tbuckley/cabot-search huggingface dataset:
Clustering of sex hormone disruptors in Singapore's marine environment.
Authors: Yinhan Gong, Hong Soon Chin, Lis Sa Elissa Lim, Chong Jin Loy, Jeffrey P Obbard, E L Yong
Journal: Environmental Health Perspectives (2003)

Abnormal sexual differentiation and other reproductive abnormalities in marine animals indicate the presence in seawater of endocrine-disrupting compounds (EDCs) that perturb the function of the sex hormone signaling pathways. However, most studies to date have reported on EDC effects in freshwater and sewage samples, and there is a paucity of bioassay data on the effects of EDCs in marine waters. Our aims in this study were to devise robust methodologies suitable for extracting potential EDCs and to measure their summated effects on activities of androgen receptors (ARs) and estrogen receptors (ER-alpha and ER-beta) in marine samples from Singapore's coastal waters. In this study, we examined the ability of C18, hydrophilic and lipophilic balance, and diol cartridges to extract potential EDCs from seawater samples. Extracts from C18 cartridges exhibited the highest sex hormone bioactivities in reporter gene assays based on a human cell line expressing AR, ER-alpha, and ER-beta. Examination of extracts from 20 coastal locations showed high androgenic and estrogenic agonist activities in confined clusters closest to the main island of Singapore. Sex hormone activity declined rapidly in clusters farther from the main coastline and in more open waters. Unexpectedly, surface and mid-depth samples from the confined high-activity clusters, in the presence of hormone, exhibited AR and ER-alpha activities that were 200-900% higher than those observed for the cognate hormone alone. This enhanced sex hormone activity suggests that analyses of complex seawater mixtures may uncover unusual bioactivities that may not be obvious by studying individual compounds. Our data present a "snapshot" of the sex hormone disruptor activity in Singapore's marine environment and indicate that C18 extraction for EDCs used in conjunction with reporter gene bioassays represents a robust and sensitive methodology for measuring summated androgenic and estrogenic activities in seawater.
Science, medicine, and the future: Alzheimer's disease
Authors: C. L Masters, K. Beyreuther
Journal: BMJ (1998)

There is a noticeable air of optimism in the research community studying Alzheimer's disease.This because the molecular basis of Alzheimer's disease and other neurodegenerative conditions, such as Parkinson's and Huntington's diseases, is rapidly being elucidated.From these molecular insights, it is likely that effective therapeutic strategies will be developed within the next 10 years.Future treatment will probably be based on combination therapies-such as neurotransmitter replacement combined with a drug to protect against the toxic effect of A amyloid-tailored to the genetic profile of an individual.Assuming proved efficacy and safety, these forms of treatment are likely to be as widespread and acceptable as cholesterol lowering treatment is today.In the past few years there has been an avalanche of knowledge surrounding the genesis of A amyloid plaques, one of the principal pathological hallmarks of this disease (see fig 1).In the absence of a serious candidate for the pathway leading to the neurofibrillary tangle, the other major pathological lesion in Alzheimer's disease (fig 1), the focus will probably remain on amyloid plaques.Strong genetic risk factors have been identified for Alzheimer's disease, all of which interact directly or indirectly with the A amyloid pathway.Undoubtedly, other genetic factors remain to be discovered, some of which might open the door to the neurofibrillary tangle.More importantly, the major environmental risk factors for Alzheimer's disease remain elusive.This is not surprising, given the relatively few analytical epidemiological studies that have been conducted and the difficulty of case ascertainment, particularly in the early stages of the disease.We review briefly where the research is heading and give some predictions on where our concepts might lie a decade from now (for more details see recent reviews [1][2][3] ).
Hemodynamics of Aortic Valve Atresia
Authors: L. JEROME KROVETZ, RICHARD D. ROWE, GEROLD L. SCHEIBLER
Journal: Circulation (1970)

Hemodynamic data on 12 infants with aortic valve atresia, ranging from 1 to 3 mo of age, are presented. Peripheral arterial oxygen saturations ranged from 19 to 93%. The lowest saturations were found in patients with closed foramen ovales. Increasing age, increasing pulmonary vascular resistance, and a decrease in the pulmonary-to-systemic blood flow ratio all correlated with decreasing systemic arterial oxygen saturation. In seven of the nine infants under 1 mo of age, systemic arterial saturations ranged from 81 to 93%. Thus, we feel that the classification of this lesion as a form of cyanotic congenital heart disease is misleading and prefer to classify aortic valve atresia as an obligatory admixture lesion. Criteria for selection of patients for surgery are discussed and the minimum amount of hemodynamic data needed for such selection is outlined.
Married to Medicine: An Intimate Portrait of Doctors' Wives
Authors: Carol Nadelson
Journal: JAMA (1981)

In<i>Married to Medicine</i>Carla Fine has interviewed a wide cross-section of women who are married to physicians. Although she did not intend a formal research study, nor did she use a statistical sample, she finds common themes among the wide variety of women she has interviewed. Life as a physician's wife is hard, and the rewards are often not those fantasized. This book certainly bursts the bubble of a "perfect" relationship with a "perfect" man. In fact, the wife of a physician does not even seem to be entitled to complain or expect sympathy: because she is married to a man who has a major commitment to serve others, she must therefore relinquish her own needs. Of course, financial rewards and higher social status compensate for this, giving her even less cause for complaint. The book presents more woe than gratification. Although I admit to being a bit jaded,
Review: Minimal interventions (e.g., a letter) reduce long-term benzodiazepine use in primary care
Authors: Brian A. Primack
Journal: Annals of Internal Medicine (2012)

Source Citation Mugunthan K, McGuire T, Glasziou P. Minimal interventions to decrease long-term use of benzadiazepines in primary care: a systematic review and meta-analysis. Br J Gen Pract. 2011;61:573-8. 22152740
Hysteresis of left ventricular end ejection pressure-dimension relations after acute pressure loading in the intact canine heart
Authors: B. WAY, J. VICTORY, M. M LEWINTER, W. Y LEW, R. DOYLE, P. FOEX, W A. RYDER, L. A JONES
Journal: Cardiovascular Research (1986)

The left ventricular end systolic pressure-volume relation of the isolated canine heart is linear and independent of the loading conditions. The effects of acute pressure loading on the left ventricular end ejection pressure-length relations were studied in the intact canine heart. The lengths of two wall segments of the left ventricle parallel to the minor axis were measured with pairs of miniature piezoelectric crystals. At two levels of filling pressure, with and without control of heart rate, acute increases in left ventricular afterload were produced for six successive beats by occluding the thoracic aorta. After abrupt release of this occlusion, at left ventricular end diastolic pressure < 10 mmHg, end ejection lengths were longer than before the occlusion for both segments despite the same or lower end ejection pressures. When heart rate was not controlled the mean(SD) difference in end ejection length was 0.46(0.21) mm (n=100). When heart rate was controlled by atrial pacing after autonomic blockade the difference was 0.37(0.11) mm (n=80). In contrast, at left ventricular end diastolic pressure > 10 mmHg there was no significant difference between end ejection lengths before and after release of the aortic occlusion. Gradual release of the aortic occlusion over 4–5 beats produced clockwise hysteresis of the left ventricular end ejection pressure-length relation when left ventricular end diastolic pressure was < 10 mmHg. No hysteresis occurred when left ventricular end diastolic pressure was >10 mmHg. Hysteresis of the end systolic pressure-dimension relation was also seen when major and minor axis dimensions of the left ventricular were measured. Hysteresis was unaffected by autonomic blockade and control of heart rate. Viscoelastic properties of myocardial muscle may explain this behaviour.
TCT-56 PEPCAD China ISR: A Prospective, Multicenter, Randomized Trial of Paclitaxel-Coated Balloon versus Paclitaxel-Eluting Stent for the Treatment of DES In-Stent Restenosis - 9-Month Angiographic and 12-Month Clinical Results
Authors: Bo Xu, Run-Lin Gao, Jian'an Wang, Yuejin Yang, Shao Liang Chen, Bin Liu, Fang Chen, Zhanquan Li, Yaling Han, Guosheng Fu, Yelin Zhao, Junbo Ge
Journal: Journal of the American College of Cardiology (2013)
The price isn't right
Authors: A. Dyson
Journal: BMJ (2001)

As practising doctors we both knew the diagnosis. But there is still a seismic shock to the soul when the words multiple sclerosis pass the neurologist's lips. My wife's mildly inconvenient limp had suddenly become a life sentence of wondering what terror each new day would bring, and a sense of loss of one's future, not unlike a bereavement.

> Why does a drug that costs £6000 in Australia cost £13 800 in the UK? 

A few days later we went on holiday. The limp was no worse and we needed time to think. We decided to try to carry on as normal for as long as possible, my wife as part time specialist registrar in microbiology and myself as a consultant anaesthetist. Our two children were too young to understand any implications.

Stupidly, we thought that some form of treatment would be available, certainly physiotherapy, possibly interferon. In fact, physiotherapy took many weeks to arrive. As for interferon, neither of us was keen. We read about the trials, we learned of the side effects, and we thought that perhaps …
Prevention of cognitive deficits in Alzheimer’s mouse model by elevating brain magnesium
Authors: Guosong Liu
Journal: Molecular Neurodegeneration (2012)

Memory functions decline with age, and severely deteriorate during Alzheimer’s disease (AD). Several studies suggest that dietary/environmental factors can reduce the prevalence of AD in humans. Magnesium is essential for maintaining normal body and brain functions. Here we show that increasing brain magnesium, using a newly developed magnesium compound (magnesium-L-threonate, MgT), prevents cognitive deficits and pathological changes in transgenic mice co-expressing familial AD-linked APP and PS1 variants that mimics the pathological and behavioral changes of human AD (AD mice). In intact mice, brain Mg content was found to be the lowest among all tissues tested; long-term MgT-treatment significantly elevated Mg levels in brain, and was associated with markedly improved cognitive function. In AD mice, learning and memory abilities are seriously impaired by 7 months, and completely deteriorate at 15 months. Strikingly, MgT-treatment was effective in preventing such severe learning and memory deterioration during the entire course of AD progression. At the cellular level, MgT-treatment reduced amyloid deposition in hippocampus and frontal cortex, and prevented synapse loss in the dentate gyrus (DG) and CA1 areas. The degree of memory improvement was strongly correlated with the protection of synapse loss, but did not correlate with the reduction of Aβ plaque. Thus, increased brain Mg might block Aβ-induced synaptic dysfunction. Since AD patients already have Mg deficiency, increase in brain Mg may represent a new strategy for prevention and amelioration of AD.
Free cationic liposomes inhibit the inflammatory response to cationic lipid–DNA complex injected intravenously and enhance its transfection efficiency
Authors: Abdelatif Elouahabi, Veronique Flamand, Sibel Ozkan, Frederic Paulart, Michel Vandenbranden, Michel Goldman, Jean-Marie Ruysschaert
Journal: Molecular Therapy (2003)

In this report, we show that intravenous (i.v.) injection into mice of a complex made of the cationic lipid diC14-amidine and the luciferase reporter plasmid (pCMV-luc) results in efficient gene expression in several organs but elicits an inflammatory response characterized by a release of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) into the serum of treated animals. A single preinjection of free diC14-amidine liposomes improves the i.v. transfection efficiency of the diC14-amidine/protamine/pCMV-luc complex as much as 40 times. This improvement is correlated with the ability of free liposomes to inhibit TNF-α but not IFN-γ production resulting from complex injection. TNF-α-rich serum obtained from mice injected with diC14-amidine/protamine/pCMV-luc complex inhibits luciferase expression in transfected mouse lung endothelial (MLE) cells cultured in vitro, whereas IFN-γ has no effect. This inhibitory effect can be partly abolished by treating the mouse serum with a specific anti-TNF-α antibody. These data point out that cationic lipids are potent inhibitors of the inflammatory response to the CpG motifs in plasmid DNA. This property is shown to enhance the in vivo transfection efficiency.
Nonenzymatic Functions of Acetylcholinesterase Splice Variants in the Developmental Neurotoxicity of Organophosphates: Chlorpyrifos, Chlorpyrifos Oxon, and Diazinon
Authors: Ruth R. Jameson, Frederic J. Seidler, Theodore A. Slotkin
Journal: Environmental Health Perspectives (2006)

Organophosphate pesticides affect mammalian brain development through mechanisms separable from the inhibition of acetylcholinesterase (AChE) enzymatic activity and resultant cholinergic hyperstimulation. In the brain, AChE has two catalytically similar splice variants with distinct functions in development and repair. The rare, read-through isoform, AChE-R, is preferentially induced by injury and appears to promote repair and protect against neurodegeneration. Overexpression of the more abundant, synaptic isoform, AChE-S, enhances neurotoxicity.We exposed differentiating PC12 cells, a model for developing neurons, to 30 microM chlorpyrifos (CPF) or diazinon (DZN), or CPF oxon, the active metabolite that irreversibly inhibits AChE enzymatic activity, in order to determine whether they differentially induce the formation of AChE-S as a mechanistic predictor of developmental neurotoxicity. We then administered CPF or DZN to neonatal rats on postnatal days 1-4 using daily doses spanning the threshold for AChE inhibition (0-20%); we then evaluated AChE gene expression in forebrain and brainstem on post-natal day 5.In PC12 cells, after 48 hr of exposure, CPF, CPF oxon, and DZN enhanced gene expression for AChE-R by about 20%, whereas CPF and DZN, but not CPF oxon, increased AChE-S expression by 20-40%. Thus, despite the fact that CPF oxon is a much more potent AChE inhibitor, it is the native compound (CPF) that induces expression of the neurotoxic AChE-S isoform. For in vivo exposures, 1 mg/kg CPF had little or no effect, but 0.5 or 2 mg/kg DZN induced both AChE-R and AChE-S, with a greater effect in males.Our results indicate that nonenzymatic functions of AChE variants may participate in and be predictive of the relative developmental neurotoxicity of organophosphates, and that the various organophosphates differ in the degree to which they activate this mechanism.
STUDIES IN RESUSCITATION: I. THE GENERAL CONDITIONS AFFECTING RESUSCITATION, AND THE RESUSCITATION OF THE BLOOD AND OF THE HEART
Authors: F. H. Pike, C. C. Guthrie, G. N. Stewart
Journal: The Journal of Experimental Medicine (1908)

OUR RESULTS MAY BE BRIEFLY SUMMARIZED: 1. Blood, when defibrinated, soon loses its power to maintain the activity of the higher nervous centers, and its nutritive properties for all tissues quickly diminish. 2. Artificial fluids, as a substitute for blood, are not satisfactory. 3. The proper oxygenation of the blood is an indispensable adjunct in the resuscitation of an animal. 4. The heart usually continues to beat for some minutes after it ceases to affect a mercury manometer, and resuscitation of it within this period by extra-thoracic massage and artificial respiration is sometimes successful. 5. Resuscitation of the heart by direct massage is the most certain method at our command. 6. A proper blood-pressure is an indispensable condition for the continued normal activity of the heart. 7. Anaesthetics, hemorrhage and induced currents applied to the heart render resuscitation more difficult than asphyxia alone.
Coronary Artery Spasm
Authors: Samuel Vaisrub
Journal: JAMA (1976)

Rarely has an etiologic concept bounced back so vigorously as that of coronary artery spasm. Only recently dismissed as a nonexistent entity—let alone as the cause of angina—it is now being implicated with increasing frequency in some cases, possibly types, of the anginal syndrome. The evidence stems from observations during selective coronary angiography, usually in patients with unstable angina and variant (Prinzmetal) angina.<sup>1,2</sup>Spasm has also been suspected in patients with angina without demonstrable arteriographic lesions. Although strongly suggestive, the angiographic evidence had not been conclusive because the observed spasm could well have been provoked by the tip of the catheter in the coronary artery. Occurrence of spasm unprovoked by mechanical means still remained unproved. To further explore the significance of coronary spasm, Heupler and associates<sup>3</sup>administered ergonovine maleate (0.1 to 0.4 mg) intravenously after coronary arteriography to 50 patients with no demonstrable major coronary obstruction. Eight of the
Minocycline-Associated Tooth Discoloration in Young Adults
Authors: Susana C. Poliak
Journal: JAMA (1985)

After observing a patient with adult-onset tooth discoloration coincident with minocycline administration, we retrospectively surveyed a cohort of patients with severe cystic acne during therapeutic trials with isotretinoin. Four of 72 patients who had minocycline therapy during adolescence were found to have minocycline-associated tooth discoloration, which occurred in one case after only four weeks of treatment. Thus, minocycline must be considered as an uncommon cause of tooth staining in adults. (<i>JAMA</i>1985;254:2930-2932)
The chromogranin A-derived peptides vasostatin-I and catestatin as regulatory peptides for cardiovascular functions
Authors: K. B. Helle
Journal: Cardiovascular Research (2009)

A range of inflammatory conditions is associated with pathologically high levels of circulating chromogranin A (CgA). This prohormone belongs to the family of uniquely acidic proteins co-stored and co-secreted with other hormones and peptides from the diffuse neuroendocrine system. Two highly conserved, CgA-derived peptides, vasostatin-I and catestatin, have been implicated as modulators of a wide range of cells and tissues, including those of the cardiovascular system. This review focuses on links between elevated circulating CgA and cardiovascular dysfunctions in inflammatory conditions in relation to potential beneficial effects of vasostatin-I and catestatin. Characteristic membrane-penetrating properties have been assigned to both peptides, and pertussis toxin sensitivity is shared by a number of their responses, notably in the vascular and cardiac endothelium. Pertussis toxin-sensitive, receptor-independent activation via heterotrimeric G proteins and Gαi/o subunits will be discussed as possible mechanisms for inhibitory effects of vasostatin-I and catestatin on vascular and cardiac responses. The accumulated evidence provides convincing support for vasostatin-I and catestatin as regulatory peptides for the cardiovascular system, converging on alleviation of significant dysfunctions as part of several inflammatory conditions.
Inappropriate Drug Prescribing
Authors: David M. Baughan
Journal: JAMA (1995)

<h3>To the Editor.</h3> —I strongly believe that those of us working in academic medicine have a responsibility to identify important areas where health care can possibly be improved. I think Dr Willcox and colleagues<sup>1</sup>have done that in their study of prescribing patterns for the elderly. Also, I equally strongly believe that those of us in ivory towers have no business passing judgment on our colleagues in full-time practice without a full understanding of the problems and processes involved in the issue. I am afraid it smacks of elitism to analyze a database, adopt a set of criteria not designed for the population, and then make statements about "poor prescribing patterns," "unnecessarily exposed to potentially hazardous prescribing," and not gather any information on outcomes or even talk to the prescribing physicians. The text repeatedly refers to "possibly inappropriate drug prescribing." The word "possibly" is conspicuously absent from the title.
Evolution of coronary artery pattern according to short-axis aortopulmonary rotation: A new categorization for complete transposition of the great arteries
Authors: Ing-Sh Chiu, Shu-Hsun Chu, Jou-Kou Wang, Mei-Hwan Wu, Ming-Ren Chen, Ching-Feng Cheng, Chi-Ren Hung
Journal: Journal of the American College of Cardiology (1995)
Clinical Reactivation of Herpes Simplex Virus Type 2 Infection in Seropositive Pregnant Women with No History of Genital Herpes
Authors: Lisa M. Frenkel
Journal: Annals of Internal Medicine (1993)

Objective: To determine the risk for genital herpes and asymptomatic herpes simplex virus (HSV) shedding in late pregnancy and delivery in a population of HSV type 2 (HSV-2)-seropositive but previously asymptomatic pregnant women. Design: A prospective inception cohort study. Participants: A total of 1355 pregnant women with no history of genital herpes referred from three private obstetrics practices between November 1985 and June 1988. Main Outcome Measures: Confidential questionnaires evaluated sexual risk factors in relation to HSV-2 serologic status as determined by Western blot analysis. Herpes simplex virus shedding was determined by viral culture of the cervix and vulva and of any suspicious lesions. Results: Antibody to HSV-2 was detected in 439 of 1355 pregnant women (32%) with no history of genital herpes. Asymptomatic HSV shedding was detected in 5 of 1160 cultures (0.43%) obtained in late pregnancy and during delivery. A first episode of clinical genital herpes was recognized by 43 of 264 HSV-2-seropositive women (16%) during their pregnancy. Conclusions: Serologic evidence of unknown HSV-2 infection was common in pregnant women without a history of genital herpes. Asymptomatic viral shedding in these women occurred at a rate similar to that seen in women with symptomatic genital HSV-2 infection. To improve recognition of genital herpes near term, obstetricians should counsel pregnant women about the high prevalence and mild and diverse symptoms of genital HSV-2 infection.