Autosomal dominant Stargardt-like macular dystrophy

Autosomal dominant Stargardt-like macular dystrophy is one of the early onset macular dystrophies. It is characterized clinically in its early stages by visual loss and by the presence of atrophic macular changes with or without the presence of yellowish flecks. It is an important retinal dystrophy to study, not only because it has implications in the care and treatment of patients with the condition, but because it also provides important information regarding retinal function. Review of the literature suggests that many of the reported families are linked to chromosome 6q. Genetic and genealogical evidence suggests that these families have descended from a common ancestor or founder. The recent identification of a disease-causing gene that is involved in fatty acid metabolism may have implications in the study of the more common age-related macular degeneration. We review the recent clinical, genetic, and genealogical aspects of autosomal dominant Stargardt-like macular dystrophy.     

Relation of plasma leptin concentrations to sex, body fat, dietary intake, and peak oxygen uptake in young adult women and men

The purpose of this study was to examine the relation of leptin to metabolic and dietary factors in college-age adults. Young adult women and men (n = 32) were recruited and underwent testing for measurement of body mass index, body composition, peak oxygen consumption (VO2peak), dietary intake, and plasma levels of leptin and insulin. Ln leptin was significantly greater for women than for men (2.1 versus 1.2 ng/mL, respectively). This difference remained significant even after adjusting ln leptin for fat mass and fat-free mass as covariates in separate analyses. VO2peak was higher for men than for women and this remained significant after adjustment for differences in fat-free mass and total body mass. Significant correlations were found between ln leptin and indicators of fat mass in women and men, with higher correlations for similar variables observed in men (r = 0.548, 0.674, and 0.732 for body mass index, percentage of body fat, and fat mass [kg] for women, respectively, and r = 0.740, 0.888, 0.858 for body mass index, percentage of body fat, and fat mass [kg] for men, respectively). Ln leptin showed a significant inverse relationship with VO2peak (r = -0.751) in men only. After adjusting ln leptin for body fat mass using partial correlations, ln leptin was not significantly associated with any of the measured variables. Alternatively, after normalization of ln leptin using fat mass as the divisor, a less adequate statistical analysis method, men showed statistical significant correlations between ln leptin and dietary intake and VO2peak. Although plasma leptin values were higher in women, stronger associations were evident for men than for women between leptin and metabolic and dietary factors.     

The relation between mortality from malignant melanoma and early detection in the Cancer Research Campaign Mole Watcher Study

Between 1987 and 1989 the Cancer Research Campaign funded a health education programme for the early detection of cutaneous malignant melanoma in the general population in 6 health districts of England and 1 health board in Scotland (population of 3 million). The intervention was evaluated by studying its effects on annual and cumulative mortality rates for melanoma. Population-based data on mortality from melanoma were collected in the intervention areas, the health regions covering those areas, and 5 other health regions of England from 1981 to 1996. Deaths from melanoma in cases diagnosed after the start of the intervention were used to study cumulative mortality rates. The annual mortality rates for melanoma, 1981 to 1996, showed no significant difference in their trends between the intervention areas, and other areas of England and Wales. After adjustment for pre-intervention rates, there was also no significant reduction in cumulative mortality from melanoma in the intervention areas compared with the non-intervention areas: rate ratio 1.2 (95% Cl 0.9-1.7) in men, 0.9 (95% Cl 0.7-1.3) in females. The lack of a significant reduction in melanoma mortality associated with the intervention raises questions about this approach to early detection and emphasises the need for new strategies.     

Mammography utilization after a benign breast biopsy among Hispanic and non-Hispanic women

BACKGROUND: In spite of the effectiveness of mammography screening for early detection of breast carcinoma, the use of screening mammography varies widely across racial and ethnic groups. Recently, concerns have been raised about the potential adverse effect a benign breast biopsy may have on subsequent mammography utilization, including subsequent use among minority women. METHODS: Computerized health care claims data for 1991 through 1997 from a managed care organization were used to compare mammography use among Hispanic and non-Hispanic women who had had a mammogram followed by an incisional or excisional benign breast biopsy to women who had had a mammogram and no biopsy. Through survival analysis methods, the time-to-next mammogram was compared among these three groups. RESULTS: The sample included 693 (3.2%) and 289 (1.3%) women who had had a mammogram followed by an incisional biopsy or an excisional biopsy, respectively, and 20,540 (95.4%) women who had had a mammogram and no biopsy. Both Hispanic and non-Hispanic women with a biopsy returned sooner for subsequent mammograms than women without a biopsy (P < 0.0001). Hispanic women without a biopsy returned later than non-Hispanic women without a biopsy (P < 0.0001). However, Hispanic women with an excisional biopsy returned sooner than non-Hispanic women (P < 0.05). CONCLUSIONS: Within a managed care organization, both Hispanic and non-Hispanic women who had had a mammogram followed by a benign breast biopsy returned sooner for a subsequent mammogram than women who had had a mammogram and no biopsy. However, ethnic differences in time-to-next mammogram were observed for women without a biopsy and those with an excisional biopsy. Hispanic women without a biopsy returned later for a subsequent mammogram than non-Hispanic women in similar groups, but those with an excisional biopsy returned sooner.     

Vascular endothelial growth factor reduces tamoxifen efficacy and promotes metastatic colonization and desmoplasia in breast tumors

Clinical studies have shown that decreased tamoxifen effectiveness correlates with elevated levels of vascular endothelial growth factor (VEGF)-A(165) in biopsy samples of breast cancers. To investigate the mechanisms underlying tamoxifen resistance and metastasis, we engineered the estrogen receptor (ER)-positive MCF-7 human breast cancer cell line to express VEGF to clinically relevant levels in a doxycycline-regulated manner. Induction of VEGF expression in orthotopically implanted xenografts that were initially tamoxifen responsive and noninvasive resulted in tamoxifen-resistant tumor growth and metastasis to the lungs. Lung metastases were also observed in a VEGF-dependent manner following tail vein injection of tumor cells. At both primary and metastatic sites, VEGF-overexpressing tumors exhibited extensive fibroblastic stromal content, a clinical feature called desmoplasia. VEGF-induced metastatic colonies were surrounded by densely packed stromal cells before detectable angiogenesis, suggesting that VEGF is involved in the initiation of desmoplasia. Because expression of VEGF receptors R1 and R2 was undetectable in these tumor cells, the observed VEGF effects on reduction of tamoxifen efficacy and metastatic colonization are most likely mediated by paracrine signaling that enhances tumor/stromal cell interactions and increases the level of desmoplasia. This study reveals new roles for VEGF in breast cancer progression and suggests that combination of antiestrogens and VEGF inhibitors may prolong tamoxifen sensitivity and prevent metastasis in patients with ER-positive tumors.     

The role of the avian hippocampus in orientation in space and time

We examined the effects of hippocampus (Hp) and area parahippocampalis (APH) lesions in pigeons on their ability to perform a battery of tasks including autoshaping, time discrimination, spatial memory, and pattern discrimination. Pigeons with Hp-APH lesions were impaired in the acquisition of an autoshaped response, emitting fewer pecks to the stimulus than control animals. Hp-APH pigeons were also impaired in the acquisition of a radial-arm maze analogue task, and those birds that did learn the task seemed to do so by adopting a stereotypic response strategy. In contrast, Hp-APH lesions had no effect on the ability of the birds to discriminate on the basis of either temporal or visual information. Overall, these studies complement our earlier studies and suggest that the avian hippocampus is important for the processing and retention of spatial rather than non-spatial information.