Familial breast cancer risk assessment

A family, with a strong history of dominant breast and ovarian cancer, is described. Using highly polymorphic microsatellite markers within the BRCA1 breast cancer gene on chromosome 17q21; three affected sisters, their father and a paternal second cousin once removed, are shown to share the same "abnormal" haplotype. Because of this informative linkage, the carrier status of the unaffected siblings can be established by determining whether they inherited their father's "normal" or "abnormal" haplotype. Presymptomatic diagnosis is important in decisions regarding prophylactic surgery or follow-up care. However, the widespread general population presymptomatic DNA testing of breast cancer is currently not recommended because of inherent problems in the sensitivity and specificity of DNA testing.     

Breast cancer: further metabolic-endocrine risk markers?

There is evidence that increased oestrogen receptor (ER) expression in normal mammary epithelium may be a risk marker for the development of breast cancer. Insulin-like growth factor 1 (IGF1) is a potent inducer of mitosis and has been shown to synergize with oestrogen in stimulating the growth of human breast cancer in vitro. In these cells oestradiol has been shown to upregulate IGF type 1 receptor (IGFR), and recently a similar effect has been reported in normal human breast tissue xenografts in vivo. It has been postulated that the combined effect of oestradiol and IGF1 may stimulate proliferation in normal mammary epithelium and increase breast cancer risk. The bioavailability of IGF1 to the tissues is modulated by IGF-binding proteins (IGFBPs), and higher circulating levels of IGF1 and lower levels of IGFBP3 have been reported in breast cancer patients. Breast cancer specimens show a positive correlation between ER status and IGF receptor status, and also a negative correlation between ER status and IGFBP3 expression. Finally, ectopic growth hormone expression has been shown in a majority of specimens of normal and malignant breast tissue, and this may contribute to breast cancer risk, possibly by increasing the local level of bioavailable IGF1. Expansion of such findings may provide clinically useful markers of increased risk to breast cancer in women.     

Molecular markers of IGF-I-mediated mitogenesis

The aim of these investigations was to identify a number of molecular markers that correlate to growth stimulation by IGF-I. For this purpose, we have selected four cell lines that respond equally well to growth stimulation by serum, but differ in their proliferative response to IGF-I. Two cell lines (R503 and R600 cells) respond to IGF-I with both DNA synthesis and cell division, a third cell line (R508 cells) can enter S phase after IGF-I, but the cells do not divide, and a fourth one (R12 cells) totally fails to respond to IGF-I with growth. Using these cell lines, all of which had an intact mitogenic response program to serum, we show that: (1) an increase in GTP/GDP ratio is an early event that distinguishes cells capable of entering S phase after IGF-I from cells that do not; (2) all cells that are induced to synthesize DNA by IGF-I have increased phosphorylation of MAP kinases, regardless of their ability to divide; (3) the same cell lines display a similar increase in cyclin A and B expression at early times after stimulation; and (4) cyclin levels and cyclin B-associated cdc2 kinase activity remain elevated at later times only in cells that undergo cell division. These results establish certain parameters of IGF-I-mediated mitogenesis and clearly separate the occurrence of DNA synthesis from cell division in certain situations.     

Gastric cancer and Helicobacter pylori: biologic and epidemiologic inconsistencies

This article introduces the special section of the Journal of Consulting and Clinical Psychology on empirically supported psychological therapies. After a discussion of the rationale for the selection of the specific terms in the label, several justifications are considered for conducting and learning from empirical evaluations of psychological therapies. Finally, the process that guided the special section is described.     

Prognostic risk assessment in primary breast cancer by behavioral and immunological parameters.

Investigated the predictive power of an immunologic effector cell, the natural killer (NK) cell, as well as selected psychological and demographic factors, to breast cancer prognostic risk status. 75 women (aged 28–74 yrs) with Stage I or II breast cancer were interviewed about their perceptions, attitudes, and interpersonal support. Ss also completed the SCL-90 and the Profile of Mood States. Blood was then drawn to assay NK functional activity. All assessments took place after surgery. It was found that NK activity predicted the status of cancer spread to the axillary lymph nodes. Ss who had low levels of NK activity were rated as well-adjusted to their illness; Ss who had higher NK activity appeared to be distressed or maladjusted. Findings are discussed in the light of recent animal findings linking environmental stress and behavioral responsiveness to biological vulnerability via endocrine and immune pathways. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Obstetric risk assessment

Obstetric risk assessment is an important component of comprehensive obstetric care. It is a tool used to evaluate the medical, psychosocial, familial, and environmental factors that increase the chance of an adverse outcome. Such outcomes may involve the mother, the infant, or both. Risk assessment collects and organizes data obtained from a pertinent history, physical examination, and laboratory assessment into an accurate and easily retrievable medical record. It can be used to adapt diagnostic or therapeutic management plans, arrange consultation or shared care with another specialist, or tailor anticipatory guidance and patient and family education.     

Molecular biomarkers of early responses to environmental stressors: implications for risk assessment and public health

Resistance of Candida to azoles is an increasing problem. Susceptibility testing of Candida against fluconazole and ketoconazole is now feasible and desirable. Good correlation of resistance in vitro with clinical failure of fluconazole therapy has now been shown in mucosal candidiasis. The relationship, if any, between resistance and clinical failure in the context of invasive candidiasis is not clear at present and additional correlative work needs to be done. Monitoring of resistance trends in Candida is clearly important now.     

Molecular biologic screening test (PCR) for fragile X syndrome

Fragile X syndrome is the most common inherited from of familial mental retardation. It is caused by an expanded CGG repeat in the first exon of the fragile X mental retardation gene. A polymerase chain reaction based technique was used for the identification of full mutations among men. According to our conditions full mutations failed to amplify. An internal control was used at a CG rich region 147 bp upstream of the polymorphic region. The bands were visualised on silver stained polyacrylamide gels. From the 57 individuals studied molecular analysis was performed on 38 males and 16 females. From the 26 males with suspected fragile X syndrome 9 males resulted in no amplification of the 500 kb product, all having a positive cytogenetic result for fragile X syndrome. One cytogeneticly positive male had normal results by molecular studies suggesting a different mutation. All control males had normal results. The results on the 16 females studied were inconclusive. We suggest that our method is highly sensitive and specific for screening males for fragile X syndrome.     

Dysplastic nevi and other risk markers for melanoma

Risk markers for cancer are genetic or behavioral attributes that are statistically associated with increased incidence of cancer. Risk may be assessed either in case-control studies, or in cohort studies in which individuals with particular attributes are followed and cancer risk is determined by direct observation. Both of these methods have been used to determine the major risk markers for melanoma. The single most important risk marker is the presence on the skin of dysplastic nevi. Dysplastic nevi may be regarded as intermediate lesions of tumor progression, in that approximately 30% of melanomas arise in association with a precursor nevus, which is most commonly dysplastic. However, paradoxically, because they are vastly more numerous than melanoma, most dysplastic nevi are stable lesions that do not progress. Additional important melanoma risk factors include a family and/or personal history of melanoma. A third major category of risk markers includes indicators of acute and chronic exposure to the sun, including freckles, actinic skin damage, and a history of sunburn. Evaluation of these markers in oncological patients and their first-degree relatives can identify a population of individuals whose risk for melanoma ranges from several-fold to more than 100-fold greater than that of random population members. Efforts directed at early diagnosis in these individuals can result in recognition of melanomas in their early, curable stages.     

Disability and work: risk assessment

Recent parliamentary debate has brought the rights of disabled people back into the spotlight of media attention. In the workplace, the occupational health nurse (OHN) is uniquely placed to make a positive contribution to the achievement of equal opportunities for people with disabilities. The author describes a risk assessment approach to the occupational health and safety of disabled persons and their employers. Such approaches can help to ensure that the work skills of all employees are used to maximum potential.