Calcified left ventricular thrombus in a patient after anterior myocardial infarction.
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Biomedical subjects
Publications and source records attributed to T Weber.
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Recanalization of occluded coronary arteries is the aim of percutaneous interventions with acute myocardial infarction. Moreover, chronic coronary occlusion is a common finding during diagnostic coronary angiography and is often a contributing factor in the choice of revascularisation by surgery rather than by percutaneous coronary interventions (PCI). An occluded coronary artery with some degree of collateral supply is functionally comparable to a severe coronary stenosis. Therefore, recanalization of chronic occluded coronary arteries results in less angina and often in improvement of left ventricular function. Success is limited in particular in longer lasting occlusions. Characterization of lesions, where recanalization can performed successfully is warranted. We correlated primary success rates of attempted coronary recanalizations with localisation of lesions and procedural characteristics. We analyzed records of 124 consecutive patients, who underwent attempted coronary recanalization of chronically occluded coronary arteries at our institution in 1998. Revascularisation was successful in 84 (64 male, 20 female) of 124 (92 male, 32 female) patients. Therefore, success rate was 67.7% (69.9% in men, 62.5% in women, p = 0.42). Target vessel was the left anterior descending artery (LAD) in 49 cases. Success rate in the LAD did not differ significantly from that in "non-LAD"-vessels (65.3% versus 69.3%; p = 0.35). Successful recanalizations were performed using only one guide-wire in 77.3%. More than one guide-wires were used during procedures without success in 44.5% and exceeded use in successful interventions (p < 0.05). Procedures, failing to be successful after an attempt with a first guide-wire, could be performed successfully using at least a second wire in 50%. Coronary stenting after recanalization has been performed in 84.4% in the LAD and in 59.7% in non-LAD vessels (p < 0.01). Success rate of attempted recanalizations of chronic occluded coronary arteries in unselected patients is high. Most procedures can be performed successfully using only one guidewire. Additional use of other wires can increase success rates in procedures with primary failure to pass the occlusion. Stenting has been performed in three out of four patients with successful recanalization of chronically occluded coronary arteries.
Restenosis following angioplasty represents a major clinical problem in the field of percutaneous coronary interventions. Intravascular brachytherapy reduces risk of restenosis following percutaneous interventions of native lesions and in-stent restenosis up to 50%-60%. This effect can be shown for at least one to two years. This novel therapeutic strategy is limited by a higher rate of target vessel reinterventions, and late coronary thrombosis, when platelet inhibiting drugs has been withdrawn or after implantation of multiple stents. Currently, intracoronary brachytherapy is mainly considered for treatment of in-stent-restenosis.
UNLABELLED: The efficacy of respiratory physiotherapy by combined-PEP (RC-Cornet(R) in combined-PEP-position) was evaluated in a long-term study with the following set up. STUDY DESIGN: Randomized prospective clinical trial over 2 years in 50 patients with severe COPD (12 f, 38 m, 63,1 y, FEV 1 41 %, DLCO 51 % of the normal). Patients were without infection and exsmokers at begin of the trial. One group was treated only by drug therapy (theophylline, salmeterol, ipratropiumbromide, systemic steroids 5 mg prednisolone equivalent). The second group received the same drug therapy plus physical therapy with the RC-Cornet(R) (oscillating PEP; in combined PEP-position) 3 times daily at least for 5 minutes or whenever needed. Lung function data were controlled every 3 month during first year and every 4 month in the second year. The compliance was checked by theophylline and cortisol blood levels, inspection of the functionality of the RC-Cornet(R) and by questioning the patient about compliance with the therapy. RESULTS: TGV (% of normal) and airway resistance (measured by bodyplethysmography) decreased significantly in contrast to the "mere" drug therapy (p < 0.0177, p < 0.0179). VC (% of normal) increased significant p < 0.0179 in the RC-Cornet(R) therapy group. In this group significantly less patients (13/24) needed antibiotics in comparison to the "mere" drug group (Chi-Quadrat p < 0.0004). Also the need for hospital care was significantly less in the RC-Cornet(R) group (5/12) in comparison to the drug therapy group (Chi-Quadrat < 0.000765). The length of hospital stay in the two groups was not significantly different: 16.2 +/- 6.3 days in the RC-Cornet(R)-group and 18.3 +/- 4.7 days in the drug therapy-group. CONCLUSION: This study proves the efficacy of respiratory physiotherapy with combined-PEP in addition to drug therapy in the management of COPD-patients.
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Statins significantly reduce cardiovascular-related morbidity and mortality in patients with and without coronary artery disease. The potential of this drug class has yet to be fully explored. Accumulating evidence from basic research and clinical trials indicates that statins have pleiotropic effects that may largely account for the clinical benefits observed. Potential beneficial effects of these agents include enhancement of nitric oxide production in vasculature and the kidney. Statins have been shown to stabilize unstable plaques, improve vascular relaxation, and promote new vessel formation. Clinical trials and animal studies have shown that these agents reduce cardiovascular disease (CVD) risks and events, progression of nephropathy, development of diabetes, and fracture rates; these are benefits that go beyond lipid lowering alone. Potential beneficial effects are due to the positive impact on vascular and glomerular nitric oxide (NO) production and attenuation of vascular inflammation. Effects on bone, including fracture reduction, are thought to be mediated by direct action on bone formation. Moreover, potential reduction in the development of diabetes as observed in the West of Scotland Coronary Prevention Study (WOSCOPS) may relate to the improvement in insulin sensitivity. These actions are mediated, in part, by the effects on small G-proteins, modulation of signaling cascades, transcription, and gene expression. In particular, the inhibition of small GTP-binding proteins, Rho, Ras, and Rac, whose proper membrane localization and function are dependent on isoprenylation, may play an important role in mediating the direct cellular effects of statins on the vascular wall. The clinical relevance of these effects is beginning to be recognized, and ongoing studies will be able to answer these many questions in the near future. Actions of statins on vascular, glomerular, bone, and insulin-sensitive tissue as well as effects of statins on cognitive function and oncoprotection will be discussed in this review.
BACKGROUND AND AIM: Epidemiological studies have suggested an association between higher body iron stores and coronary artery disease (CAD), but recent trials have reported conflicting data on the role of ferritin in CAD. To assess these findings, we examined the association between serum ferritin and the angiographic extent of coronary atherosclerosis in consecutive patients referred for coronary angiography. METHODS AND RESULTS: We studied 100 consecutive white subjects (41 women and 59 men; mean age 63.7 +/- 11.0 years) who underwent coronary angiography. The data collected at baseline included conventional risk factors for coronary artery disease (CAD), lipid and fasting total homocysteine levels, serum ferritin levels and transferrin saturation, and clinical characteristics. Serum ferritin levels and transferrin saturation (serum iron concentration divided by total iron-binding capacity) were used as measures of the amount of circulating iron available to tissues. Two experienced cardiologists blinded to the clinical and laboratory data reviewed the angiographic cinefilms, and defined the angiographic severity of CAD on the basis of the sum of three vessel scorring systems. The risk of CAD assessed by coronary angiography was not related to ferritin concentrations or transferrin saturation levels. The estimated relative risk of CAD for the fifth vs the first quintile of serum ferritin was 0.83 (95% CI: 0.63-1.24). Forty of the 100 patients had no or minimal CAD (group A; score 0-3), 33 moderate CAD (group B; score 4-8) and 27 severe CAD (group C; score > 8): the serum ferritin levels in the three groups were respectively 165 +/- 126, 167 +/- 121 and 164 +/- 110 ng/ml, and did not represent an independent risk factor for CAD (p = 0.98). Transferrin saturation in the three groups was 22.9 +/- 10%, 21 +/- 9% and 19.9 +/- 10%, with no significant relationship to the severity of CAD (p = 0.23). The presence of angiographic CAD was associated with patient age (p = 0.048), male gender (p < 0.01), high lowdensity lipoprotein cholesterol levels (p = 0.02), low high-density lipoprotein cholesterol levels (p = 0.02), high plasma fibrinogen levels (p < 0.01) and high fasting total homocysteine levels (p = 0.04). CONCLUSION: In patients referred for coronary angiography, higher ferritin concentrations and transferrin saturation levels were not associated with an increased extent of coronary atherosclerosis.
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Tardive dyskinesia (TD) is a common side effect of long-term medication with typical neuroleptics. TD presents itself by abnormal involuntary movements and may lead to a potentially disabling and chronic clinical course. A vast majority of patients suffering from schizophrenia are smokers. Smoking has been reported to induce the activity of the CYP1A2 enzyme, which is an established metabolic pathway within the disposition of antipsychotics. Recently, a C-->A genetic polymorphism in the first intron of the CYP1A2 gene was reported to influence CYP1A2 activity in smokers. Subsequently, a pharmacogenetic study in 85 U.S. patients with schizophrenia (44 smokers, 41 individuals with unknown smoking status) showed the C/C genotype to be associated with higher TD severity (measured by the Abnormal Involuntary Movement Scale, AIMS) than the A/C or A/A genotype. This finding prompted us to investigate whether this effect was also present in a larger German sample of 119 patients with schizophrenia (82 smokers, 37 individuals with unknown smoking status). However, we could not replicate the reported association. The median AIMS scores did not differ between individuals with the A/A, A/C, or C/C genotypes. In an additional analysis, we compared the genotypic and allelic distribution among individuals grouped according to the criteria established by Schooler and Kane [1982: Arch Gen Psychiatry 39:486-487] (persistent TD vs. absent TD). We did not observe a differential genotypic or allelic distribution between the two diagnostic groups. Thus, our results do not support the hypothesis that the C-->A polymorphism in the CYP1A2 gene is involved in the etiology of TD in the German population.
The complex diffraction pattern of the heavily disordered co-crystals of perhydrotriphenylene and 1-(4-nitrophenyl)piperazine (5C(18)H(30) x C(10)H(13)N(3)O(2)) has been investigated with synchrotron radiation and an area detector. Five (almost) complete, three-dimensional data sets have been obtained from the tips and the centre of a needle-like crystal at room temperature and 120 K. They revealed a rich variety of features including one,- two- and three-dimensional diffuse scattering, as well as incommensurate satellites. At the centre and one tip of the crystal the symmetry appears to be orthorhombic, whereas at the other tip the symmetry of the satellites and of some of the diffuse scattering is clearly monoclinic, indicating that the crystal is not homogeneous. Most of the scattering could be assigned to R/S occupational disorder of the chiral host molecules, to positional disorder of the guest molecules or to local distortions of the average structure. Assignments are based on the disorder deduced from the average structure and the molecular form factors of host and guest molecules which show characteristic patterns in reciprocal space. Two smaller, orthorhombic twin fragments and an additional phase with hexagonal symmetry have also been found.
We demonstrate the use of a multiparticle coincidence technique to image the diffraction of an electron wave whose source is placed at a specific site in a free molecule. Core-level photoelectrons are used to illuminate the molecule from within. By measuring the vector momenta of two molecular fragments and the photoelectron, a richly structured electron diffraction pattern is obtained in a body-fixed frame of the randomly oriented molecule in the gas phase. We illustrate this technique for CO, creating a photoelectron from the C(1s) shell and scanning its energy from zero to 30 eV.
The aim of this study was to assess the implementation of the recommendations of the Danish National Health Service concerning screening of women from hepatitis B (HB) endemic areas and follow-up vaccination of infants of carrier mothers. We examined all birth notification (n = 836) at Hvidovre Hospital during the first three months of 1999. Among 188 women from HB endemic areas only 134 (71%) women had been screened for HBsAg before delivery. Six women were HBsAg positive one of whom was examined after the delivery. Four out of six infants (67%) received Aunativ and Engerix-B within 12 hours of birth, one infant received Aunativ and Engerix-B at four days of age, the infant born of the mother who was screened after delivery didn't receive either Aunativ or Engerix-B. Three out of the six infants (50%) had received all the scheduled Engerix-B vaccinations. Our results suggest it may be necessary to reconsider the current screening and vaccination procedures to prevent an increase in the number of children becoming chronic HB carriers in Denmark.
Suppression of NF kappa B activation has been involved in the elimination of survival programs during endothelial cell (EC) apoptosis. We used alpha-tocopheryl succinate (alpha-TOS) to trigger apoptosome formation and the subsequent activation of executioner caspases. The level of bcl-2 was reduced by alpha-TOS, and its downregulation potentiated and its overexpression suppressed pro-apoptotic effects of alpha-TOS, indicating a mitochondrial role in alpha-TOS-induced apoptosis in EC. alpha-TOS treatment was associated with induction of TUNEL-positive apoptosis in EC with a high but not with a low proliferation index. The use of the pan-caspase inhibitor z-VAD.fmk suggested the involvement of caspases in cleavage of p65, and in inhibition of nuclear translocation of p65 and NF kappa B-dependent transactivation of a gene construct encoding the green fluorescence protein elicited by TNF alpha in contact-arrested EC. The suppression by alpha-TOS of inflammatory EC responses induced by TNF alpha such as VCAM-1 mRNA and surface protein expression and shear-resistant arrest of monocytic cells were also reversed by z-VAD.fmk. NF kappa B-dependent transactivation was preserved in alpha-TOS-treated EC stably transfected with a caspase-noncleavable p65 mutant but not with its truncated form, thus establishing a direct link between alpha-TOS-induced effects and p65 cleavage. Our data infer a pathway by which caspase activation in EC inhibits NF kappa B-dependent inflammatory activation and monocyte recruitment, and provide evidence for a relationship between pro-apoptotic and anti-inflammatory pathways.
We present measurements of time-dependent CP-violating asymmetries in neutral B decays to several CP eigenstates. The measurement uses a data sample of 23x10(6) Upsilon(4S)-->BbarB decays collected by the BABAR detector at the PEP-II asymmetric B Factory at SLAC. In this sample, we find events in which one neutral B meson is fully reconstructed in a CP eigenstate containing charmonium and the flavor of the other neutral B meson is determined from its decay products. The amplitude of the CP-violating asymmetry, which in the standard model is proportional to sin2beta, is derived from the decay time distributions in such events. The result is sin2beta = 0.34+/-0.20 (stat)+/-0.05 (syst).
The four-particle process of proton-helium transfer ionization has been studied using cold target recoil ion momentum spectroscopy to measure the momenta of all three particles in the final state. Most of the electrons are emitted in the H0 scattering plane and in the backward direction. The final state momentum distributions show discrete structures very different from those expected for uncorrelated capture and ionization. The measured momentum pattern is interpreted to be due to a new transfer ionization reaction channel which results from strong correlations in the initial He ground state momentum wave function.
The synapsins constitute a family of synaptic vesicle-associated phosphoproteins essential for regulating neurotransmitter release and synaptogenesis. The molecular mechanisms underlying the selective targeting of synapsin I to synaptic vesicles are thought to involve specific protein-protein interactions, while the high-affinity binding to the synaptic vesicle membrane may involve both protein-protein and protein-lipid interactions. The highly hydrophobic N-terminal region of the protein has been shown to bind with high affinity to the acidic phospholipids phosphatidylserine and phosphatidylinositol and to penetrate the hydrophobic core of the lipid bilayer. To precisely identify the domains of synapsin I which mediate the interaction with lipids, synapsin I was bound to liposomes containing the membrane-directed carbene-generating reagent 3-(trifluoromethyl)-3-(m-[125I]iodophenyl)diazirine and subjected to photolysis. Isolation and N-terminal amino acid sequencing of 125I-labelled synapsin I peptides derived from CNBr cleavage indicated that three distinct regions in the highly conserved domain C of synapsin I insert into the hydrophobic core of the phospholipid bilayer. The boundaries of the regions encompass residues 166-192, 233-258 and 278-327 of bovine synapsin I. These regions are surface-exposed in the crystal structure of domain C of bovine synapsin I and are evolutionarily conserved among isoforms across species. The present data offer a molecular explanation for the high-affinity binding of synapsin I to phospholipid bilayers and synaptic vesicles.