The effect of volume currents due to myocardial anisotropy on body surface potentials

Changes in anterior and posterior body surface potential maps (BSPMs) due to myocardial anisotropy were examined using a highly heterogeneous finite element model of an adult male subject constructed from segmented magnetic resonance images. A total of 23 different tissue types were identified in the whole torso. The myocardial fibre orientations in the human heart wall were mapped from the fibre orientations of a canine heart which are available in the literature using deformable mapping techniques. The current and potential distributions in the whole torso were computed using dipolar sources in the septum, apical area, left ventricular wall or right ventricular wall. For each dipole x, y, z orientations were studied. An adaptive finite element solver was used to compute currents and potential distributions in the whole torso with an element size of 0.78 x 0.78 x 3 mm in the myocardium and larger elements in other parts of the torso. For each dipole position two cases were studied. In one case the myocardium was isotropic and in the other it was anisotropic. It was found that BSPMs showed a very notable difference between the isotropic and the anisotropic myocardium for all dipole positions with the largest difference for the apical dipoles. The correlation coefficients for the BSPMs between the isotropic and anisotropic cases ranged from 0.83 for an apical dipole to 0.99 for an RV wall dipole. These results suggest that myocardial fibre anisotropy plays an important role in determining the body surface potentials.     

Differential localization of IL-2- and -15 receptor chains in membrane rafts of human T cells

We studied whether cytokine receptors (Rs) on T cells associate with lipid microdomains ("rafts"). Low-dose phytohemagglutinin (PHA)-stimulated human T cells were separated into cytoplasmic, membrane, and raft fractions by buoyant density centrifugation. Examination of these fractions for the presence of interleukin (IL)-2- and -15R chains and associated signaling molecules by Western blotting revealed marked, selective enrichment of the IL-2/15R beta-chain in rafts before IL-2 stimulation. After IL-2 stimulation, a substantial amount of the beta-chain was found in the membrane fraction. This partial translocation was also observed for the beta-chain-associated molecules JAK-1, p56(lck), and grb-2. Finally, raft disruption with methyl-beta-cyclodextrin (MBCD) attenuated IL-2-induced tyrosine phosphorylation events and selectively decreased the surface expression of the IL-2/15R beta-chain detected by flow cytometry. These results show that the IL-2/15R beta-chain is enriched in rafts obtained from low-dose, PHA-stimulated T cells, that IL-2 binding alters this enrichment, and that this enrichment may be functionally relevant as a possible mechanism to ensure cytokine selectivity and specificity.     

Preventive Measures in Mite Asthma

To evaluate the effect of preventive measures 46 patients, all allergic to house-dust mites (Dermatophagoides spp.), were randomly allocated to a study and a control group. According to the patients' subjective recordings of symptom score and use of medicine, compared with the control group, the study group had improved. There was, however, no improvement when comparing the objective recordings of morning and evening peak flow and use of medicine, and it is concluded that the preventive measures in this programme are not very effective for patients allergic to house-dust mites. The reduction in indoor humidity in the study group was limited and, as a high indoor humidity is the cause of huge populations of house-dust mites in homes, it is emphasized that future programmes of preventive measures should focus more on damp problems, particularly those related to bad housing construction.     

Mechanics of porcine coronary arteries<Emphasis Type="Italic">ex vivo</Emphasis> employing impedance planimetry: A new intravascular technique

Our objective was to evaluate methodological aspects of impedance planimetry, a new balloon catheter-based technique, for the investigation of coronary artery mechanical wall properties. We used a four ring-electrode electrical impedance measuring system that was located inside a balloon. Two of the electrodes were used for excitation and connected to a generator producing a constant alternating current of 250 mA at 5 kHz. The other two electrodes for detection were placed midway between the excitation electrodes. The balloon was distended with electrically conducting fluid through an infusion channel. The vessel cross-sectional area (CSA) was measured according to the field gradient principle by measuring the impedance of the fluid inside the balloon. Impedance planimetry was applied in the three major branches of the coronary arteries of seven extracted porcine hearts to assess luminal CSAs in response to internal pressurization. The biomechanical wall properties were evaluated by computing the strain [(r?r ₀)·r ₀ ^?1, wherer is the vessels inner radius computed as (CSA · π^?1)^½ andr ₀ is the radius of the vessel at a minimal distension pressure], the tension [(r·dP), wheredP is the transmural pressure difference], and the pressure elastic modulus (ΔP·r·Δr ^?1). We found thatin vitro testing demonstrated that impedance planimetry was accurate and reproducible. The technique has controllable sources of crror. Measurements were performed with consecutively increasing pressures in the range 1–25 kPa (8–188 mmHg, 0.01–0.25 atm). The CSAs increased nonlinearly and were significantly larger in the left anterior descendent coronary artery (LAD) (1 kPa, mean 5.0 mm²; 25 kPa, mean 21.8 mm²) than in both the left circumflex (Cx) (4.5–16.0 mm²) and the right coronary artery (RCA) (2.8–15.6 mm²) (analysis of variance,P<0.001 for both). The circumferential wall tension-strain relation showed exponential behavior. For a given strain, tension values for LAD were significantly lower than those of Cx (P<0.01). The pressure elastic modulus-strain relation also was exponential, and values for Cx were significantly lower than values for LAD (P<0.001) and RCA (P<0.05). Impedance planimetry was applied to the study of coronary artery biomechanicsex vivo. The LAD had the largest CSA, and the Cx was the least compliant. Methodological aspects of anin vivo introduction of the method require additional evaluation.     

The effect of anti-IgE treatment on in vitro leukotriene release in children with seasonal allergic rhinitis

BACKGROUND: Binding of allergens with IgE to the IgE receptors on mast cells and basophils results in the release of inflammatory mediators as sulfidoleukotrienes (SLTs), triggering allergic cascades that result in allergic symptoms, such as asthma and rhinitis. OBJECTIVE: We sought to investigate whether anti-IgE (Oma-lizumab), a humanized monoclonal anti-IgE antibody, in addition to specific immunotherapy (SIT) affects the leukotriene pathway. METHODS: Ninety-two children (age range, 6-17 years) with sensitization to birch and grass pollens and with seasonal allergic rhinitis were included in a phase III, placebo- controlled, multicenter clinical study. All subjects were randomized to one of 4 treatment groups. Two groups subcutaneously received birch SIT and 2 groups received grass SIT for at least 14 weeks before the start of the birch pollen season. After 12 weeks of SIT titration, placebo or anti-IgE was added for 24 weeks. The primary clinical efficacy variable was symptom load (ie, the sum of daily symptom severity score and rescue medication score during pollen season). Blood samples taken at baseline and at the end of study treatment after the grass pollen season were used for separation of leukocytes in this substudy. After in vitro stimulation of the blood cells with grass and birch pollen allergens, SLT release (LTC4, LTD4, and LTE4) was quantified by using the ELISA technique. RESULTS: Before the study treatment, SLT release to birch and grass pollen exposure did not differ significantly among the 4 groups. Under treatment with anti-IgE + SIT-grass (n = 23), a lower symptom load occurred during the pollen season compared to placebo + SIT-grass (n = 24, P =.012). The same applied to both groups receiving birch SIT (n = 23 and n = 22, respectively; P =.03). At the end of treatment, the combination of anti-IgE plus grass SIT, as well as anti-IgE plus birch SIT, resulted in significantly lower SLT release after stimulation with the corresponding allergen (416 ng/L [5th-95th percentile, 1-1168] and 207 ng/L [1-860 ng/L], respectively) compared with placebo plus SIT (2490 ng/L [384-6587 ng/L], P =.001; 2489 ng/L [1-5670 ng/L], P =.001). In addition, treatment with anti-IgE was also followed by significantly lower SLT releases to the allergens unrelated to SIT (grass SIT: 300 ng/L [1-2432 ng/L] in response to birch allergen; birch SIT: 1478 ng/L [1-4593 ng/L] in response to grass pollen) in comparison with placebo (grass SIT: 1850 ng/L [1-5499 ng/L], P =.001; birch SIT: 2792 ng/L [154-5839 ng/L], P =.04]. CONCLUSION: Anti-IgE therapy reduces leukotriene release of peripheral leukocytes stimulated with allergen in children with allergic rhinitis undergoing allergen immunotherapy independent of the type of SIT allergen used.     

Development of a Cell Patterning Technique Using Poly(Ethylene Glycol) Disilane

A simple technique for controlling cell adhesion on glass substrates by surface modification using a commercially available poly(ethylene glycol) (PEG) disilane, which can bind directly to glass in a single step, in combination with photolithographic micropatterning, was developed, characterized, and evaluated for patterning of HepG2 hepatoma cells and 3T3 fibroblasts. The optimal concentration of PEG-disilane for surface modification was 5 mM, and patterning of strongly adherent cells such as HepG2 required the chelation of divalent metal cations in order to inhibit nonspecific binding and cell aggregation. Whereas the average thickness of the PEG-disilane layer was 18±3.5 nm, the perimeters of patterned areas of exposed glass exhibited ridges of average height 857±50 nm, which may have aided in constraining cell spreading and migration. Although unpatterned PEG-treated substrates were hydrophilic (contact angle 46±1°), micropatterned surfaces behaved as if they were somewhat hydrophobic (contact angle 90°), necessitating special protocols for preventing deleterious dewetting of cells. For optimized protocols, the probability of adhesion of HepG2 cells to a patterned area of exposed glass was almost 15 times higher than the probability of adhesion to a PEG-treated background region of equal area. Our technique is useful for short- to intermediate-term patterning of cell or tissue morphology, e.g., for investigation of the effects of cell–cell interactions or cell geometry.     

Severe calcification in left main stem coronary artery stenosis visible on routine chest radiograph

Coronary calcification is a strong predictor of significant coronary stenosis in symptomatic patients. While discrete calcification within coronary arteries is only detected by sensitive methods such as computed tomography, severe calcification can already be seen on the plain chest radiograph. In this article, we describe a patient with a high grade left main stem coronary artery stenosis who presented with a severe focal calcification on the plain chest radiograph in projection of the offspring of the left coronary artery.