No abstract

This study was undertaken to assess the utility of whole‐body turbo short tau inversion recovery (STIR) magnetic resonance imaging (MRI) to detect metastases to liver, brain, and bone as a single examination in women with breast cancer. Seventeen patients with biopsy‐proven breast cancer and suspected metastatic disease attending over a 12‐month period referred for both conventional imaging and whole‐body MRI were included in the study. Three patients were found to be free of metastases at both conventional and MR imaging. Appendicular or axial skeletal metastases were identified in 11 of 17 patients, with correlation between findings at whole‐body MRI and scintigraphy in 15 of the 17 patients. Five patients had evidence of hepatic metastases on whole‐body MRI, of which metastases were identified in only three patients at CT despite contrast enhancement. Four patients had brain abnormalities (metastases in three patients, meningioma in one patient) detected on both whole‐body and dedicated brain MRI. Preliminary clinical experience suggests that turbo STIR whole‐body MRI may represent a convenient and cost‐effective method of total body screening for metastases in patients with breast carcinoma. J. Magn. Reson. Imaging 2000;11:343–350. © 2000 Wiley‐Liss, Inc.

Contrast enhanced magnetic resonance imaging (CE MRI) is the most sensitive tool for screening women who are at high familial risk of breast cancer. Our aim in this study was to assess the cost-effectiveness of X-ray mammography (XRM), CE MRI or both strategies combined. In total, 649 women were enrolled in the MARIBS study and screened with both CE MRI and mammography resulting in 1881 screens and 1 -7 individual annual screening events. Women aged 35 -49 years at high risk of breast cancer, either because they have a strong family history of breast cancer or are tested carriers of a BRCA1, BRCA2 or TP53 mutation or are at a 50% risk of having inherited such a mutation, were recruited from 22 centres and offered annual MRI and XRM for between 2 and 7 years. Information on the number and type of further investigations was collected and specifically calculated unit costs were used to calculate the incremental cost per cancer detected. The numbers of cancer detected was 13 for mammography, 27 for CE MRI and 33 for mammography and CE MRI combined. In the subgroup of BRCA1 (BRCA2) mutation carriers or of women having a first degree relative with a mutation in BRCA1 (BRCA2) corresponding numbers were 3 (6), 12 (7) and 12 (11), respectively. For all women, the incremental cost per cancer detected with CE MRI and mammography combined was d28 284 compared to mammography. When only BRCA1 or the BRCA2 groups were considered, this cost would be reduced to d11 731 (CE MRI vs mammography) and d15 302 (CE MRI and mammography vs mammography). Results were most sensitive to the unit cost estimate for a CE MRI screening test. Contrast-enhanced MRI might be a cost-effective screening modality for women at high risk, particularly for the BRCA1 and BRCA2 subgroups. Further work is needed to assess the impact of screening on mortality and health-related quality of life.

Administration of methoxamine (10 microM, 2 min) to perfused rat hearts increased the rate at which subsequently isolated mitochondria accumulated Ca2+. Methoxamine did not change significantly the development of delta phi with time or the basal rates of Ca2+ flux on inhibition of the uniporter with Ruthenium Red. With 200 microM-Pi, the rates of Ca2+ uptake at constant delta phi were unaffected by the small variations in endogenous [Pi] between mitochondrial preparations, and were also unaffected by changes in internal Ca2+ over the approximate range 8-43 nmol of Ca2+/mg. At low internal Ca2+ (about 8 nmol/mg of protein) the rates of Ca2+ uptake at constant delta phi were unaffected by addition of 200 microM-Pi. Under these conditions, the uniporter activity and the uniporter conductance were increased by 38-40% by methoxamine pretreatment. The endogenous Ca2+ content of mitochondria from control heart was about 1.8 nmol of Ca2+/mg of protein. Perfusion with agonist increased the Ca2+ content as follows: 10 microM-methoxamine (2 min), 48%; 1 microM-isoprenaline (2 min), 100%; 1 microM-adrenaline (2 min), 140%. The implications of the data for the adrenergic control of oxidative metabolism by intramitochondrial Ca2+ is discussed.

1. Noradrenaline stimulates gluconeogenesis through an alpha-adrenoceptor in renal cortical tubule fragments from fed rats incubated with 5 mM-lactate. 2. The selective alpha 1-adrenoreceptor agonist methoxamine stimulated gluconeogenesis, but the selective alpha 2-adrenoceptor agonist clonidine was ineffective. 3. The selective alpha 1-adrenoceptor antagonist thymoxamine blocked the stimulatory effects on gluconeogenesis of noradrenaline and of oxymetazoline (a synthetic alpha-agonist). The selective alpha 2-adrenoceptor antagonist yohimbine was ineffective in this respect. 4. It is concluded that noradrenaline and oxymetazoline stimulate gluconeogenesis in rat kidney via an alpha 1-rather than an alpha 2-type of adrenoceptor.

Mitochondria isolated from rat hearts perfused with adrenaline, and from hearts excised from adrenaline-treated rats, showed an enhanced rate of respiration-dependent Ca2+ uptake. Adrenaline pretreatment did not change the activity of the Na+/Ca2+-antiporter of isolated heart mitochondria. Simultaneous measurements of the membrane potential revealed that perfusion with adrenaline has no significant effect on this parameter during Ca2+ accumulation. The activation of Ca2+ uptake was induced also by the alpha-adrenergic agonist, methoxamine, but not by the beta-adrenergic agonist, isoprenaline. Methoxamine pretreatment also increased the sensitivity of alpha-oxoglutarate dehydrogenase in intact mitochondria to 10 nM--300 nM extramitochondrial Ca2+ during steady-state Ca2+ recycling across the inner membrane. Possible implications of these data for the adrenergic regulation of oxidative metabolism are discussed.

Br J Clin Pharmacol 59:2 244-248 244

Abstract. In this study we investigated whether automatic refinement of manually segmented MR breast lesions improves the discrimination of benign and malignant breast lesions. A constrained maximum a-posteriori scheme was employed to extract the most probable lesion for a user-provided coarse manual segmentation. Standard shape, texture and contrast enhancement features were derived from both the manual and the refined segmentations for 10 benign and 16 malignant lesions and their discrimination ability was compared. The refined segmentations were more consistent than the manual segmentations from a radiologist and a non-expert. The automatic refinement was robust to inaccuracies of the manual segmentation. Classification accuracy improved on average from 69% to 82% after segmentation refinement.