tbuckley/cabot-search huggingface dataset:
Foxa2 regulates multiple pathways of insulin secretion
Authors: Kristen A. Lantz, Marko Z. Vatamaniuk, John E. Brestelli, Joshua R. Friedman, Franz M. Matschinsky, Klaus H. Kaestner
Journal: Journal of Clinical Investigation (2004)

The regulation of insulin secretion by pancreatic β cells is perturbed in several diseases, including adult-onset (type 2) diabetes and persistent hyperinsulinemic hypoglycemia of infancy (PHHI). The first mouse model for PHHI has a conditional deletion of the gene encoding the winged-helix transcription factor Foxa2 (Forkhead box a2, formerly Hepatocyte nuclear factor 3β) in pancreatic β cells. Using isolated islets, we found that Foxa2 deficiency resulted in excessive insulin release in response to amino acids and complete loss of glucose-stimulated insulin secretion. Most PHHI cases are associated with mutations in SUR1 (Sulfonylurea receptor 1) or KIR6.2 (Inward rectifier K+ channel member 6.2), which encode the subunits of the ATP-sensitive K+ channel, and RNA in situ hybridization of mutant mouse islets revealed that expression of both genes is Foxa2 dependent. We utilized expression profiling to identify additional targets of Foxa2. Strikingly, one of these genes, Hadhsc, encodes short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase, deficiency of which has been shown to cause PHHI in humans. Hadhsc is a direct target of Foxa2, as demonstrated by cotransfection as well as in vivo chromatin immunoprecipitation experiments using isolated islets. Thus, we have established Foxa2 as an essential activator of genes that function in multiple pathways governing insulin secretion.
Influence of hyperosmolar agents on hypoxic cat papillary muscle function
Authors: J. T. WILLERSON, M. L. WEISFELDT, C. A. SANDERS, W. J. POWELL
Journal: Cardiovascular Research (1974)

The influence of hypertonic agents on 64 isolated hypoxic cat papillary muscles was examined under isometric conditions in Krebs-Ringer bicarbonate solution with 18 mM glucose at 29°C. Nine papillary muscles pretreated before hypoxia and eight muscles exposed to hypertonic mannitol 6 min following hypoxia demonstrated a significantly reduced decline from prehypoxia control values for developed tension and its first derivative compared to the same muscles in the control solution. There was no significant change in resting tension. This improvement in muscle performance during hypoxia was present at osmolalities of 60 mOsm above control values. The performance of papillary muscles during hypoxia was similar for hypertonic mannitol, sucrose, and urea when the muscles were exposed to the agents for 30 min before hypoxia. However, longer periods (2 hours) of exposure to hypertonic mannitol or urea before hypoxia resulted in a reduced decline in developed tension and its first derivative during hypoxia only in the case of mannitol. These studies suggest that the beneficial effect of hyperosmolar agents on muscle performance during hypoxia may not be totally dependent on blood flow changes and may be associated with changes in cell size.
Comparative effects of vasodilator drugs on large and small coronary resistance vessels in the dog
Authors: R. FORMAN, E. S KIRK
Journal: Cardiovascular Research (1980)

One of the mechanisms whereby nitroglycerin is considered to reduce myocardial ischaemia and spasm is its preferential reduction of resistance of large compared with small coronary arteries. Accordingly, the action of nitroglycerin on these two resistance beds was compared with newer coronary vasodilator drugs. Following intracoronary administration of boluses of each drug, large and small vessel coronary resistance was measured in 14 dogs by recording the pressure drop across each vascular bed while flow was held constant. The dose of each drug was given to reduce small vessel resistance by 30% (range means 27 to 32%) which peaked at 5 to 10 s and declined to 8 to 18% at 1 min when reduction in large vessel resistance was at its maximum. At 1 min the large vessel resistance was decreased 56±5% by nitroglycerin, 23±5% by nitroprusside, 8±4% by perhexiline, 0±5% by verapamil and increased 8±5% by nifedipine. Nitroprusside reduced the large vessel resistance significantly less than nitroglycerin (P <0.001) for an equivalent reduction in small vessel resistance. Perhexiline, verapamil and nifedipine did not significantly reduce large vessel resistance and the discrepancy between these results and their antianginal and antispasm effect in humans was not apparent from these experiments. However, a suitable model of coronary spasm in the dog following ergonovine injection could not be created.
Multicenter, double-blind, multiple-dose, parallel-groups efficacy and safety trial of azelastine, chlorpheniramine, and placebo in the treatment of spring allergic rhinitis
Authors: J WEILER, A DONNELLY, B CAMPBELL, J CONNELL, L DIAMOND, L HAMILTON, R ROSENTHAL, G HEMSWORTH, J PERHACHJR
Journal: Journal of Allergy and Clinical Immunology (1988)
Circadian variation of acute myocardial infarction and the effect of low-dose aspirin in a randomized trial of physicians.
Authors: P M Ridker, J E Manson, J E Buring, J E Muller, C H Hennekens
Journal: Circulation (1990)

Increased platelet aggregation in the morning and upon assuming an upright posture may account at least in part for the observed circadian variation in onset of acute myocardial infarction. The Physicians' Health Study, a randomized, double-blind, placebo-controlled trial of alternate-day aspirin intake (325 mg) among 22,071 US male physicians, afforded the opportunity to assess this circadian pattern and examine whether it is altered by aspirin therapy. During a 5-year period of follow-up, 342 cases of nonfatal myocardial infarction were confirmed, of which the time of onset was available in 211 (62%). The placebo group showed a bimodal circadian variation in onset of myocardial infarction with a primary peak between 4:00 AM and 10:00 AM (p less than 0.001). In the aspirin group, however, this circadian variation was minimal (p = 0.16), due primarily to a marked reduction in the morning peak of infarction. Specifically, aspirin was associated with a 59.3% reduction in the incidence of infarction during the morning waking hours, compared with a 34.1% reduction for the remaining hours of the day. The greater reduction was observed during the 3-hour interval immediately after awakening, a period with a risk of infarction twice that of any other comparable time interval (p less than 0.001). Aspirin intake was associated with a mean reduction in the incidence of infarction of 44.8% over the entire 24-hour cycle. These data support the hypothesis that increased platelet aggregability in the morning and upon arising contributes to the occurrence of myocardial infarction and that aspirin reduces the risk of infarction by inhibiting platelet aggregation during these critical periods.
Efficacy and tolerability of combined topical treatment of acne vulgaris with adapalene and clindamycin: a multicenter, randomized, investigator-blinded study
Authors: John E Wolf, David Kaplan, Stephen J Kraus, Keith H Loven, Toivo Rist, Leonard J Swinyer, Michael D Baker, Yin S Liu, Janusz Czernielewski
Journal: Journal of the American Academy of Dermatology (2003)
Endoscopic Variceal Sclerosis Compared with Distal Splenorenal Shunt To Prevent Recurrent Variceal Bleeding in Cirrhosis
Authors: J. Michael Henderson, Michael H. Kutner, William J. Millikan, John T. Galambos, Stanley P. Riepe, W. Scott Brooks, F. Curtis Bryan, W. Dean Warren
Journal: Annals of Internal Medicine (1990)

Study Objective: To define the roles of endoscopic variceal sclerosis and distal splenorenal shunt in the prevention of recurrent variceal bleeding in patients with cirrhosis. Design: A prospective, randomized clinical trial with crossover for those failing therapy. The median follow-up was 61 months. Setting: A private, tertiary-referral university hospital. Patients: Seventy-two patients fulfilling inclusion criteria were drawn from a total of 420 patients treated during a 4.5-year interval. Treatments: Endoscopic variceal sclerosis or distal splenorenal shunt. Measurements and Main Results: Survival was significantly (P = 0.02) improved in patients randomly assigned to receive sclerotherapy: 13 of these 37 (35%) patients failed sclerotherapy and required surgical rescue. A survival advantage (P = 0.01) was seen in patients with alcoholic cirrhosis who had this combined therapy; however, in patients with nonalcoholic cirrhosis, survival for those receiving sclerotherapy and surgical rescue was not significantly (P = 0.36) different from that of patients receiving distal splenorenal shunt. Control of variceal bleeding was significantly (P < 0.001) better in the distal splenorenal shunt group (34 of 35 [97%] compared with 15 of 37 [41%] in the sclerotherapy group). Using death, uncontrolled rebleeding, or shunt thrombosis as the endpoints resulted in no significant difference between treatment groups. Hepatocyte function and portal perfusion were significantly better maintained in patients with alcoholic cirrhosis who were managed by sclerotherapy rather than shunt (P = 0.01 and P = 0.001, respectively). Conclusions: Endoscopic sclerotherapy with surgical rescue for uncontrolled bleeding is the optimum therapy for patients with alcoholic cirrhosis and variceal bleeding. Survival is similar in nonalcoholic patients treated with either distal splenorenal shunt or endoscopic sclerotherapy, but shunting provides better control of variceal bleeding.
1168-162 Targeted ablation of myocardium using high intensity focused ultrasound in beating dog hearts
Authors: Ryo Otsuka, Kana Fujikura, Todd Pulerwitz, Kumiko Hirata, Jie Wang, Daniel Burkhoff, Robert Muratore, Fred Lizzi, Shunichi Homma
Journal: Journal of the American College of Cardiology (2004)
China joins global effort over pneumonia virus
Authors: J. Parry
Journal: BMJ (2003)

The Chinese authorities have joined the global effort to discover the origin of the virus that has caused a worldwide epidemic of severe acute respiratory syndrome (SARS). A team of investigators from the World Health Organization was allowed into Guangdong province last week to examine records of the cases that had occurred there and to meet health workers.

WHO now cites southern China as the place where the virus emerged. A spokesman for the WHO team said that the evidence they had gathered pointed to the coronavirus as the most likely cause of the outbreak but that it was too early to say if there was any link between …
Nuclear terrorism Commentary: The myth of nuclear deterrence in south Asia Commentary: The psychology of terrorists
Authors: I. Helfand
Journal: BMJ (2002)

# Nuclear terrorism {#article-title-2} Three members of International Physicians for the Prevention of Nuclear War and Physicians for Social Responsibility discuss the threat of nuclear terrorism and conclude that the only effective way to tackle it is to abolish nuclear weapons The attack on the World Trade Center in New York clearly showed that there are terrorists who are willing to inflict civilian casualties on the scale that would be expected with the use of a weapon of mass destruction. In this article we consider the form that nuclear terrorism could take and estimate the casualties that would occur if a nuclear bomb the size of that dropped on Hiroshima was detonated in a large urban area. The enormous casualties to be expected from such an attack argue strongly for a strategy of primary prevention. #### Summary points In the aftermath of 11 September 2001 nuclear terrorism has emerged as a real threat Nuclear terrorism could take several forms, from an attack on nuclear power plants and reactors to the detonation of a nuclear bomb in an urban area The international community urgently needs to expand its efforts to secure existing stockpiles of nuclear weapons and materials, particularly in Russia, Pakistan, and India The elimination of nuclear weapons should be high on the global public health agenda Nuclear terrorism might take several forms. An attack on a nuclear power plant or other nuclear installation could result in a massive release of radioactive material. Despite initial statements by the US Nuclear Regulatory Commission that commercial power plants could withstand an aircraft crashing into them, it seems likely these plants are highly vulnerable. As early as 1982 a study by the Argonne National Laboratory of the US Department of Energy found that, if a jet aircraft crashed into a nuclear reactor and only 1% of its fuel ignited after … Correspondence to: Z A Bhutta
Lewis A. Conner Memorial Lecture. Choices that must not be made.
Authors: R D Remington
Journal: Circulation (1982)

Throughout our professional lifetimes, we are conditioned by the need to choose; among careers, among treatments for our patients, among health habits and lifestyles. After detailing the extent to which a choice-making orientation has dominated our lives, our society, our health system, our science, this paper describes areas in which it is crucial that choices not be made. These include the choice between basic and applied research, between targeted and investigator-initiated research, between prevention and treatment of cardiovascular disease, and between the need to know (research on mechanisms of disease) and the need to take action (intervention in the individual and the community to control disease). In each of these areas, a decision to emphasize either alternative at the expense of the other is undesirable and defeats the basic goals of understanding and controlling heart and vascular disease. In discussing these sets of alternatives, the three major cardiovascular risk factors are discussed: cigarette smoking, high blood pressure and diet. Examples are chosen from research investigations on risk, intervention, treatment, prevention and community control.
A new development of high fidelity canine DNA microarray: application for the assessment of gene expressions of reversibly or irreversibly injured ischemic myocardium
Authors: Masanori Asakura, Masafumi Kitakaze, Shoji Sanada, Hiroshi Asanuma, Seiji Takashima, Tetsuji Minamino, Koichi Node, Hisakazu Ogita, Yoshiro Asano, Yasunori Shintani, Liao Yulin, Masatsugu Hori
Journal: Journal of the American College of Cardiology (2002)
Expulsion of Placenta Before Birth of Child.
Authors: H. A. Haskell
Journal: JAMA (1905)

Chicago, July 4, 1905. <h3>To the Editor:</h3> —Relevant to the inquiry of Dr. Butt inThe Journal, July 1, page 60, I would say that I was called on June 15 by a midwife to a case in which the third stage of labor had preceded the second, the placenta having been delivered about half an hour before my arrival. The os was the size of a silver dollar, with a right sacro-anterior presentation of the fetus. The woman's pulse was 90, small. She was pale and weak, but her condition was not alarming. Hemorrhage had ceased. In about forty minutes she expelled, unassisted, an exsanguinated male fetus, apparently at term. The midwife was reticent as to the history of the case and her connection with it, but I gathered from the husband, who could speak little or no English, that there had been hemorrhages for some weeks prior to
Rapid Access of Antibodies to α5β1 Integrin Overexpressed on the Luminal Surface of Tumor Blood Vessels
Authors: Anette Magnussen, Ian M. Kasman, Scott Norberg, Peter Baluk, Richard Murray, Donald M. McDonald
Journal: Cancer Research (2005)

Abstract Integrin α5β1 is overexpressed on endothelial cells of tumor vessels and is uniformly and rapidly accessible to antibodies in the bloodstream. Here, we determined whether antibodies rapidly gain access to integrin overexpressed on the abluminal (basolateral) surface of endothelial cells through vascular leakiness or whether the rapid accessibility results instead because the integrin is overexpressed on the luminal (apical) surface of endothelial cells due to loss of cell polarity. Using tumors in RIP-Tag2 transgenic mice as a model, we first compared the binding pattern of intravascular anti-α5β1 integrin antibody with the leakage pattern of nonspecific IgG. The distributions did not match: anti-α5β1 integrin antibody uniformly labeled the tumor vasculature, but IgG was located in patchy sites of leakage. We next injected an antibody to fibrinogen/fibrin, which resulted in patchy labeling of tumors that matched the leakage of IgG and the overall distribution of fibrin in tumors. Similarly, injected antibodies to the basement membrane protein fibronectin, a ligand of α5β1 integrin, or type IV collagen produced patchy sites of leakage instead of uniform labeling of vascular basement membrane. Differences in the kinetics of labeling, which for α5β1 integrin antibody was near maximal by 10 minutes but for the other antibodies gradually increased over 6 hours, indicated differences in accessibility of their respective targets. Isosurface rendering of confocal microscopic images was consistent with antibody binding to α5β1 integrin on the luminal surface of endothelial cells. Together, these findings indicate that the rapid accessibility of α5β1 integrin in RIP-Tag2 tumors results from overexpression of the integrin on the luminal surface of tumor vessels.
Treatment of acute myocardial infarction with anisoylated plasminogen streptokinase activator complex.
Authors: S Ikram, S Lewis, C Bucknall, I Sram, N Thomas, R Vincent, D Chamberlain
Journal: BMJ (1986)

A controlled trial in 149 patients admitted to a district hospital with probable myocardial infarction tested the effect of 30 units of anisoylated plasminogen streptokinase activator complex (APSAC) on indices of infarct size. Patients were grouped prospectively according to whether they entered the trial within two and a half hours (early entry) or between two and a half and four hours (late entry) after onset of the symptoms. Sixty seven of 73 patients in the control group showed increased plasma activity of myocardial creatine kinase isoenzyme that was diagnostic of infarction compared with only 60 of 76 who received APSAC. The difference was significant overall but occurred predominantly in the early entry group. The patients who received APSAC had more early ventricular arrhythmias, compatible with reperfusion, and showed greater preservation of R waves during admission to hospital. Unwanted effects were generally minor and more common in the actively managed group than the control group (26% v 3%). After nine to 12 months of follow up 12 patients in the control group had died compared with seven in the actively managed group. The ease of administration and the apparent efficacy of APSAC suggest that it is suitable for use in a district hospital for patients with suspected acute myocardial infarction.
Positive Spiking: A Double-Blind Control Study on Its Significance in Behavior Disorders, Both Diagnostically and Therapeutically
Authors: CORNELIUS BOELHOUWER, CHARLES E. HENRY, BERNARD C. GLUECK
Journal: American Journal of Psychiatry (1968)

To examine the diagnostic and therapeutic significance of the EEG pattern called 14 and 6 per second positive spiking, when it occurs in patients with behavior disorders, the authors studied 78 adolescent and young adult inpatients. Although they did find some support for their hypothesis that positive spiking might be regarded as a neurophysiological handicap which varies as a function of the patient's environment, they conclude that further investigation is warranted.
Effect of Nonpayment for Hospital-Acquired, Catheter-Associated Urinary Tract Infection
Authors: Jennifer A. Meddings, Heidi Reichert, Mary A.M. Rogers, Sanjay Saint, Joe Stephansky, Laurence F. McMahon
Journal: Annals of Internal Medicine (2012)

Background: Most (59% to 86%) hospital-acquired urinary tract infections (UTIs) are catheter-associated urinary tract infections (CAUTIs). As of 2008, claims data are used to deny payment for certain hospital-acquired conditions, including CAUTIs, and publicly report hospital performance. Objective: To examine rates of UTIs in adults that are coded in claims data as hospital-acquired and catheter-associated events and evaluate how often nonpayment for CAUTI lowers hospital payment. Design: Before-and-after study of all-payer cross-sectional claims data. Setting: 96 nonfederal acute care Michigan hospitals. Patients: Nonobstetric adults discharged in 2007 (n = 767 531) and 2009 (n = 781 343). Measurements: Hospital rates of UTIs (categorized as catheter-associated or hospital-acquired) and frequency of reduced payment for hospital-acquired CAUTIs. Results: Hospitals frequently requested payment for non-CAUTIs as secondary diagnoses: 10.0% (95% CI, 9.5% to 10.5%) of discharges in 2007 and 10.3% (CI, 9.8% to 10.9%) in 2009. Hospital rates of CAUTI were very low: 0.09% (CI, 0.06% to 0.12%) in 2007 and 0.14% (CI, 0.11% to 0.17%) in 2009. In 2009, 2.6% (CI, 1.6% to 3.6%) of hospital-acquired UTIs were described as CAUTIs. Nonpayment for hospital-acquired CAUTIs reduced payment for 25 of 781 343 (0.003%) hospitalizations in 2009. Limitations: Data are from only 1 state and involved only 1 year before and after nonpayment for complications. Hospital prevention practices were not examined. Conclusion: Catheter-associated UTI rates determined by claims data seem to be inaccurate and are much lower than expected from epidemiologic surveillance data. The financial impact of current nonpayment policy for hospital-acquired CAUTI is low. Claims data are currently not valid data sets for comparing hospital-acquired CAUTI rates for the purpose of public reporting or imposing financial incentives or penalties. Primary Funding Source: Blue Cross Blue Shield of Michigan Foundation.
Pancreatic Cancer Clinical Trials and Accrual in the United States
Authors: William A. Hoos, Porsha M. James, Lola Rahib, Anitra W. Talley, Julie M. Fleshman, Lynn M. Matrisian
Journal: Journal of Clinical Oncology (2013)

Pancreatic cancer clinical trials open in the United States and their accrual were examined to identify opportunities to accelerate progress in the treatment of pancreatic cancer.Pancreatic cancer-specific clinical trials open in the United States in the years 2011 and 2012 were obtained from the Pancreatic Cancer Action Network database. Accrual information was obtained from trial sponsors.The portfolio of pancreatic cancer clinical trials identified by type (adenocarcinoma or neuroendocrine), phase, disease stage, and treatment approach is reported. More than half of trials for patients with pancreatic ductal adenocarcinoma applied biologic insights to new therapeutic approaches, and 38% focused on optimization of radiation or chemotherapy delivery or regimens. In 2011, pancreatic cancer trials required total enrollment of 11,786 patients. Actual accrual to 93.2% of trials was 1,804 patients, an estimated 4.57% of the patients with pancreatic cancer alive in that year. The greatest need was for patients with resectable cancer. Trials open in 2011 enrolled an average of 15% of their total target accrual. Physician recommendations greatly influenced patients' decision to enroll or not enroll onto a clinical trial. Matching to a clinical trial within a 50-mile radius and identifying trials for recurrent/refractory disease were documented as challenges for patient accrual.Overall trial enrollment indicates that pancreatic cancer trials open in 2011 would require 6.7 years on average to complete accrual. These results suggest that harmonizing patient supply and demand for clinical trials is required to accelerate progress toward improving survival in pancreatic cancer.
GLICEMIC VARIABILITY EVALUATED BY CONTINUOUS GLUCOSE MONITORING SYSTEM I-PRO&amp;trade; AND RENAL FUNCTION DETERIORATION AFTER PERCUTANEOUS CORONARY INTERVENTION: PRELIMINARY RESULTS OF A PROSPECTIVE STUDY
Authors: Claudio Proscia, Annunziata Nusca, Rosetta Melfi, Giuseppe Patti, Andrea D&apos;Ambrosio, Germano Di Sciascio
Journal: Journal of the American College of Cardiology (2012)