Macromolecular contrast medium (feruglose) versus small molecular contrast medium (gadopentetate) enhanced magnetic resonance imaging: differentiation of benign and malignant breast lesions

RATIONALE AND OBJECTIVES: To compare the diagnostic performance of the blood pool agent feruglose and the standard extracellular contrast agent gadopentetate in their abilities to differentiate benign and malignant breast tumors. PATIENTS AND METHODS: Fourteen women, aged 35-77 years (mean, 55 years), with 19 breast lesions underwent dynamic fast field echo 14/1/30 degrees (TR/TE/alpha) magnetic resonance imaging of the breast after bolus injection of feruglose (Clariscan; Amersham Health, Amersham, UK: dose, 2 mg Fe/kg) and an additional, comparative gadopentetate (dose, 0.2 mmol gadolinium/kg)-enhanced fast field echo 10/4/30 degrees (TR/TE/alpha) magnetic resonance study within 1-11 days (mean, 4.8 days) before or after the feruglose study. All breast tumors were surgically excised within 1-6 days (mean, 2.5 days) after completion of the magnetic resonance studies. Data were analyzed by measuring quantitative enhancement data and qualitatively by categorizations of the shape of the tumor enhancement curves. Group differences between quantitative data of the two contrast agents and between benign and malignant tumors were evaluated using a two-tailed paired-sample t test. Differences in curve type distribution between benign and malignant tumors were tested with the chi2 test. RESULTS: Histopathology showed a spectrum of 10 benign and nine malignant breast lesions: five mastopathies, two fibroadenomas, two chronic inflammations, and one papillomatosis, as well as five invasive ductal carcinomas and four invasive lobular carcinomas. Substantial differences were observed between feruglose- and gadopentetate-enhanced images: the mean tumor deltaSI(%) peak enhancement and wash-in rate were significantly higher for gadopentetate- as compared with feruglose-enhanced images (P < .05). Using either contrast agent, morphologic enhancement characteristics showed a considerable overlap between benign and malignant breast lesions. However, the kinetic enhancement profiles of benign and malignant lesions were significantly different based on feruglose-enhanced data (chi2 = 9.017; P = .0027) but not gadopentetate-enhanced data (chi2 = 2.239; P = .3264). CONCLUSION: Compared with gadopentetate, the new blood pool agent feruglose provided an improved characterization of the evaluated breast lesions; however, at the cost of weaker overall tumor enhancement.     

Genome-wide screening for complete genetic loss in prostate cancer by comparative hybridization onto cDNA microarrays

We demonstrate that comparative genomic hybridization (CGH) onto cDNA microarrays may be used to carry out genome-wide screens for regions of genetic loss, including homozygous (complete) deletions that may represent the possible location of tumour suppressor genes in human cancer. Screening of the prostate cancer cell lines LNCaP, PC3 and DU145 allowed the mapping of specific regions where genome copy number appeared altered and led to the identification of two novel regions of complete loss at 17q21.31 (500 kb spanning STAT3) and at 10q23.1 (50-350 kb spanning SFTPA2) in the PC3 cell line.     

Mechanisms underlying DNA damage resistance in a Xiphophorus melanoma cell line

The Xiphophorus hybrid fish model is an important resource for investigating the genetics and molecular biology of melanoma. Consistent with studies using human melanoma cell lines, the Xiphophorus melanoma cell line PSM, survives the lethal effects of ultraviolet-B radiation (UV-B) radiation much better than a cell line derived from normal fish tissue. In contrast to human melanoma cells, which show enhanced nucleotide excision repair, we do not see any differences in the efficiencies of photoenzymatic or nucleotide excision repair in normal and melanoma cell lines. We do, however, observe a significantly reduced growth rate in the melanoma cell line compared with the normal cell line and considerably less effect of UV-B radiation on DNA synthesis. The data suggest that the UV resistance phenotype of PSM cells is due more to the rate of proliferation and increased ability to replicate on a damaged template rather than enhanced repair of DNA photoproducts as observed in human melanoma cells. The putative increase in lesion bypass by DNA polymerase could result in higher mutation frequencies and enhanced genetic lability in fish melanoma cells.     

Accountability in the pesticide industry

To counter the lack of corporate accountability of the agrochemical industry for the damage caused by its perpetuation of the use of harmful chemical pesticides, the Rockefeller Brothers Fund staff in June 2002 brought together concerned scientists, lawyers, socially responsible investment professionals, and sustainable agriculture advocates at their Pocantico Conference Center. The group's objective was to communicate to market analysts the long-term downside risks of investments in pesticides, in the hope that dissemination of this information would contribute to increasing corporate accountability and safeguarding public and environmental health. Excerpts from its proceedings are presented.     

Leptospirosis in "Eco-Challenge" athletes,Malaysian Borneo, 2000

Adventure travel is becoming more popular, increasing the likelihood of contact with unusual pathogens. We investigated an outbreak of leptospirosis in "Eco-Challenge" multisport race athletes to determine illness etiology and implement public health measures. Of 304 athletes, we contacted 189 (62%) from the United States and 26 other countries. Eighty (42%) athletes met our case definition. Twenty-nine (36%) case-patients were hospitalized; none died. Logistic regression showed swimming in the Segama River (relative risk [RR]=2.0; 95% confidence interval [CI]=1.3 to 3.1) to be an independent risk factor. Twenty-six (68%) of 38 case-patients tested positive for leptospiral antibodies. Taking doxycycline before or during the race was protective (RR=0.4, 95% CI=0.2 to 1.2) for the 20 athletes who reported using it. Increased adventure travel may lead to more frequent exposure to leptospires, and preexposure chemoprophylaxis for leptospirosis (200 mg oral doxycycline/week) may decrease illness risk. Efforts are needed to inform adventure travel participants of unique infections such as leptospirosis.     

First incursion of Salmonella enterica serotype typhimurium DT160 into New Zealand

An outbreak of human Salmonella enterica serotype Typhimurium DT160 infection in New Zealand was investigated from May to August 2001. Handling of dead wild birds, contact with persons with diarrheal illness, and consumption of fast food were associated with infection. Contaminated roof-collected rainwater was also detected.     

Survival of Batrachochytrium dendrobatidis in water: quarantine and disease control implications

Amphibian chytridiomycosis is an emerging infectious disease of amphibians thought to be moved between countries by trade in infected amphibians. The causative fungus, Batrachochytrium dendrobatidis, produces aquatic, motile zoospores; infections have been achieved in experiments by exposing amphibians to water containing zoospores. However, the ability of this fungus to survive in the environment in the absence of an amphibian host is unknown. We show that B. dendrobatidis will survive in tap water and in deionized water for 3 and 4 weeks, respectively. In lake water, infectivity was observed for 7 weeks after introduction. The knowledge that water can remain infective for up to 7 weeks is important for the formulation of disease control and quarantine strategies for the management of water that has been in contact with amphibians.     

Characteristics of selenazolidine prodrugs of selenocysteine: toxicity and glutathione peroxidase induction in V79 cells

Novel selenazolidine prodrugs of selenocysteine are being developed as potential selenium delivery agents for cancer chemoprevention and other clinical uses. The 2-unsubstituted compound, selenazolidine-4(R)-carboxylic acid (L-SCA), and the 2-oxo- and 2-methyl analogues possessing D-stereochemistry (D-OSCA and D-MSCA, respectively) were synthesized and chemically characterized. L/D pairs, along with other organoselenium compounds and common inorganic forms, were studied in cultured V79 cells to understand their inherent toxicity and their ability to induce selenium-dependent glutathione peroxidase (GPx) activity, which indicates the provision of biologically available selenium. All of the selenazolidines were much less toxic to the cells than was sodium selenite (IC(50) approximately 17 microM) or the parent selenolamines, L- or D-selenocystine (IC(50) approximately 34 or 39 microM, respectively); OSCA was less toxic than MSCA. The stereoisomers of OSCA produced very different IC(50) values (L-OSCA, approximately 451 microM; D-OSCA, >3000 microM), while the IC(50) values derived for the stereoisomers of MSCA were of the same order of magnitude (L-MSCA, approximately 79 microM; D-MSCA, approximately 160 microM). Compounds possessing L-stereochemistry were at least as active with respect to GPx induction as was sodium selenite (2.2-fold increase at 15 microM). L-Selenocystine produced a 4.2-fold increase in GPx activity at 30 microM, while L-SCA produced a 5.9-fold increase, followed by L-OSCA (4.6-fold) and L-MSCA (2.1-fold), all at 100 microM. Compounds possessing D-stereochemistry showed minimal ability to induce GPx activity (D-selenocystine, 1.0-fold increase; D-OSCA, 1.4-fold increase; D-MSCA, 1.3-fold increase).     

The effects of avoidance on cytotoxic/suppressor T cells in women with cervical lesions

The purpose of this study was to examine the relationship between avoidant and intrusive ideation about cancer risk and immune responses among women with mild cervical dysplasia. Participants were 54 women undergoing diagnostic follow-up (i.e. colposcopy) for an abnormal Pap smear test result. Baseline assessments, collected prior to the colposcopy appointment, included demographic and medical history, levels of depression, and the intrusion and avoidance subscales of the Revised Impact of Events Scale. In addition, a sample of blood was obtained at baseline and 6-month follow-up for immune assessments. Hierarchical regression analyses revealed that higher levels of cognitive and behavioral avoidance at baseline predicted a significantly lower percentage of circulating cytotoxic/suppressor T cells (CD3(+)/CD8(+)) at 6-month follow-up, after controlling for baseline levels of cytotoxic/suppressor T cells and potential confounding variables (e.g. age, smoking status). Baseline intrusive ideation was unrelated to changes in percentage of cytotoxic/suppressor T cells. Avoidant ideation, but not intrusive ideation or depression, appears to be associated with alterations in immunologic measures in women with cervical lesions. The findings suggest that it may be important to evaluate the impact of cognitive and behavioral avoidance on progression of precancerous cervical lesions.