tbuckley/cabot-search huggingface dataset:
Genome-wide profiling of DNA copy number abnormalities in adult acute myeloid leukemia (AML) using high density single nucleotide polymorphism array
Authors: E. Ottaviani, I. Iacobucci, A. Astolfi, F. Salmi, N. Testoni, T. Storlazzi, C. Papayannidis, P. Giannoulia, D. Cilloni, G. Martinelli
Journal: Journal of Clinical Oncology (2008)

7023 Background: Acute myeloid leukemia (AML) is a heterogeneous disease with various chromosomal aberrations. The karyotype at diagnosis provides important prognostic information that influences therapy and outcome of this disease. However, using conventional chromosome banding techniques alone, karyotype abnormalities are detected in only half of all AML cases. We performed a genome-wide, single-nucleotide polymorphism (SNP) analysis in order (i) to identify novel genomic regions of interest in normal karyotype AML; (ii) novel candidate regions and disease-related genes, in patients with complex karyotypes. Methods: 20 AML patients were analyzed until now. Cases included FAB-M0, M1, M2, M4, M5, miscellaneous cytogenetic abnormalities and normal karyotype. 250 ng of genomic DNA were processed on 500K SNP array according to protocols provided by the manufacturer. Copy number state was calculated with respect to a set of 48 Hapmap normal individuals and a set of samples obtained from acute leukaemia cases in remission using Partek Genomics Suite. Results: An enormous spectrum of different genetic lesions (gains/losses) involving complete chromosome arms (del 16q, i(13q10), del 3p, del 7p, monosomy 9) or submicroscopic genomic intervals were identified in a substantial proportion of cases without differences in the frequency of losses or gains. The most frequent genomic gains affected: 9p12 (ZNF658B, FOXD4L2), 10q11.2 (PPYR1), 5q31-q33 (CDX1) and 8p23.2 (CSMD1). The most frequent deletions were identified in regions lacking annotated genes. Other recurring genetic lesions were uncommon. Marked differences in the combination of copy number anomalies were identified across the different genetic subtypes of AML. Some lesions affected regions with a single gene, such as: ETAA1, FIGN, STK32B, PRAGMIN, PCM1, GLIS3, MRGPRX1, SESN3, BCL2L14. Conclusions: Different genetic anomalies were identified by using an SNP-based chip array. Genetic abnormalities are associated with disease subtype. Supported by: European LeukemiaNet, AIL, AIRC, FIRB 2006, Fondazione del Monte di Bologna e Ravenna, PIO project 2007, Strategico di Ateneo. No significant financial relationships to disclose.
The psychiatrist: in the mainstream or on the banks of medicine?
Authors: T P Hackett
Journal: American Journal of Psychiatry (1977)

The author discusses psychiatry's historical estrangement from general medicine, beginning with its isolation in mental hospitals, aggravated by a deterioration in medical school teaching of clinical psychiatry and by limited psychiatric training programs, and further alienated by much of psychosomatic theory and practice. He sees hope for reconciliation, however, in the recent progress of psychopharmacology and liaison psychiatry within the general hospital.
Successful Intravenous Pyelography in Advanced Uremia — Visualization in the Post-Dialytic State
Authors: Robert Matalon, Robert P. Eisinger
Journal: New England Journal of Medicine (1970)

In eight patients with chronic renal disease (creatinine clearance of 0.4 to 10.0 ml per minute and urine-plasma creatinine ratio between 4.0 and 9.0), drip-infusion intravenous pyelography did not visualize the renal collecting systems. When pyelography was performed within 12 hours of vigorous dialysis, adequate visualization of the collecting systems was obtained in the six patients whose urine-plasma creatinine ratio exceeded 15 after dialysis. Under such circumstances, radiologic study of the renal collecting systems may be possible in patients with chronic renal disease without requiring the use of instrumentation.
Nutrition and the War
Authors: John B. Youmans
Journal: New England Journal of Medicine (1946)

IT IS a distinct honor to be invited to give the Shattuck Lecture, with its long list of distinguished former lecturers and its tradition of excellence of the addresses. I therefore appreciate greatly this honor that has come to me and the opportunity to address the Massachusetts Medical Society on this occasion.So far as the practice of medicine is concerned, the title of my lecture is somewhat of a misnomer, because the direct contribution of the war to clinical nutrition was not very great. Actual nutritional-deficiency disease was not common in the troops. Most of the actual work in . . .
Echocardiographic Measurement of the Left Ventricular Outflow Gradient in Idiopathic Hypertrophic Subaortic Stenosis
Authors: Walter L. Henry, Chester E. Clark, D. Luke Glancy, Stephen E. Epstein
Journal: New England Journal of Medicine (1973)

The characteristic hemodynamic abnormality in idiopathic hypertrophic subaortic stenosis is a highly variable subaortic obstruction to left ventricular ejection. Previous studies have shown that during systole, the left ventricular outflow tract is narrowed by motion of the anterior mitral leaflet toward the ventricular septum. If this were responsible for the obstruction, we believed it would be possible to predict quantitatively the gradient in the disease from echocardiograms. We computed an obstruction index by dividing the duration of outflow narrowing by the mean septal-anterior mitral-leaflet distance and compared the result with the simultaneously measured peak left ventricular outflow pressure gradient in 56 beats from 11 patients with this form of subaortic stenosis. The correlation between the obstruction index and gradient was highly significant (gradient = 1.8 obstruction index - 35; r = 0.95). Echocardiography thus confirms that the pressure gradient in the disorder is caused by narrowing of the left ventricular outflow tract between the anterior mitral leaflet and ventricular septum, and the technic may be used to quantitate the gradient. (N Engl J Med 288: 989–993, 1973)
Psychiatric diagnosis of morbidly obese gastric bypass patients
Authors: K A Halmi, M Long, A J Stunkard, E Mason
Journal: American Journal of Psychiatry (1980)

Eighty morbidly obese patients who had had gastric bypass operations were interviewed for psychiatric diagnoses using DSM-III criteria. The lifetime prevalence of Axis I clinical psychiatric diagnoses was 47.5%, with depressive disorders occurring in 28.7% of the total sample. No other diagnosis exceeded a 2.5% prevalence. The authors believe there is no evidence of an increased prevalence of major psychiatric disorder in obese persons when strictly defined diagnostic criteria are used.
Late Reaction to Hydralazine (Apresoline) Therapy
Authors: Wilbur B. Manter
Journal: New England Journal of Medicine (1954)

THERE have been few reports on late reactions to hydralazine (Apresoline) therapy. Attention was recently called to a syndrome resembling acute systemic lupus erythematosus associated with prolonged treatment of hypertension with large doses of hydralazine.1 Two reports2 , 3 have appeared describing a syndrome resembling early rheumatoid arthritis or disseminated lupus erythematosus occurring in 13 of 139 and 14 of 253 patients whose treatment included hydralazine. It is of particular interest that all the patients with this syndrome had received relatively large doses of the drug for at least three months. Remission followed the cessation of the drug, usually within a few . . .
Gastric Secretory and Other Laboratory Studies on Two Patients with Zollinger-Ellison Syndrome
Authors: William R. Waddell, Anthony J. Leonsins, George D. Zuidema
Journal: New England Journal of Medicine (1959)

THE first cases of gastrointestinal ulceration associated with gastric hypersecretion and tumors of the pancreas were described in 1955 by Zollinger and Ellison.1 In the following year Ellison2 discussed 24 cases from the world literature, and recently Zollinger and McPherson3 mentioned a total of 48 cases. There are undoubtedly many more cases that have not been reported. It is thought that the gastric hypersecretion results from stimulation of the stomach by some agent produced by and released from the islet-cell tumors. The nature of this stimulation is unknown. There is no evidence that hypoglycemia is involved, and the suggestion that . . .
Pressure Ulcers among the Elderly
Authors: Jane F. Desforges, Richard M. Allman
Journal: New England Journal of Medicine (1989)

PRESSURE ulcers are a serious and all too common complication of immobility among the elderly. The prevalence of pressure ulcers is 3 to 11 percent in acute care hospitals and nursing homes.1 2 3 One study has suggested that the incidence over a three-week period among bedridden and chairbound patients is 7.7 percent.1 As many as 50 percent of patients with pressure ulcers are over the age of 70.4 Among geriatric patients and nursing home residents, pressure ulcers are associated with a fourfold increase in the risk of death.5 6 7 The in-hospital mortality rate among patients with pressure ulcers is between 23 and . . .
Molecular pathogenesis of human hepatocellular carcinoma: Mechanistic and prognostic significance of aberrant methylation
Authors: Diego F. Calvisi, Sara Ladu, Alexis Gorden, Miriam Farina, Ju-Seog Lee, Elizabeth A. Conner, Insa S. Schroeder, Valentina M. Factor, Snorri S. Thorgeirsson
Journal: Cancer Research (2006)

3238   Aberrant methylation is implicated in the development of a variety of solid tumors, including hepatocellular carcinoma (HCC). We show here that genome wide hypomethylation and CpG hypermethylation correlate with biological features and clinical outcome of human HCC. Both parameters reached the highest levels in HCCs from patients with shorter survival length, in parallel with increasing genomic instability and upregulation of de novo DNA Methyltransferases (DNMTs) 1, 3A, and 3b. A progressive rise in Interleukin 6 and Fli-1 levels was responsible for upregulation of DNMT1, but not DNMT3s, in surrounding non-neoplastic livers and HCCs. Methylation-specific PCR and combined bisulphite restriction analyses of 100 putative tumor suppressor gene promoters identified the genes both universally and specifically inactivated in distinct subgroups of HCCs based on the length of patient’s survival. In particular, we identified activation of the Ras, Jak/Stat, and canonical Wnt/β-catenin pathways via epigenetic silencing on of Ras (ARHI, LOX, NORE1A, RASSF1A, and RIG), Jak/Stat (CIS, PIAS-1, PIAS-γ, SOCS1, 2, 3, and SHP1), and Wnt/β-catenin (APC, E-cadherin, SFRP1, 2, 4, 5, and WIF-1) inhibitors in the majority of HCCs, regardless of clinicopathological features of HCC patients. Furthermore, selective inactivation of genes controlling EGFR signaling and angiogenesis (e.g. SPRY1, 2, SOCS4, 5, EGLN2, BNIP3) was associated with an unfavorable outcome. Taken together, our results assign a therapeutic significance to methylation patterns in human HCC. Treatment approaches aimed at modifying the methylation status and utilizing novel molecular targets identified in this study may inhibit HCC development and progression.
Case 34-1982
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Stephen C. Schoenbaum, Thomas H. Aretz
Journal: New England Journal of Medicine (1982)

Presentation of CaseA 72-year-old woman was admitted to the hospital because of the recent onset of atrial fibrillation.Five years earlier hypertension was found, with a Grade 2 systolic ejection murmur at the cardiac apex that radiated to the carotid arteries. An intravenous pyelographic examination showed that the left kidney was 14.5 cm and the right 11.5 cm; bilateral equal nephrograms were seen at one minute, and at four minutes there was equal appearance of contrast material in both collecting systems; no evidence of obstructive uropathy or a mass was observed. The hypertension was managed with hydrochlorothiazide, propranolol, and . . .
Education about smoking cessation should start in grammar school
Authors: Z. Lissanu, N. Mullai
Journal: Journal of Clinical Oncology (2005)

1029 Background: The major cause of lung cancer is smoking. Age at the initiation of smoking inversely associates with DNA adducts levels found in the bronchial tissue of lung cancer patients. The earlier one smokes the worse the long-term damage seen in the lungs. Methods: Records of 125 patients with lung cancer, who were diagnosed and treated in rural Kentucky, were analyzed for smoking history. Results: Out of the 125 patients, 77 were Male. 86% was diagnosed between age 51–80. Non Small Cell Lung Cancer (NSCLC) was seen more frequently (76%). Adeno carcinoma was the common histology (42%). 65% of patients were inoperable with stage IIIB or IV. 29 patients had small cell histology and were evenly distributed between limited and extensive stages. Only two patients denied personal history of smoking, but had family history of smoking. Majority of patients has started smoking before age 20, especially as a teenager or younger. The youngest age to start smoking was 4 years. Most of them smoked more than 1–2 pkt/day. 78% of patients had family history of smoking-related illnesses including cancer. Conclusions: Smoking is the main risk factor for many illnesses and is preventable by health education. It is associated with many cancers and has direct relationship with lung cancer. Education about smoking cessation is currently offered widely in USA. It is very popular in large cities. However rural America, where smoking problem is more wide spread and starts early, is out of reach to most of these programs due to financial and practical reasons. Our study shows that the association of smoking and lung cancer was seen in more than 98% of the time and started in the early ages, the youngest being 4 years. Further it shows family and personal smoking related health problems did not deter the patients from tobacco exposure. Any educational program to change this damaging trend should focus on children in addition to community-wide adult education. Hence health education regarding smoking should be geared towards children and program materials should be developed accordingly to make a positive impression. Like “teen age pregnancy” and “safe sex” health education in high schools, “smoking cessation” should be a part of curriculum starting from grammar schools. No significant financial relationships to disclose.
Down-regulation of Fibulin-5 is associated with aortic dilation: role of inflammation and epigenetics
Authors: Mar Orriols, Saray Varona, Ingrid Martí-Pàmies, María Galán, Anna Guadall, José Román Escudero, José Luis Martín-Ventura, Mercedes Camacho, Luis Vila, José Martínez-González, Cristina Rodríguez
Journal: Cardiovascular Research (2016)

Destructive remodelling of extracellular matrix (ECM) and inflammation lead to dilation and ultimately abdominal aortic aneurysm (AAA). Fibulin-5 (FBLN5) mediates cell–ECM interactions and elastic fibre assembly and is critical for ECM remodelling. We aimed to characterize FBLN5 regulation in human AAA and analyse the underlying mechanisms. FBLN5 expression was significantly decreased in human aneurysmatic aortas compared with healthy vessels. Local FBLN5 knockdown promoted aortic dilation and enhanced vascular expression of inflammatory markers in Ang II-infused C57BL/6J mice. Inflammatory stimuli down-regulated FBLN5 expression and transcriptional activity in human aortic vascular smooth muscle cells (VSMC). Further, aortic FBLN5 expression was reduced in LPS-challenged mice. A SOX response element was critical for FBLN5 promoter activity. The SOX9 expression pattern in human AAA parallels that of FBLN5, and like FBLN5, it was reduced in TNFα-stimulated VSMC. Interestingly, SOX9 over-expression prevented the cytokine-mediated reduction of FBLN5 expression and transcription. The inhibition of Class I histone deacetylases (HDACs) by MS-275 or gene silencing attenuated the inflammation-mediated decrease of FBLN5 expression in VSMC and in the vascular wall. Consistently, HDAC inhibition counteracted the reduction of SOX9 expression induced by inflammatory stimuli and prevented the TNFα-mediated decrease in the binding of SOX9 to FBLN5 promoter normalizing FBLN5 expression. We evidence the deregulation of FBLN5 in human AAA and identify a SOX9/HDAC-dependent mechanism involved in the down-regulation of FBLN5 by inflammation. HDAC inhibitors or pharmacological approaches that aimed to preserve FBLN5 could be useful to prevent the disorganization of ECM induced by inflammation in AAA.
Endpiece: Second opinions
Authors: Jeremy Hugh Baron
Journal: BMJ (2005)

In this country it is the usage frequently to employ practitioners who are considered as of less note at the beginning of a complaint; and afterwards, if he should not be thought capable of conducting, or if he should not cure the disease, another is sent for, as supposed of greater skill. I do not mean to argue the propriety of this usage; but as it exists that this second practitioner can obtain very little authentic evidence of what went before in this disease, by which he can judge of it.

Fordyce G. An attempt to improve the evidence of medicine. Trans Soc Impr Med Chir Knowl 1793;1: 244
Demographic and treatment characteristics for advanced basal cell carcinoma (aBCC) in an oncology outpatient setting.
Authors: A. D. Joshi, M. T. Forsyth, D. C. Fryefield, W. Lopez, D. M. Chen, D. D. Ramanan
Journal: Journal of Clinical Oncology (2011)

e19001 Background: aBCC is defined as (1) locally advanced BCC (inoperable or surgery contraindicated) with disease progression after radiation (unless radiation contraindicated), or (2) metastatic BCC. Information on aBCC patient demographics, or clinical and treatment characteristics is limited. The purpose of this descriptive study is to characterize aBCC patients receiving care within the US Oncology (USO) network. Methods: Patients with a diagnosis of aBCC between July 1, 2006 to June 30, 2010 were included. From an initial pool of 278 BCC patients, AJCC staging 6th ed. (Stage III, IV) and metastatic status were used to identify aBCC patients. Detailed Electronic Medical Records (EMR) and physical chart reviews were conducted on identified patients to collect information on patient demographics, clinical characteristics, and current and historical treatment characteristics. Analyses were primarily descriptive. Results: 41 patients were treated at USO clinics for aBCC. Mean age was 72 years, males comprised 68%, and mean Charlson Comorbidity Score was 0.97. 11 patients developed metastases. Sites of advanced disease were in the head/neck area (54%), extremities (10%), trunk (5%) and other (32%). Before progression to aBCC, patients received BCC-related surgeries (12 or 29%), radiation (9 or 22%) and chemotherapy (1 or 2%) while post aBCC diagnosis, patients received surgeries (24 or 59%), radiation (28 or 68%) and chemotherapy (13 or 32%), where each patient could have more than one procedure. Before progression to aBCC, there were 2 Moh’s surgeries and 2 excisions while post aBCC diagnosis, there were 6 Moh’s surgeries and 15 excisions. Among 20 chemotherapy regimens post diagnosis to aBCC, 15 were platinum based. These patients saw several types of physicians, namely radiation oncologists (34%), medical oncologists (29%), dermatologists (21%), surgical specialists (12%), and primary care physicians (4%). Conclusions: aBCC is an uncommon but serious condition, for which there appears to be no commonly accepted approach to therapy. Even in a national oncology community group, there is no consistent pattern of care for aBCC patients, suggesting that more research and options are needed.
Antiarrhythmic Prophylaxis with Procainamide in Acute Myocardial Infarction
Authors: Jan Koch-Weser, Stuart W. Klein, Lourdes L. Foo-Canto, John A. Kastor, Roman W. DeSanctis
Journal: New England Journal of Medicine (1969)

The effectiveness of prophylactic therapy with procainamide in preventing active ventricular arrhythmias after acute myocardial infarction was determined in a double-blind study using electrocardiographic monitoring of 70 patients with acute infarctions uncomplicated by shock, heart block or severe heart failure. After a loading dose, 250, 375 or 500 mg of procainamide or placebo were administered every three hours according to patient weight. Procainamide afforded highly significant protection against all types of active ventricular arrhythmias, markedly reduced the need for acute therapy of arrhythmias, and prevented death from active arrhythmias. Adverse effects of procainamide therapy occurred only in patients with excessive plasma concentrations. The effective plasma procainamide concentration for suppressing active ventricular arrhythmias after acute myocardial infarction is 4 to 6 mg per liter. Lower plasma levels protect incompletely whereas concentrations above 7 mg per liter can produce adverse cardiovascular effects. Plasma procainamide concentrations vary widely among patients, and their measurement is helpful in establishing proper individual dosage.
Merkel-Cell Carcinomas in Patients Treated with Methoxsalen and Ultraviolet A Radiation
Authors: Elissa J. Lunder, Robert S. Stern
Journal: New England Journal of Medicine (1998)

To the Editor: Merkel-cell carcinoma is a very rare small-cell carcinoma of the skin.1 Probably derived from Merkel cells, the mechanoreceptors located in the basal layer of the epidermis, these tu...
The Development of the State Child-Guidance Clinics in Massachusetts
Authors: Edgar C. Yerbury, Nancy Newell
Journal: New England Journal of Medicine (1945)

THE Commonwealth of Massachusetts was the first state to provide by legislation (in 1922) for a division of mental hygiene,1 with the establishment of child-guidance clinics financed by state funds as one of its major activities. A review of the diversely related developments in psychiatric therapy that culminated in the child-guidance movement shows the state guidance clinics emerging at the peak of the mental-hygiene movement as the logical but unforeseen outcome of efforts to promote mental health by preventive and early correctional treatment.The mental-hygiene movement expanded with remarkable rapidity through the years 1912 to 1922 under the impact of . . .