Transforming growth factor-beta signaling leads to uPA/PAI-1 activation and metastasis: a study on human breast cancer tissues.

Metastasis represents a major problem in the treatment of patients with advanced primary breast cancer. Both Transforming Growth Factor-Beta (TGF-ß) signaling and Plasminogen Activator (PA) components, urokinase-type Plasminogen Activator (uPA) and Plasminogen Activator Inhibitor-1 (PAI-1) represent a complex network crucial for such enhanced invasiveness of tumors and imply high prognostic/predictive and promising therapeutic potential. Therefore, protein expression of specific effector molecules comprising the main parts of the TGF-ß signaling pathway were determined in HOPE-fixed human tumor tissues through IHC (Scoring) using tissue microarray (TMA) technique and correlated with respective uPA and PAI-1 levels determined earlier in the same TMAs through optimized IHC and semi-quantitative image analysis. TGF-ß signaling was active in vast majority (96 %) of the tumor samples and 88 % of all cases were significantly correlated with established metastasis markers uPA and PAI-1. In addition, TGF-ß was also closely associated with tumor size, nodal status and two steroid hormone receptors. Consistent interrelationships between TGF-ß, PA components and additional tumor characteristics underline the superiority of such more comprising data with regards to confirming TGF-ß signaling as a promising target system to inhibit metastasis in advanced breast cancer.

Optimized immunohistochemistry in combination with image analysis: a reliable alternative to quantitative ELISA determination of uPA and PAI-1 for routine risk group discrimination in breast cancer.

The determination of the invasion markers urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) has further improved the possibilities for individualized therapy of breast cancer. To date, quantitative measurement by ELISA, that needs large amounts of fresh, frozen material, is the only standardized procedure for diagnostic purposes. Therefore, the aim of this study was the establishment of a reliable alternative method based on immunohistochemistry (IHC) and image analysis requiring only small amounts of fixed tumor tissue. Protein expression of uPA and PAI-1 was analyzed in HOPE-fixed tumor samples using tissue microarrays (TMAs) and semiquantitative image analysis. The results of both methods were significantly correlated and risk assessment showed an overall concordance of 78% (83/107; high- and low-risk) and of 94% (74/79) regarding only high-risk patients. The data demonstrate that optimized IHC in combination with image analysis can provide adequate clinical significance compared to ELISA-derived determination of uPA and PAI-1.

Unanswered questions and ethical issues concerning US biodefence research.

Unanswered questions and ethical issues associated with US biodefence medical research over the past five decades are discussed. Objective scientific standards are essential for making policy decisions that can stand the test of time. For decades, scholars have reported that the human anthrax vaccine field trials conducted in the 1950s by Brachman and his colleagues were single-blind rather than double-blind. Nevertheless, in March 2005, Dr Philip S Brachman reported in a letter to the US Food and Drug Administration that his study had been double-blind. It is here argued that, rather, the field trial of a human anthrax vaccine should continue to be deemed as single-blind unless more detailed information is provided to explain exactly how the investigators were kept unaware of which subjects were in the treatment and control groups. Moreover, a number of other questions about the details of this critically important study have remained unanswered and are discussed. More recently, similar concerns have arisen with respect to more contemporary biodefence research, especially with reference to the Federal Bureau of Investigation's allegations that Dr Bruce Ivins, a US government biodefence researcher, was responsible for the anthrax letter attacks of fall 2001. The medical ethics and related issues involved with continuing to base national biodefence and public health policy on unclear, if not contradictory, research are discussed.

[Risk profiling of postoperative complications in 17,644 total knee replacements]. / Identifizierung von Risikofaktoren postoperativer Komplikationen in der primären Knieendoprothetik.

AIM: Postoperative complications following primary total knee replacement performed between 2000 and 2002 were assessed to determine perioperative patient- and procedure-related risks associated with the procedure. METHODS: For this analysis, the data collected during postoperative hospitalization for 17,644 total knee arthroplasties were assessed. The analysis included two steps. First, using logistic regression, we identified and quantified significant risk factors for the occurrence of general postoperative complications. Second, univariate analysis was utilized to qualitatively and quantitatively analyze the influence of these significant risk factors on the occurrence of major complications (hematoma, cardiovascular complication, deep venous thrombosis, pulmonary embolism, joint infection, and pneumonia). RESULTS: General postoperative complications were reported in 11.3%. Major postoperative complications occurred in 7.2% with hematoma in 2.9%, cardiovascular complications in 1.8%, deep venous thrombosis in 1.2%, pulmonary embolism in 0.2%, joint infection in 0.8%, and pneumonia in 0.3%. Patient-related risk factors such as age, surgery time, gender, high ASA classification as well as procedure-related risk factors such as allogeneic blood transfusions and lateral release significantly increased the rate of postoperative complications. Males were more prone to hematoma, joint infection, and pneumonia in the immediate postoperative course than females, who were more in danger of developing deep venous thrombosis. Allogeneic blood transfusions increased the risk for postoperative hematoma, infection, and cardiovascular complication. Regional anesthesia was shown to decrease the risk for the occurrence of postoperative deep venous thrombosis and pulmonary embolism. CONCLUSIONS: Postoperative complications in total knee replacement are increased in males and elder patients. Increased time of surgery and allogeneic blood transfusions also represent important risk factors for postoperative complications following primary total knee replacement.

Predicting the extent and stressfulness of problem rumors at home among Army wives of soldiers deployed overseas on a humanitarian mission.

Nearly 500 civilian wives of enlisted soldiers from Fort Drum, New York were surveyed about the extent to which they experienced, as problems, rumors about what was happening in Somalia and when their soldier would return from the Operation Restore Hope deployment to Somalia in 1993. Rumors, as problems, were cited less frequently than loneliness, fears about the soldier's safety, or ignorance of the situation in Somalia but more frequently than problems with communication, finances, or legal issues. The strongest initial predictor of such problems was having communication problems with the soldier. Other significant predictors included length of deployment, soldier's rank, and unit support systems. More frequent use of telephone or regular mail, however, did not appear to reduce such rumors. Stressfulness of rumors appeared to be reduced by good unit leadership, good family support groups, and better emotional adaptability to deployment by spouses, while increased by reliance on surface mail for communication with one's deployed spouse. Subsequent analyses indicated that having fears about the safety of one's soldier or concerns about not knowing what was going on in Somalia were also significantly correlated with rumors as problems. Our results may support hypotheses that rumors serve to fill gaps in official information and justify spouses' anxieties regarding the safety of their deployed soldier.

Recent research on family factors and readiness: implications for military leaders.

Past research on the relationship between family factors and military readiness in the Army has suggested that family issues affect retention far more than readiness. New data on individual soldier readiness were analyzed to assess the relative importance of family factors (internal and external family adaptation) compared to unit readiness, longevity, rank, and gender. Family factors were significant predictors, although external family adaptation appeared to be more important than internal family adaptation. Although variables related to retention were more strongly related to family factors than our readiness variables, the differences were less substantial than those reported previously. The data seemed to suggest that reserve-component readiness might be more affected by family stress than the active component and that officer readiness might be more strongly affected by family worries than enlisted personnel readiness, but more research is needed to confirm those results.

Development of three new scales for assessing clients' perspectives on premarital counseling.

Within a subsample of 73 men and 179 women from a larger study of current and former members of the Christian Church (Disciples of Christ), three new scales were developed to assess the value attributed to premarital counseling, quality of premarital counseling received, and a pastor's competence at premarital counseling. Although internal consistency reliability as measured by Cronbach alpha was marginally acceptable (.61) for the latter three-item scale, it was adequate for the three-item value (.84) and the seven-item quality (.87) scales. Evidence for construct validity was limited with respect to demographic variables for social class, sex, and religiosity. Those who attended church more frequently and women reported lower quality of premarital counseling.

Family strengths and the Kansas Marital Satisfaction Scale: a factor analytic study.

20 new items were developed to measure six concepts of family strengths and were administered, along with the Kansas Marital Satisfaction Scale, to over 266 married subjects as part of a larger survey of current and former members of the Christian Church (Disciples of Christ). A common factor analysis suggested that most of the items were associated with their expected factors, while reliability analyses indicated that most of the scales had acceptable estimates of internal consistency. The marital satisfaction items clearly were associated with their own factor and not other factors, providing support for the unidimensional nature of the Kansas Marital Satisfaction Scale and for its construct validity.

A brief measure of intrinsic religiosity used with a sample of military veterans.

A brief, three-item measure of intrinsic religiosity adapted from Gorsuch and Venable (1983) was used with over 900 male and female Reserve Component veterans who had been serving in the military during the Persian Gulf War. In general, approximately two-thirds of the veterans indicated agreement or strong agreement with an internal commitment to their religious beliefs. Despite its brevity, the scale demonstrated adequate estimates of internal consistency reliability (alpha = .93). It was also found that the female veterans reported a significantly higher mean on intrinsic religiosity as measured by this scale than did the male veterans.

Pyridostigmine bromide and the long-term subjective health status of a sample of female reserve component Gulf War veterans: a brief report.

The role of pyridostigmine bromide (PB) pills in explaining the long-term subjective health status of a sample of over 100 female Reserve Component Gulf War veterans was examined through regression analysis. Results fell just short of significance (p < .06) for the prediction of subjective health approximately six years after the war and were clearly not significant for the prediction of subjective health at previous times. Results parallel Golomb's 1999 RAND report, which found suggestive but not conclusive evidence for the possible adverse effects of Gulf War veterans' consumption of pyridostigmine bromide pills. Our data suggest that use of more than 10 pills may have been especially risky with respect to long-term subjective health.

Soldiers at risk for individual readiness or morale problems during a six-month peacekeeping deployment to the Sinai.

Longitudinal data were examined to predict soldiers' morale, satisfaction with Army life, and the effects of family issues on performance of duties during an overseas deployment (Sinai peacekeeping force during the spring of 1995). Few variables were significant predictors of the outcome measures; however, rank, leaders' support for families, prior satisfaction with Army life and with information released about the deployment appeared to predict better outcomes during the deployment. Rank and leaders' support for families appeared to be more important for married soldiers while satisfaction with predeployment information seemed to be more important for single soldiers. Those who were worried about the effects of the deployment on their families also tended to report interference with their duty performance because of family concerns, but that effect was offset by perceived leaders' concern for families. In conclusion, it appears to the authors that the pre-existing factors studied had much less to do with deployment outcomes than did leadership success before and during the deployment. That's good news for Army leaders about their power to have a positive effect on soldiers' morale during overseas deployments but may be bad news for anyone hoping to find a "magic bullet" for pre-identification of soldiers most likely to retain high morale, regardless of their leadership's competence during an overseas deployment.

Characteristics of families of soldiers who return prematurely from overseas deployments: an assessment from Operation Restore Hope (Somalia).

Nearly 500 wives, married to enlisted soldiers who deployed to Somalia for Operation Restore Hope, participated in a postdeployment study in the summer of 1993. About 10% of their husbands had returned early from Somalia for family reasons. Analysis of their wives' reports suggests that early returns were associated most often with childbirth or problematic pregnancies rather than other factors such as inexperience with deployments, negative attitudes towards the military, a lack of support services, or lower coping abilities. However, in hindsight, our results probably reflect compliance with military policy at that time for that deployment, under which pregnancy-related concerns were one of the most legitimate reasons for permitting an early return. The results support sociological theories that highlight the importance of macrosocial factors in influencing the lives of individual families somewhat independently of the microsocial environment of the families.

Factors associated with spouses moving away from their military installation during an overseas deployment.

During overseas deployments, many spouses and families move away from their initial military installation, usually to live with or near relatives. Relatively little has been known about those who move away even though the issue is of importance to the military because its support systems are designed on the assumption that family members are living in proximity to those support systems. The purpose of this research was to describe the characteristics of those who actually moved away during a deployment compared to those who stayed but wanted to leave and to those who stayed. Results generally fit a social exchange model of reasons for moving, staying, or wanting to move but staying. High stress appears to lead to a desire to move but other factors act as barriers or facilitators to actually moving. Military family support did not predict moving away or staying. Implications for military support services are discussed.

Perceived premarital counseling outcomes among recently married army personnel.

Data from 1,285 recently married soldiers who participated in the 1989 Army Family Research Program survey indicated that premarital counseling by itself had little effect on subsequent marital satisfaction. However, those who had premarital counseling were more likely to use marital and family therapy services, at both subclinical and clinical levels of distress, than others who had not had such counseling before marriage.

Psychology of the scientist: LXXXIII. An assessment of Herek's critique of the Cameron group's survey studies.

Herek's criticisms of the research on sexuality by Paul Cameron's research group are evaluated. While the Cameron group's research has many limitations, these limitations are not uncommon in contemporary research, especially research that concerns specialized, hard-to-find populations. The best response from a scientific perspective, it is argued, is better research, not merely critical comments on existing research.

Effects of a military overseas peacekeeping deployment on marital quality, satisfaction, and stability.

Changes in self-reported soldier marital satisfaction and marital quality were assessed at three points in time, 1994-1997, before, during, and after a 1995 peacekeeping deployment of approximately 100 married soldiers to the Sinai peninsula. Analysis shows a moderate decline in marital satisfaction during the deployment (effect size of 0.27-0.29) but no overall change in the long term. Marital quality did not change significantly over time. Marital stability rates were especially low for soldiers who reported that their marriage was in trouble prior to the deployment. It appears that stable marriages can survive 6-mo. deployments without long-term decrements in satisfaction or quality. How many couples will continue to accept voluntarily a military lifestyle that requires frequent sacrifices of marital satisfaction as may occur during separations and deployments remains an open question, even though intentions for retention did not appear correlated with marital satisfaction or changes in marital satisfaction over the deployment in this study.

Understanding mail survey response rates among male reserve component Gulf War era veterans.

In this study of current and former male Reserve and National Guard members from the State of Ohio, it was expected that veterans who were older, had more years of military service, who had participated in the Persian Gulf War, who were Euro-Americans, who were higher in rank, who had higher residential stability in Ohio, who belonged to the Air Force, who had higher formal education, and who belonged to the National Guard would have a greater investment in U.S. society as defined by 11 demographic variables. It was assumed that those with greater investment in society would more often have valid addresses and would be more likely to respond to a survey on military issues, thereby biasing sample outcomes in those directions. Results for male veterans were consistent with the hypothesis that investment in the society system would predict validity of addresses and response rates. In other words, results supported the idea that those veterans who might be expected to have a greater investment in U.S. society were more likely to be located and to respond (once located) to a survey concerning Desert Storm-era military service and its aftermath. Implications for future Desert Storm research are discussed.

Improving practice in marriage preparation.

Developments over the past 2 decades concerning research on marriage preparation programs are reviewed. Suggestions for designing effective programs are presented. Issues reviewed include assessing client needs, the timing and duration of programs, formats and methods, program content, provider characteristics, and promotion and marketing strategies.

Gender and marital satisfaction: data from the National Survey of Families and Households.

In 1972, Bernard argued that marriage was good for men and bad for women. Subsequent research noted that wives, on average, reported lower marital satisfaction than husbands. Furthermore, when differences within couples existed on marital satisfaction, the wife was usually the less satisfied spouse; however, most previous studies of the gender/marital satisfaction relationship had not been based on nationally representative samples. A nationally representative sample from the 1988 Survey of Families and Households was used to assess the relationship of gender with marital satisfaction. Within-couple analyses indicated that wives were less satisfied with their marriages than husbands and that, when substantial within-couple differences occurred with respect to marital satisfaction, the wife was usually the less satisfied spouse. Results provide at least small support for feminist assertions about the relatively adverse nature of marriage for women in the United States.

Premarital counseling and marital satisfaction among civilian wives of military service members.

Wives' marital satisfaction was evaluated as a function of a premarital counseling typology in an analysis of data from several thousand military couples surveyed in 1992. Among couples who jointly reported participation in premarital counseling, results indicated that both having premarital counseling and reporting higher satisfaction with the counseling experience were associated with higher levels of marital satisfaction. Among couples who disagreed about having had premarital counseling, results were still favorable but less consistent. Implications for clinical practice are discussed.