Aims Arterial stiffening may lead to hypertension, greater left ventricular after-load and adverse clinical outcomes. The underlying mechanisms influencing arterial elasticity may involve oxidative injury to the vessel wall. We sought to examine the relationship between novel markers of oxidative stress and arterial elastic properties in healthy humans. Methods & Results We studied 169 subjects (mean age 42.6 ± 14 years, 51.6% male) free of traditional cardiovascular risk factors. Indices of arterial stiffness and wave reflections measured included carotid-femoral Pulse Wave Velocity (PWV), Augmentation index (Aix) and Pulse Pressure Amplification (PPA). Non-free radical oxidative stress was assessed as plasma oxidized and reduced amino-thiol levels (cysteine/cystine, glutathione/GSSG) and their ratios (redox potentials), and free radical oxidative stress as derivatives of reactive oxygen metabolites (dROMs). Inflammation was assessed as hsCRP and interleukin-6 levels. The non-free radical marker of oxidative stress, cystine was significantly correlated with all arterial indices; PWV (r= 0.38, p<0.001), Aix (r=0.35, p<0.001) and PPA (r=−0.30, p<0.001). Its redox potential, was also associated with PWV (r=0.22, p=0.01), while the free radical marker of oxidative stress dROMS was associated with Aix (r=0.25, p<0.01). After multivariate adjustment for age, gender, arterial pressure, height, weight, heart rate and CRP, of these oxidative stress markers, only cystine remained independently associated with PWV (p=0.03), Aix (p=0.01) and PPA (p=0.05). Conclusions In healthy subjects without confounding risk factors or significant systemic inflammation, a high cystine level, reflecting extracellular oxidant burden, is associated with increased arterial stiffness and wave reflections. This has implications for understanding the role of oxidant burden in pre-clinical vascular dysfunction.

Adult granulosa cell tumor (GCT) of the ovary is mostly diagnosed in postmenopausal women. They typically secrete estrogen, which stimulates the endometrium to proliferate and cause abnormal bleeding. This study reviews the cytologic features of adult GCT of the ovary diagnosed by fine-needle aspiration (FNA). We reviewed slides from ten cases diagnosed by CT guided FNA from 1995 to 2007 at our institutions. Smears were stained with Diff-Quik and Papanicolaou stains. Patient's history and histologic diagnosis were also available and reviewed for all cases. The patients ranged in age from 39 to 83 yr. All 10 cases were hypercellular with both large and small overlapping cell clusters and individual cells. The cytologic features identified included: naked nuclei (10/10 cases), Call-Exner bodies (7/10 cases), blood vessels with prominent perivascular tumor cell growth (4/10 cases), spindle-shaped hyperchromatic stromal cells within cellular clusters (6/10 cases), mixed inflammation (3/10 cases), tumor cell necrosis (1/10 cases), and prominent metachromatic stroma seen in association with blood vessels (1/10 cases). Moderate to scant delicate cytoplasm was also seen (10/10 cases). Small, punctuate cytoplasmic vacuoles were also noted (7/10 cases) and were occasionally prominent (3/10 cases). In general nuclear to cytoplasmic ratios were high although lower than those typically seen in a lymphoma or small-cell carcinoma. Nuclei were generally centrally located although eccentrically located nuclei were consistently seen in a minority of cells. Nuclei were monotonous in size showing slightly convoluted (occasional rentiform and fetiform nuclei) to polygonal outlines. Prominent, central nucleoli were also seen (4/10 cases). Nuclear grooves were also seen (9/10 cases). No atypical mitotic activity was identified in any of the 10 cases (0/10 cases). In summary, the above cytologic features can also help in the cytologic diagnosis of adult GCTs.

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Pancreatic adenocarcinoma is a genetic disease showing somatic mutations of multiple genes, including SMAD4. SMAD4 is a tumor suppressor gene that is inactivated in a sub-set of pancreatic adenocarcinoma, either by the intragenic mutation of one allele in combination with the loss of the other allele or by homozygous deletion of both alleles. This study examines SMAD4 expression in fine-needle aspiration cell blocks from patients with pancreatic adenocarcinoma, as well as a variety of human cancers, in order to assess its viability as a tumor marker. A total of 100 patients with pancreatic adenocarcinoma, with diagnostic material from fine-needle aspiration cell blocks were selected for this study. In addition cancers from different sites were examined in multitumor tissue microarrays, which included two tissue cores from neoplastic surgical resection specimens. Cancers studied included endometrium (n = 100), colon (n = 100), ovary (n = 100), lung (n = 100), breast (n = 100), and malignant melanoma (n = 100). The sections were immunostained with SMAD4 using pressure cooker antigen retrieval labeled polymer horseradish peroxidase (DAKO), and the DAKO autostainer. Immunohistochemical expression was scored as negative, 1+, 2+, 3+. Only 2+ and 3+ staining was considered as positive staining. SMAD4 staining was nuclear and the results for tumor cell positivity for primary sites studied are as follows: Pancreas (80/100; 80%), endometrium (0/100; 0%), colon (0/100; 0%), ovary (3/100; 3%), lung (0/100; 0%), breast (2/100; 2%), and malignant melanoma (4/100; 4%). This study suggests that SMAD4 is an important marker for confirming a diagnosis of pancreatic adenocarcinoma as a primary tumor, as well as when it presents as a metastatic tumor on small fine-needle aspirate samples.

Intratumor C-reactive protein may be a robust biomarker of prognosis in patients with localized renal cell carcinoma.