Possibilities of using non-invasive techniques to predict pulmonary arterial pressure in chronic respiratory diseases]

The value of non-invasive procedures for predicting pulmonary arterial pressure (PAP) was assessed in 297 patients with chronic obstructive lung disease (COLD) and in 73 patients with alveolitis in multicenter trials at 9 centres in 6 European countries. FEV1, blood gases, ECG, radiographic dimensions of the pulmonary artery, right ventricle dimensions measured with M-mode echocardiography, and 201Ta heart scintigraphy together with clinical examinations served the purpose. No single variable was correlated closely enough to allow precise prediction of PAP. In patients with COLD multiple stepwise analysis of regression explained 49% of the variance in PAP but was not useful for prediction. Discriminant analysis allowed patients allocation to PAP bands similarly to 2 non-parametric procedures in which decision trees were established with the aid of either Kolmogoroff-Smirnoff statistics or Fishers' exact test. Patients with PAP of 30 mm Hg or higher were identified with sensitivity of 83% and specificity of 91%. Non-parametric tests produced better results than discriminant functions. Additional 54 patients were tested to validate these functions. Ninety percent of them with PAP > 20 mm Hg, and 80% with PAP > 29 mm Hg were identified correctly. Similar results were achieved in patients with fibrosing alveolitis. These mathematical functions allow the use of non-invasive procedures combinations to select those individuals out the populations at risk of pulmonary hypertension in whom direct PAP measurements are required. These mathematical functions may further be widen by addition of other variables obtained from newer non-invasive techniques.     

Effects of longitudinal stretch on VSM tone and distensibility of muscular conduit arteries

With progressing age, large arteries diminish their longitudinal stretch, which in extreme cases results in tortuosity. Increased age is also associated with loss of vessel distensibility. We measured pressure-diameter curves from muscular porcine carotid arteries ex vivo at different longitudinal stretch ratios (lambda(z) = 1.4 and 1.8) and under different vascular smooth muscle (VSM) conditions (fully relaxed, normal VSM tone, and maximally contracted). Distensibility was found to be halved by decreasing longitudinal stretch from lambda(z) = 1.8 to 1.4 at physiological pressures. This counterintuitive observation is possible because highly nonlinear elastic modulus of the artery and anisotropic properties. Furthermore, a significantly larger basal VSM contraction was observed at lambda(z) = 1.8 than 1.4, although this was clearly not related to a myogenic response during inflation. This dependence of VSM tone to longitudinal stretch may have possible implications on the functional characteristics of the arterial wall.     

Maximal wall shear stress in arterial stenoses: application to the internal carotid arteries

Maximal wall shear stress (MWSS) in the convergent part of a stenosis is calculated by the interactive boundary-layer theory. A dimensional analysis of the problem shows that MWSS depends only on a few measurable parameters. A simple relationship between MWSS and these parameters is obtained, validated, and used to calculate the magnitude of MWSS in a carotid stenosis, as a function of the patency of the circle of Willis and the stenotic pattern. This demonstrates the huge effect of collateral pathways. Elevated MWSS are observed even in moderate stenoses, provided they are associated with a contralateral occlusion, a large anterior, and narrow posterior communicating arteries, suggesting a potential risk of embolus release in this configuration.     

Operations on large arteries; application of recent advances

With the use of anticoagulants to prevent recurrence of thrombosis it is now possible to open a major artery which has been occluded by a thrombus, remove the thickened lining with the clot and restore the continuity of the vessel. Free vein grafts have been used successfully to replace arterial segments in the extremities. Vein inlay grafts are preferred in dealing with aneurysms of the abdominal aorta. The aneurysmal wall can be used to support the venous segments. It has been possible to by-pass aneurysms of the abdominal aorta by anastomosing the splenic artery to the left iliac artery. The use of the left superficial femoral artery as a by-pass to supply blood to the right leg is described.     

Approaches for non-invasive assessment of endothelial function: focus on peripheral arterial tonometry

The arterial endothelium is a complex organ that modulates vascular tone by release of various substances to control perfusion. Endothelial function reflects vascular ageing and health. Already at the earliest stages of atherosclerosis the delicate balance between arterial constriction and relaxation is disturbed. Therefore, non-invasive assessment of endothelial function is a means to identify patients at increased cardiovascular risk, even at levels of disease that cannot be identified with classical imaging techniques that depict arterial wall and/or lumen or with functional assessment of ischaemia. Currently, there is an increasing interest in the early recognition of endothelial dysfunction to streamline and optimise preventive therapeutic measures. In this article, several methods for the assessment of endothelial function are briefly reviewed. In particular, we discuss the fast bed-side assessment of endothelial function by the reactive hyperaemia peripheral arterial tonometry (RH-PAT) method.     

Transdermal sensing: in-situ non-invasive techniques for monitoring of human biochemical status

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On the application of wave scattering theory for the diagnosis of muscle diseases

This investigation is concerned with a scattering matrix approach which is proposed for the non-destructive, differential diagnosis of muscle diseases. A number of muscle diseases are classified according to their various pathological indications and appropriate material parameters are derived for utilization as input data for a theoretical model. In the mathematical analysis phase of the model, Waterman's T-matrix approach in conjunction with statistical averaging for both position and orientation of muscle fibers are employed to obtain the attenuation due to geometric dispersion for a wide range of frequencies. The numerical results not only exhibit qualitative agreement with existing experimental data for normal muscle but also display differentiable patterns for the various muscle disease cases. The formulation is an improvement over the previously applied scattering theory in that it obtains the attenuation over a continuous frequency spectrum.     

重复引物PCR技术在超大片段动态突变疾病基因检测中的应用进展

动态突变疾病是指基因编码区或非编码区发生核苷酸重复序列异常扩增所导致的一类遗传性疾病。发生于非翻译区的动态突变常常伴有超大片段重复序列,应用普通PCR法无法对该片段进行扩增,而传统的Southern blot等技术费时费力,无法应用于临床基因诊断。在此背景下,重复引物PCR技术应运而生。本文将分别阐述重复引物PCR技术在强直性肌营养不良症、Friedreich共济失调、脊髓小脑性共济失调10型及C9orf72基因突变引起的额颞叶痴呆或肌萎缩侧索硬化等疾病基因检测中的应用进展。     

Contribution of large airway to the input impedance of the respiratory system

To evaluate the contribution of the large airway to total respiratory impedance, we develop a one-dimensional model of pressure and flow in these airways by coupling conservation of mass and momentum equations with the geometric information obtained by the acoustic reflection technique. We use this model to calculate the impedance of the respiratory system distal to the carina from impedance data estimated at the airway opening by the forced oscillation technique. Simulations show that the real part of the impedance distal to the carina is uniformly decreased from the impedance at the airway opening, indicating a resistive loss, while the imaginary part is increased as a function of frequency. We estimate parameter values for a six-parameter two-compartment lung model and for a three-parameter reduction of this model before and after the application of the upper airway data to the impedance spectrum. Although compliance terms seem to be minimally affected by the manipulation of the data, resistance and inertance terms are influenced in a fashion that suggests that the resistive contribution of the upper airway to total respiratory impedance is significant. Furthermore it appears that the elastic nature of the walls of the upper airway also impact on estimates of total respiratory impedance at the airway opening.     

Production of recombinant fragment of VacA protein and development of non-invasive method for the diagnosis of Helicobacter pylori infection

Vacuolizing toxin (VacA) Helicobacter pylori is an important factor of pathogenicity of Helicobacter pylori and a basic marker in the diagnosis of helicobacteriosis and related diseases. A coagulation-based diagnostic test-system was elaborated for the detection of VacA in clinical samples. A fragment of vacA was cloned, for the purpose, in Escherichia coli and expressed in preparative quantities; the coded protein was purified and used in raising the diagnostic serum. The thus designed coagulating test-system was successfully tested under the modeling conditions with clinical samples. Therefore, the designed express method can be used for the invasion-free determination of VacA in patients with gastric and duodenal pathologies.     

Transposition of the great arteries: logical anatomical arterial correction.

In a 20-month-old child with classic transposition of the great arteries the pulmonary artery, coronary arteries, and aorta were successfully retransposed at arterial level. It was difficult to reimplant the coronary arteries in the dilated pulmonary artery root without damaging the attachments of the valve cusps, and it may be better to divide the pulmonary artery first to avoid this hazard. Retransposition at arterial level will not be suitable for all patients with transposition of the great arteries, and many questions about long-term outcome remain to be answered.     

Models for the longitudinal genetic analysis of same-age twins: application to HDL cholesterol.

Models are presented for the analysis of longitudinal data from same-age twins which permit the exploration of a remarkably diverse array of alternative explanations for continuity and change during development. Data of this type permit the detection of new sources of genetic or environmental covariation during development that are not expressed at earlier ages and, because they include the effects of age-specific genes, the resulting heritability estimates are more reliable than those obtained from relatives who differ in age. The proposed models were applied to measurements of HDL cholesterol obtained on 81 pairs of monozygotic (MZ) twins and 69 dizygotic (DZ) pairs at 11, 12.5 and 14 years of age. All three MZ co-twin correlations were substantially higher than the self correlations across occasions, suggesting that new sources of genetic or environmental covariation must be expressed during early adolescence. This interpretation was confirmed by analysis of the full covariance matrices which showed that only models which assumed the expression of new or age-specific genes could explain the observed pattern of covariation. Because they include the effects of age-specific genes, the resulting heritabilities (0.80-0.83) were substantially higher than many previous estimates.     

Influence of mechanical impedance on root exudation of maize seedlings at two development stages

Studies were undertaken to evaluate the effects of mechanical impedance on root exudation by maize (Zea mays L., var Dea) and to examine the importance of these effects in relation to the stage of plant development. Plants were grown under sterile and hydroponic conditions. Mechanical impedance was simulated using glass beads of 1 mm diameter. This treatment was compared with a control without beads. Results demonstrated that plant growth was influenced by mechanical impedance. Mechanical impedance markedly affected the growth of the shoot, whether this was measured as leaf area or total dry matter. Besides increasing root/shoot biomass ratios, mechanical impedances also stimulated root exudation of organic and inorganic compounds. Stressed plants lost more nitrogenous compounds than control plants. Otherwise, the percentage of released carbon decreased. Depending on the developmental stage of the plant, there was a large variation in the magnitude and time course on mechanical impedance effects. The effects of mechanical impedance persist and accentuate with time.     

Subset of cells immunopositive for neurokinin-1 receptor identified as arterial interstitial cells of Cajal in human large arteries

In the adventitia of large arteries, dendritic cells are located between nerve fibers, some of which contain substance P. The aim of the present study was to examine whether neurokinin 1 receptor (NK-1R) was expressed by dendritic cells in the arterial wall. Parallel sections of aortic and carotid artery segments were immunostained with anti-NK-1R and cell-type-specific antibodies. Dendritic cells in the arterial wall expressed NK-1R, albeit at a low level. Other cells, which intensely expressed NK-1R, were located along the border between the media and adventitia. They did not co-express any dendritic cell markers, including fascin, CD1a, S100, or Lag-antigen, and were negative for CD68, CD3, and mast cell tryptase. These NK-1R⁺ cells were laser-capture microdissected and studied by means of electron-microscopic analysis. The microdissected cells were in direct contact with nerve endings, and their ultrastructure was typical of the interstitial cells of Cajal present in the gastrointestinal tract. Further systematic electron-microscopic analysis revealed that the cells displaying the features typical of interstitial cells of Cajal were a basic element of the human arterial wall architectonics. Arterial interstitial cells of Cajal were negative for c-kit but they expressed vasoactive intestinal peptide receptor 1 (VIPR1). Destructive alterations of contacts between arterial interstitial cells of Cajal and nerve endings were observed in arterial segments with atherosclerotic lesions. The functional significance of the arterial interstitial cells of Cajal and their possible involvement in atherosclerosis and other vascular diseases need clarification.This work was supported by the St Vincents Clinic Foundation, Sydney, Australia.     

Trophoblasts isolated from the maternal circulation: in vitro expansion and potential application in non-invasive prenatal diagnosis.

Prenatal diagnosis based on rare fetal cells in maternal blood is currently not a feasible option. An effort was made to improve cell yields by targeting trophoblast cells. After sorting, the HLA-G-positive cell fraction was analyzed directly or after culture. In situ hybridization technology was applied to prove fetal cell source in samples from women carrying a male fetus and to predict gender in samples without previous knowledge of fetal sex. In vitro culture led to a significant increase in fetal cells and accurate gender prediction in 93% of these samples. This approach might be useful for non-invasive prenatal diagnosis.     

A model for the nonlinear elastic response of large arteries

The nonlinear elastic response of large arteries subjected to finite deformations due to action of biaxial principal stresses, is described by simple constitutive equations. Generalized measures of strain and stress are introduced to account for material nonlinearity. This also ensures the existence of a strain energy density function. The orthotropic elastic response is described via quasi-linear relations between strains and stresses. One nonlinear parameter which defines the measures of strain and stress, and three elastic moduli are assumed to be constants. The lateral strain parameters (equivalent to Poisson's ratios in infinitesimal deformations) are deformation dependent. This dependence is defined by empirical relations developed via the incompressibility condition, and by the introduction of a fifth material parameter. The resulting constitutive model compares well with biaxial experimental data of canine carotid arteries.