Abstracts
* Denotes Abstract Winner
† Denotes Powell Center Internship Project
Listed Alphabetically by Authors
Rehana L. Ahmed MD, PhD, Anna Prizment MPH, DeAnn Lazovich PhD, Kathryn H Schmitz PhD MPH, Aaron Folsom PhD
Lymphedema and Quality of Life in Breast Cancer Survivors, the Iowa Women’s Health Study (22)
Purpose: The impact of lymphedema or related arm symptoms on health-related quality of life (HRQOL) in breast cancer (BrCa) survivors has not been examined using a large population-based cohort.
Methods: The Iowa Women’s Health Study (IWHS) collected self-report data for lymphedema, arm symptoms, and HRQOL (Medical Outcomes Study Short Form-36) in 2004, and cancer diagnosis, treatment, behavioral and health characteristics between 1986-2003. We studied 1,287 women, ages 55-69 at baseline, who developed unilateral BrCa. We used cross-sectional analyses to describe the prevalence of lymphedema and arm symptoms, and multivariate-adjusted generalized linear models to compare HRQOL (physical functioning, bodily pain, general health, role limitations physical and emotional, vitality, social functioning, and mental health) between three survivor groups: n=104 with lymphedema, n=475 with arm symptoms without diagnosed lymphedema, and n=708 without lymphedema or arm symptoms.
Results: The mean time between BrCa diagnosis and lymphedema survey was 8.1 +/- 0.2 (mean SE) years. 8.1% of survivors self-reported diagnosed lymphedema; another 37.2% self-reported arm symptoms. Knowledge of lymphedema was low among survivors without diagnosed lymphedema (n=1183). After multivariate-adjustment, women with diagnosed lymphedema or arm symptoms without diagnosed lymphedema had lower physical and mental HRQOL compared to women without lymphedema or arm symptoms. Effect sizes were mild-to-moderate. There was a dose-response between number of arm symptoms and lower HRQOL.
Conclusions: In the IWHS, HRQOL was lower for BrCa survivors with diagnosed lymphedema and for those with arm symptoms without diagnosed lymphedema. Clinical trials are needed to determine whether or not interventions designed to improve lymphedema impact HRQOL for BrCa survivors.
Sanjeev Akkina M.D., Erin Leister M.S., Arthur Matas M.D. & Hassan Ibrahim M.D., M.S.
Pregnancy Outcomes after Kidney Donation (47)
Context: The outcome of pregnancy in living kidney donors has generally been viewed to be favorable, but previous studies have been small.
Objective: We assessed fetal and maternal outcomes in a large cohort of female kidney donors at the University of Minnesota.
Design, Setting, and Participants: We sent female kidney donors self-administered questionnaires that addressed fetal (e.g., full-term deliveries and fetal loss) and maternal (e.g., preeclampsia, gestational hypertension, gestational diabetes) outcomes.
Main outcome measures: We looked at fetal and maternal outcomes in pregnancies occurring before and after kidney donation.
Results: Since June 1963, a total of 2,025 women have donated kidneys at our institution. Of these, 965 reported ever becoming pregnant (822 donors reported 2,416 pregnancies before donation and 223 reported 459 pregnancies after donation). Pre-donation (vs. post-donation) pregnancies were associated with a higher likelihood of full-term deliveries (83.7% vs. 72.3%, p<0.0001) and a lower likelihood of fetal loss (11% vs. 19.8%, p=0.006). Pre-donation (vs. post-donation) pregnancies were also associated with a lower risk of gestational diabetes (0.7% vs. 2.4%, p=0.0004), gestational hypertension (0.4% vs. 4.4%, p<0.0001), and preeclampsia (0.7% vs. 5.2%, p<0.0001). Logistic regression analysis identified having a post-donation pregnancy as a risk factor for both adverse fetal (prematurity: odds ratio [OR], 2.3; 95% confidence intervals [CI], 1.27 to 4.17; fetal loss: OR, 2.2; 95% CI, 1.5 to 3.2) and maternal (combined gestational diabetes, hypertension, or preeclampsia: OR, 5.81; 95% CI, 3.5 to 9.6) outcomes
Janice H. Alexander R.N.M.D.
Successful Pregnancy and Premature Delivery after Microwave Endometrial Ablation: What to Look for and How to Manage (56)
Objective: Pregnancy after endometrial ablation is a growing concern since this procedure became popularized over the past decade. This procedure should only be done on women who have finished their childbearing. Concommittent sterilization procedures are recommended, but not always possible. Patients who fail to use birth control are putting themselves and their babies at risk. After a review of the literature, it is clear that these patients must be watched closely. Although many of these pregnancies result in miscarriage or abortion, those that survive often deliver prematurely and precipitously. Experience gained by this author will be described.
Design: A 36 year-old GV PIV became pregnant while not using birth control seven months after a microwave endometrial ablation. Post-op MEA Hysteroscopy revealed good ischemic effect throughout the cavity. The patient tried a Mirena IUD after the procedure for birth control, however, she was unable to tolerate this form of birth control. The patient was watched with Ultrasound and BPP and developed subtle changes including premature descent at 28 weeks. Prior to delivery, the patient developed ballooning of the lower uterine segment and pain when the baby moved. She was delivered urgently by C-Section at 31 weeks.
Conclusion: Patients who become pregnant after any type of endometrial ablation are at risk for complications including pre-term delivery and pregnancy loss. Patients whose pregnancy makes it past viability must be watched closely for signs of pre-term labor and other complications. The changes may be subtle and precipitous.
Noel Aldrich BS, Marla Reicks, PhD RD, Bruce Redmon MD, Susan Raatz PhD RD
Total weight and body composition changes in response to weight reduction diets of varied protein content in midlife women (19)
Background: The 2003-2004 NHANES survey estimated that the prevalence of being overweight/obese for women aged 40-59 years in the U.S. was 68%. Age-related changes in body composition for women include loss of lean mass and gains in total weight, fat mass and central fat deposition. There is growing evidence that diets with low-to-moderate carbohydrate and fat content and increased levels of high quality protein are effective for weight loss. Greater subjective satiety is reported by subjects following test meals containing whey protein compared to other protein sources. The beneficial effects of whey protein on satiety, thermogenesis, and lean body mass protection suggest that whey may be a preferred protein source for weight loss treatment.
Objective/Hypothesis: Reduced energy diets containing whey protein will result in greater weight loss and improvements in body composition compared to reduced energy diets with a mixed protein source. The specific aims of this study are to assess weight loss in subjects receiving energy reduced dietary regimens and to evaluate parameters of weight and body mass change between the three treatment groups.
Study Design: We are conducting a randomized, controlled pilot feeding study to evaluate the effect of different dietary protein sources on weight loss. Fifteen subjects with a BMI of 27 - 32 will be randomized between three study groups. The reduced energy diets being tested in the
8 week feeding periods include a control diet (15% protein, CD), a high mixed protein diet (30% protein; HP) and a high whey protein diet (15% mixed protein and 15% whey protein; WP). Endpoint measures include body weight and body composition data obtained at baseline and at 8 weeks for dietary treatment.
Preliminary Data: Subjects on the high protein diets (HP & WP) demonstrated greater weight loss compared to the CD. Those subjects on the WP diet lost the most weight. The HP diet and the WP diet produced greater total fat loss and less total lean tissue loss than the CD. Bone mineral content remained stable across treatment groups.
Conclusions: Preliminary data shows that across treatment groups, the high protein diets conserved lean tissue and promoted reduction of fat tissue. Between the two high protein diets, a small benefit was seen with the WP diet on fat loss.
Karishma Firoz Ali
Nurses role in decreasing prevalence rate of HIV (34)
Purpose: The aim of this paper is to highlight the nurse’s role in reducing the prevalence rate of HIV in developing countries.
Design: A comprehensive review of literature.
Results and Conclusion: HIV is a leading infectious cause of death in the world. In 2005, HIV related illnesses caused the deaths of 3.1 million people worldwide. According to WHO, around 90 % of people living with HIV belong to the developing countries. Nurses need to work at all the three levels of health i.e. primary, secondary and tertiary. At the primary level they should strive to bring awareness so that the occurrence of HIV can be prevented. They need to make women conscious about their sexual right so that sexually transmitted diseases and unprotected sex, which are a major cause of HIV, can be prevented. They need to make people aware about the modes of transmission of HIV. If HIV has occurred nurses should work at the secondary level. Many new therapies have been invented for the treatment of HIV. Nurses in the developing world should work collaboratively with health care agencies to make these therapies accessible for the local people. They should try to resolve misconceptions about HIV so that people can comply with the treatment. They need to make people aware about the risk and prevention of transmission from an HIV infected person. At the tertiary level nurse need to provide moral support to the HIV infected people so that they can peacefully spend their lives. Constant and devoted efforts are required from nurses to decrease the burden of HIV in developing countries.
Sonia Hassan Ali
Nurses role: Preventing mother to child HIV transmission through breast feeding (38)
Purpose: The purpose of this paper is to highlight the risk of HIV transmission through breast-feeding and the nurse’s role in preventing this transmission.
Design: A comprehensive review of literature.
Results and Conclusion: HIV has been named as the plaque of 20th century. According to UNADIS estimation, by 2004 women accounted for 47 % of all people living with HIV. The rising prevalence of HIV in women has significant impact on children. Taking into account the benefits of breast-feeding, health professionals are striving to strengthen the breast-feeding practices among women. However, researches have been done which advised that women with HIV should restrain from feeding their child and they should use alternatives to breast-feeding. On the other hand, it has been said that in developing countries where formula feeding triples the risk of infant death due to infectious disease, it is safer to exclusively breast-feed, so that atleast the child can get immunity through the breast-feed. Though there is no evidence which supports that breast feed of an immunologically weak woman can provide immunity to the child. Comprehensive researches are required to address this issue. Nurses should play their role in making women aware about the risk of transmission. They should help women decide about the method of feeding based on availability of resources. If women have decided to formula feed their child, nurses should teach them other ways, which can increase mother child bonding. Moreover nurses need to advocate for their clients and work collaboratively with environmental and health care agencies, to provide hygienic environment and resolve the issues of water and sanitation so that the use of formula feeding can be facilitated.
*Andersen, JD, Harrington, KM, Weivoda, S, Boylan, KLM, Misemer, B, Witthuhn, B, Geller, M, Jemmerson, R, Skubitz, APN
Leucine-rich alpha-2-glycoprotein-1: A potential serum biomarker and therapeutic target for ovarian cancer (20)
An estimated 22,000 women will be diagnosed with ovarian cancer in the U.S. in 2008, while 16,000 patients will succumb to the disease. The incidence and mortality for ovarian cancer have changed little in the past 30 years, indicating that current methods for detection need improvement. New biomarkers that either replace or are used in conjunction with the current ovarian cancer diagnostic antigen, CA125, are needed for early detection. The mass spectrometry-based proteomic techniques of iTRAQ® and differential in-gel electrophoresis (DIGE) were used to compare the serum proteins of healthy and diseased patients. Leucine-rich alpha-2-glycoprotein-1 (LRG1) was identified as an upregulated protein present in the sera of ovarian cancer patients by both techniques. LRG1 levels in the sera of 60 ovarian cancer patients were quantified by an ELISA and shown to be significantly higher than the levels in the sera of noncancer-control women. In order to determine whether the ovarian cancer cells were contributing to the elevated levels of LRG1 protein in the sera, a series of experiments were undertaken. Gene microarray analysis was performed on over 100 ovarian cancer tissues and normal ovaries; LRG1 mRNA expression was approximately 3-fold higher in the cancer tissues. Reverse-transcriptase polymerase chain reaction (RT-PCR) and quantitative-PCR experiments using ovarian cancer tissues, normal ovaries, ovarian cancer cell lines, and normal ovarian surface epithelial cell lines showed higher levels of LRG1 mRNA in the ovarian cancer samples compared to their normal counterpart. These tissues and cell lines were then used to investigate the expression levels and localization of LRG1 protein. By Western immunoblotting, immunocytochemistry, and flow cytometry, LRG1 protein expression was found to be upregulated in the ovarian cancer samples and was localized to the plasma membrane and cytoplasm. By mass spectrometry, three unique peptide products of LRG1 were identified in serum-free conditioned media of the ovarian cancer cell line, NIH:OVCAR5. These findings were confirmed by ELISA, whereby LRG1 protein was detected in the serum-free conditioned media of the NIH:OVCAR5 cells. By Western immunoblotting, the LRG1 protein was differentially expressed in the serum-free conditioned media of NIH:OVCAR5 cells compared to the immortalized normal ovarian epithelial cell line, 1816-575. Taken together, these results suggest that ovarian cancer cells may contribute to the elevated LRG1 protein levels observed in the sera of ovarian cancer patients. Thus, LRG1 may serve as a potential biomarker in a diagnostic assay for ovarian cancer and/or as a potential target for therapeutic treatment.
Christopher M. Antolak, MD; Stanley J. Antolak Jr., MD
Pudendal neuropathy as a source of chronic pelvic pain in women (41)
Introduction: and Objectives: Chronic pelvic pain syndrome (CPPS) is a challenging condition for both patients and physicians. CPPS may be difficult to diagnose and treat given its wide array of symptoms including genital or rectal pain, dysuria, bowel dysmotility, and sexual dysfunction. CPPS may have a neuropathic basis. One process, pudendal neuropathy, may elicit any or all of these symptoms. Many patients with CPPS due to pudendal neuropathy are misdiagnosed and therefore undergo extensive treatments which are ineffective and possibly harmful and life-altering. Pudendal neuropathy is a tunnel syndrome and responds to a progression of treatments beginning with nerve protection, then perineural steroid injections, and, in some sufferers, decompression surgery.
Our objectives are to 1) correlate pains with neuropathy based on symptom history, physical examination, and confirmed using simple neurophysiological testing; 2) demonstrate an effective treatment regimen for women with CPPS.
Methods: From a group of several hundred patients with pudendal neuralgia, two cases of women with chronic pelvic pain syndrome (CPPS) will be reviewed. Symptom scores, symptom history, pinprick testing of the pudendal distribution, a warm detection threshold test (WDT) and a pudendal nerve latency test (PNTMLT) will illustrate the process of diagnosing pudendal neuropathy.
Results: Two women with CPPS were found to have symptoms consistent with pudendal neuropathy. Simple neurological examination showed evidence of neuropathy which was confirmed by WDT and PNTMLT. Symptom scores monitor pain, voiding, and sexual function improve after initiation of our treatment program. The program involves cessation of aggravating activities, use of sitting pad, and a series of three pudendal nerve perineural injections.
Conclusion: Pudendal neuropathy is a significant source of chronic pelvic pain and pelvic dysfunction in women. Simple medical history, examination, and testing will allow an accurate diagnosis and spare women from expensive, ineffective, and potentially harmful treatments.
StanleyJ. Antolak, Jr. MD; Christopher M. Antolak, MD
Multiple neuropathic causes of chronic pelvic pain (49)
Introduction and objectives: Physicians consistently evaluate for visceral causes of chronic pelvic pain. A neuropathic basis should always be considered, especially in women in whom laparoscopy or surgical interventions fail to diagnose or relieve the pain. Pudendal neuropathy is a frequent cause of non-malignant chronic pelvic pain. However, other pelvic neuropathies must be considered. These include ilioinguinal and iliohypogastric and iliohypogastric neuropathies, the Maigne syndrome (thoracolumbar junction syndrome), and middle cluneal neuropathy due to episacroiliac lipoma (back mouse).
Our objective is to present a demonstrative case of each of these processes to reinforce the concept of neuropathic pelvic pain and to identify simple examination and treatment techniques.
Methods: Cases are selected from lists of patients with each diagnosis. The examination needed to confirm the diagnosis will be demonstrated using photographs. Discussion of treatment for each problem include photographs.
Results: The use of pinprick testing of the abdominal wall and pudendal distribution can identify neuropathies. Skin-rolling (a mild compression of the skin and subcutaneous tissues) may cause pain called cellulalgia. Pressure above and below the pubic tubercle will identify painful ilioinguinal and iliohypogastric nerves. Pressure over the sacrum can identify subcutaneous lipomas and tenderness of the S2-3-4 middle cluneal nerves. Simple treatments can relieve the pains.
Conclusions: At least five peripheral nerve processes can produce chronic pelvic pain symptoms. A brief, informed physical examination can demonstrate these problems. Treatment of neuropathic pains precludes the need for surgical interventions.
Berge, J. M., Wall, M., Bauer, KW. & Neumark-Sztainer, D.
Familial and Gender Influences on Adolescent Weight Status and Weight-Related Behaviors: A Latent Class Analysis (31)
Background: Recent studies have shown that a variety of factors within the home environment may be potential predictors of adolescent obesity. Family meal frequency, family support for physical activity, parental modeling, and parenting style have been linked to healthful dietary behaviors and increased physical activity among youth. However, previous research has identified these potential predictors almost in isolation of each other and gender influences on these variables have been overlooked. Therefore, little is known about how these factors co-occur within families, and the influence of the co-existence of these factors within families on adolescentsý behavior.
Objectives: (1) To use latent class analysis to identify distinct classes of home environments based on the co-existence of multiple weight-related family factors; (2) To examine effects of gender differences between opposite sex and same sex parent/child dyads; (3) To examine the relationship between home environment classes and adolescents’ weight status and weight-related behaviors.
Methods: Project EAT (Eating Among Teens) data, a population-based study with an ethnically and socioeconomically diverse sample (n = 4746) of adolescents, was used to identify sub-types of home environments using adolescents reporting of characteristics within the home. A latent class analysis was conducted with 23 measures of the home environment to identify distinct classes. Regression analyses were conducted to examine the relationship between these home environment classes and adolescents’ weight status.
Results: Four classes of home environments were identified, each consisting of distinct combinations of levels of modeling and encouragement of physical activity and healthy dietary intake, parenting styles, and family meals habits. Father/daughter dyads were found to have higher levels of modeling and encouraging healthy dietary intake and physical activity versus mother/son dyads or same gender dyads.
Conclusions: Developing home environment classes to understand how various weight-related factors co-exist within families can provide new insight into the dynamics of the home environment and the influence of gender on adolescents’ weight and weight-related behaviors. This information can inform future research targeting the obesity epidemic in youth.
Bishop, LA, Eisenberg, ME., Larson, N., Neumark-sztainer, D.
Does disordered eating predict substance use in adolescent girls? (8)
Objective: To examine 5-year longitudinal associations between family meal frequency and disordered eating behaviors in adolescents. Design: Longitudinal study. Setting: Participants from 31 Minnesota schools completed in-class assessments in 1999 (time 1) and mailed surveys in 2004 (time 2).
Participants: Adolescents (N=2516) who completed Project EAT (Eating Among Teens) I (time 1) and II (time 2) assessments. Main Outcome Measures: Time 1 disordered eating behaviors, including extreme weight control behaviors (self-induced vomiting and use of laxatives, diet pills, or diuretics), less extreme unhealthy weight control behaviors (eating very little, fasting, using food substitutes, skipping meals, or smoking), binge eating, and chronic dieting and time 2 substance use, smoking, alcohol consumption, marijuana, and other substances (cocaine, crack, ecstasy, heroin etc.)
Results: Among adolescent girls at time 1, with extreme weight control behaviors and chronic dieting, had over twice the risk of being smokers at time 2 (odds ratio, 2.370, 95% confidence interval 1-167-.4.813, and 2.280 confidence interval1.320-3.940), after adjusting for substance use and depression at time 1, the association was not statistically significant. Similar results were found for the older adolescent girls. Boys did not show statistical significance even in the unadjusted model. Smoking behaviors were found to increase over time in those with disordered eating and depression symptoms at time 1. In adolescent girls with less extreme weight control behaviors, (adjusted for depression symptoms and smoking at time 1) had an odds ratio of 8.8 with 95% confidence intervals of 3.710-20.948. In older adolescent girls, the odds ratio had increased to 11.894 with confidence intervals of 8.125-17.412 for smoking behaviors compared to controls. A similar trend was shown in adolescent boys. To a lesser extent, alcohol behaviors had also reflected this trend but only in girls.
Conclusions: Disordered eating is common in adolescent girls and the association with substance use has been well documented. The temporality of these behaviors has yet to be established. It appears that they are part of a complex interaction of factors leading to dysregulation. Disordered eating behaviors should be actively be assessed during encounters with adolescents and may be the smoking gun for other unhealthy behaviors. It is clear from this study that the co-occurrence of unhealthy behaviors increases over time and therefore early intervention is warranted. Further studies to evaluate temporality of these behaviors are indicated to better understand causality and interventions.
Julie K. Bower, Pamela J. Schreiner, Barbara Sternfeld, and Cora E. Lewis
The Influence of Race on the Prevalence of Hysterectomy in the Coronary Artery Risk Development in Young Adults Study (43)
Hysterectomy is one of the most frequently performed surgeries among women in the United States. Because most hysterectomies are performed for causes unrelated to cancer, there is growing interest in understanding differences in correlates of hysterectomy that might explain the disproportionately higher frequency of the procedure among Black women. Establishing attributes related to current racial disparities might reveal modifiable factors that influence decisions to undergo hysterectomy (with the ultimate goal of better identifying candidates for alternative and less radical treatments). Further, this work could inform tailored interventions that more effectively help women consider the multiple available treatment options.
This study evaluated the cross-sectional association between race and hysterectomy prevalence in a population-based cohort of U.S. women. The cohort consisted of 1,863 Black and White women enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study during 2000-2002 (Years 15 and 16 after baseline). Unadjusted and multivariable adjusted odds ratios were examined using logistic regression.
Black women demonstrated greater odds of hysterectomy compared to White women (OR = 3.52, 95% CI = 2.52-4.90). Adjustment for age, educational attainment, perceived barriers to accessing medical care, body mass index, polycystic ovarian syndrome, tubal ligation, depressive symptomatology, age at menarche, and geographic location minimally altered the association (OR = 3.70, 95% CI = 2.44-5.61). In a subset of the study population with self-reported and directly imaged uterine fibroids (which are believed to occur in higher frequency in Black women), the association was not materially different than for the entire cohort (OR=3.47, 95% CI = 2.23-5.40). The fibroids themselves were associated with increased odds of hysterectomy in unadjusted analyses (OR = 1.59, 95% CI = 1.15-2.19), but became non-significant when adjusted for all other covariates (OR = 1.12, 95% CI = 0.78-1.62).
In summary, Black women had increased odds of hysterectomy compared to White women that persisted despite adjustment for participant characteristics and factors that may influence the decision to undergo hysterectomy. Findings from this study emphasize the need for further investigation into the practice of hysterectomy and greater efforts to disseminate information regarding non-hysterectomy alternatives for treatment of nonmalignant conditions during or prior to the decision-making process, particularly among minority populations.
Burgart J, Frohnert B, Nguyen RH
Health-Related Factors Associated with Postpartum Depression in Minnesota (15)
Background: Postpartum depression (PPD) is a serious disorder affecting women in the months after childbirth. 10-15% of women experience PPD after giving birth, but the true prevalence could be significantly higher. Possible underestimation is a concern since women may not be accurately diagnosed. PPD not only affects women themselves but their entire family. Very little is currently known about PPD in Minnesota women. This analysis identifies possible health-related factors associated with PPD that may be unique to this population.
Methods: This study used Minnesota PRAMS data. PRAMS is a population-based self-report survey of women who have had a live birth; this analysis (n=4671) focused on births from 2004 - 2006. Descriptive statistics were computed using SUDAAN software.
Results:Pre-pregnancy health-related behaviors and conditions were significantly associated with symptoms of PPD. Women who smoked before, during, or after pregnancy were more likely to develop PPD (16.28% who smoked before pregnancy vs. 10.35% who did not, p-value= 0.00, 18.15% who smoked during last trimester vs. 10.89% , p-value= 0.00, and 18.83% who smoked in the postpartum vs. 10.25%, p-value= 0.00). Women with diabetes were also more likely to develop PPD than those without diabetes (27.33% vs. 11.91%, respectively, p-value = 0.05), as were women with high blood pressure (24.71% vs. 11.85%, p-value= 0.03), and women with asthma (18.88% vs. 11.5%, p-value= 0.00). Women who were obese (BMI >29) or underweight (BMI < 19.8) prior to conception were also at an increased risk for PPD symptoms (15.3% for obese women, 12.98% for underweight vs. 10.15% for normal BMI, p-value= 0.00). Women who described their general health prior to pregnancy as “fair” or “poor” had a 29.48% prevalence of PPD symptoms as opposed to 15.98% who described their health as “good” and 9.26 % who described their health as “excellent” or “very good” (p-value= 0.00).
Conclusion: Minnesota women with certain health-related behaviors or diseases prior to pregnancy may be at an increased risk for PPD.
†Rima Chakraborty, Sharon Allen, Alicia Allen, Marc Mooney
Diurnal Smoking Patterns during Ad Libitum Smoking by Menstrual Cycle Phase (3)
Women have more difficulties quitting smoking than men indicating there may be a gender related difference in addiction to smoking. Literature has shown that diurnal patterns of smoking and nicotine gum use showed a similar trend of increased use during the morning hours. Gender differences in nicotine metabolism have been observed where women metabolize nicotine faster than men, especially women using combined estrogen-progesterone versus the progesterone-only contraceptives. Our hypothesis is that diurnal patterns of self-administration of nicotine via cigarette smoking will vary by menstrual cycle phase, such that women will smoke more during the morning hours in the follicular phase, when estrogen is relatively high compared to the luteal phase.
Regularly menstruating women smokers age 18-40 (n=31), not using hormones or psychotropic medications, were recruited for a randomized intent-to-treat study of menstrual cycle effects on smoking relapse. Subjects tracked of the time of day each cigarette was smoked, and menstrual cycle with daily diaries for one complete menstrual cycle of ad libitum smoking. Four menstrual phases were defined: menses - days of bleeding, follicular phase - days between menses and luteal phase, luteal - days 8-14 prior to the onset of bleeding, and late luteal - days 1-7 prior to the onset of bleeding. Analyses included Poisson regression to assess variations in the frequency of cigarettes smoked during two-hour blocks of time between the hours of 6:00 am and midnight by menstrual phase.
Subjects were, on average, 29.61 (±5.43) years old with 13.90 (±3.46) years of education. They smoked an average of 16.93 (±5.37) cigarettes per day and had a Fagerstrom Test of Nicotine Dependence score of 4.67 (±2.08). Analyses revealed significant differences in smoking rate as a function of phase [F(8,247)=3.77, p=0.0003], time of day [F(3,72)=10.56, p<0.0001] and their interaction [F(24,523)=9.58, p<0.0001). Women smoked fewer cigarettes per day during menses (6.80±0.61) than during the follicular (11.60±1.20), luteal (11.50±1.20) and late luteal (10.90±0.91) phases (p<0.0001). Temporal diurnal variation reflected a steep rise in smoking in the hours from 6:00 am to 8:00 am, followed by relatively constant smoking during the rest of the day.
The results suggest that smoking patterns of smoking may vary by menstrual phase. Women smoked significantly fewer cigarettes per day during menses than the other phases, possibly related to the lower levels of hormone levels during this phase. Larger studies are needed to assess variations in smoking patterns by menstrual cycle phase.
NIDA 5R01DA08075-10; MSROP Grant
Diane L. Dahm, M.D., Peter C. Rhee, D.O., Aynsley M. Smith,PhD, Matthew C. Sorenson, M.S., Tanya L. Hoskin, M.S., Jay Smith, M.D.
Prospective Evaluation of Bone Mineral Density Loss in Women Following Anterior Cruciate Ligament Reconstruction (30)
Background: Decrease in bone mineral density (BMD) has been shown to occur after ACL reconstruction. Postoperative bone loss after ACL reconstruction may predispose women to the development of early osteoarthritis or osteoporotic fractures in their lifetime.
Hypothesis: An accelerated rehabilitation program may blunt decreases in BMD and facilitate full recovery of bone loss after ACL reconstruction.
Study Design: Prospective, case series.
Methods: A 2-year, clinical and dual-energy x-ray absorptiometric (DEXA) investigation of BMD changes after ACL reconstruction in female patients. The intra-limb changes in BMD (g/cm2) at the femoral neck, distal femur, patella, and proximal tibia was determine from baseline (preoperative) to 6 weeks, 3 months, 6 months, 1 year, and 2 years post-operatively. Inter-limb differences in BMD were assessed at baseline and 2 years. Functional (single leg hop, triple jump, vertical jump, and isokinetic quadriceps/hamstring strength) and clinical outcomes (body max index, Tegner activity level, quadriceps circumference, and KT-2000 laxity measurements) were also evaluated at those intervals and analyzed for any association with changes in BMD.
Results: Twenty two patients were initially enrolled with 4 patients lost to follow up (n=21 at 1 year and n=18 at 2 years). The mean patient age was 26.1 years (range 16 to 40 years) and the mean body mass index (BMI) was 27.1 kg/m2. There was no significant inter-limb BMD difference at baseline (preoperatively). Significant decrease in BMD occurred in the injured extremity. Maximum mean bone loss, reported as a percentage decrease from baseline, occurred at the distal femur (-11.4% [p<0.0001]) and proximal tibia (-7.3% [p=0.002]) at 3 months postoperatively, and at the proximal tibia (-6.8% [p=0.001]) and femoral neck (-2.0% [p=0.02]) at 6 months. Decreased BMD in the entire index limb was noted at 1 year, with partial recovery of bone loss in the proximal tibia and patella at 2 years. Persistent BMD loss was noted in the ACL reconstructed distal femur and bilateral femoral necks at 2 years. Larger Tegner scores were associated with improved patellar BMD (ρ=0.03 {p=0.23)]. BMD deficits were not significantly associated with isokinetic muscle strength, function ability (single leg hope, triple and vertical jump), quadriceps circumference, or KT-2000 measurements at 2 years.
Conclusions: Female patients experienced significant BMD loss about the knee following ACL reconstruction in the affected lower extremity with only partial recovery at 2 year follow up despite an accelerated rehabilitation program and early return to activity.
Key Terms: Bone mineral density, anterior cruciate ligament reconstruction, female, osteoporosis
Melissa S. DeRycke, Katherine M. Harrington, Stefan E. Pambuccian, Steve E. Kalloger, Kristin L.M. Boylan, and Amy P.N. Skubitz
Overexpression of Nectin 4 in Ovarian Cancer (25)
Novel biomarkers for ovarian cancer diagnosis are needed for earlier detection. Additionally, biomarkers may potentially be used as innovative therapeutic targets that may result in increased survival for ovarian cancer patients. By gene microarray analysis, we found nectin 4 to be overexpressed in ovarian cancer tissues compared to normal ovaries and other normal, diseased, and cancerous tissues. Nectins are Ig-superfamily member proteins that contain one V and two C Ig-loops and are important in the formation and maintenance of adherens and tight junctions between cells. Nectin 4 expression in normal tissues is restricted to the placenta. However, other groups have recently discovered nectin 4 in breast carcinoma. In those studies, it was shown that the ectodomain of nectin 4 can be cleaved by the metalloproteinase ADAM17, and the extracellular fragment can be detected in the sera of breast cancer patients by an ELISA.
In this study, we have investigated nectin 4 expression levels in ovarian cancer, so as to determine its usefulness as a disease biomarker or a therapeutic target. Overexpression of nectin 4 mRNA in ovarian cancer was validated by RT-PCR analysis of cancerous ovarian tissues and cell lines compared to normal ovarian tissues and immortalized normal ovarian surface epithelial cell lines. Nectin 4 protein was expressed in approximately half of the ovarian cancer cell lines tested by both Western immunoblotting and flow cytometry. Immunohistochemical analysis of tissue microarrays composed of 500 early stage ovarian cancer tissues (n=205, stage I; n=211, stage II; n=84, stage III) detected nectin 4 protein in the cytoplasm in 50% of the ovarian cancer tissues, with the greatest number of samples staining in endometrioid and serous subtypes. No significant differences were observed across Silverberg grade or between early and late stages of disease within each histopathologic subtype. ADAM17, an enzyme that can cleave nectin 4, was detected in all ovarian cell lines tested to date, suggesting that the extracellular domain of nectin 4 may be cleaved from the ovarian cancer cells, potentially serving as a serum biomarker for the detection of ovarian cancer. We have cloned full-length nectin 4 into the pcDNA 3.1 vector, transfected an ovarian cancer cell line, and verified the expression of nectin 4 by Western immunoblotting and flow cytometry. Functional studies leading to a better understanding of the role of nectin 4 overexpression in ovarian cancer are currently underway.
Christopher DeStephano, B.S., Priscilla Flynn, DrPH, Brian Brost, MD
Results of a Pilot Project to Evaluate Somali Prenatal Education Videos in a Clinical Setting (40)
Broad differences in pregnancy-related health care expectations exist between Somali women and obstetrics practitioners. Focus groups identifying key themes led to the development of six targeted prenatal educational videos in Somali. Originally developed for Somali TV, topics include preparation for pregnancy, nutrition and exercise, pregnancy myths and facts, the father’s role, episiotomies, and cesarean sections. The purpose of this study was to evaluate the videos in a clinical setting. Patient acceptability and improved patient-provider communication were key outcomes. Study participants were recruited when presenting for regularly scheduled prenatal appointments. Programs were viewed prior to the clinical appointment and participants completed an 8-item survey. Following the clinical visit, providers completed a 4-item survey to indicate the video’s helpfulness in facilitating patient-provider interaction. Twenty-two patients (mean age 29.2 years, gravida 4.3, and para 2.7) viewed at least one video. Results showed that all women rated the videos as “appropriate” for Somali patients, 71% were rated as “extremely clear”, 61% indicated the information was “just the right amount” and extremely helpful. The language primarily spoken at home was Somali (82%) and 64% indicated Somali as the preferred language to receive their health information. Providers completing surveys indicated 26% of appointments were “more interactive” with 94% finding the videos as “somewhat” or “extremely helpful.” 96% of providers “recommended” or “strongly recommended” that prenatal educational material be presented using a culturally-appropriate, video format. These results will inform a larger study measuring the quality of patient-provider communication comparing the intervention to a control group (standard of care).
Wynette M. Dietz and Christopher A. Pennell
Immunity to Antigens Expressed on Tumor-Initiating Cells Leads to Tumor Eradication (28)
Cancer is a leading cause of morbidity and mortality worldwide. Current cancer therapeutics target rapidly dividing cells which constitute the bulk of the tumor. There is, however, a small percentage of tumor cells (1% - 10%) that are often resistant to chemotherapy and radiation. These cells, called tumor-initiating cells, maintain the properties of self-renewal and differentiation and can drive the formation of large heterogeneous tumors. Consequently, we propose to create a novel DNA vaccine aimed at targeting these cells. We hypothesize that by killing the tumor-initiating cells, the rest of the tumor will disappear due to the limited proliferative potential of the remaining cells. Tumor-initiating cells have been identified in many tumor types including brain, melanoma, breast and cutaneous lymphomas. Thus, this strategy may be applicable for the treatment of many tumors and may revolutionize cancer therapy. The 4T1 mouse mammary tumor model will be used to test this hypothesis since it is well characterized, mimics human stage IV breast cancer and its tumor-initiating cells preferentially express AN2, a chondroitin sulfate proteoglycan. Hsp70 will be used as an adjuvant in the DNA vaccines since it has potent immunostimulatory properties and can lead to the cross-presentation of tumor antigens to CD8+ T cells which can then selectively kill these tumor cells. Hypothesis: Immunity elicited by Hsp70 fused to an antigen expressed on tumor-initiating cells will lead to tumor eradication.
P. L. Faris, E. Vandenlangenberg, E. D. Eckert, R. S. Daughters, L. F. Iversen, K. Borgen, J. Cici, O. Kozak, R. E. Maxwell, B. K. Hartman
Treatment of severe bulimia nervosa patients is associated with a return to normal meal satiety (12)
Previously, we have proposed that voluntary binge-eating and vomiting in bulimia nervosa progressively stimulates the vagus nerve at higher intensities. To date, our studies have focused on the use of ondansetron, a 5-HT3 antagonist, in women with bulimia. Our findings have lead us to the conclusion that the vagus nerve plays a major role in the pathophysiology of the disorder and that the perpetuation of bulimic symptoms is driven by dysregulation of the positive vago-vagal feedback loop, i.e. induction of an oscillatory pattern. (Lancet 355:792, 2000). Several studies have suggested that in bulimia patients the satiety response to a standardized meal is blunted compared to control subjects (Halmi & Sunday, 1991; Hardigan et al, 1992; Kissileff et al, 1996). Bulimia subjects require a larger volume of food to reach the same level of fullness as the control subjects. In this study we used Vagus Nerve Stimulation (VNS) Therapy (Cyberonics, Inc.) to investigate the effects of directly stimulating the vagus nerve on frequency of binge/vomit episodes. To date, 10 women with severe unremitting bulimia have received unilateral implantation of a VNS Therapy System to the left cervical vagus. All 10 VNS subjects were administered a 450 mL milk-based liquid meal challenge at baseline and study exit to determine the effects on secondary indicators of disease recovery, including parameters related to satiety compared to 10 control subjects. The main effect on the mean number of bulimic episodes was significantly decreased from an average of 31.43 at baseline to 7.86 at the end of the 8 week acute stimulation phase (F=5.254, p<0.0001). In response to the meal challenge at their baseline visit, VNS subjects showed a significant decrease in reported feelings of satiety as compared to control subjects (p=0.044). After 8 weeks of vagal nerve stimulation, VNS subjects satiety response had normalized, as they reported a significant increase in feelings of satiety compared to baseline visit (p=0.042), approaching the satiety responses in control subjects. Therefore, we conclude that direct stimulation of the vagus nerve can significantly decrease binge/vomit episodes and that recovery from bulimic behaviors is associated with a return to normal satiety.
*Priscilla M. Flynn, PhD
The effects of acculturation on Somali women’s birth outcomes: Implications for health care policy (45)
Foreign birth is largely protective against infant preterm birth as noted by the “Latina paradox”. As women acculturate to American lifestyles, this protective effect dissipates. This study investigated the effect of acculturation on Somali refugee women’s birth outcomes. Results indicated that while individual factors identified to reflect acculturation changed significantly over time, changes in birth outcomes in Somali women were not attributable to these factors.
Methods: Data were extracted from medical records of 584 Somali women delivering infants at a Minnesota hospital between 1993 and 2006. Independent variables included maternal factors, fertility history, pregnancy complications, health behaviors, adequacy of prenatal care (APNCU) and acculturation. Dependent variables were infant birthweight and gestational age. Bivariate analyses measured relationships between independent and dependent variables for the total sample and between two time periods (1993-1999 and 2000-2006). Structural equation modeling (SEM) measured the fit between factors hypothesized to reflect acculturation (structural model) and the data (measurement model).
Results. Significant increases between groups with time include substance use/exposure (chi-square = 4.83, p = .0280), BMI (chi-square = 4.19, p = .0406), hemoglobin (t = 6.96, p = .0086), gestational diabetes (chi-square = 6.0, p = .0140) and preterm birth (chi-square = 3.87, p = .0491). A significant reduction in interpreter use was noted between groups (chi-square = 9.47, p = .0021). Bivariate analyses showed significance between increased APNCU and reductions in both preterm birth and gestational age. Post hoc SEM model results indicated a moderate to good fit between the structural and measurement models (CFI = .985, NFI = .979, RMSEA = .067). However, a comparison between time periods showed no differences in the composite factors hypothesized to reflect acculturation (CFI = .996, NFI = .909, RMSEA = .016).
Conclusion. Individual factors shown to reflect acculturation in foreign-born women have increased significantly in Somali women over time. While preterm births among Somali women increased significantly, factors identified to reflect acculturation in this study were not significantly related to this change. However, the increase in maternal obesity, gestational diabetes and preterm birth are of concern among this population.
Recommendations. Clinicians should prospectively collect data hypothesized to reflect acculturation to identify foreign-born women at increased risk of poor birth outcomes. Policy makers should support and clinicians should implement programs to provide prenatal education for Somali women aimed at reducing risk factors shown to compromise birth outcomes.
Patricia Fontaine, MD, MS, Nancy Sherwood, PhD, Melanie Wall, PhD, Terese A. Defor
Predictors of optimal pregnancy weight gain in a diverse Twin Cities population (44)
The Institute of Medicine (IOM) has established guidelines for optimal weight gain in pregnancy, yet only 30 to 40 percent of women achieve them.
Objective: To examine the weight and weight-gain characteristics of a large and diverse population of pregnant women as a first step in developing interventions to promote healthy weight gain.
Setting: The Minnesota Academy of Family Physicians Research Network, a large network of community-based and academic primary care practices, and HealthPartners Medical Clinics in the HMO Research Network (HMORN). Participants: 1,680 women aged 18 to 40 with measured baseline and prenatal weights, with term, singleton pregnancies delivered between July 2004 and July 2007.
Intervention/ Essential Feature: Demographic and clinical data were abstracted from electronic prenatal records at HealthPartners Clinics, using programming created for this study. Two MAFPRN clinics with paper charts were included to add Asian and African American women to the sample.
Measures: Multivariate analysis was performed with pregnancy weight gain outside IOM guidelines adjusted for baseline BMI, age, insurance status (commercial, subsidized or none), and self-identified race.
Results: 37% of women achieved weight gain within the IOM guidelines, 38% gained too much and 25% too little. Baseline BMI (p <.0001), race (p=.0007), and age (p=.002) were significant predictors of exceeding guidelines. White women, younger women, and women in high BMI categories were more likely to exceed guidelines. Baseline BMI (p=.02) and race (p=.0007) also predicted insufficient weight gain, with obese and African American and Asian women more likely to gain too little.
Conclusion: Similar to previous studies, we found that most pregnant women do not meet IOM recommendations for optimal pregnancy weight gain. Racial/ethnic differences are significant and will need to be addressed when developing appropriate interventions. African American women, for example, are more likely to enter pregnancy above normal BMI, but are at risk for insufficient weight gain. Obese women present a particular challenge, as they are more likely than those with BMIs in the normal range to be both over and under recommendations.
Elizabeth Ford, Sharon Allen, John Sirard & Alicia Allen
Differences in Self-Efficacy & Social Support for Exercise by Level of Nicotine Dependence among Female Smokers ages 50 and Over (33)
The aim of this study was to assess the differences in self-efficacy and social support for exercise, as well as baseline physical activity level by nicotine dependence among female smokers over the age of 50. We hypothesized that those with higher dependence may report lower levels of self-efficacy, social support and physical activity compared to those with lower levels of dependence.
Study participants (n=24) were recruited for an ongoing study aimed at assessing the feasibility of an adjunct exercise intervention for smoking cessation in women over the age of 50. Participants completed the Fagerstrom Test of Nicotine Dependence (FTND), Stages of Change, Social Support & Exercise (SSE), and Self-Efficacy for Exercise Scale (SEES) at their baseline visit during ad libitum smoking. Height and weight was also collected at this visit. Participants received a pedometer with instructions to wear it and record the number of steps taken per day for the next week without making any changes to their daily routine.
Participants were divided into two groups based on a median split of their FTND scores. High dependence was defined as a score of 5 or higher (n=13) and low dependence was defined as a score of less than 5 (n=11). Means were computed for each of the following: Family Participation (SSE subscale), Family Rewards & Punishments (SSE subscale), Friends Participation (SSE subscale), Friends Rewards & Punishments (SSE subscale), Sticking to It (SEES subscale), Making Time for Exercise (SEES subscale), Body Mass Index (BMI), and steps per day. T-tests were done to assess differences in the means of the six subscale scores, BMI and steps per day by nicotine dependence group. Fisher’s exact test was used to compute differences in stages of change by nicotine dependence group.
Participants were, on average 55.04 (±6.94) years old. They smoked an average of 18.65 (±8.79) cigarettes per day. Participants in the low dependence group scored significantly higher on the “Making Time for Exercise” subscale than the women in the high dependence group (16.46±2.03 v. 13.64±2.80, t-value=2.86, p-value=0.009). There were no other statistically significant differences between low and high nicotine dependence groups in terms of stage of change, self-efficacy, social support, baseline steps per day or baseline BMI.
These data may suggest that women who are less dependent on nicotine may be more
willing to make time for exercise. More research is needed to determine the validity of and the reason behind these preliminary findings.
Research Center Pilot Grant 2P50 DA013333-0'
Carolyn Garcia, PhD, MPH, RN
Feasibility of a school-based coping intervention for Latina adolescents (14)
Background: Latino girls (Latinas) experience higher rates of depression and suicidal ideation than other girls their age and Latino boys. Latina adolescents may benefit from preventive interventions that improve their ability to respond to and cope with life stressors. A coping intervention grounded in the knowledge about healthy youth development was developed for Latina adolescents.
Objective: To evaluate the feasibility and acceptability of a school-based coping intervention for Latina adolescents.
Methods: Latina adolescents, 15-21 years old, were recruited from two schools to participate in a 14-week coping intervention. Participants met weekly for a two-hour program, facilitated by two bilingual staff, consisting of dialogue, exercise, and skills-building. To assess feasibility and acceptability, weekly participation and attendance, and post-intervention focus group data were analyzed.
Results: Twenty-one Latina adolescents were successfully recruited. The fall semester intervention (n=10) occurred during school and had a 72% attendance rate; the spring semester intervention (n=11) was held after school and had an 84% attendance rate. Nine of the 21 (42%) participants attended all sessions. Three (14%) attended fewer than half of the sessions and unofficially dropped out. Three participants had limited involvement due to deportation issues involving themselves or a family member. Focus group data demonstrate participant acceptability, “I liked the discussions” and skills gained, “like coping skills to control stress. So when you learn ways to lessen your stress then you learn to make your life a little easier.”
Conclusions: The intervention appears feasible and acceptable. A randomized controlled trial is warranted to examine intervention effectiveness.
Geller MA, Petzel S, Godfrey K, Isaksson R.
Developing and Evaluating Health Education Materials for Women with Newly Diagnosed Ovarian Cancer (21)
Objective: Ovarian cancer, the 4th leading cause of cancer death in women, often occurs with little warning or disease knowledge. Women undergoing treatment report being uninformed regarding diagnosis, treatment, and potential chemotherapy side effects. They report greatest dissatisfaction with information received concerning nonmedical topics and management of emotional reactions. The objective was to develop and evaluate an informational video for women newly diagnosed with ovarian cancer. Three outcomes were studied: information acquired (learning), attitudes about learning, and distress.
Methods: A 30-minute video was designed in which oncology professionals, women with ovarian cancer, and their relatives discussed information about ovarian cancer. Women admitted for initial surgery were recruited and randomized to one of two video treatment groups: interventional or placebo. Subjects completed a pre- and post-treatment survey including: an Ovarian Cancer Information Quiz and 3 measures of emotional distress--general | 
