Quantitative analysis of myocardial blood flow in surgically revascularized and not revascularized myocardial segments. A pilot PET study.

PURPOSE: To prospectively compare changes in myocardial blood flow (MBF) and myocardial flow reserve (MFR) in multivessel coronary artery disease (MVCAD) patients undergoing incomplete revascularization (IR) versus complete revascularization (CR) by coronary artery bypass grafting (CABG). METHODS: Seven male patients (age 68 ± 9 years) with MVCAD underwent myocardial perfusion PET/CT with [13N]ammonia before and at least 4 months after CABG. Segmental resting and stress MBF as well as MFR were measured. Resting and during stress left ventricle ejection fraction (LVEF) were also calculated. RESULTS: Three patients (43%) underwent CR and four (57%) IR. Among 119 myocardial segments, 101 (85%) were revascularized, and 18 (15%) were not. After CABG, stress MBF (mL/min/gr) and MFR are significantly increased in all myocardial segments, with a greater increase in the revascularized segments (p = 0.013). In both groups, LVEF significantly decreased during stress at baseline PET (p = 0.04), but not after CABG. CONCLUSION: Stress MBF and MFR significantly improve after CABG in both revascularized and not directly revascularized myocardial segments. IR strategy may be considered in patients with high surgical risk for CR.

Breast cancer and distress resulting from Magnetic Resonance Imaging (MRI): the impact of a psychological intervention of emotional and informative support.

The present study assesses the adaptation of a group of female patients with either manifest or suspected breast cancer who have undergone Magnetic Resonance Imaging (MRI) after receiving psychological support. Several studies in literature have reported the effectiveness of such support in reducing anti-oxidant and depression aspects related to MRI. Two random groups of patients, from the Service of Diagnostics Imaging of the Oncological Unit of the Regina Elena Institute of Rome, were enrolled. The experimental group (EG) received routine information together with extra psychological. The control group (CG) received only routine information. All the patients underwent a psychological evaluation, before (TO) and after (T1) the exam. The following evaluation instruments were used: the Crown Crisp Experimental Index (C.C. E.I.), the State-Trait Anxiety Inventory (S.T.A.I. Y1-Y2) and the Self Rating Depression Scale (S.D.S.) for TO and the State-Trait Anxiety Inventory (S.T.A.I. Y1 and the Self Rating Depression Scale (S.D.S.) for T1. Results prior to the MRI exam (TO), show that the women receiving extra information and emotional support (EG) suffer considerably less anxiety and depression compared to the control group. Results after the MRI exam (T1), indicate that the way the exam is carried out is also relevant in reducing anxiety. The level of anxiety, however, was significantly lower in the experimental group compared to the control. Depression levels, on the other hand, remained unaltered. Our results indicate that a psychological intervention aimed at providing more information and giving more emotional support helps patients adapt with a reduction of anxiety and depression.

Imbalance in the antioxidant pool in melanoma cells and normal melanocytes from patients with melanoma.

In order to evaluate the free radical defense systems of melanocytes and their possible correlation with melanoma, we have studied in cultured normal human melanocytes (20), normal melanocytes from melanoma patients (15), and melanoma cells (40) the fatty acid pattern of membrane phospholipids as a target of peroxidative damage and the superoxide dismutase and catalase activities, vitamin E, and ubiquinone levels as intracellular antioxidants. Cells were cultured in the same medium and analyzed at III or IV passage. Compared to the values obtained in normal human melanocytes, melanoma cells showed on average: a) higher levels of polyunsaturated fatty acids, b) increased superoxide dismutase and decreased catalase activities, higher vitamin E, and lower ubiquinone levels. Among the normal melanocytes from melanoma patients studied, two groups were differentiated: a) cultures (7) with enzymatic and non-enzymatic antioxidants level similar to those of normal human melanocytes; b) cultures (8) with antioxidant patterns similar to those observed in melanoma cells. Polyunsaturated fatty acids were also increased in the latter group. The results indicate that in melanoma cells and in a percentage of normal melanocytes from melanoma patients, an imbalance in the antioxidant system can be detected that can lead to endogenous generation of reactive oxygen species and to cellular incapability of coping with exogenous peroxidative attacks. These alterations could be correlated with the malignant transformation of cells and with the progression of the disease.

Technetium-99m-MIBI scintigraphy in the assessment of neoadjuvant chemotherapy in breast carcinoma.

UNLABELLED: Presurgical neoadjuvant chemotherapy (PSNC) is the treatment of choice for patients with locally advanced breast carcinoma (LABC). Accurate assessment of tumor response is important in planning subsequent treatments. Conventional response assessment by mammography and clinical evaluation is not fully reliable. This study evaluates the diagnostic yield of serial 99mTc-MIBI scintigraphy in the assessment of LABC response to PSNC. METHODS: Twenty-nine patients affected by LABC underwent clinical, mammographic and 99mTc-MIBI scintigraphy before and after 3 cycles of FEC (500 mg/m2 5-fluorouracil, 50 mg/m2 epirubicin and 400 mg/m2 cyclophosphamide) on Days 1 and 8. Surgery was planned for 15 days after the third cycle of chemotherapy. Pathological status was obtained after surgery in all patients. RESULTS: Sensitivities (i.e., true-positive ratios) for a correct prediction of tumor presence after PSNC were 65% for scintigraphy, 35% for clinical evaluation and 69% for mammography. Specificities (i.e., true-negative ratios) for a correct prediction of tumor absence after PSNC were 100% for scintigraphy, 67% for clinical evaluation and 33% for mammography. Technetium-99m-MIBI uptake in this series did not correlate with P-170 expression, proliferating cell nuclear antigen, Her-2/neu oncogene protein, antihuman endothelial cell CD31 antigen and estrogenic and progestinic receptor status. CONCLUSION: Technetium-99m-MIBI scintigraphy is effective in monitoring the response to PSNC in LABC patients. Its diagnostic yield is clearly superior to clinical evaluation alone. Scintigraphy performs as does mammography in patients with negative response, but it is clearly superior in patients with positive response.

Blood antioxidant status and urinary levels of catecholamine metabolites in beta-thalassemia.

It has been reported that iron overload in beta-thalassemia leads to an enhanced generation of reactive oxygen species and to oxidative stress. We have studied the oxidant/antioxidant imbalance in the blood of 48 transfusion-dependent beta-thalassemic patients (TLP) (17 males, 31 females, 11-22 year), under chelation therapy, and in 40 sex and age matched healthy controls (CTR). Plasma and lymphocyte levels of vitamin E (Vit E), ubiquinol (CoQ10H2), ubiquinone (CoQ10), plasma concentrations of vitamin A (Vit A), beta-carotene, lycopene, vitamin C (Vit C), total thiols, fatty acid patterns of phospholipids (PL-FA), and plasma and urinary markers of lipoperoxidation (TBA-RM, conjugated dienes, and azelaic acid (AZA), as well as the urinary levels of catecholamine and serotonin metabolites, were evaluated by gas chromatography-mass spectrometry (GC-MS), HPLC and spectrophotometry. Routine laboratory blood analyses were performed on the same samples; 39/48 TLP were HCV positive. Blood samples were collected just before transfusion, the 24 h urine samples the day before. Our results clearly showed that a severe oxidative stress occurs in the plasma of TLP in comparison with CTR. In fact, the levels of lipophilic antioxidants and ascorbate were severely depleted: CoQ10H2 (-62.5%), total CoQ10 (-35.1%), Vit E (-43.8%), beta-carotene (-31.1%), lycopene (-63.7%), Vit A (-35.9%), Vit C (-23.1%). The impairment of the antioxidant status was associated with elevated plasma levels of by-products of lipoperoxidation and urinary concentrations of catecholamine metabolites and of AZA, indicating a high degree of both neurological stress and lipoperoxidation. A significant positive correlation was found between vitamin E and non-transferrin-bound iron (NTBI) (r = -0.81; p < 0.001), while no correlation was found between antioxidant depletion and ferritin serum levels, average blood consumption, or the presence of clinical complications. The administration of selective antioxidants along with an appropriate diet might represent a promising way of counteracting oxidative damage and its deleterious effects on the progression of the disease.

The Italian multi-centre project on evaluation of MRI and other imaging modalities in early detection of breast cancer in subjects at high genetic risk.

This report presents the preliminary results of the first phase (21 months) of a multi-centre, non-randomised, prospective study, aimed at evaluating the effectiveness of contrast-enhanced magnetic resonance imaging (MRI), X-ray mammography (XM) and ultrasound (US) in early diagnosis of breast cancer (BC) in subjects at high genetic risk. This Italian national trial (coordinated by the Istituto Superiore di Sanità, Rome) so far recruited 105 women (mean age 46.0 years; median age 51.0; age range 25-77 years), who were either proven BRCA1 or BRCA2 mutation carriers or had a 1 in 2 probability of being carriers (40/105 with a previous personal history of BC). Eight cases of breast carcinomas were detected in the trial (mean age 55.3 years, median age 52.5; age range 35-70 years; five with previous personal history of BC). All trial-detected BC cases (8/8) were identified by MRI, while XM and US correctly classified only one. MRI had one false positive case, XM and US none. Seven "MRI-only" detected cancers (4 invasive, 3 in situ) occurred in both pre- (n = 2) and post-menopausal (n = 5) women. With respect to the current XM screening programmes addressed to women in the age range 50-69 years, the global incidence of BC in the trial (7.6%) was over ten-fold higher. The cost per "MRI-only" detected cancer in this particular category of subjects at high genetic risk was substantially lower than that of an XM-detected cancer in the general women population. These preliminary results confirmed that MRI is a very useful tool to screen subjects at high genetic risk for breast carcinoma, not only in pre-, but also in post-menopausal age, with a low probability of false positive cases.

Antioxidant status in the blood of patients with active vitiligo.

We have previously reported that patients with active vitiligo (AVP) have elevated urinary levels of catecholamine metabolites, such as homovanillic and vanilmandelic acids, irrespective of the form of the disease (acrofacial, segmental, generalized). We have suggested that abnormal release of catecholamines from autonomic nerve endings might play an etiological role in the onset and development of vitiligo through an overproduction of toxic (oxy)radicals in the microenvironment of melanocytes in the affected areas. In the present study we have investigated whether this suggested increase in radicals might be associated with an oxidative stress in the blood of AVP. We have analyzed by gas-chromatography mass-spectrometry, by high pressure liquid chromatography, by spectrophotometry plasma levels of vitamin E (Vit E), lipoperoxides (LIP), and polyunsaturated fatty acids of phospholipids (PL-FA), erythrocyte reduced glutathione (GSH), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) activities in 62 patients affected with different forms of active vitiligo (acrofacial, segmental, generalized) and in 60 age-matched controls. Our results show that blood levels of Vit E, SOD, GSH, GSH-Px activity, LIP and PL-FA in AVP were not significantly different from those of healthy age matched controls, indicating that melanocyte damage in vitiligo is not linked with a generalized oxidative stress.

[Pain and anxiety related to mammography in breast cancer patients. Psychological evaluation in an experimental study]. / Dolore ed ansia associate alla mammografia in pazienti con tumore mammario. Valutazione psicologica in uno studio sperimentale.

PURPOSE: Previous research focusing on one-time screening rather than repeat adherence, have largely pointed out that anxiety levels and pain expectation are the most common factors which may act as a barrier to mammography. These studies also show that anxiety pain and depression are very often associated with the experience of mammography. The aim of this study was to evaluate whether a supportive psychological intervention can be effective in reducing these feelings in patients undergoing follow-up mammography MATERIAL AND METHODS: The study was performed on 60 women who had already received a diagnosis of breast cancer. In order to detect the variables of depression, anxiety and pain before and after mammography the following questionnaires were administered to the patients: State-Trait Anxiety Inventory (STAI), Self-rating Depression Scale (SDS), Visual Analog Scale (VAS). RESULTS AND CONCLUSION: The results of this study show that our psychological intervention significantly lowered the levels of state anxiety and pain but it had no effect on depression. A psychological approach giving patients both emotional and informational support about the examination, may significantly reduce state anxiety levels and the pain felt during mammography.

Epidermal oxidative stress in vitiligo.

Epidermal levels of enzymatic and non-enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), vitamin E (Vit E), ubiquinol (CoQ10H2), and reduced glutathione (GSH), as well as polyunsaturated fatty acids of phospholipids (PL-PUFA), were evaluated in the affected epidermis of 15 patients with active vitiligo (AVP) and in the corresponding epidermis of 15 healthy phototype matched controls. The epidermal levels of CoQ10H2, Vit E, GSH, and CAT activity were significantly reduced in AVP and were associated with a marked increase of oxidized glutathione, whereas SODs and GSH-Px activities and ubiquinone concentration remained similar to control values. Antioxidant deficiency, in particular the decline of lipophilic antioxidants, i.e., CoQ10H2 and Vit E, accounts well for PL-PUFA reduction observed in vitiligo epidermis, mainly affecting C18:3 n-3, C20:3 n-6, C20:4 n-6, and C22:6 n-3 fatty acids and suggesting the occurrence of a lipoperoxidative process. In conclusion, both an imbalance of the intracellular redox status and a significant depletion of enzymatic and non-enzymatic antioxidants feature the epidermis of AVP, and represent a fingerprint of an abnormal oxidative stress leading to epidermal cell injury.

Paraphenylene diamine, a contact allergen, induces oxidative stress in normal human keratinocytes in culture.

During the course of evaluating the interaction between allergens and keratinocytes in the pre-immunological phase of contact sensitization, we have studied the effects of paraphenylene diamine (pPD) on membrane lipid peroxidation and on intracellular antioxidant levels in cultured human keratinocytes. pPD is an aromatic amine which undergoes spontaneous oxidation in culture medium, generating short-lived free radical species including oxyradicals. Following exposure to non-toxic concentrations of pPD (0.5-10 micrograms/ml), we have evaluated the fatty acid pattern of membrane phospholipids as a target of peroxidative damage, and the intracellular level of reduced glutathione (GSH), the activity of superoxide dismutase (SOD), and that of catalase (CAT) as parameters of the antioxidant system. Depending on pPD concentration and the period of exposure, peroxidative damage with a significant decrease in membrane polyunsaturated fatty acids, was detected. Concentrations between 0.5 and 2 micrograms/ml produced an initial increase and then a decrease in both SOD and CAT activities, and in the oxidation of GSH, up to 12 h. After 24 h, when all the pPD had decomposed, recovery of the initial levels of the antioxidants was detected. Concentrations over 5 micrograms/ml induced a progressive decrease in both the enzymatic activities and the GSH concentrations. These results are consistent with the view that oxidative stress can be an essential event in the pre-immunological phase of contact sensitization.

[Magnetic resonance in hepatic lesions. Experience with a 1.5-T magnetic field]. / La Risonanza Magnetica nelle lesioni epatiche. Esperienza con campo magnetico da 1,5 T.

Forty-one patients with histologically proven hepatic lesions (6 cysts, 6 hemangiomas, 8 hepatomas, 19 metastases and 2 negative cases) were studied with Magnetic Resonance (MR) imaging at 1.5 T, and with US and CT. This prospective study was aimed at evaluating: the comparative accuracy of MR, US and CT; the sensitivity and specificity of spin-echo (SE) vs FISP pulse sequences; the efficacy of T1 and T2 relaxation time values in differentiating hemangiomas from hepatomas and metastases. MR diagnostic accuracy was 94.7% vs 89.4% of CT and 84.2% of US. FISP sequences provided 60% sensitivity and 66% specificity. T2 relaxation time values were statistically significant (p less than 0.05) in differentiating hemangiomas (T2 range: 80.9-218.9 ms) from hepatomas (T2 range: 59.4-83.2 ms). The differences in mean T2 values between hemangiomas and metastases (T2 range 54.3-177.3 ms) were not statistically significant (p greater than 0.25).

[Angiography with magnetic resonance in the study of portal hypertension. Clinical applications]. / Angiografia con risonanza magnetica nello studio della ipertensione portale. Applicazioni cliniche.

The role of MR angiography (MRA) was investigated in 31 patients with portal hypertension. The 2D time-of-flight (TOF) technique was used. All patients underwent CT first. MR angiograms were compared with DSA images in 15 cases and to duplex or color Doppler US scans in 16 cases. In 5 low-grade portal hypertension cases MRA showed splenoportal trunk enlargement and portal vein verticalization. In 26 patients with high-grade portal hypertension MRA allowed portosystemic shunts extent to be evaluated. Portal flow reduction or inversion and left gastric vein enlargement were always demonstrated by MRA in the patients with esophageal varices and azygos vein enlargement. MRA always correctly visualized cavernoma (5 cases) and portal vein thrombosis (9 cases). The diagnostic yield of MRA was greater than that of CT and SE MR sequences in 91% of cases. MRA provided the same information as (or more than) DSA and duplex US in 66% of cases.

[MR staging in renal neoplasms. Comparison with surgical data]. / Stadiazione con RM delle neoplasie renali. Confronto con i dati chirurgici.

Forty-six patients bearing renal lesions were studied with magnetic resonance (MR) imaging. A superconductive magnet (1.5 T) was used to stage the lesions according to Robson's criteria. A positive correlation between MR and pathologic results was observed in 40 cases. MR imaging overstaged 4 lesions: 2 of them for suspected infiltration of perirenal fat (MR stage II, versus pathologic stage I), one was a false-positive finding for lymph node metastasis (MR stage IIIb, versus pathologic stage II) and another one for suspected bowel loop infiltration (MR stage IVa, versus pathologic stage II). Two lesions were understaged: in one case bowel loop infiltration was missed by MR imaging (MR stage II, versus pathologic stage IVa) and another one for a false-negative lymph node metastasis (MR stage II, versus pathologic stage IIIb). In all the cases with involvement of renal vein and vena cava, MR imaging correctly demonstrated the presence of neoplastic thrombi.

[Magnetic resonance angiography in the study of neoplastic cerebral pathology]. / L'angiografia con Risonanza Magnetica nello studio della patologia neoplastica cerebrale.

To date, magnetic resonance angiography (MRA) has been used in neuroradiology mainly to study vascular malformations and atherosclerotic changes of the carotid bifurcation. Our study was aimed at investigating the role of MRA with the time-of-flight technique in the study of intracranial neoplasms; a superconductive 1.5 T magnet was used, and FLASH and FISP 2D and 3D pulse sequences were acquired before and after Gd-DTPA administration. Fifty-five MRA examinations were performed. Our series consists in 32 meningiomas, 14 glial tumors, 3 hypophysis adenomas, 2 metastases, 1 NF2, 2 craniopharyngiomas, 1 lymphoma and 1 rhinopharyngeal carcinoma with intracranial involvement. In 27 patients MRA results were compared with DSA findings. The results showed high agreement relative to indirect angiographic patterns (dislocations, encasement, dural sinuses involvement) and poor accuracy in the demonstration of tumor vascularization (inflow and outflow, vascular neoformation).

Recurrence of ovarian and uterine neoplasms: diagnosis with transrectal US.

Twenty-one patients with clinically suspected recurrence of ovarian (n = 3) or uterine (n = 18) carcinoma were examined with suprapubic ultrasound (US) and transrectal US with high-frequency linear probes. The examinations were performed 3, 6, 9, and 15 months after surgery and radiation therapy. Eight patients underwent radiation therapy before surgery and ten after surgery; three underwent only surgery. Criteria for recurrence included increased anteroposterior diameter of the vaginal cuff (greater than 2.2 cm); structural alterations or presence of a mass in the vaginal cuff; and infiltration of the rectovaginal septum, bladder, and parametria. Transrectal US findings were true positive for recurrence in nine cases, true negative in ten, and false positive in two. US findings were true positive in three cases, true negative in seven, false positive in two, and false negative in three. In six cases results from US were technically poor, and no diagnosis could be made. Transrectal US was highly sensitive in detection of pelvic recurrent carcinomas, while US had little diagnostic value. The authors believe transrectal US can replace US in the evaluation of patients at risk for recurrent pelvic neoplasm.

[Transvaginal echography: initial experiences in oncologic gynecology]. / L'ecografia transvaginale: prime esperienze in ginecologia oncologica.

The authors report their initial experience in a selected group of 30 patients with suspected gynecological neoplasms (10 ovarian tumors, 8 recurrences of ovarian tumors, 6 cervical carcinomas, 3 ovarian cysts, 3 fibromyomas) who underwent both transabdominal (US) and transvaginal (TV) sonography. All the scans were retrospectively reviewed. In 18 cases US and TV provided equivalent information as to the organ of origin of the mass, while TV was more useful in 9 cases, and US in 3 cases. The anatomical relationship of the mass to the adjacent organs was better demonstrated by TV in 15 cases, while in 15 cases the information provided by US and TV was equivalent. The two techniques yielded the same results as to the internal architectural details of the mass in 9 cases, while TV was superior in 18 cases and US in 3 cases. TV allowed the early identification of: small amounts of free fluid in the cul-de-sac in 3 cases, compression of the ureter in 1 case, and compression of the uterine vessels in 1 case. These findings had not been demonstrated by US. Our preliminary results indicate that adjuvant TV sonography provides important diagnostic information in gynecological neoplasms in about 39% of patients.

[Preoperative staging and recurrence of rectal tumors. Comparison of transrectal ultrasonography and magnetic resonance]. / Stadiazione preoperatoria e recidive dei tumori del retto. Confronto tra ecotomografia transrettale e Risonanza Magnetica.

The accuracy of transrectal US (TRUS) and of MRI was evaluated in the preoperative staging and in local recurrences of rectal cancers. Fifty-four patients were examined: 45, with known rectal cancer, for preoperative staging, and 9 for the evaluation of local recurrences. Nineteen patients were examined with MRI in basal conditions, 21 after rectal air enema and 5 after paramagnetic contrast enema (Gd-DTPA). The following parameters were evaluated for preoperative staging: wall infiltration, invasion of perirectal fat and adjacent structures, lymph node involvement. Morphologic and signal intensity (on MRI) changes were evaluated for the diagnosis of local recurrences. TRUS provided 2 false positives. In the same patients, basal MRI results were poor, owing to difficult demonstration of the different wall layers, while in the patients studied after air enema, the lesion was hyperintense. In 20 patients with a fat-infiltrating tumor, TRUS provided 3 false negatives and 2 false positives; basal MRI yielded poor results, while air enema and paramagnetic contrast enema clearly demonstrated all fat-infiltrating lesions, with only one false positive.

Apoptosis in the dorsal lateral geniculate nucleus after monocular deprivation involves glutamate signaling, NO production, and PARP activation.

In mammals, visual experience during early postnatal life is critical for normal development of the visual system. Here we report that monocular deprivation for 2, 7, and 14 consecutive days causes p53 accumulation, cell death, and progressive loss of neurones in the dorsal lateral geniculate nucleus (dLGN) of newborn rats and these are prevented by NMDA and non-NMDA glutamate receptor antagonists, and by L-NAME, an inhibitor of nitric oxide synthesis. Monocular deprivation also increases dLGN levels of citrulline, the coproduct of nitric oxide synthesis, and this, as well as cell death and neuronal loss, is abolished by antagonists of glutamate receptors and by L-NAME. Finally, poly-(ADP-ribose) polymerase (PARP) knock-out mice appear to be protected from monocular deprivation-induced cell death. In conclusion, during early postnatal development of the rat visual system monocular deprivation causes excitotoxic, nitric oxide-mediated, cell death in the dLGN that appears to be apoptotic and also requires activation of PARP.

[Oral contrast media in the study of the esophagus with magnetic resonance. Proposal of a new preparation]. / I mezzi di contrasto orali nello studio dell'esofago con risonanza magnetica. Proposta di una nuova preparazione.

The major problem in MRI of the esophagus is the lack of a reliable oral contrast agent. To determine the value of Gd-DTPA as an oral contrast medium for the esophagus as a part of phase III clinical trial, 17 patients (10 esophageal neoplasms, 4 neoplasms of the pharyngo-laryngeal tract, 3 Zenker's diverticula) underwent MRI. The oral contrast medium is proposed in a new preparation: 5 cc of oral Gd-DTPA were emulsionated with 30 g of a low-density barium paste for esophageal CT (3% p/v). High signal intensity in the esophageal lumen was observed in all patients and in all sequences. In neoplastic lesions, the c.m. improved the definition of both the level of stenosis and the longitudinal extent of the lesion. In diverticula, the real and the false lumen could be demonstrated. In one patient the exam could not be completed. No adverse reactions were observed.