Sensitivity of different spirometric tests for detecting airway obstruction in childhood asthma.

OBJECTIVE: The objective of this study was to compare different measures of airflow obstruction by spirometry in childhood asthma. The objectives were; (a) to compare sensitivity of large airway tests (FEV1 and PEFR) with tests at low lung volumes (small airways) (FEF25-75, FEF50 and FEF75); (b) compare within each group which individual tests are more sensitive. METHODS: This was a retrospective analysis of 2307 spirometry tests performed during outpatient visits on 821 doctor-diagnosed asthma patients aged 6-18. Tests were deemed acceptable if they were acceptable and repeatable by American Thoracic Society (ATS) criteria. RESULTS: In mild obstruction, FEV1 detected 6.8% abnormal tests while FEF75 detected 33% (p < 0.0001). In more severe obstruction, the difference was more obvious (FEV1 14.8%; FEF75 71%). Tests at low lung volumes (small airway tests) were also more sensitive than PEFR. Within groups, FEV1 was more sensitive than PEFR in the large airway tests and FEF75 was more sensitive than FEF25-75 and FEF50 among the tests at low lung volumes (small airway tests). The FEV1/FVC ratio correlated more closely with tests at low lung volumes (small airway tests), than with large airway tests. CONCLUSIONS: (1) Tests at low lung volumes (small airway tests) are more sensitive than large airway tests; (2) Within groups, the FEV1 is better than PEFR and FEF75 is better than FEF25-75 or FEF50.

Quantitative evaluation of DNA hypermethylation in malignant and benign breast tissue and fluids.

The assessment of DNA had demonstrated altered methylation in malignant compared to benign breast tissue. The purpose of our study was to (i) confirm the predictive ability of methylation assessment in breast tissue, and (ii) use the genes found to be cancer predictive in tissue to evaluate the diagnostic potential of hypermethylation assessment in nipple aspirate fluid (NAF) and mammary ductoscopic (MD) samples. Quantitative methylation specific (qMS)-PCR was conducted on three specimen sets: 44 malignant (CA) and 34 normal (NL) tissue specimens, 18 matched CA, adjacent normal (ANL) tissue and NAF specimens, and 119 MD specimens. Training and validation tissue sets were analyzed to determine the optimal group of cancer predictive genes for NAF and MD analysis. NAF and MD cytologic review were also performed. Methylation of CCND-2, p16, RAR-beta and RASSF-1a was significantly more prevalent in tumor than in normal tissue specimens. Receiver operating characteristic curve analysis demonstrated an area under the curve of 0.96. For the 18 matched CA, ANL and NAF specimens, the four predictive genes identified in cancer tissue contained increased methylation in CA vs. ANL tissue; NAF samples had higher methylation than ANL specimens. Methylation frequency was higher in MD specimens from breasts with cancer than benign samples for p16 and RASSF-1a. In summary, i) routine quantitative DNA methylation assessment in NAF and MD samples is possible, and ii) genes hypermethylated in malignant breast tissue are also altered in matched NAF and in MD samples, and may be useful to assist in early breast cancer detection.

Carbohydrate antigens in nipple aspirate fluid predict the presence of atypia and cancer in women requiring diagnostic breast biopsy.

BACKGROUND: The goal of this prospective study was to determine (a) concentrations of the carbohydrate biomarkers Thomsen Friedenreich (TF) antigen and its precursor, Tn antigen, in nipple discharge (ND) collected from women requiring biopsy because of a suspicious breast lesion; and (b) if concentration levels predicted pathologic diagnosis. METHODS: Adult women requiring biopsy to exclude breast cancer were enrolled and ND obtained. The samples from 124 women were analyzed using an anti-TF and anti-Tn monoclonal antibodies in direct immunoassay. RESULTS: The highest median concentration in ND for TF and Tn was in women with ductal carcinoma in situ (DCIS). TF was higher in women with 1) cancer (DCIS or invasive) vs. either no cancer (atypia or benign pathology, p = .048), or benign pathology (p = .018); and 2) abnormal (atypia or cancer) versus benign pathology (p = .016); and was more predictive of atypia or cancer in post- compared to premenopausal women. Tn was not predictive of disease. High TF concentration and age were independent predictors of disease, correctly classifying either cancer or abnormal vs. benign pathology 83% of the time in postmenopausal women. CONCLUSIONS: TF concentrations in ND were higher in women with precancer and cancer compared to women with benign disease, and TF was an independent predictor of breast atypia and cancer. TF may prove useful in early breast cancer detection.

Soy isoflavones have an antiestrogenic effect and alter mammary promoter hypermethylation in healthy premenopausal women.

We determined if soy isoflavones have dose-related estrogenic and methylation effects. Thirty-four healthy premenopausal women were randomized to 40 mg or 140 mg isoflavones daily through one menstrual cycle. Breast specific and systemic estrogenic effects were assessed measuring the estrogenic marker complement (C)3 and changes in cytology, whereas methylation assessment of 5 cancer related genes (p16, RASSF1A, RARbeta2, ER, and CCND2) was performed on intraductal specimens. Serum genistein significantly increased after consuming both isoflavone doses. Cytology did not significantly change at either isoflavone dose. Serum C3 levels posttreatment were inversely related to change in serum genistein (r =-0.76, P = 0.0045) in women consuming low but not high dose isoflavones. The RAR beta 2 hypermethylation increase posttreatment correlated with the posttreatment genistein level considering the entire group (r = 0.67, P = 0.0017) and those receiving high-dose isoflavones (r = 0.68, P = 0.021). At the low but not the high isoflavone dose, CCND2 hypermethylation increase correlated with posttreatment genistein levels (r = 0.79, P = 0.011). In summary, the inverse correlation between C3 and genistein suggests an antiestrogenic effect. Isoflavones induced dose-specific changes in RARbeta2 and CCND2 gene methylation, which correlated with genistein levels. This work provides novel insights into estrogenic and methylation effects of dietary isoflavones.

Celecoxib concentration predicts decrease in prostaglandin E2 concentrations in nipple aspirate fluid from high risk women.

BACKGROUND: Epidemiologic studies suggest that long term low dose celecoxib use significantly lowers breast cancer risk. We previously demonstrated that 400 mg celecoxib taken twice daily for 2 weeks lowered circulating plasma and breast nipple aspirate fluid (NAF) prostaglandin (PG)E2 concentrations in post- but not premenopausal high risk women. We hypothesized that circulating concentrations of celecoxib influenced PGE2 response, and that plasma levels of the drug are influenced by menopausal status. To address these hypotheses, the aims of the study were to determine: 1) if circulating plasma concentrations of celecoxib correlated with the change in plasma or NAF PGE2 concentrations from baseline to end of treatment, and 2) whether menopausal status influenced circulating levels of celecoxib. METHODS: Matched NAF and plasma were collected from 46 high risk women who were administered celecoxib twice daily for two weeks, 20 subjects receiving 200 mg and 26 subjects 400 mg of the agent. NAF and plasma samples were collected before and 2 weeks after taking celecoxib. RESULTS: In women taking 400 mg bid celecoxib, plasma concentrations of the agent correlated inversely with the change in NAF PGE2 levels from pre- to posttreatment. Nonsignificant trends toward higher celecoxib levels were observed in post- compared to premenopausal women. There was a significant decrease in NAF but not plasma PGE2 concentrations in postmenopausal women who took 400 mg celecoxib (p = 0.03). CONCLUSION: In high risk women taking 400 mg celecoxib twice daily, plasma concentrations of celecoxib correlated with downregulation of PGE2 production by breast tissue. Strategies synergistic with celecoxib to downregulate PGE2 are of interest, in order to minimize the celecoxib dose required to have an effect.

uPA is upregulated by high dose celecoxib in women at increased risk of developing breast cancer.

BACKGROUND: While increased urokinase-type plasminogen activator (uPA) expression in breast cancer tissue is directly associated with poor prognosis, recent evidence suggests that uPA overexpression may suppress tumor growth and prolong survival. Celecoxib has been shown to have antiangiogenic and antiproliferative properties. We sought to determine if uPA, PA inhibitor (PAI)-1 and prostaglandin (PG)E2 expression in nipple aspirate fluid (NAF) and uPA and PGE2 expression in plasma were altered by celecoxib dose and concentration in women at increased breast cancer risk. METHODS: NAF and plasma samples were collected in women at increased breast cancer risk before and 2 weeks after taking celecoxib 200 or 400 mg twice daily (bid). uPA, PAI-1 and PGE2 were measured before and after intervention. RESULTS: Celecoxib concentrations trended higher in women taking 400 mg (median 1025.0 ng/mL) compared to 200 mg bid (median 227.3 ng/mL), and in post- (534.6 ng/mL) compared to premenopausal (227.3 ng/mL) women. In postmenopausal women treated with the higher (400 mg bid) celecoxib dose, uPA concentrations increased, while PAI-1 and PGE2 decreased. In women taking the higher dose, both PAI-1 (r = -.97, p = .0048) and PGE2 (r = -.69, p = .019) in NAF and uPA in plasma (r = .45, p = .023) were correlated with celecoxib concentrations. CONCLUSION: Celecoxib concentrations after treatment correlate inversely with the change in PAI-1 and PGE2 in the breast and directly with the change in uPA in the circulation. uPA upregulation, in concert with PAI-1 and PGE2 downregulation, may have a cancer preventive effect.

Is an FEV1 of 80% predicted a normal spirometry in cystic fibrosis children and adults?

INTRODUCTION: FEV1 is considered the gold standard spirometric measure for the assessment and management of cystic fibrosis lung disease. Recent evidence suggests that tests at lower lung volumes may be more sensitive. OBJECTIVES: To assess how many other spirometric tests are abnormal in the presence of a normal FEV1 (≥80%) and which spirometric tests are most sensitive in detecting airway obstruction. METHODS: This was a retrospective analysis of 3169 spirometry tests on 184 patients with cystic fibrosis aged 6-57 years. Tests were acceptable if they met ATS criteria. RESULTS: Tests with normal FEV1 , FEF75 showed obstruction in 58% of tests, FEF25-75 in 31% and FEV1 /FVC ratio in 72%. Overall 75% of tests had an abnormality. FEF75 , FEF25-75 , FEF50 and FEV1 /FVC ratio were all significantly more sensitive in identifying obstruction than FEV1 . The FEV1 /FVC ratio was the most sensitive of all tests in identifying obstruction except in adults (> 20 years), in whom FEF75 at 90%, was more sensitive than the ratio at 85%. FEF25-75 was also at 85% sensitive. Even though the FEV1 /FVC ratio was the most sensitive of all tests, in the presence of a normal ratio, 35% other tests were abnormal. CONCLUSIONS: Normal FEV1 , is not indicative of normal spirometry. FEV1 /FVC is the most sensitive measure of early or mild airway obstruction in children with cystic fibrosis. If only the FEV1 /FVC ratio was considered, many cases of obstruction would be missed, therefore all spirometric measures should be considered in the clinical evaluation of airway obstruction.

Prospective multicenter trial to determine the feasibility of collection and predictive ability of breast fluid analysis in postmenopausal women receiving SERMs.

We conducted a prospective ancillary study to the study of tamoxifen and raloxifene (STAR) trial involving 4 institutions to determine: (1) our ability to collect nipple aspirate fluid (NAF) in postmenopausal women taking medication to decrease breast proliferation and (2) NAF biomarkers associated with breast cancer. NAF was collected before and 6 months after starting treatment. Three biomarkers, cytology, fluid volume, and prostate-specific antigen (PSA), were analyzed. NAF was collected from 26 of 33 (79%) enrolled subjects at baseline. We were able to collect fluid in 84% of the subjects who produced NAF at baseline and returned for second aspiration after 6 months of treatment. In these women, cytology was unchanged in 85%, improved in 11%, and worsened in 4% of breasts. Median PSA increased from 37.5 to 112 ng/L after treatment. NAF volume did not significantly change. In conclusion, after treatment with tamoxifen or raloxifene, changes in both NAF cytology and PSA were generally favorable, consistent with their expected antiproliferative effective effect on the breast. Multiinstitutional clinical trials in postmenopausal women using NAF biomarkers as the primary endpoints are feasible.

Rural hospital patient safety systems implementation in two States.

CONTEXT AND PURPOSE: With heightened attention to medical errors and patient safety, we surveyed Utah and Missouri hospitals to assess the "state of the art" in patient safety systems and identify changes over time. This study examines differences between urban and rural hospitals. METHODS: Survey of all acute care hospitals in Utah and Missouri at 2 points in time (2002 and 2004). Factor analysis was used to develop 7 latent variables to summarize the data, comparing rural and urban hospitals at each point in time and on change between the 2 survey times. FINDINGS: On 3 of the 7 latent variables, there was a statistically significant difference between rural and urban hospitals at the first survey, with rural hospitals indicating lower levels of implementation. The differences remained present on 2 of those latent variables at the second survey. In both cases, 1 of those variables was computerized physician order entry (CPOE) systems. Rural hospitals reported more improvement in systems implementation between the 2 survey times, with the difference statistically significant on 1 of the 7 latent variables; the greatest improvement was in implementation of "root cause analysis." CONCLUSIONS: Adoption of patient safety systems overall is low. Although rates of adoption among rural versus urban hospitals appear lower, most differences are not statistically significant; the gap between rural and urban hospitals relative to quality measures is narrowing. Change in rural and urban hospitals is in the right direction, with the rate of change higher in rural hospitals for many systems.

Hospital patient safety: characteristics of best-performing hospitals.

Hospitals have made slow progress in meeting the Institute of Medicine's patient safety goals, and implementation of safety systems has been inconsistent. The next logical question is this: What organizational characteristics predict greater implementation of patient safety systems, in terms of both extent of systems and progress over time? To answer this question, a survey was administered to 107 hospitals at two points in time. Data were consolidated into seven latent variables measuring progress in specific areas. Using the overall measure, Joint Commission-accredited hospitals showed statistically significant improvement, as reflected in the sum score (p = .01); nonaccredited hospitals did not show statistically significant improvement (p = .21). Joint Commission accreditation was the key predictor of patient safety system implementation. Management type and urban/rural status were secondary predictors. Several factors may account for the strong association between accreditation and patient safety system implementation. In 2003, the Joint Commission began tying accreditation to patient safety goals. Also, Joint Commission data are now widely available to the public and may stimulate hospitals to address safety issues. Healthcare executives, hospital trustees, regulators, and policymakers should encourage Joint Commission accreditation and reward hospital efforts toward meeting Joint Commission standards. The Joint Commission should continually strive to maintain evidence-based and state-of-the-art standards that advance the aim of providing the best possible care for hospitalized patients.

Celecoxib decreases prostaglandin E2 concentrations in nipple aspirate fluid from high risk postmenopausal women and women with breast cancer.

BACKGROUND: Celecoxib inhibits PGE2 production in cancerous tissue. We previously reported that PGE2 levels in nipple aspirate fluid (NAF) and plasma were not decreased in women at increased breast cancer risk who received celecoxib 200 mg twice daily (bid). The endpoints of the current study were to determine if a short course of celecoxib 400 mg bid would decrease PGE2 levels in women 1) at increased breast cancer risk, and 2) with established breast cancer. METHODS: NAF and plasma samples were collected before, 2 weeks after taking celecoxib 400 mg bid, and two weeks after washout from 26 women who were at increased breast cancer risk. From 13 women with newly diagnosed breast cancer, NAF from the incident breast and plasma were collected before and on average 2 weeks after taking celecoxib. Additionally, in nine of the 13 women with breast cancer, NAF was collected from the contralateral breast. RESULTS: No consistent change in NAF or plasma PGE2 levels was noted in high risk premenopausal women. NAF PGE2 levels decreased after celecoxib administration in postmenopausal high risk women (p = 0.02), and in both the NAF (p = 0.02) and plasma (p = 0.03) of women with breast cancer. CONCLUSION: Celecoxib 400 mg bid taken on average for 2 weeks significantly decreased NAF, but not plasma, PGE2 levels in postmenopausal high risk women, and decreased both NAF and plasma PGE2 levels in women with newly diagnosed breast cancer. PGE2 levels may predict celecoxib breast cancer prevention and treatment efficacy. Our observations are preliminary, and larger studies to confirm and extend these findings are warranted.

The long road to patient safety: A status report on Missouri acute-care hospitals.

We surveyed Missouri's acute-care hospitals twice to assess the "state of the art" in patient safety systems. We found improvements in all areas studied, but progress is modest and falls short of national recommendations. We urge all Missourians to become more knowledgeable and assertive consumers of hospital care, and we ask them to support Missouri hospitals in their patient safety efforts, including provision of financial resources to put necessary systems in place.

Characteristics of smoking cessation guideline use by primary care physicians.

This study, based on a random sample mail survey of Missouri primary care physicians, identifies: (1) the extent and predictors of these physicians' awareness, agreement, adoption, and adherence to tobacco cessation guidelines; and (2) their knowledge/ beliefs about tobacco interventions. While primary care physicians play a key role in helping patients quit smoking, guidelines are not widely followed. "Reliance on respected colleagues for advice" was the one variable consistently identified as a predictor of guideline compliance.

The long road to patient safety: a status report on patient safety systems.

CONTEXT: Since the Institute of Medicine (IOM) reports on medical errors and quality, national attention has focused on improving patient safety through changes in "systems" of care. These reports resulted in a new paradigm that, rather than centering on individual errors, focuses on the "systems" necessary to facilitate and enhance quality and protect patients. OBJECTIVES: To assess the status of hospital patient safety systems since the release of the IOM reports and to identify changes over time in 2 states that collaborated on a patient safety project funded by the Agency for Healthcare Research and Quality. DESIGN, SETTING, AND PARTICIPANTS: Survey of all acute care hospitals in Missouri and Utah at 2 points in time, in 2002 and 2004, using a 91-item comprehensive questionnaire (n = 126 for survey 1 and n = 128 for survey 2). To assess changes over time, we also studied the cohort of 107 hospitals that responded to both surveys. MAIN OUTCOME MEASURES: Responses to the 91-question survey as well as changes in responses to the survey questions over an 18-month period. Seven latent variables were constructed to represent the most important patient safety constructs studied: computerized physician order entry systems, computerized test results, and assessments of adverse events; specific patient safety policies; use of data in patient safety programs; drug storage, administration, and safety procedures; manner of handling adverse event/error reporting; prevention policies; and root cause analysis. For each hospital, the 7 latent variables were summed to give an overall measure of the patient safety status of the hospital. RESULTS: Development and implementation of patient safety systems is at best modest. Self-reported regression in patient safety systems was also found. While 74% of hospitals reported full implementation of a written patient safety plan, nearly 9% reported no plan. The area of surgery appears to have the greatest level of patient safety systems. Other areas, such as medications, with a long history of efforts in patient safety and error prevention, showed improvements, but the percentage of hospitals with various safety systems was already high at baseline for many systems. Some findings are surprising, given the overall trends; for example, while a substantial percentage of hospitals have medication safety systems, only 34.1% [corrected] reported full implementation at survey 2 of computerized physician order entry systems for medications, despite the growth of computer technology in general and in hospital billing systems in particular. CONCLUSIONS: The current status of hospital patient safety systems is not close to meeting IOM recommendations. Data are consistent with recent reports that patient safety system progress is slow and is a cause for great concern. Efforts for improvement must be accelerated.

Lack of effect of celecoxib on prostaglandin E2 concentrations in nipple aspirate fluid from women at increased risk of breast cancer.

BACKGROUND: Cyclooxygenase enzymes (COX-1, COX-2, and COX-3) convert arachidonic acid to prostaglandins, prostacyclins, thromboxanes, and other hydroxy fatty acids. Among these, prostaglandin E(2) (PGE(2)) has tumor growth-promoting activity. The COX-2 isoform is the primary enzyme involved in PGE(2) production in cancerous tissue. OBJECTIVE/HYPOTHESIS: We administered the COX-2 inhibitor celecoxib (200 mg b.i.d.) to women at increased breast cancer risk. Our hypothesis was that PGE(2) would be secreted in breast nipple aspirate fluid (NAF), that levels in NAF would be higher than in corresponding plasma, and that celecoxib would decrease PGE(2) levels in NAF (reflecting a decreased breast tissue eicosanoid production) and plasma. SPECIFIC AIM: To determine if PGE(2) concentrations in NAF and plasma decrease after a 2-week course of celecoxib and then return to baseline 2 weeks after stopping the medication (washout). STUDY DESIGN: NAF and plasma were collected before celecoxib treatment, 2 weeks after taking celecoxib, and 2 weeks after washout. Each woman served as her own control. RESULTS: PGE(2) concentrations in NAF and plasma were detectable in samples using two measurement techniques. On average, NAF PGE(2) levels were 81-fold higher in NAF than in matched plasma. Technically, there were differences in PGE(2) concentrations measured in similar fluids depending on the assay technique used (RIA versus chemiluminescence immunoassay). There were no significant decreases in PGE(2) concentrations after celecoxib administration. CONCLUSIONS: PGE(2) can be measured in NAF. PGE(2) levels are concentrated in NAF when compared with matched plasma samples. Celecoxib 200 mg b.i.d. does not appear to significantly decrease PGE(2) concentrations in NAF and plasma.

Health locus of control, gender differences and adjustment to persistent pain.

Locus of control (LOC) beliefs, long thought important in adjustment to persistent pain, were studied among 160 subjects (67 males and 93 females) referred to a comprehensive pain rehabilitation program. The subscale structure of the Multidimensional Health Locus of Control (MHLC) was factorially replicated in our sample. Three unique MHLC profile clusters were identified for both males and females. Among men, cluster assignment was related to age only. The younger male patients reported a stronger internal attributional style. Older male patients relied more heavily on both chance and powerful other factors. Among women, cluster assignment was related to the use of coping strategies. For example, patients with high internal scores only, reflecting a strong internal orientation towards self-management of health care needs, were more likely to utilize Information-Seeking, Self-Blame, and Threat Minimization coping strategies than patients with high scores on both the Internal and Powerful Other factors. It appears that the presence of both Internal and Powerful Other health attributional styles is associated with less frequent use of cognitive self-management techniques. In understanding the LOC scores it is important to rely on pattern analysis of scores. Implications for clinical treatment are discussed.

Self-efficacy and pain behavior among subjects with fibromyalgia.

Given the lack of objective physical measures for assessing fibromyalgia syndrome (FS), the role of pain assessment is particularly important. The role of psychological factors is controversial among FS patients. This study was designed to better understand the relationship between pain behaviors and psychological variables. Specifically, this study (1) refined a pain behavior observation (PBO) methodology for use with FS patients, (2) determined whether stretching is a valid pain behavior, and (3) assessed whether psychological variables including self-efficacy and/or depression can predict pain behaviors after controlling for disease severity and age. The 73 FS subjects meeting the American College of Rheumatology classification system completed questionnaires measuring self-efficacy, depression, and pain. Trained physicians conducted tender-point examinations. Subjects were video-taped using a standardized procedure. Two trained raters independently coded all pain behaviors. Kappa coefficients and correlations among pain behaviors and self-reported pain indicated that the PBO method was both reliable and valid. However, the newly defined pain behavior 'stretching' was found to be negatively associated with self-reported pain. Hierarchical multiple regression (MR) analyses revealed that depression did not predict pain behavior over and above myalgic scores and age; however, in 3 separate MR analyses, self-efficacy for function, pain, and other symptoms each predicted pain behavior over and above myalgic scores and age. This study indicated that the original pain behavior scoring methodology is appropriate for use with the FS population and should not be modified to include the pain behavior 'stretching'. Self-efficacy was related to pain behavior while depression was not among this FS sample.

Pain behavior predictors among fibromyalgia patients.

This study was designed to assess the reliability and validity of a Pain Behavior Observation method with fibromyalgia syndrome (FS) subjects and to determine the factors which predict pain behavior among FS subjects. Fifty-eight female FS subjects participated in the videotaped Pain Behavior Observation method. Subjects also completed the McGill Pain Questionnaire (MPQ), the Arthritis Impact Measurement Scale (AIMS), and the Symptoms Checklist-90-Revised (SCL-90-R). Pain behavior totals were derived using the Pain Behavior Observation method of McDaniel et al. (1986). Results indicated that the scoring method of Keefe and Block (1982) developed for use with back pain patients was more generalizable to this FS sample. Total pain behavior score using the Keefe and Block scoring method was correlated with self-report pain. Interrater reliability ranged from 0.9 to 0.99. Hierarchical multiple regression analyses revealed that age and physical disability predicted the total pain behaviors. The Pain Behavior Observation method appears a valid pain measurement technique independent of depression among FS patients. Directions for future research are discussed.

The association of bloody nipple discharge with breast pathology.

BACKGROUND: It is believed that bloody spontaneous nipple discharge (SND) portends a greater chance of malignancy than nonbloody discharge, and that cytologic evaluation of SND assists in treatment planning. Our aims were to assess (1) the pathology of women with/without SND who require diagnostic breast surgery, (2) whether bloody SND is associated with a different spectrum of pathologic findings than nonbloody, and (3) whether SND cytology is influenced by pathologic findings. METHODS: One hundred seventy-five women who underwent breast operation were enrolled. Cytologic evaluation was performed on Papanicolaou-stained cytospin preparations of SND. RESULTS: Papilloma and hyperplasia (both without atypia) were more frequent in breasts with than without SND; breast cancer was more common in breasts without SND (P <.001 for all). All cases of breast cancer with SND, but only 33% without, contained a papilloma or papillary features. Seventy-five percent of cancers presenting with SND were nonbloody. Papilloma was the most common diagnosis in breasts with bloody SND and was more common (P=.017) than in breasts without, whereas hyperplasia was the most common diagnosis in breasts with nonbloody SND and was more common (P=.031) than in breasts with bloody SND. SND cytology was not significantly influenced by pathology. CONCLUSIONS: Breast cancer can present as unilateral nonbloody SND, indicating the importance of surgical intervention. Papilloma was more common in women with SND than without and most often presented as bloody SND.

A randomized prospective trial to assess the role of saline hydration on the development of contrast nephrotoxicity.

Though simple and attractive, the role of hydration for the prophylaxis of contrast nephrotoxicity has not been definitively established. We prospectively evaluated the role of deliberate saline hydration in patients undergoing nonemergency cardiac catheterization. Patients (n = 53) were randomized on the day prior to scheduled catheterization to one of two groups - group 1 (n = 27) received normal saline for 24 h (at a rate of 1 ml/kg/h) beginning 12 h prior to scheduled catheterization, and group 2 (n = 26) were allowed unrestricted oral fluids. Serum creatinine measured 24 and 48 h postcardiac catheterization was compared to the pre-randomization baseline value. The mean baseline calculated creatinine clearance was 79.6 +/- 31.9 ml/min and the mean baseline creatinine was 106 +/- 28 micromol/l. An increase in serum creatinine by at least 44.2 micromol/l (0.5 mg/dl), within 48 h of contrast exposure, was considered to represent clinically significant acute renal insufficiency. Ten subjects (18.9%) developed acute renal insufficiency. The incidence of acute renal insufficiency was significantly lower in group 1 (1 out of 27) as compared to group 2 (9 out of 26; p = 0.005 for comparison between groups; relative risk 0.11, 95% confidence interval 0.015 to 0.79). Twenty-four hours after contrast exposure, the mean increase in creatinine was less in group 1 vs. group 2 (8 +/- 11 vs. 20 +/- 21 micromol/l, p = 0.02). The increase in creatinine was not significantly different in group 1 vs. group 2 48 h after contrast exposure (12 +/- 21 vs. 29 +/- 40 micromol/l, p = 0.17). Deliberate saline hydration decreases the incidence of contrast-related acute renal failure and the severity of contrast-induced renal dysfunction in patients undergoing non-emergency cardiac catheterization.