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15546377 | Live three-dimensional transthoracic echocardiographic assessment of transcatheter closure of atrial septal defect and patent foramen ovale. | We report the usefulness of live three-dimensional transthoracic echocardiography in the accurate assessment of the morphology and efficacy of Amplatzer transcatheter devices used for closure of atrial septal defect and patent foramen ovale. |
15546376 | Live three-dimensional transthoracic echocardiographic delineation of ventricular septal rupture following myocardial infarction. | We present an elderly patient with ventricular septal rupture following myocardial infarction in whom live three-dimensional transthoracic echocardiography allowed comprehensive noninvasive assessment of the location, shape, and size of the septal defect, which could be clearly visualized en face from both left and right ventricular aspects. |
15546375 | Quantification of mitral regurgitation by live three-dimensional transthoracic echocardiographic measurements of vena contracta area. | We evaluated 44 consecutive patients who underwent standard two-dimensional (2D) and live three-dimensional (3D) transthoracic echocardiography (TTE), as well as left heart catheterization with left ventriculography. Mitral regurgitant vena contracta area (VCA) was obtained by 3D TTE by systematic and sequential cropping of the acquired 3D TTE data set. Assessment of mitral regurgitation (MR) by ventriculography was compared to measurements of VCA by 3D TTE and to 2D TTE measurements of MR jet area to left atrial area (RJA/LAA), RJA alone, vena contracta width (VCW), and calculated VCA. VCA from 3D TTE closely correlated with angiographic grading (rs=0.88) with very little overlap. VCA of <0.2 cm2 correlated with mild MR, 0.2-0.4 cm2 with moderate MR, and >0.4 cm2 with severe MR by angiography. Ventriculographic grading also correlated well with 2D TTE measurements of RJA/LAA (rs=0.79) and RJA alone (rs=0.76) but with more overlap. Assessment of VCW and calculated VCA by 2D TTE agreed least with ventriculography (rs=0.51 and rs=0.55, respectively). Live 3D TTE color Doppler measurements of VCA can be used for quantitative assessment of MR and is comparable to assessment by ventriculography. |
15546374 | Methodological analysis of diagnostic dobutamine stress echocardiography studies. | Dobutamine stress echocardiography (DSE) is an accepted test for the diagnosis of coronary artery disease (CAD), despite its wide diagnostic accuracy. Which factors cause test variability of DSE for the diagnosis of CAD. In a retrospective analysis of 46 studies in 5,353 patients, the potential causes of diagnostic variability were systematically analyzed, including patient selection, definition of CAD, chest pain characteristics, confounding factors for DSE (left ventricular hypertrophy, left bundle branch block, female gender), work-up bias (present when patient's chance to undergo coronary angiography is influenced by the result of DSE), review bias (present when DSE is interpreted in relation to CAG), DSE protocol and definition of a positive DSE. Diagnostic variability was related to definition of a positive test, but not related to the definition of CAD or DSE protocol. However, only three of eight methodological standards for research design found general compliance. Differences in the selection of the study population (quality of echocardiographic window, angina pectoris), handling of confounding factors and analysis of disease in individual coronary arteries were observed. Lack of data on analysis of relevant chest pain syndromes and handling of nondiagnostic test results hampered further evaluation of these standards. Methodological problems may explain the wide range in diagnostic variability of DSE. An improvement of clinical relevance of DSE testing is possible by stronger adherence to common and new methodological standards. |
15546373 | Transesophageal echocardiography-guided transvenous biopsy of an intracardiac tumor. | Transesophageal echocardiography with simultaneous fluoroscopic guidance during a transvenous biopsy of an intracardiac tumor is a valuable technique. We present the case of a 67-year-old man with a metastasis in the right atrium from which histological examination of the tumor was indicated. The inaccessible location of the primary tumor in the liver and impaired hemostasis due to cirrhosis necessitated a transvenous biopsy of the metastasis. The procedure and the associated techniques are discussed in this case. |
15546372 | Atypical echocardiographic findings of endocarditis in an immunocompromised patient. | Cardiovascular manifestations in patients infected with human immunodeficiency virus (HIV) have been altered by the introduction of highly active antiretroviral therapy regimens that allow more effective prophylactic treatment and an increased time of survival. Because of this, noninfectious cardiac conditions associated with HIV disease are being recognized with increasing frequency in these patients. Cardiac involvement in HIV-infected patients varies from clinically silent to overtly symptomatic disease. By some estimates a direct cardiac cause of mortality is between 1% and 6% of all cases. Pericardial effusion, pericarditis, myocarditis, cardiomyopathy, endocarditis, and pulmonary hypertension are well-recognized cardiac illnesses associated with HIV infection. Echocardiography has been crucial in evaluating HIV-infected patients to assess the extent of cardiac involvement. This case report illustrates atypical echocardiographic manifestations of endocarditis and paravalvular abscess in an immunocompromised patient. |
15546371 | Usefulness of live three-dimensional transthoracic echocardiography in the characterization of atrial septal defects in adults. | In this report we present 12 adult patients in whom surgical or percutaneous intervention was considered for repair of atrial septal defect (ASD). Location, size, and surrounding atrial anatomy of the ASD were assessed prior to intervention in all patients with standard and live three-dimensional transthoracic echocardiography (3D TTE). In the four patients in whom intraoperative three-dimensional transesophageal echocardiographic reconstruction (3D TEE) was done, 3D TTE measurements of maximum dimension, maximum circumference, and maximum area of ASD agreed well with 3D TEE. In the seven patients who underwent transcatheter closure device insertion, live 3D TTE measurements of maximum dimension, maximum circumference, and maximum area of ASD agreed well with the sizing balloon. Additionally, since the sizing balloon measures a stretched diameter and area, a live 3D TTE stretched ASD diameter and area (derived from the actual live 3D TTE maximum circumference) were calculated and demonstrated improved agreement with the sizing balloon measurements. In all patients, > or =5 mm of atrial tissue was visualized surrounding the ASD. Further, with the addition of contrast enhancement, characterization of a small patent foramen ovale (<5 mm) was possible in one patient. Live 3D TTE accurately defined ASD location, size, and surrounding atrial anatomy in all patients studied by us. ASD characterization by live 3D TTE agreed well with 3D TEE and sizing balloon measurements. |
15546370 | Live three-dimensional transthoracic echocardiographic assessment of left ventricular hydatid cyst. | We report an adult patient in whom live three-dimensional transthoracic echocardiography (3DTTE) complemented two-dimensional transthoracic echocardiography (2DTTE) in making a definitive diagnosis of a hydatid cyst located in the left ventricular cavity. The parent hydatid cyst, as well as the daughter cysts, contained within it could be delineated by both 2DTTE and live 3DTTE. However, the tertiary or granddaughter cysts originating from the daughter cysts as well as great-granddaughter cysts budding from tertiary cysts could be visualized only when the live 3DTTE data sets were cropped and sectioned sequentially using multiple cutting planes. In addition, apparent intrinsic mobility of some of the tertiary cysts implying viability was detected only by 3DTTE. |
15546369 | Electromechanical coupling, uncoupling, and ventricular function in patients with bundle branch block: a tissue-Doppler echocardiographic study. | Left bundle branch block (LBBB) is associated with impaired left ventricular (LV) function and increased morbidity and mortality, especially in patients with structural heart diseases. The mechanisms are poorly understood. Subjects with isolated LBBB (n=20), right bundle branch block (RBBB, n=20), and controls (C, n=20) were studied with standard two-dimensional (2D), and color-encoded tissue-Doppler echocardiography (TDE). Inter- and intraventricular systolic and diastolic coordination were assessed from the TDE velocity profiles. LV function was assessed by 2D echocardiography, by TDE-derived peak systolic velocities, and the atrioventricular (AV) plane displacement. Subjects with LBBB had longer electromechanical delays and longer isovolumic relaxation times than did the C and RBBB groups (P <0.001). For the LBBB subjects compared with the RBBB and C groups, ejection times were shorter, peak systolic velocities and AV plane displacements were lower, they had larger LV end-systolic volumes and lower LV ejection fraction (all P <0.001), and the atrial contribution to A-V plane displacement was higher (P <0.01). There were no differences in diastolic or filling times among the groups. In patients with LBBB, delayed regional electromechanical coupling and uncoupling leads to generalized intra- and interventricular asynchrony, thereby explaining the depressed regional and global LV functions. Assessment of the electromechanical coupling and uncoupling processes and their consequences on cardiac function in patients with BBB and structural heart diseases may be possible using TDE. |
15546368 | Inducible left ventricular outflow tract gradient during dobutamine stress echocardiography: an association with intraoperative hypotension but not a contraindication to liver transplantation. | Dobutamine stress echocardiography (DSE) is frequently used in the evaluation of cardiac risk prior to orthotopic liver transplantation (OLT). In the general cardiac population, an inducible left ventricular outflow tract gradient (LVOT Delta) during DSE has variable prognostic importance. The purpose of this study was to determine the prevalence and clinical significance of LVOT Delta in patients undergoing OLT during DSE. Consecutive medical records of 106 patients who had undergone OLT at our institution from January 1997 until January 2002 were retrospectively analyzed and divided into two groups based on the presence (Group I, LVOT Delta >36 mmHg) or absence (Group II, LVOT Delta< or = 36 mmHg) of a significant LVOT Delta measured during DSE. We determined any outcome differences between these two groups with regard to intraoperative hypotension, cardiac mortality, length of hospital stay, graft function, and renal function post-OLT. Forty-six patients had an LVOT Delta > 36 mmHg (Group I) and 60 patients had LVOT Delta< or = 36 mmHg (Group II). Baseline demographics were similar in both groups. There was no significant overall difference in cardiac mortality between Group I versus Group II patients (0 versus 1 patient, respectively, P=0.57). Intraoperative hypotension occurred in 4 patients in Group I versus 0 patient in Group II (P=0.03). Length of stay, graft function, and postoperative renal function were similar in both groups. A significant LVOT Delta >36 mmHg is a frequent finding occurring in 46/106 (43%) of patients who have DSE pre-OLT. Intraoperative hypotension is associated with patients having an LVOT Delta. However, post-OLT patients with significant LVOT Delta have a similar in-hospital outcome compared to patients without significant LVOT Delta. |
15546367 | A novel method to estimate pulmonary artery wedge pressure using the downslope of the Doppler mitral regurgitant velocity profile. | Continuous-wave (CW) Doppler recording of mitral regurgitation (MR) is a reflection of the left ventriculoatrial pressure gradient. Accordingly, this jet may yield information about pulmonary artery wedge pressure (PAWP). In this study, we derived and then evaluated a novel method for prediction of PAWP. Patients (n=80) with moderate to severe MR and left ventricular dysfunction were included in the study. Transthoracic echocardiography was performed in patients during pulmonary artery pressure monitoring. A satisfactory CW Doppler recording of MR was obtained in 63/80 (78%). On the late descending portion of the CW recording, the time from a velocity of 4 m/sec to the end of the jet was defined as t1, and from 3 m/sec to the end of the jet as t2. Mathematical derivation of t1/t2 as a predictor of PAWP, was performed based on Weiss' derivation. If t1/t2 was <1.30, the PAWP was normal. If t1/t2 > 1.44, the PAWP was > 16 mmHg. With this new mathematical derivation, it appears that the downslope of the CW Doppler MR waveform may be able to distinguish a normal from elevated PAWP. |
15546365 | In vitro culture of Arabidopsis embryos within their ovules. | Embryogenesis of flowering plants establishes a basic body plan with apical-basal, radial and bilateral patterns from the single-celled zygote. Arabidopsis embryogenesis exhibits a nearly invariant cell division pattern and therefore is an ideal system for studies of early plant development. However, plant embryos are difficult to access for experimental manipulation, as they develop deeply inside maternal tissues. Here we present a method for the culture of zygotic Arabidopsis embryos in vitro. The technique omits excision of the embryo by culturing the entire ovule, thus greatly facilitating the time and effort involved. It enables external manipulation of embryo development and culture from the earliest developmental stages up to maturity. Administration of various chemical treatments as well as the use of different molecular markers is demonstrated together with standard techniques for visualizing gene expression and protein localization in in vitro cultivated embryos. The presented set of techniques allows for so far unavailable molecular physiology approaches in the study of early plant development. |
15546364 | Hypocotyl growth orientation in blue light is determined by phytochrome A inhibition of gravitropism and phototropin promotion of phototropism. | How developing seedlings integrate gravitropic and phototropic stimuli to determine their direction of growth is poorly understood. In this study we tested whether blue light influences hypocotyl gravitropism in Arabidopsis. Phototropin1 (phot1) triggers phototropism under low fluence rates of blue light but, at least in the dark, has no effect on gravitropism. By analyzing the growth orientation of phototropism-deficient seedlings in response to gravitropic and phototropic stimulations we show that blue light not only triggers phototropism but also represses hypocotyl gravitropism. At low fluence rates of blue light phot1 mutants were agravitropic. In contrast, phyAphot1 double mutants grew exclusively according to gravity demonstrating that phytochrome A (phyA) is necessary to inhibit gravitropism. Analyses of phot1cry1cry2 triple mutants indicate that cryptochromes play a minor role in this response. Thus the optimal growth orientation of hypocotyls is determined by the action of phyA-suppressing gravitropism and the phototropin-triggering phototropism. It has long been known that phytochromes promote phototropism but the mechanism involved is still unknown. Our data show that by inhibiting gravitropism phyA acts as a positive regulator of phototropism. |
15546363 | ACC synthase expression regulates leaf performance and drought tolerance in maize. | Ethylene regulates entry into several types of plant developmental cell death and senescence programs besides mediating plant responses to biotic and abiotic stress. The response of cereals to conditions of drought includes loss of leaf function and premature onset of senescence in older leaves. In this study, ACC synthase (ACS) mutants, affecting the first step in ethylene biosynthesis, were isolated in maize and their effect on leaf function examined. Loss of ZmACS6 expression resulted in delayed leaf senescence under normal growth conditions and inhibited drought-induced senescence. Zmacs6 leaves continued to be photosynthetically active under both conditions indicating that leaf function was maintained. The delayed senescence phenotype associated with loss of ZmACS6 expression was complemented by exogenous ACC. Surprisingly, elevated levels of foliar chlorophyll, Rubisco, and soluble protein as well as improved leaf performance was observed for all Zmasc6 leaves, including young and fully expanded leaves which were far from initiating senescence. These observations suggest that ethylene may serve to regulate leaf performance throughout its lifespan as well as to determine the onset of natural senescence and mediate drought-induced senescence. |
15546362 | Chloride fluxes in lily pollen tubes: a critical reevaluation. | Microelectrodes, made from a Cl(-)-selective liquid ion exchanger previously used to measure putative Cl- fluxes in Lilium longiflorum pollen tubes, were characterized. The electrodes were poorly selective, possessing only about 10-fold selectivity for Cl- over other anions tested. They had only 2.4-fold selectivity for Cl- over the anionic form of the H+ buffer, MES, indicating that the electrode can indirectly detect H+ gradients. Apparent anion influx was detected along the pollen tube shafts and at the grains while apparent anion efflux was detected near the tip of the tube. During oscillating growth, the peak of the oscillating apparent anion efflux at the tip occurred, on average, 7.9 sec after the peak of the growth oscillations. Consideration of the previously characterized H+ fluxes in lily pollen grains and tubes, as well as the poor anion selectivity of the Cl- electrodes, indicates that the putative Cl- fluxes are in fact changes in the anionic concentration of the buffer resulting from H+ gradients and not changes in Cl- concentration. The claim of a central role for Cl- in lily pollen tube growth is further undermined by the fact that these tubes grow at the same rate if the Cl- content of the growth medium is reduced to trace levels (< or =31 microM), and that the grains have only small reserves of Cl-. These results lead to the conclusion that Cl- fluxes are not a significant component of pollen tube growth and Cl- itself is not required for growth. |
15546361 | The Pseudomonas syringae type III effector AvrRpt2 promotes virulence independently of RIN4, a predicted virulence target in Arabidopsis thaliana. | AvrRpt2, an effector protein from Pseudomonas syringae pv. tomato (Pst), behaves as an avirulence factor that activates resistance in Arabidopsis thaliana lines expressing the resistance gene RPS2. AvrRpt2 can also enhance pathogen fitness by promoting the ability of the bacteria to grow and to cause disease on susceptible lines of A. thaliana that lack functional RPS2. The activation of RPS2 is coupled to the AvrRpt2-induced disappearance of the A. thaliana RIN4 protein. However, the significance of this RIN4 elimination to AvrRpt2 virulence function is unresolved. To clarify our understanding of the contribution of RIN4 disappearance to AvrRpt2 virulence function, we generated new avrRpt2 alleles by random mutagenesis. We show that the ability of six novel AvrRpt2 mutants to induce RIN4 disappearance correlated well with their avirulence activities but not with their virulence activities. Moreover, the virulence activity of wild-type AvrRpt2 was detectable in an A. thaliana line lacking RIN4. Collectively, these results indicate that the virulence activity of AvrRpt2 in A. thaliana is likely to rely on the modification of host susceptibility factors other than, or in addition to, RIN4. |
15546360 | Functional differentiation of endosomes in Arabidopsis cells. | Endocytosis plays an important role in plant physiology, but how endocytic organelles are organized remains unknown. We present the evidence that endosomes are functionally differentiated in Arabidopsis cells. Two types of Rab5-related GTPases are localized on distinct population of endosomes in a partially overlapping manner. Ara7 and Rha1 are on an early type of endosomes with AtVamp727, where recycling of plasma membrane proteins occurs. In contrast, the plant-unique Rab5, Ara6, resides on distinct endosomes with the prevacuolar SNAREs. Partially overlapping localization of Ara6 and Ara7/Rha1 with reciprocal gradients suggests maturation of endosomes from one to the other. |
15546359 | The IAA1 protein is encoded by AXR5 and is a substrate of SCF(TIR1). | Recent studies of auxin response have focused on the functions of three sets of proteins: the auxin (Aux) response factors (ARFs), the Aux/IAAs, and the F-box protein TIR1. The ARF proteins bind DNA and directly activate or repress transcription of target genes while the Aux/IAA proteins repress ARF function. TIR1 is part of a ubiquitin protein ligase required for degradation of Aux/IAA proteins. Here we report the isolation and characterization of a novel mutant of Arabidopsis called axr5-1. Mutant plants are resistant to auxin and display a variety of auxin-related growth defects including defects in root and shoot tropisms. Further, the axr5-1 mutation results in a decrease in auxin-regulated transcription. The molecular cloning of AXR5 revealed that the gene encodes the IAA1 protein, a member of the Aux/IAA family of proteins. AXR5 is expressed throughout plant development consistent with the pleiotropic mutant phenotype. The axr5-1 mutation results in an amino acid substitution in conserved domain II of the protein, similar to gain-of-function mutations recovered in other members of this gene family. Biochemical studies show that IAA1/AXR5 interacts with TIR1 in an auxin-dependent manner. The mutation prevents this interaction suggesting that the mutant phenotype is caused by the accumulation of IAA1/AXR5. Our results provide further support for a model in which most members of the Aux/IAA family are targeted for degradation by SCFTIR1 in response to auxin. |
15546358 | DNA array analyses of Arabidopsis thaliana lacking a vacuolar Na+/H+ antiporter: impact of AtNHX1 on gene expression. | AtNHX1, a vacuolar cation/proton antiporter of Arabidopsis, plays an important role in salt tolerance, ion homeostasis and development. We used the T-DNA insertional mutant of AtNHX1 (nhx1 plants) and Affymetrix ATH1 DNA arrays to assess differences in transcriptional profiles and further characterize the roles of a vacuolar cation/proton antiporter. Mature, soil-grown plants were used in this study to approximate typical physiological growing conditions. A comparison of plants grown in the absence of salt stress yielded many transcripts that were affected by the absence of the AtNHX1 vacuolar antiporter. Furthermore, changes in gene expression due to a non-lethal salt stress (100 mm NaCl) in the nhx1 plants were significantly different from the changes seen in wild-type plants. The nhx1 transcriptome was differentially affected when the plants were grown in the absence or presence of salt. In conclusion, in addition to the known role(s) of AtNHX1 on ion homeostasis, the vacuolar cation/proton antiporter plays a significant role in intracellular vesicular trafficking, protein targeting, and other cellular processes. |
15546357 | The effect of intron location on intron-mediated enhancement of gene expression in Arabidopsis. | Introns are often required for full expression of genes in organisms as diverse as plants, insects, nematodes, yeast, and mammals. To explore the potential mechanisms of intron-mediated enhancement in Arabidopsis thaliana, the effect of varying the position of an intron was determined using a series of reporter gene fusions between TRYPTOPHAN BIOSYNTHESIS1 (TRP1) and GUS. Two introns that differ in the degree to which they stimulate expression were individually tested at six locations within coding sequences and two positions in the 3'-UTR. The ability of the first introns from both the TRP1 and POLYUBIQUITIN10 (UBQ10) genes to elevate mRNA accumulation in transgenic plants was found to decline with distance from the promoter, despite their being efficiently spliced from all coding sequence locations. Neither intron significantly enhanced mRNA accumulation when positioned 1.1 kb or more from the start of transcription. In addition, measurements of GUS enzyme activity revealed that both introns at all locations elevated GUS activity more than they enhanced mRNA accumulation. The stimulation mediated by two of four other introns tested at the position nearest the promoter was also greater at the level of GUS activity than mRNA accumulation. These findings support a model in which introns increase transcription and promote translation by two distinct mechanisms. |
15546356 | Engineering of ubiquinone biosynthesis using the yeast coq2 gene confers oxidative stress tolerance in transgenic tobacco. | Ubiquinone (UQ), an electron carrier in the respiratory chain ranging from bacteria to humans, shows antioxidative activity in vitro, but its physiological role in vivo is not yet clarified in plants. UQ biosynthesis was modified by overexpressing the yeast gene coq2, which encodes p-hydroxybenzoate:polyprenyltransferase, to increase the accumulation of UQ-6 in yeast and UQ-10 in tobacco. The yeast and tobacco transgenic lines showed about a three- and six-fold increase in UQ, respectively. COQ2 polypeptide, the localization of which was forcibly altered to the endoplasmic reticulum, had the same or a greater effect as mitochondria-localized COQ2 on the increase in UQ in both the yeast and tobacco transformants, indicating that the UQ intermediate is transported from the endoplasmic reticulum to the mitochondria. Plants with a high UQ level are more resistant to oxidative stresses caused by methyl viologen or high salinity. This is attributable to the greater radical scavenging ability of the transgenic lines when compared with the wild type. |
15546355 | Conservation of the microstructure of genome segments in Brassica napus and its diploid relatives. | The cultivated Brassica species are the group of crops most closely related to Arabidopsis thaliana (Arabidopsis). They represent models for the application in crops of genomic information gained in Arabidopsis and provide an opportunity for the investigation of polyploid genome formation and evolution. The scientific literature contains contradictory evidence for the dynamics of the evolution of polyploid genomes. We aimed at overcoming the inherent complexity of Brassica genomes and clarify the effects of polyploidy on the evolution of genome microstructure in specific segments of the genome. To do this, we have constructed bacterial artificial chromosome (BAC) libraries from genomic DNA of B. rapa subspecies trilocularis (JBr) and B. napus var Tapidor (JBnB) to supplement an existing BAC library from B. oleracea. These allowed us to analyse both recent polyploidization (under 10,000 years in B. napus) and more ancient polyploidization events (ca. 20 Myr for B. rapa and B. oleracea relative to Arabidopsis), with an analysis of the events occurring on an intermediate time scale (over the ca. 4 Myr since the divergence of the B. rapa and B. oleracea lineages). Using the Arabidopsis genome sequence and clones from the JBr library, we have analysed aspects of gene conservation and microsynteny between six regions of the genome of B. rapa with the homoeologous regions of the genomes of B. oleracea and Arabidopsis. Extensive divergence of gene content was observed between the B. rapa paralogous segments and their homoeologous segments within the genome of Arabidopsis. A pattern of interspersed gene loss was identified that is similar, but not identical, to that observed in B. oleracea. The conserved genes show highly conserved collinearity with their orthologues across genomes, but a small number of species-specific rearrangements were identified. Thus the evolution of genome microstructure is an ongoing process. Brassica napus is a recently formed polyploid resulting from the hybridization of B. rapa (containing the Brassica A genome) and B. oleracea (containing the Brassica C genome). Using clones from the JBnB library, we have analysed the microstructure of the corresponding segments of the B. napus genome. The results show that there has been little or no change to the microstructure of the analysed segments of the Brassica A and C genomes as a consequence of the hybridization event forming natural B. napus. The observations indicate that, upon polyploid formation, these segments of the genome did not undergo a burst of evolution discernible at the scale of microstructure. |
15546354 | Mutation of a UDP-glucose-4-epimerase alters nematode susceptibility and ethylene responses in Arabidopsis roots. | In Arabidopsis, mutation of RHD1, a UDP-glucose-4-epimerase, causes root-specific phenotypes, including hypersusceptibility to the cyst nematode Heterodera schachtii, increased root hair elongation, decreased root length, and root epidermal bulging. Previous experiments suggested that increased ethylene sensitivity or production mediated the rhd1-4 phenotypes. In the present study, double mutant analyses revealed that only rhd1-4 hypersusceptibility to H. schachtii and increased root hair elongation were dependent upon the ethylene signaling genes EIN2 and EIN3 but not upon ethylene signaling mediated by the auxin efflux carrier EIR1. In contrast, the rhd1-4 short root and root epidermal bulging phenotypes did not require EIN2, EIN3, or EIR1. A time-course analysis of RHD1 transcript levels in wild-type plants treated with the ethylene precursor 1-aminocyclopropane-1-carboxylic acid showed a root-specific downregulation of RHD1 expression by ethylene. This observation was corroborated by our finding of increased RHD1 transcript levels in roots of the ethylene-insensitive mutants etr1 and ein2. In addition to ethylene, auxin strongly influences H. schachtii susceptibility and root hair elongation. Therefore, we investigated the sensitivity of rhd1-4 roots to indole-3-acetic acid (IAA). Equivalent IAA concentrations caused a greater reduction in rhd1-4 root elongation compared with wild-type roots. Finally, H. schachtii parasitism was found to strongly downregulate RHD1 expression in the root 3 days after inoculation. We conclude that RHD1 is a likely target of root-specific negative regulation by ethylene and that loss of RHD1 function results in a heightened sensitivity of root tissues to both ethylene and auxin. |
15546353 | Molecular characterization of the tobacco SET domain protein NtSET1 unravels its role in histone methylation, chromatin binding, and segregation. | Plants contain a great number of genes encoding a distinctive class of SET domain proteins which harbor a plant-specific N-terminal part together with a C-terminal part showing highest sequence similarity to the catalytic domain of the yeast CLR4, the human SUV39H1 and G9a histone-methyltransferases (HMTases). Here we show that NtSET1, a representative member of this class from tobacco, methylated both K9 and K27 of histone H3 in vitro. Ectopic expression of NtSET1, by an inducible promoter, increased the amount of dimethylated H3K9 and induced chromosome-segregation defects in tobacco BY2 cells. Deletion analyses show that the HMTase activity, the association with specific chromatin regions and with condensed chromosomes, and the cellular effects largely depended on the C-terminal region including the SET domain of the protein. Nevertheless, the N-terminal part of NtSET1 was capable of targeting the green fluorescent protein to interphase chromatin. Finally, we show that NtSET1 bound LHP1, the Arabidopsis homolog of animal heterochromatin protein 1 (HP1), and that LHP1 co-localized with heterochromatin containing high amounts of dimethylated H3K9, suggesting a role for NtSET1 in heterochromatic function. Taken together, our results provide new insights into the molecular and global chromatin-binding activities of this particular class member of plant SET domain proteins. |
15546352 | The Arabidopsis COW1 gene encodes a phosphatidylinositol transfer protein essential for root hair tip growth. | Root hairs are a major site for the uptake of water and nutrients into plants, and they form an increasingly important model system for the study of development in higher plants. We now report on the molecular genetic analysis of the srh1 mutant in Arabidopsis thaliana impaired in root hair tip growth. We show that srh1 is a new allele of cow1 (can of worms1) and we identified the COW1 gene using a positional cloning strategy. The N-terminus of the COW1 protein is 32% identical to an essential phosphatidylinositol transfer protein (PITP), the yeast Sec14 protein (sec14p) while the C-terminus is 34.5% identical to a late nodulin of Lotus japonicus, Nlj16. We show that expression of the COW1 lipid-binding domain complements the growth defect associated with Sec14p dysfunction in yeast. In addition, we show that GFP fused to the COW1 protein specifically accumulates at the site of root hair outgrowth. We conclude that the COW1 protein is a PITP, essential for proper root hair growth. |
15546351 | The nuclear genes Lhcb and HEMA1 are differentially sensitive to plastid signals and suggest distinct roles for the GUN1 and GUN5 plastid-signalling pathways during de-etiolation. | Feedback mechanisms are critical to the regulation of chloroplast development and signals from functional plastids are required to maintain nuclear gene expression of chloroplast proteins. To understand the role of these signals in de-etiolating Arabidopsis thaliana L. seedlings, we followed the expression of three nuclear genes, Lhcb, HEMA1 and GSA, under a variety of treatments (Norflurazon, lincomycin and a far-red light pre-treatment) leading to plastid damage in white light and in a range of genetic backgrounds known to modulate plastid signalling: the genomes uncoupled mutants, gun1, gun4, gun5 and the gun1,5 double mutant, and in a transgenic line over-expressing NADPH:protochlorophyllide oxidoreductase. The three nuclear genes were differentially sensitive to changes in plastid signalling, with Lhcb the most strongly repressed and GSA insensitive to all but the most severe treatments. Analysis of plastid morphology in seedlings grown under identical conditions demonstrated that these responses corresponded closely to the degree of plastid damage. Furthermore, although Lhcb and HEMA1 were responsive to both GUN1 and GUN5 signals, the relative inputs from these pathways differed for each transcript with GUN1 being dominant for HEMA1 regulation. Further analysis of HEMA1 expression in gun1 seedlings under non-photobleaching conditions indicates that GUN1 is an important suppressor of HEMA1 expression in the dark and under saturating white light. These results are consistent with plastid signals functioning in a feedback regulatory mechanism during chloroplast biogenesis, and suggest a key role for GUN1 during the early stages of chloroplast development. |
15546350 | The chromatin remodelling complex FACT associates with actively transcribed regions of the Arabidopsis genome. | The packaging of the genomic DNA into chromatin in the cell nucleus requires machineries that facilitate DNA-dependent processes such as transcription in the presence of repressive chromatin structures. Using co-immunoprecipitation we have identified in Arabidopsis thaliana cells the FAcilitates Chromatin Transcription (FACT) complex, consisting of the 120-kDa Spt16 and the 71-kDa SSRP1 proteins. Indirect immunofluorescence analyses revealed that both FACT subunits co-localize to nuclei of the majority of cell types in embryos, shoots and roots, whereas FACT is not present in terminally differentiated cells such as mature trichoblasts or cells of the root cap. In the nucleus, Spt16 and SSRP1 are found in the cytologically defined euchromatin of interphase cells independent of the status of DNA replication, but the proteins are not associated with heterochromatic chromocentres and condensed mitotic chromosomes. FACT can be detected by chromatin immunoprecipitation over the entire transcribed region (5'-UTR, coding sequence, 3'-UTR) of actively transcribed genes, whereas it does not occur at transcriptionally inactive heterochromatic regions and intergenic regions. FACT localizes to inducible genes only after induction of transcription, and the association of the complex with the genes correlates with the level of transcription. Collectively, these results indicate that FACT assists transcription elongation through plant chromatin. |
15546349 | Signaling requirements and role of salicylic acid in HRT- and rrt-mediated resistance to turnip crinkle virus in Arabidopsis. | Inoculation of turnip crinkle virus (TCV) on the resistant Arabidopsis ecotype Di-17 elicits a hypersensitive response (HR), which is accompanied by increased expression of pathogenesis-related (PR) genes. Previous genetic analyses revealed that the HR to TCV is conferred by HRT, which encodes a coiled-coil (CC), nucleotide-binding site (NBS) and leucine-rich repeat (LRR) class resistance (R) protein. In contrast to the HR, resistance to TCV requires both HRT and a recessive allele at a second locus designated rrt. Here, we demonstrate that unlike most CC-NBS-LRR R genes, HRT/rrt-mediated resistance is dependent on EDS1 and independent of NDR1. Resistance is also independent of RAR1 and SGT1. HRT/rrt-mediated resistance is compromised in plants with reduced salicylic acid (SA) content as a consequence of mutations eds5, pad4, or sid2. By contrast, HR is not affected by mutations in eds1, eds5, pad4, sid2, ndr1, rar1, or sgt1b. Resistance to TCV is restored in both SA-deficient Di-17 plants expressing the nahG transgene and mutants containing the eds1, eds5, or sid2 mutations by exogenous application of SA or the SA analog benzo(1,2,3)thiadiazole-7-carbothioic acid (BTH). In contrast, SA/BTH treatment failed to enhance resistance in HRT pad4, Col-0, or hrt homozygous progeny of a cross between Di-17 and Col-0. Thus, HRT and PAD4 are required for SA-induced resistance. Exogenously supplied SA or high endogenous levels of SA, due to the ssi2 mutation, overcame the suppressive effects of RRT and enhanced resistance to TCV, provided the HRT allele was present. High levels of SA upregulate HRT expression via a PAD4-dependent pathway. As Col-0 transgenic lines expressing high levels of HRT were resistant to TCV, but lines expressing moderate to low levels of HRT were not, we conclude that SA enhances resistance in the RRT background by upregulating HRT expression. These data suggest that the HRT-TCV interaction is unable to generate sufficient amounts of SA required for a stable resistance phenotype, and the presence of rrt possibly corrects this deficiency. |
15546348 | Host and non-host pathogens elicit different jasmonate/ethylene responses in Arabidopsis. | Arabidopsis does not support the growth and asexual reproduction of the barley pathogen, Blumeria graminis f. sp. hordei Bgh). A majority of germlings fail to penetrate the epidermal cell wall and papillae. To gain additional insight into this interaction, we determined whether the salicylic acid (SA) or jasmonate (JA)/ethylene (ET) defence pathways played a role in blocking barley powdery mildew infections. Only the eds1 mutant and NahG transgenics supported a modest increase in penetration success by the barley powdery mildew. We also compared the global gene expression patterns of Arabidopsis inoculated with the non-host barley powdery mildew to those inoculated with a virulent, host powdery mildew, Erysiphe cichoracearum. Genes repressed by inoculations with non-host and host powdery mildews relative to non-inoculated control plants accounted for two-thirds of the differentially expressed genes. A majority of these genes encoded components of photosynthesis and general metabolism. Consistent with this observation, Arabidopsis growth was inhibited following inoculation with Bgh, suggesting a shift in resource allocation from growth to defence. A number of defence-associated genes were induced during both interactions. These genes likely are components of basal defence responses, which do not effectively block host powdery mildew infections. In addition, genes encoding defensins, anti-microbial peptides whose expression is under the control of the JA/ET signalling pathway, were induced exclusively by non-host pathogens. Ectopic activation of JA/ET signalling protected Arabidopsis against two biotrophic host pathogens. Taken together, these data suggest that biotrophic host pathogens must either suppress or fail to elicit the JA/ET signal transduction pathway. |
15546345 | Role of 14-bp deletion in the HLA-G gene in the maintenance of pregnancy. | Differential expression of human leukocyte antigens (HLAs) on trophoblast has been the focus of many studies, specially on extravillous cytotrophoblast cells, which migrates into the maternal uterine tissues. These invading cells do not express classical major histocompatibility complex class I (-A and -B) and class II molecules, along with low expression of HLA-C. HLA-G is the predominantly expressed antigen along with HLA-E. Hence, it is believed that expressed antigens may be involved in materno-fetal tolerance. In the present study, we have studied 14-bp deletion polymorphism in the exon-8 of the non-classical HLA-G antigen. There was no difference in the frequency of deletion/insertion polymorphism in fertile normal women and recurrent spontaneous abortion (RSA) women. However, the number of heterozygotes (-14b/+14b) were increased in RSA women. The probable mechanism for the increase of heterozygotes in recurrent fetal loss is discussed in light of soluble HLA-G. |
15546344 | HLA-Cw*1214 allele arisen via recombination between HLA-Cw*070201 and HLA-Cw*120201. | Allelic polymorphism of the major histocompatibility complex arises mostly from gene conversion. Intralocus gene conversion usually involves limited fragments of DNA, whereas recombination involving large fragments of DNA is considered to be a rare event. During routine sequencing-based typing of donors for the National Marrow Donor Program, a new HLA-C allele was identified in a Caucasian donor. The allele, HLA-Cw*1214, proved to be the product of recombination between HLA-Cw*070201 and HLA-Cw*120201. Exons 1, 2, the 3' end of exon 3 and exon 4 (with one mismatch) belong to HLA-Cw*120201, whereas part of exon 3 belongs to HLA-Cw*070201. Sequencing with primers based in exon 2 and exon 3 showed that intron 2 of the new allele also belonged completely to HLA-Cw*1202. The recombination event apparently occurred within exon 3 with the first point of recombination somewhere between codons 92 and 134 and the second one between codons 157 and 181. |
15546343 | Loss of heterozygosity in the HLA class I region in human pancreatic cancer. | An altered human leukocyte antigen (HLA) class I expression constitutes an important tumor-escape mechanism counteracting T-cell mediated immune responses. We utilized the technique of microsatellite analysis to characterize the loss of heterozygosity (LOH) in the HLA class I region in 24 samples of patients with human ductal pancreatic carcinoma. The expression of HLA class I and the infiltration by T cells were studied in parallel by standard immunohistochemistry. The present study demonstrates LOH in the HLA class I region in five patients with pancreatic carcinoma. Immunohistochemical analysis showed that pancreatic carcinomas were frequently characterized by a total or partial loss of expression in HLA class I antigen. The positive or negative LOH status corresponded with the expression analysis in eight cases. Reduction of HLA class I expression without LOH was found in 14 cases. Lymphocyte infiltration with CD3+, CD4+, and CD8+ T cells did not show significant differences between LOH-positive and LOH-negative tumors. In conclusion, LOH does not seem to be the only factor for the reduced expression of HLA class I antigen as well as for the T-cell infiltration in this type of tumor. |
15546342 | Immunogenetics of HLA null alleles: implications for blood stem cell transplantation. | The transplantation of haematopoietic stem cells is a potentially curative therapy for a variety of haematological and non-haematological diseases. Matching of donor and recipient for human leucocyte antigens (HLA) is pivotal for the success of blood stem cell transplantation. HLA null alleles are characterized by the lack of a serologically detectable product. Because serological HLA diagnostics are increasingly replaced by DNA-based typing methods considering only small regions of the genes, null alleles may be misdiagnosed as normally expressed variants. The failure to identify an HLA null allele as a non-expressed variant in the stem cell transplantation setting may result in an HLA mismatch that is highly likely to stimulate allogeneic T cells and to trigger graft-vs-host disease. For some HLA null alleles, the translation into a truncated polypeptide chain seems possible, which thus might act as minor histocompatibility antigens. Because the prevalence of HLA null alleles may be around 0.3% or even higher, a screening strategy for HLA null alleles should, therefore, be implemented in the clinical laboratory. It may consist of the combination of serology and standard molecular typing techniques. As the standard molecular techniques are sometimes troublesome especially for characterizing the cytosine island at the 5' end of HLA class I exon 4 and need continuously be updated, an alternative approach may consist of sequencing all samples from genomic DNA for exons 2-3 or 4 (class I) or exon 2 (class II), including the adjacent intron splicing sites. This approach will detect 36/40 so far known non-expressed variants and has the potential to easily uncover novel variants, thus essentially minimizing the risk of overlooking these challenging variants. |
15546341 | HLA class-I and class-II allele frequencies and two-locus haplotypes in Melanesians of Vanuatu and New Caledonia. | HLA class-I and class-II allele frequencies and two-locus haplotypes were examined in 367 unrelated Melanesians living on the islands of Vanuatu and New Caledonia. Diversity at all HLA class-I and class-II loci was relatively limited. In class-I loci, three HLA-A allelic groups (HLA-A*24, HLA-A*34 and HLA-A*11), seven HLA-B alleles or allelic groups (HLA-B*1506, HLA-B*5602, HLA-B*13, HLA-B*5601, HLA-B*4001, HLA-B*4002 and HLA-B*2704) and four HLA-C alleles or allelic groups (HLA-Cw*04, HLA-Cw*01, HLA-Cw*0702 and HLA-Cw*15) constituted more than 90% of the alleles observed. In the class-II loci, four HLA-DRB1 alleles (HLA-DRB1*15, HLA-DRB1*11, HLA-DRB1*04 and HLA-DRB1*16), three HLA-DRB3-5 alleles (HLA-DRB3*02, HLA-DRB4*01 and HLA-DRB5*01/02) and five HLA-DQB1 alleles (HLA-DQB1*0301, HLA-DQB1*04, HLA-DQB1*05, HLA-DQB1*0601 and HLA-DQB1*0602) constituted over 93, 97 and 98% of the alleles observed, respectively. Homozygosity showed significant departures from expected levels for neutrality based on allele frequency (i.e. excess diversity) at the HLA-B, HLA-Cw, HLA-DQB1 and HLA-DRB3/5 loci on some islands. The locus with the strongest departure from neutrality was HLA-DQB1, homozygosity being significantly lower than expected on all islands except New Caledonia. No consistent pattern was demonstrated for any HLA locus in relation to malaria endemicity. |
15546340 | Major histocompatibility complex haplotypes in Spanish immunoglobulin A deficiency patients: a comparative fine mapping microsatellite study. | The most consistent finding in Immunoglobulin A deficiency (IgAD) genetics is the presence of susceptibility factors located in the major histocompatibility complex (MHC). We have described the existence of at least two distinct susceptibility genes in the MHC present in different haplotypes. The aim of the present study was to locate with precision the susceptibility genes present in DR1- and DR7-positive haplotypes, taking advantage of their structural diversity, as opposed to the conserved nature of the DR3-extended susceptibility haplotype (DR3/B8), that hampers a more exhaustive scrutiny. A detailed analysis with 20 markers along the MHC in the 400 haplotypes present in 100 IgAD families, with special density at Class II locations, was performed to define the minimal shared susceptibility region present in all haplotypes carrying DR1 and, on the other hand, in all DR7-positive haplotypes. A comparison of the fine microsatellite allele structure of DR-extended haplotypes in the Spanish population with those described for Swedish and British families revealed no difference in DRB1*0101 and DRB1*0102 haplotypes between both populations. Our data suggest that the etiologic mutation present in DRB1*0101 and DRB1*0102 in North Europe (Sweden and UK) is missing in the Spanish DRB1*0101 haplotypes but is present in the DQB1/DRB1 region in DRB1*0102 haplotypes. The results obtained also indicated that the most likely susceptibility gene in the DR7 haplotypes is either DQA1 or DRB1. |
15546339 | Cytotoxic T-lymphocyte antigen-4-CT60 polymorphism in rheumatoid arthritis. | Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a functional candidate gene with susceptibility to rheumatoid arthritis (RA). The aim of this work was to investigate the possible influence of the recently described CT60A/G dimorphism of the CTLA-4 gene in the susceptibility to RA in Spanish patients. A total of 433 RA patients and 398 control subjects were included in the study. Genotyping of CTLA-4 CT60 was performed using two different methods: polymerase chain reaction restriction fragment length polymorphism system using an amplification-created restriction site and a TaqMan 5'-allelic discrimination assay. In order to validate results obtained by different methods, a quality-control exercise was performed. No significant deviation in the distribution of the alleles or genotypes of the CT60 was found when we compared RA patient and control groups. In addition, no differences in CTLA-4 CT60 genotypic distribution was found when RA patients and controls were stratified by the presence or absence of the shared epitope. In conclusion, our results do not support an association between CT60A/G polymorphism and susceptibility to RA in the Spanish population, although the contribution of other positions located within the 3' region of the CTLA-4 gene to RA susceptibility cannot be discarded. |
15546338 | TNF-alpha and TGF-beta1 gene polymorphisms and renal allograft rejection in Koreans. | This study was performed in order to evaluate the association of tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) gene polymorphisms with renal allograft rejection in Koreans. Five TNF-alpha (-1031T/C, -863C/A, -857C/T, -308G/A and -238G/A) and two TGF-beta1 (codon 10 T/C and codon 25 G/C) single-nucleotide polymorphism (SNP) sites were studied by using polymerase chain reaction (PCR) single-strand conformation polymorphism and PCR restriction fragment length polymorphism methods in 100 controls and 164 patients. The patients underwent renal transplantation, having one or more Human leukocyte antigen (HLA)-A, HLA-B and HLA-DR antigens mismatched with their donors. For the TGF-beta1 gene, we also studied the polymorphism of donors. The allele frequencies of each SNP site in controls were not different from those of patients. The frequency of TNF-alpha high-producer genotype, -308GA, and TGF-beta1 lower (intermediate)-producer genotype, codon 10 CC and codon 25 GG, were significantly higher in patients with recurrent acute rejection episodes (REs), compared to those in patients with no or one RE. The highest risk group for developing recurrent REs showed the combination of TNF-alpha high- and TGF-beta1 lower-producer genotypes. Analysis of chronic renal allograft dysfunction (CRAD) revealed that TGF-beta1 high-producer genotype of donors, codon 10 TT/TC and codon 25 GG, is associated with CRAD especially in patients with recurrent REs. The highest risk group for developing CRAD showed the combination of recipient's TNF-alpha high- and donor's TGF-beta1 high-producer genotypes. These results would be useful for predicting high-risk group for acute rejection or CRAD in renal transplantation. |
15546337 | Identification of an epitope from the epithelial cell adhesion molecule eliciting HLA-A*2402-restricted cytotoxic T-lymphocyte responses. | Because the epithelial cell adhesion molecule (Ep-CAM) is expressed in almost all carcinomas and human leucocyte antigen (HLA)-A*2402 is the most common allele in many ethnic groups, including Japanese, the identification of peptide sequences, which elicit HLA-A*2402-restricted Ep-CAM-specific cytotoxic T-lymphocyte (CTL) responses, would facilitate specific immunotherapy for various histological types of carcinomas. An epitope was identified through the following steps: (i) computer-based epitope prediction from the amino acid sequence of Ep-CAM, (ii) major histocompatibility complex (MHC) stabilization assay to determine the affinity of the predicted peptide with HLA-A*2402 molecules, (iii) stimulation of CD8+ T cells with peptide-pulsed dendritic cells and (iv) testing the CTL specificity by means of enzyme-linked immunospot (ELISPOT) assays, CTL assays and MHC/peptide-tetramer staining. Peripheral CD8+ T cells of four of five healthy donors after three rounds of stimulation with the peptide Ep-CAM173-181 (RYQLDPKFI) secreted interferon-gamma in ELISPOT assays when exposed to the peptide. A CTL clone specific to the peptide efficiently lysed Ep-CAM-expressing cancer cell lines in an HLA-A*2402-restricted fashion. Endogenous processing and presentation of the peptide in a lung cancer cell line were confirmed by means of cold target inhibition assays. The CTL clone was also lytic to normal bronchial epithelial cells but to a lesser extent at low effector: target ratios. All these data suggest that the peptide-specific CTL responses may play some roles both in anti-cancer and autoimmune reactions. The peptide should prove useful to study anti-Ep-CAM CTL responses among population possessing HLA-A*2402. |
15546336 | An update of the HLA genomic region, locus information and disease associations: 2004. | The human major histocompatibility (MHC) genomic region at chromosomal position 6p21 encodes the six classical transplantation HLA genes and many other genes that have important roles in the regulation of the immune system as well as in some fundamental cellular processes. This small segment of the human genome has been associated with more than 100 diseases, including common diseases--such as diabetes, rheumatoid arthritis, psoriasis, asthma and various autoimmune disorders. The MHC 3.6 Mb genomic sequence was first reported in 1999 with the annotation of 224 gene loci. The locus and allelic information of the MHC continue to be updated by identifying newly mapped expressed genes and pseudogenes based on comparative genomics, SNP analysis and cDNA projects. Since 1999, new innovations in bioinformatics and gene-specific functional databases and studies on the MHC genes have resulted in numerous changes to gene names and better ways to update and link the MHC gene symbols, names and sequences together with function, variation and disease associations. In this study, we present a brief overview of the MHC genomic structure and the recent information that we have gathered on the MHC gene loci via LocusLink at the National Centre for Biological Information (http://www.ncbi.nih.gov/.) and the MHC genes' association with various diseases taken from publications and records in public databases, such as the Online Mendelian Inheritance in Man and the Genetic Association Database. |
15546334 | A 10-year follow-up study of pulmonary function in symptomatic elite cross-country skiers--athletes and bronchial dysfunctions. | A high prevalence of asthma-like symptoms and abnormal bronchial reactivity to various stimuli has been reported among endurance athletes. This report presents the cases of three cross-country skiers who have shown a progressive development of airway obstruction during their sport careers. The observed decline in FEV1, FEV1/FVC and/or FVC (FEV, forced expiratory volume; FVC, forced expiratory vital capacity) was greater than expected from longitudinal regression equations describing the ageing effect on pulmonary function. The three subjects encountered abnormal respiratory discomfort during their sport activity which was not systematically associated with abnormal bronchial reactivity (either to methacholine or exercise hyperventilation). At the end of the follow-up periods (9-12 years), all three skiers presented objective signs of airflow limitations during intense exercise. This report suggests that repeated chronic hyperventilation of cold dry air in cross-country skiers for several years can induce permanent bronchial disorders which may include remodeling processes and induce ventilatory limitations during intense exercise. |
15546333 | The role of exercise and gender for physical self-perceptions and importance ratings in Swedish university students. | The purpose of this study was to investigate how scores on the Physical Self-Perception Profile (PSPP), including scores on the Perceived Importance Profile (PIP), were related to self-reported exercise frequency, duration, and gender in sample of Swedish university students. A total of 164 participants completed the PSPP, PIP, and a questionnaire focusing on frequency and duration of exercise. Exercise frequency, duration, and gender predicted best the PSPP sub-domains of Sport Competence and Physical Conditioning. Exercising more frequently, and for a longer time on each occasion was associated with higher PSPP and PIP scores. Women generally displayed lower PSPP scores than men. These results suggest that exercise professionals need to master a range of appropriate exercise strategies, since doubts concerning self-presentation may work against establishing a regular exercise routine. |
15546332 | Mild eccentric stretch injury in skeletal muscle causes transient effects on tensile load and cell proliferation. | The biomechanical and regenerative responses in rabbit tibialis anterior muscle following a single eccentric stretch injury were investigated 1, 3 and 7 days after traumatization. The stretch injury produced a transient biomechanical effect. On day 1, the load at failure was decreased in the injured muscles compared with the uninjured controls (P<0.05), but on days 3 and 7 significant biomechanical differences were no longer recorded between the injured and control muscles. In immunohistochemical analyses, no overt myonecrosis or connective tissue disruption was observed in any of the stretch-injured muscles. Yet satellite cells were activated to incorporate a thymidine analogue, bromodeoxyuridine indicating mitotic activity. They did not, however, produce muscle-specific proteins, i.e., they did not differentiate further. Furthermore, the intact appearing but mildly injured myofibers of the stretched muscles expressed both neonatal myosin and vimentin near the myotendinous junctions. Collectively, these results suggest that a single mild eccentric stretch of skeletal muscle which does not cause gross structural alterations results in a short-term decrease in tensile load and induces transient proliferation of satellite cells and fibroblasts together with expression of primitive proteins in myofibers. |
15546331 | Relationship of leg muscle strength and knee function in the early period after anterior cruciate ligament reconstruction. | The purpose of this descriptive study was to assess the relationship between knee function and the strength testing performance of various leg muscles in the early period after anterior cruciate ligament reconstruction (ACLR). Twenty-four patients who had recent ACLR (seven females and 17 males, mean age=27 years) were tested for leg muscle strength and knee function 2 weeks after surgery. The concentric peak torques of the hip and knee extensors and knee flexors were measured at 210 degrees s(-1). In addition, the latter two muscle groups were measured at 60 degrees s(-1), and also isometrically (at a knee angle of 60 degrees). Knee function was assessed using a three-dimensional motion analysis system combined with a force platform. This system determined knee joint angles, torques and powers during level walking, stair ascent and stair descent. Pearson's correlation coefficients were calculated to assess the relationships between the injured knee function variables and the injured/uninjured strength ratios. The correlation coefficients ranged (in absolute value) from 0.03 to 0.81, and were generally higher for the stair tasks compared with level walking, and highest for the knee extensors (as compared with the knee flexors and hip extensors), and the strength test velocity appears much less important than the muscle group tested. These results contribute evidence indicating the importance of knee extensor strength to knee function in the early period after ACLR. |
15546330 | Associations between activities and low back pain in adolescents. | The aim of this cross-sectional study was to explore associations between self-reported leisure activities and low back pain (LBP). The material included all adolescents in eighth and ninth grade in two geographical areas in the school year 1996-1997. Eighty-eight adolescents participated (mean age 14.7 years), making the response rate 84%. LBP during the preceding year was reported by 57%. Sixty-six percent reported physical activity 3 times weekly or more. The median time spent on television or computer was 15 h. In multivariate analyses, LBP was inversely associated with time spent on physical activity, in particular with regular walking or bicycling. LBP was associated with the use of television or computer more than 15 h weekly, but not with the time spent reading. The results confirm studies showing inverse associations between walking and LBP. Future research should involve prospective studies of the potential effects of walking or bicycling and other specific activities on LBP. |
15546329 | Returning athletes with severe low back pain and spondylolysis to original sporting activities with conservative treatment. | The purpose of this study was to clarify the efficacy of conservative treatment in athletes with severe low back pain and spondylolysis, especially focusing on returning to original sporting activities. One hundred and four athletes (96 males and eight females), who consulted our sports medicine clinic during the 11-year period between September 1991 and October 2002 because of low back pain with an apparent defect of the pars interarticularis on plain radiographs, were subjected to conservative treatment. The mean age of the patients was 20.7 years. Of all the patients, 40 (38.5%) discontinued sporting activities due to severe low back pain, and were conservatively treated with activity restriction and antilordotic lumbosacral bracing, aimed at relieving low back pain by achieving stability of the fracture partly associated with fibrous union. After their low back pain was markedly reduced, the brace was removed and then individual training to return to the original sporting activities was started. Thirty-five patients (87.5%) could return to their original sporting activities in an average of 5.4 months (range: 1.0-11.5 months) after the onset of treatment, and could continue the activities for at least 6 months despite non-bony union. These results suggest that the outcome of conservative treatment with activity restriction and bracing appears to be satisfactory in controlling symptoms and returning to original sporting activities. Randomized controlled trials or comparative follow-up studies are needed to confirm our results. |
15546328 | Evidence for exercise therapy in the treatment of chronic disease based on at least three randomized controlled trials--summary of published systematic reviews. | Final evidence for the overall benefits of exercise therapy in the treatment/rehabilitation of specific chronic disease comes from randomized controlled trials (RCTs). This paper summarizes current evidence that is based on a systematic review including data from at least three RCTs with contrast for exercise only. The quality of specific RCTs as well as the quality of systematic reviews varies, the newest ones usually being of higher quality than the older ones. The most consistent finding of the studies is that aerobic capacity and muscular strength of patients can be improved without causing detrimental effects on disease progression. Severe complications during these carefully tailored programs were rare. The treatment periods and follow-up times of the majority of the RCTs are of a too short duration to document group differences in disease progression. However, exercise reduces disease-related symptoms in many diseases, such as osteoarthritis, asthma and chronic obstructive pulmonary disorder. Also, RCTs studying patients with coronary heart disease as well as patients with heart failure show that all-cause mortality is lower in exercisers than in controls. |
15546319 | An unusual obstacle in lead extraction. | This case report deals with an unusual complication in the removal of an active fixation implantable cardioverter defibrillator (ICD) lead. We were not able to pass the stylet beyond the point of lead fracture and this was subsequently found to be due to the stylet passing between the electrode and the outer layer of the lead insulation. The lead was removed by rotation extraction of the entire lead. |
15546318 | Subtotal innominate vein occlusion after unsuccessful pacemaker implantation for resynchronization therapy. | Cardiac resynchronization therapy is increasingly used to treat patients with poor left ventricular function and asynchronous left ventricular contraction. Generally, a transvenous approach is used for implantation of pacing leads. However, coronary sinus lead implantation may be associated with various problems that may result in abandoning of the procedure. In this report a patient is described with subtotal innominate vein occlusion after such a procedure who underwent video-assisted thoracoscopic surgery (VATS) for implantation of epicardial left ventricular pacemaker leads for resynchronization therapy. |
15546317 | Hypersensitive carotid sinus syndrome due to neurofibromatosis-1 and manifested by repeated episodes of syncope. | A 28-year-old patient with neurofibromatosis-1 presented with syncope. The exam demonstrated a mass adjacent and inferior to the right occiput that extended to the posterior lateral right-sided neck. Initial invasive and noninvasive testing was negative. Imaging of her head and neck demonstrated a large neurofibroma enveloping her right carotid sinus without vessel occlusion or evidence of malignancy. An event recorder documented asystole. A pacemaker was implanted to avoid the surgical morbidity of removing the neck mass. The patient has since been free of syncope. We believe neurofibromatosis-1 should be included in the differential of syncope. |
15546316 | Extraction of a defibrillator lead through an inferior vena cava filter. | We report an extraction of a chronic, previously cut and abandoned, active-fixation implantable cardioverter-defibrillator lead through an inferior vena cava filter. A long workstation sheath that crossed the filter was used, allowing the lead and all hardware to be withdrawn through a single opening in the filter. |
15546315 | Thebesian valve imaging with electron beam CT angiography: implications for resynchronization therapy. | We report visualization of a prominent coronary sinus os valve (Thebesian valve), by electron beam computed tomographic angiography, which impeded an endocardial approach to left ventricular pacing. Resynchronization therapy was therefore performed with an epicardial approach to left ventricular lead placement. Electron beam computed tomographic angiography can provide detailed information for coronary sinus instrumentation, including anomalies potentially affecting the approach to resynchronization therapy. |
15546314 | T wave oversensing by a cardioverter defibrillator implanted in a patient with the Brugada syndrome. | Oversensing of electrical signals in recipients of ICDs is a common complication causing the delivery of inappropriate therapy. The Brugada syndrome has a characteristic ECG pattern with dynamic temporal changes in response to various physiological or environmental conditions. This case report presents a patient with the Brugada syndrome and intermittent T wave oversensing by an ICD due to changes in T wave amplitude which could not be resolved by device reprogramming and required repositioning of the electrode. |
15546313 | Postprandial variations in ST-segment in a patient with Brugada syndrome and partial gastrectomy. | A 74-year-old man with a history of partial gastrectomy presented with an electrocardiogram consistent with Brugada syndrome and marked meal related fluctuations in the ST segment. ST-segment elevation was prominently attenuated at 30 minutes and increased at 120 minutes after meals. Analysis of heart rate variability revealed a relationship between postprandial heightened parasympathetic activity and increase in Brugada-type ECG abnormality. A rapid postprandial increase in blood glucose may initially stimulate sympathetic nervous activity and secondarily increase parasympathetic tone. Food intake can be associated with fluctuations in ST-segment elevation in patients with the Brugada syndrome. |
15546312 | Pulmonary veins: anatomy, electrophysiology, tachycardia, and fibrillation. | Recent years have seen an enormous amount of experimental and clinical research into role of the pulmonary veins (PVs) in atrial fibrillation (AF). Advanced imaging techniques have confirmed the findings of earlier postmortem studies and added further dimension to our knowledge of PV anatomy. Such work is vital for an effective approach to successful ablation of AF. Detailed mapping studies suggest that reentry within the PVs is most likely responsible for their arrhythmogenicity, although focal or triggered activity cannot be excluded. Further work also implicates the posterior left atrium in the genesis of AF. Investigation into the interplay between the PVs and left atrium has led to a reevaluation of the mechanisms underlying AF and suggests that the PVs may play a role in both the initiation and maintenance of this arrhythmia. In order for electrophysiologists to further develop the technical approach to ablation of AF and improve the clinical outcomes, these crucial issues must be resolved. |
15546310 | Evaluation of the early hemodynamic changes in carotid arteries during ventricular and dual chamber pacing. | In spite of a wide choice of pacemakers, there are some problems in making more rational clinical decisions for individual patients since mode selection and programming is usually performed on the basis of a clinical hunch. The aim of this study was to measure the differences in carotid flow in patients with a pacemaker programmed in the dual chamber and in the single chamber pacing modes. Sixty patients with implanted bipolar DDD pacemakers were enrolled in this study. Blood peak systolic velocity (PSV) and end-diastolic velocity (EDV), cross-sectional area, resistive index (RI), and pulsatility index (PI) were measured in the common (CCA), internal (ICA), and external (ECA) carotid arteries before pacemaker implantation and after dual chamber and ventricular pacing at 60 beats/min. PSVs in the left CCA (79.3 +/- 24.9 cm/s) and right CCA (84.1 +/- 18.7) were shown to significantly decrease after VVI pacing (60.1 +/- 16.6 and 62.1 +/- 20.0, respectively). There was also a similar significant decrease in PSV in the left and right ICAs and ECAs. Besides PSV, RI, and PI in the left and right CCAs, ICAs, and ECAs significantly decreased after VVI pacing. There was no similar decrease after DDD pacing. Cross-sectional area and flow volume in the CCA, ICA, and ECA were similar after DDD and VVI pacing and before pacemaker implantation suggesting that cardiac output was similar when the measurements were recorded. Carotid artery PSVs, pulsatility, and RIs were found to be significantly decreased during VVI pacing compared to baseline and DDD pacing. The greater incidence of adverse cerebral outcomes in patients with VVI rather than DDD pacing may be partly due to decreased carotid PSVs. |
15546309 | Feasibility of catheter cryoablation in normal ventricular myocardium and healed myocardial infarction. | Although novel cryoablation systems have recently been introduced into clinical practice for catheter ablation of supraventricular tachycardia, the feasibility of catheter cryoablation of VT is unknown. Thus, the present study evaluates catheter cryoablation of the ventricular myocardium (1) in healthy sheep and (2) of VT in chronic myocardial infarction (MI). In three healthy sheep, 21 ventricular lesions (12 left and 9 right ventricle) were created with a catheter cryoablation system. Different freeze/thaw characteristics were used for lesion creation. The mean nadir temperature was -84.1 degrees C +/- 0.9 degrees C, mean lesion volume was 175.8 +/- 170.3 mm3, and 5 of 21 lesions were transmural. Lesion dimensions were 7.5 +/- 3.1 mm (width) and 4.2 +/- 2.5 mm (depth). Left ventricular lesions were significantly larger than right ventricular lesions (262 +/- 166 vs 60.5 +/- 91.6 mm3, P=0.0025). There was no difference in lesion volume with respect to different freeze/thaw characteristics. Anatomically (n=3) or electrophysiologically (n=3) guided catheter cryoablation was attempted in six sheep 105 +/- 56 days after MI, three of six animals had reproducibly inducible VT with a mean cycle length of 215 +/- 34 ms prior to ablation. In these animals, five VTs were targeted for ablation. A mean of 6 +/- 3 applications for nine left ventricular lesions were applied, six of nine lesions were transmural. The mean lesion volume was 501 +/- 424 mm3. No VT was inducible in two of three animals after cryoablation using an identical stimulation protocol. Therefore, catheter cryoablation of VT in healed MI is feasible, and no acute complications were observed. |
15546308 | Pacemakers and implantable cardioverter defibrillators: device longevity is more important than smaller size: the patient's viewpoint. | The size of pacemakers and implantable cardioverter defibrillators (ICDs) has been diminishing progressively. If two devices are otherwise identical in components, features and technology, the one with a larger battery should have a longer service life. Therefore, patients who receive smaller devices may require more frequent surgery to replace the devices. It is uncertain whether this tradeoff for smaller size is desired by patients. We surveyed 156 patients to determine whether patients prefer a larger, longer-lasting device, or a smaller device that is less noticeable but requires more frequent surgery. The effects of subgroups were evaluated; these included body habitus, age, gender, and patients seen at time of pulse generator replacement (PGR), initial implant, or follow-up. Among 156 patients surveyed, 151 expressed a preference. Of these, 90.1% preferred the larger device and 9.9% the smaller device (P <0.0001). Among thin patients, 79.5% preferred a larger device. Ninety percent of males and 89.2% of females selected the larger device. Among younger patients (< or =72 years), 89.6% preferred the larger device, as did 90.5% of older patients (>72 years). Of patients undergoing PGR or initial implants, 95% favored the larger device, as did 86% of patients presenting for follow-up. The vast majority of patients prefer a larger device to reduce the number of potential replacement operations. This preference crosses the spectrum of those with a previously implanted device, those undergoing initial implants, those returning for routine follow-up, and patients of various ages, gender, and habitus. |
15546307 | Effect of amiodarone dose on the risk of permanent pacemaker insertion. | Bradyarrhythmia requiring permanent pacemaker insertion has been associated with amiodarone use but the effect of amiodarone dose has not been investigated. In order to determine the effect of amiodarone dose on the risk of requiring permanent pacemaker insertion, a cohort of 15,824 subjects with atrial fibrillation (AF) and prior myocardial infarction was established. This study included 1,340 subjects who received a first prescription of amiodarone at > 65 years of age. Cox regression with daily dose and cumulative dose (weighted for recency of exposure) represented by time dependent covariates was performed, adjusting for baseline risk factors and time dependent exposure to other cardiac medications. The incidence of pacemaker insertion was 2.2% per person-year during a mean of 1.8 +/- 1.5 years of follow-up, and 5.2% per person-year during the first 90 days of amiodarone exposure. Amiodarone daily doses > 200 mg were associated with an increased risk during the entire follow-up HR 2.0; 95% CI 1.0 to 4.1) as well as during the first 90 days (HR 3.1; 95% CI 1.1 to 9.0). Cumulative doses greater than the equivalent of continuous therapy with 200 mg per day were also associated with an increased risk (HR 2.8; 95% CI 1.4 to 5.5). Baseline conduction disorder or sinus node dysfunction was the only other significant predictor of pacemaker insertion. This study suggests that there is a dose dependent increased risk of permanent pacemaker insertion associated with amiodarone use that appears to be greatest during the initial months of treatment. |
15546306 | Relationship of baseline electrocardiographic characteristics with the response to cardiac resynchronization therapy for heart failure. | Prospective identification of patients most and least likely to respond to cardiac resynchronization therapy (CRT) for congestive heart failure (CHF) will allow clinicians to target this intervention most efficiently. The authors hypothesized that ECG variables including RBBB and indicators of RV dysfunction and extensive prior myocardial infarction would correlate with diminished response to CRT. This study analyzed preimplantation ECGs in 110 patients with ICD indications and CHF due to left ventricular systolic dysfunction randomized to active biventricular pacing in the MIRACLE ICD trial. Clinical and ECG variables on the outcome of change in peak oxygen consumption from baseline to 6 months (Delta-VO2 ) were evaluated. For this cohort, average peak VO2 improved from 13.4 to 14.3 mL/kg per minute. Among clinical variables, the strongest predictors of increasing Delta-VO2 were reduced exercise time and peak VO2 at baseline. A dominant R wave in lead a VR, RBBB, and evidence of prior anterior infarction were each associated with significantly smaller average improvements in Delta-VO2 than their absence in univariate analysis. Alternative ECG criteria, including QRS duration, had no relationship with the outcome. In a multivariate model, only baseline VO2 (beta=-0.3, P=0.001) and ECG evidence of prior anterior infarction (beta=-1.3, P=0.03) were associated with the outcome. ECG markers of anterior infarction and RV dilation may help identify CHF patients unlikely to benefit from biventricular pacing. Further assessment is needed of these and other predictors of therapeutic response to CRT. |
15546305 | Different clinical courses and predictors of atrial fibrillation occurrence after transisthmic ablation in patients with preablation lone atrial flutter, coexistent atrial fibrillation, and drug induced atrial flutter. | The aim of this prospective study was to compare the long-term follow-up after transisthmic ablation of patients with preablation lone atrial flutter, coexistent AF, and drug induced atrial flutter to determine if postablation AF followed a different clinical course and displayed different predictors in these groups. The study evaluated 357 patients who underwent transisthmic ablation for typical atrial flutter. These were divided into four groups according to their preablation history. Group A included patients with typical atrial flutter and without preablation AF (n=120, 33.6%). Group B included patients with preablation AF and spontaneous atrial flutter (n=132, 37.0%). Group C patients had preablation AF and atrial flutter induced by treatment with IC drugs (propafenone or flecainide) (n=63, 17.6%) Group D included patients with preablation AF and atrial flutter induced by treatment with amiodarone (n=42, 11.8%). During a mean follow-up of 15.2 double dagger 10.6 months (range 6-55 months) AF occurred more frequently in groups B (56.1%) and C (57.1%) patients than in groups A (20.8%, P <0.0001) and D (31.0%, P <0.0001) patients. The results of multivariate analysis revealed that different clinical and echocardiographical variables were correlated with postablation AF occurrence in the different groups. Patients with atrial flutter induced by amiodarone have a significantly lower risk of postablation AF than patients with spontaneous atrial flutter and AF, and those with atrial flutter induced by IC drugs. Different clinical and echocardiographical variables predict postablation AF occurrence in different subgroups of patients. |
15546304 | An epicardial subxiphoid implantable defibrillator lead: superior effectiveness after failure of standard implants. | A single epicardial implantable lead using the subxiphoid approach is described in this article. It consists of a single halo-shaped coil that is implanted under the inferior surface of the heart, including the right and left inferior ventricular surfaces. It has been implanted in four patients who could not be defibrillated with a transvenous system, even with the adjunct use of subcutaneous leads or left chest wall patch. Three of the patients had progressive heart failure due to ischemic myocardiopathy; the fourth patient had a dilated idiopathic myocardiopathy. The approach is simple and appears to be effective due to its ability to encompass the left and right ventricles. This vector seems to significantly lower the threshold for defibrillation, and may offer substantial benefit in the setting of high defibrillation thresholds with conventional leads, or when conventional systems are inadequate to achieve consistent defibrillation. |
15546303 | Direct comparison of a contractility and activity pacemaker sensor during treadmill exercise testing. | There are limited data about the chronotropic capacity of the peak endocardial acceleration (PEA) sensor. This study directly compared the chronotropic function from the PEA and the activity (ACT) sensor. The study included 18 patients (age 73 +/- 7 years) with > or = 75% pacemaker-driven heart rate (HR) and a PEA sensor and 11 healthy controls (age 67 +/- 7 years) underwent a chronotropic assessment exercise protocol (CAEP) exercise test with the pacemaker patients in VVIR mode after programming the sensors in the default setting with adjustment of the upper sensor rate as an age related maximum value (220-age). The ACT sensor was externally strapped on the thorax. Achieved exercise duration for the patients and controls was, respectively, 9.2 +/- 3 vs 18.4 +/- 4 minutes (P <0.001). The maximal achieved HR with the PEA sensor was 124 +/- 25 beats/min, versus the ACT with 140 +/- 23, versus the controls with 153 +/- 26 beats/min (P <0.001 between the groups). For the PEA, ACT, and controls, the time to peak HR was, respectively, 11 +/- 3, 7 +/- 3.6, and 18 +/- 4 (P <0.001 between groups) and HR after 10 minutes recovery was, respectively, 80 +/- 20, 65 +/- 15, and 82 +/- 4 beats/min (P <0.001 between groups). The PEA sensor functions hypochonotroop during exercise programmed as a single sensor system. It is, therefore, preferable to combine the PEA sensor with an activity-based sensor in a dual sensor system. Although both groups had normal left ventricular functions, the exercise capacity of pacemaker patients is significantly lower than in the controls. |
15546302 | Autonomic modulation of the u wave during sympathomimetic stimulation and vagal inhibition in normal individuals. | Prolonged repolarization time, an important contributor to the pathogenesis of ventricular arrhythmias, is usually identified by a long QT interval (QT) on the ECG but is frequently confounded by the presence of a U wave. The physiological basis and clinical relevance of the U wave is unresolved. To better understand the relationship between the T and U waves, this study examined their behavior during nonresting autonomic conditions. Twenty-five healthy subjects were evaluated during sympathomimetic infusion with isoproterenol and vagal inhibition with atropine. As heart rate (HR) increased in response to isoproterenol, the QU interval (QU) decreased by an eightfold greater extent than QT. Furthermore, a marked increase in U wave amplitude and decrease in T wave amplitude were observed with T and U wave fusion at higher HRs. During atropine, QU decreased by only a threefold greater extent than QT, T and U wave amplitudes were affected only minimally, and T-U wave fusion was not observed. These results demonstrate that sympathomimetic stimulation causes striking alterations in the timing and amplitude of U waves that differ from effects on the T wave. These effects are not observed during vagal inhibition. Thus, the U wave represents a component of cardiac repolarization that is electrocardiographically and physiologically distinct from the T wave with a unique response to sympathomimetic stimulation. |
15546301 | Stability of ventricular repolarization in conscious dogs with chronic atrioventricular dissociation and his-bundle pacing. | Following AVN ablation, eight dogs were surgically instrumented for chronic (continuous) HIS-bundle pacing. For data collection, implanted pacemakers were transiently programmed to pace in stepwise ascending ramps at rates from 50 to 200 beats/min in 30-beat/min steps. Each rate was held for 60 seconds. At each rate, ECG signals were collected from conscious dogs for measurements of QT intervals during the last 10 seconds of each paced rate to construct a QT-HR ramp. This QT-HR ramp was repeated twice on each day of study 10 minutes apart. Dogs were randomly assigned to two groups and studied weekly for a minimum of 6 weeks. Group 1 dogs had pacemakers programmed to a rate of 80 beats/min for the duration of the study. Group 2 dogs were paced at 80 beats/min for weeks 1-3, then increased to 140 beats/min for weeks 4-6. The difference between paired QT-HR ramps within 1 day was <3 ms. QT-HR ramps were statistically indistinguishable over the 6-week study for group 1 dogs. Group 2 dogs experienced a slight flattening in the slope of the QT-HR ramps from week 3 to week 6 due to a reduction in QT interval at low HRs (50 and 80 beats/min) only. This conscious HIS-pacing model in dogs is a sensitive, stable, and reproducible method to define ventricular repolarization characteristics over a range of programmable HRs and experimental conditions. |
15546300 | Endocardial pacemaker implantation in infants weighing < or = 10 kilograms. | Epicardial pacemaker implantation is the most common approach for small children requiring pacemaker implantation, though it is not free from complications. This article reviews the experience with endocardial pacemaker implantation, as an alternative approach, in children < or =10 kg at two centers. Thirty-nine children, median age 3.8 months (2 days-35 months), weight 4.6 kg (2.3-10 kg) underwent endocardial permanent pacing (VVI/R in 38, DDDR in 1). Indications for pacing were complete heart block (CHB) in 34 (congenital in 21, postsurgical in 12, congenitally corrected transposition of the great arteries 1), long QT syndrome in 3, and sinus bradycardia in 2 children. Two children with postsurgical CHB died 7 days and 3 weeks after implantation, respectively, due to heart failure and septicemia, despite appropriate pacemaker therapy. Over a median follow-up of 4.3 years (9 months-15.3 years), 12 patients underwent 18 generator replacements. Five patients were upgraded to physiological pacing. Ten patients underwent 12 ventricular lead advancements. Ventricular lead extraction was attempted 11 times in nine patients and succeeded 10 times. Two patients were converted to epicardial dual chamber systems. Two prepectorally placed generators required resiting due to threatened skin necrosis. Infective endocarditis on the lead, 9 months postimplant required removal of the system in one patient. The subclavian vein was found to be asymptomatically thrombosed in four patients. Endocardial permanent pacing is feasible and effective in children < or = 10 kg and an acceptable alternative to epicardial pacing. |
15546298 | Influence of doxycycline on clinical and angiographic outcome following percutaneous coronary intervention. | Infection with Chlamydia pneumoniae may be involved in atherosclerosis. Neointima proliferation after percutaneous coronary intervention (PCI) could be aggravated by proinflammatory action of chronic vascular chlamydial infection. We investigated the influence of doxycycline therapy on restenosis rate and adverse clinical event rates after PCI. We followed 1,019 consecutive patients in a single center nonrandomized observational study. During a 3-month period, all patients having PCI (n = 541; treatment group) received oral doxycycline 100 mg/day for 50 days starting from the day of the procedure. A control group (n = 478) consisted of consecutive post-PCI patients recruited from immediately preceding (n = 250) and ensuing periods. Event rates were gained by questionnaires after 259 +/- 57 days. Restenosis rate was derived from the routine angiographic restudies after 172 +/- 15 days. No significant differences between treatment and control group were found in adverse clinical event rates (myocardial infarction: 0.7% vs 1.3%; repeat-PCI: 24.0% vs 20.9%; coronary bypass grafting: 5% vs 3.9%; overall death after 6 months: 3.5% vs 2.1%) and overall restenosis rate (21.6% vs 23.4%). A subgroup analysis of nondiabetic male smokers revealed a lower restenosis rate in the treatment group (10.9% vs 30.9%; P = 0.0195). Doxycycline therapy for 50 days following PCI does not appear to have a substantial influence on the clinical and angiographic outcome in unselected patients. The observed reduction in restenosis rate among nondiabetic male smokers defines a new hypothesis that should stimulate further investigations. |
15546297 | Abdominal aortic aneurysm: a review of endoluminal treatment. | Abdominal aortic aneurysm (AAA) carries a high mortality if left untreated. Until recently, most patients with AAA were treated with surgical repair. However, endoluminal graft treatment is rapidly becoming an alternative to surgical repair due to lower morbidity and comparable perioperative mortality rates. Despite this optimism patients and operators should keep in mind the palliative nature of these endovascular repairs and the lifelong need for surveillance, before embarking on these procedures. Endoleaks remain to be a significant problem leading to aneurysm expansion and occasionally rupture. Durability of the existing endograft devices remains to be seen. Careful patient selection is critical to success with these procedures. With future advancements in the endograft device technology, methods of patient surveillance, and patient care, there may be a shift from conventional surgical approaches to endovascular repair for the treatment of AAA. |
15546296 | Endovascular interventions in iliac and infrainguinal occlusive artery disease. | Percutaneous endovascular procedures are increasingly applied to treat symptomatic peripheral occlusive artery disease. While the primary technical success and recanalization rates in iliac and infrainguinal interventions are high, differences in the long-term patency rates exist with respect to the anatomic localization, separating the iliac, femoropopliteal, and infrapopliteal arterial regions. In iliac arteries, even complex lesions can be recanalized with good long-term patency rates, especially when using self-expanding nitinol stents. In the infrainguinal arteries the method of choice is still under debate (e.g., balloon angioplasty vs stent implantation). A high restenosis rate represents one of the major limitations in femoropopliteal and infrapopliteal interventions. Therefore, additional methods and treatment strategies for peripheral interventions with the potential for future applications are under investigation and will be discussed such as drug-eluting stents, brachytherapy, subintimal angioplasty, laser angioplasty, atherectomy/thrombectomy, cutting balloon, polytetrafluoroethylene (PTFE)-covered stent grafts, biodegradable stents, and cryoplasty. The increasing amount of data on successful peripheral interventions supports the necessity to adapt and reevaluate the current consensus guidelines that were put together in 2000. |
15546295 | Carotid artery stenting: state of the art. | Carotid artery stenting (CAS) is growing as an alternative to carotid artery endarterectomy. Nowadays, it is performed routinely in many centers worldwide. Still, it is discussed controversially although several clinical trials have shown equivalency or superiority of catheter treatment at least in high-risk patients. What is still missing is a randomized trial in non-high-risk patients. This is an overview about the completed and ongoing trials as well as the current stent and embolic protection technology. |
15546294 | Novel approaches for the treatment of chronic total coronary occlusions. | Despite major advancements in the technology used for the percutaneous treatment of coronary artery disease, chronic total occlusions (CTOs) persist as a major challenge to the interventional cardiologist with relatively low success rates. CTOs are evident in 20% of patients undergoing cardiac catheterization and are responsible for the majority of cases that are referred to bypass surgery. There is growing evidence that patients may benefit from recanalization of a CTO by alleviation of angina, improving left ventricular function, and potentially long-term survival. The major obstacle to percutaneous recanalization of CTOs is the inability to cross the occlusion with coronary guidewires. Even when crossed, the operator has to deal with the exact location of the distal wire (e.g., dissection or true lumen) and the existence of relatively long lesion requiring multiple stents with high restenosis rates. New technologies for CTO revascularization have been focused mainly on a mechanical approach including specialized guidewires and more recently, specific devices using highly sophisticated technology such as laser guidewire, optical coherence reflectometry, and a blunt microdissection catheter. An alternate biological approach involves the local administration of enzymes such as plasminogen activators (urokinase) or collagenase, which can act locally to specifically degrade the collagen content of the CTO, thereby "softening" the occlusion and allowing easier guidewire crossing. In conclusion, CTOs emerge as a great technical challenge and are the focus of novel series of mechanical and biological approaches. |
15546293 | New approaches to long lesions. | Long coronary lesions, comprising up to 20% of the interventional practice, pose a significant challenge to the interventionalist. Several approaches have been described to treat long coronary lesions with long-term suboptimal outcomes. Atherectomy and laser treatments with or without adjunctive balloon angioplasty have not been shown to be superior to conventional balloon angioplasty alone. Preliminary data with the use of drug-eluting stents in the treatment of long coronary lesions appears to be promising even in small vessels and may eventually become the mainstay treatment of long lesions. |
15546292 | New approaches to ostial and bifurcation lesions. | Percutaneous coronary intervention of bifurcation lesions is associated with lower procedural success rates, and an increased subsequent rate of major adverse cardiac events and restenosis. Currently, an array of stenting possibilities suggests a rational approach to treat various bifurcation lesions with appropriate techniques. This is however seldom the case. The main problems of treating bifurcation lesions remain plaque shift leading to (threatened) side branch occlusion, and either too much or insufficient side branch ostial stent coverage predisposing to impaired side branch access or restenosis, respectively. This paper reviews the available technologies and their relative merits. |
15546291 | Drug-eluting bioabsorbable magnesium stent. | Current stent technology is based on the use of permanent implants that remain life long in the vessel wall, far beyond the time required for the prosthesis to accomplish its main goals of sealing dissection and preventing wall recoil. With the possibility to implant long vessel segments using antiproliferative drugs to prevent restenosis, the practice of transforming the coronary vessels into stiff tubes with a full metal jacket covering all side branches and being unable to adjust to the long-term wall changes, including wall remodeling with lumen ectasia becomes a serious concern. In this article, we describe the first biodegradable stent based on a magnesium alloy that allows controlled corrosion with release to the vessel wall and the blood stream of a natural body component such as magnesium with beneficial antithrombotic, antiarrhythmic, and antiproliferative properties. We also discuss the animal experiments and the initial clinical applications in 20 patients with implants below the knee, with final results soon to be released, and the plans for the first coronary study. The results of these last two studies will indicate whether the absence of a permanent implant and the antiproliferative properties shown in animals are sufficient to prevent the restenotic process in humans or whether the prosthesis must be modified by adding the biodegradable coating with conventional antiproliferative drugs. |
15546290 | Clinical experiences using everolimus-eluting stents in patients with coronary artery disease. | Despite the growing use of drug-eluting stents, restenosis remains to occur especially in high risk subgroups like patients with diffuse in-stent restenosis. This observation is supporting the search for new and potentially even more effective drug eluting stent systems. Everolimus has been used in conjunction with a new bioabsorbable polymer and gave promising results in initial clinical studies. In FUTURE I, a single-center, single-blinded randomized safety and feasibility study enrolling 15 patients with bare metal stents and 27 patients with everolimus-coated stents, 30-day MACE rate was 0% in both groups. In-stent late loss at six months was 0.83 mm in the control group and 0.10 mm in the everolimus group (p < 0.0001). In FUTURE II, a randomized multi-center study, a total of 64 patients were enrolled confirming safety and feasibility. After 6 months late loss was 0.85 mm in the control group and 0.12 mm in the everolimus group (p < 0.001). |
15546289 | Which parameter should be chosen as primary endpoint for randomized drug-eluting stent studies? | In Europe, 1,108 percutaneous coronary interventions (PCIs) per one Mio inhabitants are currently annually performed, most of them with stent implantation. Drug-eluting stents have been the focus of attention of interventional coronary therapy since the RAVEL study was first presented in September 2001 at the European Society of Cardiology Meeting. Ever since, numerous studies have assessed the effects of various antiproliferative and anti-inflammatory substances and a variety of different stents was used as platform, either covered with polymer carriers of different chemical and physical properties or without a polymer carrier. CE- or FDA-certified drug-eluting stents are increasingly replacing the use of bare metal stents to reduce in-stent restenosis. Today, physicians have a choice of several approved drug-eluting stents and, therefore, need some evidence-based guidance through the "jungle of information" to make the right decisions. Even when focusing on randomized trials, differences between the studies regarding primary endpoints and sample sizes exist, making it difficult to compare the various drug-eluting stent studies. Randomized studies use either nonclinical (i.e., angiographic diameter stenosis, in-stent MLD, or in-stent late lumen loss) or clinical (i.e., TVF, TVR, and MACE) parameters as primary endpoints. Choosing an angiographic parameter as primary endpoint results in two major limitations: first, a significant improvement of an angiographic "surrogate" parameter does not necessarily translate into a better clinical outcome (DELIVER-I); second, conclusions regarding possible improvements of clinical outcome are underpowered, because the sample size calculation is based on the primary endpoint. Usually the number of patients needed is lower for angiographic than for clinical endpoints. Until today, only three trials with a primary clinical endpoint have shown a significantly positive impact on patients' outcome: the SIRIUS trial (Cypher stent) with its reduction of primary endpoint TVF (21.0% vs 8.6%), the TAXUS-IV trial (Taxus stent) with its reduction of primary endpoint TVR (12.0% vs 4.7%) and TAXUS-VI in long lesions with its reduction of primary endpoint TVR (19.4% vs 9.1%). Although the angiographic results of other drug-eluting stents are encouraging, they will have to prove their clinical impact based on adequately powered randomized trials with a primary clinical endpoint at an adequate time interval. |
15546288 | Relationship between size of myocardial infarctions assessed by delayed contrast-enhanced MRI after primary PCI, biochemical markers, and time to intervention. | The quantitative assessment of myocardial infarctions using delayed contrast-enhanced magnetic resonance imaging (MRI) has recently been validated using postmortem histopathological animal studies. In a prospective study, we investigated the correlation between infarct size as assessed by delayed contrast-enhanced MRI, elevation of creatine kinase (CK), and c-reactive protein (CRP) as well as the time from onset of symptoms to intervention. Four to 10 days after immediate PCI in 45 acute ST-segment elevation myocardial infarction (STEMI) patients (<24 hour) with stenting of the infarct-related artery and treatment with abciximab, we performed gadolinium contrast-enhanced three-dimensional inversion recovery gradient-echo MR sequences with complete coverage of the LV-myocardium in short-axis slices. The mass of infarcted tissue based on the volume of hyperenhanced myocardium was calculated and linear regression analysis was performed to assess the correlation between absolute size of infarctions (g) as well as relative size (LV%) with peak values of CK, CRP, and the time to PCI. There was a significant correlation between absolute size of infarctions (g) and peak CK values (r = 0.72; P < 0.001) as well as the relative size (LV%) and peak CK (r = 0.77; P < 0.001). No correlations were found between absolute size (r = 0.33) as well as relative size (r = 0.27) of infarctions and peak CRP. There was also no correlation between absolute (r = 0.29) as well as relative size of infarctions (r = 0.27) and the time from onset of symptoms to PCI. In patients with acute STEMI (<24 hour) undergoing immediate PCI with stenting and treatment with abciximab, peak CK values correlated well with infarct size as assessed by delayed contrast-enhanced MRI. There were no correlations between infarct size and peak CRP as well as the time to intervention. |
15546287 | Autologous skeletal myoblasts for myocardial regeneration. | We overview the current knowledge about the use of skeletal myoblasts in regeneration of infarcted myocardium. Myoblasts are attractive candidates for cell source for cardiomyoplasty in chronic postmyocardial injury as indicated by experimental and initial clinical experience. We also review the recent developments in skeletal myoblasts transplantation techniques with special attention to percutaneous transvenous approach to deliver therapeutic agents into myocardium from the lumen of coronary veins under intravascular guidance. |
15546286 | Stress echocardiography: basics and noninvasive assessment of myocardial viability. | Myocardial viability within the infarct zone is an important determinant for left ventricular (LV) function recovery after interventional coronary revascularization. Echocardiographic techniques are highly valuable in identifying hibernation, especially in conjunction with dobutamine titration. Low doses may detect the inotropic reserve by significant enhancement of segmental wall motion abnormalities while high doses may surpass the ischemic threshold and wall motion deteriorates (biphasic response). According to the Task Forces on Clinical Application of Echocardiography by the American Heart Association (AHA) in cooperation with the American College of Cardiology (ACC), dobutamine echocardiography (DE) is officially recommended for the purpose of clinical decision making in respect of revascularization therapies (whether during the subacute infarct period or especially in chronic LV dysfunction due to coronary artery disease (CAD)). New methods such as strain rate imaging implemented in DE are on the way to give us quantitative measures of the amount of viability. |
15546274 | Pharmacoeconomics: the cost of prophylactic migraine treatments. | Migraine preventive medications considered effective reduce headache frequency by 50 percent in approximately 50 percent of treated patients. In spite of similar effectiveness, these medications vary tremendonsly in their prices. Knowledge of medication prices and employing cost-effective strategies may greatly reduce treatment costs. |
15546273 | New onset migraine with aura following head injury: a case report. | A patient is described who developed recurrent headaches following a traumatic injury in the vicinity of the right greater occipital nerve (GON) that fulfill IHS criteria for migraine with aura. Both aura and headache can be triggered by pressure over the GON and relieved by local anesthetic blockade. |
15546272 | Focal hypertrophic pachymeningitis in association with temporal arteritis. | We present an extremely rare case of a patient with focal hypertrophic pachymeningitis in association with histologically proven temporal arteritis (giant cell arteritis). It is proposed that focal hypertrophic pachymeningitis in itself is the contributing factor to severe headache rather than temporal arteritis alone. |
15546271 | Trigeminal neuralgia due to pontine infarction. | Trigeminal neuralgia (TN) is most commonly caused by vascular compression of the trigeminal nerve root entry zone. Secondary trigeminal neuralgia due to ischemic lesion of the pons is very rare. Here we report a patient with a pontine infarct transecting the central trigeminal pathways resulting with trigeminal neuralgia. |
15546267 | Preventing disturbing migraine aura with lamotrigine: an open study. | Lamotrigine has been suggested as possibly effective for preventing migraine aura. To describe our experience with a series of patients with disturbing migraine aura treated with lamotrigine. The members of the Headache Group of the Spanish Society of Neurology were sent an ad hoc questionnaire to collect patients treated with lamotrigine due to disturbing migraine aura. The main outcome parameter ("response") was a >50% reduction in the mean frequency of migraine auras at 3 to 6 months of treatment. A total of 47 patients had been treated with lamotrigine due to severe migraine aura. Three could not complete the protocol as a result of developing skin rashes. Thirty (68%) patients responded. These were 21 females and 9 males whose ages ranged from 19 to 71 years. Eight suffered from migraine with "prolonged" aura, 8 typical aura with migraine headache (but had frequent episodes including speech symptoms), 6 basilar-type migraine, 6 typical aura without headache, and 2 hemiplegic migraine. Fifteen had been previously treated, without response, with other preventatives. The mean monthly frequency of migraine auras in these 30 patients changed from 4.2 (range: 1 to 15) to 0.7 (range: 0 to 6). Response was considered as excellent (>75% reduction) in 21 cases (70% of responders). Auras reappeared in 2 months in 9 out of 13 patients where lamotrigine was stopped, and ceased as soon as this drug was reintroduced. Lamotrigine should be considered in clinical practice for the preventive treatment of selected patients with disturbing migraine auras. Lamotrigine seems worthy of a controlled trial as prophylaxis of migraine aura. |
15546268 | Dextroamphetamine pilot crossover trials and n of 1 trials in patients with chronic tension-type and migraine headache. | To examine the preventive effects of dextroamphetamine in select small groups of patients with chronic tension-type and migraine headache. Neither amphetamine nor methylphenidate is used as a headache preventive. This study was undertaken after a chance observation led one of us to prescribe dextroamphetamine with apparent successes in specific patients with chronic tension-type or migraine headaches. Two pilot trials were done. Trial 1 tested patients who were taking dextroamphetamine, while Trial 2 tested patients who had never taken this drug. Each trial obtained full data on eight subjects with chronic tension-type headache and eight subjects with migraine headache. A randomized, double-blinded, controlled, multiple-crossover design was used. Subjects took capsules containing dextroamphetamine or equi-stimulatory caffeine (the control) during four alternating 20-day periods. Trial 1 subjects took their pretrial dextroamphetamine dose at breakfast and lunch. Trial 2 subjects took 10 mg at these times. Subjects recorded the integer from 0 to 3 that represented their headache intensity during the previous 24 hours. The subject's data were the average daily headache grade for the two dextroamphetamine periods and for the two caffeine periods. The differential effect of amphetamine and caffeine on each group of eight subjects and on each individual was analyzed by t-tests. In both trials, the tension-type and migraine groups had lower mean daily headache grades in the amphetamine than in the caffeine periods. P values for these differences indicated that there were real drug effects, on the average, in the migraine groups (P<.05) and suggestive but inconclusive effects in the tension-type groups (P<.10). The individual n of 1 analyses showed that five tension-type and three migraine subjects in Trial 1 and three tension-type and three migraine subjects in Trial 2 had considerably lower mean daily headache grades on amphetamine with P values indicating, at various levels of significance (from P<.05 to P<.001), real amphetamine effects. Twelve of the remaining 18 patients had lower, albeit not significant, mean daily grades with amphetamine. No subject in either trial had a significantly lower mean daily headache grade on caffeine. Dextroamphetamine had real preventive effects on chronic tension-type and migraine headaches in some subjects. These results should encourage other investigators to study its effects on these headaches. |
15546266 | Osmophobia and taste abnormality in migraineurs: a tertiary care study. | This study assesses osmophobia and taste abnormality for the first time in a large sample of migraine patients. Seven hundred and twenty seven migraineurs were evaluated. Osmophobia, taste abnormality, and perfume or odor trigger were graded from 0 to 3. In patients with data, 24.7% of 673 patients complained of osmophobia (12.5% occasional, 7% frequent, and 5.2% very frequent) and 24.6% of 505 of taste abnormality (13.5% occasional, 6.1% frequent, and 5.0% very frequent). Perfume or odor trigger of acute migraine occurred in 45.5% of 724 patients (22.7% occasional, 10.2% frequent, and 12.6% very frequent). Perfume or odor trigger was associated with osmophobia in 61.5% and taste abnormality 62.1%. Osmophobia without taste abnormality occurred in 28.3% and taste abnormality without osmophobia in 40.3%. A greater percentage of females than males had osmophobia (25.7 vs. 17.5), taste abnormality (25.4 vs. 17.9), and perfume or odor trigger (49.3 vs. 22.1), all P<.0001. Osmophobia and taste abnormality occur in about one quarter of migraineurs during an acute migraine attack while perfume or odor trigger migraine in almost 50% of patients. Osmophobia and taste abnormality in the acute migraine attack, as well as perfumes or odor as a migraine trigger, are more common in females than in males. |
15546265 | Individualizing treatment with verapamil for cluster headache patients. | Verapamil is currently the best available prophylactic drug for patients experiencing cluster headaches (CHs). Published papers usually state 240 to 480 mg taken in three divided doses give good results, ranging from 50% to 80%; others mention higher doses--720, even 1200 mg per day. In clinical practice we found we needed to adapt dosage to individual's time of attacks, in particular giving higher doses before going to bed to suppress severe nocturnal episodes. A few only required 120 mg daily. We therefore evolved a scheme for steady and progressive drug increase until satisfactory control had been achieved. To find the minimum dose of verapamil required to prevent episodic and chronic cluster headaches by supervising each individual and adjusting the dosage accordingly. Consecutive patients with episodic or chronic CH (satisfying International Headache Society (IHS) criteria) were started on verapamil 40 mg in the morning, 80 mg early afternoon, and 80 mg before going to bed. Patients kept a diary of all attacks, recording times of onset, duration, and severity. They were advised, verbally and in writing, to add 40 mg verapamil on alternate days, depending on their attack timing: with nocturnal episodes the first increase was the evening dose and next the afternoon one; when attacks occurred on or soon after waking, we advised setting an alarm clock 2 hours before the usual waking time and then taking the medication. Patients were followed-up at weekly intervals until attacks were controlled. They were also reviewed when a cluster period had ended, and advised to continue on the same dose for a further 2 weeks before starting systematic reduction. Chronic cluster patients were reviewed as often as necessary. Seventy consecutive patients, 52 with episodic CH during cluster periods and 18 with chronic CH, were all treated with verapamil as above. Complete relief from headaches was obtained in 49 (94%) of 52 with episodic, and 10 (55%) of 18 with chronic CH; the majority needed 200 to 480 mg, but 9 in the episodic, and 3 in the chronic group, needed 520 to 960 mg for control. Ten, 2 in the episodic and 8 in the chronic group, with incomplete relief, required additional therapy-lithium, sumatriptan, or sodium valproate. One patient withdrew because verapamil made her too tired, another developed Stevens-Johnson syndrome, and the drug was withdrawn. Providing the dosage for each individual is adequate, preventing CH with verapamil is highly effective, taken three (occasionally with higher doses, four) times a day. In the majority (94%) with episodic CH steady dose increase under supervision, totally suppressed attacks. However in the chronic variety only 55% were completely relieved, 69% men, but only 20% women. In both groups, for those with partial attack suppression, additional prophylactic drugs or acute treatment was necessary. |
15546264 | Dynamic mechanical (brush) allodynia in cluster headache. | To examine the occurrence of dynamic mechanical (brush) allodynia (BA) in patients with cluster headache (CH). Cutaneous allodynia was described in migraine. It was related to sensitization of neurons in the trigeminal nucleus caudalis (TNC). This phenomenon has not been previously described in cluster headache. We examined adult patients with episodic or chronic CH for the presence of BA. Demographic data and the characteristics of CH were obtained through a questionnaire. Allodynia testing was performed by repetitively applying a 4x4-inch gauze pad to skin areas in the trigeminal and cervical dermatomes. Degree of allodynia was measured on a 100-mm visual analog scale (VAS). The relations between the location and severity of headache and allodynia were assessed. Ten patients (all male, mean age 39.3) were included in the study. Seven had episodic CH (ECH) and 3 had chronic CH (CCH). Two patients were in acute attack when tested for BA. In total, 4 (40%) of the 10 patients had BA (2 [28.6%] of the 7 with ECH and 2 [66.7%] of the 3 with CCH). Median disease duration was 22 years for patients with BA and 12 years for patients without BA. Of the two patients in acute attack, one had BA, ipsilateral to the headache, which was reduced 20 minutes after treatment, along with reduced headache severity. This is the first report on the occurrence of cutaneous allodynia in CH. The presence of BA in CH may be related to CH type (episodic vs. chronic) and to the duration of disease. These results support the concept that allodynia in CH may result from a time-dependent process of neuronal sensitization. |
15546263 | Serotonin transporter polymorphism and harm avoidance personality in chronic tension-type headache. | To investigate the 5-HTT-gene-linked polymorphic region (5-HTTLPR) genotypes and harm avoidance (HA) dimension in chronic tension-type headache (CTH). Serotonin transporter protein (5-HTT) is a key modulating protein in synaptic serotonergic neurotransmission. Among serotonin gene-linked polymorphism, promoter located in the regulatory region of the 5-HTTLPR has two alleles (short and long) with different transcriptional efficiencies. The HA personality trait may be heritable and associated with serotonergic neurotransmitter activity. We amplified the 5-HTTLPR by means of polymerase chain reaction and performed genotype polymorphism analyses and we investigated the serotonin-related personality trait by evaluating the HA dimension in tridimensional personality questionnaire (TPQ) in 107 patients with CTH and in 100 healthy controls. We found an excess frequency of the short allele and a different genotype distribution in patients with CTH. S/S genotype frequency was significantly higher in patients with CTH (76%) than in those with controls (59%; P=.02). Patients with CTH had significantly higher HA scores (21.4+/6.3) than controls (16.3+/-6.1). This suggests a serotonergic activity might be involved in the development of CTH and 5-HTTLPR might be one of the genetically contributing factors. |
15546262 | Genomic abnormalities in patients with migraine and chronic migraine: preliminary blood gene expression suggests platelet abnormalities. | Migraine has strong genetic and environmental components and may also be a significant contributor to chronic migraine (CM). It is hypothesized that gene expression changes in peripheral blood cells can be used to detect the interaction of these influences. Distinct genomic expression patterns for migraine and CM will be present. These genomic profiles will help clarify the interactions of inheritance and environment. This initial study begins to examine the feasibility of peripheral blood cell genomic analysis to assist in the understanding of the pathophysiology of migraine and CM. Blood samples from patients were obtained either during an acute migraine or CM. Genomic expression patterns were analyzed using Affymetrix U95A microarrays. Expression patterns of 7 migraine and 15 CM patients were compared to four distinct control groups (total patients, n=56) including healthy subjects. A group of platelet genes were upregulated in both migraine and CM samples. Different gene expression patterns were also seen between migraine and CM. A group of immediate early genes including c-fos and cox-2 were expressed at higher levels in migraine, whereas specific mitochondrial genes were expressed at higher levels in CM. Increased expression of platelet genes in patients with migraine and CM suggests similar underlying pathophysiology. The differences seen between migraine and CM in other genes suggest an overlapping but not identical pathophysiology. Further genomic profiling studies will help define these relationships and provide further insights into headache pathogenesis. |
15546261 | Somatic symptoms in headache patients: the influence of headache diagnosis, frequency, and comorbidity. | Mood disorders of anxiety and depression are well known to be comorbid with primary headache disorders. Less is known of the comorbidity of other somatic symptoms with headache. Headache Clinic patients were screened with the Primary Care Evaluation of Mental Disorders (PRIME-MD), a multidimensional psychiatric screening tool. The prevalence of somatic symptoms was compared by headache diagnosis, frequency of severe headache, and psychiatric diagnosis. Follow-up data were obtained 6 months after consultation. Clinical diagnoses and PRIME-MD data were available for 289 patients. Associated somatic symptoms were more frequent in patients with chronic migraine (mean 5.5, P<.001) and chronic daily headache (CDH) (6.3, P=.008) compared to episodic migraine (4.0); in patients with severe headache >2 days per week compared to <or=2 days per week (6.15 vs. 4.15, P<.001); and in patients with a clinical diagnosis of anxiety or depression, or both, compared to no anxiety or depression, (5.7, P=.05, 5.2, P<.05, and 6.8, P<.001, respectively, vs. 4.5). The most common specific symptoms were fatigue (73%), sleep difficulty (60%), and nausea/indigestion (55%). Compared to a primary care sample, patients with severe headache >2 days per week had significantly higher somatic counts (P=.01). Six-month follow-up data were available for 140 patients. Associated symptoms decreased both for patients with and without decrease in severe headache frequency (mean reduction of 1.0, P=.01 and 0.8, P=.003, respectively). Associated somatic symptoms are more common in patients with chronic migraine and CDH, with more frequent severe headaches, and with associated anxiety or depression. Patients with episodic migraine have similar somatic prevalence as a previously studied primary care population. The spectrum of headache disorders may be characterized as showing increasing somatic prevalence as headaches, particularly severe headaches, become more frequent. |
15546260 | Assessment of adverse events associated with triptans--methods of assessment influence the results. | A recent study conducted in triptan-naive migraine patients showed that tolerability was the second most important attribute of an acute treatment. However, the proportion of patients reporting side effects after any acute treatment may vary with regard to the method of assessment. To contrast two methods of assessing adverse events (prompted and unprompted) in those with headache using triptans. This study was conducted in two sites, a headache center in the United States, and a neurology office focusing on headache in Italy. We prospectively surveyed 415 adults with headache, who had been using the same triptan for at least 3 months. Participants were asked about their headache and treatment history. Subjects then completed a standardized questionnaire, assessing adverse events in two different ways. First, subjects were asked if they had any adverse events when using the triptan. After returning the first part of the questionnaire, subjects received a second form, where 49 possible adverse events were listed. We contrasted and correlated both sets of answers. Most patients (U.S.=74.9%, Italy=65.5%) reported no side effects in the unprompted questionnaire. However, most of them (U.S.=62.9%, Italy=54.1%) reported at least one side effect in the prompted questionnaire. Most patients that reported side effects in the unprompted questionnaire said they had just one adverse event, while most reported two or more side effects in the prompted questionnaire. Both in the unprompted and in the prompted questionnaires, most side effects were rated as mild or moderate. Interestingly, 31 (7.5%) subjects (pooling data from both sites together) graded their adverse events as severe in the prompted questionnaire, but had not self-reported them. (1) When assessing adverse events, the method of data collection may dramatically influence the results. (2) From those subjects who did not self-report adverse events after using a triptan, most of them will report positively if presented with a list of side effects. |
15546259 | Long-term tolerability of sumatriptan nasal spray in adolescent patients with migraine. | This 1-year, open-label, multicenter study was designed to assess the long-term tolerability and efficacy of sumatriptan nasal spray 20 mg in adolescent patients with migraine. A prospective, multicenter, open-label study was conducted in patients aged 12 to 17 years who were allowed to treat an unlimited number of migraines at severe, moderate, or mild pain intensity with sumatriptan nasal spray for up to 1 year. All patients started the study at the 20-mg dose of sumatriptan nasal spray. Dose could be adjusted downward to 5 mg at the discretion of the investigator to optimize therapy. A total of 484 adolescent migraineurs treated 4676 migraines with sumatriptan nasal spray 20 mg (3593 during the first 6 months and 1083 during the second 6 months). A total of 3940 migraines and 699 migraines were treated with one and two 20-mg doses of sumatriptan nasal spray, respectively. Only 10 patients (treating 42 migraines) took the 5-mg dose of sumatriptan nasal spray. The overall percentage of migraines treated with either one 20-mg dose or one, two, or three 20-mg doses with at least 1 drug-related adverse event was 19%. The most common specific drug-related adverse event was unpleasant taste, reported in 17% of migraines. No other single drug-related adverse event was reported in more than 1% of migraines over the 1-year treatment period. When unpleasant taste was excluded from the adverse-event tabulations, the percentages of migraines with at least 1 drug-related adverse event after one or one, two, or three 20-mg doses declined to 4% and 3%, respectively. No patient experienced any drug-related changes in 12-lead ECGs, vital signs, or nasal assessments; and no clinically meaningful changes in clinical laboratory values were observed. Across all migraines with evaluable efficacy data (n=4334), headache relief was reported in 43% of migraines at 1 hour and in 59% at 2 hours after dosing with sumatriptan nasal spray 20 mg. Of the 2561 migraines with headache relief 2 hours postdose, headache recurrence was reported within 24 hours of initial dosing in 7% of migraines. None of the efficacy or tolerability results varied as a function of time in the study (ie, first 6 months vs. second 6 months). Sumatriptan nasal spray 20 mg is generally well tolerated and may be beneficial during long-term use by adolescent migraineurs ages 12 to 17 years. |
15546258 | Chemokine levels in the jugular venous blood of migraine without aura patients during attacks. | To investigate changes in the levels of calcitonin gene-related peptide and its intracellular messenger cyclic adenosine monophosphate in serial samples of internal jugular blood taken from migraine patients without aura assessed during attacks, and to assess their relationship with the levels of IL-8, MCP-1, and RANTES in the same samples. Calcitonin gene-related peptide, the marker of trigeminovascular activation, is released in both the internal and external jugular venous blood of migraine patients during attacks. Experimental evidence demonstrated that when released from C-type sensory neurons in inflammatory pain models, it differentially induced expression of neutrophil chemotactic chemokine IL-8, but not monocyte chemotactic chemokine MCP-1 or lymphocyte chemotactic chemokine RANTES. These chemokines were never investigated in migraine. Eight migraine without aura patients were admitted to the hospital during the attacks. Internal jugular venous blood samples were taken immediately after catheter insertion, at the 1st, 2nd, and 4th hours after attack onset, and within 2 hours from its cessation. The levels of the sensory neuropeptide calcitonin gene-related peptide and the messenger cyclic adenosine monophosphate were measured by RIA method, and those of IL-8, MCP-1, and RANTES were measured by ELISA method. Higher calcitonin gene-related peptide levels were found in the internal jugular venous blood of migraine without aura patients compared with the time of catheter insertion (ANOVA: P<.0001) with a peak at the first hour (52.6+/-9.2 ng/mL). A transient increase in IL-8 was observed at the 2nd and 4th hours (P<.01 and P<.002, respectively), whereas no changes in the levels of MCP-1 and RANTES were found at any time of the study. The increase in IL-8 was accompanied by a parallel increase in cyclic adenosine monophosphate. The present study confirms previous findings of an increase in calcitonin gene-related peptide in internal jugular venous blood of migraine without aura patients during attacks. The transient increase in the levels of IL-8 concurs with the results of recent experimental research showing a calcitonin gene-related peptide-induced activation of IL-8 gene expression, but not RANTES and MCP-1, via the transcriptional factor AP-2, which mediates transduction in response to cyclic adenosine monophosphate. Although IL-8 is transiently increased during migraine attacks, an accumulation of leukocytes secondary to neurogenic inflammation is unlikely, as it is for other inflammatory events, because they are self limiting. Other events, including nitric oxide production, may contribute to counteract meningeal transvascular leukocyte migration during migraine attacks, as suggested by the model of sterile inflammation. |
15546257 | Topographic and dipolar analysis of laser-evoked potentials during migraine attack. | The aim of this study was to perform further evaluation of laser-evoked potentials (LEPs) during migraine attacks using multichannel recording and topographic analysis. Specifically, this study aimed to confirm the pattern previously observed in acute migraine, while also defining the components of LEPs that are mainly modified during headache, as well as the correlation between features of LEPs and clinical variables. In addition, we aimed to conduct a dipolar source analysis of the main LEP waves in migraine patients to check the variability in the source location of LEPs during acute migraine. An amplitude enhancement of LEPs was previously detected during migraine attack using a single scalp derivation on the vertex; hyperalgesia to heat stimuli was also detected for both the face and hand. Eighteen patients suffering from migraine without aura were analyzed. The supraorbital zones and the dorsum of the hand were stimulated on both the symptomatic and nonsymptomatic sides in all patients. The LEPs were recorded via 25 scalp electrodes. Dipolar source analysis of the P2 components was performed using a spherical model in all patients and using a realistic Magnetic Resonance model in four patients. During attacks, the later waves, and particularly the P2 component, were significantly enhanced; the amplitude of the P2 component obtained during the attack by stimulation of the supraorbital zone on the side of the headache was significantly correlated with the intensity of pain and the frequency of headache. In our patients, the P2 wave was generated in the anterior cingulate cortex, with a shift toward its rostrocaudal portion, and was mainly devoted to elaboration of the emotive compound of pain during migraine attack. Cortical activation by laser stimuli during migraine attack was confirmed. This effect was more pronounced in patients with a higher frequency of migraine attacks. This may be due to a lack of inhibitory control over the transmission of pain to the cortex. The increased activation of cortical areas devoted to attention and emotion may be linked to headache. |
15546256 | Triple combination of thymalfasin, peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior interferon and ribavirin treatment: 24-week interim results of a pilot study. | Despite steady progress in antiviral treatment for patients with chronic hepatitis C virus (HCV), many patients still have detectable serum HCV RNA levels by the end of interferon-based treatment and are known as virological non-responders. Re-treatment of these patients not responding to previous therapy remains challenging. Studies of the dynamics of the HCV population show a marked decline in new cases since 1996; however, the relative proportion of non-responders is expected to increase over time and, similarly, the number of patients eligible for first-line treatment is expected to decrease. The current standard of care for treatment involves the use of pegylated interferons in combination with ribavirin. However, many difficult-to-treat groups still have low response rates. Newer combinations are being investigated to optimize chances of attaining a sustained response in these groups: one such triple therapy regimen is peginterferon alfa-2a, ribavirin and thymalfasin, which was given to 23 previously non-responder patients. Viral response was 60.8% at week 12 and 47.8% at week 24. These preliminary results encourage further evaluation of this promising combination. |
15546255 | Combination therapy of thymalfasin (thymosin-alpha 1) and peginterferon alfa-2a in patients with chronic hepatitis C virus infection who are non-responders to standard treatment. | The worldwide spread of hepatitis C virus is enormous; chronic hepatitis C virus infection is a leading cause of liver cirrhosis and hepatocellular carcinoma. While treatment options have improved substantially over the last decade, responses are still disappointing, particularly in certain difficult-to-treat groups such as patients who are immunosuppressed or have decompensated disease. Preliminary studies have indicated that combined treatment strategies may provide effective approaches for the future. The combination of thymalfasin with pegylated interferon is currently a promising option for the treatment of patients with chronic hepatitis C virus infection. An ongoing phase 3 study in the USA should provide much needed data to improve the outcome for these patients. |
15546254 | Thymalfasin (thymosin-alpha 1) therapy in patients with chronic hepatitis B. | Chronic hepatitis B virus (HBV) infection is a serious clinical problem because of its worldwide distribution and potential adverse sequelae. Globally, there are approximately 350 million people infected with chronic HBV, 75% of whom live in the Asia-Pacific region. Interferon-alfa and direct antiviral agents such as lamivudine and adefovir are effective in the therapy of chronic HBV infection but the efficacy is far from satisfactory, particularly in perinatally infected patients, patients with lower ALT levels and those with HBeAg-negative chronic hepatitis B. Thymalfasin (thymosin-alpha1) is an immunoregulatory agent able to enhance Th1 response. It has been shown to trigger maturational events in lymphocytes, to augment T-cell function, and to promote reconstitution of immune defects. Studies are underway in both monotherapy and combination therapy with thymalfasin and interferon and results are promising. |
15546253 | Thymalfasin: an immune system enhancer for the treatment of liver disease. | Thymalfasin (thymosin-alpha 1) is an immunomodulating agent able to enhance the Th1 immune response. It has been evaluated for its immunomodulatory activities and related therapeutic potential in several diseases, including chronic hepatitis B and C, AIDS, primary immunodeficiency diseases, depressed response to vaccination and cancer. The basis for effectiveness in these conditions is primarily through modulation of immunological responsiveness, as thymalfasin has been shown to have beneficial effects on numerous immune system parameters and to increase T-cell differentiation and maturation. Thymalfasin is responsible for reconstitution of immune function when thymic tissue is given back to thymectomized animals. In addition, thymalfasin has been shown to have efficacy in multiple experimental models of immune dysfunction, mainly, infectious diseases such as hepatitis (woodchuck) and influenza (mouse), and cancer such as melanoma (mouse) and colorectal carcinoma (rat) where thymalfasin has shown antitumor effects. |
15546251 | Inhibitory effects of crude alpha-mangostin, a xanthone derivative, on two different categories of colon preneoplastic lesions induced by 1, 2-dimethylhydrazine in the rat. | The purpose of this study was to examine whether crude alpha-mangostin (a major xanthone derivative in mangosteen pericarp (Garcinia mangostana)) has short-term chemopreventive effects on putative preneoplastic lesions involved in rat colon carcinogenesis. The crude preparation was obtained by simple recrystallization of an ethylacetate extract of mangosteen pericarps. A total of 33 five-week-old male F344 rats were randomly divided into 5 experimental groups. Rats in groups 1-3 were given a subcutaneous injection of 1,2-dimethylhydrazine (DMH)(40 mg/kg body weight) once a week for 2 weeks. Starting one week before the first injection of DMH, rats in groups 2 and 3 were fed a diet containing 0.02% and 0.05% crude alpha-mangostin, respectively, for 5 weeks. Rats in group 4 also received the diet containing 0.05% crude alpha-mangostin, while rats in group 5 served as untreated controls. The experiment was terminated 5 weeks after the start. Dietary administration of crude alpha-mangostin at both doses significantly inhibited the induction and/or development of aberrant crypt foci (ACF) (P<0.05 for 0.02% crude alpha-mangostin, P<0.01 for 0.05% crude alpha-mangostin), when compared to the DMH-treated group (group 1). Moreover, treatment of rats with 0.05% crude alpha-mangostin significantly decreased dysplastic foci (DF) (P<0.05) and beta-catenin accumulated crypts (BCAC) (P<0.05), to below the group 1 values. The proliferating cell nuclear antigen (PCNA) labeling indices of colon epithelium and focal lesions in groups 2 and 3 were also significantly lower than in group 1 and this effect occurred in a dose dependent manner of the crude alpha-mangostin. This finding that crude alpha-mangostin has potent chemopreventive effects in our short-term colon carcinogenesis bioassay system suggests that longer exposure might result in suppression of tumor development. |
15546250 | "I don't really know, so it's a guess": women's reasons for breast cancer risk estimation. | Women of all ages have been found to overestimate both the incidence and the mortality rate from breast cancer and the reasons for this are unclear. A qualitative study asked eighty three women (mean age = 44 years) how likely they thought they were to get breast cancer and to explain the reasoning behind their choice. Based on their responses, women's perceptions were categorised as: no risk (5%); reasonably accurate (30%); overestimated (22%); and greatly overestimated (43%). Four main themes emerged from the reasons given: 'Don't know/guess', 'family history' of breast cancer,'age' related reasoning, and making their decision from the information sheet read prior to answering the questions. The information currently available to women may be creating falsely high estimates of their risk of developing breast cancer as the risk factors of age and family history appear to be poorly understood. Meaningful communication of health risk in need of further improvement if it is to be useful in changing health related knowledge and behaviours. |
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