The effect of fluid overload in the presence of an epidural on the strength of colonic anastomoses.

BACKGROUND: Despite the beneficial effects of epidurals in intra-abdominal surgery, the incidence of anastomotic leak remains controversial when used. Moreover, studies have also shown that fluid overload may be deleterious to anastomoses. The purpose of this paper is to evaluate the effects of varying intraoperative fluid protocols, in the presence of an epidural, on the burst pressure strength of colonic anastomoses. METHODS: An epidural was installed in 18 rabbits, divided into three groups. Group 1 received 30 mL/kg/h Ringer's lactate, Group 2 received 100 mL/kg/h Ringer's lactate, and Group 3 received 30 mL/kg/h Pentaspan. Two colo-colonic anastomoses were performed per rabbit. On postoperative day 7 the anastomoses were resected and their burst pressures measured as a surrogate for anastomotic leak. RESULTS: When comparing the average burst pressures of all three groups, there was a significant difference (P = 0.04). The anastomoses in the 100 mL/kg/h Ringer's lactate group were shown to be the weakest, with 64% of the anastomoses having burst under 120 mm Hg. The rabbits hydrated with Pentaspan had the highest strength, with no anastomoses bursting under 120 mm Hg. This translated into significant burst pressure differences (P = 0.02) between Group 2 and Group 3. CONCLUSION: These results suggest that fluid overload with a crystalloid, in the presence of an epidural, may be deleterious to the healing of colonic anastomoses, creating a higher risk of anastomotic leak. Intraoperative resuscitation should thus focus on goal-directed euvolemia with appropriate amounts of colloids and/or crystalloids to prevent the risk of weakening anastomoses, especially in patients with epidurals.

The synthetic heat shock protein 90 (Hsp90) inhibitor EC141 induces degradation of Bcr-Abl p190 protein and apoptosis of Ph-positive acute lymphoblastic leukemia cells.

The prognosis of patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) is poor. Chemotherapy is rarely curative and tyrosine kinase inhibitors (TKIs) induce only transient responses. Heat shock protein 90 (Hsp90) is a chaperone protein that is important in signal transduction, cell cycle control, and transcription regulation in both normal and leukemia cells. In the current study, we tested the growth inhibitory and apoptotic effects of a novel Hsp90 inhibitor, EC141 on the Ph+ ALL lines Z-119, Z-181, and Z-33, as well as primary bone marrow-derived blasts from patients with newly diagnosed Ph+ ALL. We found that EC141 inhibited the growth of Ph+ ALL cells in a concentration-dependent manner with IC(50) ranged from 1 to 10 nM. EC141 also inhibited the proliferation of primary bone marrow-derived blasts using the ALL blast colony assay. EC141 down-regulated Hsp90 and up-regulated Hsp70 protein levels, inhibited CrkL phosphorylation, and induced degradation of Bcr-Abl p190 protein through ubiquitin-dependent proteasomal pathway. Furthermore, exposure of Ph+ ALL cells to EC141 resulted in activation of caspase-3, cleavage of poly (ADP-ribose) polymerase (PARP), and induction of apoptosis. In conclusion, our data suggest that EC141 is a potent Hsp90 inhibitor with activity against Ph+ ALL. Further studies to investigate the anticancer effect of EC141 either as a single agent, or in combination in Ph+ ALL and other hematological malignancies are warranted.

Correlates and Predictors of Sexual Satisfaction for Older Adults in Same-Sex Relationships.

Study explored correlates and predictors of sexual satisfaction among older adults in same-sex relationships by examining internalized homophobia, resilience, sexual communication, and relationship satisfaction. Online survey elicited 265 participants (54% female, 46% male), aged 60-75, in same-sex relationships from 1 to 47 years. Participants reported high levels of relationship satisfaction and resilience, moderate levels of sexual communication and sexual satisfaction, and low levels of internalized homophobia. Stepwise multiple regression analysis indicated relationship satisfaction contributed uniquely to the prediction of sexual satisfaction. Relationship satisfaction was positively correlated with sexual satisfaction and resilience and negatively correlated with internalized homophobia. Internalized homophobia was also negatively correlated with resilience. Recent estimates indicate there are over three million U.S. citizens over 65 who consider themselves LGBTQ, many of whom are in same-sex relationships. Therefore, given the paucity of research and misconceptions about this population, findings, and recommendations are of value to educators, clinicians, and policymakers.

The menstrual cycle and adolescent health.

Early reproductive characteristics, including menarcheal age, may have significant effects on later health outcomes. While early exposure to ovarian hormones may influence the risk for certain diseases, the degree to which this exposure is mediated by other factors is not well understood. Research on secular trends in age at menarche and subsequent outcomes in women's health across the lifespan can help to clarify the importance of age at menarche. Since 1934, the TREMIN Research Program on Women's Health has collected longitudinal data on menstruation and reproductive health. Recently we examined the age at menarche across the entire population of TREMIN participants, across the two major cohorts of this research program (participants initially enrolled in the 1930s and in the 1960s), and within families where mothers and daughters participated in the study. Our results indicated that age at menarche among the 4,444 mainly European American girls in our sample decreased in the first part of the twentieth century, and then began to increase in the late 1940s. The comparison of age at menarche across the two major cohorts reinforced this analysis: age at menarche was slightly but significantly lower (P < .001) in the second cohort (12.66), most of whom were born in the 1940s, than in the first cohort (12.89), those women born before 1920. In analyzing data from 380 mother-daughter pairs, there was no significant difference between mothers' and daughters' mean age at menarche and no significant correlation between them.

Negotiating sexual agency: postmenopausal women's meaning and experience of sexual desire.

The purpose of this feminist grounded theory study was to understand the meaning and experience of postmenopausal women's sexual desire. Data collection from 22 postmenopausal women who were ongoing participants of the TREMIN Research Program on Women's Health occurred via audiotaped, telephone-based, semistructured interviews. Women's descriptions of their sexual needs and desires led to the discovery of the core category, negotiating sexual agency, which refers to women's ability to act on behalf of their sexual needs, desires, and wishes. Women negotiated their sexual agency within three main domains (or axial codes): their own sexual self, their partners, and the medical system. An important finding was women's internalization of sociocultural assumptions that privilege their male partners' sexual needs over their own. The findings of this study, especially the contexts in which women negotiate their sexual agency, are important for women, women's health care providers, and women's life partners to understand.

Women's sexual desire: a feminist critique.

This paper offers a critical feminist analysis of the biomedical conceptualization of women's sexual desire. The five major features of the biomedical model of female sexual desire examined and critiqued are: 1) use of the male model as the standard, 2) use of a linear model of sexual response, 3) biological reductionism, 4) depoliticalization, and 5) medicalization of variation. A "New View", an alternative to the biomedical model, is offered for reconceptualizing women's sexual problems. This analysis concludes with recommendations for feminist-based biopsychosocial research.

"Feeling frumpy": the relationships between body image and sexual response changes in midlife women.

This study investigated the relationships between self-rated attractiveness and self-reported sexual response changes (over the past decade) and current sexual satisfaction in 307 heterosexual, midlife women. Results indicated that regardless of the woman's specific age, she was more likely to consider herself more attractive when she was 10 years younger and her self-perceived attractiveness did not significantly differ based on her menopausal status. The more a woman perceived herself as less attractive than before, the more likely she was to report a decline in sexual desire or frequency of sexual activity. The more she perceived herself as attractive, the more likely she was to experience an increase in sexual desire, orgasm, enjoyment, or frequency of sexual activity. There were no significant statistical relationships between a woman's perception of her own attractiveness as she aged and her current sexual satisfaction.

Work-Family Conflict, Task Interruptions, and Influence at Work Predict Musculoskeletal Pain in Operating Room Nurses.

BACKGROUND: The aim of this study is to examine the prevalence of musculoskeletal complaints in Swiss operating room (OR) nurses, and to investigate how work-family conflict, work interruptions, and influence at work are related to lumbar and cervical back pain. METHODS: Participants in this correlational questionnaire study included 116 OR nurses from eight different hospitals in Switzerland. RESULTS: We found that 66% of the OR staff suffered from musculoskeletal problems. The most prevalent musculoskeletal complaints were lumbar (52.7%) and cervical pain (38.4%). Furthermore, 20.5% reported pain in the mid spine region, 20.5% in the knees and legs, and 9.8% in the hands and feet. Multiple linear regression analyses showed that work-family conflict (p < 0.05) and interruptions (p < 0.05) significantly predicted lumbar and cervical pain in OR nurses, while influence at work (p < 0.05) only predicted lumbar pain. CONCLUSION: These results suggest that reducing the work-family conflict and interruptions at work, as well as offering opportunities to influence one's workplace, help to promote OR nurses' health.

Tissue-based assay for ornithine decarboxylase to identify patients likely to respond to difluoromethylornithine.

In a previous publication, we showed that a clinical trial of DL-alpha-difluoromethyl ornithine (DFMO), in combination with PCV (procarbazine, CCNU, vincristine) increased survival of patients with anaplastic gliomas (WHO III) but not glioblastoma multiforme (WHO IV). We believe that treatment outcome (survival) is inversely related to tumor ornithine decarboxylase (ODC) levels. To prove this, we needed to develop an assay to quantify ODC levels in formalin-fixed tumor tissues, which would enable a retrospective study of tumor biopsy specimens from the landmark clinical trial. We developed an assay using a specific polyclonal antibody coupled to an Alexa fluorescent dye. Transgenic MHC-ODC mice with differing levels of ODC in heart muscle were used to establish the relationship between mean gray-scale intensity and enzymatic ODC activity. We found a direct relationship between mean gray-scale intensity of the ODC antibody coupled to Alexa 647 dye and enzymatic activity. Preliminary analysis of a human glioma tissue array shows that tumor-specific variations in levels of ODC can be semiquantitated. We show that mean gray-scale intensity of astrocytoma:glioblastoma is 1:6 and of anaplastic astrocytoma:glioblastoma is 1:4. We also compared the intensity of antibody to Ki67 coupled with phycoerythrin simultaneously in cells but failed to see a relationship that crossed histologies. We conclude that we can measure levels of ODC in formalin-fixed tumor tissue using an antibody to ODC coupled to Alexa 647 dye, and this will enable us to conduct a future study to correlate survival of patients with gliomas of different histologies treated with DFMO to tumor ODC levels.

Staging the menopausal transition: data from the TREMIN Research Program on Women's Health.

The present study was conducted to test the assumptions of a staging system of reproductive aging that was proposed at the Stages of Reproductive Aging Workshop (STRAW) in 2001. Using longitudinal data provided by 100 women over a period of 3-12 years, we asked whether midlife women move in a uniform progression from pre- to peri- to postmenopause, as refuted by earlier studies but proposed by the STRAW model, or whether they differ from this assumed pattern. Participants were recruited from the TREMIN Research Program on Women's Health, the oldest ongoing study of menstruation and women's health in the world. Eligibility criteria included reaching menopause during the course of the study and not using exogenous hormones. Participants provided annual self-reports of menopausal stage based on observations of their menstrual cycles ("regular," "changing," and "menopausal"). Findings revealed a lack of uniformity as women progressed toward menopause. From 8 to over 20 different perimenopausal stage patterns were observed, depending on the analysis. While the most common pattern was to progress from regular to changing to menopause, some women experienced menstrual bleeding after a year or more of amenorrhea, others flip-flopped between stages, and still others skipped directly from regular bleeding to menopause. We conclude that there is considerable variation in women's movement across menopausal status categories and urge researchers to accommodate such findings in their model building.

Association between psychological stress and menstrual cycle characteristics in perimenopausal women.

In previous studies of the relationship between stress and menstrual cycles, stress has been found to be associated with longer cycles, to be associated with shorter cycles, and to have no association with cycle length. Some of the menstrual cycle changes that have been attributed to stress are similar to those experienced by women during perimenopause. In an effort to see whether an association between psychological stress and menstrual cycle characteristics can be detected in women approaching menopause, this study examines this relationship in perimenopausal women who are participants in the Tremin Research Program on Women's Health. The analyses used prospectively recorded bleeding data and retrospectively captured life-event data. A single-year cross-sectional analysis of data from 206 women shows no correlation between stress level, as measured by total number and severity of stressful life events, and cycle characteristics, including interval length, duration of bleed, and variability in both of these factors, nor are there significant differences in cycle characteristics between subgroups of women with different overall levels of stress. In analyzing stress levels and cycle characteristics across 2 years, however, women with marked increases in their level of stress (n = 30) are shown to have decreased length (-0.2 days/cycle) of menstrual cycle intervals and decreased duration of bleed (-0.1 day/cycle) compared with increases in these measures (+2.9 days/cycle for cycle interval; +0.3 days/cycle for duration of bleed) among women with no marked change in stress level (n = 103); t-tests indicate that these differences are significant (p < .05).

Workflow interruptions and failed action regulation in surgery personnel.

BACKGROUND: Workflow interruptions during surgery may cause a threat to patient's safety. Workflow interruptions were tested to predict failure in action regulation that in turn predicts near-accidents in surgery and related health care. METHODS: One-hundred-and-thirty-three theater nurses and physicians from eight Swiss hospitals participated in a cross-sectional questionnaire survey. The study participation rate was 43%. RESULTS: Structural equation modeling confirmed an indirect path from workflow interruptions through cognitive failure in action regulation on near-accidents (p < 0.05). The indirect path was stronger for workflow interruptions by malfunctions and task organizational blockages compared with workflow interruptions that were caused by persons. The indirect path remained meaningful when individual differences in conscientiousness and compliance with safety regulations were controlled. CONCLUSION: Task interruptions caused by malfunction and organizational constraints are likely to trigger errors in surgery. Work redesign is recommended to reduce workflow interruptions by malfunction and regulatory constraints.

"Nobody told me nothin": communication about menstruation among low-income African-American women.

The purpose of this study was to explore communication about menstruation among low-income African American women and the impact of this communication on their understanding of and attitudes toward the menstrual events that will occur throughout their lives. This is of particular importance since minority women disproportionately face greater menstrual problems than those experienced by majority women in the United States. A grounded theory design was used for this study. Seventeen African American women from a public housing project were interviewed. The core theme that emerged from the qualitative data was the avoidance or negative discussion of menstrual events throughout the women's lives. The women had few sources of and very limited menstrual learning from school, their mothers, and other women. This led to confusion and inaccurate beliefs about and negative attitudes toward menstruation, menopause, and menstrual-related health conditions. While these women desired to have better communication, their history of avoidance of and negative discussions surrounding menstruation will likely continue to make it difficult for them to have positive and informative discussions with others in the future unless some type of educational intervention occurs.

Is my period normal? How college-aged women determine the normality or abnormality of their menstrual cycles.

The purpose of this descriptive, qualitative study was to explore young adult women's conceptualizations of their menstruation experiences using a feminist approach. Grounded theory was used to understand how 15 college-aged women (ages 18-22 years, 86% white) evaluate their menstrual patterns as "normal" or "abnormal." Data analysis of the semi-structured interviews revealed four themes that the women used to judge the pattern of their menstruation (i.e., interval, duration, discomfort, and volume) as normal: (1) Pattern resembled learned norms, (2) consistent pattern discordant from learned norms, (3) predictably variable pattern, and (4) absence of problems. Two distinct themes informed their decisions to consider a menstrual pattern as abnormal: (1) Unpredictable variability, and (2) extreme experiences. The core variable emerging from data analysis, establishing a personal norm, illuminated the two major sources that women relied on in trying to interpret their menstrual patterns: the limited and often inaccurate information that they had been taught and their own menstrual experiences. Implications include the need to improve education about menstrual variability throughout the life cycle and about the diversity of women's normal menstrual patterns and experiences.

WP1066 disrupts Janus kinase-2 and induces caspase-dependent apoptosis in acute myelogenous leukemia cells.

Several cytokines and growth factors that stimulate the proliferation of acute myelogenous leukemia (AML) cells transduce their signals by activating the transcription factor Janus-activated kinase 2 (JAK2). Accordingly, the inhibition of JAK2 or of its downstream signaling pathways suppresses the proliferation of AML cells. Because (E)-3(6-bromopyridin-2-yl)-2-cyano-N-((S0-1-phenylethyl)acrylamide) (WP1066) is a novel analogue of the JAK2 inhibitor AG490, we tested its activity in AML cells and investigated its mechanism of action. Using clonogenic assays, we found that although WP1066 had a marginal effect on normal marrow progenitors, it inhibited the proliferation of AML colony-forming cells obtained from patients with newly diagnosed AML and that of the AML cell lines OCIM2 and K562. WP1066 inhibited OCIM2 cell multiplication by inducing accumulation of cells at the G(0)-G(1) phase of the cell cycle. Similar to its parent compound AG490, WP1066 inhibited the phosphorylation of JAK2, but unlike AG490, WP1066 also degraded JAK2 protein, thereby blocking its downstream signal transducer and activator of transcription (STAT) and phosphoinositide-3-kinase pathways. These effects resulted in the activation of the caspase pathway. Incubation of both OCIM2 and K562 cells with WP1066 activated caspase-3, induced cleavage of poly(ADP-ribose) polymerase, and caused caspase-dependent apoptotic cell death. Thus, WP1066 is a potent JAK2 inhibitor whose effects in AML and other hematologic malignancies merit further investigation.

Husbands' support of their perimenopausal wives.

The purpose of this study was to investigate the social support provided by husbands to their perimenopausal wives. Ninety-six husbands of women who were participating in the longitudinal Midlife Women's Health Survey answered open-ended questions concerning how supportive they perceived themselves to be, what information they had concerning menopause, and what kinds of stress they were experiencing in their own lives. One-third of the husbands believed they were not supportive, but the majority said they provided mostly emotional support. Most husbands had some information about menopause, but more than one in four knew little or nothing. The majority of the husbands got their information from their wives. Husbands reported numerous stressors in their lives, including work and financial problems and declining health and sexual response. Lack of information, negative effects of their wives' menopausal transition, and their own stresses may have interfered with husbands' ability to provide social support. Future research with a larger and more diverse sample that includes wives as well as husbands is recommended.