tbuckley/cabot-search huggingface dataset:
In Vivo Evidence for Nitric Oxide–Mediated Calcium-Activated Potassium-Channel Activation During Human Endotoxemia
Authors: Peter Pickkers, Mirrin J. Dorresteijn, Martijn P.W.J.M. Bouw;, Johannes G. van der Hoeven, Paul Smits
Journal: Circulation (2006)

During septic shock, the vasoconstrictor response to norepinephrine is seriously blunted. Animal experiments suggest that hyperpolarization of smooth muscle cells by opening of potassium (K) channels underlies this phenomenon. In the present study, we examined whether K-channel blockers and/or nitric oxide (NO) synthase inhibition could restore norepinephrine sensitivity during experimental human endotoxemia.Volunteers received 2 ng/kg Escherichia coli endotoxin intravenously. Forearm blood flow (FBF) was measured with venous occlusion plethysmography. Infusion of 4 dose steps of norepinephrine into the brachial artery decreased the FBF ratio (ratio of FBF in the experimental arm to FBF in the control arm) to 84 +/- 4%, 70 +/- 4%, 55 +/- 4%, and 38 +/- 4% (mean +/- SEM) of its baseline value. After endotoxin administration, norepinephrine-induced vasoconstriction was attenuated (FBF ratio, 101 +/- 4%, 92 +/- 4%, 83 +/- 6%, and 56 +/- 7%; n = 30; P = 0.0018; pooled data). Intrabrachial infusion of the K-channel blocker tetraethylammonium (TEA) completely restored the vasoconstrictor response to norepinephrine from 104 +/- 5%, 93 +/- 7%, 93 +/- 12%, and 69 +/- 12% to 89 +/- 9%, 73 +/- 4%, 59 +/- 5%, and 46 +/- 8% (n = 6; P = 0.045). Other K-channel blockers did not affect the response to norepinephrine. The NO synthase inhibitor N(G)-monomethyl-l-arginine (L-NMMA; 0.2 mg x min(-1) x dL(-1) intra-arterially) also restored the norepinephrine sensitivity. In the presence of L-NMMA, TEA did not have an additional effect on the norepinephrine-induced vasoconstriction (n = 6; P = 0.9).The K-channel blocker TEA restores the attenuated vasoconstrictor response to norepinephrine during experimental human endotoxemia. Coadministration of L-NMMA abolishes this potentiating effect of TEA, suggesting that NO mediates the endotoxin-induced effect on vascular K channels. In the absence of an effect of the selective adenosine triphosphate-dependent K-channel blocker tolbutamide, we conclude that the blunting effect of endotoxin on norepinephrine-induced vasoconstriction is caused by NO-mediated activation of calcium-activated K channels in the vascular wall.
Congenital Hypoplastic Thrombocytopenia
Authors: A. D. Bell, S. Shaw, R. A. M. Oliver
Journal: BMJ (1958)

<h3>Objectives</h3> To determine the agreement of fingertip and sternum capillary refill time (CRT) in children. <h3>Design</h3> Prospective, method-comparison study. <h3>Setting</h3> Single children9s emergency department, UK <h3>Participants</h3> 92 children aged 0–12 years, with clinical observations within normal ranges for their age, no relevant medical history and presenting to hospital with a minor illness or injury. <h3>Main outcome measures</h3> Agreement between fingertip and sternum CRT measurements. <h3>Results</h3> Fingertip CRT ranged from 0.05 to 2.78 s with a mean of 1.08±0.44 and sternum CRT ranged from 0.85 to 2.38 s with a mean of 1.5±0.33. There was a significant difference between fingertip and sternum CRT (t=−9.2, df=91, p=&lt;0.001) and a weak association between the two measurements (r=0.18, p=0.9). A Bland Altman comparison showed the mean difference between fingertip and sternum CRT was −0.49±0.51 with an upper and lower limit of agreement ranging from −1.5 (95% CI −1.69 to −1.32) to 0.53 (95% CI 0.34 to 0.71). <h3>Conclusions</h3> Measurements of CRT taken at the fingertip and sternum are not comparable. Fingertip CRT was faster than sternum CRT. Normal CRT is 2–3 s. The current study questions the usefulness of CRT in the assessment of circulation in children.
Neonatal Complications after the Administration of Indomethacin for Preterm Labor
Authors: Mary E. Norton, Jeffrey Merrill, Bruce Cooper, Jeffrey A. Kuller, Ronald I. Clyman
Journal: New England Journal of Medicine (1993)

The use of indomethacin as a tocolytic agent in pregnant women appears to be accompanied by a low incidence of neonatal complications. However, the neonatal effects of indomethacin have been studied primarily in infants born after 32 weeks' gestation. This study was designed to examine the incidence of neonatal complications in very premature infants.We identified 57 infants delivered at or before 30 weeks' gestation whose mothers had been treated with indomethacin for preterm labor and matched them with 57 infants whose mothers had not received indomethacin. The infants in the two groups were matched for sex, gestational age at delivery (mean [+/- SD], 27.6 +/- 2.0 weeks), exposure to betamethasone for 24 hours or more before delivery, and rupture of membranes 24 hours or more before delivery.There were no significant differences between the two groups in birth weight, Apgar scores, cord-blood gas values, frequency of multiple gestation, or incidence of respiratory distress syndrome. The proportion of infants who required exogenous surfactant was similar, as were ventilator settings at 24 hours, the incidence of chronic lung disease, and the incidence of sepsis. The infants exposed to indomethacin had a lower urine output and higher serum creatinine concentrations during the first three days after delivery. More indomethacin-exposed infants had necrotizing enterocolitis (29 percent vs. 8 percent, P = 0.005), intracranial hemorrhage grade II to IV (28 percent vs. 9 percent, P = 0.02), and patent ductus arteriosus (62 percent, vs. 44 percent, P = 0.05). More indomethacin-exposed infants with a patent ductus arteriosus required surgical ligation because of either a lack of initial response or a reopening of the duct after postnatal indomethacin therapy (50 percent vs. 20 percent of the unexposed infants, P = 0.05).Antenatal indomethacin therapy for preterm labor appears to increase the risk of serious neonatal complications in infants born at or before 30 weeks' gestation.
Insulin Modulation of β-Adrenergic Vasodilator Pathway in Human Forearm
Authors: Giuseppe Lembo, Guido Iaccarino, Carmine Vecchione, Virgilio Rendina, Lucia Parrella, Bruno Trimarco
Journal: Circulation (1996)

Insulin modulates sympathetic vasoconstriction, but the mechanisms underlying this effect are not completely elucidated. We have recently investigated the insulin effect on the alpha 1- and alpha 2-adrenergic vasoconstriction pathway, where it is still conflicting with the possible insulin influence on the beta-adrenergic vasodilator pathway. The aim of the present study was to investigate this issue.The study was performed on the forearm of healthy humans, and all test substances were infused into the brachial artery at systemically ineffective rates. In five subjects, we evaluated isoproterenol-induced vasodilation (1, 3, 6, and 9 ng. kg-1. min-1) both under control conditions and during insulin infusion (0.05 mU. kg-1. min-1). In another group of five subjects, we tested whether the vasorelaxant effect of sodium nitroprusside (1, 2, 4, and 8 ng . kg-1 . min-1) was modified by insulin. Moreover, to explore whether the interaction between insulin and forearm beta-adrenergic pathway participates in insulin modulation of sympathetic-evoked vasoconstriction, we measured in six normal subjects the forearm vascular response to lower-body negative pressure under control conditions and during intrabrachial infusion of insulin alone and in combination with a selective beta-adrenergic blocking agent (propranolol 10 micrograms/100 mL per minute). Finally, to verify whether insulin interaction with the beta-adrenergic pathway may also account for insulin modulation of alpha 2-adrenergic vasoconstriction, we assessed the vascular response to a selective alpha 2-adrenergic agonist before and after propranolol administration. Insulin exposure potentiated the vascular responsiveness to isoproterenol but did not affect the vasodilator response to sodium nitroprusside. Furthermore, the insulin-induced attenuation of sympathetic vasoconstriction was partially corrected by propranolol. In contrast, the insulin modulation of alpha 2-adrenergic vasoconstriction was not influenced by beta-adrenergic blockade.Taken together, our results suggest that insulin modulation of sympathetic-induced vasoconstriction is carried out through an interaction of the hormone with the pathways of both alpha 2-and beta -adrenergic receptors.
Problems of Chronic Pyelonephritis
Authors: M. L. Rosenheim
Journal: BMJ (1963)

The small contracted kidney of chronic pyelonephritis remains one of the enigmas of medicine.Ever since it was fully reviewed in the classical paper by Soma Weiss and Parker in 1939, chronic pyelonephritis has become an increasingly popular diagnosis.As a patho- logical process its progress is often slow and insidious, and, while it frequently presents clinically as a recurrent or refractory urinary infection, patients are often first seen because of hypertension or proteinuria, or because
<i>Helicobacter pylori</i>in the Stomach — A Paradox Unmasked
Authors: Julie Parsonnet
Journal: New England Journal of Medicine (1996)

In 1993, a National Institutes of Health Consensus Conference declared infection with Helicobacter pylori to be an important cause of duodenal and gastric ulcers.1 Soon thereafter, the International Agency for Research on Cancer classified H. pylori as a group 1 carcinogen, a definite cause of gastric adenocarcinoma in humans.2 In this issue of the Journal, Hansson and colleagues report that patients with duodenal ulcers have a decreased risk of gastric cancer, whereas those with gastric ulcers have an increased risk.3 Thus, a paradox in the epidemiology of gastric disease is unmasked. The incidence of gastric cancer correlates positively with the . . .
Polyethylenimine combined with liposomes and with decreased numbers of primary amine residues strongly enhanced therapeutic antiviral efficiency against herpes simplex virus type 2 in a mouse model
Authors: Yoshie Maitani, Kenji Ishigaki, Yuta Nakazawa, Daisuke Aragane, Tomoya Akimoto, Masatoshi Iwamizu, Takashi Kai, Kyoko Hayashi
Journal: Journal of Controlled Release (2013)
Availability of the Calcium of Milk
Authors: K. H. Coward, E. W. Kassner, L. W. Waller
Journal: BMJ (1943)

ConclusionNothing perhaps requires greater emphasis in this paper than that all these points concerning technique should be thoroughly understood by the nursing staff.Some of them may seem trivial, but it is only by constant attention to these details that this method of continuous intravenous drip transfusion will consistently give the good results which are justly claimed for it.
The Saphenous Vein
Authors: Norman R. Hertzer
Journal: JAMA (1977)

At the symposium on venous problems sponsored by Northwestern University in honor of the eminent surgeon and scholar, Geza de Takats, MD, (Chicago, Dec 2-4, 1976) a number of distinguished participants agreed that unnecessary surgical removal of the greater saphenous vein seriously compromises later arterial reconstruction required by some patients. This opinion deserves amplification for the benefit of every physician and surgeon not in attendance. Autogenous saphenous vein unquestionably is the best graft currently available for replacement of diseased arteries of medium and small diameter, and probably will remain so through the foreseeable future. Although the techniques of endarterectomy and fabric graft bypass are quite satisfactory when applied to the aorta and its large branches, it is likely that many stunning advances in the surgical treatment of arteriosclerosis of the coronary, renal, popliteal, and tibial arteries would have been postponed, if not impossible, without the availability of saphenous vein. In
The Use and Abuse of the Broad Spectrum Antibiotics
Authors: Edwin M. Ory
Journal: JAMA (1963)

The term "broad spectrum antibiotics" was originally used to designate antibiotics that were effective against both gram-positive and gram-negative bacteria, in contrast to penicillin, which is effective chiefly against gram-positive organisms, and streptomycin, which is active primarily against gram-negative bacteria. The broad spectrum antibiotics have an antimicrobial spectrum which includes some gram-positive and some gram-negative organisms, as well as certain rickettsiae, larger viruses, protozoa, and pleuropneumonia-like organisms. Although the antimicrobial spectra of other antibiotics vary in their breadth of coverage, this article will be limited to a discussion of the tetracyclines and chloramphenicol. <h3>The Tetracyclines</h3> There are four basic tetracycline homologues. The first two were prepared entirely by fermentation methods. Chlortetracycline hydrochloride was isolated from<i>Streptomyces aureofaciens</i>by Duggar<sup>1</sup>in 1948 and oxytetracycline, produced by S<i>rimosus</i>, was introduced in 1950. Tetracycline was prepared by catalytic hydrogenation of the chlorine radical and introduced for clinical use in 1953. Demethylchlortetracycline,
Developing structured representations
Authors: Leonidas A. A. Doumas, Lindsey E. Richland
Journal: Behavioral and Brain Sciences (2008)

Abstract Leech et al.'s model proposes representing relations as primed transformations rather than as structured representations (explicit representations of relations and their roles dynamically bound to fillers). However, this renders the model unable to explain several developmental trends (including relational integration and all changes not attributable to growth in relational knowledge). We suggest looking to an alternative computational model that learns structured representations from examples.
Nidation of the Ovum
Authors: Bent G. Böving
Journal: JAMA (1961)

<h3>To the Editor:—</h3> The editorial on "Nidation of the Ovum" (<i>JAMA</i>, Nov. 5, 1960) is welcomed as a recognition of growing interest in the subject, but it is unfortunately misleading in several respects. The principal reason for error is the great variation among species and the failure to specify the species to which a number of statements refer. Three such errors, and certain errors in the references, may deserve correction. "The maternal component of the placenta, the decidual cells of the endometrium, make ready for implantation in the prenidation hours," may apply to some rodents, but it does not apply to the human, where decidual changes occur not before, but a matter of days after, implantation. The importance of this distinction is its implication that, in the human at least, the decidual reaction is a rather late consequence or step of implantation rather than an early and purely uterine
Fairness of financial penalties to improve control of Clostridium difficile
Authors: A S. Walker, D. Spiegelhalter, D. W Crook, D. Wyllie, J. Morris, T. E A Peto
Journal: BMJ (2008)

Trusts in England have been given targets to reduce <i>C difficile </i>infection rates. But <b>Sarah Walker and colleagues</b> argue that the way they are calculated makes financial penalties almost impossible to avoid
Life expectancy in relation to cardiovascular risk factors: 38 year follow-up of 19 000 men in the Whitehall study
Authors: R. Clarke, J. Emberson, A. Fletcher, E. Breeze, M. Marmot, M. J Shipley
Journal: BMJ (2009)

<b>Objective</b> To assess life expectancy in relation to cardiovascular risk factors recorded in middle age. <b>Design</b> Prospective cohort study. <b>Setting</b> Men employed in the civil service in London, England. <b>Participants</b> 18 863 men examined at entry in 1967-70 and followed for 38 years, of whom 13 501 died and 4811 were re-examined in 1997. <b>Main outcome measures</b> Life expectancy estimated in relation to fifths and dichotomous categories of risk factors (smoking, “low” or “high” blood pressure (≥140 mm Hg), and “low” or “high” cholesterol (≥5 mmol/l)), and a risk score from these risk factors. <b>Results</b> At entry, 42% of the men were current smokers, 39% had high blood pressure, and 51% had high cholesterol. At the re-examination, about two thirds of the previously “current” smokers had quit smoking shortly after entry and the mean differences in levels of those with high and low levels of blood pressure and cholesterol were attenuated by two thirds. Compared with men without any baseline risk factors, the presence of all three risk factors at entry was associated with a 10 year shorter life expectancy from age 50 (23.7 <i>v</i> 33.3 years). Compared with men in the lowest 5% of a risk score based on smoking, diabetes, employment grade, and continuous levels of blood pressure, cholesterol concentration, and body mass index (BMI), men in the highest 5% had a 15 year shorter life expectancy from age 50 (20.2 <i>v</i> 35.4 years). <b>Conclusion</b> Despite substantial changes in these risk factors over time, baseline differences in risk factors were associated with 10 to 15 year shorter life expectancy from age 50.
Anorectal Disease in the Community
Authors: George S. Speare
Journal: New England Journal of Medicine (1956)

THE material in this paper is derived from an analysis of 400 cases seen in the Rectal Clinic of the Brusch Medical Center in Cambridge during the last two years. The purpose of the study is twofold: to show the incidence and discuss the diagnosis and treatment of the more common anorectal diseases in the community; and to consider early detection of rectal cancer and precancerous conditions, such as polyps.The patients fall into two groups: 250 with symptoms of anorectal disease; and 150 who reported for general health examination and were given proctoscopic examinations for the detection of rectal . . .
Don't mention it
Authors: Ike Iheanacho
Journal: BMJ (2007)

Flick through a few newspapers and you'll repeatedly come across a stark warning: “Your home may be repossessed if you do not keep up repayments on your mortgage.” This threat isn't some random frightener but a standard feature in advertisements for property loans. As such, it provides tangible balance for those contemplating the real or imagined advantages of the deals in question.

If only the possible harms of medicines were contextualised so clearly. Instead, it's often assumed that the general public just cannot understand risk …
Overcoming Chemotherapy Resistance in Prostate Cancer
Authors: Ravi A. Madan, Sumanta Kumar Pal, Oliver Sartor, William L. Dahut
Journal: Clinical Cancer Research (2011)

Abstract Although treatment for prostate cancer has improved over the past several years, taxanes remain the only form of chemotherapy that improves survival in patients with metastatic castration-resistant prostate cancer (mCRPC). In addition to the promising therapeutic cancer vaccines and newly developed agents targeting androgen receptor signaling, chemotherapy-based treatments will likely continue to play a significant role in patients with mCRPC. Recently published data that showed that a second taxane (cabazitaxel) extends survival after progression on docetaxel was a significant step forward, but also highlighted the need to overcome taxane resistance in prostate cancer. Preliminary evidence suggests that several treatment strategies may improve the activity of taxanes in prostate cancer and perhaps enhance clinical outcomes. Clin Cancer Res; 17(12); 3892–902. ©2011 AACR.
Performance of the Pictorial Representation of Illness and Self Measure in Individuals with Alcohol Dependence, Alcohol Abuse or At-Risk Drinking
Authors: Susa Reinhardt, Gallus Bischof, Janina Grothues, Ulrich John, Hans-Jürgen Rumpf
Journal: Psychotherapy and Psychosomatics (2006)

&lt;i&gt;Background:&lt;/i&gt; The impact of chronic illnesses is not only influenced by one’s physical functioning but also by its subjective importance to the individual’s life. However, it is often difficult to asses such an impact in an appropriate way. PRISM (pictorial representation of illness and self measure) measures the perception of illness and first data on its validity have been published. The aim of the present study was to prove the applicability of PRISM regarding alcohol-dependent patients. Therefore, a comparison was made between alcohol-dependent patients, alcohol abusers and at-risk drinkers. &lt;i&gt;Method:&lt;/i&gt; The sample consisted of 763 general practice patients, who scored above the cutoff in alcohol-related screening questionnaires. Of this sample, 330 were diagnosed as alcohol dependent, alcohol abusers (both according to DSM-IV) or at-risk drinkers. To prove the applicability, PRISM was put in context with the severity of alcohol dependence and the core constructs of the transtheoretical model of behavior change. &lt;i&gt;Results:&lt;/i&gt; PRISM was related to the severity of the drinking problem: the severer the drinking problem, the shorter the distance between self and illness. High correlations with aspects of alcohol consumption – such as adverse consequences from drinking, temptation to drink, and self-efficacy to abstain – were found. Concerning stages of change according to the transtheoretical model of behavior change, data show a significant difference in the self-illness separation between patients in the stage of contemplation compared to those in the precontemplation or action stage. &lt;i&gt;Conclusions:&lt;/i&gt; The PRISM task is applicable to patients with alcohol use disorders. Within this group and in contrast to other chronic diseases, PRISM reveals a significant relationship not only to the severity of drinking, but also to the readiness to change one’s drinking behavior.
Abnormal contractile function due to induction of nitric oxide synthesis in rat cardiac myocytes follows exposure to activated macrophage-conditioned medium.
Authors: J L Balligand, D Ungureanu, R A Kelly, L Kobzik, D Pimental, T Michel, T W Smith
Journal: Journal of Clinical Investigation (1993)

The mechanism by which soluble mediators of immune cell origin depress myocardial contractility, either globally as in systemic sepsis, or regionally in areas of inflammatory myocardial infiltrates, remains unclear. When freshly isolated ventricular myocytes from adult rat hearts were preincubated for at least 24 h in medium conditioned by endotoxin (LPS)-activated rat alveolar macrophages, their subsequent inotropic response to the beta-adrenergic agonist isoproterenol was reduced from 225 +/- 19% to 155 +/- 10% of the baseline amplitude of shortening (mean +/- SEM, P < 0.05). Neither baseline contractile function nor the contractile response to high extracellular calcium were affected. To determine whether an endogenous nitric-oxide (NO)-signaling pathway within ventricular myocytes was responsible for their decreased responsiveness to isoproterenol, the L-arginine analogue L-NMMA was added to the preincubation medium. While L-NMMA did not affect baseline contractile function or the response of control myocytes to isoproterenol, it completely restored the positive inotropic response to isoproterenol in myocytes preincubated in LPS-activated macrophage medium. Release of NO by ventricular myocytes following exposure to activated macrophage medium was detected as an increase in cGMP content in a reporter-cell (RFL-6) bioassay and also as increased nitrite content in myocyte-conditioned medium. Thus, the depressed contractile response of adult rat ventricular myocytes to beta-adrenergic agonists by a 24-h exposure to soluble inflammatory mediators is mediated at least in party by induction of an autocrine NO signaling pathway.