tbuckley/cabot-search huggingface dataset:
Mooren's Corneal Ulcers and Hepatitis C Virus Infection
Authors: Steven E. Wilson, William M. Lee, Carol Murakami, Jian Weng, George A. Moninger
Journal: New England Journal of Medicine (1993)

To the Editor: Mooren's corneal ulcer is a chronic, painful, progressive disorder that characteristically affects the peripheral cornea in a circumferential manner1. The disease may be unilateral or bilateral and may progress to involve the entire cornea, resulting in severe visual loss. Although it is occasionally associated with eye surgery, trauma, or herpes zoster, most cases are idiopathic. Treatment with immunosuppression may be beneficial,2 but many cases are refractory to all forms of therapy. We have identified the presence of hepatitis C virus (HCV) infection in two consecutive patients with this condition. One patient had previously received blood transfusions, . . .
The Outlook for the Eventual Control of Leukemia
Authors: William Dameshek
Journal: New England Journal of Medicine (1954)

IN any attempt to discuss the outlook for the eventual control of leukemia, it may as well be conceded that as of today efforts have been pitifully disappointing. Whether all this is due entirely to the inherent difficulties of the problem or to insufficient application of all available resources is debatable. In any event, to dismiss leukemia as hopeless is far from accurate, since many potential accomplishments are on the horizon, and at least a few important steps have already been made.What can be done to further the cause against what is admittedly the foremost problem in hematology? There . . .
Hypogonadotropic Hypogonadism in a Female Caused by an X-Linked Recessive Mutation in the<i>DAX1</i>Gene
Authors: Deborah P. Merke, Toshihiro Tajima, Jeffrey Baron, Gordon B. Cutler
Journal: New England Journal of Medicine (1999)

Adrenal hypoplasia congenita is a rare X-linked disorder characterized by primary adrenal insufficiency and hypogonadotropic hypogonadism.1 All patients described to date have been male, and female...
Abstract 2415: Development of a clinical cell-free DNA assay for cancer molecular profiling
Authors: Travis Clark, Mark Kennedy, Geneva Young, Lauren Young, Jie He, Roman Yelensky, Siraj Ali, Geoff Otto, Doron Lipson, Vince Miller, Phil Stephens
Journal: Cancer Research (2015)

Abstract Background: Profiling cell-free circulating tumor DNA (ctDNA) for the genomic alterations which drive oncogenesis in patients with cancer promises to provide information important for understanding cancer biology, informing therapy selection when conventional biopsies are unobtainable and monitoring response to therapy. Facile collection of ctDNA samples could enable recurrent molecular profiling of an individual patient's disease with lower cost, discomfort and risk as compared to conventional biopsies. To assess the clinical validity of profiling cancer genomics in ctDNA, a highly accurate targeted NGS-based assay was developed and ctDNA results were compared to patient-matched FFPE tumor biopsies characterized by comprehensive genomic profiling using the FoundationOne assay from over 150 patients with lung, breast and other cancer types. Methods: To ensure robust performance, the ctDNA assay was developed as part of an integrated workflow including primary sample collection, storage and transport, and ctDNA purification, followed by optimized construction of adaptor-ligated sequencing libraries and enrichment by solution hybridization and then sequencing to high depth (Illumina HiSeq). Computational methodologies were developed to enable sensitive and specific detection of base substitutions, indels, genomic rearrangements and high-level amplificagtions from ctDNA. Accuracy and reproducibility was assessed using cell-line mixtures designed to simulate the limited DNA inputs and low tumor purity expected in routine clinical samples. Results: The ctDNA assay enabled accurate detection of most genomic alterations in cell-line mixtures. Short variants (base substitutions and indels) and genomic rearrangements in ALK and RET were detected with high sensitivity and specificity at &amp;lt;1% tumor. Comparative results from patient-matched ctDNA isolated from plasma and FFPE biopsies across more than 150 lung, breast and other cancer samples will be presented. Conclusions: Accurate profiling of ctDNA can enable detection of biologically and clinically relevant genomic alterations in clinical plasma samples. These results demonstrate the potential utility of ctDNA molecular profiling for the management of patients with cancer, but prior to integration into routine practice, extensive rigorous tumor-type specific studies of patient-matched ctDNA and solid biopsy specimens are required. Citation Format: Travis Clark, Mark Kennedy, Geneva Young, Lauren Young, Jie He, Roman Yelensky, Siraj Ali, Geoff Otto, Doron Lipson, Vince Miller, Phil Stephens. Development of a clinical cell-free DNA assay for cancer molecular profiling. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2415. doi:10.1158/1538-7445.AM2015-2415
Case 13-1999
Authors: David M. Vernick, Suzanne B. Keel
Journal: New England Journal of Medicine (1999)

Presentation of CaseA 20-year-old woman was admitted to the hospital because of chronic right otitis media.The patient had been well until one year earlier, when a “bad cold” developed, with a sore throat. The sore throat subsided after one week, but nasal congestion and the sensation that her ears were blocked persisted for a month. A physician made a diagnosis of sinusitis and prescribed a nasal spray and an unknown antibiotic. The left ear became clear, but the right ear remained symptomatic. Treatment with trimethoprim–sulfamethoxazole provoked a rash and was discontinued, and a third antibiotic was ineffective. Painless . . .
Outcome of Pregnancy in Women with Moderate or Severe Renal Insufficiency
Authors: David C. Jones, John P. Hayslett
Journal: New England Journal of Medicine (1996)

Pregnant women with mild preexisting renal disease have relatively few complications of pregnancy, but the risks of maternal and obstetrical complications in women with moderate or severe renal insufficiency remain uncertain.We determined the frequency and types of maternal and obstetrical complications and the outcomes of pregnancy in 67 women with primary renal disease (82 pregnancies). All the women had initial serum creatinine concentrations of at least 1.4 mg per deciliter (124 mumol per liter) and gestations that continued beyond the first trimester.The mean (+/- SD) serum creatinine concentration increased from 1.9 +/- 0.8 mg per deciliter (168 +/- 71 mumol per liter) in early pregnancy to 2.5 +/- 1.3 mg per deciliter (221 +/- 115 mumol per liter) in the third trimester. The frequency of hypertension rose from 28 percent at base line to 48 percent in the third trimester, and that of high-grade proteinuria (urinary protein excretion, > 3000 mg per liter) from 23 percent to 41 percent. For the 70 pregnancies (57 women) for which data were available during pregnancy and immediately post partum, pregnancy-related loss of maternal renal function occurred in 43 percent. Eight of these pregnancies (10 percent of the total) were associated with rapid acceleration of maternal renal insufficiency. Obstetrical complications included a high rate of preterm delivery (59 percent) and growth retardation (37 percent). The infant survival rate was 93 percent.Among pregnant women with moderate or severe renal insufficiency, the rates of complications due to worsening renal function, hypertension, and obstetrical complications are increased, but fetal survival is high.
Assessment of Adrenocortical Function
Authors: James C. Melby
Journal: New England Journal of Medicine (1971)

OF the steroid hormones secreted by the human adrenal cortex into the adrenal venous effluent, only cortisol and aldosterone are essential to life processes. These steroids account for most of the biologic activity in the venous effluent, and they possess 21 carbon atoms and four or more oxygen atoms. Dehydroepiandrosterone (DHEA) as a sulfate ester is the principal adrenal androgen and has 19 carbon atoms.Secretion and Metabolism of CortisolAdrenocorticotropic hormone (ACTH) is the sole physiologic agent known that will stimulate cortisol biosynthesis from the zona fasciculata of the adrenal cortex. A neurohormone, corticotropin-releasing factor (CRF), when elaborated by . . .
The Enigma of Glucose and Lipid Metabolism
Authors: Neha J. Pagidipati, Michael Pencina, Allan D. Sniderman
Journal: JAMA Cardiology (2016)

Sagar B. Dugani, MD, PhD; Akintunde O. Akinkuolie, MBBS, MPH; Nina Paynter, PhD; Robert J. Glynn, PhD; Paul M Ridker, MD, MPH; Samia Mora, MD, MHS
Endochondral Ossification in Achondroplastic Dwarfism
Authors: David L. Rimoin, Gary N. Hughes, Robert L. Kaufman, Ronald E. Rosenthal, William H. McAlister, Ruth Silberberg
Journal: New England Journal of Medicine (1970)

The literature concerning endochondral histopathology in the chondrodystrophies is misleading because the true heterogeneity of this group of disorders was not recognized until relatively recently. Accordingly, biopsies of the chondro-osseous junctions of rib and iliac crest were performed on seven typical achondroplastic dwarfs ranging in age from 14 months to 35 years. In contrast to previous reports, histologic studies of this biopsy material demonstrate regular, well organized endochondral ossification in classic achondroplasia. These observations suggest that the basic defect in achondroplasia may be a quantitative decrease in the rate of endochondral ossification, which, in conjunction with undisturbed periosteal bone formation, results in the short, squat shape of the tubular bones. These findings necessitate a reclassification of the many animal chondrodystrophic mutants, some of which have been mislabeled as models of achondroplasia because of their abnormal endochondral histopathology.
Targeting a Cancer-Specific Epitope of the Epidermal Growth Factor Receptor in Triple-Negative Breast Cancer
Authors: Nathan Simon, Antonella Antignani, Robert Sarnovsky, Stephen M. Hewitt, David FitzGerald
Journal: JNCI Journal of the National Cancer Institute (2016)

Triple-negative breast cancers (TNBCs) are typically more aggressive and result in poorer outcomes than other breast cancers because treatment options are limited due to lack of hormone receptors or amplified human epidermal growth factor receptor 2 (HER2). Many TNBCs overexpress the epidermal growth factor receptor (EGFR) or manifest amplification of theEGFRgene, supporting EGFR as a therapeutic target. While EGFR-directed small molecule inhibitors have shown limited effectiveness in clinical settings, use of EGFR as a mechanism of delivering enzymatic cytotoxins to TNBC has not been demonstrated.Using the single-chain variable fragment (scFv) of the 806 antibody that binds only cells with overexpressed, misfolded, or mutant variants of the EGFR, a recombinant immunotoxin was engineered through gene fusion withPseudomonas aeruginosaExotoxin A (806-PE38). The potency of 806-PE38 on reducing TNBC cell growth in vitro and in xenograft models (n ≥ 6) was examined for six TNBC cell lines. All statistical tests were two-sided.806-PE38 statistically significantly reduced the viability of all tested TNBC lines, with IC50values below 10 ng/mL for three of six cell lines, while not affecting cells with wild-type EGFR (IC50>300 ng/mL). Systemic treatments with 806-PE38 vs vehicle resulted in statistically significantly reduced tumor burdens (806-PE38 mean = 128 mm(3)[SD = 46 mm(3)] vs vehicle mean = 749 mm(3)[SD = 395 mm(3)], P = .001) and increased median survival (806-PE38 median = 82 days vs vehicle median = 50 days,P= .01) in a MDA-MB-468 TNBC mouse xenograft. Deletion of the catalytic residue eliminated both cytotoxic activity in vitro and the reduction in tumor burden and survival (P= .52).These data support the further development of the 806-PE38 immunotoxin as a therapeutic agent for the treatment of patients with EGFR-positive TNBC. Follow-up experiments with combination therapies will be attempted to achieve full remissions.
Pathology of Hepatomas and Other Liver Abnormalities in English Sole ( Parophrys vetulus ) From the Duwamish River Estuary, Seattle, Washington 2
Authors: Kenneth V. Pierce, Bruce B. McCain, S. R. Wellings
Journal: JNCI Journal of the National Cancer Institute (1978)

Liver abnormalities were found, by gross and histopathologic examination, in 92% of the English sole (Parophrys vetulus) from the Duwamish River Estuary, Seattle, Washington. Hepatomas were found in 32% (20 of 62) of the English sole. Other observed liver aberrations included increased fatty vacuolation, congestion, structure disarray, increased size and number of melanin-macrophage centers, centrolobular fatty degeneration and necrosis, increased amounts of perivascular connective tissue, intercellular melanin deposits, and hepatocellular hypertrophy often associated with the presence of bizarre nuclei and/or multiple nucleoli. Livers evidencing microscopic lesions were usually discolored. Livers containing hepatomas were often mottled yellow or tan and brown; occasionally, hepatomas were visible as tan or white nodules. Although the cause(s) of the liver abnormalities has not been conclusively identified, chemical analyses of Duwamish River English sole have detected polychlorinated biphenyl (PCB) levels of about 1.5 ppm (dry wt) in total body tissue. Many of the above-mentioned abnormalities, with the exception of hepatomas, have been observed in fish exposed to PCB's.
GP services in England get multibillion cash injection in landmark deal
Authors: Gareth Iacobucci
Journal: BMJ (2016)

General practice services in England are to receive a multibillion pound cash injection as part of a radical plan to redress years of underinvestment in primary care.

In a move hailed by GP leaders as “a turning point” for the profession, NHS England will invest extra money in general practice each year, rising to an extra £2.4bn (€3bn; $3.5bn) by 2020-21. The extra funding means that investment in primary care will rise from £9.6bn in 2016-17 to over £12bn by 2021, representing a 14% increase in real terms.

The funding includes a £500m national “turnaround” package to help struggling practices ease workload pressures, develop their workforce, and redesign care.

NHS England said the overall proportion of NHS investment going into general practice would exceed 10% by 2020-21 and would rise further with new additional investment from local clinical commissioning groups (CCGs).

The plans were unveiled on 21 April by NHS England’s chief executive, Simon Stevens, in the General Practice Forward View , a new blueprint …
Comparison of effectiveness and safety of imipenem/clavulanate-<i>versus</i>meropenem/clavulanate-containing regimens in the treatment of MDR- and XDR-TB
Authors: Simon Tiberi, Giovanni Sotgiu, Lia D'Ambrosio, Rosella Centis, Marcos Abdo Arbex, Edith Alarcon Arrascue, Jan Willem Alffenaar, Jose A. Caminero, Mina Gaga, Gina Gualano, Alena Skrahina, Ivan Solovic, Giorgia Sulis, Marina Tadolini, Valentina Alarcon Guizado, Saverio De Lorenzo, Aurora Jazmín Roby Arias, Anna Scardigli, Onno W. Akkerman, Alena Aleksa, Janina Artsukevich, Vera Auchynka, Eduardo Henrique Bonini, Félix Antonio Chong Marín, Lorena Collahuazo López, Gerard de Vries, Simone Dore, Heinke Kunst, Alberto Matteelli, Charalampos Moschos, Fabrizio Palmieri, Apostolos Papavasileiou, Marie-Christine Payen, Andrea Piana, Antonio Spanevello, Dante Vargas Vasquez, Pietro Viggiani, Veronica White, Alimuddin Zumla, Giovanni Battista Migliori
Journal: European Respiratory Journal (2016)

No large study to date has ever evaluated the effectiveness, safety and tolerability of imipenem/clavulanate versus meropenem/clavulanate to treat multidrug- and extensively drug-resistant tuberculosis (MDR- and XDR-TB). The aim of this observational study was to compare the therapeutic contribution of imipenem/clavulanate versus meropenem/clavulanate added to background regimens to treat MDR- and XDR-TB cases. 84 patients treated with imipenem/clavulanate-containing regimens showed a similar median number of antibiotic resistances (8 versus 8) but more fluoroquinolone resistance (79.0% versus 48.9%, p&lt;0.0001) and higher XDR-TB prevalence (67.9% versus 49.0%, p=0.01) in comparison with 96 patients exposed to meropenem/clavulanate-containing regimens. Patients were treated with imipenem/clavulanate- and meropenem/clavulanate-containing regimens for a median (interquartile range) of 187 (60–428) versus 85 (49–156) days, respectively. Statistically significant differences were observed on sputum smear and culture conversion rates (79.7% versus 94.8%, p=0.02 and 71.9% versus 94.8%, p&lt;0.0001, respectively) and on success rates (59.7% versus 77.5%, p=0.03). Adverse events to imipenem/clavulanate and meropenem/clavulanate were reported in 5.4% and 6.5% of cases only. Our study suggests that meropenem/clavulanate is more effective than imipenem/clavulanate in treating MDR/XDR-TB patients.
Carry-over effects of marijuana intoxication on aircraft pilot performance: a preliminary report
Authors: J A Yesavage, V O Leirer, M Denari, L E Hollister
Journal: American Journal of Psychiatry (1985)

Ten experienced licensed private pilots were trained for 8 hours on a flight simulator landing task. They each smoked a cigarette containing 19 mg of delta 9-tetrahydrocannabinol (THC), and 24 hours later their mean performance on the flight task showed trends toward impairment on all variables, with significant impairment in number and size of aileron changes, size of elevator changes, distance off center on landing, and vertical and lateral deviation on approach to landing. Despite these deficits, the pilots reported no awareness of impaired performance. These results may have implications for performance of complex tasks the day after smoking marijuana.
PTPS-20THE GD3 ACETYLATION PATHWAY AS A POTENTIAL THERAPEUTIC TARGET FOR PAEDIATRIC MEDULLOBLASTOMA
Authors: Rebecca Mather, Katie Stephenson, Laura Donovan, Michael Taylor, Reinhard Vlasak, Geoffrey Pilkington, Helen Fillmore
Journal: Neuro-Oncology (2015)

Medulloblastoma (MB), the most common malignant paediatric brain tumour, is associated with high mortality rates. Survivors frequently suffer from low quality-of-life as a result of aggressive treatment. Genomic studies have led to novel classification of molecularly and clinically distinct subgroups and are paving the way for novel targeted therapies. GD3, an oncofoetal ganglioside is re-expressed in some cancers of the neural crest. GD3, central to cell movement in developing brain, is internalised during maturation of residual supernumerary cells leading to cell death. When GD3 is re-expressed in cancers, the intracellular form of GD3 is acetylated (GD3A) and is thought to protect cells from mitochondrially-mediated apoptosis. Sialate-O-acetylesterase (SIAE) is responsible for cleaving the acetyl group from GD3A. A genome-wide transcriptional analysis of 103 MB patients revealed that this enzyme is significantly down-regulated in MB tissue compared to non-neoplastic foetal and adult brain (p > 0.02). This suggests that GD3A may be deacetylated at low levels and thus the balance of GD3 to GD3A favours GD3A. Using flow cytometry to examine expression, results revealed that in MB cell lines RES256 and UW402 GD3A expression was higher (84.5% and 74.5%) than GD3 (56.6% and 61.3%) The fluorescent intensity of GD3A expression was 9.9 and 11.4 fold higher and GD3, 4.4 and 6.1 fold higher than negative controls. Immunocytochemical results were in agreement, providing additional evidence that these cells have a balance in favour of GD3A. Previous studies from our group have shown that cell surface expression of GD3 correlates with invasion and in MB cell lines tested surface expression was 31.7% and 65.7% compared to GD3A (29.5% and 11.5%). Inducible SIAE and SIAE catalytically mutated cell lines have been generated and verified in protein and esterase activity assays and will be used to evaluate this pathway as a potential therapeutic target for MB.
Bioterror and “Bioart” — A Plague o' Both Your Houses
Authors: George J. Annas
Journal: New England Journal of Medicine (2006)

In response to the September 11, 2001, attacks and heightened concern about bioterrorism, the U.S. government increased research funding for developing countermeasures to bioterrorism and passed new biosafety legislation. In this article, Annas discusses the legal and ethical issues raised by two cases involving scientists accused of violating biosafety laws.
Treatment response with mepolizumab in severe eosinophilic asthma patients with previous omalizumab treatment
Authors: A. Magnan, A. Bourdin, C-M Prazma, F.C. Albers, R-G Price, S. Yancey, H. Ortega
Journal: Allergy (2016)

Abstract Background We performed post hoc analyses to evaluate the effect of humanized monoclonal antibody mepolizumab in patients with severe eosinophilic asthma previously treated with omalizumab. Methods Data were collected from two randomized double‐blind, placebo‐controlled studies: MENSA (NCT01691521: 32‐week treatment phase) and SIRIUS (NCT01691508: 24‐week treatment phase). Active treatment was 75 mg intravenous mepolizumab (MENSA) or 100 mg subcutaneous mepolizumab (MENSA, SIRIUS). Patients had evidence of eosinophilic inflammation ≥150 cells/μl (at screening) or ≥300 cells/μl (during the previous year). Primary outcomes were the rate of exacerbations (MENSA) and the percentage reduction in oral corticosteroid (OCS) dose (SIRIUS). Other outcomes included lung function (forced expiratory volume in 1 s and morning peak expiratory flow), Asthma Control Questionnaire (ACQ‐5), St George's Respiratory Questionnaire (SGRQ) scores, and safety. Results Overall, 576 patients were included from MENSA and 135 from SIRIUS, with 13% and 33% previously receiving omalizumab, respectively. In MENSA, mepolizumab reduced the rate of exacerbations by 57% (prior omalizumab) and 47% (no prior omalizumab) vs placebo. In SIRIUS, reductions in OCS use were comparable regardless of prior omalizumab use. Despite reducing chronic OCS use, mepolizumab also resulted in similar reductions in exacerbation rate relative to placebo in both subgroups. Asthma control and quality of life improved with mepolizumab vs placebo in both studies independent of prior omalizumab use, as shown by ACQ‐5 and SGRQ scores. Adverse events were also comparable irrespective of prior omalizumab use. Conclusions These post hoc analyses indicate that patients with severe eosinophilic asthma respond positively to mepolizumab regardless of prior use of omalizumab.
Personality, sexual adjustment, and brain lesions in patients with conversion symptoms
Authors: H Merskey, M Trimble
Journal: American Journal of Psychiatry (1979)

To clarify the interrelationships of conversion symptoms, hysterical personality, sexual adjustment, and cerebral organic disorders the authors studied 89 patients with classic motor conversion symptoms (group L) and compared a subgroup of 24 of these patients (group H) with 24 matched control patients (group C). They found hysterical personality in 19% of group L, 21% of group H, and none of group C and passive-immature-dependent personality in 19% of group L, 21% of group H, and none of group C. Forty-eight percent of group L, 50% of group H, and 58% of group C had some cerebral disorder. Patients with conversion symptoms who also had hysterical and passive-immature-dependent personalities were especially likely to have sexual abnormalities.
Aeroallergen and Food Sensitization Patterns in Adults with Eosinophilic Esophagitis
Authors: Hoang Pham, Zave H. Chad, Gordon L. Sussman, Jacques Hébert, Charles W. Frankish, Timothy Olynych, Amarjit Singh Cheema, Jaime Del Carpio, Rachel Harrison, Stephanie Santucci, Paul Keith, William H. Yang
Journal: Journal of Allergy and Clinical Immunology (2016)