Abnormal response of costal chondrocytes to acidosis in patients with chest wall deformity.

Costal cartilage is much understudied compared to the load bearing cartilages. Abnormally grown costal cartilages are associated with the inherited chest wall deformities pectus excavatum and pectus carinatum resulting in sunken or pigeon chest respectively. A lack of understanding of the ultrastructural and molecular biology properties of costal cartilage is a major confounder in predicting causes and outcomes of these disorders. Due to the avascular nature of cartilage, chondrocytes metabolize glycolytically, producing an acidic environment. During physical activity hydrogen ions move within cartilage driven by compressive forces, thus at any one time, chondrocytes experience transient changes in pH. A variety of ion channels on chondrocytes plasma membrane equip them to function in the rapidly changing conditions they experience. In this paper we describe reduced expression of the ASIC2 gene encoding the acid sensing ion channel isoform 2 (previously referred to as ACCN1 or ACCN) in patients with chest wall deformities. We hypothesized that chondrocytes from these patients cannot respond normally to changes in pH that are an integral part of the biology of this tissue. Activation of ASICs indirectly creates a cascade ultimately dependent on intracellular calcium transients. The objective of this paper was to compare internal calcium signaling in response to external pH changes in costal chondrocytes from patients with chest wall deformities and healthy individuals. Although the molecular mechanism through which chondrocytes are regulated by acidosis remains unknown, we observed reduced amplitudes of calcium rise in patient chondrocytes exposed to low pH that become further impaired upon repeat exposure.

Moment fluid equations for ions in weakly ionized plasma.

A one-dimensional fluid model for ions in weakly ionized plasma is proposed. The model differs from the existing ones in two aspects. First, a more accurate approximation of the collision terms in the fluid equations is suggested. For this purpose, the results obtained using the Monte Carlo kinetic model of the ion swarm experiments are considered. Second, the ion energy equation is taken into account. The fluid equations are closed using a simple model of the ion velocity distribution function. The accuracy of the fluid model is examined by comparing with the results of particle-in-cell Monte Carlo simulations. In particular, several test problems are considered using a parallel plate model of the capacitively coupled radio-frequency discharge. It is shown that the results obtained using the proposed fluid model are in good agreement with those obtained from the simulations over a wide range of discharge conditions. An approximation of the ion velocity distribution function for the problem under consideration is also discussed.

Capacitively coupled rf discharge with a large amount of microparticles: Spatiotemporal emission pattern and microparticle arrangement.

The effect of micron-sized particles on a low-pressure capacitively coupled rf discharge is studied both experimentally and using numerical simulations. In the laboratory experiments, microparticle clouds occupying a considerable fraction of the discharge volume are supported against gravity with the help of the thermophoretic force. The spatiotemporally resolved optical emission measurements are performed with different arrangements of microparticles. The numerical simulations are carried out on the basis of a one-dimensional hybrid (fluid-kinetic) discharge model describing the interaction between plasma and microparticles in a self-consistent way. The study is focused on the role of microparticle arrangement in interpreting the spatiotemporal emission measurements. We show that it is not possible to reproduce simultaneously the observed microparticle arrangement and emission pattern in the framework of the considered one-dimensional model. This disagreement can be attributed to the two-dimensional effects (e.g., radial diffusion of the plasma components) or to the lack of the proper description of the sharp void boundary in the frame of fluid approach.

Quasi-two-dimensional complex plasma containing spherical particles and their binary agglomerates.

A unique type of quasi-two-dimensional complex plasma system was observed which consisted of monodisperse microspheres and their binary agglomerations (dimers). The particles and their dimers levitated in a plasma sheath at slightly different heights and formed two distinct sublayers. The system did not crystallize and may be characterized as a disordered solid. The dimers were identified based on their characteristic appearance in defocused images, i.e., rotating interference fringe patterns. The in-plane and interplane particle separations exhibit nonmonotonic dependence on the discharge pressure.

[The use of SPECT-CT for visualization of sentinel lymph nodes and lymph drainage pathways in prostate cancer patients].

There was studied the use of SPECT-CT for visualization of sentinel lymph nodes and lymph drainage pathways in 35 patients with localized prostate cancer (cT1-T2 N0 M0). Sentinel lymph nodes were imaged in 31 (89%) patients. There were advantageously detected drainage pathways to exterior (77%) and internal iliac (58%) lymph nodes. Visceral (29%) lymph nodes (paraprostatic, paravesical and mesorectal) were less determined. There was established high informative value of SPECT-CT for imaging sentinel lymph nodes, determining their location as well as identification of lymph drainage pathways in patients with prostate cancer.

[Use of SPECT-CT for visualization of sentinel lymph nodes in breast cancer patients].

This study was performed in order to determine individual variability of axillary sentinel lymph nodes (SLN) localization in patient with breast cancer (BC). Individual topography of axillary SLN was determined in 182 patients with early BC. All women were candidates for conservative surgical treatment with postoperative radiotherapy. SPECT-CT visualization of SLN started 120-240 min after intratumoral injection of 74-150MBq of 99mTc-radiocolloids. Distribution of axillary SLN was allocated to following subregions: central (C), pectoral (P), apical (AP), lateral (L), subscapular (SSc). SLN visualization by SPECT-CT was successful in 153 cases (84%). AP nodes were detected in 7 patients (5%). SLN were localized on thoracic wall in 34 cases (22%), in the intrapectoral region--in 3 (2%) women. According to axillary levels they were detected on level I--in 149 (97%), level II--15 (10%), level III-- (7.5%) cases.

[METHODOLOGIC PROBLEMS OF SENTINEL LYMPH NODE BIOPSY IN PATIENTS WITH BREAST CANCER].

The study included data on 168 patients with breast cancer, surgical treatment of whom was supplemented by axillary dissection (133 patients or 79.2%) or biopsy of sentinel lymph nodes (35 patients or 20.8%). The examination included ultrasound, planar scintigraphy of the breast and zones of regional lymph drainage. In 122 patients with primary breast cancer stage cT1-2N0M0 retrospective analysis of radionuclide imaging sentinel lymph node was performed. In 89 patients the introduction of colloidal radiopharmaceutical was carried out using a particle diameter of not more than 80-100 nm, in 33 patients study was conducted after administration of radiocolloid with a particle diameter of 200 to 1000 nm. Based on the data obtained by scintigraphy and ultrasonography of zones of regional lymph drainage there were offered two diagnostics models: the first, in which the presence of metastatic axillary lymph nodes was established when there were changes according to at least one of the diagnostic methods--scintigraphy or ultrasound; the second, in which the defeat of lymph nodes was determined only in the case of simultaneous detection of ultrasound and scintigraphic evidence of axillary lymph nodes. Sensitivity, specificity, and overall accuracy of the combination of ultrasound and planar scintigraphy axillary lymph nodes using the first model accounted for 82.7%, 67.7% and 74.4%, respectively. In the second model, the specificity was 94.6%, sensitivity--56%. Rapid transport of radiopharmaceuticals from the injection site, a high gradient of radiopharmaceuticals accumulation in sentinel lymph nodes, effective their visualization, approaching to 100%, were undoubted advantages of radiocolloids having a particle diameter up to 100 nm.

[Treatment of patients with disseminated testicular germ cell tumors].

Testicular germ cell tumors are rare diseases of young age with high sensitive to cytostatic therapy. Their complex treatment should be based on prognostic factors and individual properties of disease. It includes chemotherapy followed by cytoreductive surgery of residual lesions according to international standards and guidelines. This approach is highly effective and allows curing the majority of patients with advanced disease.

[Role of single-photon emission-computed tomography and x-ray computed tomography in diagnosing lymphatic metastases in patients with non-small cell lung cancer].

Single photon emission tomography (SPECT) with 99mTc-MIBI was performed after conventional staging in 83 operated non-small cell lung cancer (NSCLC) patients. Diagnostic results of SPECT and conventional computerized tomography (CT) staging were validated by histological examinations of operation material. According to histological verification 35 of 83 evaluated patients had lymph node (LN) invasion by NSCLC. SPECT detected LN involvement in 28 of these 35 patients and was false positive in additional 16 patients. Pneumonia or atelectasis were detected in 12 of 16 patients with false positive SPECT results. Sensitivity (Sen), specificity (Sp), accuracy (Ac), positive (PPV) and negative (NPV) predictive values of SPECT in diagnosis of LN invasion by NSCLC was as follows: 80%, 66%, 72%, 65%, 82%. Diagnostic accuracy of CT for detection of LN involvement was inferior to SPECT: Sen--71%, Sp--62%, Ac--66%, PPV--58%, NPV--75%. Combination of SPECT and CT data offer promising solutions with Sen reached 94% or high Sp which in patients without atelectasis or pneumonia can reach 96%.

[The role of spiral computed tomography in planning the surgical interventions for non-organ retroperitoneal tumors].

The surgical operation is a principal and in most cases a solitary treatment for non-organ retroperitoneal tumors. High risk of recurrence, aptitude to large local extension dictates necessity of individual surgical plan. An equality of approach is excluded. Pre-operative specified diagnostics of tumor extension is extremely important. We present an experience of determination of such characteristics of non-organ retroperitoneal tumors, which influence the extent of surgery (multiple lesions, invasion of adjacent vessels and organs).

[Combined use of 99mTc-MIBI scintigraphy and ultrasonography (US) in the diagnosis of axillary lymphatic metastasis in patients with breast cancer].

We aimed to evaluate different imaging strategies for diagnosis of axillary LNMs in patients with primary breast cancer (BC). 168 consecutive patients with primary BC were included in the study. Functional imaging by scintigraphy (AxSc) with 99mTc-MIBI was performed in static and tomography modes 15 min after i/v injection. Focal areas of tracer accumulation in axial region were considered as sings of LNMs. Ultrasound (US) examination of axillary region was performed on 7.5 kH scanner. Nodes with diameter more than 1 cm were considered abnormal. All patients were operated with axial LN dissection and subsequent histological evaluation. Scintigraphic signs of LNMs revealed in 65 patients: 48--true positive, 17--false positive. Among 103 women with normal AxSc results 27 had LNMs and 76--uninvolved nodes. Sensitivity (Sen), Specificity (Sp) and Accuracy (Ac) of AxSc were as follows: 64%, 82% and 74%. Sonography diagnosed LNMs in 74 women: 56 were metastatic on histology while other 18--uninvolved. On the contrary, 19 of 94 US normal sized nodes were metastatic on histology. US had following values when used for diagnosis of axillary LNMs: Sen--75%, Sp--81%, Ac--78%. When LNMs were diagnosed as the combination of concordantly abnormal US and AxSc examinations Sp reached 95%, Sen dropped down to 56% and Ac--to 77%. Another model was based on the assumption that LNMs must be diagnosed in all patients with abnormal US or AxSc examinations. According to this strategy Sen reached 83%, Sp--68% and Ac--74%. Thus, we found comparative accuracy of US and AxSc in diagnosis of axillary LNMs in patients with primary BC. Combination of both modalities can significantly improve sensitivity (83%) or specificity (95%) of final conclusion which is determined by established diagnostic strategy and criteria's that are used for BC diagnosis.

[Use of simultaneous double-tracer SPECT with 99m-Tc-technetril and 67-Ga-citrate for follow-up of patients with non-small cell lung cancer].

In 20 primary patients with focal abnormalities on conventional CT we evaluated diagnostic properties of simultaneous double-tracer SPECT. Scintigraphy was performed as a single examination with simultaneous registration of 67Ga and 99mTc-MIBI. Image acquisition was started 48-74 hours after IV injection of 130-175 MBq 67Ga-citrate and immediately after IV injection of 500-740 MBq of 99mTc-MIBI. All images for each agent were classified as positive and negative for primary tumor, N1 and N2 lymph-nodes (LN). According to histology 18 of 20 evaluated patients had non-small cell lung cancer (NSCLC), the other two patients had tuberculosis and nonspecific inflammation. SPECT with 99mTc-MIBI correctly visualized tumor in 18, 67Ga allowed correct visualization in 16 cases. Both tracers were truly negative in a patient with tuberculosis and false positive in a patient with nonspecific inflammation. Double-tracer SPECT was slightly more specific than CT in primary lesions. In 18 patients histological verification of LN status was obtained: NO was revealed in 9 cases, N1 in 4 and N2 in 5 cases. Both tracers correctly discriminated LN-positive and LN-negative cases with 94% specificity. On the contrary, CT was false-positive in 3 and false-negative in another 5 patients. Differentiation between N1 and N2 LN involvement is crucial for therapy planning. 99mTc MIBI and 67Ga revealed N1 in 2 cases and N2 in 4 cases, the diagnosis was later verified by postoperative morphology. In 2 patients SPECT overestimated extent of LN involvement and LN status was changed after surgery from N2 to N1. In 18 patients results of 99mTc-MIBI and 67Ga augmented each other. Accuracy of LN staging by SPECT with 99mTc-MIBI and 67Ga was 83%. CT accurately determined LN stage only in 7 patients, it was overestimated in 7 and underestimated in 4 cases. SPECT with 99mTc-MIBI and 67Ga demonstrated high overall accuracy in diagnostics of regional LN invasion for patients with NSCLC. Diagnostic value of conventional CT was significantly lower. Correct level of LN involvement was determined by SPECT in 83% of cases.

[Pharmacoeconomic analysis of gefitinib therapy in patients with non-cell cell lung cancer].

We performed a treatment efficacy analysis for non-small cell lung cancer (NSCLC) patients' population with EGFR mutation aimed at optimization of pharmacoeconomic factors. The employment of gefitinib leads to an increase in patients' life expectancy for a median of 1.05 years. The average cost-effectiveness of this therapy is 934.8 thousand rubles per additional year (903.9-1100.5 thousand rubles for each year). If gefitinib therapy is given only to patients with proved EGFR mutation it can decrease the average expenses by 211.6-251.8 thousand rubles per patient in comparison to undiagnosed patients's population receiving gefitinib without a decrease in clinical effect. Comparison of selective gefitinib administration with isolated chemotherapy (CT) yields an incremental cost-effectiveness ratio of 960.7 to 1010.0 thousand rubles per additional year. Therefore, the strategy of EGFR gene mutations testing in patients with inoperable NSCLC with consequent gefitinib therapy administration in patients positive for mutation lead to an increase in life expectancy and is characterized by acceptable cost-effectiveness.

[Sonoelastography in the diagnosis of breast tumors smaller than 2 cm].

This is an analysis of the use of sonoelastography as part of complex instrumental diagnostic procedure (mammography, gray-scale and Doppler ultrasonography) for small breast tumors. A total of 126 patients with breast lesions below 20 mm in diameter were divided into two groups depending on lesion size. The first group consisted of women with 5-10 mm lesions (21 patients with carcinoma and 20 patients with benign tumors), the second group was characterized by 11-20 mm lesions (69 carcinoma patients and 16 patients with benign lesions). According to analysis results the diagnostic complex of gray-scale ultrasonography and sonoelastography is most sensitive, the sensitivity is higher in the second group (89.1% and 97.7% respectively). The complex ultrasonography procedure yielded better overall results than mammography in both patients' groups.

[Sonographic imaging of soft tissue tumors].

In the course of this study 651 patients with morphologically confirmed soft tissue tumors of different localizations underwent gray-scale sonography, Doppler sonography and energetic Doppler carting. Hitachi HI Vision 900, Logiq-400, Aloka-650, Aloka-2000 scanners wih 5-13 MHz sensors were used. Lipomas, fibrolipomas, benign angioneoplasms and some of the desmoids were shown to have a characteristic sonographical picture. The potential sonographic symptom complexes were determined. Among the malignant tumors the distinct sonographic features were observed in liposarcoma and peripheral nerve sheath tumors. The other soft tissue sarcomas have no characteristic sonographic pattern. In this cases the differential diagnosis could be assisted by clinical signs and medical history analysis.

Excitation-contraction coupling in ventricular myocytes is enhanced by paracrine signaling from mesenchymal stem cells.

In clinical trials mesenchymal stem cells (MSCs) are transplanted into cardiac ischemic regions to decrease infarct size and improve contractility. However, the mechanism and time course of MSC-mediated cardioprotection are incompletely understood. We tested the hypothesis that paracrine signaling by MSCs promotes changes in cardiac excitation-contraction (EC) coupling that protects myocytes from cell death and enhances contractility. Isolated mouse ventricular myocytes (VMs) were treated with control tyrode, MSC conditioned-tyrode (ConT) or co-cultured with MSCs. The Ca handling properties of VMs were monitored by laser scanning confocal microscopy and whole cell voltage clamp. ConT superfusion of VMs resulted in a time dependent increase of the Ca transient amplitude (ConT(15min): ΔF/F(0)=3.52±0.38, n=14; Ctrl(15min): ΔF/F(0)=2.41±0.35, n=14) and acceleration of the Ca transient decay (τ: ConT: 269±18ms n=14; vs. Ctrl: 315±57ms, n=14). Voltage clamp recordings confirmed a ConT induced increase in I(Ca,L) (ConT: -5.9±0.5 pA/pF n=11; vs. Ctrl: -4.04±0.3 pA/pF, n=12). The change of τ resulted from increased SERCA activity. Changes in the Ca transient amplitude and τ were prevented by the PI3K inhibitors Wortmannin (100nmol/L) and LY294002 (10µmol/L) and the Akt inhibitor V (20µmol/L) indicating regulation through PI3K signal transduction and Akt activation which was confirmed by western blotting. A change in τ was also prevented in eNOS(-/-) myocytes or by inhibition of eNOS suggesting an NO mediated regulation of SERCA activity. Since paracrine signaling further resulted in increased survival of VMs we propose that the Akt induced change in Ca signaling is also a mechanism by which MSCs mediate an anti-apoptotic effect.

[Elastographic visualization of soft tissue tumors and its role in the diagnostic process].

A total of 110 patients with malignant (n=54, 49,1%), intermediate (n=24, 21.8%) or benign (n=31, 28.2%) soft tissue tumors were included in the study aimed to determine the soft tissue tumor elastographic picture and the overall role of elastographic visualization in soft-tissue tumor diagnostics. All the patients underwent grey-scale real-time elastography, colored Doppler mapping, energy Doppler mapping and ultrasonic elastography. The ultrasonic elastography included the quality assay of tissue color mapping and tissue stiffness index assay. All the tests were performed with Hitachi HI Vision 900 US scanner with 5-13 MHz US-sensors. In soft tissue tumors the elastography had 97% sensitivity equal to grey-scale US-scan sensitivity. Based on the results of the study, the elastography doesn't lead to any benefits as a stand-alone diagnostic technique. In most cases it doesn't lend any additional value compared to grey-scale US-scan. The only exceptions are the low-grade lyposarcomas, diffuse lypomas and fibrolypomas and desmoids. Nevertheless, elastography is still a useful method in surgical treatment planning as it allows to pinpoint the exact amount of involved tissues more effective than grey-scale US-scan techniques.

Micro-rheology on (polymer-grafted) colloids using optical tweezers.

Optical tweezers are experimental tools with extraordinary resolution in positioning (± 1 nm) a micron-sized colloid and in the measurement of forces (± 50 fN) acting on it-without any mechanical contact. This enables one to carry out a multitude of novel experiments in nano- and microfluidics, of which the following will be presented in this review: (i) forces within single pairs of colloids in media of varying concentration and valency of the surrounding ionic solution, (ii) measurements of the electrophoretic mobility of single colloids in different solvents (concentration, valency of the ionic solution and pH), (iii) similar experiments as in (i) with DNA-grafted colloids, (iv) the nonlinear response of single DNA-grafted colloids in shear flow and (v) the drag force on single colloids pulled through a polymer solution. The experiments will be described in detail and their analysis discussed.

[Role of computerized tomography in the diagnosis of gastrointestinal stromal tumors].

In this study we present an analysis of our own data on computerized tomography (CT) employment in patients with gastrointestinal stromal tumors (GIST) and the review of the literature. The CT data for 21 patients with GIST was compared with operation and morphology data. Difficulties of GIST timely diagnostic are described.

[Effectiveness of gefitinib (Iressa) as first-line therapy for inoperable non-small-cell lung cancer with mutated EGFR gene (phase II study)].

Tumor regression was reported in 20-30% of patients with inoperable non-small-cell lung cancer (NSLC) following standard first-line chemotherapy. Clinical trials with second-line gefitinib (Iressa) showed a strikingly high response in patients with mutated EGFR. However, clinical experience with gefitinib as first-line therapy had been limited to small-scale trials mostly among subjects of Asian origin. Our study was not associated with the drug manufacturer and included 25 chemotherapy-naive patients with mutated EGFR inoperable lung adenocarcinoma. Standard dose was 250 mg/day. Complete response was observed in 1 patient (4%), partial--11 (44%), sustained stabilization--13 (52%); median time until tumor progression--186 days. Median overall survival failed to be registered within the duration of the study. Among most frequent side-effects were skin rash (19; 76%) and diarrhea (14; 56%): marked side-effect -toxicity grade III (4; 16%). Gefitinib appeared highly efficient and tolerable and may be recommended as first-line treatment of mutated EGFR inoperable NSLC.