tbuckley/cabot-search huggingface dataset:
Vascular Endothelial Growth Factor/Vascular Permeability Factor Augments Nitric Oxide Release From Quiescent Rabbit and Human Vascular Endothelium
Authors: Rien van der Zee, Toyoaki Murohara, Zhengyu Luo, Frank Zollmann, Jonathan Passeri, Carsten Lekutat, Jeffrey M. Isner
Journal: Circulation (1997)

Background Vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF) is an endothelial cell (EC) mitogen. This feature is considered central to the documented role of VEGF/VPF in promoting angiogenesis. More recent evidence suggests that VEGF/VPF may also serve a “maintenance” function, modulating various aspects of EC biology. In the present study, we sought to determine the extent to which VEGF/VPF may stimulate the release of NO from normal ECs. Methods and Results VEGF/VPF produced a dose-dependent rise in NO concentration ([NO]) from vascular segments of rabbit thoracic aorta, pulmonary artery, and inferior vena cava. In comparison to stimulation with acetylcholine, the onset of increased [NO] after administration of VEGF/VPF was slower, reaching a maximum value after 8 minutes. Preincubation of the aortic segments with l -arginine raised by twofold both baseline [NO] and [NO] stimulated by addition of 2.5 μg/mL VEGF/VPF. Removal of CaCl 2 from the Krebs solution, disruption of the endothelium, and administration of N G -monomethyl- l -arginine abrogated the stimulatory effect of 10 μg/mL VEGF/VPF. Similar findings were documented with an NO-specific polarographic electrode to measure NO released from cultured human umbilical vein ECs. Conclusions VEGF/VPF stimulates production of NO from rabbit and human ECs. This finding (1) constitutes inferential evidence for the presence of functional VEGF/VPF receptors on quiescent endothelium of the adult rabbit as well as human ECs and (2) supports the notion that putative maintenance functions of VEGF/VPF may include regulation of baseline synthesis and/or release of EC NO.
Treatment of Snakebite
Authors: Arthur N. Ward
Journal: JAMA (1976)

<h3>To the Editor.—</h3> The communication by Dr Glass ("Early Debridement in Pit Viper Bites") contains a number of statements to which I take vigorous exception, his vast surgical experience notwithstanding. First of all he states that, on envenomation, ischemia develops; he then goes on to recommend not only proximal but distal tourniquets, despite apparently believing that there is little lymphatic absorption of venin. I have always felt that tourniquets were placed<i>solely</i>to retard lymphatic spread of venin, especially its lysolecithin fraction, which is extremely destructive of tissue and is also a potent kinin releaser. If, as he states, he believes venin is not significantly transported by lymphatics then he is apparently recommending tourniquets to obstruct venous absorption of venins: this would require a very tight tourniquet in an admittedly ischemic extremity and would therefore substantially increase the chance of ischemic tissue loss. He then goes on, without saying why,
Haploinsufficiency of the IKZF1 (IKAROS) tumor suppressor gene cooperates with BCR-ABL in a transgenic model of acute lymphoblastic leukemia
Authors: C Virely, S Moulin, C Cobaleda, C Lasgi, A Alberdi, J Soulier, F Sigaux, S Chan, P Kastner, J Ghysdael
Journal: Leukemia (2010)
Cholera outbreak in Darfur is made worse by advent of rains
Authors: Peter Moszynski
Journal: BMJ (2006)

The spread of cholera to Sudan's Darfur region has caused international alarm, especially as it has arrived just at the start of the rainy season. Large areas are already cut off because of factional fighting, and the onset of the rains not only means that health workers can't reach many people but also heightens the risks of transmission.

The World Health Organization says that 96 cases of acute watery diarrhoea and four deaths had been identified in the state of South Darfur by 14 June. A sample from one person who died, sent to Khartoum for …
Ethanol causes epicardial coronary artery vasoconstriction in the intact dog.
Authors: S N Hayes, A A Bove
Journal: Circulation (1988)

Ethanol produces in vitro vasoconstriction of coronary arteries and can precipitate angina in patients with coronary obstructive disease. To demonstrate the in vivo effect of ethanol on coronary dynamics, baseline measurements of left anterior descending (LAD) coronary artery dimension by quantitative angiography, hemodynamics, arterial and coronary sinus blood gases, and blood ethanol levels were obtained in 14 closed-chest mongrel dogs. Three ethanol levels were established by intravenous bolus followed by 1-hour maintenance infusions. All measurements made at baseline were recorded every 30 minutes. Phentolamine (5 mg i.v.) and nicardipine (0.15 mg/kg i.v.) were given to evaluate constrictor mechanisms. Blood ethanol levels achieved at 60, 120, and 180 minutes were 649 +/- 48, 1,285 +/- 81, and 2,546 +/- 130 micrograms/ml, respectively. LAD cross-sectional area was reduced significantly from control at the end of each of the three dosing periods (-24 +/- 5%, -40 +/- 3%, and -53 +/- 3%; p less than 0.004). alpha-Adrenergic blockade had no effect on LAD cross-sectional area, while nicardipine partially reversed the ethanol-induced vasoconstriction. No significant change in vessel cross-sectional area took place in control dogs. These data suggest that ethanol induces epicardial coronary artery vasoconstriction in dogs at clinically important blood levels. alpha-Adrenergic blockade does not alter or reverse ethanol-induced vasoconstriction, while calcium channel blockade appears to be an effective vasodilator of ethanol-constricted vessels.
Opening up the merit award system
Authors: P. Steadman
Journal: BMJ (1993)

between patient and doctor, facilitating diagnosis and management, but in hospital it is neglected.In Bath we are setting up video facilities in outpatient clinics to assess, analyse, and, hopefully, improve our techniques.Two weeks' introduction covering all aspects of practice work is not considered unusual for a trainee in general practice.Neither was the protected three hours a week of tutorials, lunchtime lectures, and a day release course and the encouragement to attend outside courses.There was a half day off a week.Learning was centred on the trainee and not arbitrary, responding to the needs of the student.This sort of arrangement, which is structured but in which the student is not spoon fed, puts many hospital specialties to shame; The Royal College of General Practitioners is beginning to put pressure on those hospital posts incorporated into vocational training schemes to offer similar educa- tional programmes.Hopefully, this will filter through to the less privileged members of other institutions.All too often in hospital the reality is of a world that struggles to find adequate time for study, where there is little structured training and no half days to relieve the pressure.Morale is low among juniors; I wonder why.Just as general practitioners spend a proportion of their time training in hospitals so hospital practice can learn from primary care.I join with Cubitt in recommending that all hospital practitioners, trained or in training, should try to spend some time in general practice.
Long-term Survival with Six Inches of Small Intestine
Authors: C. M. Anderson
Journal: BMJ (1965)

In March 1957 the patient, a girl aged 141 years, had a severe attack of abdominal pain associated with vomiting.She had suffered from mild attacks of a similar nature since the age of 10, but otherwise had been well and had grown normally.The pain and vomiting continued for some days and she became very ill, being admitted to hospital in a state of dehydration and circulatory failure.General peritonitis was diagnosed and after resuscitation an emer- gency laparotomy was performed.Volvulus of the small intestine had occurred and the whole of the bowel concerned in the volvulus was gangrenous.All but 3 in.(7.5 cm.) of the jejunum beyond the duodeno-jejunal flexture, and 3 in.(7.5 cm.) of ileum proximal on 19 July
Abstract 342: Silencing of IGF1R induces mesenchymal-to-epithelial transition and inhibits the metastatic properties of triple negative breast cancer cells
Authors: LaTonia D. Taliaferro-Smith, Elaine M. Oberlick, Tongriu Liu, Amy Adams, Carrie Eggers, Erik Kline, Ganji P. Nagaraju, Cynthia Cohen, Adam Marcus, Ruth O'Regan
Journal: Cancer Research (2012)

Abstract Next to skin cancer, breast cancer is the second most common cancer diagnosed among American women and affects nearly 1.3 million women worldwide each year. Aggressive, metastatic disease is directly responsible for the majority of breast cancer-related deaths. Breast tumors lacking expression of three receptors, estrogen receptor (ER), progesterone receptor (PR), and HER2, are commonly referred to as triple negative breast cancers (TNBCs) and make up 15-20% of all diagnosed breast cancers cases. Disparities exist in terms of survival following diagnosis of TNBC, and a devastating reality is that this diagnosis is highly correlated with incurable, metastatic disease. Despite tremendous advantages in treatments for hormone-sensitive breast tumors, a significant number of women with TNBC experience disease progression due to the unavailability of targeted therapies. Insulin-like growth factor-1 receptor (IGF1R) plays a role in breast cancer proliferation, adhesion, invasion, and migration. Overexpression of IGF1R has been noted in 50% of primary breast tumors and in nearly 65% of TNBCs. Consequently, high IGF1R expression in breast cancers correlates well with, high tumor grade, shorter disease-free survival, and poor prognosis. We report the in vitro effects of IGF1R inhibition on the metastatic properties of mesenchymal TNBC cells lines using two methods: (1) shRNA lentiviral system and (2) picropodophyllin (PPP), an IGF1R tyrosine kinase inhibitor. Stably transfected mesenchymal TNBC cells showed down-regulation of IGF1R protein levels, which resulted in mesenchymal-epithelial-transition (MET), as confirmed by up-regulation of epithelial marker, E-cadherin, and down-regulation of mesenchymal marker, vimentin. Importantly, this MET was accompanied by reduced colony formation, cell motility, and invasion. Cell survival assays and fluorescence-activated cell sorting (FACS) analysis revealed that PPP also effectively decreased cell viability and induced cell death, respectively, in TNBC cells. Furthermore, PPP dramatically inhibited cell invasion and migration. Our findings indicate that inhibitors of IGF1R exhibit promising anti-cancer activity in TNBC cells of mesenchymal origin by triggering MET, inducing cell death, and reducing invasive and metastatic properties. Given the very poor outcomes for patients with metastatic TNBCs, we believe the use of IGF1R inhibitors warrant further investigation as prospective anti-cancer options for treating a subset of mesenchymal TN breast carcinomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 342. doi:1538-7445.AM2012-342
In-Water Resuscitation
Authors: James L. Ghaphery
Journal: JAMA (1981)

To the Editor.—  March and Matthews should be congratulated on their efforts to improve in-water resuscitation, as evidenced by their article published in Undersea Biomedical Research (1980;7:141-148) and a similar article published inThe Journal(1980;244-1229-1232).  There are, however, several areas in the technique that are bothersome. The victim, as depicted, is not wearing any scuba gear, and I would think it difficult to compress the victim's chest effectively while he is wearing a scuba tank and an inflated buoyancy compensator. If the victim's equipment is to be removed as part of the procedure, the rescuer may find himself below the surface of the water while towing the victim and in need of his own regulator.  Second, the peak inspiratory pressure of the regulator is 40 mm Hg. I am aware that the Standards and Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiac Care (1974;227[suppl]:833-868) and the more recent guidelines (1980;
Mutations in SWI/SNF chromatin remodeling complex gene ARID1B cause Coffin-Siris syndrome
Authors: Gijs W E Santen, Emmelien Aten, Yu Sun, Rowida Almomani, Christian Gilissen, Maartje Nielsen, Sarina G Kant, Irina N Snoeck, Els A J Peeters, Yvonne Hilhorst-Hofstee, Marja W Wessels, Nicolette S den Hollander, Claudia A L Ruivenkamp, Gert-Jan B van Ommen, Martijn H Breuning, Johan T den Dunnen, Arie van Haeringen, Marjolein Kriek
Journal: Nature Genetics (2012)
87 New sterol regulatory element dependent pathway for activation of endothelial caveolin-1 gene transcription by lipoprotein depletion: Implications for caveolin-1 upregulation in cirrhosis and portal hypertension
Authors: S CAO, D JIN, V SHAH
Journal: Hepatology (2003)

Familial hypercholesterolemia (FH), Niemann–Pick disease type C (NPC) and Tangier disease (TD) are genetic inherited disorders with impaired processing of cholesterol, caused by mutations in genes that regulate cellular uptake, intracellular movement and transport of cholesterol. Various studies have shown a crucial regulatory role of the SREBP-pathway for cellular cholesterol homeostasis in these diseases. Since cholesterol is an essential structural component of cells, we assessed the impact of a severe FH causing LDLR mutation (FH p.W556R) on the SREBP pathway in primary FH fibroblasts. Primary FH fibroblasts derived from patients with the LDL receptor mutation p.W556R were used for gene expression experiments. Gene expression studies revealed increased expressions of SREBP regulated genes HMGCR, LDLR, SREBP-2, SREBP-1, SR-BI, INSIG-1, but interestingly not SCAP. In contrast expression of ABCA1, was strongly decreased in homozygous, but not in heterozygous p.W556R fibroblasts. Gene expression experiments with LDL receptor lacking primary FH fibroblasts, revealed that SR-BI and ABCA1 are important regulators for cholesterol acquisition in FH cells, consistent with findings in cells from NPC and TD patients.
Salutary effects of intravenous ajmaline in patients with paroxysmal supraventricular tachycardia mediated by dual atrioventricular nodal pathways: blockade of the retrograde fast pathway.
Authors: K K Sethi, S Jaishankar, M P Gupta
Journal: Circulation (1984)

Electrophysiologic effects of 50 mg iv ajmaline were evaluated in 10 patients with atrioventricular nodal reentrant paroxysmal supraventricular tachycardia (PSVT) utilizing the slow pathway for antegrade and the fast pathway for retrograde conduction. Ajmaline terminated the PSVT in all 10 patients in 17 to 165 sec (mean 94 +/- 49 sec): by ventriculoatrial block in eight, AH block in one, and intra-atrial reentry in one patient. The predrug mean PSVT cycle length of 289 +/- 44 msec (range 240 to 350) increased significantly to 373.5 +/- 60 msec (range 263 to 464; p less than .01) before the tachycardia was terminated. The increase in cycle length was a function of both AH and HA prolongation. In all 10 patients ajmaline depressed conduction through the retrograde fast pathway, as evidenced by the increase in mean ventricular paced cycle length producing ventriculoatrial block from less than or equal to 280 +/- 40 to 438 +/- 93 msec (p less than .001), and the increase in the effective refractory period of the ventriculoatrial conduction system from less than or equal to 241 +/- 42 to less than or equal to 298 +/- 62 msec (p less than .05); the drug abolished ventriculoatrial conduction in four cases. The effective refractory period of the antegrade fast pathway was unchanged after ajmaline (less than or equal to 281 +/- 31 vs less than or equal to 275 +/- 38 msec; p = NS), but conduction through the antegrade slow pathway was depressed (atrial paced cycle length producing AH block 269 +/- 30 msec before and 312 +/- 44 msec after drug; p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Radiofrequency Ablation of Atrial Fibrillation
Authors: Claudio Pratola, Elisa Baldo, Pasquale Notarstefano, Tiziano Toselli, Roberto Ferrari
Journal: Circulation (2007)

Background— Several approaches have been developed for radiofrequency catheter ablation of atrial fibrillation, but the correct intraprocedural end point is still under debate, and few data exist about the destiny of ablation lesions over time. The aim of the present study was to evaluate the long-term maintenance of intraprocedural end points of ablation procedures. Methods and Results— Inclusion criteria were (1) a previous ablation procedure of pulmonary vein (PV) encircling performed for drug-refractory persistent atrial fibrillation; (2) a “complete” intraprocedural end point, which consisted of voltage abatement inside the lesions, PV disconnection, and exit-block pacing from inside the lesions, attained in all PVs; and (3) stable sinus rhythm documented during a minimum follow-up of 2.5 years after the procedure. Twenty volunteers were selected (12 males, mean age 59±7 years) and underwent a repeat electrophysiological study. After a follow-up of 36.4±4.7 months, complete voltage abatement was maintained around 32 PVs (40.0%), PV disconnection persisted in 12 (37.5%) of the previously isolated PVs, and exit block was present in 39 PVs (48.7%). Ten patients who underwent a redo ablation procedure because of recurrences of atrial fibrillation were used as the control group. Differences in intraprocedural end-point maintenance between the 2 groups were not statistically significant. Conclusions— Common intraprocedural end points such as voltage abatement, PV disconnection, and exit block persist only in a limited number of patients, even when the outcome is favorable during follow-up. Further investigation will be required to determine whether such data will have implications for ablation strategies.
TCT-753 Impact of bivalirudin on peri-procedural events in patients undergoing rotational atherectomy: a subanalysis of the randomized ROTAXUS trial
Authors: Mohamed Abdel-Wahab, Ahmed Khattab, Heinz Joachim Büttner, Ralph Toelg, Volker Geist, Thomas Meinertz, Franz-Josef Neumann, Gert Richardt
Journal: Journal of the American College of Cardiology (2012)
Counselling and Therapy with Refugees
Authors: D. Summerfield
Journal: BMJ (1995)

Guus van der Veer, Wiley, pounds sterling14.95, pp 275, ISBN 0 471 95175 7

The past five years have seen striking increases in the number of refugees from organised violence seeking sanctuary in Western countries and a burgeoning medical and psychological literature to match. Many such books and papers discuss “trauma” and “torture” as if they were definitive and can be isolated, but this practical guide offers a more contextualised account. The main author is a psychotherapist at the Social Psychiatric Service for Refugees in Amsterdam. Half of his patients have been tortured, but he seeks to ground their …
1, 25-DIHYDROXYCHOLECALCIFEROL IN THE PATHOGENESIS OF THE HYPERCALCÆMIA OF SARCOIDOSIS
Authors: S.E Papapoulos, L.J Fraher, L.M Sandler, T.L Clemens, I.G Lewin, J.L.H O'Riordan
Journal: The Lancet (1979)
Fibroblast Growth Factor 1 Gene and Hypertension
Authors: Maciej Tomaszewski, Fadi J. Charchar, Mark D. Lynch, Sandosh Padmanabhan, William Y.S. Wang, William H. Miller, Wladyslaw Grzeszczak, Christine Maric, Ewa Zukowska-Szczechowska, Anna F. Dominiczak
Journal: Circulation (2007)

Background— The distal portion of the long arm of chromosome 5 is linked to hypertension and contains functional candidate blood pressure–regulating genes. Methods and Results— Tightening the grid of microsatellite markers under this quantitative trait locus in the Silesian Hypertension Study (629 individuals from 207 Polish hypertensive families) provided enhanced support for linkage of this region to blood pressure (maximal Z =3.51, P =0.0002). The fine mapping, comparative genomics, and functional prioritization identified fibroblast growth factor 1 gene (FGF1) as the positional candidate. Linkage disequilibrium mapping based on 51 single nucleotide polymorphisms spanning the locus showed no overlap between 3 independent haploblocks of FGF1 and the adjacent extragenic chromosomal regions. Single and multilocus family-based analysis revealed that genetic variation within FGF1 haploblock 1 was associated with hypertension and identified a common intronic single nucleotide polymorphism, rs152524, as the major driver of this association ( P =0.0026). Real-time quantitative polymerase chain reaction and Western blotting analysis of renal tissue obtained from subjects undergoing unilateral nephrectomy showed an increase in both mRNA and protein FGF1 expression in hypertensive patients compared with normotensive controls. Renal immunohistochemistry revealed that FGF1 was expressed exclusively within the glomerular endothelial and mesangial cells. Conclusions— Our data demonstrate that genetic variation within FGF1 cosegregates with elevated blood pressure in hypertensive families and that this association is likely to be mediated by upregulation of renal FGF1 expression. The results of our study will need to be replicated in other cohorts.
Challenge in the Treatment of Estrogen-Receptor–Negative Ductal Carcinoma in Situ
Authors: Kadri Altundag
Journal: Journal of Clinical Oncology (2005)

of the Journal of Clinical Oncology, as well as the accompanying rebuttal by Wieand and Murphy. 1,2 Both articles raise valid points, but both neglect a relevant ethical question regarding equipoise and uncertainty: How does one justify the lack of information from an ongoing trial?Let us assume a randomized trial for regimen A compared with regimen B, and also assume it is agreed, on the basis of current knowledge, that neither can be considered superior.When any results become available from the trial, one of the regimens will more likely appear superior, at which point, ethical considerations arise regarding whether to advise patients and physicians of that information.For illustration, assume that analysis of the study reveals a borderline, but not quite statistically significant finding: that regimen A is more likely to cure than regimen B (P ϭ .06).If the study is to be halted when some arbitrary probability is reached-say P Ͻ .05-whatare the ethical responsibilities to patients randomly assigned to the inferior arm just before that limit is reached?The initial equipoise is severely compromised, and the degree of uncertainty is seriously reduced.In current practice, patients may be continued on study because treating physicians and patients are not made aware of ongoing study information, which is artificially unavailable by protocol rules that clearly favor obtaining a valid scientific result over full disclosure of information to study participants.If survival were the end point in the example above, how many patients would opt to be the last person to die to try to prove with P Ͻ .05rather than P Ͻ .06 that regimen B really is inferior?From a stringent ethical point of view, the difference between strict equipoise and any change in probable outcome (eg, that based on any information derived from the study) is one of degree rather than principle.Even minimal differences in probable outcomes may be important to patients. 3 Adaptive randomization schemes may improve, but do not eliminate ethical issues derived from withholding data.