We report the case of a 42-year-old woman with inflammatory cancer of the right breast treated with neoadjuvant chemotherapy, surgery, additional chemotherapy, and consolidative radiotherapy (RT), ...that has metastatized to the chest wall and presented a resumption of disease on the contralateral breast. Magnetic Resonance (MR), performed after the second phase's fourth round of additional chemotherapy, showed a modest reduction of scar metastases on the right and a contralateral anomalous skin thickening with high signal intensity in T2 weighted images (WI) with multiple mass-like enhancements located in a wide area of the central region at the union of higher quadrants. These findings were suggestive for resumption of contralateral disease; the biopsy confirmed an inflammatory breast cancer (IBC) infiltrating lobular type with high mitotic rate. A retrospective evaluation of the previous MR exam, performed 5 months before, was conducted: on the left side only a modest skin thickening was found as an early sign. A careful review of the literature has confirmed that skin thickening, increased density and clinical signs of inflammation are the most common findings in inflammatory cancer. We report the case of a patient affected by IBC whose unique early sign of resumption on the contralateral breast was skin thickening.
The clotting activity of human fibrinogen was fully inhibited in vitro by peroxynitrite. The decrease of activity followed an exponential function and the concentration of peroxynitrite needed to ...inhibit 50% of fibrinogen clotting was 22 μM at 25°C. The oxidative modification(s) induced by the peroxynitrite system (i.e. ONOO
−, ONOOH and ONOOH*) appeared specifically to affect fibrin clot formation (through the inhibition of fibrinogen polymerization) since the interaction of peroxynitrite-modified fibrinogen with thrombin appeared to be unaffected. The addition of NaHCO
3 decreased the peroxynitrite effect on fibrinogen clotting, suggesting that the reactive species formed by the reaction of CO
2 with peroxynitrite are less efficient oxidants of peroxynitrite itself. Similar effects were observed after addition of bilirubin, which also exerted a significant protection against peroxynitrite-mediated modification of fibrinogen.
The effect of oxidative stress induced by neurotoxic metal ions on the properties of the brain 20S proteasome or multicatalytic proteinase complex (MPC) has been studied. Exposure of the 20S ...proteasome to increasing amounts of Fe(III), Fe(II), Cu(II) or Zn(II) affects its main hydrolytic activities: trypsin-like (T-L), chymotrypsin-like (ChT-L), peptidylglutamyl-peptide hydrolase (PGPH), branched-chain amino acid preferring (BrAAP) and caseinolytic activities, although in different ways. T-L activity showed gradual activation by both iron ions but inhibition by Cu(II) and Zn(II). ChT-L and PGPH activities were inhibited whereas BrAAP activity was widely activated by all the tested metal salts except for zinc ions. Moreover, the exposure to ferrous salt increased the degradation rate of casein. The functional effects appear to be linked to oxidation-induced modifications, as demonstrated by an increase of carbonyl groups following the exposure to metal ions. In addition, modifications induced by ferrous salt on the catalytic subunits were also supported by western blot analyses performed using anti-X, anti-Y and anti-Z antibodies. The results obtained clearly indicate that metal-catalyzed oxidation strongly affects the functions of the brain 20S proteasome, even though the catalytic subunits seem to be differently influenced by oxidative phenomena.
To assess the diagnostic utility and additional cost of combined breast ultrasonography and mammography in the evaluation of asymptomatic women with mammographically dense breasts.
Of 5108 ...asymptomatic women, who underwent mammography, 1754 had dense breasts (BI-RADS 3 or 4) and negative mammographic outcome. They were divided in 4 subgroups according to their age (<40 yrs; 40–49 yrs; 50–59 yrs; >59 yrs). Breast ultrasonography was performed immediately after mammography. Lesions detected at ultrasonography were examined cytologically/histologically. Mammograms from women, who were diagnosed carcinoma at ultrasonography, were reviewed by an external radiologist. Costs per diagnosed carcinoma and per examined woman were calculated on the basis of current regional charges.
Mammographies (5108) were performed, 67 cancers were detected (cancer detection rate 13.1‰): mammography identified 55 carcinomas and ultrasonography performed in women with dense breasts identified 12 cancers (17.9% of all cancers detected, overall cancer detection rate 6.8‰). Ultrasonography identified a benign condition in 1567 out of 1754 women (89.3%) (in 925 absence of focal lesions; 438 simple cysts; 56 ductal ectasia; 148 benign solid lesions); 97 complex cysts, 52 lesions that could not be differentiated as liquid or solid lesions, and 38 solid lesions suspicious for malignancy in the remaining 187 out of 1754 patients (10.7%). Cytology/histology confirmed carcinoma in 12 women (overall biopsy rate 26.2‰, benign biopsy rate 19.4‰). The additional costs were: € 6,123.45 per detected cancer, € 41.89 per examined woman.
Breast ultrasonography immediately after mammography in women with dense breasts is useful to avoid diagnostic delays and inconvenient medico-legal implications even though this procedure involves increased costs.
Valutare utilità diagnostica e costi aggiuntivi dell'associazione dell'ecografia mammaria alla mammografia nella valutazione di donne asintomatiche con seno denso.
Di 5108 donne asintomatiche sottoposte a mammografia, 1754 con mammografia negativa e seno denso (BI-RADS 3 o 4) suddivise in 4 gruppi di età (<40; 40–49; 50–59; >59 anni) hanno effettuato immediatamente l'ecografia. Le alterazioni rilevate ecograficamente sono state verificate con esame cito/istologico. Le mammografie dei carcinomi diagnosticati ecograficamente sono state rivalutate da un radiologo esterno. I costi per carcinoma diagnosticato e donna esaminata sono stati calcolati in base alle tariffe regionali.
Su 5108 mammografie sono stati riscontrati 67 carcinomi (tasso diagnostico di carcinoma 13,1‰): la mammografia ne ha riconosciuti 55; l'ecografia eseguita nelle donne con seno denso 12 (17,9% del totale, tasso diagnostico globale 6,8‰). L'ecografia ha evidenziato: quadri di benignità in 1567/1754 donne (89,3%) (925 assenza di lesioni focali; 438 cisti semplici; 56 ectasie duttali; 148 lesioni solide benigne); 97 cisti complesse, 52 lesioni che non è stato possibile ulteriormente differenziare in lesioni cistiche o solide e 38 lesioni solide sospette per malignità nelle restanti 187/1754 pazienti (10,7%). L'esame cito/istologico ha confermato la presenza di 12 carcinomi (tasso bioptico globale 26,2 ‰ e tasso di biopsie benigne 19,4‰). I costi aggiuntivi sono risultati: € 6123,45 per carcinoma diagnosticato, € 41,89 per donna esaminata.
L'esecuzione immediata dell'ecografia dopo la mammografia in donne con seni densi, seppure non scevra da un aumento dei prezzi complessivi, è utile per evitare ritardi diagnostici e spiacevoli contenziosi medico–legali.
Objective - The Gubbio Study is an Italian population study measuring risk factors for and incidence of major cardiovascular diseases.This analysis investigates the association of serum uric acid ...with the incidence of coronary and cardiovascular events.
Methods - A population sample of 2469 men and women aged 35-74 years, free from major cardiovascular diseases and in whom serum uric acid was measured in 1983 along with other standard risk factors, were followed up for 6 years and the incidence of coronary heart disease (CHD) and all cardiovascular atherosclerotic (CVD) events, both fatal and non-fatal, was computed. Proportional hazards models were used for the prediction of these events.
Results - In six years 61 CHD hard criteria, 109 CHD any criterion and 149 CVD events were recorded. Age-adjusted rates per 1000 of the 3 event categories were computed in sex-specific quintiles (Q) of serum uric acid with 428 ± 76 (Q
5
) and 198 ± 42 (Q
1
) μmol/l, respectively. Although higher rates were seen in Q
5
as compared to Q1 for all three first event categories considered (relative risks 6.2, 3.6 and 3.7, respectively), a statistically significant trend was seen only for CVD all criteria (t = 3.63, p < 0.036). These trends were borderline significant for CHD any criterion (t = 2.92, p < 0.06) and not significant for CHD hard criteria (t = 2.23, p < 0.11). In multivariate models, adjusted for 8 other risk factors, serum uric acid showed a statistically significant contribution to predict CVD incidence relative risk (RR) for 92 μmol/l difference of 1.24 with 95% confidence intervals (CI) 1.05-1.45, whereas the statistical contribution to predict CHD any criterion (RR = 1.19 with CI 0.98-1.45) and CHD hard criteria (RR = 1.20 with CI 0.93-1.55) was not significant. Diuretic treatment and blood urea, as further confounders, were positively and significantly related to event incidence (RR ranging from 1.21 to 2.00) but serum uric acid maintained its independent and statistically significant role in the prediction of CVD events (RR = 1.18 with CI 1.00-1.39). Presence of specific treatments to lower serum uric acid levels (in 1.13% of the population), tested as final confounders, was not statistically contributory.
Conclusions - Increased serum uric acid levels are independently and significantly associated with risk of CVD events in the 6-year follow-up of the Gubbio Study. Longer follow-up is needed before the contributory role of serum uric acid can be properly assessed to explain CHD incidence.
Materials and Methods After a retrospective review of 338 breast magnetic resonance imaging (MRI) scans performed for the evaluation of a suspicious lesion, we selected a group of 65 mass-like ...enhancements ranging from 5 to 20 mm, classified as BIRADS assessment categories 2, 3, 4, or 5, histologically proved.
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