tbuckley/cabot-search huggingface dataset:
Preliminary Results of a Double-Blind, Randomized, Placebo-Controlled Trial of Cyclosporine in Myasthenia Gravis
Authors: Richard S.A. Tindall, Julia A. Rollins, J. Theodore Phillips, Ralph G. Greenlee, Lieselotte Wells, George Belendiuk
Journal: New England Journal of Medicine (1987)

We randomly assigned 20 patients with progressively worsening generalized myasthenia gravis of recent onset whose illness was not controlled by anticholinesterase therapy to treatment with either cyclosporine (6 mg per kilogram of body weight per day) or placebo. Patients who had been treated with thymectomy, steroids, or other immunosuppressive agents were excluded. The duration of treatment was 12 months. Disease activity was assessed by quantified strength testing and by measurements of antihuman acetylcholine-receptor antibody. Patients were assessed at 6 months and 12 months, or at the following early end points: drug failure (doubling of creatinine), treatment failure (respiratory or swallowing difficulty), or protocol violation (stopping medication for more than five days). At six months, patients in the cyclosporine group had had significantly more objective improvement in strength; one early end point had been reached (drug failure; no treatment failures). In the placebo group, three early end points had been reached (all treatment failures). The decline in titers of acetylcholine-receptor antibody was larger in the treated group, although the difference was not statistically significant. At the end of the study (after 12 months of treatment or arrival at an earlier end point), improvement in strength and reduction in titers of antireceptor antibody continued to be greater in the cyclosporine group. Nephrotoxicity occurred in three patients receiving cyclosporine but was nonprogressive with a reduction in dosage and reversible with discontinuation of the drug. These results are preliminary and need confirmation, but we conclude that cyclosporine is probably an effective therapy in some patients with myasthenia gravis. (N Engl J Med 1987;316:719–24.)
Patterns of Cardiovascular Dysfunction in Chronic Obstructive Lung Disease
Authors: Benjamin Burrows, Louis J. Kettel, Albert H. Niden, Murray Rabinowitz, Carl F. Diener
Journal: New England Journal of Medicine (1972)

Abstract A longitudinal seven-year study of 50 patients with chronic airway obstruction, whose cardiovascular function had been evaluated by cardiac catheterization when their condition was stable, showed that their survival was inversely related to pulmonary vascular resistance. Fourteen patients with high vascular resistances showed two different patterns of cardiovascular abnormality. Nine had relatively normal blood gases, low cardiac outputs, and near normal resting pulmonary-artery pressures; they had an emphysematous type of lung disease. The five with more severe blood gas abnormalities who had a more bronchitic type of disease, had well maintained cardiac outputs and more severe pulmonary hypertension. They more regularly presented the classic clinical and electrocardiographic features of cor pulmonale. Left ventricular dysfunction appeared to be an important determinant of pulmonary hypertension in only one patient.
Case 14-1997
Authors: David W. Roberts, Kathy L. Newell
Journal: New England Journal of Medicine (1997)

Presentation of CaseA 30-year-old woman was admitted to the hospital because of intractable seizures.The patient was born of an uneventful full-term pregnancy. Her first seizure, at the age of 23 years, was characterized by an aura of “dizziness” with a “disconnected” feeling, followed by confusion with impaired consciousness that lasted about two minutes. She continued to have complex partial seizures with occasional secondary generalization despite anticonvulsant medications. Thirty-four months before admission, video electroencephalographic monitoring for five days indicated that the seizures arose from the right temporal region. Electroencephalographic abnormalities consisted of rhythmic activity of up to 6 Hz . . .
Abstract 17123: Association of Apolipoprotein(a) Isoforms With Coronary Heart Disease is Mediated Through Plasma Lipoprotein(a) Levels
Authors: Jemma C Hopewell, Robert Clarke, Udo Seedorf, Martin Farrall, Anders Hamsten, Rory Collins, Hugh Watkins
Journal: Circulation (2010)

Background:  Increased plasma levels of lipoprotein(a) (Lp(a)) and smaller apolipoprotein(a) (apo(a)) isoforms have both been associated with higher risks of coronary heart disease (CHD), but their independent relevance is uncertain.   Methods:  The apo(a) isoform size, as measured by the number of Kringle IV-2 (KIV-2) repeats, was measured in 1000 cases and 1000 controls matched for age, sex, and country of recruitment for whom plasma levels of Lp(a) were also available. Logistic regression analyses were used to assess the associations of quintiles of Lp(a) levels with risk of CHD, before and after adjustment for KIV-2 repeats. The analyses also assessed the converse associations of quintiles of KIV-2 repeats with risk of CHD, before and after adjustment for Lp(a).   Results:  Plasma levels of Lp(a) were inversely correlated with the number of KIV-2 repeats (ρ spearman = -0.58). The geometric mean Lp(a) level was higher in cases than controls (15.6 mg/dL [95% CI: 14.5-16.8] vs 11.7 mg/dL [95% CI: 11.0-12.5]) and the median number of KIV-2 repeats was lower (25 in cases vs 26 in controls). Individuals in the top quintile of Lp(a) levels had a 2.5-fold higher risk of CHD compared with those in the bottom quintile, which was materially unaltered by adjustment for KIV-2 repeats. Individuals in the bottom quintile of KIV-2 repeats also had a 2.5-fold higher risk of CHD compared with those in the top quintile, but this increase in risk was completely attenuated after adjustment for plasma levels of Lp(a) (p=0.19).   Conclusions:  While higher plasma levels of Lp(a) are strongly and inversely correlated with smaller isoforms and both are strongly related to CHD risk, these results suggest that the association of Lp(a) levels with CHD risk is independent of KIV-2 repeats, and that the effect of apo(a) isoform size is mediated through the effect on plasma levels of Lp(a).
Prevalence of rare EGFR gene mutations in nonsmall-cell lung cancer: a multicenter study on 3856 Polish Caucasian patients
Authors: P. Krawczyk, K. Reszka, R. Ramlau, T. Powrózek, J. Pankowski, K. Wojas-Krawczyk, E. Kalinka-Warzocha, A. Szczęsna, M. Nicoś, B. Jarosz, K. Szyszka-Barth, M. Bryl, K. Adamowicz, J. Szumiło, J. Milanowski
Journal: Annals of Oncology (2015)
Metabolism of Third Complement Component (C3) in Nephritis
Authors: L. G. Hunsicker, S. Ruddy, C. B. Carpenter, P. H. Schur, J. P. Merrill, H. J. Müller-Eberhard, K. F. Austen
Journal: New England Journal of Medicine (1972)

Original Article from The New England Journal of Medicine — Metabolism of Third Complement Component (C3) in Nephritis — Involvement of the Classic and Alternate (Properdin) Pathways for Complement Activation
The Effect of Cortisone Therapy on the Incidence of Rheumatic Heart Disease
Authors: Arnold L. Johnson, Charlotte Ferencz
Journal: New England Journal of Medicine (1953)

THE purpose of this report is to attempt to assess the effect of cortisone in rheumatic heart disease by consideration of a group of 100 patients treated with cortisone and, for purposes of comparison, a group of 80 patients cared for under similar circumstances, before cortisone was utilized in this hospital. Since the original contribution of Hench and his co-workers1 pointed the way to the use of cortisone in the treatment of rheumatic fever, there has been a constantly glowing list of valuable communications reporting experience with series of patients of variable size and from slightly different points of view. . . .
MPTH-17CLINICAL AND MOLECULAR CHARACTERIZATION OF LONG-TERM GLIOBLASTOMA SURVIVORS
Authors: Franziska Loebel, Andrew S. Chi, Daniel P. Cahill, Jorg Dietrich
Journal: Neuro-Oncology (2015)

BACKGROUND: Glioblastoma (GBM) is a challenging disease with ultimately fatal outcome in the majority of patients. Despite improved treatment modalities, median overall survival (OS) rates range between 15-18 months. However, some patients show remarkably longer OS, although the underlying factors associated with prolonged survival remain largely unknown. We here present the clinical and pathological characteristics of a cohort of patients considered long-term survivors. METHODS: Long-term survival (LTS) was defined as OS >3 years after initial diagnosis. Long-term survivors were retrospectively identified from a systematic departmental clinical database from a single institution, and both medical and pathology records were reviewed to identify demographic and clinical characteristics. Tumors were molecularly profiled using a standard clinical panel used for all glioma patients treated at our center. Kaplan-Meier and multivariate analysis was used to identify factors associated with LTS. RESULTS: We identified a total of 23 long-term survivors, including 14 cases with OS >5 years. Median age at initial diagnosis was 41 years (range 25-68). There was no difference in gender distribution. The majority of tumors were located in the frontal lobes (16/23, 69.5%). 13/23 (57%) of patients underwent gross-total resection. 9/23 tumors (39.1%) featured an oligodendroglial component in histopathological analysis. All patients received adjuvant concurrent radiation and temozolomide and subsequent chemotherapy (with regimens of either PCV, n = 2, gefitinib, n = 1, or temozolomide, n = 20). 9/23 patients showed MGMT-promoter methylation, 4 were non-methylated and 10 remained undetermined. The majority of patients (13/23, 56.6%) were TP53-wildtype. IDH1-mutation was present in 19/23 patients, 82.6% (17 R132H, 2 R132C). All IDH1-wildtype cases were both MGMT-promoter methylated and TP53-wildtype. CONCLUSIONS: IDH1-mutation, MGMT-promoter methylation, TP53-wildtype status, oligo-component, and frontal lobe location seem to be favorable prognostic factors for LTS. Interestingly, in our cohort gross-total surgical resection was not an absolute prerequisite for LTS and IDH1-wildtype status did not preclude long-term survival.
Testosterone-Secreting Adrenal Adenoma under Gonadotropin Control
Authors: Emile E. Werk, Leon J. Sholiton, Lea Kalejs
Journal: New England Journal of Medicine (1973)

A 51-year-old woman with virilization had markedly elevated levels of testosterone, which increased further following stimulation with human chorionic gonadotropin. Urinary excretion of 17-ketosteroids was normal or slightly elevated. After removal of both ovaries, which showed only mild strumal hyperplasia, testosterone levels and responsiveness to human chorionic gonadotropin remained unchanged. Administration of conjugated estrogens suppressed testosterone and gonadotropin levels. Subsequently, a small adrenal adenoma was removed, and androgen levels returned to normal. The androgens in the adenoma were mainly testosterone. Thus, this patient had the unusual occurrence of a small adrenal adenoma that produced testosterone and was responsive to gonadotropin. (N Engl J Med 289:767–770, 1973)
Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial
Authors: Andrea Sartore-Bianchi, Livio Trusolino, Cosimo Martino, Katia Bencardino, Sara Lonardi, Francesca Bergamo, Vittorina Zagonel, Francesco Leone, Ilaria Depetris, Erika Martinelli, Teresa Troiani, Fortunato Ciardiello, Patrizia Racca, Andrea Bertotti, Giulia Siravegna, Valter Torri, Alessio Amatu, Silvia Ghezzi, Giovanna Marrapese, Laura Palmeri, Emanuele Valtorta, Andrea Cassingena, Calogero Lauricella, Angelo Vanzulli, Daniele Regge, Silvio Veronese, Paolo M Comoglio, Alberto Bardelli, Silvia Marsoni, Salvatore Siena
Journal: The Lancet Oncology (2016)
Effects of the Infusion of Insulin-like Growth Factor I in a Child with Growth Hormone Insensitivity Syndrome (Laron Dwarfism)
Authors: J L Walker, M Ginalska-Malinowska, T E Romer, J B Pucilowska, L E Underwood
Journal: New England Journal of Medicine (1991)

THE clinical manifestations of the growth hormone insensitivity syndrome (Laron dwarfism) result from the inability of growth hormone to exert its biologic actions.1 , 2 Affected children have the ...
Case 50-1991
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, D. Leifer, R.A. Sobel
Journal: New England Journal of Medicine (1991)

Case Records of the Massachusetts General Hospital from The New England Journal of Medicine — Case 50-1991 — A 71-Year-Old Woman with a Sensorimotor Neuropathy and Radiographically Demonstrable Abnormalities
Exacerbation of Seizures in Children by Carbamazepine
Authors: O. Carter Snead, Lynn C. Hosey
Journal: New England Journal of Medicine (1985)

We studied 15 children with complex partial seizures in whom one or more seizure type was exacerbated during treatment with carbamazepine. The most common seizure type that was exacerbated was generalized atypical absence (11 patients). Four patients had more frequent and severe generalized convulsive seizures. Monitoring with video-electroencephalographic telemetry suggested that the electroencephalogram can be used to predict the risk of seizure exacerbation with carbamazepine. A bilaterally synchronous spike-and-wave discharge of 2.5 to 3 cycles per second is predictive of increased atypical absence seizures with carbamazepine, whereas generalized bursts of spikes and slow waves of 1 to 2 cycles per second suggest a risk of increased generalized convulsive seizures. Carbamazepine should be used with caution in children with a mixed seizure disorder, particularly those with a generalized bilaterally synchronous discharge of 2.5 to 3 cycles per second on the electroencephalogram. The drug should be considered a possible precipitating factor in any child with an increased frequency of generalized convulsive or generalized absence seizures concomitant with administration of this anticonvulsant agent.
An expansion of rare lineage intestinal microbes characterizes rheumatoid arthritis
Authors: Jun Chen, Kerry Wright, John M. Davis, Patricio Jeraldo, Eric V. Marietta, Joseph Murray, Heidi Nelson, Eric L. Matteson, Veena Taneja
Journal: Genome Medicine (2016)

The adaptive immune response in rheumatoid arthritis (RA) is influenced by an interaction between host genetics and environment, particularly the host microbiome. Association of the gut microbiota with various diseases has been reported, though the specific components of the microbiota that affect the host response leading to disease remain unknown. However, there is limited information on the role of gut microbiota in RA. In this study we aimed to define a microbial and metabolite profile that could predict disease status. In addition, we aimed to generate a humanized model of arthritis to confirm the RA-associated microbe. To identify an RA biomarker profile, the 16S ribosomal DNA of fecal samples from RA patients, first-degree relatives (to rule out environment/background as confounding factors), and random healthy non-RA controls were sequenced. Analysis of metabolites and their association with specific taxa was performed to investigate a potential mechanistic link. The role of an RA-associated microbe was confirmed using a human epithelial cell line and a humanized mouse model of arthritis. Patients with RA exhibited decreased gut microbial diversity compared with controls, which correlated with disease duration and autoantibody levels. A taxon-level analysis suggested an expansion of rare taxa, Actinobacteria, with a decrease in abundant taxa in patients with RA compared with controls. Prediction models based on the random forests algorithm suggested that three genera, Collinsella, Eggerthella, and Faecalibacterium, segregated with RA. The abundance of Collinsella correlated strongly with high levels of alpha-aminoadipic acid and asparagine as well as production of the proinflammatory cytokine IL-17A. A role for Collinsella in altering gut permeability and disease severity was confirmed in experimental arthritis. These observations suggest dysbiosis in RA patients resulting from the abundance of certain rare bacterial lineages. A correlation between the intestinal microbiota and metabolic signatures could determine a predictive profile for disease causation and progression.
RARE-22MIXED GLIONEURONAL TUMORS WITH DNET AND RGNT FEATURES: CASE REPORT AND LITERATURE REVIEW
Authors: Brett Theeler, Laurence Davidson, Patrick Malafronte
Journal: Neuro-Oncology (2015)

OBJECTIVE: Case report and literature review of mixed glioneuronal tumors with rosette-forming glioneuronal tumor (RGNT) and dysplastic neuroepithelial tumor (DNET) histology. METHODS/RESULTS: A 35 y/o male presented with a third ventricular mass. The mass was sub-totally resected with residual tumor in the thalamus. Pathologic features of a RGNT and DNET were present. The tumor was BRAF V600E wild-type and a PIK3CA mutation (E545K, c.1633G > A) was found. Searching the English literature we found 4 other cases of mixed glioneuronal tumors with RGNT/DNET features; PIK3CA mutations were not assessed in these cases. There are 6 cases of pure RGNTs in the literature with PIK3CA mutations. CONCLUSIONS: A rare sub-set of glioneuronal tumors have mixed RGNT/DNET features. PIK3CA mutations are present in some pure RGNTs, and our case suggests this mutation may be present in cases with mixed DNET/RGNT histology. This finding may have implications for defining tumor biology and pursuing targeted therapy in select cases.
An Outbreak of Thyrotoxicosis Caused by the Consumption of Bovine Thyroid Gland in Ground Beef
Authors: Craig W. Hedberg, Daniel B. Fishbein, Robert S. Janssen, Bruce Meyers, J. Michael McMillen, Kristine L. MacDonald, Karen E. White, Linda J. Huss, Eugene S. Hurwitz, Janet R. Farhie, Jerry L. Simmons, Lewis E. Braverman, Sidney H. Ingbar, Lawrence B. Schonberger, Michael T. Osterholm
Journal: New England Journal of Medicine (1987)

We report an outbreak of thyrotoxicosis without true hyperthyroidism that occurred between April 1984 and August 1985 among residents of southwestern Minnesota and adjacent areas of South Dakota and Iowa. One hundred twenty-one cases were identified through surveillance of medical clinics, laboratories, hospitals, and physicians' offices. Investigation of the outbreak demonstrated an association between the occurrence of thyrotoxicosis and the consumption of ground beef prepared from neck trimmings processed by a single slaughtering plant (odds ratio, 19.0; P = 0.0001). The cause was confirmed by the findings of bovine thyroid tissue in samples of these trimmings and high concentrations of thyroid hormone in implicated samples of ground beef and the demonstration of prompt increases in serum thyroid hormone concentrations in volunteers who ate the implicated ground beef. Bovine thyroid tissue had been introduced into the neck trimmings inadvertently during the process of "gullet trimming," a procedure that harvests muscles from the bovine larynx. The outbreak resolved after this procedure was discontinued at the plant. The clinical features of the illness suggested the diagnosis of silent thyroiditis, and it is possible that sporadic cases--or even outbreaks--of thyrotoxicosis factitia caused by this mechanism may have occurred in the past but were not recognized.
C1 Inhibitor for Routine Prophylaxis in Patients with Hereditary Angioedema: Interim Results from a European Registry Study
Authors: Emel Aygören-Pürsün, Markus Magerl, Inmaculada Martinez-Saguer, Hilary J. Longhurst, Ulrich Straßen, Ludovic Martin, Teresa Caballero, Petra Staubach, Marcus Maurer, Mohamed Hamdani, Irmgard Andresen
Journal: Journal of Allergy and Clinical Immunology (2016)
Adrenocortical Function in Chronic Pulmonary Disease
Authors: O. M. Sjaastad, Harold Brown, Jerome E. Cohn, Charles D. West, L. F. Kumagai
Journal: New England Journal of Medicine (1962)

RECENT reviews have emphasized the fact that in patients with pulmonary emphysema, there is an extraordinarily high incidence of peptic ulceration.1 2 3 4 It has further been shown that complications of peptic ulcer are more common in these patients than in those without pulmonary disease. The incidence of peptic ulcer in subjects with chronic obstructive pulmonary disease ranges in different series from 19 to 43 per cent. It has been postulated that patients with chronic obstructive airway disease are in a state of constant stress that induces hyperadrenocorticism, with a resultant high incidence of peptic ulcer. However, definitive studies to substantiate this . . .
First-in-human phase I study of EGF816, a third generation, mutant-selective EGFR tyrosine kinase inhibitor, in advanced non-small cell lung cancer (NSCLC) harboring T790M.
Authors: Daniel Shao-Weng Tan, Takashi Seto, Natasha B. Leighl, Gregory J. Riely, Lecia V. Sequist, Enriqueta Felip, Juergen Wolf, James Chih-Hsin Yang, Igor Matushansky, Xiaolu Yu, Shu-Fang Hsu Schmitz, Xiaoming Cui, Dong-Wan Kim
Journal: Journal of Clinical Oncology (2015)

8013 Background: The emergence of T790M resistance mutations (mt) occurs in up to 50% of patients (pt) with NSCLC harboring a sensitizing EGFR mt treated with erlotinib or gefitinib. EGF816 is a covalent, irreversible, EGFR TKI that has nanomolar inhibitory potency against activating mt (L858R, ex19del) and T790M mt, with up to 60-fold selectivity over wild type (wt) EGFR in vitro. Methods: This multicenter, dose escalation study to determine the safety, tolerability and antitumor activity of EGF816, enrolled NSCLC pts with locally or centrally confirmed T790M status. Oral EGF816 was administered on a continuous 28-day schedule. Dose escalation started from 75 mg QD and was guided by an adaptive Bayesian logistic regression model to determine the maximum tolerated dose. Paired tumor biopsies were performed to evaluate pharmacodynamics. NCT02108964. Results: As of 26 Jan 2015, 57 pts have been treated (51 capsules, CAP; 6 tablets, TAB) across 6 cohorts (75, 150, 225, 300, and 350 mg for CAP; 225 mg for TAB). At the 4 Dec 2014 cutoff, 40 pts were evaluable for safety, median age 58.5y (range 34–76), 48% male and 80% East Asian. 2/6 pts experienced DLT at 350 mg (rash, n = 2; acute renal injury, n = 1). The most common adverse events (AE) regardless of study drug relationship were diarrhea (25%), stomatitis (22.5%), rash (17.5%) and pruritus (15%). The most common Grade 3/4 drug-related AE was rash (5%). RECIST responses and reduced pEGFR were observed at all dose levels. Amongst 22 evaluable pts, including 1 with de novo T790M mt, ORR (including unconfirmed responses) and disease control rate was 54.5% and 86.4% respectively. Only 1 pt experienced progressive disease at first evaluation – repeat testing revealed the tumor to be EGFR wt. PK shows rapid absorption with a median Tmax of 3h and dose-proportional increases in Cmax and AUC(0-tau) observed after single and multiple dosing. Conclusions: EGF816 is well tolerated with a manageable safety profile and antitumor activity against T790M mt NSCLC across all dose levels examined. Further study is ongoing to establish the optimal dose range to maximize therapeutic potential and facilitate future combinations. Clinical trial information: NCT02108964.