Direct visualization of aorto-coronary bypass grafts by two-dimensional echocardiography: A new clinical application

An attempt was made to assess noninvasively the patency of aorto-coronary bypass grafts by two-dimensional echocardiography (2-D echo) in 21 patients who underwent myocardial revascularization. Fifteen patients had one graft while the other six had two grafts. All 21 patients underwent angiography 6–18 months after operation. A day before angiography a 2-D echo was performed with the aim of visualizing the bypass grafts. In 18 patients with 23 grafts (13 with 1 graft and 5 with 2 grafts) it was possible to visualize the tract of the graft, by 2-D echo; 16 were judged patent on 2-D echo and confirmed by selective angiography, while 5 grafts were considered occluded both on 2-D echo and angiography. The other 2 grafts were considered to be occluded on 2-D echo but angiographic control displayed their patency. In 3 patients 2-D echo failed to visualize grafts that were patent angiographically. These data must be considered preliminary and need validation in a larger number of patients. However it is reasonable to conclude that 2-D echo has a reliable capacity to predict graft patency. Such an application may be of value in sequential control of patients with aorto-coronary bypass surgery, especially when combined with other clinical and/or technical data.     

Endovascular treatment for superior vena cava obstruction in Behçet disease

Beh?et disease is a heterogeneous, multisystem inflammatory disorder; vascular involvement has been considered to result from systemic vasculitis, which most frequently affects veins and occurs in 5% to 10% of these patients. However, superior vena cava (SVC) involvement is rare; it accounts for only 6% of the cases. The aim of this article is to a report on a case of SVC recanalization through the use of fibrinolysis and self-expanding stents as treatment of life-threatening SVC syndrome in a young male patient with Beh?et disease.     

Different patterns of extracellular matrix protein expression in the convexity and the concavity of the dilated aorta with bicuspid aortic valve: preliminary results

OBJECTIVE: This study aimed to assess extracellular matrix protein expression patterns at the convexity (right anterolateral wall) and the concavity of the dilated ascending aorta in patients with bicuspid aortic valve disease. METHODS: Aortic wall specimens were retrieved from the convexity and the concavity in 27 bicuspid aortic valve patients (12 with stenosis and 15 with regurgitation) and 6 heart donors (controls). Morphometry, immunohistochemistry, Western blot, and polymerase chain reaction were performed, focusing on matrix proteins involved in vascular remodeling. RESULTS: Type I and III collagens were significantly decreased in bicuspid-associated dilated aortas versus controls (P < .001), particularly at the convexity (P < .05 vs concavity). Expression of messenger RNA for collagens was lower than normal only in the regurgitant subgroup. At immunohistochemistry, proteins whose overproduction has been demonstrated in response to abnormal wall stress, such as tenascin and fibronectin, were more expressed in the convexity than in the concavity, especially in the stenosis subgroup. Tenascin, which is produced by smooth muscle cells in the synthetic phenotype, was nearly undetectable in controls. Fewer smooth muscle cells (stenosis, P = .017; regurgitation, P = .008) and more severe elastic fiber fragmentation (P = .029 and P < .001) were observed in the convexity versus the concavity. CONCLUSIONS: In bicuspid-associated aortic dilations, an asymmetric pattern of matrix protein expression was found that was consistent with the asymmetry in wall-stress distribution reported previously. Differences exist between patients with stenosis and those with regurgitation in terms of protein expression and content in the aortic wall. Further studies could clarify the relations between these findings and the pathogenesis of aortic dilatation in bicuspid aortic valve patients.     

Malignant melanoma in a candidate for heart transplantation

A superficial spreading melanoma (Breslow thickness 0.4 mm) was diagnosed in a 65-year-old candidate for heart transplantation due to refractory end stage heart failure. After extensive review of the literature (USA and Europe), no clear guidelines about the management of candidates for transplantation with a previous diagnosis of melanoma were found. As this patient had a 5-year probability of survival higher than 95% and heart transplantation was necessary for saving his life, the final decision was to perform the transplantation. Unfortunately, the patient died of heart failure before a suitable heart became available. This case stresses the need for early and continuous dermatological evaluation of all candidates for solid organ transplantation. Clear guidelines for screening of skin cancer before transplantation are needed.     

The role of interventional radiology in the management of kidney transplant complications

PURPOSE: To evaluate the role and the effectiveness of interventional radiology in the treatment of renal transplant complications. MATERIALS AND METHODS: From 1996 to 2004 a total of 288 kidney transplants from cadavers were performed in our Institute. The kidney was always collocated in iliac fossa by creating a vascular anastomosis with the external iliac artery and vein; in all cases the ureter was implanted into the recipient bladder. During the follow-up, 34 complications were observed. Twenty-seven complications in 25 patients (20 males and 5 females; age 35-65 years) were treated by a radiologic procedure: 9 renal artery stenosis and 1 native external iliac artery stenosis (by PTA), 5 ureteral obstructions (by nephrostomy and ureteral stenting), 8 ureteral leaks (by nephrostomy, in 2 cases associated to ureteral stenting) and 4 limphoceles (by percutaneous ultrasound-guided catheter drainage). RESULTS: Primary technical success was obtained in 20/27 cases (74%). Success was obtained with a second interventional procedure in 3/27 cases, 2 limphoceles and 1 ureteral fistula (secondary technical success: 85.2%), with a clinical final success in 23/27 cases (85.2%). We observed a peri-procedural complication rate of 3.7% (1 renal artery post-PTA dissection during a restenosis treatment). Four cases (1 renal arterial post-PTA dissection, 1 ureteral obstruction, 1 ureteral leak and 1 limphocele) needed a surgical correction (14.8%). CONCLUSIONS: Interventional radiology is the first therapeutic approach to treat renal transplant complications. It shows good technical and clinical results and a low complication rate. Surgery had to be considered only if minimally invasive procedures are infeasible or ineffective.     

Contrast-enhanced MR Angiography of the renal arteries: blinded multicenter crossover comparison of gadobenate dimeglumine and gadopentetate dimeglumine

PURPOSE: To prospectively and intraindividually compare 0.1 mmol/kg gadobenate dimeglumine with 0.2 mmol/kg gadopentetate dimeglumine for contrast material-enhanced magnetic resonance (MR) angiography of the renal arteries. MATERIALS AND METHODS: Institutional review board approval was granted by each of three participating centers. The study accorded with international standards for good clinical practice and Declaration of Helsinki and subsequent amendments. Patients gave written informed consent before enrollment. Patients (n = 34) underwent two MR angiographic examinations more than 48 hours but less than 12 days apart. Gadobenate dimeglumine followed by gadopentetate dimeglumine was administered in 18 patients; the order of administration was reversed in 16 patients. A 1.5-T MR imager was used with a phase-encoded three-dimensional spoiled breath-hold pulse sequence. Two blinded independent readers qualitatively assessed randomized subtracted maximum intensity projection images. A three-point scale for diagnostic quality (0, poor; 1a or 1p, moderate; and 2a or 2p, adequate [a and p refer, respectively, to absence and presence of vascular lesions]) was used to score each of nine segments of the abdominal aorta and both renal arteries (possible overall score, 18). Quantitative assessment (vessel signal-to-noise ratio [SNR], vessel-muscle contrast-to-noise ratio [CNR]) of source images was performed for regions of interest in supra-, juxta-, and infrarenal aorta segments and psoas muscle. Data were tested with analysis of variance for two-period crossover design. Interreader agreement was evaluated with Cohen kappa statistics. RESULTS: No difference in mean image quality between the two contrast agents was observed; scores for gadobenate dimeglumine and gadopentetate dimeglumine were 15.15 and 15.23 for reader 1 and 16.77 and 17.01 for reader 2. The order of contrast material administration likewise produced no quality differences: readers 1 and 2 reported scores of 14.4 +/- 4.2 (standard deviation) and 16.7 +/- 2.3, respectively, when gadobenate dimeglumine was given first, and 15.2 +/- 1.8 and 16.6 +/- 1.6, respectively, when gadopentetate dimeglumine was given first. Results of quantitative evaluation showed increasing SNR and CNR with gadobenate dimeglumine in segments at progressively lower levels of the aorta, but increases in SNR and CNR at the infrarenal aorta (48.3 vs 40.6 and 44.2 vs 36.4, respectively) were not significant (P = .05 for both). CONCLUSION: Gadobenate dimeglumine at a dose of 0.1 mmol/kg is comparable to gadopentetate dimeglumine at 0.2 mmol/kg for contrast-enhanced renal MR angiography.     

Promoter methylation controls the expression of MAGE2, 3 and 4 genes in human cutaneous melanoma

Cancer-testis antigens expressed by different-histotype transformed cells are suitable targets for tumor immunotherapy. However, their heterogeneous expression in neoplastic lesions limits the eligibility of patients for cancer-testis antigen-directed vaccination, and low levels of cancer-testis antigens' expression may impair immune recognition of malignant cells. Because of the primary clinical relevance of cancer-testis antigens' expression in neoplastic tissues, 68 unrelated or sequential metastatic lesions from 56 patients were used to characterize the molecular mechanisms regulating the presence and levels of expression of different cancer-testis antigens of the MAGE family (i.e., MAGE2, 3 and 4) in cutaneous melanoma. Polymerase chain reaction-based methylation analyses showed that methylation status of specific cytosine-guanine dinucleotides in the promoters of investigated cancer-testis antigens correlated with their heterogeneous expression within unrelated metastatic melanoma lesions, and with their homogeneous expression among sequential metastases from three patients with melanoma. Unlike methylated promoters, unmethylated promoters of MAGE2, 3 and 4 genes drove the expression of reporter gene-enhanced green fluorescent protein after transient transfection of cancer-testis antigen-positive Mel 142 melanoma cells. Furthermore, de novo expression of MAGE3 gene induced by the treatment of Mel 195 melanoma cells with the DNA hypomethylating agent 5-aza-2'-deoxycytidine was associated with a 6%-12% demethylation of selected cytosine-guanine dinucleotides in its promoter. Finally, 5-aza-2'-deoxycytidine induced a 16-fold increase of MAGE3 expression in Mel 313 melanoma cells expressing constitutively low levels of the antigen, but did not affect that of Mel 275 melanoma cells expressing high baseline levels of MAGE3. Overall, these findings identify promoter methylation as a shared mechanism directly regulating the expression of therapeutic cancer-testis antigens in metastatic melanomas, and foresee the clinical use of 5-aza-2'-deoxycytidine to design new chemoimmunotherapeutic strategies in patients with melanoma.     

Leeches: immune response,angiogenesis and biomedical applications

The innate immune response is the first line of defence strategies in invertebrates against attack of infectious agents. A detailed analysis of the immune mechanisms involved in annelids has been performed in oligochaets, but few data are available in polichaets and hirudineans. The aim of this review is to describe the responses of leeches to different kinds of stimuli (infections following non-self agent attacks, surgical lesions, grafts). Furthermore, the use of this invertebrate as a novel experimental model to be used to screen drugs and genes, which are responsible for positive and negative modulation of angiogenesis, is discussed.     

Comparative analysis of immune responses and cytokine profiles elicited in rabbits by the combined use of recombinant fowlpox viruses,plasmids and virus-like particles in prime-boost vaccination protocols against SHIV

Three different prime-boost immunization protocols were tested in rabbits and their immune response was evaluated and compared with the final aim of identifying a vaccine strategy that might be able to protect non-human primates from infection with the pathogenic chimera simian/human immunodeficiency virus (SHIV)(89.6P). Protocols were based on priming with two fowlpox (FP) recombinant vectors and two expression plasmids, which express either the simian immunodeficiency virus (SIV)mac(239) gag/pol or the human immunodeficiency virus (HIV-1)env(89.6P) genes, followed by boosting with virus-like particles (VLP). All protocols were effective in eliciting homologous neutralizing Ab and highlighted the efficacy of VLP boosting. The FP vector was less efficient than plasmid DNA in inducing Ab against the gag core proteins. Analysis of cytokine expression 5 months after last immunization indicated that priming with pcDNA3gag/pol(SIV) and FPenv(89.6P) followed by VLP boosting generated a T helper (Th0) profile and a good Ab titer, suggesting a potential protocol to be tested in the SHIV-macaque model of HIV-1 infection.