Study
Authors: Eric Lippert, Francois Girodon, Susanne Schnittger, Serge Carillo, Caroline Riley, Beatriz Bellosillo, Maj K. Westman, Ole Weis Bjerrum, Marzena Wojtaszewska, Thomas Kristensen, Melanie Percy, Mary Frances McMullin, MRCPath, Maruska Marusic, Caroline Rosmond, Lars Palmqvist, Sylvie Hermouet, Hans Carl Hasselbalch
Journal: Blood (2013)
Malnutrition of the Newborn Secondary to Placental Abnormalities
Authors: Walter Pick
Journal: New England Journal of Medicine (1954)

SINCE statements of neither the day of conception nor the date of the last menstruation are usually reliable, most physicians consider an infant weighing less than 2.5 kg. (5/2 pounds) to be premature. The diagnosis of "prematurity by weight only" is frequently made when information indicates a full-term pregnancy.Some of these infants regarded as premature solely because of their weight can be assumed to be hereditarily small. Others are malnourished.Recently, 3 such undernourished infants, whose poor nutritional status presumably was caused by abnormalities of the placenta, came to my attention. The clinical course was similar in all and . . .
The Management of Abnormal Uterine Bleeding
Authors: George Van S. Smith
Journal: New England Journal of Medicine (1949)

EXCEPT for the stain of newborn females and the normal menstruation of constitutional precocity, all the rare cases of uterine bleeding during the period of childhood and preadolescence are but one manifestation of the precocious puberty associated with the following unusual conditions: certain cases of midbrain damage, Albright's disease, exceptional cases of tumor of the adrenal cortex, granulosa-cell tumor of the ovary and, very exceptionally, chorioncarcinomatous teratoma of the ovary. The observation of premature growth and development, then, is the signal for immediate investigation and possible operation. Uterine bleeding after the establishment of the menopause is due most often to . . .
Case 10-1982
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, John A. Kirkpatrick, David L. Gang
Journal: New England Journal of Medicine (1982)

Presentation of CaseA 19-month-old boy was admitted to the hospital because of atelectasis of the left lung.The child was born of a full-term pregnancy, which was not associated with the ingestion of medications or alcohol, although his mother smoked half a pack of cigarettes daily during the pregnancy. The birth weight was 3.15 kg. He was kept in the hospital an additional two days because of maternal fever. Examination of the child's cerebrospinal fluid was negative. He experienced symptoms of respiratory-tract infection almost monthly. During the month before admission he had a dry cough. Two weeks before entry . . .
Delirium and Coma Precipitated by Oxygen in Bronchial Asthma Complicated by Respiratory Acidosis
Authors: Henry D. Beale, Irving W. Schiller, Meyer H. Halperin, William Franklin, Francis C. Lowell
Journal: New England Journal of Medicine (1951)

ALTHOUGH the hazards of many therapeutic procedures are reasonably well known, clinicians need to be reminded occasionally that measures thought to be perfectly safe may be dangerous under certain special circumstances. Oxygen in high concentrations, as often administered to patients with a variety of respiratory, cardiovascular and neuromuscular conditions, may at times be more harmful than beneficial. From the manner in which oxygen is prescribed, however, one would doubt that its potentially deleterious effects are widely recognized, although they have been known for some time.Oxygen given in high concentrations (50 to 100 per cent) for long periods may be . . .
The Relationship Between Cytokine Levels and Symptoms in Patients (Pts) With Myelofibrosis (MF) From COMFORT-II, a Phase 3 Study of Ruxolitinib (RUX) Vs Best Available Therapy (BAT)
Authors: Matthew Squires, Claire N Harrison, Giovanni Barosi, Alessandro M Vannucchi, Tiziano Barbui, Heinz Gisslinger, Francesco Passamonti, Haifa Kathrin Al-Ali, Jean-Jacques Kiladjian, Mahtab T. Marker, Estella T. Mendelson, Viktoriya Stalbovskaya, Francisco Cervantes, Laurent Knoops
Journal: Blood (2013)
Screening for Gestational Diabetes Mellitus
Authors: Michael F. Greene
Journal: New England Journal of Medicine (1997)

Gestational diabetes mellitus was originally defined by O'Sullivan and Mahan1 in a group of 752 unselected pregnant women in Boston as indicated by two or more blood glucose concentrations that were more than 2 SD above the mean after a three-hour oral glucose-tolerance test. The investigators' initial interest was in the ability of such a finding to predict the development of diabetes in later life. Currently, gestational diabetes is defined more broadly as carbohydrate intolerance, with onset or first recognition during pregnancy and without reference to a specific testing procedure.2 Just as the definition has changed, so too has the . . .