bluuebunny/crossref_metadata_2025 huggingface dataset:
Continuously assessed right ventricular end-diastolic volume as a marker of cardiac preload and fluid responsiveness in mechanically ventilated cardiac surgical patients
Authors: Wiesenack Christoph , Fiegl Christoph , Keyser Andreas , Laule Sven , Prasser Christopher , Keyl Cornelius
Published: April 2005

Introduction

Assessing cardiac preload and fluid responsiveness accurately is important when attempting to avoid unnecessary volume replacement in the critically ill patient, which is associated with increased morbidity and mortality. The present clinical trial was designed to compare the reliability of continuous right ventricular end-diastolic volume (CEDV) index assessment based on rapid response thermistor technique, cardiac filling pressures (central venous pressure [CVP] and pulmonary capillary wedge pressure [PCWP]), and transesophageal echocardiographically derived evaluation of left ventricular end-diastolic area (LVEDA) index in predicting the hemodynamic response to volume replacement.

Methods

We studied 21 patients undergoing elective coronary artery bypass grafting. After induction of anesthesia, hemodynamic parameters were measured simultaneously before (T1) and 12 min after volume replacement (T2) by infusion of 6% hydroxyethyl starch 200/0.5 (7 ml/kg) at a rate of 1 ml/kg per min.

Results

The volume-induced increase in thermodilution-derived stroke volume index (SVITD) was 10% or greater in 19 patients and under 10% in two. There was a significant correlation between changes in CEDV index and changes in SVITD (r2 = 0.55; P < 0.01), but there were no significant correlations between changes in CVP, PCWP and LVEDA index, and changes in SVITD. The only variable apparently indicating fluid responsiveness was LVEDA index, the baseline value of which was weakly correlated with percentage change in SVITD (r2 = 0.38; P < 0.01).

Conclusion

An increased cardiac preload is more reliably reflected by CEDV index than by CVP, PCWP, or LVEDA index in this setting of preoperative cardiac surgery, but CEDV index did not reflect fluid responsiveness. The response of SVITD following fluid administration was better predicted by LVEDA index than by CEDV index, CVP, or PCWP.
Conceptual issues in the analysis of cost data within cluster randomized trials
Authors: Flynn Terry , Peters Tim
Published: April 2005

Cluster randomized controlled trials (RCTs) are increasingly used in economic evaluations of social, educational and health care interventions. Methodological research has, therefore, been spread across several disciplines, with the result that it has taken many years for guidelines on good statistical practice in the design and analysis of such trials to become easily accessible to health service researchers. These guidelines remain incomplete, however, because they do not take account of issues specific to the analysis of cost data. In particular, they fail to recognize that the calculation of confidence intervals around costs needed to inform health care priority setting raises unique methodological issues. If poorly designed trials are to be avoided in future (including those by the authors), then collaboration between triallists and health economists is required. This paper sets out a framework that should facilitate such collaboration and draws attention to problems that must be addressed quickly in the design of cluster-based economic evaluations.
Health status and health care of immigrants in Canada: a longitudinal analysis
Authors: Newbold Bruce
Published: April 2005

Objectives: This paper focuses upon health status, need for care, and use of health care from 1994/95 to 2000/01 in the Canadian foreign-born population.

Methods: Using Statistics Canada's longitudinal National Population Health Survey, descriptive and survival analyses are used to explore immigrant health status and health care.

Results: The health status of immigrants quickly declines after arrival, with a concomitant increase in use of health care services. However, survival analysis of the risk of a change to poor health indicates no difference between immigrants and the native-born. Similarly, there is no difference in the risk of hospital use between the two populations.

Conclusions: The health status of recent immigrant arrivals is observed to decline towards that of the native-born population, while health care utilization increases. However, increased use may not be sufficient to offset declines in health, meaning that need for health care within the immigrant population may be unmet.
Phototherapy-Mediated Syndrome of Inappropriate Secretion of Antidiuretic Hormone in an In Utero Selective Serotonin Reuptake Inhibitor–Exposed Newborn Infant
Authors: Vanhaesebrouck Piet , De Bock Freia , Zecic Alexandra , De Praeter Claudine , Smets Koenraad , De Coen Kris , Goossens Linde
Published: April 2005

Although selective serotonin reuptake inhibitors (SSRIs) have gained wide acceptance in the off-label treatment of mental disorders in pregnant women, there seems to be an increased risk for serotonergic adverse effects in newborn infants who are exposed to SSRIs during late pregnancy. Hyponatremia as a result of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a relatively common serious side effect of the use of SSRIs in (mostly elderly) adults. Severe hyponatremia as a result of an SIADH is proposed here as part of a neonatal serotonin toxicity syndrome in a newborn infant who was exposed prenatally to an SSRI. The definite reversal to normal serum sodium levels after fluid restriction, the lack of any alternative cause for the SIADH, and the positive temporal relation with a high score on a widely used adverse drug reaction probability scale offer solid support for the hypothesis of a causal relationship between the SIADH and the prenatal sertraline exposure in our neonate. Moreover, accumulative data on the acute enhancement of serotonergic transmission by intense illumination led us to hypothesize that phototherapy used to treat hyperbilirubinemia in the newborn infant could have been the ultimate environmental trigger for this proposed new cause of iatrogenic neonatal SIADH. The speculative role of phototherapy as a physical trigger for this drug-related adverse event should be confirmed in other cases by thorough study of the serotonin metabolism, assay of SSRI levels in cord blood, and serial measurement of plasma levels in exposed neonates. As phototherapy is used frequently in jaundiced neonates and an apparently increasing number of infants are born to mothers who take SSRIs, serotonin toxicity in neonates deserves increased attention.
Glucose metabolism at high density growth of E. coli B and E. coli K: Differences in metabolic pathways are responsible for efficient glucose utilization in E. coli B as determined by microarrays and Northern blot analyses
Authors: Phue Je‐Nie , Noronha Santosh B. , Hattacharyya Ritabrata , Wolfe Alan J. , Shiloach Joseph
Published: April 2005

In a series of previous reports it was established by implementing metabolic flux, NMR/MS, and Northern blot analysis that the glyoxylate shunt, the TCA cycle, and acetate uptake by acetyl‐CoA synthetase are more active in Escherichia coli BL21 than in Escherichia coli JM109. These differences were accepted as the reason for the differences in the glucose metabolism and acetate excretion of these two strains. Examination of the bacterial metabolism by microarrays and time course Northern blot showed that in addition to the glyoxylate shunt, the TCA cycle and the acetate uptake, other metabolic pathways are active differently in the two strains. These are gluconeogenesis, sfcA shunt, ppc shunt, glycogen biosynthesis, and fatty acid degradation. It was found that in E. coli JM109, acetate is produced by pyruvate oxidase (poxB) using pyruvate as a substrate rather than by phosphotransacetylase‐acetate kinase (Pta‐AckA) system which uses acetyl‐CoA. The inactivation of the gluconeogenesis enzyme phosphoenolpyruvate synthetase (ppsA), the activation of the anaplerotic sfcA shunt, and low and stable pyruvate dehydrogenase (aceE, aceF) cause pyruvate accumulation which is converted to acetate by pyruvate oxidase B. The behavior of the ppsA, acs, and aceBAK in JM109 was dependent on the glucose supply strategy. When the glucose concentration was high, no transcription of these genes was observed and acetate concentration increased, but at low glucose concentrations these genes were expressed and the acetate concentration decreased. It is possible that there is a major regulatory molecule that controls not only ppsA and aceBAK but also acs. The gluconeogenesis pathway (fbp, pckA, and ppsA) which leads to glycogen accumulation is constitutively active in E. coli BL21 regardless of glucose feeding strategy. Published 2005 Wiley Periodicals, Inc.
Childbirth in Palestine
Authors: Wick L. , Mikki N. , Giacaman R. , Abdul‐Rahim H.
Published: April 2005

Objective

This study describes staffing, caseloads and reported routine practices for normal childbirth in Palestinian West Bank (WB) governmental maternity facilities and compares these practices with evidence‐based care.

Methods

Data on routine childbirth practices in all eight governmental hospitals were obtained through interviews with head obstetricians and midwives. Data on staffing and monthly number of births were collected by phone or personal interview from all 37 WB hospitals.

Results

Forty‐eight percent of WB deliveries took place in crowded and understaffed governmental hospitals. Reported practices were not consistently in line with evidence‐based care. Lack of knowledge and structural barriers were reasons for this gap.

Conclusion

The implications of limiting unnecessary interventions in the normal birth process are particularly important in a context of limited access and scarce resources. More skilled birth attendants and a universal commitment to effective care are needed.
Management of Posttraumatic Vertigo
Authors: Ernst Arne , Basta Dietmar , Seidl Rainer O. , Todt Ingo , Scherer Hans , Clarke Andrew
Published: April 2005

OBJECTIVE:

To evaluate patients after blunt trauma of the head, neck, and craniocervical junction (without fractures) with vertigo and to report the results of treatment after extensive diagnostics.

STUDY DESIGN:

Prospective study of consecutive new cases with vertigo after trauma at different periods of onset. During 2000–2002, 63 patients were examined and treated.

SETTING:

Regional trauma medical center for the greater Berlin Area, tertiary referral unit.

RESULTS:

The primary disorders included labyrinthine concussion (18), rupture of the round window membrane (6), and cervicogenic vertigo (12). The secondary disorders included otolith disorders (5), delayed endolymphatic hydrops (12), and canalolithiasis (9). The patients were free of vertigo symptoms (except cervicogenic and otolith disorder) after treatment, which consisted of habituation training, medical and surgical therapy options. The follow‐up was 1 year.

CONCLUSION:

Posttraumatic vertigo can be treated with a high success rate once the underlying disorder has been identified. The extent of the neurotological test battery determines the precision and quality of diagnostics. Surgical measures should be an integral part of treatment modalities if conservative treatment is not effective.

SIGNIFICANCE:

Minor trauma of the head, neck, and craniocervical junction can have major impact on the vestibular system at different sites. Patients need to be carefully diagnosed, even if the onset of vertigo occurs a few weeks or months after the initial trauma.
Use of Mitomycin C for Treatment of Keloid: A Preliminary Report
Authors: Talmi Yoav P. , Orenstein Arie , Wolf Michael , Kronenberg Jona
Published: April 2005

OBJECTIVES:

Mitomycin C (MC) is an anti‐neoplastic agent with an anti‐proliferative effect on fibroblasts. We set out to evaluate the effect of MC application following keloid excision.

STUDY DESIGN AND SETTING:

Patients with keloid in a tertiary referral center were enrolled in a prospective study. The scar was excised and prior to skin closure, a pledget with 1 cc of MC 0.4 mg/mL was applied for 5 minutes. Patient satisfaction and keloid thickness were assessed.

RESULTS:

All patients were satisfied with the results, although complete disappearance of the keloid was evident only in two. Keloid thickness was measured and ranged from 5 to 26 mm. Following surgery and treatment at 2 months thickness ranged from 0 to 8 mm.

CONCLUSIONS:

MC application following scar resection appears to be effective in treatment of keloid.

SIGNIFICANCE:

As no specific effective treatment for keloid is currently available, utilization of this readily available therapeutic agent may improve treatment outcome.
Intratympanic Steroid Perfusion for Refractory Sudden Sensorineural Hearing Loss
Authors: Herr Brian D. , Marzo Sam J.
Published: April 2005

OBJECTIVE:

Patients with sudden sensorineural hearing loss (SSHL) can benefit from systemic steroid therapy. Unfortunately, some patients are not candidates for steroid therapy due to concern over possible complications. Furthermore, not all patients will benefit from steroid administration. This study evaluates the potential benefits and safety of treating patients with SSHL refractory to oral steroids with intratympanic steroid therapy.

METHODS:

A retrospective case review was performed on all patients who presented with sudden sensorineural hearing loss refractory to oral steroid therapy during the past year. Seventeen patients were identified. All patients underwent intratympanic steroid administration, via MicroWick placement and/or round window catheter placement.

RESULTS:

Nine patients with sudden sensorineural hearing loss showed an improvement with intratympanic steroid therapy, consisting of MicroWick placement with dexamethasone drop (Decadron) administration for 1–2 weeks and/or round window catheter placement with steroid perfusion. Only one of the patients presenting with hearing loss present for greater than 8 weeks benefited from intratympanic therapy. Complications were few and included tympanic membrane perforation, chronic otitis media, dysequilibrium, and dysguesia.

CONCLUSIONS:

Intratympanic steroid therapy can be beneficial in treating patients with sudden sensorineural hearing loss refractory to oral steroid use. EBM rating: C.
The Utility of Serum PTH Assessment 24 Hours after Total Thyroidectomy
Authors: Del Rio Paolo , Arcuri Maria Francesca , Ferreri Giovanni , Sommaruga Lucia , Sianesi Mario
Published: April 2005

BACKGROUND:

Hypocalcemia is the most frequent complication following total thyroidectomy. This prospective study examines the predictive value of parathyroid hormone (PTH) levels measured 24 hours after surgery.

MATERIAL AND METHODS:

A total of 1006 consecutive patients (mean age, 54.8 years; female/male ratio, 4/1) underwent total thyroidectomy for benign or malignant thyroid from January 1995 to November 2003. Serum calcium, phosphorus, and PTH were measured preoperatively and at 24 hours after surgery. All patients underwent preoperative examination to assess cord motility.

RESULTS:

A total of 253 (25.1%) patients presented with hypocalcemia demonstrated by clinical and laboratory findings. In 101 cases the hypocalcemic syndrome manifested after 24 to 36 hours whereas in 5 of 101 cases, symptom onset was between 48 and 72 hours. Serum calcium levels lower than 7.5 mg/dL were recorded in all the 101 cases. In 239 of 253 cases serum calcium returned to normal values within 7 days following surgery. PTH at 24 hours was below normal levels in 49 of the 101 patients but was within normal limits in 52 cases. The incidence of hypocalcemia was higher in patients undergoing surgery for malignant thyroid (P < 0.05).

CONCLUSIONS:

We do not consider PTH levels at 24 hours postoperatively as predictive of hypocalcemia.
The Role of Adjustment of Expiratory Effort in the Control of Vocal Intensity: Clinical Assessment of Phonatory Function
Authors: Makiyama Kiyoshi , Yoshihashi Hidetaka , Mogitate Manabu , Kida Akinori
Published: April 2005

OBJECTIVE:

To determine the role of the adjustment of expiratory effort in the control of vocal intensity.

STUDY DESIGN:

An intensity‐loading test was performed by using the airway interruption method. Three groups of subjects were used: a control group thought to resemble normal vocal fold closure, a group of patients with Reinke's edema thought to represent increased mass at the level of the vocal folds, and a group with vocal fold paralysis that was thought to represent a group with lack of adequate vocal fold closure.

RESULTS:

In the control group, expiratory lung pressure and airway resistance slightly increased. In the patients with Reinke's edema, expiratory lung pressure, and airway resistance significantly increased. In this group, the voice intensity was controlled by laryngeal adjustment, but a greater expiratory effort was needed because of a greater increase in glottal resistance. In the patients with vocal cord paralysis, airway resistance did not increase even with a high‐intensity voice. Vocal intensity was controlled by expiratory effort.

CONCLUSIONS:

If there is sufficient ability for laryngeal adjustment, vocal intensity is controlled primarily by laryngeal adjustment and by expiratory adjustment in response to increased glottal resistance. However, vocal intensity is controlled by expiratory effort when laryngeal adjustment ability is poor.
Domain III of
Plasmodium falciparum
apical membrane antigen 1 binds to the erythrocyte membrane protein Kx
Authors: Kato Kentaro , Mayer D. C. Ghislaine , Singh Sanjay , Reid Marion , Miller Louis H.
Published: April 2005

Plasmodium falciparum
apical membrane antigen 1 (AMA1) is located in the merozoite micronemes, an organelle that contains receptors for invasion, suggesting that AMA1 may play a role in this process. However, direct evidence that
P. falciparum
AMA1 binds to human erythrocytes is lacking. In this study, we determined that domain III of AMA1 binds to the erythrocyte membrane protein, Kx, and that the rate of invasion of Kx
null
erythrocytes is reduced, indicating a significant but not unique role of AMA1 and Kx in parasite invasion of erythrocytes. Domains I/II/III, domains I/II and domain III of AMA1 were expressed on the surface of CHO-K1 cells, and their ability to bind erythrocytes was determined. We observed that each of these domains failed to bind untreated human erythrocytes. In contrast, domain III, but not the other domains of AMA1, bound to trypsin-treated human erythrocytes. We tested the binding of AMA1 to trypsin-treated genetically mutant human erythrocytes, missing various erythrocyte membrane proteins. AMA1 failed to bind trypsin-treated Kx
null
(McLeod) erythrocytes, which lack the Kx protein. Furthermore, treatmentofhumanerythrocyteswithtrypsin, followed by α-chymotrypsin, cleaved Kx and destroyed the binding of AMA1 to human erythrocytes. Lastly, the rate of invasion of Kx null erythrocytes by
P. falciparum
was significantly lower than Kx-expressing erythrocytes. Taken together, our data suggest that AMA1 plays an important, but not exclusive, role in invasion of human erythrocytes through a process that involves exposure or modification of the erythrocyte surface protein, Kx, by a trypsin-like enzyme.
Virus Induction of Heat Shock Protein 70 Reflects a General Response to Protein Accumulation in the Plant Cytosol
Authors: Aparicio Frederic , Thomas Carole L. , Lederer Carsten , Niu Yan , Wang Daowen , Maule Andrew J.
Published: April 2005

Different cytoplasmically replicating RNA viruses were shown to induce a specific subset of heat-inducible heat shock protein 70 (HSP70) genes in Arabidopsis (Arabidopsis thaliana). To identify the inducing principle, a promoter∷reporter system was developed for the facile analysis of differentially responding Arabidopsis HSP70 genes, by infiltration into Nicotiana benthamiana leaves. Through transient expression of individual viral cistrons or through deletion analysis of a viral replicon, we were unable to identify a unique inducer of HSP70. However, there was a positive correlation between the translatability of the test construct and the differential induction of HSP70. Since these data implied a lack of specificity in the induction process, we also expressed a random series of cytosolically targeted Arabidopsis genes and showed that these also differentially induced HSP70. Through a comparison of different promoter∷reporter constructs and through measurements of the steady-state levels of the individual proteins, it appeared that the HSP70 response reflected the ability of the cytosol to sense individual properties of particular proteins when expressed at high levels. This phenomenon is reminiscent of the unfolded protein response observed when the induced accumulation of proteins in the endoplasmic reticulum also induces a specific suite of chaperones.
A Two-Edged Role for the Transposable ElementKiddoin therice ubiquitin2Promoter
Authors: Yang Guojun , Lee Yeon-Hee , Jiang Yiming , Shi Xiangyu , Kertbundit Sunee , Hall Timothy C.
Published: April 2005

Miniature inverted repeat transposable elements (MITEs) are thought to be a driving force for genome evolution. Although numerous MITEs are found associated with genes, little is known about their function in gene regulation. Whereas the rice ubiquitin2 (rubq2) promoter in rice (Oryza sativa) line IR24 contains two nested MITEs (Kiddo and MDM1), that in line T309 has lost Kiddo, providing an opportunity to understand the role of MITEs in promoter function. No difference in endogenous rubq2 transcript levels between T309 and IR24 was evident using RT-PCR. However, promoter analysis using both transient and stably transformed calli revealed that Kiddo contributed some 20% of the total expression. Bisulfite genomic sequencing of the rubq2 promoters revealed specific DNA methylation at both symmetric and asymmetric cytosine residues on the MITE sequences, possibly induced by low levels of homologous transcripts. When methylation of the MITEs was blocked by 5-azacytidine treatment, a threefold increase in the endogenous rubq2 transcript level was detected in IR24 compared with that in T309. Together with the observed MITE methylation pattern, the detection of low levels of transcripts, but not small RNAs, corresponding to Kiddo and MDM1 suggested that RNA-dependent DNA methylation is induced by MITE transcripts. We conclude that, although Kiddo enhances transcription from the rubq2 promoter, this effect is mitigated by sequence-specific epigenetic modification.
Comprehensive Interaction Map of the Arabidopsis MADS Box Transcription Factors
Authors: de Folter Stefan , Immink Richard G.H. , Kieffer Martin , Pařenicová Lucie , Henz Stefan R. , Weigel Detlef , Busscher Marco , Kooiker Maarten , Colombo Lucia , Kater Martin M. , Davies Brendan , Angenent Gerco C.
Published: April 2005

Interactions between proteins are essential for their functioning and the biological processes they control. The elucidation of interaction maps based on yeast studies is a first step toward the understanding of molecular networks and provides a framework of proteins that possess the capacity and specificity to interact. Here, we present a comprehensive plant protein–protein interactome map of nearly all members of the Arabidopsis thaliana MADS box transcription factor family. A matrix-based yeast two-hybrid screen of >100 members of this family revealed a collection of specific heterodimers and a few homodimers. Clustering of proteins with similar interaction patterns pinpoints proteins involved in the same developmental program and provides valuable information about the participation of uncharacterized proteins in these programs. Furthermore, a model is proposed that integrates the floral induction and floral organ formation networks based on the interactions between the proteins involved. Heterodimers between flower induction and floral organ identity proteins were observed, which point to (auto)regulatory mechanisms that prevent the activity of flower induction proteins in the flower.
MATERIALS CHARACTERIZATION IN THE ABERRATION-CORRECTED SCANNING TRANSMISSION ELECTRON MICROSCOPE
Authors: Varela M. , Lupini A.R. , Benthem K. van , Borisevich A.Y. , Chisholm M.F. , Shibata N. , Abe E. , Pennycook S.J.
Published: April 2005

▪ Abstract  In the nanoscience era, the properties of many exciting new materials and devices will depend on the details of their composition down to the level of single atoms. Thus the characterization of the structure and electronic properties of matter at the atomic scale is becoming ever more vital for economic and technological as well as for scientific reasons. The combination of atomic-resolution Z-contrast scanning transmission electron microscopy (STEM) and electron energy loss spectroscopy (EELS) represents a powerful method to link the atomic and electronic structure to macroscopic properties, allowing materials, nanoscale systems, and interfaces to be probed in unprecedented detail. Z-contrast STEM uses electrons that have been scattered to large angles for imaging. The relative intensity of each atomic column is roughly proportional to Z2, where Z is the atomic number. Recent developments in correcting the aberrations of the lenses in the electron microscope have pushed the achievable spatial resolution and the sensitivity for imaging and spectroscopy in the STEM into the sub-Ångstrom (sub-Å) regime, providing a new level of insight into the structure/property relations of complex materials. Images acquired with an aberration-corrected instrument show greatly improved contrast. The signal-to-noise ratio is sufficiently high to allow sensitivity even to single atoms in both imaging and spectroscopy. This is a key achievement because the detection and measurement of the response of individual atoms has become a challenging issue to provide new insight into many fields, such as catalysis, ceramic materials, complex oxide interfaces, or grain boundaries. In this article, the state-of-the-art for the characterization of all of these different types of materials by means of aberration-corrected STEM and EELS are reviewed.
Hemin induces active chloride secretion in Caco-2 cells
Authors: Uc Aliye , Husted Russell F. , Giriyappa Radhamma L. , Britigan Bradley E. , Stokes John B.
Published: April 2005

Enterocytes maintain fluid-electrolyte homeostasis by keeping a tight barrier and regulating ion channels. Carbon monoxide (CO), a product of heme degradation, modulates electrolyte transport in kidney and lung epithelium, but its role in regulating intestinal fluid-electrolyte homeostasis has not been studied. The major source of endogenous CO formation comes from the degradation of heme via heme oxygenase. We hypothesized that heme activates electrolyte transport in intestinal epithelial cells. Basolateral hemin treatment increased baseline Caco-2 cell short-circuit currents ( Isc) twofold (control = 1.96 ± 0.14 μA/cm2vs. hemin = 4.07 ± 0.16 μA/cm2, P < 0.01); apical hemin had no effect. Hemin-induced Iscwas caused by Cl−secretion because it was inhibited in Cl−-free medium, with ouabain, 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), or DIDS. Apical electrogenic Na+channel inhibitor benzamil had no effect on hemin-induced Isc. Hemin did not alter the ability of Caco-2 cells to respond maximally to forskolin, but a soluble guanylate cyclase inhibitor, [1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) inhibited the effects of hemin. A CO-releasing molecule, tricarbonyldichlororuthenium II, induced active Cl−secretion that was also inhibited with ODQ. We conclude that hemin induces active Cl−secretion in Caco-2 cells via a cGMP-dependent pathway. These effects are probably the consequence of CO formation. Heme and CO may be important regulators of intestinal fluid-electrolyte homeostasis.
Revealing anti-inflammatory mechanisms of soy isoflavones by flow: modulation of leukocyte-endothelial cell interactions
Authors: Chacko Balu K. , Chandler Robert T. , Mundhekar Ameya , Khoo Nicholas , Pruitt Heather M. , Kucik Dennis F. , Parks Dale A. , Kevil Christopher G. , Barnes Stephen , Patel Rakesh P.
Published: April 2005

The antiatherogenic effects of soy isoflavone consumption have been demonstrated in a variety of studies. However, the mechanisms involved remain poorly defined. Adhesion of monocytes to vascular endothelial cells is a key step within the inflammatory cascade that leads to atherogenesis. Many factors, including the physical forces associated with blood flow, regulate this process. Using an in vitro flow assay, we report that genistein, a principal component of most isoflavone preparations, inhibits monocyte adhesion to cytokine (TNF-α)-stimulated human vascular endothelial cells at physiologically relevant concentrations (0–1 μM). This effect is absolutely dependent on flow and is not observed under static conditions. Furthermore, this inhibition was dependent on activation of endothelial peroxisomal proliferator-activated receptor-γ. No significant role for other reported properties of genistein, including antioxidant effects, inhibition of tyrosine kinases, or activation of estrogen receptors, was observed. Furthermore, the antiadhesive effects of genistein did not occur via modulation of the adhesion molecules E-selectin, ICAM-1, VCAM-1, or platelet-endothelial cell adhesion molecule-1. These data reveal a novel anti-inflammatory mechanism for isoflavones and identify the physical forces associated with blood flow and a critical mediator of this function.
Nuclear localization of leukotriene A4hydrolase in type II alveolar epithelial cells in normal and fibrotic lung
Authors: Brock Thomas G. , Lee Young-Jik , Maydanski Elana , Marburger Tessa L. , Luo Ming , Paine Robert , Peters-Golden Marc
Published: April 2005

Leukotriene A4(LTA4) hydrolase catalyzes the final step in leukotriene B4(LTB4) synthesis. In addition to its role in LTB4synthesis, the enzyme possesses aminopeptidase activity. In this study, we sought to define the subcellular distribution of LTA4hydrolase in alveolar epithelial cells, which lack 5-lipoxygenase and do not synthesize LTA4. Immunohistochemical staining localized LTA4hydrolase in the nucleus of type II but not type I alveolar epithelial cells of normal mouse, human, and rat lungs. Nuclear localization of LTA4hydrolase was also demonstrated in proliferating type II-like A549 cells. The apparent redistribution of LTA4hydrolase from the nucleus to the cytoplasm during type II-to-type I cell differentiation in vivo was recapitulated in vitro. Surprisingly, this change in localization of LTA4hydrolase did not affect the capacity of isolated cells to convert LTA4to LTB4. However, proliferation of A549 cells was inhibited by the aminopeptidase inhibitor bestatin. Nuclear accumulation of LTA4hydrolase was also conspicuous in epithelial cells during alveolar repair following bleomycin-induced acute lung injury in mice, as well as in hyperplastic type II cells associated with fibrotic lung tissues from patients with idiopathic pulmonary fibrosis. These results show for the first time that LTA4hydrolase can be accumulated in the nucleus of type II alveolar epithelial cells and that redistribution of the enzyme to the cytoplasm occurs with differentiation to the type I phenotype. Furthermore, the aminopeptidase activity of LTA4hydrolase within the nucleus may play a role in promoting epithelial cell growth.
Phylogeny and antiquity of M macrohaplogroup inferred from complete mt DNA sequence of Indian specific lineages
Authors: Rajkumar Revathi , Banerjee Jheelam , Gunturi Hima Bindu , Trivedi R , Kashyap VK
Published: April 2005

Background

Analysis of human complete mitochondrial DNA sequences has largely contributed to resolve phylogenies and antiquity of different lineages belonging to the majorhaplogroups L, N and M (East-Asian lineages). In the absence of whole mtDNA sequence information of M lineages reported in India that exhibits highest diversity within the sub-continent, the present study was undertaken to provide a detailed analysis of this macrohaplogroup to precisely characterize and unravel the intricate phylogeny of the lineages and to establish the antiquity of M lineages in India.

Results

The phylogenetic tree constructed from sequencing information of twenty-four whole mtDNA genome revealed novel substitutions in the previously defined M2a and M6 lineages. The most striking feature of this phylogenetic tree is the recognition of two new lineages, M30 and M31, distinguished by transitions at 12007 and 5319, respectively. M30 comprises of M18 and identifies a potential new sub-lineage possessing substitution at 16223 and 16300. It further branches into M30a sub-lineage, defined by 15431 and 195A substitution. The age of M30 lineage was estimated at 33,042 YBP, indicating a more recent expansion time than M2 (49,686 YBP). The M31 branch encompasses the M6 lineage along with the previously defined M3 and M4 lineages. Contradictory to earlier reports, the M5 lineage does not always include a 12477 substitution, and is more appropriately defined by a transversion at 10986A. The phylogenetic tree also identifies a potential new lineage in the M* branch with HVSI sequence as 16223,16325. Substitutions in M25 were in concordance with previous reports.

Conclusion

This study describes five new basal mutations and recognizes two new lineages, M30 and M31 that substantially contribute to the present understanding of macrohaplogroup M. These two newly erected lineages include the previously independent lineages M18 and M6 as sub-lineages within them, respectively, suggesting that most mt DNA genomes might arise as limited offshoots of M trunk. Furthermore, this study supports the non existence of lineages such as M3 and M4 that are solely defined on the basis of fast mutating control region motifs and hence, establishes the importance of coding region markers for an accurate understanding of the phylogeny. The deep roots of M phylogeny clearly establish the antiquity of Indian lineages, especially M2, as compared to Ethiopian M1 lineage and hence, support an Asian origin of M majorhaplogroup.
Identification and characterization of a novel mammalian Mg2+ transporter with channel-like properties
Authors: Goytain Angela , Quamme Gary A
Published: April 2005

Background

Intracellular magnesium is abundant, highly regulated and plays an important role in biochemical functions. Despite the extensive evidence for unique mammalian Mg2+ transporters, few proteins have been biochemically identified to date that fulfill this role. We have shown that epithelial magnesium conservation is controlled, in part, by differential gene expression leading to regulation of Mg2+ transport. We used this knowledge to identify a novel gene that is regulated by magnesium.

Results

Oligonucleotide microarray analysis was used to identify a novel human gene that encodes a protein involved with Mg2+-evoked transport. We have designated this magnesium transporter (MagT1) protein. MagT1 is a novel protein with no amino acid sequence identity to other known transporters. The corresponding cDNA comprises an open reading frame of 1005 base pairs encoding a protein of 335 amino acids. It possesses five putative transmembrane (TM) regions with a cleavage site, a N- glycosylation site, and a number of phosphorylation sites. Based on Northern analysis of mouse tissues, a 2.4 kilobase transcript is present in many tissues. When expressed in Xenopus laevis oocytes, MagT1 mediates saturable Mg2+ uptake with a Michaelis constant of 0.23 mM. Transport of Mg2+ by MagT1 is rheogenic, voltage-dependent, does not display any time-dependent inactivation. Transport is very specific to Mg2+ as other divalent cations did not evoke currents. Large external concentrations of some cations inhibited Mg2+ transport (Ni2+, Zn2+, Mn2+) in MagT1-expressing oocytes. Ca2+and Fe2+ were without effect. Real-time reverse transcription polymerase chain reaction and Western blot analysis using a specific antibody demonstrated that MagT1 mRNA and protein is increased by about 2.1-fold and 32%, respectively, in kidney epithelial cells cultured in low magnesium media relative to normal media and in kidney cortex of mice maintained on low magnesium diets compared to those animals consuming normal diets. Accordingly, it is apparent that an increase in mRNA levels is translated into higher protein expression.

Conclusion

These studies suggest that MagT1 may provide a selective and regulated pathway for Mg2+ transport in epithelial cells.
Two cases of "cannabis acute psychosis" following the administration of oral cannabis
Authors: Favrat Bernard , Ménétrey Annick , Augsburger Marc , Rothuizen Laura E , Appenzeller Monique , Buclin Thierry , Pin Marie , Mangin Patrice , Giroud Christian
Published: April 2005

Background

Cannabis is the most commonly used illegal drug and its therapeutic aspects have a growing interest. Short-term psychotic reactions have been described but not clearly with synthetic oral THC, especially in occasional users.

Case presentations

We report two cases of healthy subjects who were occasional but regular cannabis users without psychiatric history who developed transient psychotic symptoms (depersonalization, paranoid feelings and derealisation) following oral administration of cannabis. In contrast to most other case reports where circumstances and blood concentrations are unknown, the two cases reported here happened under experimental conditions with all subjects negative for cannabis, opiates, amphetamines, cocaine, benzodiazepines and alcohol, and therefore the ingested dose, the time-events of effects on behavior and performance as well as the cannabinoid blood levels were documented.

Conclusion

While the oral route of administration achieves only limited blood concentrations, significant psychotic reactions may occur.
Developing essential professional skills: a framework for teaching and learning about feedback
Authors: Henderson Penny , Ferguson-Smith Anne C , Johnson Martin H
Published: April 2005

Background

The ability to give and receive feedback effectively is a key skill for doctors, aids learning between all levels of the medical hierarchy, and provides a basis for reflective practice and life-long learning. How best to teach this skill?

Discussion

We suggest that a single "teaching the skill of feedback" session provides superficial and ineffective learning in a medical culture that often uses feedback skills poorly or discourages feedback. Our experience suggests that both the skill and the underlying attitude informing its application must be addressed, and is best done so longitudinally and reiteratively using different forms of feedback delivery. These feedback learning opportunities include written and oral, peer to peer and cross-hierarchy, public and private, thereby addressing different cognitive processes and attitudinal difficulties.

We conclude by asking whether it is possible to build a consensus approach to a framework for teaching and learning feedback skills?
BCG vaccination at three different age groups: response and effectiveness
Authors: Briassoulis George , Karabatsou Irene , Gogoglou Vasilis , Tsorva Athina
Published: April 2005

Background

The protection, which some BCG vaccines could confer against the development of tuberculosis (TB) in childhood, might be indirectly reflected by the subsequent development of BCG immune response. The objectives of the study were to examine effectiveness and possible differences of post-vaccination reaction to a lyophilized BCG at different age groups and to evaluate its protection against TB in a decade's period.

Methods

We studied the post-vaccination PPD-skin reaction and scar formation at three different school levels, corresponding to ages of 6, 12 and 15 years old, vaccinated by a lyophilized BCG vaccine (Pasteur Institute), currently used in our country. During a 10-year follow up the reported TB cases in vaccinated and non-vaccinated adolescences up to 24-years old were analyzed and compared to the number of cumulative cases observed in the adult population of two neighboring territories (vaccinated and non-vaccinated).

Results and Discussion

There was a significant correlation (r2 = 0.87, p < 0.0001) between tuberculin induration and scar formation. There was no statistically significant difference between the three age groups (6, 12, and 15 year-old, respectively) in regard to the diameter of tuberculin induration or scar formation. Although 34% of 10-year later indurations were unpredictably related to the initial ones (increased or decreased), they were significantly correlated (r2 = 0.45, p = 0.009). The relative percentage of TB for the 14–24 years-age group to the adult studied population was significantly lower among the immunized children compared to the non-immunized population of the same age group (17/77, 22% vs. 71/101, 70%, p < .0001).

Conclusion

Our data suggest that the lyophilized BCG vaccine used for BCG programs at different age groups is equally effective and may confer satisfactory protection against tuberculosis in puberty.
The active metabolite of leflunomide, A77 1726, interferes with dendritic cell function
Authors: Kirsch Bernhard M , Zeyda Maximilian , Stuhlmeier Karl , Grisar Johannes , Smolen Josef S , Watschinger Bruno , Stulnig Thomas M , Hörl Walter H , Zlabinger Gerhard J , Säemann Marcus D
Published: April 2005

Leflunomide, a potent disease-modifying antirheumatic drug used in the treatment of rheumatoid arthritis (RA), exhibits anti-inflammatory, antiproliferative and immunosuppressive effects. Although most of the beneficial effects of leflunomide have been attributed to its antimetabolite activity, mainly in T cells, other targets accounting for its potency might still exist. Because of mounting evidence for a prominent role of dendritic cells (DCs) in the initiation and maintenance of the immune response in RA, we analyzed the effect of the active metabolite of leflunomide (A77 1726; LEF-M) on phenotype and function of human myleloid DCs at several stages in their life cycle. Importantly, DCs differentiated in the presence of LEF-M exhibited an altered phenotype, with largely reduced surface expression of the critical co-stimulatory molecules CD40 and CD80. Furthermore, treatment of DCs during the differentiation or maturation phase with LEF-M aborted successful DC maturation. Exogenous addition of uridine revealed that DC modulation by LEF-M was independent of its proposed ability as an antimetabolite. In addition, the ability of DCs to initiate T-cell proliferation and to produce the proinflammatory cytokines IL-12 and tumour necrosis factor-α was markedly impaired by LEF-M treatment. As a molecular mechanism, transactivation of nuclear factor-κB, an transcription factor essential for proper DC function, was completely suppressed in DCs treated with LEF-M. These data indicate that interference with several aspects of DC function could significantly contribute to the beneficial effects of leflunomide in inflammatory diseases, including RA.
Regeneration of the immunoglobulin heavy-chain repertoire after transient B-cell depletion with an anti-CD20 antibody
Authors: Rouzière Anne-Sophie , Kneitz Christian , Palanichamy Arumugam , Dörner Thomas , Tony Hans-Peter
Published: April 2005

B-cell depletive therapies have beneficial effects in patients suffering from rheumatoid arthritis. Nevertheless, the role of B cells in the pathogenesis of the disease is not clear. In particular, it is not known how the regeneration of the B-cell repertoire takes place. Two patients with active rheumatoid arthritis were treated with rituximab, and the rearranged immunoglobulin heavy-chain genes (Ig-VH) were analysed to follow the B-cell regeneration. Patient A was treated with two courses of rituximab, and B-cell regeneration was followed over 27 months by analysing more than 680 Ig-VH sequences. Peripheral B-cell depletion lasted 7 months and 10 months, respectively, and each time was accompanied by a clinical improvement. Patient B received one treatment course. B-cell depletion lasted 5 months and was accompanied by a good clinical response. B cells regenerated well in both patients, and the repopulated B-cell repertoire was characterised by a polyclonal and diverse use of Ig-VH genes, as expected in adult individuals. During the early phase of B-cell regeneration we observed the expansion and recirculation of a highly mutated B-cell population. These cells expressed very different Ig-VH genes. They were class-switched and could be detected for a short period only. Patient A was followed long term, whereby some characteristic changes in the VH2 family as well as in specific mini-genes like VH3–23, VH 4–34 or VH 1–69 were observed. In addition, rituximab therapy resulted in the loss of clonal B cells for the whole period.

Our data show that therapeutic transient B-cell depletion by anti-CD20 antibodies results in the regeneration of a diverse and polyclonal heavy-chain repertoire. During the early phase of B-cell regeneration, highly mutated B cells recirculate for a short time period in both the patients analysed. The longitudinal observation of a single patient up to 27 months shows subtle intraindividual changes, which may indicate repertoire modulation.
Effect of the hospital nursing environment on patient mortality: a systematic review
Authors: Kazanjian Arminée , Green Carolyn , Wong Jennifer , Reid Robert
Published: April 2005

Objective: Research has examined the effect of the structure of health systems on health outcomes, but not how outcomes are affected by the nursing environments in hospitals. Our objective was to gather, critically appraise and synthesize all relevant primary research on the effect of the nursing environment on patient mortality.

Methods: Five electronic bibliographic databases were searched from their beginning through to May/June 2001, and Medline and CINAHL were updated to March 2004, using pre-determined search strategies and inclusion criteria. Studies were included if they met pre-determined criteria, reporting primary data both on a hospital environment and patient mortality. Methodological rigour was appraised using accepted criteria for the evaluation of research protocols, including case-mix adjustment.

Results: This paper focuses on 27 identified studies that investigated the impact of one or more attributes of the nursing environment on patient mortality. Nineteen studies found an association between one or more unfavourable attributes and higher mortality. There was considerable variability in attribute and outcome measures, settings and research quality across studies. This precluded statistical pooling of results.

Conclusions: On balance, current evidence indicates that social and environmental attributes of hospital nursing practice have an effect on the outcomes of care. Before optimal practice settings can be designed, further research of greater rigour is needed to provide a better understanding of the mechanisms that link the nursing environment to patient outcomes.