Reduction in fat intake is not associated with weight loss in most women after breast cancer diagnosis: evidence from a randomized controlled trial.

BACKGROUND: A reduction in dietary fat intake has been suggested as a method to promote weight loss in women at risk for breast cancer recurrence. METHODS: Weight change in response to diet intervention was examined in 1010 women who had completed treatment for Stage I, Stage II, or Stage IIIA (American Joint Committee on Cancer staging system) primary operable breast cancer during their first year of participation in a randomized, controlled, diet intervention trial to reduce risk of recurrence. Diet intervention was performed by telephone counseling and promoted a low fat diet that also was high in fiber, vegetables, and fruit. The comparison group was provided with general dietary guidelines to reduce disease risk. Multiple linear regression models were used to examine the relations among demographic and personal characteristics, changes in diet composition and exercise level, and change in body weight or body mass index. RESULTS: The average weight change in the 1-year period was 0.04 kg for the intervention group and 0.46 kg for the comparison group. For the total group, body weight was stable (+/- 5% baseline weight) for 743 women (74%), whereas 114 (11%) lost weight, and 153 (15%) gained weight. These distributions were similar in the two study groups inclusive of all study participants and for only those women with a baseline body mass index of > or = 25 kg/m2. Initial body mass index and changes in fiber and vegetable intakes, but not change in percent of energy obtained from fat, were associated independently with change in weight or body mass index. CONCLUSIONS: For most women at risk for breast cancer recurrence, diet intervention to promote a reduction in fat intake was not associated with significant weight loss. Testing the effect of a substantial change in diet composition on risk for breast cancer recurrence is unlikely to be confounded by weight loss in subjects who were the recipients of intensive intervention efforts.

Low-energy reporting in women at risk for breast cancer recurrence. Women's Healthy Eating and Living Group.

This study examined the extent of low-energy reporting and its relationship with demographic and lifestyle factors in women previously treated for breast cancer. This study used data from a large multisite clinical trial testing the efficacy of a dietary intervention to reduce risk for breast cancer recurrence (Women's Healthy Eating and Living Study). Using the Schofield equation to estimate energy needs and four 24-h dietary recalls to estimate energy intakes, we identified women who reported lower than expected energy intakes using criteria developed by G. R. Goldberg et al. (Eur. J. Clin. Nutr., 45: 569-581, 1991). We examined data from 1137 women diagnosed with stage I, stage II, or stage IIIA primary, operable breast cancer. Women were 18-70 years of age at diagnosis and were enrolled in the Women's Healthy Eating and Living Study between August 19, 1995, and April 1, 1998, within 4 years after diagnosis. The Goldberg criteria classified about one-quarter (25.6%) as low-energy reporters (LERs) and 10.8% as very LERs. Women who had a body mass index >30 were almost twice (odds ratio, 1.95) as likely to be LERs. Women with a history of weight gain or weight fluctuations were one and a half times as likely (odds ratio, 1.55) to be LERs as those who were weight stable or weight losers. Age, ethnicity, alcohol intake, supplement use, and exercise level were also related to LER. Characteristics (such as body mass index, age, ethnicity, and weight history) that are associated with low-energy reporting in this group of cancer survivors are similar to those observed in other populations and might affect observed diet and breast cancer associations in epidemiological studies.

Role of DNA methylation at GATC sites in the dnaA promoter, dnaAp2.

DnaA protein is required for the initiation of DNA replication at the bacterial chromosomal origin, oriC, and at the origins of many plasmids. The concentration of DnaA protein is an important factor in determining when initiation occurs during the cell cycle. Methylation of GATC sites in the dnaAp2 promoter, two of which are in the -35 and -10 sequences, has been predicted to play an important role in regulating dnaA gene expression during the cell cycle because the promoter is sequestered from methylation immediately following replication. Mutations that eliminate these two GATC sites but do not substantially change the activity of the promoter were introduced into a reporter gene fusion and into the chromosome. The chromosomal mutants are able to initiate DNA replication synchronously at both moderately slow and fast growth rates, demonstrating that GATC methylation at these two sites is not directly involved in providing the necessary amount of DnaA for precise timing of initiation during the cell cycle. Either sequestration does not involve these GATC sites, or cell cycle control of DnaA expression is not required to supply the concentration necessary for correct timing of initiation.

Late abdominal aortic aneurysm rupture after AneuRx repair: a report of three cases.

Rupture due to device failure and/or endoleak is the most feared complication of endoluminal grafting for exclusion of abdominal aortic aneurysm. We present three previously unreported cases of abdominal aortic aneurysm rupture 23 months after AneuRx "repair" and describe the mechanisms of failure and discuss instructive technical aspects of their management.

A novel alveolar type I cell-specific biochemical marker of human acute lung injury.

Currently there is no recognized biochemical or molecular marker for human parenchymal lung injury analogous to markers for acute myocardial injury. Injury to the alveolar epithelial barrier is of central importance in the pathogenesis of and recovery from acute lung injury. In animal models, an alveolar type I cell-specific protein, RTI(40), has been shown to be an accurate marker of alveolar epithelial damage. We now report that HTI(56), a novel apical plasma membrane protein specific to the human type I cell, is a biochemical marker for lung injury. Using a sensitive, quantitative, light-based ELISA, we measured HTI(56) in pulmonary edema fluid from 15 patients with a clinical diagnosis of acute lung injury and 12 control patients with hydrostatic (cardiogenic) pulmonary edema. HTI(56) was also measured in plasma from these two groups and from 11 normal volunteers. The amount of HTI(56) was 4. 3-fold higher (p < 0.0001) in alveolar edema fluid and 1.4-fold higher (p < 0.05) in plasma from the patients with acute lung injury, compared with patients with hydrostatic pulmonary edema. To our knowledge, this study is the first to utilize a specific marker of alveolar epithelial damage in human disease and demonstrates the feasibility of using a blood test to detect lung parenchymal damage.

Plasma carotenoids are biomarkers of long-term high vegetable intake in women with breast cancer.

We investigated predictors of change in plasma carotenoids from baseline to 3 y and examined plasma carotenoid concentrations at 1 and 3 y in response to a high vegetable diet. Participants were 56 women diagnosed with breast cancer and enrolled in a randomized feasibility study for a trial examining the effect of a diet high in vegetables and fruits on the risk of breast cancer recurrence. Independent t test analysis revealed that the intervention group had significantly higher vegetable and fruit servings and fiber at 12 mo and significantly higher vegetable servings at 36 mo compared with the control group (P < 0.05). Energy intake from fat was significantly lower in the intervention group at 12 and 36 mo. The intervention group had significantly higher consumption of beta-carotene, alpha-carotene, lutein and beta-cryptoxanthin at 12 mo (P < 0.05). beta-Carotene, alpha-carotene and lutein intakes also were significantly higher at 36 mo (P < 0.05). At 36 mo, the intervention group had significantly higher plasma concentrations of alpha-carotene and beta-carotene compared with the control group. Repeated-measures ANOVA revealed that the intervention group had significantly increased (P < 0.05 with Bonferroni correction) plasma beta-carotene, alpha-carotene, lutein and lycopene concentrations at 12 and 36 mo compared with baseline. Baseline carotenoid concentrations were significantly inversely predictive (P < 0.05) of plasma carotenoid change. In addition, change in body mass index (BMI) and plasma cholesterol concentrations were predictive of plasma carotenoid change from baseline to 3 y. Results of this study demonstrate that change in plasma carotenoid concentrations is associated with change in BMI, change in plasma cholesterol and baseline carotenoid concentrations. Plasma carotenoid response can be an indicator of long-term high vegetable intake for women at risk of breast cancer recurrence.

Factors associated with weight gain in women after diagnosis of breast cancer. Women's Healthy Eating and Living Study Group.

OBJECTIVE: To identify the factors associated with weight gain after diagnosis of breast cancer in a heterogeneous population of women. DESIGN: Descriptive cross-sectional study. SUBJECTS: 1,116 patients who had been diagnosed with stage I, stage II, or stage IIIA primary, operable breast cancer within the previous 4 years. Patients were recruited during enrollment into a diet intervention trial to reduce risk for breast cancer recurrence. Analysis Demographic data, weight history, and physical activity information obtained by questionnaire and medical information obtained by chart review; dietary assessment based on four 24-hour dietary recalls collected by telephone. Associations between weight change after the diagnosis of breast cancer and prediction variables were examined using univariate and multiple linear regression analyses. RESULTS: Overall, 60% of the subjects reported weight gain, 26% reported weight loss, and 14% reported no change in weight after the diagnosis of breast cancer. The overall mean weight change was a gain of 2.7 kg (6 lb). Factors positively and independently associated with weight gain were time since diagnosis of breast cancer, adjuvant chemotherapy, African-American ethnicity, current energy intake, and postmenopausal status at time of study entry. Factors inversely and independently associated with weight gain were prediagnosis body mass index, age at diagnosis, education level, and exercise index score. APPLICATIONS: Higher energy intake and lower level of physical activity are independently associated with increased risk for weight gain after the diagnosis of breast cancer. Strategies to modify these behaviors are likely to influence the long-term pattern of weight change.

Comparison of serum carotenoid responses between women consuming vegetable juice and women consuming raw or cooked vegetables.

The objective of this study was to examine serum concentrations of alpha-carotene, beta-carotene, lutein, lycopene, and beta-cryptoxanthin due to consumption of vegetable juice versus raw or cooked vegetables. Subjects included female breast cancer patients who had undergone surgical resection and who were enrolled in a feasibility study for a trial examining the influence of diet on breast cancer recurrence. A high-vegetable, low-fat diet was the focus of the intervention, and some of the subjects were specifically encouraged to consume vegetable juice. At 12 months, blood samples were collected and analyzed for carotenoid concentrations via high-performance liquid chromatography methodology. Matched analysis and paired t test were conducted on two groups: those who consumed vegetable juice (the juice group) and those who consumed raw or cooked vegetables (no juice group). Serum concentrations of alpha-carotene and lutein were significantly higher in the vegetable juice group than in the raw or cooked vegetable group (P < 0.05 and P = 0.05, respectively). Paired t test analysis did not demonstrate a significant difference in serum values of beta-carotene, lycopene, and beta-cryptoxanthin between subjects consuming juice and those not consuming any juice. These results suggest that alpha-carotene and lutein appear to be more bioavailable in the juice form than in raw or cooked vegetables. Therefore, the food form consumed may contribute to the variability in serum carotenoid response to vegetable and fruit interventions in clinical studies.

Chitobiase, a new reporter enzyme.

N,N'-diacetylchitobiase (chitobiase) from the marine organism Vibrio harveyi is a highly stable reporter enzyme for gene fusions. This enzyme hydrolyzes the disaccharide chitobiose to N-acetyl glucosamine. The advantages of the reporter gene encoding chitobiase (chb) are: (i) that chitobiase and N-acetyl-beta-D-glucosaminidase activities are missing in E. coli strains, (ii) chitobiase can be monitored using blue/white colony indicator plates and (iii) convenient substrates for this enzyme are commercially available. The use of chitobiase as a reporter enzyme is generally applicable to the study of gene expression in those bacteria that do not contain N-acetyl-beta-D-glucosaminidases. We constructed plasmid vectors containing a multiple cloning site for producing in-frame fusions to chitobiase, the attP of lambda phase for movement into the bacterial chromosome for single-copy analysis, the gene encoding chloramphenicol acetyltransferase (cat), the pACYC184 origin of replication and the rrnBt1t2 terminator region upstream of the chb gene to prevent read-through from other promoters. In-frame fusions between the dnaA gene and chb were moved to the chromosome by site-specific recombination with the chromosomal attB site. These single-copy fusions were assayed for chitobiase to examine the effects of a deletion in the dnaA regulatory region.

Dietary supplement use by women at risk for breast cancer recurrence. The Women's Healthy Eating and Living Study Group.

OBJECTIVE: To develop a method of collecting, organizing, and analyzing information on nutrient and nonnutrient dietary supplement use by women at risk for breast cancer recurrence as a component of nutrition assessment and monitoring, and to describe the characteristics associated with dietary supplement use in this population at enrollment in a clinical trial to prevent breast cancer recurrence. DESIGN: Cross-sectional descriptive study design. SUBJECTS: Women diagnosed with breast cancer within the previous 4 years (n=435). ANALYSIS: Dietary supplements reported in four 24-hour dietary recalls were categorized according to primary nutrient and nonnutrient contents. Prevalence of dietary supplement use is described. Associations between supplement use and demographic and participant characteristics were examined using chi(2) analysis and logistic regression. RESULTS: Dietary supplement use was reported by 80.9% of the women. Increased likelihood of supplement use was associated with demographic (eg, older age, higher level of education, white race vs other ethnic groups) and personal (eg, lower body mass index, moderate alcohol consumption) characteristics. Use of vitamin C and related compounds, other nutrients (eg, n-3 fatty acids, evening primrose oil), and herbal products was inversely associated with months since diagnosis; use of miscellaneous supplements (eg, shark cartilage) was directly associated with more advanced stage at diagnosis. APPLICATIONS: Monitoring dietary supplement use is an important aspect of nutrition assessment, especially in populations with chronic health conditions or medical diagnoses. Demographic and personal characteristics, time passed since diagnosis, and stage of cancer at diagnosis are predictive of dietary supplement use by women at risk for breast cancer recurrence. Associations in this population may be present in other groups that are the object of nutrition intervention efforts.

Responsiveness of carotenoids to a high vegetable diet intervention designed to prevent breast cancer recurrence.

Epidemiological studies suggest that a high vegetable diet may reduce risk for breast cancer and may also improve prognosis after the diagnosis of breast cancer. Circulating carotenoids may serve as a biomarker of vegetable and fruit intake, although several factors affect their bioavailability from food sources and may influence concentrations. One purpose of this study was to identify factors predictive of serum carotenoid, retinol, and alpha-tocopherol concentrations in 79 postsurgically resected breast cancer patients at enrollment and at 12 months in a feasibility study of a high vegetable, low fat diet intervention to reduce risk for cancer recurrence. Another purpose was to identify variables associated with change in these serum concentrations 12 months after randomization into control and intervention groups. The diet intervention (versus control) group had significantly greater increases in carotenoid intakes (P < 0.03) and significantly greater increases in serum concentrations of lutein, alpha- and beta-carotene, lycopene, and retinol (P < 0.04). Stepwise multiple regression revealed the level of dietary intake to be predictive of most serum carotenoid concentrations at baseline and 12 months, with additional associations between selected micronutrient concentrations and serum cholesterol, body mass index, age, percentage of energy intake from fat, and alcohol intake also observed at these time points. Intervention group change in serum carotenoid concentrations was inversely associated with baseline level, age, and change in serum cholesterol concentration and positively associated with change in carotenoid and alcohol intake. Circulating carotenoid concentrations are responsive to a high vegetable diet intervention, which also included reduced dietary fat and increased fiber intakes, to reduce risk for breast cancer recurrence.

Feasibility of a randomized trial of a high-vegetable diet to prevent breast cancer recurrence.

Epidemiologic evidence supports the concept that diet influences risk for breast cancer and suggests that prognosis after the diagnosis of breast cancer may also be related to modifiable nutritional factors. The purpose of this study was to investigate the feasibility of a randomized trial of a high-vegetable, reduced-fat, and increased-fiber diet intervention to reduce risk for recurrence among breast cancer survivors. This major change in dietary pattern was promoted through intensive telephone counseling. Participants were 93 women who had been diagnosed with breast cancer (stages I, II, and IIIA) within the previous four years and who had completed their initial treatment. We assessed adherence to the study diet using repeated 24-hour dietary recalls at 6 and 12 months and measurement of circulating carotenoid concentrations. Six months after randomization, the intervention group had significantly increased their mean intake of vegetables (+4.6 servings/day), fruit (+0.7 servings/day), and fiber (+6.4 g/1,000 kcal) and significantly reduced their intake of dietary fat (-9.9% of energy) compared with the control group. Circulating concentrations of carotenoids also increased in the intervention group. These changes persisted at the 12-month visit. Results of this study demonstrate that telephone counseling can be a useful approach in diet intervention and that breast cancer survivors can adopt and maintain a high-vegetable, reduced-fat dietary pattern.

Nutrient intakes from foods and dietary supplements in women at risk for breast cancer recurrence. The Women's Healthy Eating and Living Study Group.

Dietary supplements have been suggested to have a role in cancer prevention and treatment. The purpose of this study was to describe the nutrient intakes from foods and dietary supplements in women at the time of enrollment into a clinical trial to prevent breast cancer recurrence. Subjects were within four years of diagnosis with Stage I, II, or IIIA breast cancer and had completed medical treatment (n = 435). Intakes were assessed with four 24-hour recalls over two weeks. Dietary nutrient intakes in supplement users were compared with intakes in nonusers, and supplement nutrient intakes in participants consuming diets providing < 75% were compared with those in participants consuming > or = 75% of recommended levels. Intakes of participants with diets meeting general guidelines for disease prevention were compared with intakes of those whose diets did not meet these guidelines. Dietary supplement use was reported by 352 (80.9%) of the participants, but frequency of excess intakes did not exceed 5% for all micronutrients examined. Women whose diets provided higher levels of most vitamins and minerals were more likely to obtain additional amounts of these micronutrients from dietary supplements. Participants reporting use of any supplement consumed diets providing more dietary fiber (p < 0.04) and less dietary fat (p < 0.001) than nonusers of any supplement. These results illustrate the importance of monitoring dietary supplement use in clinical trials with a focus on preventing cancer recurrence, because supplements can contribute substantially to nutrient intakes in the population under study.

Do admitted patients held in the emergency department impact the throughput of treat-and-release patients?

OBJECTIVE: To examine the impact of reducing ED "boarders" (through the use of a short-stay inpatient medicine unit) on the amount of time that treat-and-release patients spend in the ED. METHODS: A retrospective analysis of hours spent in the ED was made at a university hospital teaching ED for treat-and-release patients in 4 clinical categories: chest pain, asthma exacerbation, sickle-cell crisis, and seizure. The average hours per patient spent in the ED during the 4-month intervals before (August-November 1993) and after (August-November 1994) the establishment of the short-stay medicine unit were compared. Data were analyzed using the 2-tailed, unpaired t-test. RESULTS: This short-stay inpatient medicine unit received on average 135 patients per month from the ED, with an average length of stay of 2.4 days. The mean (+/-SD) number of admitted patients per day waiting in the ED > 8 hours for an inpatient bed dropped from 9.6 +/- 4.2., before the institution of this unit, to 2.3 +/- 2.6. There was a significant reduction in the average number of hours spent in the ED by treat-and-release patients with chest pain (from 7.3 +/- 6.0 to 5.5 +/- 4.8 hr/patient, p < 0.001) and asthma exacerbation (from 5.0 +/- 3.6 to 4.2 +/- 2.9 hr/patient, p < 0.05), but not with sickle-cell crisis or seizure, after the implementation of the short-stay unit. CONCLUSION: Reducing the number of admitted patients waiting in the ED for inpatients beds, in this case by establishment of a short-stay medicine unit, is associated with a decrease in the interval that treat-and-release patients spend in the ED.

A method to evaluate the elastic behavior of vascular stents.

PURPOSE: To develop a simple method for determining the elastic behavior of vascular stents. MATERIALS AND METHODS: An experimental apparatus was constructed to determine the elastic behavior of four different vascular stents. Each stent was expanded within an artificial compliant vessel and was subjected to an increasing external pressure. The cross-sectional area of each stent was recorded at incremental changes in pressure. Compliance was estimated from the slope of a linear regression analysis fit to the pressure-area data in the elastic range of deformation. RESULTS: The self-expandable stents were the most compliant, and balloon-expandable stents exhibited the least compliance. The balloon- expandable stents initially deformed in an elastic manner and then yielded irrecoverably at higher pressures. CONCLUSION: A simple method has been devised that allows the elastic behavior of stents to be assessed. Quantification of stent compliance with this method is important as a predictor of stent resistance to compression in vivo.

Effects of vascular stent surface area and hemodynamics on intimal thickening.

PURPOSE: To compare the in vivo response to a new mechanically expandable vascular stent with the response to an existing type of balloon-expandable stent. MATERIALS AND METHODS: Prototype stents were deployed by means of a balloon catheter in the left iliac arteries of four healthy dogs. Palmaz stents were deployed in the contralateral iliac arteries to act as a control, and all stents were explanted after 6 weeks. Arteriography was performed at the time of insertion and before harvest, and pressure gradients were measured across each stent. The stents were then harvested and submitted for histologic examination. RESULTS: The performance of the prototype stent was similar to that of the Palmaz stent with respect to structural integrity, migration, maintenance of intraluminal diameter, ease of deployment, radiopacity, and pressure gradients. Unlike the Palmaz stent, the prototype stent did not foreshorten during expansion. The stents showed a lack of uniformity in terms of the measured luminal area and neointimal accumulation. Neointimal accumulation was more confined to the struts of the prototype stent; the lumen therefore had a fluted appearance. Neointimal accumulation was more broadly distributed around the circumference of the vessel wall of the Palmaz stent. CONCLUSION: In vivo performance of the prototype stent was similar to that of the Palmaz stent. Stent geometry may be an important determinant of neointimal response and resultant long-term patency.

Ischemic nephropathy as an indication for renal artery reconstruction in renovascular hypertension.

The utility of renal revascularization to control hypertension secondary to renal artery occlusive disease is widely recognized. However, revascularization for purposes of renal salvage, although performed successfully in many instances, is a more difficult issue, owing to the higher morbidity and mortality rates associated with operative intervention in an older patient population with significant comorbid conditions. It is therefore imperative to appropriately select patients who may benefit from revascularization, and the aim of our discussion is to aid in this selection process.