Usefulness of clearance parametric images in detection of regional renal parenchyma dysfunction

BACKGROUND: The aim of the study was to examine whether parametric clearance images (PAR) enhance diagnostic potential of a dynamic renal scintigraphy with detection of local dysfunction of kidneys, on a model of kidneys after treatment with extracorporeal shock wave lithotripsy (ESWL), MATERIAL AND METHODS: Kidneys after ESWL were accepted as a proper model for the implementation of this objective because of the previously proven damaging effect of a shock wave on renal parenchyma and known region of ESWL application. Forty patients (23 males and 17 females) at the age of 37 to 70 years (mean value 54) with untreated earlier single, one-sided nephrolithiasis, currently treated with ESWL, underwent a study. A dynamic renal 99mTc-EC scintigraphy was performed three times: before ESWL, a week and a month after this therapeutic intervention. PAR images generated with use of an in-house developed software were compared with summation (SUM) of images obtained from radiopharmaceutical uptake phase and quantitative global function parameters (GFP) of each kidney, like split function, MTT — mean transit time and PTT — parenchymal transit time. RESULTS: PAR and SUM images of all 40 kidneys before ESWL were normal. PAR images revealed local or diffused defects a week and a month after therapeutic intervention in statistically significantly larger numbers of kidneys than SUM images (19 vs. 6, p = 0.002 and 16 vs. 5, p = 0.003, respectively). A week after ESWL, when defects in PAR images were observed in about a half of all renal segments (29/57 — 51%) all GFP values were significantly worse than in kidneys without defects. A month after ESWL defects in PAR images could be observed in ab. 1/3 (17/48 — 35%) of segments and were less extensive, whereas GFP values did not differ significantly from values in kidneys without clearance function impairment in the PAR images. CONCLUSIONS: PAR images enhance diagnostic potential of a dynamic renal scintigraphy with detection of local function defects. These images allow to detect more local renal function defects than SUM images

Doxazosin induces apoptosis in PTEN–positive androgen-independent PC cells via inhibition of Akt activation

Doxazosin, a selective α1-adrenoreceptor antagonist widely used in the management of benign prostatic hyperplasia (BPH), has been shown to induce apoptosis in androgen-independent (AI) and PTEN (phosphatases and tensin homolog)-negative prostate cancer (PC) cells. The objective of this study was to assess the effects of doxazosin on the growth of PC cells with a functional PTEN/PI3K/Akt pathway in relation to cell androgen sensitivity and Bcl-2 expression. Material and methods. The DU145 cell line and two derivatives: 1) DKC9 [DU145 (Bcl2 +/+)] and 2) DAR19 [DU145 (AR+/+)] were used. The effect of doxazosin on i) cell proliferation and ii) Akt phosphorylation was measured using the MTT assay and Western blotting, respectively. Results. Doxazosin caused significant concentration, but not time-dependent, decrease in cell viability. The threshold of sensitivity to the compound differed between the cell lines and was the lowest in the parental cell line. In DAR 19 cells, AR-mediated signaling further increased cell resistance to doxazosin. In all cell lines, doxazosin-induced apoptosis was rescued by EGF stimulation and, in DAR19 cells, by AR activation. Doxazosin reduced basal and EGF-/DHT-induced Akt phosphorylation. Conclusions. This study demonstrates that doxazosin induces apoptosis in PTEN-positive AI PC cells, at least partially, via Akt deactivation and that over-expression of Bcl-2 or AR increases cell resistance to the drug. These results imply that translational potential of doxazosin depends on phenotypic characteristics of PC cells and provide evidence for limitations to its application in hormone refractory tumors

Features of impaired seminiferous tubule differentiation are associated with germ cell neoplasia in adult men surgically treated in childhood because of cryptorchidism.

Seminiferous tubule differentiation was related to the occurrence of germ cell neoplasia in 38 men, aged 17-47, treated surgically in childhood for cryptorchidism. Tissues from 46 testes obtained from biopsies taken as a neoplastic preventive procedure or whole testes removed because of GCT were evaluated quantitatively. Paraffin sections were treated with antibodies against placental like alkaline phosphatase (PLAP), a marker of germ cell neoplasia, and cytokeratin 18 (CK-18), a marker of immature Sertoli cells. Quality of spermatogenesis and number Leydig cells were assessed with a score count. Seminiferous tubules diameter, thickness of basal membrane and size of intertubular spaces were measured with image analysis software. In 17.4% of testes spermatogenesis was normal (9.9 points) (N) and neoplasia was not found there. In the other 38 specimens (83%) spermatogenesis was abnormal (A). When spermatogenesis was arrested or when germ cells were absent (3.7+/-1.8 points), neoplastic lesions were found in 13.1% of the specimens. In A group 5.1+/-7.1% of tubules contained immature Sertoli cells, while in N they were not found. Tubular diameter was significantly lower in A (161.5+/-31.8 microm) than in N (184.6+/-24.3 microm) and the percentage of seminiferous tubules with the thickening of tubular basal membrane was also greater in A. Intertubular spaces were significantly larger in A (49.9+/-18.6%) in comparison to N group (32.6+/-12.5%). Mean number of Leydig cells was similar in both groups. To conclude, in most of the formerly cryptorchid testes, despite surgical treatment, impaired seminiferous tubules differentiation is predominant. Germ cell neoplasia is present in testes with retarded seminiferous tubules differentiation. Retardation of seminiferous tubule differentiation consists of inhibited spermatogenesis, presence of tubules with immature Sertoli cells, decreased tubular diameter, increased thickness of basal membrane and enlarged intertubular spaces. Examination of testicular biopsy with respect to the state of seminiferous tubule differentiation may be helpful to predict the appearance of germ cell neoplasia in adult men with cryptorchidism in anamnesis. Orchiopexy of cryptorchid testes may not prevent the occurrence of features of testicular dysgenesis and the associated germ cell neoplasia

Factors affecting the structure and elasticity of thoracic aorta

Wstęp Celem pracy była ocena za pomocą echokardiograficznego badania przezprzełykowego (TEE) czynników wpływających na strukturę i elastyczność aorty piersiowej. Materiał i metody Badaniami objęto 102 chorych (26 kobiet) w wieku 57 &plusmn; 10 lat. Na podstawie danych z wywiadu analizowano obecność czynników ryzyka miażdżycy. U wszystkich chorych wykonano ze wskazań klinicznych badanie TEE, które rozszerzono o ocenę aorty piersiowej. Analizowano średnicę aorty, grubość błony środkowo-wewnętrznej oraz wskaźniki elastyczności aorty. Wyniki Średnica aorty oraz grubość błony środkowo- wewnętrznej była dodatnio skorelowana z wiekiem (odpowiednio: r = 0,22, p = 0,03; r = 0,27, p = 0,005). Moduł Younga i moduł elastyczności &#946; również były dodatnio skorelowane z wiekiem (odpowiednio: r = 0,42, p < 0,0001; r = 0,37, p = 0,0002). Chorzy z nadciśnieniem tętniczym charakteryzowali się grubszą błoną środkowo-wewnętrzną (0,10 &plusmn; 0,03 vs. 0,13 &plusmn; 0.04, p < 0,05). Zaawansowana miażdżyca wiązała się ze zwiększoną sztywnością jej ściany. Wniosek Głównymi czynnikami determinującymi sztywność aorty są wiek i zaawansowanie miażdżycy.Background The purpose of the study was to evaluate by means of transesophageal echocardiography (TEE) the factors affecting the structure and elasticity of the thoracic aorta. Material and methods The study population consisted of 102 patients (26 women) aged 57 &plusmn; 10 years. Information of risk factors of atherosclerosis was obtained by interview. All patients underwent TEE for other reasons, examination was completed by imaging of the thoracic aorta. Results Aortic diameter, the intima-media thickness and distensibility indices were measured. Diameter and thickness of thoracic aorta were positively correlated with age (r = 0.22, p = 0.03; r = 0.27 p = 0.005 respectively). Young&#8217;s modulus and B modulus were also related to age (r = 0.42, p < 0.0001; r = 0.37, p = 0.0002 respectively). Hypertensive subjects had higher wall thickness (0.10 &plusmn; 0.03 vs. 0.13 &plusmn; 0.04, p < 0.05). Advanced atherosclerosis of the aorta was related to higher stiffness of the aorta. Conclusion Aortic elasticity is related mostly to age and atherosclerosis

Leczenie nadciśnienia tętniczego u pacjenta z towarzyszącym łagodnym rozrostem stercza. Punkt widzenia hipertensjologa i urologa

U mężczyzn w podeszłym wieku nadciśnienie tętnicze często współistnieje z rozrostem gruczołu krokowego. Grupą leków wykorzystywaną w leczeniu obu tych chorób są &#945;1-adrenolityki. W związku z tym przez wiele lat, zgodnie z zasadami indywidualizacji terapii hipotensyjnej, &#945;1-adrenolityki uznawano za leki z wyboru w przypadku współistniejącego rozrostu stercza. Sytuację zmieniło ukazanie się wyników badania ALLHAT, w którym wykazano, że ryzyko incydentów sercowo-naczyniowych, a szczególnie nowych przypadków niewydolności serca, u pacjentów leczonych &#945;1-adrenolitykiem jest istotnie większe niż w przypadku leczenia diuretykiem tiazydowym. Od tego czasu &#945;1-adrenolityki nie są rekomendowane jako leki I rzutu również u pacjentów z towarzyszącym łagodnym rozrostem stercza, natomiast stanowią możliwy element terapii skojarzonej w III i IV rzucie. Istnieją trzy podtypy receptorów &#945;1: A i D, zlokalizowane głównie w dolnych drogach moczowych i gruczole krokowym oraz receptory B, umiejscowione preferencyjnie w mięśniówce tętnic. Blokada receptorów &#945;1A i &#945;1D umożliwia poprawę zespołu dolegliwości ze strony dolnych dróg moczowych (LUTS) związanych z łagodnym rozrostem stercza, natomiast blokada receptorów &#945;1B jest odpowiedzialna za efekt hipotensyjny, ale także za typowe objawy niepożądane &#945;1-adrenolityków (hipotonia ortostatyczna, omdlenia związane z efektem pierwszej dawki). Leki &#945;1-adrenolityczne dzieli się na nieuroselektywne (np. doksazosyna), czyli blokujące receptory &#945;1A i &#945;1B oraz uroselektywne (tamsulosyna), czyli blokujące preferencyjnie receptory &#945;1A w sterczu. Jedynie &#945;1-adrenolityki nieuroselektywne posiadają istotne działanie hipotensyjne, ale częściej wywołują działania niepożądane ze strony układu krążenia. Stosowane obecnie &#945;1-adrenolityki posiadają preparaty o przedłużonym uwalnianiu, które stwarzają znacznie mniejsze ryzyko hipotonii ortostatycznej i powinny być preferowane. Leczenie nadciśnienia tętniczego i łagodnego rozrostu stercza powinno być prowadzone niezależnie przez hipertensjologa i urologa. Decyzja o wyborze leków hipotensyjnych leży w rękach hipertensjologa, który powinien kierować się ogólnymi zasadami terapii nadciśnienia u osób w podeszłym wieku. Decyzja o zastosowaniu &#945;1-adrenolityka ze względu na objawy rozrostu stercza powinna należeć do urologa, z uwzględnieniem optymalnie bezpiecznego preparatu uroselektywnego, na przykład tamsulosyny, niezależnie od obecności nadciśnienia tętniczego. W przypadku konieczności intensyfikacji leczenia hipotensyjnego, hipertensjolog może podjąć, w porozumieniu z urologiem, decyzję o dołączeniu w III rzucie lub zamianie &#945;1-adrenolityka uroselektywnego na nieuroselektywny, na przykład doksazosynę, o działaniu hipotensyjnym. Forum Medycyny Rodzinnej 2010, vol. 4, no 2, 97-10

The structure and stability of beta-Ta thin films

Ta films with tetragonal crystalline structure (beta-phase), deposited by magnetron sputtering on different substrates (steel, silicon and silicon dioxide), have been studied. In all cases, very highly preferred (001) orientation was observed in x-ray diffraction (XRD) measurements. All diffraction data revealed two weak reflections corresponding to d-spacing of 0.5272 and 0.1777 nm. The presence of the two peaks, attributed to (001) and (003) reflections, indicates that beta-Ta films exhibit a high preference for the space group of P-421m over P42/mnm, previously proposed for beta-Ta. Differences in relative intensities of (00l) reflections, calculated for single crystal beta-Ta sigma-type Frank-Kasper structure and those measured in the films, are attributed to defects in the films. Molecular dynamics simulations performed on tantalum clusters with six different initial configurations using the embedded-atom-method (EAM) potential revealed the stability of beta-Ta, which might explain its growth on many substrates under various deposition conditions.Comment: 27 pages, 6 figures,1 tabl

Preoperative quantification of aortic valve stenosis: comparison of 64-slice computed tomography with transesophageal and transthoracic echocardiography and size of implanted prosthesis

Precise measurements of aortic complex diameters are essential for preoperative examinations of patients with aortic stenosis (AS) scheduled for aortic valve (AV) replacement. We aimed to prospectively compare the accuracy of transthoracic echocardiography (TTE), transoesophageal echocardiography (TEE) and multi-slice computed tomography (MSCT) measurements of the AV complex and to analyze the role of the multi-modality aortic annulus diameter (AAd) assessment in the selection of the optimal prosthesis to be implanted in patients surgically treated for degenerative AS. 20 patients (F/M: 3/17; age: 69 ± 6.5 years) with severe degenerative AS were enrolled into the study. TTE, TEE and MSCT including AV calcium score (AVCS) assessment were performed in all patients. The values of AAd obtained in the long AV complex axis (TTE, TEE, MSCT) and in multiplanar perpendicular imaging (MSCT) were compared to the size of implanted prosthesis. The mean AAd was 24 ± 3.6 mm using TTE, 26 ± 4.2 mm using TEE, and 26.9 ± 3.2 in MSCT (P = 0.04 vs. TTE). The mean diameter of the left ventricle out-flow tract in TTE (19.9 ± 2.7 mm) and TEE (19.5 ± 2.7 mm) were smaller than in MSCT (24.9 ± 3.3 mm, P < 0.001 for both). The mean size of implanted prosthesis (22.2 ± 2.3 mm) was significantly smaller than the mean AAd measured by TTE (P = 0.0039), TEE (P = 0.0004), and MSCT (P < 0.0001). The implanted prosthesis size correlated significantly to the AAd: r = 0.603, P = 0.005 for TTE, r = 0.592, P = 0.006 for TEE, and r = 0.791, P < 0.001 for MSCT. Obesity and extensive valve calcification (AV calcium score ≥ 3177Ag.U.) were identified as potent factors that caused a deterioration of both TTE and MSCT performance. The accuracy of AAd measurements in TEE was only limited by AV calcification. In multivariate regression analysis the mean value of the minimum and maximum AAd obtained in MSCT-multiplanar perpendicular imaging was an independent factor (r = 0.802, P < 0.0001) predicting the size of implanted prosthesis. In patients with AS echocardiography remains the main diagnostics tool in clinical practice. MSCT as a 3-dimentional modality allows for accurate measurement of entire AV complex and facilitates optimal matching of prosthesis size