tbuckley/cabot-search huggingface dataset:
Vasodilatory effect of arginine vasopressin is mediated by nitric oxide in human forearm vessels.
Authors: T Tagawa, T Imaizumi, T Endo, M Shiramoto, Y Hirooka, S Ando, A Takeshita
Journal: Journal of Clinical Investigation (1993)

Arginine vasopressin (AVP) causes biphasic changes in vascular resistance in human forearms; vasoconstriction at lower doses and vasodilation at higher doses. Vasoconstriction is mediated by the V1 receptor. However, the mechanism of AVP-induced vasodilation is not known. We investigated whether AVP-induced vasodilation is mediated by nitric oxide (NO) in human forearms by examining the effects of L-arginine (a precursor of NO) and NG-monomethyl-L-arginine (L-NMMA, a blocker of NO synthase) on AVP-induced vasodilation. AVP was infused intraarterially at doses of 0.05, 0.1, 0.2, 0.5, and 1.0 ng/kg per min (n = 8). The lower doses of AVP (< or = 0.1 ng/kg per min) increased, whereas the higher doses of AVP (> or = 0.5 ng/kg per min) decreased forearm vascular resistance (FVR) (P < 0.01). Intraarterially infused L-arginine at 10 mg/min did not alter arterial pressure, baseline FVR, or heart rate. L-arginine did not alter the magnitude of AVP-induced vasoconstriction at the lower doses, but L-arginine augmented the magnitude of AVP-induced vasodilation at doses of 0.2 (P < 0.05), 0.5 (P < 0.01), and 1.0 (P < 0.05) ng/kg per min. In another group (n = 6), intraarterially infused L-NMMA (4 mumol/min for 5 min) increased baseline FVR without systemic effects, and inhibited acetylcholine-induced vasodilation (P < 0.01). L-NMMA at this dose inhibited AVP-induced vasodilation (P < 0.01) but did not affect vasoconstriction. L-arginine reversed the inhibitory effect of L-NMMA. Our results suggest that the vasodilatory effect of AVP may be mediated by NO in human forearms.
Hormonal regulation of human lower esophageal sphincter competence: interaction of gastrin and secretin
Authors: Sidney Cohen, William Lipshutz
Journal: Journal of Clinical Investigation (1971)

The interaction of gastrin and secretin, in the regulation of human lower esophageal sphincter competence, was studied in 54 normal subjects. A dose-response curve, for the lower esophageal sphincter, was constructed from the rapid intravenous injections of synthetic gastrin I (amino acid sequence 2-17). This curve was sigmoid shaped and showed a peak response that was 460.0 +/-24.0% (mean +/-2 SE) of the initial sphincter pressure, at a dose of 0.7 mug/kg of gastrin I. Secretin, either endogenously released by duodenal acidification, or exogenously administered as a single intravenous injection, markedly reduced the peak response of the sphincter to gastrin I. To ascertain the character of this inhibition, a gastrin I dose-response curve was obtained during a continuous intravenous secretin infusion. This curve showed a parallel shift to the right, with the maximal sphincter response to gastrin I still attainable at higher doses. A sphincter, endogenously stimulated by gastrin, showed a dose-related reduction in pressure with rapid intravenous injections of secretin. At the level of resting sphincter pressure, response to secretin diminished, and larger doses were required for comparable reduction in pressure. These studies indicate; (a) Secretin interacts with gastrin in the physiological regulation of human lower esophageal sphincter competence; (b) Secretin is a sensitive inhibitor to gastrin stimulation of the lower esophageal sphincter; (c) This inhibitory effect of secretin is competitive in character.
A few lessons in screening for Gordon Brown
Authors: Julian Tudor Hart
Journal: BMJ (2008)

The prime minister seems just to want to offer more consumer choice for the worried well

Prime Minister Gordon Brown has just announced that he will allocate funding for a national screening programme concentrated on diabetes, cardiovascular and renal diseases, and stroke ( BMJ 2008;336:62-3 doi:10.1136/bmj.39454.738912.4E). He said these were now seldom available except through private care but would, over the next three years, be made available to everyone.

The politicians, civil servants, and managers who devised this plan may believe it is evidence based. I’m not so sure. So far as I know, there has been only one controlled trial of such a policy. This compared age standardised mortality over five years associated with traditional demand-led care alone in Blaengwynfi, against similar care in Glyncorrwg, where this had been integrated with proactive screening and follow-up for chronic conditions (which included those listed by the prime minister) over the previous 20 years.1 The two communities were socially almost identical. Both were in the bottom 5% of social ranking by Townsend index within the 55 local authorities then composing West Glamorgan. Apparent results were remarkable. Standardised mortality ratios for deaths at all ages were 36% above the UK mean in Blaengwynfi, 2% below it in Glyncorrwg. For deaths under age 65, the SMR was 60% above the UK mean in Blaengwynfi, 6% below it in Glyncorrwg.

This was not an ideal experiment. The actual numbers of deaths under 65 were small—in Glyncorrwg, 21 deaths against 22 expected at UK rates; in Blaengwynfi, 48 deaths against 30 expected—so confidence intervals must be wide. The anticipatory care programme in Glyncorrwg evolved over 20 years, starting with blood pressure control and personal interventions on smoking, ending with a large bundle of interventions of many kinds, but all covering the entire population at risk. …
LC–MS-based metabolomics in profiling of drug metabolism and bioactivation
Authors: Feng Li, Frank J. Gonzalez, Xiaochao Ma
Journal: Acta Pharmaceutica Sinica B (2012)

Since metabolism significantly affects drug safety and efficacy, determining the metabolic profile of a drug is a critical part of drug development. The application of an LC–MS-based metabolomic approach has gained more widespread use in identifying drug metabolites, developing metabolic maps and lending clues to mechanisms of bioactivation. Thus, the LC–MS-based metabolomic approach is a powerful tool for profiling of drug metabolism and bioactivation.
Glucocorticoid Receptor Nuclear Translocation in Airway Cells after Inhaled Combination Therapy
Authors: Omar S. Usmani, Kazuhiro Ito, Kittipong Maneechotesuwan, Misako Ito, Malcolm Johnson, Peter J. Barnes, Ian M. Adcock
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Clinical evidence is accumulating for the efficacy of adding inhaled long-acting beta(2)-agonists (LABAs) to corticosteroids in asthma. Corticosteroids bind to cytoplasmic glucocorticoid receptors (GRs), which then translocate to the nucleus where they regulate gene expression. This article reports the first evidence in vivo of an interaction between inhaled LABA and corticosteroid on GR nuclear translocation in human airway cells using immunocytochemistry. We initially demonstrated significant GR activation 60 minutes after inhalation of 800 microg beclomethasone dipropionate in six healthy subjects. Subsequently, we determined the effects of salmeterol and fluticasone propionate (FP) in seven steroid-naive patients with asthma. We observed dose-dependent GR activation with 100- and 500-microg doses of FP, and to a lesser extent with 50 microg salmeterol alone. However, combination therapy with 100 microg FP and salmeterol augmented the action of FP on GR nuclear localization. In vitro, salmeterol enhanced FP effects on GR nuclear translocation in epithelial and macrophage-like airway cell lines. In addition, salmeterol in combination with FP enhanced glucocorticoid response element (GRE)-luciferase reporter gene activity and mitogen-activated protein kinase phosphatase 1 (MKP-1) and secretory leuko-proteinase inhibitor (SLPI) gene induction. Together, our data confirm that GR nuclear translocation may underlie the complementary interactions between LABAs and corticosteroids, although the precise signal transduction mechanisms remain to be determined.
Setting standards for long term care of the elderly in hospital.
Authors: I Philp, S Mawhinney, W J Mutch
Journal: BMJ (1991)

We derived a manageable number of standards for the wards that most of the staff and patients agreed with. The patients had lower expectations than the staff. Although we cold not obtain the views of most of the patients in the wards, mainly because of cognitive impairment, we believe that most of the standards would improve the patients' quality of live-not by imposing practice on them but by increasing their opportunities
Fat content of expressed breast milk: a case for quality control.
Authors: S A Spencer, D Hull
Journal: BMJ (1981)

Expressed breast milk used to feed preterm infants is precious and so, despite heterogeneity of composition, all available milk is used. A study of 274 samples of expressed breast milk supplied by preterm mothers and National Childbirth Trust donors showed pronounced variation in fat content as measured by the "creamatocrit" method. This was not due to differences between term and preterm mothers or between transitional and mature milk. The composition was affected by diurnal variation and method of collection. Substantial amounts of fat were also wasted as a result of continuous nasogastric feeding. Several milk samples did not contain enough fat to supply even a fraction of the recommended energy requirements of these infants. Some type of quality control over samples of expressed breast milk is clearly essential. The creamatocrit method is simple and feasible.
IMPACT OF YOGA ON ARRHYTHMIA BURDEN AND QUALITY OF LIFE (QOL) IN PATIENTS WITH SYMPTOMATIC PAROXYSMAL ATRIAL FIBRILLATION: THE YOGA MY HEART STUDY
Authors: Dhanunjaya Lakkireddy, Jayasree Pillarisetti, Donita Atkins, Subba Reddy Vanga, Martin Emert, Rhea Pimentel, Caroline Murray, Sudharani Bommana, Kay Ryschon, Loren Berenbom, Buddhadeb Dawn, Raghu Dendi, Jeanne Drisko
Journal: Journal of the American College of Cardiology (2011)
Loss of RAGE Defense: A Cause of Charcot Neuroarthropathy?
Authors: Kara A. Witzke, Aaron I. Vinik, Lisa M. Grant, William P. Grant, Henri K. Parson, Gary L. Pittenger, Niculina Burcus
Journal: Diabetes Care (2011)

This study investigated the relationship between circulating soluble receptor for advanced glycation end products (sRAGE) and parameters of bone health in patients with Charcot neuroarthropathy (CNA).Eighty men (aged 55.3±9.0 years), including 30 healthy control subjects, 30 type 2 diabetic patients without Charcot, and 20 type 2 diabetic patients with stage 2 (nonacute) CNA, underwent evaluations of peripheral and autonomic neuropathy, nerve conduction, markers of bone turnover, bone mineral density, and bone stiffness of the calcaneus.CNA patients had worse peripheral and autonomic neuropathy and a lower bone stiffness index than diabetic or control individuals (77.1, 103.3, and 105.1, respectively; P<0.05), but no difference in bone mineral density (P>0.05). CNA subjects also had lower sRAGE levels than control (162 vs. 1,140 pg/mL; P<0.01) and diabetic (162 vs. 522 pg/mL; P<0.05) subjects, and higher circulating osteocalcin levels.CNA patients had significantly lower circulating sRAGE, with an accompanying increase in serum markers of bone turnover, and reduced bone stiffness in the calcaneus not accompanied by reductions in bone mineral density. These data suggest a failure of RAGE defense mechanisms against oxidative stress in diabetes. Future studies should determine if medications that increase sRAGE activity could be useful in mitigating progression to CNA.
Budesonide Aqueous Nasal Spray (BANS) is preferred over Fluticasone Propionate Nasal Spray (FPNS) based on specific sensory attributes
Authors: S.R. Shah, C. Miller, N. Pethick, T. Uryniak, K.C. Jones, L. O'Dowd
Journal: Journal of Allergy and Clinical Immunology (2003)
Differential effects of troglitazone and d-chiroinositol on glucosamine-induced insulin resistance in vivo in rats
Authors: Koji Yoshino, Noriyuki Takeda, Miyuki Sugimoto, Kazuya Nakashima, Shoji Okumura, Junko Hattori, Akihiko Sasaki, Shinichi Kawachi, Kazuhisa Takami, Rieko Takami, Keigo Yasuda
Journal: Metabolism (1999)
Irrigated Sump Tube Drainage Following Open-Heart Surgery
Authors: Stanley Gianelli
Journal: JAMA (1970)

<h3>To the Editor.—</h3> Following openheart surgery, relatively small amounts of clots around the heart may critically impair cardiac function, even when the pericardium is left widely open. In a satisfactory system of thoracic drainage the drainage tubes should be located where blood is likely to accumulate, and the tubes should remain patent. During the past 18 months, in over 150 cases, we have employed a system which appears to meet these criteria. All our patients are operated on through a median sternotomy. The pleural cavities are not entered until bypass is completed. Then a wide communication is made between the pericardial sac and the right pleural space, extending posteriorly to within several millimeters of the phrenic nerve. The pericardium is left open in the midline from the diaphragm to the reflection over the aorta. The right pleural space is drained by a large sump tube in the posterior gutter. A
Improved glycemic control reduces the impact of weight gain on cardiovascular risk factors in type 1 diabetes. The Epidemiology of Diabetes Complications Study.
Authors: K V Williams, J R Erbey, D Becker, T J Orchard
Journal: Diabetes Care (1999)

OBJECTIVE: To assess the prevalence and incidence of being overweight in type 1 diabetes, to identify factors associated with weight gain and improved glycemic control, and to examine relationships among weight gain, glycemic control, and cardiovascular risk factors. RESEARCH DESIGN AND METHODS: The prevalence and incidence of being overweight in the Pittsburgh Epidemiology of Diabetes Complications (EDC) cohort (n = 441) were compared with the general population (National Health and Nutrition Examination Survey [NHANES]). Factors associated with weight gain and improved glycemic control were identified, and relationships among weight gain, glycemic control, and cardiovascular risk factors were examined over a 6.9 +/- 2.2-year period. RESULTS: At baseline, the prevalence of being overweight (BMI &amp;gt; 27.8 kg/m2 for men and &amp;gt; 27.3 kg/m2 for women) was 10.4 and 11.4%, respectively, and was lower than the age- and sex-specific estimate for the general population (P &amp;lt; 0.05). The incidence of being overweight was comparable in men (12.6%) and women (11.8%) and did not differ from the general population (P = 0.98). Weight gain correlated with improvements in HbA1c (r = -0.21, P &amp;lt; 0.001). Patients with the highest baseline HbA1c levels gained the most weight and had the greatest improvement in glycemic control. A lower baseline BMI was also associated with a greater improvement in glycemic control. Weight gain favorably influenced the lipid profile in the setting of improved glycemic control, but adversely influenced the lipid profile in the absence of improved glycemic control. Weight change was directly associated with blood pressure change, but the incidence of hypertension was more strongly influenced by the development of nephropathy. CONCLUSIONS: The prevalence of being overweight in type 1 diabetes remains lower than that in the general population. Moderate weight gain did not adversely affect the cardiovascular risk profile in the setting of improved glycemic control.
IFP News Section
Authors: Nicoletta Sonino, Giovanni A. Fava, Chantal Henry, Katia M’Baïlara, Rollon Poinsot, Anne-Aurelie Casteret, Frédéric Sorbara, Marion Leboyer, Eduard Vieta, Ludwig Grepmair, Ferdinand Mitterlehner, Thomas Loew, Egon Bachler, Wolfhardt Rother, Marius Nickel, Axel Schweickhardt, Astrid Larisch, Michael Wirsching, Kurt Fritzsche, Carlo Faravelli, Mario Catena, Alessandra Scarpato, Valdo Ricca, Michael Martini Jørgensen, Martin Härter, Harald Baumeister, Katrin Reuter, Frank Jacobi, Michael Höfler, Jürgen Bengel, Hans-Ulrich Wittchen, Robert Zachariae, Axel Skytthe, Kirsten Kyvik, R. Zachariae, K. Paulsen, M. Mehlsen, A.B. Jensen, A. Johansson, H. von der Maase, Fabio Facchinetti, Fedra Ottolini, Marta Fazzio, Marco Rigatelli, Annibale Volpe, Naheed K. Hossain, Jane Irvine, Paul Ritvo, Helen S. Driver, Colin M. Shapiro, Constance Dalenberg, Richard Loewenstein, David Spiegel, Chris Brewin, Ruth Lanius, Steven Frankel, Steven Gold, Bessel Van der Kolk, Daphne Simeon, Eric Vermetten, Lisa Butler, Cheryl Koopman, Christine Courtois, Paul Dell, Ellert Nijenhuis, James Chu, Vedat Sar, Oxana Palesh, Carlos Cuevas, Kelsey Paulson, Harrison G. Pope, Steven Barry, J. Alexander Bodkin, James Hudson, Carlo Lai, Silvia Daini, Maria Lucia Calcagni, Isabella Bruno, Sergio De Risio, Marco Chiesa, Peter Fonagy, Sabine Loeber, Bernhard Croissant, Helmut Nakovics, Anke Zimmer, Alexander Georgi, Sabine Klein, Carsten Diener, Andreas Heinz, Karl Mann, Herta Flor
Journal: Psychotherapy and Psychosomatics (2007)
Understanding Hepatitis B Virus Infection
Authors: Darius Moradpour, Jack R. Wands
Journal: New England Journal of Medicine (1995)

Infection with hepatitis B virus (HBV) results in a broad spectrum of liver disease, ranging from subclinical infection to acute, self-limited hepatitis and fatal, fulminant hepatitis. Exposure to HBV, particularly when it occurs early in life, may also result in an asymptomatic carrier state that can progress to chronic active hepatitis, cirrhosis of the liver, and eventually hepatocellular carcinoma. Complex viral and host factors determine this variable clinical outcome. Fundamental questions about the biologic aspects of hepatitis B that have direct relevance to clinical practice remain unresolved. It is estimated that there are 400 to 500 million HBV carriers in . . .
Medullary Thyroid Carcinoma Arises in the Absence of Prolactin Signaling
Authors: Cécile Kedzia, Ludovic Lacroix, Nabahet Ameur, Thierry Ragot, Paul A. Kelly, Bernard Caillou, Nadine Binart
Journal: Cancer Research (2005)

Prolactin, a pituitary hormone, exerts pleiotropic effects in various cells. These effects are mediated by a membrane receptor highly expressed in many tissues. To analyze prolactin effects on the thyroid gland, we first identified prolactin receptor (PRLR) mRNAs by in situ hybridization. To further evaluate the physiologic relevance of PRLR actions in the thyroid in vivo, we used PRLR knockout mice. Whereas the histologic structure of thyroid of PRLR-null mice was not disturbed, we show that T4 levels are lower in null animals (13.63 +/- 2.98 versus 10.78 +/- 2.25 pmol/L in null mice), confirming that prolactin participates in the control of thyroid metabolism. To further investigate thyroid effects in mice, we measured body temperature and thyroid-stimulating hormone in young and adult male and/or female PRLR-null mice and their normal siblings. Surprisingly, in null animals, we saw medullary thyroid carcinoma (MTC) arising from parafollicular C cells producing calcitonin. The incidence of these carcinomas attained 41% in PRLR-null mice, whereas this malignant tumor occurs sporadically or as a component of the familial cancer syndrome in humans. This finding suggests that PRLR-null mice could represent a valuable animal model for MTC, which could be compared with existing MTC models. These observations suggest a possible link between the appearance of this carcinoma and the absence of prolactin signaling.
Return to work after aortofemoral bypass surgery
Authors: F. Edwards
Journal: BMJ (1977)

Whether Drs Brooks and Harrington's patient developed malignancy after the diagnosis of coeliac disease was made and some clinical improvement was obtained after gluten withdrawal or whether it was present initially, precipitating overt manifestations of gluten intolerance, it is not possible to say.It is certainly believed that failure of a patient with newly diagnosed coeliac disease to respond to gluten withdrawal or relapse occurring after previous control by diet is suggestive of the development of malignancy.'The view that intestinal malignancy may cause flattening of the jejunal mucosa and present as "the coeliac syndrome" is no longer held.
House‐dust‐mite allergen (Der p 1) levels in university colleges
Authors: A. Mahmic, E. R. Tovey
Journal: Allergy (1998)

Background In coastal Australia, mean house‐dust‐mite allergen concentration is 20‐40 times higher in homes than in public buildings. Allergen concentrations in university colleges, which share some eharacteristics of both homes and public buildings, are not known. The study aimed to compare bed mite‐allergen concentration in colleges with local homes. Methods Mattress dust was collected from three colleges (n = 60 m each) and local homes (N=68) during summer, Der p 1 was measured by ELISA. Information was collected on the floor plan of the colleges, cleaning practices, age of building, and orientation of room. Results Most college mattresses (94%) had Der p 1 concentrations less than the mean of homes in the same climate. The geometric means of Der p 1 m the mattresses of the colleges were as follows: A, 8.9 pg Der p 1/g fme dust (95% CI 6.9,11.5); B, 1.9 (1.5,2.3); and C, 1.5 (1.2,2.0), compared to homes, 22,5 (17.6, 28.7). The percentages of college mattresses with less than 2 jig/ g were 7%, 48%, and 58%, respectively, compared to 4% for homes. Higher Der p 1 concentrations were weakly associated with age of building in college A, and orientation in college B, Der p 1 concentrations were independent of floor level and age of mattress. Conclusions These findings indicate that low allergen concentrations are achievable without extreme hygiene and cleaning measures in a climate which supports mite proliferation in homes.
Spontaneous venous thrombosis in a young patient with combined factor V Leiden and lupus anticoagulant
Authors: Francisco F. Lopez, Joseph D. Sweeney, Abbe J. Blair, William M. Sikov
Journal: American Journal of Hematology (1999)

We describe a case of a 28-year-old man who developed an extensive spontaneous deep venous thrombosis. Testing revealed heterozygotic factor V Leiden mutation, and the presence of both lupus anticoagulant (LA) and elevated IgM anticardiolipin antibody (ACA). Several family members were found to be heterozygous for factor V Leiden. A paternal aunt had the factor V Leiden mutation, an elevated plasma homocysteine and a borderline increased IgG ACA level. No other family member had a history of a venous thrombotic event. This case illustrates that evaluation of young patients who present with venous thrombosis should be performed for both hereditary and acquired thrombophilic defects. The family studies suggest that the presence of a lupus anticoagulant may be more clinically significant then elevated ACA in risk assessment. Although screening family members when the proband carries factor V Leiden is controversial, psychological reassurance of those who test negative and simple advice on occupations or social habits (e.g., smoking) for those who test positive may be important benefits. Am. J. Hematol. 62:58–60, 1999. © 1999 Wiley-Liss, Inc.