The binding of blood-borne estrogens in normal vegetarian and omnivorous women and the risk of breast cancer

Serial blood samples were taken at two-hour intervals over a 24-hour period from 25 premenopausal vegetarians (12 vegans and 13 ovolactovegetarians) and from 21 omnivorous controls. All members of the former group had been on a vegetarian diet for a minimum of three years. The mean proportion of estradiol unbound to blood proteins was similar in both vegetarians (1.26%) and meat eaters (1.16%). However, the amount bound to albumin was significantly raised in vegetarians (50.1% vs. 43.1%, p less than 0.009), whereas that bound to sex hormone-binding globulin (SHBG) was correspondingly lower (48.7% vs. 55.8%, p = 0.01). Mean levels of SHBG were similar in vegetarians (59.9 nmole/l) and omnivores (62.0 nmole/l), as was the total amount of free fatty acid (0.42 mmole/l for both). Within the vegetarian group, no differences were detected between vegans and ovolactovegetarians.     

Practical applications of decision analysis

The number and complexity of available tests and therapies is expanding and financial resources are shrinking. Clinicians must now consider how to give the best care while limiting health expenses. Decision analysis is a tool used to guide clinicians in the practice of medicine, and to supplement and enhance intuitive decision making based on clinical experience.     

Confounders contributing to the reported associations of coffee or caffeine with disease

The role of caffeine or coffee in causing or promoting the incidence of serious disease is equivocal. Two design factors may account for the discrepancies in reported findings on the effects of coffee drinking: (a) imprecision of measurement and (b) confounding variables. A study of 2,714 white U.S. adults disclosed that, of 32 risk factors analyzed by linear and logistic regression, only sex and cigarette smoking were found to be important potential confounders of caffeine and coffee intake. Partial R2 values of the other 30 risk factors were relatively small and were inconsistent for each sex. It is unlikely that any of these factors could explain any of the reported associations between caffeine or coffee consumption and certain diseases. However, certain weak associations with caffeine or coffee intake should be included in the study design when they are known to be risk factors of a disease under investigation. These factors for men are dietary fat intake, vitamin C intake, and body mass index; and for women are vitamin use, alcohol intake, stress, and perceived health status.     

Segregation analysis of leprosy in families of northern Thailand

Sixty-three families with multiple instances of leprosy were identified through a major leprosy treatment center in northern Thailand. Complex segregation analyses for single major genes or polygenic inheritance were performed using the maximum-likelihood routine POINTER to determine the most likely etiologic model of genetic susceptibility. Liability differences between men and women were considered in these models. When individuals were considered to be affected because they had any form of leprosy, a generalized major gene model with nearly dominant parameters on the liability scale, but additive penetrances, was found to be the most likely. When only those individuals who had tuberculoid forms of leprosy were considered to be affected, a recessive model was found to be the most likely; however, the discrimination between various models was poor. Further analyses are necessary to delineate genetic mechanisms to explain these apparently divergent results. In particular, methods of testing two locus models should be considered.     

The origin and nature of stromal osteoclast-like multinucleated giant cells in breast carcinoma: implications for tumour osteolysis and macrophage biology

The origin and nature of osteoclast-like multinucleated giant cells (OMGCs), in extraskeletal neoplasms, is uncertain. The ultrastructure, antigenic phenotype and function of OMGCsm in a breast carcinoma were studied in order to clarify the relationship between OMGCs, osteoclasts and other cells of the mononuclear phagocyte system (MPS). OMGCs resorbed cortical bone in a manner similar to osteoclasts. However, unlike osteoclasts, OMGCs did not possess a ruffled border or clear zone, and expressed HLA-DR and Fc receptors and CD14, CD16, CD18 and CD11 (p150,95) antigens. In addition, OMGCs failed to respond morphologically to calcitonin and were directly stimulated by parathyroid hormone (PTH) to increase bone resorption. These findings suggest that OMGCs are a specific type of macrophage polykaryon distinct from both osteoclasts and other types of inflammatory polykaryon. Occasional smaller (20-25 microns) macrophage-like cells were also associated with resorption pits. Bone resorption by OMGCs isolated from the breast indicates that a cell of the MPS can be transplanted to a new tissue location and perform a highly specialised function appropriate to an MPS cell of that tissue (i.e. the osteoclast). PTH stimulation of bone resorption by OMGCs suggests that PTH or a PTH-like protein, may be involved in the bone resorption and consequent hypercalcaemia associated with metastatic breast cancer.     

Laser-induced fluorescence studies of the biodistribution of carotenoporphyrins in mice.

The biodistribution of two recently developed tumour markers, trimethylated (CP(Me)3) and trimethoxylated (CP(OMe)3) carotenoporphyrin, was investigated by means of laser-induced fluorescence (LIF) after i.v. injection into 38 tumour-bearing (MS-2 fibrosarcoma) female Balb/c mice. At 3, 24, 48 or 96 h after administration, the carotenoporphyrin fluorescence was measured in tumoral and peritumoral tissue, as well as in the abdominal, thoracic and cranial cavities. The fluorescence was induced by a nitrogen laser-pumped dye laser, emitting light at 425 nm, and analysed by a polychromator equipped with an image-intensified CCD camera. The fluorescence was evaluated at 490, 655 and 720 nm: the second and third wavelengths represent the carotenoporphyrin (CP)-related peaks, whereas the first one is close to the peak of the tissue autofluorescence. The tumour and the liver were the two tissue types showing the strongest carotenoporphyrin-related fluorescence, whereas the cerebral cortex and muscle consistently exhibited weak substance-related fluorescence. In most tissue types, the fluorescence intensities decreased over time. A few exceptions were observed, notably the liver, in which the intensity remained remarkably constant over the time period investigated.