tbuckley/cabot-search huggingface dataset:
Abstract 18058: Circulating Tetrahydrobiopterin as a Biomarker for Abdominal Aortic Aneurysm Development, and a Predictor of Treatment Efficacies, in Angiotensin II-infused hph-1 and apoE Null Mice
Authors: Kin L Siu, Hua Cai
Journal: Circulation (2012)

Surgical treatment of the abdominal aortic aneurysm (AAA) has been met with success for aneurysms larger than 5cm. However, detection of smaller aneurysms, particularly those asymptomatic, has remained problematic, resulting in potential silent growth, sudden rupture and death. We have shown that restoration of tetrahydrobiopterin (H4B) levels via oral folic acid (FA) treatment in a novel murine model of AAA, the hph-1 mice, was successful in the prevention of AAA (Hypertension 2012, 59(1):158-66). Of note, in that study aortic levels of H4B decreased with the treatment of Ang II, which was restored by oral treatment of FA. We therefore investigated whether H4B levels can be used as a biomarker for AAA. In this study, we used both hph-1 mice as well as another established AAA model of Ang II infused apoE null mice. In apoE null mice, H4B measured using HPLC showed that in the aortas, H4B levels decreased with Ang II infusion (4.86±0.32 to 2.72±0.26 pmol/mg, n=6 each), and increased with oral administration of FA (6.60±0.62pmol/mg, n=6). A similar trend was observed when H4B was measured from plasma (3.31±0.13, 1.87±0.11, 5.80±0.30 pmol/mg, vehicle, Ang II, FA, respectively, n=6 each). Identically in hph-1 mice, aortic levels of H4B came out to be at 1.87±0.25, 0.99±0.11, 3.00±0.64, and plasma levels being 1.37±0.05, 0.92±0.06, and 2.36±0.25 pmol/mg (for vehicle, Ang II & AngII/FA respectively, n=3 each). Further, linear correlation between plasma and aortic H4B levels shows a R2 of 0.86 for the apoE null mice, and 0.85 for the hph-1, suggesting a linear relationship between the two measurements. This linear relationship between the two measurements is extremely important, as this will allow for a less invasive method of measuring local vascular H4B bioavailability, which is believed to be essential for predicting AAA development. In conclusion, these data indicate that a decreased H4B bioavailability is associated with AAA formation while a restored H4B bioavailability is associated with prevention of AAA development. Furthermore, changes in aortic H4B values are reflected in the plasma. Taken together, these data suggest that circulating H4B levels can serve as a biomarker for AAA development, as well as a predictor of treatment efficacies.
P139 The use of venturi masks with oxygen concentrators
Authors: J. C. T. Pepperell, C. Fraser, G. McClue
Journal: Thorax (2011)

<h3>Background</h3> Venturi masks are commonly used in the hospital setting to deliver controlled percentages of oxygen. This is important for those at risk of hypercapnic respiratory failure and to accurately assess ventilation and gas exchange. Hospital oxygen supplies deliver high velocity and pressure, which are required for Venturi masks to operate as designed. Home oxygen is commonly delivered via concentrators, which work at lower pressures and this may affect the performance of Venturi masks if they are requested for home use. <h3>Aim</h3> We aimed to review the oxygen delivered by the concentrator and the performance of Venturi barrels (24%, 28% 31% and 35%) with the Intensity concentrator at the usual flow rates used. <h3>Methods</h3> Venturi barrels from the three manufacturers were tested using a TSI® Certifier® FA Test system, pressure gauge, flow metre and oxygen sensor. The Intensity concentrator was set at the specified flow rate and allowed to stabilise, oxygen concentration and outlet pressure were noted. We attached the Venturi barrels and recorded the flow rate, back pressure and delivered oxygen concentration. If the Venturi under performed we adjusted the concentrator to deliver the stated FiO2 and noted the flow rate required. <h3>Results</h3> The concentrator delivered between 95.8 % and 84.7% oxygen, with concentration reducing at higher flows (see Abstract P139 table 1). Most Venturi barrels delivered a lower FiO2 than intended. Those closest to the desired FiO2 were designed to work at higher flow rates. The 24% Venturi barrels caused significant back pressure which reduced delivered FiO2 and caused the concentrator to alarm. <h3>Conclusions</h3> Venturi barrels used with oxygen concentrators in the home are likely to deliver a lower oxygen concentration than expected and are unlikely to lead to hypercapnic respiratory failure. For a controlled FiO2 to be delivered, the chosen concentrator and Venturi need to be tested so flow rate can be set accordingly but concentrators alarm systems may prevent practical use.
A Regulatory Loop Involving miR-22, Sp1, and c-Myc Modulates CD147 Expression in Breast Cancer Invasion and Metastasis
Authors: Ling-Min Kong, Cheng-Gong Liao, Yang Zhang, Jing Xu, Yu Li, Wan Huang, Yi Zhang, Huijie Bian, Zhi-Nan Chen
Journal: Cancer Research (2014)

Abstract Breast cancer is the most common cancer in women for which the metastatic process is still poorly understood. CD147 is upregulated in breast cancer and has been associated with tumor progression, but little is known about its regulatory mechanisms. In this study, we demonstrated that CD147 was overexpressed in breast cancer tissues and cell lines, and the high expression correlated with tumor invasion and metastasis. We also found that the transcription factors Sp1 and c-Myc could bind to the CD147 promoter and enhance its expression. The CD147 mRNA has a 748-bp 3′-untranslated region (UTR) with many miRNA target sites, suggesting possible regulation by miRNAs. We discovered that miR-22 repressed CD147 expression by directly targeting the CD147 3′UTR. We also determined that miR-22 could indirectly participate in CD147 modulation by downregulating Sp1 expression. miR-22 could form an autoregulatory loop with Sp1, which repressed miR-22 transcription by binding to the miR-22 promoter. Together with the c-Myc–mediated inhibition of miR-22 expression, our investigation identified a miR-22/Sp1/c-Myc network that regulates CD147 gene transcription. In addition, miR-22 overexpression suppressed breast cancer cell invasion, metastasis, and proliferation by targeting CD147 in vitro and in vivo. Furthermore, we found that miR-22 was significantly downregulated in breast cancer tissues and that its expression was inversely correlated with the tumor–node–metastasis stage and lymphatic metastasis in patients. Our study provides the first evidence that an miR-22/Sp1/c-Myc network regulates CD147 upregulation in breast cancer and that miR-22 represses breast cancer invasive and metastatic capacities. Cancer Res; 74(14); 3764–78. ©2014 AACR.
Neoadjuvant treatment with docetaxel plus lapatinib, trastuzumab, or both followed by an anthracycline-based chemotherapy in HER2-positive breast cancer: results of the randomised phase II EORTC 10054 study
Authors: H. Bonnefoi, W. Jacot, M. Saghatchian, C. Moldovan, L. Venat-Bouvet, K. Zaman, E. Matos, T. Petit, A. Bodmer, N. Quenel-Tueux, C. Chakiba, P. Vuylsteke, G. Jerusalem, E. Brain, O. Tredan, C.G.M. Messina, L. Slaets, D. Cameron
Journal: Annals of Oncology (2014)
Prevalence, Awareness, Treatment, and Control of Hypertension in China
Authors: Yangfeng Wu, Rachel Huxley, Liming Li, Vibeke Anna, Gaoqiang Xie, Chonghua Yao, Mark Woodward, Xian Li, John Chalmers, Runlin Gao, Lingzhi Kong, Xiaoguang Yang
Journal: Circulation (2008)

Background— The present article aims to provide accurate estimates of the prevalence, awareness, treatment, and control of hypertension in adults in China. Methods and Results— Data were obtained from sphygmomanometer measurements and an administered questionnaire from 141 892 Chinese adults ≥18 years of age who participated in the 2002 China National Nutrition and Health Survey. In 2002, ≈153 million Chinese adults were hypertensive. The prevalence was higher among men than women (20% versus 17%; P &lt;0.001) and was higher in successive age groups. Overall, the prevalence of hypertension was higher in urban compared with rural areas in men (23% versus 18%; P &lt;0.01) and women (18% versus 16%; P &lt;0.001). Of the 24% affected individuals who were aware of their condition, 78% were treated and 19% were adequately controlled. Despite evidence to suggest improved levels of treatment in individuals with hypertension over the past decade, compared with estimates from 1991, the ratio of controlled to treated hypertension has remained largely unchanged at 1:4. Conclusions— One in 6 Chinese adults is hypertensive, but only one quarter are aware of their condition. Despite increased rates of blood pressure–lowering treatment, few have their hypertension effectively controlled. National hypertension programs must focus on improving awareness in the wider community, as well as treatment and control, to prevent many tens of thousands of cardiovascular-related deaths.
Effect of somatostatin on the sphincter of Oddi in patients with acute non-biliary pancreatitis
Authors: K-H Lai
Journal: Gut (2001)

<h3>BACKGROUND</h3> Somatostatin has been used to prevent pancreatitis after endoscopic retrograde cholangiopancreatography but its effect on acute non-biliary pancreatitis is still unclear. <h3>AIM</h3> The purpose of this study was to evaluate the function of the sphincter of Oddi (SO) and the effect of somatostatin on patients with non-biliary pancreatitis. <h3>METHODS</h3> Twenty patients (18 males, two females) with acute pancreatitis (alcoholic 18, idiopathic two) received SO manometry within one week after admission. After baseline measurement, a bolus dose of somatostatin (Stilamin, Serono) 250 μg was infused slowly, and SO manometry was repeated after five minutes. Continuous infusion of somatostatin 250 μg/h was given for 12 hours after SO manometry. Serum amylase, lipase, glucose, and C reactive protein (CRP) levels were examined before and after somatostatin infusion. <h3>RESULTS</h3> SO manometry was unsuccessful in six patients due to contracted sphincter. In the remaining 14 patients, high SO basal pressure (SOBP &gt;40 mm Hg) was found in seven patients. After somatostatin infusion, mean SOBP decreased from 48.8 (29) to 31.9 (22) mm Hg (p&lt;0.01). One patient had a paradoxical reaction to somatostatin (SOBP increased from 30 to 50 mm Hg) while the other 13 patients had a fall in SOBP after somatostatin. One patient developed abdominal pain with a serum amylase level of 2516 IU/l after SO manometry. No other side effects or changes in amylase, lipase, glucose, or CRP levels were observed in the other 19 patients after SO manometry and somatostatin infusion. <h3>DISCUSSION</h3> Sphincter of Oddi dysfunction is common in patients with acute non-biliary pancreatitis and in most cases somatostatin can relax the sphincter.
Letter: Aetiology of chronic renal failure and renal osteodystrophy.
Authors: J A Kanis, R G Henderson, J G Ledingham
Journal: BMJ (1975)

Patients ToxicNon-toxic Controls (n = 9) (n = 71) (n = 22) Plasma digoxin 2-91 i 090 1-42 ±0-82 (nmol/l) Plasma magnesium 0-885 ± 011 0-83 ± 011 0-855 0-06 (mmol/l) Erythrocyte magnesium 2-215 0-345 2-32 ± 0-365 2-085 0-225 (mmol/l) Conversion: SI to Traditional Units-Plasma digoxin: 1 nmol/l 0-78 ng/ml.Plasma and erythrocyte magnesium: 1 mmol/l 2 mEq/l.
The arm-ankle pressure gradient in relation to cardiovascular risk factors in intermittent claudication.
Authors: L Janzon, S E Bergentz, B F Ericsson, S E Lindell
Journal: Circulation (1981)

The arm-ankle systolic pressure gradient was measured in 165 male patients with intermittent claudication and was correlated with different combinations of known cardiovascular risk factors. The pressure gradient increased with increasing number of risk factors. We conclude that intermittent claudication may be used as a simple model for studies of arteriosclerosis, the arm-ankle systolic pressure gradient being a measure of the degree of arteriosclerosis between heart and ankle.
International Funding for Malaria Control in Relation to Populations at Risk of Stable Plasmodium falciparum Transmission
Authors: Robert W Snow, Carlos A Guerra, Juliette J Mutheu, Simon I Hay
Journal: PLoS Medicine (2008)

Background The international financing of malaria control has increased significantly in the last ten years in parallel with calls to halve the malaria burden by the year 2015. The allocation of funds to countries should reflect the size of the populations at risk of infection, disease, and death. To examine this relationship, we compare an audit of international commitments with an objective assessment of national need: the population at risk of stable Plasmodium falciparum malaria transmission in 2007. Methods and Findings The national distributions of populations at risk of stable P. falciparum transmission were projected to the year 2007 for each of 87 P. falciparum–endemic countries. Systematic online- and literature-based searches were conducted to audit the international funding commitments made for malaria control by major donors between 2002 and 2007. These figures were used to generate annual malaria funding allocation (in US dollars) per capita population at risk of stable P. falciparum in 2007. Almost US$1 billion are distributed each year to the 1.4 billion people exposed to stable P. falciparum malaria risk. This is less than US$1 per person at risk per year. Forty percent of this total comes from the Global Fund to Fight AIDS, Tuberculosis and Malaria. Substantial regional and national variations in disbursements exist. While the distribution of funds is found to be broadly appropriate, specific high population density countries receive disproportionately less support to scale up malaria control. Additionally, an inadequacy of current financial commitments by the international community was found: under-funding could be from 50% to 450%, depending on which global assessment of the cost required to scale up malaria control is adopted. Conclusions Without further increases in funding and appropriate targeting of global malaria control investment it is unlikely that international goals to halve disease burdens by 2015 will be achieved. Moreover, the additional financing requirements to move from malaria control to malaria elimination have not yet been considered by the scientific or international community.
Atherosclerosis in Marek's disease virus infected hypercholesterolemic roosters is reduced by HMGCoA reductase and ACE inhibitor therapy
Authors: A Lucas
Journal: Cardiovascular Research (1998)

Objective: Accelerated atherosclerosis is associated with herpesviral infection both in transplant patients and after balloon angioplasty. Marek's disease virus (MDV) is a herpesvirus that induces accelerated atherosclerosis associated with the development of an invasive lymphoma in hyperlipemic roosters. We have examined the effects of pravastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase inhibitor and quinapril, an angiotensin converting enzyme (ACE) inhibitor, on atherosclerosis development in MDV infected, cholesterol fed rooster chicks. Methods: The effects of these drugs on plaque growth after MDV infection were examined in two studies. In Study 1, MDV infected White Leghorn rooster chicks were divided into 4 groups assigned to normal or high cholesterol diet, and treated at three months of age with either pravastatin or saline. In Study 2, cholesterol fed rooster chicks infected with MDV were divided into 3 groups for treatment with either pravastatin, quinapril, or saline control. Results: A significant decrease in plaque area was detected after 60 days of treatment with both pravastatin and quinapril in cholesterol fed chicks (P<0.001). Lymphocyte infiltration into the arterial wall or target organs was not inhibited by treatment with either drug. Conclusions: (1) HMGCoA reductase inhibitor and ACE inhibitor therapy reduce atherosclerosis induced by virus infection and cholesterol diet, but this decrease in plaque growth is not due to a reduction in lymphocyte invasion. (2) MDV infection in cholesterol fed roosters provides a model for virus-induced arterial injury in atherogenesis.
Stem Cells Probed as Diabetes Treatment
Authors: Tracy Hampton
Journal: JAMA (2006)

New York City—While an autoimmune disease of any type is a serious condition that is often difficult to treat, finding a cure for type 1 diabetes is particularly daunting because of the nature of the pancreas and its insulinproducing beta cells. “The pancreas is pathetic at regeneration,” said Douglas Melton, PhD, of the Harvard Stem Cell Institute at Harvard University, in Cambridge, Mass. Thus, finding a way to generate beta cells poses a difficult challenge for researchers. The promise and shortcomings of various options were discussed by Melton and others at the New York Stem Cell Foundation’s recent Translat ional Stem Cell Research Conference.
Effect of Pravastatin sodium, a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on very-low-density lipoprotein composition and kinetics in hyperlipidemia associated with experimental nephrosis
Authors: Tsutomu Hirano, Fumiko Komuro, Seiich Furukawa, Seishi Nagano, Terumi Takahashi
Journal: Metabolism (1990)
Regulation of net bicarbonate transport in rabbit cortical collecting tubule by peritubular pH, carbon dioxide tension, and bicarbonate concentration.
Authors: M D Breyer, J P Kokko, H R Jacobson
Journal: Journal of Clinical Investigation (1986)

The effects of changes in peritubular pH, carbon dioxide tension (PCO2), and HCO3- concentration on net HCO3- transport was examined in in vitro perfused cortical collecting tubules (CCTs) from unpretreated New Zealand white rabbits. Lowering peritubular HCO3- concentration and pH by reciprocal replacement of HCO3- with Cl-, significantly stimulated net HCO3- absorption. Lowering peritubular HCO3- concentration and pH, by substitution of HCO3- with gluconate, while keeping Cl- concentration constant, also stimulated net HCO3- absorption. Raising peritubular HCO3- concentration and pH, by reciprocal replacement of Cl- with HCO3-, inhibited net HCO3- absorption (or stimulated net HCO3- secretion). When the tubule was cooled, raising peritubular HCO3- concentration had no effect on net HCO3- transport, suggesting these results are not due to the passive flux of HCO3- down its concentration gradient. The effect of changes in ambient PCO2 on net HCO3- transport were also studied. Increasing the ambient PCO2 from 40 mmHg to either 80 or 120 mmHg, allowing pH to fall, had no effect on net HCO3- transport. Similarly, lowering ambient PCO2 to 14 mmHg had no effect on net HCO3- transport. Simultaneously increasing peritubular HCO3- concentration and PCO2, without accompanying changes in peritubular pH, i.e., isohydric changes, stimulated net HCO3- secretion to the same degree as nonisohydric increases in peritubular HCO3- concentration. Likewise, isohydric lowering of peritubular HCO3- concentration and PCO2 stimulated net HCO3- absorption. We conclude that: acute changes in peritubular HCO3- concentration regulate acidification in the CCT and these effects are mediated by a transcellular process; acute changes in ambient PCO2 within the physiologic range have no effect on HCO3- transport in the in vitro perfused CCT; and acute in vitro regulation of CCT acidification is independent of peritubular pH.
Non-attendance or non-invitation? A case-control study of failed outpatient appointments.
Authors: S. Frankel, A. Farrow, R. West
Journal: BMJ (1989)

OBJECTIVE--To determine the causes of non-attendance at new outpatient appointments. DESIGN--Case-control study of non-attenders and attenders. SETTING--Outpatient department of a general hospital. SUBJECTS--All non-attenders (n = 277) for first outpatient appointments in six specialties during a three month period were included. Controls (n = 135) were the attenders who followed every second non-attender; thus they attended the same consultant on the same day that the non-attenders were expected. INTERVENTIONS--None. MEASUREMENTS AND MAIN RESULTS--Information on the clinical problem, difficulties in attending the hospital, and reasons for non-attendance from the questionnaire were coded and classified. Non-attenders had received shorter notice of their appointment than attenders (14% v 1% had received three days9 notice or less). There were small differences in the seriousness of patients9 clinical condition. CONCLUSIONS--Client factors are less important than aspects of the service in explaining non-attendance at outpatient appointments.
Urinary cyclic AMP analyzed as a function of the serum calcium and parathyroid hormone in the idfferential diagnosis of hypercalcemia.
Authors: J W Shaw, S B Oldham, L Rosoff, J E Bethune, M P Fichman
Journal: Journal of Clinical Investigation (1977)

Urinary cyclic AMP (UcAMP) appropriate for the serum calcium concentration was determined in normal subjects during the base-line state and during alteration in their serum calcium concentrations by saline and calcium infusions. This was compared to the UcAMP in 76 patients with hypercalcemia and 5 patients with hypocalcemia. In 54 of 56 patients with primary hyperparathyroidism, the UcAMP was inappropriately high for their serum calcium concentration, the 2 exceptions having renal failure. In four patients with vitamin D intoxication, sarcoidosis, milkalkali syndrome, and thiazide-induced hypercalcemia and in five patients with hypocalcemia due to hypoparathyroidism, the UcAMP was appropriately low for their serum calcium concentration. In 16 patients with nonparathyroid neoplasms, 10 had UcAMP levels that were inappropriately high suggesting ectopic parathyroid hormone (PTH)-mediated hypercalcemia and 6 had UcAMP levels that were appropriately low suggesting that their hypercalcemia was due to osteolytic factors other than PTH. Correlations between UcAMP, serum calcium concentration, and carboxyl-terminal immunoreactive PTH suggest that random UcAMP is a sensitive accurate reflection of circulating biologically active PTH. If there is adequate renal function (serum creatinine concentration less than 2.0 mg/dl), a random UcAMP expressed as mumol/g creatinine and analyzed as a function of the serum calcium concentration completely separates patients with PTH and non-PTH-mediated hypercalcemia.
UK government supports measures to cut drug prices in developing countries
Authors: S. Mayor
Journal: BMJ (2003)

The UK government has given qualified support to measures that could lift barriers to providing cheaper generic drugs in developing countries, in a response announced last week to a report on intellectual property.

The government agreed that intellectual property rights (such as patents on drugs and manufacturing processes) “can and should be tailored to take into account individual country's circumstances within the framework of international agreements.” However, it said that the use of compulsory licensing—in which countries can import generic drugs …