tbuckley/cabot-search huggingface dataset:
Results of Treating Childhood Cushing's Disease with Pituitary Irradiation
Authors: Anthony S. Jennings, Grant W. Liddle, David N. Orth
Journal: New England Journal of Medicine (1977)

To determine the usefulness of conventional pituitary irradiation in childhood Cushing's disease, we reviewed the results of this treatment in 15 patients. Twelve were cured (mean plasma cortisol of less than 10 μg per deciliter and 24-hour urinary 17-hydroxycorticosteroid excretion of less than 7 mg per gram of creatinine) within 18 months, and 10 of the 15 were cured within nine months. Three failures required bilateral adrenalectomy. Growth resumed in 12, with adult heights of 156 to 166 cm. Sexual development proceeded normally in all 15, with normal secondary sexual characteristics and sexual function, and demonstrated fertility in four married adults. Intellectual function appeared normal. Basal and stimulated hormone levels were normal, except for subnormal (5 ng per milliliter or less) growth hormone levels after hypoglycemia in one of 12 patients. There were no complications of therapy and no progressive pituitary enlargement or hyperpigmentation. Pituitary irradiation is safe and effective therapy for childhood Cushing's disease. (N Engl J Med 297:957–962, 1977)
Harnessing Gene Expression Profiling In Search Of New Candidate Genes For Ara-C Resistance In Acute Myeloid Leukemia
Authors: Ajay Abraham, Savitha Varatharajan, Sreeja Karathedath, Shaji R Velayudhan, Alok Srivastava, Vikram Mathews, Poonkuzhali Balasubramanian
Journal: Blood (2013)
Novel MET/TIE2/VEGFR2 inhibitor altiratinib inhibits tumor growth and invasiveness in bevacizumab-resistant glioblastoma mouse models
Authors: Yuji Piao, Soon Young Park, Verlene Henry, Bryan D. Smith, Ningyi Tiao, Daniel L. Flynn, John F. de Groot
Journal: Neuro-Oncology (2016)

Glioblastoma highly expresses the proto-oncogene MET in the setting of resistance to bevacizumab. MET engagement by hepatocyte growth factor (HGF) results in receptor dimerization and autophosphorylation mediating tumor growth, invasion, and metastasis. Evasive revascularization and the recruitment of TIE2-expressing macrophages (TEMs) are also triggered by anti-VEGF therapy. We investigated the activity of altiratinib (a novel balanced inhibitor of MET/TIE2/VEGFR2) against human glioblastoma stem cell lines in vitro and in vivo using xenograft mouse models. The biological activity of altiratinib was assessed in vitro by testing the expression of HGF-stimulated MET phosphorylation as well as cell viability after altiratinib treatment. Tumor volume, stem cell and mesenchymal marker levels, microvessel density, and TIE2-expressing monocyte infiltration were evaluated in vivo following treatment with a control, bevacizumab alone, bevacizumab combined with altiratinib, or altiratinib alone. In vitro, HGF-stimulated MET phosphorylation was completely suppressed by altiratinib in GSC17 and GSC267, and altiratinib markedly inhibited cell viability in several glioblastoma stem cell lines. More importantly, in multiple xenograft mouse models, altiratinib combined with bevacizumab dramatically reduced tumor volume, invasiveness, mesenchymal marker expression, microvessel density, and TIE2-expressing monocyte infiltration compared with bevacizumab alone. Furthermore, in the GSC17 xenograft model, altiratinib combined with bevacizumab significantly prolonged survival compared with bevacizumab alone. Together, these data suggest that altiratinib may suppress tumor growth, invasiveness, angiogenesis, and myeloid cell infiltration in glioblastoma. Thus, altiratinib administered alone or in combination with bevacizumab may overcome resistance to bevacizumab and prolong survival in patients with glioblastoma.
Somatostatinoma of the minor duodenal papilla associated with pancreas divisum treated by endoscopic papillectomy
Authors: Daniela Jara Letelier, Michele Bonotto, José Ardengh
Journal: Endoscopy (2016)

Somatostatinomas are found in the major duodenal papilla (MaDP), but their diagnosis is difficult because of their absence of symptoms and small size, and because the tumor emerges from the submucosa [1]. Somatostatinomas in the minor duodenal papilla (MiDP) are extremely rare [2]. Most MiDP tumors are asymptomatic, while those of the MaDP more often cause jaundice and pain [3].
Decreased Plasma Free Fatty Acids and Urinary Epinephrine in Bronchial Asthma
Authors: Aleksander A. Mathé, Peter H. Knapp
Journal: New England Journal of Medicine (1969)

Plasma free fatty acids, urinary epinephrine, norepinephrine and vanyllylmandelic acid, measured in six young male students with perennial, mild to moderate asthma in remission, and six matched healthy controls, on successive days under conditions of "stress" (exposure to mental arithmetic and a film) and "relaxation," demonstrated significant biochemical differences although both groups were equally aroused emotionally. The control subjects showed a marked mobilization of free fatty acids and marked rise in urinary epinephrine under stress, whereas the patients had low and relatively constant levels for both substances under both conditions. In contrast, norepinephrine and vanyllylmandelic acid did not differentiate between the two groups. These findings are consistent with the hypothesis that there is decreased activity of the adrenal medulla but normal activity of the sympathetic nervous system in bronchial asthma.
Importance of Clinical Worsening of Heart Failure Treated in the Outpatient Setting
Authors: Naoki Okumura, Pardeep S. Jhund, Jianjian Gong, Martin P. Lefkowitz, Adel R. Rizkala, Jean L. Rouleau, Victor C. Shi, Karl Swedberg, Michael R. Zile, Scott D. Solomon, Milton Packer, John J.V. McMurray
Journal: Circulation (2016)

Background— Many episodes of worsening of heart failure (HF) are treated by increasing oral therapy or temporary intravenous treatment in the community or emergency department (ED), without hospital admission. We studied the frequency and prognostic importance of these episodes of worsening in the Prospective Comparison of ARNI (angiotensin-receptor-neprilysin inhibitor) with ACEI (angiotensin-converting enzyme inhibitor) to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial (PARADIGM-HF). Methods and Results— Outpatient intensification of HF therapy was added to an expanded composite outcome with ED visits, HF hospitalizations, and cardiovascular deaths. In an examination of first nonfatal events, 361 of 8399 patients (4.3%) had outpatient intensification of HF therapy without a subsequent event (ie, ED visit/HF hospitalizations) within 30 days; 78 of 8399 (1.0%) had an ED visit without previous outpatient intensification of HF therapy or a subsequent event within 30 days; and 1107 of 8399 (13.2%) had HF hospitalizations without a preceding event. The risk of death (in comparison with no-event patients) was similar after each manifestation of worsening: outpatient intensification of HF therapy (hazard ratio, 4.8; 95% confidence interval, 3.9–5.9); ED visit (hazard ratio, 4.5; 95% confidence interval, 3.0–6.7); HF hospitalizations (hazard ratio, 5.9; 95% confidence interval, 5.2–6.6). The expanded composite added 14% more events and shortened time to accrual of a fixed number of events. The benefit of sacubitril/valsartan over enalapril was similar to the primary outcome for the expanded composite (hazard ratio, 0.79; 95% confidence interval, 0.73–0.86) and was consistent across the components of the latter. Conclusions— Focusing only on HF hospitalizations underestimates the frequency of worsening and the serious implications of all manifestations of worsening. For clinical trials conducted in an era of heightened efforts to avoid HF hospitalizations, inclusion of episodes of outpatient treatment intensification (and ED visits) in a composite outcome adds an important number of events and shortens the time taken to accrue a target number of end points in an event-driven trial. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01035255.
MTR-05ANTI-ANGIOGENIC STRESS DRIVES A c-Met/ß1 INTEGRIN COMPLEX PROMOTING ALLOSTERIC ACTIVATION DRIVING INVASION
Authors: Arman Jahangiri, Maxim Sidorov, Sung-Won Han, Smita Mascharak, Michael De Lay, Jeffrey Wagner, Brandyn Castro, Brandon Imber, Kan Lu, Gabriel Bergers, William Weiss, Manish K. Aghi
Journal: Neuro-Oncology (2015)

Invasive resistance limits anti-angiogenic therapy's efficacy. We previously reported upregulated c-Met and b1 integrin in bevacizumab-resistant glioblastomas. We hypothesized chemotactic c-Met/HGF and haptotactic b1 integrin physically interact, forming an alliance driving invasive growth. Immunoprecipitated lysates of intracranial xenografts of U87-BevR and U87-BevS, models of bevacizumab-resistance and responsiveness, revealed robust c-Met/b1 integrin interactions in bevacizumab-treated U87-BevRs, and minimal complex in bevacizumab-treated U87-BevS, IgG-treated U87-BevR, or U87-BevS. Proximity ligation assays (PLAs) mirrored results of our immunopreicipitation. In culture, complex formation increased dose-dependently by bevacizumab-induced VEGF depletion, exposure to c-Met ligand HGF, and hypoxia. Complex formation was inhibited by VEGF165, the predominant VEGF isoform, and endothelial cell conditioned medium. Far-western blotting demonstrated only extracellular c-Met domain to bind b1 integrin. The c-Met/b1 integrin interaction led to cross-activation, with increasing concentrations of b1 integrin ligand fibronectin which increased c-Met phosphorylation. This was inhibited with integrin-linked kinase (ILK) knockdown. Complex induction via iDimerize, where b1 integrin/c-Met were tagged with complementary proteins, forming a complex upon heterodimer addition, increased migration substantially (P < 0.05). Site-directed biopsy of bevacizumab-resistant glioblastoma patient revealed increased complex formation progressing from core to enhancing edge to invasive cells outside enhancement. PLAs revealed 20-fold more c-Met/b1 complexes after bevacizumab resistance in patient-specimens compared to bevacizumab-naive glioblastomas at recurrence (P < 0.05). Furthermore, the percentage of cMet/b1 integrin from 20 patients taken at diagnosis correlated inversely with survival (P < 0.05). Anti-angiogenic therapy dose on complex formation in vivo by treating xenografts with 3 mg/kg bevacizumab was as effective as 10 mg/kg; however, only the latter contained c-Met/b1 complexes. A patient receiving 5mg/kg of bevacizumab, had no increased complex under PLA. In summary, we have demonstrated a mechanism where b1 integrin forms a complex with c-Met in bevacizumab-resistant glioblastoma, leading to allosteric cross-activation, driving the invasive resistant phenotype.
Cellular and Molecular Mechanisms of Mechanotransduction Involved in Metastasis - an in Vitro Study in Hepatocarcinoma and Breast Cancer Cell Lines
Authors: J.P. Folques Vicente, J. Balça, D. Matias, H. Girão, A.B. Sarmento-Ribeiro, J.M. Nascimento-Costa
Journal: Annals of Oncology (2014)
Case 19-1992
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, R.D. Granstein, R.L. Barnhill
Journal: New England Journal of Medicine (1992)

Presentation of CaseA 56-year-old man with Waldenström's macroglobulinemia and severe immunodeficiency was admitted to the hospital because of multiple cutaneous vesicles and oral ulcers.There was a two-year history of Waldenström's macroglobulinemia, with a low-grade B-cell lymphoma. Chlorambucil, cyclophosphamide, vincristine, and prednisone were administered, with little improvement. One year before admission the concentration of IgG was 278 mg, IgA 26 mg, and IgM 5710 mg per 100 ml. Fludarabine monophosphate was administered for nine cycles. The IgM fell to 2.1 g per 100 ml, with a rise in the hematocrit and symptomatic improvement; the concentrations of IgG and IgA . . .
Case 56-1962
Authors: Charles S. Kubik, Edward P. Richardson
Journal: New England Journal of Medicine (1962)

Presentation of CaseA sixty-five-year-old man was referred to the hospital because of weakness and mental confusion.Two months before entry the patient began to experience aching pain in the neck, right shoulder and right arm, and weakness and numbness of the right hand, anorexia and the loss of an unknown amount of weight ensued. He began to drop objects and could not feed himself with the right hand. Weakness of the right eyelid with diplopia developed three weeks before admission, and within a few days he was unable to open the right eye. Episodic vertigo and weakness occurred, and . . .
Nursing-Home Care in the United States
Authors: Nicholas Rango
Journal: New England Journal of Medicine (1982)

Caring for the severely impaired elderly is a social problem of serious and growing proportions. This article describes and analyzes nursing-home care in the United States with particular emphasis on economic aspects and their implications for public policy. Two questions will be addressed. First of all, how do market forces and government regulations interact to affect the critical variables of supply, demand, price, access, and quality of nursing-home services? Secondly, what effect will the federal government's recent actions to reduce its contributions to Medicaid have on the already difficult problems of access and quality in nursing-home care?Restrained SupplyDuring . . .
Tumor Localization of Radio-Labeled Antibodies against Carcinoembryonic Antigen in Patients with Carcinoma
Authors: Jean-Pierre Mach, Stephan Carrel, Michel Forni, Jürg Ritschard, Alfred Donath, Pierre Alberto
Journal: New England Journal of Medicine (1980)

Purified, [131I]-labeled goat antibodies against carcinoembryonic antigen, which have been shown to localize in human carcinoma in nude mice, were injected into 27 patients with carcinoma. Patients were scanned with a scintillation camera at various intervals. In 11 patients, radioactivity was detectable in the tumor 48 hours after injection. Computerized subtraction of blood-pool radioactivity provided clearer pictures in positive cases, but in 16 patients the scans remained doubtful or negative. To study the specificity of [131I]-antibody localization, we gave some patients simultaneous injections of [125I]-labeled normal IgG. Both isotopes were measured by means of scintillation counting in tumors and normal tissues recovered after surgery. The results demonstrated that only the anti-CEA antibodies localized in tumors. However, the total antibody-derived radioactivity in the tumor was only about 0.001 of the injected dose. We conclude that, despite the present demonstration of specificity, this method of tumor detection is not yet clinically useful.
Risk of stroke after transient ischaemic attack is lower than previously thought, study finds
Authors: Susan Mayor
Journal: BMJ (2016)

The risk of cardiovascular events, including stroke, after a transient ischaemic attack (TIA) or minor stroke is much lower than previously reported, shows a study whose authors say that this finding may be due to improved risk factor management.1

Researchers set up an international registry to collect data on patients aged over 18 who had had a TIA or minor stroke in the previous seven days. They included centres with …
Case 9-1993
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, John J. Reilly, Eugene J. Mark
Journal: New England Journal of Medicine (1993)

Presentation of CaseA 23-year-old man was admitted to the hospital because of fever, bilateral pulmonary infiltrates, and worsening hypoxia.The patient was apparently in excellent health until about one week earlier, when a dry cough developed, with a rise in the temperature to 38.9 °C and chilliness. A physician prescribed a cough preparation, without improvement. During the next few days diffuse arthralgias and myalgias appeared, with increasing fatigue. Two days before entry the patient became dyspneic, with pleuritic left-sided chest pain, and coughed up scanty amounts of blood.On the same day the patient was admitted to another hospital, . . .
Enhancement of the Amylase-Creatinine Clearance Ratio in Disorders Other Than Acute Pancreatitis
Authors: Richard I. Levine, Frederick L. Glauser, J. Edward Berk, Katherine Montgomery, Deborah Wong
Journal: New England Journal of Medicine (1975)

The ratio of amylase to creatinine clearance was determined during 10 episodes of ketoacidosis occurring in nine patients with diabetes mellitus and in six patients with burns. Similar determinations were made for the purpose of comparison in 10 diabetic outpatients managed with insulin or oral hypoglycemic agents and 12 normal subjects. The ratios in the ketoacidotic diabetic patients were significantly greater than those in the normal subjects (p < 0.001) as well as those in the nonacidotic diabetic patients (p < 0.001). The burned patients also displayed values that were significantly greater than those in the normal subjects, but to a lesser degree (p < 0.05). Serum amylase activity was slightly increased during three episodes of ketoacidosis in two of the diabetic patients with this complication and was markedly elevated in one of the burned patients. These observations indicate that increased ratios of amylase to creatinine clearance may occur in situations other than acute pancreatitis, both with and without elevated serum amylase activity (N Engl J Med 292:329–332,1975)
A Duodenal Gastrinoma in a Patient with Diarrhea and Normal Serum Gastrin Concentrations
Authors: Thomas Zimmer, Ulrich Stölzel, Michael Bäder, Ute Fett, Hans-Dieter Foss, Ernst-Otto Riecken, Jens F. Rehfeld, Bertram Wiedenmann
Journal: New England Journal of Medicine (1995)

The Zollinger–Ellison syndrome manifests itself in 90 to 95 percent of cases as severe peptic ulcer disease.1 About half the time, the ulcer disease is associated with diarrhea, and in approximately 10 percent of patients, diarrhea is the only clinical manifestation.2,3 Basal serum gastrin concentrations are usually elevated in patients with this syndrome.4 Normal basal serum gastrin values with abnormal results of secretin tests have been reported, however, in a few patients.5–7 We describe a patient with a duodenal gastrinoma, a two-year history of diarrhea, and no peptic ulcer disease. The patient had persistently normal serum gastrin concentrations, . . .
Cardiovascular Disease in Women
Authors: Mariana Garcia, Sharon L. Mulvagh, C. Noel Bairey Merz, Julie E. Buring, JoAnn E. Manson
Journal: Circulation Research (2016)

Cardiovascular disease continues to be the leading cause of death among women in the United States, accounting for ≈1 of every 3 female deaths. Sex-specific data focused on cardiovascular disease have been increasing steadily, yet is not routinely collected nor translated into practice. This comprehensive review focuses on novel and unique aspects of cardiovascular health in women and sex differences as they relate to clinical practice in the prevention, diagnosis, and treatment of cardiovascular disease. This review also provides current approaches to the evaluation and treatment of acute coronary syndromes that are more prevalent in women, including myocardial infarction associated with nonobstructive coronary arteries, spontaneous coronary artery dissection, and stress-induced cardiomyopathy (Takotsubo Syndrome). Other cardiovascular disease entities with higher prevalence or unique considerations in women, such as heart failure with preserved ejection fraction, peripheral arterial disease, and abdominal aortic aneurysms, are also briefly reviewed. Finally, recommendations for cardiac rehabilitation are addressed.
The dexamethasone suppression test in bulimia
Authors: D C Lindy, B T Walsh, S P Roose, M Gladis, A H Glassman
Journal: American Journal of Psychiatry (1985)

Nineteen (35%) of 55 women with bulimia failed to exhibit cortisol suppression after dexamethasone administration. Although there was no statistically significant difference between suppressors and nonsuppressors on any clinical variable, there was a higher frequency of major depression among nonsuppressors.
Measures of Psychosis Proneness and Genetic Risk for Schizophrenia
Authors: Jim van Os
Journal: JAMA Psychiatry (2016)

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Endostatin and transglutaminase 2 are involved in fibrosis of the aging kidney
Authors: Chi Hua Sarah Lin, Jun Chen, Zhongtao Zhang, Gail V.W. Johnson, Arthur J.L. Cooper, Julianne Feola, Alexander Bank, Jonathan Shein, Heli J. Ruotsalainen, Taina A. Pihlajaniemi, Michael S. Goligorsky
Journal: Kidney International (2016)
Assay of an Activity in the Serum of Patients with Disorders of Thrombopoiesis That Stimulates Formation of Megakaryocytic Colonies
Authors: Ronald Hoffman, Eric Mazur, Edward Bruno, Victoria Floyd
Journal: New England Journal of Medicine (1981)

We have recently described an in vitro clonal assay system for human megakaryocyte-progenitor cells or megakaryocytic colony-forming units (CFU-M). Serum specimens from patients with quantitative platelet disorders were screened for the capacity to alter in vitro megakaryocyte-colony formation. Serum from 11 patients with hypomegakaryocytic thrombocytopenia significantly enhanced the formation of CFU-M-derived colonies (200 to 1840 per cent). Neither serum from eight patients with thrombocytopenia and normal or increased numbers of marrow megakaryocytes nor serum from 11 patients with thrombocytosis altered colony formation. This stimulatory activity has been termed megakaryocytic-colony-stimulating activity (Meg-CSA). The number of megakaryocytic colonies formed was directly proportional to the quantity of stimulatory serum added. Meg-CSA levels appeared to be inversely related to marrow megakaryocyte numbers. The variations in Meg-CSA levels that were detected in different disease states suggest that alterations in the production of this stem-cell regulator have physiologic importance. (N Engl J Med. 1981; 305:533–8.)