bluuebunny/crossref_metadata_2025 huggingface dataset:
Health care‐associated infections after major cancer surgery
Authors: Sammon Jesse , Trinh Vincent Q. , Ravi Praful , Sukumar Shyam , Gervais Mai‐Kim , Shariat Shahrokh F. , Larouche Alexandre , Tian Zhe , Kim Simon P. , Kowalczyk Keith J. , Hu Jim C. , Menon Mani , Karakiewicz Pierre I. , Trinh Quoc‐Dien , Sun Maxine
Published: March 2013

BACKGROUND

Approximately 1.7 million individuals per year are affected with health care‐associated infections (HAIs) in the United States. The authors examined trends in the incidence of HAI after major cancer surgery (MCS) and risk factors for HAI to describe the effects of HAI on mortality after MCS.

METHODS

Patients undergoing 1 of 8 MCS procedures within the Nationwide Inpatient Sample between 1999 and 2009 were identified (n = 2,502,686). Generalized linear regression models were used to estimate the impact of the primary predictors (procedure type, age, sex, race, insurance status, Charlson comorbidity index, hospital volume, and hospital bed size) on the odds of HAI and in‐hospital mortality. Trends in incidence were evaluated with linear regression.

RESULTS

Overall, MCS‐associated HAI incidence increased 2.7% per year (P < .001), whereas mortality decreased 1.3% per year (P < .001). Male gender (odds ratio [OR], 1.12, 95% confidence interval [CI], 1.10‐1.14), advancing age (OR, 1.02; 95% CI, 1.02‐1.02), black race (OR, 1.26; 95% CI, 1.21‐1.31), ≥1 comorbidities (OR, from 1.08 [95% CI, 1.04‐1.13] to 1.31 [95% CI, 1.27‐1.35]), and nonprivate insurance (OR, from 1.18 [95% CI, 1.15‐1.22] to 1.67 [95% CI, 1.59‐1.76]) were associated with an increased odds of HAI on multivariable analysis. Conversely, increasing hospital volume was associated with lower odds of HAI (OR, 0.999; 95% CI, 0.99‐0.99). Patients with MCS‐associated HAI had increased odds of mortality (OR, 8.66; 95% CI, 8.51‐8.82).

CONCLUSIONS

Between 1999 and 2009, the incidence of MCS‐associated HAI events increased; however, HAI‐associated mortality decreased. That said, significant disparities exist in the hospital and demographic attributes associated with MCS‐associated HAI, with attendant health policy implications. Moreover, HAI remains detrimentally linked to mortality during hospitalization. Cancer 2013;119:2317–2324. © 2013 American Cancer Society.
Improvement of Solar Energy Conversion with Nb‐Incorporated TiO2 Hierarchical Microspheres
Authors: Hoang Son , Ngo Thong Q. , Berglund Sean P. , Fullon Raymond R. , Ekerdt John G. , Mullins C. Buddie
Published: March 2013

Niobium‐modified TiO2 hierarchical spherical micrometer‐size particles, which consist of many nanowires, are synthesized by solvothermal synthesis and studied as photoelectrodes for water photo‐oxidation and dye‐sensitized solar cell (DSSC) applications. Incorporation of Nb leads to a rutile‐to‐anatase TiO2 phase transition in the TiO2 hierarchical spheres (HSs), with the anatase percentage increasing from 0 % for the pristine TiO2 HSs to 47.6 % for the 1.82 at. % Nb‐incorporated TiO2 sample. Incorporation of Nb leads to significant improvements in water photo‐oxidation with the photocurrents reaching 70.5 μA cm−2 at 1.23 V versus the reversible hydrogen electrode, compared with 28.3 μA cm−2 for the pristine TiO2 sample. The photoconversion efficiency of Nb:TiO2 HS‐based DSSCs reaches 6.09±0.15 % at 0.25 at. % Nb, significantly higher than that for the pristine TiO2 HS cells (3.99±0.02 %). In addition, the incident‐photon‐to‐current efficiency spectra for DSSCs show that employing TiO2 and Nb:TiO2 HSs provides better light harvesting, especially of long‐wavelength photons, than anatase TiO2 nanoparticle‐based DSSCs.
Intensive Protein Digestion Using Cross‐Linked Trypsin Aggregates in Proteomics Analysis
Authors: Wang Meng‐Fan , Mu Yang‐Yang , Qi Wei , Su Rong‐Xin , He Zhi‐Min
Published: March 2013

In this study, cross‐linked enzyme aggregates of tissue‐culture‐grade trypsin (CLEAs‐T) were prepared and introduced to the proteomics analysis instead of the expensive proteomics‐grade trypsin, which benefits from the protein purification during the preparation of the CLEAs. Bovine serum albumin, lysozyme, bovine hemoglobin, and α‐casein were used as model proteins, and three intensive strategies (high‐enzyme‐concentration, high‐temperature, and ultrasound‐assisted digestion) were applied to the rapid and efficient digestion of model proteins by CLEAs‐T. The peptide fragments were then identified by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry, which revealed the higher sequence coverage and sharply reduced digestion time of these strategies compared with the conventional in‐solution 12 h digestion method. Morphology studies demonstrated that the excellent performance of CLEAs‐T in proteomics analysis came from the “scaffoldlike” supermolecular structure, which provided a high resistance to the autolysis and denaturation of trypsin under high‐enzyme‐concentration, high‐temperature, and ultrasound‐assisted digestion.
Direct Fluorination of Cyclic Carbonates and closo‐K2[B12H12] in a Slug‐Flow Ministructured Reactor
Authors: Hill Mathias , Baron Patrick , Cobry Keith , Goll Sascha K. , Lang Philipp , Knapp Carsten , Scherer Harald , Woias Peter , Zhang Pengcheng , Krossing Ingo
Published: March 2013

Invited for this month’s cover are the groups of Prof. Ingo Krossing and Prof. Peter Woias based at Albert‐Ludwigs‐Universität Freiburg as well as Prof. Carsten Knapp who is now at Bergische Universität Wuppertal. The background of the cover picture shows the Rhine Falls (Schaffhausen, Switzerland), which is the largest waterfall in Europe and only one hour away from the laboratories in Freiburg. The waterfall symbolizes flow chemistry and the wild nature of direct fluorination reactions.
Normalization of mass cytometry data with bead standards
Authors: Finck Rachel , Simonds Erin F. , Jager Astraea , Krishnaswamy Smita , Sachs Karen , Fantl Wendy , Pe'er Dana , Nolan Garry P. , Bendall Sean C.
Published: March 2013

Mass cytometry uses atomic mass spectrometry combined with isotopically pure reporter elements to currently measure as many as 40 parameters per single cell. As with any quantitative technology, there is a fundamental need for quality assurance and normalization protocols. In the case of mass cytometry, the signal variation over time due to changes in instrument performance combined with intervals between scheduled maintenance must be accounted for and then normalized. Here, samples were mixed with polystyrene beads embedded with metal lanthanides, allowing monitoring of mass cytometry instrument performance over multiple days of data acquisition. The protocol described here includes simultaneous measurements of beads and cells on the mass cytometer, subsequent extraction of the bead‐based signature, and the application of an algorithm enabling correction of both short‐ and long‐term signal fluctuations. The variation in the intensity of the beads that remains after normalization may also be used to determine data quality. Application of the algorithm to a one‐month longitudinal analysis of a human peripheral blood sample reduced the range of median signal fluctuation from 4.9‐fold to 1.3‐fold. © 2013 International Society for Advancement of Cytometry
Facing the crowd: intruder pressure, within‐group competition, and the resolution of conflicts over group‐membership
Authors: Port Markus , Johnstone Rufus A.
Published: March 2013

Recent theory in social evolution has been mainly concerned with competition and cooperation within social groups of animals and their impact on the stability of those groups. Much less attention has been paid to conflicts arising as a result of solitary floaters (outsiders) attempting to join groups of established residents (insiders). We model such conflicts over group‐membership using a demographically explicit approach in which the rates of births and deaths in a population determine the availability of group‐vacancies and the number of floaters competing over these vacancies. We find that the outcome of within‐group competition, reflected in the partitioning of reproduction among group members, exerts surprisingly little influence on the resolution of insider‐outsider conflict. The outcome of such conflict is also largely unaffected by differences in resource holding potential between insiders and outsiders. By contrast, whether or not groups form is mainly determined by demographic factors (variation in vital rates such as fecundity and mortality) and the resulting population dynamics. In particular, at high floater densities territory defense becomes too costly, and groups form because insiders give in to the intruder pressure imposed on them by outsiders. We emphasize the importance of insider‐outsider conflicts in social evolution theory and highlight avenues for future research.
Estimating the water balance of a thermokarst lake in the middle of the Lena River basin, eastern Siberia
Authors: Fedorov A. N. , Gavriliev P. P. , Konstantinov P. Y. , Hiyama T. , Iijima Y. , Iwahana G.
Published: March 2013

Permafrost degradation and changes in water balance in a thermokarst lake in the middle part of the Lena River basin in eastern Siberia were investigated. We analysed the role of permafrost thawing in the water balance of a growing thermokarst lake. Long‐term observations during the last two decades (1992–2008) at our thermokarst monitoring site, Yukechi, showed significant modifications of the landforms. Observations included ground temperature, thawing depth, soil moisture content in the active layer, surface subsidence rate, and ecological changes in the surrounding environment. We also used data obtained at the Yakutsk weather station to estimate the potential evaporation. During the observation period, the water surface area increased steadily from 195 m2 in 1993 to 3135 m2 in 2008, and the lake water increased from 33·7 m3 in 1993 to 3503 m3 in 2008. Water balance estimations showed that ground ice melt made up to one third of the total water input into the lake. The rapid development of growing thermokarst lakes indicates an ecological risk on the edges of cryogenic landscapes. Finally, we found that climate change and anthropogenic impacts have led to enhanced activity of cryogenic processes in the region. In particular, cultivated fields underlying ice‐rich permafrost face enhanced degradation by cryogenic and hydrological processes because of recent climate change in the region. Copyright © 2013 John Wiley & Sons, Ltd.
Oligo(naphthylene–ethynylene) Molecular Rods
Authors: Cramer Jacob R. , Ning Yanxiao , Shen Cai , Nuermaimaiti Ajiguli , Besenbacher Flemming , Linderoth Trolle R. , Gothelf Kurt V.
Published: March 2013

Molecular rods designed for surface chirality studies have been synthesized in high yields. The molecules are composed of oligo(naphthylene–ethynylene) skeletons and functionalized at their two termini with carboxylic acids and hydrophobic groups. The molecular skeletons were constructed by means of palladium‐catalyzed Sonogashira reactions between naphthyl halides and acetylenes. The triazene functionality was used as a protected iodine precursor to allow linear extension of the molecular rods during the syntheses. The carboxylic acid groups in the target molecules were protected as esters during the synthesis to keep the large aromatic molecules soluble during their syntheses. These rigid oligomers were designed to form lamella‐like structures when adsorbed on a surface, through which multiple distinguishable surface conformations should be obtainable. Preliminary scanning tunneling microscopy imaging confirmed these properties.
An Efficient Formal Total Synthesis of Cladosporin
Authors: Mohapatra Debendra K. , Maity Saurabh , Rao T. Srinivasa , Yadav J. S. , Sridhar B.
Published: March 2013

A highly diasteroselective and efficient approach for the formal total synthesis of cladosporin is described. Cross‐metathesis, iodocyclization to construct the trans‐2,6‐disubstituted dihydropyran ring system, and an Alder–Rickert reaction to form the aromatic ring were used as the key steps.
Controversy Over LNG Exports Heats Up as Production Expands
Authors: Dotten Michael , Till Dustin
Published: March 2013

President Obama is expected to address a broad array of energy and energy‐related policies during his second term—particularly those that relate to the dramatic surge in domestic natural gas and oil production. Not since the first OPEC oil embargo in 1973–74 has the United States been presented with the opportunity to dramatically reduce its dependence on foreign energy suppliers. The United States is projected to become a net exporter of natural gas by 2020.1 America is similarly projected to become the largest global oil producer around 2020, and a net oil exporter by 2030.2
Transmission & Pipelines: Avoidance, Conservation, and Mitigation of Biological Resources on Linear Projects
Authors: Rowland Scott , Lambert Dean
Published: March 2013

There are many factors to be considered during the process of determining the best route for a linear project to most effectively link a generation facility or resource extraction site to a market or end‐user.
Electric Regulation: Renewable Incentives Have Led to Job Creation
Authors: Bowden Nicholas S.
Published: March 2013

Job creation appears to be priority number one for the Obama administration in its second term, and investments in renewable electricity infrastructure are seen as a means to achieve this goal while also meeting social concerns about the environment. In order to continue federal government support for these investments, the American Taxpayer Relief Act of 2012 extended the production tax credit (PTC) for utility‐scale wind farms.
Energy and the Environment: A Fractured Europe Debates Fracking
Authors: Lesser Jonathan A.
Published: March 2013

The United States is not the only country with shale gas reserves. According to a 2011 report prepared by the US Energy Information Administration (EIA),1 Europe, most of which is beholden to Russia for its natural gas supplies, has perhaps 600 trillion cubic feet of technically recoverable shale gas reserves. In comparison, that same report estimated US shale gas reserves at 862 trillion cubic feet. Of the 14 countries the EIA report evaluated, Poland and France have the largest estimated reserves by far, at 187 trillion cubic feet and 180 trillion cubic feet, respectively.
Characteristics of magma‐driven hydrothermal systems at oceanic spreading centers
Authors: Lowell Robert P. , Farough Aida , Hoover Joshua , Cummings Kylin
Published: March 2013

We use one‐ and two‐limb single‐pass models to de termine vent field characteristics such as mass flow rate Q, bulk permeability in the discharge zone kd, thickness of the conductive boundary layer at the base of the system δ, magma replenishment rate, and residence time in the discharge zone. Data on vent temperature, vent field area, heat output, and the surface area and depth of the subaxial magma chamber (AMC) constrain the models. The results give Q ~ 100 kg/s, kd ~ 10−13 m2, and δ ~ 10 m, essentially independent of spreading rate, and detailed characteristics of the AMC. In addition, we find no correlation between heat output at individual vent fields and spreading rate or depth to the AMC. We conclude that high‐temperature hydrothermal systems are driven by local magma supply rates in excess of that needed for steady state crustal production and that crustal permeability enables hydrothermal circulation to tap magmatic heat regardless of AMC depth. Using data on partitioning of heat flow between focused and diffuse flow, we find that 80–90% of the hydrothermal heat output is derived from high‐temperature fluid, even though much of the heat output discharges as low‐temperature fluid. In some cases, diffuse flow fluids may exhibit considerable conductive cooling or heating. By assuming conservative mixing of diffuse flow fluids at East Pacific Rise 9°50′N, we find that most transport of metals such as Fe and Mn occurs in diffuse flow and that CO2, H2, and CH4 are taken up by microbial activity.
Hepatocyte Divalent Metal-Ion Transporter-1 Is Dispensable for Hepatic Iron Accumulation and Non-Transferrin-Bound Iron Uptake in Mice
Authors: Wang Chia-Yu , Knutson Mitchell D.
Published: March 2013

Divalent metal-ion transporter-1 (DMT1) is required for iron uptake by the intestine and developing erythroid cells. DMT1 is also present in the liver, where it has been implicated in the uptake of transferrin-bound iron (TBI) and non-transferrin-bound iron (NTBI), which appears in the plasma during iron overload. To test the hypothesis that DMT1 is required for hepatic iron uptake, we examined mice with the

Dmt1

gene selectively inactivated in hepatocytes (

Dmt1liv/liv

). We found that

Dmt1liv/liv

mice and controls (

Dmt1flox/flox

) did not differ in terms of hepatic iron concentrations or other parameters of iron status. To determine whether hepatocyte DMT1 is required for hepatic iron accumulation, we crossed

Dmt1liv/liv

mice with

Hfe−

/

−

and hypotransferrinemic (

Trfhpx/hpx

) mice that develop hepatic iron overload. Double-mutant

Hfe−
/
−Dmt1liv/liv

and

Trfhpx/hpx;Dmt1liv/liv

mice were found to accumulate similar amounts of hepatic iron as did their respective controls. To directly assess the role of DMT1 in NTBI and TBI uptake, we injected 59Fe-labeled ferric citrate (for NTBI) or 59Fe-transferrin into plasma of

Dmt1liv/liv

and

Dmt1flox/flox

mice and measured uptake of 59Fe by the liver.

Dmt1liv/liv

mice displayed no impairment of hepatic NTBI uptake, but TBI uptake was 40% lower. Hepatic levels of transferrin receptors 1 and 2 and ZRT/IRT-like protein 14, which may also participate in iron uptake, were unaffected in

Dmt1liv/liv

mice. Additionally, liver iron levels were unaffected in

Dmt1liv/liv

mice fed an iron-deficient diet.

Conclusion

: Hepatocyte DMT1 is dispensable for hepatic iron accumulation and NTBI uptake. Although hepatocyte DMT1 is partially required for hepatic TBI uptake, hepatic iron levels were unaffected in

Dmt1liv/liv

mice, suggesting that this pathway is a minor contributor to the iron economy of the liver. (Hepatology 2013;58:788–798)
Core Self‐Evaluation and Goal Orientation: Understanding Work Stress
Authors: Morris Michael Lane , Messal Carrie B. , Meriac John P.
Published: March 2013

This study investigates the dispositional factors related to work stress. Specifically, previous research has demonstrated a relationship between core self‐evaluation (CSE) and general life stress. This article extends past research by examining the relationship between CSE and work stress, and includes goal orientation as a potential mediator of this relationship. Learning goal orientation and performance goal orientation are two variables that are salient to HRD scholarship interests. The study results supported the hypothesis that CSE is negatively related to work stress, and that performance‐prove goal orientation partially mediates this relationship. Given Russ‐Eft's (2001) call for additional research exploring work stress and learning, and a recent meta‐analysis exploring the relationship between another core personality trait (psychological capital) and work stress (Avey, Reichard, Luthans, & Mhatre, 2011), the results of this study make an important contribution to our understanding of the relationship between core personality traits and work stress research. Furthermore, managers and executive coaches can use the results of this study to develop interventions designed to address the stress‐related problems of individuals and organizations.
Assessment of climate change impacts on river discharge in Japan using the super‐high‐resolution MRI‐AGCM
Authors: Sato Yoshinobu , Kojiri Toshiharu , Michihiro Yuri , Suzuki Yasushi , Nakakita Eiichi
Published: March 2013

To evaluate the impacts of climate change on river discharge, we applied a hydrological simulation to several major river basins in Japan, using a super‐high‐resolution atmospheric general circulation model (AGCM) with a horizontal resolution of about 20 km that was developed by the Meteorological Research Institute (MRI) of the Japan Meteorological Agency. For our analysis, we used two AGCM datasets corresponding to the current climate (1980–1999) and future climate (2080–2099) based on the sea surface temperature ensemble projected by the Coupled Model Intercomparison Project phase 3, assuming the A1B scenario of the Intergovernmental Panel on Climate Change Special Report on Emission Scenarios. River discharge was estimated using a distributed hydrological model that was calibrated in advance with observed river discharge. We investigated the impact of climate change on river discharge by comparing hydrological simulations of current and future climate conditions. The results showed that the latest version of the AGCM (MRI‐AGCM3.2S) performs better hydrological simulations than the previous version (MRI‐AGCM3.1S). Even if the amount of precipitation does not change greatly in the future, river discharges will change significantly as air temperature rises, owing to increased rainfall, decreased snowmelt, and increased evapotranspiration. The impact of climate change on river discharge will become more significant in northern Japan, especially in the Tohoku and Hokuriku regions. Our results imply that the increase in air temperature will have important consequences on the hydrological cycle, particularly in regions where the water supply is currently domi\nated by snowmelt. Copyright © 2013 John Wiley & Sons, Ltd.
Projection of “strong wind” events related to recovery from hypoxia in Tokyo Bay, Japan
Authors: Nakayama Keisuke , Maruya Yasuyuki , Nakaegawa Tosiyuki , Komai Katsuaki , Kokubo Kazuki , Ishida Tetsuya , Okada Tomonari
Published: March 2013

This study describes the projection of sudden recovery from hypoxia in Tokyo Bay. Three different horizontal resolution of the Meteorological Research Institute Atmospheric General Circulation models (with a 20‐km mesh resolution), and eight Coupled Model Intercomparison Project phase 3 (CMIP3 models) outputs were applied to project the occurrence of strong negative (south–west) winds, which enhance rapid recovery from hypoxia in the bay. South–west wind energy, KEw, was successfully reproduced in all models by using bias correction based on a cumulative distribution function from the present day (1980–1998). The MRI‐AGCM3.1S with a 20‐km mesh resolution suggested an increase in the number of days with the square of southwesterly winds > 100 m2 s−2, but the other 10 models showed no significant difference in the future. As a result, it appears likely that recovery from hypoxia will not occur more frequently in the future if we assume that the other meteorological and hydrological conditions remain constant. Copyright © 2013 John Wiley & Sons, Ltd.
Safety and Efficacy of Chronic Therapy with Captopril in Hypertensive Patients: An Update
Authors: WAEBER BERNARD , GAVRAS IRENE , BRUNNER HANS R. , GAVRAS HARALAMBOS
Published: March 2013

Abstract: Captopril, an orally active angiotensin‐converting enzyme inhibitor, has been administered to 81 patients with different types of clinical hypertension. Most of the patients had previously uncontrollable high blood pressure. In order to achieve a satisfactory blood pressure control during long‐term captopril therapy, a concomitant decrease in total body sodium was required in more than half of the patients. During our first two years of clinical experience with this new antihypertensive agent, side effects developed in 46.9 per cent of the patients and necessitated the withdrawal of the drug in 23.4 per cent of all patients. Only a few side effects such as hypotensive or syncopal episodes and cold extremities appeared to be due to the chronic blockade of the renin‐angiotensin system. The most frequent and the most serious adverse reactions such as skin rash, altered taste, pancytopenia, and pemphigus foliaceus seemed to be specifically drug related. The incidence of cutaneous and taste problems was markedly higher in patients with impaired renal function in whom retention of captopril has been previously demonstrated. This suggests that the occurrence of adverse reactions to captopril could be lowered in the future by using smaller daily doses and by titrating them according to the renal function.
Sites and Mechanisms of Action of Diuretics in the Kidney
Authors: PUSCHETT JULES B.
Published: March 2013

Abstract: Utilization of classical clearance methodology for the determination of diuretic mechanism and site of action is based on four kinds of observations: (1) the effects of diuretic agents on the concentrating and diluting mechanism; (2) an analysis of the pattern of anionic excretion produced by the drug; (3) determination of the action of the agent on acid excretion and on acid‐base status; (4) an evaluation of the effects of the diuretic on potassium excretion. Agents (such as acetazolamide) that act in the proximal convoluted tubule cause an enhancement of solute‐free water generation (CH2O), induce a phosphaturia and an increase in bicarbonate excretion, alkalinize the urine, and cause a kaliuresis. Those agents which inhibit sodium chloride transport in the loop of Henle (for example, furosemide and ethacrynic acid) reduce both CH2O and the abstraction of tubular water from the collecting duct (TCH2O). They are the most potent natriuretic agents currently available, causing increments in the excretion of sodium in the urine of 15 to 25 per cent of filtered load. Those drugs which act in the early portion of the distal convolution (the thiazides, metolazone) reduce (CH2O) modestly or not at all and have no effect on TCH2O. They are capable of increasing urinary sodium by 5 to 8 per cent of the filtered load. The special‐purpose agents such as triamterene and spironolactone are only mildly effective as natriuretic agents. While they augment fractional sodium excretion by only 2 to 3 per cent, they are useful because of their capacity to reduce urinary potassium excretion, either by a direct renal tubular effect (triamterene) or by competitive inhibition of aldosterone (spironolactone).
Comparative Efficacy and Safety of Bumetanide and Furosemide in Long‐Term Treatment of Edema Due to Congestive Heart Failure
Authors: DIXON DONALD W. , BARWOLF‐GOHLKE CHRISTA , GUNNAR ROLF M.
Published: March 2013

Abstract: Bumetanide and furosemide were compared for efficacy in reducing edema due to congestive heart failure in 28 patients (21 receiving bumetanide and seven receiving furosemide) in a long‐term study for periods from one week to 18 months. In both groups the patients showed decreases in body weight, abdominal girth, edema, hepatomegaly, blood pressure, and heart rate. Commonly observed decreases frequently achieved statistical significance, more often with bumetanide, but the differences between treatments were rarely statistically significant. Both drugs were generally well tolerated. A breast nodule and gynecomastia were each reported once in the bumetanide group as was gynecomastia in one patient who had been on furosemide, all remotely related to test drugs. Soft stools, flatulence, mild constipation, and diminished vision each reported once in the bumetanide group were judged to be unrelated or remotely related to the drug therapy. Tendencies toward hypokalemia, hypochloremia, alkalosis, and hyperuricemia without clinical gout were deemed the result of the pharmacologic action of the diuretics. Others were attributable to the underlying disease state of these patients. Both diuretics proved to be effective in the treatment of cardiac edema and other manifestations of heart failure. Bumetanide treatment beyond six months in 11 patients indicated continued safety as well as efficacy.
Clinical Trial of Bumetanide Versus Furosemide in Patients with Congestive Heart Failure
Authors: KONECKE LEE L.
Published: March 2013

Abstract: A clinical trial was conducted in open, randomized, parallel fashion to determine the effectiveness and safety of bumetanide compared with those of furosemide in 42 outpatients with edema due to congestive heart failure. All patients were free from any significant hepatic or renal disease. The duration of the study was six months, except for 12 patients who were continued under treatment with bumetanide for an additional six months. Changes in body weight, edema, abdominal girth, hepatomegaly and other signs of congestive heart failure were evaluated. No statistically significant differences between bumetanide and furosemide were noted in these clinical parameters. Blood pressure was decreased in both groups, more consistently with furosemide, but without statistical significance. Laboratory tests revealed only minor changes in serum sodium, potassium, chloride, and uric acid in both groups throughout the treatment period, with the exception of chloride in the bumetanide group at 8 and 16 weeks. The patients who received extended treatment maintained a relatively stable state. No clinical adverse reactions were considered to be related to either drug. Both diuretics proved equally effective in reducing edema. The effective dose ratio of bumetanide:furosemide was 1:25.
Bumetanide in Refractory Ascites of Cirrhosis of the Liver: A Comparison with Furosemide
Authors: IBER FRANK L. , BAUM RICHARD A.
Published: March 2013

Abstract: Bumetanide and furosemide were compared in the treatment of resistant ascites in patients with liver disease of alcoholic origin. In a prospective randomized trial, no significant difference was found in the ability of these two agents to promote natriuresis or diuresis. The duration of action was 12 hours for bumetanide and 6 hours for furosemide, but this difference was of no clinical significance.
Gastroscopic Evaluation of the Effect of Aspirin and Oxaprozin on the Gastric Mucosa
Authors: LANZA FRANK L. , HUBSHER JEROME A. , WALKER BARRY R.
Published: March 2013

Abstract: Oxaprozin, a new long‐acting, antiinflammatory agent, and aspirin were compared utilizing gastroscopic evaluation and photography of the gastric mucosa in a double‐blind, crossover study in normal volunteers. Submucosal hemorrhages or mucosal bleeding was observed in seven of eight subjects on aspirin and in only two of eight on oxaprozin (P = 0.061). Adverse effects were experienced by seven of eight subjects after the aspirin treatment period—tinnitus in five and gastrointestinal symptoms in four. Only one patient had mild diarrhea on oxaprozin. The incidence of adverse effects was found significantly higher with aspirin therapy (P < 0.001). No laboratory abnormalities of clinical significance were attributed to either drug administration. Results after ten days of treatment show that oxaprozin in therapeutic dose levels (1200 mg once a day) produces significantly fewer changes in the gastric mucosa than aspirin (975 mg administered four times a day, total daily dose 3.9 Gm) in the same subjects, who received both drugs in this double‐blind, crossover experiment with a four‐week washout period between treatments.
Crossover and Parallel Study of Oral Analgesics
Authors: WANG RICHARD I. H. , WAITE ELIZABETH
Published: March 2013

Abstract: Ten years ago, analgesics were studied using crossover designs. In recent years, analgesics have been studied only in parallel designs primarily because biostatisticians do not like crossover studies. The advantages of crossover studies are numerous: (1) patients serve as their own control; (2) there is less variability of responses among patients; and (3) a smaller number of patients is needed to provide statistically significant data. As long as crossover of treatment medications does not occur within 4 to 6 hours, the problem of carryover effect of the previous medication is insignificant or negligible. Two studies will be presented. One is a crossover study of Percodan with and without naloxone to placebo. The other is a parallel study comparing the effects of propoxyphene with naloxone to those of propoxyphene alone. The results of these studies reaffirm the value of the crossover method of evaluating analgesics.
Dose‐Response Study of Prazosin in Raynaud's Phenomenon: Clinical Effectiveness Versus Side Effects
Authors: Wollersheim Hub , Thien Theo
Published: March 2013

In a dose‐response study of prazosin in 24 patients with Raynaud's phenomenon, the clinical effectiveness and side effects of 3, 6, and 12 mg prazosin administered daily were compared. Diary analysis and measurement of finger skin blood flow and temperature before, during, and after cold challenge showed no major differences among these three dose regimens. Standing systolic blood pressure decreased significantly during the 12‐mg period in comparison with the 6‐mg (P < .05) and with the 3‐mg period (P < .02), whereas heart rate increased in the 6‐mg and 3‐mg periods (P < .05). In the higher dosage ranges, spontaneous mentioned side effects were noticed most often, which was in accordance with the results of a checklist analysis on adverse effects. Three patients withdrew from the study because of complaints that might be due to orthostatic hypotension. Most patients that wanted to continue prazosin after this study (n = 13) did so on a 3‐mg basis (n = 10). Because prazosin 3 mg daily is more effective in treating of Raynaud's phenomenon than is placebo, the study shows that in a dosage of 3 mg daily, the best balance between clinical effectiveness and side effects is obtained.
The Hemodynamic Effects of Intravenous Ranitidine in Intensive Care Unit Patients: A Double‐Blind Prospective Study
Authors: Onofrey David , Kelly Kathleen M. , Gentili David R. , Benjamin Ernest , Iberti Thomas J.
Published: March 2013

The hemodynamic effects of intravenous ranitidine were studied in a prospective double‐blind fashion in postoperative intensive care unit patients to determine if this H2 blocker produced the same transient fall in mean arterial pressure and systemic vascular resistance known to occur with cimetidine infusion. We found no statistically significant hemodynamic changes from baseline associated with infusion of 50 mg ranitidine over a 5‐minute period. The different chemical ring structure of ranitidine and its effect on H2 vascular and cardiac receptors may account for these observations.
Drug‐Induced Parenchymal Renal Disease in Outpatients
Authors: Beard Keith , Perera David R. , Jick Hershel
Published: March 2013

Hospitalizations for patients with newly diagnosed renal disease were reviewed for the period 1972 to 1983 at Group Health Cooperative of Puget Sound to identify those instances where the renal disease might have been caused by a drug(s). After careful review of 496 admissions, only nine instances were found in which a drug etiology of the renal disease could not be safely ruled out on a case history basis. From this study, it is estimated that the frequency of newly diagnosed, outpatient drug‐induced renal disease requiring hospitalization is rare, on the order of one per 300,000 persons per year.
An Examination of the Site and Mechanism of Action of Torasemide in Man
Authors: Lupinacci Lillian , Puschett Jules B.
Published: March 2013

Acute clearance studies were performed in normal subjects to determine the site and mechanism of action of torasemide (isopropyl‐1‐methyl‐3 phenylamino‐4 pyridil‐3 sul‐phonyl‐3‐urea), a new diuretic agent, in the human kidney. The drug caused no change in glomerular filtration rate or effective renal plasma flow. Sodium excretion rose to 16% of filtered load, whereas there was a chloriuresis of 23%. During maximal water diuresis, the drug caused an increase in urine flow rate and a decrease in solute‐free water clearance. Administration of the drug during hypertonic saline infusion into hydropenic subjects resulted in a marked decrease in water reabsorption from the collecting duct. Torasemide caused no change in phosphate excretion or in the percentage of filtered bicarbonate excreted, nor was urinary pH or net hydrogen ion excretion affected by the drug. The data suggest that the primary site of action of torasemide is the medullary portion of the ascending limb of the loop of Henle.
Antihypertensive Drug Therapy Does Not Perturb the Circadian Blood Pressure Pattern
Authors: Materson Barry J. , Preston Richard A.
Published: March 2013

The literature was reviewed to determine whether failure of older antihypertensive drugs to suppress the early morning increase of blood pressure was responsible, in part, for the less than satisfactory rate of reduction in cardiovascular mortality rates in the United States. The authors found that neither the old nor the new antihypertensive drugs altered the 24‐hour Wood pressure curve pattern, although Jong‐acting drugs did show continued effect at the end of the 24‐hour period when compared with placebo. The efficacy of these drugs most likely lies with their blood pressure lowering and other ancillary effects and not with pattern changes. More importantly, examination of new data (1989) shows that the rate of decline in death due to diseases of the heart has exceeded that for cerebrovascular diseases. Our overall health care effort may be more successful than we thought.
Big Platelets in Hyperlipidemic Patients
Authors: Fuchs J. , Beigel Y. , Green P. , Zlotikamien B. , Davidson E. , Rotenberg Z. , Weinberger I.
Published: March 2013

Both “big” platelets and hyperlipidemia are associated with increased coronary risk. This study was undertaken to search for a possible effect of various hypolipidemic drugs on big platelets. The percentage of big platelets, assessed microscopically, was measured in 66 patients who had hyperlipidemia of various types. Twenty‐seven patients with hypertriglyceridemia were randomly selected to receive either fish oil or placebo in a crossover study. Another group of 39 patients with hypercholesterolemia, among them 13 with heterozygous familial hypercholesterolemia (FH), received lovastatin. The pretreatment level of big platelets was elevated, and similar in all groups: 23.3 ± 12% versus 22 ± 9%, in the fish oil versus placebo group, 19.1 ± 6.3% versus 24 ± 11% in the FH versus non‐FH primary hypercholesterolemia group (reference value, 6.8 ± 3.5%). After treatment, despite the improvement in lipoprotein profile, the percentage of big platelets did not change. The relationship between lipid reduction and big platelets is thus questionable, and necessitates further study.
Comparative Effects of a New Cardioselective Beta‐Blocker Nebivolol and Nifedipine Sustained‐Release on 24‐Hour Ambulatory Blood Pressure and Plasma Lipoproteins
Authors: Lacourcière Yves , Poirier Luc , Lefebvre Jean , Provencher Pierre , Arnott Wendy
Published: March 2013

This double‐blind, parallel‐group study compared the effects of Nebivolol, a novel cardioselective β‐blocker, with those of nifedipine sustained‐release on 24‐hour ambulatory blood pressure and plasma lipoprotein levels. After a washout period of 8 weeks, 51 patients with mild to moderate essential hypertension were randomized to double‐blind treatment with either nebivolol 5 mg once a day (n = 26) or nifedipine sustained‐release 20 mg bid (n = 25) over a period of 12 weeks. Both treatments produced similar and significant (P = .0001) reduction in office blood pressure as well as in 24‐hour, work, awake, and sleep ambulatory blood pressure. The clinical response (diastolic blood pressure < 90 mmHg or decreased by ≥10 mmHg) rate was 69% for nebivolol and 59% for nifedipine, respectively. Moreover, the nebivolol and nifedipine treatment‐induced decreases in mean 24‐hour ambulatory blood pressure were similar to the decreases in clinic blood pressure. Furthermore, the percentages of “blood pressure loads” (awake > 140/90 mmHg and asleep > 120/80 mmHg) were lowered significantly (P = .0001), from 60% to 29% with nebivolol and from 60% to 39% with nifedipine. Mean ambulatory heart rate was reduced (P = .0001) from 79 ± 7 to 68 ± 7 beats/minute during nebivolol therapy and from 80 ± 9 to 79 ± 7 (not significant) with nifedipine. Total plasma cholesterol and low‐density lipoprotein levels decreased significantly (P < .05) by 5 and 8%, respectively, after nebivolol treatment, and each decreased by 3% after nifedipine treatment. The results showed that both drugs controlled blood pressure during the 24‐hour period and seemed devoid of untoward effects on lipid profile.
Effects of a Long‐Term Treatment with Alacepril on Left Ventricular Hypertrophy and Function in Patients with Essential Hypertension
Authors: Sumimoto Takumi , Ochi Takaaki , Hiwada Kunio
Published: March 2013

The authors examined the effects of a long‐term treatment with the angiotensin‐converting enzyme inhibitor, alacepril, with respect to the reversal of left ventricular hypertrophy and the improvement of left ventricular function. Ten uncomplicated essential hypertensive patients with left ventricular hypertrophy, aged 53 ± 8 years, were treated with alacepril alone for 12 months. All patients underwent echocardiography to assess left ventricular dimensions and function before and after the treatment. After the treatment, blood pressure was decreased significantly from 163 ± 14.1/98 ± 4.2 to 142 ± 20.3/86 ± 11.0 mm Hg (each, P < .01), whereas heart rate did not change (66 ± 6 versus 69 ± 8 beats/min). The left ventricular mass index was decreased significantly from 146 ± 27 to 119 ± 29 g/m2 (P < .01). Ejection fraction, fractional shortening, peak shortening rate, and peak lengthening rate all improved significantly after the treatment. There was a significant inverse relationship between fractional shortening and end‐systolic wall stress before the treatment (r = .63, P < .05), and this relationship did not change after the treatment. It is concluded that alacepril improved both left ventricular systolic and diastolic function without causing any consistent augmentation of left ventricular contractility.
Raman spectroscopy of combinatory anticancer drug release from gold nanoparticles inside a single leukemia cell
Authors: Ganbold E.‐O. , Byun J. K. , Lee S. Y. , Joo S.‐W.
Published: March 2013

Combinatory anticancer drug release from gold nanoparticles (AuNPs) in K562 human myeloid leukemia cells was performed using Raman spectroscopy. We fabricated the anticancer drug of imatinib as a BCR‐ABL tyrosine kinase inhibitor on AuNP surfaces along with a transferrin (Tf)‐targeting moiety to treat the leukemia cells. DNA topoisomerase I inhibitor topotecan was also assembled to monitor its fluorescence onto AuNPs. The linker group of 4‐carboxylic benzoic acid was used to conjugate to targeting the Tf protein. Our Raman data indicated that the drug molecules were not detached in the cell culture media but released after treatment with glutathione (2 mM). Intracellular distribution and release of the anticancer drug–AuNP conjugates in K562 cells were examined by both fluorescence microscopy and dark‐field microscopy with surface‐enhanced Raman scattering. Copyright © 2013 John Wiley & Sons, Ltd.
Improved efficiency on editing MRS of lactate and γ‐aminobutyric acid by inclusion of frequency offset corrected inversion pulses at high fields
Authors: Arteaga de Castro C. S. , Boer V. O. , Andreychenko A. , Wijnen J. P. , van der Heide U. A. , Luijten P. R. , Klomp D. W. J.
Published: March 2013

γ‐Aminobutyric acid (GABA) and lactate are metabolites which are present in the brain. These metabolites can be indicators of psychiatric disorders or tumor hypoxia, respectively. The measurement of these weakly coupled spin systems can be performed using MRS editing techniques; however, at high field strength, this can be challenging. This is due to the low available B1+ field at high fields, which results in narrow‐bandwidth refocusing pulses and, consequently, in large chemical shift displacement artifacts. In addition, as a result of the increased chemical shift displacement artifacts and chemical shift dispersion, the efficiency of the MRS method is reduced, even when using adiabatic refocusing pulses. To overcome this limitation, frequency offset corrected inversion (FOCI) pulses have been suggested as a mean to substantially increase the bandwidth of adiabatic pulses. In this study, a Mescher–Garwood semi‐localization by adiabatic selection and refocusing (MEGA‐sLASER) editing sequence with refocusing FOCI pulses is presented for the measurement of GABA and lactate in the human brain. Metabolite detection efficiencies were improved by 20% and 75% for GABA and lactate, respectively, when compared with editing techniques that employ adiabatic radiofrequency refocusing pulses. The highly efficient MEGA‐sLASER sequence with refocusing FOCI pulses is an ideal and robust MRS editing technique for the measurement of weakly coupled metabolites at high field strengths. Copyright © 2013 John Wiley & Sons, Ltd.
Non‐steroidal anti‐inflammatory drugs and venous thromboembolism in women
Authors: Bergendal Annica , Adami Johanna , Bahmanyar Shahram , Hedenmalm Karin , Lärfars Gerd , Persson Ingemar , Sundström Anders , Kieler Helle
Published: March 2013

Background

Non‐steroidal anti‐inflammatory drugs (NSAIDs) might increase the risk of venous thromboembolism (VTE), and risks might differ by type of NSAID. Compared with men, women have a higher incidence of VTE at younger age, and they more often use NSAIDs.

Objectives

To assess risks of VTE in young and middle‐aged women in association with use of NSAIDs.

Patients/Methods

In a nationwide case–control study (Thrombo Embolism Hormone Study) performed in Sweden 2003–2009, we included as cases 1433 women, 18 to 64 years of age with a first time VTE. Controls were 1402 randomly selected women, frequency matched by age. Information was obtained by telephone interviews and DNA analyses of blood samples. We calculated adjusted odds ratios (ORs) with 95% confidence intervals (CIs) adjusting for degree of immobilization, chronic disease, smoking, body mass index, use of hormonal contraception, hormone therapy or other NSAIDs.

Results

Use of NSAIDs was not associated with increased risks of VTE (OR = 0.98, 95% CI 0.80–1.19). The OR was 0.88 for propionic acid derivatives (95% CI 0.72–1.10), 1.18 for acetic acid derivatives (95% CI 0.82–1.70) and 1.76 for coxibs (95% CI 0.73–4.27). For users of acetic acid derivatives and coxibs, the ORs increased by cumulative dose. Carriership of the prothrombin gene mutation or factor V Leiden had only minor effects on the results.

Conclusions

We found no increased risks of VTE in association with use of NSAIDs. Users of high cumulative doses of acetic acid derivatives and coxibs had the highest risks, suggesting a relationship with cyclooxygenase selectivity and dose. Copyright © 2013 John Wiley & Sons, Ltd.
A Simple Thaw‐Freeze Algorithm for a Multi‐Layered Soil using the Stefan Equation
Authors: Changwei Xie , Gough William A.
Published: March 2013

The Stefan equation is one of the simplest approximate analytical solutions for the thaw‐freeze problem. It provides a useful method for predicting the depth of thawing/freezing in soils when little site‐specific information is available. The limited number of parameters in the Stefan equation makes possible its application in a multi‐layered system. We demonstrate that a widely used algorithm (JL‐algorithm), which has been frequently used in permafrost regions, was derived by an incorrect mathematical method. It will inevitably result in systematic errors in the simulation if this algorithm is used in a multi‐layered soil.

We present another simple thaw‐freeze algorithm (XG‐algorithm) for multi‐layered soils. The new algorithm can be used to determine the freeze/thaw front in multi‐layered soils no matter how thick each layer is and how many layers the soil profile contains. Simulation results of the JL‐algorithm and the XG‐algorithm are compared using hypothetical soil profiles, and the XG‐algorithm is also used to simulate the thaw depth at three permafrost monitoring sites on the Qinghai‐Tibet Plateau and one on the Loess Plateau, China. These applications show that the XG‐algorithm could be readily used to analyse the factors that affect active‐layer thickness. It can also be coupled with hydrological or land surface models to simulate the freeze‐thaw cycles in permafrost regions and for related engineering applications. Copyright © 2013 John Wiley & Sons, Ltd.