tbuckley/cabot-search huggingface dataset:
Enalapril in patients with chronic heart failure: a placebo-controlled, randomized, double-blind study.
Authors: D N Sharpe, J Murphy, R Coxon, S F Hannan
Journal: Circulation (1984)

A number of studies have shown short-term hemodynamic and symptomatic improvement in patients with congestive heart failure treated with angiotensin converting-enzyme inhibitors. The long-term efficacy of the oral long-acting converting-enzyme inhibitor enalapril remains to be established in controlled studies. We evaluated this drug in 36 patients with New York Heart Association functional class II to III heart failure who were clinically stable on digoxin and diuretic therapy. After baseline assessment of symptoms, exercise capacity, and results of echocardiographic examination and right heart catheterization, patients were randomly assigned to treatment with 5 mg enalapril twice daily (n = 18) or placebo (n = 18) in a double-blind fashion. The two groups had similar clinical, echocardiographic, and hemodynamic characteristics before treatment. After 3 months of treatment, the enalapril group showed a significant improvement as judged by subjective patient impression, functional class, and exercise duration (9.3 +/- 5.7 vs 17.6 +/- 5.6 min; p less than .001). Diuretic dosage was reduced in six patients and increased in one patient, one patient had died and another had been withdrawn from the study. In the placebo group there was no significant change with respect to patient impression, functional class, or exercise duration; diuretic dosage was increased in seven patients and four patients had died. Echocardiographic left ventricular dimensions were significantly reduced and left ventricular shortening fraction significantly increased in the enalapril group but were unchanged in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)
Leukemia in Children
Authors: S. Spence Meighan
Journal: JAMA (1965)

<h3>To the Editor:—</h3> While I agree fully with Dr. Meighan (Leukemia in Children,<i>JAMA</i><b>190</b>:578 [Nov 16] 1964) that one needs to look with a critical eye at recent reports on survival rates of children with leukemia and that the assessment of the prognosis of children with leukemia requires study of unselected data, I am afraid that he has done little to clarify the situation. Indeed, in obtaining his data in what seems to be an extremely roundabout fashion, he may well have become a party to the system which he so heartily decries, namely the leaving out of patients. Anyone who has ever filled out death certificates, or tried to compile data from them, knows of the inaccuracies which they contain. Patients are often signed out as having had pneumonia or heart failure when their primary disease was something else. Secondly, it is entirely possible that there may
The $800 million pill: The truth behind the cost of new drugs
Authors: John P. Moore
Journal: Journal of Clinical Investigation (2004)

Does it really take the oft-quoted $800 million to make a new drug? Merrill Goozner would argue not — a more accurate figure might be about one-fifth that sum, although the range is considerable and all the estimates are dependent upon which particular economic theory one chooses to believe in. Whatever the reason, Goozner pillories the price of pills and places the blame squarely on the pharmaceutical industry, backing his case by presenting fascinating histories of the development of individual drugs by both Big Pharma and smaller biotechnology companies. Goozner’s central premise is that the industrial development of almost all drugs is heavily reliant on basic research funded by the taxpayer and conducted by scientists working for universities, nonprofit research centers, or the NIH. There’s no doubt that Goozner’s sympathies lie with the traditional academic. He views the pharmaceutical and biotechnological industries rather less favorably, particularly in their marketing practices. Overall, I enjoyed reading this book and was impressed by its thoroughness. Goozner writes well, has a command of his subject, and makes very few scientific errors. Hence it seems reasonable to assume that he also has his facts straight when covering the economic and political aspects of his subject — his specialties, but not mine.
Effects of density and of dehydration of sickle cells on their adhesion to cultured endothelial cells
Authors: P.C. W. Stone, J. Stuart, G. B. Nash
Journal: American Journal of Hematology (1996)

Abnormal adhesion of sickle cells to vascular endothelium may be a factor in the initiation of painful vaso-occlusive crisis. The sickle cell population contains an unusually large number of less dense reticulocytes that are known to be more adhesive than mature red cells, but there is contradictory evidence regarding the adhesiveness of dense sickle cells. We used a flow-based assay of adhesion to cultured human umbilical vein endothelial cells to test the properties of density fractions of sickle cells, prepared either by density gradient or by centrifugation of packed cells. We also examined the effects of incubating sickle cells with or without cyclical deoxygenation on their adhesion. After fractionation on a Percoll-Isopaque gradient, the less dense 10% (reticulocyte-rich) cells and the most dense 10% cells adhered in greater number than the remainder (by about twofold). However, after centrifugation of packed cells, the less dense 10% were again more adhesive than the “middle” cells, but the most dense were not. Exposing sickle cells to constituents of the gradient had no consistent effect on adhesion, while centrifugal packing induced a degree of hemolysis, and tended to reduce adhesiveness of the dense fraction previously obtained from a gradient. Incubation in air at 37°C for 15 hr reduced the number of reticulocytes and the adhesiveness of less dense sickle cells compared to those held at 4°C. On the other hand, incubation at 37°C for 15 hr with cyclical deoxygenation caused formation of dense cells and increased adhesiveness compared to incubation without cyclical deoxygenation. We conclude that young, less dense sickle cells are unusually adhesive, but that this adhesiveness is reduced during maturation. However, repeated sickling in vivo causes formation of an abnormally dense subpopulation of cells which either redevelop an increased tendency to adhere to endothelial cells or preserve their initial adhesiveness. Both adhesive cell populations may be implicated in promoting vascular obstruction. © 1996 Wiley-Liss, Inc.
Combination Insulin-Sulfonylurea Therapy
Authors: Harold E Lebovitz, RoseMarie Pasmantier
Journal: Diabetes Care (1990)

Combination sulfonylurea-insulin therapy for patients with diabetes mellitus has been evaluated by numerous investigators with various experimental designs. Much of the data are conflicting, and clear conclusions do not seem justified. Insulin-sulfonylurea therapy is probably not clinically useful in most patients with insulindependent diabetes mellitus. Most non-insulindependent diabetic (NIDOM) patients are also unlikely to have meaningful improvement in glycemic regulation on insulin-sulfonylurea therapy. A subset of NIDDM patients who are mildly to moderately obese, have adequate endogenous insulin secretory reserve, and are in poor glycemic regulation (fasting plasma glucose &amp;gt;11mM and/or HbA1 &amp;gt;10%), despite twice-daily insulin administration of &amp;gt;70 U/day, may show significant improvement of glycemic regulation and/or decreases in insulin daily dose on insulin-sulfonylurea therapy. The mechanisms by which insulin-sulfonylurea therapy improves glycemic regulation and decreases insulin requirements involve an increase in endogenous insulin secretion and possibly some extrapancreatic actions of the sulfonylureas on muscle and liver.
Homologous blood use and conservation techniques for cardiac surgery in the United Kingdom.
Authors: G. N. Russell, S. Peterson, S. J. Harper, M. A. Fox
Journal: BMJ (1988)

The transfusion laboratories of 32 cardiothoracic surgical centres for adults were surveyed to determine the donor blood requirement for open heart surgery in the United Kingdom. Details of the transfusion practice and the use of blood conservation techniques were sought from a representative senior cardiac anaesthetist at each centre. Suitable data were received from 24 transfusion laboratories (75%) and 29 anaesthetists (90%). The mean (SD) blood use was 5.07 (1.53) units per operation. Seven centres routinely transfused fresh frozen plasma to all patients postoperatively. Experience with autologous deposit (three centres), "cell separators" (four centres), and the reinfusion of shed mediastinal blood (four centres) was limited. Prebypass phlebotomy for postbypass reinfusion (14 centres) and the infusion of residual oxygenator blood (27 centres) were the conservation techniques most commonly applied. In only nine centres was a postoperative normovolaemic anaemia to a haemoglobin concentration of less than 100 g/l accepted. Applying blood conservation techniques more widely would help to maintain blood supplies and reduce morbidity and mortality related to transfusion.
Urinary VEGF and MMP Levels As Predictive Markers of 1-Year Progression-Free Survival in Cancer Patients Treated With Radiation Therapy: A Longitudinal Study of Protein Kinetics Throughout Tumor Progression and Therapy
Authors: Linda W. Chan, Marsha A. Moses, Elizabeth Goley, Mary Sproull, Thierry Muanza, C. Norman Coleman, William D. Figg, Paul S. Albert, Cynthia Ménard, Kevin Camphausen
Journal: Journal of Clinical Oncology (2004)

Purpose To determine the predictive value of urinary levels of two angiogenic factors, vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMPs), in a longitudinal study to determine their correlation with 1-year progression-free survival in patients with cancer. Patients and Methods VEGF and MMP levels were measured in the urine of 65 cancer patients at first evaluation, during therapy, and at follow-up (n = 242); normalized by creatinine levels; and compared with 16 healthy controls. The correlation of initial levels and trends of VEGF and MMPs with 1-year progression-free survival was assessed using two-sample tests and stepwise logistic regression. Results Urinary VEGF levels at presentation were different between patients with local-regional cancer and normal controls, and between patients with metastatic prostate cancer and local-regional disease (P = .04 and .01, respectively). Similar results were found with MMP measurement (P = .03 and .0001, respectively). Of those patients subsequently treated with radiation, VEGF levels at presentation between patients with no evidence of disease (NED) after radiation and those who had persistent or recurrent disease after radiotherapy were also different (P = .039). The comparison between angiogenic factor levels taken at least 1 month postradiotherapy and the last level taken during treatment was the strongest predictor of patient 1-year progression-free survival (P = .004). Similarly, the overall MMP trend was also significantly associated with 1-year progression-free survival, as was the individual MMP-2 trend (P = .004 and .001, respectively). Stepwise logistic regression revealed that the VEGF trend comparing postradiation levels with last level taken during treatment was an independent predictor of progression-free survival (P = .02). Conclusion This small exploratory study suggests that the angiogenic urinary trends of VEGF and MMPs may be useful predictive markers for progression-free survival in cancer patients after the completion of radiotherapy.
Prevention of Perinatal Morbidity by Tight Metabolic Control in Gestational Diabetes Mellitus
Authors: Heinz Drexel, Alfred Bichler, Sigurd Sailer, Christoph Breier, Hans-Jörg Lisch, Herbert Braunsteiner, Josef R Patsch
Journal: Diabetes Care (1988)

In a prospective controlled trial, we studied the effect of tight metabolic control on the outcomes of 102 gestational diabetes mellitus (GDM) pregnancies compared with outcomes of 102 matched nondiabetic control pregnancies. Women with GDM were treated to achieve and maintain a blood glucose concentration of &amp;lt;130 mg/dl at 1 h after breakfast. Treatment consisted of a diet low in oligosaccharides and fat and, if necessary, once daily insulin. By the end of gestation, 88 of the 102 women with GDM received insulin at a mean dose of 18 U/day. Duration of insulin therapy ranged from 3 to 32 wk with a median of 11 wk. Perinatal outcome of GDM pregnancies under this management equaled that of control pregnancies. The full spectrum of excess morbidity from GDM was prevented, and normal distribution of birth weight and normal rates of macrosomia, dystrophy, hypoglycemia, hypocalcemia, hyperbilirubinemia, fetal acidosis, and low Apgar scores were achieved. No mortality was observed. In addition to the two main study groups, we also studied a third group of 24 women with GDM whose treatment lasted ≤5 wk due to late diagnosis. This suboptimally treated group demonstrated a significant (P &amp;lt; .05) increase of macrosomia and umbilical artery acidosis compared with the well-treated GDM group. The study reported herein demonstrates that excess mortality and morbidity typically observed in GDM can be prevented by early institution of tight metabolic control, which required insulin in 86% of our patients.
Distal cap to facilitate removal of blood clots during endoscopic hemostasis for upper gastrointestinal bleeding
Authors: T. Moreels, M. Lotry, B. Roth, P. Pelckmans
Journal: Endoscopy (2009)

Endoscopic treatment is available for variceal and nonvariceal upper gastrointestinal (UGI) bleeding [1] [2]. Blood clots in the stomach hamper endoscopic treatment by obscuring the bleeding source. Aspiration of clots, however, results in obstruction of the working channel, while grasping clots with a basket or snare leads to cutting up of the clots [3]. We describe the usefulness of an attachable distal cap to remove blood clots from the stomach during endoscopic treatment of UGI bleeding.
Poliovirus Antibody Two Years After Oral Trivalent Vaccine (Sabin Strains)
Authors: Victor J. Cabasso, James M. Ruegsegger, Herald R. Cox
Journal: JAMA (1964)

IN A MASS poliomyelitis vaccination program in Hillsborough County, Florida, almost 200,000 persons were fed trivalent vaccine given in two doses eight weeks apart.<sup>1</sup>Among them were 142 children without antibody to any type of poliovirus before vaccination, whose antibody levels one year later were previously reported.<sup>2</sup>The antibody levels of 107 of these children exactly two years after their second dose of vaccine are reported here. <h3>Materials and Methods</h3><h3>Sample population.—</h3> The 142 children whose one-year antibody status was studied were not selected in any way except that they were those without antibody to any type of poliovirus before vaccination from whom serum specimens could be obtained about a year later. The 107 children reported here are those in the original sample group from whom serum specimens could be obtained the following year. The distributions of their ages and the vaccine lots they and the entire original
An Emerging Role for Endothelial Nitric Oxide Synthase in Chronic Inflammation and Cancer
Authors: Lei Ying, Lorne J. Hofseth
Journal: Cancer Research (2007)

Abstract Nitric oxide (NO) is a free radical that is involved in carcinogenesis. Recent literature indicates that endothelial NO synthase (eNOS) can modulate cancer-related events (angiogenesis, apoptosis, cell cycle, invasion, and metastasis). We review the literature linking eNOS to carcinogenesis to encourage future research assessing the role of eNOS in cancer prevention and treatment. [Cancer Res 2007;67(4):1407–10]
Agitation-increased electromyogram activity in the corrugator muscle region: a possible explanation of the "Omega sign"?
Authors: Greden Jf, Genero N, Price Hl
Journal: American Journal of Psychiatry (1985)

The corrugator muscle region of the forehead has special significance in producing facial expressions associated with depression. Darwin observed in 1872 that contractions in the corrugator region produce peculiarly formed wrinkles on the forehead, referred to as "Omega Melancholium." In the present study, results from 61 right-handed, drug-free women with major depressive disorder showed a significant positive correlation between facial corrugator EMG values and psychomotor agitation. Results were not due to differences in severity of depression. These data offer preliminary evidence that agitation is reflected in corrugator muscle activity and may explain the "Omega sign" of melancholia.
The Selfish Brain: Learning From Addiction
Authors: Edward J. Khantzian
Journal: JAMA (1997)

This is a remarkable book in its scope, conviction, and perspective. The author, Dr Robert L. Dupont, has been a prominent figure and voice for the prevention and treatment of substance use disorders for the past quarter of a century. He is not dispassionate about his subject matter. This is evident not only in the amount of material that he covers (from economic costs and epidemiology to cleardescriptions ofthe pertinent neurotransmitters and brain anatomy), but in his dogged persistence, convictions, and perspective about the nature of addictions and what people need to do to prevent and overcome them. DuPont is equally forceful on public policy, expressing strong and provocative ideas about what we should do as a people and a community to prevent and counter the ravages of addictive illness. Dr. Dupont and I both trained in psychiatry together at the same time (1964-1967) and place (Massachusetts Mental Health Center), and over the course of our respective careers we have both pur
Arsenic Trioxide: New Clinical Experience With an Old Medication in Hematologic Malignancies
Authors: Dan Douer, Martin S. Tallman
Journal: Journal of Clinical Oncology (2005)

Arsenic trioxide has shown great promise in the treatment of patients with relapsed or refractory acute promyelocytic leukemia (APL). In clinical trials, arsenic trioxide induces complete remission in 87% of patients and molecular remission in 83% of patients. Two-year overall and relapse-free survival estimates are 63% and 49%, respectively. Treatment with arsenic trioxide may be associated with the APL differentiation syndrome, leukocytosis, and electrocardiographic abnormalities. The expanded use of arsenic trioxide in APL for postremission therapy, in conjunction with transplantation, and in patients with newly diagnosed APL is under investigation. The multiple mechanisms of action of arsenic trioxide suggest that it may have antitumor activity in malignancies other than APL and that it may be used in combination with other agents to expand its potential use. This article reviews the clinical use of arsenic trioxide to date and discusses new therapeutic strategies evolving from its diverse biologic activities.
Abstract 4623: HDAC6 inhibition is a novel strategy to selectively impact inflammatory breast cancer cell survival
Authors: Preeti Putcha, Jiyang Yu, Andrea Califano, Jose Silva
Journal: Cancer Research (2014)

Abstract Inflammatory breast cancer (IBC) is a lethal and understudied variant of breast cancer, presenting with a signature clinical phenotype of rapidly metastasizing diffuse tumor emboli and rapid resistance to traditional chemotherapeutics. In an unbiased, highthroughput search for novel genes and therapeutics which specifically impact IBC cell survival, we performed a genome wide shRNA screen on two IBC cell lines and identified Histone Deacetylase 6 (HDAC6) as vital for IBC vs non-IBC breast cancer cell line survival. In IBC vs non-IBC breast cancer cell lines, individual knockdown of HDAC6 decreases cell viability and causes apoptosis via cleaved PARP expression and annexin V assays. Importantly, HDAC6 is a therapeutically viable candidate. The orally bioavailable next generation HDAC6-selective inhibitor, Rocilinostat, also preferentially impacts IBC vs non-IBC cell survival. We transitioned these findings in vivo by treating a well-established mouse xenograft model of IBC with Rocilinostat and found significant slowing of tumor growth rates. Taken together, these data represent a new and tailored treatment option for IBC. Note: This abstract was not presented at the meeting. Citation Format: Preeti Putcha, Jiyang Yu, Andrea Califano, Jose Silva. HDAC6 inhibition is a novel strategy to selectively impact inflammatory breast cancer cell survival. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4623. doi:10.1158/1538-7445.AM2014-4623
His Bundle Electrocardiography during Bidirectional Tachycardia
Authors: STEPHEN N. MORRIS, DOUGLAS P. ZIPES
Journal: Circulation (1973)

His bundle electrocardiography in a patient with a digitalis-induced bidirectional tachycardia revealed absence of His spike preceding earliest onset of ventricular activation during the bidirectional tachycardia. However, His potential preceded ventricular activation of normal complexes at a constant H-V interval of 35 msec. The presence of fusion QRS complexes, capture QRS complexes, the analysis of cycle lengths, and response to carotid sinus massage all favor a ventricular origin for this tachycardia in the patient presented.
Prospective screening of 205 patients with ITP, including diagnosis, serological markers, and the relationship between platelet counts, endogenous thrombopoietin, and circulating antithrombopoietin antibodies
Authors: Louis M. Aledort, Catherine P.M. Hayward, Mon‐Gy Chen, Janet L. Nichol, James Bussel
Journal: American Journal of Hematology (2004)

Abstract Immune thrombocytopenia purpura (ITP) is characterized by destruction of circulating platelets and the presence of antiplatelet antibodies. Many of the current immunomodulatory therapies act by reducing platelet destruction and usually do not have a lasting effect. This prospective, exploratory study characterized patients with ITP by identifying their demographic and comorbid clinical factors, use of treatments, serologic markers of autoimmunity, and possible relationships between platelet counts, concentrations of endogenous thrombopoietin (eTPO), and the presence of circulating anti‐TPO antibodies. Data including medical history and laboratory evaluations were collected at a single patient visit on 205 patients (19 children, 186 adults). Reported histories revealed a 5% rate of thrombotic/ischemic events. Autoimmune markers including direct antiglobulin test and antinuclear antibodies were found more frequently than in the normal population; antiplatelet antibody testing was not done. eTPO concentrations were comparable to concentrations found in healthy volunteers. Our study confirmed that no significant inverse correlation occurred between circulating concentrations of eTPO and platelet counts in patients with ITP (Spearman r = −0.15). Two of the 205 patients tested (1%) had neutralizing activity of recombinant human TPO in a biological assay; however, this activity was confirmed to be anti‐TPO antibody in only 1 patient. Am. J. Hematol. 76:205–213, 2004. © 2004 Wiley‐Liss, Inc.
Am I safe to fly? Am I safe to anaesthetise?
Authors: G R Park
Journal: BMJ (2005)

On a recent trip I arrived at to Mexico City airport for an overnight flight back to London at 9 40 pm to find the flight postponed to 6 am the next day. The reason was that the flight crew's hotel had caught fire and the crew had had to go to hospital, disrupting their rest pattern, and so they needed to sleep. Like the other 351 passengers I was disappointed. Just before this trip I had worked several days and nights on call for a busy intensive care unit, and I was looking forward to recovering after my trip and then having a normal Sunday at home before my week back at work as an intensive care doctor and anaesthetist began. I realised that if the crew members were tired and made a mistake I might never get home again, so I accepted the hotel voucher, had dinner, and went to my room.

During the flight the captain took time to speak with me and we were able to discuss the …