bluuebunny/crossref_metadata_2025 huggingface dataset:
Design considerations for a wearable monitor to measure finger posture
Authors: Simone Lisa K , Kamper Derek G
Published: March 2005

Background

Objective measures of hand function as individuals participate in home and community activities are needed in order to better plan and evaluate rehabilitation treatments. Traditional measures collected in the clinical setting are often not reflective of actual functional performance. Recent advances in technology, however, enable the development of a lightweight, comfortable data collection monitor to measure hand kinematics.

Methods

This paper presents the design analysis of a wearable sensor glove with a specific focus on the sensors selected to measure bend. The most important requirement for the glove is easy donning and removal for individuals with significantly reduced range of motion in the hands and fingers. Additional requirements include comfort and durability, cost effectiveness, and measurement repeatability. These requirements eliminate existing measurement gloves from consideration. Glove construction is introduced, and the sensor selection and glove evaluation process are presented.

Results

Evaluation of commercial bend sensors shows that although most are not appropriate for repeatable measurements of finger flexion, one has been successfully identified. A case study for sensor glove repeatability using the final glove configuration and sensors does show a high degree of repeatability in both the gripped and flat hand positions (average coefficient of variability = 2.96% and 0.10%, respectively).

Conclusion

Measuring functional outcomes in a portable manner can provide a wealth of information important to clinicians for the evaluation and treatment of movement disorders in the hand and fingers. This device is an important step in that direction as both a research and an evaluation method.
A wireless body area network of intelligent motion sensors for computer assisted physical rehabilitation
Authors: Jovanov Emil , Milenkovic Aleksandar , Otto Chris , de Groen Piet C
Published: March 2005

Background

Recent technological advances in integrated circuits, wireless communications, and physiological sensing allow miniature, lightweight, ultra-low power, intelligent monitoring devices. A number of these devices can be integrated into a Wireless Body Area Network (WBAN), a new enabling technology for health monitoring.

Methods

Using off-the-shelf wireless sensors we designed a prototype WBAN which features a standard ZigBee compliant radio and a common set of physiological, kinetic, and environmental sensors.

Results

We introduce a multi-tier telemedicine system and describe how we optimized our prototype WBAN implementation for computer-assisted physical rehabilitation applications and ambulatory monitoring. The system performs real-time analysis of sensors' data, provides guidance and feedback to the user, and can generate warnings based on the user's state, level of activity, and environmental conditions. In addition, all recorded information can be transferred to medical servers via the Internet and seamlessly integrated into the user's electronic medical record and research databases.

Conclusion

WBANs promise inexpensive, unobtrusive, and unsupervised ambulatory monitoring during normal daily activities for prolonged periods of time. To make this technology ubiquitous and affordable, a number of challenging issues should be resolved, such as system design, configuration and customization, seamless integration, standardization, further utilization of common off-the-shelf components, security and privacy, and social issues.
Wearable Conductive Fiber Sensors for Multi-Axis Human Joint Angle Measurements
Authors: Gibbs Peter T , Asada HHarry
Published: March 2005

Background

The practice of continuous, long-term monitoring of human joint motion is one that finds many applications, especially in the medical and rehabilitation fields. There is a lack of acceptable devices available to perform such measurements in the field in a reliable and non-intrusive way over a long period of time. The purpose of this study was therefore to develop such a wearable joint monitoring sensor capable of continuous, day-to-day monitoring.

Methods

A novel technique of incorporating conductive fibers into flexible, skin-tight fabrics surrounding a joint is developed. Resistance changes across these conductive fibers are measured, and directly related to specific single or multi-axis joint angles through the use of a non-linear predictor after an initial, one-time calibration. Because these sensors are intended for multiple uses, an automated registration algorithm has been devised using a sensitivity template matched to an array of sensors spanning the joints of interest. In this way, a sensor array can be taken off and put back on an individual for multiple uses, with the sensors automatically calibrating themselves each time.

Results

The wearable sensors designed are comfortable, and acceptable for long-term wear in everyday settings. Results have shown the feasibility of this type of sensor, with accurate measurements of joint motion for both a single-axis knee joint and a double axis hip joint when compared to a standard goniometer used to measure joint angles. Self-registration of the sensors was found to be possible with only a few simple motions by the patient.

Conclusion

After preliminary experiments involving a pants sensing garment for lower body monitoring, it has been seen that this methodology is effective for monitoring joint motion of the hip and knee. This design therefore produces a robust, comfortable, truly wearable joint monitoring device.
Soilborne wheat mosaic virus (SBWMV) 19K protein belongs to a class of cysteine rich proteins that suppress RNA silencing
Authors: Te Jeannie , Melcher Ulrich , Howard Amanda , Verchot-Lubicz Jeanmarie
Published: March 2005

Amino acid sequence analyses indicate that the Soilborne wheat mosaic virus (SBWMV) 19K protein is a cysteine-rich protein (CRP) and shares sequence homology with CRPs derived from furo-, hordei-, peclu- and tobraviruses. Since the hordei- and pecluvirus CRPs were shown to be pathogenesis factors and/or suppressors of RNA silencing, experiments were conducted to determine if the SBWMV 19K CRP has similar activities. The SBWMV 19K CRP was introduced into the Potato virus X (PVX) viral vector and inoculated to tobacco plants. The SBWMV 19K CRP aggravated PVX-induced symptoms and restored green fluorescent protein (GFP) expression to GFP silenced tissues. These observations indicate that the SBWMV 19K CRP is a pathogenicity determinant and a suppressor of RNA silencing.
The mechanism of low-concentration sodium nitroprusside-mediated protection of chondrocyte death
Authors: Kim Hyun A , Lee Ki Byoung , Bae Sang-cheol
Published: March 2005

Sodium nitroprusside (SNP), a widely used nitric oxide donor, has recently been shown to mediate chondrocyte apoptosis by generating reactive oxygen species, whereas more potent nitric oxide donors do not induce chondrocyte apoptosis. The present study was performed to investigate the protective effect of a low concentration of SNP upon the cytotoxicity of chondrocytes to higher concentrations of SNP, and to elucidate the underlying mechanism. Human osteoarthritis chondrocytes were cultured as monolayers, and first-passage cells were used for the experiments. Chondrocyte death induced by 1 mM SNP was completely inhibited by pretreating with 0.1 mM SNP. This protective effect of SNP was replicated by the guanosine-3',5'κ-cyclic monophosphate analog, DBcGMP. Protection from chondrocyte death conferred by 0.1 mM SNP was mediated by heme oxygenase 1 (HO-1), as was revealed by the increased expression of HO-1 in 0.1 mM SNP pretreated chondrocytes and by the reversal of this protective effect by the HO-1 inhibitor, zinc protoporphyrin. SNP-mediated chondrocyte protection correlated with the downregulation of both extracellular signal-regulated protein kinase 1/2 and p38 kinase activation. SNP at 0.1 mM induced significant NF-κB activation as revealed by electrophoretic mobility shift assays, and the inhibition of NF-κB by MG132 or Bay 11-7082 nullified 0.1 mM SNP-mediated chondrocyte protection. The upregulation of p53 and the downregulation of Bcl-XL and Mcl-1 by 1 mM SNP were reversed by 0.1 mM SNP pretreatment at the protein level by western blotting. Our study shows that priming with 0.1 mM SNP confers complete protection against cell death induced by 1 mM SNP in human articular chondrocytes. This protective effect was found to be correlated with the upregulation of both HO-1 and NF-κB and with the concomitant downregulation of both extracellular signal-regulated protein kinase 1/2 and p38 activation.
Synovial microparticles from arthritic patients modulate chemokine and cytokine release by synoviocytes
Authors: Berckmans René J , Nieuwland Rienk , Kraan Maarten C , Schaap Marianne CL , Pots Desirée , Smeets Tom JM , Sturk Augueste , Tak Paul P
Published: March 2005

Synovial fluid from patients with various arthritides contains procoagulant, cell-derived microparticles. Here we studied whether synovial microparticles modulate the release of chemokines and cytokines by fibroblast-like synoviocytes (FLS). Microparticles, isolated from the synovial fluid of rheumatoid arthritis (RA) and arthritis control (AC) patients (n = 8 and n = 3, respectively), were identified and quantified by flow cytometry. Simultaneously, arthroscopically guided synovial biopsies were taken from the same knee joint as the synovial fluid. FLS were isolated, cultured, and incubated for 24 hours in the absence or presence of autologous microparticles. Subsequently, cell-free culture supernatants were collected and concentrations of monocyte chemoattractant protein-1 (MCP-1), IL-6, IL-8, granulocyte/macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF) and intracellular adhesion molecule-1 (ICAM-1) were determined. Results were consistent with previous observations: synovial fluid from all RA as well as AC patients contained microparticles of monocytic and granulocytic origin. Incubation with autologous microparticles increased the levels of MCP-1, IL-8 and RANTES in 6 of 11 cultures of FLS, and IL-6, ICAM-1 and VEGF in 10 cultures. Total numbers of microparticles were correlated with the IL-8 (r = 0.91, P < 0.0001) and MCP-1 concentrations (r = 0.81, P < 0.0001), as did the numbers of granulocyte-derived microparticles (r = 0.89, P < 0.0001 and r = 0.93, P < 0.0001, respectively). In contrast, GM-CSF levels were decreased. These results demonstrate that microparticles might modulate the release of chemokines and cytokines by FLS and might therefore have a function in synovial inflammation and angiogenesis.
Quantitative ultrasound can assess the regeneration process of tissue-engineered cartilage using a complex between adherent bone marrow cells and a three-dimensional scaffold
Authors: Hattori Koji , Takakura Yoshinori , Ohgushi Hajime , Habata Takashi , Uematsu Kota , Yamauchi Jun , Yamashita Kenji , Fukuchi Takashi , Sato Masao , Ikeuchi Ken
Published: March 2005

Articular cartilage (hyaline cartilage) defects resulting from traumatic injury or degenerative joint disease do not repair themselves spontaneously. Therefore, such defects may require novel regenerative strategies to restore biologically and biomechanically functional tissue. Recently, tissue engineering using a complex of cells and scaffold has emerged as a new approach for repairing cartilage defects and restoring cartilage function. With the advent of this new technology, accurate methods for evaluating articular cartilage have become important. In particular, in vivo evaluation is essential for determining the best treatment. However, without a biopsy, which causes damage, articular cartilage cannot be accurately evaluated in a clinical context. We have developed a novel system for evaluating articular cartilage, in which the acoustic properties of the cartilage are measured by introducing an ultrasonic probe during arthroscopy of the knee joint. The purpose of the current study was to determine the efficacy of this ultrasound system for evaluating tissue-engineered cartilage in an experimental model involving implantation of a cell/scaffold complex into rabbit knee joint defects. Ultrasonic echoes from the articular cartilage were converted into a wavelet map by wavelet transformation. On the wavelet map, the percentage maximum magnitude (the maximum magnitude of the measurement area of the operated knee divided by that of the intact cartilage of the opposite, nonoperated knee; %MM) was used as a quantitative index of cartilage regeneration. Using this index, the tissue-engineered cartilage was examined to elucidate the relations between ultrasonic analysis and biochemical and histological analyses. The %MM increased over the time course of the implant and all the hyaline-like cartilage samples from the histological findings had a high %MM. Correlations were observed between the %MM and the semiquantitative histologic grading scale scores from the histological findings. In the biochemical findings, the chondroitin sulfate content increased over the time course of the implant, whereas the hydroxyproline content remained constant. The chondroitin sulfate content showed a similarity to the results of the %MM values. Ultrasonic measurements were found to predict the regeneration process of the tissue-engineered cartilage as a minimally invasive method. Therefore, ultrasonic evaluation using a wavelet map can support the evaluation of tissue-engineered cartilage using cell/scaffold complexes.
Systemic lupus erythematosus induced by anti-tumour necrosis factor alpha therapy: a French national survey
Authors: De Bandt Michel , Sibilia Jean , Le Loët Xavier , Prouzeau Sebastian , Fautrel Bruno , Marcelli Christian , Boucquillard Eric , Siame Jean Louis , Mariette Xavier ,   the Club Rhumatismes et Inflammation
Published: March 2005

The development of drug-induced lupus remains a matter of concern in patients treated with anti-tumour necrosis factor (TNF) alpha. The incidence of such adverse effects is unknown. We undertook a retrospective national study to analyse such patients.

Between June and October 2003, 866 rheumatology and internal medicine practitioners from all French hospital centres prescribing anti-TNF in rheumatic diseases registered on the website of the 'Club Rhumatismes et Inflammation' were contacted by email to obtain the files of patients with TNF-induced systemic lupus erythematosus. Twenty-two cases were collected, revealing two aspects of these manifestations. Ten patients (six patients receiving infliximab, four patients receiving etanercept) only had anti-DNA antibodies and skin manifestations one could classify as 'limited skin lupus' or 'toxidermia' in a context of autoimmunity, whereas 12 patients (nine patients receiving infliximab, three patients receiving etanercept) had more complete drug-induced lupus with systemic manifestations and at least four American Congress of Rheumatology criteria. One patient had central nervous system manifestations. No patients had lupus nephritis. The signs of lupus occurred within a mean of 9 months (range 3–16 months) in patients treated with infliximab and within a mean of 4 months (range 2–5 months) in patients treated with etanercept. In all cases after diagnosis was determined, anti-TNF was stopped and specific treatment introduced in eight patients: two patients received intravenous methylprednisolone, four patients received oral steroids (15–35 mg/day), and two patients received topical steroids. Lupus manifestations abated within a few weeks (median 8 weeks, standard deviation 3–16) in all patients except one with longer-lasting evolution (6 months). At that time, cautious estimations (unpublished data from Schering Plough Inc. and Wyeth Inc.) indicated that about 7700 patients had been exposed to infliximab and 3000 to etanercept for inflammatory arthritides in France. It thus appears that no drug was more implicated than the other in lupus syndromes, whose incidence was 15/7700 = 0.19% with infliximab and 7/3800 = 0.18% with etanercept.

Clinicians should be aware that lupus syndromes with systemic manifestations may occur in patients under anti-TNF alpha treatment.
Nectin-like molecule-1/TSLL1/SynCAM3: a neural tissue-specific immunoglobulin-like cell-cell adhesion molecule localizing at non-junctional contact sites of presynaptic nerve terminals, axons and glia cell processes
Authors: Kakunaga Shigeki , Ikeda Wataru , Itoh Shinsuke , Deguchi-Tawarada Maki , Ohtsuka Toshihisa , Mizoguchi Akira , Takai Yoshimi
Published: March 2005

Nectins are Ca2+-independent immunoglobulin-like cell-cell adhesion molecules and comprise a family of four members. At the mossy fiber terminals of hippocampus, nectin-1 and nectin-3 localize at the presynaptic and postsynaptic sides of synaptic junctions, respectively, and their trans-interactions play a role in formation of synapses in cooperation with N-cadherin. Nectins are associated with the actin cytoskeleton through afadin, a nectin- and actin-filament-binding protein. Five nectin-like molecules (Necls) which have domain structures similar to those of nectins have been identified and here we characterize Necl-1/TSLL1/SynCAM3, from now on referred to as Necl-1. Tissue distribution analysis showed that Necl-1 was specifically expressed in the neural tissue. Immunofluorescence and immunoelectron microscopy revealed that Necl-1 localized at the contact sites among axons, their terminals, and glia cell processes that cooperatively formed synapses, axon bundles and myelinated axons. Necl-1 showed Ca2+-independent homophilic cell-cell adhesion activity. It furthermore showed Ca2+-independent heterophilic cell-cell adhesion activity with Necl-2/IGSF4/RA175/SgIGSF/TSLC1/SynCAM1 from now on referred to as Necl-2, nectin-1 and nectin-3, but not with Necl-5 or nectin-2. The C-terminal cytoplasmic region of Necl-1 did not bind afadin but bound membrane-associated guanylate kinase subfamily members that contain the L27 domain, including Dlg3, Pals2 and CASK. These results indicate that Necl-1 is a neural-tissue-specific Ca2+-independent immunoglobulin-like cell-cell adhesion molecule which potentially has membrane-associated guanylate kinase subfamily member-binding activity and localizes at the non-junctional cell-cell contact sites.
The neurogene BTG2TIS21/PC3 is transactivated by ΔNp73α via p53 specifically in neuroblastoma cells
Authors: Goldschneider David , Million Karine , Meiller Anne , Haddada Hedi , Puisieux Alain , Bénard Jean , May Evelyne , Douc-Rasy Sétha
Published: March 2005

The p53 gene and its homologue p73 are rarely mutated in neuroblastoma. In recent studies, we showed that overexpression of ΔNp73α, an isoform lacking the N-terminal transactivation (TA) domain, surprisingly induces p53 protein accumulation in the wild-type (wt) p53 human neuroblastoma line SH-SY5Y. As can be expected owing to its dominant-negative effect, ΔNp73α inhibits Waf1/p21 gene expression, but equally importantly, it upregulates BTG2TIS21/PC3, another p53 target gene. This effect is not observed in neuroblastoma cells that express a mutated p53. To better understand the ΔNp73-mediated transactivation of the BTG2TIS21/PC3 gene we performed luciferase assays with two reporter plasmids harboring long and short BTG2 promoter sequences in three human neuroblastoma cell lines and one breast cancer cell line. Our results demonstrate that BTG2TIS21/PC3 transactivation by ΔNp73α depends on both p53 status (as it is not observed in a p53–/– neuroblastoma cell line) and cellular context (as it occurs in a p53+/+ neuroblastoma cell line but not in a p53+/+ breast tumor cell line). The fact that ΔNp73α may either inhibit or stimulate wt-p53 transcriptional activity, depending on both the p53 target gene and the cellular context, was confirmed by real-time quantitative PCR. Moreover, transactivation of the BTG2TIS21/PC3 promoter requires a complete ΔNp73α C-terminus sequence as it is not observed with ΔNp73β, which lacks most of the C-terminal domain. We have previously shown that ΔNp73α is the only p73 isoform expressed in undifferentiated neuroblastoma tumors. In light of all these findings, we propose that ΔNp73α not only acts as an inhibitor of p53/TAp73 functions in neuroblastoma tumors, but also cooperates with wt-p53 in playing a physiological role through the activation of BTG2TIS21/PC3 gene expression.
Higher-order nuclear organization in growth arrest of human mammary epithelial cells: a novel role for telomere-associated protein TIN2
Authors: Kaminker Patrick , Plachot Cedric , Kim Sahn-Ho , Chung Peter , Crippen Danielle , Petersen Ole W. , Bissell Mina J. , Campisi Judith , Lelièvre Sophie A.
Published: March 2005

Nuclear organization, such as the formation of specific nuclear subdomains, is generally thought to be involved in the control of cellular phenotype; however, there are relatively few specific examples of how mammalian nuclei organize during radical changes in phenotype, such as those occurring during differentiation and growth arrest. Using human mammary epithelial cells in which growth arrest is essential for morphological differentiation, we show that the arrest of cell proliferation is accompanied by a reorganization of the telomere-associated protein, TIN2, into one to three large nuclear subdomains. The large TIN2 domains do not contain telomeres and occur concomitant with the continued presence of TIN2 at telomeres. The TIN2 domains were sensitive to DNase, but not RNase, occurred frequently, but not exclusively near nucleoli, and overlapped often with dense domains containing heterochromatin protein 1γ. Expression of truncated forms of TIN2 simultaneously prevented the formation of TIN2 domains and relaxed the stringent morphogenesis-induced growth arrest in human mammary epithelial cells. Here we show that a novel extra-telomeric organization of TIN2 is associated with the control of cell proliferation and identify TIN2 as an important regulator of mammary epithelial differentiation.
A dynamin-3 spliced variant modulates the actin/cortactin-dependent morphogenesis of dendritic spines
Authors: Gray Noah W. , Kruchten Anne E. , Chen Jing , McNiven Mark A.
Published: March 2005

Immature dendrites extend many actin-rich filopodial structures that can be replaced by synapse-containing dendritic spines as the neuron matures. The large GTPase dynamin-3 (Dyn3) is a component of the postsynapse in hippocampal neurons but its function is undefined. Here, we demonstrate that a specific Dyn3 variant (Dyn3baa) promotes the formation of immature dendritic filopodia in cultured neurons. This effect is dependent upon Dyn3 GTPase activity and a direct interaction with the F-actin-binding protein cortactin. Consistent with these findings, Dyn3baa binds to cortactin with a 200% higher affinity than Dyn3aaa, a near identical isoform that does not induce dendritic filopodia when expressed in cultured neurons. Finally, levels of Dyn3baa-encoding mRNA are tightly regulated during neuronal maturation and are markedly upregulated during synaptogenesis. Together, these findings provide the first evidence that an enhanced interaction between a specific Dyn3 splice variant and cortactin modulate actin-membrane dynamics in developing neurons to regulate the morphogenesis of dendritic spines.
p25/Cdk5-mediated retinoblastoma phosphorylation is an early event in neuronal cell death
Authors: Hamdane Malika , Bretteville Alexis , Sambo Anne-Véronique , Schindowski Katharina , Bégard Séverine , Delacourte André , Bertrand Philippe , Buée Luc
Published: March 2005

In large models of neuronal cell death, there is a tight correlation between Cdk5 deregulation and cell-cycle dysfunction. However, pathways that link Cdk5 to the cell cycle during neuronal death are still unclear. We have investigated the molecular events that precede p25/Cdk5-triggered neuronal death using a neuronal cell line that allows inducible p25 expression. In this system, no sign of apoptosis was seen before 24 hours of p25 induction. Thus, at that time, cell-cycle-regulatory proteins were analysed by immunoblotting and some of them showed a significant deregulation. Interestingly, after time-course experiments, the earliest feature correlated with p25 expression was the phosphorylation of the retinoblastoma protein (Rb). Indeed, this phosphorylation was observed 6 hours after p25 induction and was abolished in the presence of a Cdk5 inhibitor, roscovitine, which does not inhibit the usual Rb cyclin-D kinases Cdk4 and Cdk6. Furthermore, analyses of levels and subcellular localization of Cdk-related cyclins did not reveal any change following Cdk5 activation, arguing for a direct effect of Cdk5 activity on Rb protein. This latter result was clearly demonstrated by in vitro kinase assays showing that the p25-Cdk5 complex in our cell system phosphorylates Rb directly without the need for any intermediary kinase activity. Hence, Rb might be an appropriate candidate that connects Cdk5 to cell-cycle deregulation during neuronal cell death.
Intracellular fate of LDL receptor family members depends on the cooperation between their ligand-binding and EGF domains
Authors: Van Hoof Dennis , Rodenburg Kees W. , Van der Horst Dick J.
Published: March 2005

The insect low-density lipoprotein (LDL) receptor (LDLR) homologue LpR mediates endocytosis of an insect lipoprotein (lipophorin) that is structurally related to LDL. Despite these similarities, lipophorin and LDL follow distinct intracellular routes upon endocytosis by their receptors. Whereas LDL is degraded in lysosomes, lipophorin is recycled in a transferrin-like manner. We constructed several hybrid receptors composed of Locusta migratoria LpR and human LDLR regions to identify the domains implicated in LpR-mediated ligand recycling. Additionally, the triadic His562 residue of LDLR, which is putatively involved in ligand uncoupling, was mutated to Asn, corresponding to Asn643 in LpR, to analyse the role of the His triad in receptor functioning. The familial hypercholesterolaemia (FH) class 5 mutants LDLRH562Y and LDLRH190Y were also analysed in vitro. Fluorescence microscopic investigation and quantification suggest that LpR-mediated ligand recycling involves cooperation between the ligand-binding domain and epidermal growth factor (EGF) domain of LpR, whereas its cytosolic tail does not harbour motifs that affect this process. LDLR residue His562 appears to be essential for LDLR recycling after ligand endocytosis but not for constitutive receptor recycling. Like LDLRH562N, LDLRH562Y did not recycle bound ligand; moreover, the intracellular distribution of both mutant receptors after ligand incubation coincides with that of a lysosomal marker. The LDLR mutant characterization in vitro suggests that LDLR FH class 5 mutations might be divided into two subclasses.
Signal recognition particle assembly in relation to the function of amplified nucleoli ofXenopusoocytes
Authors: Sommerville John , Brumwell Craig L. , Politz Joan C. Ritland , Pederson Thoru
Published: March 2005

The signal recognition particle (SRP) is a ribonucleoprotein machine that controls the translation and intracellular sorting of membrane and secreted proteins. The SRP contains a core RNA subunit with which six proteins are assembled. Recent work in both yeast and mammalian cells has identified the nucleolus as a possible initial site of SRP assembly. In the present study, SRP RNA and protein components were identified in the extrachromosomal, amplified nucleoli of Xenopus laevis oocytes. Fluorescent SRP RNA microinjected into the oocyte nucleus became specifically localized in the nucleoli, and endogenous SRP RNA was also detected in oocyte nucleoli by RNA in situ hybridization. An initial step in the assembly of SRP involves the binding of the SRP19 protein to SRP RNA. When green fluorescent protein (GFP)-tagged SRP19 protein was injected into the oocyte cytoplasm it was imported into the nucleus and became concentrated in the amplified nucleoli. After visiting the amplified nucleoli, GFP-tagged SRP19 protein was detected in the cytoplasm in a ribonucleoprotein complex, having a sedimentation coefficient characteristic of the SRP. These results suggest that the amplified nucleoli of Xenopus oocytes produce maternal stores not only of ribosomes, the classical product of nucleoli, but also of SRP, presumably as a global developmental strategy for stockpiling translational machinery for early embryogenesis.
Stimulation of erythrocyte ceramide formation by platelet-activating factor
Authors: Lang Philipp A. , Kempe Daniela S. , Tanneur Valerie , Eisele Kerstin , Klarl Barbara A. , Myssina Svetlana , Jendrossek Verena , Ishii Satoshi , Shimizu Takao , Waidmann Marc , Hessler Gabriele , Huber Stephan M. , Lang Florian , Wieder Thomas
Published: March 2005

Osmotic erythrocyte shrinkage leads to activation of cation channels with subsequent Ca2+ entry and stimulates a sphingomyelinase with subsequent formation of ceramide. Ca2+ and ceramide then activate a scramblase leading to breakdown of phosphatidylserine asymmetry of the cell membrane. The mediators accounting for activation of erythrocyte sphingomyelinase and phosphatidylserine exposure remained elusive. The study demonstrates that platelet-activating factor (PAF) is released from erythrocytes upon hyperosmotic cell shrinkage. The experiments further disclose the presence of PAF receptors in erythrocytes and show that PAF stimulates the breakdown of sphingomyelin and the release of ceramide from erythrocytes at isotonic conditions. PAF further triggers cell shrinkage (decrease of forward scatter) and phosphatidylserine exposure (annexin binding) of erythrocytes. The stimulation of annexin-binding is blunted by a genetic knockout of PAF receptors, by the PAF receptor antagonist ABT491 or by inhibition of sphingomyelinase with urea. In conclusion, PAF activates an erythrocyte sphingomyelinase and the then formed ceramide leads to the activation of scramblase with subsequent phosphatidylserine exposure.
Effects of Natural Health Products on Blood Pressure
Authors: Richard Cynthia L , Jurgens Tannis M
Published: March 2005

OBJECTIVE:

To review the scientific literature to identify reports of the effects of natural health products (NHPs) on blood pressure. DATA SOURCES: Electronic databases (MEDLINE [1965–May 2004] via PubMed, the Cochrane Library [1995–May 2004], International Pharmaceutical Abstracts [1970–May 2004], Iowa Drug Information Services [1965–May 2004]) were searched using the key words medicine, herbal plants, medicinal plant preparations, phytotherapy, angiosperms/therapeutic use, gymnosperms/therapeutic use, ethnopharmacology, pharmacognosy, blood pressure, hypertension, hypotension, and diuretic. Searches were not limited by date, language, or publication type. Review articles and texts, as well as reference lists of relevant articles, were used to identify additional reports.

STUDY SELECTION AND DATA EXTRACTION:

Articles (English-language after 1980) were assigned to the following categories: human study, case report, animal study, in vitro study, or theoretical prediction based on chemical constituents. Discussions of mechanisms of action were noted.

DATA SYNTHESIS:

A comprehensive search of the scientific literature identified NHPs capable of affecting blood pressure. Case reports and clearly defined mechanisms of action provided strong evidence for the ability of ephedra and licorice to increase blood pressure. Coenzyme Q10 was reported to decrease systolic and diastolic blood pressure, although the mechanism is unclear. The clinical significance of the blood pressure effects of other NHPs is unclear due to lack of conclusive in vivo data, as well as substantial variability in the chemical content of preparations of NHPs.

CONCLUSIONS:

Among published information, there is little definitive evidence with regard to the impact of NHPs on blood pressure. Additionally, effects may vary in a given patient with the formulation and standardization of a particular product. Until research better characterizes the effect of NHPs on blood pressure, patients should be encouraged to talk with their healthcare provider before starting or stopping any herbal product.
Can 1 μg of Cosyntropin Be Used to Evaluate Adrenal Insufficiency in Critically Ill Patients?
Authors: Kozyra Elizabeth F , Wax Randy S , Burry Lisa D
Published: March 2005

OBJECTIVE:

To evaluate the utility of cosyntropin 1 μg in assessing adrenal function in critically ill patients.

DATA SOURCES:

A computerized literature search using MEDLINE, EMBASE, International Pharmaceutical Abstracts, and the Cochrane Database (1966–August 2004) was undertaken for trials evaluating cosyntropin 1 μg using the following search terms: adrenocorticotropin-releasing hormone (ACTH), cosyntropin, adrenal insufficiency, cortisol, corticosteroids, glucocorticoids, sepsis, septic shock, diagnosis, critically ill, intensive care, and critical care.

STUDY SELECTION AND DATA SYNTHESIS:

Identifying patients with sepsis with relative adrenal insufficiency (AI) using cosyntropin testing may identify those likely to benefit from corticosteroids. The results of 5 heterogeneous studies in non—intensive care unit (ICU) patients suggest that both 1 μg and 250 μg of cosyntropin stimulate similar cortisol responses and that testing using both doses correlates well with results from insulin tolerance testing. Some data from non-ICU patients suggest that the 1-μg test may be more sensitive to detect AI; 3 heterogeneous studies in ICU patients confirmed the improved sensitivity of the 1-μg test.

CONCLUSIONS:

Use of cosyntropin 1 μg should detect AI in all patients who would have been diagnosed using 250 μg. Unfortunately, all of the clinical trials evaluating the role of corticosteroids in septic shock that used the cosyntropin stimulation test administered 250 μg. Extrapolation of the existing guidelines to treat patients with septic shock testing positive for relative AI using the 1-μg test may provide effective therapy to appropriate patients not diagnosed by the 250-μg testing or may introduce additional adverse effects in patients who should not receive corticosteroids. Large-scale, head-to-head comparison data of steroid effectiveness after 1- and 250-μg ACTH stimulation tests are needed to expand upon these promising results.
Use of a Modified Dosing Weight for Heparin Therapy in a Morbidly Obese Patient
Authors: Schwiesow Sarah J , Wessell Andrea M , Steyer Terrence E
Published: March 2005

OBJECTIVE:

To report a case of successful anticoagulation using a modified dosing weight (DW) for unfractionated heparin (UFH) therapy in a morbidly obese female.

CASE SUMMARY:

A 54-year-old morbidly obese (182.4 kg, 155 cm) white female presented to the emergency department with tachycardia, shortness of breath, and chest pain, and was diagnosed with a pulmonary embolism. Anticoagulation with UFH was initiated. A modified DW of 120 kg was obtained from the average of the actual body weight (ABW) and ideal body weight (~50 kg). We selected this modified DW to account for heparin's altered volume of distribution in an obese patient and avoid potentially supratherapeutic activated partial thromboplastin times (aPTTs) using ABW and subtherapeutic aPTTs using DW. Therapy was initiated with a bolus dose of 9600 units (80 units/kg x 120 kg) and continuous infusion rate of 2160 units/h (18 units/kg/h x 120 kg). This infusion rate was maintained throughout the course of heparin therapy and was successful in maintaining therapeutic aPTTs.

DISCUSSION:

Proper diagnosis and rapid initiation of therapy prevent mortality in patients with PE. Although weight-based heparin nomograms provide standardization through initial bolus and continuous infusion recommendations, many do not address dosing in morbidly obese patients. Several retrospective studies have evaluated actual, dosing, and ideal body weights for heparin therapy in obese patients; however, none has evaluated modified DW. In our patient, successful anticoagulation was objectively confirmed.

CONCLUSIONS:

Further investigation is necessary to determine the optimal DW for UFH in morbidly obese patients presenting with acute thrombosis.
Cost-Effectiveness of Fluvastatin following Successful First Percutaneous Coronary Intervention
Authors: Delea Thomas E , Jacobson Terry A , Serruys Patrick WJC , Edelsberg John S , Oster Gerry
Published: March 2005

BACKGROUND:

In the LIPS (Lescol Intervention Prevention Study), fluvastatin 80 mg/day reduced the risk of major adverse cardiac events (MACE) by 22% versus placebo (p = 0.01) following successful first percutaneous coronary intervention (PCI) in patients with stable or unstable angina or silent ischemia. The cost-effectiveness of such therapy is unknown.

OBJECTIVE:

To evaluate the cost-effectiveness of fluvastatin following successful first PCI from a US healthcare system perspective.

METHODS:

We used a Markov model to estimate expected outcomes and costs of 2 alternative treatment strategies following successful first PCI in patients with stable or unstable angina or silent ischemia: (1) diet/lifestyle counseling plus immediate fluvastatin 80 mg/day; and (2) diet/lifestyle counseling only, with initiation of fluvastatin 80 mg/day following occurrence of future nonfatal MACE. The model was estimated with data from LIPS and other published sources. Cost-effectiveness was calculated as the ratio of the difference in expected medical-care costs to the expected difference in life-years (LYs) and quality-adjusted life-years (QALYs) alternatively.

RESULTS:

Treatment with fluvastatin following successful first PCI was found to increase life expectancy by 0.78 years (QALYs 0.68). Cost-effectiveness of fluvastatin following successful first PCI is $13 505 per LY ($15 454 per QALY) saved. Ratios are lower for patients with diabetes ($9396 per LY; $10 718 per QALY) and those with multivessel disease ($9662 per LY; $11 076 per QALY). Findings were robust with respect to changes in key model parameters and assumptions.

CONCLUSIONS:

Fluvastatin therapy following PCI is cost-effective compared with other generally accepted medical interventions.
Esomeprazole-Induced Central Fever with Severe Myalgia
Authors: Grattagliano Ignazio , Portincasa Piero , Mastronardi Mauro , Palmieri Vincenzo O , Palasciano Giuseppe
Published: March 2005

OBJECTIVE:

To report a case of central fever associated with severe myalgia following esomeprazole.

CASE SUMMARY:

A 64-year-old man presented with intense cephalalgia; severe, diffuse myalgia; and fever (>40°C) after esomeprazole initiation for treatment of gastritis. Five hours after ingestion of the first esomeprazole pill (40 mg), the patient developed fever associated with cephalalgia and myalgia. This condition lasted about 40 hours and disappeared spontaneously. Symptoms partially responded to acetaminophen. Four days later, the patient received a second dose of esomeprazole 40 mg. Subsequently, 4 hours later, fever (>40°C), headache, and difficulty in the movement of all parts of the body recurred. Neurologic examination was negative except for a minor state of disorientation. All reflexes were normal or slightly decreased. No skin lesions or breathing difficulty was noted. Routine blood tests were normal. Again, symptoms resolved spontaneously about 40 hours later.

DISCUSSION:

The temporal connection between esomeprazole intake and the onset of fever suggests a probable causal link, as confirmed by the Naranjo probability scale. However, the pathogenic mechanism remains unclear. Considering that esomeprazole is able to cross the blood—brain barrier, its peak serum concentration is reached 90–180 minutes after oral administration, and its serum half-life is approximately 2 hours, we assume that the appearance of fever with accompanying neurologic and muscular symptoms might result from the drug interference with the hypothalamic regulatory center of body temperature.

CONCLUSIONS:

Hyperpyrexia of central origin associated with intense cephalalgia and myalgia may occur as an adverse effect of esomeprazole therapy.
Treatment of Seasonal Allergic Rhinitis Using Homeopathic Preparation of Common Allergens in the Southwest Region of the US: A Randomized, Controlled Clinical Trial
Authors: Kim Linda S , Riedlinger June E , Baldwin Carol M , Hilli Lisa , Khalsa Sarv Varta , Messer Stephen A , Waters Robert F
Published: March 2005

BACKGROUND:

Studies using homeopathy have reported beneficial effects from treating allergy-related conditions.

OBJECTIVE:

To investigate the effects of a homeopathic drug prepared from common allergens (tree, grass, weed species) specific to the Southwest region of the US.

METHODS:

A 4-week, double-blind clinical trial comparing homeopathic preparations with placebo was conducted in the Phoenix metropolitan area during the regional allergy season from February to May. Participants included 40 men and women, 26–63 years of age, diagnosed with moderate to severe seasonal allergic rhinitis symptoms. Study outcomes included allergy-specific symptoms using the rhinoconjunctivitis quality-of-life questionnaire (RQLQ), functional quality of life using the Medical Outcomes Study Short Form-36 (MOS SF-36), and the work productivity and activity impairment (WPAI) questionnaire.

RESULTS:

Scales from the RQLQ, MOS SF-36, and WPAI questionnaire showed significant positive changes from baseline to 4 weeks in the homeopathic group compared with the placebo group (p < 0.05). Subjects reported no adverse effects during the intervention period.

CONCLUSIONS:

These preliminary findings indicate potential benefits of the homeopathic intervention in reducing symptoms and improving quality of life in patients with seasonal allergic rhinitis in the Southwestern US.
Medication Use Patterns after Gastric Bypass Surgery for Weight Management
Authors: Malone Margaret , Alger-Mayer Sharon A
Published: March 2005

BACKGROUND:

Bariatric surgery, commonly gastric bypass, is an effective intervention in achieving sustained weight loss in patients with a body mass index (BMI) >40 kg/m2. Currently, there are few data in the literature describing medication use after bariatric surgery.

OBJECTIVE:

To document the change in medication use patterns over a 2-year period in patients who had gastric bypass surgery. METHODS: Institutional review board approval was obtained for this ongoing, prospective longitudinal study. Adults (>18 y) scheduled for gastric bypass surgery were recruited. Clinical and demographic data, including age, gender, weight, height, BMI, number of obesity-related comorbidities, and number of medications and nutritional supplements, were obtained by medical chart review.

RESULTS:

One hundred fourteen patients (87 females) were recruited. The mean ± SD age was 45 ± 9 years. Patients had multiple obesity-related comorbid diseases for which they were receiving medication. Drug therapy for diabetes and hypertension was significantly reduced (p < 0.05). All patients were required to take additional nutritional supplements and medications associated with surgery postoperatively.

CONCLUSIONS:

Bariatric surgery has a positive benefit in terms of reduction intake of medication associated with obesity-related comorbid disease. However, there is limited reduction in the overall number of drugs and supplements being consumed by the patient, especially during the first year postoperatively.
Leflunomide and Azathioprine Combination in Refractory Adult-Onset Still's Disease
Authors: Cefle Ayse
Published: March 2005

OBJECTIVE:

To present a case of Adult-onset Still's disease (ASD) in a patient who was successfully treated with leflunomide and azathioprine.

CASE SUMMARY:

A 24-year-old woman with ASD was initially treated with indomethacin, corticosteroids, and hydroxychloroquine; there was no clinical improvement. Methotrexate was added to the regimen, followed by azathioprine. The patient still experienced disease flares with this treatment, and cyclophosphamide was started. However, because of persisting disease activity, leflunomide combined with azathioprine was given. Only on this regimen was complete disease control achieved, with a normal erythrocyte sedimentation rate as well as normal C-reactive protein and ferritin levels. No recurrences or adverse effects attributable to leflunomide or azathioprine were observed at the one-year follow-up.

DISCUSSION:

Clinical experience concerning leflunomide and azathioprine combination in ASD is limited. This combination may be modifying the clinical expression of ASD through its effects on T lymphocyte clonal expansion and production of proinflammatory cytokines.

CONCLUSIONS:

Leflunomide combined with azathioprine appears to be an effective and safe treatment of ASD.
Herbal Use among US Elderly: 2002 National Health Interview Survey
Authors: Bruno Jeffrey J , Ellis Jeffrey J
Published: March 2005

BACKGROUND:

Use of herbal products among the elderly is an important concern for healthcare professionals. The presence of polypharmacy and multiple comorbidities places the elderly at high risk for herb—drug and herb—disease interactions. Limited data exist regarding herbal use among the US elderly population.

OBJECTIVE:

To evaluate the incidence of and attitudes toward herbal use in a nationally representative sample of US elderly patients ⩾65 years of age.

METHODS:

We performed a descriptive analysis of public domain data collected in the 2002 National Health Interview Survey. Statistical analyses were conducted through use of SUDAAN software with Taylor series linearization for variance estimation.

RESULTS:

Analysis of weighted data revealed that 12.9% ± 0.5% (mean ± SE) of US elderly people had used an herbal supplement within the past 12 months. Use was greatest among individuals 65–69 years of age, females, Hispanic and non-Hispanic ethnic minorities, and respondents with a greater income, higher education level, or more positive self-reported health status. Among elderly people purchasing over-the-counter and prescription drugs, herbal use was 13.9% ± 0.6% and 12.8% ± 0.6%, respectively. Glucosamine, echinacea, and garlic supplements represented the most common herbals used. Benefit from combined herbal and conventional therapy was the most common reason cited for use; however, 50.9% ± 2.2% of users did not discuss herbal therapy with a medical professional. Several theoretical herb—disease interactions were identified.

CONCLUSIONS:

The use of herbal products among the US elderly has risen over the past 5 years, whereas discussion of such use with medical professionals remains suboptimal.
When Does Pharmaceutical Care Impact Health Outcomes? A Comparison of Community Pharmacy—Based Studies of Pharmaceutical Care for Patients with Asthma
Authors: McLean William M , MacKeigan Linda D
Published: March 2005

BACKGROUND:

Pharmaceutical care (PC) as a philosophy of care and practice model is now >14 years old. It is important to determine whether PC influences health outcomes. Such outcomes are best studied in specific disease states where variables are minimized and specific outcomes have been established. We analyzed 4 multi-site controlled studies that evaluated PC in community pharmacies for patients with asthma. Study results varied widely.

OBJECTIVE:

To understand factors contributing to positive outcomes from PC for asthma.

METHODS:

The 4 studies were compared on the basis of 10 aspects of their research design, as well as 10 elements of PC. Dr. McLean conducted the initial analysis, and his assessments were confirmed by Dr. MacKeigan.

RESULTS:

Important differences were found in the type of pharmacy where PC was delivered (chain vs independent), how pharmacies were selected (required vs volunteered), patient selection (on asthma medication vs uncontrolled disease), pharmacist training (4-h workshop vs certification over several weeks), the nature of PC protocol (computer reminders vs detailed care protocol), rigor of the protocol (intervention vs requirement to reach self-management), and the level of pharmacist adherence to the PC protocol (<50% vs 90%). Differences were also found in study design.

CONCLUSIONS:

More favorable PC outcomes were associated with use of all elements of PC, independent pharmacies, pharmacist certification, a detailed PC protocol, targeting patients with uncontrolled asthma, and a practice system facilitating PC.