The value of clinical characteristics and breast-imaging studies in predicting a histopathologic diagnosis of cancer or high-risk lesion in patients with spontaneous nipple discharge

BACKGROUND: The purpose of this study was to determine the utility of breast-imaging studies in identifying cancer and high-risk lesions among patients with spontaneous, single-duct, nipple discharge (SSND). METHODS: The medical records of 168 cases with SSND treated with duct excision between June 1998 and May 2004 were reviewed. The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of mammogram, ultrasound, and ductogram in predicting high-risk lesions and cancer were calculated. RESULTS: The sensitivity of mammography was 10%, the specificity 94%, the NPV 88%, and the PPV 18%. Ultrasonography had a sensitivity of 36%, specificity of 68%, PPV of 14%, and NPV of 89%. Ductography had a sensitivity of 75%, specificity of 49%, and NPV and PPV of 93% and 18%, respectively. CONCLUSIONS: Conventional imaging studies do not accurately identify cancer or high-risk lesions in patients with SSND.All patients with SSND should be offered duct excision.     

Coenzyme Q10 therapy before cardiac surgery improves mitochondrial function and in vitro contractility of myocardial tissue

OBJECTIVES: Previous clinical trials suggest that coenzyme Q(10) might afford myocardial protection during cardiac surgery. We sought to measure the effect of coenzyme Q(10) therapy on coenzyme Q(10) levels in serum, atrial trabeculae, and mitochondria; to assess the effect of coenzyme Q(10) on mitochondrial function; to test the effect of coenzyme Q(10) in protecting cardiac myocardium against a standard hypoxia-reoxygentation stress in vitro; and to determine whether coenzyme Q(10) therapy improves recovery of the heart after cardiac surgery. METHODS: Patients undergoing elective cardiac surgery were randomized to receive oral coenzyme Q(10) (300 mg/d) or placebo for 2 weeks preoperatively. Pectinate trabeculae from right atrial appendages were excised, and mitochondria were isolated and studied. Trabeculae were subjected to 30 minutes of hypoxia, and contractile recovery was measured. Postoperative cardiac function and troponin I release were assessed. RESULTS: Patients receiving coenzyme Q(10) (n = 62) had increased coenzyme Q(10) levels in serum (P = .001), atrial trabeculae (P = .0001), and isolated mitochondria (P = .0002) compared with levels seen in patients receiving placebo (n = 59). Mitochondrial respiration (adenosine diphosphate/oxygen ratio) was more efficient (P = .012), and mitochondrial malondialdehyde content was lower (P = .002) with coenzyme Q(10) than with placebo. After 30 minutes of hypoxia in vitro, pectinate trabeculae isolated from patients receiving coenzyme Q(10) exhibited a greater recovery of developed force compared with those in patients receiving placebo (46.3% +/- 4.3% vs 64.0% +/- 2.9%, P = .001). There was no between-treatment difference in preoperative or postoperative hemodynamics or in release of troponin I. CONCLUSIONS: Preoperative oral coenzyme Q(10) therapy in patients undergoing cardiac surgery increases myocardial and cardiac mitochondrial coenzyme Q(10) levels, improves mitochondrial efficiency, and increases myocardial tolerance to in vitro hypoxia-reoxygenation stress.     

Molecular mechanisms of the chemopreventive effects of resveratrol and its analogs in colorectal cancer: key role of polyamines?

Resveratrol (3,4',5-trihydroxy-trans-stilbene), a phytoalexin found in grape skins, peanuts, and red wine, has been reported to exhibit a wide range of biological and pharmacological properties. It has been speculated that dietary resveratrol may act as an antioxidant, promote nitric oxide production, inhibit platelet aggregation, and increase high-density lipoprotein cholesterol and thereby serve as a cardioprotective agent (the so-called "French paradox"). Recently, it was demonstrated that resveratrol can function as a cancer chemopreventive agent, and there has been a great deal of experimental effort directed toward defining this effect. It has been shown that resveratrol and some of its analogues interfere with signal transduction pathways. Thus the activities of various protein kinases are inhibited, the expression of nuclear proto-oncogenes declines, and the activity of ornithine decarboxylase (ODC) is reduced. ODC, which catalyzes the rate-limiting step in the biosynthesis of polyamines, is closely linked with cellular proliferation and carcinogenesis. This review summarizes the recent advances that have provided new insights into the molecular mechanisms underlying the promising properties of resveratrol focusing on the key role of the polyamine metabolism in colorectal cancer cells.     

Non-small cell lung cancer: evaluation of pleural abnormalities on CT scans with 18F FDG PET

PURPOSE: To evaluate the accuracy of fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in differentiation of pleural malignancy and cancer-unrelated pleural disease in patients with non-small cell lung cancer (NSCLC) and pleural abnormalities at computed tomography (CT). MATERIALS AND METHODS: In 92 patients, pleural abnormalities were detected at contrast material-enhanced thoracic CT, which was performed for newly diagnosed NSCLC (n = 41) or restaging (n = 51). CT findings were negative for pleural malignancy when pleural effusion with attenuation of 10 HU or less and/or rib fractures with no evidence of pathologic fracture were present; findings were indeterminate when pleural effusion with attenuation greater than 10 HU and/or solid pleural abnormalities without osseous destruction of the chest wall were present; and findings were positive if any osseous destruction of the chest wall adjacent to a pleural mass was present. All patients underwent FDG PET. Findings were negative for pleural malignancy if pleural activity was absent, equal to, or less than mediastinal background activity; findings were positive if pleural activity was higher than mediastinal background activity. Reading of CT and FDG PET scans was first performed separately and then was combined. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPP), and accuracy were calculated for CT and FDG PET separately and for CT and FDG PET combined, with cytologic and/or histologic analysis as standard of reference. RESULTS: In detection of pleural malignancies, CT findings were indeterminate in 65 (71%) patients and true-negative in 27 (29%). Respective sensitivity, specificity, PPV, NPV, and accuracy of FDG PET in detection of pleural malignancies were 100%, 71%, 63%, 100%, and 80%; and those of CT and FDG PET combined, 100%, 76%, 67%, 100%, and 84%. CONCLUSION: Findings suggest that a negative FDG PET scan for indeterminate pleural abnormalities at CT indicates a benign character, while positive findings on an FDG PET scan are sensitive for malignancy.     

Cognitive representations of future gains,maintenance, and losses in the second half of life

The aim of this study is to explore three different developmental dimensions in an aging population. Based on sentence completion responses, the investigation examines personal anticipations of possible gains, maintenance, and losses. Additionally, the effects of age and other personal and situational factors are examined. The study sample consists of 2,934 participants ranging from 40 to 85 years of age, who participated in the German Aging Survey of 1996. Study findings indicate that, to a large extent, the anticipated gains include positive changes in the way of life and increased leisure projects while anticipated maintenance refer to physical and behavioral resources and to life style. Anticipated losses are related to concerns about external living conditions and physical decline. There is a strong association of anticipated gains and maintenance with age, while present health conditions are related to expectations of loss. The implications of the study results for lifespan expectations in the second half of life and for lifespan theory are discussed.     

Site-directed mutations in the FAD-binding domain of glycerophosphate dehydrogenase: catalytic defects with preserved mitochondrial anchoring of the enzyme in transfected COS-7 cells

Single-strand conformational polymorphism analysis of mitochondrial FAD-linked glycerophosphate dehydrogenase (mGDH) gene has revealed mutations in both the calcium- and FAD-binding domains of this enzyme in some diabetic patients. It was now investigated whether site-directed mutations in the FAD-binding domain of the mGDH gene may affect the mitochondrial anchoring and catalytic activity of the enzyme. COS-7 cells were transfected with plasmid cDNA coding for either wild-type or mutated human mGDH (G --> A substitutions at positions 352, 355, and 364 and A --> C substitution at position 390) fused, when required, at the N-terminus of green fluorescent protein. The activity of mGDH was measured by both radioisotopic ((3)HOH production from l-[2-(3)H]glycerol 3-phosphate) and colorimetric (iodoformazan formation) procedures. In cells transfected with the mGDHwt-EGFP or mGDHmut-EGFP constructs, the fused protein was found by confocal microscopy exclusively in the mitochondria, colocalized with a mitochondrial marker. In homogenates of COS-7 cells transfected with mGDHmut, however, the catalytic activity of the enzyme was decreased, this coinciding with low ratios between both the activities measured in the absence/presence of exogenous FAD and the results obtained by the colorimetric/radioisotopic procedure. Thus, although the present site-directed mutations of the mGDH gene failed to impair the mitochondrial anchoring of the enzyme, they led to catalytic defects that were, in some respect, comparable to those previously encountered in the lymphocytes or islets of type 2 diabetic patients.