Sonographic appearance of gestational trophoblastic disease evolving into epithelioid trophoblastic tumor

Epithelioid trophoblastic tumor is a distinctive but rare trophoblastic tumor. It derives from intermediate trophoblastic cells of the chorion laeve and is usually associated with a previous gestational event. We report the case of a patient who had undergone dilatation and curettage for a missed miscarriage. Three months later gestational trophoblastic disease was suspected because of persistent vaginal bleeding and high levels of beta-human chorionic gonadotropin (beta-hCG). Transvaginal ultrasound revealed irregular echolucent lacunae within the myometrium, some of them filled with low-resistance, turbulent blood flow on Doppler examination, emphasizing the diagnosis of gestational trophoblastic disease. The patient was treated with 12 courses of multiagent chemotherapy. After a 2-year remission, a low rise in serum beta-hCG was observed. Transvaginal ultrasound revealed a well-circumscribed echogenic lesion with a diameter of 1.8 cm in the uterine fundus, with no detectable blood flow on Doppler imaging. A diagnosis of tumor of intermediate trophoblastic cells was suspected and total hysterectomy was performed. On pathological examination, the histological and immunohistochemical features were characteristic of epithelioid trophoblastic tumor. Most reported cases of epithelioid trophoblastic tumor have solitary nodules with sharp margins, which is consistent with our ultrasound findings. Ultrasound may be helpful in differentiating epithelioid trophoblastic tumor from placental-site trophoblastic tumor, another tumor of intermediate trophoblastic cells, which shows infiltrative growth insinuating between muscle fibers. Copyright (C) 2010 ISUOG. Published by John Wiley & Sons, Ltd.

The Versatile Adani`s Flap for Fingertip Coverage Indications and Case Reports

Heterodigital pedicle flaps have 2 possible patters of vascularization: anterograde flow (Littler) or reverse flow (Adani). The Adani`s flap uses the Y-V pedicle lengthening principle. The flap is raised from the adjacent uninjured finger based on the digital artery. The common digital artery is ligated and a long pedicle is formed from the 2 converging digital arteries to supply a reverse flow flap. Four patients with severe fingertips injuries were submitted to surgical treatment with the Adani`s flap. All flaps integrated and provided skin coverage. The Adani`s flap has a long vascular pedicle that allows a wide arch of transposition. An easier vascular dissection in a site distant from the trauma which evolves a higher diameter digital artery and proximal interphalangeal arterial system promotes a high survival rate and good functional results. Adani`s flap is a reliable technique for severe fingertip injuries.

Induction of CRP3/MLP expression during vein arterialization is dependent on stretch rather than shear stress

Aims Cysteine- and glycine-rich protein 3/muscle LIM-domain protein (CRP3/MLP) mediates protein-protein interaction with actin filaments in the heart and is involved in muscle differentiation and vascular remodelling. Here, we assessed the induction of CRP3/MLP expression during arterialization in human and rat veins. Methods and results Vascular CRP3/MLP expression was mainly observed in arterial samples from both human and rat. Using quantitative real time RT-PCR, we demonstrated that the CRP3/MLP expression was 10 times higher in smooth muscle cells (SMCs) from human mammary artery (h-MA) vs. saphenous vein (h-SV). In endothelial cells (ECs), CRP3/MLP was scarcely detected in either h-MA or h-SV. Using an ex vivo flow through system that mimics arterial condition, we observed induction of CRP3/MLP expression in arterialized h-SV. Interestingly, the upregulation of CRP3/MLP was primarily dependent on stretch stimulus in SMCs, rather than shear stress in ECs. Finally, using a rat vein in vivo arterialization model, early (1-14 days) CRP3/MLP immunostaining was observed predominantly in the inner layer and later (28-90 days) it appeared more scattered in the vessel layers. Conclusion Here we provide evidence that CRP3/MLP is primarily expressed in arterial SMCs and that stretch is the main stimulus for CRP3/MLP induction in veins exposed to arterial haemodynamic conditions.

Human choriogonadotropin prior to controlled ovarian stimulation and in vitro fertilization improves implantation, and pregnancy rates

Our purpose was to retrospectively compare controlled ovarian stimulation(COH) in IVF cycles with administration of hCG on the day of menses (D1-hCG) with women not receiving hCG at day 1 of menses (Control). Data on maternal age, endocrine profile, amount of rFSH required, embryo characteristics, implantation and pregnancy rates were recorded for comparison between D1-hCG (n = 36) and Control (n = 64). Dose of rFSH required to accomplish COH was significantly lower in D1-hCG. Following ICSI, more top-quality embryos were available for transfer per patient in the D1-hCG and biochemical pregnancy rates per transfer were significantly higher in the D1-hCG. Significantly higher implantation and on-going pregnancy rates per embryo transfer were observed in D1-hCG (64%) compared to Control (41%). Administration of D1-hCG prior to COH reduces rFSH use and enhances oocyte developmental competence to obtain top quality embryos, and improves implantation and on-going pregnancy rates. At present it is not clear if the benefit is related to producing an embryo that more likely to implant or a more receptive uterus, or merely fortuitous and related to the relatively small power of the study.

Effects of Chronic Exposure to Crack Cocaine on the Respiratory Tract of Mice

Smoked cocaine (crack cocaine) causes several forms of injury to the respiratory tract, including asthma exacerbations, lung edema and hemorrhage, and nasal mucosal alterations. Few studies, however, have assessed respiratory tract pathology in habitual users of crack cocaine. Here, we describe the histological alterations in the respiratory tract of mice caused by chronic inhalation of crack cocaine. Twenty 2-month-old BALB/c mice were exposed to the smoke of 5 g crack cocaine in an inhalation chamber once a day for two months and compared to controls (n = 10). We then morphometrically analyzed nose and bronchiolar epithelial alterations, bronchiolar and alveolar macrophage cell density, alveolar hemosiderin content, and in addition determined the vasoconstriction index and the wall thickness of pulmonary arteries. The serum cocaine level was 212.5 ng/mL after a single inhalation. The mucus content of the nasal epithelium increased in crack-exposed animals, and the nasal and bronchial epithelium thickness decreased significantly. The alveolar hemosiderin content and the alveolar and bronchiolar macrophage cell density increased in animals exposed to crack. The vasoconstriction index increased in the pulmonary arteries of the exposed group. Chronic crack cocaine inhalation causes extensive histological changes along the entire respiratory tract.

Conus perimedullary arteriovenous fistula in a child: unusual angio-architectural features and pathophysiology

Introduction The perimedullary arteriovenous fistulas are located on the pial surface and are usually supplied by spinal medullary arteries, that is, either by the anterior or posterior spinal arteries, with no intervening nidus between the feeder arteries and the venous drainage. The clinical findings are, more commonly, caused by progressive radiculomedullary ischemic processes secondary to steal vascular mechanism. As the vascular supply to the spinal cord and to the arteriovenous fistulas (AVF) is not shared with one another, the vascular steal phenomenon cannot be implicated in this case`s physiopathology. Most probably, the mass effect caused by the giant venous dilatation was the pathophysiological mechanism involved in this lesion Case report The authors describe the case of a 6-year-old girl with an intradural ventral arteriovenous fistula, with a giant venous dilatation, fed directly by L2 and L3 radiculomedullary arteries at the conus medullaris. There was no arterial supply to the fistula from the anterior or posterior spinal arteries. Selective spinal angiography showed an arteriovenous fistula supplied directly by two radiculomedullary arteries, with a large draining vein caudally. Interposing the arterial and venous vessels was a giant venous aneurysmal dilatation located ventral to the conus medullaris and extending from L3 to T6. The patient was successfully treated by a surgical approach through a laminotomy from L3 to T11. Conclusion The type IV-C spinal arteriovenous malformations or perimedullary AVFs are rare lesions predominately described at the conus medullaris with various types of angio-architecture and controversial treatment.

Cellular prion protein (PrP(C)) and superoxide dismutase (SOD) in vascular cells under oxidative stress

The PrP(C) is expressed in several cell types but its physiological function is unknown. Some studies associate the PrP(C) with copper metabolism and the antioxidant activity of SOD. Our hypothesis was that changes in PrP(C) expression lead to abnormal copper regulation and induce SOD downregulation in the vascular wall. Objectives: to study whether the PrP(C) expression undergoes induction by agents that trigger endoplasmic reticulum stress (ERS) and, in this context, to evaluate the SOD activity. Methods: To trigger ERS, in vitro, rabbit aortic smooth muscle cells were challenged for 4, 8 and 18 hours, with angiotensin-II, tunicamycin and 7-ketocholesterol. For in vivo studies rabbit aortic arteries were subjected to injury by balloon catheter. Results: In vitro baseline SOD activity, determined through inhibition of cytochrome-c reduction, was 13.9 +/- 1.2 U/mg protein, angiotensin-II exposed for 8 hours produced an increase in SOD activity, and cellular copper concentration was about 9 times greater only under these conditions. Western blotting analysis for SOD isoenzymes showed an expression profile that was not correlated with the enzymatic activity. PrP(C) expression decreased after exposure to all agents after different incubation periods. RT-PCR assay showed increased mRNA expression for PrP(C) only in cells stimulated for 8 hours with the different stressors. The PrP(C) mRNA expression in rabbit aortic artery fragments, subjected to balloon catheter injury, showed a pronounced increase immediately after overdistension. The results obtained indicated a PrP(C) protection factor during the early part of the ERS exposure period, but did not demonstrate a SOD-like profile for the PrP(C). (C) 2009 Elsevier GmbH. All rights reserved.

Change in blood flow velocity demonstrated by Doppler ultrasound in upper limb after axillary dissection surgery for the treatment of breast cancer

The aim of this study was to evaluate the arterial and venous blood flow in women who underwent upper limb axillary dissection surgery for the treatment of breast cancer. Sixty women were divided into two groups: group 1 (G1)-30 women who underwent breast surgery with axillary dissection level II or III (55.6 +/- A 8.6 years); group 2 (G2)-control, 30 women with no breast cancer (57.4 +/- A 7.0 years). Blood flow profile was evaluated by a continuous wave ultrasound Doppler device (Nicolet Vascular Versalab SE(A (R))) with an 8 MHz probe. Axillary, brachial arteries and veins, arm circumference, volumes, and the ankle-brachial index (ABI) were examined. Wilcoxon test and Mann-Whitney tests were applied to analyze blood flow velocity intra-group and between G1 and G2, respectively. The G1 results showed no lymphedema and no peripheral arterial disease (ABI > 0.9). Moreover, the mean blood flow velocity of the vessels ipsilateral to the surgery was significantly higher than the contralateral ones for all vessels examined (P < 0.05). The mean velocity of blood flow of the vessels contralateral to surgery was significantly higher than the axillary artery in G2 (P < 0.05). It can be concluded that women who underwent axillary dissection due to breast cancer showed probable stenosis in the arterial and venous axillary and brachial vessels of the upper limb ipsilateral to the surgery, confirmed by the increase of blood flow velocity, and such obstruction might affect the limb contralateral to the operation site.

Asymmetric dimethylarginine endogenous inhibition of nitric oxide synthase causes differential vasculature effects

Background: Asymmetric dimethylarginine (ADMA), produced during protein metabolism, is an endogenous inhibitor of nitric oxide synthase, but little is known about its direct vasoactive properties in different arterial beds. Material/Methods: Segments of canine coronary, renal, and femoral arteries were pretreated with increasing concentrations of ADMA, and endothelial function was evaluated in organ chambers. Results: In precontracted canine coronary arteries, the highest concentrations of ADMA inhibited endothelium-dependent relaxation mediated by acetylcholine (n=7), but no concentration of ADMA inhibited receptor-independent relaxation mediated by calcium ionophore (n=7) (P<.001). The effect of ADMA on acetylcholine-mediated relaxation was shown to be competitive inhibition of the nitric oxide synthase pathway, because the addition of L-arginine (10(-3) M), but not D-arginine (101 M), reversed the effect produced by 10(-5) M ADMA. Further, ADMA did not alter endothelium-independent relaxation mediated by sodium nitroprusside (10(-9) to 10(-6) M; n=7). Femoral arteries (n=7) and renal arteries (n=7) were more sensitive to ADMA than were coronary arteries, and they demonstrated significant ADMA inhibition to receptor dependent relaxation induced by acetylcholine (P=.03 and P=.01, respectively) and to receptor-independent relaxation induced by calcium ionophore (P=.02 and P=.01, respectively). Conclusions: Endothelium-dependent relaxation mediated by ADMA is more marked in femoral and renal arteries than in coronary arteries. The response in coronary arteries may be overall protective. Considering these different effects in various artery types, the role of ADMA as a confiable and specific cardiovascular risk factor is questioned.

An anatomical study on the lingual-facial trunk

Purpose We quantified variations of the lingual artery origin, measured the lingual artery origin distance from clinical relevant landmarks and compared the lingual artery diameters with normal and variable origin. Methods Forty-two formalin fixed male cadavers were bilaterally evaluated. Measurements were performed with the aid of an electronic digital caliper. Results The origin distances from the common carotid artery bifurcation was 1.05 +/- 0.11 and 1.02 +/- 0.11 cm for the right and left lingual arteries respectively with no differences compared to the lingual-facial trunks. The diameters of the lingual arteries were 0.25 +/- 0.01 and 0.26 +/- 0.01 cm for the right and left sides, respectively, while the lingual facial trunks showed diameters of 0.21 +/- 0.02 and 0.24 +/- 0.02 cm for the right and left sides, respectively. Conclusions The present study adds information on the lingual artery diameter and its anatomical relation to clinically useful landmarks.

Plasma nitrate/nitrite (NOx) is not a useful biomarker to predict inherent cardiopulmonary bypass inflammatory response

Background and Aim: There were strong evidences that nitric oxide has capital importance in the progressive vasodilatation associated with varied circulatory shock forms, including systemic inflammatory response syndrome (SIRS), in patients undergoing cardiac surgeries for cardiopulmonary bypass (CPB). If CPB procedures, per se, are the inciting stimulus for inflammation, plasma nitrate/nitrite (NOx) excretion would be expected to be higher in these patients rather than in patients operated without CPB. In consequence, we hypothesized that increased levels of NOx would be predictive for vasoplegic syndrome. Methods: Thirty patients were assigned to three groups: Group 1-coronary artery bypass graft (CABG) roller pump CPB; Group 2-CABG centrifugal vortex pump CPB; and Group 3-heart valve surgery roller pump CPB. Sampling of venous blood for chemiluminescence plasma NOx dosage was achieved at the following time points: (1) before anesthesia induction; (2) after anesthesia induction; (3) before heparin infusion; (4) after heparin infusion; (5) CPB-30 minutes; (6) CPB-60 minutes; (7) before protamine infusion; (8) after protamine infusion; and (9) on return to the recovery area. Results: There were no intergroup differences regarding age and anesthetic regimen, and the number of arteries grafted was not different between the CABG groups. There were no NOx statistic differences, neither among the three groups of patients or among the surgery time. In addition, there was no correlation among NOx, lactate, and hemoglobin. Conclusions: Considering the inflammatory process intrinsic to CPB, this study reinforces the idea that plasma NOx is not useful as a biomarker of inflammatory response onset, which may or may not lead to SIRS and/or vasoplegic syndrome.

Changes in Myocardial Perfusion Correlate With Deterioration of Left Ventricular Systolic Function in Chronic Chagas` Cardiomyopathy

OBJECTIVES This study aimed at analyzing the association between myocardial perfusion changes and the progression of left ventricular systolic dysfunction in patients with chronic Chagas` cardiomyopathy (CCC). BACKGROUND Pathological and experimental studies have suggested that coronary microvascular derangement, and consequent myocardial perfusion disturbance, may cause myocardial damage in CCC. METHODS Patients with CCC (n = 36, ages 57 +/- 10 years, 17 males), previously having undergone myocardial perfusion single-positron emission computed tomography and 2-dimensional echocardiography, prospectively underwent a new evaluation after an interval of 5.6 +/- 1.5 years. Stress and rest myocardial perfusion defects were quantified using polar maps and normal database comparison. RESULTS Between the first and final evaluations, a significant reduction of left ventricular ejection fraction was observed (55 +/- 11% and 50 +/- 13%, respectively; p = 0.0001), as well as an increase in the area of the perfusion defect at rest (18.8 +/- 14.1% and 26.5 +/- 19.1%, respectively; p = 0.0075). The individual increase in the perfusion defect area at rest was significantly correlated with the reduction in left ventricular ejection fraction (R = 0.4211, p = 0.0105). Twenty patients with normal coronary arteries (56%) showed reversible perfusion defects involving 10.2 +/- 9.7% of the left ventricle. A significant topographic correlation was found between reversible defects and the appearance of new rest perfusion defects at the final evaluation. Of the 47 segments presenting reversible perfusion defects in the initial study, 32 (68%) progressed to perfusion defects at rest, and of the 469 segments not showing reversibility in the initial study, only 41 (8.7%) had the same progression (p < 0.0001, Fisher exact test). CONCLUSIONS In CCC patients, the progression of left ventricular systolic dysfunction was associated with both the presence of reversible perfusion defects and the increase in perfusion defects at rest. These results support the notion that myocardial perfusion disturbances participate in the pathogenesis of myocardial injury in CCC. (J Am Coll Cardiol Img 2009;2:164-72) (c) 2009 by the American College of Cardiology Foundation

Turbulent blood flow plays an essential localizing role in the development of atherosclerotic lesions in experimentally induced hypercholesterolaemia in rats

Taking into account that atherosclerosis is a focal disease and high levels of plasma cholesterol are closely correlated with its pathogenesis, it is a challenge to explain how equal concentrations of cholesterol bathing the endothelium can produce local, rather than global, effects on arteries. The focal distribution of atherosclerotic lesions has been considered to be dependent, at least in part, on hydrodynamic factors. The present study was carried out to further test the hypothesis that these forces are an important localizing factor in rats feeding a hypercholesterolaemic diet and submitted to infra-diaphragmatic aortic constriction. These animals develop a normotensive prestenotic region with laminar blood flow that serves as control for a normotensive poststenotic region with turbulent blood flow. Our findings clearly demonstrated that the combination of turbulent blood flow and low wall shear stress (WSS) in the presence of hypercholesterolaemia and oxidative stress creates conditions to the formation of focally distributed incipient atherosclerotic lesions observed in the poststenotic segment. In contrast, only diffuse fatty streaks could be observed in the normotensive prestenotic segment with laminar blood flow and normal WSS in the presence of hypercholesterolaemia and oxidative stress. Although haemodynamic forces are not by themselves responsible for the pathogenesis of atherosclerosis, they prime the local vascular wall in which the lesion develop. Further studies are required to establish how haemodynamic forces are detected and transduced into chemical signalling by the cells of the artery wall and then converted into pathophysiologically relevant phenotypic changes.

Sildenafil inhibits duodenal contractility via activation of the NO-K+ channel pathway

Phosphodiesterase type-5 (PDE5) specifically cleaves cyclic guanosine monophosphate (cGMP), a key intracellular secondary messenger. The PDE5 inhibitor sildenafil is a well-known vasodilator that also has gastrointestinal myorelaxant properties. In the present study, we further investigated sildenafil-induced myorelaxation in rat isolated duodenum, assessing its interaction with nitric oxide (NO) synthase and K+ channel opening. The spontaneous contractions of duodenal strips were reversibly inhibited by sildenafil (0.1-300 mu M) in a concentration-dependent manner [mean (95% confidence interval); EC50 = 6.8 (2.7-17.3) mu M]. The sildenafil-induced myorelaxation was significantly decreased by the NO synthase inhibitor N-nitro-L-arginine methyl ester [increasing the EC50 value to 41.9 (26.1-67.3) mu M]. Sodium nitroprusside or forskolin pretreatments enhanced the sildenafil-induced myorelaxation. In isolated strips pretreated with BaCl2 (0.2 mM), 4-aminopyridine (4-AP, 3 mM), or glybenclamide (1 mu M), the sildenafil-induced EC50 value was significantly increased to 32.8 (19.1-56.4), 27.1 (15.2-48.3) and 20.1 (16.4-24.7) mu M, respectively. Minoxidil (50 mu M) or diazoxide (100 mu M) also significantly attenuated the sildenafil-induced potency. In conclusion, the NO synthase/cyclic nucleotide pathway activation is involved in sildenafil-induced inhibition of spontaneous duodenal contractions. Its pharmacological action seems to be influenced by K+ channel opening, especially the voltage-sensitive ones, being inhibited by 4-AP and K-ATP channels, sensitive to glybenclamide.

Assessment of Vascular Effects of Tamoxifen and Its Metabolites on the Rat Perfused Hindquarter Vascular Bed

Tamoxifen has been suggested to produce beneficial cardiovascular effects, although the mechanisms for these effects are not fully known. Moreover, although tamoxifen metabolites may exhibit 30-100 times higher potency than the parent drug, no previous study has compared the effects produced by tamoxifen and its metabolites on vascular function. Here, we assessed the vascular responses to acetylcholine and sodium nitroprusside on perfused hindquarter vascular bed of rats treated with tamoxifen or its main metabolites (N-desmethyl-tamoxifen, 4-hydroxy-tamoxifen, and endoxifen) for 2 weeks. Plasma and whole-blood thiobarbituric acid reactive substances (TBARS) concentrations were determined using a fluorometric method. Plasma nitrite and NOx (nitrite + nitrate) concentrations were determined using an ozone-based chemiluminescence assay and Griess reaction, respectively. Treatment with tamoxifen reduced the responses to acetylcholine (pD(2) = 2.2 +/- 0.06 and 1.9 +/- 0.05 after vehicle and tamoxifen, respectively; P < 0.05), while its metabolites improved these responses (pD(2) = 2.5 +/- 0.04 after N-desmethyl-tamoxifen, 2.5 +/- 0.03 after 4-hydroxy-tamoxifen, and 2.6 +/- 0.08 after endoxifen; P < 0.01). Tamoxifen and its metabolites showed no effect on endothelial-independent responses to sodium nitroprusside (P > 0.05). While tamoxifen treatment resulted in significantly higher plasma and whole blood lipid peroxide levels (37% and 62%, respectively; both P < 0.05), its metabolites significantly decreased lipid peroxide levels (by approximately 50%; P < 0.05). While treatment with tamoxifen decreased the concentrations of markers of nitric oxide formation by approximately 50% (P < 0.05), tamoxifen metabolites had no effect on these parameters (P > 0.05). These results suggest that while tamoxifen produces detrimental effects, its metabolites produce counteracting beneficial effects on the vascular system and on nitric oxide/reactive oxygen species formation.