Short-Ti inversion-recovery pulse sequence: analysis and initial experience in cancer imaging

Inversion recovery (IR), commonly considered a pulse sequence capable of producing T1-weighted images with excellent display of normal anatomy, is versatile: The null point and peak time provide a useful, succinct summary of the properties of IR and its capacity for producing both T1- and T2-weighted images. Shortening of the inversion time (TI) and creation of a short-TI inversion-recovery (STIR) pulse sequence increases sensitivity to malignancy and other abnormalities by making the effects of prolonged T1 and T2 on signal intensity additive and by nulling the signal from fat. The authors examined over 300 patients with various malignancies and compared STIR images with T1- and T2-weighted images obtained at 0.5 T. In 43 cases, signal-difference-to-noise ratios (SD/Ns) were calculated between tumor, fat, and muscle. In general, STIR images demonstrated tumor as a conspicuously high-intensity area in a background of muted, discernible anatomic detail. The good contrast achieved with STIR sequences between tumor and fat (SD/N = 18.1) and tumor and muscle (SD/N = 12.9) consolidated into a single image the information contained separately on T1- and T2-weighted images, which facilitates efficient detection and localization of malignancy.     

The effects of antioxidant supplementation during Percoll preparation on human sperm DNA integrity

The integrity of sperm DNA is crucial for the maintenance of genetic health. A major source of damage is reactive oxygen species (ROS) generation; therefore, antioxidants may afford protection to sperm DNA. The objectives of the study were, first, to measure the effects of antioxidant supplementation in vitro on endogenous DNA damage in spermatozoa using the single cell gel electrophoresis (comet) assay and, second, to assess the effect of antioxidant supplementation given prior to X-ray irradiation on induced DNA damage. Spermatozoa from 150 patients were prepared by Percoll centrifugation in the presence of ascorbic acid (300, 600 microM), alpha tocopherol (30, 60 microM), urate (200, 400 microM), or acetyl cysteine (5, 10 microM). DNA damage was induced by 30 Gy X-irradiation. DNA strand breakage was measured using the comet assay. Sperm DNA was protected from DNA damage by ascorbic acid (600 microM), alpha tocopherol (30 and 60 microM) and urate (400 microM). These antioxidants provided protection from subsequent DNA damage by X-ray irradiation. In contrast, acetyl cysteine or ascorbate and alpha tocopherol together induced further DNA damage. Supplementation in vitro with the antioxidants ascorbate, urate and alpha tocopherol separately has beneficial effects for sperm DNA integrity.      

How to use Chlamydia antibody testing in subfertility patients

Screening for tubal factor subfertility by means of Chlamydia antibody testing (CAT) was introduced into the initial work-up of subfertile couples several years ago. The results reported, however, are heterogeneous, and no uniformity exists in cut-off levels of titres, or in definitions of tubal factor subfertility. We performed a prospective cohort study to evaluate the implications of varying the definitions of tubal pathology and of modifying the cut-off levels on the clinical impact of CAT in predicting tubal factor subfertility. In 227 consecutive patients who attended our fertility clinic, the Chlamydia IgG antibody titre was determined and related to tuboperitoneal abnormalities at laparoscopy as a reference standard. According to received operating characteristic (ROC) curve analysis, a titre of 16 is the optimum cut-off level. Increasing the cut-off level improves specificity and positive likelihood ratio (LR+), at the expense of sensitivity and negative LR (LR-). Changing the definition of tubal factor subfertility from unspecified tuboperitoneal abnormalities into extensive adhesions and/or bilateral distal tubal occlusion improves LR+, LR- and kappa significantly. We conclude that CAT is more accurate in predicting severe distal tubal pathology than unspecified tuboperitoneal abnormalities. Although from a statistical point of view a titre of 16 is the optimum cut-off level, from a clinical point of view 32 or 64 may be preferable, depending on the aim of screening and the inception cohort.      

Toremifene in the treatment of breast cancer

Although more widespread screening and routine adjuvant therapy has improved the outcome for breast cancer patients in recent years, there remains considerable scope for improving the efficacy, safety and tolerability of adjuvant therapy in the early stage disease and the treatment of advanced disease. Toremifene is a selective estrogen receptor modifier (SERM) that has been widely used for decades in hormone receptor positive breast cancer both in early and late stage disease. Its efficacy has been well established in nine prospective randomized phase III trials compared to tamoxifen involving more than 5500 patients, as well as in several large uncontrolled and non-randomized studies. Although most studies show therapeutic equivalence between the two SERMs, some show an advantage for toremifene. Several meta-analyses have also confirmed that the efficacy of toremifene is at least as good as that of tamoxifen. In terms of safety and tolerability toremifene is broadly similar to tamoxifen although there is some evidence that toremifene is less likely to cause uterine neoplasms, serious vascular events and it has a more positive effect on serum lipids than does tamoxifen. Toremifene is therefore effective and safe in the treatment of breast cancer. It provides not only a useful therapeutic alternative to tamoxifen, but may bring specific benefits.     

von Willebrand factor released from Weibel-Palade bodies binds more avidly to extracellular matrix than that secreted constitutively

Large multimers of von Willebrand factor (vWf) are released from the Weibel-Palade bodies of cultured endothelial cells following treatment with a secretagogue (Sporn et al, Cell 46:185, 1986). These multimers were shown by immunofluorescent staining to bind more extensively to the extracellular matrix of human foreskin fibroblasts than constitutively secreted vWf, which is composed predominantly of dimeric molecules. Increased binding of A23187-released vWf was not due to another component present in the releasate, since releasate from which vWf was adsorbed, when added together with constitutively secreted vWf, did not promote binding. When iodinated plasma vWf was overlaid onto the fibroblasts, the large forms bound preferentially to the matrix. These results indicated that the enhanced binding of the vWf released from the Weibel-Palade bodies was likely due to its large multimeric size. It appears that multivalency is an important component of vWf interaction with the extracellular matrix, just as has been shown for vWf interaction with platelets. The pool of vWf contained within the Weibel-Palade bodies, therefore, is not only especially suited for platelet binding, but also for interaction with the extracellular matrix.     

Detection of circulating crosslinked fibrin derivatives by a heat extraction-SDS gradient gel electrophoretic technique

A technique has been developed to identify and quantitate unique plasmic degradation products of crosslinked fibrin in plasma. In this method, fibrin derivatives are extracted by heat precipitation and dissolved with disulfide bond reduction, after which the crosslinked gamma-gamma chain remnants are identified by SDS-polyacrylamide gradient gel electrophoresis and quantitated by densitometric analysis. A heterogenous group of gamma-gamma chains with molecular weights between 100,000 and 76,000 daltons was identified in lysates of crosslinked fibrin during plasmic degradation in vitro. Three stages of crosslinked fibrin degradation have been arbitrarily defined based primarily on the extent of degradation of these gamma-gamma polypeptide chains. As little as 20 microgram of crosslinked fibrin digests added to 1 ml of normal plasma could be detected by the heat-extraction--gel- electrophoresis technique, identifying the gamma-gamma derivatives with molecular weights of 96,000, 86,000, 82,000, and 76,000 daltons. Plasmic derivatives of gamma-gamma chains were not found in normal plasma, but they were identified in the plasma of patients with disseminated intravascular coagulation and deep-vein thrombosis, both before and in increased quantity during successful thrombolytic therapy.     

Associations of Adolescent Hopelessness and Self-Worth With Pregnancy Attempts and Pregnancy Desire

Objectives. We examined the associations of pregnancy desire (ambivalence or happiness about a pregnancy in the next year) and recent pregnancy attempts with hopelessness and self-worth among low-income adolescents.Methods. To evaluate independent associations among the study variables, we conducted gender-stratified multivariable logistic regression analyses with data derived from 2285 sexually experienced 9- to 18-year-old participants in the Mobile Youth Survey between 2006 and 2009.Results. Fifty-seven percent of youths reported a desire for pregnancy and 9% reported pregnancy attempts. In multivariable analyses, hopelessness was positively associated and self-worth was negatively associated with pregnancy attempts among both female and male youths. Hopelessness was weakly associated (P = .05) with pregnancy desire among female youths.Conclusions. The negative association of self-worth and the positive association of hopelessness with pregnancy attempts among young men as well as young women and the association of hopelessness with pregnancy desire among young women raise questions about why pregnancy is apparently valued by youths who rate their social and cognitive competence as low and who live in an environment with few options for material success.Rates of adolescent pregnancy and childbearing in the United States are among the highest in the developed world.1 Each year, approximately 750 000 women younger than 20 years become pregnant,2 and about 400 000 give birth.3 In the United States, adolescent pregnancy rates are about two thirds higher among non-White young women than among White young women, and childbearing rates are approximately one third higher2; 57% of births to adolescents in 2010 were to African American or Hispanic/Latino mothers.3 Surveillance data for 9th- to 12th-grade US students show that Blacks and Hispanics are more likely than Whites to engage in risk behaviors associated with pregnancy (e.g., vaginal intercourse at an early age, nonuse of hormonal contraceptives).4Race and ethnicity do not, in themselves, explain adolescent pregnancy risk. Kirby identified more than 100 antecedents of adolescent pregnancy, primarily related to the types of physical and social environments in which minority youths in the United States are disproportionately represented.5 He concluded that most risk factors, including poor school performance6 and residence in a socioeconomically disadvantaged neighborhood,7–9 reflected dysfunction, disadvantage, or disorganization. Offspring of adolescent parents or sisters of women who began childbearing in adolescence are at high risk for adolescent parenthood, suggesting a cultural or intergenerational component.8–10 Family quality, especially parent characteristics and relationships9,11–16; the quality of relationships with one’s school, residential community, and peers6,7,9,12,14; and substance use and mental health,9,17–22 are associated with pregnancy or pregnancy risk behaviors among both female and male adolescents.Youths who live in challenging social and physical environments typically have negative psychological and cognitive responses to their surroundings (e.g., low self-worth and hopelessness).23,24 Although the evidence is mixed,20–22,25,26 it is generally assumed that poor self-image, poor self-worth, and poor self-esteem in girls are associated with pregnancy or pregnancy risk markers, including early age at first vaginal intercourse and an inability to negotiate condom use. Hopelessness reflects negative expectations about future desired or valued outcomes and helplessness with respect to one’s ability to change the odds that negative outcomes will occur.27 Hopelessness has been identified as a risk marker for youth violence and self-harm and poor adult social trajectories.24,28–31 In industrialized countries, adolescent pregnancy (and the decision to continue a pregnancy) may be a consequence of a lack of hope and the perception of too few positive life options,32,33 although only a limited number of studies have directly examined hopelessness and pregnancy risk.Kogan et al. examined a related phenomenon, conventional future orientation, and found associations with decreased sexual risk taking at age 16 and avoidance of pregnancy at age 19 years.34 A 2013 study of Mobile Youth Survey (MYS) participants showed that having a positive feeling about the future was marginally associated with older age at first intercourse, a risk factor for adolescent pregnancy.35 Neither study examined female and male youths separately. Despite the health, social, and economic burdens associated with pregnancy involvement among boys,9,36,37 little is known about the psychological or cognitive correlates of adolescent paternity risk.Adolescent pregnancy and childbearing disproportionately occur among historically marginalized youths and present significant, and often lifelong, social and health risks to parents and their offspring.37 Many known antecedents, including poverty, neighborhood quality, and quality of the parental relationship, may be intractable. However, learned cognitive factors such as hopelessness and low self-worth may be modifiable.27Because of our overarching interest in identifying potentially intervenable correlates of pregnancy involvement among high-risk youths, we examined the hypotheses that hopelessness is positively associated and self-worth is negatively associated with 2 known risk markers of adolescent pregnancy: pregnancy attempts and pregnancy desire.15,26,38–42 Our analyses involved a cross-sectional sample of adolescent female and male participants in the MYS,43 a study of primarily African American and impoverished young people with little variation in their social risk for pregnancy. Because there may be gendered cultural meanings or consequences associated with early pregnancy and parenting (especially in communities where rates of adolescent pregnancy are disproportionately high) and because the psychological or cognitive correlates of pregnancy risk may vary according to gender,21,22 we examined female and male youths separately.