tbuckley/cabot-search huggingface dataset:
Abstract P5-04-15: Investigating the role of the AMPK signaling cascade in breast cancer tumor dormancy
Authors: KL Sullivan, KN Phoenix, MM Fox, S Kopsiaftis, KP Claffey
Journal: Cancer Research (2013)

Abstract Breast cancer can recur in patients long after treatment for initial disease. The mechanisms underlying recurrence as well as the characteristics of these dormant tumor cells remain poorly understood. AMPK (AMP-activated protein kinase) is the central metabolic regulator of the cell, and has two catalytic isoforms, a1 and α2. The loss of AMPK, more specifically AMPKα2, is observed in primary breast cancer and its expression could function to limit tumor expansion in vivo. We hypothesize that the expression of AMPKα2 will confer a survival advantage in dormant breast cancer cells by upregulating the p38MAPK signaling axis. In order to investigate breast cancer dormancy mechanisms in vitro, we generated mammospheres using the estrogen-dependent MCF-7 human breast cancer cell line, which has low expression of AMPKα2. Control MCF-7 cells expressing GFP and MCF-7 cells overexpressing the AMPKα1 or AMPKα2 isoforms were cultured as mammospheres and exposed to various metabolic stressors including estrogen, glucose, and serum deprivation. Spheroids were evaluated for size, viability, gene expression at the RNA level by qRT-PCR, and intracellular signaling by immunoblot as well as immunohistochemistry. AMPKα2 expressing mammospheres were larger and more viable than either the GFP or AMPKα1 expressing spheres. In addition, these cells were resistant to serum deprivation, and upregulated members of the p38MAPK signaling axis, a key player in tumor dormancy. To evaluate estrogen deprivation-induced dormancy in vivo, MCF-7 cell lines expressing either GFP or AMPKα2 embedded in a matrigel matrix were implanted in athymic nude mice containing supplemental slow-release estradiol pellets. After one week, estradiol pellets were removed to induce a dormant period for roughly thirty days. Evaluation of matrigel plugs at this time indicated that AMPKα2 expressing cells demonstrated significant survival whereas GFP expressing cells were significantly depleted. Estadiol pellets were then re-implanted for five weeks to determine if the AMPKα2 expressing cells still responded to estradiol supplementation.This resulted in the AMPKα2 expressing tumors rapidly expanding to a maximal size as compared to the GFP expressing tumors. Consistent with our findings in vitro using mammosphere cultures, the AMPKα2 expressing cells had higher levels of phospho-p38MAPK than the GFP expressing cells, as seen by immunofluorescence. We conclude that the expression of AMPKα2 promotes both survival and dormancy in estrogen-sensitive breast tumor cells, thus implying a significant role in breast cancer recurrence. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-04-15.
RESULTS OF ANTE-NATAL ADMINISTRATION OF QUININE
Authors: P. J. Ganner
Journal: BMJ (1935)

some of her housework.The best result was obtained - in Case 2 (coronary sclerosis, angina pectoris).Before the operation the patient could walk only a few yards without being stopped by pain.He is now back at full heavy work, with little or no pain.We think it fair to say that the two deaths from cerebral haemorrhage were secondary to the hypertension, which is not affected by the operation.The cardiac symptoms were improved in both, in one greatly.Of the remaining five cases two were failures, the others successful in varying degree, in one with return to full activity.When it is recalled that all seemed to be hopeless cases, in which every other form of treatment had failed, we feel that the measure of success attained has been gratifying.The two failures, however, show that further investigation is required in order to work out more clearly the indications for the operation.
Pentraxins Coordinate Excitatory Synapse Maturation and Circuit Integration of Parvalbumin Interneurons
Authors: Kenneth A. Pelkey, Elizabeth Barksdale, Michael T. Craig, Xiaoqing Yuan, Madhav Sukumaran, Geoffrey A. Vargish, Robert M. Mitchell, Megan S. Wyeth, Ronald S. Petralia, Ramesh Chittajallu, Rose-Marie Karlsson, Heather A. Cameron, Yasunobu Murata, Matthew T. Colonnese, Paul F. Worley, Chris J. McBain
Journal: Neuron (2015)
Factors Leading to Dependence on Hypnotic Drugs
Authors: A. D. Clift
Journal: BMJ (1972)

Patients in general practice complaining of insomnia of recent origin have been studied in order to ascertain which factors may be of value in the detection of those more susceptible to drug dependence. The type of sleep disturbance was found to be of importance and a personal disturbance scale was found useful as a screening test in two-thirds of the patients. No difference was found in the development of dependence on amylobarbitone and nitrazepam. One of the most important factors in the prevention of drug dependence seems to be frequent review by the doctor after the first prescription and his cautionary advice to the patient.
Empirical Evidence of Design-Related Bias in Studies of Diagnostic Tests
Authors: J G Lijmer, B W Mol, S Heisterkamp, G J Bonsel, M H Prins, J H van der Meulen, P M Bossuyt
Journal: JAMA (1999)

The literature contains a large number of potential biases in the evaluation of diagnostic tests. Strict application of appropriate methodological criteria would invalidate the clinical application of most study results.To empirically determine the quantitative effect of study design shortcomings on estimates of diagnostic accuracy.Observational study of the methodological features of 184 original studies evaluating 218 diagnostic tests. Meta-analyses on diagnostic tests were identified through a systematic search of the literature using MEDLINE, EMBASE, and DARE databases and the Cochrane Library (1996-1997). Associations between study characteristics and estimates of diagnostic accuracy were evaluated with a regression model.Relative diagnostic odds ratio (RDOR), which compared the diagnostic odds ratios of studies of a given test that lacked a particular methodological feature with those without the corresponding shortcomings in design.Fifteen (6.8%) of 218 evaluations met all 8 criteria; 64 (30%) met 6 or more. Studies evaluating tests in a diseased population and a separate control group overestimated the diagnostic performance compared with studies that used a clinical population (RDOR, 3.0; 95% confidence interval [CI], 2.0-4.5). Studies in which different reference tests were used for positive and negative results of the test under study overestimated the diagnostic performance compared with studies using a single reference test for all patients (RDOR, 2.2; 95% CI, 1.5-3.3). Diagnostic performance was also overestimated when the reference test was interpreted with knowledge of the test result (RDOR, 1.3; 95% CI, 1.0-1.9), when no criteria for the test were described (RDOR, 1.7; 95% CI, 1.1-2.5), and when no description of the population under study was provided (RDOR, 1.4; 95% CI, 1.1-1.7).These data provide empirical evidence that diagnostic studies with methodological shortcomings may overestimate the accuracy of a diagnostic test, particularly those including nonrepresentative patients or applying different reference standards.
Hypernatremia in Hyperosmotic Coma?
Authors: Robert S. Brown
Journal: Annals of Internal Medicine (1971)

Letters and Comments1 April 1971Hypernatremia in Hyperosmotic Coma?ROBERT S. BROWN, M.D.ROBERT S. BROWN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-74-4-642 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In the ANNALSof December 1970 (1) Dr. Raja and his associates described a patient with hyperosmotic coma, which followed 72 hr of peritoneal dialysis using hypertonic sorbitol dialysate. The patient's serum osmolality was 408 mOsm/liter; blood urea nitrogen, 94 mg/100 ml; glucose, 264 mg/100 ml; and sorbitol, 750 mg/100 ml. At the end of the dialysis the patient had lost 32 lb, and his hematocrit had risen from 28 to 40. He developed progressive coma, became hypotensive, and died. While the elevated blood sorbitol level contributed about 40 mOsm/liter to the serum osmolality, the serum sodium,...References1. RAJA R, MOROS J, and KRAMER M: Hyperosmotic coma complicating peritoneal dialysis with sorbitol dialysate. Ann Intern Med 73:993-994, 1970 LinkGoogle Scholar2. NOLPH K, HANO J, and TESCHAN P: Peritoneal sodium transport during hypertonic peritoneal dialysis: physiologic mechanisms and clinical implications. Ann Intern Med 70:931-941, 1969 LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: ROBERT S. BROWN, M.D.Affiliations: School of Medicine Yale University New Haven, Conn. 06510 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1971Volume 74, Issue 4Page: 642-643KeywordsBloodBlood urea nitrogenComaGlucoseHematocritHypernatremiaMedical dialysisPeritoneal dialysisSodium ePublished: 1 December 2008 Issue Published: 1 April 1971 PDF downloadLoading ...
Role of the Sympathetic Nervous System in Regulating Renin and Aldosterone Production in Man *
Authors: Richard D. Gordon, Oto Küchel, Grant W. Liddle, Donald P. Island
Journal: Journal of Clinical Investigation (1967)

Several lines of evidence have been developed indicating that the sympathetic nervous system may play a role in mediating the renal and adrenocortical secretory responses to upright posture and sodium deprivation. Despite concurrent increases in arterial blood pressure, the plasma renin activity of normal subjects increased both in response to the infusion of catecholamines (norepinephrine: epinephrine, 10:1) and in response to stimulation of the sympathetic nervous system by cold. Aldosterone excretion was also increased by catecholamine infusion. In normal subjects the stimuli of upright posture and of sodium depletion both resulted in increases in urinary catecholamines, plasma renin activity, and urinary aldosterone. A patient with severe autonomic insufficiency did not experience normal elevations of urinary catecholamines, plasma renin activity, or urinary aldosterone in response to upright posture or sodium deprivation, despite a substantial fall in arterial blood pressure. When orthostatic hypotension was prevented by infusion of catecholamines, however, increases in plasma renin activity and in aldosterone excretion were observed. We suggest that both upright posture and sodium depletion lead to decreases in effective plasma volume and increases in sympathetic nervous system activity. This increase in sympathetic activity is then responsible for an increase in renal afferent arteriolar constriction, leading to an increase in renin secretion and, ultimately, an increase in aldosterone secretion.
In vivo targeting of intestinal and extraintestinal transglutaminase 2 by coeliac autoantibodies
Authors: I R Korponay-Szabo
Journal: Gut (2004)

<h3>Background</h3> Increased time to operative intervention is associated with a greater risk of mortality and complications in adults with a hip fracture. This study sought to determine factors associated with timeliness of operation in elderly patients presenting with an isolated hip fracture and the influence of surgical delay on outcomes. <h3>Methods</h3> Trauma quality collaborative data (July 2016 to June 2019) were analyzed. Inclusion criteria were patients ≥65 years with an injury mechanism of fall, Abbreviated Injury Scale (AIS) 2005 diagnosis of hip fracture, and AIS extremity ≤3. Exclusion criteria included AIS in other body regions &gt;1 and non-operative management. We examined the association of demographic, hospital, injury presentation, and comorbidity factors on a surgical delay &gt;48 hours and patient outcomes using multivariable regression analysis. <h3>Results</h3> 10 182 patients fit our study criteria out of 212 620 patients. Mean age was 82.7±8.6 years and 68.7% were female. Delay in operation &gt;48 hours occurred in 965 (9.5%) of patients. Factors that significantly increased mortality or discharge to hospice were increased age, male gender, emergency department hypotension, functionally dependent health status (FDHS), advanced directive, liver disease, angina, and congestive heart failure (CHF). Delay &gt;48 hours was associated with increased mortality or discharge to hospice (OR 1.52; 95% CI 1.13 to 2.06; p&lt;0.01). Trauma center verification level, admission service, and hip fracture volume were not associated with mortality or discharge to hospice. Factors associated with operative delay &gt;48 hours were male gender, FDHS, CHF, chronic renal failure, and advanced directive. Admission to the orthopedic surgery service was associated with less incidence of delay &gt;48 hours (OR 0.43; 95% CI 0.29 to 0.64; p&lt;0.001). <h3>Discussion</h3> Hospital verification level, admission service, and patient volume did not impact the outcome of mortality/discharge to hospice. Delay to operation &gt;48 hours was associated with increased mortality. The only measured modifiable characteristic that reduced delay to operative intervention was admission to the orthopedic surgery service. <h3>Level of evidence</h3> III.
Copy Number Gain of 1q25 Predicts Poor Progression-Free Survival for Pediatric Intracranial Ependymomas and Enables Patient Risk Stratification: A Prospective European Clinical Trial Cohort Analysis on Behalf of the Children's Cancer Leukaemia Group (CCLG), Société Française d'Oncologie Pédiatrique (SFOP), and International Society for Pediatric Oncology (SIOP)
Authors: John-Paul Kilday, Biswaroop Mitra, Caroline Domerg, Jennifer Ward, Felipe Andreiuolo, Teresa Osteso-Ibanez, Audrey Mauguen, Pascale Varlet, Marie-Cecile Le Deley, James Lowe, David W. Ellison, Richard J. Gilbertson, Beth Coyle, Jacques Grill, Richard G. Grundy
Journal: Clinical Cancer Research (2012)

The high incidence of recurrence and unpredictable clinical outcome for pediatric ependymoma reflect the imprecision of current therapeutic staging and need for novel risk stratification markers. We therefore evaluated 1q25 gain across three age- and treatment-defined European clinical trial cohorts of pediatric intracranial ependymoma.Frequency of 1q gain was assessed across 48 ependymomas (42 primary, 6 recurrent) using Affymetrix 500K single-nucleotide polymorphism arrays. Gain of 1q25 was then evaluated by interphase FISH across 189 tumors treated on the Children's Cancer Leukaemia Group/International Society for Pediatric Oncology (SIOP) CNS9204 (n = 60) and BBSFOP (n = 65) adjuvant chemotherapy trials, or with primary postoperative radiotherapy (SIOP CNS9904/RT, n = 64). Results were correlated with clinical, histologic, and survival data.Gain of 1q was the most frequent imbalance in primary (7/42, 17%) and recurrent ependymomas (2/6, 33%). Gain of 1q25 was an independent predictor of tumor progression across the pooled trial cohort [HR = 2.55; 95% confidence interval (CI): 1.56-4.16; P = 0.0002] and both CNS9204 (HR = 4.03; 95% CI: 1.88-8.63) and BBSFOP (HR = 3.10; 95% CI: 1.22-7.86) groups. The only clinical variable associated with adverse outcome was incomplete tumor resection. Integrating tumor resectability with 1q25 status enabled stratification of cases into disease progression risk groups for all three trial cohorts.This is the first study to validate a prognostic genomic marker for childhood ependymoma across independent trial groups. 1q25 gain predicts disease progression and can contribute to patient risk stratification. We advocate the prospective evaluation of 1q25 gain as an adverse marker in future international clinical trials.
Recurrent Acute Idiopathic Thrombocytopenic Purpura
Authors: William Dameshek, Shirley Ebbe, Lowell Greenberg, Mario Baldini
Journal: New England Journal of Medicine (1963)

IN recent years it has become apparent that the syndrome called idiopathic thrombocytopenic purpura consists of a complex of disorders. This syndrome, as we have defined it,1 is characterized by thrombocytopenic purpura, a normal or increased number of megakaryocytes in the bone marrow and no apparent splenomegaly. Perhaps the most striking evidence that the disease represents a syndrome rather than a well defined entity comes from the diversity of clinical situations in which it occurs. It may be truly "idiopathic" in the present state of limited knowledge, but, on the other hand, an identical thrombocytopenic state may be related to . . .
Elevation of IgA Levels in the Non-insulin-dependent (Type II) Diabetic Patient
Authors: Charles W Gill, W Stephen Bush, William M Burleigh, Deborah Cooke-Gomes
Journal: Diabetes Care (1981)

Serum immunoglobulin (G, A, M) levels were performed on 66 patients with non-insulin-dependent (type II) diabetes mellitus (NIDDM). When compared with 30 age-matched normal controls and 32 hospitalized controls there was no significant difference between the mean IgG and IgM levels. The IgA levels were significantly higher (P &amp;lt; 0.005) in the diabetic group when compared with both control groups. This is true regardless of age, sex, duration of disease, and type of treatment (insulin/diet or oral hypoglycemic agents and/or diet). Thirty-six percent of the diabetic patients' IgA levels exceeded the mean ± 2 SD of the normal control group. There were no significant differences in immunoglobulin levels between insulin-treated and non-insulin-treated diabetic groups. Since diabetic patients may have a number of secondary diseases, attempts were made to correlate the most common of these (acute and/or chronic bacterial infections, hypertension, arteriosclerotic heart disease, and diabetic neuropathy) with elevated IgA levels. Only IgA levels of diabetic patients with infections versus diabetic patients without infections were significantly different (P &amp;lt; 0.05). However, IgA levels of uninfected diabetic patients remained significantly higher than those of normal controls (P &amp;lt; 0.005), hospitalized controls (P &amp;lt; 0.01), and hospitalized controls with bacterial infections (P &amp;lt; 0.005). Possible reasons for the isolated elevations of IgA are discussed.
A model of measured percussive mechanical trauma and its effects on skin
Authors: C.J. GRAVES, C. EDWARDS, R. MARKS
Journal: British Journal of Dermatology (1993)

In this study, the role of mechanical trauma to skin in industrial dermatitis is considered. The percussive component of mechanical trauma to skin is investigated by modelling it, using an oscillating device which can supply a range of percussive trauma doses. The instrument is electronically controlled, and contains sensors which monitor the force and displacement throughout each impact. From this information, a value proportional to the dose delivered to the skin is calculated and used, rather than the driving power of the percussor. The rate of dose is also controlled. In this study, doses were delivered at a frequency of 7 Hz. Eight volunteers were given regimens of percussive trauma at regular intervals over a 5‐day period. Half the group received a dose of 4 mJ/cm2 per impact, the other half received double this dose. The skin response was evaluated using non‐invasive measurements of transepidermal water loss, skin thickness, and erythema. The results demonstrate that erythema, skin thickness and transepidermal water loss are all increased after mechanical challenge—erythema and water loss by amounts dependent upon the trauma dose applied. The transepidermal water loss results indicate that for the subjects used in our study, there was a trauma threshold reached after a cumulative dose of greater than 250 J/cm2.
'Confidentiality' issues may cloud epidemiologic studies of AIDS
Authors: Charles Marwick
Journal: JAMA (1983)

Questions have been raised about the Centers for Disease Control's policies on confidentiality after the agency admitted releasing the names of acquired immune deficiency syndrome (AIDS) victims to health agencies not affiliated with the federal government. Since the majority of AIDS victims are homosexuals, gay rights groups are concerned about the consequences if names are released to law enforcement officials, despite CDC assurances that nonhealth agencies do not have access to its records. Failure on the part of the CDC to convince the gay community of the need for some identifying information on AIDS records could compromise epidemiological research on the disease.
Status of the adult and adolescent after repair of tetralogy of Fallot.
Authors: A Garson, M R Nihill, D G McNamara, D A Cooley
Journal: Circulation (1979)

Because increasing numbers of patients with surgically repaired tetralogy of Fallot (TOF) are surviving to adulthood, this study was done to provide follow-up data for physicians concerned with their care.We reviewed the current status of 233 patients born before January 1962 who had repair of TOF at a me- dian age of 9.7 years (range 11 months to 36 years).There were 26 surgical deaths (11.1%), 12 late cardiac- related deaths (5.9%) and three noncardiac deaths (1.3%).Eight of the 12 late deaths occurred suddenly and unexpectedly.In each of these eight patients we had previously documented elevated right ventricular systolic pressure as well as ventricular premature depolarizations (VPDs).Among the 95 patients who responded to a questionnaire, 84 denied symptoms, 28 were married, 44 had attended college and all were employed.Cardiac catheterization revealed an unsatisfactory hemodynamic result in 39 of 120 patients, 30 of whom were asymptomatic.The poor result was due to a large left-to-right ventricular shunt in eight patients, persistent right ven- tricular outflow obstruction in 25 patients, pulmonary vascular obstructive disease in five patients, and left ven- tricular cardiomyopathy in one patient.Among the 21 patients with VPDs, 17 underwent cardiac catheterization: 15 had a right ventricular systolic pressure > 60 mm Hg and all had elevated right ventricular end-diastolic pressure.We conclude that 1) clinical assessment alone is nonpredictive of the hemodynamic result and thus cardiac catheterization is indicated in all patients; 2) the combination of persistent elevation of right ventricular systolic pressure above 60 mm Hg and VPDs placed the patient at risk for sudden death; and 3) over 80% of adults with repaired TOF can lead a normal life without impairment of intellect, exercise tolerance or fertility.IN THE UNITED STATES each year an estimated 24,500 newborns have a congenital heart defect.1 2 Approximately 1%, or 2700, have tetralogy of Fallot (TOF).3-5Based on current surgical treatment, we esti- mate that 89% of these patients, or 2400 per year, will survive to adulthood.The purposes of this study were: 1) to present the characteristics of these patients; 2) to determine if symptomatology, physical examination and laboratory findings are adequate predictors of the postoperative hemodynamic result; and 3) to examine the late complications and causes of late death in an effort to predict and prevent these occurrences by identifying patients at risk. Materials and Methods DefinitionPatients were included if they had typical anatomy of TOF with a nonrestrictive ventricular septal defect and pulmonary stenosis with essentially equal peak systolic pressure in two ventricles.Patients were excluded from the study if they had preoperative right ventricular outflow or main pulmonary artery atresia
Balloon Occlusion of the Internal Spermatic Vein for the Treatment of Varicoceles
Authors: Patrick C. Walsh, Robert I. White
Journal: JAMA (1981)

Varicocele is one of the most common causes of male infertility. We have developed a technique for the treatment of this disorder in which occlusion of the internal spermatic vein is accomplished percutaneously using a detachable balloon. Twenty-one varicocceles in 20 patients have been treated successfully without complication. This procedure can be performed easily, without general anesthesia or surgical incision, on an outpatient basis.