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Modeling the toxicity of aromatic compounds to tetrahymena pyriformis: the response surface methodology with nonlinear methods.

Response surface models based on multiple linear regression had previously been developed for the toxicity of aromatic chemicals to Tetrahymena pyriformis. However, a nonlinear relationship between toxicity and one of the molecular descriptors in the response surface model was observed. In this study, response surface models were established using six nonlinear modeling methods to handle the nonlinearity exhibited in the aromatic chemicals data set. All models were validated using the method of cross-validation, and prediction accuracy was tested on an external data set. Results showed that response surface models based on locally weighted regression scatter plot smoothing (LOESS), multivariate adaptive regression splines (MARS), neural networks (NN), and projection pursuit regression (PPR) provided satisfactory power of model fitting and prediction and had similar applicabilities. The response surface models based on nonlinear methods were difficult to interpret and conservative in discriminating toxicity mechanisms.

Animals↗

Risk for hypertension in workers exposed to carbon disulfide in the viscose rayon industry.

BACKGROUND: Chronic exposure to carbon disulfide (CS(2)) has been associated with hypertension, elevated cholesterol, arteriosclerosis, ischemic heart disease and related mortality, adverse nervous and reproductive health effects, and hearing impairment. This study assessed the hypertension risk for male rayon workers exposed to CS(2). METHODS: A total of 251 rayon workers and 226 administrative clerks at two plants in Taiwan received health examination and interviews, and were compared for hypertension risk. On-site CS(2) levels were measured. RESULTS: The hypertension was more prevalent in the exposure group (43.4%) than in controls (7.1%) with greater impact on systolic blood pressure than diastolic. Multivariate logistic regression analysis showed a significant dose-response relationship between hypertensive risk and cumulative exposure index (CEI) with an odds ratio of 15.1 for workers exposed to 343-468 year-ppm of CS(2). The overall risk was elevated to 7.6 times higher for rayon workers. The risk increased significantly after more than 10 years of employment. CONCLUSIONS: This study suggests that it takes a long exposure period to develop hypertension for rayon workers with CS(2) exposure.

Adult↗

A clinical nomogram for predicting long-term survival in advanced colorectal cancer.

From our prospectively accrued database of patients with gastrointestinal cancer, 1057 patients with advanced colorectal cancer were identified with the aim of determining predictive factors for survival of greater than 2 years and to use this information to develop a predictive nomogram. Patient's baseline characteristics, type and number of chemotherapy regimens received, and response to chemotherapy were assessed by univariate and multivariate logistic regression comparing those who survived greater than or less than 2 years. A total of 161 (15.2%) patients survived more than 2 years, so-called long survivors (LS). In multivariate analysis, positive predictive factors for LS were: good performance status (PS), normal serum carcinoembryonic antigen (CEA), rectal primary, Dukes' stage A-B, well or moderate differentiation, two or less disease sites, response to chemotherapy and treatment used protracted venous infusion (PVI) 5-fluorouracil (5-FU) in first-line chemotherapy, and the increasing number of chemotherapy treatments received. From these PS, CEA, number of sites and response to first-line chemotherapy were used to develop a nomogram capable of predicting the probability of survival beyond 2 years for an individual patient. This large study confirmed the relevance of known prognostic factors in metastatic colorectal cancer and demonstrated the importance of response to chemotherapy as an independent factor to predict LS. By combining these, we developed a nomogram which provides information which is likely to prove useful in the management of patients with advanced colorectal cancer.

Adolescent↗

A prospective study of age and lifestyle factors in relation to community-acquired pneumonia in US men and women.

BACKGROUND: Information is limited on risk factors for community-acquired pneumonia (CAP) in free-living populations. We examined the associations of age, smoking status, body mass index (BMI), weight change during adulthood, physical activity, and alcohol intake with risk of CAP among men and women. METHODS: The study population included 26,429 men aged 44 to 79 years from the Health Professionals Follow-up Study and 78,062 women aged 27 to 44 years from the Nurses' Health Study II. Information was collected by biennial mailed questionnaires and the main outcome was physician-diagnosed incident pneumonia. RESULTS: There were 290 cases among men (6 years of follow-up) and 305 cases among women (2 years of follow-up). Age, smoking status, BMI, physical activity, and alcohol intake were taken into account in the multivariate logistic regression model. There was a dose-response relation between aging and risk of CAP among men. Compared with never smokers, current smoking was associated with risk of CAP among men (relative risk, 1.46; 95% confidence interval, 1.00-2.14) and women (relative risk, 1.55; 95% confidence interval, 1.15-2.10). In addition, BMI was directly associated with an increased risk of CAP among women. Compared with the participants who maintained their weight during adulthood, the risks were nearly 2-fold higher among men and women who gained 40 lb or more (> or =18 kg). The risk of CAP decreased with increasing physical activity among women. We also found no significant relation between alcohol intake and risk of CAP among men and women. CONCLUSIONS: Smoking and excessive weight gain are risk factors for CAP among men and women, and physical activity was inversely associated with risk of CAP only among women. The incidence of CAP could possibly be decreased by lifestyle factors.

Adult↗

Adrenal function following high-dose steroids in ovarian cancer patients.

PURPOSE: Steroid doses similar to those used to prevent paclitaxel-associated hypersensitivity reactions and cisplatin-induced nausea have been associated with hypothalamic-pituitary-adrenal (HPA) axis suppression. We assessed HPA function in patients receiving high-dose steroids as part of their chemotherapy regimen for epithelial ovarian cancer. PATIENTS AND METHODS: From January to July 1994, a cross-sectional study of HPA function was performed on patients receiving dexamethasone (DEX) as part of their paclitaxel and cisplatin chemotherapy regimen (n = 9). Patients received 20 mg of DEX orally, 6 and 12 hr prior to paclitaxel (135 mg/m2) and 10-20 mg intravenously before cisplatin (50-100 mg/m2). In addition, patients received approximately 12 mg/day of DEX orally for 4 days after their chemotherapy as an antiemetic. HPA integrity was evaluated by the administration of synthetic adrenocorticotropic hormone (ACTH). The ACTH stimulation test was performed 11-19 days after the completion of the course of DEX. Patients had fasting baseline cortisol levels drawn at approximately 0800 followed by a 25-unit intravenous injection of ACTH. Post-ACTH cortisol levels were repeated at 30 and 60 min. RESULTS: The mean (+/- SEM) fasting baseline level of cortisol was 12.4 +/- 2.3 micrograms/dl (normal, 7-23 micrograms/dl). At 30 min following ACTH administration, the mean cortisol level rose 17.1 micrograms to 29.5 +/- 1.8 micrograms/dl; at 60 min it rose 21.4 micrograms to 33.8 +/- 2.5 micrograms/dl [P < 0.001] (normal increase 9-39 micrograms). All patients demonstrated a sufficient increase in their plasma cortisol after ACTH stimulation, indicating normal HPA function on the days tested. However, there was a significant trend toward lower increases in plasma cortisol at 30 and 60 min as the interval from ACTH stimulation testing to the DEX regimen decreased (r = 0.986; P < 0.0001). The chemotherapy cycle number had no impact on cortisol response in the multivariate analysis. Based on multiple linear regression, HPA function may be suppressed for approximately 8 days, but up to 14 days from the start of this DEX regimen. CONCLUSION: Current steroid regimens prescribed with chemotherapy transiently decrease HPA function, but do not appear to inhibit the HPA axis long term. HPA function may be suppressed for approximately 8 days from the commencement of chemotherapy cycles involving DEX. Patients presenting within the first 8 days of a chemotherapy cycle using steroids with symptoms attributable to HPA suppression may benefit from HPA axis testing.

Antiemetics↗

Hyperhomocysteinemia, and low intakes of folic acid and vitamin B12 in urban North India.

BACKGROUND AND AIM: An adverse coronary risk profile has been reported amongst rural-to-urban migrant population living in urban slums undergoing stressful socio-economic transition. These individuals are likely to have low intakes of folic acid and vitamin B12, which may have an adverse impact on serum levels of homocysteine (Hcy). To test this hypothesis, we studied serum levels of Hcy in subjects living in an urban slum of North India and healthy subjects from urban nonslum area. METHODS: Group I consisted of 46 subjects (22 males and 24 females) living in an urban slum, while group II consisted of healthy subjects (n = 26, 13 males and 13 females) living in the adjacent non-slum area. Anthropometric measurements, biochemical profile (fasting blood glucose, total cholesterol, serum triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol) and fasting serum levels of Hcy were measured. Dietary intakes of folic acid, vitamin B12, vitamin B1, and iron were calculated by the 24-hour dietary recall method. Serum levels of Hcy were correlated with dietary intakes of nutrients, anthropometry, and metabolic variables. RESULTS: Sex-adjusted serum levels of Hcy in micromol/L (Mean +/- SD) were high, though statistically comparable, in both the groups (group I: 20.8 +/- 5.9 and group II: 23.2 +/- 5.9). Overall, higher than normal serum levels of Hcy (> 15 micromol/L) were recorded in 84% of the subjects. A substantial proportion of subjects in both groups had daily nutrient intakes below that recommended for the Asian Indian population (folic acid: 93.4% in group I and 96.7% in group II, vitamin B12: 76.1 % in group I and 88.4% in group II). However, between the two groups, average daily dietary intakes of both the nutrients were statistically comparable. As compared to non-vegetarians, vegetarians showed lower intakes of folic acid (p < 0.01) and vitamin B12 (p < 0.01) in both groups. On multivariate linear regression analysis with serum Hcy as the response variable and vegetarian/non-vegetarian status and sex (male/female) as predictor variables, higher serum levels of Hcy were observed in vegetarians vs non-vegetarians (1 = 4.6, p < 0.05) and males vs females (beta = 5.3, p < 0.01). CONCLUSIONS: Low intakes of folic acid and vitamin B12, and hyperhomocysteinemia, in both the healthy population living in urban slums and adjacent urban non-slum areas, are important observations for the prevention of nutritional and cardiovascular diseases in the Indian subcontinent.

Adult↗

Basal and postprandial serum-promoted cholesterol efflux in normolipidemic subjects: Importance of fat mass distribution.

Excess of adipose tissue may affect the reverse cholesterol transport mediated by high-density lipoprotein (HDL). Impairments in this system may be one possible factor favoring atherosclerosis development in obesity. To investigate if gender and regional fat mass distribution independently influence reverse cholesterol transport (RCT), we studied in vitro the capacity of serum to promote the cell cholesterol efflux. Measurements were performed both in the fasting state and in the postprandial state, a setting known to stimulate cholesterol transport and altered in obesity. Thirteen obese women with an android phenotype, waist-to-hip ratio (WHR): 0.98 to 0.85 and 51 normal-weight subjects: 25 women and 26 men, with a similar WHR range: 0.96 to 0.67, were recruited. All the participants were normolipoproteinemic in the fasting state and were given an oral fat load. Blood samples were taken before giving the oral fat load and after every 2 hours. The measurements of the ability of serum to promote cholesterol efflux from cells were performed using 3H-cholesterol labeled Fu5AH hepatoma cells in the fasting state 6 and 8 hours after the lipid rich meal. Incremental serum triglyceride (TG), area under the curve (iAUC) and AUC of retinyl palmitate (RP) for the obese women and nonobese subjects were similar. Basal cholesterol efflux was reduced in obese women compared with normal-weight women (26.75% +/- 3.1% v 30.81% +/- 4.2%, P =.004). However, the magnitude of cholesterol efflux promoted by whole serum increased similarly in all the groups. In the subjects with similar WHR, no gender difference was observed in the postprandial TG response and in the first step of RCT. Multivariate regression analyses indicated that plasma HDL-cholesterol (HDL-C) concentration is the best predictor of cholesterol efflux in the fasting state with an independent mild additive effect of WHR. Conversely, postprandial efflux appeared to be mostly related to the WHR with a mild additive effect of HDL-C. Our results indicate that alterations in the first step of RCT can occur in normolipidemic obese subjects and are tightly associated with the abdominal distribution of fat mass. Android obesity in women brings them to the level of men with respect to RCT.

Administration, Oral↗

Atopic phenotype is an important determinant of immunoglobulin E-mediated inflammation and expression of T helper cell type 2 cytokines to ascaris antigens in children exposed to ascariasis.

Studies have shown a strong inverse relationship between atopy and geohelminth infection, indicating that atopy may protect against geohelminth infection. Resistance to ascariasis in atopic individuals may occur through greater immunoglobulin E-mediated responses and expression of T helper cell type 2 (Th2) cytokines to parasite antigens. To investigate the effect that atopy has on the immune response to Ascaris antigens, school-age children were recruited from rural schools in Ecuador. Immunologic variables were compared between children stratified by atopic and/or A. lumbricoides-infection status; the variables included cytokine expression by peripheral-blood mononuclear cells (PBMCs) and histamine release in response to Ascaris antigens. Atopic children had both greater frequencies of PBMCs expressing interleukin (IL)-4 and IL-5 and enhanced histamine release, compared with those in nonatopic children. Stratification by atopic and A. lumbricoides-infection status revealed the greatest histamine and Th2 cytokine responses in the stratum of atopic, noninfected children. Multivariate regression analyses showed significant effects for atopic status but not for infection status on Th2 cytokine expression and histamine release.

Adolescent↗

Parental presence during induction of anesthesia. A randomized controlled trial.

BACKGROUND: To determine whether parental presence during induction of anesthesia is an effective preoperative behavioral intervention, a randomized controlled trial with children undergoing outpatient surgery was conducted. METHODS: Eighty-four children were randomly assigned to a parent-present or parent-absent group. Using multiple behavioral and physiologic measures of anxiety, the effect of the intervention on the children and their parents was assessed. Predictors for the response to the intervention were examined using multivariate linear regression analysis. RESULTS: When the intervention group (parent-present) was compared to the control group (parent-absent), overall there were no significant differences in any of the behavioral or physiologic measures of anxiety tested during induction of anesthesia. Using the child's serum cortisol concentration as the outcome, parental presence, the child's age and baseline temperament, and trait anxiety of the parent, were identified as predictors of the child's anxiety during induction. Analysis of variance demonstrated that three groups showed diminished cortisol concentrations with parental presence: children older than 4 yr (P = 0.001), children whose parent had a low trait anxiety (P = 0.02), and children who had a low baseline level of activity as assessed by temperament (P = 0.05). CONCLUSIONS: Children who were older than 4 yr or those with a parent with a low trait anxiety or who had a low baseline level of activity/temperament benefited from parental presence during induction.

Anesthesia↗

Postpartum discharge preferences of pediatricians: results from a national survey.

OBJECTIVE: To identify practice/physician characteristics that influence pediatricians' self-reported newborn discharge practices. METHODS: Of the pediatricians randomly surveyed through a national American Academy of Pediatrics periodic survey conducted in 2000, 490 were identified as routinely providing care for newborns in the nursery. These respondents rated the importance of 22 infant, maternal, and peripartum factors in determining readiness for nursery discharge on a 5-point Likert scale and reported their perceptions of optimal and minimal lengths of stay (LOS) for healthy term newborns. Importance of readiness factors was dichotomized as "high" (very important or important) versus "low" (neither, unimportant, or very unimportant). Relationships between pediatricians' responses and demographic information were explored using multivariate logistic regression. RESULTS: Most pediatricians (at least 81%) rated all 7 infant clinical factors (eg, stable, normal vital signs, successful feeding) as highly important determinants of discharge readiness. Women were 2 to 3 times more likely to rate maternal and peripartum factors such as maternal fatigue and stress, demonstration of maternal skills, breastfeeding knowledge or experience, adequacy of social support, maternal age <18 years, and low income/lack of financial resources as highly important. With respect to hospital LOS, women were twice as likely to identify an optimal LOS as >36 hours and a minimal LOS as >24 hours. Pediatricians in group settings were 3 times as likely as those in solo or 2-physician practices to advocate an optimal LOS >36 hours, and those with a high proportion of publicly insured or uninsured patients were less likely to identify an optimal LOS as >36 hours (odds ratio: 0.53). CONCLUSIONS: Female pediatricians report a more biopsychosocial approach to determining discharge readiness than their male counterparts, taking into account infant characteristics, maternal skills, and socioemotional issues that may affect the mother-infant pair's adjustment at home. The finding that those who provide care for the most financially vulnerable patients do not see the need for longer LOS is both surprising and of concern. The results support the need for a prospective critical examination of perinatal hospital discharge practices, such as the Pediatric Research in Office Settings Life Around Newborn Discharge Study.

Attitude of Health Personnel↗

Emotional dysfunction associated with diabetes in Mexican adolescents and young adults with type-1 diabetes.

OBJECTIVE: To assess the emotional dysfunction associated with diabetes in Mexican young individuals with type-1 diabetes. MATERIAL AND METHODS: A cross-sectional survey was conducted to perform a complete clinical and psychosocial evaluation of 93 consecutive type-1 diabetes patients, and 14 to 30 years. RESULTS: Adolescents had higher scores of emotional dysfunction related to diabetes and a diminished knowledge in diabetes-related areas. A multivariate logistic regression model showed that an inadequate emotional response to diabetes (high problem areas in diabetes or PAID scores) was mainly associated with a poor glycemic control (OR = 2.9, 95% CI 0.9-9.7, p = 0.09). Apprehension about the future and the possibility of serious complications had the highest mean PAID score in all age groups. CONCLUSIONS: New strategies should be developed to improve the routine care and support of young individuals with type-1 diabetes.

Adolescent↗

The effect of body build, diet and endocrine factors on the extrinsic fibrinolytic system in healthy young women.

In this study, the importance of anthropometric, nutritional and endocrine variables on the plasma concentrations of tissue plasminogen activator antigen (tPA) and plasminogen activator inhibitor (PAI-l) were investigated. Tissue plasminogen activator concentration and PAI-l activity in plasma were studied in 24 healthy young women after diet periods which caused depletion or filling of hepatic glycogen stores. Plasminogen activator inhibitor levels in the glycogen-depleted state and the glycogen-repleted state were positively correlated, as were also tPA levels. In fasting subjects with repleted glycogen stores, tPA values correlated with fasting insulin concentration and blood pressures. In fasting subjects depleted of glycogen stores, PAI-l correlated with tPA, plasma insulin, triglycerides, and waist-to-hip girth ratio; triglycerides and waist-to-hip girth ratio also correlated with tPA. Over a 4-h period following intake of a test-meal, the glucose and insulin responses were not correlated with the fibrinolytic variables. Multivariate regression analysis suggested that waist-to-hip girth ratio and diastolic blood pressure were independently associated with tPA concentrations both in subjects with depleted and repleted glycogen stores. Thus, both constitutional factors such as anthropometric variables and blood pressure, and nutritional status of the subjects may be related to tPA and PAI- levels in plasma. This should be taken into account in clinical studies on fibrinolysis.

Adult↗

Early detection and screening for ovarian cancer: does physician specialty matter?

OBJECTIVE: To examine physician factors associated with ovarian cancer screening. METHODS: Postal questionnaires to Maryland primary care physicians. Bivariate tests for statistical significance used X-Square and Student's t tests. Multivariate analysis and logistic regression were used to analyze responses based on specialty type, gender, and work experience. RESULTS: Fifty-six percent of the 375 were male, 44%, females; 33%, OB/GYN; and 67%, family/internal medicine (FM/IM). The mean age was 47 and the mean number of years in practice was 16. OB/GYNs provided more ovarian cancer counseling, OR 2.64 (CI 1.55, 4.48) and were more likely to respond correctly to knowledge questions--i.e., reduction of ovarian cancer risk with oral contraceptive (OCP) use than IM/FM, OR 8.57 (CI 3.54, 20.8). Overall, there were few gender differences in approach to evaluation, but male physicians were less likely to be aware of the relationship of OCP use to ovarian cancer risk than females, OR 0.48 (CI 0.25, 0.91). IF/FM physicians were less likely to order CA-125 for patients (of any age) based upon symptoms of bloating or physical examination alone. OB/GYN physicians, OR 4.77 (2.73, 8.34) and physicians with > 15 years in practice, OR 2.79 (1.46, 5.35) attended more meetings on ovarian cancer than non OB/GYNs or those with less experience. Although 74% indicated access to the Internet, just 16% to 26% used the Internet for cancer information; OB/GYNs used the Internet less frequently than FM/IMs, OR 0.53 (0.28, 0.97). CONCLUSIONS: Specialty was more predictive of knowledge, approach to evaluation, and counseling than gender or experience.

Clinical Competence↗

Immune tolerance in hemophilia-principal results from the International Registry. Report of the factor VIII and IX Subcommittee.

40 Hemophilia Centers from the USA, Canada, Europe and Japan referred to the International Registry 204 patients with haemophilia A, treated by Immune Tolerance (IT) Protocols over the past two decades because of the presence of an inhibitor to FVIII. 82% of the patients were high responders, while IT was started with low levels of inhibitor (< 10 BU) in most (57.3%) of the cases. 69 patients (33.8%) were given the highest FVIII dosage (> or = 200 IU/kg/day), 71 (34.8%) intermediate dosages (50- < 200) and 64 (31.4%) the lowest dosages (< 50). Of 158 patients persevering with treatment long enough to judge the outcome thereof, 107 (67.7%) achieved tolerance, 12 (7.6%) had a partial response, while 39 (24.7%) did not respond. Multivariate logistic regression analysis showed that two variables were independently associated with the highest probability of success: the use of high dose protocols (> or = 100 IU/kg/day) (p < .0001) and the presence of low levels of inhibitor (< 10 BU) at enrollment (p = .004). The Kaplan-Meier inhibitor-free survival curve showed that tolerance is longlasting: only 1 out of 107 patients relapsed and the longest documented tolerant patient has been inhibitor-free for 16 years. 129 hemophiliacs were HIV Ab-negative at enrollment; of the 118 HIV-screened after the treatment, 18 (13.9%) were found to be HIV Ab-positive. IT can indeed modify the natural history of inhibitors to FVIII in hemophilia.

Adolescent↗

Prediction of conductive hearing loss based on acoustic ear-canal response using a multivariate clinical decision theory.

This study evaluated the accuracy of acoustic response tests in predicting conductive hearing loss in 161 ears of subjects from the age of 2 to 10 yr, using as a "gold standard" the air-bone gap to classify ears as normal or impaired. The acoustic tests included tympanometric peak-compensated static admittance magnitude (SA) and tympanometric gradient at 226 Hz, and admittance-reflectance (YR) measurements from 0.5 to 8 kHz. The performance of individual, frequency-specific, YR test variables as predictors was assessed. By applying logistic regression (LR) and discriminant analysis (DA) techniques to the multivariate YR response, two univariate functions were calculated as the linear combinations of YR variables across frequency that best separated normal and impaired ears. The tympanometric and YR tests were also combined in a multivariate manner to test whether predictive efficacy improved when 226-Hz tympanometry was added to the predictor set. Conductive hearing loss was predicted based on air-bone gap thresholds at 0.5 and 2 kHz, and on a maximum air-bone gap at any octave frequency from 0.5 to 4 kHz. Each air-bone gap threshold ranged from 5 to 30 dB in 5-dB steps. Areas under the relative operating characteristic curve for DA and LR were larger than for reflectance at 2 kHz, SA and Gr. For constant hit rates of 80% and 90%, both DA and LR scores had lower false-alarm rates than tympanometric tests-LR achieved a false-alarm rate of 6% for a sensitivity of 90%. In general, LR outperformed DA as the multivariate technique of choice. In predicting an impairment at 0.5 kHz, the reflectance scores at 0.5 kHz were less accurate predictors than reflectance at 2 and 4 kHz. This supports the hypothesis that the 2-4-kHz range is a particularly sensitive indicator of middle-ear status, in agreement with the spectral composition of the output predictor from the multivariate analyses. When tympanometric and YR tests were combined, the resulting predictor performed slightly better or the same as the predictor calculated from the use of the YR test alone. The main conclusion is that these multivariate acoustic tests of the middle ear, which are analyzed using a clinical decision theory, are effective predictors of conductive hearing loss.

Acoustic Impedance Tests↗

Urokinase-type plasminogen activator and its inhibitor PAI-1: predictors of poor response to tamoxifen therapy in recurrent breast cancer.

BACKGROUND: Urokinase-type plasminogen activator (uPA) is a proteolytic enzyme thought to be involved in processes leading to tumor cell invasion of surrounding tissues. Its activity during metastasis may be regulated by an inhibitor, PAI-1. Previous work has shown that high levels of uPA and PAI-1 are associated with poor prognosis in primary breast cancers. PURPOSE: In this pilot study, we explored possible associations between the expression levels of uPA or PAI-1 and the efficacy of tamoxifen treatment in breast cancer patients with relapsed disease. METHODS: Levels of uPA, PAI-1, estrogen receptor (ER), and progesterone receptor (PgR) were assayed in cytosolic extracts derived from the primary breast tumors of 235 tamoxifennaive patients who had recurrent disease. The extracts were classified as positive or negative for each assayed factor. In some analyses, ER and PgR levels were evaluated together. In these analyses, three ER/PgR subsets were defined: low, intermediate, and high. All patients in the study received tamoxifen therapy upon relapse (median follow-up, 57 months). Association of the tested factors with the response to tamoxifen treatment was studied by logistic regression analysis. Association of the factors with progression-free and overall survival was further evaluated by Cox univariate and multivariate regression analyses. RESULTS: Patients with uPA-negative tumors exhibited a better response (tumor regression or stable disease, maintained for more than 6 months) to tamoxifen treatment than those with uPA-positive tumors (51% versus 26% response; odds ratio [OR] = 0.34; 95% confidence interval [CI] = 0.18-0.65). The response rate was also better for patients with PAI-1-negative tumors than for those with PAI-1-positive tumors (49% versus 35% response; OR = 0.57; 95% CI = 0.32-1.01). In addition, patients with uPA-positive or PAI-1-positive tumors showed shorter progression-free survival (P = .001 and P < .05, respectively) and total survival after relapse (P = .005 and P < .005, respectively). When patients were stratified by ER/PgR status, the only statistically significant association between uPA levels and reduced tamoxifen response was seen in the subset whose tumors possessed intermediate levels of ER/PgR (16% response in uPA-positive versus 60% response in uPA-negative tumors; OR = 0.13; 95% CI = 0.04-0.41). Overall, uPA status appeared independent of association with ER/PgR status in its ability to predict response to tamoxifen treatment. The association of PAI-1 expression and the response to tamoxifen was less pronounced when patients were stratified by ER/PgR status. CONCLUSION: Measurement of primary breast tumor uPA levels may be useful in predicting the overall response of metastatic disease to tamoxifen therapy.

Adult↗

Age and radiation response in glioblastoma multiforme.

OBJECTIVE: Advanced age is a strong predictor of shorter survival in patients with glioblastoma multiforme (GM), especially for those who receive multimodality treatment. Radiographically assessed tumor response to external beam radiation therapy is an important prognostic factor in GM. We hypothesized that older GM patients might have more radioresistant tumors. METHODS: We studied radiographically assessed response to external beam radiation treatment (five-level scale) in relation to age and other prognostic factors in a cohort of 301 GM patients treated on two prospective clinical protocols. A total of 223 patients (74%) were assessable for radiographically assessed radiation response. A proportional odds ordinal regression model was used for univariate and multivariate analysis. RESULTS: Younger age (P = 0.006), higher Karnofsky Performance Scale score before radiotherapy (P = 0.027), and more extensive surgical resection (P = 0.028) predicted better radiation response in univariate analyses. Results were similar when clinical criteria were used to classify an additional 61 patients without radiographically assessed radiation response (stable versus progressive disease). In multivariate analyses, age and extent of resection were significant independent predictors of radiation response (P < 0.05); Karnofsky Performance Scale score was of borderline significance (P = 0.07). CONCLUSION: Older GM patients are less likely to have good responses to postoperative external beam radiation therapy. Karnofsky Performance Scale score before radiation treatment and extent of surgical resection are additional predictors of radiographically assessed radiation response in GM.

Brain Neoplasms↗

Adolescent HMO enrollees' utilization of out-of-plan services.

PURPOSE: To examine use of reproductive health services, correlates of out-of-plan care, and reasons for seeking out-of-plan care among adolescent health maintenance organization (HMO) enrollees. METHODS: We mailed a self-administered questionnaire to a population-based random sample of 18-year-old members of Group Health Cooperative of Puget Sound (GHC) who had been enrolled for at least 12 months. The sample was selected from GHC's computerized enrollment database. Questionnaire topics included reproductive history, sexual behavior, and use of health services. Analysis included Chi-square tests to examine differences by gender and out-of-plan status and multivariate analysis using logistic regression. RESULTS: About one-half of the 997 respondents (69% response rate) reported using out-of-plan care. In multivariate analysis, the strongest correlate of out-of-plan care was having had sexual intercourse [odds ratio (OR) = 1.84; 95% confidence interval (CI) = 1.35-2.52]. Other correlates were using alcohol (OR = 1.79; 95% CI = 1.29-2.48), living with parents (OR = 0.65; 95% CI =.46-.92), and being female (OR = 1.60; 95% CI = 1.21-2.11). During the prior year, over 80% of sexually active respondents had obtained contraceptives out-of-plan and 45% of those tested for sexually transmitted diseases (STDs) reported out-of-plan testing. The primary reasons reported for using any out-of-plan care were lack of convenience (28%), being out of town (26%), and confidentiality (23%; only reported by sexually active respondents). CONCLUSIONS: A substantial proportion of GHC-enrolled adolescents used out-of-plan care. Those who did were more likely to have had STDs and other health problems than those who used only in-plan services. Without continuity of care, these at-risk adolescents may not be receiving optimal services.

Adolescent↗