bluuebunny/crossref_metadata_2025 huggingface dataset:
Regression of Hypertensive Left Ventricular Hypertrophy by Losartan Compared With Atenolol
Authors: Devereux Richard B. , Dahlöf Björn , Gerdts Eva , Boman Kurt , Nieminen Markku S. , Papademetriou Vasilios , Rokkedal Jens , Harris Katherine E. , Edelman Jonathan M. , Wachtell Kristian
Published: August 2004

Background—

An echocardiographic substudy of the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) trial was designed to test the ability of losartan to reduce left ventricular (LV) mass more than atenolol.

Methods and Results—

A total of 960 patients with essential hypertension and LV hypertrophy (LVH) on screening ECG were enrolled at centers in 7 countries and studied by echocardiography at baseline and after 1, 2, 3, 4, and 5 years’ randomized therapy. Clinical examination and blinded readings of echocardiograms in 457 losartan-treated and 459 atenolol-treated participants with ≥1 follow-up measurement of LV mass index (LVMI) were used in an intention-to-treat analysis. Losartan-based therapy induced greater reduction in LVMI from baseline to the last available study than atenolol with adjustment for baseline LVMI and blood pressure and in-treatment pressure (−21.7±21.8 versus −17.7±19.6 g/m
2
;
P
=0.021). Greater LVMI reduction with losartan was observed in women and men, participants >65 or <65 years of age, and with mild or more severe baseline hypertrophy. The difference between treatment arms in LVH regression was due mainly to reduced concentricity of LV geometry in both groups and lesser increase in LV internal diameter in losartan-treated patients.

Conclusions—

Antihypertensive treatment with losartan, plus hydrochlorothiazide and other medications when needed for pressure control, resulted in greater LVH regression in patients with ECG LVH than conventional atenolol-based treatment. Thus, angiotensin receptor antagonism by losartan has superior efficacy for reversing LVH, a cardinal manifestation of hypertensive target organ damage.
Arterial Pressure Lowering Effect of Chronic Atenolol Therapy in Hypertension and Vasoconstrictor Sympathetic Drive
Authors: Burns Joanna , Mary David A.S.G. , Mackintosh Alan F. , Ball Stephen G. , Greenwood John P.
Published: August 2004

Although the β
1
-adrenergic blocking agent atenolol is an established antihypertensive therapy, its effect on peripheral sympathetic vasoconstrictor drive has remained controversial. In patients with hypertension, atenolol therapy has been reported to either increase or have no effect on peripheral vascular resistance, despite other reports showing no change or a decrease in peripheral sympathetic drive. This study was designed, in patients with untreated essential hypertension (EHT), to quantify changes in simultaneously measured peroneal muscle sympathetic nerve activity (MSNA) and calf vascular resistance (CVR) accompanying atenolol therapy. MSNA was quantified as the mean frequency of single units (s-MSNA) and as multiunit bursts (MSNA bursts) using the technique of microneurography, and CVR was measured using a standard plethysmographic technique. Firstly, by comparing two age- and body weight- matched groups, each of 14 patients with hypertension, we found that the group on atenolol therapy (treated-HT) had similar MSNA values counted over the same number of cardiac beats and similar CVR levels (at least
P
>0.40) to the group without therapy (untreated-HT). Secondly, we examined 10 EHT patients before and after 8±0.4 weeks of oral atenolol therapy (HT-A) in comparison to seven control patients with hypertension and no treatment (HT-C) who were examined over a similar period of time. We found that the measures of MSNA and CVR did not significantly change in both groups. We conclude that the arterial pressure lowering effect of atenolol was not related to significant changes in central vasoconstrictor sympathetic drive to the periphery.
Norepinephrine-Induced Changes in Cardiac Transforming Growth Factor-β Isoform Expression Pattern of Female and Male Rats
Authors: Briest Wilfried , Homagk Lars , Raβler Beate , Ziegelhöffer-Mihalovicová Barbara , Meier Henning , Tannapfel Andrea , Leiblein Sabine , Saalbach Anja , Deten Alexander , Zimmer Heinz-Gerd
Published: August 2004

Transforming growth factor-β (TGF-β) is a ubiquitous growth-regulating protein with an essential role in tissue repair and formation of extracellular matrix (ECM). To better understand the role of different isoforms of TGF-β in the cardiac remodeling process induced by norepinephrine (NE), the expression of TGF-β1, TGF-β2, and TGF-β3 was studied and compared with the expression of collagen. NE (0.1 mg/kg · h) was intravenously infused in female and male Sprague-Dawley rats for several time periods, and freshly obtained ventricular myocardium after 1 day was dissociated into myocyte and nonmyocyte fractions. Prazosin (0.1 mg/kg · h) and metoprolol (1 mg/kg · h) were used to block α- and β-adrenoceptors, respectively. After NE infusion, the three isoforms of TGF-β were differentially induced as far as the magnitude and the time course is concerned. The increased expression of TGF-β2 started earlier with a maximum after 12 hours and was more pronounced (10-fold elevation) than that of the other two isoforms, with a clear specificity for the left ventricle in female hearts. This specificity was also seen in male rats with 16-fold elevation of TGF-β2 after 1 day of NE-stimulation. The increase of TGF-β2 was significant only in the myocyte fraction obtained from female as well as from male hearts. The expression of the mRNA of all TGF-β isoforms of collagen type I and type III, and of the matrix metalloproteinase (MMP)-2 and its inhibitor TIMP-2 was reduced predominantly by α-adrenoceptor blockade with prazosin. The increase in TGF-β isoforms correlated with that of the mRNA expression of collagens, MMP-2 and TIMP-2.
The Convention to Combat Desertification and the Role of Innovative Policy-Making Discourses: The Case of Burkina Faso
Authors: Bruyninckx Hans
Published: August 2004

The UN Convention to Combat Desertification is a mix of traditional regime elements with a set of innovations. These innovative elements can be interpreted as emanations of policy discourses that have been gaining in importance since the introduction and the fairly broad acceptance of sustainable development and Agenda 21 as guiding conceptual frameworks. In this article I first elaborate on three of those discourses: the participatory, the decentralization and the local knowledge discourses. In a second part, I will look at Burkina Faso as an example of UNCCD policy implementation at the national and the local level (Yatenga region). It will become clear that although changes are visible in policy-making dynamics, major difficulties and obstacles remain. The CCD undeniably has an impact at the national level of policy-making. It has provided support for decentralization, for more participatory processes of policy-making and for the inclusion of local knowledge in the policy process. At the more decentralized level the impact is less clear and more difficult to distinguish.
Who Ratifies Environmental Treaties and Why? Institutionalism, Structuralism and Participation by 192 Nations in 22 Treaties
Authors: Roberts J. Timmons , Parks Bradley C. , Vásquez Alexis A.
Published: August 2004

International environmental accords have become important mechanisms by which nations make promises to administer natural resources and manage the global environment. Previous studies, relying mainly on single cases or small-n data sets, have shed light on the proximate political causes of participation in these agreements. However, no study has yet systematically explained the deeper social determinants of why nations sign, ignore or resist environmental treaties. We offer a theoretically-sequenced model that exploits complementarities between rational choice institutionalism and world-systems theory. Key variables posited by realists and constructivists are also examined, using a new environmental treaty participation index based on ratifications of 22 major environmental agreements by 192 nations. Cross-sectional OLS regression and path analysis strongly supports the institutionalist claim that credibility—the willingness and ability to honor one's international environmental commit-ments—“matters.” But these measures also lend considerable support to the world-systems hypothesis that state credibility is strongly influenced by a legacy of colonial incorporation into the world economy. Narrow export base—our proxy for disadvantaged position in the world-economy—directly and indirectly (through institutions and civil society strength) explains nearly six-tenths of national propensity to sign environmental treaties. A nation's natural capital, its ecological vulnerability, and international environmental NGO memberships had no explanatory power in the path analysis. Our results indicate that new theoretical, methodological and policy approaches are needed to address structural barriers to international cooperation.
Dynamics of the Southern Collective: Developing Countries in Desertification Negotiations
Authors: Najam Adil
Published: August 2004

This paper seeks to understand how the collective South, as institutionally represented by the Group of 77 (G77), manages its unity as a negotiating collective despite its many internal differences and in the face of external pressures. Negotiations leading to the United Nations Convention to Combat Desertification (CCD) are used as an empirical case study. This is a particularly interesting case because a) it was manifestly South-driven, b) it saw uncommonly intense South-South bargaining within the context of a global environmental negotiation, and c) it also saw intense North-South differences. In focusing on how the G77 managed its internal (South-South) as well as external (South-North) negotiations, the paper uses a negotiation analytical framework to derive generalizable lessons about the collective negotiating behavior of the developing countries' caucus in global environmental politics.
Globalization and Disease: The Case of SARS
Authors: Lee Jong-Wha , McKibbin Warwick J.
Published: August 2004

The purpose of this paper is to provide an assessment of the global economic impacts of severe acute respiratory syndrome (SARS) as well as to provide a more comprehensive approach to estimating the global consequences of major disease outbreaks. Our empirical estimates of the economic effects of the SARS epidemic are based on a global model called the G-Cubed (Asia Pacific) model. Most previous studies on the economic effects of epidemics focus on the disease-associated medical costs or forgone incomes resulting from disease-related morbidity and mortality, but the most significant real costs of SARS have been generated by changes in spending behavior by households and firms in affected countries. This study estimates the cost of the SARS outbreak by focusing on the impacts on consumption and investment behavior through changes in the cost and risk of doing business. Through increased economic interdependence, these changes in behavior have wide-ranging general equilibrium consequences for the world economy that can lead to economic losses well in excess of the traditional estimates of the cost of disease.
The Impact of SARS on Asian Economies
Authors: Hanna Donald , Huang Yiping
Published: August 2004

This paper describes the economic implications of the SARS outbreak that hit many Asian economies in spring 2003. Without a workable diagnostic test and a treatment for the illness, surveillance and quarantine were the key weapons against SARS last year. In general, risks are greater in countries with poor public health care, poor sanitation systems, high mobility, or high population density. During the height of the SARS outbreak, we estimated that the total costs of the epidemic would be about 1.5 percent of GDP for China. Better-than-expected containment of the virus reduced the impact to only about 0.5 percent of GDP. The experiences of the SARS outbreak point to the strong need to improve both the public health system and the governance structure in Asia.
Financial Sector Restructuring in South Korea: Accomplishments and Unfinished Agenda
Authors: Ahn Choong Yong , Cha Baekin
Published: August 2004

South Korea has undertaken major and far-reaching actions to rebuild and improve its financial sector since the financial crisis of 1997. Various measures to clean up the balance sheets of financial institutions have helped to normalize the financial system earlier than expected and have significantly eased the credit crunch. Despite the many significant changes in the South Korean economy brought about by financial reform, the country must continue with further improvements if it expects to build a stronger and more competitive financial industry that can thrive in the international market. To sustain the momentum of its initial reform effort, South Korea should institute additional financial reforms, eliminate moral hazard, and establish new market-based rules.
Effect of pulse frequency in gas tungsten arc welding of powder metallurgical preforms
Authors: Suresh M.V. , Vamsi Krishna B. , Venugopal P. , Prasad Rao K.
Published: August 2004

Pulsing of the welding current is one approach for refining the fusion zone microstructure in materials joined by fusion welding. The effect of current pulse frequency on weld bead microstructure, tensile strength, and hardness in joining of powder metallurgical steel preform sheets to wrought copper was studied. Considering weld strength as the quality characteristic in the selection of process parameters, the Taguchi method is used to analyse the effect of each process parameter individually and of their interaction on weld strength, and subsequently to determine the process parameters leading to optimum weld strength. The application of pulsed current causes iron dendrites to become more equiaxed and uniformly distributed owing to dendrite fragmentation. Further, there was an optimum frequency range over which the microstructural refinement was maximal. The same optimum frequency range corresponded to maximum tensile strength. Enhanced fluid flow and reduced thermal gradients are thought to be responsible for refining the solidification structure and the resulting stronger welds.
Image analysis of electrode degradation in resistance spot welding of aluminium
Authors: Peng J. , Fukumoto S. , Brown L. , Zhou N.
Published: August 2004

A study was carried out of the characteristics of electrode degradation in resistance spot welding of aluminium, and its influence on weld quality. Based on analysis of electrode life test results, an imaging approach was developed to determine quantitatively the status of electrode degradation, in which three parameters were defined to represent the tip surface characteristics, namely, relative radius, edge concentration, and eccentricity. This image analysis revealed a clear relationship between these defined electrode surface features and the weld quality, based on which a reasonable understanding was achieved of the causes of weld quality deterioration in electrode life tests.
Welding of titanium alloys with activating flux
Authors: Sun Z. , Pan D.
Published: August 2004

In the present paper, the effects of an activating flux on Ti–6Al–4V alloy welding were investigated. Tungsten inert gas welding was used to weld 8.0 mm thickness Ti–6Al–4V alloy plates. Results show that applying the activating flux on the Ti–6Al–4V alloy surface leads to an increase in weld penetration depth, whereas the corresponding weld bead width is reduced. It was also found that various welding conditions, particularly flux thickness, influence the effectiveness of the activating flux. Furthermore, a data acquisition system was used to monitor the current and voltage signals during welding. Results from monitoring of the welding current and voltage signals reveal that there is a clear correlation between the signals and the weld penetration when the welding arc is steady. Analysis of the acquired signals can be used to identify inconsistencies in weld penetration. In summary, to take advantage of the use of activating flux in Ti alloy welding, it is important that a uniform flux layer is present at the alloy plate surface and suitable welding parameters are selected.
Analysis of electrical characteristics for hybrid pulsed micro-tungsten inert gas welding arc
Authors: Wang J. , Kusumoto K. , Nezu K.
Published: August 2004

The present paper experimentally investigates and analyses in detail the electrical characteristics of the arc for the hybrid pulsed micro-tungsten inert gas process. In particular, an average voltage–current (V–I) graph plotting approach is proposed to describe the dynamic characteristics of the hybrid arcs using the filtered voltage and current of the arc. It is shown that the average voltage and electrical resistance of the heavily hybrid pulsating (HHP) arc are lower than those of the slightly hybrid pulsating (SHP) arc, particularly during the background current stage. Furthermore, the analyses reveal that the average V–I characteristic graph for the arc forms a hysteresis loop, primarily because of the thermal inertia of the arc, during a pulse period. This closed loop is larger for the SHP arc than for the HHP arc, and shrinks longitudinally with increasing frequency and width of the current pulse. These results thus demonstrate that the HHP arc has a greater thermal inertia, particularly at higher current and pulse frequency. Experimental results show also that the mean voltage of the arc and the features of the hysteresis loop vary markedly with weld penetration in addition to pulsating frequency and pattern, and thus suggest the possibility of monitoring the hybrid pulsed weld penetration via arc sensing.
Suppression of porosity in beam weaving laser welding
Authors: Zhang X. , Chen W. , Bao G. , Zhao L.
Published: August 2004

The present paper describes a beam weaving laser welding technique to suppress argon or nitrogen porosity, which may appear during laser welding of low carbon steel. Bead on plate welding was performed using a 3 kW CO2 laser. The weaving frequency was varied within 0–30 Hz and the weaving amplitude within 0–2 mm during welding. The experimental results show that under 2.4 kW laser power and 1.0 m min-1 welding speed, the nitrogen porosity decreases remarkably with increasing frequency, and it can be eliminated for a weaving frequency of 22 Hz with 0.5 mm weaving amplitude. Under 2.4 kW laser power and 1.5 m min-1 welding speed, beam weaving laser welding can also effectively reduce argon porosity at a weaving frequency of 22 Hz and amplitude of 1.0–1.5 mm.
Development of Trivex friction stir welding tool Part 2 – three-dimensional flow modelling
Authors: Colegrove P.A. , Shercliff H.R.
Published: August 2004

This paper describes the application of the computational fluid dynamics (CFD) code, FLUENT, to modelling the metal flow in friction stir welding (FSW). Building on a two-dimensional model, and preliminary trials with a novel ‘Trivex’ tool design, discussed in the companion paper immediately before this one, a full three-dimensional model was developed. The model predicted the temperature, and the traversing and down forces, which were compared against experiments. The model incorporated a novel ‘slip’ boundary condition, based on that developed in two dimensions. A conventional ‘Triflute’ tool was modelled and compared with the new ‘Trivex’ tool design. The model correctly predicted that the Trivex tool had lower traversing and down forces than its Triflute counterpart. To assist understanding of the material flow, streamlines around each of the tools were plotted. Ultimately the technique could be used to size the pin features reducing the need for costly experiments.
Development of Trivex friction stir welding tool Part 1 – two-dimensional flow modelling and experimental validation
Authors: Colegrove P.A. , Shercliff H.R.
Published: August 2004

This paper describes the application of the computational fluid dynamics (CFD) code, FLUENT, to modelling the metal flow in friction stir welding (FSW). Through the use of a novel slip model, a two-dimensional pin profile was optimised to minimise the traversing force. Two versions of a tool based on the optimised profile were developed: the plain ‘Trivex’ and the threaded ‘MX-Trivex’. These were tested against one version of the ‘MX-Triflute’ tool that had comparable pin and shoulder diameters. Experiments showed that the traversing force was reduced by between 18 and 25% and the down force was reduced by approximately 12% when compared with the MX-Triflute tool. The different pin designs had little effect on the heat input and the tensile strengths of the welds were comparable. The development and validation of the full three-dimensional model for both the Trivex and Triflute tools is described in Part 2.
Secondary austenite and chromium nitride precipitation in simulated heat affected zones of duplex stainless steels
Authors: Ramirez A.J. , Brandi S.D. , Lippold J.C.
Published: August 2004

Primary and secondary intragranular austenite precipitation and its relationship with chromium nitride (Cr2N) were studied in a simulated multipass heat affected zone (HAZ) of five duplex stainless steel alloys (UNS S32304, S32205, S32550, S32750, and S32760). The Gleeble thermal-mechanical simulator was used to perform short duration and high cooling rate ferritisation and reheating heat treatments. TEM and FEG-SEM analysis, coupled with a specially developed electrolytic etching technique, revealed the cooperative growth of secondary austenite and Cr2N precipitation along the ferrite/austenite (α/γ) interfaces. Additionally, the observed close coexistence of intragranular nitride (Cr2N) and intragranular secondary austenite suggests the heterogeneous nucleation of secondary austenite from the nitrides as supported by previously reported low energy nitride/austenite (Cr2N/γ) interfaces for the observed orientation relationship between both phases. Based on these observations, a new mechanism is proposed for intragranular secondary austenite nucleation related to the intragranular nitride precipitates.
Oxidation of mudstone in a tunnel (Tournemire, France): consequences for the mineralogy and crystal chemistry of clay minerals
Authors: Charpentier D. , Mosser-Ruck R. , Cathelineau M. , Guillaume D.
Published: August 2004

The excavation of a tunnel through a mudstone formation provides an opportunity to examine the effects of the modification of the physical and chemical environment on the rock. The mineralogical and chemical consequences of hydration-dehydration cycles and of oxidation have been evaluated in the case of the Toarcian mudstone formation at the Tournemire experimental site (France). Studies by X-ray diffraction and tansmission electron microscopy of both altered and preserved samples show that the introduction of air and condensed water causes the oxidation of pyrite and the subsequent generation of acid and sulphate-rich waters at the micron scale, in the local environment of pyrites. The fluid-clay particle interactions around the oxidized pyrites induce: (1) a statistical enrichment in Si of the I-S clay minerals; (2) an increase in the Fe(III)/Fe total ratio in some of the I-S particles; and (3) the dissolution of illite layers in mixed-layer I-S. These evolutions are consistent with the results of numerical modelling which reproduced the interaction between the clay particles and the acid water.
Significance of K-Ar dating of very low-grade metamorphism in Triassic-Jurassic pelites from the Coastal Range of central Chile
Authors: Belmar M. , Morata D. , Munizaga F. , Pérez de Arce C. , Morales S. , Carrillo F. J.
Published: August 2004

K-Ar isotopic dating of very low-grade metamorphism affecting Triassic-Jurassic rocks in the Coastal Range of central Chile was carried out on whole rocks and their <2 mm size fractions. In the study area, a regional-burial low-grade metamorphism at anchizone conditions (T≤190°C) and low-pressure conditions (P≥1.3 kbar) has been described. The highest observed temperatures are related to a contact metamorphism produced by nearby Jurassic intrusions, with aP-Testimate at the immediate contact zone of ~650–690°C and 4 kbar.

The whole-rock K-Ar age of 174±5 Ma is interpreted as belonging to the contact metamorphism due to the intrusion of Jurassic plutons (165±5 Ma to 175±5 Ma). A time-interval of ~20 Ma between the diagenesis (206 Ma) and the anchizonal very low-grade metamorphism (181–184 Ma) is obtained, and a rate of subsidence of ~120 m/Ma is proposed for these Triassic-Jurassic basins. A thermal influence on the burial, very low-grade, regional metamorphism is invoked.
Time trends in personnel certification and turnover in the Collaborative Ocular Melanoma Study
Authors: Mobley Reńe Y , Moy Claudia S , Reynolds Sandra M , Diener-West Marie , Newhouse M Marvin , Kerman Jonathan S , Hawkins Barbara S ,   Collaborative Ocular Melanoma Study Group
Published: August 2004

Background The purpose of this analysis was to examine and quantify the coordinating center workload in regard to certification and turnover of clinical personnel who participated in the Collaborative Ocular Melanoma Study (COMS).

Methods The COMS was a set of multicenter, multidisciplinary randomized clinical trials conducted to evaluate radiotherapy for initial treatment of choroidal melanoma, a primary eye cancer. Patients were screened, enrolled, treated, and followed for mortality and clinical outcomes at 43 clinical centers in the United States and Canada, beginning late in 1986. Clinical centers were added to the COMS during three calendar periods. Training and certification of clinical personnel was performed by five resource centers and coordinated at the COMS coordinating center. A personnel database was maintained at the coordinating center for tracking certification progress, recertification, transfers and resignations. Certification records were analyzed for the period 1986 through 1998 when patient accrual and treatment were completed.

Results Clinical personnel (929 individuals) were certified for one or more of nine distinct roles in the COMS, resulting in 1342 certifications; 26% were certified for two or more positions. The total number certified for each role ranged from 114 to 208. Certifications per year ranged from 260 in 1987 to 35 in 1997. The certification workload at the coordinating center rose following addition of each group of new clinical centers. It also increased in 1995 as a result of recertification of current personnel mandated by the external data monitoring committee.

Conclusions This analysis documented that training and certification were continuing tasks, and not limited to initiation of the study. Resignations and reassignments of certified personnel were responsible for 642 decertifications.
Use of joint models to assess treatment effects on disease markers and clinical events: the ProscarTM Long-Term Efficacy and Safety Study (PLESS)
Authors: He Weili , Shih Weichung Joe
Published: August 2004

Clinical trials often collect longitudinal measurements of a disease marker and time to a major clinical event of the disease to assess treatment effects. It makes sense to combine the treatment effects on both the longitudinal disease marker and the time to clinical event, especially when the clinical event is also mediated through the disease marker over time. In this paper we apply a joint modeling approach in the assessment of the treatment effects in treating benign prostatic hyperplasia (BPH) for the ProscarTM Long-Term Efficacy and Safety Study (PLESS).
Web-based communications and management of a multi-center clinical trial: the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) project
Authors: Wisniewski Stephen R , Eng Heather , Meloro Leslie , Gatt Robert , Ritz Louise , Stegman Diane , Trivedi Madhukar , Biggs Melanie M , Friedman Edward , Shores-Wilson Kathy , Warden Diane , Bartolowits Douglas , Martin Jeffrey P , Rush A John
Published: August 2004

While efficient methods of communication are known to be essential in conducting large multicenter clinical trials, very little information is provided on actual methods that can be implemented to improve communication. An integrated technology-based communication system was developed for the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) project, which prospectively defines treatments that are most effective for participants with a diagnosis of a nonpsychotic major depressive disorder (MDD) who report an unsatisfactory clinical outcome to an initial and, if necessary, subsequent treatment(s). This web-based communication system is comprised of a multi-faceted study Web site, including a help desk, document sharing, a project directory and reports. In addition, automated reporting via e-mail and an online data correction mechanism are also available. The STARD communication system improves communication between study personnel and improves the quality of the study's data through the integration of system elements, the integration of those elements with traditional forms of communication, by filling the gaps not addressed by those traditional methods and by reducing the staff workload burden.
Meta-Analysis of Randomized Clinical Trials Comparing Cisplatin to Carboplatin in Patients With Advanced Non–Small-Cell Lung Cancer
Authors: Hotta Katsuyuki , Matsuo Keitaro , Ueoka Hiroshi , Kiura Katsuyuki , Tabata Masahiro , Tanimoto Mitsune
Published: August 2004

Purpose

It remains undetermined whether cisplatin and carboplatin are equally effective for advanced non–small-cell lung cancer (NSCLC). We therefore did a meta-analysis of trials that compared cisplatin-based chemotherapy with carboplatin-based chemotherapy.

Methods

We performed a literature search to identify trials that had investigated the substitution of carboplatin for cisplatin in the treatment of advanced NSCLC. We evaluated these trials for inclusion, rated methodologic quality, and abstracted relevant data.

Results

Of 1,191 reports, eight trials (2,948 patients) were identified, five of which investigated drug regimens containing platinum plus a new agent. Cisplatin-based chemotherapy produced a higher response rate, but the survival advantage was not significant (hazard ratio = 1.050; 95% CI, 0.907 to 1.216; P = .515). Subgroup analysis revealed that combination chemotherapy consisting of cisplatin plus a new agent yields 11% longer survival than carboplatin plus the same new agent (hazard ratio = 1.106; 95% CI, 1.005 to 1.218; P = .039). Patients on cisplatin-based chemotherapy frequently developed nausea and vomiting; thrombocytopenia was more frequent during carboplatin-based chemotherapy. No significant difference in treatment-related mortality was observed.

Conclusion

We found that combination chemotherapy consisting of cisplatin plus a new agent yields a substantial survival advantage compared with carboplatin plus a new agent in patients with advanced NSCLC, although we failed to find any survival difference in an analysis that included both new and old agents. The strength of our conclusion is limited because we used abstracted data, and careful interpretation is thus required. Nevertheless, our results raise a critical point that needs to be evaluated in future studies.
Intraspecific divergence of ionoregulatory physiology in the euryhaline teleostFundulus heteroclitus: possible mechanisms of freshwater adaptation
Authors: Scott Graham R. , Rogers Joseph T. , Richards Jeff G. , Wood Chris M. , Schulte Patricia M.
Published: August 2004

We examined intraspecific variation in ionoregulatory physiology within euryhaline killifish, Fundulus heteroclitus, to understand possible mechanisms of freshwater adaptation in fish. Pronounced differences in freshwater tolerance existed between northern (2% mortality) and southern (19%mortality) killifish populations after transfer from brackish water (10 g l-1) to freshwater. Differences in Na+ regulation between each population might partially account for this difference in tolerance, because plasma Na+ was decreased for a longer period in southern survivors than in northerns. Furthermore, northern fish increased Na+/K+-ATPase mRNA expression and activity in their gills to a greater extent 1-14 days after transfer than did southerns, which preceded higher whole-body net flux and unidirectional influx of Na+ at 14 days. All observed differences in Na+regulation were small, however, and probably cannot account for the large differences in mortality. Differences in Cl- regulation also existed between populations. Plasma Cl- was maintained in northern fish, but in southerns, plasma Cl- decreased rapidly and remained low for the duration of the experiment. Correspondingly, net Cl-loss from southern fish remained high after transfer, while northerns eliminated Cl- loss altogether. Elevated Cl- loss from southern fish in freshwater was possibly due to a persistence of seawater gill morphology, as paracellular permeability (indicated by extrarenal clearance rate of PEG-4000) and apical crypt density in the gills (detected using scanning electron microscopy) were both higher than in northern fish. These large differences in the regulation of Cl- balance probably contributed to the marked differences in mortality after freshwater transfer. Glomerular filtration rate and urination frequency were also lower in southerns. Taken together, these data suggest that northern killifish are better adapted to freshwater environments and that minimizing Cl-imbalance appears to be the key physiological difference accounting for their greater freshwater tolerance.
Molecular biology of ion motive proteins in comparative models
Authors: Wheatly Michele G. , Gao Yongping
Published: August 2004

This article will review the utility of comparative animal models in understanding the molecular biology of ion transport. Due to the breadth of this field some `disclaimers' need to be established up front. `Comparative'will be defined as non-mammalian. `Genetic species' will be defined as organisms that have been selected as models for genetic studies and for which the genome has been largely sequenced. `Non-genetic species' will include other non-mammalian organisms. The review will be limited to ions that play a major role in extracellular (EC) ionoregulation (Na/K/Ca/Cl) and not to micronutrients (Fe) or heavy metals (Cd, Zn). The review will focus only on ion motive proteins that have been associated with vectorial transfer at epithelial tissues. The review is therefore intended as a guidepost to researchers new to the field as well as to inform biologists of the power of comparative genomics.
The hydrodynamics of eel swimming II. Effect of swimming speed
Authors: Tytell Eric D.
Published: August 2004

Simultaneous swimming kinematics and hydrodynamics are presented for American eels, Anguilla rostrata, swimming at speeds from 0.5 to 2 L s-1. Body outlines and particle image velocimetry (PIV)data were collected using two synchronized high-speed cameras, and an empirical relationship between swimming motions and fluid flow is described. Lateral impulse in the wake is estimated assuming that the flow field represents a slice through small core vortex rings and is shown to be significantly larger than forces estimated from the kinematics viaelongated body theory (EBT) and via quasi-steady resistive drag forces. These simple kinematic models predict only 50% of the measured wake impulse, indicating that unsteady effects are important in undulatory force production. EBT does, however, correctly predict both the magnitude and time course of the power shed into the wake. Other wake flow structures are also examined relative to the swimming motions. At all speeds, the wake contains almost entirely lateral jets of fluid, separated by an unstable shear layer that rapidly breaks down into two vortices. The jet's mean velocity grows with swimming speed, but jet diameter varies only weakly with swimming speed. Instead, it follows the body wavelength, which changes more among individuals than at different speeds. Circulation of the stop-start vortex, shed each time the tail changes direction, can also be predicted at low speeds by the integral of squared tail velocity over half of a tail beat. At high speeds,these kinematics predict more circulation than is actually present in the stop-start vortex. Finally, the cost of producing the wake, one component of the total cost of transport, increases with swimming speed to the 1.48 power,lower than would be expected if the power coefficient remained constant over the speed range examined.
Limited extracellular but complete intracellular acid-base regulation during short-term environmental hypercapnia in the armoured catfish,Liposarcus pardalis
Authors: Brauner C. J. , Wang T. , Wang Y. , Richards J. G. , Gonzalez R. J. , Bernier N. J. , Xi W. , Patrick M. , Val A. L.
Published: August 2004

Environmental hypercapnia induces a respiratory acidosis that is usually compensated within 24-96 h in freshwater fish. Water ionic composition has a large influence on both the rate and degree of pH recovery during hypercapnia. Waters of the Amazon are characteristically dilute in ions, which may have consequences for acid-base regulation during environmental hypercapnia in endemic fishes. The armoured catfish Liposarcus pardalis, from the Amazon, was exposed to a water PCO2 of 7, 14 or 42 mmHg in soft water (in μmol l-1: Na+, 15,Cl-, 16, K+, 9, Ca2+, 9, Mg2+, 2). Blood pH fell within 2 h from a normocapnic value of 7.90±0.03 to 7.56±0.04, 7.34±0.05 and 6.99±0.02, respectively. Only minor extracellular pH (pHe) recovery was observed in the subsequent 24-96 h. Despite the pronounced extracellular acidosis,intracellular pH (pHi) of the heart, liver and white muscle was tightly regulated within 6 h (the earliest time at which these parameters were measured) via a rapid accumulation of intracellular HCO3-. While most fish regulate pHi during exposure to environmental hypercapnia, the time course for this is usually similar to that for pHe regulation. The degree of extracellular acidosis tolerated by L. pardalis, and the ability to regulate pHi in the face of an extracellular acidosis, are the greatest reported to date in a teleost fish. The preferential regulation of pHi in the face of a largely uncompensated extracellular acidosis in L. pardalis is rare among vertebrates, and it is not known whether this is associated with the ability to air-breathe and tolerate aerial exposure, or living in water dilute in counter ions, or with other environmental or evolutionary selective pressures. The ubiquity of this strategy among Amazonian fishes and the mechanisms employed by L. pardalis are clearly worthy of further study.
Characterization ofFxr1inDanio rerio; a simple vertebrate model to study costamere development
Authors: Engels Bart , van 't Padje Sandra , Blonden Lau , Severijnen Lies-anne , Oostra Ben A. , Willemsen Rob
Published: August 2004

The X-linked FMR1 gene, which is involved in the fragile X syndrome, forms a small gene family with its two autosomal homologs, FXR1 and FXR2. Mouse models for the FXR genes have been generated and proved to be valuable in elucidating the function of these genes, particularly in adult mice. Unfortunately, Fxr1 knockout mice die shortly after birth, necessitating an animal model that allows the study of the role of Fxr1p, the gene product of Fxr1, in early embryonic development. For gene function studies during early embryonic development the use of zebrafish as a model organism is highly advantageous.

In this paper the suitability of the zebrafish as a model organism to study Fxr1p function during early development is explored. As a first step, we present here the initial characterization of Fxr1p in zebrafish. Fxr1p is present in all the cells from zebrafish embryos from the 2/4-cell stage onward; however, during late development a more tissue-specific distribution is found, with the highest expression in developing muscle. In adult zebrafish, Fxr1p is localized at the myoseptum and in costamere-like granules in skeletal muscle. In the testis, Fxr1p is localized in immature spermatogenic cells and in brain tissue Fxr1p displays a predominantly nuclear staining in neurons throughout the brain. Finally, the different tissue-specific isoforms of Fxr1p are characterized.

Since the functional domains and the expression pattern of Fxr1p in zebrafish are comparable to those in higher vertebrates such as mouse and human, we conclude that the zebrafish is a highly suitable model for functional studies of Fxr1p.
Cadmium-induced apoptosis in oyster hemocytes involves disturbance of cellular energy balance but no mitochondrial permeability transition
Authors: Sokolova I. M. , Evans S. , Hughes F. M.
Published: August 2004

Exposure to environmentally prevalent heavy metals such as cadmium can have detrimental effects on a variety of commercially and ecologically important species such as oysters. Since Cd2+ is known to induce apoptosis in immune cells of vertebrates, we have investigated the effects of this metal on isolated oyster hemocytes, the main cellular immune defense in mollusks. Enhanced apoptosis of these cells could conceivably create immunosuppressed conditions in these organisms and result in reduced disease resistance and increased opportunistic infection, resulting in decline of their populations. Cd2+ exposure induced apoptosis in oyster hemocytes in a dose-dependent manner in the range of 10-100 μmol l-1, as indicated by the translocation of phosphatidylserine to the outer leaflet of the plasma membrane. At higher concentrations (200-1000 μmol l-1), there was no further increase in apoptosis but a significant increase in the level of necrosis. In stark contrast to vertebrate immune cells, there was no decrease in the mitochondrial membrane potential or activation of caspases in response to Cd2+ in the apoptotic range. Surprisingly, Cd2+ exposure in this range did cause a significant decrease in intracellular ATP levels, indicating a severe disturbance of energy metabolism. Similarly, Cd2+ exposure of isolated mitochondria resulted in partial uncoupling of mitochondria but no difference in mitochondrial membrane potential. The results demonstrate that the important environmental pollutant Cd2+ induces apoptosis in oyster immune cells and does so through a mitochondria/caspase-independent pathway,suggesting that a novel, perhaps ancient, apoptotic pathway is active in these cells. Furthermore, it appears that the observed decrease in ATP production during apoptosis is not due to the loss of the mitochondrial proton-motive force but is more likely to be due to inhibition of the F0/F1-ATPase and/or mitochondrial ADP/ATP or substrate transport.
Grouping of visual objects by honeybees
Authors: Zhang Shaowu , Srinivasan Mandyam V. , Zhu Hong , Wong Jason
Published: August 2004

Recent work has revealed that monkeys as well as pigeons are able to categorise complex visual objects. We show here that the ability to group similar, natural, visual images together extends to an invertebrate - the honeybee. Bees can be trained to distinguish between different types of naturally occurring scenes in a rather general way, and to group them into four distinct categories: landscapes, plant stems and two different kinds of flowers. They exhibit the same response to novel visual objects that differ greatly in their individual, low-level features, but belong to one of the four categories. We exclude the possibility that they might be using single,low-level features as a cue to categorise these natural visual images and suggest that the categorisation is based on a combination of low-level features and configurational cues.
A conserved domain of alkaline phosphatase expression in the Malpighian tubules of dipteran insects
Authors: Cabrero Pablo , Pollock Valerie P. , Davies Shireen A. , Dow Julian A. T.
Published: August 2004

Malpighian (renal) tubules are key components of the insect osmoregulatory system and show correspondingly great diversity in both number and length. Recently, the organisation of the Drosophila melanogaster tubule has been elucidated by enhancer trapping, and an array for functional properties has been shown to align with the functional domains. In Drosophila,there is a lower tubule domain, which coincides with expression of alkaline phosphatase and delineates the absorptive region of the tubule. Here, these observations are extended to three dipteran vectors of disease (Aedes aegypti, Anopheles stephensii and Glossina morsitans) and a non-dipteran out-group, Schistocerca gregaria (Orthoptera). Despite a huge range in cell number and size, alkaline phosphatase was found on the apical surface of the lower 10% of each of the dipteran tubules but nowhere within the orthopteran tubule. An alkaline phosphatase lower tubule domain is thus conserved among Diptera.

Cell counts are also provided for each species. As in Drosophila,stellate cells are not found in the lower tubule domain of Anophelesor Aedes tubules, confirming the unique genetic identity of this domain. As previously reported, we failed to find stellate cells in Schistocerca but, remarkably, also failed to find them in Glossina, the dipteran most closely related to Drosophila. The orthodoxy that stellate cells are unique to, and general among, Diptera may thus require revision.
Structural basis for control of secondary vessels in the long-finned eel Anguilla reinhardtii
Authors: Skov Peter Vilhelm , Bennett Michael Brian
Published: August 2004

Histological sections of primary segmental arteries and associated interarterial anastomoses and secondary vessels from the long-finned eel Anguilla reinhardtii were examined by light and transmission electron microscopy. Interarterial anastomoses were found to originate from the primary vasculature as depressions through the tunica intima and media, from where they ran perpendicularly to the adventitial layer, before coiling extensively. From here the anastomoses travelled a relatively linear path in the outer margin of the adventitia to anastomose with a secondary vessel running in parallel with the primary counterpart. In contrast to findings from other species, secondary vessels had a structure quite similar to that of primary vessels; they were lined by endothelial cells on a continuous basement membrane, with a single layer of smooth muscle cells surrounding the vessel. Smooth muscle cells were also found in the vicinity of interarterial anastomoses in the adventitia, but these appeared more longitudinally orientated. The presence of smooth muscle cells on all aspects of the secondary circulation suggests that this vascular system is regulated in a similar manner as the primary vascular system. Because interarterial anastomoses are structurally integrated with the primary vessel from which they originate, it is anticipated that flow through secondary vessels to some extent is affected by the vascular tone of the primary vessel. Immunohistochemical studies showed that primary segmental arteries displayed moderate immunoreactivity to antibodies against 5-hydroxytryptamine and substance P, while interarterial anastomoses and secondary vessels showed dense immunoreactivity. No immunoreactivity was observed on primary or secondary arteries against neuropeptide Y or calcitonin gene-related peptide.