tbuckley/cabot-search huggingface dataset:
Linkage of the Angiotensinogen Gene to Essential Hypertension
Authors: Mark Caulfield, Paul Lavender, Martin Farrall, Patricia Munroe, Mary Lawson, Paul Turner, Adrian Clark
Journal: New England Journal of Medicine (1994)

The renin-angiotensin system is a powerful pressor system with a major influence on salt and water homeostasis. Angiotensinogen (also called renin substrate) is a key component of this system; it is cleaved by renin to yield angiotensin I, which is then cleaved by angiotensin-converting enzyme to yield angiotensin II. The observation that plasma angiotensinogen levels correlate with blood pressure and track through families suggests that angiotensinogen may have a role in essential hypertension. We therefore investigated whether there is linkage between the angiotensinogen gene on chromosome 1q42-43 and essential hypertension.
An Outbreak of Infectious Hepatitis in Two Arctic Villages
Authors: Thomas R. A. Davis
Journal: New England Journal of Medicine (1957)

AVAILABLE evidence indicates that virus A, the etiologic agent of infectious hepatitis, has a world-wide distribution. The short duration since infectious hepatitis has been reportable is such that available information has resulted mainly from epidemics whose proportions were large enough to attract attention. Because of the lack of a suitable laboratory animal, full knowledge of the problems associated with the disease is lacking, and evidence so far indicates a fecal-oral route of transmission. Although epidemics of hepatitis due to virus A have resulted from fecal contamination of water,1 , 2 milk3 and food,4 it is considered that the usual mode of spread . . .
Clinical Results of Treatment of Diabetes Insipidus with Drugs of the Chlorothiazide Series
Authors: John D. Crawford, Gordon C. Kennedy, Lisa E. Hill
Journal: New England Journal of Medicine (1960)

DIABETES insipidus ordinarily is due to lack of the neurohypophyseal hormone, vasopressin, which enables the kidneys to form concentrated urine. Treatment consists of administering material obtained from animal sources intranasally, sublingually or intramuscularly. To control polyuria adequately with the first two routes, treatment must be repeated on the average four times daily whereas the preparation for intramuscular use, in which the hormone is tannated and suspended in oil, provides relief for approximately forty-eight hours. Less commonly, a nephrogenic type of the disease is encountered. Here, endogenous hormone is formed in abundance, but the kidney fails to respond to it. Moreover, . . .
Complete Acromioclavicular Dislocation
Authors: Boardman Marsh Bosworth
Journal: New England Journal of Medicine (1949)

FOR a lesion that appears to be so simple, complete acromioclavicular dislocation can be one of the least satisfactory of traumatic injuries to treat. It is rarely difficult to reduce the dislocation but to hold the reduction is another matter.Structure and FunctionThis problem is best approached by a brief consideration of the structure and function of the parts involved. In man, the upper extremity is not normally used for weight bearing but largely for prehension and tactile information — uses that require an extreme degree of freedom and as full a range of motion as possible. Such mobility . . .
Blue Sclerae in Osteogenesis Imperfecta
Authors: G Leidig-Bruckner, A Grauer
Journal: New England Journal of Medicine (1998)

Figure 1. A 26-year-old woman (Panel A) and her 6-year-old daughter (Panel B) were evaluated for recurrent bone fractures. Both had blue sclerae. The mother had had a femoral-neck fracture at the age of 3 years and fractures of the elbow and wrist at the age of 10 and 13 years, respectively. All fractures occurred after minimal trauma. The mother also had progressive hearing loss and had lost nearly all her upper and lower molars. Her medical history was otherwise normal. She was short (147 cm) and had no overt skeletal deformities. Biochemical markers of bone metabolism were in the . . .
Claudin-18 deficiency is associated with airway epithelial barrier dysfunction and asthma
Authors: Kelly Sweerus, Marrah Lachowicz-Scroggins, Erin Gordon, Michael LaFemina, Xiaozhu Huang, Mihir Parikh, Cindy Kanegai, John V. Fahy, James A. Frank
Journal: Journal of Allergy and Clinical Immunology (2016)
Rice-Based Oral Electrolyte Solutions for the Management of Infantile Diarrhea
Authors: Daniel Pizarro, Gloria Posada, Leyla Sandi, J. Roberto Moran
Journal: New England Journal of Medicine (1991)

In infants the treatment of acute diarrhea with glucose-based solutions results in rehydration but does not reduce the severity of diarrhea. Oral rehydration with solutions based on rice powder may reduce stool output as well as restore fluid volume.
Liver Iron Concentration By MRI In Chronically Transfused Children With Sickle Cell Anemia In The Twitch Trial
Authors: John C. Wood, Zora R. Rogers, Isaac Odame, Janet Kwiatkowski, Margaret Lee, William C. Owen, Alan Cohen, Timothy St. Pierre, Barry R Davis, Crystal Parker, William Herbert Schultz, Russell E. Ware
Journal: Blood (2013)
Case 9-2004
Authors: Julie L. Gerberding, John G. Morgan, Jo-Anne O. Shepard, Richard L. Kradin
Journal: New England Journal of Medicine (2004)

Cough, fever, and myalgias developed in an 18-year-old college student; five days later he was admitted to the hospital in shock. Despite intensive fluid resuscitation and pressor administration, his condition deteriorated, and he died the next day. An autopsy was performed.
Oxidized mitochondrial nucleoids released by neutrophils drive type I interferon production in human lupus
Authors: Simone Caielli, Shruti Athale, Bojana Domic, Elise Murat, Manjari Chandra, Romain Banchereau, Jeanine Baisch, Kate Phelps, Sandra Clayton, Mei Gong, Tracey Wright, Marilynn Punaro, Karolina Palucka, Cristiana Guiducci, Jacques Banchereau, Virginia Pascual
Journal: The Journal of Experimental Medicine (2016)

Autoantibodies against nucleic acids and excessive type I interferon (IFN) are hallmarks of human systemic lupus erythematosus (SLE). We previously reported that SLE neutrophils exposed to TLR7 agonist autoantibodies release interferogenic DNA, which we now demonstrate to be of mitochondrial origin. We further show that healthy human neutrophils do not complete mitophagy upon induction of mitochondrial damage. Rather, they extrude mitochondrial components, including DNA (mtDNA), devoid of oxidized (Ox) residues. When mtDNA undergoes oxidation, it is directly routed to lysosomes for degradation. This rerouting requires dissociation from the transcription factor A mitochondria (TFAM), a dual high-mobility group (HMG) protein involved in maintenance and compaction of the mitochondrial genome into nucleoids. Exposure of SLE neutrophils, or healthy IFN-primed neutrophils, to antiribonucleotide protein autoantibodies blocks TFAM phosphorylation, a necessary step for nucleoid dissociation. Consequently, Ox nucleoids accumulate within mitochondria and are eventually extruded as potent interferogenic complexes. In support of the in vivo relevance of this phenomenon, mitochondrial retention of Ox nucleoids is a feature of SLE blood neutrophils, and autoantibodies against Ox mtDNA are present in a fraction of patients. This pathway represents a novel therapeutic target in human SLE.
An Appraisal of the Newer Electrocardiography: Correlations in One Hundred and Fifty Consecutive Autopsied Cases
Authors: Harold D. Levine, Edward Phillips
Journal: New England Journal of Medicine (1951)

LARGELY as a result of the brilliant fundamental studies of Wilson and the Ann Arbor school, the last decade has witnessed a large-scale change in electrocardiograph technics and in the thoroughness with which electrocardiograms are recorded. Whereas routine studies formerly included the three conventional bipolar extremity leads of Einthoven and a single or perhaps two "precordial" leads, likewise utilizing a bipolar technic, the recent trend, except in a few clinics, has been to include the three conventional limb leads, three unipolar limb leads and six (or in some quarters seven) unipolar chest leads. It is the current consensus, as indicated . . .
Blood Lactate, Pyruvate and Lactate-Pyruvate Ratios in Congenital Heart Disease
Authors: Nicholas M. Greene, Norman S. Talner
Journal: New England Journal of Medicine (1964)

THE equilibrium (Equation 1, below) which exists between lactic acid and pyruvic acid is, in the presence of normal lactic dehydrogenase (LDH) activity, dependent upon the ratio of oxidized (DPN) to reduced (DPNH2) diphosphopyridine nucleotide (that is, NAD and NADH, oxidized and reduced nicotinamide-adenine dinucleotide, respectively, according to recent nomenclature), and so is controlled, through electron-transfer systems, by molecular oxygen. In the presence of decreased amounts of molecular oxygen the normal DPN:DPNH2 ratio cannot be maintained, and Equation 1 shifts to the right, with a consequent accumulation of lactic acid. For this reason the ratio between lactate . . .
Activation by Extracellular Nucleotides of Chloride Secretion in the Airway Epithelia of Patients with Cystic Fibrosis
Authors: Michael R. Knowles, Lane L. Clarke, Richard C. Boucher
Journal: New England Journal of Medicine (1991)

Cystic fibrosis is characterized by abnormal electrolyte transport across the epithelia of the airways. In particular, there is excessive sodium absorption and de..cient chloride secretion. Drugs that block excessive sodium absorption may provide clinical benefit in cystic fibrosis, but there are no available therapeutic agents to improve chloride secretion. In vitro studies in cultured human-airway epithelia indicate that triphosphate nucleotides (ATP and UTP) induce chloride secretion through apical-membrane purinergic receptors.
P96 Interstitial lung disease caused by STING-associated vasculopathy with onset in infancy (SAVI)
Authors: EJ Pellowe, SLN Clarke, TN Hilliard, AV Ramanan
Journal: Thorax (2015)

<h3>Introduction</h3> An increasing number of monogenic auto-inflammatory conditions known as primary type I interferonopathies are being recognised. We present a case of the newly described condition, stimulator of interferon gene (STING) associated vasculopathy with onset in infancy (SAVI), with significant respiratory involvement. <h3>Presentation</h3> A male infant, born to healthy non-consanguineous parents, presented to his local hospital with tachypnoea, intermittent fever and failure to thrive from 5 weeks of age. Over the following months, episodes of increased respiratory effort, cough and fever were attributed to infection. He subsequently developed a papular rash in discrete clusters over his back. At presentation to our centre at 7 months of age, he was tachypnoeic but not hypoxaemic. A chest radiograph showed extensive airspace shadowing with chest computed tomography demonstrating interstitial changes. Bronchoalveolar lavage was negative for infection. Laboratory tests revealed microcytic anaemia, raised inflammatory markers, positive anti-nuclear antibody, raised IgA and IgG and abnormal lymphocyte proliferation. A lung biopsy showed a mixed pattern of inflammation, with type 2 pneumocyte hyperplasia and endothelial tuboreticular inclusions on electron microscopy. Given the combination of interstitial lung disease, skin rash and likely vasculopathy, SAVI was suspected. This was confirmed on genetic testing with a heterozygous somatic mutation (c.463G &gt;A, p. V155M) in exon 5 of the <i>TMEM173</i>, the gene encoding STING. <h3>Treatment</h3> Treatment with pulsed methylprednisolone was commenced without improvement. He gained weight with supplemental feeding but had persistent tachynoea, subsequently becoming hypoxaemic requiring low flow oxygen therapy. He commenced on a trial of monthly intravenous immunoglobulin (IVIg) with evidence of clinical efficacy awaited. We are considering the use of the Janus kinase inhibitor, baricitinib, as a specific targeted therapy to block interferon signalling. <h3>Conclusion</h3> SAVI is a recently described interferonopathy in which lung involvement is a major clinical feature with consequent significant morbidity and mortality. Twelve patients have been reported so far in the literature, with overall poor response to glucocorticoids and disease modifying anti-rheumatic drugs. In the context of failure to thrive, fevers, rash and interstitial lung disease in early life, we urge clinicians to consider SAVI as a differential diagnosis and to seek testing for <i>TMEM173</i> mutations.
ATCT-17IMPACT OF ADVERSE RADIOLOGICAL AND HISTOPATHOLOGIC CHARACTERISTICS ON OUTCOME OF AGGRESSIVE ADULT LOW GRADE GLIOMAS TREATED UNIFORMLY WITH RADIOTHERAPY AND CONCURRENT AND ADJUVANT TEMOZOLOMIDE: AN ANALYSIS OF 47 PATIENTS
Authors: Rakesh Jalali, Nikhil Kalyani, Sridhar Epari, Sona Pungavkar, Jayant Godasastri, Aliasgar Moiyadi, Prakash Shetty, Shraddha Churi, Tejpal Gupta
Journal: Neuro-Oncology (2015)

BACKGROUND: We investigate the impact of adverse radiology and histopathologic characteristics in adult low-grade gliomas (LGG) treated uniformly with post-operative radiotherapy with concurrent and adjuvant Temozolomide (TMZ). We also compare outcomes with published RTOG-9802 and RTOG-0424 trials data. METHODS: Between February 2009 to March 2014, 47 patients with supratentorial aggressive LGG selected meticulously based on predefined high-risk features on pre-operative MRI and histomorphology [nuclear pleomorphism suggesting atypical histology, high cellularity/mitosis, high Mib-1 index, and/or radiological features like definite gadolinium enhancement or considerable heterogeneity on T2 fluid-attenuated inversion recovery (FLAIR)]) were treated with post-operative RT with concurrent (75mg/m2) and adjuvant TMZ (150-200 mg/m2) for 6-12 cycles. All patients had either subtotal resection/biopsy/or had 3 or more Pignatti's high risk factors. RESULTS: Median age of the cohort was 35 years. Histologies included astrocytoma in 17 patients, oligodendrogliomas in 11 patients and mixed in remaining. Median RT dose was 55.8 Gy, median TMZ cycles were 6. The median Mib-1 index was 4 (range 2-15%). P53 mutation was present in 19/25 tested samples. 1p19q co-deletion was found in 11/22 tested samples. IDH 1 was mutated in 5/9 cases tested. At a mean follow up of 31 months, the 3 year and 5 year OS was 86% and 73% respectively, while PFS was 82% and 61% respectively. For 31 patients having 3 or more Pignatti's high risk factors, 3 year OS and PFS were 85% and 73% respectively. Five patients had clinic-radiological progression, while two patients had transformation to glioblastoma. No grade III/beyond toxicity was reported. CONCLUSION: Our experience of employing TMZ in concurrent and adjuvant setting along with focal irradiation in aggressive adult LGG, based on adverse radiological and histopathologic factors, even without all molecular markers is encouraging. Future work will include late follow-up data and impact of molecular markers in this cohort.
Coronary-Artery Stenting Compared with Balloon Angioplasty for Restenosis after Initial Balloon Angioplasty
Authors: Raimund Erbel, Michael Haude, Hans W. Höpp, Damian Franzen, Hans Jürgen Rupprecht, Bernd Heublein, Klaus Fischer, Peter de Jaegere, Patrick Serruys, Wolfgang Rutsch, Peter Probst
Journal: New England Journal of Medicine (1998)

Intracoronary stenting reduces the rate of restenosis after angioplasty in patients with new coronary lesions. We conducted a prospective, randomized, multicenter study to determine whether intracoronary stenting, as compared with standard balloon angioplasty, reduces the recurrence of luminal narrowing in restenotic lesions.
The Natural History of Prediabetes
Authors: W. P. U. Jackson, N. Woolf
Journal: New England Journal of Medicine (1956)

YEARS before a woman becomes overtly diabetic she may produce babies who are large and who are often stillborn or die in the neonatal period.1 2 3 Such babies show specific abnormalities, especially of the pancreas. The underlying state of these women, destined later to become diabetic, is called "prediabetes." The patient in the case reported below represents to us the personification of prediabetes.Mrs. S. is an intelligent 38-year-old colored woman, a nurseryman's wife, weighing 97.5 kg. (215 pounds). Her mother was diabetic. Before the birth of her 1st child she was slim, but her weight progressively increased with each of . . .
Metabolic reprogramming of bone marrow stromal cells by leukemic extracellular vesicles in acute lymphoblastic leukemia
Authors: Suzanne M. Johnson, Clare Dempsey, Amy Chadwick, Stephanie Harrison, Jizhong Liu, Yujun Di, Owen J. McGinn, Marco Fiorillo, Federica Sotgia, Michael P. Lisanti, Mayur Parihar, Shekhar Krishnan, Vaskar Saha
Journal: Blood (2016)
A Comparison of Aspirin with Placebo in Patients Treated with Warfarin after Heart-Valve Replacement
Authors: Alexander Turpie, Michael Gent, Andreas Laupacis, Yves Latour, John Gunstensen, Fadi Basile, Marian Klimek, Jack Hirsh
Journal: New England Journal of Medicine (1993)

Despite the use of warfarin, major systemic embolism remains an important complication in patients with heart-valve replacement. Although the addition of antiplatelet agents has the potential to reduce this complication, their efficacy and safety when given in combination with warfarin are uncertain.
Congenital Hypothyroidism Caused by Mutations in the Thyrotropin-Receptor Gene
Authors: Heiki Biebermann, Annette Grüters, Torsten Schöneberg, Thomas Gudermann
Journal: New England Journal of Medicine (1997)

To the Editor: The causes of congenital hypothyroidism are poorly understood. Recently, two different missense mutations in the extracellular domain of the thyrotropin receptor were identified in three siblings who had elevated serum thyrotropin concentrations but were euthyroid and had thyroid glands of normal size.1 We describe a patient with congenital hypothyroidism and thyroid hypoplasia due to two loss-of-function mutations in exon 10 of the thyrotropin-receptor gene. At birth the patient, the firstborn infant of nonconsanguineous parents, had a blood thyrotropin concentration of 89 mU per liter. Reexamination revealed a serum thyrotropin concentration of 82 mU per liter (normal, <10) . . .
Cross-Sensitivity to Diphenylhydantoin Sodium and to Phenobarbital
Authors: George E. Morris, Jack D. Cohen
Journal: New England Journal of Medicine (1953)

THE phenyl-derived anticonvulsant drugs described by Putnam and Merritt1 have been in use for over fifteen years. Although they have been found to be of great value in the control of epilepsy, both mild and serious side effects have occasionally followed their administration. Gingival hypertrophy, dermatoses, ataxia, bone-marrow depression, hepatitis, nephrosis, twitching of the muscles, lapses into gradual sleep or coma, pancytopenia and fatal aplastic anemia have resulted from the use of these drugs.2 3 4 Phenobarbital has been widely used for several years, and its administration has resulted in such side effects as skin eruptions, incapacitating drowsiness, headaches, apathy and ataxia. . . .
Clofarabine plus cytarabine (ara-C) is an active induction regimen for newly diagnosed patients (pts) ≥ age 50 with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS)
Authors: S. Faderl, V. Gandhi, F. Giles, E. Estey, G. Garcia-Manero, S. O Brien, W. Wierda, M. Kwari, A. Craig, H. M. Kantarjian
Journal: Journal of Clinical Oncology (2004)

6609 Background: Clofarabine is a new-generation nucleoside analog with activity in acute leukemias. As a potent inhibitor of ribonucleotide reductase, it is also suited for biochemical modulation strategies with other nucleoside analogs. In a phase I/II study of clofarabine + ara-C in pts with relapsed/refractory AML/MDS, we reported a response rate of 41% (24% CR, 17% CRp) (Blood 102:615a, 2003). Cellular pharmacology studies suggested that accumulation of intracellular clofarabine triphosphate resulted in higher ara-CTP accumulation of the leukemia blasts. Methods: We are conducting a phase II study of clofarabine + ara-C to evaluate efficacy and safety of this combination in pts ≥ 50 years (yrs) with newly diagnosed AML and high-risk MDS (≥ 10% marrow blasts). Pts with good prognosis karyotypes [t(8;21), inv(16), t(15;17)], ECOG PS > 2, and age ≥ 75 are excluded. Clofarabine is given at 40mg/m2/d as a 1-hour (hr) i.v. infusion for 5 days (d2–6) followed 4 hrs later by ara-C at 1g/m2/d as a 2-hr i.v. infusion for 5 days (d1–5). Results: 31 (28 AML, 3 MDS) of 37 pts are evaluable. Median age 61 yrs (range 50–72). Cytogenetics: diploid in 16 and abnormal in 15 pts. Median WBC 9.1 x 109/L (1–135.8). Median platelet count 44 x 109/L (8–871). 16 pts (52%) achieved CR after one induction course; another 4 pts (13%) achieved CRp. Of 6 pts who received a second induction course, one pt (CRp) responded. The CR rate was 63% (10/16 pts) in the diploid and 40% (6/15) in the abnormal group. Median time to CR: 28 days (23–56). 4 pts (13%) died on study: 1 pt died on d35 of complications due to sepsis; the remaining 3 pts died following a second induction course (d 47, 52, 78) due to prolonged cytopenias and sepsis. Clofarabine infusion related adverse events included facial flushing and headaches (< gr. 3) and were transient. Other toxicities included hyperbilirubinemia (gr. 3 in 3 pts) and pancreatitis (1 pt). Conclusions: The combination of clofarabine + ara-C is active in older pts with newly diagnosed AML/high-risk MDS. The toxicity profile is acceptable. An update of response and toxicity data will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ILEX ILEX Oncology ILEX Oncology
The cost-effectiveness of psychotherapy: a plan for research
Authors: J L Krupnick, H A Pincus
Journal: American Journal of Psychiatry (1992)

The authors assess gaps in the current knowledge base on psychotherapy research and the cost-effectiveness of psychotherapy. Despite the considerable and increasingly sophisticated body of research on the efficacy of psychotherapy, there is an alarming paucity of studies focusing on the cost-effectiveness of psychotherapy. This problem is particularly evident in the absence of studies exploring nonclinical effects of treatment and the broader range of domains in which intervention may have an impact. Initiation of research on the cost-effectiveness of psychotherapy is important for ensuring good clinical practice and data-based policy formulation. What is needed is greater specificity regarding the populations and problems for which psychotherapy can provide the greatest benefits, identification of the variables, measures, and methodological approaches that are most useful in yielding these important data, and comprehensive quantification of the costs and effects of psychotherapy.